Synthetic Method for Oligonucleotide Block by Using Alkyl-Chain-Soluble Support.

Science.gov (United States)

Matsuno, Yuki; Shoji, Takao; Kim, Shokaku; Chiba, Kazuhiro

2016-02-19

A straightforward method for the synthesis of oligonucleotide blocks using a Cbz-type alkyl-chain-soluble support (Z-ACSS) attached to the 3'-OH group of 3'-terminal nucleosides was developed. The Z-ACSS allowed for the preparation of fully protected deoxyribo- and ribo-oligonucleotides without chromatographic purification and released dimer- to tetramer-size oligonucleotide blocks via hydrogenation using a Pd/C catalyst without significant loss or migration of protective groups such as 5'-end 4,4'-dimethoxtrityl, 2-cyanoethyl on internucleotide bonds, or 2'-TBS.

Mixing vane grid spacer

International Nuclear Information System (INIS)

Patterson, J.F.; Galbraith, K.P.

1978-01-01

An improved mixing vane grid spacer having enhanced flow mixing capability by virtue of mixing vanes being positioned at welded intersecting joints of the spacer wherein each mixing vane has an opening or window formed therein substantially directly over the welded joint to provide improved flow mixing capability is described. Some of the vanes are slotted, depending on their particular location in the spacers. The intersecting joints are welded by initially providing consumable tabs at and within each window, which are consumed during the welding of the spacer joints

Molecular Strain Typing of Mycobacterium tuberculosis: a Review of Frequently Used Methods

Science.gov (United States)

2016-01-01

Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, remains one of the most serious global health problems. Molecular typing of M. tuberculosis has been used for various epidemiologic purposes as well as for clinical management. Currently, many techniques are available to type M. tuberculosis. Choosing the most appropriate technique in accordance with the existing laboratory conditions and the specific features of the geographic region is important. Insertion sequence IS6110-based restriction fragment length polymorphism (RFLP) analysis is considered the gold standard for the molecular epidemiologic investigations of tuberculosis. However, other polymerase chain reaction-based methods such as spacer oligonucleotide typing (spoligotyping), which detects 43 spacer sequence-interspersing direct repeats (DRs) in the genomic DR region; mycobacterial interspersed repetitive units–variable number tandem repeats, (MIRU-VNTR), which determines the number and size of tandem repetitive DNA sequences; repetitive-sequence-based PCR (rep-PCR), which provides high-throughput genotypic fingerprinting of multiple Mycobacterium species; and the recently developed genome-based whole genome sequencing methods demonstrate similar discriminatory power and greater convenience. This review focuses on techniques frequently used for the molecular typing of M. tuberculosis and discusses their general aspects and applications. PMID:27709842

Influence of the linking spacer length and type on the enantioseparation ability of β-cyclodextrin functionalized monoliths.

Science.gov (United States)

Guo, Jialiang; Xiao, Yuan; Lin, Yuanjing; Zhang, Qiaoxuan; Chang, Yiqun; Crommen, Jacques; Jiang, Zhengjin

2016-05-15

In order to investigate the effect of the linking spacer on the enantioseparation ability of β-cyclodextrin (β-CD) functionalized polymeric monoliths, three β-CD-functionalized organic polymeric monoliths with different spacer lengths were prepared by using three amino-β-CDs, i.e. mono-6-amino-6-deoxy-β-CD, mono-6-ethylenediamine-6-deoxy-β-CD, mono-6-hexamethylenediamine-6-deoxy-β-CD, as starting materials. These amino-β-CDs reacted with glycidyl methacrylate to produce functional monomers which were then copolymerized with ethylene dimethacrylate. The enantioseparation ability of the three monoliths was evaluated using 14 chiral acidic compounds, including mandelic acid derivatives, nonsteroidal anti-inflammatory drugs, N-derivatized amino acids, and chiral herbicides under optimum chromatographic conditions. Notably, the poly(GMA-NH2-β-CD-co-EDMA) column provides higher enantioresolution and enantioselectivity than the poly(GMA-EDA-β-CD-co-EDMA) and poly(GMA-HDA-β-CD-co-EDMA) columns for most tested chiral analytes. Furthermore, the enantioseparation performance of triazole-linker containing monoliths was compared to that of ethylenediamine-linker containing monoliths. The results indicate that the enantioselectivity of β-CD monolithic columns is strongly related to the length and type of spacer tethering β-CD to the polymeric support. Copyright © 2016 Elsevier B.V. All rights reserved.

Fouling resistant membrane spacers

KAUST Repository

Ghaffour, Noreddine

2017-10-12

Disclosed herein are spacers having baffle designs and perforations for efficiently and effectively separating one or more membrane layers a membrane filtration system. The spacer (504) includes a body (524) formed at least in part by baffles (520) that are interconnected, and the baffles define boundaries of openings or apertures (525) through a thickness direction of the body of the spacer. Alternatively or additionally, passages or perforations (526A, 526B) may be present in the spacer layer or baffles for fluid flow there through, with the passages and baffles having a numerous different shapes and sizes.

Structural Stator Spacers

DEFF Research Database (Denmark)

Rasmussen, Peter Omand; Andreasen, Jens H.; Pijanowski, J. M.

2001-01-01

This paper presents a powerful new design aspect to reduce acoustic noise and vibration of electro-magnetic origin for electrical machines, by introducing improved slot wedges referred to as "Structural Stator Spacers". These spacers, by using a very stiff dielectric and non magnetic material...

Analytical prediction of fuel assembly spacer grid loss coefficient

International Nuclear Information System (INIS)

Lim, J. S.; Nam, K. I.; Park, S. K.; Kwon, J. T.; Park, W. J.

2002-01-01

The analytical prediction model of the fuel assembly spacer grid pressure loss coefficient has been studied. The pressure loss of gap between the test section wall and spacer grid was separated from the current model and the different friction drag coefficient on spacer straps from high Reynolds number region were used to low Reynolds number region. The analytical model has been verified based on the hydraulic pressure drop test results for the spacer grids of three types for 5x5, 16x16(or 17x17) arrays. The analytical model predicts the pressure loss coefficients obtained from test results within the maximum errors of 12% and 7% for 5x5 test bundle and full size bundle, respectively, at Reynolds number 500,000 of the core operating condition. This result shows that the analytical model can be used for research and design change of the nuclear fuel assembly

On the Origin of Reverse Transcriptase-Using CRISPR-Cas Systems and Their Hyperdiverse, Enigmatic Spacer Repertoires

Directory of Open Access Journals (Sweden)

Sukrit Silas

2017-07-01

Full Text Available Cas1 integrase is the key enzyme of the clustered regularly interspaced short palindromic repeat (CRISPR-Cas adaptation module that mediates acquisition of spacers derived from foreign DNA by CRISPR arrays. In diverse bacteria, the cas1 gene is fused (or adjacent to a gene encoding a reverse transcriptase (RT related to group II intron RTs. An RT-Cas1 fusion protein has been recently shown to enable acquisition of CRISPR spacers from RNA. Phylogenetic analysis of the CRISPR-associated RTs demonstrates monophyly of the RT-Cas1 fusion, and coevolution of the RT and Cas1 domains. Nearly all such RTs are present within type III CRISPR-Cas loci, but their phylogeny does not parallel the CRISPR-Cas type classification, indicating that RT-Cas1 is an autonomous functional module that is disseminated by horizontal gene transfer and can function with diverse type III systems. To compare the sequence pools sampled by RT-Cas1-associated and RT-lacking CRISPR-Cas systems, we obtained samples of a commercially grown cyanobacterium—Arthrospira platensis. Sequencing of the CRISPR arrays uncovered a highly diverse population of spacers. Spacer diversity was particularly striking for the RT-Cas1-containing type III-B system, where no saturation was evident even with millions of sequences analyzed. In contrast, analysis of the RT-lacking type III-D system yielded a highly diverse pool but reached a point where fewer novel spacers were recovered as sequencing depth was increased. Matches could be identified for a small fraction of the non-RT-Cas1-associated spacers, and for only a single RT-Cas1-associated spacer. Thus, the principal source(s of the spacers, particularly the hypervariable spacer repertoire of the RT-associated arrays, remains unknown.

Spacer capture and integration by a type I-F Cas1-Cas2-3 CRISPR adaptation complex.

Science.gov (United States)

Fagerlund, Robert D; Wilkinson, Max E; Klykov, Oleg; Barendregt, Arjan; Pearce, F Grant; Kieper, Sebastian N; Maxwell, Howard W R; Capolupo, Angela; Heck, Albert J R; Krause, Kurt L; Bostina, Mihnea; Scheltema, Richard A; Staals, Raymond H J; Fineran, Peter C

2017-06-27

CRISPR-Cas adaptive immune systems capture DNA fragments from invading bacteriophages and plasmids and integrate them as spacers into bacterial CRISPR arrays. In type I-E and II-A CRISPR-Cas systems, this adaptation process is driven by Cas1-Cas2 complexes. Type I-F systems, however, contain a unique fusion of Cas2, with the type I effector helicase and nuclease for invader destruction, Cas3. By using biochemical, structural, and biophysical methods, we present a structural model of the 400-kDa Cas1 4 -Cas2-3 2 complex from Pectobacterium atrosepticum with bound protospacer substrate DNA. Two Cas1 dimers assemble on a Cas2 domain dimeric core, which is flanked by two Cas3 domains forming a groove where the protospacer binds to Cas1-Cas2. We developed a sensitive in vitro assay and demonstrated that Cas1-Cas2-3 catalyzed spacer integration into CRISPR arrays. The integrase domain of Cas1 was necessary, whereas integration was independent of the helicase or nuclease activities of Cas3. Integration required at least partially duplex protospacers with free 3'-OH groups, and leader-proximal integration was stimulated by integration host factor. In a coupled capture and integration assay, Cas1-Cas2-3 processed and integrated protospacers independent of Cas3 activity. These results provide insight into the structure of protospacer-bound type I Cas1-Cas2-3 adaptation complexes and their integration mechanism.

Buckling behavior analysis of spacer grid by lateral impact load

International Nuclear Information System (INIS)

Yoon, Kyung Ho; Kang, Heung Seok; Kim, Hyung Kyu; Song, Kee Nam

2000-05-01

The spacer grid is one of the main structural components in the fuel assembly, Which supports the fuel rods, guides cooling water, and protects the system from an external impact load, such as earthquakes. Therefore, the mechanical and structural properties of the spacer grids must be extensively examined while designing it. In this report, free fall type shock tests on the several kinds of the specimens of the spacer grids were also carried out in order to compare the results among the candidate grids. A free fall carriage on the specimen accomplishes the test. In addition to this, a finite element method for predicting the critical impact strength of the spacer grids is described. FE method on the buckling behavior of the spacer grids are performed for a various array of sizes of the grids considering that the spacer grid is an assembled structure with thin-walled plates and imposing proper boundary conditions by nonlinear dynamic impact analysis using ABAQUS/explicit code. The simulated results results also similarly predicted the local buckling phenomena and were found to give good correspondence with the shock test results

Heterogeneous diversity of spacers within CRISPR

Science.gov (United States)

Deem, Michael; He, Jiankui

2011-03-01

Clustered regularly interspaced short palindromic repeats (CRISPR) in bacterial and archaeal DNA have recently been shown to be a new type of anti-viral immune system in these organisms. We here study the diversity of spacers in CRISPR under selective pressure. We propose a population dynamics model that explains the biological observation that the leader-proximal end of CRISPR is more diversified and the leader-distal end of CRISPR is more conserved. This result is shown to be in agreement with recent experiments. Our results show that the CRISPR spacer structure is influenced by and provides a record of the viral challenges that bacteria face. 1) J. He and M. W. Deem, Phys. Rev. Lett. 105 (2010) 128102

Vibration characteristics of a PWR fuel rod supported by optimized H type spacer grids

International Nuclear Information System (INIS)

Choi, M. H.; Kang, H. S.; Yoon, K. H.; Kim, H. K.; Song, K. N.

2002-01-01

The spacer grids are one of the main structural components in the fuel assembly, which supports and protects the fuel rods from the external loads by seismic and coolant flow. In this study, a modal test and a FE vibration analysis using ABAQUS are performed on a PWR dummy fuel rod of 3.847 m which is continuously supported by eight Optimized H type spacer grids. The experimental results agree with previous works that the natural frequencies decrease, while the amplitudes increase, with the increase of the excitation force. The force levels showing the maximum displacement of 0.2 mm are in the range from 0.2 N to 0.3 N, and at the same force range the fundamental frequencies are measured around 42.0 Hz, at which the relatively big displacements are observed at the 7th span. The results from the modal tests and the FE analyses are compared by both Modal Assurance Criteria (MAC) values and mode shapes. The MAC values at 2nd, 4th, and 7th mode are below 50%. It is believed that the reason of the low MACs at those modes is that the vibration amplitudes of the modes are more distorted by the excitation force than those of the other modes

Effects of Atelocollagen Formulation Containing Oligonucleotide on Endothelial Permeability

Directory of Open Access Journals (Sweden)

Koji Hanai

2012-01-01

Full Text Available Atelocollagen is a major animal protein that is used as a highly biocompatible biomaterial. To date, atelocollagen has been used as an effective drug delivery technology to sustain the release of antitumor proteins and to enhance the antitumor activity of oligonucleotides in in vivo models. However, the biological effects of this technology are not fully understood. In the present study, we investigated the effects of atelocollagen on endothelial paracellular barrier function. An atelocollagen formulation containing oligonucleotides specifically increased the permeability of two types of endothelial cells, and the change was dependent on the molecular size, structure of the oligonucleotides used and the concentrations of the oligonucleotide and atelocollagen in the formulation. An immunohistochemical examination revealed that the formulation had effects on the cellular skeleton and intercellular structure although it did not affect the expression of adherens junction or tight junction proteins. These changes were induced through p38 MAP kinase signaling. It is important to elucidate the biological functions of atelocollagen in order to be able to exploit its drug delivery properties.

