Scaffolding along Nucleic Acid Duplexes Using 2'-Amino-Locked Nucleic Acids

DEFF Research Database (Denmark)

Astakhova, I Kira; Wengel, Jesper

2014-01-01

-LNA nucleotides. By application of different chemical reactions, modification of 2'-amino-LNA scaffolds can be efficiently performed in high yields and with various tags, postsynthetically or during the automated oligonucleotide synthesis. The choice of a synthetic method for scaffolding along 2'-amino-LNA mainly....../DNA probes bind nucleic acid targets with advantages of high affinity and specificity. Thus, molecular motion of nanodevices and programmable self-assembly of chemically modified LNA/DNA nanomaterials can be followed by bright fluorescence signaling from the functionalized LNA units. Another appealing aspect...

Comparative crystallization and preliminary X-ray diffraction studies of locked nucleic acid and RNA stems of a tenascin C-binding aptamer

International Nuclear Information System (INIS)

Förster, Charlotte; Brauer, Arnd B. E.; Brode, Svenja; Schmidt, Kathrin S.; Perbandt, Markus; Meyer, Arne; Rypniewski, Wojciech; Betzel, Christian; Kurreck, Jens; Fürste, Jens P.; Erdmann, Volker A.

2006-01-01

Locked nucleic acid (LNA) nucleotides are RNA analogues with a useful additional conformational constraint; the current investigation will provide the first crystallographic view of an all-LNA duplex. The pharmacokinetic properties of an aptamer against the tumour-marker protein tenascin-C have recently been successfully improved by the introduction of locked nucleic acids (LNAs) into the terminal stem of the aptamer. Since it is believed that this post-SELEX optimization is likely to provide a more general route to enhance the in vitro and in vivo stability of aptamers, elucidation of the structural basis of this improvement was embarked upon. Here, the crystallographic and X-ray diffraction data of the isolated aptamer stem encompassed in a six-base-pair duplex both with and without the LNA modification are presented. The obtained all-LNA crystals belong to space group P4 1 2 1 2 or P4 3 2 1 2, with unit-cell parameters a = b = 52.80, c = 62.83 Å; the all-RNA crystals belong to space group R32, with unit-cell parameters a = b = 45.21, c = 186.97 Å, γ = 120.00°

Short (16-mer locked nucleic acid splice-switching oligonucleotides restore dystrophin production in Duchenne Muscular Dystrophy myotubes.

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Vanessa Borges Pires

Full Text Available Splice-switching antisense oligonucleotides (SSOs offer great potential for RNA-targeting therapies, and two SSO drugs have been recently approved for treating Duchenne Muscular Dystrophy (DMD and Spinal Muscular Atrophy (SMA. Despite promising results, new developments are still needed for more efficient chemistries and delivery systems. Locked nucleic acid (LNA is a chemically modified nucleic acid that presents several attractive properties, such as high melting temperature when bound to RNA, potent biological activity, high stability and low toxicity in vivo. Here, we designed a series of LNA-based SSOs complementary to two sequences of the human dystrophin exon 51 that are most evolutionary conserved and evaluated their ability to induce exon skipping upon transfection into myoblasts derived from a DMD patient. We show that 16-mers with 60% of LNA modification efficiently induce exon skipping and restore synthesis of a truncated dystrophin isoform that localizes to the plasma membrane of patient-derived myotubes differentiated in culture. In sum, this study underscores the value of short LNA-modified SSOs for therapeutic applications.

The free energy of locking a ring: Changing a deoxyribonucleoside to a locked nucleic acid.

Science.gov (United States)

Xu, You; Villa, Alessandra; Nilsson, Lennart

2017-06-05

Locked nucleic acid (LNA), a modified nucleoside which contains a bridging group across the ribose ring, improves the stability of DNA/RNA duplexes significantly, and therefore is of interest in biotechnology and gene therapy applications. In this study, we investigate the free energy change between LNA and DNA nucleosides. The transformation requires the breaking of the bridging group across the ribose ring, a problematic transformation in free energy calculations. To address this, we have developed a 3-step (easy to implement) and a 1-step protocol (more efficient, but more complicated to setup), for single and dual topologies in classical molecular dynamics simulations, using the Bennett Acceptance Ratio method to calculate the free energy. We validate the approach on the solvation free energy difference for the nucleosides thymidine, cytosine, and 5-methyl-cytosine. © 2017 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc. © 2017 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.

Ultraselective electrochemiluminescence biosensor based on locked nucleic acid modified toehold-mediated strand displacement reaction and junction-probe.

Science.gov (United States)

Zhang, Xi; Zhang, Jing; Wu, Dongzhi; Liu, Zhijing; Cai, Shuxian; Chen, Mei; Zhao, Yanping; Li, Chunyan; Yang, Huanghao; Chen, Jinghua

2014-12-07

Locked nucleic acid (LNA) is applied in toehold-mediated strand displacement reaction (TMSDR) to develop a junction-probe electrochemiluminescence (ECL) biosensor for single-nucleotide polymorphism (SNP) detection in the BRCA1 gene related to breast cancer. More than 65-fold signal difference can be observed with perfectly matched target sequence to single-base mismatched sequence under the same conditions, indicating good selectivity of the ECL biosensor.

Conformationally locked aryl C-nucleosides: synthesis of phosphoramidite monomers and incorporation into single-stranded DNA and LNA (locked nucleic acid)

DEFF Research Database (Denmark)

Babu, B. Ravindra; Prasad, Ashok K.; Trikha, Smriti

2002-01-01

. The phosphoramidite approach was used for automated incorporation of the LNA-type beta-configured C-aryl monomers 17a-17e into short DNA and 2'-OMe-RNA/LNA strands. It is shown that universal hybridization can be obtained with a conformationally restricted monomer as demonstrated most convincingly for the pyrene LNA...... monomer 17d, both in a DNA context and in an RNA-like context. Increased binding affinity of oligonucleotide probes for universal hybridization can be induced by combining the pyrene LNA monomer 17d with affinity-enhancing 2'-OMe-RNA/LNA monomers....

Development of bis-locked nucleic acid (bisLNA) oligonucleotides for efficient invasion of supercoiled duplex DNA

DEFF Research Database (Denmark)

Moreno, Pedro M D; Geny, Sylvain; Pabon, Y Vladimir

2013-01-01

In spite of the many developments in synthetic oligonucleotide (ON) chemistry and design, invasion into double-stranded DNA (DSI) under physiological salt and pH conditions remains a challenge. In this work, we provide a new ON tool based on locked nucleic acids (LNAs), designed for strand invasi...

Dramatically improved RNA in situ hybridization signals using LNA-modified probes

DEFF Research Database (Denmark)

Thomsen, Rune; Nielsen, Peter Stein; Jensen, Torben Heick

2005-01-01

. This increases the thermal stability of hybrids formed with RNA. The LNA-based probes detect specific RNAs in fixed yeast cells with an efficiency far better than conventional DNA oligonucleotide probes of the same sequence. Using this probe design, we were also able to detect poly(A)+ RNA accumulation within......In situ detection of RNA by hybridization with complementary probes is a powerful technique. Probe design is a critical parameter in successful target detection. We have evaluated the efficiency of fluorescent DNA oligonucleotides modified to contain locked nucleic acid (LNA) residues...

C5-Alkynyl-Functionalized ?-L-LNA: Synthesis, Thermal Denaturation Experiments and Enzymatic Stability

OpenAIRE

Kumar, Pawan; Baral, Bharat; Anderson, Brooke A.; Guenther, Dale C.; ?stergaard, Michael E.; Sharma, Pawan K.; Hrdlicka, Patrick J.

2014-01-01

Major efforts are currently being devoted to improving the binding affinity, target specificity, and enzymatic stability of oligonucleotides used for nucleic acid targeting applications in molecular biology, biotechnology, and medicinal chemistry. One of the most popular strategies toward this end has been to introduce additional modifications to the sugar ring of affinity-inducing conformationally restricted nucleotide building blocks such as locked nucleic acid (LNA). In the preceding artic...

Locked Nucleic Acid-Based In Situ Hybridization Reveals miR-7a as a Hypothalamus-Enriched MicroRNA with a Distinct Expression Pattern

DEFF Research Database (Denmark)

Herzer, S; Silahtaroglu, A; Meister, B

2012-01-01

, a part of the brain that controls vital bodily functions, we employed locked nucleic acid (LNA) - fluorescent in situ hybridization (FISH). The expression pattern of the mature miRNAs miR-7a, miR-7b, miR-137 and miR-153 in mouse brain tissue sections was investigated. Whereas all studied miRNAs were......R-7a expression was particularly prominent in the subfornical organ, suprachiasmatic, paraventricular, periventricular, supraoptic, dorsomedial and arcuate nuclei. Identical expression patterns for miR-7a was seen in mouse and rat hypothalamus. By combining LNA-FISH with immunohistochemistry...

Rapid genotyping using pyrene-perylene locked nucleic acid complexes

DEFF Research Database (Denmark)

Kumar, Santhosh T.; Myznikova, Anna; Samokhina, Evgeniya

2013-01-01

We have developed an assay for single strand DNA and RNA detection which is based on novel pyrene-perylene FRET pairs attached to short LNA/DNA probes. The assay is based on ratiometric emission upon binding of target DNA/RNA by three combinations of fluorescent LNA/DNA reporter strands. Specific...... geometry of the pyrene fluorophore attached to the 2'-amino group of 2'-amino-LNA in position 4 allows for the first time to efficiently utilize dipole-dipole orientation parameter for sensing of single-nucleotide polymorphisms (SNPs) in nucleic acid targets by FRET. Using novel probes, SNP detection......-perylene FRET pairs, e.g., in imaging and clinical diagnostics....

Synthesis and Characterization of Oligodeoxyribonucleotides Modified with 2'-Amino-α-l-LNA Adenine Monomers

DEFF Research Database (Denmark)

Andersen, Nicolai K; Anderson, Brooke A; Wengel, Jesper

2013-01-01

The development of conformationally restricted nucleotide building blocks continues to attract considerable interest because of their successful use within antisense, antigene, and other gene-targeting strategies. Locked nucleic acid (LNA) and its diastereomer α-l-LNA are two interesting examples...... (ONs) modified with 2'-amino-α-l-LNA adenine monomers W-Z. The synthesis of the target phosphoramidites 1-4 is initiated from pentafuranose 5, which upon Vorbrüggen glycosylation, O2'-deacylation, O2'-activation and C2'-azide introduction yields nucleoside 8. A one-pot tandem Staudinger....... ONs modified with pyrene-functionalized 2'-amino-α-l-LNA adenine monomers X-Z display greatly increased affinity toward DNA targets (ΔTm/modification up to +14 °C). Results from absorption and fluorescence spectroscopy suggest that the duplex stabilization is a result of pyrene intercalation...

Electronic Structures of LNA Phosphorothioate Oligonucleotides

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Henrik G. Bohr

2017-09-01

Full Text Available Important oligonucleotides in anti-sense research have been investigated in silico and experimentally. This involves quantum mechanical (QM calculations and chromatography experiments on locked nucleic acid (LNA phosphorothioate (PS oligonucleotides. iso-potential electrostatic surfaces are essential in this study and have been calculated from the wave functions derived from the QM calculations that provide binding information and other properties of these molecules. The QM calculations give details of the electronic structures in terms of e.g., energy and bonding, which make them distinguish or differentiate between the individual PS diastereoisomers determined by the position of sulfur atoms. Rules are derived from the electronic calculations of these molecules and include the effects of the phosphorothioate chirality and formation of electrostatic potential surfaces. Physical and electrochemical descriptors of the PS oligonucleotides are compared to the experiments in which chiral states on these molecules can be distinguished. The calculations demonstrate that electronic structure, electrostatic potential, and topology are highly sensitive to single PS configuration changes and can give a lead to understanding the activity of the molecules. Keywords: LNA phosphorothioate, DNA/LNA oligonucleotide, diastereoisomers, Hartree-Fock calculations, iso-potential surface, anion chromatograms

Next-generation bis-locked nucleic acids with stacking linker and 2'-glycylamino-LNA show enhanced DNA invasion into supercoiled duplexes

DEFF Research Database (Denmark)

Geny, Sylvain; Moreno, Pedro M D; Krzywkowski, Tomasz

2016-01-01

Targeting and invading double-stranded DNA with synthetic oligonucleotides under physiological conditions remain a challenge. Bis-locked nucleic acids (bisLNAs) are clamp-forming oligonucleotides able to invade into supercoiled DNA via combined Hoogsteen and Watson-Crick binding. To improve the b...

LNA probe-based assay for the detection of Tomato black ring virus isolates.

Science.gov (United States)

Hasiów-Jaroszewska, Beata; Rymelska, Natalia; Borodynko, Natasza

2015-02-01

Tomato black ring virus (TBRV) infects a wide range of economically important plant species worldwide. In the present study we developed a locked nucleic acid (LNA) real-time RT-PCR assay for accurate detection of genetically diverse TBRV isolates collected from different hosts. The assay based on the LNA probe has a wide detection range, high sensitivity, stability and amplification efficiency. The assay amplified all tested TBRV isolates, but no signal was observed for the RNA from other nepoviruses and healthy plant species. Under optimum reaction conditions, the detection limit was estimated around 17 copies of the TBRV target region in total RNA. Real-time RT-PCR with the LNA probe described in this paper will serve as a valuable tool for robust, sensitive and reliable detection of TBRV isolates. Copyright © 2014 Elsevier Ltd. All rights reserved.

Crystallization and preliminary X-ray diffraction data of an LNA 7-mer duplex derived from a ricin aptamer

International Nuclear Information System (INIS)

Förster, Charlotte; Oberthuer, Dominik; Gao, Jiang; Eichert, André; Quast, Frederick G.; Betzel, Christian; Nitsche, Andreas; Erdmann, Volker A.; Fürste, Jens P.

2009-01-01

An all-LNA duplex was designed from the stem region of an RNA aptamer which has been generated against ricin. The LNA duplex was crystallized and preliminary X-ray diffraction analysis revealed diffraction to a resolution of up to 2.8 Å. Locked nucleic acids (LNAs) are modified nucleic acids which contain a modified sugar such as β-d-2′-O,4′-C methylene-bridged ribofuranose or other sugar derivatives in LNA analogues. The β-d-2′-O,4′-C methylene ribofuranose LNAs in particular possess high stability and melting temperatures, which makes them of interest for stabilizing the structure of different nucleic acids. Aptamers, which are DNAs or RNAs targeted against specific ligands, are candidates for substitution with LNAs in order to increase their stability. A 7-mer helix derived from the terminal part of an aptamer that was targeted against ricin was chosen. The ricin aptamer originally consisted of natural RNA building blocks and showed high affinity in ricin binding. For future stabilization of the aptamer, the terminal helix has been constructed as an ‘all-locked’ LNA and was successfully crystallized in order to investigate its structural properties. Optimization of crystal growth succeeded by the use of different metal salts as additives, such as CuCl 2 , MgCl 2 , MnCl 2 , CaCl 2 , CoCl 2 and ZnSO 4 . Preliminary X-ray diffraction data were collected and processed to 2.8 Å resolution. The LNA crystallized in space group P6 5 , with unit-cell parameters a = 50.11, b = 50.11, c = 40.72 Å. The crystals contained one LNA helix per asymmetric unit with a Matthews coefficient of 3.17 Å 3 Da −1 , which implies a solvent content of 70.15%

LNA-enhanced detection of single nucleotide polymorphisms in the apolipoprotein E

DEFF Research Database (Denmark)

Jacobsen, Nana; Bentzen, Joan; Meldgaard, Michael

2002-01-01

Genotyping of single nucleotide polymorphisms (SNPs) in large populations presents a great challenge, especially if the SNPs are embedded in GC-rich regions, such as the codon 112 SNP in the human apolipoprotein E (apoE). In the present study, we have used immobilized locked nucleic acid (LNA...... was applied to a panel of patient samples with simultaneous genotyping of the patients by DNA sequencing. The apoE genotyping assays for the codons 112 and 158 SNPs resulted in unambiguous results for all patient samples, concurring with those obtained by DNA sequencing....

Crystallization and X-ray diffraction analysis of an ‘all-locked’ nucleic acid duplex derived from a tRNASer microhelix

International Nuclear Information System (INIS)

Behling, Katja; Eichert, André; Fürste, Jens P.; Betzel, Christian; Erdmann, Volker A.; Förster, Charlotte

2009-01-01

A completely ‘all-locked’ nucleic acid duplex was designed from an E. coli tRNA Ser microhelix. The helix consists exclusively of LNA building blocks and was crystallized. The crystals diffracted to 1.9 Å resolution. Modified nucleic acids are of great interest with respect to their nuclease resistance and enhanced thermostability. In therapeutical and diagnostic applications, such molecules can substitute for labile natural nucleic acids that are targeted against particular diseases or applied in gene therapy. The so-called ‘locked nucleic acids’ contain modified sugar moieties such as 2′-O,4′-C-methylene-bridged β-d-ribofuranose and are known to be very stable nucleic acid derivatives. The structure of locked nucleic acids in single or multiple LNA-substituted natural nucleic acids and in LNA–DNA or LNA–RNA heteroduplexes has been well investigated, but the X-ray structure of an ‘all-locked’ nucleic acid double helix has not been described to date. Here, the crystallization and X-ray diffraction data analysis of an ‘all-locked’ nucleic acid helix, which was designed as an LNA originating from a tRNA Ser microhelix RNA structure, is presented. The crystals belonged to space group C2, with unit-cell parameters a = 77.91, b = 40.74, c = 30.06 Å, β = 91.02°. A high-resolution and a low-resolution data set were recorded, with the high-resolution data showing diffraction to 1.9 Å resolution. The crystals contained two double helices per asymmetric unit, with a Matthews coefficient of 2.48 Å 3 Da −1 and a solvent content of 66.49% for the merged data

Pharmacokinetics and Pharmacodynamics of a 13-mer LNA-inhibitor-miR-221 in Mice and Non-human Primates

Directory of Open Access Journals (Sweden)

Maria Eugenia Gallo Cantafio

2016-01-01

Full Text Available Locked nucleic acid (LNA oligonucleotides have been successfully used to efficiently inhibit endogenous small noncoding RNAs in vitro and in vivo. We previously demonstrated that the direct miR-221 inhibition by the novel 13-mer LNA-i-miR-221 induces significant antimyeloma activity and upregulates canonical miR-221 targets in vitro and in vivo. To evaluate the LNA-i-miR-221 pharmacokinetics and pharmacodynamics, novel assays for oligonucleotides quantification in NOD.SCID mice and Cynomolgus monkeys (Macaca fascicularis plasma, urine and tissues were developed. To this aim, a liquid chromatography/mass spectrometry method, after solid-phase extraction, was used for the detection of LNA-i-miR-221 in plasma and urine, while a specific in situ hybridization assay for tissue uptake analysis was designed. Our analysis revealed short half-life, optimal tissue biovailability and minimal urine excretion of LNA-i-miR-221 in mice and monkeys. Up to 3 weeks, LNA-i-miR-221 was still detectable in mice vital organs and in xenografted tumors, together with p27 target upregulation. Importantly, no toxicity in the pilot monkey study was observed. Overall, our findings indicate the suitability of LNA-i-miR-221 for clinical use and we provide here pilot data for safety analysis and further development of LNA-miRNA-based therapeutics for human cancer.

Structure Activity Relationships of α-L-LNA Modified Phosphorothioate Gapmer Antisense Oligonucleotides in Animals

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Punit P Seth

2012-01-01

Full Text Available We report the structure activity relationships of short 14-mer phosphorothioate gapmer antisense oligonucleotides (ASOs modified with α-L-locked nucleic acid (LNA and related modifications targeting phosphatase and tensin homologue (PTEN messenger RNA in mice. α-L-LNA represents the α-anomer of enantio-LNA and modified oligonucleotides show LNA like binding affinity for complementary RNA. In contrast to sequence matched LNA gapmer ASOs which showed elevations in plasma alanine aminotransferase (ALT levels indicative of hepatotoxicity, gapmer ASOs modified with α-L-LNA and related analogs in the flanks showed potent downregulation of PTEN messenger RNA in liver tissue without producing elevations in plasma ALT levels. However, the α-L-LNA ASO showed a moderate dose-dependent increase in liver and spleen weights suggesting a higher propensity for immune stimulation. Interestingly, replacing α-L-LNA nucleotides in the 3′- and 5′-flanks with R-5′-Me-α-L-LNA but not R-6′-Me- or 3′-Me-α-L-LNA nucleotides, reversed the drug induced increase in organ weights. Examination of structural models of dinucleotide units suggested that the 5′-Me group increases steric bulk in close proximity to the phosphorothioate backbone or produces subtle changes in the backbone conformation which could interfere with recognition of the ASO by putative immune receptors. Our data suggests that introducing steric bulk at the 5′-position of the sugar-phosphate backbone could be a general strategy to mitigate the immunostimulatory profile of oligonucleotide drugs. In a clinical setting, proinflammatory effects manifest themselves as injection site reactions and flu-like symptoms. Thus, a mitigation of these effects could increase patient comfort and compliance when treated with ASOs.

Inhibition of hepatitis B virus (HBV) by LNA-mediated nuclear interference with HBV DNA transcription

International Nuclear Information System (INIS)

Sun, Zhen; Xiang, Wenqing; Guo, Yajuan; Chen, Zhi; Liu, Wei; Lu, Daru

2011-01-01

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

Inhibition of hepatitis B virus (HBV) by LNA-mediated nuclear interference with HBV DNA transcription

Energy Technology Data Exchange (ETDEWEB)

Sun, Zhen [The State Key Laboratory of Genetic Engineering and The MOE Key Laboratory of Contemporary Anthropology, School of Life Science, Fudan University, Shanghai 200433 (China); Department of Biochemistry and Molecular Biology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058 (China); Xiang, Wenqing; Guo, Yajuan [Department of Biochemistry and Molecular Biology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058 (China); Chen, Zhi [The State Key Laboratory for Infectious Disease, Institute of Infectious Disease, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003 (China); Liu, Wei, E-mail: liuwei666@zju.edu.cn [Department of Biochemistry and Molecular Biology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058 (China); Lu, Daru, E-mail: drlu@fudan.edu.cn [The State Key Laboratory of Genetic Engineering and The MOE Key Laboratory of Contemporary Anthropology, School of Life Science, Fudan University, Shanghai 200433 (China)

2011-06-10

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

Formation of (DNA)2-LNA triplet with recombinant base recognition: A quantum mechanical study

Science.gov (United States)

Mall, Vijaya Shri; Tiwari, Rakesh Kumar

2018-05-01

The formation of DNA triple helix offers the verity of new possibilities in molecular biology. However its applications are limited to purine and pyrimidine rich sequences recognized by forming Hoogsteen/Reverse Hoogsteen triplets in major groove sites of DNA duplex. To overcome this drawback modification in bases backbone and glucose of nucleotide unit of DNA have been proposed so that the third strand base recognized by both the bases of DNA duplex by forming Recombinant type(R-type) of bonding in mixed sequences. Here we performed Quanrum Mechanical (Hartree-Fock and DFT) methodology on natural DNA and Locked Nucleic Acids(LNA) triplets using 6-31G and some other new advance basis sets. Study suggests energetically stable conformation has been observed for recombinant triplets in order of G-C*G > A-T*A > G-C*C > T-A*T for both type of triplets. Interestingly LNA leads to more stable conformation in all set of triplets, clearly suggests an important biological tool to overcome above mentioned drawbacks.

Novel (Phenylethynyl)pyrene-LNA Constructs for Fluorescence SNP Sensing in Polymorphic Nucleic Acid Targets

DEFF Research Database (Denmark)

Astakhova, Irina Kira; Samokhina, Evgeniya; Babu, B Ravindra

2012-01-01

We describe fluorescent oligonucleotide probes labeled with novel (phenylethynyl)pyrene dyes attached to locked nucleic acids. Furthermore, we prove the utility of these probes for the effective detection of single-nucleotide polymorphisms in natural nucleic acids. High-affinity hybridization......DNA and RNA gene fragments. Target sequences were obtained by analysis of 200 clinical samples from patients currently receiving anti-HIV/AIDS combination therapy at the Russian Federal AIDS Center. Using these fluorescent oligonucleotides, we were able to detect the target mutation despite all the challenges...

Detection of single-nucleotide polymorphisms using an ON-OFF switching of regenerated biosensor based on a locked nucleic acid-integrated and toehold-mediated strand displacement reaction.

Science.gov (United States)

Gao, Zhong Feng; Ling, Yu; Lu, Lu; Chen, Ning Yu; Luo, Hong Qun; Li, Nian Bing

2014-03-04

Although various strategies have been reported for single-nucleotide polymorphisms (SNPs) detection, development of a time-saving, specific, and regenerated electrochemical sensing platform still remains a realistic goal. In this study, an ON-OFF switching of a regenerated biosensor based on a locked nucleic acid (LNA)-integrated and toehold-mediated strand displacement reaction technique is constructed for detection of SNPs. The LNA-integrated and methylene blue-labeled capture probe with an external toehold is designed to switch on the sensing system. The mutant-type DNA probe completes complementary with the capture probe to trigger the strand displacement reaction, which switches off the sensing system. However, when the single-base mismatched wild-type DNA probe is presented, the strand displacement reaction cannot be achieved; therefore, the sensing system still keeps the ON state. This DNA sensor is stable over five reuses. We further testify that the LNA-integrated sequence has better recognition ability for SNPs detection compared to the DNA-integrated sequence. Moreover, this DNA senor exhibits a remarkable discrimination capability of SNPs among abundant wild-type targets and 6000-fold (m/m) excess of genomic DNA. In addition, it is selective enough in complex and contaminant-ridden samples, such as human urine, soil, saliva, and beer. Overall, these results demonstrate that this reliable DNA sensor is easy to be fabricated, simple to operate, and stable enough to be readily regenerated.

Selection of G-quadruplex folding topology with LNA-modified human telomeric sequences in K+ solution

DEFF Research Database (Denmark)

Pradhan, Devranjan; Hansen, Lykke H; Vester, Birte

2011-01-01

G-rich nucleic acid oligomers can form G-quadruplexes built by G-tetrads stacked upon each other. Depending on the nucleotide sequence, G-quadruplexes fold mainly with two topologies: parallel, in which all G-tracts are oriented parallel to each other, or antiparallel, in which one or more G......-tracts are oriented antiparallel to the other G-tracts. In the former topology, all glycosidic bond angles conform to anti conformations, while in the latter topology they adopt both syn and anti conformations. It is of interest to understand the molecular forces that govern G-quadruplex folding. Here, we approach...... this problem by examining the impact of LNA (locked nucleic acid) modifications on the folding topology of the dimeric model system of the human telomere sequence. In solution, this DNA G-quadruplex forms a mixture of G-quadruplexes with antiparallel and parallel topologies. Using CD and NMR spectroscopies, we...

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

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Wengel Jesper

2006-06-01

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

Role of the heat capacity change in understanding and modeling melting thermodynamics of complementary duplexes containing standard and nucleobase-modified LNA.

Science.gov (United States)

Hughesman, Curtis B; Turner, Robin F B; Haynes, Charles A

2011-06-14

Melting thermodynamic data obtained by differential scanning calorimetry (DSC) are reported for 43 duplexed oligonucleotides containing one or more locked nucleic acid (LNA) substitutions. The measured heat capacity change (ΔC(p)) for the helix-to-coil transition is used to compute the changes in enthalpy and entropy for melting of an LNA-bearing duplex at the T(m) of its corresponding isosequential unmodified DNA duplex to allow rigorous thermodynamic analysis of the stability enhancements provided by LNA substitutions. Contrary to previous studies, our analysis shows that the origin of the improved stability is almost exclusively a net reduction (ΔΔS° thermodynamics and the increased melting temperature (ΔT(m)) of heteroduplexes formed between an unmodified DNA strand and a complementary strand containing any number and configuration of standard LNA nucleotides A, T, C, and G. This single-base thermodynamic (SBT) model requires only four entropy-related parameters in addition to ΔC(p). Finally, DSC data for 20 duplexes containing the nucleobase-modified LNAs 2-aminoadenine (D) and 2-thiothymine (H) are reported and used to determine SBT model parameters for D and H. The data and model suggest that along with the greater stability enhancement provided by D and H bases relative to their corresponding A and T analogues, the unique pseudocomplementary properties of D-H base pairs may make their use appealing for in vitro and in vivo applications.

Demonstration of Hepatitis C Virus RNA with In Situ Hybridization Employing a Locked Nucleic Acid Probe in Humanized Liver of Infected Chimeric Mice and in Needle-Biopsied Human Liver

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Kazuya Shiogama

2013-01-01

Full Text Available Background. In situ hybridization (ISH with high sensitivity has been requested to demonstrate hepatitis C virus (HCV RNA in formalin-fixed, paraffin-embedded (FFPE sections of the liver. Methods. ISH employing a locked-nucleic-acid- (LNA-modified oligonucleotide probe and biotin-free catalyzed signal amplification system (CSAII was applied to HCV-RNA detection in the liver tissue. Nested reverse-transcription polymerase chain reaction (RT-PCR was performed for HCV genotyping using total RNA extracted from FFPE sections. The target tissues included FFPE tissue sections of humanized livers in HCV-infected chimeric mice (HCV genotypes 1a, 1b, and 2a and noninfected and of needle-biopsied livers from HCV-infected patients. Results. HCV-RNA was demonstrated with the ISH technique in HCV-infected liver tissues from both chimeric mice and 9 (82% of 11 patients with HCV infection. The HCV signals were sensitive to RNase. Nested RT-PCR confirmed the genotype in 8 (73% of 11 livers (type 1b: 6 lesions and type 2a: 2 lesions. HCV-RNA was not identified in chronic hepatitis B lesions, fatty liver, autoimmune hepatitis, and hepatocellular carcinoma. Conclusion. ISH using the LNA-modified oligonucleotide probe and CSAII was applicable to detecting HCV-RNA in routinely prepared FFPE liver specimens.

Mapping photothermally induced gene expression in living cells and tissues by nanorod-locked nucleic acid complexes.

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Riahi, Reza; Wang, Shue; Long, Min; Li, Na; Chiou, Pei-Yu; Zhang, Donna D; Wong, Pak Kin

2014-04-22

The photothermal effect of plasmonic nanostructures has numerous applications, such as cancer therapy, photonic gene circuit, large cargo delivery, and nanostructure-enhanced laser tweezers. The photothermal operation can also induce unwanted physical and biochemical effects, which potentially alter the cell behaviors. However, there is a lack of techniques for characterizing the dynamic cell responses near the site of photothermal operation with high spatiotemporal resolution. In this work, we show that the incorporation of locked nucleic acid probes with gold nanorods allows photothermal manipulation and real-time monitoring of gene expression near the area of irradiation in living cells and animal tissues. The multimodal gold nanorod serves as an endocytic delivery reagent to transport the probes into the cells, a fluorescence quencher and a binding competitor to detect intracellular mRNA, and a plasmonic photothermal transducer to induce cell ablation. We demonstrate the ability of the gold nanorod-locked nucleic acid complex for detecting the spatiotemporal gene expression in viable cells and tissues and inducing photothermal ablation of single cells. Using the gold nanorod-locked nucleic acid complex, we systematically characterize the dynamic cellular heat shock responses near the site of photothermal operation. The gold nanorod-locked nucleic acid complex enables mapping of intracellular gene expressions and analyzes the photothermal effects of nanostructures toward various biomedical applications.

Establishment of real time allele specific locked nucleic acid quantitative PCR for detection of HBV YIDD (ATT mutation and evaluation of its application.

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Yongbin Zeng

Full Text Available BACKGROUND: Long-term use of nucleos(tide analogues can increase risk of HBV drug-resistance mutations. The rtM204I (ATT coding for isoleucine is one of the most important resistance mutation sites. Establishing a simple, rapid, reliable and highly sensitive assay to detect the resistant mutants as early as possible is of great clinical significance. METHODS: Recombinant plasmids for HBV YMDD (tyrosine-methionine-aspartate-aspartate and YIDD (tyrosine-isoleucine-aspartate-aspartate were constructed by TA cloning. Real time allele specific locked nucleic acid quantitative PCR (RT-AS-LNA-qPCR with SYBR Green I was established by LNA-modified primers and evaluated with standard recombinant plasmids, clinical templates (the clinical wild type and mutant HBV DNA mixture and 102 serum samples from nucleos(tide analogues-experienced patients. The serum samples from a chronic hepatitis B (CHB patient firstly received LMV mono therapy and then switched to LMV + ADV combined therapy were also dynamically analyzed for 10 times. RESULTS: The linear range of the assay was between 1×10(9 copies/μl and 1 × 10(2 copies/μl. The low detection limit was 1 × 10(1 copies/μl. Sensitivity of the assay were 10(-6, 10(-4 and 10(-2 in the wild-type background of 1 × 10(9 copies/μl, 1 × 10(7 copies/μl and 1 × 10(5 copies/μl, respectively. The sensitivity of the assay in detection of clinical samples was 0.03%. The complete coincidence rate between RT-AS-LNA-qPCR and direct sequencing was 91.2% (93/102, partial coincidence rate was 8.8% (9/102, and no complete discordance was observed. The two assays showed a high concordance (Kappa = 0.676, P = 0.000. Minor variants can be detected 18 weeks earlier than the rebound of HBV DNA load and alanine aminotransferase level. CONCLUSIONS: A rapid, cost-effective, high sensitive, specific and reliable method of RT-AS-LNA-qPCR with SYBR Green I for early and absolute quantification of HBV YIDD (ATT coding for isoleucine

A new general model for predicting melting thermodynamics of complementary and mismatched B-form duplexes containing locked nucleic acids: application to probe design for digital PCR detection of somatic mutations.

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Hughesman, Curtis; Fakhfakh, Kareem; Bidshahri, Roza; Lund, H Louise; Haynes, Charles

2015-02-17

Advances in real-time polymerase chain reaction (PCR), as well as the emergence of digital PCR (dPCR) and useful modified nucleotide chemistries, including locked nucleic acids (LNAs), have created the potential to improve and expand clinical applications of PCR through their ability to better quantify and differentiate amplification products, but fully realizing this potential will require robust methods for designing dual-labeled hydrolysis probes and predicting their hybridization thermodynamics as a function of their sequence, chemistry, and template complementarity. We present here a nearest-neighbor thermodynamic model that accurately predicts the melting thermodynamics of a short oligonucleotide duplexed either to its perfect complement or to a template containing mismatched base pairs. The model may be applied to pure-DNA duplexes or to duplexes for which one strand contains any number and pattern of LNA substitutions. Perturbations to duplex stability arising from mismatched DNA:DNA or LNA:DNA base pairs are treated at the Gibbs energy level to maintain statistical significance in the regressed model parameters. This approach, when combined with the model's accounting of the temperature dependencies of the melting enthalpy and entropy, permits accurate prediction of T(m) values for pure-DNA homoduplexes or LNA-substituted heteroduplexes containing one or two independent mismatched base pairs. Terms accounting for changes in solution conditions and terminal addition of fluorescent dyes and quenchers are then introduced so that the model may be used to accurately predict and thereby tailor the T(m) of a pure-DNA or LNA-substituted hydrolysis probe when duplexed either to its perfect-match template or to a template harboring a noncomplementary base. The model, which builds on classic nearest-neighbor thermodynamics, should therefore be of use to clinicians and biologists who require probes that distinguish and quantify two closely related alleles in either a

Survivin mRNA antagonists using locked nucleic acid, potential for molecular cancer therapy

DEFF Research Database (Denmark)

Fisker, Niels; Westergaard, Majken; Hansen, Henrik Frydenlund

2007-01-01

We have investigated the effects of different locked nucleic acid modified antisense mRNA antagonists against Survivin in a prostate cancer model. These mRNA antagonists were found to be potent inhibitors of Survivin expression at low nanomolar concentrations. Additionally there was a pronounced ...

Specific RNP capture with antisense LNA/DNA mixmers.

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Rogell, Birgit; Fischer, Bernd; Rettel, Mandy; Krijgsveld, Jeroen; Castello, Alfredo; Hentze, Matthias W

2017-08-01

RNA-binding proteins (RBPs) play essential roles in RNA biology, responding to cellular and environmental stimuli to regulate gene expression. Important advances have helped to determine the (near) complete repertoires of cellular RBPs. However, identification of RBPs associated with specific transcripts remains a challenge. Here, we describe "specific ribonucleoprotein (RNP) capture," a versatile method for the determination of the proteins bound to specific transcripts in vitro and in cellular systems. Specific RNP capture uses UV irradiation to covalently stabilize protein-RNA interactions taking place at "zero distance." Proteins bound to the target RNA are captured by hybridization with antisense locked nucleic acid (LNA)/DNA oligonucleotides covalently coupled to a magnetic resin. After stringent washing, interacting proteins are identified by quantitative mass spectrometry. Applied to in vitro extracts, specific RNP capture identifies the RBPs bound to a reporter mRNA containing the Sex-lethal (Sxl) binding motifs, revealing that the Sxl homolog sister of Sex lethal (Ssx) displays similar binding preferences. This method also revealed the repertoire of RBPs binding to 18S or 28S rRNAs in HeLa cells, including previously unknown rRNA-binding proteins. © 2017 Rogell et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Diagnostic PCR: Comparative sensitivity of four probe chemistries

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Josefsen, Mathilde Hartmann; Löfström, Charlotta; Sommer, Helle Mølgaard

2009-01-01

Three probe chemistries: locked nucleic acid (LNA), minor groove binder (MGB) and Scorpion were compared with a TaqMan probe in a validated real-time PCR assay for detection of food-borne thermotolerant Campylobacter. The LNA probe produced significantly lower Ct-values and a higher proportion of...

Synthetic oligonucleotide antigens modified with locked nucleic acids detect disease specific antibodies

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Samuelsen, Simone V; Solov'yov, Ilia A.; Balboni, Imelda M.

2016-01-01

New techniques to detect and quantify antibodies to nucleic acids would provide a significant advance over current methods, which often lack specificity. We investigate the potential of novel antigens containing locked nucleic acids (LNAs) as targets for antibodies. Particularly, employing...... molecular dynamics we predict optimal nucleotide composition for targeting DNA-binding antibodies. As a proof of concept, we address a problem of detecting anti-DNA antibodies that are characteristic of systemic lupus erythematosus, a chronic autoimmune disease with multiple manifestations. We test the best...... that the novel method is a promising tool to create antigens for research and point-of-care monitoring of anti-DNA antibodies....

Locked nucleic acid inhibits amplification of contaminating DNA in real-time PCR

DEFF Research Database (Denmark)

Hummelshoj, Lone; Ryder, Lars P; Madsen, Hans O

2005-01-01

and real-time PCR, the addition of LNA showed blocking of the amplification of genomic XBP1 but not cDNA XBP1. To test the effect of melting temperature (Tm) on the LNA, we investigated the number of LNA nucleotides that could be replaced with DNA nucleotides and still retain the blocking activity. More...

Kinetics of membrane damage to high (HNA) and low (LNA) nucleic acid bacterial clusters in drinking water by ozone, chlorine, chlorine dioxide, monochloramine, ferrate(VI), and permanganate.

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Ramseier, Maaike K; von Gunten, Urs; Freihofer, Pietro; Hammes, Frederik

2011-01-01

Drinking water was treated with ozone, chlorine, chlorine dioxide, monochloramine, ferrate(VI), and permanganate to investigate the kinetics of membrane damage of native drinking water bacterial cells. Membrane damage was measured by flow cytometry using a combination of SYBR Green I and propidium iodide (SGI+PI) staining as indicator for cells with permeabilized membranes and SGI alone to measure total cell concentration. SGI+PI staining revealed that the cells were permeabilized upon relatively low oxidant exposures of all tested oxidants without a detectable lag phase. However, only ozonation resulted in a decrease of the total cell concentrations for the investigated reaction times. Rate constants for the membrane damage reaction varied over seven orders of magnitude in the following order: ozone > chlorine > chlorine dioxide ≈ ferrate > permanganate > chloramine. The rate constants were compared to literature data and were in general smaller than previously measured rate constants. This confirmed that membrane integrity is a conservative and therefore safe parameter for disinfection control. Interestingly, the cell membranes of high nucleic acid (HNA) content bacteria were damaged much faster than those of low nucleic acid (LNA) content bacteria during treatment with chlorine dioxide and permanganate. However, only small differences were observed during treatment with chlorine and chloramine, and no difference was observed for ferrate treatment. Based on the different reactivity of these oxidants it was suggested that HNA and LNA bacterial cell membranes have a different chemical constitution. Copyright © 2010 Elsevier Ltd. All rights reserved.

Synthesis of locked cyclohexene and cyclohexane nucleic acids (LCeNA and LCNA) with modified adenosine units

Czech Academy of Sciences Publication Activity Database

Šála, Michal; Dejmek, Milan; Procházková, Eliška; Hřebabecký, Hubert; Rybáček, Jiří; Dračínský, Martin; Novák, Pavel; Rosenbergová, Šárka; Fukal, J.; Sychrovský, Vladimír; Rosenberg, Ivan; Nencka, Radim

2015-01-01

Roč. 13, č. 9 (2015), s. 2703-2715 ISSN 1477-0520 R&D Projects: GA ČR GPP207/12/P625 Institutional support: RVO:61388963 Keywords : locked nucleosides * locked nucleic acids * bicyclo[3.2.1]octene Subject RIV: CC - Organic Chemistry Impact factor: 3.559, year: 2015 http://pubs.rsc.org/en/content/articlepdf/2015/ob/c4ob02193b

Thermal stability of G-rich anti-parallel DNA triplexes upon insertion of LNA and α-l-LNA

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Kosbar, Tamer R.; Sofan, Mamdouh A.; Abou-Zeid, Laila

2015-01-01

G-rich anti-parallel DNA triplexes were modified with LNA or α-l-LNA in their Watson-Crick and TFO strands. The triplexes were formed by targeting a pyrimidine strand to a putative hairpin formed by Hoogsteen base pairing in order to use the UV melting method to evaluate the stability...... of the triplexes. Their thermal stability was reduced when the TFO strand was modified with LNA or α-l-LNA. The same trend was observed when the TFO strand and the purine Watson-Crick strand both were modified with LNA. When all triad components were modified with α-l-LNA and LNA in the middle of the triplex...

Synthetic LNA/DNA nano-scaffolds for highly efficient diagnostics of nucleic acids and autoimmune antibodies

DEFF Research Database (Denmark)

Astakhova, Irina Kira

2014-01-01

) strands and a series of fluorescent azides. The multiply labeled fluorescent LNA/DNA probes prepared herein generally display high binding affinity to complementary DNA/RNA, high quantum yields and, hence, high fluorescence brightness values. With the novel fluorescent probes, specific sensing...

Peptide-LNA oligonucleotide conjugates

DEFF Research Database (Denmark)

Astakhova, I Kira; Hansen, Lykke Haastrup; Vester, Birte

2013-01-01

properties, peptides were introduced into oligonucleotides via a 2'-alkyne-2'-amino-LNA scaffold. Derivatives of methionine- and leucine-enkephalins were chosen as model peptides of mixed amino acid content, which were singly and doubly incorporated into LNA/DNA strands using highly efficient copper......(i)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry. DNA/RNA target binding affinity and selectivity of the resulting POCs were improved in comparison to LNA/DNA mixmers and unmodified DNA controls. This clearly demonstrates that internal attachment of peptides to oligonucleotides can significantly...

Does the high nucleic acid content of individual bacterial cells allow us to discriminate between active cells and inactive cells in aquatic systems?

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Lebaron, P; Servais, P; Agogué, H; Courties, C; Joux, F

2001-04-01

The nucleic acid contents of individual bacterial cells as determined with three different nucleic acid-specific fluorescent dyes (SYBR I, SYBR II, and SYTO 13) and flow cytometry were compared for different seawater samples. Similar fluorescence patterns were observed, and bacteria with high apparent nucleic acid contents (HNA) could be discriminated from bacteria with low nucleic acid contents (LNA). The best discrimination between HNA and LNA cells was found when cells were stained with SYBR II. Bacteria in different water samples collected from seven freshwater, brackish water, and seawater ecosystems were prelabeled with tritiated leucine and then stained with SYBR II. After labeling and staining, HNA, LNA, and total cells were sorted by flow cytometry, and the specific activity of each cellular category was determined from leucine incorporation rates. The HNA cells were responsible for most of the total bacterial production, and the specific activities of cells in the HNA population varied between samples by a factor of seven. We suggest that nucleic acid content alone can be a better indicator of the fraction of growing cells than total counts and that this approach should be combined with other fluorescent physiological probes to improve detection of the most active cells in aquatic systems.

Efficient reverse transcription using locked nucleic acid nucleotides towards the evolution of nuclease resistant RNA aptamers

DEFF Research Database (Denmark)

Crouzier, Lucile; Dubois, Camille; Edwards, Stacey L

2012-01-01

We found that SuperScript® III Reverse Transcriptase is an efficient enzyme for the recognition of LNA nucleotides, making it a prime candidate to be used in de novo selection of LNA containing RNA aptamers....

Characterizing Slow Chemical Exchange in Nucleic Acids by Carbon CEST and Low Spin-Lock Field R1ρ NMR Spectroscopy

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Zhao, Bo; Hansen, Alexandar L.; Zhang, Qi

2016-01-01

Quantitative characterization of dynamic exchange between various conformational states provides essential insights into the molecular basis of many regulatory RNA functions. Here, we present an application of nucleic-acid-optimized carbon chemical exchange saturation transfer (CEST) and low spin-lock field R1ρ relaxation dispersion (RD) NMR experiments in characterizing slow chemical exchange in nucleic acids that is otherwise difficult if not impossible to be quantified by the ZZ-exchange NMR experiment. We demonstrated the application on a 47-nucleotide fluoride riboswitch in the ligand-free state, for which CEST and R1ρ RD profiles of base and sugar carbons revealed slow exchange dynamics involving a sparsely populated (p ~ 10%) and shortly lived (τ ~ 10 ms) NMR “invisible” state. The utility of CEST and low spin-lock field R1ρ RD experiments in studying slow exchange was further validated in characterizing an exchange as slow as ~60 s−1. PMID:24299272

Characterizing slow chemical exchange in nucleic acids by carbon CEST and low spin-lock field R(1ρ) NMR spectroscopy.

Science.gov (United States)

Zhao, Bo; Hansen, Alexandar L; Zhang, Qi

2014-01-08

Quantitative characterization of dynamic exchange between various conformational states provides essential insights into the molecular basis of many regulatory RNA functions. Here, we present an application of nucleic-acid-optimized carbon chemical exchange saturation transfer (CEST) and low spin-lock field R(1ρ) relaxation dispersion (RD) NMR experiments in characterizing slow chemical exchange in nucleic acids that is otherwise difficult if not impossible to be quantified by the ZZ-exchange NMR experiment. We demonstrated the application on a 47-nucleotide fluoride riboswitch in the ligand-free state, for which CEST and R(1ρ) RD profiles of base and sugar carbons revealed slow exchange dynamics involving a sparsely populated (p ~ 10%) and shortly lived (τ ~ 10 ms) NMR "invisible" state. The utility of CEST and low spin-lock field R(1ρ) RD experiments in studying slow exchange was further validated in characterizing an exchange as slow as ~60 s(-1).

Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection

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Lanford, Robert E; Hildebrandt-Eriksen, Elisabeth S; Petri, Andreas

2010-01-01

The liver-expressed microRNA-122 (miR-122) is essential for hepatitis C virus (HCV) RNA accumulation in cultured liver cells, but its potential as a target for antiviral intervention has not been assessed. We found that treatment of chronically infected chimpanzees with a locked nucleic acid (LNA...

A ratiometric electrochemical biosensor for the exosomal microRNAs detection based on bipedal DNA walkers propelled by locked nucleic acid modified toehold mediate strand displacement reaction.

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Zhang, Jing; Wang, Liang-Liang; Hou, Mei-Feng; Xia, Yao-Kun; He, Wen-Hui; Yan, An; Weng, Yun-Ping; Zeng, Lu-Peng; Chen, Jing-Hua

2018-04-15

Sensitive and selective detection of microRNAs (miRNAs) in cancer cells derived exosomes have attracted rapidly growing interest owing to their potential in diagnostic and prognostic applications. Here, we design a ratiometric electrochemical biosensor based on bipedal DNA walkers for the attomolar detection of exosomal miR-21. In the presence of miR-21, DNA walkers are activated to walk continuously along DNA tracks, resulting in conformational changes as well as considerable increases of the signal ratio produced by target-respond and target-independent reporters. With the signal cascade amplification of DNA walkers, the biosensor exhibits ultrahigh sensitivity with the limit of detection (LOD) down to 67 aM. Furthermore, owing to the background-correcting function of target-independent reporters termed as reference reporters, the biosensor is robust and stable enough to be applied in the detection of exosomal miR-21 extracted from breast cancer cell lines and serums. In addition, because locked nucleic acid (LNA) modified toehold mediate strand displacement reaction (TMSDR) has extraordinary discriminative ability, the biosensor displays excellent selectivity even against the single-base-mismatched target. It is worth mentioning that our sensor is regenerative and stable for at least 5 cycles without diminution in sensitivity. In brief, the high sensitivity, selectivity and reproducibility, together with cheap, make the proposed biosensor a promising approach for exosomal miRNAs detection, in conjunction with early point-of-care testing (POCT) of cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis and Biophysical Investigations of Oligonucleotides Containing Galactose-Modified DNA, LNA and 2'-Amino-LNA Monomers

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Ries, Annika; Kumar, Rajesh; Lou, Chenguang

2016-01-01

Galactose-modified thymidine, LNA-T and 2'-amino-LNA-T nucleosides were synthesized, converted into the corresponding phosphoramidite derivatives and introduced into short oligonucleotides. Compared to the unmodified control strands, the galactose-modified oligonucleotides in general, and the N2'...

Reliable allele detection using SNP-based PCR primers containing Locked Nucleic Acid: application in genetic mapping

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Trognitz Friederike

2007-02-01

Full Text Available Abstract Background The diploid, Solanum caripense, a wild relative of potato and tomato, possesses valuable resistance to potato late blight and we are interested in the genetic base of this resistance. Due to extremely low levels of genetic variation within the S. caripense genome it proved impossible to generate a dense genetic map and to assign individual Solanum chromosomes through the use of conventional chromosome-specific SSR, RFLP, AFLP, as well as gene- or locus-specific markers. The ease of detection of DNA polymorphisms depends on both frequency and form of sequence variation. The narrow genetic background of close relatives and inbreds complicates the detection of persisting, reduced polymorphism and is a challenge to the development of reliable molecular markers. Nonetheless, monomorphic DNA fragments representing not directly usable conventional markers can contain considerable variation at the level of single nucleotide polymorphisms (SNPs. This can be used for the design of allele-specific molecular markers. The reproducible detection of allele-specific markers based on SNPs has been a technical challenge. Results We present a fast and cost-effective protocol for the detection of allele-specific SNPs by applying Sequence Polymorphism-Derived (SPD markers. These markers proved highly efficient for fingerprinting of individuals possessing a homogeneous genetic background. SPD markers are obtained from within non-informative, conventional molecular marker fragments that are screened for SNPs to design allele-specific PCR primers. The method makes use of primers containing a single, 3'-terminal Locked Nucleic Acid (LNA base. We demonstrate the applicability of the technique by successful genetic mapping of allele-specific SNP markers derived from monomorphic Conserved Ortholog Set II (COSII markers mapped to Solanum chromosomes, in S. caripense. By using SPD markers it was possible for the first time to map the S. caripense alleles

Activity and phylogenetic diversity of bacterial cells with high and low nucleic acid content and electron transport system activity in an upwelling ecosystem.

Science.gov (United States)

Longnecker, K; Sherr, B F; Sherr, E B

2005-12-01

We evaluated whether bacteria with higher cell-specific nucleic acid content (HNA) or an active electron transport system, i.e., positive for reduction of 5-cyano-2,3-ditolyl tetrazolium chloride (CTC), were responsible for the bulk of bacterioplankton metabolic activity. We also examined whether the phylogenetic diversity of HNA and CTC-positive cells differed from the diversity of Bacteria with low nucleic acid content (LNA). Bacterial assemblages were sampled both in eutrophic shelf waters and in mesotrophic offshore waters in the Oregon coastal upwelling region. Cytometrically sorted HNA, LNA, and CTC-positive cells were assayed for their cell-specific [3H]leucine incorporation rates. Phylogenetic diversity in sorted non-radioactively labeled samples was assayed using denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S rRNA genes. Cell-specific rates of leucine incorporation of HNA and CTC-positive cells were on average only slightly greater than the cell-specific rates of LNA cells. HNA cells accounted for most bacterioplankton substrate incorporation due to high abundances, while the low abundances of CTC-positive cells resulted in only a small contribution by these cells to total bacterial activity. The proportion of the total bacterial leucine incorporation attributable to LNA cells was higher in offshore regions than in shelf waters. Sequence data obtained from DGGE bands showed broadly similar phylogenetic diversity across HNA, LNA, and CTC-positive cells, with between-sample and between-region variability in the distribution of phylotypes. Our results suggest that LNA bacteria are not substantially different from HNA bacteria in either cell-specific rates of substrate incorporation or phylogenetic composition and that they can be significant contributors to bacterial metabolism in the sea.

MicroRNA expression in the adult mouse central nervous system

DEFF Research Database (Denmark)

Bak, Mads; Silahtaroglu, Asli; Møller, Morten

2008-01-01

distinct areas of the adult mouse central nervous system (CNS). Microarray profiling in combination with real-time RT-PCR and LNA (locked nucleic acid)-based in situ hybridization uncovered 44 miRNAs displaying more than threefold enrichment in the spinal cord, cerebellum, medulla oblongata, pons......RNA-related gene regulatory networks in the mammalian central nervous system. Udgivelsesdato: 2008-Mar...

Towards Fluorescence In Vivo Hybridization (FIVH) Detection of H. pylori in Gastric Mucosa Using Advanced LNA Probes

Science.gov (United States)

Fontenete, Sílvia; Leite, Marina; Guimarães, Nuno; Madureira, Pedro; Ferreira, Rui Manuel; Figueiredo, Céu; Wengel, Jesper; Azevedo, Nuno Filipe

2015-01-01

In recent years, there have been several attempts to improve the diagnosis of infection caused by Helicobacter pylori. Fluorescence in situ hybridization (FISH) is a commonly used technique to detect H. pylori infection but it requires biopsies from the stomach. Thus, the development of an in vivo FISH-based method (FIVH) that directly detects and allows the visualization of the bacterium within the human body would significantly reduce the time of analysis, allowing the diagnosis to be performed during endoscopy. In a previous study we designed and synthesized a phosphorothioate locked nucleic acid (LNA)/ 2’ O-methyl RNA (2’OMe) probe using standard phosphoramidite chemistry and FISH hybridization was then successfully performed both on adhered and suspended bacteria at 37°C. In this work we simplified, shortened and adapted FISH to work at gastric pH values, meaning that the hybridization step now takes only 30 minutes and, in addition to the buffer, uses only urea and probe at non-toxic concentrations. Importantly, the sensitivity and specificity of the FISH method was maintained in the range of conditions tested, even at low stringency conditions (e.g., low pH). In conclusion, this methodology is a promising approach that might be used in vivo in the future in combination with a confocal laser endomicroscope for H. pylori visualization. PMID:25915865

Towards Fluorescence In Vivo Hybridization (FIVH Detection of H. pylori in Gastric Mucosa Using Advanced LNA Probes.

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Sílvia Fontenete

Full Text Available In recent years, there have been several attempts to improve the diagnosis of infection caused by Helicobacter pylori. Fluorescence in situ hybridization (FISH is a commonly used technique to detect H. pylori infection but it requires biopsies from the stomach. Thus, the development of an in vivo FISH-based method (FIVH that directly detects and allows the visualization of the bacterium within the human body would significantly reduce the time of analysis, allowing the diagnosis to be performed during endoscopy. In a previous study we designed and synthesized a phosphorothioate locked nucleic acid (LNA/ 2' O-methyl RNA (2'OMe probe using standard phosphoramidite chemistry and FISH hybridization was then successfully performed both on adhered and suspended bacteria at 37°C. In this work we simplified, shortened and adapted FISH to work at gastric pH values, meaning that the hybridization step now takes only 30 minutes and, in addition to the buffer, uses only urea and probe at non-toxic concentrations. Importantly, the sensitivity and specificity of the FISH method was maintained in the range of conditions tested, even at low stringency conditions (e.g., low pH. In conclusion, this methodology is a promising approach that might be used in vivo in the future in combination with a confocal laser endomicroscope for H. pylori visualization.

Sphingosine kinase 1 is a relevant molecular target in gastric cancer

DEFF Research Database (Denmark)

Fuereder, Thorsten; Hoeflmayer, Doris; Jaeger-Lansky, Agnes

2011-01-01

Sphingosine kinase 1 (Sphk1), a lipid kinase implicated in cell transformation and tumor growth, is overexpressed in gastric cancer and is linked with a poor prognosis. The biological relevance of Sphk1 expression in gastric cancer is unclear. Here, we studied the functional significance of Sphk1...... as a novel molecular target for gastric cancer by using an antisense oligonucleotide approach in vitro and in vivo. Gastric cancer cell lines (MKN28 and N87) were treated with Sphk1 with locked nucleic acid-antisense oligonucleotides (LNA-ASO). Sphk1 target regulation, cell growth, and apoptosis were...... assessed for single-agent Sphk1 LNA-ASO and for combinations with doxorubicin. Athymic nude mice xenografted with gastric cancer cells were treated with Sphk1 LNA and assessed for tumor growth and Sphk1 target regulation, in vivo. In vitro, nanomolar concentrations of Sphk1 LNA-ASO induced an approximately...

Short locked nucleic acid antisense oligonucleotides potently reduce apolipoprotein B mRNA and serum cholesterol in mice and non-human primates

DEFF Research Database (Denmark)

Straarup, Ellen Marie; Fisker, Niels; Hedtjärn, Maj

2010-01-01

-life as longer oligonucleotides. Pharmacology studies in both mice and non-human primates were conducted with a 13-mer LNA oligonucleotide against apoB, and the data showed that repeated dosing of the 13-mer at 1-2 mg/kg/week was sufficient to provide a significant and long lasting lowering of non...... using the LNA chemistry. Conclusively, we present a 13-mer LNA oligonucleotide with therapeutic potential that produce beneficial cholesterol lowering effect in non-human primates....

Predictive efficacy of low burden EGFR mutation detected by next-generation sequencing on response to EGFR tyrosine kinase inhibitors in non-small-cell lung carcinoma.

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Hye Sook Kim

Full Text Available Direct sequencing remains the most widely used method for the detection of epidermal growth factor receptor (EGFR mutations in lung cancer; however, its relatively low sensitivity limits its clinical use. The objective of this study was to investigate the sensitivity of detecting an epidermal growth factor receptor (EGFR mutation from peptide nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR clamp and Ion Torrent Personal Genome Machine (PGM techniques compared to that by direct sequencing. Furthermore, the predictive efficacy of EGFR mutations detected by PNA-LNA PCR clamp was evaluated. EGFR mutational status was assessed by direct sequencing, PNA-LNA PCR clamp, and Ion Torrent PGM in 57 patients with non-small cell lung cancer (NSCLC. We evaluated the predictive efficacy of PNA-LNA PCR clamp on the EGFR-TKI treatment in 36 patients with advanced NSCLC retrospectively. Compared to direct sequencing (16/57, 28.1%, PNA-LNA PCR clamp (27/57, 47.4% and Ion Torrent PGM (26/57, 45.6% detected more EGFR mutations. EGFR mutant patients had significantly longer progressive free survival (14.31 vs. 21.61 months, P = 0.003 than that of EGFR wild patients when tested with PNA-LNA PCR clamp. However, no difference in response rate to EGFR TKIs (75.0% vs. 82.4%, P = 0.195 or overall survival (34.39 vs. 44.10 months, P = 0.422 was observed between the EGFR mutations by direct sequencing or PNA-LNA PCR clamp. Our results demonstrate firstly that patients with EGFR mutations were detected more frequently by PNA-LNA PCR clamp and Ion Torrent PGM than those by direct sequencing. EGFR mutations detected by PNA-LNA PCR clamp may be as a predicative factor for EGFR TKI response in patients with NSCLC.

Understanding the effect of locked nucleic acid and 2'-O-methyl modification on the hybridization thermodynamics of a miRNA-mRNA pair in the presence and absence of AfPiwi protein.

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Kumar, Santosh; Mapa, Koyeli; Maiti, Souvik

2014-03-18

miRNAs are some of the key epigenetic regulators of gene expression. They act through hybridization with their target mRNA and modulate the level of respective proteins via different mechanisms. Various cancer conditions are known to be associated with up- and downregulation of the oncogenic and tumor suppressor miRNAs, respectively. The levels of aberrantly expressed oncogenic miRNAs can be downregulated in different ways. Similarly, restoration of tumor suppressor miRNAs to their normal levels can be achieved using miRNA mimics. However, the use of miRNA mimics is limited by their reduced biostability and function. We have studied the hybridization thermodynamics of the miRNA 26a (11-mer, including the seed sequence) guide strand with the mRNA (11-mer) target strand in the absence and presence of AfPiwi protein. We have also inserted locked nucleic acids (LNAs) and 2'-O-methyl-modified nucleotides into the guide strand, in a walk-through manner, to assess their effect on the binding efficiency between guide and target RNA. Insertion of LNA and 2'-O-methyl-modified nucleotides into the guide strand helped to strengthen the binding affinity irrespective of the position of insertion. However, in the presence of AfPiwi protein, these modifications reduced the binding affinity to different extents depending on the position of insertion. Insertion of a modification leads to an increase in the enthalpic contribution with an increased unfavorable entropic contribution, which negatively compensates for the higher favorable enthalpy.

Experimental Warming Decreases the Average Size and Nucleic Acid Content of Marine Bacterial Communities

KAUST Repository

Huete-Stauffer, Tamara M.

2016-05-23

Organism size reduction with increasing temperature has been suggested as a universal response to global warming. Since genome size is usually correlated to cell size, reduction of genome size in unicells could be a parallel outcome of warming at ecological and evolutionary time scales. In this study, the short-term response of cell size and nucleic acid content of coastal marine prokaryotic communities to temperature was studied over a full annual cycle at a NE Atlantic temperate site. We used flow cytometry and experimental warming incubations, spanning a 6°C range, to analyze the hypothesized reduction with temperature in the size of the widespread flow cytometric bacterial groups of high and low nucleic acid content (HNA and LNA bacteria, respectively). Our results showed decreases in size in response to experimental warming, which were more marked in 0.8 μm pre-filtered treatment rather than in the whole community treatment, thus excluding the role of protistan grazers in our findings. Interestingly, a significant effect of temperature on reducing the average nucleic acid content (NAC) of prokaryotic cells in the communities was also observed. Cell size and nucleic acid decrease with temperature were correlated, showing a common mean decrease of 0.4% per °C. The usually larger HNA bacteria consistently showed a greater reduction in cell and NAC compared with their LNA counterparts, especially during the spring phytoplankton bloom period associated to maximum bacterial growth rates in response to nutrient availability. Our results show that the already smallest planktonic microbes, yet with key roles in global biogeochemical cycling, are likely undergoing important structural shrinkage in response to rising temperatures.

Experimental Warming Decreases the Average Size and Nucleic Acid Content of Marine Bacterial Communities

KAUST Repository

Huete-Stauffer, Tamara M.; Arandia-Gorostidi, Nestor; Alonso-Sá ez, Laura; Moran, Xose Anxelu G.

2016-01-01

Organism size reduction with increasing temperature has been suggested as a universal response to global warming. Since genome size is usually correlated to cell size, reduction of genome size in unicells could be a parallel outcome of warming at ecological and evolutionary time scales. In this study, the short-term response of cell size and nucleic acid content of coastal marine prokaryotic communities to temperature was studied over a full annual cycle at a NE Atlantic temperate site. We used flow cytometry and experimental warming incubations, spanning a 6°C range, to analyze the hypothesized reduction with temperature in the size of the widespread flow cytometric bacterial groups of high and low nucleic acid content (HNA and LNA bacteria, respectively). Our results showed decreases in size in response to experimental warming, which were more marked in 0.8 μm pre-filtered treatment rather than in the whole community treatment, thus excluding the role of protistan grazers in our findings. Interestingly, a significant effect of temperature on reducing the average nucleic acid content (NAC) of prokaryotic cells in the communities was also observed. Cell size and nucleic acid decrease with temperature were correlated, showing a common mean decrease of 0.4% per °C. The usually larger HNA bacteria consistently showed a greater reduction in cell and NAC compared with their LNA counterparts, especially during the spring phytoplankton bloom period associated to maximum bacterial growth rates in response to nutrient availability. Our results show that the already smallest planktonic microbes, yet with key roles in global biogeochemical cycling, are likely undergoing important structural shrinkage in response to rising temperatures.

Activity and Phylogenetic Diversity of Bacterial Cells with High and Low Nucleic Acid Content and Electron Transport System Activity in an Upwelling Ecosystem

OpenAIRE

Longnecker, K.; Sherr, B. F.; Sherr, E. B.

2005-01-01

We evaluated whether bacteria with higher cell-specific nucleic acid content (HNA) or an active electron transport system, i.e., positive for reduction of 5-cyano-2,3-ditolyl tetrazolium chloride (CTC), were responsible for the bulk of bacterioplankton metabolic activity. We also examined whether the phylogenetic diversity of HNA and CTC-positive cells differed from the diversity of Bacteria with low nucleic acid content (LNA). Bacterial assemblages were sampled both in eutrophic shelf waters...

Lack of anti-tumor activity with the β-catenin expression inhibitor EZN-3892 in the C57BL/6J Min/+ model of intestinal carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Hasson, Rian M.; Briggs, Alexandra; Rizvi, Hira; Carothers, Adelaide M.; Davids, Jennifer S.; Bertagnolli, Monica M.; Cho, Nancy L., E-mail: nlcho@partners.org

2014-02-14

Highlights: • Wnt/β-catenin signaling is aberrantly activated in most colorectal cancers. • Locked nucleic acid (LNA)-based antisense is a novel tool for cancer therapy. • β-Catenin inhibition was observed in mature intestinal tissue of LNA-treated mice. • Further investigation of Wnt/β-catenin targeted therapies is warranted. - Abstract: Background: Previously, we showed that short-term inhibition of β-catenin expression and reversal of aberrant β-catenin subcellular localization by the selective COX-2 inhibitor celecoxib is associated with adenoma regression in the C57BL/6J Min/+ mouse. Conversly, long-term administration resulted in tumor resistance, leading us to investigate alternative methods for selective β-catenin chemoprevention. In this study, we hypothesized that disruption of β-catenin expression by EZN-3892, a selective locked nucleic acid (LNA)-based β-catenin inhibitor, would counteract the tumorigenic effect of Apc loss in Min/+ adenomas while preserving normal intestinal function. Materials and methods: C57BL/6J Apc{sup +/+} wild-type (WT) and Min/+ mice were treated with the maximum tolerated dose (MTD) of EZN-3892 (30 mg/kg). Drug effect on tumor numbers, β-catenin protein expression, and nuclear β-catenin localization were determined. Results: Although the tumor phenotype and β-catenin nuclear localization in Min/+ mice did not change following drug administration, we observed a decrease in β-catenin expression levels in the mature intestinal tissue of treated Min/+ and WT mice, providing proof of principle regarding successful delivery of the LNA-based antisense vehicle. Higher doses of EZN-3892 resulted in fatal outcomes in Min/+ mice, likely due to β-catenin ablation in the intestinal tissue and loss of function. Conclusions: Our data support the critical role of Wnt/β-catenin signaling in maintaining intestinal homeostasis and highlight the challenges of effective drug delivery to target disease without permanent

A Locked Nucleic Acid Probe Based on Selective Salt-Induced Effect Detects Single Nucleotide Polymorphisms

Directory of Open Access Journals (Sweden)

Jing Zhang

2015-01-01

Full Text Available Detection of single based genetic mutation by using oligonucleotide probes is one of the common methods of detecting single nucleotide polymorphisms at known loci. In this paper, we demonstrated a hybridization system which included a buffer solution that produced selective salt-induced effect and a locked nucleic acid modified 12 nt oligonucleotide probe. The hybridization system is suitable for hybridization under room temperature. By using magnetic nanoparticles as carriers for PCR products, the SNPs (MDR1 C3435T/A from 45 volunteers were analyzed, and the results were consistent with the results from pyrophosphoric acid sequencing. The method presented in this paper differs from the traditional method of using molecular beacons to detect SNPs in that it is suitable for research institutions lacking real-time quantitative PCR detecting systems, to detect PCR products at room temperature.

Mismatch discrimination of lipidated DNA and LNA-probes (LiNAs) in hybridization-controlled liposome assembly

DEFF Research Database (Denmark)

Jakobsen, Ulla; Vogel, Stefan

2016-01-01

Assays for mismatch discrimination and detection of single nucleotide variations by hybridization-controlled assembly of liposomes, which do not require tedious surface chemistry, are versatile for both DNA and RNA targets. We report herein a comprehensive study on different DNA and LNA (locked...... assay in the context of mismatch discrimination and SNP detection are presented. The advantages of membrane-anchored LiNA-probes compared to chemically attached probes on solid nanoparticles (e.g. gold nanoparticles) are described. Key functionalities such as non-covalent attachment of LiNA probes...... without the need for long spacers and the inherent mobility of membrane-anchored probes in lipid-bilayer membranes will be described for several different probe designs....

A wideband Noise-Canceling CMOS LNA exploiting a transformer

NARCIS (Netherlands)

Blaakmeer, S.C.; Klumperink, Eric A.M.; Leenaerts, Domine M.W.; Nauta, Bram

2006-01-01

Abstract — A broadband LNA incorporating single-ended to differential conversion, has been successfully implemented using a noise-canceling technique and a single on-chip transformer. The LNA achieves a high voltage gain of 19dB, a wideband input match (2.5–4.0 GHz), and a Noise Figure of 4–5.4 dB,

A wideband Noise-Canceling CMOS LNA exploiting a transformer

NARCIS (Netherlands)

Blaakmeer, S.C.; Klumperink, Eric A.M.; Leenaerts, Domine M.W.; Nauta, Bram

2006-01-01

A broadband LNA incorporating single-ended to differential conversion, has been successfully implemented using a noise-canceling technique and a single on-chip transformer. The LNA achieves a high voltage gain of 19dB, a wideband input match (2.5–4.0 GHz), and a Noise Figure of 4–5.4 dB, while

Fluorescence In Vivo Hybridization (FIVH) for Detection of Helicobacter pylori Infection in a C57BL/6 Mouse Model

DEFF Research Database (Denmark)

Fontenete, Sílvia; Leite, Marina; Cappoen, Davie

2016-01-01

). Finally, the efficiency of FIVH to detect H. pylori SS1 strain in C57BL/6 infected mice was evaluated ex vivo in mucus samples, in cryosections and paraffin-embedded sections by epifluorescence and confocal microscopy. RESULTS: H. pylori SS1 strain infecting C57BL/6 mice was successfully detected...... by the Cy3_HP_LNA/2OMe_PS probe in the mucus, attached to gastric epithelial cells and colonizing the gastric pits. The specificity of the probe for H. pylori was confirmed by microscopy. CONCLUSIONS: In the future this methodology can be used in combination with a confocal laser endomicroscope for in vivo......INTRODUCTION: In this study, we applied fluorescence in vivo hybridization (FIVH) using locked nucleic acid (LNA) probes targeting the bacterial rRNA gene for in vivo detection of H. pylori infecting the C57BL/6 mouse model. A previously designed Cy3_HP_LNA/2OMe_PS probe, complementary...

Photoligation of self-assembled DNA constructs containing anthracene-functionalized 2'-amino-LNA monomers

DEFF Research Database (Denmark)

Pasternak, Karol; Pasternak, Anna; Gupta, Pankaj

2011-01-01

Efficient synthesis of a novel anthracene-functionalized 2'-amino-LNA phosphoramidite derivative is described together with its incorporation into oligodeoxynucleotides. Two DNA strands with the novel 2'-N-anthracenylmethyl-2'-amino-LNA monomers can be effectively cross-linked by photoligation...... at 366nm in various types of DNA constructs. Successful application of three differently functionalized 2'-amino-LNA monomers in self-assembled higher ordered structures for simultaneous cross-linking and monitoring of assembly formation is furthermore demonstrated....

A high linearity SiGe HBT LNA for GPS receiver

International Nuclear Information System (INIS)

Luo Yanbin; Shi Jian; Ma Chengyan; Gan Yebing; Qian Min

2014-01-01

A high linearity 1.575 GHz SiGe:HBT low noise amplifier (LNA) for global positioning system applications is described. The bipolar cascoded with an MOSFET LNA was fabricated in a commercial 0.18 μm SiGe BiCMOS process. A resistor bias feed circuit with a feedback resistor was designed for the LNA input transistor to improve its intermodulation and compression performance. The packaged chip tested on board has displayed a noise figure of 1.11 dB, a power gain of 18 dB, an output 1 dB compression point of +7.8 dBm and an input third-order intercept point of +1.8 dBm. The chip occupies a 500 × 560 μm 2 area and consumes 3.6 mA from a 2.85 V power supply. (semiconductor integrated circuits)

Oligodeoxynucleotides containing 2'-amino-LNA nucleotides as constrained morpholino phosphoramidate and phosphorodiamidate monomers

DEFF Research Database (Denmark)

Kristensen, Kim Vejlegaard; Paul, Sibasish; Kosbar, Tamer

2017-01-01

Incorporation in a 2'→5' direction of a phosphorodiamidite 2'-amino-LNA-T nucleotide as the morpholino phosphoramidate and N,N-dimethylamino phosphorodiamidate monomers into six oligonucleotides is reported. Thermal denaturation studies showed that the novel 2'-amino-LNA-based morpholino monomers...

Selection of LNA-containing DNA aptamers against recombinant human CD73

DEFF Research Database (Denmark)

Elle, Ida C; Karlsen, Kasper K; Terp, Mikkel G

2015-01-01

tested by surface plasmon resonance. Truncated variants of these aptamers and variants where the LNA nucleotides were substituted for the DNA equivalent also exhibited affinity for the recombinant CD73 in the low nanomolar range. In enzyme inhibition assays with recombinant CD73 the aptamer sequences......LNA-containing DNA aptamers against CD73 (human ecto-5'-nucleotidase), a protein frequently overexpressed in solid tumours, were isolated by SELEX. A pre-defined stem-loop library, containing LNA in the forward primer region, was enriched with CD73 binding sequences through six rounds of SELEX...... with recombinant his-tagged CD73 immobilised on anti-his plates. Enriched pools isolated from rounds one, three and six were subjected to next-generation sequencing and analysed for enrichment using custom bioinformatics software. The software identified aptamer sequences via the primers and then performed several...

Molecular detection of foodborne pathogens

DEFF Research Database (Denmark)

Josefsen, Mathilde Hartmann

Microbiological Methods (NordVal) in comparative and collaborative trials, and was approved for detection of Campylobacter in chicken neck skin, cloacal swab and boot swab samples. A comparison study on probe chemistries for real-time PCR was performed on locked nucleic acid (LNA), minor groove binder (MGB...... of the optimization strategy were observed from increasing 1) the sampling volume from the pre-enrichment, 2) the paramagnetic particles applied in the DNA extraction procedure, and 3) the amount of DNA template in the PCR. This method was subsequently validated according to the recommendations of NordVal...

PAM, OLA, and LNA are Differentially Taken Up and Trafficked Via Different Metabolic Pathways in Porcine Adipocytes.

Science.gov (United States)

Yu, Caihua; Xi, Lingling; Chen, Jin; Jiang, Qin; Yi, Hongbo; Wang, Yizhen; Wang, Xinxia

2017-11-01

Dietary fatty acids have different effects on fat deposition in pigs. To clarify the underlying mechanisms of this difference, we compared the metabolism of palmitic (PAM, saturated), oleic (OLA, monounsaturated) and linoleic acid (LNA, polyunsaturated) in porcine adipocytes treated with 100 μM PAM, OLA or LNA. We observed that the adipocytes incubated with LNA accumulated more lipids compared with those treated with PAM and OLA. We then probed the metabolism of these fatty acids in porcine adipocytes by using isotope-labelled fatty acids. The results showed that 42% of the [1- 14 C] LNA, 34% of the [1- 14 C] PAM and 28% of the [1- 14 C] OLA were recovered in the cellular lipids. The gene expression analyses showed that LNA significantly increased the expression of adipogenesis- and oxidation-related genes including PPARγ, C/EBPα, ap2 and NRF1. In addition, the cells incubated with LNA showed a decreased Ser 112 phosphorylation in PPARγ compared to those incubated with PAM and OLA. Furthermore, when PPARγ Ser 112 phosphorylation was inhibited, no significant difference in the triacylglycerol contents in the adipocytes was observed. These results showed the dietary fatty acids had different metabolism pathways in porcine adipocytes, and LNA significantly promoted lipid accumulation, probably by regulating PPARγ phosphorylation in adipocytes.

A sensitive detection method for MPLW515L or MPLW515K mutation in chronic myeloproliferative disorders with locked nucleic acid-modified probes and real-time polymerase chain reaction.

OpenAIRE

Alessandro, Pancrazzi; Paola, Guglielmelli; Vanessa, Ponziani; Gaetano, Bergamaschi; Alberto, Bosi; Giovanni, Barosi; Alessandro M, Vannucchi

2008-01-01

Acquired mutations in the juxtamembrane region of MPL (W515K or W515L), the receptor for thrombopoietin, have been described in patients with primary myelofibrosis or essential thrombocythemia, which are chronic myeloproliferative disorders. We have developed a real-time polymerase chain reaction assay for the detection and quantification of MPL mutations that is based on locked nucleic acid fluorescent probes. Mutational analysis was performed using DNA from granulocytes. Reference curves we...

A Wideband Balun LNA I/Q-Mixer combination in 65nm CMOS

NARCIS (Netherlands)

Blaakmeer, S.C.; Klumperink, Eric A.M.; Leenaerts, D.M.W.; Nauta, Bram

2008-01-01

An inductor-less LNA-mixer topology merges an I/Q current-commutating mixer with a noise-canceling balun/LNA. The topology achieves >18dB conversion gain, a flat NF<5.5dB, IIP2=+20dBm and IIP3=-3dBm from 500MHz to 7GHz. The core circuit consumes 16mW and occupies less than 0.01mm2 in 65nm CMOS.

Design of 2.4Ghz CMOS Floating Active Inductor LNA using 130nm Technology

Science.gov (United States)

Muhamad, M.; Soin, N.; Ramiah, H.

2018-03-01

This paper presents about design and optimization of CMOS active inductor integrated circuit. This active inductor implements using Silterra 0.13μm technology and simulated using Cadence Virtuoso and Spectre RF. The center frequency for this active inductor is at 2.4 GHz which follow IEEE 802.11 b/g/n standard. To reduce the chip size of silicon, active inductor is used instead of passive inductor at low noise amplifier LNA circuit. This inductor test and analyse by low noise amplifier circuit. Comparison between active with passive inductor based on LNA circuit has been performed. Result shown that the active inductor has significantly reduce the chip size with 73 % area without sacrificing the noise figure and gain of LNA which is the most important criteria in LNA. The best low noise amplifier provides a power gain (S21) of 20.7 dB with noise figure (NF) of 2.1dB.

A wideband LNA employing gate-inductive-peaking and noise-canceling techniques in 0.18 μm CMOS

International Nuclear Information System (INIS)

Bao Kuan; Fan Xiangning; Li Wei; Zhang Li; Wang Zhigong

2012-01-01

This paper presents a wideband low noise amplifier (LNA) for multi-standard radio applications. The low noise characteristic is achieved by the noise-canceling technique while the bandwidth is enhanced by gate-inductive-peaking technique. High-frequency noise performance is consequently improved by the flattened gain over the entire operating frequency band. Fabricated in 0.18 μm CMOS process, the LNA achieves 2.5 GHz of −3 dB bandwidth and 16 dB of gain. The gain variation is within ±0.8 dB from 300 MHz to 2.2 GHz. The measured noise figure (NF) and average IIP3 are 3.4 dB and −2 dBm, respectively. The proposed LNA occupies 0.39 mm 2 core chip area. Operating at 1.8 V, the LNA drains a current of 11.7 mA. (semiconductor integrated circuits)

LNA-modified oligonucleotides mediate specific inhibition of microRNA function

DEFF Research Database (Denmark)

Ørom, Ulf Andersson; Kauppinen, Sakari; Lund, Anders H

2006-01-01

microRNAs are short, endogenous non-coding RNAs that act as post-transcriptional modulators of gene expression. Important functions for microRNAs have been found in the regulation of development, cellular proliferation and differentiation, while perturbed miRNA expression patterns have been...... observed in many human cancers. Here we present a method for specific inhibition of miRNA function through interaction with LNA-modified antisense oligonucleotides and report the specificity of this application. We show that LNA-modified oligonucleotides can inhibit exogenously introduced miRNAs with high...... specificity using a heterologous reporter assay, and furthermore demonstrate their ability to inhibit an endogenous miRNA in Drosophila melanogaster cells, leading to up-regulation of the cognate target protein. The method shows stoichiometric and reliable inhibition of the targeted miRNA and can thus...

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

LNA A 1.9 GHZ low noise amplifier

Directory of Open Access Journals (Sweden)

Jorge Julián Moreno-Rubio

2006-12-01

Full Text Available This paper shows the design, the simulation, and the layout from a low noise amplifier (LNA, designed with and approximate band from 25 to 80 MHz. The design results of the matching neworks are shown, its noise figure, its available and transduced gain according to its non lineal model (TOM, the DC network, crash inductors and matching capacitors with the large impedance transmission lines.

Influence of the Antenna Impedance Variation and Input Matching Network Q on LNA Key Figures

DEFF Research Database (Denmark)

Ruaro, Andrea; Kvist, Søren Helstrup; Gülstorff, Steen

2012-01-01

In this paper we present an analysis of the behaviour of a 2:4 GHz Low Noise Amplifier (LNA) for Wireless Body Area Network (WBAN) applications facing antennadetuning issue. An amplifier with ultra-low power, low voltage, and with reduced component count is prototyped to validate simulation results......, then the behaviour is analyzed through simulations based on data measured on real users. The analysis shows that the designed LNA is stable to the antenna impedance variation expectable in most cases, while highlights the possible risks associated to a high-Q input matching network when used in a context prone...

Evaluation of miR-21 Inhibition and its Impact on Cancer Susceptibility Candidate 2 Long Noncoding RNA in Colorectal Cancer Cell Line

Directory of Open Access Journals (Sweden)

Miganoosh Simonian

2018-01-01

Full Text Available Background: Both microRNAs (miRNAs and long noncoding RNAs (lncRNAs have been shown to have a critical role in the regulation of cellular processes such as cell growth and apoptosis, as well as cancer progression and metastasis. lncRNAs are aberrantly expressed in many diseases including cancer. Although it is well known that miRNAs can target a large number of protein-coding genes, little is known whether miRNAs can also target lncRNAs. In the present study, we determine whether miR-21 can regulate lncRNA cancer susceptibility candidate 2 (CASC2 in colorectal cancer. Materials and Methods: LS174T cells were transfected with locked nucleic acid (LNA-anti-miR-21 and scrambled LNA for 24, 48 and 72 h. The expression of miR-21 and lncCASC2 was evaluated by quantitative reverse transcriptase polymerase chain reaction. Results: However, contrary to what we expected and reported by others, lncCASC2 quantity was significantly reduced in LNA treated LS174T cells compared to the scrambled treated and normal untreated cells (P < 0.05. Conclusion: The interaction of miRNA and lncRNA are not as simple as suggested by other reports. Moreover, it could be complex molecular mechanisms underlying the communication of various noncoding RNA elements.

The BLIXER, a Wideband Balun-LNA-I/Q-Mixer Topology

NARCIS (Netherlands)

Blaakmeer, S.C.; Klumperink, Eric A.M.; Leenaerts, Domine M.W.; Nauta, Bram

2008-01-01

Abstract—This paper proposes to merge an I/Q current-commutating mixer with a noise-canceling balun-LNA. To realize a high bandwidth, the real part of the impedance of all RF nodes is kept low, and the voltage gain is not created at RF but in baseband where capacitive loading is no problem. Thus a

Tunable diode-pumped-LNA laser

International Nuclear Information System (INIS)

Cassimi, A.; Hardy, V.; Hamel, J.; Leduc, M.

1987-01-01

Diode-pumped crystals provided recently new compact laser devices. We report the first end pumping of a La x Nd 1-x MgAl 11 O 19 (LNA) crystal using a 200mW diode array (Spectra Diode Lab). We also report the first results obtained with a 1mW diode (SONY). This C.W. laser can be tuned from 1.048μm to 1.086μm. Without selective elements in the cavity, the laser emits around 1.054μm with a threshold of 24mW and a slope efficiency of 4.4% (output mirror of transmission T = 1%) when pumped by the diode array. With the selective elements, the threshold increases to 100mW and we obtain a power of 4mW for a pump power of 200mW

A Wide-Band High-Gain Compact SIS Receiver Utilizing a 300-μW SiGe IF LNA

Science.gov (United States)

Montazeri, Shirin; Grimes, Paul K.; Tong, Cheuk-Yu Edward; Bardin, Joseph C.

2017-06-01

Low-power low-noise amplifiers integrated with superconductor-insulator-superconductor (SIS) mixers are required to enable implementation of large-scale focal plane arrays. In this work, a 220-GHz SIS mixer has been integrated with a high-gain broad-band low-power IF amplifier into a compact receiver module. The low noise amplifier (LNA) was specifically designed to match to the SIS output impedance and contributes less than 7 K to the system noise temperature over the 4-8 GHz IF frequency range. A receiver noise temperature of 30-45 K was measured for a local oscillator frequency of 220 GHz over an IF spanning 4-8 GHz. The LNA power dissipation was only 300-μW. To the best of the authors' knowledge, this is the lowest power consumption reported for a high-gain wide-band LNA directly integrated with an SIS mixer.

A Small-Area Self-Biased Wideband CMOS Balun LNA with Noise Cancelling and Gain Enhancement

DEFF Research Database (Denmark)

Bruun, Erik; Andreani, Pietro; Custódio, J. R.

2010-01-01

In this paper we present a low-power and small-area balun LNA. The proposed inverter-based topology uses selfbiasing and noise cancelling, yielding a very robust LNA with a low NF. Comparing this circuit with a conventional inverterbased circuit, we obtain a ∼3 dB enhancement in voltage gain......, with improved robustness against PVT variations. Simulations results in a 130 nm CMOS technology show a 17.7dB voltage gain, nearly flat over a wide bandwidth (200MHz-1GHz), and an NF of approximately 4dB. The total power consumption is below 7.5 mW, with a very small die area of 0.007 mm2. All data...

Wideband Balun-LNA with Simultaneous Output Balancing, Noise-Canceling and Distortion-Canceling

NARCIS (Netherlands)

Blaakmeer, S.C.; Klumperink, Eric A.M.; Leenaerts, D.M.W.; Nauta, Bram

2008-01-01

An inductorless low-noise amplifier (LNA) with active balun is proposed for multi-standard radio applications between 100 MHz and 6 GHz. It exploits a combination of a common-gate (CGH) stage and an admittance-scaled common-source (CS) stage with replica biasing to maximize balanced operation, while

Liver conversion of docosahexaenoic and arachidonic acids from their 18-carbon precursors in rats on a DHA-free but α-LNA-containing n-3 PUFA adequate diet.

Science.gov (United States)

Gao, Fei; Kim, Hyung-Wook; Igarashi, Miki; Kiesewetter, Dale; Chang, Lisa; Ma, Kaizong; Rapoport, Stanley I

2011-01-01

The long-chain polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), and arachidonic acid (AA, 20:4n-6), are critical for health. These PUFAs can be synthesized in liver from their plant-derived precursors, α-linolenic acid (α-LNA, 18:3n-3) and linoleic acid (LA, 18:2n-6). Vegetarians and vegans may have suboptimal long-chain n-3 PUFA status, and the extent of the conversion of α-LNA to EPA and DHA by the liver is debatable. We quantified liver conversion of DHA and other n-3 PUFAs from α-LNA in rats fed a DHA-free but α-LNA (n-3 PUFA) adequate diet, and compared results to conversion of LA to AA. [U-(13)C]LA or [U-(13)C]α-LNA was infused intravenously for 2h at a constant rate into unanesthetized rats fed a DHA-free α-LNA adequate diet, and published equations were used to calculate kinetic parameters. The conversion coefficient k(⁎) of DHA from α-LNA was much higher than for AA from LA (97.2×10(-3) vs. 10.6×10(-3)min(-1)), suggesting that liver elongation-desaturation is more selective for n-3 PUFA biosynthesis on a per molecule basis. The net daily secretion rate of DHA, 20.3μmol/day, exceeded the reported brain DHA consumption rate by 50-fold, suggesting that the liver can maintain brain DHA metabolism with an adequate dietary supply solely of α-LNA. This infusion method could be used in vegetarians or vegans to determine minimal daily requirements of EPA and DHA in humans. Published by Elsevier B.V.

An inductorless wideband LNA with a new noise canceling technique

OpenAIRE

MOGHADAM, POURIA PAZHOUHESH; ABRISHAMIFAR, ADIB

2017-01-01

An inductorless wideband low-noise amplifier (LNA) employing a new noise canceling technique for multistandard applications is presented. The main amplifier has a cascode common gate structure, which provides good input impedance matching and isolation. The proposed noise canceling technique not only improves the noise figure and power gain but also embeds a g$_{m}$-boosting technique in itself, which reduces the power consumption of the main amplifier. Using current-steering and ...

An inductorless wideband Balun-LNA in 65nm CMOS with balanced output

NARCIS (Netherlands)

Blaakmeer, S.C.; Klumperink, Eric A.M.; Nauta, Bram; Leenaerts, D.M.W.

2007-01-01

Abstract — An inductorless LNA with active balun is designed for multi-standard radio applications between 100MHz and 6GHz. It exploits a combination of a common gate stage and a common source stage with replica biasing to maximize balanced operation. The NF is designed to be around 3dB by using the

High-performance CPW MMIC LNA using GaAs-based metamorphic HEMTs for 94-GHz applications

International Nuclear Information System (INIS)

Ryu, Keun-Kwan; Kim, Sung-Chan; An, Dan; Rhee, Jin-Koo

2010-01-01

In this paper, we report on a high-performance low-noise amplifier (LNA) using metamorphic high-electron-mobility transistor (MHEMT) technology for 94-GHz applications. The 100 nm x 60 μm MHEMT devices for the coplanar MMIC LNA exhibited DC characteristics with a drain current density of 655 mA/mm and an extrinsic transconductance of 720 mS/mm. The current gain cutoff frequency (f T ) and the maximum oscillation frequency (f max ) were 195 GHz and 305 GHz, respectively. Based on this MHEMT technology, coplanar 94-GHz MMIC LNAs were realized, achieving a small signal gain of more than 13 dB between 90 and 100 GHz and a small signal gain of 14.8 dB and a noise figure of 4.7 dB at 94 GHz.

Hybridization-Based Detection of Helicobacter pylori at Human Body Temperature Using Advanced Locked Nucleic Acid (LNA) Probes

DEFF Research Database (Denmark)

Fontenete, Sílvia; Guimarães, Nuno; Leite, Marina

2013-01-01

The understanding of the human microbiome and its influence upon human life has long been a subject of study. Hence, methods that allow the direct detection and visualization of microorganisms and microbial consortia (e.g. biofilms) within the human body would be invaluable. In here, we assessed...

Quantification of low-expressed mRNA using 5' LNA-containing real-time PCR primers

International Nuclear Information System (INIS)

Malgoyre, A.; Banzet, S.; Mouret, C.; Bigard, A.X.; Peinnequin, A.

2007-01-01

Real-time RT-PCR is the most sensitive and accurate method for mRNA quantification. Using specific recombinant DNA as a template, real-time PCR allows accurate quantification within a 7-log range and increased sensitivity below 10 copies. However, when using RT-PCR to quantify mRNA in biological samples, a stochastic off-targeted amplification can occur. Classical adjustments of assay parameters have minimal effects on such amplification. This undesirable amplification appears mostly to be dependent on specific to non-specific target ratio rather than on the absolute quantity of the specific target. This drawback, which decreases assay reliability, mostly appears when quantifying low-expressed transcript in a whole organ. An original primer design using properties of LNA allows to block off-target amplification. 5'-LNA substitution strengthens 5'-hybridization. Consequently on-target hybridization is stabilized and the probability for the off-target to lead to amplification is decreased

Synthesis and Excellent Duplex Stability of Oligonucleotides Containing 2'-Amino-LNA Functionalized with Galactose Units

DEFF Research Database (Denmark)

Kumar, Rajesh; Ries, Annika; Wengel, Jesper

2017-01-01

A convenient method for the preparation of oligonucleotides containing internally-attached galactose and triantennary galactose units has been developed based on click chemistry between 2'-N-alkyne 2'-amino-LNA nucleosides and azido-functionalized galactosyl building blocks. The synthesized...

An UWB LNA Design with PSO Using Support Vector Microstrip Line Model

Directory of Open Access Journals (Sweden)

Salih Demirel

2015-01-01

Full Text Available A rigorous and novel design procedure is constituted for an ultra-wideband (UWB low noise amplifier (LNA by exploiting the 3D electromagnetic simulator based support vector regression machine (SVRM microstrip line model. First of all, in order to design input and output matching circuits (IMC-OMC, source ZS and load ZL termination impedance of matching circuit, which are necessary to obtain required input VSWR (Vireq, noise (Freq, and gain (GTreq, are determined using performance characterisation of employed transistor, NE3512S02, between 3 and 8 GHz frequencies. After the determination of the termination impedance, to provide this impedance with IMC and OMC, dimensions of microstrip lines are obtained with simple, derivative-free, easily implemented algorithm Particle Swarm Optimization (PSO. In the optimization of matching circuits, highly accurate and fast SVRM model of microstrip line is used instead of analytical formulations. ADCH-80a is used to provide ultra-wideband RF choking in DC bias. During the design process, it is aimed that Vireq = 1.85, Freq = Fmin, and GTreq = GTmax all over operating frequency band. Measurements taken from the realized LNA demonstrate the success of this approximation over the band.

The Interactions between ZnO Nanoparticles (NPs and α-Linolenic Acid (LNA Complexed to BSA Did Not Influence the Toxicity of ZnO NPs on HepG2 Cells

Directory of Open Access Journals (Sweden)

Yiwei Zhou

2017-04-01

Full Text Available Background: Nanoparticles (NPs entering the biological environment could interact with biomolecules, but little is known about the interaction between unsaturated fatty acids (UFA and NPs. Methods: This study used α-linolenic acid (LNA complexed to bovine serum albumin (BSA for UFA and HepG2 cells for hepatocytes. The interactions between BSA or LNA and ZnO NPs were studied. Results: The presence of BSA or LNA affected the hydrodynamic size, zeta potential, UV-Vis, fluorescence, and synchronous fluorescence spectra of ZnO NPs, which indicated an interaction between BSA or LNA and NPs. Exposure to ZnO NPs with the presence of BSA significantly induced the damage to mitochondria and lysosomes in HepG2 cells, associated with an increase of intracellular Zn ions, but not intracellular superoxide. Paradoxically, the release of inflammatory cytokine interleukin-6 (IL-6 was decreased, which indicated the anti-inflammatory effects of ZnO NPs when BSA was present. The presence of LNA did not significantly affect all of these endpoints in HepG2 cells exposed to ZnO NPs and BSA. Conclusions: the results from the present study indicated that BSA-complexed LNA might modestly interact with ZnO NPs, but did not significantly affect ZnO NPs and BSA-induced biological effects in HepG2 cells.

Multiplexed Detection of Attomoles of Nucleic Acids Using Fluorescent Nanoparticle Counting Platform.

Science.gov (United States)

Pei, Xiaojing; Yin, Haoyan; Lai, Tiancheng; Zhang, Junlong; Liu, Feng; Xu, Xiao; Li, Na

2018-01-16

The sensitive multiplexed detection of nucleic acids in a single sample by a simple manner is of pivotal importance for the diagnosis and therapy of human diseases. Herein, we constructed an automatic fluorescent nanoparticle (FNP) counting platform with a common fluorescence microscopic imaging setup for nonamplification multiplexed detection of attomoles of nucleic acids. Taking the advantages of the highly bright, multicolor emitting FNPs and magnetic separation, the platform enables sensitive multiplexed detection without the need for extra fluorescent labels. Quantification for multiplex DNAs, multiplex microRNAs (miRNA), as well as a DNA and miRNA mixture was achieved with a similar dynamic range, a limit of detection down to 5 amol (5 μL detection volume), and a 81-115% spike recovery from different biological sample matrices. In particular, the sensitivity for multiplex miRNA is by far among the highest without using amplification or the lock nucleic acid hybridization enhancement strategy. Results regarding miRNA-141 from four different cell lines were agreeable with those of the quantitative reverse transcription polymerase chain reaction. Simultaneous detection of miRNA-141 and miRNA-21 in four different cell lines yielded consistent results with publications, indicating the potential for monitoring multiplex miRNA expression associated with the collaborative regulation of important cellular events. This work expands the rule set of multiplex nucleic acid detection strategies and shows promising potential application in clinical diagnosis.

Automatic locking radioisotope camera lock

International Nuclear Information System (INIS)

Rosauer, P.J.

1978-01-01

The lock of the present invention secures the isotope source in a stored shielded condition in the camera until a positive effort has been made to open the lock and take the source outside of the camera and prevents disconnection of the source pigtail unless the source is locked in a shielded condition in the camera. It also gives a visual indication of the locked or possible exposed condition of the isotope source and prevents the source pigtail from being completely pushed out of the camera, even when the lock is released. (author)

Enrichment of methylated molecules using enhanced-ice-co-amplification at lower denaturation temperature-PCR (E-ice-COLD-PCR) for the sensitive detection of disease-related hypermethylation.

Science.gov (United States)

Mauger, Florence; Kernaleguen, Magali; Lallemand, Céline; Kristensen, Vessela N; Deleuze, Jean-François; Tost, Jörg

2018-05-01

The detection of specific DNA methylation patterns bears great promise as biomarker for personalized management of cancer patients. Co-amplification at lower denaturation temperature-PCR (COLD-PCR) assays are sensitive methods, but have previously only been able to analyze loss of DNA methylation. Enhanced (E)-ice-COLD-PCR reactions starting from 2 ng of bisulfite-converted DNA were developed to analyze methylation patterns in two promoters with locked nucleic acid (LNA) probes blocking amplification of unmethylated CpGs. The enrichment of methylated molecules was compared to quantitative (q)PCR and quantified using serial dilutions. E-ice-COLD-PCR allowed the multiplexed enrichment and quantification of methylated DNA. Assays were validated in primary breast cancer specimens and circulating cell-free DNA from cancer patients. E-ice-COLD-PCR could prove a useful tool in the context of DNA methylation analysis for personalized medicine.

Smart Sensing Based on DNA-Metal Interaction Enables a Label-Free and Resettable Security Model of Electrochemical Molecular Keypad Lock.

Science.gov (United States)

Du, Yan; Han, Xu; Wang, Chenxu; Li, Yunhui; Li, Bingling; Duan, Hongwei

2018-01-26

Recently, molecular keypad locks have received increasing attention. As a new subgroup of smart biosensors, they show great potential for protecting information as a molecular security data processor, rather than merely molecular recognition and quantitation. Herein, label-free electrochemically transduced Ag + and cysteine (Cys) sensors were developed. A molecular keypad lock model with reset function was successfully realized based on the balanced interaction of metal ion with its nucleic acid and chemical ligands. The correct input of "1-2-3" (i.e., "Ag + -Cys-cDNA") is the only password of such molecular keypad lock. Moreover, the resetting process of either correct or wrong input order could be easily made by Cys, buffer, and DI water treatment. Therefore, our system provides an even smarter system of molecular keypad lock, which could inhibit illegal access of unauthorized users, holding great promise in information protection at the molecular level.

Antisense locked nucleic acids targeting agrA inhibit quorum sensing and pathogenesis of community-associated methicillin-resistant Staphylococcus aureus.

Science.gov (United States)

Da, F; Yao, L; Su, Z; Hou, Z; Li, Z; Xue, X; Meng, J; Luo, X

2017-01-01

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is commonly associated with nonnosocomial skin and soft tissue infections due to its virulence, which is mainly controlled by the accessory gene regulator (agr) quorum sensing (QS) system. In this study (KFF) 3 K peptide-conjugated locked nucleic acids (PLNAs) targeting agrA mRNA were developed to inhibit agr activity and arrest the pathogenicity of CA-MRSA. Two PLNAs were designed, and synthesized, after predicting the secondary structure of agrA mRNA. The influence on bacterial growth was tested using a growth curve assay. RT-qPCR, haemolysis assay, lactate dehydrogenase release assay and chemotaxis assay were used to evaluate the effects of the PLNAs on inhibiting agr QS. A mouse skin infection model was employed to test the protective effect of the PLNAs in vivo. None of the PLNAs were found to be bacteriostatic or bactericidal in vitro. However, one PLNA, PLNA34, showed strong ability to suppress expression of agrA and the effector molecule RNAIII in USA300 LAC strain. Furthermore, PLNA34 inhibited the expression of virulence genes that are upregulated by agr, including hla, psmα, psmβ and pvl. The haemolytic activity of the supernatants from PLNA34-treated bacteria was also dramatically reduced, as well as the capacity to lyse and recruit neutrophils. Moreover, PLNA34 showed high levels of protection in the CA-MRSA mouse skin infection model. The anti-agrA PLNA34 can effectively inhibit the agr QS and suppress CA-MRSA pathogenicity. agrA is a promising target for the development of antisense oligonucleotides to block agr QS. Journal of Applied Microbiology © 2016 The Society for Applied Microbiology.

Inhibition of miR-15 Protects Against Cardiac Ischemic Injury

Science.gov (United States)

Hullinger, Thomas G.; Montgomery, Rusty L.; Seto, Anita G.; Dickinson, Brent A.; Semus, Hillary M.; Lynch, Joshua M.; Dalby, Christina M.; Robinson, Kathryn; Stack, Christianna; Latimer, Paul A.; Hare, Joshua M.; Olson, Eric N.; van Rooij, Eva

2012-01-01

Rationale Myocardial infarction (MI) is a leading cause of death worldwide. Because endogenous cardiac repair mechanisms are not sufficient for meaningful tissue regeneration, MI results in loss of cardiac tissue and detrimental remodeling events. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression in a sequence dependent manner. Our previous data indicate that miRNAs are dysregulated in response to ischemic injury of the heart and actively contribute to cardiac remodeling after MI. Objective This study was designed to determine whether miRNAs are dysregulated on ischemic damage in porcine cardiac tissues and whether locked nucleic acid (LNA)-modified anti-miR chemistries can target cardiac expressed miRNAs to therapeutically inhibit miR-15 on ischemic injury. Methods and Results Our data indicate that the miR-15 family, which includes 6 closely related miRNAs, is regulated in the infarcted region of the heart in response to ischemia-reperfusion injury in mice and pigs. LNA-modified chemistries can effectively silence miR-15 family members in vitro and render cardiomyocytes resistant to hypoxia-induced cardiomyocyte cell death. Correspondingly, systemic delivery of miR-15 anti-miRs dose-dependently represses miR-15 in cardiac tissue of both mice and pigs, whereas therapeutic targeting of miR-15 in mice reduces infarct size and cardiac remodeling and enhances cardiac function in response to MI. Conclusions Oligonucleotide-based therapies using LNA-modified chemistries for modulating cardiac miRNAs in the setting of heart disease are efficacious and validate miR-15 as a potential therapeutic target for the manipulation of cardiac remodeling and function in the setting of ischemic injury. PMID:22052914

LNA-modified isothermal oligonucleotide microarray for ...

Indian Academy of Sciences (India)

2014-10-20

Oct 20, 2014 ... the advent of DNA microarray techniques (Lee et al. 2007). ... atoms of ribose to form a bicyclic ribosyl structure. It is the .... 532 nm and emission at 570 nm. The signal ..... sis and validation using real-time PCR. Nucleic Acids ...

A 5.4mW GPS CMOS quadrature front-end based on a single-stage LNA-mixer-VCO

DEFF Research Database (Denmark)

Liscidini, Amtonio; Mazzanti, Andrea; Tonietto, Riccardo

2006-01-01

A GPS RF front-end combines the LNA, mixer, and VCO in a single stage and can operate from a 1.2V supply. The chip is implemented in a 0.13um CMOS process and occupies 1.5mm2 active area. It consumes 5.4mW with a 4.8dB NF, 36dB gain, and a P1dB of -31dBm.......A GPS RF front-end combines the LNA, mixer, and VCO in a single stage and can operate from a 1.2V supply. The chip is implemented in a 0.13um CMOS process and occupies 1.5mm2 active area. It consumes 5.4mW with a 4.8dB NF, 36dB gain, and a P1dB of -31dBm....

A hyaluronic acid-based hydrogel enabling CD44-mediated chondrocyte binding and gapmer oligonucleotide release for modulation of gene expression in osteoarthritis

DEFF Research Database (Denmark)

Cai, Yunpeng; López-Ruiz, Elena; Wengel, Jesper

2017-01-01

Hyaluronic acid (HA) is an attractive biomaterial for osteoarthritis (OA) treatment due to inherent functional and compatibility properties as an endogenous knee joint component. In this work, we describe a HA-based hydrogel with the dual functionality of increased CD44-dependent chondrocyte......:3) for identifying designs displaying optimal engagement of OA patient-derived CD44-expressing chondrocytes. Correlation was found between cell binding and CD44 expression, with maximal binding exhibited at a HA/chitosan ratio of 7:3, that was 181% higher than CD44-negative MCF-7 cell control cells. Transfection...... agent-free uptake into OA chondrocytes of fluorescent 13-mer DNA oligonucleotides with a flanked locked nucleic acid (LNA) gapmer design, in contrast to naked siRNA, was demonstrated by confocal and flow cytometric analysis. A sustained and complete release over 5days was found with the 7:3 hydrogel...

MicroRNA-146a Regulates Perfusion Recovery in Response to Arterial Occlusion via Arteriogenesis

Directory of Open Access Journals (Sweden)

Joshua L. Heuslein

2018-01-01

Full Text Available The growth of endogenous collateral arteries that bypass arterial occlusion(s, or arteriogenesis, is a fundamental shear stress-induced adaptation with implications for treating peripheral arterial disease. MicroRNAs (miRs are key regulators of gene expression in response to injury and have strong therapeutic potential. In a previous study, we identified miR-146a as a candidate regulator of vascular remodeling. Here, we tested whether miR-146a regulates in vitro angiogenic endothelial cell (EC behaviors, as well as perfusion recovery, arteriogenesis, and angiogenesis in response to femoral arterial ligation (FAL in vivo. We found miR-146a inhibition impaired EC tube formation and migration in vitro. Following FAL, Balb/c mice were treated with a single, intramuscular injection of anti-miR-146a or scramble locked nucleic acid (LNA oligonucleotides directly into the non-ischemic gracilis muscles. Serial laser Doppler imaging demonstrated that anti-miR-146a treated mice exhibited significantly greater perfusion recovery (a 16% increase compared mice treated with scramble LNA. Moreover, anti-miR-146a treated mice exhibited a 22% increase in collateral artery diameter compared to controls, while there was no significant effect on in vivo angiogenesis or muscle regeneration. Despite exerting no beneficial effects on angiogenesis, the inhibition of mechanosensitive miR-146a enhances perfusion recovery after FAL via enhanced arteriogenesis.