Label-Free Electrochemical Detection of the Specific Oligonucleotide Sequence of Dengue Virus Type 1 on Pencil Graphite Electrodes

Science.gov (United States)

Souza, Elaine; Nascimento, Gustavo; Santana, Nataly; Ferreira, Danielly; Lima, Manoel; Natividade, Edna; Martins, Danyelly; Lima-Filho, José

2011-01-01

A biosensor that relies on the adsorption immobilization of the 18-mer single-stranded nucleic acid related to dengue virus gene 1 on activated pencil graphite was developed. Hybridization between the probe and its complementary oligonucleotides (the target) was investigated by monitoring guanine oxidation by differential pulse voltammetry (DPV). The pencil graphite electrode was made of ordinary pencil lead (type 4B). The polished surface of the working electrode was activated by applying a potential of 1.8 V for 5 min. Afterward, the dengue oligonucleotides probe was immobilized on the activated electrode by applying 0.5 V to the electrode in 0.5 M acetate buffer (pH 5.0) for 5 min. The hybridization process was carried out by incubating at the annealing temperature of the oligonucleotides. A time of five minutes and concentration of 1 μM were found to be the optimal conditions for probe immobilization. The electrochemical detection of annealing between the DNA probe (TS-1P) immobilized on the modified electrode, and the target (TS-1T) was achieved. The target could be quantified in a range from 1 to 40 nM with good linearity and a detection limit of 0.92 nM. The specificity of the electrochemical biosensor was tested using non-complementary sequences of dengue virus 2 and 3. PMID:22163916

Numerical analysis of the spacer grids' compression strength

International Nuclear Information System (INIS)

Schettino, C.F.M.; Gouvea, J.P.; Medeiros, N.

2013-01-01

Among the components of the fuel assembly, the spacer grids play an important structural role during the energy generation process, mainly for their requirement to have enough structural strength to withstand lateral impact loads, due to fuel assembly shipping/handling and due to forces outcome from postulated accidents (earthquake and LOCA). This requirement ensures a proper geometry for cooling and for guide thimble straightness in the fuel assembly. In this way, the understanding of the macroscopic mechanical behavior of this component becomes essential even to any subsequent geometrical modifications to optimize the flue assemblies' structural behavior. In the present work, three-dimensional finite element models destined to provide consistent predictions of 16X16-type spacer grids lateral strength were proposed. Firstly, buckling tests based on results available in the literature were performed to establish a methodology for spacer grid finite element-based modeling. The, by considering a spacer grid interesting geometry and some possible variations associated to its fabrication, tolerance, the proposed numerical models were submitted to compression conditions to calculate the buckling force. Also, these models were validated for comparison with experimental buckling load results. Comparison of buckling predictions combined to observations of actual and simulated deformed spacer grids geometries permitted to verify the consistency and applicability of the proposed models. Thus, these numerical results show a good agreement between the and the experimental results. (author)

Spacer st4ructure

International Nuclear Information System (INIS)

Masetti, W.R.

1978-01-01

A spacer structure is described for maintaining a spaced relation between a plurality of generally parallel fuel rods within a housing in a nuclear reactor. The spacer structure is comprised of a grid pattern of ribs slotted to interlock with each other. The slots are arranged in such a way that when the ribs are welded to each other, the weld shrinkage is distributed uniformly in all directions to reduce or eliminate the amount of rework necessary in manufacturing the spacer structure

Ertapenem Articulating Spacer for the Treatment of Polymicrobial Total Knee Arthroplasty Infection

Directory of Open Access Journals (Sweden)

Dragan Radoicic

2016-01-01

Full Text Available Introduction. Periprosthetic joint infections (PJIs are the primary cause of early failure of the total knee arthroplasty (TKA. Polymicrobial TKA infections are often associated with a higher risk of treatment failure. The aim of the study was to assess the efficacy of ertapenem loaded spacers in the treatment of polymicrobial PJI. Methods. There were 18 patients enrolled; nine patients with polymicrobial PJI treated with ertapenem loaded articulating spacers were compared to the group of 9 patients treated with vancomycin or ceftazidime loaded spacers. Results. Successful reimplantation with revision implants was possible in 66.67%. Ertapenem spacers were used in 6 cases in primary two-stage procedure and in 3 cases in secondary spacer exchange. Successful infection eradication was achieved in all cases; final reimplantation with revision knee arthroplasty implants was possible in 6 cases. Conclusion. Ertapenem can be successfully used as antimicrobial addition to the cement spacers in two-stage revision treatment of polymicrobial PJIs. However, this type of spacer may also be useful in the treatment of infections caused by monomicrobial extended spectrum beta-lactamases producing gram-negative bacilli. Further clinical studies are required to evaluate the efficacy and safety of ertapenem spacers in the treatment of polymicrobial and monomicrobial PJIs.

Transcriptional regulator-mediated activation of adaptation genes triggers CRISPR de novo spacer acquisition

DEFF Research Database (Denmark)

Liu, Tao; Li, Yingjun; Wang, Xiaodi

2015-01-01

Acquisition of de novo spacer sequences confers CRISPR-Cas with a memory to defend against invading genetic elements. However, the mechanism of regulation of CRISPR spacer acquisition remains unknown. Here we examine the transcriptional regulation of the conserved spacer acquisition genes in Type I......, it was demonstrated that the transcription level of csa1, cas1, cas2 and cas4 was significantly enhanced in a csa3a-overexpression strain and, moreover, the Csa1 and Cas1 protein levels were increased in this strain. Furthermore, we demonstrated the hyperactive uptake of unique spacers within both CRISPR loci...... in the presence of the csa3a overexpression vector. The spacer acquisition process is dependent on the CCN PAM sequence and protospacer selection is random and non-directional. These results suggested a regulation mechanism of CRISPR spacer acquisition where a single transcriptional regulator senses the presence...

The Medicinal Chemistry of Therapeutic Oligonucleotides.

Science.gov (United States)

Wan, W Brad; Seth, Punit P

2016-11-10

Oligonucleotide-based therapeutics have made rapid progress in the clinic for treatment of a variety of disease indications. Unmodified oligonucleotides are polyanionic macromolecules with poor drug-like properties. Over the past two decades, medicinal chemists have identified a number of chemical modification and conjugation strategies which can improve the nuclease stability, RNA-binding affinity, and pharmacokinetic properties of oligonucleotides for therapeutic applications. In this perspective, we present a summary of the most commonly used nucleobase, sugar and backbone modification, and conjugation strategies used in oligonucleotide medicinal chemistry.

Microbial fuel cells with an integrated spacer and separate anode and cathode modules

KAUST Repository

He, Weihua

2016-01-01

A new type of scalable MFC was developed based on using alternating graphite fiber brush array anode modules and dual cathode modules in order to simplify construction, operation, and maintenance of the electrodes. The modular MFC design was tested with a single (two-sided) cathode module with a specific surface area of 29 m2 m−3 based on a total liquid volume (1.4 L; 20 m2 m−3 using the total reactor volume of 2 L), and two brush anode modules. Three different types of spacers were used in the cathode module to provide structural stability, and enhance air flow relative to previous cassette (combined anode–cathode) designs: a low-profile wire spacer; a rigid polycarbonate column spacer; and a flexible plastic mesh spacer. The best performance was obtained using the wire spacer that produced a maximum power density of 1100 ± 10 mW m−2 of cathode (32 ± 0.3 W m−3 based on liquid volume) with an acetate-amended wastewater (COD = 1010 ± 30 mg L−1), compared to 1010 ± 10 mW m−2 for the column and 650 ± 20 mW m−2 for the mesh spacers. Anode potentials were unaffected by the different types of spacers. Raw domestic wastewater produced a maximum of 400 ± 8 mW m−2 under fed batch conditions (wire-spacers), which is one of the highest power densities for this fuel. Over time the maximum power was reduced to 300 ± 10 mW m−2 and 275 ± 7 mW m−2 for the two anode compartments, with only slightly less power of 250 ± 20 mW m−2 obtained under continuous flow conditions. In fixed-resistance tests, the average COD removal was 57 ± 5% at a hydraulic retention time of 8 h. These results show that this modular MFC design can both simplify reactor construction and enable relatively high power generation from even relatively dilute wastewater.

Impact of feed spacer and membrane modification by hydrophilic, bactericidal and biocidal coating on biofouling control

KAUST Repository

Araújo, Paula A.

2012-06-01

The influence of polydopamine- and polydopamine-. graft-poly(ethylene glycol)-coated feed spacers and membranes, copper-coated feed spacers, and commercially-available biostatic feed spacers on biofouling has been studied in membrane fouling simulators. Feed spacers and membranes applied in practical membrane filtration systems were used; biofouling development was monitored by feed channel pressure drop increase and biomass accumulation. Polydopamine and polydopamine-. g-PEG are hydrophilic surface modification agents expected to resist protein and bacterial adhesion, while copper feed spacer coatings and biocides infused in feed spacers are expected to restrict biological growth. Our studies showed that polydopamine and polydopamine-. g-PEG coatings on feed spacers and membranes, copper coatings on feed spacers, and a commercial biostatic feed spacer did not have a significant impact on feed channel pressure drop increase and biofilm accumulation as measured by ATP and TOC content. The studied spacer and membrane modifications were not effective for biofouling control; it is doubtful that feed spacer and membrane modification, in general, may be effective for biofouling control regardless of the type of applied coating. © 2012 Elsevier B.V.

Nuclear reactor spring strip grid spacer

International Nuclear Information System (INIS)

Patterson, J.F.; Flora, B.S.

1980-01-01

An improved and novel grid spacer for maintaining the fuel rods of a nuclear reactor fuel assembly in substantially parallel array is described. The invention provides for spring strips to maintain the fuel elements in their desired orientation which have more positive alignment than previous types while allowing greater flexibility to counterbalance the effects of differential thermal expansion. (UK)

Air-water flooding in multirod channels: effects of spacer grids and blockages

International Nuclear Information System (INIS)

Cha, Jong Hee; Jun, Hyung Gil

1993-01-01

This paper presents the experimental results on flooding of countercurrent flow in vertical multirod channels, which consists of falling water film and upward air flow. In particular, the effects of spacer grids, with and without mixing vane, and of blockage in the multirod bundle on the behaviour of flooding were investigated. The 5 x 5 zircaloy tube bundle was used for the test section. The comparison of previous analytical models and empirical correlations with present data on flooding showed that the existing models and correlations predict much higher flooding curves. The spacer grid causes the lower flooding air flow rate to compare with the bare rod bundle. However, the mixing spacer grids need a higher flooding air flow rate for a constant liquid flow rate than the spacer grids without mixing vanes. The bundle containing blockages has the highest flooding air flow rate among the bundles with spacer grids and blokages. Empirical flooding correlations for the three types of test section have been made. (Author)

Numerical analysis of the spacer grids' compression strength

Energy Technology Data Exchange (ETDEWEB)

Schettino, C.F.M.; Gouvea, J.P.; Medeiros, N., E-mail: carlosschettino@inb.gov.br, E-mail: jpg@metal.eeimvr.uff.br [Universidade Federal Fluminense (UFF), Volta Redonda, RJ (Brazil). Programa de Engenharia Metalurgica

2013-07-01

Among the components of the fuel assembly, the spacer grids play an important structural role during the energy generation process, mainly for their requirement to have enough structural strength to withstand lateral impact loads, due to fuel assembly shipping/handling and due to forces outcome from postulated accidents (earthquake and LOCA). This requirement ensures a proper geometry for cooling and for guide thimble straightness in the fuel assembly. In this way, the understanding of the macroscopic mechanical behavior of this component becomes essential even to any subsequent geometrical modifications to optimize the flue assemblies' structural behavior. In the present work, three-dimensional finite element models destined to provide consistent predictions of 16X16-type spacer grids lateral strength were proposed. Firstly, buckling tests based on results available in the literature were performed to establish a methodology for spacer grid finite element-based modeling. The, by considering a spacer grid interesting geometry and some possible variations associated to its fabrication, tolerance, the proposed numerical models were submitted to compression conditions to calculate the buckling force. Also, these models were validated for comparison with experimental buckling load results. Comparison of buckling predictions combined to observations of actual and simulated deformed spacer grids geometries permitted to verify the consistency and applicability of the proposed models. Thus, these numerical results show a good agreement between the and the experimental results. (author)

Template-Directed Ligation of Peptides to Oligonucleotides

Science.gov (United States)

Bruick, Richard K.; Dawson, Philip E.; Kent, Stephen BH; Usman, Nassim; Joyce, Gerald F.

1996-01-01

Synthetic oligonucleotides and peptides have enjoyed a wide range of applications in both biology and chemistry. As a consequence, oligonucleotide-peptide conjugates have received considerable attention, most notably in the development of antisense constructs with improved pharmacological properties. In addition, oligonucleotide-peptide conjugates have been used as molecular tags, in the assembly of supramolecular arrays and in the construction of encoded combinatorial libraries. To make these chimeric molecules more accessible for a broad range of investigations, we sought to develop a facile method for joining fully deprotected oligonucleotides and peptides through a stable amide bond linkage. Furthermore, we wished to make this ligation reaction addressable, enabling one to direct the ligation of specific oligonucleotide and peptide components.To confer specificity and accelerate the rate of the reaction, the ligation process was designed to be dependent on the presence of a complementary oligonucleotide template.