Branched DNA nanostructures efficiently stabilised and monitored by novel pyrene-perylene 2'-α-l-amino-LNA FRET pairs

DEFF Research Database (Denmark)

Astakhova, I Kira; Santhosh Kumar, T; Campbell, Meghan A

2013-01-01

Novel pyrene-perylene α-l-LNA FRET pairs described herein effectively detect assembly of 2- and 3-way branched DNA nanostructures prepared by postsynthetic microwave-assisted CuAAC click chemistry. The fluorescent signalling of assembly by internally positioned FRET pairs is achieved with low...

Design of a low-power 433/915-MHz RF front-end with a current-reuse common-gate LNA

International Nuclear Information System (INIS)

Jing Yiou; Lu Huaxiang

2013-01-01

This paper presents a wideband RF front-end with novel current-reuse wide band low noise amplifier (LNA), current-reuse V—I converter, active double balanced mixer and transimpedance amplifier for short range device (SRD) applications. With the proposed current-reuse LNA, the DC consumption of the front-end reduces considerably while maintaining sufficient performance needed by SRD devices. The RF front-end was fabricated in 0.18 μm RFCMOS process and occupies a silicon area of just 0.11 mm 2 . Operating in 433 MHz band, the measurement results show the RF front-end achieves a conversion gain of 29.7 dB, a double side band noise figure of 9.7 dB, an input referenced third intercept point of −24.9 dBm with only 1.44 mA power consumption from 1.8 V supply. Compared to other reported front-ends, it has an advantage in power consumption. (semiconductor integrated circuits)

49 CFR 236.330 - Locking dog of switch-and-lock movement.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Locking dog of switch-and-lock movement. 236.330 Section 236.330 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD... Rules and Instructions § 236.330 Locking dog of switch-and-lock movement. Locking dog of switch-and-lock...

Heterotrophic bacterial responses to the winter–spring phytoplankton bloom in open waters of the NW Mediterranean

KAUST Repository

Gomes, Ana; Gasol, Josep M.; Estrada, Marta; Franco-Vidal, Leticia; Dí az-Pé rez, Laura; Ferrera, Isabel; Moran, Xose Anxelu G.

2014-01-01

and bacterioplankton biomass and production were complemented with an insight into bacterial physiological structure by single-cell analysis of nucleic acid content [low (LNA) vs. high (HNA)] and membrane integrity (“Live” vs. “Dead” cells). Bacterial production

Portable nucleic acid thermocyclers.

Science.gov (United States)

Almassian, David R; Cockrell, Lisa M; Nelson, William M

2013-11-21

A nucleic acid thermal cycler is considered to be portable if it is under ten pounds, easily carried by one individual, and battery powered. Nucleic acid amplification includes both polymerase chain reaction (e.g. PCR, RT-PCR) and isothermal amplification (e.g. RPA, HDA, LAMP, NASBA, RCA, ICAN, SMART, SDA). There are valuable applications for portable nucleic acid thermocyclers in fields that include clinical diagnostics, biothreat detection, and veterinary testing. A system that is portable allows for the distributed detection of targets at the point of care and a reduction of the time from sample to answer. The designer of a portable nucleic acid thermocycler must carefully consider both thermal control and the detection of amplification. In addition to thermal control and detection, the designer may consider the integration of a sample preparation subsystem with the nucleic acid thermocycler. There are a variety of technologies that can achieve accurate thermal control and the detection of nucleic acid amplification. Important evaluation criteria for each technology include maturity, power requirements, cost, sensitivity, speed, and manufacturability. Ultimately the needs of a particular market will lead to user requirements that drive the decision between available technologies.

High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients

DEFF Research Database (Denmark)

Nielsen, Boye Schnack; Jørgensen, Stine; Fog, Jacob Ulrik

2011-01-01

Approximately 25% of all patients with stage II colorectal cancer will experience recurrent disease and subsequently die within 5 years. MicroRNA-21 (miR-21) is upregulated in several cancer types and has been associated with survival in colon cancer. In the present study we developed a robust...... in situ hybridization assay using high-affinity Locked Nucleic Acid (LNA) probes that specifically detect miR-21 in formalin-fixed paraffin embedded (FFPE) tissue samples. The expression of miR-21 was analyzed by in situ hybridization on 130 stage II colon and 67 stage II rectal cancer specimens. The mi...... relative to the nuclear density (TBR) obtained using a red nuclear stain. High TBR (and TB) estimates of miR-21 expression correlated significantly with shorter disease-free survival (p = 0.004, HR = 1.28, 95% CI: 1.06-1.55) in the stage II colon cancer patient group, whereas no significant correlation...

Peptide Nucleic Acids

DEFF Research Database (Denmark)

2003-01-01

A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

Peptide Nucleic Acids

DEFF Research Database (Denmark)

1998-01-01

A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

Peptide Nucleic Acids

DEFF Research Database (Denmark)

2004-01-01

A novel class of compounds known as peptide nucleic acids, bind complementary DNA and RNA strands, and generally do so more strongly than the corresponding DNA or RNA strands while exhibiting increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from...

Effect of Native Gastric Mucus on in vivo Hybridization Therapies Directed at Helicobacter pylori

DEFF Research Database (Denmark)

Santos, Rita S; Dakwar, George R; Xiong, Ranhua

2015-01-01

Helicobacter pylori infects more than 50% of the worldwide population. It is mostly found deep in the gastric mucus lining of the stomach, being a major cause of peptic ulcers and gastric adenocarcinoma. To face the increasing resistance of H. pylori to antibiotics, antimicrobial nucleic acid...... barriers-the highly viscoelastic gastric mucus and the bacterial cell envelope. We found that LNA/2'OMe is capable of diffusing rapidly through native, undiluted, gastric mucus isolated from porcine stomachs, without degradation. Moreover, although LNA/2'OMe hybridization was still successful without...

Double-Stranded Peptide Nucleic Acids

DEFF Research Database (Denmark)

2001-01-01

A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.......A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

Molecular Structure of Nucleic Acids

Indian Academy of Sciences (India)

Molecular Structure of Nucleic Acids. A Structure for Deoxyribose Nucleic Acid. J. D. Watson and F. H. C. Crick. Medical Research Council Unit for the Study of the Molecular Structure of Biological. Systems, Cavendish Laboratory, Cambridge. April 2. We wish to suggest a structure for the salt of deoxyribose nucleic acid ...

Quantitative thermodynamic predication of interactions between nucleic acid and non-nucleic acid species using Microsoft excel.

Science.gov (United States)

Zou, Jiaqi; Li, Na

2013-09-01

Proper design of nucleic acid sequences is crucial for many applications. We have previously established a thermodynamics-based quantitative model to help design aptamer-based nucleic acid probes by predicting equilibrium concentrations of all interacting species. To facilitate customization of this thermodynamic model for different applications, here we present a generic and easy-to-use platform to implement the algorithm of the model with Microsoft(®) Excel formulas and VBA (Visual Basic for Applications) macros. Two Excel spreadsheets have been developed: one for the applications involving only nucleic acid species, the other for the applications involving both nucleic acid and non-nucleic acid species. The spreadsheets take the nucleic acid sequences and the initial concentrations of all species as input, guide the user to retrieve the necessary thermodynamic constants, and finally calculate equilibrium concentrations for all species in various bound and unbound conformations. The validity of both spreadsheets has been verified by comparing the modeling results with the experimental results on nucleic acid sequences reported in the literature. This Excel-based platform described here will allow biomedical researchers to rationalize the sequence design of nucleic acid probes using the thermodynamics-based modeling even without relevant theoretical and computational skills. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

An automatic mode-locked system for passively mode-locked fiber laser

Science.gov (United States)

Li, Sha; Xu, Jun; Chen, Guoliang; Mei, Li; Yi, Bo

2013-12-01

This paper designs and implements one kind of automatic mode-locked system. It can adjust a passively mode-locked fiber laser to keep steady mode-locked states automatically. So the unsteadiness of traditional passively mode-locked fiber laser can be avoided. The system transforms optical signals into electrical pulse signals and sends them into MCU after processing. MCU calculates the frequency of the signals and judges the state of the output based on a quick judgment algorithm. A high-speed comparator is used to check the signals and the comparison voltage can be adjusted to improve the measuring accuracy. Then by controlling two polarization controllers at an angle of 45degrees to each other, MCU extrudes the optical fibers to change the polarization until it gets proper mode-locked output. So the system can continuously monitor the output signal and get it back to mode-locked states quickly and automatically. States of the system can be displayed on the LCD and PC. The parameters of the steady mode-locked states can be stored into an EEPROM so that the system will get into mode-locked states immediately next time. Actual experiments showed that, for a 6.238MHz passively mode-locked fiber lasers, the system can get into steady mode-locked states automatically in less than 90s after starting the system. The expected lock time can be reduced to less than 20s after follow up improvements.

Cleaving Double-Stranded DNA with Peptide Nucleic Acids

DEFF Research Database (Denmark)

1997-01-01

Peptide nucleic acids and analogues of peptide nucleic acids are used to form duplex, triplex, and other structures with nucleic acids and to modify nucleic acids. The peptide nucleic acids and analogues thereof also are used to modulate protein activity through, for example, transcription arrest......, transcription initiation, and site specific cleavage of nucleic acids....

Identifying a base in a nucleic acid

Science.gov (United States)

Fodor, Stephen P. A.; Lipshutz, Robert J.; Huang, Xiaohua

2005-02-08

Devices and techniques for hybridization of nucleic acids and for determining the sequence of nucleic acids. Arrays of nucleic acids are formed by techniques, preferably high resolution, light-directed techniques. Positions of hybridization of a target nucleic acid are determined by, e.g., epifluorescence microscopy. Devices and techniques are proposed to determine the sequence of a target nucleic acid more efficiently and more quickly through such synthesis and detection techniques.

Peptide Nucleic Acids (PNA)

DEFF Research Database (Denmark)

2002-01-01

A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

Peptide Nucleic Acid Synthons

DEFF Research Database (Denmark)

2004-01-01

A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

Interband optical pulse injection locking of quantum dot mode-locked semiconductor laser.

Science.gov (United States)

Kim, Jimyung; Delfyett, Peter J

2008-07-21

We experimentally demonstrate optical clock recovery from quantum dot mode-locked semiconductor lasers by interband optical pulse injection locking. The passively mode-locked slave laser oscillating on the ground state or the first excited state transition is locked through the injection of optical pulses generated via the opposite transition bands, i.e. the first excited state or the ground state transition from the hybridly mode-locked master laser, respectively. When an optical pulse train generated via the first excited state from the master laser is injected to the slave laser oscillating via ground state, the slave laser shows an asymmetric locking bandwidth around the nominal repetition rate of the slave laser. In the reverse injection case of, i.e. the ground state (master laser) to the first excited state (slave laser), the slave laser does not lock even though both lasers oscillate at the same cavity frequency. In this case, the slave laser only locks to higher injection rates as compared to its own nominal repetition rate, and also shows a large locking bandwidth of 6.7 MHz.

Double pass locking and spatial mode locking for gravitational wave detectors

CERN Document Server

Cusack, B J; Slagmolen, B; Vine, G D; Gray, M B; McClelland, D E

2002-01-01

We present novel techniques for overcoming problems relating to the use of high-power lasers in mode cleaner cavities for second generation laser interferometric gravitational wave detectors. Rearranging the optical components into a double pass locking regime can help to protect locking detectors from damage. Modulator thermal lensing can be avoided by using a modulation-free technique such as tilt locking, or its recently developed cousin, flip locking.

Hydrogel-Assisted Antisense LNA Gapmer Delivery for In Situ Gene Silencing in Spinal Cord Injury

DEFF Research Database (Denmark)

Moreno, Pedro M.D.; Ferreira, Ana R.; Salvador, Daniela

2018-01-01

)-modified AON gapmers in combination with a fibrin hydrogel bridging material to induce gene silencing in situ at a SCI lesion site. LNA gapmers were effectively developed against two promising gene targets aiming at enhancing axonal regeneration—RhoA and GSK3β. The fibrin-matrix-assisted AON delivery system......After spinal cord injury (SCI), nerve regeneration is severely hampered due to the establishment of a highly inhibitory microenvironment at the injury site, through the contribution of multiple factors. The potential of antisense oligonucleotides (AONs) to modify gene expression at different levels...

Automatic NMR field-frequency lock-pulsed phase locked loop approach.

Science.gov (United States)

Kan, S; Gonord, P; Fan, M; Sauzade, M; Courtieu, J

1978-06-01

A self-contained deuterium frequency-field lock scheme for a high-resolution NMR spectrometer is described. It is based on phase locked loop techniques in which the free induction decay signal behaves as a voltage-controlled oscillator. By pulsing the spins at an offset frequency of a few hundred hertz and using a digital phase-frequency discriminator this method not only eliminates the usual phase, rf power, offset adjustments needed in conventional lock systems but also possesses the automatic pull-in characteristics that dispense with the use of field sweeps to locate the NMR line prior to closure of the lock loop.

Histidine-Containing Peptide Nucleic Acids

DEFF Research Database (Denmark)

2000-01-01

Peptide nucleic acids containing histidine moieties are provided. These compounds have applications including diagnostics, research and potential therapeutics.......Peptide nucleic acids containing histidine moieties are provided. These compounds have applications including diagnostics, research and potential therapeutics....

Locke and botany.

Science.gov (United States)

Anstey, Peter R; Harris, Stephen A

2006-06-01

This paper argues that the English philosopher John Locke, who has normally been thought to have had only an amateurish interest in botany, was far more involved in the botanical science of his day than has previously been known. Through the presentation of new evidence deriving from Locke's own herbarium, his manuscript notes, journal and correspondence, it is established that Locke made a modest contribution to early modern botany. It is shown that Locke had close and ongoing relations with the Bobarts, keepers of the Oxford Botanic Garden, and that Locke distributed seeds and plant parts to other botanists, seeds of which the progeny almost certainly ended up in the most important herbaria of the period. Furthermore, it is claimed that the depth of Locke's interest in and practice of botany has a direct bearing on our understanding of his views on the correct method of natural philosophy and on the interpretation of his well known discussion of the nature of species in Book III of his Essay concerning human understanding.

Analysis of Human TAAR8 and Murine Taar8b Mediated Signaling Pathways and Expression Profile

Directory of Open Access Journals (Sweden)

Jessica Mühlhaus

2014-11-01

Full Text Available The thyroid hormone derivative 3-iodothyronamine (3-T1AM exerts metabolic effects in vivo that contradict known effects of thyroid hormones. 3-T1AM acts as a trace amine-associated receptor 1 (TAAR1 agonist and activates Gs signaling in vitro. Interestingly, 3-T1AM-meditated in vivo effects persist in Taar1 knockout-mice indicating that further targets of 3-T1AM might exist. Here, we investigated another member of the TAAR family, the only scarcely studied mouse and human trace-amine-associated receptor 8 (Taar8b, TAAR8. By RT-qPCR and locked-nucleic-acid (LNA in situ hybridization, Taar8b expression in different mouse tissues was analyzed. Functionally, we characterized TAAR8 and Taar8b with regard to cell surface expression and signaling via different G-protein-mediated pathways. Cell surface expression was verified by ELISA, and cAMP accumulation was quantified by AlphaScreen for detection of Gs and/or Gi/o signaling. Activation of G-proteins Gq/11 and G12/13 was analyzed by reporter gene assays. Expression analyses revealed at most marginal Taar8b expression and no gender differences for almost all analyzed tissues. In heart, LNA-in situ hybridization demonstrated the absence of Taar8b expression. We could not identify 3-T1AM as a ligand for TAAR8 and Taar8b, but both receptors were characterized by a basal Gi/o signaling activity, a so far unknown signaling pathway for TAARs.

Synergy of Two Highly Specific Biomolecular Recognition Events

DEFF Research Database (Denmark)

Ejlersen, Maria; Christensen, Niels Johan; Sørensen, Kasper K

2018-01-01

Two highly specific biomolecular recognition events, nucleic acid duplex hybridization and DNA-peptide recognition in the minor groove, were coalesced in a miniature ensemble for the first time by covalently attaching a natural AT-hook peptide motif to nucleic acid duplexes via a 2'-amino......-LNA scaffold. A combination of molecular dynamics simulations and ultraviolet thermal denaturation studies revealed high sequence-specific affinity of the peptide-oligonucleotide conjugates (POCs) when binding to complementary DNA strands, leveraging the bioinformation encrypted in the minor groove of DNA...

Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver

DEFF Research Database (Denmark)

Elmen, Joachim; Lindow, Morten; Silahtaroglu, Asli

2008-01-01

’end of miR-122 leads to specific, dose-dependent silencing of miR-122 and shows no hepatotoxicity in mice. Antagonism of miR-122 is due to formation of stable heteroduplexes between the LNA-antimiR and miR-122 as detected by northern analysis. Fluorescence in situ hybridization demonstrated uptake...... of the LNA-antimiR in mouse liver cells, which was accompanied by markedly reduced hybridization signals for mature miR-122 in treated mice. Functional antagonism of miR-122 was inferred from a low cholesterol phenotype and derepression within 24 h of 199 liver mRNAs showing significant enrichment for mi...

miR-221 stimulates breast cancer cells and cancer-associated fibroblasts (CAFs) through selective interference with the A20/c-Rel/CTGF signaling.

Science.gov (United States)

Santolla, Maria Francesca; Lappano, Rosamaria; Cirillo, Francesca; Rigiracciolo, Damiano Cosimo; Sebastiani, Anna; Abonante, Sergio; Tassone, Pierfrancesco; Tagliaferri, Pierosandro; Di Martino, Maria Teresa; Maggiolini, Marcello; Vivacqua, Adele

2018-05-02

MicroRNA (miRNAs) are non-coding small RNA molecules that regulate gene expression by inhibiting the translation of target mRNAs. Among several dysregulated miRNAs in human cancer, the up-regulation of miR-221 has been associated with development of a variety of hematologic and solid malignancies. In this study, we investigated the involvement of miR-221 in breast cancer. TaqMan microRNA assay was used to detect the miR-221 levels in normal cells and in MDA-MB 231 and SkBr3 breast cancer cells as well as in main players of the tumor microenvironment, namely cancer-associated fibroblasts (CAFs). miR-221 mimic sequence and locked nucleic acid (LNA)-i-miR-221 construct were used to induce or inhibit, respectively, the miR-221 expression in cells used. Quantitative PCR and western blotting analysis were performed to evaluate the levels of the miR-221 target gene A20 (TNFAIP3), as well as the member of the NF-kB complex namely c-Rel and the connective tissue growth factor (CTGF). Chromatin immunoprecipitation (ChIP) assay was performed to ascertain the recruitment of c-Rel to the CTFG promoter. Finally, the cell growth and migration in the presence of LNA-i-miR-221 or silencing c-Rel and CTGF by specific short hairpin were assessed by cell count, colony formation and boyden chambers assays. Statistical analysis was performed by ANOVA. We first demonstrated that LNA-i-miR-221 inhibits both endogenous and ectopic expression of miR-221 in our experimental models. Next, we found that the A20 down-regulation, as well as the up-regulation of c-Rel induced by miR-221 were no longer evident using LNA-i-miR-221. Moreover, we established that the miR-221 dependent recruitment of c-Rel to the NF-kB binding site located within the CTGF promoter region is prevented by using LNA-i-miR-221. Furthermore, we determined that the up-regulation of CTGF mRNA and protein levels by miR-221 is no longer evident using LNA-i-miR221 and silencing c-Rel. Finally, we assessed that cell growth and

Innovation and Lock-in

DEFF Research Database (Denmark)

Cantner, Uwe; Vannuccini, Simone

2016-01-01

This study focuses on a well-known but yet elusive concept: (technological) lock-in. We summarize what is known about the nature of lock-in and offer a critical view on history-dependent processes based on recent contributions to the literature. We discuss if lock-ins are really inescapable......, especially when innovation is concerned. Also, we address the question if lock-in is a well-defined concept at all. To offer a fresh view on lock-in and to tackle the issues just raised, we employ the replicator dynamics model. By making a parallel between monopolization in the replicator dynamics...... and the occurrence of lock-ins, we show that the convergence of a system to a given outcome can be reversed, under certain conditions. We highlight the need for a more precise demarcation of the conceptual boundaries of lock-in and path dependence, both from the formal and the empirical side, and suggest...

Comparing the Overhead of Lock-based and Lock-free Implementations of Priority Queues

DEFF Research Database (Denmark)

Passas, Stavros; Karlsson, Sven

2011-01-01

. In this paper, we compare a lock-free implementation of a priority queue with a lock-based implementation. We perform experiments with processors of different generations and observe large performance differences for lock-free data structures depending on the processor generation. The lock-free implementation...... performs much better on the most recent processor generation. We investigate this performance trend, using a set of micro-benchmarks and show a significant difference in the overhead of atomic operations between processor generations. The lock-free implementation executes approximately three times as many...

Outdraft at Lock Approach, Tom Bevill Lock and Dam, Alabama: Hydraulic Model Investigation

National Research Council Canada - National Science Library

Lynch, Gary

2001-01-01

.... The lock is connected to the dam with a 150-ft abutment wall. A strong crosscurrent or outdraft existing in and around the upstream lock entrance causes difficulty for tow traffic navigating the lock...

Use of Nucleic Acid Analogs for the Study of Nucleic Acid Interactions

Directory of Open Access Journals (Sweden)

Shu-ichi Nakano

2011-01-01

Full Text Available Unnatural nucleosides have been explored to expand the properties and the applications of oligonucleotides. This paper briefly summarizes nucleic acid analogs in which the base is modified or replaced by an unnatural stacking group for the study of nucleic acid interactions. We also describe the nucleoside analogs of a base pair-mimic structure that we have examined. Although the base pair-mimic nucleosides possess a simplified stacking moiety of a phenyl or naphthyl group, they can be used as a structural analog of Watson-Crick base pairs. Remarkably, they can adopt two different conformations responding to their interaction energies, and one of them is the stacking conformation of the nonpolar aromatic group causing the site-selective flipping of the opposite base in a DNA double helix. The base pair-mimic nucleosides can be used to study the mechanism responsible for the base stacking and the flipping of bases out of a nucleic acid duplex.

49 CFR 236.338 - Mechanical locking required in accordance with locking sheet and dog chart.

Science.gov (United States)

2010-10-01

... locking sheet and dog chart. 236.338 Section 236.338 Transportation Other Regulations Relating to... in accordance with locking sheet and dog chart. Mechanical locking shall be in accordance with locking sheet and dog chart currently in effect. ...

Method of Identifying a Base in a Nucleic Acid

Science.gov (United States)

Fodor, Stephen P. A.; Lipshutz, Robert J.; Huang, Xiaohua

1999-01-01

Devices and techniques for hybridization of nucleic acids and for determining the sequence of nucleic acids. Arrays of nucleic acids are formed by techniques, preferably high resolution, light-directed techniques. Positions of hybridization of a target nucleic acid are determined by, e.g., epifluorescence microscopy. Devices and techniques are proposed to determine the sequence of a target nucleic acid more efficiently and more quickly through such synthesis and detection techniques.

Detection of nucleic acid sequences by invader-directed cleavage

Science.gov (United States)

Brow, Mary Ann D.; Hall, Jeff Steven Grotelueschen; Lyamichev, Victor; Olive, David Michael; Prudent, James Robert

1999-01-01

The present invention relates to means for the detection and characterization of nucleic acid sequences, as well as variations in nucleic acid sequences. The present invention also relates to methods for forming a nucleic acid cleavage structure on a target sequence and cleaving the nucleic acid cleavage structure in a site-specific manner. The 5' nuclease activity of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof. The present invention further relates to methods and devices for the separation of nucleic acid molecules based by charge.

Air lock

International Nuclear Information System (INIS)

Palkovich, P.; Gruber, J.; Madlener, W.

1974-01-01

The patent refers to an air lock system preferably for nuclear stations for the transport of heavy loads by means of a trolley on rails. For opening and closing of the air lock parts of the rails are removed, e.g. by a second rail system perpendicular to the main rails. (P.K.)

POLARIMETRIA ÓPTICA E MODELAGEM DE POLARES OBSERVADAS NO OPD/LNA NO PERÍODO DE 2010-2012

Directory of Open Access Journals (Sweden)

Karleyne M. G. Silva Silva

2013-12-01

Full Text Available Neste trabalho apresentamos os primeiros resultados do estudo de uma nova amostra de 7candidatas a polares a partir de dados polarimétricos obtidos no observatório do Pico dos Dias / LNA. Dos 4objetos analisados até o momento, confirmamos a presença de polarização alta e variável em 3, o que indica apresença de emissão ciclotrônica e sua classificação como polares. Esses dados serão modelados utilizando-seo código CYCLOPS.

POLARIMETRIA ÓPTICA E MODELAGEM DE POLARES OBSERVADAS NO OPD/LNA NO PERÍODO DE 2010-2012

OpenAIRE

Silva, Karleyne M. G. Silva; Divisão de Astrofísica - Instituto Nacional de Pesquisas Espacias - INPE; Rodrigues, Cláudia V.; INPE; Costa, Joaquim E. R.; INPE; Cieslinski, Deonísio; INPE; Almeida, Leonardo A.; INPE; Magalhães, Victor S.; INPE

2013-01-01

Neste trabalho apresentamos os primeiros resultados do estudo de uma nova amostra de 7candidatas a polares a partir de dados polarimétricos obtidos no observatório do Pico dos Dias / LNA. Dos 4objetos analisados até o momento, confirmamos a presença de polarização alta e variável em 3, o que indica apresença de emissão ciclotrônica e sua classificação como polares. Esses dados serão modelados utilizando-seo código CYCLOPS.

Quantum noise locking

International Nuclear Information System (INIS)

McKenzie, Kirk; Mikhailov, Eugeniy E; Goda, Keisuke; Lam, Ping Koy; Grosse, Nicolai; Gray, Malcolm B; Mavalvala, Nergis; McClelland, David E

2005-01-01

Quantum optical states which have no coherent amplitude, such as squeezed vacuum states, cannot rely on standard readout techniques to generate error signals for control of the quadrature phase. Here we investigate the use of asymmetry in the quadrature variances to obtain a phase-sensitive readout and to lock the phase of a squeezed vacuum state, a technique which we call noise locking (NL). We carry out a theoretical derivation of the NL error signal and the associated stability of the squeezed and anti-squeezed lock points. Experimental data for the NL technique both in the presence and absence of coherent fields are shown, including a comparison with coherent locking techniques. Finally, we use NL to enable a stable readout of the squeezed vacuum state on a homodyne detector

''Old'' locked inflation

International Nuclear Information System (INIS)

Liu, Yang; Piao, Yun-Song; Si, Zong-Guo

2009-01-01

In this paper, we revisit the idea of locked inflation, which does not require a potential satisfying the normal slow-roll condition, but suffers from the problems associated with ''saddle inflation''. We propose a scenario based on locked inflation, however, with an alternative evolution mechanism of the ''waterfall field'' φ. Instead of rolling down along the potential, the φ field will tunnel to end the inflation stage like in old inflation, by which the saddle inflation could be avoided. Further, we study a cascade of old locked inflation, which can be motivated by the string landscape. Our model is based on the consideration of making locked inflation feasible so as to give a working model without slow roll; It also can be seen as an effort to embed the old inflation in string landscape

Frequency-Locked Detector Threshold Setting Criteria Based on Mean-Time-To-Lose-Lock (MTLL) for GPS Receivers.

Science.gov (United States)

Jin, Tian; Yuan, Heliang; Zhao, Na; Qin, Honglei; Sun, Kewen; Ji, Yuanfa

2017-12-04

Frequency-locked detector (FLD) has been widely utilized in tracking loops of Global Positioning System (GPS) receivers to indicate their locking status. The relation between FLD and lock status has been seldom discussed. The traditional PLL experience is not suitable for FLL. In this paper, the threshold setting criteria for frequency-locked detector in the GPS receiver has been proposed by analyzing statistical characteristic of FLD output. The approximate probability distribution of frequency-locked detector is theoretically derived by using a statistical approach, which reveals the relationship between probabilities of frequency-locked detector and the carrier-to-noise ratio ( C / N ₀) of the received GPS signal. The relationship among mean-time-to-lose-lock (MTLL), detection threshold and lock probability related to C / N ₀ can be further discovered by utilizing this probability. Therefore, a theoretical basis for threshold setting criteria in frequency locked loops for GPS receivers is provided based on mean-time-to-lose-lock analysis.

Synthetic Procedures for Peptide Nucleic Acids

DEFF Research Database (Denmark)

2004-01-01

A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

49 CFR 236.766 - Locking, movable bridge.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Locking, movable bridge. 236.766 Section 236.766... Locking, movable bridge. The rail locks, bridge locks, bolt locks, circuit controllers, and electric locks used in providing interlocking protection at a movable bridge. ...

A new allelic discrimination assay using locked nucleic acid-modified nucleotides (LNA) probes for detection of JAK2 V617F mutation

Czech Academy of Sciences Publication Activity Database

Marková, J.; Průková, Dana; Volková, Z.; Schwarz, J.

2007-01-01

Roč. 48, č. 3 (2007), s. 638-641 ISSN 1042-8194 Institutional research plan: CEZ:AV0Z50520514 Keywords : Ph1-negative myeloproliferative disorders * JAK2V617F mutation * allelic discrimination Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.512, year: 2007

Hybridization and sequencing of nucleic acids using base pair mismatches

Science.gov (United States)

Fodor, Stephen P. A.; Lipshutz, Robert J.; Huang, Xiaohua

2001-01-01

Devices and techniques for hybridization of nucleic acids and for determining the sequence of nucleic acids. Arrays of nucleic acids are formed by techniques, preferably high resolution, light-directed techniques. Positions of hybridization of a target nucleic acid are determined by, e.g., epifluorescence microscopy. Devices and techniques are proposed to determine the sequence of a target nucleic acid more efficiently and more quickly through such synthesis and detection techniques.

Probe kit for identifying a base in a nucleic acid

Science.gov (United States)

Fodor, Stephen P. A.; Lipshutz, Robert J.; Huang, Xiaohua

2001-01-01

Devices and techniques for hybridization of nucleic acids and for determining the sequence of nucleic acids. Arrays of nucleic acids are formed by techniques, preferably high resolution, light-directed techniques. Positions of hybridization of a target nucleic acid are determined by, e.g., epifluorescence microscopy. Devices and techniques are proposed to determine the sequence of a target nucleic acid more efficiently and more quickly through such synthesis and detection techniques.

Multiplexed microfluidic approach for nucleic acid enrichment

Science.gov (United States)

VanderNoot, Victoria A.; Langevin, Stanley Alan; Bent, Zachary; Renzi, Ronald F.; Ferko, Scott M.; Van De Vreugde, James L.; Lane, Todd; Patel, Kamlesh; Branda, Steven

2016-04-26

A system for enhancing a nucleic acid sample may include a one pump, a denaturing chamber; a microfluidic hydroxyapatite chromatography device configured for performing hydroxyapatite chromatography on the nucleic acid sample, a sample collector, and tubing connecting the pump with the denaturing chamber, the hydroxyapatite chromatography device and the sample collector such that the pump may be used to move the nucleic acid sample from the denaturing chamber to the hydroxyapatite chromatography device and then to the sample collector.

Research of mechanism of density lock

International Nuclear Information System (INIS)

Wang Shengfei; Yan Changqi; Gu Haifeng

2010-01-01

Mechanism of density lock was analyzed according to the work conditions of density lock. The results showed that: the stratification with no disturbance satisfied the work conditions of density lock; fluids between the stratification were not mixed at the condition of connected to each other; the density lock can be open automatically by controlled the pressure balance at the stratification. When disturbance existed, the stratification might be broken and mass would be transferred by convection. The stability of stratification can be enhanced by put the special structure in density lock to ensure the normal work of density lock. At last, the minimum of heat loss in density lock was also analyzed. (authors)

A sensitive detection method for MPLW515L or MPLW515K mutation in chronic myeloproliferative disorders with locked nucleic acid-modified probes and real-time polymerase chain reaction.

Science.gov (United States)

Pancrazzi, Alessandro; Guglielmelli, Paola; Ponziani, Vanessa; Bergamaschi, Gaetano; Bosi, Alberto; Barosi, Giovanni; Vannucchi, Alessandro M

2008-09-01

Acquired mutations in the juxtamembrane region of MPL (W515K or W515L), the receptor for thrombopoietin, have been described in patients with primary myelofibrosis or essential thrombocythemia, which are chronic myeloproliferative disorders. We have developed a real-time polymerase chain reaction assay for the detection and quantification of MPL mutations that is based on locked nucleic acid fluorescent probes. Mutational analysis was performed using DNA from granulocytes. Reference curves were obtained using cloned fragments of MPL containing either the wild-type or mutated sequence; the predicted sensitivity level was at least 0.1% mutant allele in a wild-type background. None of the 60 control subjects presented with a MPLW515L/K mutation. Of 217 patients with myelofibrosis, 19 (8.7%) harbored the MPLW515 mutation, 10 (52.6%) with the W515L allele. In one case, both the W515L and W515K alleles were detected by real-time polymerase chain reaction. By comparing results obtained with conventional sequencing, no erroneous genotype attribution using real-time polymerase chain reaction was found, whereas one patient considered wild type according to sequence analysis actually harbored a low W515L allele burden. This is a simple, sensitive, and cost-effective procedure for large-scale screening of the MPLW515L/K mutation in patients suspected to have a myeloproliferative disorder. It can also provide a quantitative estimate of mutant allele burden that might be useful for both patient prognosis and monitoring response to therapy.

Performance of arm locking in LISA

International Nuclear Information System (INIS)

McKenzie, Kirk; Spero, Robert E.; Shaddock, Daniel A.

2009-01-01

For the Laser Interferometer Space Antenna (LISA) to reach its design sensitivity, the coupling of the free-running laser frequency noise to the signal readout must be reduced by more than 14 orders of magnitude. One technique employed to reduce the laser frequency noise will be arm locking, where the laser frequency is locked to the LISA arm length. In this paper we detail an implementation of arm locking. We investigate orbital effects (changing arm lengths and Doppler frequencies), the impact of errors in the Doppler knowledge that can cause pulling of the laser frequency, and the noise limit of arm locking. Laser frequency pulling is examined in two regimes: at lock acquisition and in steady state. The noise performance of arm locking is calculated with the inclusion of the dominant expected noise sources: ultrastable oscillator (clock) noise, spacecraft motion, and shot noise. We find that clock noise and spacecraft motion limit the performance of dual arm locking in the LISA science band. Studying these issues reveals that although dual arm locking [A. Sutton and D. A. Shaddock, Phys. Rev. D 78, 082001 (2008)] has advantages over single (or common) arm locking in terms of allowing high gain, it has disadvantages in both laser frequency pulling and noise performance. We address this by proposing a modification to the dual arm-locking sensor, a hybrid of common and dual arm-locking sensors. This modified dual arm-locking sensor has the laser frequency pulling characteristics and low-frequency noise coupling of common arm locking, but retains the control system advantages of dual arm locking. We present a detailed design of an arm-locking controller and perform an analysis of the expected performance when used with and without laser prestabilization. We observe that the sensor phase changes beneficially near unity-gain frequencies of the arm-locking controller, allowing a factor of 10 more gain than previously believed, without degrading stability. With a time

Escaping carbon lock-in

International Nuclear Information System (INIS)

Unruh, G.C.

2002-01-01

This article explores the climate policy implications of the arguments made in ''Understanding carbon lock-in'' (Unruh, 2000), which posited that industrial countries have become locked-into fossil fuel-based energy systems through path dependent processes driven by increasing returns to scale. Carbon lock-in arises through technological, organizational, social and institutional co-evolution, ''culminating'' in what was termed as techno-institutional complex (TIC). In order to resolve the climate problem, an escape from the lock-in condition is required. However, due to the self-referential nature of TIC, escape conditions are unlikely to be generated internally and it is argued here that erogenous forces are probably required. (author)

Homodyne locking of a squeezer.

Science.gov (United States)

Heurs, M; Petersen, I R; James, M R; Huntington, E H

2009-08-15

We report on the successful implementation of an approach to locking the frequencies of an optical parametric oscillator (OPO)-based squeezed-vacuum source and its driving laser. The technique allows the simultaneous measurement of the phase shifts induced by a cavity, which may be used for the purposes of frequency locking, as well as the simultaneous measurement of the sub-quantum-noise-limited (sub-QNL) phase quadrature output of the OPO. The homodyne locking technique is cheap, easy to implement, and has the distinct advantage that subsequent homodyne measurements are automatically phase locked. The homodyne locking technique is also unique in that it is a sub-QNL frequency discriminator.

49 CFR 236.765 - Locking, mechanical.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Locking, mechanical. 236.765 Section 236.765 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Locking, mechanical. An arrangement of locking bars, dogs, tappets, cross locking and other apparatus by...

Nucleic acid drugs: a novel approach

African Journals Online (AJOL)

Administrator

Nucleic acid base sequence of proteins plays a crucial role in the expression of gene. The gene is responsible for the synthesis of proteins and these proteins, which are synthesized, are responsible for the biological process and also for dreadful diseases as well. Once if the nucleic acid sequence is altered, we would be ...

Soybean phytase and nucleic acid encoding the same

OpenAIRE

1999-01-01

Isolated soybean phytase polypeptides and isolated nucleic acids encoding soybean phytases are provided. The invention is also directed to nucleic acid expression constructs, vectors, and host cells comprising the isolated soybean phytase nucleic acids, as well as methods for producing recombinant and non-recombinant purified soybean phytase. The invention also relates to transgenic plants expressing the soybean phytase, particularly expression under seed-specific expression control elements.

Protective air lock

International Nuclear Information System (INIS)

Evans, H.W.

1976-01-01

A device suitable for preventing escape and subsequent circulation of toxic gases is described. An enclosure is sealed by a surrounding air lock, and an automatic mechanism partially evacuates the enclosure and air lock. The enclosure ventilating mechanism can be disconnected so that a relatively undisturbed atmosphere is created in the enclosure

The Advanced Thread-Locking Mechanism

Science.gov (United States)

Weiss, Wolfgang

2005-12-01

Locking of threaded members is accomplished by a wide variety of engineering solutions. Generally, in terms of separate locking devices or by built-in locking features such as friction generating means.In regard of space flight vehicles, threaded joints are subject to severe vibration loads during launch, maneuvering, and reentry. This requires fastening systems which are capable to join structural members and attach accessories or equipment in a secure manner. However, manned spacecraft and especially payload components will be subject to installation activity during orbital or interstellar flight maintenance, repair, or mission modification. This, in turn, requires fast separation and engaging of the concerned fasteners, yet providing performance characteristics for high reliable and safe joints.The further described Advanced Thread Locking Mechanism (ATLM) has been developed to combine the merits of both, safe joining technique and a fast installation process. The ATLM uses a freewheel which is securely installed in one part of the threaded member and releasable coupled with the engaged counterpart. While screwing the threaded members together, once coupled, the freewheel will allow free mating of the threaded members including torquing to the desired value. The moment, the pair of threaded fasteners is forced to unscrew (by intended or unintended occurrence of torque in the undoing direction) the freewheel does lock instantly. Disengaging the coupling between the members of the threaded joint takes a separate release action.Owing to the nature of the ATLM, there are a number of design variants ready for implementation.Threaded fasteners in ATLM design are highly recommended for mechanical joints subject to fastening and unfastening during Extra Vehicular Activity (EVA) in course of space flight operations. This is justified through:1. Threaded members mate free running, thus, torque values preset at the wrenching tool are not influenced by varying prevailing

Pressure locking test results

Energy Technology Data Exchange (ETDEWEB)

DeWall, K.G.; Watkins, J.C.; McKellar, M.G.; Bramwell, D. [Idaho National Engineering Lab., Idaho Falls, ID (United States)] [and others

1996-12-01

The U.S. Nuclear Regulatory Commission (NRC), Office of Nuclear Regulatory Research, is funding the Idaho National Engineering Laboratory (INEL) in performing research to provide technical input for their use in evaluating responses to Generic Letter 95-07, {open_quotes}Pressure Locking and Thermal Binding of Safety-Related Power-Operated Gate Valves.{close_quotes} Pressure locking and thermal binding are phenomena that make a closed gate valve difficult to open. This paper discusses only the pressure locking phenomenon in a flexible-wedge gate valve; the authors will publish the results of their thermal binding research at a later date. Pressure locking can occur when operating sequences or temperature changes cause the pressure of the fluid in the bonnet (and, in most valves, between the discs) to be higher than the pressure on the upstream and downstream sides of the disc assembly. This high fluid pressure presses the discs against both seats, making the disc assembly harder to unseat than anticipated by the typical design calculations, which generally consider friction at only one of the two disc/seat interfaces. The high pressure of the bonnet fluid also changes the pressure distribution around the disc in a way that can further contribute to the unseating load. If the combined loads associated with pressure locking are very high, the actuator might not have the capacity to open the valve. The results of the NRC/INEL research discussed in this paper show that the relationship between bonnet pressure and pressure locking stem loads appears linear. The results also show that for this valve, seat leakage affects the bonnet pressurization rate when the valve is subjected to thermally induced pressure locking conditions.

Pressure locking test results

International Nuclear Information System (INIS)

DeWall, K.G.; Watkins, J.C.; McKellar, M.G.; Bramwell, D.

1996-01-01

The U.S. Nuclear Regulatory Commission (NRC), Office of Nuclear Regulatory Research, is funding the Idaho National Engineering Laboratory (INEL) in performing research to provide technical input for their use in evaluating responses to Generic Letter 95-07, open-quotes Pressure Locking and Thermal Binding of Safety-Related Power-Operated Gate Valves.close quotes Pressure locking and thermal binding are phenomena that make a closed gate valve difficult to open. This paper discusses only the pressure locking phenomenon in a flexible-wedge gate valve; we will publish the results of our thermal binding research at a later date. Pressure locking can occur when operating sequences or temperature changes cause the pressure of the fluid in the bonnet (and, in most valves, between the discs) to be higher than the pressure on the upstream and downstream sides of the disc assembly. This high fluid pressure presses the discs against both seats, making the disc assembly harder to unseat than anticipated by the typical design calculations, which generally consider friction at only one of the two disc/seat interfaces. The high pressure of the bonnet fluid also changes the pressure distribution around the disc in a way that can further contribute to the unseating load. If the combined loads associated with pressure locking are very high, the actuator might not have the capacity to open the valve. The results of the NRC/INEL research discussed in this paper show that the relationship between bonnet pressure and pressure locking stem loads appears linear. The results also show that for this valve, seat leakage affects the bonnet pressurization rate when the valve is subjected to thermally induced pressure locking conditions

PWR integral tie plate and locking mechanism

International Nuclear Information System (INIS)

Flora, B.S.; Osborne, J.L.

1980-01-01

A locking mechanism for securing an upper tie plate to the tie rods of a nuclear fuel bundle is described. The mechanism includes an upper tie plate assembly and locking sleeves fixed to the ends of the tie rods. The tie plate is part of the upper tie plate assembly and is secured to the fuel bundle by securing the entire upper tie plate assembly to the locking sleeves fixed to the tie rods. The assembly includes, in addition to the tie plate, locking nuts for engaging the locking sleeves, retaining sleeves to operably connect the locking nuts to the assembly, a spring biased reaction plate to restrain the locking nuts in the locked position and a means to facilitate the removal of the entire assembly as a unit from the fuel bundle

Safety lock for radiography exposure device

International Nuclear Information System (INIS)

Gaines, T.M.

1982-01-01

A safety lock for securing a radiation source in a radiography exposure device is disclosed. The safety lock prevents the inadvertent extension of the radiation source from the exposure device. The exposure devices are used extensively in industry for nondestructive testing of metal materials for defect. Unnecessary exposure of the radiographer or operator occurs not infrequently due to operator's error in believing that the radiation source is secured in the exposure device when, in fact, it is not. The present invention solves this problem of unnecessary exposure by releasingly trapping the radiation source in the shield of the radiography exposure device each time the source is retracted therein so that it is not inadvertently extended therefrom without the operator resetting the safety lock, thereby releasing the radiation source. Further, the safety lock includes an indicator which indicates when the source is trapped in the exposure device and also when it is untrapped. The safety lock is so designed that it does not prevent the return of the source to the trapped, shielded position in the exposure device. Further the safety lock includes a key means for locking the radiation source in the trapped position. The key means cannot be actuated until said radiation source is in said trapped position to further insure the safety lock cannot be inadvertently locked with the source untrapped and thus still extendable from the exposure device

Nucleic acid-functionalized transition metal nanosheets for biosensing applications.

Science.gov (United States)

Mo, Liuting; Li, Juan; Liu, Qiaoling; Qiu, Liping; Tan, Weihong

2017-03-15

In clinical diagnostics, as well as food and environmental safety practices, biosensors are powerful tools for monitoring biological or biochemical processes. Two-dimensional (2D) transition metal nanomaterials, including transition metal chalcogenides (TMCs) and transition metal oxides (TMOs), are receiving growing interest for their use in biosensing applications based on such unique properties as high surface area and fluorescence quenching abilities. Meanwhile, nucleic acid probes based on Watson-Crick base-pairing rules are also being widely applied in biosensing based on their excellent recognition capability. In particular, the emergence of functional nucleic acids in the 1980s, especially aptamers, has substantially extended the recognition capability of nucleic acids to various targets, ranging from small organic molecules and metal ions to proteins and cells. Based on π-π stacking interaction between transition metal nanosheets and nucleic acids, biosensing systems can be easily assembled. Therefore, the combination of 2D transition metal nanomaterials and nucleic acids brings intriguing opportunities in bioanalysis and biomedicine. In this review, we summarize recent advances of nucleic acid-functionalized transition metal nanosheets in biosensing applications. The structure and properties of 2D transition metal nanomaterials are first discussed, emphasizing the interaction between transition metal nanosheets and nucleic acids. Then, the applications of nucleic acid-functionalized transition metal nanosheet-based biosensors are discussed in the context of different signal transducing mechanisms, including optical and electrochemical approaches. Finally, we provide our perspectives on the current challenges and opportunities in this promising field. Copyright © 2016 Elsevier B.V. All rights reserved.

Nucleic Acid-Based Nanoconstructs

Science.gov (United States)

Focuses on the design, synthesis, characterization, and development of spherical nucleic acid constructs as effective nanotherapeutic, single-entity agents for the treatment of glioblastoma multiforme and prostate cancers.

Globalizing carbon lock-in

International Nuclear Information System (INIS)

Unruh, Gregory C.; Carrillo-Hermosilla, Javier

2006-01-01

This paper extends the arguments surrounding carbon lock-in elaborated in Unruh (Energy Policy 28 (2000) 817; 30 (2002) 317) to countries currently undergoing industrialization. It argues that, for numerous reasons, industrializing countries are unlikely to leapfrog carbon intensive energy development. On the contrary, carbon lock-in may be globalizing and could further constrain climate change mitigation options. It is then argued that many policy recommendations ignore carbon lock-in, possibly limiting their potential for successful implementation. The paper then discusses four policy approaches that appear to have advantages given lock-in conditions. It is recognized, however, that relative ease of implementation does not necessarily equate with superiority. Instead, it is merely a path dependent outcome of past development decisions. Pursuing policies on the basis of relative implementation ease may help address the issue of climate change, but could also result in sub-optimal outcomes along other dimensions of sustainable development

LOCKS AND KEYS SERVICE

CERN Multimedia

Locks and Keys Service

2002-01-01

The Locks and Keys service (ST/FM) will move from building 55 to building 570 from the 2nd August to the 9th August 2002 included. During this period the service will be closed. Only in case of extreme urgency please call the 164550. Starting from Monday, 12th August, the Locks and Keys Service will continue to follow the activities related to office keys (keys and locks) and will provide the keys for furniture. The service is open from 8h30 to 12h00 and from 13h00 to 17h30. We remind you that your divisional correspondents can help you in the execution of the procedures. We thank you for your comprehension and we remain at your service to help you in solving all the matters related to keys for offices and furniture. Locks and Keys Service - ST Division - FM Group

Single-stranded nucleic acids promote SAMHD1 complex formation.

Science.gov (United States)

Tüngler, Victoria; Staroske, Wolfgang; Kind, Barbara; Dobrick, Manuela; Kretschmer, Stefanie; Schmidt, Franziska; Krug, Claudia; Lorenz, Mike; Chara, Osvaldo; Schwille, Petra; Lee-Kirsch, Min Ae

2013-06-01

SAM domain and HD domain-containing protein 1 (SAMHD1) is a dGTP-dependent triphosphohydrolase that degrades deoxyribonucleoside triphosphates (dNTPs) thereby limiting the intracellular dNTP pool. Mutations in SAMHD1 cause Aicardi-Goutières syndrome (AGS), an inflammatory encephalopathy that mimics congenital viral infection and that phenotypically overlaps with the autoimmune disease systemic lupus erythematosus. Both disorders are characterized by activation of the antiviral cytokine interferon-α initiated by immune recognition of self nucleic acids. Here we provide first direct evidence that SAMHD1 associates with endogenous nucleic acids in situ. Using fluorescence cross-correlation spectroscopy, we demonstrate that SAMHD1 specifically interacts with ssRNA and ssDNA and establish that nucleic acid-binding and formation of SAMHD1 complexes are mutually dependent. Interaction with nucleic acids and complex formation do not require the SAM domain, but are dependent on the HD domain and the C-terminal region of SAMHD1. We finally demonstrate that mutations associated with AGS exhibit both impaired nucleic acid-binding and complex formation implicating that interaction with nucleic acids is an integral aspect of SAMHD1 function.

49 CFR 236.761 - Locking, electric.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Locking, electric. 236.761 Section 236.761 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Locking, electric. The combination of one or more electric locks and controlling circuits by means of...

49 CFR 236.105 - Electric lock.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Electric lock. 236.105 Section 236.105 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION...: All Systems Inspections and Tests; All Systems § 236.105 Electric lock. Electric lock, except forced...

Assessing carbon lock-in

International Nuclear Information System (INIS)

Erickson, Peter; Kartha, Sivan; Lazarus, Michael; Tempest, Kevin

2015-01-01

The term ‘carbon lock-in’ refers to the tendency for certain carbon-intensive technological systems to persist over time, ‘locking out’ lower-carbon alternatives, and owing to a combination of linked technical, economic, and institutional factors. These technologies may be costly to build, but relatively inexpensive to operate and, over time, they reinforce political, market, and social factors that make it difficult to move away from, or ‘unlock’ them. As a result, by investing in assets prone to lock-in, planners and investors restrict future flexibility and increase the costs of achieving agreed climate protection goals. Here, we develop a straight-forward approach to assess the speed, strength, and scale of carbon lock-in for major energy-consuming assets in the power, buildings, industry, and transport sectors. We pilot the approach at the global level, finding that carbon lock-in is greatest, globally, for coal power plants, gas power plants, and oil-based vehicles. The approach can be readily applied at the national or regional scale, and may be of particular relevance to policymakers interested in enhancing flexibility in their jurisdictions for deeper emissions cuts in the future, and therefore in limiting the future costs associated with ‘stranded assets’. (letter)

Phase-locked Josephson soliton oscillators

DEFF Research Database (Denmark)

Holst, T.; Hansen, Jørn Bindslev; Grønbech-Jensen, N.

1991-01-01

Detailed experimental characterization of the phase-locking at both DC and at microwave frequencies is presented for two closely spaced Josephson soliton (fluxon) oscillators. In the phase-locked state, the radiated microwave power exhibited an effective gain. With one common bias source......, a frequency tunability of the phase-locked oscillators up to 7% at 10 GHz was observed. The interacting soliton oscillators were modeled by two inductively coupled nonlinear transmission lines...

Dissecting the hybridization of oligonucleotides to structured complementary sequences.

Science.gov (United States)

Peracchi, Alessio

2016-06-01

When oligonucleotides hybridize to long target molecules, the process is slowed by the secondary structure in the targets. The phenomenon has been analyzed in several previous studies, but many details remain poorly understood. I used a spectrofluorometric strategy, focusing on the formation/breaking of individual base pairs, to study the kinetics of association between a DNA hairpin and >20 complementary oligonucleotides ('antisenses'). Hybridization rates differed by over three orders of magnitude. Association was toehold-mediated, both for antisenses binding to the target's ends and for those designed to interact with the loop. Binding of these latter, besides being consistently slower, was affected to variable, non-uniform extents by the asymmetric loop structure. Divalent metal ions accelerated hybridization, more pronouncedly when nucleation occurred at the loop. Incorporation of locked nucleic acid (LNA) residues in the antisenses substantially improved the kinetics only when LNAs participated to the earliest hybridization steps. The effects of individual LNAs placed along the antisense indicated that the reaction transition state occurred after invading at least the first base pair of the stem. The experimental approach helps dissect hybridization reactions involving structured nucleic acids. Toehold-dependent, nucleation-invasion models appear fully appropriate for describing such reactions. Estimating the stability of nucleation complexes formed at internal toeholds is the major hurdle for the quantitative prediction of hybridization rates. While analyzing the mechanisms of a fundamental biochemical process (hybridization), this work also provides suggestions for the improvement of technologies that rely on such process. Copyright © 2016 Elsevier B.V. All rights reserved.

Accelerated digestion of nucleic acids by pepsin from the stomach of chicken.

Science.gov (United States)

Liu, Y; Zhang, Y; Guo, H; Wu, W; Dong, P; Liang, X

2016-10-01

Nucleic acids have become an important nutritional supplement in poultry feed; however, the digestion of nucleic acids in poultry is unclear. The objective of this study was to investigate the digestion of nucleic acids by chicken pepsin in vitro. The extracted pepsinogen from the stomach of the chicken was purified to homogeneity. Upon activation at pH 2.0, chicken pepsinogen was converted to its active form. Nucleic acids, including λ-DNA, salmon sperm DNA and single-strand DNA (ssDNA), can be used as substrates and digested into short-chain oligonucleotides by pepsin. Interestingly, the digestion of the nucleic acids was inhibited when pepsin was treated by alkaline solution (pH 8.0) or pepstatin A. Also, the digestion of the nucleic acids was not affected by the addition of haemoglobin or bovine serum albumin. The results suggested that nucleic acids could be digested by chicken pepsin. Thus pepsin may have a role in digesting nucleic acids in vivo. Nucleic acids added to poultry fed may be digested, starting from the stomach.

Breaking Carbon Lock-in

DEFF Research Database (Denmark)

Driscoll, Patrick Arthur

2014-01-01

This central focus of this paper is to highlight the ways in which path dependencies and increasing returns (network effects) serve to reinforce carbon lock-in in large-scale road transportation infrastructure projects. Breaking carbon lock-in requires drastic changes in the way we plan future...

Selenium Derivatization of Nucleic Acids for Phase and Structure Determination in Nucleic Acid X-ray Crystallography

Directory of Open Access Journals (Sweden)

Zhen Huang

2008-03-01

Full Text Available Selenium derivatization (via selenomethionine of proteins for crystal structure determination via MAD phasing has revolutionized protein X-ray crystallography. It is estimated that over two thirds of all new crystal structures of proteins have been determined via Se-Met derivatization. Similarly, selenium functionalities have also been successfully incorporated into nucleic acids to facilitate their structure studies and it has been proved that this Se-derivatization has advantages over halogen strategy, which was usually used as a traditional method in this field. This review reports the development of site-specific selenium derivatization of nucleic acids for phase determination since the year of 2001 (mainly focus on the 2’-position of the ribose. All the synthesis of 2’-SeMe modified phosphoramidite building blocks (U, C, T, A, G and the according oligonucleotides are included. In addition, several structures of selenium contained nucleic acid are also described in this paper.

A photovoltaic module diagnostic setup for lock-in-thermography and lock-in electroluminescence imaging

DEFF Research Database (Denmark)

Parikh, Harsh; Spataru, Sergiu; Sera, Dezso

2018-01-01

Electroluminescence (EL) imaging and infrared (IRT) thermography techniques have become indispensable tools in recent years for health diagnostic of PV modules in solar industry application. Complementary to these imaging methods, lock-in techniques can effectively remove noise by periodically...... modulating the input signal and averaging it over a desired number of periods. We propose a combined lock-in EL and lock-in IRT diagnostic setup for accurate analysis of different types of faults occurring in a solar module. The setup is built around a Goldeye CL-033 high-speed SWIR camera, which can acquire...... experimental work on a (36/72) cell solar module using combined (EL) or (IRT) lock-in-thermography. The setup allows one to investigate the different technological problems that can occur when performing PV diagnostics in drone-based inspections....

Non-enzymatic Polymerization of Nucleic Acids from Monomers

DEFF Research Database (Denmark)

Dörr, Mark; Löffler, Philipp M. G.; Monnard, Pierre-Alain

2012-01-01

synthesis of long nucleic acid polymers or to sequence-specifically amplify nucleic acid polymers, respectively. Starting from molecular requirements, details of the polymerization mechanisms and strategies are first presented and then compared. Finally, we discuss the relevance of these strategies...

Selected topics in photochemistry of nucleic acids. Recent results and perspectives

International Nuclear Information System (INIS)

Loeber, G.; Kittler, L.

1977-01-01

Recent results on the following photoreactions of nucleic acids are reported: photochemistry of aza-bases and minor bases, formation of photoproducts of the non-cyclobutane type, formations of furocoumarin-pyrimidine photoadducts, fluorescence of dye-nucleic acid complexes and their role in chromosomal fluorescence staining, and mechanisms of the photochemical reaction. Results are discussed with respect to: (i) photobiological relevance of light-induced defects in nucleic acids; (ii) possibilities of achieving higher selectivity of light-induced defects in nucleic acids; (iii) the use of nucleic acid photochemistry to analyze genetic material. An extensive bibliography is included. (author)

49 CFR 236.705 - Bar, locking.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Bar, locking. 236.705 Section 236.705..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.705 Bar, locking. A bar in an interlocking machine to which the locking dogs are attached. ...

49 CFR 236.768 - Locking, time.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Locking, time. 236.768 Section 236.768... Locking, time. A method of locking, either mechanical or electrical, which, after a signal has been caused to display an aspect to proceed, prevents, until after the expiration of a predetermined time...

Phase locking between Josephson soliton oscillators

DEFF Research Database (Denmark)

Holst, T.; Hansen, Jørn Bindslev; Grønbech-Jensen, N.

1990-01-01

We report observations of phase-locking phenomena between two Josephson soliton (fluxon) oscillators biased in self-resonant modes. The locking strength was measured as a function of bias conditions. A frequency tunability of the phase-locked oscillators up to 7% at 10 GHz was observed. Two coupled...... perturbed sine-Gordon equations were derived from an equivalent circuit consisting of inductively coupled, nonlinear, lossy transmission lines. These equations were solved numerically to find the locking regions. Good qualitative agreement was found between the experimental results and the calculations...

Low-power wide-locking-range injection-locked frequency divider for OFDM UWB systems

Energy Technology Data Exchange (ETDEWEB)

Yin Jiangwei; Li Ning; Zheng Renliang; Li Wei; Ren Junyan, E-mail: lining@fudan.edu.c [State Key Laboratory of ASIC and System, Fudan University, Shanghai 201203 (China)

2009-05-01

This paper describes a divide-by-two injection-locked frequency divider (ILFD) for frequency synthesizers as used in multiband orthogonal frequency division multiplexing (OFDM) ultra-wideband (UWB) systems. By means of dual-injection technique and other conventional tuning techniques, such as DCCA and varactor tuning, the divider demonstrates a wide locking range while consuming much less power. The chip was fabricated in the Jazz 0.18 mum RF CMOS process. The measurement results show that the divider achieves a locking range of 4.85 GHz (6.23 to 11.08 GHz) at an input power of 8 dBm. The core circuit without the test buffer consumes only 3.7 mA from a 1.8 V power supply and has a die area of 0.38 x 0.28 mm{sup 2}. The wide locking range combined with low power consumption makes the ILFD suitable for its application in UWB systems.

Low-power wide-locking-range injection-locked frequency divider for OFDM UWB systems

International Nuclear Information System (INIS)

Yin Jiangwei; Li Ning; Zheng Renliang; Li Wei; Ren Junyan

2009-01-01

This paper describes a divide-by-two injection-locked frequency divider (ILFD) for frequency synthesizers as used in multiband orthogonal frequency division multiplexing (OFDM) ultra-wideband (UWB) systems. By means of dual-injection technique and other conventional tuning techniques, such as DCCA and varactor tuning, the divider demonstrates a wide locking range while consuming much less power. The chip was fabricated in the Jazz 0.18 μm RF CMOS process. The measurement results show that the divider achieves a locking range of 4.85 GHz (6.23 to 11.08 GHz) at an input power of 8 dBm. The core circuit without the test buffer consumes only 3.7 mA from a 1.8 V power supply and has a die area of 0.38 x 0.28 mm 2 . The wide locking range combined with low power consumption makes the ILFD suitable for its application in UWB systems.

MEANS AND METHODS FOR CLONING NUCLEIC ACID SEQUENCES

NARCIS (Netherlands)

Geertsma, Eric Robin; Poolman, Berend

2008-01-01

The invention provides means and methods for efficiently cloning nucleic acid sequences of interest in micro-organisms that are less amenable to conventional nucleic acid manipulations, as compared to, for instance, E.coli. The present invention enables high-throughput cloning (and, preferably,

Peptide Nucleic Acids Having Amino Acid Side Chains

DEFF Research Database (Denmark)

1998-01-01

A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than the corresponding DNA or RNA strands, and exhibit increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from a group consisting...

Self-locking degree-4 vertex origami structures.

Science.gov (United States)

Fang, Hongbin; Li, Suyi; Wang, K W

2016-11-01

A generic degree-4 vertex (4-vertex) origami possesses one continuous degree-of-freedom for rigid folding, and this folding process can be stopped when two of its facets bind together. Such facet-binding will induce self-locking so that the overall structure stays at a pre-specified configuration without additional locking elements or actuators. Self-locking offers many promising properties, such as programmable deformation ranges and piecewise stiffness jumps, that could significantly advance many adaptive structural systems. However, despite its excellent potential, the origami self-locking features have not been well studied, understood, and used. To advance the state of the art, this research conducts a comprehensive investigation on the principles of achieving and harnessing self-locking in 4-vertex origami structures. Especially, for the first time, this study expands the 4-vertex structure construction from single-component to dual-component designs and investigates their self-locking behaviours. By exploiting various tessellation designs, this research discovers that the dual-component designs offer the origami structures with extraordinary attributes that the single-component structures do not have, which include the existence of flat-folded locking planes, programmable locking points and deformability. Finally, proof-of-concept experiments investigate how self-locking can effectively induce piecewise stiffness jumps. The results of this research provide new scientific knowledge and a systematic framework for the design, analysis and utilization of self-locking origami structures for many potential engineering applications.

Optical double-locked semiconductor lasers

Science.gov (United States)

AlMulla, Mohammad

2018-06-01

Self-sustained period-one (P1) nonlinear dynamics of a semiconductor laser are investigated when both optical injection and modulation are applied for stable microwave frequency generation. Locking the P1 oscillation through modulation on the bias current, injection strength, or detuning frequency stabilizes the P1 oscillation. Through the phase noise variance, the different modulation types are compared. It is demonstrated that locking the P1 oscillation through optical modulation on the output of the master laser outperforms bias-current modulation of the slave laser. Master laser modulation shows wider P1-oscillation locking range and lower phase noise variance. The locking characteristics of the P1 oscillation also depend on the operating conditions of the optical injection system

First Metatarsophalangeal Joint Arthrodesis: A Retrospective Comparison of Crossed-screws, Locking and Non-Locking Plate Fixation with Lag Screw

Directory of Open Access Journals (Sweden)

Leif Claassen

2017-07-01

Full Text Available Background:Locking plate fixation is increasingly used for first metatarsophalangeal joint (MTP-I arthrodesis. Still there is few comparable clinical data regarding this procedure. Methods:We retrospectively evaluated 60 patients who received an arthrodesis of the MTP-I between January 2008 and June 2010. With 20 patients each we performed a locking plate fixation with lag screw, arthrodesis with crossed-screwsor with a nonlocking plate with lag screw. Results: There were four non-unions in crossed-screws patients and one nonunion in non-locked plate group. All the patients in locking plate group achieved union. 90% of the patients were completely or mildly satisfied in locking plate group, whereas this rate was 80% for patients in both crossed screws and non-locking plate groups. Conclusions: Use of dorsal plating for arthrodesis of MTP1 joint either locking or non-locking were associated with high union rate and acceptable and comparable functional outcome. Although nonunion rate was high using two crossed screws but functional outcome was not significantly different compare to dorsal plating. Level of evidence:Ш, retrospective comparative study

Bicycle Parking and Locking

DEFF Research Database (Denmark)

Larsen, Jonas

2017-01-01

. This article contributes with new insights into parking and locking - ‘moorings’ - to cycling literature. It presents an ethnography of ‘design moorings’ and practices associated with parking and locking bikes. The main case study is the very pro-cycling city of Copenhagen. Yet to explore what is unique about...

49 CFR 236.757 - Lock, electric.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Lock, electric. 236.757 Section 236.757... Lock, electric. A device to prevent or restrict the movement of a lever, a switch or a movable bridge, unless the locking member is withdrawn by an electrical device, such as an electromagnet, solenoid or...

Novel Biochip Platform for Nucleic Acid Analysis

Directory of Open Access Journals (Sweden)

Juan J. Diaz-Mochon

2012-06-01

Full Text Available This manuscript describes the use of a novel biochip platform for the rapid analysis/identification of nucleic acids, including DNA and microRNAs, with very high specificity. This approach combines a unique dynamic chemistry approach for nucleic acid testing and analysis developed by DestiNA Genomics with the STMicroelectronics In-Check platform, which comprises two microfluidic optimized and independent PCR reaction chambers, and a sequential microarray area for nucleic acid capture and identification by fluorescence. With its compact bench-top “footprint” requiring only a single technician to operate, the biochip system promises to transform and expand routine clinical diagnostic testing and screening for genetic diseases, cancers, drug toxicology and heart disease, as well as employment in the emerging companion diagnostics market.

Peptide Nucleic Acids Having 2,6-Diaminopurine Nucleobases

DEFF Research Database (Denmark)

2003-01-01

A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than a corresponding DNA strand, and exhibit increased sequence specificity and binding affinity. The peptide nucleic acids of the invention comprise ligands selected from a group...

EGVII endoglucanase and nucleic acids encoding the same

Science.gov (United States)

Dunn-Coleman, Nigel [Los Gatos, CA; Goedegebuur, Frits [Vlaardingen, NL; Ward, Michael [San Francisco, CA; Yao, Jian [Sunnyvale, CA

2009-05-05

The present invention provides an endoglucanase nucleic acid sequence, designated egl7, and the corresponding EGVII amino acid sequence. The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding EGVII, recombinant EGVII proteins and methods for producing the same.

Robust tilt and lock mechanism for hopping actuator

Energy Technology Data Exchange (ETDEWEB)

Salton, Jonathan R.; Buerger, Stephen; Dullea, Kevin J.; Marron, Lisa C.; Salisbury, Curt Michael; Spletzer, Barry Louis

2017-02-07

A tilt and lock apparatus that includes a tilt servomechanism, a spiral torsion spring, a lock wheel, and a lock hook is described herein. The spiral torsion spring is mechanically coupled to the tilt servomechanism and the lock wheel (which includes an opening). When a shaft is positioned through the opening, rotation of the lock wheel is in unison with rotation of the shaft. An external surface of the lock wheel includes one or more grooves. The lock hook includes a head that engages and disengages the grooves. The lock wheel is stationary when the head engages one of the grooves and is rotatable when the head disengages the grooves. The head and the grooves are geometrically aligned when engaged to prevent creation of a force that acts to disengage the head responsive to an applied force acting on the shaft.

Assembly of barcode-like nucleic acid nanostructures.

Science.gov (United States)

Wang, Pengfei; Tian, Cheng; Li, Xiang; Mao, Chengde

2014-10-15

Barcode-like (BC) nanopatterns from programmed self-assembly of nucleic acids (DNA and RNA) are reported. BC nanostructures are generated by the introduction of open spaces at selected sites to an otherwise closely packed, plain, rectangle nucleic acid nanostructure. This strategy is applied to nanostructures assembled from both origami approach and single stranded tile approach. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nucleic acid-binding glycoproteins which solubilize nucleic acids in dilute acid: re-examination of the Ustilago maydis glycoproteins

Energy Technology Data Exchange (ETDEWEB)

Unrau, P.; Champ, D.R.; Young, J.L.; Grant, C.E.

1980-01-01

Holloman reported the isolation from Ustilago maydis of a glycoprotein which prevented the precipitation of nucleic acids in cold 5% trichloroacetic acid. Two glycoprotein fractions from U. maydis with this nucleic acid-solubilizing activity were isolated in our laboratory using improved purification procedures. The activity was not due to nuclease contamination. The glycoproteins are distinguished by: their ability to bind to concanavalin A-Sepharose; their differential binding to double- and single-stranded deoxyribonucleic acid, and to ribonucleic acid; their molecular weights (46,000 and 69,000); and the relative amounts present in growing versus nongrowing cells. Both fractions required sulfhydryl-reducing conditions for optimal yields, specific activity, and stability. Nucleic acid binding was cooperative, the minimum number of glycoproteins required to make a native T7 DNA molecule soluble in dilute acid being estimated at 2 and 15, respectively.

Universal nucleic acids sample preparation method for cells, spores and their mixture

Science.gov (United States)

Bavykin, Sergei [Darien, IL

2011-01-18

The present invention relates to a method for extracting nucleic acids from biological samples. More specifically the invention relates to a universal method for extracting nucleic acids from unidentified biological samples. An advantage of the presently invented method is its ability to effectively and efficiently extract nucleic acids from a variety of different cell types including but not limited to prokaryotic or eukaryotic cells and/or recalcitrant organisms (i.e. spores). Unlike prior art methods which are focused on extracting nucleic acids from vegetative cell or spores, the present invention effectively extracts nucleic acids from spores, multiple cell types or mixtures thereof using a single method. Important that the invented method has demonstrated an ability to extract nucleic acids from spores and vegetative bacterial cells with similar levels effectiveness. The invented method employs a multi-step protocol which erodes the cell structure of the biological sample, isolates, labels, fragments nucleic acids and purifies labeled samples from the excess of dye.

Microcontroller-based locking in optics experiments

International Nuclear Information System (INIS)

Huang, K.; Le Jeannic, H.; Ruaudel, J.; Morin, O.; Laurat, J.

2014-01-01

Optics experiments critically require the stable and accurate locking of relative phases between light beams or the stabilization of Fabry-Perot cavity lengths. Here, we present a simple and inexpensive technique based on a stand-alone microcontroller unit to perform such tasks. Easily programmed in C language, this reconfigurable digital locking system also enables automatic relocking and sequential functioning. Different algorithms are detailed and applied to fringe locking and to low- and high-finesse optical cavity stabilization, without the need of external modulations or error signals. This technique can readily replace a number of analog locking systems advantageously in a variety of optical experiments

Microcontroller-based locking in optics experiments.

Science.gov (United States)

Huang, K; Le Jeannic, H; Ruaudel, J; Morin, O; Laurat, J

2014-12-01

Optics experiments critically require the stable and accurate locking of relative phases between light beams or the stabilization of Fabry-Perot cavity lengths. Here, we present a simple and inexpensive technique based on a stand-alone microcontroller unit to perform such tasks. Easily programmed in C language, this reconfigurable digital locking system also enables automatic relocking and sequential functioning. Different algorithms are detailed and applied to fringe locking and to low- and high-finesse optical cavity stabilization, without the need of external modulations or error signals. This technique can readily replace a number of analog locking systems advantageously in a variety of optical experiments.

Microcontroller-based locking in optics experiments

Energy Technology Data Exchange (ETDEWEB)

Huang, K. [Laboratoire Kastler Brossel, UPMC-Sorbonne Universités, CNRS, ENS-PSL Research University, Collège de France, 4 place Jussieu, 75005 Paris (France); State Key Laboratory of Precision Spectroscopy, East China Normal University, Shanghai 200062 (China); Le Jeannic, H.; Ruaudel, J.; Morin, O.; Laurat, J., E-mail: julien.laurat@upmc.fr [Laboratoire Kastler Brossel, UPMC-Sorbonne Universités, CNRS, ENS-PSL Research University, Collège de France, 4 place Jussieu, 75005 Paris (France)

2014-12-15

Optics experiments critically require the stable and accurate locking of relative phases between light beams or the stabilization of Fabry-Perot cavity lengths. Here, we present a simple and inexpensive technique based on a stand-alone microcontroller unit to perform such tasks. Easily programmed in C language, this reconfigurable digital locking system also enables automatic relocking and sequential functioning. Different algorithms are detailed and applied to fringe locking and to low- and high-finesse optical cavity stabilization, without the need of external modulations or error signals. This technique can readily replace a number of analog locking systems advantageously in a variety of optical experiments.

A 0.18 μm CMOS inductorless complementary-noise-canceling-LNA for TV tuner applications

International Nuclear Information System (INIS)

Yuan Haiquan; Lin Fujiang; Fu Zhongqian; Huang Lu

2010-01-01

This paper presents an inductorless complementary-noise-canceling LNA (CNCLNA) for TV tuners. The CNCLNA exploits single-to-differential topology, which consists of a common gate stage and a common source stage. The complementary topology can save power and improve the noise figure. Linearity is also enhanced by employing a multiple gated transistors technique. The chip is implemented in SMIC 0.18 μm CMOS technology. Measurement shows that the proposed CNCLNA achieves 13.5-16 dB voltage gain from 50 to 860 MHz, the noise figure is below 4.5 dB and has a minimum value of 2.9 dB, and the best P 1dB is -7.5 dBm at 860 MHz. The core consumes 6 mA current with a supply voltage of 1.8 V, while the core area is only 0.2 x 0.2 mm 2 . (semiconductor integrated circuits)

Heterogeneous Silicon III-V Mode-Locked Lasers

Science.gov (United States)

Davenport, Michael Loehrlein

Mode-locked lasers are useful for a variety of applications, such as sensing, telecommunication, and surgical instruments. This work focuses on integrated-circuit mode-locked lasers: those that combine multiple optical and electronic functions and are manufactured together on a single chip. While this allows production at high volume and lower cost, the true potential of integration is to open applications for mode-locked laser diodes where solid state lasers cannot fit, either due to size and power consumption constraints, or where small optical or electrical paths are needed for high bandwidth. Unfortunately, most high power and highly stable mode-locked laser diode demonstrations in scientific literature are based on the Fabry-Perot resonator design, with cleaved mirrors, and are unsuitable for use in integrated circuits because of the difficulty of producing integrated Fabry-Perot cavities. We use silicon photonics and heterogeneous integration with III-V gain material to produce the most powerful and lowest noise fully integrated mode-locked laser diode in the 20 GHz frequency range. If low noise and high peak power are required, it is arguably the best performing fully integrated mode-locked laser ever demonstrated. We present the design methodology and experimental pathway to realize a fully integrated mode-locked laser diode. The construction of the device, beginning with the selection of an integration platform, and proceeding through the fabrication process to final optimization, is presented in detail. The dependence of mode-locked laser performance on a wide variety of design parameters is presented. Applications for integrated circuit mode-locked lasers are also discussed, as well as proposed methods for using integration to improve mode-locking performance to beyond the current state of the art.

Nucleic acid and nucleotide-mediated synthesis of inorganic nanoparticles

Science.gov (United States)

Berti, Lorenzo; Burley, Glenn A.

2008-02-01

Since the advent of practical methods for achieving DNA metallization, the use of nucleic acids as templates for the synthesis of inorganic nanoparticles (NPs) has become an active area of study. It is now widely recognized that nucleic acids have the ability to control the growth and morphology of inorganic NPs. These biopolymers are particularly appealing as templating agents as their ease of synthesis in conjunction with the possibility of screening nucleotide composition, sequence and length, provides the means to modulate the physico-chemical properties of the resulting NPs. Several synthetic procedures leading to NPs with interesting photophysical properties as well as studies aimed at rationalizing the mechanism of nucleic acid-templated NP synthesis are now being reported. This progress article will outline the current understanding of the nucleic acid-templated process and provides an up to date reference in this nascent field.

Nucleic acid detection system and method for detecting influenza

Science.gov (United States)

Cai, Hong; Song, Jian

2015-03-17

The invention provides a rapid, sensitive and specific nucleic acid detection system which utilizes isothermal nucleic acid amplification in combination with a lateral flow chromatographic device, or DNA dipstick, for DNA-hybridization detection. The system of the invention requires no complex instrumentation or electronic hardware, and provides a low cost nucleic acid detection system suitable for highly sensitive pathogen detection. Hybridization to single-stranded DNA amplification products using the system of the invention provides a sensitive and specific means by which assays can be multiplexed for the detection of multiple target sequences.

LNA effects on DNA binding and conformation

DEFF Research Database (Denmark)

Pabon-Martinez, Y Vladimir; Xu, You; Villa, Alessandra

2017-01-01

-substitution in the duplex pyrimidine strand alters the double helix structure, affecting x-displacement, slide and twist favoring triplex formation through enhanced TFO major groove accommodation. Collectively, these findings should facilitate the design of potent anti-gene ONs.......The anti-gene strategy is based on sequence-specific recognition of double-strand DNA by triplex forming (TFOs) or DNA strand invading oligonucleotides to modulate gene expression. To be efficient, the oligonucleotides (ONs) should target DNA selectively, with high affinity. Here we combined...... hybridization analysis and electrophoretic mobility shift assay with molecular dynamics (MD) simulations to better understand the underlying structural features of modified ONs in stabilizing duplex- and triplex structures. Particularly, we investigated the role played by the position and number of locked...

30 CFR 56.12068 - Locking transformer enclosures.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Locking transformer enclosures. 56.12068 Section 56.12068 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... § 56.12068 Locking transformer enclosures. Transformer enclosures shall be kept locked against...

Bilateral locked facets in the thoracic spine

NARCIS (Netherlands)

M.H.A. Willems; Braakman, R. (Reinder); B. van Linge (Bert)

1984-01-01

textabstractTwo cases of traumatic bilateral locked facets in the thoracic spine are reported. Both patients had only minor neurological signs. They both made a full neurological recovery after surgical reduction of the locked facets. Bilateral locked facets are very uncommon in the thoracic spine.

Computation of the lock-in ranges of phase-locked loops with PI filter

OpenAIRE

Aleksandrov, Konstantin D.; Kuznetsov, Nikolay; Leonov, Gennady A.; Neittaanmäki, Pekka; Yuldashev, Marat V.; Yuldashev, Renat V.

2016-01-01

In the present work the lock-in range of PLL-based circuits with proportionallyintegrating filter and sinusoidal phase-detector characteristics are studied. Considered circuits have sinusoidal phase detector characteristics. Analytical approach based on the methods of phase plane analysis is applied to estimate the lock-in ranges of the circuits under consideration. Obtained analytical results are compared with simulation results.

Biomechanics of far cortical locking.

Science.gov (United States)

Bottlang, Michael; Feist, Florian

2011-02-01

The development of far cortical locking (FCL) was motivated by a conundrum: locked plating constructs provide inherently rigid stabilization, yet they should facilitate biologic fixation and secondary bone healing that relies on flexible fixation to stimulate callus formation. Recent studies have confirmed that the high stiffness of standard locked plating constructs can suppress interfragmentary motion to a level that is insufficient to reliably promote secondary fracture healing by callus formation. Furthermore, rigid locking screws cause an uneven stress distribution that may lead to stress fracture at the end screw and stress shielding under the plate. This review summarizes four key features of FCL constructs that have been shown to enhance fixation and healing of fractures: flexible fixation, load distribution, progressive stiffening, and parallel interfragmentary motion. Specifically, flexible fixation provided by FCL reduces the stiffness of a locked plating construct by 80% to 88% to actively promote callus proliferation similar to an external fixator. Load is evenly distributed between FCL screws to mitigate stress risers at the end screw. Progressive stiffening occurs by near cortex support of FCL screws and provides additional support under elevated loading. Finally, parallel interfragmentary motion by the S-shaped flexion of FCL screws promotes symmetric callus formation. In combination, these features of FCL constructs have been shown to induce more callus and to yield significantly stronger and more consistent healing compared with standard locked plating constructs. As such, FCL constructs function as true internal fixators by replicating the biomechanical behavior and biologic healing response of external fixators.

Electricity-free, sequential nucleic acid and protein isolation.

Science.gov (United States)

Pawlowski, David R; Karalus, Richard J

2012-05-15

Traditional and emerging pathogens such as Enterohemorrhagic Escherichia coli (EHEC), Yersinia pestis, or prion-based diseases are of significant concern for governments, industries and medical professionals worldwide. For example, EHECs, combined with Shigella, are responsible for the deaths of approximately 325,000 children each year and are particularly prevalent in the developing world where laboratory-based identification, common in the United States, is unavailable (1). The development and distribution of low cost, field-based, point-of-care tools to aid in the rapid identification and/or diagnosis of pathogens or disease markers could dramatically alter disease progression and patient prognosis. We have developed a tool to isolate nucleic acids and proteins from a sample by solid-phase extraction (SPE) without electricity or associated laboratory equipment (2). The isolated macromolecules can be used for diagnosis either in a forward lab or using field-based point-of-care platforms. Importantly, this method provides for the direct comparison of nucleic acid and protein data from an un-split sample, offering a confidence through corroboration of genomic and proteomic analysis. Our isolation tool utilizes the industry standard for solid-phase nucleic acid isolation, the BOOM technology, which isolates nucleic acids from a chaotropic salt solution, usually guanidine isothiocyanate, through binding to silica-based particles or filters (3). CUBRC's proprietary solid-phase extraction chemistry is used to purify protein from chaotropic salt solutions, in this case, from the waste or flow-thru following nucleic acid isolation(4). By packaging well-characterized chemistries into a small, inexpensive and simple platform, we have generated a portable system for nucleic acid and protein extraction that can be performed under a variety of conditions. The isolated nucleic acids are stable and can be transported to a position where power is available for PCR amplification

A novel mode-locking technique

International Nuclear Information System (INIS)

Chen Shaoh; Chen Youming; Chen Taolue; Si Xiangdong; Yang Yi; Deng Ximing

1993-01-01

A novel mode-locked Nd:YAG oscillator has been developed by using an ultrafast photoconductive feedback controlled loop, and mode-locked pulses with a duration of 100ps have been obtained. The energy instability of the pulse trains is ±5%. In this type of mode-locking technology, a type of deep-level doped GaAs (Cr-doped) photoconductive switch, which has a fast response in time and is free of avalance process, is used to drive a Pockels' cell to realize mode-locking. The dark resistance of this type of photoconductive switch is 6 orders of magnitude higher than that of the intrinsic single-crystal silicon, and it can reach a level as high as 10 9 ohms. Consequently, it is able to withstand longterm operation at several thousand DC volts. By means of the photoconductive ohmic switch characteristics, the authors have designed a positive feedback control network which has a very fast response time, and can couple a voltage of up to a thousand volts. Using this unit in a Nd:YAG laser, they have successfully realized a very stable mode-locked pulse train with pulse width shorter than 100 ps. The operation principle, and the results of the preliminary experiments are presented here. 1 ref., 3 figs

Power spectrum of an injection-locked Josephson oscillator

International Nuclear Information System (INIS)

Stancampiano, C.V.; Shapiro, S.

1975-01-01

Experiments have shown that a Josephson oscillator, exposed to a weak narrow-band input signal, exhibits behavior characteristic of an injection-locked oscillator. When in lock, Adler's theory of injection locking describes the experimental observations reasonably well. The range of applicability of the theory is extended to the out-of-lock regime where a spectrum of output frequencies is observed. Obtaining the theoretical output power spectrum requires solving a differential equation having the same form as the equation describing the resistively shunted junction model of Stewart and of McCumber. Experimental measurements of the output spectrum of a nearly locked Josephson oscillator are shown to be in reasonable agreement with the theory. Additional results discussed briefly include the observation of a frequency dependence of the locked Josephson oscillator output and experiments in which a Josephson oscillator-mixer was injection locked by a weak signal at the rf

The variable finesse locking technique

International Nuclear Information System (INIS)

Acernese, F; Al-Shourbagy, M

2006-01-01

Virgo is a power recycled Michelson interferometer, with 3 km long Fabry-Perot cavities in the arms. The locking of the interferometer has been obtained with an original lock acquisition technique. The main idea is to lock the instrument away from its working point. Lock is obtained by misaligning the power recycling mirror and detuning the Michelson from the dark fringe. In this way, a good fraction of light escapes through the antisymmetric port and the power build-up inside the recycling cavity is extremely low. The benefit is that all the degrees of freedom are controlled when they are almost decoupled, and the linewidth of the recycling cavity is large. The interferometer is then adiabatically brought on to the dark fringe. This technique is referred to as variable finesse, since the recycling cavity is considered as a variable finesse Fabry-Perot. This technique has been widely tested and allows us to reach the dark fringe in few minutes, in an essentially deterministic way

Nucleic acids in circulation

Indian Academy of Sciences (India)

Elevated blood levels of extracellular nucleic acids have been reported in various disease conditions; such as ageing and age-related degenerative disorders, cancer; acute and chronic inflammatory conditions, severe trauma and autoimmune disorders. In addition to genomic DNA and nucleosomes, mitochondrial DNA is ...

Fluorescent oligonucleotides containing a novel perylene 2′-amino-α-L-LNA monomer: Synthesis and analytical potential

DEFF Research Database (Denmark)

Astakhova, Irina; Kumar, Santhosh T.; Wengel, Jesper

2011-01-01

efficiency of the resulting perylene-2'-amino-alpha-L-LNA monomer (T*) into synthetic oligonucleotides was significantly improved by replacement of the typically used 1H-tetrazole activator with pyridine hydrochloride. Generally, oligonucleotides containing monomer T* showed high binding affinity towards...... incorporations of monomers T* was quenched (quantum yield Phi(F) = 0.21) relative to duplexes of this probe with complementary DNA and RNA (Phi(F) = 0.42 and 0.35, respectively). On the contrary, a strong fluorescence quenching upon target binding was demonstrated by two short oligonucleotides of analogues...... sequences containing monomers T* at 5'- and 3'-terminal positions. We explain the hybridization-induced light-up effect observed for double-labeled probe by a reduction of fluorescence quenching due to precise positioning of the fluorophores within the double-stranded complexes. Furthermore, we propose...

Nucleic acid-induced antiviral immunity in invertebrates: an evolutionary perspective.

Science.gov (United States)

Wang, Pei-Hui; Weng, Shao-Ping; He, Jian-Guo

2015-02-01

Nucleic acids derived from viral pathogens are typical pathogen associated molecular patterns (PAMPs). In mammals, the recognition of viral nucleic acids by pattern recognition receptors (PRRs), which include Toll-like receptors (TLRs) and retinoic acid-inducible gene (RIG)-I-like receptors (RLRs), induces the release of inflammatory cytokines and type I interferons (IFNs) through the activation of nuclear factor κB (NF-κB) and interferon regulatory factor (IRF) 3/7 pathways, triggering the host antiviral state. However, whether nucleic acids can induce similar antiviral immunity in invertebrates remains ambiguous. Several studies have reported that nucleic acid mimics, especially dsRNA mimic poly(I:C), can strongly induce non-specific antiviral immune responses in insects, shrimp, and oyster. This behavior shows multiple similarities to the hallmarks of mammalian IFN responses. In this review, we highlight the current understanding of nucleic acid-induced antiviral immunity in invertebrates. We also discuss the potential recognition and regulatory mechanisms that confer non-specific antiviral immunity on invertebrate hosts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hersendood. Mackies leibniziaanse herinterpretatie van Lockes theorie van persoonsidentiteit

OpenAIRE

De Vleeschouwer, Gregory

2009-01-01

In his book, 'Problems from Locke', John Leslie Mackie presents a theory of personal identity (pi) that is meant to be a supplement and correction of Locke's pi-theory. In a first part I introduce the criterion of pi that was standard before Locke's pi-theory. By showing in a second part how Locke reacted against this traditional criterion, I show wherein the singularity of Locke's pi-theory exists. In a third part I explain how Leibniz is moved by the same solicitude as Locke, but also how h...

Photochemical reactions of nucleic acids and their constituents of photobiological relevance

International Nuclear Information System (INIS)

Saito, I.; Sugiyama, H.; Matsuura, T.

1983-01-01

A review is given of the papers published from 1977 to May 1983 on the UV-induced photochemical reactions of nucleic acids and their constituents of photobiological relevance where the structures of photoproducts have been fully characterized. Among the topics discussed are photoadditions relevant to nucleic acid-protein photocrosslinking, photoreactions with psoralens and nucleic acids and photochemical reactions of polynucleotides. (U.K.)

Brain communication in the locked-in state.

Science.gov (United States)

De Massari, Daniele; Ruf, Carolin A; Furdea, Adrian; Matuz, Tamara; van der Heiden, Linda; Halder, Sebastian; Silvoni, Stefano; Birbaumer, Niels

2013-06-01

Patients in the completely locked-in state have no means of communication and they represent the target population for brain-computer interface research in the last 15 years. Although different paradigms have been tested and different physiological signals used, to date no sufficiently documented completely locked-in state patient was able to control a brain-computer interface over an extended time period. We introduce Pavlovian semantic conditioning to enable basic communication in completely locked-in state. This novel paradigm is based on semantic conditioning for online classification of neuroelectric or any other physiological signals to discriminate between covert (cognitive) 'yes' and 'no' responses. The paradigm comprised the presentation of affirmative and negative statements used as conditioned stimuli, while the unconditioned stimulus consisted of electrical stimulation of the skin paired with affirmative statements. Three patients with advanced amyotrophic lateral sclerosis participated over an extended time period, one of which was in a completely locked-in state, the other two in the locked-in state. The patients' level of vigilance was assessed through auditory oddball procedures to study the correlation between vigilance level and the classifier's performance. The average online classification accuracies of slow cortical components of electroencephalographic signals were around chance level for all the patients. The use of a non-linear classifier in the offline classification procedure resulted in a substantial improvement of the accuracy in one locked-in state patient achieving 70% correct classification. A reliable level of performance in the completely locked-in state patient was not achieved uniformly throughout the 37 sessions despite intact cognitive processing capacity, but in some sessions communication accuracies up to 70% were achieved. Paradigm modifications are proposed. Rapid drop of vigilance was detected suggesting attentional

Geometric properties of nucleic acids with potential for autobuilding

International Nuclear Information System (INIS)

Gruene, Tim; Sheldrick, George M.

2011-01-01

Algorithms and geometrical properties are described for the automated building of nucleic acids in experimental electron density. Medium- to high-resolution X-ray structures of DNA and RNA molecules were investigated to find geometric properties useful for automated model building in crystallographic electron-density maps. We describe a simple method, starting from a list of electron-density ‘blobs’, for identifying backbone phosphates and nucleic acid bases based on properties of the local electron-density distribution. This knowledge should be useful for the automated building of nucleic acid models into electron-density maps. We show that the distances and angles involving C1′ and the P atoms, using the pseudo-torsion angles η' and θ' that describe the …P—C1′—P—C1′… chain, provide a promising basis for building the nucleic acid polymer. These quantities show reasonably narrow distributions with asymmetry that should allow the direction of the phosphate backbone to be established

Locked modes and magnetic field errors in MST

International Nuclear Information System (INIS)

Almagri, A.F.; Assadi, S.; Prager, S.C.; Sarff, J.S.; Kerst, D.W.

1992-06-01

In the MST reversed field pinch magnetic oscillations become stationary (locked) in the lab frame as a result of a process involving interactions between the modes, sawteeth, and field errors. Several helical modes become phase locked to each other to form a rotating localized disturbance, the disturbance locks to an impulsive field error generated at a sawtooth crash, the error fields grow monotonically after locking (perhaps due to an unstable interaction between the modes and field error), and over the tens of milliseconds of growth confinement degrades and the discharge eventually terminates. Field error control has been partially successful in eliminating locking

Integrated sample-to-detection chip for nucleic acid test assays.

Science.gov (United States)

Prakash, R; Pabbaraju, K; Wong, S; Tellier, R; Kaler, K V I S

2016-06-01

Nucleic acid based diagnostic techniques are routinely used for the detection of infectious agents. Most of these assays rely on nucleic acid extraction platforms for the extraction and purification of nucleic acids and a separate real-time PCR platform for quantitative nucleic acid amplification tests (NATs). Several microfluidic lab on chip (LOC) technologies have been developed, where mechanical and chemical methods are used for the extraction and purification of nucleic acids. Microfluidic technologies have also been effectively utilized for chip based real-time PCR assays. However, there are few examples of microfluidic systems which have successfully integrated these two key processes. In this study, we have implemented an electro-actuation based LOC micro-device that leverages multi-frequency actuation of samples and reagents droplets for chip based nucleic acid extraction and real-time, reverse transcription (RT) PCR (qRT-PCR) amplification from clinical samples. Our prototype micro-device combines chemical lysis with electric field assisted isolation of nucleic acid in a four channel parallel processing scheme. Furthermore, a four channel parallel qRT-PCR amplification and detection assay is integrated to deliver the sample-to-detection NAT chip. The NAT chip combines dielectrophoresis and electrostatic/electrowetting actuation methods with resistive micro-heaters and temperature sensors to perform chip based integrated NATs. The two chip modules have been validated using different panels of clinical samples and their performance compared with standard platforms. This study has established that our integrated NAT chip system has a sensitivity and specificity comparable to that of the standard platforms while providing up to 10 fold reduction in sample/reagent volumes.

Shareholder Lock-In Contracts : Share Price and Trading Volume Effects at the Lock-In Expiry

NARCIS (Netherlands)

Angenandt, P.P.; Goergen, M.; Renneboog, L.D.R.

2005-01-01

This paper unveils the diversity in lock-in agreements of firms listed on the Nouveau Marche stock exchange in France.We give the main economic reasons why shareholders adopt lock-in agreements that are more stringent than legally required.We relate the abnormal returns and the abnormal volume at

Artificial Specific Binders Directly Recovered from Chemically Modified Nucleic Acid Libraries

Directory of Open Access Journals (Sweden)

Yuuya Kasahara

2012-01-01

Full Text Available Specific binders comprised of nucleic acids, that is, RNA/DNA aptamers, are attractive functional biopolymers owing to their potential broad application in medicine, food hygiene, environmental analysis, and biological research. Despite the large number of reports on selection of natural DNA/RNA aptamers, there are not many examples of direct screening of chemically modified nucleic acid aptamers. This is because of (i the inferior efficiency and accuracy of polymerase reactions involving transcription/reverse-transcription of modified nucleotides compared with those of natural nucleotides, (ii technical difficulties and additional time and effort required when using modified nucleic acid libraries, and (iii ambiguous efficacies of chemical modifications in binding properties until recently; in contrast, the effects of chemical modifications on biostability are well studied using various nucleotide analogs. Although reports on the direct screening of a modified nucleic acid library remain in the minority, chemical modifications would be essential when further functional expansion of nucleic acid aptamers, in particular for medical and biological uses, is considered. This paper focuses on enzymatic production of chemically modified nucleic acids and their application to random screenings. In addition, recent advances and possible future research are also described.

Artificial specific binders directly recovered from chemically modified nucleic acid libraries.

Science.gov (United States)

Kasahara, Yuuya; Kuwahara, Masayasu

2012-01-01

Specific binders comprised of nucleic acids, that is, RNA/DNA aptamers, are attractive functional biopolymers owing to their potential broad application in medicine, food hygiene, environmental analysis, and biological research. Despite the large number of reports on selection of natural DNA/RNA aptamers, there are not many examples of direct screening of chemically modified nucleic acid aptamers. This is because of (i) the inferior efficiency and accuracy of polymerase reactions involving transcription/reverse-transcription of modified nucleotides compared with those of natural nucleotides, (ii) technical difficulties and additional time and effort required when using modified nucleic acid libraries, and (iii) ambiguous efficacies of chemical modifications in binding properties until recently; in contrast, the effects of chemical modifications on biostability are well studied using various nucleotide analogs. Although reports on the direct screening of a modified nucleic acid library remain in the minority, chemical modifications would be essential when further functional expansion of nucleic acid aptamers, in particular for medical and biological uses, is considered. This paper focuses on enzymatic production of chemically modified nucleic acids and their application to random screenings. In addition, recent advances and possible future research are also described.

Nucleic Acid Therapy: from humble beginnings a dynamic technology

CSIR Research Space (South Africa)

Millroy, L

2011-02-01

Full Text Available The term “nucleic acid therapy” encompasses a wide range of technologies for the treatment of a range of plant and animal ailments. As the name implies, it makes use of nucleic acid (either DNA or RNA) as a therapeutic agent. There are six branches...

Ionizing radiation induced attachment reactions of nucleic acids and their components

International Nuclear Information System (INIS)

Myers, L.S. Jr.

1975-01-01

An extensive bibliographic review is given of experimental and theoretical data on radiation-induced attachment reactions of nucleic acids and their components. Mechanisms of these reactions are reviewed. The reactions with water, formate, and alcohols, with amines and other small molecules, and with radiation sensitizers and nucleic acid-nucleic acid reactions are discussed. Studies of the reaction mechanisms show that many of the reactions occur by radical-molecule reactions, but radical-radical reactions also occur. Radiation modifiers become attached to nucleic acids in vitro and in vivo and there are indications that attachment may be necessary for the action of some sensitizers. (U.S.)

Optimizing the specificity of nucleic acid hybridization.

Science.gov (United States)

Zhang, David Yu; Chen, Sherry Xi; Yin, Peng

2012-01-22

The specific hybridization of complementary sequences is an essential property of nucleic acids, enabling diverse biological and biotechnological reactions and functions. However, the specificity of nucleic acid hybridization is compromised for long strands, except near the melting temperature. Here, we analytically derived the thermodynamic properties of a hybridization probe that would enable near-optimal single-base discrimination and perform robustly across diverse temperature, salt and concentration conditions. We rationally designed 'toehold exchange' probes that approximate these properties, and comprehensively tested them against five different DNA targets and 55 spurious analogues with energetically representative single-base changes (replacements, deletions and insertions). These probes produced discrimination factors between 3 and 100+ (median, 26). Without retuning, our probes function robustly from 10 °C to 37 °C, from 1 mM Mg(2+) to 47 mM Mg(2+), and with nucleic acid concentrations from 1 nM to 5 µM. Experiments with RNA also showed effective single-base change discrimination.

BIOPHYSICAL PROPERTIES OF NUCLEIC ACIDS AT SURFACES RELEVANT TO MICROARRAY PERFORMANCE.

Science.gov (United States)

Rao, Archana N; Grainger, David W

2014-04-01

Both clinical and analytical metrics produced by microarray-based assay technology have recognized problems in reproducibility, reliability and analytical sensitivity. These issues are often attributed to poor understanding and control of nucleic acid behaviors and properties at solid-liquid interfaces. Nucleic acid hybridization, central to DNA and RNA microarray formats, depends on the properties and behaviors of single strand (ss) nucleic acids (e.g., probe oligomeric DNA) bound to surfaces. ssDNA's persistence length, radius of gyration, electrostatics, conformations on different surfaces and under various assay conditions, its chain flexibility and curvature, charging effects in ionic solutions, and fluorescent labeling all influence its physical chemistry and hybridization under assay conditions. Nucleic acid (e.g., both RNA and DNA) target interactions with immobilized ssDNA strands are highly impacted by these biophysical states. Furthermore, the kinetics, thermodynamics, and enthalpic and entropic contributions to DNA hybridization reflect global probe/target structures and interaction dynamics. Here we review several biophysical issues relevant to oligomeric nucleic acid molecular behaviors at surfaces and their influences on duplex formation that influence microarray assay performance. Correlation of biophysical aspects of single and double-stranded nucleic acids with their complexes in bulk solution is common. Such analysis at surfaces is not commonly reported, despite its importance to microarray assays. We seek to provide further insight into nucleic acid-surface challenges facing microarray diagnostic formats that have hindered their clinical adoption and compromise their research quality and value as genomics tools.

BIOPHYSICAL PROPERTIES OF NUCLEIC ACIDS AT SURFACES RELEVANT TO MICROARRAY PERFORMANCE

Science.gov (United States)

Rao, Archana N.; Grainger, David W.

2014-01-01

Both clinical and analytical metrics produced by microarray-based assay technology have recognized problems in reproducibility, reliability and analytical sensitivity. These issues are often attributed to poor understanding and control of nucleic acid behaviors and properties at solid-liquid interfaces. Nucleic acid hybridization, central to DNA and RNA microarray formats, depends on the properties and behaviors of single strand (ss) nucleic acids (e.g., probe oligomeric DNA) bound to surfaces. ssDNA’s persistence length, radius of gyration, electrostatics, conformations on different surfaces and under various assay conditions, its chain flexibility and curvature, charging effects in ionic solutions, and fluorescent labeling all influence its physical chemistry and hybridization under assay conditions. Nucleic acid (e.g., both RNA and DNA) target interactions with immobilized ssDNA strands are highly impacted by these biophysical states. Furthermore, the kinetics, thermodynamics, and enthalpic and entropic contributions to DNA hybridization reflect global probe/target structures and interaction dynamics. Here we review several biophysical issues relevant to oligomeric nucleic acid molecular behaviors at surfaces and their influences on duplex formation that influence microarray assay performance. Correlation of biophysical aspects of single and double-stranded nucleic acids with their complexes in bulk solution is common. Such analysis at surfaces is not commonly reported, despite its importance to microarray assays. We seek to provide further insight into nucleic acid-surface challenges facing microarray diagnostic formats that have hindered their clinical adoption and compromise their research quality and value as genomics tools. PMID:24765522

Prediction of molecular alignment of nucleic acids in aligned media

International Nuclear Information System (INIS)

Wu Bin; Petersen, Michael; Girard, Frederic; Tessari, Marco; Wijmenga, Sybren S.

2006-01-01

We demonstrate - using the data base of all deposited DNA and RNA structures aligned in Pf1-medium and RDC refined - that for nucleic acids in a Pf1-medium the electrostatic alignment tensor can be predicted reliably and accurately via a simple and fast calculation based on the gyration tensor spanned out by the phosphodiester atoms. The rhombicity is well predicted over its full range from 0 to 0.66, while the alignment tensor orientation is predicted correctly for rhombicities up to ca. 0.4, for larger rhombicities it appears to deviate somewhat more than expected based on structural noise and measurement error. This simple analytical approach is based on the Debye-Huckel approximation for the electrostatic interaction potential, valid at distances sufficiently far away from a poly-ionic charged surface, a condition naturally enforced when the charge of alignment medium and solute are of equal sign, as for nucleic acids in a Pf1-phage medium. For the usual salt strengths and nucleic acid sizes, the Debye-Huckel screening length is smaller than the nucleic acid size, but large enough for the collective of Debye-Huckel spheres to encompass the whole molecule. The molecular alignment is then purely electrostatic, but it's functional form is under these conditions similar to that for steric alignment. The proposed analytical expression allows for very fast calculation of the alignment tensor and hence RDCs from the conformation of the nucleic acid molecule. This information provides opportunities for improved structure determination of nucleic acids, including better assessment of dynamics in (multi-domain) nucleic acids and the possibility to incorporate alignment tensor prediction from shape directly into the structure calculation process. The procedures are incorporated into MATLAB scripts, which are available on request

BIOPHYSICAL PROPERTIES OF NUCLEIC ACIDS AT SURFACES RELEVANT TO MICROARRAY PERFORMANCE

OpenAIRE

Rao, Archana N.; Grainger, David W.

2014-01-01

Both clinical and analytical metrics produced by microarray-based assay technology have recognized problems in reproducibility, reliability and analytical sensitivity. These issues are often attributed to poor understanding and control of nucleic acid behaviors and properties at solid-liquid interfaces. Nucleic acid hybridization, central to DNA and RNA microarray formats, depends on the properties and behaviors of single strand (ss) nucleic acids (e.g., probe oligomeric DNA) bound to surface...

Tidal locking of habitable exoplanets

Science.gov (United States)

Barnes, Rory

2017-12-01

Potentially habitable planets can orbit close enough to their host star that the differential gravity across their diameters can produce an elongated shape. Frictional forces inside the planet prevent the bulges from aligning perfectly with the host star and result in torques that alter the planet's rotational angular momentum. Eventually the tidal torques fix the rotation rate at a specific frequency, a process called tidal locking. Tidally locked planets on circular orbits will rotate synchronously, but those on eccentric orbits will either librate or rotate super-synchronously. Although these features of tidal theory are well known, a systematic survey of the rotational evolution of potentially habitable exoplanets using classic equilibrium tide theories has not been undertaken. I calculate how habitable planets evolve under two commonly used models and find, for example, that one model predicts that the Earth's rotation rate would have synchronized after 4.5 Gyr if its initial rotation period was 3 days, it had no satellites, and it always maintained the modern Earth's tidal properties. Lower mass stellar hosts will induce stronger tidal effects on potentially habitable planets, and tidal locking is possible for most planets in the habitable zones of GKM dwarf stars. For fast-rotating planets, both models predict eccentricity growth and that circularization can only occur once the rotational frequency is similar to the orbital frequency. The orbits of potentially habitable planets of very late M dwarfs ([InlineEquation not available: see fulltext.]) are very likely to be circularized within 1 Gyr, and hence, those planets will be synchronous rotators. Proxima b is almost assuredly tidally locked, but its orbit may not have circularized yet, so the planet could be rotating super-synchronously today. The evolution of the isolated and potentially habitable Kepler planet candidates is computed and about half could be tidally locked. Finally, projected TESS planets

Universal spin-momentum locked optical forces

Energy Technology Data Exchange (ETDEWEB)

Kalhor, Farid [Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta T6G 1H9 (Canada); Thundat, Thomas [Department of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta T6G 1H9 (Canada); Jacob, Zubin, E-mail: zjacob@purdue.edu [Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta T6G 1H9 (Canada); Birck Nanotechnology Center, Department of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana 47906 (United States)

2016-02-08

Evanescent electromagnetic waves possess spin-momentum locking, where the direction of propagation (momentum) is locked to the inherent polarization of the wave (transverse spin). We study the optical forces arising from this universal phenomenon and show that the fundamental origin of recently reported non-trivial optical chiral forces is spin-momentum locking. For evanescent waves, we show that the direction of energy flow, the direction of decay, and the direction of spin follow a right hand rule for three different cases of total internal reflection, surface plasmon polaritons, and HE{sub 11} mode of an optical fiber. Furthermore, we explain how the recently reported phenomena of lateral optical force on chiral and achiral particles are caused by the transverse spin of the evanescent field and the spin-momentum locking phenomenon. Finally, we propose an experiment to identify the unique lateral forces arising from the transverse spin in the optical fiber and point to fundamental differences of the spin density from the well-known orbital angular momentum of light. Our work presents a unified view on spin-momentum locking and how it affects optical forces on chiral and achiral particles.