Flow behavior of droplets downstream of the spacer

International Nuclear Information System (INIS)

Kodama, Eiichiro; Morishita, Kiyohide; Aritomi, Masanori; Yano, Takashi

1998-01-01

The fuel spacer, of which role is to maintain an appropriate rod-to-rod clearance, is one of the components of a Boiling Water Reactor (BWR) fuel rod bundles. The fuel spacer influences flow characteristics of the liquid film in fuel rod bundles, so that its geometry influences greatly thermal hydraulics such as critical power and pressure drop therein. The purpose of this study is to clarify the effect of the spacer geometry on the core flow split downstream of the spacer. Phase Doppler Anemometry (PDA) was used for their meausrement under the conditions of a small amount of droplets in mist flows. From the experimental results, the normalized droplet velocity profiles with a spacer were split by the spacer and were different between a wider and a narrower regions in the channel, however, they became uniform at the distance far 100mm from the spacer. In the case without a spacer, the velocity was monotonously increasing nearer the rod surface with going toward the center of the channel. In the case with a spacer, the velocity profile downstream of the spacer changed in the narrower region of the channel. This tendency became more remarkable with thickening the spacer and widening clearance between the spacer and the wall. In this paper, 'drift' velocity effect was applied for the spacer model, due to the gas flows were split by the spacer which is based on the momentum balance between the narrower and wider channels. This model was confirmed from the experimental results that the droplet flowed from a wider region to a narrower one. This drift effect appeared more strongly as the spacer became thicker and the clearance did narrower. The analytical results explained qualitatively the measured ones. It is clarified that the drift effect proposed in this work was a dominant factor on droplet deposition downstream of the spacer

Fouling Resilient Perforated Feed Spacers for Membrane Filtration

KAUST Repository

Kerdi, Sarah

2018-04-24

The improvement of feed spacers with optimal geometry remains a key challenge for spiral-wound membrane systems in water treatment due to their impact on the hydrodynamic performance and fouling development. In this work, novel spacer designs are proposed by intrinsically modifying cylindrical filaments through perforations. Three symmetric perforated spacers (1-Hole, 2-Hole, and 3-Hole) were in-house 3D-printed and experimentally evaluated in terms of permeate flux, feed channel pressure drop and membrane fouling. Spacer performance is characterized and compared with standard no perforated (0-Hole) design under constant feed pressure and constant feed flow rate. Perforations in the spacer filaments resulted in significantly lowering the net pressure drop across the spacer filled channel. The 3-Hole spacer was found to have the lowest pressure drop (50% - 61%) compared to 0-Hole spacer for various average flow velocities. Regarding permeate flux production, the 0-Hole spacer produced 5.7 L.m-2.h-1 and 6.6 L.m-2.h-1 steady state flux for constant pressure and constant feed flow rate, respectively. The 1-Hole spacer was found to be the most efficient among the perforated spacers with 75% and 23% increase in permeate production at constant pressure and constant feed flow, respectively. Furthermore, membrane surface of 1-Hole spacer was found to be cleanest in terms of fouling, contributing to maintain higher permeate flux production. Hydrodynamic understanding of these perforated spacers is also quantified by performing Direct Numerical Simulation (DNS). The performance enhancement of these perforated spacers is attributed to the formation of micro-jets in the spacer cell that aided in producing enough unsteadiness/turbulence to clean the membrane surface and mitigate fouling phenomena. In the case of 1-Hole spacer, the unsteadiness intensity at the outlet of micro-jets and the shear stress fluctuations created inside the cells are higher than those observed with

Fouling resilient perforated feed spacers for membrane filtration.

Science.gov (United States)

Kerdi, Sarah; Qamar, Adnan; Vrouwenvelder, Johannes S; Ghaffour, Noreddine

2018-04-24

The improvement of feed spacers with optimal geometry remains a key challenge for spiral-wound membrane systems in water treatment due to their impact on the hydrodynamic performance and fouling development. In this work, novel spacer designs are proposed by intrinsically modifying cylindrical filaments through perforations. Three symmetric perforated spacers (1-Hole, 2-Hole, and 3-Hole) were in-house 3D-printed and experimentally evaluated in terms of permeate flux, feed channel pressure drop and membrane fouling. Spacer performance is characterized and compared with standard no perforated (0-Hole) design under constant feed pressure and constant feed flow rate. Perforations in the spacer filaments resulted in significantly lowering the net pressure drop across the spacer filled channel. The 3-Hole spacer was found to have the lowest pressure drop (50%-61%) compared to 0-Hole spacer for various average flow velocities. Regarding permeate flux production, the 0-Hole spacer produced 5.7 L m -2 .h -1 and 6.6 L m -2 .h -1 steady state flux for constant pressure and constant feed flow rate, respectively. The 1-Hole spacer was found to be the most efficient among the perforated spacers with 75% and 23% increase in permeate production at constant pressure and constant feed flow, respectively. Furthermore, membrane surface of 1-Hole spacer was found to be cleanest in terms of fouling, contributing to maintain higher permeate flux production. Hydrodynamic understanding of these perforated spacers is also quantified by performing Direct Numerical Simulation (DNS). The performance enhancement of these perforated spacers is attributed to the formation of micro-jets in the spacer cell that aided in producing enough unsteadiness/turbulence to clean the membrane surface and mitigate fouling phenomena. In the case of 1-Hole spacer, the unsteadiness intensity at the outlet of micro-jets and the shear stress fluctuations created inside the cells are higher than those

Challenges to oligonucleotides-based therapeutics for Duchenne muscular dystrophy

Directory of Open Access Journals (Sweden)

Goyenvalle Aurélie

2011-02-01

Full Text Available Abstract Antisense oligonucleotides are short nucleic acids designed to bind to specific messenger RNAs in order to modulate splicing patterns or inhibit protein translation. As such, they represent promising therapeutic tools for many disorders and have been actively developed for more than 20 years as a form of molecular medicine. Although significant progress has been made in developing these agents as drugs, they are yet not recognized as effective therapeutics and several hurdles remain to be overcome. Within the last few years, however, the prospect of successful oligonucleotides-based therapies has moved a step closer, in particular for Duchenne muscular dystrophy. Clinical trials have recently been conducted for this myopathy, where exon skipping is being used to achieve therapeutic outcomes. In this review, the recent developments and clinical trials using antisense oligonucleotides for Duchenne muscular dystrophy are discussed, with emphasis on the challenges ahead for this type of therapy, especially with regards to delivery and regulatory issues.

Development of a High Performance Spacer Grid

Energy Technology Data Exchange (ETDEWEB)

Song, Kee Nam; Song, K. N.; Yoon, K. H. (and others)

2007-03-15

A spacer grid in a LWR fuel assembly is a key structural component to support fuel rods and to enhance the heat transfer from the fuel rod to the coolant. In this research, the main research items are the development of inherent and high performance spacer grid shapes, the establishment of mechanical/structural analysis and test technology, and the set-up of basic test facilities for the spacer grid. The main research areas and results are as follows. 1. 18 different spacer grid candidates have been invented and applied for domestic and US patents. Among the candidates 16 are chosen from the patent. 2. Two kinds of spacer grids are finally selected for the advanced LWR fuel after detailed performance tests on the candidates and commercial spacer grids from a mechanical/structural point of view. According to the test results the features of the selected spacer grids are better than those of the commercial spacer grids. 3. Four kinds of basic test facilities are set up and the relevant test technologies are established. 4. Mechanical/structural analysis models and technology for spacer grid performance are developed and the analysis results are compared with the test results to enhance the reliability of the models.

Boiling transition phenomenon in BWR fuel assemblies effect of fuel spacer shape on critical power

International Nuclear Information System (INIS)

Yamamoto, Yasushi; Morooka, Shin-ichi; Mitsutake, Toru; Yokobori, Seiichi; Kimura, Jiro.

1996-01-01

A thorough understanding of the thermal-hydraulic phenomena near fuel spacer is necessary for the accurate prediction of the critical power of BWR fuel assemblies, and is thus essential for effective developments of a new BWR fuel assembly. The main purpose of this study is to develop an accurate method for predicting the effect of spacer shapes on critical power. Tests have been conducted under actual BWR operating conditions, using an annulus flow channel consisting of a heated rod and circular-tube channel, and BWR simulated 4x4 rod bundles with heater rods unheated just upsteam of spacer. The effect of spacer shapes on critical power was predicted analytically based on the droplet deposition rate estimation. The droplet deposition rate for different spacer shapes was calculated using a single-phase flow model. The prediction results were compared with the test results for the annulus flow channel using ring-type spacers. Analytical results of critical power agreed with measured critical power from point of the effects of changes in the rod-spacer clearance and the spacer thickness on critical power. (author)

Static magnetic field reduced exogenous oligonucleotide uptake by spermatozoa using magnetic nanoparticle gene delivery system

International Nuclear Information System (INIS)

Katebi, Samira; Esmaeili, Abolghasem; Ghaedi, Kamran

2016-01-01

Spermatozoa could introduce exogenous oligonucleotides of interest to the oocyte. The most important reason of low efficiency of sperm mediated gene transfer (SMGT) is low uptake of exogenous DNA by spermatozoa. The aim of this study was to evaluate the effects of static magnetic field on exogenous oligonucleotide uptake of spermatozoa using magnetofection method. Magnetic nanoparticles (MNPs) associated with the labeled oligonucleotides were used to increase the efficiency of exogenous oligonucleotide uptake by rooster spermatozoa. We used high-field/high-gradient magnet (NdFeB) to enhance and accelerate exogenous DNA sedimentation at the spermatozoa surface. Flow cytometry analysis was performed to measure viability and percentage of exogenous oligonucleotide uptake by sperm. Flow cytometry analysis showed a significant increase in exogenous oligonucleotide uptake by rooster spermatozoa (P<0.001) when spermatozoa were incubated in exogenous oligonucleotide solution and MNPs. However, by applying static magnetic field during magnetofection method, a significant decrease in exogenous oligonucleotide uptake was observed (P<0.05). Findings of this study showed that MNPs were effective to increase exogenous oligonucleotide uptake by rooster spermatozoa; however unlike others studies, static magnetic field, was not only ineffective to enhance exogenous oligonucleotide uptake by rooster spermatozoa but also led to reduction in efficiency of magnetic nanoparticles in gene transfer. - Highlights: • Core/shell type Iron oxide nanoparticles were used as a novel and efficient method. • This method increases exogenous DNA uptake by rooster spermatozoa. • Static magnetic field decreased DNA uptake by rooster spermatozoa.

Static magnetic field reduced exogenous oligonucleotide uptake by spermatozoa using magnetic nanoparticle gene delivery system

Energy Technology Data Exchange (ETDEWEB)

Katebi, Samira; Esmaeili, Abolghasem, E-mail: aesmaeili@sci.ui.ac.ir; Ghaedi, Kamran

2016-03-15

Spermatozoa could introduce exogenous oligonucleotides of interest to the oocyte. The most important reason of low efficiency of sperm mediated gene transfer (SMGT) is low uptake of exogenous DNA by spermatozoa. The aim of this study was to evaluate the effects of static magnetic field on exogenous oligonucleotide uptake of spermatozoa using magnetofection method. Magnetic nanoparticles (MNPs) associated with the labeled oligonucleotides were used to increase the efficiency of exogenous oligonucleotide uptake by rooster spermatozoa. We used high-field/high-gradient magnet (NdFeB) to enhance and accelerate exogenous DNA sedimentation at the spermatozoa surface. Flow cytometry analysis was performed to measure viability and percentage of exogenous oligonucleotide uptake by sperm. Flow cytometry analysis showed a significant increase in exogenous oligonucleotide uptake by rooster spermatozoa (P<0.001) when spermatozoa were incubated in exogenous oligonucleotide solution and MNPs. However, by applying static magnetic field during magnetofection method, a significant decrease in exogenous oligonucleotide uptake was observed (P<0.05). Findings of this study showed that MNPs were effective to increase exogenous oligonucleotide uptake by rooster spermatozoa; however unlike others studies, static magnetic field, was not only ineffective to enhance exogenous oligonucleotide uptake by rooster spermatozoa but also led to reduction in efficiency of magnetic nanoparticles in gene transfer. - Highlights: • Core/shell type Iron oxide nanoparticles were used as a novel and efficient method. • This method increases exogenous DNA uptake by rooster spermatozoa. • Static magnetic field decreased DNA uptake by rooster spermatozoa.

Effect of PEG biofunctional spacers and TAT peptide on dsRNA loading on gold nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Sanz, Vanesa; Conde, Joao; Hernandez, Yulan [Universidad de Zaragoza, Instituto de Nanociencia de Aragon (Spain); Baptista, Pedro V. [Universidade Nova de Lisboa, Departamento de Ciencias da Vida, Faculdade de Ciencias e Tecnologia, Centro de Investigacao em Genetica Molecular Humana (Portugal); Ibarra, M. R.; Fuente, Jesus M. de la, E-mail: jmfuente@unizar.es [Universidad de Zaragoza, Instituto de Nanociencia de Aragon (Spain)

2012-06-15

The surface chemistry of gold nanoparticles (AuNPs) plays a critical role in the self-assembly of thiolated molecules and in retaining the biological function of the conjugated biomolecules. According to the well-established gold-thiol interaction the undefined ionic species on citrate-reduced gold nanoparticle surface can be replaced with a self-assembled monolayer of certain thiolate derivatives and other biomolecules. Understanding the effect of such derivatives in the functionalization of several types of biomolecules, such as PEGs, peptides or nucleic acids, has become a significant challenge. Here, an approach to attach specific biomolecules to the AuNPs ({approx}14 nm) surface is presented together with a study of their effect in the functionalization with other specific derivatives. The effect of biofunctional spacers such as thiolated poly(ethylene glycol) (PEG) chains and a positive peptide, TAT, in dsRNA loading on AuNPs is reported. Based on the obtained data, we hypothesize that loading of oligonucleotides onto the AuNP surface may be controlled by ionic and weak interactions positioning the entry of the oligo through the PEG layer. We demonstrate that there is a synergistic effect of the TAT peptide and PEG chains with specific functional groups on the enhancement of dsRNA loading onto AuNPs.

Effect of PEG biofunctional spacers and TAT peptide on dsRNA loading on gold nanoparticles

International Nuclear Information System (INIS)

Sanz, Vanesa; Conde, João; Hernández, Yulán; Baptista, Pedro V.; Ibarra, M. R.; Fuente, Jesús M. de la

2012-01-01

The surface chemistry of gold nanoparticles (AuNPs) plays a critical role in the self-assembly of thiolated molecules and in retaining the biological function of the conjugated biomolecules. According to the well-established gold–thiol interaction the undefined ionic species on citrate-reduced gold nanoparticle surface can be replaced with a self-assembled monolayer of certain thiolate derivatives and other biomolecules. Understanding the effect of such derivatives in the functionalization of several types of biomolecules, such as PEGs, peptides or nucleic acids, has become a significant challenge. Here, an approach to attach specific biomolecules to the AuNPs (∼14 nm) surface is presented together with a study of their effect in the functionalization with other specific derivatives. The effect of biofunctional spacers such as thiolated poly(ethylene glycol) (PEG) chains and a positive peptide, TAT, in dsRNA loading on AuNPs is reported. Based on the obtained data, we hypothesize that loading of oligonucleotides onto the AuNP surface may be controlled by ionic and weak interactions positioning the entry of the oligo through the PEG layer. We demonstrate that there is a synergistic effect of the TAT peptide and PEG chains with specific functional groups on the enhancement of dsRNA loading onto AuNPs.