Miniaturized isothermal nucleic acid amplification, a review.

Science.gov (United States)

Asiello, Peter J; Baeumner, Antje J

2011-04-21

Micro-Total Analysis Systems (µTAS) for use in on-site rapid detection of DNA or RNA are increasingly being developed. Here, amplification of the target sequence is key to increasing sensitivity, enabling single-cell and few-copy nucleic acid detection. The several advantages to miniaturizing amplification reactions and coupling them with sample preparation and detection on the same chip are well known and include fewer manual steps, preventing contamination, and significantly reducing the volume of expensive reagents. To-date, the majority of miniaturized systems for nucleic acid analysis have used the polymerase chain reaction (PCR) for amplification and those systems are covered in previous reviews. This review provides a thorough overview of miniaturized analysis systems using alternatives to PCR, specifically isothermal amplification reactions. With no need for thermal cycling, isothermal microsystems can be designed to be simple and low-energy consuming and therefore may outperform PCR in portable, battery-operated detection systems in the future. The main isothermal methods as miniaturized systems reviewed here include nucleic acid sequence-based amplification (NASBA), loop-mediated isothermal amplification (LAMP), helicase-dependent amplification (HDA), rolling circle amplification (RCA), and strand displacement amplification (SDA). Also, important design criteria for the miniaturized devices are discussed. Finally, the potential of miniaturization of some new isothermal methods such as the exponential amplification reaction (EXPAR), isothermal and chimeric primer-initiated amplification of nucleic acids (ICANs), signal-mediated amplification of RNA technology (SMART) and others is presented.

Multiprocessor Real-Time Locking Protocols for Replicated Resources

Science.gov (United States)

2016-07-01

assignment problem, the ac- tual identities of the allocated replicas must be known. When locking protocols are used, tasks may experience delays due to both...Multiprocessor Real-Time Locking Protocols for Replicated Resources ∗ Catherine E. Jarrett1, Kecheng Yang1, Ming Yang1, Pontus Ekberg2, and James H...replicas to execute. In prior work on replicated resources, k-exclusion locks have been used, but this restricts tasks to lock only one replica at a time. To

Locking of intrinsic angular momentum in collision complexes

International Nuclear Information System (INIS)

Berengolts, Alexander.

1995-04-01

A concept of locking of the intrinsic angular momentum of a fragment of a collision complex to a body-fixed axis is widely used in the description of heavy-particle dynamics. The aim of this work is to provide a semiclassical description of the locking phenomenon which occur in diatomic and three atomic collision complexes. The first part of this work is devoted to the semiclassical study of the locking of the electronic angular momentum that occurs in slow collisions of two atoms, one in the spherically symmetric state and the other in state with j= 1. Here we calculate explicitly the complete locking matrix for different types of interatomic interactions. The elements of this matrix directly enter into the semiclassical expression for the different cross sections of polarized atoms. Limitations to the notion of the the locking radius and slipping probability are discussed in connection with the steepness of the interaction. Numerical calculations confirm analytical result: the optimal criterion for determination of the locking radius is a condition for the accumulated phase difference between two molecular states. Analytical expressions are suggested for the locking angle and the slipping probability. Implication of the locking approximation for calculation of the quasiclassical scattering matrix is discussed. The second part considers the locking of the rotational angular momentum of a diatom in the decomposition of a triatomic complexes. We discuss here cases J = 1,2,3 and 4, but restrict ourselves to calculation of the so-called dynamic orientation of the diatomic fragment. The letter represents one of the characteristics of the locking matrix which in principle can be measured experimentally. The orientation is created as a result of the interplay between the adiabatic interaction in the atom- diatom exit channel and the rotationally non adiabatic coupling in the perturbed rotor region

Injection locking of optomechanical oscillators via acoustic waves.

Science.gov (United States)

Huang, Ke; Hossein-Zadeh, Mani

2018-04-02

Injection locking is an effective technique for synchronization of oscillator networks and controlling the phase and frequency of individual oscillators. As such, exploring new mechanisms for injection locking of emerging oscillators is important for their usage in various systems. Here, we present the first demonstration of injection locking of a radiation pressure driven optomechanical oscillator (OMO) via acoustic waves. As opposed to previously reported techniques (based on pump modulation or direct application of a modulated electrostatic force), injection locking of OMO via acoustic waves does not require optical power modulation or physical contact with the OMO and it can be easily implemented on various platforms to lock different types of OMOs independent of their size and structure. Using this approach we have locked the phase and frequency of two distinct modes of a microtoroidal silica OMO to a piezoelectric transducer (PZT). We have characterized the behavior of the injection locked OMO with three acoustic excitation configurations and showed that even without proper acoustic impedance, matching the OMO can be locked to the PZT and tuned over 17 kHz with only -30 dBm of RF power fed to the PZT. The high efficiency, simplicity, and scalability of the proposed approach paves the road toward a new class of photonic systems that rely on synchronization of several OMOs to a single or multiple RF oscillators with applications in optical communication, metrology, and sensing. Beyond its practical applications, injection locking via acoustic waves can be used in fundamental studies in quantum optomechanics where thermal and optical isolation of the OMO are critical.

No Snowball on Habitable Tidally Locked Planets

Science.gov (United States)

Checlair, Jade; Menou, Kristen; Abbot, Dorian S.

2017-08-01

The TRAPPIST-1, Proxima Centauri, and LHS 1140 systems are the most exciting prospects for future follow-up observations of potentially inhabited planets. All of the planets orbit nearby M-stars and are likely tidally locked in 1:1 spin–orbit states, which motivates the consideration of the effects that tidal locking might have on planetary habitability. On Earth, periods of global glaciation (snowballs) may have been essential for habitability and remote signs of life (biosignatures) because they are correlated with increases in the complexity of life and in the atmospheric oxygen concentration. In this paper, we investigate the snowball bifurcation (sudden onset of global glaciation) on tidally locked planets using both an energy balance model and an intermediate-complexity global climate model. We show that tidally locked planets are unlikely to exhibit a snowball bifurcation as a direct result of the spatial pattern of insolation they receive. Instead, they will smoothly transition from partial to complete ice coverage and back. A major implication of this work is that tidally locked planets with an active carbon cycle should not be found in a snowball state. Moreover, this work implies that tidally locked planets near the outer edge of the habitable zone with low CO2 outgassing fluxes will equilibrate with a small unglaciated substellar region rather than cycling between warm and snowball states. More work is needed to determine how the lack of a snowball bifurcation might affect the development of life on a tidally locked planet.

No Snowball on Habitable Tidally Locked Planets

International Nuclear Information System (INIS)

Checlair, Jade; Abbot, Dorian S.; Menou, Kristen

2017-01-01

The TRAPPIST-1, Proxima Centauri, and LHS 1140 systems are the most exciting prospects for future follow-up observations of potentially inhabited planets. All of the planets orbit nearby M-stars and are likely tidally locked in 1:1 spin–orbit states, which motivates the consideration of the effects that tidal locking might have on planetary habitability. On Earth, periods of global glaciation (snowballs) may have been essential for habitability and remote signs of life (biosignatures) because they are correlated with increases in the complexity of life and in the atmospheric oxygen concentration. In this paper, we investigate the snowball bifurcation (sudden onset of global glaciation) on tidally locked planets using both an energy balance model and an intermediate-complexity global climate model. We show that tidally locked planets are unlikely to exhibit a snowball bifurcation as a direct result of the spatial pattern of insolation they receive. Instead, they will smoothly transition from partial to complete ice coverage and back. A major implication of this work is that tidally locked planets with an active carbon cycle should not be found in a snowball state. Moreover, this work implies that tidally locked planets near the outer edge of the habitable zone with low CO 2 outgassing fluxes will equilibrate with a small unglaciated substellar region rather than cycling between warm and snowball states. More work is needed to determine how the lack of a snowball bifurcation might affect the development of life on a tidally locked planet.

Soni-removal of nucleic acids from inclusion bodies.

Science.gov (United States)

Neerathilingam, Muniasamy; Mysore, Sumukh; Gandham, Sai Hari A

2014-05-23

Inclusion bodies (IBs) are commonly formed in Escherichia coli due to over expression of recombinant proteins in non-native state. Isolation, denaturation and refolding of these IBs is generally performed to obtain functional protein. However, during this process IBs tend to form non-specific interactions with sheared nucleic acids from the genome, thus getting carried over into downstream processes. This may hinder the refolding of IBs into their native state. To circumvent this, we demonstrate a methodology termed soni-removal which involves disruption of nucleic acid-inclusion body interaction using sonication; followed by solvent based separation. As opposed to conventional techniques that use enzymes and column-based separations, soni-removal is a cost effective alternative for complete elimination of buried and/or strongly bound short nucleic acid contaminants from IBs. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Commonwealth Edison Company pressure locking test report

Energy Technology Data Exchange (ETDEWEB)

Bunte, B.D.; Kelly, J.F.

1996-12-01

Pressure Locking is a phenomena which can cause the unseating thrust for a gate valve to increase dramatically from its typical static unseating thrust. This can result in the valve actuator having insufficient capability to open the valve. In addition, this can result in valve damage in cases where the actuator capability exceeds the valve structural limits. For these reasons, a proper understanding of the conditions which may cause pressure locking and thermal binding, as well as a methodology for predicting the unseating thrust for a pressure locked or thermally bound valve, are necessary. This report discusses the primary mechanisms which cause pressure locking. These include sudden depressurization of piping adjacent to the valve and pressurization of fluid trapped in the valve bonnet due to heat transfer. This report provides a methodology for calculating the unseating thrust for a valve which is pressure locked. This report provides test data which demonstrates the accuracy of the calculation methodology.

Commonwealth Edison Company pressure locking test report

International Nuclear Information System (INIS)

Bunte, B.D.; Kelly, J.F.

1996-01-01

Pressure Locking is a phenomena which can cause the unseating thrust for a gate valve to increase dramatically from its typical static unseating thrust. This can result in the valve actuator having insufficient capability to open the valve. In addition, this can result in valve damage in cases where the actuator capability exceeds the valve structural limits. For these reasons, a proper understanding of the conditions which may cause pressure locking and thermal binding, as well as a methodology for predicting the unseating thrust for a pressure locked or thermally bound valve, are necessary. This report discusses the primary mechanisms which cause pressure locking. These include sudden depressurization of piping adjacent to the valve and pressurization of fluid trapped in the valve bonnet due to heat transfer. This report provides a methodology for calculating the unseating thrust for a valve which is pressure locked. This report provides test data which demonstrates the accuracy of the calculation methodology

Solving nucleic acid structures by molecular replacement: examples from group II intron studies

International Nuclear Information System (INIS)

Marcia, Marco; Humphris-Narayanan, Elisabeth; Keating, Kevin S.; Somarowthu, Srinivas; Rajashankar, Kanagalaghatta; Pyle, Anna Marie

2013-01-01

Strategies for phasing nucleic acid structures by molecular replacement, using both experimental and de novo designed models, are discussed. Structured RNA molecules are key players in ensuring cellular viability. It is now emerging that, like proteins, the functions of many nucleic acids are dictated by their tertiary folds. At the same time, the number of known crystal structures of nucleic acids is also increasing rapidly. In this context, molecular replacement will become an increasingly useful technique for phasing nucleic acid crystallographic data in the near future. Here, strategies to select, create and refine molecular-replacement search models for nucleic acids are discussed. Using examples taken primarily from research on group II introns, it is shown that nucleic acids are amenable to different and potentially more flexible and sophisticated molecular-replacement searches than proteins. These observations specifically aim to encourage future crystallographic studies on the newly discovered repertoire of noncoding transcripts

Revealing Nucleic Acid Mutations Using Förster Resonance Energy Transfer-Based Probes

Directory of Open Access Journals (Sweden)

Nina P. L. Junager

2016-07-01

Full Text Available Nucleic acid mutations are of tremendous importance in modern clinical work, biotechnology and in fundamental studies of nucleic acids. Therefore, rapid, cost-effective and reliable detection of mutations is an object of extensive research. Today, Förster resonance energy transfer (FRET probes are among the most often used tools for the detection of nucleic acids and in particular, for the detection of mutations. However, multiple parameters must be taken into account in order to create efficient FRET probes that are sensitive to nucleic acid mutations. In this review; we focus on the design principles for such probes and available computational methods that allow for their rational design. Applications of advanced, rationally designed FRET probes range from new insights into cellular heterogeneity to gaining new knowledge of nucleic acid structures directly in living cells.

Polymerase chain reaction system using magnetic beads for analyzing a sample that includes nucleic acid

Science.gov (United States)

Nasarabadi, Shanavaz [Livermore, CA

2011-01-11

A polymerase chain reaction system for analyzing a sample containing nucleic acid includes providing magnetic beads; providing a flow channel having a polymerase chain reaction chamber, a pre polymerase chain reaction magnet position adjacent the polymerase chain reaction chamber, and a post pre polymerase magnet position adjacent the polymerase chain reaction chamber. The nucleic acid is bound to the magnetic beads. The magnetic beads with the nucleic acid flow to the pre polymerase chain reaction magnet position in the flow channel. The magnetic beads and the nucleic acid are washed with ethanol. The nucleic acid in the polymerase chain reaction chamber is amplified. The magnetic beads and the nucleic acid are separated into a waste stream containing the magnetic beads and a post polymerase chain reaction mix containing the nucleic acid. The reaction mix containing the nucleic acid flows to an analysis unit in the channel for analysis.

Locked and proteolysis-based transcription activator-like effector (TALE) regulation.

Science.gov (United States)

Lonzarić, Jan; Lebar, Tina; Majerle, Andreja; Manček-Keber, Mateja; Jerala, Roman

2016-02-18

Development of orthogonal, designable and adjustable transcriptional regulators is an important goal of synthetic biology. Their activity has been typically modulated through stimulus-induced oligomerization or interaction between the DNA-binding and activation/repression domain. We exploited a feature of the designable Transcription activator-like effector (TALE) DNA-binding domain that it winds around the DNA which allows to topologically prevent it from binding by intramolecular cyclization. This new approach was investigated through noncovalent ligand-induced cyclization or through a covalent split intein cyclization strategy, where the topological inhibition of DNA binding by cyclization and its restoration by a proteolytic release of the topologic constraint was expected. We show that locked TALEs indeed have diminished DNA binding and regain full transcriptional activity by stimulation with the rapamycin ligand or site-specific proteolysis of the peptide linker, with much higher level of activation than rapamycin-induced heterodimerization. Additionally, we demonstrated reversibility, activation of genomic targets and implemented logic gates based on combinations of protein cyclization, proteolytic cleavage and ligand-induced dimerization, where the strongest fold induction was achieved by the proteolytic cleavage of a repression domain from a linear TALE. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Gene Targeting and Expression Modulation by Peptide Nucleic Acids (PNA)

DEFF Research Database (Denmark)

Nielsen, Peter E

2010-01-01

Peptide nucleic acids (PNA) are artificial structural mimics of nucleic acids capable of sequence specific hybridization to both RNA and DNA. Thus they have obvious potential as gene targeting agents for drug discovery approaches. An overview with emphasis on recent progress on RNA "interference...

Wall locking and multiple nonlinear states of magnetic islands

International Nuclear Information System (INIS)

Persson, Mikael; Australian National Univ., Canberra, ACT

1994-01-01

The nonlinear evolution of magnetic islands is analysed in configurations with multiple resonant magnetic surfaces. The existence of multiple nonlinear steady states, is discussed. These are shown to be associated with states where the dynamics around the different rational surfaces are coupled or decoupled and in the presence of a wall of finite resistivity may correspond wall-locked or non-wall-locked magnetic islands. For the case of strong wall stabilization the locking is shown to consist of two different phases. During the first phase the locking of the plasma at the different rational surfaces occurs. Only when the outermost resonant magnetic surface has locked to the inner surfaces can the actual wall locking process take place. Consequently, wall locking, of a global mode, involving more than one rational surface, can be prevented by the decoupling of the resonant magnetic surfaces by plasma rotation. Possible implications on tokamak experiments are discussed. (author)

No Snowball on Habitable Tidally Locked Planets

Energy Technology Data Exchange (ETDEWEB)

Checlair, Jade; Abbot, Dorian S. [Department of the Geophysical Sciences, University of Chicago, 5734 South Ellis Avenue, Chicago, IL 60637 (United States); Menou, Kristen, E-mail: jadecheclair@uchicago.edu [Centre for Planetary Sciences, Department of Physical and Environmental Sciences, University of Toronto at Scarborough, Toronto, ON M1C 1A4 (Canada)

2017-08-20

The TRAPPIST-1, Proxima Centauri, and LHS 1140 systems are the most exciting prospects for future follow-up observations of potentially inhabited planets. All of the planets orbit nearby M-stars and are likely tidally locked in 1:1 spin–orbit states, which motivates the consideration of the effects that tidal locking might have on planetary habitability. On Earth, periods of global glaciation (snowballs) may have been essential for habitability and remote signs of life (biosignatures) because they are correlated with increases in the complexity of life and in the atmospheric oxygen concentration. In this paper, we investigate the snowball bifurcation (sudden onset of global glaciation) on tidally locked planets using both an energy balance model and an intermediate-complexity global climate model. We show that tidally locked planets are unlikely to exhibit a snowball bifurcation as a direct result of the spatial pattern of insolation they receive. Instead, they will smoothly transition from partial to complete ice coverage and back. A major implication of this work is that tidally locked planets with an active carbon cycle should not be found in a snowball state. Moreover, this work implies that tidally locked planets near the outer edge of the habitable zone with low CO{sub 2} outgassing fluxes will equilibrate with a small unglaciated substellar region rather than cycling between warm and snowball states. More work is needed to determine how the lack of a snowball bifurcation might affect the development of life on a tidally locked planet.

Nucleic acids for the rational design of reaction circuits.

Science.gov (United States)

Padirac, Adrien; Fujii, Teruo; Rondelez, Yannick

2013-08-01

Nucleic acid-based circuits are rationally designed in vitro assemblies that can perform complex preencoded programs. They can be used to mimic in silico computations. Recent works emphasized the modularity and robustness of these circuits, which allow their scaling-up. Another new development has led to dynamic, time-responsive systems that can display emergent behaviors like oscillations. These are closely related to biological architectures and provide an in vitro model of in vivo information processing. Nucleic acid circuits have already been used to handle various processes for technological or biotechnological purposes. Future applications of these chemical smart systems will benefit from the rapidly growing ability to design, construct, and model nucleic acid circuits of increasing size. Copyright © 2012 Elsevier Ltd. All rights reserved.

Short locking time and low jitter phase-locked loop based on slope charge pump control

International Nuclear Information System (INIS)

Guo Zhongjie; Liu Youbao; Wu Longsheng; Wang Xihu; Tang Wei

2010-01-01

A novel structure of a phase-locked loop (PLL) characterized by a short locking time and low jitter is presented, which is realized by generating a linear slope charge pump current dependent on monitoring the output of the phase frequency detector (PFD) to implement adaptive bandwidth control. This improved PLL is created by utilizing a fast start-up circuit and a slope current control on a conventional charge pump PLL. First, the fast start-up circuit is enabled to achieve fast pre-charging to the loop filter. Then, when the output pulse of the PFD is larger than a minimum value, the charge pump current is increased linearly by the slope current control to ensure a shorter locking time and a lower jitter. Additionally, temperature variation is attenuated with the temperature compensation in the charge pump current design. The proposed PLL has been fabricated in a kind of DSP chip based on a 0.35 μm CMOS process. Comparing the characteristics with the classical PLL, the proposed PLL shows that it can reduce the locking time by 60% with a low peak-to-peak jitter of 0.3% at a wide operation temperature range. (semiconductor integrated circuits)

Arm locking with Doppler estimation errors

Energy Technology Data Exchange (ETDEWEB)

Yu Yinan; Wand, Vinzenz; Mitryk, Shawn; Mueller, Guido, E-mail: yinan@phys.ufl.ed [Department of Physics, University of Florida, Gainesville, FL 32611 (United States)

2010-05-01

At the University of Florida we developed the University of Florida LISA Interferometer Simulator (UFLIS) in order to study LISA interferometry with hardware in the loop at a system level. One of the proposed laser frequency stabilization techniques in LISA is arm locking. Arm locking uses an adequately filtered linear combination of the LISA arm signals as a frequency reference. We will report about experiments in which we demonstrated arm locking using UFLIS. During these experiments we also discovered a problem associated with the Doppler shift of the return beam. The initial arm locking publications assumed that this Doppler shift can perfectly be subtracted inside the phasemeter or adds an insignificant offset to the sensor signal. However, the remaining Doppler knowledge error will cause a constant change in the laser frequency if unaccounted for. Several ways to circumvent this problem have been identified. We performed detailed simulations and started preliminary experiments to verify the performance of the proposed new controller designs.

BGL6 beta-glucosidase and nucleic acids encoding the same

Science.gov (United States)

Dunn-Coleman, Nigel [Los Gatos, CA; Ward, Michael [San Francisco, CA

2009-09-01

The present invention provides a novel .beta.-glucosidase nucleic acid sequence, designated bgl6, and the corresponding BGL6 amino acid sequence. The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding BGL6, recombinant BGL6 proteins and methods for producing the same.

Investigation on Locking and Pulling Modes in Analog Frequency Dividers

Directory of Open Access Journals (Sweden)

Antonio Buonomo

2013-01-01

Full Text Available We compare the main analytical results available to estimate the locking range, which is the key figure-of-merit of LC frequency dividers based on the injection locking phenomenon. Starting from the classical result by Adler concerning injection-locked oscillators, we elucidate the merits and the shortcomings of the different approaches to study injection-locked frequency dividers, with particular emphasis on divider-by-2. In particular, we show the potential of a perturbation approach which enables a more complete analysis of frequency dividers, making it possible to calculate not only the amplitude and the phase of the locked oscillation, but also the region where it exists and is stable, which defines the locking region. Finally, we analyze the dynamical behaviour of the dividers in the vicinity of the boundary of the locking region, showing that there exists a border region where the occurrence of the locking or the pulling operation mode is possible, depending on the initial conditions of the system.

Towards Fluorescence In Vivo Hybridization (FIVH) Detection of H. pylori in Gastric Mucosa Using Advanced LNA Probes

DEFF Research Database (Denmark)

Fontenete, Sílvia; Leite, Marina; Guimarães, Nuno

2015-01-01

acid (LNA)/ 2' O-methyl RNA (2'OMe) probe using standard phosphoramidite chemistry and FISH hybridization was then successfully performed both on adhered and suspended bacteria at 37°C. In this work we simplified, shortened and adapted FISH to work at gastric pH values, meaning that the hybridization...... step now takes only 30 minutes and, in addition to the buffer, uses only urea and probe at non-toxic concentrations. Importantly, the sensitivity and specificity of the FISH method was maintained in the range of conditions tested, even at low stringency conditions (e.g., low pH). In conclusion......In recent years, there have been several attempts to improve the diagnosis of infection caused by Helicobacter pylori. Fluorescence in situ hybridization (FISH) is a commonly used technique to detect H. pylori infection but it requires biopsies from the stomach. Thus, the development of an in vivo...

The strength of polyaxial locking interfaces of distal radius plates.

Science.gov (United States)

Hoffmeier, Konrad L; Hofmann, Gunther O; Mückley, Thomas

2009-10-01

Currently available polyaxial locking plates represent the consequent enhancement of fixed-angle, first-generation locking plates. In contrast to fixed-angle locking plates which are sufficiently investigated, the strength of the new polyaxial locking options has not yet been evaluated biomechanically. This study investigates the mechanical strength of single polyaxial interfaces of different volar radius plates. Single screw-plate interfaces of the implants Palmar 2.7 (Königsee Implantate und Instrumente zur Osteosynthese GmbH, Allendorf, Germany), VariAx (Stryker Leibinger GmbH & Co. KG, Freiburg, Germany) und Viper (Integra LifeSciences Corporation, Plainsboro, NJ, USA) were tested by cantilever bending. The strength of 0 degrees, 10 degrees and 20 degrees screw locking angle was obtained during static and dynamic loading. The Palmar 2.7 interfaces showed greater ultimate strength and fatigue strength than the interfaces of the other implants. The strength of the VariAx interfaces was about 60% of Palmar 2.7 in both, static and dynamic loading. No dynamic testing was applied to the Viper plate because of its low ultimate strength. By static loading, an increase in screw locking angle caused a reduction of strength for the Palmar 2.7 and Viper locking interfaces. No influence was observed for the VariAx locking interfaces. During dynamic loading; angulation had no influence on the locking strength of Palmar 2.7. However, reduction of locking strength with increasing screw angulation was observed for VariAx. The strength of the polyaxial locking interfaces differs remarkably between the examined implants. Depending on the implant an increase of the screw locking angle causes a reduction of ultimate or fatigue strength, but not in all cases a significant impact was observed.

Performance Monitoring System: Summary of Lock Statistics. Revision 1.

Science.gov (United States)

1985-12-01

2751 84 4057 4141 526 798 18 1342 5727 19 5523 3996 4587 8583 1056 1630 35 2721 6536LOCK A DAMI 2 AUXILIARY I Ins NO DATA RECORDD FOR THIS LOCK- " LOCK I...TOTAL (KTOMS) ’ - (AVt OPNP ETC) ’’ ,q [ " ARKANSAS RIVER "" FORRELL LOCK IP 7A/3TRC 9/N83 UPBOUID STATISTICS ISO 53 42 M6 553 356 909 221 41 21 M8

Key-lock colloids in a nematic liquid crystal.

Science.gov (United States)

Silvestre, Nuno M; Tasinkevych, M

2017-01-01

The Landau-de Gennes free energy is used to study theoretically the effective interaction of spherical "key" and anisotropic "lock" colloidal particles. We assume identical anchoring properties of the surfaces of the key and of the lock particles, and we consider planar degenerate and perpendicular anchoring conditions separately. The lock particle is modeled as a spherical particle with a spherical dimple. When such a particle is introduced into a nematic liquid crystal, it orients its dimple at an oblique angle θ_{eq} with respect to the far field director n_{∞}. This angle depends on the depth of the dimple. Minimization results show that the free energy of a pair of key and lock particles exhibits a global minimum for the configuration when the key particle is facing the dimple of the lock colloidal particle. The preferred orientation ϕ_{eq} of the key-lock composite doublet relative to n_{∞} is robust against thermal fluctuations. The preferred orientation θ_{eq}^{(2)} of the dimple particle in the doublet is different from the isolated situation. This is related to the "direct" interaction of defects accompanying the key particle with the edge of the dimple. We propose that this nematic-amplified key-lock interaction can play an important role in self-organization and clustering of mixtures of colloidal particles with dimple colloids present.

[Blood Test Patterns for Blood Donors after Nucleic Acid Detection in the Blood Center].

Science.gov (United States)

Men, Shou-Shan; Lv, Lian-Zhi; Chen, Yuan-Feng; Han, Chun-Hua; Liu, Hong-Yu; Yan, Yan

2017-12-01

To investigate the blood test patterns for blood donors after nucleic acid detection in blood center. The collected blood samples after voluntary blood donors first were detected by conventional ELISA, then 31981 negative samples were detected via HBV/HCV/HIV combined nucleic acid test of 6 mixed samples(22716 cases) or single samples(9265 cases) by means of Roche cobas s201 instrument. The combined detection method as follows: the blood samples were assayed by conventional nucleic acid test of 6 mixed samples, at same time, 6 mixed samples were treated with polyethylene glycol precipitation method to concentrate the virus, then the nucleic acid test of blood samples was performed; the single detection method as follows: firstly the conventional nucleic acid test of single sample was performed, then the positive reactive samples after re-examination were 6-fold diluted to simulate the nucleic acid test of 6-mixed samples. The positive rate of positive samples detected by combined nucleic acid test, positive samples detected by nucleic acid test of mixed virus concentration and positive samples detected by single nucleic acid test was statistically analyzed. In addition, for HBV + persons the serological test yet should be performed. In 22 716 samples detected by nucleic acid test of 6 mixed samples (MP-6-NAT) , 9 cases were HBV + (0.40‰, 9/22716); at same time, the detection of same samples by nucleic acid test of mixed sample virus concentration showed 29 cases of HBV + (1.28‰, 29/22716). In 9265 samples detected by single nucleic acid test(ID-NAT) 12 cases showed HBV + (1.30‰, 12/9265), meanwhile the detection of these 12 samples with HBV + by 6-fold dilution for virus concentration found only 4 samples with HBV + . In serological qualified samples, ID-NAT unqualified rate was 1.28‰, which was higher than that of MP-6-NAT(0.4‰) (χ 2 =8.11, P0.05). In 41 samples with HBsAg - HBV DNA + detected by ELISA, 36 samples were confirmed to be occult HBV

Monolithic Hybrid and Passive Mode-Locked 40GHz Quantum Dot Laser Diodes

DEFF Research Database (Denmark)

Thompson, M. G.; Larsson, David; Rae, A. R.

2006-01-01

For the first time hybrid and passive mode-locking jitter performance is investigated in 40GHz quantum-dot mode-locked lasers. Record low passive mode-locking jitter of 219fs is presented, along with promising hybrid mode-locking results of 124fs.......For the first time hybrid and passive mode-locking jitter performance is investigated in 40GHz quantum-dot mode-locked lasers. Record low passive mode-locking jitter of 219fs is presented, along with promising hybrid mode-locking results of 124fs....

Nucleic acid purification from plants, animals and microbes in under 30 seconds.

Directory of Open Access Journals (Sweden)

Yiping Zou

2017-11-01

Full Text Available Nucleic acid amplification is a powerful molecular biology tool, although its use outside the modern laboratory environment is limited due to the relatively cumbersome methods required to extract nucleic acids from biological samples. To address this issue, we investigated a variety of materials for their suitability for nucleic acid capture and purification. We report here that untreated cellulose-based paper can rapidly capture nucleic acids within seconds and retain them during a single washing step, while contaminants present in complex biological samples are quickly removed. Building on this knowledge, we have successfully created an equipment-free nucleic acid extraction dipstick methodology that can obtain amplification-ready DNA and RNA from plants, animals, and microbes from difficult biological samples such as blood and leaves from adult trees in less than 30 seconds. The simplicity and speed of this method as well as the low cost and availability of suitable materials (e.g., common paper towelling, means that nucleic acid extraction is now more accessible and affordable for researchers and the broader community. Furthermore, when combined with recent advancements in isothermal amplification and naked eye DNA visualization techniques, the dipstick extraction technology makes performing molecular diagnostic assays achievable in limited resource settings including university and high school classrooms, field-based environments, and developing countries.

Ion-pair chromatography of nucleic acid derivatives

International Nuclear Information System (INIS)

Perrone, P.A.; Brown, P.R.

1985-01-01

Little work has been done on the ion-pair chromatography of nucleic acid constituents, although there is a great potential for the use of this technique in the field. Since the classic work in 1949, nucleotides, as well as nucleosides and bases, have been separated by ion-exchange chromatography. However, ion exchange is a difficult mode and most researchers prefer the use of reversed-phase whenever possible. Although reversed-phase is now the method of choice, ionic compounds like nucleotides and some of the more polar bases are not adequately retained by many systems of this type. In addition, it is difficult to analyze simultaneously members of all three classes of nucleic acid compounds (bases, nucleosides, and nucleotides) using a reversed-phase system, even with gradient elution. Ion pairing can be a useful technique because, theoretically, the separation of nonionic bases and nucleosides along with the ionic nucleotides can be achieved. Additionally, each group of compounds may be separated isocratically. In this chapter, they will discuss ion-pair chromatography as applied to nucleic acid constituents. The current theories, advantages and disadvantages, a limited number of applications, and potential for future work are presented

Methods of introducing nucleic acids into cellular DNA

Energy Technology Data Exchange (ETDEWEB)

Lajoie, Marc J.; Gregg, Christopher J.; Mosberg, Joshua A.; Church, George M.

2017-06-27

A method of introducing a nucleic acid sequence into a cell is provided where the cell has impaired or inhibited or disrupted DnaG primase activity or impaired or inhibited or disrupted DnaB helicase activity, or larger or increased gaps or distance between Okazaki fragments or lowered or reduced frequency of Okazaki fragment initiation, or the cell has increased single stranded DNA (ssDNA) on the lagging strand of the replication fork including transforming the cell through recombination with a nucleic acid oligomer.

Locks at reactor safety containments of nuclear power plants

International Nuclear Information System (INIS)

1978-12-01

The rule is to be applied for material access locks. A material access lock as defined by this rule is a pressure resistant and technically gas-tight hollow body that is connected with the containment and has got two doors, the inner door of which connects the lock chamber with the interior of the containment and the outer door connects the lock chamber with the outside. It serves exclusively for transferring material or objects. (orig./HP) [de

Characteristics of picoplankton abundances during a Thalassiosira diporocyclus bloom in the Taiwan Bank in late winter.

Science.gov (United States)

Jiang, Xin; Li, Jiajun; Ke, Zhixin; Xiang, Chenhui; Tan, Yehui; Huang, Liangmin

2017-04-15

To understand the variations of picoplankton (Prochlorococcus, Synechococcus, picoeukaryotes, and heterotrophic bacteria) abundances during diatom bloom, the distribution of picoplankton in the Taiwan Bank, South China Sea was investigated using flow cytometry during a Thalassiosira diporocyclus bloom in March 2016. The results indicated an abrupt abundance decrease for Prochlorococcus, Synechococcus, and picoeukaryotes within the bloom area while the abundance of heterotrophic bacteria showed no significant difference between the bloom and non-bloom areas. We found two sub-groups of heterotrophic bacteria: high- and low-nucleic acid content (HNA and LNA) bacteria with HNA dominated in the bloom area whereas LNA dominated in the non-bloom area. Among the picoplankton components, HNA represented the highest (61.1%) carbon biomass in the bloom area while picoeukaryotes represented the highest (37.6%) in the non-bloom area. Our findings implied that heterotrophic bacteria, especially HNA, played an essential role during the diatom bloom. Copyright © 2017 Elsevier Ltd. All rights reserved.

Digital Microfluidics for Nucleic Acid Amplification

Directory of Open Access Journals (Sweden)

Beatriz Coelho

2017-06-01

Full Text Available Digital Microfluidics (DMF has emerged as a disruptive methodology for the control and manipulation of low volume droplets. In DMF, each droplet acts as a single reactor, which allows for extensive multiparallelization of biological and chemical reactions at a much smaller scale. DMF devices open entirely new and promising pathways for multiplex analysis and reaction occurring in a miniaturized format, thus allowing for healthcare decentralization from major laboratories to point-of-care with accurate, robust and inexpensive molecular diagnostics. Here, we shall focus on DMF platforms specifically designed for nucleic acid amplification, which is key for molecular diagnostics of several diseases and conditions, from pathogen identification to cancer mutations detection. Particular attention will be given to the device architecture, materials and nucleic acid amplification applications in validated settings.

''Old'' locked inflation

Energy Technology Data Exchange (ETDEWEB)

Liu, Yang; Piao, Yun-Song [College of Physical Sciences, Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Si, Zong-Guo, E-mail: liuyangbyf@mail.sdu.edu.cn, E-mail: yspiao@gucas.ac.cn, E-mail: zgsi@sdu.edu.cn [Department of Physics, Shandong University, Jinan 250100 (China)

2009-05-15

In this paper, we revisit the idea of locked inflation, which does not require a potential satisfying the normal slow-roll condition, but suffers from the problems associated with ''saddle inflation''. We propose a scenario based on locked inflation, however, with an alternative evolution mechanism of the ''waterfall field'' {phi}. Instead of rolling down along the potential, the {phi} field will tunnel to end the inflation stage like in old inflation, by which the saddle inflation could be avoided. Further, we study a cascade of old locked inflation, which can be motivated by the string landscape. Our model is based on the consideration of making locked inflation feasible so as to give a working model without slow roll; It also can be seen as an effort to embed the old inflation in string landscape.

Improving generalized inverted index lock wait times

Science.gov (United States)

Borodin, A.; Mirvoda, S.; Porshnev, S.; Ponomareva, O.

2018-01-01

Concurrent operations on tree like data structures is a cornerstone of any database system. Concurrent operations intended for improving read\\write performance and usually implemented via some way of locking. Deadlock-free methods of concurrency control are known as tree locking protocols. These protocols provide basic operations(verbs) and algorithm (ways of operation invocations) for applying it to any tree-like data structure. These algorithms operate on data, managed by storage engine which are very different among RDBMS implementations. In this paper, we discuss tree locking protocol implementation for General inverted index (Gin) applied to multiversion concurrency control (MVCC) storage engine inside PostgreSQL RDBMS. After that we introduce improvements to locking protocol and provide usage statistics about evaluation of our improvement in very high load environment in one of the world’s largest IT company.

Nucleic Acid Extraction from Synthetic Mars Analog Soils for in situ Life Detection.

Science.gov (United States)

Mojarro, Angel; Ruvkun, Gary; Zuber, Maria T; Carr, Christopher E

2017-08-01

Biological informational polymers such as nucleic acids have the potential to provide unambiguous evidence of life beyond Earth. To this end, we are developing an automated in situ life-detection instrument that integrates nucleic acid extraction and nanopore sequencing: the Search for Extra-Terrestrial Genomes (SETG) instrument. Our goal is to isolate and determine the sequence of nucleic acids from extant or preserved life on Mars, if, for example, there is common ancestry to life on Mars and Earth. As is true of metagenomic analysis of terrestrial environmental samples, the SETG instrument must isolate nucleic acids from crude samples and then determine the DNA sequence of the unknown nucleic acids. Our initial DNA extraction experiments resulted in low to undetectable amounts of DNA due to soil chemistry-dependent soil-DNA interactions, namely adsorption to mineral surfaces, binding to divalent/trivalent cations, destruction by iron redox cycling, and acidic conditions. Subsequently, we developed soil-specific extraction protocols that increase DNA yields through a combination of desalting, utilization of competitive binders, and promotion of anaerobic conditions. Our results suggest that a combination of desalting and utilizing competitive binders may establish a "universal" nucleic acid extraction protocol suitable for analyzing samples from diverse soils on Mars. Key Words: Life-detection instruments-Nucleic acids-Mars-Panspermia. Astrobiology 17, 747-760.

Programming the Assembly of Unnatural Materials with Nucleic Acids

Science.gov (United States)

Mirkin, Chad

Nature directs the assembly of enormously complex and highly functional materials through an encoded class of biomolecules, nucleic acids. The establishment of a similarly programmable code for the construction of synthetic, unnatural materials would allow researchers to impart functionality by precisely positioning all material components. Although it is exceedingly difficult to control the complex interactions between atomic and molecular species in such a manner, interactions between nanoscale components can be directed through the ligands attached to their surface. Our group has shown that nucleic acids can be used as highly programmable surface ligands to control the spacing and symmetry of nanoparticle building blocks in structurally sophisticated and functional materials. These nucleic acids function as programmable ``bonds'' between nanoparticle ``atoms,'' analogous to a nanoscale genetic code for assembling materials. The sequence and length tunability of nucleic acid bonds has allowed us to define a powerful set of design rules for the construction of nanoparticle superlattices with more than 30 unique lattice symmetries, tunable defect structures and interparticle spacings, and several well-defined crystal habits. Further, the nature of the nucleic acid bond enables an additional level of structural control: temporal regulation of dynamic material response to external biomolecular and chemical stimuli. This control allows for the reversible transformation between thermodynamic states with different crystal symmetries, particle stoichiometries, thermal stabilities, and interparticle spacings on demand. Notably, our unique genetic approach affords functional nanoparticle architectures that, among many other applications, can be used to systematically explore and manipulate optoelectronic material properties, such as tunable interparticle plasmonic interactions, microstructure-directed energy emission, and coupled plasmonic and photonic modes.

John locke on personal identity.

Science.gov (United States)

Nimbalkar, Namita

2011-01-01

John Locke speaks of personal identity and survival of consciousness after death. A criterion of personal identity through time is given. Such a criterion specifies, insofar as that is possible, the necessary and sufficient conditions for the survival of persons. John Locke holds that personal identity is a matter of psychological continuity. He considered personal identity (or the self) to be founded on consciousness (viz. memory), and not on the substance of either the soul or the body.

John Locke on Personal Identity**

OpenAIRE

Nimbalkar, Namita

2011-01-01

John Locke speaks of personal identity and survival of consciousness after death. A criterion of personal identity through time is given. Such a criterion specifies, insofar as that is possible, the necessary and sufficient conditions for the survival of persons. John Locke holds that personal identity is a matter of psychological continuity. He considered personal identity (or the self) to be founded on consciousness (viz. memory), and not on the substance of either the soul or the body.

A DNA origami nanorobot controlled by nucleic acid hybridization.

Science.gov (United States)

Torelli, Emanuela; Marini, Monica; Palmano, Sabrina; Piantanida, Luca; Polano, Cesare; Scarpellini, Alice; Lazzarino, Marco; Firrao, Giuseppe

2014-07-23

A prototype for a DNA origami nanorobot is designed, produced, and tested. The cylindrical nanorobot (diameter of 14 nm and length of 48 nm) with a switchable flap, is able to respond to an external stimulus and reacts by a physical switch from a disarmed to an armed configuration able to deliver a cellular compatible message. In the tested design the robot weapon is a nucleic acid fully contained in the inner of the tube and linked to a single point of the internal face of the flap. Upon actuation the nanorobot moves the flap extracting the nucleic acid that assembles into a hemin/G-quadruplex horseradish peroxidase mimicking DNAzyme catalyzing a colorimetric reaction or chemiluminescence generation. The actuation switch is triggered by an external nucleic acid (target) that interacts with a complementary nucleic acid that is beard externally by the nanorobot (probe). Hybridization of probe and target produces a localized structural change that results in flap opening. The flap movement is studied on a two-dimensional prototype origami using Förster resonance energy transfer and is shown to be triggered by a variety of targets, including natural RNAs. The nanorobot has potential for in vivo biosensing and intelligent delivery of biological activators. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A DNA origami nanorobot controlled by nucleic acid hybridization

KAUST Repository

Torelli, Emanuela

2014-03-20

A prototype for a DNA origami nanorobot is designed, produced, and tested. The cylindrical nanorobot (diameter of 14 nm and length of 48 nm) with a switchable flap, is able to respond to an external stimulus and reacts by a physical switch from a disarmed to an armed configuration able to deliver a cellular compatible message. In the tested design the robot weapon is a nucleic acid fully contained in the inner of the tube and linked to a single point of the internal face of the flap. Upon actuation the nanorobot moves the flap extracting the nucleic acid that assembles into a hemin/G-quadruplex horseradish peroxidase mimicking DNAzyme catalyzing a colorimetric reaction or chemiluminescence generation. The actuation switch is triggered by an external nucleic acid (target) that interacts with a complementary nucleic acid that is beard externally by the nanorobot (probe). Hybridization of probe and target produces a localized structural change that results in flap opening. The flap movement is studied on a two-dimensional prototype origami using Förster resonance energy transfer and is shown to be triggered by a variety of targets, including natural RNAs. The nanorobot has potential for in vivo biosensing and intelligent delivery of biological activators. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Injection locking of optomechanical oscillators via acoustic waves

Science.gov (United States)

Huang, Ke; Hossein-Zadeh, Mani

2018-04-01

Injection locking is a powerful technique for synchronization of oscillator networks and controlling the phase and frequency of individual oscillators using similar or other types of oscillators. Here, we present the first demonstration of injection locking of a radiation-pressure driven optomechanical oscillator (OMO) via acoustic waves. As opposed to previously reported techniques (based on pump modulation or direct application of a modulated electrostatic force), injection locking of OMO via acoustic waves does not require optical power modulation or physical contact with the OMO and it can easily be implemented on various platforms. Using this approach we have locked the phase and frequency of two distinct modes of a microtoroidal silica OMO to a piezoelectric transducer (PZT). We have characterized the behavior of the injection locked OMO with three acoustic excitation configurations and showed that even without proper acoustic impedance matching the OMO can be locked to the PZT and tuned over 17 kHz with only -30 dBm of RF power fed to the PZT. The high efficiency, simplicity and scalability of the proposed approach paves the road toward a new class of photonic systems that rely on synchronization of several OMOs to a single or multiple RF oscillators with applications in optical communication, metrology and sensing. Beyond its practical applications, injection locking via acoustic waves can be used in fundamental studies in quantum optomechanics where thermal and optical isolation of the OMO are critical.

Taurolidine lock is superior to heparin lock in the prevention of catheter related bloodstream infections and occlusions.

Directory of Open Access Journals (Sweden)

Evelyn D Olthof

Full Text Available Patients on home parenteral nutrition (HPN are at risk for catheter-related complications; mainly infections and occlusions. We have previously shown in HPN patients presenting with catheter sepsis that catheter locking with taurolidine dramatically reduced re-infections when compared with heparin. Our HPN population therefore switched from heparin to taurolidine in 2008. The aim of the present study was to compare long-term effects of this catheter lock strategy on the occurrence of catheter-related bloodstream infections and occlusions in HPN patients.Data of catheter-related complications were retrospectively collected from 212 patients who received HPN between January 2000 and November 2011, comprising 545 and 200 catheters during catheter lock therapy with heparin and taurolidine, respectively. We evaluated catheter-related bloodstream infection and occlusion incidence rates using Poisson-normal regression analysis. Incidence rate ratios were calculated by dividing incidence rates of heparin by those of taurolidine, adjusting for underlying disease, use of anticoagulants or immune suppressives, frequency of HPN/fluid administration, composition of infusion fluids, and duration of HPN/fluid use before catheter creation.Bloodstream infection incidence rates were 1.1/year for heparin and 0.2/year for taurolidine locked catheters. Occlusion incidence rates were 0.2/year for heparin and 0.1/year for taurolidine locked catheters. Adjusted incidence ratios of heparin compared to taurolidine were 5.9 (95% confidence interval, 3.9-8.7 for bloodstream infections and 1.9 (95% confidence interval, 1.1-3.1 for occlusions.Given that no other procedural changes than the catheter lock strategy were implemented during the observation period, these data strongly suggest that taurolidine decreases catheter-related bloodstream infections and occlusions in HPN patients compared with heparin.

Coupled optical resonance laser locking.

Science.gov (United States)

Burd, S C; du Toit, P J W; Uys, H

2014-10-20

We have demonstrated simultaneous laser frequency stabilization of a UV and IR laser, to coupled transitions of ions in the same spectroscopic sample, by detecting only the absorption of the UV laser. Separate signals for locking the different lasers are obtained by modulating each laser at a different frequency and using lock-in detection of a single photodiode signal. Experimentally, we simultaneously lock a 369 nm and a 935 nm laser to the (2)S(1/2) → (2)(P(1/2) and (2)D(3/2) → (3)D([3/2]1/2) transitions, respectively, of Yb(+) ions generated in a hollow cathode discharge lamp. Stabilized lasers at these frequencies are required for cooling and trapping Yb(+) ions, used in quantum information and in high precision metrology experiments. This technique should be readily applicable to other ion and neutral atom systems requiring multiple stabilized lasers.

Genomic and Functional Characterization of the Unusual pLOCK 0919 Plasmid Harboring the spaCBA Pili Cluster in Lactobacillus casei LOCK 0919

Science.gov (United States)

Aleksandrzak-Piekarczyk, Tamara; Koryszewska-Bagińska, Anna; Grynberg, Marcin; Nowak, Adriana; Cukrowska, Bożena; Kozakova, Hana; Bardowski, Jacek

2016-01-01

Here, we report the extensive bioinformatic and functional analyses of the unusual pLOCK 0919, a plasmid originating from the probiotic Lactobacillus casei LOCK 0919 strain. This plasmid is atypical because it harbors the spaCBA-srtC gene cluster encoding SpaCBA pili. We show that all other spaCBA-srtC sequences of the Lactobacillus genus that have been previously described and deposited in GenBank are present in the chromosomal DNA. Another important observation for pLOCK 0919 is that the spaCBA-srtC gene cluster and its surrounding genes are highly similar to the respective DNA region that is present in the most well-known and active SpaCBA pili producer, the probiotic Lactobacillus rhamnosus GG strain. Our results demonstrate that the spaCBA-srtC clusters of pLOCK 0919 and L. rhamnosus GG are genealogically similar, located in DNA regions that are rich in transposase genes and are poorly conserved among the publicly available sequences of Lactobacillus sp. In contrast to chromosomally localized pilus gene clusters from L. casei and Lactobacillus paracasei, the plasmidic spaC of L. casei LOCK 0919 is expressed and undergoes a slight glucose-induced repression. Moreover, results of series of in vitro tests demonstrate that L. casei LOCK 0919 has an adhesion potential, which is largely determined by the presence of the pLOCK 0919 plasmid. In particular, the plasmid occurrence positively influenced the hydrophobicity and aggregation abilities of L. casei LOCK 0919. Moreover, in vivo studies indicate that among the three Lactobacillus strains used to colonize the gastrointestinal tract of germ-free mice, already after 2 days of colonization, L. casei LOCK 0919 became the dominant strain and persisted there for at least 48 days. PMID:26637469

Biomechanical comparison of double-row locking plates versus single- and double-row non-locking plates in a comminuted metacarpal fracture model.

Science.gov (United States)

Gajendran, Varun K; Szabo, Robert M; Myo, George K; Curtiss, Shane B

2009-12-01

Open or unstable metacarpal fractures frequently require open reduction and internal fixation. Locking plate technology has improved fixation of unstable fractures in certain settings. In this study, we hypothesized that there would be a difference in strength of fixation using double-row locking plates compared with single- and double-row non-locking plates in comminuted metacarpal fractures. We tested our hypothesis in a gap metacarpal fracture model simulating comminution using fourth-generation, biomechanical testing-grade composite sawbones. The metacarpals were divided into 6 groups of 15 bones each. Groups 1 and 4 were plated with a standard 6-hole, 2.3-mm plate in AO fashion. Groups 2 and 5 were plated with a 6-hole double-row 3-dimensional non-locking plate with bicortical screws aimed for convergence. Groups 3 and 6 were plated with a 6-hole double-row 3-dimensional locking plate with unicortical screws. The plated metacarpals were then tested to failure against cantilever apex dorsal bending (groups 1-3) and torsion (groups 4-6). The loads to failure in groups 1 to 3 were 198 +/- 18, 223 +/- 29, and 203 +/- 19 N, respectively. The torques to failure in groups 4 to 6 were 2,033 +/- 155, 3,190 +/- 235, and 3,161 +/- 268 N mm, respectively. Group 2 had the highest load to failure, whereas groups 5 and 6 shared the highest torques to failure (p row plates had equivalent bending and torsional stiffness, significantly higher than observed for the single-row non-locking plate. No other statistical differences were noted between groups. When subjected to the physiologically relevant forces of apex dorsal bending and torsion in a comminuted metacarpal fracture model, double-row 3-dimensional non-locking plates provided superior stability in bending and equivalent stability in torsion compared with double-row 3-dimensional locking plates, whereas single-row non-locking plates provided the least stability.

Analysis of peer-to-peer locking of magnetrons

International Nuclear Information System (INIS)

Pengvanich, P.; Lau, Y. Y.; Cruz, E.; Gilgenbach, R. M.; Hoff, B.; Luginsland, J. W.

2008-01-01

The condition for mutual, or peer-to-peer, locking of two magnetrons is derived. This condition reduces to Adler's classical phase-locking condition in the limit where one magnetron becomes the ''master'' and the other becomes the ''slave.'' The formulation is extended to the peer-to-peer locking of N magnetrons, under the assumption that the electromagnetic coupling among the N magnetrons is modeled by an N-port network.

Developing nucleic acid-based electrical detection systems

Directory of Open Access Journals (Sweden)

Gabig-Ciminska Magdalena

2006-03-01

Full Text Available Abstract Development of nucleic acid-based detection systems is the main focus of many research groups and high technology companies. The enormous work done in this field is particularly due to the broad versatility and variety of these sensing devices. From optical to electrical systems, from label-dependent to label-free approaches, from single to multi-analyte and array formats, this wide range of possibilities makes the research field very diversified and competitive. New challenges and requirements for an ideal detector suitable for nucleic acid analysis include high sensitivity and high specificity protocol that can be completed in a relatively short time offering at the same time low detection limit. Moreover, systems that can be miniaturized and automated present a significant advantage over conventional technology, especially if detection is needed in the field. Electrical system technology for nucleic acid-based detection is an enabling mode for making miniaturized to micro- and nanometer scale bio-monitoring devices via the fusion of modern micro- and nanofabrication technology and molecular biotechnology. The electrical biosensors that rely on the conversion of the Watson-Crick base-pair recognition event into a useful electrical signal are advancing rapidly, and recently are receiving much attention as a valuable tool for microbial pathogen detection. Pathogens may pose a serious threat to humans, animal and plants, thus their detection and analysis is a significant element of public health. Although different conventional methods for detection of pathogenic microorganisms and their toxins exist and are currently being applied, improvements of molecular-based detection methodologies have changed these traditional detection techniques and introduced a new era of rapid, miniaturized and automated electrical chip detection technologies into pathogen identification sector. In this review some developments and current directions in

ELB-trees - Efficient Lock-free B+trees

DEFF Research Database (Denmark)

Bonnichsen, Lars Frydendal; Karlsson, Sven; Probst, Christian W.

2014-01-01

As computer systems scale in the number of processors, data structures with good parallel performance become increasingly important. Lock-free data structures promise improved parallel performance at the expense of higher complexity and sequential execution time.We present ELBtrees, a new lock-fr...

Hew Locke: House of Cards

OpenAIRE

Reckitt, Helena; Joyce, Julie; Locke, Hew

2004-01-01

‘Hew Locke: House of Cards’ featured a selection of the artist's portraits of British royalty in various media, and his response to other trappings of the monarchy and empire. The show included works previously exhibited at the Luckman Gallery, Los Angeles, in tandem with a newly commissioned coat of arms, and other recent works. \\ud \\ud Locke draws from everyday sources, ranging from items found in London's Brixton Market to discount fabric shops and thrift stores. Other sources of inspirati...

Modeling of mode-locked coupled-resonator optical waveguide lasers

DEFF Research Database (Denmark)

Agger, Christian; Skovgård, Troels Suhr; Gregersen, Niels

2010-01-01

Coupled-resonator optical waveguides made from coupled high-Q photonic crystal nanocavities are investigated for use as cavities in mode-locked lasers. Such devices show great potential in slowing down light and can serve to reduce the cavity length of a mode-locked laser. An explicit expression...... of the emerging pulse train. A range of tuning around this frequency allows for effective mode locking. Finally, noise is added to the generalized single-cavity eigenfrequencies in order to evaluate the effects of fabrication imperfections on the cold-cavity transmission properties and consequently on the locking...

Gene Therapy for Advanced Melanoma: Selective Targeting and Therapeutic Nucleic Acids

Directory of Open Access Journals (Sweden)

Joana R. Viola

2013-01-01

Full Text Available Despite recent advances, the treatment of malignant melanoma still results in the relapse of the disease, and second line treatment mostly fails due to the occurrence of resistance. A wide range of mutations are known to prevent effective treatment with chemotherapeutic drugs. Hence, approaches with biopharmaceuticals including proteins, like antibodies or cytokines, are applied. As an alternative, regimens with therapeutically active nucleic acids offer the possibility for highly selective cancer treatment whilst avoiding unwanted and toxic side effects. This paper gives a brief introduction into the mechanism of this devastating disease, discusses the shortcoming of current therapy approaches, and pinpoints anchor points which could be harnessed for therapeutic intervention with nucleic acids. We bring the delivery of nucleic acid nanopharmaceutics into perspective as a novel antimelanoma therapeutic approach and discuss the possibilities for melanoma specific targeting. The latest reports on preclinical and already clinical application of nucleic acids in melanoma are discussed.

Comparative evaluation of 2.3 mm locking plate system vs conventional 2.0 mm non locking plate system for mandibular condyle fracture fixation: a seven year retrospective study.

Science.gov (United States)

Zhang, J; Wang, X; Wu, R-H; Zhuang, Q-W; Gu, Q P; Meng, J

2015-01-01

This retrospective study evaluated the efficacy of a 2.3 mm locking plate/screw system compared with a 2.0-mm non-locking plate/screw system in fixation of isolated non comminuted mandibular condyle fractures. Surgical records of 101 patients who received either a 2.3 mm locking plate (group A, n = 51) or 2.0 mm non locking plate (group B, n = 50) were analyzed. All patients were followed up to a minimum of 6 months postoperatively and evaluated for hardware related complications, occlusal stability, need for and duration of MMF and mandibular functional results. Four complications occurred in the locking group and eighteen in the non locking group with complication rates equalling 8% and 36% respectively. When comparing the overall results according to plates used, the χ2 test showed a statistically significant difference between the locking and non locking plates (p Mandibular condyle fractures treated with a 2.3 mm locking plate exhibited stable osteosynthesis, were associated with minimal complications and resulted in acceptable mandibular range of motion compared with a 2.0 mm non locking plate.

Triptycene: A Nucleic Acid Three-Way Junction Binder Scaffold

Science.gov (United States)

Yoon, Ina

Nucleic acids play a critical role in many biological processes such as gene regulation and replication. The development of small molecules that modulate nucleic acids with sequence or structure specificity would provide new strategies for regulating disease states at the nucleic acid level. However, this remains challenging mainly because of the nonspecific interactions between nucleic acids and small molecules. Three-way junctions are critical structural elements of nucleic acids. They are present in many important targets such as trinucleotide repeat junctions related to Huntington's disease, a temperature sensor sigma32 in E. coli, Dengue virus, and HIV. Triptycene-derived small molecules have been shown to bind to nucleic acid three-way junctions, resulting from their shape complementary. To develop a better understanding of designing molecules for targeting different junctions, a rapid screening of triptycene-based small molecules is needed. We envisioned that the installation of a linker at C9 position of the bicyclic core would allow for a rapid solid phase diversification. To achieve this aim, we synthesized 9-substituted triptycene scaffolds by using two different synthetic routes. The first synthetic route installed the linker from the amidation reaction between carboxylic acid at C9 position of the triptycene and an amine linker, beta-alanine ethyl ester. This new 9-substituted triptycene scaffold was then attached to a 2-chlorotrityl chloride resin for solid-phase diversification. This enabled a rapid diversification and an easy purification of mono-, di-, and tri-peptide triptycene derivatives. The binding affinities of these compounds were investigated towards a (CAG)˙(CTG) trinucleotide repeat junction. In the modified second synthetic route, we utilized a combined Heck coupling/benzyne Diels-Alder strategy. This improved synthetic strategy reduced the number of steps and total reaction times, increased the overall yield, improved solubilities of

Delay differential equations for mode-locked semiconductor lasers.

Science.gov (United States)

Vladimirov, Andrei G; Turaev, Dmitry; Kozyreff, Gregory

2004-06-01

We propose a new model for passive mode locking that is a set of ordinary delay differential equations. We assume a ring-cavity geometry and Lorentzian spectral filtering of the pulses but do not use small gain and loss and weak saturation approximations. By means of a continuation method, we study mode-locking solutions and their stability. We find that stable mode locking can exist even when the nonlasing state between pulses becomes unstable.

30 CFR 57.12068 - Locking transformer enclosures.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Locking transformer enclosures. 57.12068 Section 57.12068 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Electricity Surface Only § 57.12068 Locking transformer enclosures. Transformer enclosures shall be kept...

Correlations between locked modes and impurity influxes

Energy Technology Data Exchange (ETDEWEB)

Fishpool, G M [Commission of the European Communities, Abingdon (United Kingdom). JET Joint Undertaking; Lawson, K D [UKAEA Culham Lab., Abingdon (United Kingdom)

1994-07-01

An analysis of pulses that were disturbed by medium Z impurity influxes (Cl, Cr, Fe and Ni) recorded during the 91/92 JET operations, has demonstrated that such influxes can result in MHD modes which subsequently ``lock``. A correlation is found between the power radiated by the influx and the time difference between the start of the influx and the beginning of the locked mode. The growth in the amplitude of the locked mode itself can lead to further impurity influxes. A correlation is noted between intense influxes (superior to 10 MW) and the mode ``unlocking``. (authors). 4 refs., 4 figs.

Squeezing in an injection-locked semiconductor laser

Science.gov (United States)

Inoue, S.; Machida, S.; Yamamoto, Y.; Ohzu, H.

1993-09-01

The intensity-noise properties of an injection-locked semiconductor laser were studied experimentally. The constant-current-driven semiconductor laser producing the amplitude-squeezed state whose intensity noise was reduced below the standard quantum limit (SQL) by 0.72 dB was injection-locked by an external master laser. The measured intensity-noise level of the injection-locked semiconductor laser was 0.91 dB below the SQL. This experimental result indicates that a phase-coherent amplitude-squeezed state or squeezed vacuum state together with a reference local oscillator wave can be generated directly by semiconductor laser systems.

Mutual phase-locking of planar nano-oscillators

Directory of Open Access Journals (Sweden)

K. Y. Xu

2014-06-01

Full Text Available Characteristics of phase-locking between Gunn effect-based planar nano-oscillators are studied using an ensemble Monte Carlo (EMC method. Directly connecting two oscillators in close proximity, e.g. with a channel distance of 200 nm, only results in incoherent oscillations. In order to achieve in-phase oscillations, additional considerations must be taken into account. Two coupling paths are shown to exist between oscillators. One coupling path results in synchronization and the other results in anti-phase locking. The coupling strength through these two paths can be adjusted by changing the connections between oscillators. When two identical oscillators are in the anti-phase locking regime, fundamental components of oscillations are cancelled. The resulting output consists of purely second harmonic oscillations with a frequency of about 0.66 THz. This type of second harmonic generation is desired for higher frequency applications since no additional filter system is required. This transient phase-locking process is further analyzed using Adler's theory. The locking range is extracted, and a criterion for the channel length difference required for realizing phased arrays is obtained. This work should aid in designing nano-oscillator arrays for high power applications and developing directional transmitters for wireless communications.

Sensitive detection of porcine DNA in processed animal proteins using a TaqMan real-time PCR assay.

Science.gov (United States)

Pegels, N; González, I; Fernández, S; García, T; Martín, R

2012-01-01

A TaqMan real-time PCR method was developed for specific detection of porcine-prohibited material in industrial feeds. The assay combines the use of a porcine-specific primer pair, which amplifies a 79 bp fragment of the mitochondrial (mt) 12 S rRNA gene, and a locked nucleic acid (LNA) TaqMan probe complementary to a target sequence lying between the porcine-specific primers. The nuclear 18 S rRNA gene system, yielding a 77 bp amplicon, was employed as a positive amplification control to monitor the total content of amplifiable DNA in the samples. The specificity of the porcine primers-probe system was verified against different animal and plant species, including mammals, birds and fish. The applicability of the real-time PCR protocol to detect the presence of porcine mt DNA in feeds was determined through the analysis of 190 industrial feeds (19 known reference and 171 blind samples) subjected to stringent processing treatments. The performance of the method allows qualitative and highly sensitive detection of short fragments from porcine DNA in all the industrial feeds declared to contain porcine material. Although the method has quantitative potential, the real quantitative capability of the assay is limited by the existing variability in terms of composition and processing conditions of the feeds, which affect the amount and quality of amplifiable DNA.

Fluorescence In Situ Hybridization for MicroRNA Detection in Archived Oral Cancer Tissues

Directory of Open Access Journals (Sweden)

Zonggao Shi

2012-01-01

Full Text Available The noncoding RNA designated as microRNA (miRNA is a large group of small single-stranded regulatory RNA and has generated wide-spread interest in human disease studies. To facilitate delineating the role of microRNAs in cancer pathology, we sought to explore the feasibility of detecting microRNA expression in formalin-fixed paraffin-embedded (FFPE tissues. Using FFPE materials, we have compared fluorescent in situ hybridization (FISH procedures to detect miR-146a with (a different synthetic probes: regular custom DNA oligonucleotides versus locked nucleic acid (LNA incorporated DNA oligonucleotides; (b different reporters for the probes: biotin versus digoxigenin (DIG; (c different visualization: traditional versus tyramide signal amplification (TSA system; (d different blocking reagents for endogenous peroxidase. Finally, we performed miR-146a FISH on a commercially available oral cancer tissue microarray, which contains 40 cases of oral squamous cell carcinoma (OSCC and 10 cases of normal epithelia from the human oral cavity. A sample FISH protocol for detecting miR-146a is provided. In summary, we have established reliable in situ hybridization procedures for detecting the expression of microRNA in FFPE oral cancer tissues. This method is an important tool for studies on the involvement of microRNA in oral cancer pathology and may have potential prognostic or diagnostic value.

Antineoplastic Effect of Decoy Oligonucleotide Derived from MGMT Enhancer

Science.gov (United States)

Refael, Miri; Zrihan, Daniel; Siegal, Tali; Lavon, Iris

2014-01-01

Silencing of O(6)-methylguanine-DNA-methyltransferase (MGMT) in tumors, mainly through promoter methylation, correlates with a better therapeutic response and with increased survival. Therefore, it is conceivable to consider MGMT as a potential therapeutic target for the treatment of cancers. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through p65/NF-kappaB homodimers. Here we show that the non-canonical NF-KappaB motif (MGMT-kappaB1) within MGMT enhancer is probably the major inducer of MGMT expression following NF-kappaB activation. Thus, in an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA) modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN). Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to the NF-KappaB motif within MGMT enhancer, the efficacy of the decoy was studied in-vitro and in-vivo. The results of these experiments show that the decoy MGMT-kB1-LODN have a substantial antineoplastic effect when used either in combination with temozolomide or as monotherapy. Our results suggest that MGMT-kB1-LODN may provide a novel strategy for cancer therapy. PMID:25460932

Antineoplastic effect of decoy oligonucleotide derived from MGMT enhancer.

Directory of Open Access Journals (Sweden)

Tamar Canello

Full Text Available Silencing of O(6-methylguanine-DNA-methyltransferase (MGMT in tumors, mainly through promoter methylation, correlates with a better therapeutic response and with increased survival. Therefore, it is conceivable to consider MGMT as a potential therapeutic target for the treatment of cancers. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through p65/NF-kappaB homodimers. Here we show that the non-canonical NF-KappaB motif (MGMT-kappaB1 within MGMT enhancer is probably the major inducer of MGMT expression following NF-kappaB activation. Thus, in an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN. Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to the NF-KappaB motif within MGMT enhancer, the efficacy of the decoy was studied in-vitro and in-vivo. The results of these experiments show that the decoy MGMT-kB1-LODN have a substantial antineoplastic effect when used either in combination with temozolomide or as monotherapy. Our results suggest that MGMT-kB1-LODN may provide a novel strategy for cancer therapy.

Histidine-lysine peptides as carriers of nucleic acids.

Science.gov (United States)

Leng, Qixin; Goldgeier, Lisa; Zhu, Jingsong; Cambell, Patricia; Ambulos, Nicholas; Mixson, A James

2007-03-01

With their biodegradability and diversity of permutations, peptides have significant potential as carriers of nucleic acids. This review will focus on the sequence and branching patterns of peptide carriers composed primarily of histidines and lysines. While lysines within peptides are important for binding to the negatively charged phosphates, histidines are critical for endosomal lysis enabling nucleic acids to reach the cytosol. Histidine-lysine (HK) polymers by either covalent or ionic bonds with liposomes augment transfection compared to liposome carriers alone. More recently, we have examined peptides as sole carriers of nucleic acids because of their intrinsic advantages compared to the bipartite HK/liposome carriers. With a protocol change and addition of a histidine-rich tail, HK peptides as sole carriers were more effective than liposomes alone in several cell lines. While four-branched polymers with a primary repeating sequence pattern of -HHK- were more effective as carriers of plasmids, eight-branched polymers with a sequence pattern of -HHHK- were more effective as carriers of siRNA. Compared to polyethylenimine, HK carriers of siRNA and plasmids had reduced toxicity. When injected intravenously, HK polymers in complex with plasmids encoding antiangiogenic proteins significantly decreased tumor growth. Furthermore, modification of HK polymers with polyethylene glycol and vascular-specific ligands increased specificity of the polyplex to the tumor by more than 40-fold. Together with further development and insight on the structure of HK polyplexes, HK peptides may prove to be useful as carriers of different forms of nucleic acids both in vitro and in vivo.

Experimental implementation of phase locking in a nonlinear interferometer

Energy Technology Data Exchange (ETDEWEB)

Wang, Hailong; Jing, Jietai, E-mail: jtjing@phy.ecnu.edu.cn [State Key Laboratory of Precision Spectroscopy, Department of Physics, East China Normal University, Shanghai 200062 (China); Marino, A. M. [Homer L. Dodge Department of Physics and Astronomy, The University of Oklahoma, 440 West Brooks Street, Norman, Oklahoma 73019 (United States)

2015-09-21

Based upon two cascade four-wave mixing processes in two identical hot rubidium vapor cells, a nonlinear interferometer has been experimentally realized [Jing et al., Appl. Phys. Lett. 99, 011110 (2011); Hudelist et al., Nat. Commun. 5, 3049 (2014)]. It has a higher degree of phase sensitivity than a traditional linear interferometer and has many potential applications in quantum metrology. Phase locking of the nonlinear interferometer is needed before it can find its way into applications. In this letter, we investigate the experimental implementation of phase locking of the relative phase between the three beams at different frequencies involved in such a nonlinear interferometer. We have utilized two different methods, namely, beat note locking and coherent modulation locking. We find that coherent modulation locking can achieve much better phase stability than beat note locking in our system. Our results pave the way for real applications of a nonlinear interferometer in precision measurement and quantum manipulation, for example, phase control in phase-sensitive N-wave mixing process, N-port nonlinear interferometer and quantum-enhanced real-time phase tracking.

Locked doors in acute inpatient psychiatry: a literature review.

Science.gov (United States)

van der Merwe, M; Bowers, L; Jones, J; Simpson, A; Haglund, K

2009-04-01

Many acute inpatient psychiatric wards in the UK are permanently locked, although this is contrary to the current Mental Health Act Code of Practice. To conduct a literature review of empirical articles concerning locked doors in acute psychiatric inpatient wards, an extensive literature search was performed in SAGE Journals Online, EBM Reviews, British Nursing Index, CINAHL, EMBASE Psychiatry, International Bibliography of the Social Sciences, Ovid MEDLINE, PsycINFO and Google, using the search terms 'open$', 'close$', '$lock$', 'door', 'ward', 'hospital', 'psychiatr', 'mental health', 'inpatient' and 'asylum'. A total of 11 empirical papers were included in the review. Both staff and patients reported advantages (e.g. preventing illegal substances from entering the ward and preventing patients from absconding and harming themselves or others) and disadvantages (e.g. making patients feel depressed, confined and creating extra work for staff) regarding locked doors. Locked wards were associated with increased patient aggression, poorer satisfaction with treatment and more severe symptoms. The limited literature available showed the urgent need for research to determine the real effects of locked doors in inpatient psychiatry.

Assessment for Melting Temperature Measurement of Nucleic Acid by HRM.

Science.gov (United States)

Wang, Jing; Pan, Xiaoming; Liang, Xingguo

2016-01-01

High resolution melting (HRM), with a high sensitivity to distinguish the nucleic acid species with small variations, has been widely applied in the mutation scanning, methylation analysis, and genotyping. For the aim of extending HRM for the evaluation of thermal stability of nucleic acid secondary structures on sequence dependence, we investigated effects of the dye of EvaGreen, metal ions, and impurities (such as dNTPs) on melting temperature ( T m ) measurement by HRM. The accuracy of HRM was assessed as compared with UV melting method, and little difference between the two methods was found when the DNA T m was higher than 40°C. Both insufficiency and excessiveness of EvaGreen were found to give rise to a little bit higher T m , showing that the proportion of dye should be considered for precise T m measurement of nucleic acids. Finally, HRM method was also successfully used to measure T m s of DNA triplex, hairpin, and RNA duplex. In conclusion, HRM can be applied in the evaluation of thermal stability of nucleic acid (DNA or RNA) or secondary structural elements (even when dNTPs are present).

Delivery Systems for In Vivo use of Nucleic Acid Drugs

Directory of Open Access Journals (Sweden)

Resende R.R

2007-01-01

Full Text Available The notorious biotechnological advance of the last few decades has allowed the development of experimental methods for understanding molecular mechanisms of genes and new therapeutic approaches. Gene therapy is maturing into a viable, practical method with the potential to cure a variety of human illnesses. Some nucleic-acid-based drugs are now available for controlling the progression of genetic diseases by inhibiting gene expression or the activity of their gene products. New therapeutic strategies employ a wide range of molecular tools such as bacterial plasmids containing transgenic inserts, RNA interference aptamers. A nucleic-acid based constitution confers a lower immunogenic potential and as result of the high stringency selection of large molecular variety, these drugs have high affi nity and selectivity for their targets. However, nucleic acids have poor biostability thus requiring chemical modifications and delivery systems to maintain their activity and ease their cellular internalization. This review discusses some of the mechanisms of action and the application of therapies based on nucleic acids such as aptamers and RNA interference as well as platforms for cellular uptake and intracellular delivery of therapeutic oligonucleotides and their trade-offs.

QPSK regeneration without active phase-locking

DEFF Research Database (Denmark)

Kjøller, Niels-Kristian; Da Ros, Francesco; Røge, Kasper Meldgaard

2016-01-01

QPSK regeneration without active phase stabilization is investigated in numerical simulations. We propose an improved scheme for phase-locking free QPSK regeneration showing significant improvements in the error vector magnitude of the signal.......QPSK regeneration without active phase stabilization is investigated in numerical simulations. We propose an improved scheme for phase-locking free QPSK regeneration showing significant improvements in the error vector magnitude of the signal....

Nanoparticulate systems for nucleic acid delivery

NARCIS (Netherlands)

Varkouhi, A.K.

2011-01-01

Development of carrier systems with controllable physicochemical and delivery properties has opened up the possibility of nanomedicines containing nucleic acids. In the last decades, much effort has been dedicated to two exciting approaches in biomedicine, namely gene and RNA interference

Localization of Bovine Papillomavirus Nucleic Acid in Equine Sarcoids.

Science.gov (United States)

Gaynor, A M; Zhu, K W; Dela Cruz, F N; Affolter, V K; Pesavento, P A

2016-05-01

Bovine papillomaviruses (BPV1/BPV2) have long been associated with equine sarcoids; deciphering their contribution has been difficult due to their ubiquitous presence on skin and in the environment, as well as the lack of decent techniques to interrogate their role in pathogenesis. We have developed and characterized an in situ hybridization (ISH) assay that uses a pool of probes complementary to portions of the E5, E6, and E7 genes. This assay is highly sensitive for direct visualization of viral transcript and nucleic acid in routinely processed histopathologic samples. We demonstrate here the visualization of BPV nucleic acid in 18 of 18 equine sarcoids, whereas no detectable viral DNA was present in 15 of 15 nonsarcoid controls by this technique. In nearly 90% (16/18) of the sarcoids, 50% or more of the fibroblastic cell nuclei distributed throughout the neoplasm had detectable hybridization. In the remaining 2 cases, fewer than half of the fibroblastic cells contained detectable hybridization, but viral nucleic acid was also detected in epithelial cells of the sebaceous glands, hair follicles and epidermis. A sensitive ISH assay is an indispensable addition to the molecular methods used to detect viral nucleic acid in tissue. We have used this technique to determine the specific cellular localization and distribution of BPV in a subset of equine sarcoids. © The Author(s) 2015.

A Digital Phase Lock Loop for an External Cavity Diode Laser

Science.gov (United States)

Wang, Xiao-Long; Tao, Tian-Jiong; Cheng, Bing; Wu, Bin; Xu, Yun-Fei; Wang, Zhao-Ying; Lin, Qiang

2011-08-01

A digital optical phase lock loop (OPLL) is implemented to synchronize the frequency and phase between two external cavity diode lasers (ECDL), generating Raman pulses for atom interferometry. The setup involves all-digital phase detection and a programmable digital proportional-integral-derivative (PID) loop in locking. The lock generates a narrow beat-note linewidth below 1 Hz and low phase-noise of 0.03rad2 between the master and slave ECDLs. The lock proves to be stable and robust, and all the locking parameters can be set and optimized on a computer interface with convenience, making the lock adaptable to various setups of laser systems.

Recent advances in delivery of drug-nucleic acid combinations for cancer treatment.

Science.gov (United States)

Li, Jing; Wang, Yan; Zhu, Yu; Oupický, David

2013-12-10

Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers. Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities like surgery or radiation. However, despite the widespread clinical use of combination therapies, relatively little attention has been given to the potential of modern nanocarrier delivery methods, like liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments. This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small molecule drugs. The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents. This review discusses recent advances in the development of delivery methods using combinations of small molecule drugs and nucleic acid therapeutics to treat cancer. This review primarily focuses on the rationale used for selecting appropriate drug-nucleic acid combinations as well as progress in the development of nanocarriers suitable for simultaneous delivery of drug-nucleic acid combinations. Copyright © 2013 Elsevier B.V. All rights reserved.

Nucleic Acid Extraction from Synthetic Mars Analog Soils for in situ Life Detection

Science.gov (United States)

Mojarro, Angel; Ruvkun, Gary; Zuber, Maria T.; Carr, Christopher E.

2017-08-01

Biological informational polymers such as nucleic acids have the potential to provide unambiguous evidence of life beyond Earth. To this end, we are developing an automated in situ life-detection instrument that integrates nucleic acid extraction and nanopore sequencing: the Search for Extra-Terrestrial Genomes (SETG) instrument. Our goal is to isolate and determine the sequence of nucleic acids from extant or preserved life on Mars, if, for example, there is common ancestry to life on Mars and Earth. As is true of metagenomic analysis of terrestrial environmental samples, the SETG instrument must isolate nucleic acids from crude samples and then determine the DNA sequence of the unknown nucleic acids. Our initial DNA extraction experiments resulted in low to undetectable amounts of DNA due to soil chemistry-dependent soil-DNA interactions, namely adsorption to mineral surfaces, binding to divalent/trivalent cations, destruction by iron redox cycling, and acidic conditions. Subsequently, we developed soil-specific extraction protocols that increase DNA yields through a combination of desalting, utilization of competitive binders, and promotion of anaerobic conditions. Our results suggest that a combination of desalting and utilizing competitive binders may establish a "universal" nucleic acid extraction protocol suitable for analyzing samples from diverse soils on Mars.

Identification of nucleic acid binding sites on translin-associated factor X (TRAX protein.

Directory of Open Access Journals (Sweden)

Gagan Deep Gupta

Full Text Available Translin and TRAX proteins play roles in very important cellular processes such as DNA recombination, spatial and temporal expression of mRNA, and in siRNA processing. Translin forms a homomeric nucleic acid binding complex and binds to ssDNA and RNA. However, a mutant translin construct that forms homomeric complex lacking nucleic acid binding activity is able to form fully active heteromeric translin-TRAX complex when co-expressed with TRAX. A substantial progress has been made in identifying translin sites that mediate its binding activity, while TRAX was thought not to bind DNA or RNA on its own. We here for the first time demonstrate nucleic acid binding to TRAX by crosslinking radiolabeled ssDNA to heteromeric translin-TRAX complex using UV-laser. The TRAX and translin, photochemically crosslinked with ssDNA, were individually detected on SDS-PAGE. We mutated two motifs in TRAX and translin, designated B2 and B3, to help define the nucleic acid binding sites in the TRAX sequence. The most pronounced effect was observed in the mutants of B3 motif that impaired nucleic acid binding activity of the heteromeric complexes. We suggest that both translin and TRAX are binding competent and contribute to the nucleic acid binding activity.

Identification of Nucleic Acid Binding Sites on Translin-Associated Factor X (TRAX) Protein

Science.gov (United States)

Gupta, Gagan Deep; Kumar, Vinay

2012-01-01

Translin and TRAX proteins play roles in very important cellular processes such as DNA recombination, spatial and temporal expression of mRNA, and in siRNA processing. Translin forms a homomeric nucleic acid binding complex and binds to ssDNA and RNA. However, a mutant translin construct that forms homomeric complex lacking nucleic acid binding activity is able to form fully active heteromeric translin-TRAX complex when co-expressed with TRAX. A substantial progress has been made in identifying translin sites that mediate its binding activity, while TRAX was thought not to bind DNA or RNA on its own. We here for the first time demonstrate nucleic acid binding to TRAX by crosslinking radiolabeled ssDNA to heteromeric translin-TRAX complex using UV-laser. The TRAX and translin, photochemically crosslinked with ssDNA, were individually detected on SDS-PAGE. We mutated two motifs in TRAX and translin, designated B2 and B3, to help define the nucleic acid binding sites in the TRAX sequence. The most pronounced effect was observed in the mutants of B3 motif that impaired nucleic acid binding activity of the heteromeric complexes. We suggest that both translin and TRAX are binding competent and contribute to the nucleic acid binding activity. PMID:22427937

Phase-locked loops. [in analog and digital circuits communication system

Science.gov (United States)

Gupta, S. C.

1975-01-01

An attempt to systematically outline the work done in the area of phase-locked loops which are now used in modern communication system design is presented. The analog phase-locked loops are well documented in several books but discrete, analog-digital, and digital phase-locked loop work is scattered. Apart from discussing the various analysis, design, and application aspects of phase-locked loops, a number of references are given in the bibliography.

Pressure locking and thermal binding of gate valves

Energy Technology Data Exchange (ETDEWEB)

Kelly, E.M.

1996-12-01

Pressure locking and thermal binding represent potential common mode failure mechanisms that can cause safety-related power-operated gate valves to fail in the closed position, thus rendering redundant safety-related systems incapable of performing their safety functions. Supplement 6 to Generic Letter 89-10, {open_quotes}Safety-Related Motor-Operated Gate Valve Testing and Surveillance,{close_quotes} provided an acceptable approach to addressing pressure locking and thermal binding of gate valves. More recently, the NRC has issued Generic Letter 95-07, {open_quotes}Pressure Locking and Thermal Binding of Safety-Related Power-Operated Gate Valves,{close_quotes} to request that licensees take certain actions to ensure that safety-related power-operated gate valves that are susceptible to pressure locking or thermal binding are capable of performing their safety functions within the current licensing bases. Over the past two years, several plants in Region I determined that valves in certain systems were potentially susceptible to pressure locking and thermal binding, and have taken various corrective actions. The NRC Region I Systems Engineering Branch has been actively involved in the inspection of licensee actions in response to the pressure locking and thermal binding issue. Region I continues to maintain an active involvement in this area, including participation with the Office of Nuclear Reactor Regulation in reviewing licensee responses to Generic Letter 95-07.

High-Order Frequency-Locked Loops

DEFF Research Database (Denmark)

Golestan, Saeed; Guerrero, Josep M.; Quintero, Juan Carlos Vasquez

2017-01-01

In very recent years, some attempts for designing high-order frequency-locked loops (FLLs) have been made. Nevertheless, the advantages and disadvantages of these structures, particularly in comparison with a standard FLL and high-order phase-locked loops (PLLs), are rather unclear. This lack...... study, and its small-signal modeling, stability analysis, and parameter tuning are presented. Finally, to gain insight about advantages and disadvantages of high-order FLLs, a theoretical and experimental performance comparison between the designed second-order FLL and a standard FLL (first-order FLL...

Mode-locked silicon evanescent lasers.

Science.gov (United States)

Koch, Brian R; Fang, Alexander W; Cohen, Oded; Bowers, John E

2007-09-03

We demonstrate electrically pumped lasers on silicon that produce pulses at repetition rates up to 40 GHz. The mode locked lasers generate 4 ps pulses with low jitter and extinction ratios above 18 dB, making them suitable for data and telecommunication transmitters and for clock generation and distribution. Results of both passive and hybrid mode locking are discussed. This type of device could enable new silicon based integrated technologies, such as optical time division multiplexing (OTDM), wavelength division multiplexing (WDM), and optical code division multiple access (OCDMA).

Novel fluorescent nanoparticles for ultrasensitive identification of nucleic acids by optical methods

DEFF Research Database (Denmark)

Mulberg, Mads Westergaard; Taskova, Maria; Thomsen, Rasmus P.

2017-01-01

For decades, the detection of nucleic acids and their interactions at low abundances has been a challenging task. Present nucleic acid diagnostics are primarily based on enzymatic reactions including sequencing, polymerase-chain reaction and microarrays. However, the use of enzymatic amplificatio...

More, smaller bacteria in response to ocean's warming?

KAUST Repository

Moran, Xose Anxelu G.

2015-06-10

Heterotrophic bacteria play a major role in organic matter cycling in the ocean. Although the high abundances and relatively fast growth rates of coastal surface bacterioplankton make them suitable sentinels of global change, past analyses have largely overlooked this functional group. Here, time series analysis of a decade of monthly observations in temperate Atlantic coastal waters revealed strong seasonal patterns in the abundance, size and biomass of the ubiquitous flow-cytometric groups of low (LNA) and high nucleic acid (HNA) content bacteria. Over this relatively short period, we also found that bacterioplankton cells were significantly smaller, a trend that is consistent with the hypothesized temperature-driven decrease in body size. Although decadal cell shrinking was observed for both groups, it was only LNA cells that were strongly coherent, with ecological theories linking temperature, abundance and individual size on both the seasonal and interannual scale. We explain this finding because, relative to their HNA counterparts, marine LNA bacteria are less diverse, dominated by members of the SAR11 clade. Temperature manipulation experiments in 2012 confirmed a direct effect of warming on bacterial size. Concurrent with rising temperatures in spring, significant decadal trends of increasing standing stocks (3% per year) accompanied by decreasing mean cell size (-1% per year) suggest a major shift in community structure, with a larger contribution of LNA bacteria to total biomass. The increasing prevalence of these typically oligotrophic taxa may severely impact marine foodwebs and carbon fluxes by an overall decrease in the efficiency of the biological pump. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Nucleic acid compositions and the encoding proteins

Science.gov (United States)

Preston, III, James F.; Chow, Virginia; Nong, Guang; Rice, John D.; St. John, Franz J.

2014-09-02

The subject invention provides at least one nucleic acid sequence encoding an aldouronate-utilization regulon isolated from Paenibacillus sp. strain JDR-2, a bacterium which efficiently utilizes xylan and metabolizes aldouronates (methylglucuronoxylosaccharides). The subject invention also provides a means for providing a coordinately regulated process in which xylan depolymerization and product assimilation are coupled in Paenibacillus sp. strain JDR-2 to provide a favorable system for the conversion of lignocellulosic biomass to biobased products. Additionally, the nucleic acid sequences encoding the aldouronate-utilization regulon can be used to transform other bacteria to form organisms capable of producing a desired product (e.g., ethanol, 1-butanol, acetoin, 2,3-butanediol, 1,3-propanediol, succinate, lactate, acetate, malate or alanine) from lignocellulosic biomass.

Experimental study on working characteristics of density lock

International Nuclear Information System (INIS)

Sun Furong; Yan Changqi; Gu Haifeng

2011-01-01

The working principle of density lock was introduced in this paper, and the experimental loop was built so that researches on working performance of density lock in the system were done at steady-state operation and pump trip conditions. The results show that at steady-state operation conditions, density lock can keep close in a long run, which will separate passive residual heat removal circuit from primary circuit. As a result, passive residual heat removal circuit is in the non-operating conditions, which dose not influence normal operation of reactors. At the pump trip conditions, density lock can be automatically opened quickly, which will make primary and passive residual heat removal system communicated. The natural circulation is well established in the two systems, and is enough to ensure removal of residual heat. (authors)

Development of thermal actuators with multi-locking positions

Science.gov (United States)

Luo, J. K.; Zhu, Y.; Fu, Y. Q.; Flewitt, A. J.; Spearing, S. M.; Miao, J. M.; Milne, W. I.

2006-04-01

To reduce power consumption and operation temperature for micro-thermal actuators, metal-based micro-mechanical locks with multi-locking positions were analyzed and fabricated. The micro-locks consist of two or three U-shaped thermal actuators. The devices were made by a single mask process using electroplated Ni as the active material. Tests showed that the metal based thermal actuators deliver a maximum displacement of ~20µm at a much lower temperature than that of Si-based actuators. However Ni-actuators showed a severe back bending, which increases with increasing applied power. The temperature to initiate the back bending is as low as ~240°C. Back bending increases the distance between the two actuators, and leads to locking function failure. For practical application, Ni-based thermal actuators must be operated below 200°C.

Active stabilization of a diode laser injection lock.

Science.gov (United States)

Saxberg, Brendan; Plotkin-Swing, Benjamin; Gupta, Subhadeep

2016-06-01

We report on a device to electronically stabilize the optical injection lock of a semiconductor diode laser. Our technique uses as discriminator the peak height of the laser's transmission signal on a scanning Fabry-Perot cavity and feeds back to the diode current, thereby maintaining maximum optical power in the injected mode. A two-component feedback algorithm provides constant optimization of the injection lock, keeping it robust to slow thermal drifts and allowing fast recovery from sudden failures such as temporary occlusion of the injection beam. We demonstrate the successful performance of our stabilization method in a diode laser setup at 399 nm used for laser cooling of Yb atoms. The device eases the requirements on passive stabilization and can benefit any diode laser injection lock application, particularly those where several such locks are employed.

A Digital Phase Lock Loop for an External Cavity Diode Laser

International Nuclear Information System (INIS)

Wang Xiao-Long; Tao Tian-Jiong; Cheng Bing; Wu Bin; Xu Yun-Fei; Wang Zhao-Ying; Lin Qiang

2011-01-01

A digital optical phase lock loop (OPLL) is implemented to synchronize the frequency and phase between two external cavity diode lasers (ECDL), generating Raman pulses for atom interferometry. The setup involves all-digital phase detection and a programmable digital proportional-integral-derivative (PID) loop in locking. The lock generates a narrow beat-note linewidth below 1 Hz and low phase-noise of 0.03rad 2 between the master and slave ECDLs. The lock proves to be stable and robust, and all the locking parameters can be set and optimized on a computer interface with convenience, making the lock adaptable to various setups of laser systems. (fundamental areas of phenomenology(including applications))

Navigation Study, Colorado Locks, Colorado River, Matagorda, Texas

National Research Council Canada - National Science Library

McCollum, Randy

2000-01-01

A 1:70 physical navigation model was built to replicate the Matagorda Locks, approximately one mile of the GIWW east of the locks, approximately one-half mile of the Colorado River north of the GIWW...

A locking compression plate versus the gold-standard non-locking plate with lag screw for first metatarsophalangeal fusion: A biomechanical comparison.

Science.gov (United States)

Mandell, Daniel; Karbassi, John; Zhou, Hanbing; Burroughs, Brian; Aurigemma, Philip; Patel, Abhay R

2018-03-01

The treatment of end-stage first metatarso-phalangeal joint (MTP) arthritis has been arthrodesis. A dorsal non-locking plate with a lag screw has been the standard traditional fixation method. This study compares the biomechanical strength of a locking compression plate (LCP) with and without internal compression versus this known gold standard. In group 1, six matched pairs of cadaver great toes were used to compare the standard non-locking dorsal plate and 3.5mm lag screw to an anatomic locking compression plate in which a lag screw was utilized rather than the internal compression features of the plate. In group 2, another six matched pairs of cadaver great toes were used to compare the gold standard to the locking compression plate, utilizing the plate's internal compression feature instead of a lag screw. A material testing system (MTS) machine applied loads to the MTP joints and measured displacement and stiffness of the constructs. The stiffness of the constructs (Young's modulus) was calculated from the force-displacement curves, and the displacement was measured. The locking compression plate group that used the compression features of the plate, without the lag screw, had less joint displacement and higher stiffness than control (p<0.05). The same plating construct in which a lag screw was used rather than internal compression of the plate was found to be stiffer than the control (p<0.05), but displacement was not statistically significant. The results suggest that a locking compression plate alone provides the stiffest construct for a first MTP joint fusion. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spatially resolved detection of mutually locked Josephson junctions in arrays

International Nuclear Information System (INIS)

Keck, M.; Doderer, T.; Huebener, R.P.; Traeuble, T.; Dolata, R.; Weimann, T.; Niemeyer, J.

1997-01-01

Mutual locking due to the internal coupling in two-dimensional arrays of Josephson junctions was investigated. The appearance of Shapiro steps in the current versus voltage curve of a coupled on-chip detector junction is used to indicate coherent oscillations in the array. A highly coherent state is observed for some range of the array bias current. By scanning the array with a low-power electron beam, mutually locked junctions remain locked while the unlocked junctions generate a beam-induced additional voltage drop at the array. This imaging technique allows the detection of the nonlocked or weakly locked Josephson junctions in a (partially) locked array state. copyright 1997 American Institute of Physics

Locking of metacarpophalangeal joints in a patient with acromegaly

Energy Technology Data Exchange (ETDEWEB)

Tani, Y.; Tanaka, N.; Isoya, Eiji [Dept. of Orthopaedic Surgery, Soseikai General Hospital, Kyoto (Japan)

1999-11-01

A 39-year-old man with acromegaly exhibited locking of metacarpophalangeal (MCP) joints of both index fingers. Large osteophytes were found at the metacarpal heads by radiography and computerized tomography (CT). Magnetic resonance (MR) images revealed hypertrophy of volar plates. We suggest that these characteristic acromegalic features caused locking of MCP joints. Surgery was required on one of the joints to release the locking. (orig.)

Locking of metacarpophalangeal joints in a patient with acromegaly

International Nuclear Information System (INIS)

Tani, Y.; Tanaka, N.; Isoya, Eiji

1999-01-01

A 39-year-old man with acromegaly exhibited locking of metacarpophalangeal (MCP) joints of both index fingers. Large osteophytes were found at the metacarpal heads by radiography and computerized tomography (CT). Magnetic resonance (MR) images revealed hypertrophy of volar plates. We suggest that these characteristic acromegalic features caused locking of MCP joints. Surgery was required on one of the joints to release the locking. (orig.)

Neural Network Prediction of Disruptions Caused by Locked Modes on J-TEXT Tokamak

International Nuclear Information System (INIS)

Ding Yonghua; Jin Xuesong; Chen Zhenzhen; Zhuang Ge

2013-01-01

Prediction of disruptions caused by locked modes using the Back-Propagation (BP) neural network is completed on J-TEXT tokamak. The network, which is based on the BP neural network, uses Mirnov coils and locked mode coils signals as input data, and outputs a signal including information of prediction of locked mode. The rate of successful prediction of locked modes is more than 90%. For intrinsic locked mode disruptions, the network can give a prewarning signal about 1 ms ahead of the locking-time. For the disruption caused by resonant magnetic perturbation (RMPs) locked modes, the network can give a prewarning signal about 10 ms ahead of the locking-time

Logic gates and antisense DNA devices operating on a translator nucleic Acid scaffold.

Science.gov (United States)

Shlyahovsky, Bella; Li, Yang; Lioubashevski, Oleg; Elbaz, Johann; Willner, Itamar

2009-07-28

A series of logic gates, "AND", "OR", and "XOR", are designed using a DNA scaffold that includes four "footholds" on which the logic operations are activated. Two of the footholds represent input-recognition strands, and these are blocked by complementary nucleic acids, whereas the other two footholds are blocked by nucleic acids that include the horseradish peroxidase (HRP)-mimicking DNAzyme sequence. The logic gates are activated by either nucleic acid inputs that hybridize to the respective "footholds", or by low-molecular-weight inputs (adenosine monophosphate or cocaine) that yield the respective aptamer-substrate complexes. This results in the respective translocation of the blocking nucleic acids to the footholds carrying the HRP-mimicking DNAzyme sequence, and the concomitant release of the respective DNAzyme. The released product-strands then self-assemble into the hemin/G-quadruplex-HRP-mimicking DNAzyme that biocatalyzes the formation of a colored product and provides an output signal for the different logic gates. The principle of the logic operation is, then, implemented as a possible paradigm for future nanomedicine. The nucleic acid inputs that bind to the blocked footholds result in the translocation of the blocking nucleic acids to the respective footholds carrying the antithrombin aptamer. The released aptamer inhibits, then, the hydrolytic activity of thrombin. The system demonstrates the regulation of a biocatalytic reaction by a translator system activated on a DNA scaffold.

Technique for Determining Lock Coefficient of Differential "Quif"

Directory of Open Access Journals (Sweden)

A. B. Fominyh

2015-01-01

Full Text Available Increasing the traction qualities of cars on the black ice and snow-covered roads is a relevant task. There are two ways to solve this task, i.e. optimize distribution of the power stream between the driving wheels of the car; introduce a differential (differentials of the increased friction in transmission.Now, an installation of the increased friction differential in transmission is the most widespread measure to increase traction properties of cars. The differential of design "Quif" is one of such differentials. To estimate the efficiency degree of using such a differential is possible either experimentally or theoretically. In case of theoretically determined usefulness of this differential design, as an estimate indicator of the differential installation in transmission a coefficient of lock is accepted.The article considers an algorithm and a technique to calculate a lock coefficient of the differential design "Quif" allowing us to define numeric values of the lock coefficient of such differential at designing stage. It also considers how the lock coefficient depends on the gearing angle and tilt angle of the gear wheel teeth of differential. The given estimating algorithm of designated parameter of differential has more logical and compact structure with regard to the known ones. The lock coefficient values calculated by the offered technique differ from the experimental data by no more than 12%. Taking into account abovementioned, the presented technique for calculating lock coefficient of differential "Quif" is advisable for practical application.

Structure, stability and behaviour of nucleic acids in ionic liquids

Science.gov (United States)

Tateishi-Karimata, Hisae; Sugimoto, Naoki

2014-01-01

Nucleic acids have become a powerful tool in nanotechnology because of their conformational polymorphism. However, lack of a medium in which nucleic acid structures exhibit long-term stability has been a bottleneck. Ionic liquids (ILs) are potential solvents in the nanotechnology field. Hydrated ILs, such as choline dihydrogen phosphate (choline dhp) and deep eutectic solvent (DES) prepared from choline chloride and urea, are ‘green’ solvents that ensure long-term stability of biomolecules. An understanding of the behaviour of nucleic acids in hydrated ILs is necessary for developing DNA materials. We here review current knowledge about the structures and stabilities of nucleic acids in choline dhp and DES. Interestingly, in choline dhp, A–T base pairs are more stable than G–C base pairs, the reverse of the situation in buffered NaCl solution. Moreover, DNA triplex formation is markedly stabilized in hydrated ILs compared with aqueous solution. In choline dhp, the stability of Hoogsteen base pairs is comparable to that of Watson–Crick base pairs. Moreover, the parallel form of the G-quadruplex is stabilized in DES compared with aqueous solution. The behaviours of various DNA molecules in ILs detailed here should be useful for designing oligonucleotides for the development of nanomaterials and nanodevices. PMID:25013178

Locked-in: the syndrome as depicted in literature.

Science.gov (United States)

Haan, Joost

2013-01-01

Protagonists who are locked-in can be found throughout fiction, probably because being locked-in serves as a strong philosophical metaphor for human existence. In this chapter, three protagonists who are locked-in due to physical/medical reasons will be described. The fictitious stories of Noirtier from The Count of Monte Cristo by Alexandre Dumas and that of Madame Raquin from Thérèse Raquin by Émile Zola are followed by the real-life story of Jean-Dominique Bauby's The Diving Bell and the Butterfly. Dumas' Noirtier is considered the first description of the locked-in syndrome in literature, and Madame Raquin appears to be locked-in also, but her description leaves many questions. Bauby's autopathography is chosen from many several similar discourses as it contains cross-references to Noirtier, Dumas' prototype of the syndrome, but also because it is of high literary value. The similarities and remarkable differences between these three case reports of this existentialistically important state of being will be highlighted, with an emphasis on the focus of their narratives. © 2013 Elsevier B.V. All rights reserved.

APR1400 Locked Rotor Transient Analysis using KNAP

International Nuclear Information System (INIS)

Lee, Dong-Hyuk; Kim, Yo-Han; Ha, Sang Jun

2007-01-01

KEPRI (Korea Electric Power Research Institute) has developed safety analysis methodology for non-LOCA (Loss Of Coolant Accident) analysis of OPR1000 (Optimized Power Reactor 1000, formerly KSNP). The new methodology, named KNAP (Korea Non-LOCA Analysis Package), uses RETRAN as the main system analysis code for most transients. For locked rotor transient DNBR analysis, UNICORN-TM code is used. UNICORN-TM is the unified code of RETRAN, MASTER and TORC. The UNICORN-TM has 1-D and 3-D neutron kinetics calculation capability. For locked rotor DNBR analysis, 1-D neutron kinetics is used. In this paper, we apply KNAP methodology to APR1400 (Advanced Power Reactor 1400) locked rotor analysis and compare the results with those in the APR1400 SSAR(Standard Safety Analysis Report). The locked rotor transient is one of the 'decrease in reactor coolant system flow rate' events and the results are typically described in the chapter 15.3.3 of SAR (Safety Analysis Report). In this study, to confirm the applicability of the KNAP methodology and code system to APR1400, locked rotor transient is analyzed using UNICORN-TM code and the results are compared with those from APR1400 SSAR

APR1400 Locked Rotor Transient Analysis using KNAP

Energy Technology Data Exchange (ETDEWEB)

Lee, Dong-Hyuk; Kim, Yo-Han; Ha, Sang Jun [Korea Electric Power Research Institute, Daejeon (Korea, Republic of)

2007-07-01

KEPRI (Korea Electric Power Research Institute) has developed safety analysis methodology for non-LOCA (Loss Of Coolant Accident) analysis of OPR1000 (Optimized Power Reactor 1000, formerly KSNP). The new methodology, named KNAP (Korea Non-LOCA Analysis Package), uses RETRAN as the main system analysis code for most transients. For locked rotor transient DNBR analysis, UNICORN-TM code is used. UNICORN-TM is the unified code of RETRAN, MASTER and TORC. The UNICORN-TM has 1-D and 3-D neutron kinetics calculation capability. For locked rotor DNBR analysis, 1-D neutron kinetics is used. In this paper, we apply KNAP methodology to APR1400 (Advanced Power Reactor 1400) locked rotor analysis and compare the results with those in the APR1400 SSAR(Standard Safety Analysis Report). The locked rotor transient is one of the 'decrease in reactor coolant system flow rate' events and the results are typically described in the chapter 15.3.3 of SAR (Safety Analysis Report). In this study, to confirm the applicability of the KNAP methodology and code system to APR1400, locked rotor transient is analyzed using UNICORN-TM code and the results are compared with those from APR1400 SSAR.

Optimizing scoring function of protein-nucleic acid interactions with both affinity and specificity.

Directory of Open Access Journals (Sweden)

Zhiqiang Yan

Full Text Available Protein-nucleic acid (protein-DNA and protein-RNA recognition is fundamental to the regulation of gene expression. Determination of the structures of the protein-nucleic acid recognition and insight into their interactions at molecular level are vital to understanding the regulation function. Recently, quantitative computational approach has been becoming an alternative of experimental technique for predicting the structures and interactions of biomolecular recognition. However, the progress of protein-nucleic acid structure prediction, especially protein-RNA, is far behind that of the protein-ligand and protein-protein structure predictions due to the lack of reliable and accurate scoring function for quantifying the protein-nucleic acid interactions. In this work, we developed an accurate scoring function (named as SPA-PN, SPecificity and Affinity of the Protein-Nucleic acid interactions for protein-nucleic acid interactions by incorporating both the specificity and affinity into the optimization strategy. Specificity and affinity are two requirements of highly efficient and specific biomolecular recognition. Previous quantitative descriptions of the biomolecular interactions considered the affinity, but often ignored the specificity owing to the challenge of specificity quantification. We applied our concept of intrinsic specificity to connect the conventional specificity, which circumvents the challenge of specificity quantification. In addition to the affinity optimization, we incorporated the quantified intrinsic specificity into the optimization strategy of SPA-PN. The testing results and comparisons with other scoring functions validated that SPA-PN performs well on both the prediction of binding affinity and identification of native conformation. In terms of its performance, SPA-PN can be widely used to predict the protein-nucleic acid structures and quantify their interactions.

Active stabilization of a diode laser injection lock

Energy Technology Data Exchange (ETDEWEB)

Saxberg, Brendan; Plotkin-Swing, Benjamin; Gupta, Subhadeep [Department of Physics, University of Washington, P.O. Box 351560, Seattle, Washington 98195-1560 (United States)

2016-06-15

We report on a device to electronically stabilize the optical injection lock of a semiconductor diode laser. Our technique uses as discriminator the peak height of the laser’s transmission signal on a scanning Fabry-Perot cavity and feeds back to the diode current, thereby maintaining maximum optical power in the injected mode. A two-component feedback algorithm provides constant optimization of the injection lock, keeping it robust to slow thermal drifts and allowing fast recovery from sudden failures such as temporary occlusion of the injection beam. We demonstrate the successful performance of our stabilization method in a diode laser setup at 399 nm used for laser cooling of Yb atoms. The device eases the requirements on passive stabilization and can benefit any diode laser injection lock application, particularly those where several such locks are employed.

Active stabilization of a diode laser injection lock

International Nuclear Information System (INIS)

Saxberg, Brendan; Plotkin-Swing, Benjamin; Gupta, Subhadeep

2016-01-01

We report on a device to electronically stabilize the optical injection lock of a semiconductor diode laser. Our technique uses as discriminator the peak height of the laser’s transmission signal on a scanning Fabry-Perot cavity and feeds back to the diode current, thereby maintaining maximum optical power in the injected mode. A two-component feedback algorithm provides constant optimization of the injection lock, keeping it robust to slow thermal drifts and allowing fast recovery from sudden failures such as temporary occlusion of the injection beam. We demonstrate the successful performance of our stabilization method in a diode laser setup at 399 nm used for laser cooling of Yb atoms. The device eases the requirements on passive stabilization and can benefit any diode laser injection lock application, particularly those where several such locks are employed.

Design and Performance Test of Locking Curved-Nut

Energy Technology Data Exchange (ETDEWEB)

Cha, Min Cheol; Kang, Ho Sung; Kim, Do Yeop; Lee, Suk Yong; Lee, Eung Suk [Chungbuk Nat’l Univ., Cheongju (Korea, Republic of); Jeong, Hui Jong [Viblock Company, Cheongwon (Korea, Republic of)

2017-03-15

Many types of locking nut are commercializing in the various industries where has heavy vibration. Because Nut's loosing causes a serious accident. But the most locking nuts are too expensive as the complicate manufacturing process. In this study, we design the new type of locking nut, 'Curved-Nut' that is relatively simple making process. We study a relation between the elastic energy and the nut loosing mechanism. So it is analysed, the elastic energy of Curved-Nut comparing with the locking test. The Curved-Nut was manufactured on the commercial nut using a milling tool with horizontal cutting, one or two time under the nut. As the result, the more elastic energy the more prevent the loosing of the nut. We verified the performance of the loosing nut using the vibration testing equipment (NAS3350).