Spacer for supporting fuel element boxes

International Nuclear Information System (INIS)

Wild, E.

1979-01-01

A spacer plate unit arranged externally on each side and at a predetermined level of a polygonal fuel element box for mutually supporting, with respect to one another, a plurality of the fuel element boxes forming a fuel element bundle, is formed of a first and a second spacer plate part each having the same length and the same width and being constituted of unlike first and second materials, respectively. The first and second spacer plate parts of the several spacer plate units situated at the predetermined level are arranged in an alternating continuous series when viewed in the peripheral direction of the fuel element box, so that any two spacer plate units belonging to face-to-face oriented sides of two adjoining fuel element boxes in the fuel element bundle define interfaces of unlike materials

Enzymatic production of 'monoclonal stoichiometric' single-stranded DNA oligonucleotides.

Science.gov (United States)

Ducani, Cosimo; Kaul, Corinna; Moche, Martin; Shih, William M; Högberg, Björn

2013-07-01

Single-stranded oligonucleotides are important as research tools, as diagnostic probes, in gene therapy and in DNA nanotechnology. Oligonucleotides are typically produced via solid-phase synthesis, using polymer chemistries that are limited relative to what biological systems produce. The number of errors in synthetic DNA increases with oligonucleotide length, and the resulting diversity of sequences can be a problem. Here we present the 'monoclonal stoichiometric' (MOSIC) method for enzyme-mediated production of DNA oligonucleotides. We amplified oligonucleotides from clonal templates derived from single bacterial colonies and then digested cutter hairpins in the products, which released pools of oligonucleotides with precisely controlled relative stoichiometric ratios. We prepared 14-378-nucleotide MOSIC oligonucleotides either by in vitro rolling-circle amplification or by amplification of phagemid DNA in Escherichia coli. Analyses of the formation of a DNA crystal and folding of DNA nanostructures confirmed the scalability, purity and stoichiometry of the produced oligonucleotides.

Success of Two-Stage Reimplantation in Patients Requiring an Interim Spacer Exchange.

Science.gov (United States)

George, Jaiben; Miller, Evan M; Curtis, Gannon L; Klika, Alison K; Barsoum, Wael K; Mont, Michael A; Higuera, Carlos A

2018-03-23

Some patients undergoing a 2-stage revision for a periprosthetic joint infection require a repeat spacer in the interim (removal of existing spacer with insertion of a new spacer or spacer exchange) due to persistent infection. The objectives of this study are to (1) determine the factors associated with patients who receive a repeat spacer and (2) compare the infection-free survival (overall and stratified by joint type) of reimplantation in patients who did or did not receive a repeat spacer. From 2001 to 2014, 347 hip or knee 2-stage revisions that finally underwent reimplantation and had a minimum 2-year follow-up were identified. An interim spacer exchange was performed in 59 (17%) patients (exchange cohort). Patient-related and organism-related factors were compared between the exchange and non-exchange cohorts. Kaplan-Meier survival curves were performed to assess the success (absence of signs of infection, reoperation for infection, periprosthetic joint infection-related mortality) of both cohorts. Patients in the exchange group had higher comorbidity score (P = .020), prolonged time to reimplantation (P exchange cohort, and 78% (knee 77%, hip 78%) in the non-exchange cohort (P = .020). Patients requiring an interim spacer exchange were found to have more comorbidities, prolonged treatment period, and were more likely to be infected with a resistant organism. About one-third of such patients became reinfected within 5 years compared to only one-fifth of the patients without an interim spacer exchange. Copyright © 2018 Elsevier Inc. All rights reserved.

Side insertable spacer

International Nuclear Information System (INIS)

Patterson, J.F.; Ewing, R.H.

1992-01-01

This patent describes a spacer for restraining the fuel rods of a nuclear fuel assembly, the assembly being formed of a plurality of parallel, elongated fuel rods so arranged that the assembly is bounded by a polygon having an even number of sides, the rods being so arranged as to lie in a plurality of sets of parallel rows, the rows of each set being perpendicular to one of the sides of the polygon. It comprises a number of spacer combs equal to at least half the number of the sides of the polygon, the spacer combs being superposed on each other, each of the spacer combs comprising: a single base strip having a length equal to that of one of the sides of the polygon and grid strips equal in number to the spaces between rows in one of the sets, and at least a majority of the grid strips being of a length sufficient to extend substantially the full length of the rows; the grid strips being provided with spring members positioned to engage each of the rods; the grid strips being provided with spring members positioned to engage each of the rods; the grid strips being secured to and extending at right angles to the base strip; the grid strips of different combs being positioned at angles to each other, so as to occupy the spaces between rows in different sets

Fouling Resilient Perforated Feed Spacers for Membrane Filtration

KAUST Repository

Kerdi, Sarah; Qamar, Adnan; Vrouwenvelder, Johannes S.; Ghaffour, NorEddine

2018-01-01

drop across the spacer filled channel. The 3-Hole spacer was found to have the lowest pressure drop (50% - 61%) compared to 0-Hole spacer for various average flow velocities. Regarding permeate flux production, the 0-Hole spacer produced 5.7 L.m-2.h-1

Electronic Structures of LNA Phosphorothioate Oligonucleotides

DEFF Research Database (Denmark)

Bohr, Henrik G.; Shim, Irene; Stein, Cy

2017-01-01

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...

Antibiotic impregnated total femur spacers: a technical tip

Directory of Open Access Journals (Sweden)

Colin D. Canham, MD

2018-03-01

Full Text Available Simultaneous prosthetic joint infection of ipsilateral hip and knee arthroplasties is often accompanied by significant bone loss and presents a challenging reconstructive problem. Two-stage reconstruction is favored and requires the placement of a total femur spacer, which is not a commercially available device. We describe a surgical technique, reporting on 2 cases in which a customized total femur antibiotic impregnated spacer was created by combining an articulating knee spacer and an articulating hip spacer with a reinforced cement dowel construct connecting the 2 spacers. Custom total femoral spacers are useful in the management of infected femoral megaprostheses and cases with ipsilateral injected hip and knee arthroplasties and severe femoral bone loss. Keywords: total femur spacer, revision arthroplasty, total hip arthroplasty, total knee arthroplasty, prosthetic joint infection

Enzymatic Production of Monoclonal Stoichiometric Single-Stranded DNA Oligonucleotides

Science.gov (United States)

Ducani, Cosimo; Kaul, Corinna; Moche, Martin; Shih, William M.; Högberg, Björn

2013-01-01

Single-stranded oligonucleotides are important as research tools as probes for diagnostics and gene therapy. Today, production of oligonucleotides is done via solid-phase synthesis. However, the capabilities of current polymer chemistry are limited in comparison to what can be produced in biological systems. The errors in synthetic DNA increases with oligonucleotide length, and sequence diversity can often be a problem. Here, we present the Monoclonal Stoichiometric (MOSIC) method for enzymatic DNA oligonucleotide production. Using this method, we amplify oligonucleotides from clonal templates followed by digestion of a cutter-hairpin, resulting in pools of monoclonal oligonucleotides with precisely controlled relative stoichiometric ratios. We present data where MOSIC oligonucleotides, 14–378 nt long, were prepared either by in vitro rolling-circle amplification, or by amplification in Escherichia coli in the form of phagemid DNA. The formation of a DNA crystal and folding of DNA nanostructures confirmed the scalability, purity and stoichiometry of the produced oligonucleotides. PMID:23727986

On the Origin of Reverse Transcriptase-Using CRISPR-Cas Systems and Their Hyperdiverse, Enigmatic Spacer Repertoires.

Science.gov (United States)

Silas, Sukrit; Makarova, Kira S; Shmakov, Sergey; Páez-Espino, David; Mohr, Georg; Liu, Yi; Davison, Michelle; Roux, Simon; Krishnamurthy, Siddharth R; Fu, Becky Xu Hua; Hansen, Loren L; Wang, David; Sullivan, Matthew B; Millard, Andrew; Clokie, Martha R; Bhaya, Devaki; Lambowitz, Alan M; Kyrpides, Nikos C; Koonin, Eugene V; Fire, Andrew Z

2017-07-11

Cas1 integrase is the key enzyme of the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas adaptation module that mediates acquisition of spacers derived from foreign DNA by CRISPR arrays. In diverse bacteria, the cas1 gene is fused (or adjacent) to a gene encoding a reverse transcriptase (RT) related to group II intron RTs. An RT-Cas1 fusion protein has been recently shown to enable acquisition of CRISPR spacers from RNA. Phylogenetic analysis of the CRISPR-associated RTs demonstrates monophyly of the RT-Cas1 fusion, and coevolution of the RT and Cas1 domains. Nearly all such RTs are present within type III CRISPR-Cas loci, but their phylogeny does not parallel the CRISPR-Cas type classification, indicating that RT-Cas1 is an autonomous functional module that is disseminated by horizontal gene transfer and can function with diverse type III systems. To compare the sequence pools sampled by RT-Cas1-associated and RT-lacking CRISPR-Cas systems, we obtained samples of a commercially grown cyanobacterium- Arthrospira platensis Sequencing of the CRISPR arrays uncovered a highly diverse population of spacers. Spacer diversity was particularly striking for the RT-Cas1-containing type III-B system, where no saturation was evident even with millions of sequences analyzed. In contrast, analysis of the RT-lacking type III-D system yielded a highly diverse pool but reached a point where fewer novel spacers were recovered as sequencing depth was increased. Matches could be identified for a small fraction of the non-RT-Cas1-associated spacers, and for only a single RT-Cas1-associated spacer. Thus, the principal source(s) of the spacers, particularly the hypervariable spacer repertoire of the RT-associated arrays, remains unknown. IMPORTANCE While the majority of CRISPR-Cas immune systems adapt to foreign genetic elements by capturing segments of invasive DNA, some systems carry reverse transcriptases (RTs) that enable adaptation to RNA molecules. From

Comparison of velocity and temperature fields for two types of spacers in an annular channel

Directory of Open Access Journals (Sweden)

Lávička David

2012-04-01

Full Text Available The paper deals with measurement of flow field using a modern laser method (PIV in an annular channel of very small dimension - a fuel cell model. The velocity field was measured in several positions and plains around the spacer. The measurement was extended also to record temperatures by thermocouples soldered into stainless-steel tube wall. The measurement was focused on cooling process of the preheated fuel cell tube model, where the tube was very slowly flooded with water. Main result of the paper is comparison of two spacer's designs with respect to measured velocity and temperature fields.

Two-stage revision of septic knee prosthesis with articulating knee spacers yields better infection eradication rate than one-stage or two-stage revision with static spacers.

Science.gov (United States)

Romanò, C L; Gala, L; Logoluso, N; Romanò, D; Drago, L

2012-12-01

The best method for treating chronic periprosthetic knee infection remains controversial. Randomized, comparative studies on treatment modalities are lacking. This systematic review of the literature compares the infection eradication rate after two-stage versus one-stage revision and static versus articulating spacers in two-stage procedures. We reviewed full-text papers and those with an abstract in English published from 1966 through 2011 that reported the success rate of infection eradication after one-stage or two-stage revision with two different types of spacers. In all, 6 original articles reporting the results after one-stage knee exchange arthoplasty (n = 204) and 38 papers reporting on two-stage revision (n = 1,421) were reviewed. The average success rate in the eradication of infection was 89.8% after a two-stage revision and 81.9% after a one-stage procedure at a mean follow-up of 44.7 and 40.7 months, respectively. The average infection eradication rate after a two-stage procedure was slightly, although significantly, higher when an articulating spacer rather than a static spacer was used (91.2 versus 87%). The methodological limitations of this study and the heterogeneous material in the studies reviewed notwithstanding, this systematic review shows that, on average, a two-stage procedure is associated with a higher rate of eradication of infection than one-stage revision for septic knee prosthesis and that articulating spacers are associated with a lower recurrence of infection than static spacers at a comparable mean duration of follow-up. IV.

Review on investigations of antisense oligonucleotides with the use of mass spectrometry.

Science.gov (United States)

Studzińska, Sylwia

2018-01-01

Antisense oligonucleotides have been investigated as potential drugs for years. They inhibit target gene or protein expression. The present review summarizes their modifications, modes of action, and applications of liquid chromatography coupled with mass spectrometry for qualitative and quantitative analysis of these compounds. The most recent reports on a given topic were given prominence, while some early studies were reviewed in order to provide a theoretical background. The present review covers the issues of using ion-exchange chromatography, ion-pair reversed-phase high performance liquid chromatography and hydrophilic interaction chromatography for the separation of antisense oligonucleotides. The application of mass spectrometry was described with regard to the ionization type used for the determination of these potential therapeutics. Moreover, the current approaches and applications of mass spectrometry for quantitative analysis of antisense oligonucleotides and their metabolites as well as their impurities during in vitro and in vivo studies were discussed. Finally, certain conclusions and perspectives on the determination of therapeutic oligonucleotides in various samples were briefly described. Copyright © 2017 Elsevier B.V. All rights reserved.

Radio-marking and in vivo imagery of oligonucleotides

International Nuclear Information System (INIS)

Kuehnast, Bertrand

2000-01-01

This research thesis is part of activities aimed at the development of new molecules like oligonucleotides. Its first objective was the development and validation of a marking method with fluorine-18 of oligonucleotides for their in-vivo pharmacological assessment with positron emission tomography (PET). Further investigations addressed the use of iodine-125 for oligonucleotide marking purpose. This radio-marking, and in vivo and ex vivo imagery techniques are described, and their potential is highlighted for the pharmacological assessment of different oligonucleotides

Genetic diversity of Mycobacterium tuberculosis in Mbarara, South ...

African Journals Online (AJOL)

Background: We determined the genetic diversity of mycobacteria isolated from tuberculosis patients in Mbarara Uganda, using region of difference (RD) analysis and spacer oligonucleotide typing (spoligotyping). Methods: Sputum samples were cultured on Lowenstein Jensen media. The isolates were characterized using ...

Microsatellite and HLA class II oligonucleotide typing in a population of Yanomami Indians.

Science.gov (United States)

Roewer, L; Nagy, M; Schmidt, P; Epplen, J T; Herzog-Schröder, G

1993-01-01

We have used three different microsatellites (on chromosome 12 and Y) together with HLA class II oligonucleotide typing (DQA and DQB) to analyze families of Yanomami indians settling in villages in Southern Venezuela. There exist complex networks of biological relationship between villages as a result of wife exchange, village fissioning and changing patterns of alliances associated with inter-village warfare. Social status in this society is largely determined by the kinship system. Polygyny is common, especially among headmen, with additional wives, frequently being chosen among the sisters of the first wife. Our preliminary results mainly obtained from inhabitants of the village HAP show the expected allele distribution in populations with a high degree of consanguinity: (i) deficiency of observed heterozygotes at the autosomal loci and (ii) almost all men carry the same Y chromosomal allele. Nevertheless in the Yanomami village two thirds of the described autosomal microsatellite alleles were identified. Several paternities were clarified.

A novel analysis strategy for HLA typing using a sequence-specific oligonucleotide probe method.

Science.gov (United States)

Won, D I

2017-11-01

The technique of reverse sequence-specific oligonucleotide probes (SSOPs) is commonly used in human leukocyte antigen (HLA) typing. In the conventional method for data analysis (exact pattern matching, EPM), the larger is the number of mismatched probes, the longer the time for final typing assignment. A novel strategy, filtering and scoring (FnS), has been developed to easily assign the best-fit allele pair. In the FnS method, candidate alleles and allele pairs were filtered based on (1) subject's ethnicity, and (2) the measured partial reaction pattern with only definitely negative or positive probes. Then, the complete reaction pattern for all probes (CRPoAPs) were compared between the raw sample and expected residual allele pairs to obtain mismatch scores. To compare the FnS and EPM methods, each analysis time (minutes:seconds) for reverse SSOP HLA typing with intermediate resolution (n = 507) was measured. The analysis time with FnS method was shorter than that of the EPM method [00:21 (00:08-01:47) and 01:04 (00:15-23:45), respectively, P typing in a comprehensive and quantitative comparison between measured and expected CRPoAPs of candidate allele pairs. Therefore, this analysis strategy might be useful in a clinical setting. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hot fuel examination facility element spacer wire-wrap machine

International Nuclear Information System (INIS)

Tobias, D.A.; Sherman, E.K.

1989-01-01

Nondestructive examinations of irradiated experimental fuel elements conducted in the Argonne National Laboratory Hot Fuel Examination Facility/North (HFEF/N) at the Idaho National Engineering Laboratory include laser and contact profilometry (element diameter measurements), electrical eddy-current testing for cladding and thermal bond defects, bow and length measurements, neutron radiography, gamma scanning, remote visual exam, and photography. Profilometry was previously restricted to spiral profilometry of the element to prevent interference with the element spacer wire wrapped in a helix about the Experimental Breeder Reactor II (EBR-II)-type fuel element from end to end. By removing the spacer wire prior to conducting profilometry examination, axial profilometry techniques may be used, which are considerably faster than spiral techniques and often result in data acquisition more important to experiment sponsors. Because the element must often be reinserted into the nuclear reactor (EBR-II) for additional irradiation, however, the spacer wire must be reinstalled on the highly irradiated fuel element by remote means after profilometry of the wireless elements. The element spacer wire-wrap machine developed at HFEF is capable of helically wrapping fuel elements with diameters up to 1.68 cm (0.660 in.) and 2.44-m (96-in.) lengths. The machine can accommodate almost any desired wire pitch length by simply inserting a new wrapper gear module

CFD modeling of turbulent mixing through vertical pressure tube type boiling water reactor fuel rod bundles with spacer-grids

Science.gov (United States)

Verma, Shashi Kant; Sinha, S. L.; Chandraker, D. K.

2018-05-01

Numerical simulation has been carried out for the study of natural mixing of a Tracer (Passive scalar) to describe the development of turbulent diffusion in an injected sub-channel and, afterwards on, cross-mixing between adjacent sub-channels. In this investigation, post benchmark evaluation of the inter-subchannel mixing was initiated to test the ability of state-of-the-art Computational Fluid Dynamics (CFD) codes to numerically predict the important turbulence parameters downstream of a ring type spacer grid in a rod-bundle. A three-dimensional Computational Fluid Dynamics (CFD) tool (STAR-CCM+) was used to model the single phase flow through a 30° segment or 1/12th of the cross segment of a 54-rod bundle with a ring shaped spacer grid. Polyhedrons were used to discretize the computational domain, along with prismatic cells near the walls, with an overall mesh count of 5.2 M cell volumes. The Reynolds Stress Models (RSM) was tested because of RSM accounts for the turbulence anisotropy, to assess their capability in predicting the velocities as well as mass fraction of potassium nitrate measured in the experiment. In this way, the line probes are located in the different position of subchannels which could be used to characterize the progress of the mixing along the flow direction, and the degree of cross-mixing assessed using the quantity of tracer arriving in the neighbouring sub-channels. The predicted dimensionless mixing scalar along the length, however, was in good agreement with the measurements downstream of spacers.

Pressure Drop Test of Hybrid Mixing Vane Spacer Grid

Energy Technology Data Exchange (ETDEWEB)

Oh, D. S.; Chang, S. K.; Kim, B. D.; Chun, S. Y.; Chun, T. H

2007-08-15

The pressure loss test has been accomplished in the test section containing 5x5 rod bundle with a length of 2 m including 3 spacer grids. The test has been performed for the 5 kinds of spacer grids to compare the pressure loss characteristics: 1. Plain spacer grid which has the same body of the Hybrid but without vane (Plain), 2. Hybrid Vane spacer grid (Hybrid), 3. Hybrid-SC spacer grid which is constructed with coined, chamfered strip and is fabricated by spot welding, 4. Hybrid-LC spacer grid which is constructed with coined, chamfered strip and is fabricated by line welding along intersection line, 5. Westinghouse spacer grid with split vane (Plus-7). The pressure loss coefficient of the Plain, Hybrid, Hybrid-SC, Hybrid-LC, and Plus-7 spacer grid is 0.93, 1.15, 1.02, 1.04, and 1.08, respectively.

Comparative studies of 111In-labeled monoclonal antibody using spacer-containing and non-spacer bifunctional chelates. 2

International Nuclear Information System (INIS)

Sun, Baofu

1994-01-01

Indium-111-labeled A7 monoclonal antibodies using two spacer-containing chelates, succinimido-EGS-DTPA (EGS-DTPA: diester spacer) and maleimido-C10-Bz-EDTA (C10-Bz-EDTA: hydrocarbon spacer) were investigated in human LS180 colon tumor bearing nude mice and were compared with two non-spacer chelates, cyclic DTPA dianhydride (cDTPAA) and isothiocyanatobenzyl-EDTA (SCN-Bz-EDTA). Compared with immunoconjugates using non-spacer chelates, immunoconjugates using spacer-containing chelates, especially C10-Bz-EDTA-A7 showed lower 111 In activity in normal organs. The radioactivity in the liver for C10-Bz-EDTA-A7 decreased continuously till 96 hrs postinjection, however, this liver radioactivity for EGS-DTPA-A7 showed little change after 24 hrs. Moreover, in liver subcellular distribution study, EGS-DTPA-A7 showed a higher activity retention in mitochondrial fraction which contained lysosome, a place for metabolizing and storing of 111 In labeled antibody, than that of C10-Bz-EDTA-A7. The C10-Bz-EDTA-A7 conjugate demonstrated more preferable tumor-to-non tumor contrast on the scintigrams than that found with other three immunoconjugates. Up to 96 hrs postinjection, tumor bearing nude mice injecting with immunoconjugates using spacer-containing chelates exreted twice radioactivity from whole body than that excreted by using non-spacer chelates. Interestingly, different from other three chelates, C10-Bz-EDTA-A7 were mainly excreted via feces. We conclude that the decrease of radioactivity in normal tissues in the case of EGS-DTPA-A7 was due to the rapid decrease of activity in the blood, while in the case of C10-Bz-EDTA-A7 it was due to the quickly excreted small metabolite through faces. 111 In labeled C10-Bz-EDTA conjugate is superior, at least when conjugated with A7, to other three chelate conjugates used in this study. (author)

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...

Oligonucleotide-based theranostic nanoparticles in cancer therapy

Science.gov (United States)

Shahbazi, Reza; Ozpolat, Bulent; Ulubayram, Kezban

2016-01-01

Theranostic approaches, combining the functionality of both therapy and imaging, have shown potential in cancer nanomedicine. Oligonucleotides such as small interfering RNA and microRNA, which are powerful therapeutic agents, have been effectively employed in theranostic systems against various cancers. Nanoparticles are used to deliver oligonucleotides into tumors by passive or active targeting while protecting the oligonucleotides from nucleases in the extracellular environment. The use of quantum dots, iron oxide nanoparticles and gold nanoparticles and tagging with contrast agents, like fluorescent dyes, optical or magnetic agents and various radioisotopes, has facilitated early detection of tumors and evaluation of therapeutic efficacy. In this article, we review the advantages of theranostic applications in cancer therapy and imaging, with special attention to oligonucleotide-based therapeutics. PMID:27102380

Pressure Drop of Chamfer on Spacer Grid Strap

Energy Technology Data Exchange (ETDEWEB)

Kim, Euijae; Kim, Kanghoon; Kim, Kyounghong; Nahm, Keeyil [KEPCO Nuclear Fuel Co., Daejeon (Korea, Republic of)

2014-05-15

A swirl flow and cross flow are generated by the spacer grid with mixing vane that enhances the thermal performance and critical heat flux (CHF). The additional pressure drop makes it difficult to meet acceptance criteria for overall pressure drop in fuel assembly depending upon the pump capacity. The chamfer on the end of spacer grid strap is one solution to reduce additional pressure drop without any adverse effect on flow fields. In this research, the pressure drop tests for spacer grid with and without chamfer were carried out at the hydraulic test facility. The result can be applied to develop high performance nuclear fuel assemblies for Pressurized Water Reactor (PWR) plants. The pressure drop tests for 5x5 spacer grid with and without chamfer as well as 6x6 spacer grid with and without chamfer were carried out at the INFINIT test facility. The Reynolds number ranged about from 16000 to 75000. The sweep-up and sweep-down test showed that the direction of sweep did not affect the pressure drop. The chamfer on spacer grid strap reduced the pressure drop due to the decreased in ratio of inlet area to outlet area. The pressure loss coefficient for spacer grid with chamfer was by up to 13.8 % lower than that for spacer grid without chamfer. Hence, the chamfer on spacer grid strap was one of effective ways to reduce the pressure drop.

The potential of standard and modified feed spacers for biofouling control

KAUST Repository

Araú jo, Paula A.; Kruithof, Joop C.; van Loosdrecht, Mark C.M.; Vrouwenvelder, Johannes S.

2012-01-01

The impact of feed spacers on initial feed channel pressure (FCP) drop, FCP increase and biomass accumulation has been studied in membrane fouling simulators using feed spacers applied in commercially available nanofiltration and reverse osmosis spiral wound membrane modules. All spacers had a similar geometry.Our studies showed that biofouling was not prevented by (i) variation of spacer thickness, (ii) feed spacer orientation, (iii) feed spacer coating with silver, copper or gold and (iv) using a biostatic feed spacer. At constant feed flow, a lower FCP and FCP increase were observed for a thicker feed spacer. At constant linear flow velocity, roughly the same FCP development and biomass accumulation were found irrespective of the feed spacer thickness: hydrodynamics and substrate load were more important for development and impact of biofouling than the thickness of currently applied spacers. Use of biostatic and metal coated spacers were not effective for biofouling control. The same small reduction of biofouling rate was observed with copper and silver coated spacers as well as uncoated 45° rotated spacers.The studied modified spacers were not effective for biofouling prevention and control. The impact of biofouling on FCP increase was reduced significantly by a lower linear flow velocity, while spacer orientation and spacer thickness in membrane modules had a smaller but still significant effect. © 2012 Elsevier B.V.

The potential of standard and modified feed spacers for biofouling control

KAUST Repository

Araújo, Paula A.

2012-06-01

The impact of feed spacers on initial feed channel pressure (FCP) drop, FCP increase and biomass accumulation has been studied in membrane fouling simulators using feed spacers applied in commercially available nanofiltration and reverse osmosis spiral wound membrane modules. All spacers had a similar geometry.Our studies showed that biofouling was not prevented by (i) variation of spacer thickness, (ii) feed spacer orientation, (iii) feed spacer coating with silver, copper or gold and (iv) using a biostatic feed spacer. At constant feed flow, a lower FCP and FCP increase were observed for a thicker feed spacer. At constant linear flow velocity, roughly the same FCP development and biomass accumulation were found irrespective of the feed spacer thickness: hydrodynamics and substrate load were more important for development and impact of biofouling than the thickness of currently applied spacers. Use of biostatic and metal coated spacers were not effective for biofouling control. The same small reduction of biofouling rate was observed with copper and silver coated spacers as well as uncoated 45° rotated spacers.The studied modified spacers were not effective for biofouling prevention and control. The impact of biofouling on FCP increase was reduced significantly by a lower linear flow velocity, while spacer orientation and spacer thickness in membrane modules had a smaller but still significant effect. © 2012 Elsevier B.V.

A non-electrostatic spacer for aerosol delivery

DEFF Research Database (Denmark)

Bisgaard, H; Anhøj, J; Klug, B

1995-01-01

to 6 years, suspected to have asthma the non-electrostatic spacer delivered a mean total dose of budesonide aerosol of 39% of the nominal dose, which was significantly higher than the Babyhaler (28%), the Nebuhaler (21%), and the AeroChamber (19%). These differences were most pronounced in children......A pear shaped non-electrostatic spacer, composed of steel with a volume of 250 ml and equipped with a facemask containing integrated inlet and outlet valves for inspiration and expiration, was compared with three plastic spacers. The plastic spacers were primed with repeated puffs from a budesonide...... was 27 seconds and independent of the use of p-MDI. In vitro the maximum dose of budesonide from a p-MDI, expressed as a percentage of the nominal dose, was 56% from the non-electrostatic spacer, 61% from the Nebuhaler, 45% from the Babyhaler, and 30% from the AeroChamber. In 124 children, age 6 months...