Physics and Control of Locked Modes in the DIII-D Tokamak

International Nuclear Information System (INIS)

Volpe, Francesco

2017-01-01

This Final Technical Report summarizes an investigation, carried out under the auspices of the DOE Early Career Award, of the physics and control of non-rotating magnetic islands (''locked modes'') in tokamak plasmas. Locked modes are one of the main causes of disruptions in present tokamaks, and could be an even bigger concern in ITER, due to its relatively high beta (favoring the formation of Neoclassical Tearing Mode islands) and low rotation (favoring locking). For these reasons, this research had the goal of studying and learning how to control locked modes in the DIII-D National Fusion Facility under ITER-relevant conditions of high pressure and low rotation. Major results included: the first full suppression of locked modes and avoidance of the associated disruptions; the demonstration of error field detection from the interaction between locked modes, applied rotating fields and intrinsic errors; the analysis of a vast database of disruptive locked modes, which led to criteria for disruption prediction and avoidance.

Physics and Control of Locked Modes in the DIII-D Tokamak

Energy Technology Data Exchange (ETDEWEB)

Volpe, Francesco [Columbia Univ., New York, NY (United States). Dept. of Applied Physics and Applied Mathematics

2017-01-30

This Final Technical Report summarizes an investigation, carried out under the auspices of the DOE Early Career Award, of the physics and control of non-rotating magnetic islands (“locked modes”) in tokamak plasmas. Locked modes are one of the main causes of disruptions in present tokamaks, and could be an even bigger concern in ITER, due to its relatively high beta (favoring the formation of Neoclassical Tearing Mode islands) and low rotation (favoring locking). For these reasons, this research had the goal of studying and learning how to control locked modes in the DIII-D National Fusion Facility under ITER-relevant conditions of high pressure and low rotation. Major results included: the first full suppression of locked modes and avoidance of the associated disruptions; the demonstration of error field detection from the interaction between locked modes, applied rotating fields and intrinsic errors; the analysis of a vast database of disruptive locked modes, which led to criteria for disruption prediction and avoidance.

Shape Memory Alloy (SMA)-Based Launch Lock

Science.gov (United States)

Badescu, Mircea; Bao, Xiaoqi; Bar-Cohen, Yoseph

2014-01-01

Most NASA missions require the use of a launch lock for securing moving components during the launch or securing the payload before release. A launch lock is a device used to prevent unwanted motion and secure the controlled components. The current launch locks are based on pyrotechnic, electro mechanically or NiTi driven pin pullers and they are mostly one time use mechanisms that are usually bulky and involve a relatively high mass. Generally, the use of piezoelectric actuation provides high precession nanometer accuracy but it relies on friction to generate displacement. During launch, the generated vibrations can release the normal force between the actuator components allowing shaft's free motion which could result in damage to the actuated structures or instruments. This problem is common to other linear actuators that consist of a ball screw mechanism. The authors are exploring the development of a novel launch lock mechanism that is activated by a shape memory alloy (SMA) material ring, a rigid element and an SMA ring holding flexure. The proposed design and analytical model will be described and discussed in this paper.

Phase locking of vortex cores in two coupled magnetic nanopillars

Directory of Open Access Journals (Sweden)

Qiyuan Zhu

2014-11-01

Full Text Available Phase locking dynamics of the coupled vortex cores in two identical magnetic spin valves induced by spin-polarized current are studied by means of micromagnetic simulations. Our results show that the available current range of phase locking can be expanded significantly by the use of constrained polarizer, and the vortices undergo large orbit motions outside the polarization areas. The effects of polarization areas and dipolar interaction on the phase locking dynamics are studied systematically. Phase locking parameters extracted from simulations are discussed by theoreticians. The dynamics of vortices influenced by spin valve geometry and vortex chirality are discussed at last. This work provides deeper insights into the dynamics of phase locking and the results are important for the design of spin-torque nano-oscillators.

Bis-Pyrene-Modified Unlocked Nucleic Acids: Synthesis, Hybridization Studies, and Fluorescent Properties

Czech Academy of Sciences Publication Activity Database

Perlíková, Pavla; Ejlersen, M.; Langkjaer, N.; Wengel, J.

2014-01-01

Roč. 9, č. 9 (2014), s. 2120-2127 ISSN 1860-7179 Grant - others:European Research Council(XE) FP7-268776 Institutional support: RVO:61388963 Keywords : fluorescence * nucleic acid hybridization * oligonucleotides * pyrenes * unlocked nucleic acids Subject RIV: CC - Organic Chemistry Impact factor: 2.968, year: 2014

Nucleic acid protocols: Extraction and optimization

Directory of Open Access Journals (Sweden)

Saeed El-Ashram

2016-12-01

Full Text Available Yield and quality are fundamental features for any researchers during nucleic acid extraction. Here, we describe a simplified, semi-unified, effective, and toxic material free protocol for extracting DNA and RNA from different prokaryotic and eukaryotic sources exploiting the physical and chemical properties of nucleic acids. Furthermore, this protocol showed that DNA and RNA are under triple protection (i.e. EDTA, SDS and NaCl during lysis step, and this environment is improper for RNase to have DNA liberated of RNA and even for DNase to degrade the DNA. Therefore, the complete removal of RNA under RNase influence is achieved when RNase is added after DNA extraction, which gives optimal quality with any protocols. Similarly, DNA contamination in an isolated RNA is degraded by DNase to obtain high-quality RNA. Our protocol is the protocol of choice in terms of simplicity, recovery time, environmental safety, amount, purity, PCR and RT-PCR applicability.

In vivo efficacy and off-target effects of locked nucleic acid (LNA) and unlocked nucleic acid (UNA) modified siRNA and small internally segmented interfering RNA (sisiRNA) in mice bearing human tumor xenografts

NARCIS (Netherlands)

Mook, O. R. F.; Vreijling, Jeroen; Wengel, Suzy L.; Wengel, Jesper; Zhou, Chuanzheng; Chattopadhyaya, Jyoti; Baas, Frank; Fluiter, Kees

2010-01-01

The clinical use of small interfering RNA (siRNA) is hampered by poor uptake by tissues and instability in circulation. In addition, off-target effects pose a significant additional problem for therapeutic use of siRNA. Chemical modifications of siRNA have been reported to increase stability and

Nucleic Acid Templated Reactions for Chemical Biology.

Science.gov (United States)

Di Pisa, Margherita; Seitz, Oliver

2017-06-21

Nucleic acid directed bioorthogonal reactions offer the fascinating opportunity to unveil and redirect a plethora of intracellular mechanisms. Nano- to picomolar amounts of specific RNA molecules serve as templates and catalyze the selective formation of molecules that 1) exert biological effects, or 2) provide measurable signals for RNA detection. Turnover of reactants on the template is a valuable asset when concentrations of RNA templates are low. The idea is to use RNA-templated reactions to fully control the biodistribution of drugs and to push the detection limits of DNA or RNA analytes to extraordinary sensitivities. Herein we review recent and instructive examples of conditional synthesis or release of compounds for in cellulo protein interference and intracellular nucleic acid imaging. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Clinical study of intermittent lock of the temporomandibular joint. Relation to frequency of intermittent lock on clinical examination and magnetic resonance imaging

Energy Technology Data Exchange (ETDEWEB)

Ide, Takashi; Nagai, Itaru; Miyazaki, Akihiro; Yamaguchi, Akira; Kohama, Geniku [Sapporo Medical Univ. (Japan). School of Medicine

2002-03-01

To examine the occurrence of intermittent lock, we investigated the correlation between the frequency of intermittent lock of the temporomandibular joint and magnetic resonance imaging (MRI) findings. The subjects consisted of 25 patients (25 joints) with unilateral intermittent lock who were treated from April 1994 through March 2000 at our department. MRI examination of the joint was performed on the affected side. We divided the patients into two groups: a high-frequency group consisting of 15 patients who had symptoms of intermittent lock every day and a low-frequency group consisting of 10 patients who did not have symptoms every day. The results showed no statistical difference between the two groups in clinical findings such as age, sex, clicking side of the joint, duration of intermittent lock, method of unlocking, muscle pain on palpation, degree of maximal mouth opening, distance between the maxillary and mandibular tooth midline, or the degree of overbite and overjet. However, the two groups differed significantly in the degree of anterior disc displacement as assessed by MRI. (author)

49 CFR 236.16 - Electric lock, main track releasing circuit.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Electric lock, main track releasing circuit. 236... Rules and Instructions: All Systems General § 236.16 Electric lock, main track releasing circuit. When an electric lock releasing circuit is provided on the main track to permit a train or an engine to...

Discretely tunable micromachined injection-locked lasers

International Nuclear Information System (INIS)

Cai, H; Yu, M B; Lo, G Q; Kwong, D L; Zhang, X M; Liu, A Q; Liu, B

2010-01-01

This paper reports a micromachined injection-locked laser (ILL) to provide tunable discrete wavelengths. It utilizes a non-continuously tunable laser as the master to lock a Fabry–Pérot semiconductor laser chip. Both lasers are integrated into a deep-etched silicon chip with dimensions of 3 mm × 3 mm × 0.8 mm. Based on the experimental results, significant improvements in the optical power and spectral purity have been achieved in the fully locked state, and optical hysteresis and bistability have also been observed in response to the changes of the output wavelength and optical power of the master laser. As a whole system, the micromachined ILL is able to provide single mode, discrete wavelength tuning, high power and direct modulation with small size and single-chip solution, making it promising for advanced optical communications such as wavelength division multiplexing optical access networks.

An Evaluation of Coarse-Grained Locking for Multicore Microkernels

OpenAIRE

Elphinstone, Kevin; Zarrabi, Amirreza; Danis, Adrian; Shen, Yanyan; Heiser, Gernot

2016-01-01

The trade-off between coarse- and fine-grained locking is a well understood issue in operating systems. Coarse-grained locking provides lower overhead under low contention, fine-grained locking provides higher scalability under contention, though at the expense of implementation complexity and re- duced best-case performance. We revisit this trade-off in the context of microkernels and tightly-coupled cores with shared caches and low inter-core migration latencies. We evaluate performance on ...

Probing the mechanical properties, conformational changes, and interactions of nucleic acids with magnetic tweezers.

Science.gov (United States)

Kriegel, Franziska; Ermann, Niklas; Lipfert, Jan

2017-01-01

Nucleic acids are central to the storage and transmission of genetic information. Mechanical properties, along with their sequence, both enable and fundamentally constrain the biological functions of DNA and RNA. For small deformations from the equilibrium conformations, nucleic acids are well described by an isotropic elastic rod model. However, external forces and torsional strains can induce conformational changes, giving rise to a complex force-torque phase diagram. This review focuses on magnetic tweezers as a powerful tool to precisely determine both the elastic parameters and conformational transitions of nucleic acids under external forces and torques at the single-molecule level. We review several variations of magnetic tweezers, in particular conventional magnetic tweezers, freely orbiting magnetic tweezers and magnetic torque tweezers, and discuss their characteristic capabilities. We then describe the elastic rod model for DNA and RNA and discuss conformational changes induced by mechanical stress. The focus lies on the responses to torque and twist, which are crucial in the mechanics and interactions of nucleic acids and can directly be measured using magnetic tweezers. We conclude by highlighting several recent studies of nucleic acid-protein and nucleic acid-small-molecule interactions as further applications of magnetic tweezers and give an outlook of some exciting developments to come. Copyright © 2016. Published by Elsevier Inc.

Molecular structure and interactions of nucleic acid components in nanoparticles: ab initio calculations

International Nuclear Information System (INIS)

Rubin, Yu.V.; Belous, L.F.

2012-01-01

Self-associates of nucleic acid components (stacking trimers and tetramers of the base pairs of nucleic acids) and short fragments of nucleic acids are nanoparticles (linear sizes of these particles are more than 10 A). Modern quantum-mechanical methods and softwares allow one to perform ab initio calculations of the systems consisting of 150-200 atoms with enough large basis sets (for example, 6-31G * ). The aim of this work is to reveal the peculiarities of molecular and electronic structures, as well as the energy features of nanoparticles of nucleic acid components. We had carried out ab initio calculations of the molecular structure and interactions in the stacking dimer, trimer, and tetramer of nucleic base pairs and in the stacking (TpG)(ApC) dimer and (TpGpC) (ApCpG) trimer of nucleotides, which are small DNA fragments. The performed calculations of molecular structures of dimers and trimers of nucleotide pairs showed that the interplanar distance in the structures studied is equal to 3.2 A on average, and the helical angle in a trimer is approximately equal to 30 o : The distance between phosphor atoms in neighboring chains is 13.1 A. For dimers and trimers under study, we calculated the horizontal interaction energies. The analysis of interplanar distances and angles between nucleic bases and their pairs in the calculated short oligomers of nucleic acid base pairs (stacking dimer, trimer, and tetramer) has been carried out. Studies of interactions in the calculated short oligomers showed a considerable role of the cross interaction in the stabilization of the structures. The contribution of cross interactions to the horizontal interactions grows with the length of an oligomer. Nanoparticle components get electric charges in nanoparticles. Longwave low-intensity bands can appear in the electron spectra of nanoparticles.

Comparative evaluation of three commercial systems for nucleic acid extraction from urine specimens.

Science.gov (United States)

Tang, Yi-Wei; Sefers, Susan E; Li, Haijing; Kohn, Debra J; Procop, Gary W

2005-09-01

A nucleic acid extraction system that can handle small numbers of specimens with a short test turnaround time and short hands-on time is desirable for emergent testing. We performed a comparative validation on three systems: the MagNA Pure compact system (Compact), the NucliSens miniMAG extraction instrument (miniMAG), and the BioRobot EZ1 system (EZ1). A total of 75 urine specimens submitted for polyomavirus BK virus detection were used. The human beta-actin gene was detected on 75 (100%), 75 (100%), and 72 (96%) nucleic acid extracts prepared by the miniMAG, EZ1, and Compact, respectively. The miniMAG produced the highest quantity of nucleic acids and the best precision among the three systems. The agreement rate was 100% for BKV detection on nucleic acid extracts prepared by the three extraction systems. When a full panel of specimens was run, the hands-on time and test turnaround time were 105.7 and 121.1 min for miniMAG, 6.1 and 22.6 min for EZ1, and 7.4 and 33.7 min for Compact, respectively. The EZ1 and Compact systems processed automatic nucleic acid extraction properly, providing a good solution to the need for sporadic but emergent specimen detection. The miniMAG yielded the highest quantity of nucleic acids, suggesting that this system would be the best for specimens containing a low number of microorganisms of interest.

Past, Present, Future Erosion at Locke Island

Energy Technology Data Exchange (ETDEWEB)

Bjornstad, Bruce N.

2006-08-08

This report describes and documents the erosion that has occurred along the northeast side of Locke Island over the last 10 to 20 years. The principal cause of this erosion is the massive Locke Island landslide complex opposite the Columbia River along the White Bluffs, which constricts the flow of the river and deflects the river's thalweg southward against the island.

Non-destructive test of lock actuator component using neutron radiography technique

International Nuclear Information System (INIS)

Juliyanti; Setiawan; Sutiarso

2012-01-01

Non-destructive test of lock actuator using neutron radiography technique has been done. The lock actuator is a mechanical system which is controlled by central lock module consisting of electronic circuit which drives the lock actuator works accordingly to open and lock the vehicle door. The non-destructive test using neutron radiography is carried out to identify the type of defect is presence by comparing between the broken and the brand new one. The method used to test the lock actuator component is film method (direct method). The result show that the radiography procedure has complied with the ASTM standard for neutron radiography with background density of 2.2, 7 lines and 3 holes was seen in the sensitivity indicator (SI) and the quite good image quality was obtained. In the brand new actuator is seen that isolator part which separated the coils has melted. By this non-destructive test using neutron radiography technique is able to detect in early stage the type of component's defect inside the lock actuator without to dismantle it. (author)

Non-viral Nucleic Acid Delivery Strategies to the Central Nervous System

Directory of Open Access Journals (Sweden)

James-Kevin Tan

2016-11-01

Full Text Available With an increased prevalence and understanding of central nervous system injuries and neurological disorders, nucleic acid therapies are gaining promise as a way to regenerate lost neurons or halt disease progression. While more viral vectors have been used clinically as tools for gene delivery, non-viral vectors are gaining interest due to lower safety concerns and the ability to deliver all types of nucleic acids. Nevertheless, there are still a number of barriers to nucleic acid delivery. In this focused review, we explore the in vivo challenges hindering non-viral nucleic acid delivery to the central nervous system and the strategies and vehicles used to overcome them. Advantages and disadvantages of different routes of administration including: systemic injection, cerebrospinal fluid injection, intraparenchymal injection, and peripheral administration are discussed. Non-viral vehicles and treatment strategies that have overcome delivery barriers and demonstrated in vivo gene transfer to the central nervous system are presented. These approaches can be used as guidelines in developing synthetic gene delivery vectors for central nervous system applications and will ultimately bring non-viral vectors closer to clinical application.

Nucleic acid polymeric properties and electrostatics: Directly comparing theory and simulation with experiment.

Science.gov (United States)

Sim, Adelene Y L

2016-06-01

Nucleic acids are biopolymers that carry genetic information and are also involved in various gene regulation functions such as gene silencing and protein translation. Because of their negatively charged backbones, nucleic acids are polyelectrolytes. To adequately understand nucleic acid folding and function, we need to properly describe its i) polymer/polyelectrolyte properties and ii) associating ion atmosphere. While various theories and simulation models have been developed to describe nucleic acids and the ions around them, many of these theories/simulations have not been well evaluated due to complexities in comparison with experiment. In this review, I discuss some recent experiments that have been strategically designed for straightforward comparison with theories and simulation models. Such data serve as excellent benchmarks to identify limitations in prevailing theories and simulation parameters. Copyright © 2015 Elsevier B.V. All rights reserved.

Temperature-insensitive laser frequency locking near absorption lines

International Nuclear Information System (INIS)

Kostinski, Natalie; Olsen, Ben A.; Marsland, Robert III; McGuyer, Bart H.; Happer, William

2011-01-01

Combined magnetically induced circular dichroism and Faraday rotation of an atomic vapor are used to develop a variant of the dichroic atomic vapor laser lock that eliminates lock sensitivity to temperature fluctuations of the cell. Operating conditions that eliminate first-order sensitivity to temperature fluctuations can be determined by low-frequency temperature modulation. This temperature-insensitive gyrotropic laser lock can be accurately understood with a simple model, that is in excellent agreement with observations in potassium vapor at laser frequencies in a 2 GHz range about the 770.1 nm absorption line. The methods can be readily adapted for other absorption lines.

Tilt-tuned etalon locking for tunable laser stabilization.

Science.gov (United States)

Gibson, Bradley M; McCall, Benjamin J

2015-06-15

Locking to a fringe of a tilt-tuned etalon provides a simple, inexpensive method for stabilizing tunable lasers. Here, we describe the use of such a system to stabilize an external-cavity quantum cascade laser; the locked laser has an Allan deviation of approximately 1 MHz over a one-second integration period, and has a single-scan tuning range of approximately 0.4  cm(-1). The system is robust, with minimal alignment requirements and automated lock acquisition, and can be easily adapted to different wavelength regions or more stringent stability requirements with minor alterations.

Highly simplified lateral flow-based nucleic acid sample preparation and passive fluid flow control

Science.gov (United States)

Cary, Robert E.

2015-12-08

Highly simplified lateral flow chromatographic nucleic acid sample preparation methods, devices, and integrated systems are provided for the efficient concentration of trace samples and the removal of nucleic acid amplification inhibitors. Methods for capturing and reducing inhibitors of nucleic acid amplification reactions, such as humic acid, using polyvinylpyrrolidone treated elements of the lateral flow device are also provided. Further provided are passive fluid control methods and systems for use in lateral flow assays.

Highly simplified lateral flow-based nucleic acid sample preparation and passive fluid flow control

Energy Technology Data Exchange (ETDEWEB)

Cary, Robert B.

2018-04-17

Highly simplified lateral flow chromatographic nucleic acid sample preparation methods, devices, and integrated systems are provided for the efficient concentration of trace samples and the removal of nucleic acid amplification inhibitors. Methods for capturing and reducing inhibitors of nucleic acid amplification reactions, such as humic acid, using polyvinylpyrrolidone treated elements of the lateral flow device are also provided. Further provided are passive fluid control methods and systems for use in lateral flow assays.

Recent progress in nucleic acids isotachophoresis

Czech Academy of Sciences Publication Activity Database

Datinská, Vladimíra; Voráčová, Ivona; Schlecht, U.; Berka, J.; Foret, František

2018-01-01

Roč. 41, č. 1 (2018), s. 236-247 ISSN 1615-9306 R&D Projects: GA ČR(CZ) GBP206/12/G014 Institutional support: RVO:68081715 Keywords : isotachophoresis * nucleic acids * sample preparation Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 2.557, year: 2016

Recent progress in nucleic acids isotachophoresis

Czech Academy of Sciences Publication Activity Database

Datinská, Vladimíra; Voráčová, Ivona; Schlecht, U.; Berka, J.; Foret, František

2018-01-01

Roč. 41, č. 1 (2018), s. 236-247 ISSN 1615-9306 R&D Projects: GA ČR(CZ) GBP206/12/G014 Institutional support: RVO:68081715 Keywords : isotachophoresis * nucleic acid s * sample preparation Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 2.557, year: 2016

Testing ultrafast mode-locking at microhertz relative optical linewidth.

Science.gov (United States)

Martin, Michael J; Foreman, Seth M; Schibli, T R; Ye, Jun

2009-01-19

We report new limits on the phase coherence of the ultrafast mode-locking process in an octave-spanning Ti:sapphire comb.We find that the mode-locking mechanism correlates optical phase across a full optical octave with less than 2.5 microHZ relative linewidth. This result is at least two orders of magnitude below recent predictions for quantum-limited individual comb-mode linewidths, verifying that the mode-locking mechanism strongly correlates quantum noise across the comb spectrum.

Testing ultrafast mode-locking at microhertz relative optical linewidth

OpenAIRE

Martin, Michael J.; Foreman, Seth M.; Schibli, T. R.; Ye, Jun

2008-01-01

We report new limits on the phase coherence of the ultrafast mode-locking process in an octave-spanning Ti:sapphire comb. We find that the mode-locking mechanism correlates optical phase across a full optical octave with less than 2.5 micro Hz relative linewidth. This result is at least two orders of magnitude below recent predictions for quantum-limited individual comb-mode linewidths, verifying that the mode-locking mechanism strongly correlates quantum noise across the comb spectrum.

Locking a molecular bond: A case study of CsI

DEFF Research Database (Denmark)

Szakács, Tamás; Amstrup, Bjarne; Gross, Peter

1994-01-01

This paper treats the problem of locking a molecular bond at a length other than the equilibrium distance, with the help of optical electric fields. Locking conditions for single-color fields are examined, and slowly decaying locked wave functions are sought. These were functions are then used...... as target functions in an optimal control procedure. The resultant solution is an optimal field that creates a wave function as close as possible to the target function, followed by the application of a locking single-color field that can keep a large part of this wave function at the given position...

Roller Locking Brake

Science.gov (United States)

Vranish, John M.

1993-01-01

Roller locking brake is normally braking rotary mechanism allowing free rotation when electromagnet in mechanism energized. Well suited to robots and other machinery which automatic braking upon removal of electrical power required. More compact and reliable. Requires little electrical power to maintain free rotation and exhibits minimal buildup of heat.

Covering all the bases : Coarse-grained model design and application for nucleic acids

NARCIS (Netherlands)

Uusitalo, Jaakko Juhani

2016-01-01

Nucleic acids play a crucial role in the storage, transportation and expression of our genetic information. They have also become an interesting tool for many applications in nanotechnology. Studying biomolecular systems containing nucleic acids using experimental and imaging techniques has its

Locking plate fixation for proximal humerus fractures.

LENUS (Irish Health Repository)

Burke, Neil G

2012-02-01

Locking plates are increasingly used to surgically treat proximal humerus fractures. Knowledge of the bone quality of the proximal humerus is important. Studies have shown the medial and dorsal aspects of the proximal humeral head to have the highest bone strength, and this should be exploited by fixation techniques, particularly in elderly patients with osteoporosis. The goals of surgery for proximal humeral fractures should involve minimal soft tissue dissection and achieve anatomic reduction of the head complex with sufficient stability to allow for early shoulder mobilization. This article reviews various treatment options, in particular locking plate fixation. Locking plate fixation is associated with a high complication rate, such as avascular necrosis (7.9%), screw cutout (11.6%), and revision surgery (13.7%). These complications are frequently due to the varus deformation of the humeral head. Strategic screw placement in the humeral head would minimize the possibility of loss of fracture reduction and potential hardware complications. Locking plate fixation is a good surgical option for the management of proximal humerus fractures. Complications can be avoided by using better bone stock and by careful screw placement in the humeral head.

Locking screw apparatus and method for underwater remote replacement

International Nuclear Information System (INIS)

Balog, L.J.

1987-01-01

A method is described for locking in place a screw which secures together first and second structures in the internal region of a nuclear reactor core. The first structure has a screw bore with a counterbore portion formed in an outer surface. The method comprises the steps of: forming a lateral recess in the counterbore portion and spaced from the outer surface, providing an elongated screw having an enlarged shoulder flange and an angular drive head with a lateral width substantially less than that of the counterbore portion, disposing the screw through the screw bore in threaded engagement with the second structure and with the shoulder rotatably seated in the counterbore portion. This provides a locking member having an angular opening and disposing it in the counterbore portion against the flange with the drive head received in the opening for engagement with the locking member to prevent rotation. This deforms a portion of the locking member into the recess for engagement to prevent movement of the locking member with respect to the first structure

Evolution of the Generic Lock System at Jefferson Lab

International Nuclear Information System (INIS)

Brian Bevins; Yves Roblin

2003-01-01

The Generic Lock system is a software framework that allows highly flexible feedback control of large distributed systems. It allows system operators to implement new feedback loops between arbitrary process variables quickly and with no disturbance to the underlying control system. Several different types of feedback loops are provided and more are being added. This paper describes the further evolution of the system since it was first presented at ICALEPCS 2001 and reports on two years of successful use in accelerator operations. The framework has been enhanced in several key ways. Multiple-input, multiple-output (MIMO) lock types have been added for accelerator orbit and energy stabilization. The general purpose Proportional-Integral-Derivative (PID) locks can now be tuned automatically. The generic lock server now makes use of the Proxy IOC (PIOC) developed at Jefferson Lab to allow the locks to be monitored from any EPICS Channel Access aware client. (Previously clients had to be Cdev aware.) The dependency on the Qt XML parser has been replaced with the freely available Xerces DOM parser from the Apache project

Weak-light phase locking for LISA

International Nuclear Information System (INIS)

McNamara, Paul W

2005-01-01

The long armlengths of the LISA interferometer, and the finite aperture of the telescope, lead to an optical power attenuation of ∼10 -10 of the transmitted to received light. Simple reflection at the end of the arm is therefore not an optimum interferometric design. Instead, a local laser is offset phase locked to the weak incoming beam, transferring the phase information of the incoming to the outgoing light. This paper reports on an experiment to characterize a weak-light phase-locking scheme suitable for LISA in which a diode-pumped, Nd:YAG, non-planar ring oscillator (NPRO) is offset phase locked to a low-power (13 pW) frequency stabilized master NPRO. Preliminary results of the relative phase noise of the slave laser shows shot noise limited performance above 0.4 Hz. Excess noise is observed at lower frequencies, most probably due to thermal effects in the optical arrangement and phase-sensing electronics

SWITCHED REFERENCE PHASE LOCK LOOP (SRPLL)

International Nuclear Information System (INIS)

KERNER, T.

2001-01-01

The Brookhaven National Laboratory Relativistic Heavy Ion Collider (RHIC) has two beam synchronous event links (BSL), one for each ring, which use the 28 MHz ring low level rf to distribute event codes synchronously with a precise phase relationship to the beam. During a cogging reset just before injection, the low level rf sine wave is interrupted which causes the BSL receivers to lose lock. Lock loss in turn causes false triggers and other undesirable-effects on the beam position monitors (BPM), ionization profile monitors (IPM), the tune meter and various experiments which use the BSLs. To rectify these problems, a SRPLL has been inserted between the beam synchronous master and the low level rf source. The SRPLL inserts a frequency and phase continuous splice over the dead-band gap in the rf source created during a cogging reset. The splice removes the gap and prevents the distributed BSL receivers from losing lock

Automatic locking knee brace joint

Science.gov (United States)

Weddendorf, Bruce (Inventor)

1995-01-01

This invention is an apparatus for controlling the pivotal movement of a knee brace comprising a tang-and-clevis joint that has been uniquely modified. Both the tang and the clevis have a set of teeth that, when engaged, can lock the tang and the clevis together. In addition, the tang is biased away from the clevis. Consequently, when there is no axial force (i.e., body weight) on the tang, the tang is free to pivot within the clevis. However, when an axial force is exerted on the tang, the tang is pushed into the clevis, both sets of teeth engage, and the tang and the clevis lock together.

Adverse effects associated with ethanol catheter lock solutions: a systematic review.

Science.gov (United States)

Mermel, Leonard A; Alang, Neha

2014-10-01

Antimicrobial lock therapy has been widely utilized internationally for the prevention and management of intravascular catheter-related bloodstream infections. One of the agents commonly utilized for lock therapy is ethanol. However, a systematic review of adverse events associated with ethanol locks has not been published. PubMed was searched to collect articles published from May 2003 through March 2014. The bibliographies of relevant articles were also reviewed. In vitro studies of the mechanical properties of catheters after ethanol immersion have revealed changes predominantly in polyurethane catheters and to a lesser extent in silicone and Carbothane catheters. An elution of polymers from polyurethane and Carbothane catheters has been observed at the ethanol concentrations used in ethanol lock therapy. Ethanol above a concentration of 28% leads to plasma protein precipitation. Ethanol locks were associated with catheter occlusion in 11 studies and independently increased the risk of thrombosis compared with heparin lock in a randomized trial. Six studies noted abnormalities in catheter integrity, including one case leading to catheter embolization. Of note, five of these studies involved silicone catheters. Ethanol lock use was associated with systemic side effects in 10 studies and possible side effects in one additional study. Four studies noted liver function test abnormalities, predominantly transaminase elevation, related to ethanol lock use. However, a prospective study did not find any difference in the risk of doubling the transaminase level above the normal range during use of ethanol locks compared with not using an ethanol lock. The use of ethanol locks has been associated with structural changes in catheters, as well as the elution of molecules from the catheter polymers. Clinical studies have revealed systemic toxicity, increased catheter occlusion and breaches in catheter integrity. © The Author 2014. Published by Oxford University Press on

[Comparison of two nucleic acid extraction methods for norovirus in oysters].

Science.gov (United States)

Yuan, Qiao; Li, Hui; Deng, Xiaoling; Mo, Yanling; Fang, Ling; Ke, Changwen

2013-04-01

To explore a convenient and effective method for norovirus nucleic acid extraction from oysters suitable for long-term viral surveillance. Two methods, namely method A (glycine washing and polyethylene glycol precipitation of the virus followed by silica gel centrifugal column) and method B (protease K digestion followed by application of paramagnetic silicon) were compared for their performance in norovirus nucleic acid extraction from oysters. Real-time RT-PCR was used to detect norovirus in naturally infected oysters and in oysters with induced infection. The two methods yielded comparable positive detection rates for the samples, but the recovery rate of the virus was higher with method B than with method A. Method B is a more convenient and rapid method for norovirus nucleic acid extraction from oysters and suitable for long-term surveillance of norovirus.

Peak-locking reduction for particle image velocimetry

International Nuclear Information System (INIS)

Michaelis, Dirk; Wieneke, Bernhard; Neal, Douglas R

2016-01-01

A parametric study of the factors contributing to peak-locking, a known bias error source in particle image velocimetry (PIV), is conducted using synthetic data that are processed with a state-of-the-art PIV algorithm. The investigated parameters include: particle image diameter, image interpolation techniques, the effect of asymmetric versus symmetric window deformation, number of passes and the interrogation window size. Some of these parameters are found to have a profound effect on the magnitude of the peak-locking error. The effects for specific PIV cameras are also studied experimentally using a precision turntable to generate a known rotating velocity field. Image time series recorded using this experiment show a linear range of pixel and sub-pixel shifts ranging from 0 to  ±4 pixels. Deviations in the constant vorticity field (ω z ) reveal how peak-locking can be affected systematically both by varying parameters of the detection system such as the focal distance and f -number, and also by varying the settings of the PIV analysis. A new a priori technique for reducing the bias errors associated with peak-locking in PIV is introduced using an optical diffuser to avoid undersampled particle images during the recording of the raw images. This technique is evaluated against other a priori approaches using experimental data and is shown to perform favorably. Finally, a new a posteriori anti peak-locking filter (APLF) is developed and investigated, which shows promising results for both synthetic data and real measurements for very small particle image sizes. (paper)

Scaling laws for mode lockings in circle maps

International Nuclear Information System (INIS)

Cvitanovic, P.; Shraiman, B.; Soederberg, B.

1985-06-01

The self-similar structure of mode lockings for circle maps is studied by means of the associated Farey trees. We investigate numerically several classes of scaling relations implicit in the Farey organization of mode lockings and discuss the extent to which they lead to universal scaling laws. (orig.)

Navigation Study of Lower Lock Approach, John Day Lock and Dam, Columbia River, Oregon

National Research Council Canada - National Science Library

Wilson, Donald

2001-01-01

Representatives of the Columbia River Towing Association reported recent structural and/or operational changes at John Day Lock and Dam have created difficult navigation conditions for tows entering...

The association between low-grade inflammation, iron status and nucleic acid oxidation in the elderly

DEFF Research Database (Denmark)

Broedbaek, Kasper; Siersma, Volkert Dirk; Andersen, Jon T

2011-01-01

This study applied a case-control approach to investigate the association between low-grade inflammation, defined by high values within the normal range of C-reactive protein (CRP) and interleukin-6 (IL-6), and urinary markers of nucleic acid oxidation. No differences in excretion of urinary...... markers of nucleic acid oxidation between cases and controls were found and multivariable linear regression analysis showed no association between urinary markers of nucleic acid oxidation and inflammatory markers. Post-hoc multivariable linear regression analysis showed significant associations between...... suggest that low-grade inflammation only has a negligible impact on whole body nucleic acid oxidation, whereas iron status seems to be of great importance....

John Locke and the right to resistance

Directory of Open Access Journals (Sweden)

Jovanov Ilija D.

2015-01-01

Full Text Available John Locke was a great thinker and many works have been devoted to clear up his theories. One of the most significant, stated in his principal work, Two Treatises of Government, is the theory of the right to resistance. It was a bit revolutionary then, and to a large extent it is today. Domination of legal positivism is negation of that, by Locke, natural right. However, the fact is that in recent times the resistance to the established power occurs in a number of countries and in different forms, so that the idea of the right to resistance becomes live question again. In this regard it is interesting to consider Locke's viewpoint on this important issue and to determine whether his theory on the resistance is applicable in modern societies.

Control of photon storage time using phase locking.

Science.gov (United States)

Ham, Byoung S

2010-01-18

A photon echo storage-time extension protocol is presented by using a phase locking method in a three-level backward propagation scheme, where phase locking serves as a conditional stopper of the rephasing process in conventional two-pulse photon echoes. The backward propagation scheme solves the critical problems of extremely low retrieval efficiency and pi rephasing pulse-caused spontaneous emission noise in photon echo based quantum memories. The physics of the storage time extension lies in the imminent population transfer from the excited state to an auxiliary spin state by a phase locking control pulse. We numerically demonstrate that the storage time is lengthened by spin dephasing time.

Control of integrated micro-resonator wavelength via balanced homodyne locking.

Science.gov (United States)

Cox, Jonathan A; Lentine, Anthony L; Trotter, Douglas C; Starbuck, Andrew L

2014-05-05

We describe and experimentally demonstrate a method for active control of resonant modulators and filters in an integrated photonics platform. Variations in resonance frequency due to manufacturing processes and thermal fluctuations are corrected by way of balanced homodyne locking. The method is compact, insensitive to intensity fluctuations, minimally disturbs the micro-resonator, and does not require an arbitrary reference to lock. We demonstrate long-term stable locking of an integrated filter to a laser swept over 1.25 THz. In addition, we show locking of a modulator with low bit error rate while the chip temperature is varied from 5 to 60° C.

Effect of ship locking on sediment oxygen uptake in impounded rivers

DEFF Research Database (Denmark)

Lorke, A.; McGinnis, D. F.; Maeck, A.

2012-01-01

In the majority of large river systems, flow is regulated and/or otherwise affected by operational and management activities, such as ship locking. The effect of lock operation on sediment-water oxygen fluxes was studied within a 12.9 km long impoundment at the Saar River (Germany) using eddy....... Additional means by which the oxygen budget of the impoundment is affected by lock-induced flow variations are discussed. Citation: Lorke, A., D. F. McGinnis, A. Maeck, and H. Fischer (2012), Effect of ship locking on sediment oxygen uptake in impounded rivers, Water Resour. Res., 48, W12514, doi: 10....... These wave-induced flow variations cause variations in sediment-water oxygen fluxes. While the mean flux during time periods without lock operation was 0.5 +/- 0.1 g m(-2) d(-1), it increased by about a factor of 2 to 1.0 +/- 0.5 g m(-2) d(-1) within time periods with ship locking. Following the daily...

Possibilities for prognostication of radiation injury in rats by leucocyte nucleic acid levels

International Nuclear Information System (INIS)

Minkova, M.; Pantev, T.

1988-01-01

The possibilities to prognosticate acute radiation injury by the changes in the amount of nucleic acids in the leucocytes was studied. Experiments were carried out on male Wistar albino rats, gamma-irradiated with nonlethal and sublethal doses of 0.5, 2 and 4 Gy and lethal dose of 8 Gy (LD 90/30 ). The nucleic acid content and the total leucocyte count were determined at definite intervals on days 1-30. The changes in the nucleic acids in nonlethally and sublethally irradiated animals had phase nature, with a clear-cut abortive increase in their amount on days 7-10. In lethally irradiated animals the phase character of the changes was lost and the abortive peak disappeared. By reducing the effectiveness of the lethal radiation dose survival of the population increased from 10-75% through physical and from 10-70% - through chemical protection. The nucleic acid dynamics showed features typical for an injury with possible survival - appearance of abortive peak and resumption of their normal values. It is assumed that determination of leucocyte nucleic acid content may be used for early prognostication of radiation injury, as it allows keen differentiation of the lethal from nonlethal outcome of radiation sickness. The absence of abortive peak (over 50%) by day 14 post-irradiation is a poor prognostic sign

Helicase-dependent amplification of nucleic acids.

Science.gov (United States)

Cao, Yun; Kim, Hyun-Jin; Li, Ying; Kong, Huimin; Lemieux, Bertrand

2013-10-11

Helicase-dependent amplification (HDA) is a novel method for the isothermal in vitro amplification of nucleic acids. The HDA reaction selectively amplifies a target sequence by extension of two oligonucleotide primers. Unlike the polymerase chain reaction (PCR), HDA uses a helicase enzyme to separate the deoxyribonucleic acid (DNA) strands, rather than heat denaturation. This allows DNA amplification without the need for thermal cycling. The helicase used in HDA is a helicase super family II protein obtained from a thermophilic organism, Thermoanaerobacter tengcongensis (TteUvrD). This thermostable helicase is capable of unwinding blunt-end nucleic acid substrates at elevated temperatures (60° to 65°C). The HDA reaction can also be coupled with reverse transcription for ribonucleic acid (RNA) amplification. The products of this reaction can be detected during the reaction using fluorescent probes when incubations are conducted in a fluorimeter. Alternatively, products can be detected after amplification using a disposable amplicon containment device that contains an embedded lateral flow strip. Copyright © 2013 John Wiley & Sons, Inc.

49 CFR 236.335 - Dogs, stops and trunnions of mechanical locking.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Dogs, stops and trunnions of mechanical locking..., AND APPLIANCES Interlocking Rules and Instructions § 236.335 Dogs, stops and trunnions of mechanical locking. Driving pieces, dogs, stops and trunnions shall be rigidly secured to locking bars. Swing dogs...

49 CFR 236.207 - Electric lock on hand-operated switch; control.

Science.gov (United States)

2010-10-01

..., AND APPLIANCES Automatic Block Signal Systems Standards § 236.207 Electric lock on hand-operated switch; control. Electric lock on hand-operated switch shall be controlled so that it cannot be unlocked... 49 Transportation 4 2010-10-01 2010-10-01 false Electric lock on hand-operated switch; control...

Aktuaalsetest tendentsidest elektroakustilise muusika alal Eestis / Gerhard Lock

Index Scriptorium Estoniae

Lock, Gerhard, 1978-

2007-01-01

Elektroakustilise muusika lähiajaloost, elektroakustilist muusikat viljelevatest Eesti heliloojatest. Age Hirv, Raun Juurikas, Liis Jürgens, Andrus Kallastu, Tatjana Kozlova, Ülo Krigul, Margo Kõlar, Märt-Matis Lill, Gerhard Lock, Hans-Gunter Lock, Malle Maltis, Jüri Reinvere, Mart Siimer, Mirjam Tally, Toomas Trass, Lauri-Dag Tüür oma muusikast

Rapid hybridization of nucleic acids using isotachophoresis

Science.gov (United States)

Bercovici, Moran; Han, Crystal M.; Liao, Joseph C.; Santiago, Juan G.

2012-01-01

We use isotachophoresis (ITP) to control and increase the rate of nucleic acid hybridization reactions in free solution. We present a new physical model, validation experiments, and demonstrations of this assay. We studied the coupled physicochemical processes of preconcentration, mixing, and chemical reaction kinetics under ITP. Our experimentally validated model enables a closed form solution for ITP-aided reaction kinetics, and reveals a new characteristic time scale which correctly predicts order 10,000-fold speed-up of chemical reaction rate for order 100 pM reactants, and greater enhancement at lower concentrations. At 500 pM concentration, we measured a reaction time which is 14,000-fold lower than that predicted for standard second-order hybridization. The model and method are generally applicable to acceleration of reactions involving nucleic acids, and may be applicable to a wide range of reactions involving ionic reactants. PMID:22733732

Tom Bevill Upper Lock Approach, Tennessee-Tombigbee Waterway, Alabama: Hydraulic Navigation Investigation

National Research Council Canada - National Science Library

Winkler, Michael

2003-01-01

.... The lock is connected to the dam with a 150-ft abutment wall. A strong crosscurrent or outdraft existing in and around the upstream lock entrance causes difficulty for tow traffic navigating the lock...

Accuracy assessment of the linear Poisson-Boltzmann equation and reparametrization of the OBC generalized Born model for nucleic acids and nucleic acid-protein complexes.

Science.gov (United States)

Fogolari, Federico; Corazza, Alessandra; Esposito, Gennaro

2015-04-05

The generalized Born model in the Onufriev, Bashford, and Case (Onufriev et al., Proteins: Struct Funct Genet 2004, 55, 383) implementation has emerged as one of the best compromises between accuracy and speed of computation. For simulations of nucleic acids, however, a number of issues should be addressed: (1) the generalized Born model is based on a linear model and the linearization of the reference Poisson-Boltmann equation may be questioned for highly charged systems as nucleic acids; (2) although much attention has been given to potentials, solvation forces could be much less sensitive to linearization than the potentials; and (3) the accuracy of the Onufriev-Bashford-Case (OBC) model for nucleic acids depends on fine tuning of parameters. Here, we show that the linearization of the Poisson Boltzmann equation has mild effects on computed forces, and that with optimal choice of the OBC model parameters, solvation forces, essential for molecular dynamics simulations, agree well with those computed using the reference Poisson-Boltzmann model. © 2015 Wiley Periodicals, Inc.

Predicting nucleic acid binding interfaces from structural models of proteins.

Science.gov (United States)

Dror, Iris; Shazman, Shula; Mukherjee, Srayanta; Zhang, Yang; Glaser, Fabian; Mandel-Gutfreund, Yael

2012-02-01

The function of DNA- and RNA-binding proteins can be inferred from the characterization and accurate prediction of their binding interfaces. However, the main pitfall of various structure-based methods for predicting nucleic acid binding function is that they are all limited to a relatively small number of proteins for which high-resolution three-dimensional structures are available. In this study, we developed a pipeline for extracting functional electrostatic patches from surfaces of protein structural models, obtained using the I-TASSER protein structure predictor. The largest positive patches are extracted from the protein surface using the patchfinder algorithm. We show that functional electrostatic patches extracted from an ensemble of structural models highly overlap the patches extracted from high-resolution structures. Furthermore, by testing our pipeline on a set of 55 known nucleic acid binding proteins for which I-TASSER produces high-quality models, we show that the method accurately identifies the nucleic acids binding interface on structural models of proteins. Employing a combined patch approach we show that patches extracted from an ensemble of models better predicts the real nucleic acid binding interfaces compared with patches extracted from independent models. Overall, these results suggest that combining information from a collection of low-resolution structural models could be a valuable approach for functional annotation. We suggest that our method will be further applicable for predicting other functional surfaces of proteins with unknown structure. Copyright © 2011 Wiley Periodicals, Inc.

Door locking and exit security measures on acute psychiatric admission wards

NARCIS (Netherlands)

Nijman, H.L.I.; Bowers, L.; Haglund, K.; Muir-Cochrane, E.; Simpson, A.; Merwe, M. van der

2011-01-01

Locking the exit doors of psychiatric wards is believed to reduce the risk of patients absconding. The aims of the study were to investigate both the prevalence of door locking and other exit security measures on UK admission wards, as well as whether door locking appears to be effective in keeping

Advances phase-lock techniques

CERN Document Server

Crawford, James A

2008-01-01

From cellphones to micrprocessors, to GPS navigation, phase-lock techniques are utilized in most all modern electronic devices. This high-level book takes a systems-level perspective, rather than circuit-level, which differentiates it from other books in the field.

Biomimetic High Density Lipoprotein Nanoparticles For Nucleic Acid Delivery

Science.gov (United States)

McMahon, Kaylin M.; Mutharasan, R. Kannan; Tripathy, Sushant; Veliceasa, Dorina; Bobeica, Mariana; Shumaker, Dale K.; Luthi, Andrea J.; Helfand, Brian T.; Ardehali, Hossein; Mirkin, Chad A.; Volpert, Olga; Thaxton, C. Shad

2014-01-01

We report a gold nanoparticle-templated high density lipoprotein (HDL AuNP) platform for gene therapy which combines lipid-based nucleic acid transfection strategies with HDL biomimicry. For proof-of-concept, HDL AuNPs are shown to adsorb antisense cholesterylated DNA. The conjugates are internalized by human cells, can be tracked within cells using transmission electron microscopy (TEM), and regulate target gene expression. Overall, the ability to directly image the AuNP core within cells, the chemical tailorability of the HDL AuNP platform, and the potential for cell-specific targeting afforded by HDL biomimicry make this platform appealing for nucleic acid delivery. PMID:21319839

Nucleic acid aptamers: an emerging frontier in cancer therapy.

Science.gov (United States)

Zhu, Guizhi; Ye, Mao; Donovan, Michael J; Song, Erqun; Zhao, Zilong; Tan, Weihong

2012-11-04

The last two decades have witnessed the development and application of nucleic acid aptamers in a variety of fields, including target analysis, disease therapy, and molecular and cellular engineering. The efficient and widely applicable aptamer selection, reproducible chemical synthesis and modification, generally impressive target binding selectivity and affinity, relatively rapid tissue penetration, low immunogenicity, and rapid systemic clearance make aptamers ideal recognition elements for use as therapeutics or for in vivo delivery of therapeutics. In this feature article, we discuss the development and biomedical application of nucleic acid aptamers, with emphasis on cancer cell aptamer isolation, targeted cancer therapy, oncology biomarker identification and drug discovery.

A scalable lock-free hash table with open addressing

DEFF Research Database (Denmark)

Nielsen, Jesper Puge; Karlsson, Sven

2016-01-01

and concurrent operations without any locks. In this paper, we present a new fully lock-free open addressed hash table with a simpler design than prior published work. We split hash table insertions into two atomic phases: first inserting a value ignoring other concurrent operations, then in the second phase......Concurrent data structures synchronized with locks do not scale well with the number of threads. As more scalable alternatives, concurrent data structures and algorithms based on widely available, however advanced, atomic operations have been proposed. These data structures allow for correct...

Experimental investigation of different regimes of mode-locking in a high repetition rate passively mode-locked semiconductor quantum-dot laser.

Science.gov (United States)

Kéfélian, Fabien; O'Donoghue, Shane; Todaro, Maria Teresa; McInerney, John; Huyet, Guillaume

2009-04-13

We report experimental investigations on a two-section 16-GHz repetition rate InAs/GaAs quantum dot passively mode-locked laser. Near the threshold current, pseudo-periodic Q-switching with complex dynamics is exhibited. Mode-locking operation regimes characterized by different repetition rates and timing jitter levels are encountered up to twice the threshold current. Evolution of the RF spectrum and optical spectrum with current is compared. The different mode-locked regimes are shown to be associated with different spectral and temporal shapes, ranging from 1.3 to 6 ps. This point is discussed by introducing the existence of two different supermodes. Repetition rate evolution and timing jitter increase is attributed to the coupling between the dominant and the secondary supermodes.

Space-time considerations in the phase locking of high harmonics

International Nuclear Information System (INIS)

Gaarde, Mette B.; Schafer, Kenneth J.

2002-01-01

The combination of several high order harmonics can produce an attosecond pulse train, provided that the harmonics are locked in phase to each other. We present calculations that evaluate the degree of phase locking that is achieved in argon and neon gases interacting with an intense, 50 fs laser pulse, for a range of macroscopic conditions. We find that phase locking depends on both the temporal and the spatial phase behavior of the harmonics, as determined by the interplay between the intrinsic dipole phase and the phase matching in the nonlinear medium. We show that, as a consequence of this, it is not possible to compensate for a lack of phase locking by purely temporal phase manipulation

Phase locking of moving magnetic vortices in bridge-coupled nanodisks

International Nuclear Information System (INIS)

Zhu, Qiyuan; Zheng, Qi; Liu, Xianyin; Liu, Qingfang; Wang, Jianbo

2015-01-01

In this paper, phase locking dynamics of vortices induced by spin transfer torque in bridge-coupled nanodisks are studied by micromagnetic simulations. In the presence of the bridge coupling, the required time for the phase locking is dramatically reduced, and the phase difference between the two vortices keeps at a nonzero value after the phase locking. Moreover, the phase difference is affected significantly by bridge coupling, Oersted field distribution, nanodisk size, as well as in-plane bias magnetic field. In addition, the coupled gyrotropic frequency of vortices depends linearly on the perpendicular magnetic field. This systematic study of phase locking parameters, especially the phase difference, is important for the applications of vortex-based spin-torque nano-oscillators

Phase locking of moving magnetic vortices in bridge-coupled nanodisks

Energy Technology Data Exchange (ETDEWEB)

Zhu, Qiyuan; Zheng, Qi; Liu, Xianyin; Liu, Qingfang, E-mail: liuqf@lzu.edu.cn [Key Laboratory for Magnetism and Magnetic Materials of the Ministry of Education, Lanzhou University, Lanzhou 730000 (China); Wang, Jianbo [Key Laboratory for Magnetism and Magnetic Materials of the Ministry of Education, Lanzhou University, Lanzhou 730000 (China); Key Laboratory of Special Function Materials and Structure Design, Ministry of Education, Lanzhou University, Lanzhou 730000 (China)

2015-05-07

In this paper, phase locking dynamics of vortices induced by spin transfer torque in bridge-coupled nanodisks are studied by micromagnetic simulations. In the presence of the bridge coupling, the required time for the phase locking is dramatically reduced, and the phase difference between the two vortices keeps at a nonzero value after the phase locking. Moreover, the phase difference is affected significantly by bridge coupling, Oersted field distribution, nanodisk size, as well as in-plane bias magnetic field. In addition, the coupled gyrotropic frequency of vortices depends linearly on the perpendicular magnetic field. This systematic study of phase locking parameters, especially the phase difference, is important for the applications of vortex-based spin-torque nano-oscillators.

Mutual phase-locking of several spin-torque nano-oscillators

International Nuclear Information System (INIS)

Prokopenko, O.V.; Sulimenko, O.R.

2011-01-01

Criterions for evaluating the effectiveness of mutual phase-locking of several spin-torque nano-oscillators (STNO) are proposed. An application of one of the criterions to describe the process of mutual phase-locking of the three almost identical STNO's is considered

New nucleic acid testing devices to diagnose infectious diseases in resource-limited settings.

Science.gov (United States)

Maffert, P; Reverchon, S; Nasser, W; Rozand, C; Abaibou, H

2017-10-01

Point-of-care diagnosis based on nucleic acid testing aims to incorporate all the analytical steps, from sample preparation to nucleic acid amplification and detection, in a single device. This device needs to provide a low-cost, robust, sensitive, specific, and easily readable analysis. Microfluidics has great potential for handling small volumes of fluids on a single platform. Microfluidic technology has recently been applied to paper, which is already used in low-cost lateral flow tests. Nucleic acid extraction from a biological specimen usually requires cell filtration and lysis on specific membranes, while affinity matrices, such as chitosan or polydiacetylene, are well suited to concentrating nucleic acids for subsequent amplification. Access to electricity is often difficult in resource-limited areas, so the amplification step needs to be equipment-free. Consequently, the reaction has to be isothermal to alleviate the need for a thermocycler. LAMP, NASBA, HDA, and RPA are examples of the technologies available. Nucleic acid detection techniques are currently based on fluorescence, colorimetry, or chemiluminescence. For point-of-care diagnostics, the results should be readable with the naked eye. Nowadays, interpretation and communication of results to health professionals could rely on a smartphone, used as a telemedicine device. The major challenge of creating an "all-in-one" diagnostic test involves the design of an optimal solution and a sequence for each analytical step, as well as combining the execution of all these steps on a single device. This review provides an overview of available materials and technologies which seem to be adapted to point-of-care nucleic acid-based diagnosis, in low-resource areas.

Experimental study of self-balanced startup characteristics of density lock

International Nuclear Information System (INIS)

Gu Haifeng; Yan Changqi; Chen Wei

2013-01-01

With passive residual heat removal system which applies the density lock as background, combining the experimental study and theoretical analysis, researches on the operating characteristics and feasibility of self-balanced startup of density lock were made in this system. The results show that self-balanced startup can be divided into two stages: Warming up stage in which the valve is closed; self-balanced stage in which the valve is open. The two requisite conditions ensuring the closure of density lock can be realized respectively in these two stages, which ensure the separation of the passive residual heat removal system from the primary circuit system by the density lock. During the stage of warming up, with the help of special structure of the density lock, the position of the transition points of the heat transfer modes is controlled effectively, and the formation of interface between the cold and hot fluids is promoted. During the self-balanced stage, with the help of the characteristics of self-stability of the hydraulic balance, the motion of interface is controlled effectively, and the hydraulic balance is established automatically in the density lock. All of the results fully prove the feasibility of self-balanced startup. (authors)

The locking and unlocking thresholds for tearing modes in a cylindrical tokamak

Energy Technology Data Exchange (ETDEWEB)

Huang, Wenlong [CAS Key Laboratory of Geospace Environment and Department of Modern Physics, University of Science and Technology of China, Hefei, Anhui 230026 (China); Zhu, Ping, E-mail: pzhu@ustc.edu.cn [CAS Key Laboratory of Geospace Environment and Department of Modern Physics, University of Science and Technology of China, Hefei, Anhui 230026 (China); Department of Engineering Physics, University of Wisconsin-Madison, Madison, Wisconsin 53706 (United States)

2016-03-15

The locking and unlocking thresholds for tearing modes are in general different. In this work, the physics origin for this difference is illustrated from theory analysis, and a numerical procedure is developed to find both locking and unlocking thresholds. In particular, a new scaling law for the unlocking threshold that is valid in both weak and strong rotation regimes has been derived from the lowest amplitude of the RMP (resonant magnetic perturbation) allowed for the locked-mode solution. Above the unlocking threshold, the criterion for the phase-flip instability is extended to identify the entire locked-mode states. Two different regimes of the RMP amplitude in terms of the accessibility of the locked-mode states have been found. In the first regime, the locked-mode state may or may not be accessible depending on the initial conditions of an evolving island. In the second regime, the locked-mode state can always be reached regardless of the initial conditions of the tearing mode. The lowest RMP amplitude for the second regime is determined to be the mode-locking threshold. The different characteristics of the two regimes above the unlocking threshold reveal the underlying physics for the gap between the locking and unlocking thresholds and provide an explanation for the closely related and widely observed hysteresis phenomena in island evolution during the sweeping process of the RMP amplitude up and down across that threshold gap.

Carbon composite micro- and nano-tubes-based electrodes for detection of nucleic acids

Directory of Open Access Journals (Sweden)

Huska Dalibor

2011-01-01

Full Text Available Abstract The first aim of this study was to fabricate vertically aligned multiwalled carbon nanotubes (MWCNTs. MWCNTs were successfully prepared by using plasma enhanced chemical vapour deposition. Further, three carbon composite electrodes with different content of carbon particles with various shapes and sizes were prepared and tested on measuring of nucleic acids. The dependences of adenine peak height on the concentration of nucleic acid sample were measured. Carbon composite electrode prepared from a mixture of glassy and spherical carbon powder and MWCNTs had the highest sensitivity to nucleic acids. Other interesting result is the fact that we were able to distinguish signals for all bases using this electrode.

Phase-locking regimes of photonic crystal nanocavity laser arrays

DEFF Research Database (Denmark)

Skovgård, Troels Suhr; Kristensen, Philip Trøst; Mørk, Jesper

2011-01-01

-difference time-domain calculations, the typical coupling strength is extracted for realistic structures. Phase-locking regimes are identified, and their stability with respect to parameter variation is investigated. The results suggest that quantum well devices are not well suited for phase-locked nanocavity...

Engineering nucleic acid structures for programmable molecular circuitry and intracellular biocomputation

Science.gov (United States)

Li, Jiang; Green, Alexander A.; Yan, Hao; Fan, Chunhai

2017-11-01

Nucleic acids have attracted widespread attention due to the simplicity with which they can be designed to form discrete structures and programmed to perform specific functions at the nanoscale. The advantages of DNA/RNA nanotechnology offer numerous opportunities for in-cell and in-vivo applications, and the technology holds great promise to advance the growing field of synthetic biology. Many elegant examples have revealed the potential in integrating nucleic acid nanostructures in cells and in vivo where they can perform important physiological functions. In this Review, we summarize the current abilities of DNA/RNA nanotechnology to realize applications in live cells and then discuss the key problems that must be solved to fully exploit the useful properties of nanostructures. Finally, we provide viewpoints on how to integrate the tools provided by DNA/RNA nanotechnology and related new technologies to construct nucleic acid nanostructure-based molecular circuitry for synthetic biology.

Key Aspects of Nucleic Acid Library Design for in Vitro Selection

Science.gov (United States)

Vorobyeva, Maria A.; Davydova, Anna S.; Vorobjev, Pavel E.; Pyshnyi, Dmitrii V.; Venyaminova, Alya G.

2018-01-01

Nucleic acid aptamers capable of selectively recognizing their target molecules have nowadays been established as powerful and tunable tools for biospecific applications, be it therapeutics, drug delivery systems or biosensors. It is now generally acknowledged that in vitro selection enables one to generate aptamers to almost any target of interest. However, the success of selection and the affinity of the resulting aptamers depend to a large extent on the nature and design of an initial random nucleic acid library. In this review, we summarize and discuss the most important features of the design of nucleic acid libraries for in vitro selection such as the nature of the library (DNA, RNA or modified nucleotides), the length of a randomized region and the presence of fixed sequences. We also compare and contrast different randomization strategies and consider computer methods of library design and some other aspects. PMID:29401748

Diode array pumped, non-linear mirror Q-switched and mode-locked

Indian Academy of Sciences (India)

A non-linear mirror consisting of a lithium triborate crystal and a dichroic output coupler are used to mode-lock (passively) an Nd : YVO4 laser, pumped by a diode laser array. The laser can operate both in cw mode-locked and simultaneously Q-switched and mode-locked (QML) regime. The peak power of the laser while ...

Performance Characterization of Loctite (Registered Trademark) 242 and 271 Liquid Locking Compounds (LLCs) as a Secondary Locking Feature for International Space Station (ISS) Fasteners

Science.gov (United States)

Dube, Michael J.; Gamwell, Wayne R.

2011-01-01

Several International Space Station (ISS) hardware components use Loctite (and other polymer based liquid locking compounds (LLCs)) as a means of meeting the secondary (redundant) locking feature requirement for fasteners. The primary locking method is the fastener preload, with the application of the Loctite compound which when cured is intended to resist preload reduction. The reliability of these compounds has been questioned due to a number of failures during ground testing. The ISS Program Manager requested the NASA Engineering and Safety Center (NESC) to characterize and quantify sensitivities of Loctite being used as a secondary locking feature. The findings and recommendations provided in this investigation apply to the anaerobic LLCs Loctite 242 and 271. No other anaerobic LLCs were evaluated for this investigation. This document contains the findings and recommendations of the NESC investigation

Narrow Q-switching pulse width and low mode-locking repetition rate Q-switched mode locking with a new coupled laser cavity

International Nuclear Information System (INIS)

Peng, J Y; Zheng, Y; Shen, J P; Shi, Y X

2013-01-01

An original diode-pumped Q-switched and mode-locked solid state Nd:GdVO 4 laser is demonstrated. The laser operates with double saturable absorbers and a new coupled laser cavity. The Q-switching envelope width is compressed to be about 15 ns and the mode-locking repetition rate is as low as 90 MHz. (paper)

RNA:DNA Ratio and Other Nucleic Acid Derived Indices in Marine Ecology

Directory of Open Access Journals (Sweden)

Luis Chícharo

2008-08-01

Full Text Available Some of most used indicators in marine ecology are nucleic acid-derived indices. They can be divided by target levels in three groups: 1 at the organism level as ecophysiologic indicators, indicators such as RNA:DNA ratios, DNA:dry weight and RNA:protein, 2 at the population level, indicators such as growth rate, starvation incidence or fisheries impact indicators, and 3 at the community level, indicators such as trophic interactions, exergy indices and prey identification. The nucleic acids derived indices, especially RNA:DNA ratio, have been applied with success as indicators of nutritional condition, well been and growth in marine organisms. They are also useful as indicators of natural or anthropogenic impacts in marine population and communities, such as upwelling or dredge fisheries, respectively. They can help in understanding important issues of marine ecology such as trophic interactions in marine environment, fish and invertebrate recruitment failure and biodiversity changes, without laborious work of counting, measuring and identification of small marine organisms. Besides the objective of integrate nucleic acid derived indices across levels of organization, the paper will also include a general characterization of most used nucleic acid derived indices in marine ecology and also advantages and limitations of them. We can conclude that using indicators, such RNA:DNA ratios and other nucleic acids derived indices concomitantly with organism and ecosystems measures of responses to climate change (distribution, abundance, activity, metabolic rate, survival will allow for the development of more rigorous and realistic predictions of the effects of anthropogenic climate change on marine systems.

John Locke on persons and personal identity

OpenAIRE

Boeker, Ruth

2013-01-01

John Locke claims both that ‘person’ is a forensic term and that personal identity consists in sameness of consciousness. The aim of my dissertation is to explain and critically assess how Locke links his moral and legal account of personhood to his account of personal identity in terms of sameness of consciousness. My interpretation of Locke’s account of persons and personal identity is embedded in Locke’s sortal-dependent account of identity. Locke’s sortal-dependent ac...

Phase-locked flux-flow Josephson oscillator

DEFF Research Database (Denmark)

Ustinov, A. V.; Mygind, Jesper; Oboznov, V. A.

1992-01-01

We report on the observation of large rf induced steps due to phase-locking of unidirectional flux-flow motion in long quasi-one-dimensional Josephson junctions. The external microwave irradiation in the frequency range 62–77 GHz was applied from the edge of the junction at which the fluxons enter....... The dependence of the amplitude of the phase-locked step on external magnetic field and microwave power has been measured. The observed zero-crossing steps have potential application in Josephson voltage standards. A simple model for the flux-flow as determined by the microwave driven boundary gate at the edge...

Chemical consequences of irradiating nucleic acids

International Nuclear Information System (INIS)

Ward, J.F.

1976-01-01

On the basis of literature data, a discussion is presented of the DNA damage which would be produced in a cellular environment and an attempt is made to place this damage in perspective as a potential hazard in food irradiation. The topics discussed are radiation damage mechanisms, OH reactions with DNA, base products, sugar products, and evaluation of damage from irradiated nucleic acids

Development of the Lock Protocol for DEPSKY Storage System

Directory of Open Access Journals (Sweden)

NASCIMENTO, P. S.

2015-06-01

Full Text Available Data management in environments based on several clouds (cloud-of-clouds should be dependable and secure. DEPSKY may assure that characteristics through mechanisms as cryptography and data replication, however DEPSKY does not support concurrent writing, a desirable functionality for many applications. This paper presents the development and a performance analysis of a lock algorithmfor DEPSKY storage system. The paper also presents validation test and performance test of the algorithm. Such protocol allows concurrent writing, through a low contention lock mechanism that uses lock filesfi to dene who is allowed to write in a data unit.

Mode locking of Yb:GdYAG ceramic lasers with an isotropic cavity

International Nuclear Information System (INIS)

Xu, C W; Tang, D Y; Zhu, H Y; Zhang, J

2013-01-01

We report on the passive mode locking of a diode pumped Yb:GdYAG ceramic laser with a near isotropic cavity. It is found that the laser could simultaneously mode lock in the two orthogonal principal polarization directions of the cavity, and the mode locked pulses of the two polarizations have identical features and are temporally perfectly synchronized. However, their pulse energy varies out-of-phase periodically, manifesting the antiphase dynamics of mode locked lasers. (letter)

Three Alternative Symbol-Lock Detectors

Science.gov (United States)

Shihabi, Mazen M.; Hinedi, Sami M.; Shah, Biren N.

1993-01-01

Three symbol-lock detectors proposed as alternatives in advanced receivers processing non-return-to-zero binary data signals. Two perform operations similar to those of older square-law and absolute-value types. However, integrals computed during nonoverlapping symbol periods and, therefore, only one integrator needed in each such detector. Proposed detectors simpler, but performances worse because noises in overlapping samples correlated, whereas noises in nonoverlapping samples not correlated. Third detector is signal-power-estimator type. Signal integrated during successive half symbol cycles, and therefore only one integrator needed. Half-cycle integrals multiplied to eliminate effect of symbol polarity, and products accumulated during M-cycle observation period to smooth out estimate of signal power. If estimated signal power exceeds threshold, delta, then lock declared.

Complication with Removal of a Lumbar Spinal Locking Plate

Directory of Open Access Journals (Sweden)

Brooke Crawford

2015-01-01

Full Text Available Introduction. The use of locking plate technology for anterior lumbar spinal fusion has increased stability of the vertebral fusion mass over traditional nonconstrained screw and plate systems. This case report outlines a complication due to the use of this construct. Case. A patient with a history of L2 corpectomy and anterior spinal fusion presented with discitis at the L4/5 level and underwent an anterior lumbar interbody fusion (ALIF supplemented with a locking plate placed anterolaterally for stability. Fifteen months after the ALIF procedure, he returned with a hardware infection. He underwent debridement of the infection site and removal of hardware. Results. Once hardware was exposed, removal of the locking plate screws was only successful in one out of four screws using a reverse thread screw removal device. Three of the reverse thread screw removal devices broke in attempt to remove the subsequent screws. A metal cutting drill was then used to break hoop stresses associated with the locking device and the plate was removed. Conclusion. Anterior locking plates add significant stability to an anterior spinal fusion mass. However, removal of this hardware can be complicated by the inherent properties of the design with significant risk of major vascular injury.

Magnetized color flavor locked state and compact stars

CERN Document Server

Felipe, R Gonzalez; Martinez, A Perez

2010-01-01

The stability of the color flavor locked phase in the presence of a strong magnetic field is investigated within the phenomenological MIT bag model, taking into account the variation of the strange quark mass, the baryon density, the magnetic field, as well as the bag and gap parameters. It is found that the minimum value of the energy per baryon in a color flavor locked state at vanishing pressure is lower than the corresponding one for unpaired magnetized strange quark matter and, as the magnetic field increases, the energy per baryon decreases. This implies that magnetized color flavor locked matter is more stable and could become the ground state inside neutron stars. The mass-radius relation for such stars is also studied.

Mode-locking behavior of Izhikevich neurons under periodic external forcing

Science.gov (United States)

Farokhniaee, AmirAli; Large, Edward W.

2017-06-01

Many neurons in the auditory system of the brain must encode periodic signals. These neurons under periodic stimulation display rich dynamical states including mode locking and chaotic responses. Periodic stimuli such as sinusoidal waves and amplitude modulated sounds can lead to various forms of n :m mode-locked states, in which a neuron fires n action potentials per m cycles of the stimulus. Here, we study mode-locking in the Izhikevich neurons, a reduced model of the Hodgkin-Huxley neurons. The Izhikevich model is much simpler in terms of the dimension of the coupled nonlinear differential equations compared with other existing models, but excellent for generating the complex spiking patterns observed in real neurons. We obtained the regions of existence of the various mode-locked states on the frequency-amplitude plane, called Arnold tongues, for the Izhikevich neurons. Arnold tongue analysis provides useful insight into the organization of mode-locking behavior of neurons under periodic forcing. We find these tongues for both class-1 and class-2 excitable neurons in both deterministic and noisy regimes.

Mechanical Design of Downhole Tractor Based on Two-Way Self-locking Mechanism

Science.gov (United States)

Fang, Delei; Shang, Jianzhong; Luo, Zirong; Wu, Guoheng; Liu, Yiying

2018-03-01

Based on the technology of horizontal well tractor, a kind of downhole tractor was developed which can realize Two-Way self-locking function. Aiming at the needs of horizontal well logging to realize the target of small size, high traction and high reliability, the tractor selects unique heart-shaped CAM as the locking mechanism. The motion principle of telescopic downhole tractor, the design of mechanical structure and locking principle of the locking mechanism are all analyzed. The mathematical expressions of traction are obtained by mechanical analysis of parallel support rod in the locking mechanism. The force analysis and contour design of the heart-shaped CAM are performed, which can lay the foundation for the development of tractor prototype.

49 CFR 236.308 - Mechanical or electric locking or electric circuits; requisites.

Science.gov (United States)

2010-10-01

..., AND APPLIANCES Interlocking Standards § 236.308 Mechanical or electric locking or electric circuits; requisites. Mechanical or electric locking or electric circuits shall be installed to prevent signals from... 49 Transportation 4 2010-10-01 2010-10-01 false Mechanical or electric locking or electric...

Lock-In Agreements in Venture Capital Backed UK IPOs

NARCIS (Netherlands)

Espenlaub, S.; Goergen, M.; Khurshed, A.; Renneboog, L.D.R.

2002-01-01

This paper examines the impact of venture-capital backing of UK companies issuing shares at flotation on the characteristics of the lock-in agreements entered into by the existing shareholders, and on the abnormal returns realised around the expiry of the directors' lock-in agreements.The study

Three-dimensional graphene based passively mode-locked fiber laser.

Science.gov (United States)

Yang, Y; Loeblein, M; Tsang, S H; Chow, K K; Teo, E H T

2014-12-15

We present an all-fiber passively mode-locked fiber laser incorporating three-dimensional (3D) graphene as a saturable absorber (SA) for the first time to the best of our knowledge. The 3D graphene is synthesized by template-directed chemical vapor deposition (CVD). The SA is then simply formed by sandwiching the freestanding 3D graphene between two conventional fiber connectors without any deposition process. It is demonstrated that such 3D graphene based SA is capable to produce high quality mode-locked pulses. A passively mode-locked fiber laser is constructed and stable output pulses with a fundamental repetition rate of ~9.9 MHz and a pulse width of ~1 ps are generated from the fiber laser. The average output power of the laser is ~10.5 mW while the output pulse is operating at single pulse region. The results imply that the freestanding 3D graphene can be applied as an effective saturable absorption material for passively mode-locked lasers.

Workshop on gate valve pressure locking and thermal binding

International Nuclear Information System (INIS)

Brown, E.J.

1995-07-01

The purpose of the Workshop on Gate Valve Pressure Locking and Thermal Binding was to discuss pressure locking and thermal binding issues that could lead to inoperable gate valves in both boiling water and pressurized water reactors. The goal was to foster exchange of information to develop the technical bases to understand the phenomena, identify the components that are susceptible, discuss actual events, discuss the safety significance, and illustrate known corrective actions that can prevent or limit the occurrence of pressure locking or thermal binding. The presentations were structured to cover U.S. Nuclear Regulatory Commission staff evaluation of operating experience and planned regulatory activity; industry discussions of specific events, including foreign experience, and efforts to determine causes and alleviate the affects; and valve vendor experience and recommended corrective action. The discussions indicated that identifying valves susceptible to pressure locking and thermal binding was a complex process involving knowledge of components, systems, and plant operations. The corrective action options are varied and straightforward

Quantum Enigma Machines and the Locking Capacity of a Quantum Channel

Directory of Open Access Journals (Sweden)

Saikat Guha

2014-01-01

Full Text Available The locking effect is a phenomenon that is unique to quantum information theory and represents one of the strongest separations between the classical and quantum theories of information. The Fawzi-Hayden-Sen locking protocol harnesses this effect in a cryptographic context, whereby one party can encode n bits into n qubits while using only a constant-size secret key. The encoded message is then secure against any measurement that an eavesdropper could perform in an attempt to recover the message, but the protocol does not necessarily meet the composability requirements needed in quantum key distribution applications. In any case, the locking effect represents an extreme violation of Shannon’s classical theorem, which states that information-theoretic security holds in the classical case if and only if the secret key is the same size as the message. Given this intriguing phenomenon, it is of practical interest to study the effect in the presence of noise, which can occur in the systems of both the legitimate receiver and the eavesdropper. This paper formally defines the locking capacity of a quantum channel as the maximum amount of locked information that can be reliably transmitted to a legitimate receiver by exploiting many independent uses of a quantum channel and an amount of secret key sublinear in the number of channel uses. We provide general operational bounds on the locking capacity in terms of other well-known capacities from quantum Shannon theory. We also study the important case of bosonic channels, finding limitations on these channels’ locking capacity when coherent-state encodings are employed and particular locking protocols for these channels that might be physically implementable.

Exploring How User Routine Affects the Recognition Performance of a Lock Pattern

NARCIS (Netherlands)

de Wide, Lisa; Spreeuwers, Lieuwe Jan; Veldhuis, Raymond N.J.

2015-01-01

To protect an Android smartphone against attackers, a lock pattern can be used. Nevertheless, shoulder-surfing and smudge attacks can be used to get access despite of this protection. To combat these attacks, biometric recognition can be added to the lock pattern, such that the lock-pattern

Nucleic acid-based diagnostics for infectious diseases in public health affairs.

Science.gov (United States)

Yu, Albert Cheung-Hoi; Vatcher, Greg; Yue, Xin; Dong, Yan; Li, Mao Hua; Tam, Patrick H K; Tsang, Parker Y L; Wong, April K Y; Hui, Michael H K; Yang, Bin; Tang, Hao; Lau, Lok-Ting

2012-06-01

Infectious diseases, mostly caused by bacteria and viruses but also a result of fungal and parasitic infection, have been one of the most important public health concerns throughout human history. The first step in combating these pathogens is to get a timely and accurate diagnosis at an affordable cost. Many kinds of diagnostics have been developed, such as pathogen culture, biochemical tests and serological tests, to help detect and fight against the causative agents of diseases. However, these diagnostic tests are generally unsatisfactory because they are not particularly sensitive and specific and are unable to deliver speedy results. Nucleic acid-based diagnostics, detecting pathogens through the identification of their genomic sequences, have shown promise to overcome the above limitations and become more widely adopted in clinical tests. Here we review some of the most popular nucleic acid-based diagnostics and focus on their adaptability and applicability to routine clinical usage. We also compare and contrast the characteristics of different types of nucleic acid-based diagnostics.

Locking screw-plate interface stability in carbon-fibre reinforced polyetheretherketone proximal humerus plates.

Science.gov (United States)

Hak, David J; Fader, Ryan; Baldini, Todd; Chadayammuri, Vivek B S

2017-09-01

Carbon-fibre reinforced polyetheretherketone (CFR-PEEK) plates have recently been introduced for proximal humerus fracture treatment. The purpose of this study was to compare the locking screw-plate interface stability in CFR-PEEK versus stainless steel (SS) proximal humerus plates. Locking screw mechanical stability was evaluated independently in proximal and shaft plate holes. Stiffness and load to failure were tested for three conditions: (1) on-axis locking screw insertion in CFR-PEEK versus SS plates, (2) on-axis locking screw insertion, removal, and reinsertion in CFR-PEEK plates, and (3) 10-degree off-axis locking screw insertion in CFR-PEEK plates. Cantilever bending at a rate of 1 mm/minute was produced by an Instron machine and load-displacement data recorded. Shaft locking screw load to failure was significantly greater in CFR-PEEK plates compared to SS plates (746.4 ± 89.7 N versus 596.5 ± 32.6 N, p PEEK plates (p PEEK plates. The mechanical stability of locking screws in CFR-PEEK plates is comparable or superior to locking screws in SS plates.

Analysis and experimental study on hydraulic balance characteristics in density lock

International Nuclear Information System (INIS)

Gu Haifeng; Yan Changqi; Sun Furong

2009-01-01

Through the simplified theoretical model, the hydraulic balance condition which should be met in the density lock is obtained, when reactor operates normally and density lock is closed. The main parameters influencing this condition are analyzed, and the results show that the hydraulic balance in the density lock is characterized with self-stability in a certain range. Meantime, a simulating experimental loop is built and experimental verification on the self-stability characteristic is done. Moreover, experimental study is done on the conditions of flow change of work fluids in the primary circuit in the process of stable operations. The experimental results show that the hydraulic balance in the density lock can recovered quickly, depending on the self-stability characteristic without influences on the sealing performance of density lock and normal operation of reactor, after the change of operation parameters breaks the hydraulic balance. (authors)

Recent Developments in Peptide-Based Nucleic Acid Delivery

Directory of Open Access Journals (Sweden)

Tobias Restle

2008-07-01

Full Text Available Despite the fact that non-viral nucleic acid delivery systems are generally considered to be less efficient than viral vectors, they have gained much interest in recent years due to their superior safety profile compared to their viral counterpart. Among these synthetic vectors are cationic polymers, branched dendrimers, cationic liposomes and cellpenetrating peptides (CPPs. The latter represent an assortment of fairly unrelated sequences essentially characterised by a high content of basic amino acids and a length of 10-30 residues. CPPs are capable of mediating the cellular uptake of hydrophilic macromolecules like peptides and nucleic acids (e.g. siRNAs, aptamers and antisenseoligonucleotides, which are internalised by cells at a very low rate when applied alone. Up to now, numerous sequences have been reported to show cell-penetrating properties and many of them have been used to successfully transport a variety of different cargos into mammalian cells. In recent years, it has become apparent that endocytosis is a major route of internalisation even though the mechanisms underlying the cellular translocation of CPPs are poorly understood and still subject to controversial discussions. In this review, we will summarise the latest developments in peptide-based cellular delivery of nucleic acid cargos. We will discuss different mechanisms of entry, the intracellular fate of the cargo, correlation studies of uptake versus biological activity of the cargo as well as technical problems and pitfalls.

A New Key-lock Method for User Authentication and Access Control

Institute of Scientific and Technical Information of China (English)

JI Dongyao; ZHANG Futai; WANG Yumin

2001-01-01

We propose a new key-lock methodfor user authentication and access control based onChinese remainder theorem, the concepts of the ac-cess control matrix, key-lock-pair, time stamp, and the NS public key protocol. Our method is dynamicand needs a minimum amount of computation in thesense that it only updates at most one key/lock foreach access request. We also demonstrate how an au-thentication protocol can be integrated into the ac-cess control method. By applying a time stamp, themethod can not only withstand replay attack, butalso strengthen the authenticating mechanism, whichcould not be achieved simultaneously in previous key-lock methods.

Mode-locking in advection-reaction-diffusion systems: An invariant manifold perspective

Science.gov (United States)

Locke, Rory A.; Mahoney, John R.; Mitchell, Kevin A.

2018-01-01

Fronts propagating in two-dimensional advection-reaction-diffusion systems exhibit a rich topological structure. When the underlying fluid flow is periodic in space and time, the reaction front can lock to the driving frequency. We explain this mode-locking phenomenon using the so-called burning invariant manifolds (BIMs). In fact, the mode-locked profile is delineated by a BIM attached to a relative periodic orbit (RPO) of the front element dynamics. Changes in the type (and loss) of mode-locking can be understood in terms of local and global bifurcations of the RPOs and their BIMs. We illustrate these concepts numerically using a chain of alternating vortices in a channel geometry.

Reusable locking tube in a reconstitutable fuel assembly

International Nuclear Information System (INIS)

Shallenberger, J.M.; Ferlan, S.J.

1987-01-01

This patent describes a reconstitutable fuel assembly including a top nozzle with an adapter plate having an interior wall forming at least one passageway, at least one guide thimble with an upper end portion, and an attaching structure having an outer socket formed by a circumferential groove defined in the adapter plate passageway wall and opening into the passageway and an inner socket formed by a circumferential bulge and at least one longitudinal slot defined in the upper end portion of the guide thimble. The circumferential bulge is capable of seating within the circumferential groove, an improved reusable tube for releasably locking the inner socket of the guide thimble upper end portion in locking engagement within the outer socket of the adapter plate passageway when the circumferential bulge is seated within the circumferential groove. The reusable tube comprises: (a) an elongated hollow tubular body capable of insertion within the adapter plate passageway and guide thimble upper end portion to a locking position therein such that the circumferential bulge of the inner socket is maintained seated in the locking engagement with the circumferential groove of the outer socket; and (b) at least a pair of dimples performed on the exterior of the tubular body prior to insertion of the body in the guide thimble upper end portion and to the locking position, the dimples being performed and configured to increase the thickness of the tubular body in relation to the remainder of the tubular body. The dimples are substantially resisting resilient yielding in relation to the remainder of the tubular body

Using river locks to teach hydrodynamic concepts

Science.gov (United States)

Carvalho-Santos, Vagson L.; Mendes, Thales C.; Silva, Enisvaldo C.; Rios, Márcio L.; Silva, Anderson A. P.

2013-11-01

In this work, the use of a river lock as a non-formal setting for teaching hydrodynamical concepts is proposed. In particular, we describe the operation of a river lock situated at the Sobradinho dam, on the São Francisco River (Brazil). A model to represent and to analyse the dynamics of river lock operation is presented and we derive the dynamical equations for the rising of the water column as an example to understand the Euler equation. Furthermore, with this activity, we enable the integration of content initially introduced in the classroom with practical applications, thereby allowing the association of physical themes to content relevant in disciplines such as history and geography. In addition, experiences of this kind enable teachers to talk about the environmental and social impacts caused by the construction of a dam and, consequently, a crossover of concepts has been made possible, leading to more meaningful learning for the students.

Using river locks to teach hydrodynamic concepts

International Nuclear Information System (INIS)

Carvalho-Santos, Vagson L; Mendes, Thales C; Silva, Enisvaldo C; Rios, Márcio L; Silva, Anderson A P

2013-01-01

In this work, the use of a river lock as a non-formal setting for teaching hydrodynamical concepts is proposed. In particular, we describe the operation of a river lock situated at the Sobradinho dam, on the São Francisco River (Brazil). A model to represent and to analyse the dynamics of river lock operation is presented and we derive the dynamical equations for the rising of the water column as an example to understand the Euler equation. Furthermore, with this activity, we enable the integration of content initially introduced in the classroom with practical applications, thereby allowing the association of physical themes to content relevant in disciplines such as history and geography. In addition, experiences of this kind enable teachers to talk about the environmental and social impacts caused by the construction of a dam and, consequently, a crossover of concepts has been made possible, leading to more meaningful learning for the students. (paper)

Nucleic acid secondary structure prediction and display.

OpenAIRE

Stüber, K

1986-01-01

A set of programs has been developed for the prediction and display of nucleic acid secondary structures. Information from experimental data can be used to restrict or enforce secondary structural elements. The predictions can be displayed either on normal line printers or on graphic devices like plotters or graphic terminals.

75 FR 71548 - Clarification of the Post Office Box Lock Replacement Fee

Science.gov (United States)

2010-11-24

... POSTAL SERVICE 39 CFR Part 111 Clarification of the Post Office Box Lock Replacement Fee AGENCY... of the lock replacement fee for Post Office TM boxes to reflect current practice. DATES: January 2... Standards for Domestic Mailing Services (75 FR 39477-39492). The applicability of the lock replacement fee...

Single-ion quantum lock-in amplifier.

Science.gov (United States)

Kotler, Shlomi; Akerman, Nitzan; Glickman, Yinnon; Keselman, Anna; Ozeri, Roee

2011-05-05

Quantum metrology uses tools from quantum information science to improve measurement signal-to-noise ratios. The challenge is to increase sensitivity while reducing susceptibility to noise, tasks that are often in conflict. Lock-in measurement is a detection scheme designed to overcome this difficulty by spectrally separating signal from noise. Here we report on the implementation of a quantum analogue to the classical lock-in amplifier. All the lock-in operations--modulation, detection and mixing--are performed through the application of non-commuting quantum operators to the electronic spin state of a single, trapped Sr(+) ion. We significantly increase its sensitivity to external fields while extending phase coherence by three orders of magnitude, to more than one second. Using this technique, we measure frequency shifts with a sensitivity of 0.42 Hz Hz(-1/2) (corresponding to a magnetic field measurement sensitivity of 15 pT Hz(-1/2)), obtaining an uncertainty of less than 10 mHz (350 fT) after 3,720 seconds of averaging. These sensitivities are limited by quantum projection noise and improve on other single-spin probe technologies by two orders of magnitude. Our reported sensitivity is sufficient for the measurement of parity non-conservation, as well as the detection of the magnetic field of a single electronic spin one micrometre from an ion detector with nanometre resolution. As a first application, we perform light shift spectroscopy of a narrow optical quadrupole transition. Finally, we emphasize that the quantum lock-in technique is generic and can potentially enhance the sensitivity of any quantum sensor. ©2011 Macmillan Publishers Limited. All rights reserved

Locks and Keys Service

CERN Multimedia

Claude Ducastel

The GS-LS-SEM section is pleased to inform you that as from Monday 30 November 2009, the opening hours of the Locks and Keys service will be the following: 08h30 - 12h30 / 13h30 - 16:30, Mondays to Fridays. GS-SEM-LS 73333

Real-time electrochemical monitoring of isothermal helicase-dependent amplification of nucleic acids.

Science.gov (United States)

Kivlehan, Francine; Mavré, François; Talini, Luc; Limoges, Benoît; Marchal, Damien

2011-09-21

We described an electrochemical method to monitor in real-time the isothermal helicase-dependent amplification of nucleic acids. The principle of detection is simple and well-adapted to the development of portable, easy-to-use and inexpensive nucleic acids detection technologies. It consists of monitoring a decrease in the electrochemical current response of a reporter DNA intercalating redox probe during the isothermal DNA amplification. The method offers the possibility to quantitatively analyze target nucleic acids in less than one hour at a single constant temperature, and to perform at the end of the isothermal amplification a DNA melt curve analysis for differentiating between specific and non-specific amplifications. To illustrate the potentialities of this approach for the development of a simple, robust and low-cost instrument with high throughput capability, the method was validated with an electrochemical system capable of monitoring up to 48 real-time isothermal HDA reactions simultaneously in a disposable microplate consisting of 48-electrochemical microwells. Results obtained with this approach are comparable to that obtained with a well-established but more sophisticated and expensive fluorescence-based method. This makes for a promising alternative detection method not only for real-time isothermal helicase-dependent amplification of nucleic acid, but also for other isothermal DNA amplification strategies.

The transient evolution of AM mode locking a TEA CO2laser

NARCIS (Netherlands)

van Goor, F.A.; Bonnie, Ronald J.M.; Witteman, W.J.

1985-01-01

The evolution of the pulse in an AM mode-locked TEA CO2laser has been investigated. The experiments have been performed by injecting the mode-locked pulses in a high-pressure slave oscillator at various time intervals after the initiation of the mode-lock process. This technique allows the

Labelling of nucleic acid components with tritium by hydrogenolysis of corresponding precursors

International Nuclear Information System (INIS)

Myasoedov, V.F.; Kvyatkovskij, Yu.G.; Sidorov, G.V.

1981-01-01

To desalt the luates of liquid column chromatography containing components of the nucleic acids different types of activated carbons are used: AG-5, Ou-4, KAD, BAU (SU), Norit (GB) and Carboafin (CS). The Carborafin (CS) carbon proved to be the most efficient for the purpose. Dependences of the adsorption degree on pH, the time of the phases contact, temperature, concentration of the salt background (ammonium formite, lithium chloride) as well as adsorption isotherm are determined for the activated carbon. Desorption conditions of the nucleic acids components from the carbon are studied. It is shown that quantitative desorption is achieved when 1n solution of ammonia is used in 50% ethanole for 50-60 min. Data on practical application of the method to desalt the eluates containing tritiated nucleic acid components with a high activity are presented [ru

Injection-locking of terahertz quantum cascade lasers up to 35GHz using RF amplitude modulation.

Science.gov (United States)

Gellie, Pierre; Barbieri, Stefano; Lampin, Jean-François; Filloux, Pascal; Manquest, Christophe; Sirtori, Carlo; Sagnes, Isabelle; Khanna, Suraj P; Linfield, Edmund H; Davies, A Giles; Beere, Harvey; Ritchie, David

2010-09-27

We demonstrate that the cavity resonance frequency - the round-trip frequency - of Terahertz quantum cascade lasers can be injection-locked by direct modulation of the bias current using an RF source. Metal-metal and single-plasmon waveguide devices with roundtrip frequencies up to 35GHz have been studied, and show locking ranges above 200MHz. Inside this locking range the laser round-trip frequency is phase-locked, with a phase noise determined by the RF-synthesizer. We find a square-root dependence of the locking range with RF-power in agreement with classical injection-locking theory. These results are discussed in the context of mode-locking operation.

Phase locking of a semiconductor double-quantum-dot single-atom maser

Science.gov (United States)

Liu, Y.-Y.; Hartke, T. R.; Stehlik, J.; Petta, J. R.

2017-11-01

We experimentally study the phase stabilization of a semiconductor double-quantum-dot (DQD) single-atom maser by injection locking. A voltage-biased DQD serves as an electrically tunable microwave frequency gain medium. The statistics of the maser output field demonstrate that the maser can be phase locked to an external cavity drive, with a resulting phase noise L =-99 dBc/Hz at a frequency offset of 1.3 MHz. The injection locking range, and the phase of the maser output relative to the injection locking input tone are in good agreement with Adler's theory. Furthermore, the electrically tunable DQD energy level structure allows us to rapidly switch the gain medium on and off, resulting in an emission spectrum that resembles a frequency comb. The free running frequency comb linewidth is ≈8 kHz and can be improved to less than 1 Hz by operating the comb in the injection locked regime.

A simplified digital lock-in amplifier for the scanning grating spectrometer.

Science.gov (United States)

Wang, Jingru; Wang, Zhihong; Ji, Xufei; Liu, Jie; Liu, Guangda

2017-02-01

For the common measurement and control system of a scanning grating spectrometer, the use of an analog lock-in amplifier requires complex circuitry and sophisticated debugging, whereas the use of a digital lock-in amplifier places a high demand on the calculation capability and storage space. In this paper, a simplified digital lock-in amplifier based on averaging the absolute values within a complete period is presented and applied to a scanning grating spectrometer. The simplified digital lock-in amplifier was implemented on a low-cost microcontroller without multipliers, and got rid of the reference signal and specific configuration of the sampling frequency. Two positive zero-crossing detections were used to lock the phase of the measured signal. However, measurement method errors were introduced by the following factors: frequency fluctuation, sampling interval, and integer restriction of the sampling number. The theoretical calculation and experimental results of the signal-to-noise ratio of the proposed measurement method were 2055 and 2403, respectively.

Nanopore biosensors for detection of proteins and nucleic acids

NARCIS (Netherlands)

Maglia, Giovanni; Soskine, Mikhael

2014-01-01

Described herein are nanopore biosensors based on a modified cytolysin protein. The nanopore biosensors accommodate macromoiecules including proteins and nucleic acids, and may additionally comprise ligands with selective binding properties.

Low-cost, digital lock-in module with external reference for coating glass transmission/reflection spectrophotometer

Science.gov (United States)

Alonso, R.; Villuendas, F.; Borja, J.; Barragán, L. A.; Salinas, I.

2003-05-01

A versatile, low-cost, digital signal processor (DSP) based lock-in module with external reference is described. This module is used to implement an industrial spectrophotometer for measuring spectral transmission and reflection of automotive and architectonic coating glasses over the ultraviolet, visible and near-infrared wavelength range. The light beams are modulated with an optical chopper. A digital phase-locked loop (DPLL) is used to lock the lock-in to the chop frequency. The lock-in rejects the ambient radiation and permits the spectrophotometer to work in the presence of ambient light. The algorithm that implements the dual lock-in and the DPLL in the DSP56002 evaluation module from Motorola is described. The use of a DSP allows implementation of the lock-in and DPLL by software, which gives flexibility and programmability to the system. Lock-in module cost, under 300 euro, is an important parameter taking into account that two modules are used in the system. Besides, the algorithms implemented in this DSP can be directly implemented in the latest DSP generations. The DPLL performance and the spectrophotometer are characterized. Capture and lock DPLL ranges have been measured and checked to be greater than the chop frequency drifts. The lock-in measured frequency response shows that the lock-in performs as theoretically predicted.

Nucleic acid detection based on the use of microbeads: a review

International Nuclear Information System (INIS)

Rödiger, Stefan; Liebsch, Claudia; Schmidt, Carsten; Schierack, Peter; Lehmann, Werner; Resch-Genger, Ute; Schedler, Uwe

2014-01-01

Microbead-based technologies represent elegant and versatile approaches for highly parallelized quantitative multiparameter assays. They also form the basis of various techniques for detection and quantification of nucleic acids and proteins. Nucleic acid-based methods include hybridization assays, solid-phase PCR, sequencing, and trapping assays. Microbead assays have been improved in the past decades and are now important tools in routine and point-of-care diagnostics as well as in life science. Its advances include low costs, low workload, high speed and high-throughput automation. The potential of microbead-based assays therefore is apparent, and commercial applications can be found in the detection and discrimination of single nucleotide polymorphism, of pathogens, and in trapping assays. This review provides an overview on microbead-based platforms for biosensing with a main focus on nucleic acid detection (including amplification strategies and on selected probe systems using fluorescent labeling). Specific sections cover chemical properties of microbeads, the coupling of targets onto solid surfaces, microbead probe systems (mainly oligonucleotide probes), microbead detection schemes (with subsections on suspension arrays, microfluidic devices, and immobilized microbeads), quantification of nucleic acids, PCR in solution and the detection of amplicons, and methods for solid-phase amplification. We discuss selected trends such as microbead-coupled amplification, heterogeneous and homogenous DNA hybridization assays, real-time assays, melting curve analysis, and digital microbead assays. We finally discuss the relevance and trends of the methods in terms of high-level multiplexed analysis and their potential in diagnosis and personalized medicine. (author)

A quantitative measure of chirality inside nucleic acid databank.

Science.gov (United States)

Pietropaolo, Adriana; Parrinello, Michele

2011-08-01

We show the capability of a chirality index (Pietropaolo et al., Proteins 2008;70:667-677) to investigate nucleic acid structures because of its high sensitivity to helical conformations. By analyzing selected structures of DNA and RNA, we have found that sequences rich in cytosine and guanine have a tendency to left-handed chirality, in contrast to regions rich in adenine or thymine which show strong negative, right-handed, chirality values. We also analyze RNA structures, where specific loops and hairpin motifs are characterized by a well-defined chirality value. We find that in nucleosome the chirality is exalted, whereas in ribosome it is reduced. Our results illustrate the sensitivity of this descriptor for nucleic acid conformations. Copyright © 2011 Wiley-Liss, Inc.

System for portable nucleic acid testing in low resource settings

Science.gov (United States)

Lu, Hsiang-Wei; Roskos, Kristina; Hickerson, Anna I.; Carey, Thomas; Niemz, Angelika

2013-03-01

Our overall goal is to enable timely diagnosis of infectious diseases through nucleic acid testing at the point-of-care and in low resource settings, via a compact system that integrates nucleic acid sample preparation, isothermal DNA amplification, and nucleic acid lateral flow (NALF) detection. We herein present an interim milestone, the design of the amplification and detection subsystem, and the characterization of thermal and fluidic control and assay execution within this system. Using an earlier prototype of the amplification and detection unit, comprised of a disposable cartridge containing flexible pouches, passive valves, and electrolysis-driven pumps, in conjunction with a small heater, we have demonstrated successful execution of an established and clinically validated isothermal loop-mediated amplification (LAMP) reaction targeting Mycobacterium tuberculosis (M.tb) DNA, coupled to NALF detection. The refined design presented herein incorporates miniaturized and integrated electrolytic pumps, novel passive valves, overall design changes to facilitate integration with an upstream sample preparation unit, and a refined instrument design that automates pumping, heating, and timing. Nucleic acid amplification occurs in a two-layer pouch that facilitates fluid handling and appropriate thermal control. The disposable cartridge is manufactured using low-cost and scalable techniques and forms a closed system to prevent workplace contamination by amplicons. In a parallel effort, we are developing a sample preparation unit based on similar design principles, which performs mechanical lysis of mycobacteria and DNA extraction from liquefied and disinfected sputum. Our next step is to combine sample preparation, amplification, and detection in a final integrated cartridge and device, to enable fully automated sample-in to answer-out diagnosis of active tuberculosis in primary care facilities of low-resource and high-burden countries.

Positioning and locking apparatus

Science.gov (United States)

Hayward, M.L.; Harper, W.H.

1985-06-19

A positioning and locking apparatus including a fixture having a rotatable torque ring provided with a plurality of cam segments for automatically guiding a container into a desired location within the fixture. Rotation of the ring turns the container into a final position in pressure sealing relation against a hatch member.

Optimum phase noise reduction and repetition rate tuning in quantum-dot mode-locked lasers

Energy Technology Data Exchange (ETDEWEB)

Habruseva, T. [CAPPA, Cork Institute of Technology, Cork (Ireland); Tyndall National Institute, Lee Maltings, Cork (Ireland); Aston University, Aston Triangle, B4 7ET Birmingham (United Kingdom); Arsenijević, D.; Kleinert, M.; Bimberg, D. [Institut für Festkörperphysik, Technische Universität Berlin, Berlin (Germany); Huyet, G.; Hegarty, S. P. [CAPPA, Cork Institute of Technology, Cork (Ireland); Tyndall National Institute, Lee Maltings, Cork (Ireland)

2014-01-13

Competing approaches exist, which allow control of phase noise and frequency tuning in mode-locked lasers, but no judgement of pros and cons based on a comparative analysis was presented yet. Here, we compare results of hybrid mode-locking, hybrid mode-locking with optical injection seeding, and sideband optical injection seeding performed on the same quantum dot laser under identical bias conditions. We achieved the lowest integrated jitter of 121 fs and a record large radio-frequency (RF) tuning range of 342 MHz with sideband injection seeding of the passively mode-locked laser. The combination of hybrid mode-locking together with optical injection-locking resulted in 240 fs integrated jitter and a RF tuning range of 167 MHz. Using conventional hybrid mode-locking, the integrated jitter and the RF tuning range were 620 fs and 10 MHz, respectively.

Optimum phase noise reduction and repetition rate tuning in quantum-dot mode-locked lasers

International Nuclear Information System (INIS)

Habruseva, T.; Arsenijević, D.; Kleinert, M.; Bimberg, D.; Huyet, G.; Hegarty, S. P.

2014-01-01

Competing approaches exist, which allow control of phase noise and frequency tuning in mode-locked lasers, but no judgement of pros and cons based on a comparative analysis was presented yet. Here, we compare results of hybrid mode-locking, hybrid mode-locking with optical injection seeding, and sideband optical injection seeding performed on the same quantum dot laser under identical bias conditions. We achieved the lowest integrated jitter of 121 fs and a record large radio-frequency (RF) tuning range of 342 MHz with sideband injection seeding of the passively mode-locked laser. The combination of hybrid mode-locking together with optical injection-locking resulted in 240 fs integrated jitter and a RF tuning range of 167 MHz. Using conventional hybrid mode-locking, the integrated jitter and the RF tuning range were 620 fs and 10 MHz, respectively

The isolation of nucleic acids from fixed, paraffin-embedded tissues-which methods are useful when?

DEFF Research Database (Denmark)

Gilbert, M Thomas P; Haselkorn, Tamara; Bunce, Michael

2007-01-01

. Cross-linking not only complicates isolation of nucleic acid but also introduces polymerase "blocks" during PCR. A wide variety of methods exists for the recovery of DNA and RNA from archival tissues, and although a number of previous studies have qualitatively compared the relative merits....... These include methods of pre-treating the samples prior to extraction, extraction and nucleic acid purification methods themselves, and a post-extraction enzymatic repair technique. We find that although many of the published methods have distinct positive effects on some characteristics of the nucleic acids...

Diode-pumped mode-locked femtosecond Tm:CLNGG disordered crystal laser.

Science.gov (United States)

Ma, J; Xie, G Q; Gao, W L; Yuan, P; Qian, L J; Yu, H H; Zhang, H J; Wang, J Y

2012-04-15

A diode-end-pumped passively mode-locked femtosecond Tm-doped calcium lithium niobium gallium garnet (Tm:CLNGG) disordered crystal laser was demonstrated for the first time to our knowledge. With a 790 nm laser diode pumping, stable CW mode-locking operation was obtained by using a semiconductor saturable absorber mirror. The disordered crystal laser generated mode-locked pulses as short as 479 fs, with an average output power of 288 mW, and repetition rate of 99 MHz in 2 μm spectral region. © 2012 Optical Society of America

Avoiding lock-in

DEFF Research Database (Denmark)

Henriksen, Ingrid

1999-01-01

The paper investigates the initial phase of the cooperative organisation of agricultural processing firms in Denmark. It argues that the variations observed can be explained within the framework of the theory of industrial organisation. The focus is on the success of cooperative creameries. In 19...... of gathering information and of preserving and transporting a perishable product, were ideally suited to overcome the problems of potential lock-in and of asymmetric information...

Recent advances in nanopore-based nucleic acid analysis and sequencing

International Nuclear Information System (INIS)

Shi, Jidong; Fang, Ying; Hou, Junfeng

2016-01-01

Nanopore-based sequencing platforms are transforming the field of genomic science. This review (containing 116 references) highlights some recent progress on nanopore-based nucleic acid analysis and sequencing. These studies are classified into three categories, biological, solid-state, and hybrid nanopores, according to their nanoporous materials. We begin with a brief description of the translocation-based detection mechanism of nanopores. Next, specific examples are given in nanopore-based nucleic acid analysis and sequencing, with an emphasis on identifying strategies that can improve the resolution of nanopores. This review concludes with a discussion of future research directions that will advance the practical applications of nanopore technology. (author)

49 CFR 236.340 - Electromechanical interlocking machine; locking between electrical and mechanical levers.

Science.gov (United States)

2010-10-01

... Electromechanical interlocking machine; locking between electrical and mechanical levers. In electro-mechanical interlocking machine, locking between electric and mechanical levers shall be maintained so that mechanical... 49 Transportation 4 2010-10-01 2010-10-01 false Electromechanical interlocking machine; locking...

Optimal database locks for efficient integrity checking

DEFF Research Database (Denmark)

Martinenghi, Davide

2004-01-01

In concurrent database systems, correctness of update transactions refers to the equivalent effects of the execution schedule and some serial schedule over the same set of transactions. Integrity constraints add further semantic requirements to the correctness of the database states reached upon...... the execution of update transactions. Several methods for efficient integrity checking and enforcing exist. We show in this paper how to apply one such method to automatically extend update transactions with locks and simplified consistency tests on the locked entities. All schedules produced in this way...

Structural aspects of catalytic mechanisms of endonucleases and their binding to nucleic acids

Energy Technology Data Exchange (ETDEWEB)

Zhukhlistova, N. E.; Balaev, V. V.; Lyashenko, A. V.; Lashkov, A. A., E-mail: alashkov83@gmail.com [Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation)

2012-05-15

Endonucleases (EC 3.1) are enzymes of the hydrolase class that catalyze the hydrolytic cleavage of deoxyribonucleic and ribonucleic acids at any region of the polynucleotide chain. Endonucleases are widely used both in biotechnological processes and in veterinary medicine as antiviral agents. Medical applications of endonucleases in human cancer therapy hold promise. The results of X-ray diffraction studies of the spatial organization of endonucleases and their complexes and the mechanism of their action are analyzed and generalized. An analysis of the structural studies of this class of enzymes showed that the specific binding of enzymes to nucleic acids is characterized by interactions with nitrogen bases and the nucleotide backbone, whereas the nonspecific binding of enzymes is generally characterized by interactions only with the nucleic-acid backbone. It should be taken into account that the specificity can be modulated by metal ions and certain low-molecular-weight organic compounds. To test the hypotheses about specific and nonspecific nucleic-acid-binding proteins, it is necessary to perform additional studies of atomic-resolution three-dimensional structures of enzyme-nucleic-acid complexes by methods of structural biology.

Stability improvement for coil position locking of joule balance

Science.gov (United States)

Bai, Yang; Liu, Yongmeng; Lu, Yunfeng; Hu, Pengcheng; Wang, Dawei; Li, Zhengkun; Tan, Jiubin; Zhang, Zhonghua

2017-08-01

The relative vertical position locking precision between the exciting and suspended coils is an important uncertainty for the Planck constant traceability in joule balance. In order to improve the relative vertical position locking precision, several stability experiments are conducted. The stability characteristics of the suspended and exciting coils are measured using a six-axis laser interferometer system; meanwhile, the effectiveness of the active vibration isolation table is measured using a vibration measurement sensor. The piezoelectric ceramic actuators with PID controller are used to compensate the relative vertical displacement drifts while a six-axis laser interferometer system is used to measure the positions of two coils. Experimental results show that the relative vertical position is stably locked.

Adaptive Injection-locking Oscillator Array for RF Spectrum Analysis

International Nuclear Information System (INIS)

Leung, Daniel

2011-01-01

A highly parallel radio frequency receiver using an array of injection-locking oscillators for on-chip, rapid estimation of signal amplitudes and frequencies is considered. The oscillators are tuned to different natural frequencies, and variable gain amplifiers are used to provide negative feedback to adapt the locking band-width with the input signal to yield a combined measure of input signal amplitude and frequency detuning. To further this effort, an array of 16 two-stage differential ring oscillators and 16 Gilbert-cell mixers is designed for 40-400 MHz operation. The injection-locking oscillator array is assembled on a custom printed-circuit board. Control and calibration is achieved by on-board microcontroller.

Wavenumber locking and pattern formation in spatially forced systems