A non-electrostatic spacer for aerosol delivery

DEFF Research Database (Denmark)

Bisgaard, H; Anhøj, J; Klug, B

1995-01-01

A pear shaped non-electrostatic spacer, composed of steel with a volume of 250 ml and equipped with a facemask containing integrated inlet and outlet valves for inspiration and expiration, was compared with three plastic spacers. The plastic spacers were primed with repeated puffs from a budesonide...... pressurised metered dose inhaler (p-MDI) to minimise the electrostatic charge on the plastic. The procedure prolonged the half life (t1/2) of the aerosol in the Nebuhaler from nine to 32 seconds. A normal cleaning procedure reduced the aerosol t1/2 back to baseline. The t1/2 of the aerosol in the metal spacer...... was 27 seconds and independent of the use of p-MDI. In vitro the maximum dose of budesonide from a p-MDI, expressed as a percentage of the nominal dose, was 56% from the non-electrostatic spacer, 61% from the Nebuhaler, 45% from the Babyhaler, and 30% from the AeroChamber. In 124 children, age 6 months...

Experimental investigations of the post-CHF heat transfer of R-134a flow-boiling in an annulus with spacer grids

International Nuclear Information System (INIS)

Lee, Kwi Lim; Chang, Soon Heung

2009-01-01

An experimental study was performed in the post-CHF condition using R-134a to investigate the effect of spacer grids on post-CHF heat transfer in an annulus channel. The experiments were conducted under the outlet pressures of 1.1 - 2.0 MPa, the mass fluxes of 100 - 400 kg/m 2 s and the inlet temperatures of 25 - 51degC. About 300 data of post-CHF data were obtained in the annular geometry without spacer grids and compared with several post-CHF correlations. The results showed the large prediction uncertainty mainly caused by the cold wall effect, so the empirical correlation for an annulus geometry without spacer grids was developed with the present experimental results. The heat transfer coefficient was calculated based on the heater rod temperature and the saturated vapor property. The average and root-mean-square(RMS) errors of the predictions were 0.17 % and 3.4 %, respectively. The experiments related to the spacer grid effects were performed with an I-type spacer grid and split-swirl mixing vane (with blockage-area ratios of 4.0 and 5.8 %). The spacer grid and mixing vane test results showed the enhancing effect on the heat transfer at the downstream location of the spacers. The experimental results from the spilt-swirl-type grid tests were more effective than the I-type grid tests. This was attributed to enhance the turbulence and increase the heat transfer caused by the mixing vane. (author)

Typing for HLA-DPB1*03 and HLA-DPB1*06 using allele-specific DNA in vitro amplification and allele-specific oligonucleotide probes. Detection of "new" DPB1*06 variants

DEFF Research Database (Denmark)

Fugger, L; Morling, N; Ryder, L P

1989-01-01

DP gene typing using in vitro DNA amplification combined with sequence-specific oligonucleotide probes has recently been reported. The resulting DNA amplification was specific for the HLA-DPB locus. Typing for the individual DPB alleles was exclusively dependent on the hybridizations of the probe...

A study on improvement of analytical prediction model for spacer grid pressure loss coefficients

International Nuclear Information System (INIS)

Lim, Jonh Seon

2002-02-01

Nuclear fuel assemblies used in the nuclear power plants consist of the nuclear fuel rods, the control rod guide tubes, an instrument guide tube, spacer grids,a bottom nozzle, a top nozzle. The spacer grid is the most important component of the fuel assembly components for thermal hydraulic and mechanical design and analyses. The spacer grids fixed with the guide tubes support the fuel rods and have the very important role to activate thermal energy transfer by the coolant mixing caused to the turbulent flow and crossflow in the subchannels. In this paper, the analytical spacer grid pressure loss prediction model has been studied and improved by considering the test section wall to spacer grid gap pressure loss independently and applying the appropriate friction drag coefficient to predict pressure loss more accurately at the low Reynolds number region. The improved analytical model has been verified based on the hydraulic pressure drop test results for the spacer grids of three types with 5x5, 16x16, 17x17 arrays, respectively. The pressure loss coefficients predicted by the improved analytical model are coincident with those test results within ±12%. This result shows that the improved analytical model can be used for research and design change of the nuclear fuel assembly

Regulation of Gene Expression with Double-Stranded Phosphorothioate Oligonucleotides

Science.gov (United States)

Bielinska, Anna; Shivdasani, Ramesh A.; Zhang, Liquan; Nabel, Gary J.

1990-11-01

Alteration of gene transcription by inhibition of specific transcriptional regulatory proteins is necessary for determining how these factors participate in cellular differentiation. The functions of these proteins can be antagonized by several methods, each with specific limitations. Inhibition of sequence-specific DNA-binding proteins was achieved with double-stranded (ds) phosphorothioate oligonucleotides that contained octamer or kappaB consensus sequences. The phosphorothioate oligonucleotides specifically bound either octamer transcription factor or nuclear factor (NF)-kappaB. The modified oligonucleotides accumulated in cells more effectively than standard ds oligonucleotides and modulated gene expression in a specific manner. Octamer-dependent activation of a reporter plasmid or NF-kappaB-dependent activation of the human immunodeficiency virus (HIV) enhancer was inhibited when the appropriate phosphorothioate oligonucleotide was added to a transiently transfected B cell line. Addition of phosphorothioate oligonucleotides that contained the octamer consensus to Jurkat T leukemia cells inhibited interleukin-2 (IL-2) secretion to a degree similar to that observed with a mutated octamer site in the IL-2 enhancer. The ds phosphorothioate oligonucleotides probably compete for binding of specific transcription factors and may provide anti-viral, immunosuppressive, or other therapeutic effects.

High corrosion-resistant fuel spacers

International Nuclear Information System (INIS)

Yoshida, Toshimi; Takase, Iwao; Ikeda, Shinzo; Masaoka, Isao; Nakajima, Junjiro.

1986-01-01

Purpose: To enable manufacturing BWR fuel spacers by prior-art production process, using a zirconium-base alloy having very excellent corrosion resistance. Method: A highly improved nodular-resistant, corrosion-resistant zirconium alloy is devised by adding a slight amount of niobium, titanium and vanadium to zircaloy, of which fuel spacers are produced. That is, there can be obtained an alloy having much more excellent nodular resistance than conventional zircaloy, and free from a large change in plasticity, workability, and weldability, by adding to zirconium about 1.5 % of tin, about 0.15 % of iron, about 0.05 % of chromium, about 0.05 % of nickel, and 0.05 to 0.5 % of at least one or two kinds of niobium, titanium and vanadium. Using this zirconium-base alloy can manufacture fuel spacers by the same manufacturing process, thus improving economy and reliability. (Kamimura, M.)

The use of oligonucleotide probes for meningococcal serotype characterization

Directory of Open Access Journals (Sweden)

SACCHI Claudio Tavares

1998-01-01

Full Text Available In the present study we examine the potential use of oligonucleotide probes to characterize Neisseria meningitidis serotypes without the use of monoclonal antibodies (MAbs. Antigenic diversity on PorB protein forms the bases of serotyping method. However, the current panel of MAbs underestimated, by at least 50% the PorB variability, presumably because reagents for several PorB variable regions (VRs are lacking, or because a number of VR variants are not recognized by serotype-defining MAbs12. We analyzed the use of oligonucleotide probes to characterize serotype 10 and serotype 19 of N. meningitidis. The porB gene sequence for the prototype strain of serotype 10 was determined, aligned with 7 other porB sequences from different serotypes, and analysis of individual VRs were performed. The results of DNA probes 21U (VR1-A and 615U (VR3-B used against 72 N. meningitidis strains confirm that VR1 type A and VR3 type B encode epitopes for serotype-defined MAbs 19 and 10, respectively. The use of probes for characterizing serotypes possible can type 100% of the PorB VR diversity. It is a simple and rapid method specially useful for analysis of large number of samples.

Electronic Structures of LNA Phosphorothioate Oligonucleotides

Directory of Open Access Journals (Sweden)

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

Mechanical Properties Of 3D-Structure Composites Based On Warp-Knitted Spacer Fabrics

Directory of Open Access Journals (Sweden)

Chen Si

2015-06-01

Full Text Available In this paper, the mechanical properties (compression and impact behaviours of three-dimension structure (3D-structure composites based on warp-knitted spacer fabrics have been thoroughly investigated. In order to discuss the effect of fabric structural parameters on the mechanical performance of composites, six different types of warp-knitted spacer fabrics having different structural parameters (such as outer layer structure, diameter of spacer yarn, spacer yarn inclination angle and thickness were involved for comparison study. The 3D-structure composites were fabricated based on a flexible polyurethane foam. The produced composites were characterised for compression and impact properties. The findings obtained indicate that the fabric structural parameters have strong influence on the compression and impact responses of 3D-structure composites. Additionally, the impact test carried out on the 3D-structure composites shows that the impact loads do not affect the integrity of composite structure. All the results reveal that the product exhibits promising mechanical performance and its service life can be sustained.

Sequence-dependent theory of oligonucleotide hybridization kinetics

International Nuclear Information System (INIS)

Marimuthu, Karthikeyan; Chakrabarti, Raj

2014-01-01

A theoretical approach to the prediction of the sequence and temperature-dependent rate constants for oligonucleotide hybridization reactions has been developed based on the theory of relaxation kinetics. One-sided and two-sided melting reaction mechanisms for oligonucleotide hybridization reactions have been considered, analyzed, modified, and compared to select a physically consistent as well as robust model for prediction of the relaxation times of DNA hybridization reactions that agrees with the experimental evidence. The temperature- and sequence-dependent parameters of the proposed model have been estimated using available experimental data. The relaxation time model that we developed has been combined with the nearest neighbor model of hybridization thermodynamics to estimate the temperature- and sequence-dependent rate constants of an oligonucleotide hybridization reaction. The model-predicted rate constants are compared to experimentally determined rate constants for the same oligonucleotide hybridization reactions. Finally, we consider a few important applications of kinetically controlled DNA hybridization reactions

Evaluation of spacer grid spring characteristics by means of physical tests and numerical simulation

Energy Technology Data Exchange (ETDEWEB)

Schettino, Carlos Frederico Mattos, E-mail: carlosschettino@inb.gov.br [Industrias Nucleares do Brasil (INB), Resende, RJ (Brazil)

2017-11-01

Among all fuel assemblies' components, the spacer grids play an important structural role during the energy generation process, mainly due for its primary functional requirement, that is, to provide fuel rod support. The present work aims to evaluate the spring characteristics of a specific spacer grid design used in a PWR fuel assembly type 16 x 16. These spring characteristics comprises the load versus deflection capability and its spring rate, which are very important, and also mandatory, to be correctly established in order to preclude spacer grid spring and fuel rod cladding fretting during operation, as well as prevent an excessive fuel rod buckling. This study includes physical tests and numerical simulation. The tests were performed on an adapted load cell mechanical device, using as a specimen a single strap of the spacer grid. Three numerical models were prepared using the Finite Element Method, with the support of the commercial code ANSYS. One model was built to validate the simulation according to the performed physical test, the others were built inserting a gradient of temperature (Beginning Of Life hot condition) and to evaluate the spacer grid spring characteristics in End Of Life condition. The obtained results from physical test and numerical model have shown a good agreement between them, therefore validating the simulation. The obtained results from numerical models make available information regarding the spacer grid design purpose, such as the behavior of the fuel rod cladding support during operation. Therewith, these evaluations could be useful to improve the spacer grid design. (author)

Evaluation of spacer grid spring characteristics by means of physical tests and numerical simulation

International Nuclear Information System (INIS)

Schettino, Carlos Frederico Mattos

2017-01-01

Among all fuel assemblies' components, the spacer grids play an important structural role during the energy generation process, mainly due for its primary functional requirement, that is, to provide fuel rod support. The present work aims to evaluate the spring characteristics of a specific spacer grid design used in a PWR fuel assembly type 16 x 16. These spring characteristics comprises the load versus deflection capability and its spring rate, which are very important, and also mandatory, to be correctly established in order to preclude spacer grid spring and fuel rod cladding fretting during operation, as well as prevent an excessive fuel rod buckling. This study includes physical tests and numerical simulation. The tests were performed on an adapted load cell mechanical device, using as a specimen a single strap of the spacer grid. Three numerical models were prepared using the Finite Element Method, with the support of the commercial code ANSYS. One model was built to validate the simulation according to the performed physical test, the others were built inserting a gradient of temperature (Beginning Of Life hot condition) and to evaluate the spacer grid spring characteristics in End Of Life condition. The obtained results from physical test and numerical model have shown a good agreement between them, therefore validating the simulation. The obtained results from numerical models make available information regarding the spacer grid design purpose, such as the behavior of the fuel rod cladding support during operation. Therewith, these evaluations could be useful to improve the spacer grid design. (author)

Nanoparticle-Based Brachytherapy Spacers for Delivery of Localized Combined Chemoradiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Kumar, Rajiv, E-mail: r.kumar@neu.edu [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts (United States); Belz, Jodi [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Markovic, Stacey [Department of Electrical and Computer Engineering, Northeastern University, Boston, Massachusetts (United States); Jadhav, Tej; Fowle, William [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Niedre, Mark [Department of Electrical and Computer Engineering, Northeastern University, Boston, Massachusetts (United States); Cormack, Robert; Makrigiorgos, Mike G. [Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts (United States); Sridhar, Srinivas [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts (United States)

2015-02-01

Purpose: In radiation therapy (RT), brachytherapy-inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits. Methods and Materials: Here we have fabricated implantable nanoplatforms or chemoradiation therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow-release drug depot for simultaneous localized chemoradiation therapy. The spacers are made of poly(lactic-co-glycolic) acid (PLGA) as matrix and are physically identical in size to the commercially available brachytherapy spacers (5 mm × 0.8 mm). The silica nanoparticles, 250 nm in diameter, were conjugated with near infrared fluorophore Cy7.5 as a model drug, and the INCeRT spacers were characterized in terms of size, morphology, and composition using different instrumentation techniques. The spacers were further doped with an anticancer drug, docetaxel. We evaluated the in vivo stability, biocompatibility, and biodegradation of these spacers in live mouse tissues. Results: The electron microscopy studies showed that nanoparticles were distributed throughout the spacers. These INCeRT spacers remained stable and can be tracked by the use of optical fluorescence. In vivo optical imaging studies showed a slow diffusion of nanoparticles from the spacer to the adjacent tissue in contrast to the control Cy7.5-PLGA spacer, which showed rapid disintegration in a few days with a burst release of Cy7.5. The docetaxel spacers showed suppression of tumor growth in contrast to control mice over 16 days. Conclusions: The imaging with the Cy7.5 spacer and therapeutic efficacy with docetaxel spacers supports the hypothesis that INCeRT spacers can be used for delivering the drugs in a slow, sustained manner in conjunction with brachytherapy, in contrast to the rapid clearance of the drugs when

Nanoparticle-Based Brachytherapy Spacers for Delivery of Localized Combined Chemoradiation Therapy

International Nuclear Information System (INIS)

Kumar, Rajiv; Belz, Jodi; Markovic, Stacey; Jadhav, Tej; Fowle, William; Niedre, Mark; Cormack, Robert; Makrigiorgos, Mike G.; Sridhar, Srinivas

2015-01-01

Purpose: In radiation therapy (RT), brachytherapy-inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits. Methods and Materials: Here we have fabricated implantable nanoplatforms or chemoradiation therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow-release drug depot for simultaneous localized chemoradiation therapy. The spacers are made of poly(lactic-co-glycolic) acid (PLGA) as matrix and are physically identical in size to the commercially available brachytherapy spacers (5 mm × 0.8 mm). The silica nanoparticles, 250 nm in diameter, were conjugated with near infrared fluorophore Cy7.5 as a model drug, and the INCeRT spacers were characterized in terms of size, morphology, and composition using different instrumentation techniques. The spacers were further doped with an anticancer drug, docetaxel. We evaluated the in vivo stability, biocompatibility, and biodegradation of these spacers in live mouse tissues. Results: The electron microscopy studies showed that nanoparticles were distributed throughout the spacers. These INCeRT spacers remained stable and can be tracked by the use of optical fluorescence. In vivo optical imaging studies showed a slow diffusion of nanoparticles from the spacer to the adjacent tissue in contrast to the control Cy7.5-PLGA spacer, which showed rapid disintegration in a few days with a burst release of Cy7.5. The docetaxel spacers showed suppression of tumor growth in contrast to control mice over 16 days. Conclusions: The imaging with the Cy7.5 spacer and therapeutic efficacy with docetaxel spacers supports the hypothesis that INCeRT spacers can be used for delivering the drugs in a slow, sustained manner in conjunction with brachytherapy, in contrast to the rapid clearance of the drugs when

Development of structural technology for a high performance spacer grid

International Nuclear Information System (INIS)

Song, Kee Nam; Kim, H. K.; Kang, H. S.

2003-03-01

A spacer grid in a LWR fuel assembly is a key structural component to support fuel rods and to enhance the heat transfer from the fuel rod to the coolant. In this research, the main research items are the development of inherent and high performance spacer grid shapes, the establishment of mechanical/structural analysis and test technology, and the set-up of basic test facilities for the spacer grid. The main research areas and results are as follows. 1. 14 different spacer grid candidates have been invented and applied for domestic and US patents. Among the candidates six are chosen from the patent. 2. Two kinds of spacer grids are finally selected for the advanced LWR fuel after detailed performance tests on the candidates and commercial spacer grids from a mechanical/structural point of view. According to the test results the features of the selected spacer grids are better than those of the commercial spacer grids. 3. Four kinds of basic test facilities are set up and the relevant test technologies are established. 4. Mechanical/structural analysis models and technology for spacer grid performance are developed and the analysis results are compared with the test results to enhance the reliability of the models

Device for a nuclear reactor. [Fuel element spacers

Energy Technology Data Exchange (ETDEWEB)

Foulds, R B; Kasberg, A H; Puechl, K H; Bleiberg, M L

1972-03-08

A spacer design for fuel element clusters for PWR type reactors is described. It consists of a frame supporting an egg-carton like grid each sector of which is provided with springs which grip the fuel pins. The spring design is such as to prevent fuel pin vibrations and at same time accommodate fuel pin deformations. Formulae for the calculation of natural frequencies, spring stiffness and friction loads are presented.

Update on Pneumocystis carinii f. sp. hominis Typing Based on Nucleotide Sequence Variations in Internal Transcribed Spacer Regions of rRNA Genes

Science.gov (United States)

Lee, Chao-Hung; Helweg-Larsen, Jannik; Tang, Xing; Jin, Shaoling; Li, Baozheng; Bartlett, Marilyn S.; Lu, Jang-Jih; Lundgren, Bettina; Lundgren, Jens D.; Olsson, Mats; Lucas, Sebastian B.; Roux, Patricia; Cargnel, Antonietta; Atzori, Chiara; Matos, Olga; Smith, James W.

1998-01-01

Pneumocystis carinii f. sp. hominis isolates from 207 clinical specimens from nine countries were typed based on nucleotide sequence variations in the internal transcribed spacer regions I and II (ITS1 and ITS2, respectively) of rRNA genes. The number of ITS1 nucleotides has been revised from the previously reported 157 bp to 161 bp. Likewise, the number of ITS2 nucleotides has been changed from 177 to 192 bp. The number of ITS1 sequence types has increased from 2 to 15, and that of ITS2 has increased from 3 to 14. The 15 ITS1 sequence types are designated types A through O, and the 14 ITS2 types are named types a through n. A total of 59 types of P. carinii f. sp. hominis were found in this study. PMID:9508304

Modeling the effect of spacers and biofouling on forward osmosis performance

KAUST Repository

Mosqueira Santillán, María José

2014-11-01

Currently, the most utilized desalination technology is reverse osmosis (RO), where a membrane is used as a physical barrier to separate the salts from the seawater, using high hydraulic pressure as driving force. A major problem in RO systems is biofouling, caused by severe growth of bacterial biofilms. Both, the need of an external energy input, as well as biofouling, impose a high cost on RO operation. Forward osmosis (FO) is an alternative membrane process that uses an osmotic pressure difference as driving force. FO uses a concentrated draw solution to generate high osmotic pressure, which extracts water across a semi permeable membrane from a feed solution. One of the main advantages of FO is the limited amount of external energy required to extract water from the feed solution. The objective of this research is the assessment of the impact of spacers, separating the membrane sheets, and biofouling on the FO system performance. This type of studies allow the optimization of membrane devices and operational conditions. For this, a two dimensional numerical model for FO systems was developed using computational fluid dynamics (CFD). This model allowed the evaluation of the impact of (i) spacers and (ii) biofilm, and (iii) the combined impact of spacers and biofilm on the performance of FO systems. The results obtained showed that the presence of spacers improved the performance of FO systems. Cavity configuration spacer gave the higher water flux across the membrane in clean systems; whereas for biofouled systems, the submerged configuration showed a better performance. In absence of spacers, the thickness or amount of biofilm is inversely proportional with the water flux. Furthermore, membrane surface coverage of the biofilm is more important than the amount of biofilm in terms of the impact on the performance. The numerical model can be adapted with other parameters (e.g. membrane and spacer thickness, feed and draw solution, solution concentration, etc.) to

Hydraulic Design Criteria for Spacer Grids of Nuclear Fuel Element

International Nuclear Information System (INIS)

Juanico, Luis; Brasnarof, Daniel

2000-01-01

In this paper a hydraulic model for calculating the pressure drop on the CARA spacer grids is extended.This model is validated and feedback from experimental hydraulic test performed in a low pressure loop.The importance of the spacer grid geometric parameter (that is, its thickness and length, the number and kind of their fix spacer), developing hydraulic design criteria for spacer grid on fuel element

Preclinical Evaluation of Bioabsorbable Polyglycolic Acid Spacer for Particle Therapy

International Nuclear Information System (INIS)

Akasaka, Hiroaki; Sasaki, Ryohei; Miyawaki, Daisuke; Mukumoto, Naritoshi; Sulaiman, Nor Shazrina Binti; Nagata, Masaaki; Yamada, Shigeru; Murakami, Masao; Demizu, Yusuke; Fukumoto, Takumi

2014-01-01

Purpose: To evaluate the efficacy and safety of a polyglycolic acid (PGA) spacer through physical and animal experiments. Methods and Materials: The spacer was produced with surgical suture material made of PGA, forming a 3-dimensional nonwoven fabric. For evaluation or physical experiments, 150-MeV proton or 320-MeV carbon-ion beams were used to generate 60-mm width of spread-out Bragg peak. For animal experiments, the abdomens of C57BL/6 mice, with or without the inserted PGA spacers, were irradiated with 20 Gy of carbon-ion beam (290 MeV) using the spread-out Bragg peak. Body weight changes over time were scored, and radiation damage to the intestine was investigated using hematoxylin and eosin stain. Blood samples were also evaluated 24 days after the irradiation. Long-term thickness retention and safety were evaluated using crab-eating macaques. Results: No chemical or structural changes after 100 Gy of proton or carbon-ion irradiation were observed in the PGA spacer. Water equivalency of the PGA spacer was equal to the water thickness under wet condition. During 24 days' observation after 20 Gy of carbon-ion irradiation, the body weights of mice with the PGA spacer were relatively unchanged, whereas significant weight loss was observed in those mice without the PGA spacer (P<.05). In mice with the PGA spacer, villus and crypt structure were preserved after irradiation. No inflammatory reactions or liver or renal dysfunctions due to placement of the PGA spacer were observed. In the abdomen of crab-eating macaques, thickness of the PGA spacer was maintained 8 weeks after placement. Conclusions: The absorbable PGA spacer had water-equivalent, bio-compatible, and thickness-retaining properties. Although further evaluation is warranted in a clinical setting, the PGA spacer may be effective to stop proton or carbon-ion beams and to separate normal tissues from the radiation field

Silver and Cyanine Staining of Oligonucleotides in Polyacrylamide Gel.

Science.gov (United States)

Tang, Weizhong; Zhou, Huafu; Li, Wei

2015-01-01

To explore why some oligonucleotides in denaturing polyacrylamide gel could not be silver-stained, 134 different oligonucleotides were analyzed using denaturing polyacrylamide gel electrophoresis stained with silver and asymmetric cyanine. As a result, we found that the sensitivity of oligos (dA), (dC), (dG) and (dT) to silver staining could be ranged as (dA) > (dG) > (dC) > (dT) from high to low. It was unexpected that oligo (dT) was hard to be silver-stained. Moreover, the silver staining of an oligonucleotide containing base T could be partially or completely inhibited by base T. The inhibition of silver staining by base T was a competitive inhibition which could be affected by the amounts of the argyrophil nucleobase and base T, the cis-distance between the argyrophil nucleobase and base T, and the gel concentration. The changes of the intensity of an oligonucleotide band caused by the changes of DNA base composition were diverse and interesting. The intensity of some oligonucleotide bands would significantly change when the changes of DNA base composition accumulated to a certain extent (usually ≥ 4 nt). The sensitivity of cyanine staining of ≤ 11-nt long oligonucleotides could be enhanced about 250-fold by fixing the gels with methanol fixing solution.

Stability of non-Watson-Crick G-A/A-G base pair in synthetic DNA and RNA oligonucleotides.

Science.gov (United States)

Ito, Yuko; Sone, Yumiko; Mizutani, Takaharu

2004-03-01

A non-Watson-Crick G-A/A-G base pair is found in SECIS (selenocysteine-insertion sequence) element in the 3'-untranslated region of Se-protein mRNAs and in the functional site of the hammerhead ribozyme. We studied the stability of G-A/A-G base pair (bold) in 17mer GT(U)GACGGAAACCGGAAC synthetic DNA and RNA oligonucleotides by thermal melting experiments and gel electrophoresis. The measured Tm value of DNA oligonucleotide having G-A/A-G pair showed an intermediate value (58 degrees C) between that of Watson-Crick G-C/C-G base pair (75 degrees C) and that of G-G/A-A of non-base-pair (40 degrees C). Similar thermal melting patterns were obtained with RNA oligonucleotides. This result indicates that the secondary structure of oligonucleotide having G-A/A-G base pair is looser than that of the G-C type Watson-Crick base pair. In the comparison between RNA and DNA having G-A/A-G base pair, the Tm value of the RNA oligonucleotide was 11 degrees C lower than that of DNA, indicating that DNA has a more rigid structure than RNA. The stained pattern of oligonucleotide on polyacrylamide gel clarified that the mobility of the DNA oligonucleotide G-A/A-G base pair changed according to the urea concentration from the rigid state (near the mobility of G-C/C-G oligonucleotide) in the absence of urea to the random state (near the mobility of G-G/A-A oligonucleotide) in 7 M urea. However, the RNA oligonucleotide with G-A/A-G pair moved at an intermediate mobility between that of oligonucleotide with G-C/C-G and of the oligonucleotide with G-G/A-A, and the mobility pattern did not depend on urea concentration. Thus, DNA and RNA oligonucleotides with the G-A/A-G base pair showed a pattern indicating an intermediate structure between the rigid Watson-Crick base pair and the random structure of non-base pair. RNA with G-A/A-G base pair has the intermediate structure not influenced by urea concentration. Finally, this study indicated that the intermediate rigidity imparted by Non

High-frequency genome editing using ssDNA oligonucleotides with zinc-finger nucleases

DEFF Research Database (Denmark)

Chen, Fuqiang; Pruett-Miller, Shondra M; Huang, Yuping

2011-01-01

Zinc-finger nucleases (ZFNs) have enabled highly efficient gene targeting in multiple cell types and organisms. Here we describe methods for using simple ssDNA oligonucleotides in tandem with ZFNs to efficiently produce human cell lines with three distinct genetic outcomes: (i) targeted point...

Stress Analysis of Single Spacer Grid Support considering Fuel Rod

Energy Technology Data Exchange (ETDEWEB)

Yoo, Y. G.; Jung, D. H.; Kim, J. H. [Chungnam National University, Daejeon (Korea, Republic of); Park, J. K.; Jeon, K. L. [Korea Nuclear Fuel, Daejeon (Korea, Republic of)

2010-10-15

Pressurized water reactor (PWR) nuclear fuel assembly is mainly composed of a top-end piece, a bottom-end piece, lots of fuel rods, and several spacer grids. Among them, the main function of spacer grid is protecting fuel rods from Fluid Induced Vibration (FIV). The cross section of spacer grid assembled by laser welding in upper and lower point. When the fuel rod inserted in spacer gird, spring and dimple and around of welded area got a stresses. The main hypothesis of this analysis is the boundary area of HAZ and base metal can get a lot of damage than other area by FIV. So, design factors of spacer grid mainly considered to preventing the fatigue failure in HAZ and spring and dimple of spacer grid. From previous researching, the environment in reactor verified. Pressure and temperature of light water observed 15MPa and 320 .deg. C, and vibration of the fuel rod observed within 0 {approx} 50Hz. In this study, mechanical properties of zirconium alloy that extracted from the test and the spacer grid model which used in the PWR were applied in stress analyzing. General-purpose finite element analysis program was used ANSYS Workbench 12.0.1 version. 3-D CAD program CATIA was used to create spacer grid model

Heterogeneous Diversity of Spacers within CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)

Science.gov (United States)

He, Jiankui; Deem, Michael W.

2010-09-01

Clustered regularly interspaced short palindromic repeats (CRISPR) in bacterial and archaeal DNA have recently been shown to be a new type of antiviral immune system in these organisms. We here study the diversity of spacers in CRISPR under selective pressure. We propose a population dynamics model that explains the biological observation that the leader-proximal end of CRISPR is more diversified and the leader-distal end of CRISPR is more conserved. This result is shown to be in agreement with recent experiments. Our results show that the CRISPR spacer structure is influenced by and provides a record of the viral challenges that bacteria face.

Biomechanical Analysis of an Expandable Lumbar Interbody Spacer.

Science.gov (United States)

Soriano-Baron, Hector; Newcomb, Anna G U S; Malhotra, Devika; Palma, Atilio E; Martinez-Del-Campo, Eduardo; Crawford, Neil R; Theodore, Nicholas; Kelly, Brian P; Kaibara, Taro

2018-06-01

Recently developed expandable interbody spacers are widely accepted in spinal surgery; however, the resulting biomechanical effects of their use have not yet been fully studied. We analyzed the biomechanical effects of an expandable polyetheretherketone interbody spacer inserted through a bilateral posterior approach with and without different modalities of posterior augmentation. Biomechanical nondestructive flexibility testing was performed in 7 human cadaveric lumbar (L2-L5) specimens followed by axial compressive loading. Each specimen was tested under 6 conditions: 1) intact, 2) bilateral L3-L4 cortical screw/rod (CSR) alone, 3) WaveD alone, 4) WaveD + CSR, 5) WaveD + bilateral L3-L4 pedicle screw/rod (PSR), and 6) WaveD + CSR/PSR, where CSR/PSR was a hybrid construct comprising bilateral cortical-level L3 and pedicle-level L4 screws interconnected by rods. The range of motion (ROM) with the interbody spacer alone decreased significantly compared with the intact condition during flexion-extension (P = 0.02) but not during lateral bending or axial rotation (P ≥ 0.19). The addition of CSR or PSR to the interbody spacer alone condition significantly decreased the ROM compared with the interbody spacer alone (P ≤ 0.002); and WaveD + CSR, WaveD + PSR, and WaveD + CSR/PSR (hybrid) (P ≥ 0.29) did not differ. The axial compressive stiffness (resistance to change in foraminal height during compressive loading) with the interbody spacer alone did not differ from the intact condition (P = 0.96), whereas WaveD + posterior instrumentation significantly increased compressive stiffness compared with the intact condition and the interbody spacer alone (P ≤ 0.001). The WaveD alone significantly reduced ROM during flexion-extension while maintaining the axial compressive stiffness. CSR, PSR, and CSR/PSR hybrid constructs were all effective in augmenting the expandable interbody spacer system and improving its stability. Copyright © 2018 Elsevier Inc. All

A new oligonucleotide microarray for detection of pathogenic and non-pathogenic Legionella spp.

Directory of Open Access Journals (Sweden)

Boyang Cao

Full Text Available Legionella pneumophila has been recognized as the major cause of legionellosis since the discovery of the deadly disease. Legionella spp. other than L. pneumophila were later found to be responsible to many non-pneumophila infections. The non-L. pneumophila infections are likely under-detected because of a lack of effective diagnosis. In this report, we have sequenced the 16S-23S rRNA gene internal transcribed spacer (ITS of 10 Legionella species and subspecies, including L. anisa, L. bozemanii, L. dumoffii, L. fairfieldensis, L. gormanii, L. jordanis, L. maceachernii, L. micdadei, L. pneumophila subspp. fraseri and L. pneumophila subspp. pasculleii, and developed a rapid oligonucleotide microarray detection technique accordingly to identify 12 most common Legionella spp., which consist of 11 pathogenic species of L. anisa, L. bozemanii, L. dumoffii, L. gormanii, L. jordanis, L. longbeachae, L. maceachernii, L. micdadei, and L. pneumophila (including subspp. pneumophila, subspp. fraseri, and subspp. pasculleii and one non-pathogenic species, L. fairfieldensis. Twenty-nine probes that reproducibly detected multiple Legionella species with high specificity were included in the array. A total of 52 strains, including 30 target pathogens and 22 non-target bacteria, were used to verify the oligonucleotide microarray assay. The sensitivity of the detection was at 1.0 ng with genomic DNA or 13 CFU/100 mL with Legionella cultures. The microarray detected seven samples of air conditioner-condensed water with 100% accuracy, validating the technique as a promising method for applications in basic microbiology, clinical diagnosis, food safety, and epidemiological surveillance. The phylogenetic study based on the ITS has also revealed that the non-pathogenic L. fairfieldensis is the closest to L. pneumophila than the nine other pathogenic Legionella spp.

A New Oligonucleotide Microarray for Detection of Pathogenic and Non-Pathogenic Legionella spp.

Science.gov (United States)

Cao, Boyang; Liu, Xiangqian; Yu, Xiang; Chen, Min; Feng, Lu; Wang, Lei

2014-01-01

Legionella pneumophila has been recognized as the major cause of legionellosis since the discovery of the deadly disease. Legionella spp. other than L. pneumophila were later found to be responsible to many non-pneumophila infections. The non-L. pneumophila infections are likely under-detected because of a lack of effective diagnosis. In this report, we have sequenced the 16S-23S rRNA gene internal transcribed spacer (ITS) of 10 Legionella species and subspecies, including L. anisa, L. bozemanii, L. dumoffii, L. fairfieldensis, L. gormanii, L. jordanis, L. maceachernii, L. micdadei, L. pneumophila subspp. fraseri and L. pneumophila subspp. pasculleii, and developed a rapid oligonucleotide microarray detection technique accordingly to identify 12 most common Legionella spp., which consist of 11 pathogenic species of L. anisa, L. bozemanii, L. dumoffii, L. gormanii, L. jordanis, L. longbeachae, L. maceachernii, L. micdadei, and L. pneumophila (including subspp. pneumophila, subspp. fraseri, and subspp. pasculleii) and one non-pathogenic species, L. fairfieldensis. Twenty-nine probes that reproducibly detected multiple Legionella species with high specificity were included in the array. A total of 52 strains, including 30 target pathogens and 22 non-target bacteria, were used to verify the oligonucleotide microarray assay. The sensitivity of the detection was at 1.0 ng with genomic DNA or 13 CFU/100 mL with Legionella cultures. The microarray detected seven samples of air conditioner-condensed water with 100% accuracy, validating the technique as a promising method for applications in basic microbiology, clinical diagnosis, food safety, and epidemiological surveillance. The phylogenetic study based on the ITS has also revealed that the non-pathogenic L. fairfieldensis is the closest to L. pneumophila than the nine other pathogenic Legionella spp. PMID:25469776

A comparative analysis of measles virus RNA by oligonucleotide fingerprinting

International Nuclear Information System (INIS)

Stephenson, J.R.; Meulen, V. ter

1982-01-01

Isolates from two cases of acute measles, one case of acute measles encephalitis and three patients with subacute sclerosing panencephalitis were compared. This comparison was based upon the electrophoretic analysis of T 1 oligonucleotides from single-stranded, full-length RNA isolated from cytoplasmic nucleocapsids. Although all viruses have oligonucleotides in common, each isolate generated a unique pattern of oligonucleotides. However, no group of oligonucleotides was observed which would allow differentiation between viruses isolated from acute infections and those isolated from CNS diseases; indicating that probably all measles viruses differ in their nucleotide sequence, regardless of origin. (Author)

CFD application to advanced design for high efficiency spacer grid

International Nuclear Information System (INIS)

Ikeda, Kazuo

2014-01-01

Highlights: • A new LDV was developed to investigate the local velocity in a rod bundle and inside a spacer grid. • The design information that utilizes for high efficiency spacer grid has been obtained. • CFD methodology that predicts flow field in a PWR fuel has been developed. • The high efficiency spacer grid was designed using the CFD methodology. - Abstract: Pressurized water reactor (PWR) fuels have been developed to meet the needs of the market. A spacer grid is a key component to improve thermal hydraulic performance of a PWR fuel assembly. Mixing structures (vanes) of a spacer grid promote coolant mixing and enhance heat removal from fuel rods. A larger mixing vane would improve mixing effect, which would increase the departure from nucleate boiling (DNB) benefit for fuel. However, the increased pressure loss at large mixing vanes would reduce the coolant flow at the mixed fuel core, which would reduce the DNB margin. The solution is to develop a spacer grid whose pressure loss is equal to or less than the current spacer grid and that has higher critical heat flux (CHF) performance. For this reason, a requirement of design tool for predicting the pressure loss and CHF performance of spacer grids has been increased. The author and co-workers have been worked for development of high efficiency spacer grid using Computational Fluid Dynamics (CFD) for nearly 20 years. A new laser Doppler velocimetry (LDV), which is miniaturized with fiber optics embedded in a fuel cladding, was developed to investigate the local velocity profile in a rod bundle and inside a spacer grid. The rod-embedded fiber LDV (rod LDV) can be inserted in an arbitrary grid cell instead of a fuel rod, and has the advantage of not disturbing the flow field since it is the same shape as a fuel rod. The probe volume of the rod LDV is small enough to measure spatial velocity profile in a rod gap and inside a spacer grid. According to benchmark experiments such as flow velocity

CFD application to advanced design for high efficiency spacer grid

Energy Technology Data Exchange (ETDEWEB)

Ikeda, Kazuo, E-mail: kazuo3_ikeda@ndc.mhi.co.jp

2014-11-15

Highlights: • A new LDV was developed to investigate the local velocity in a rod bundle and inside a spacer grid. • The design information that utilizes for high efficiency spacer grid has been obtained. • CFD methodology that predicts flow field in a PWR fuel has been developed. • The high efficiency spacer grid was designed using the CFD methodology. - Abstract: Pressurized water reactor (PWR) fuels have been developed to meet the needs of the market. A spacer grid is a key component to improve thermal hydraulic performance of a PWR fuel assembly. Mixing structures (vanes) of a spacer grid promote coolant mixing and enhance heat removal from fuel rods. A larger mixing vane would improve mixing effect, which would increase the departure from nucleate boiling (DNB) benefit for fuel. However, the increased pressure loss at large mixing vanes would reduce the coolant flow at the mixed fuel core, which would reduce the DNB margin. The solution is to develop a spacer grid whose pressure loss is equal to or less than the current spacer grid and that has higher critical heat flux (CHF) performance. For this reason, a requirement of design tool for predicting the pressure loss and CHF performance of spacer grids has been increased. The author and co-workers have been worked for development of high efficiency spacer grid using Computational Fluid Dynamics (CFD) for nearly 20 years. A new laser Doppler velocimetry (LDV), which is miniaturized with fiber optics embedded in a fuel cladding, was developed to investigate the local velocity profile in a rod bundle and inside a spacer grid. The rod-embedded fiber LDV (rod LDV) can be inserted in an arbitrary grid cell instead of a fuel rod, and has the advantage of not disturbing the flow field since it is the same shape as a fuel rod. The probe volume of the rod LDV is small enough to measure spatial velocity profile in a rod gap and inside a spacer grid. According to benchmark experiments such as flow velocity

Targeting TGF-β Signaling by Antisense Oligonucleotide-mediated Knockdown of TGF-β Type I Receptor

Directory of Open Access Journals (Sweden)

Dwi U Kemaladewi

2014-01-01

Full Text Available Duchenne muscular dystrophy (DMD is caused by lack of functional dystrophin and results in progressive myofiber damage and degeneration. In addition, impaired muscle regeneration and fibrosis contribute to the progressive pathology of DMD. Importantly, transforming growth factor-β (TGF-β is implicated in DMD pathology and is known to stimulate fibrosis and inhibit muscle regeneration. In this study, we present a new strategy to target TGF-β signaling cascades by specifically inhibiting the expression of TGF-β type I receptor TGFBR1 (ALK5. Antisense oligonucleotides (AONs were designed to specifically induce exon skipping of mouse ALK5 transcripts. AON-induced exon skipping of ALK5 resulted in specific downregulation of full-length receptor transcripts in vitro in different cell types, repression of TGF-β activity, and enhanced C2C12 myoblast differentiation. To determine the effect of these AONs in dystrophic muscles, we performed intramuscular injections of ALK5 AONs in mdx mice, which resulted in a decrease in expression of fibrosis-related genes and upregulation of Myog expression compared to control AON-injected muscles. In summary, our study presents a novel method to target TGF-β signaling cascades with potential beneficial effects for DMD.

CFD analysis on mixing effects of spacer grids with different dimples and sizes for advanced fuel assemblies

Energy Technology Data Exchange (ETDEWEB)

Yang, B.W.; Zhang, H.; Han, B.; Zha, Y.D.; Shan, J.Q. [Xi' an Jiaotong Univ. (China). School of Nuclear Science and Technology

2016-07-15

The thermal hydraulic characteristics of a mixing vane grid are largely dependent on the structure of key components, such as strip, spring, dimple, weld nugget, as well as the mixing vane configuration. In this paper, several types of spacer grids with different dimple shapes are modeled under subcooled boiling conditions. Prior to the application of CFD on the dimple shape analysis, the mixing effects of spacer grids were studied. After the dimple shape analysis, the side channel effect is discussed by comparing the simulation results of a 3 x 3 and a 5 x 5 spacer grid. The two phase flow CFD models in this study are validated through simple geometry showing that the calculated void fraction is in good agreement with the experimental data. The dimple comparison result shows that varying dimple structures can result in different temperatures, lateral velocities and void fraction distributions downstream of the spacer grids. Comparison of two sizes of spacer grids demonstrate that the side channel generates different flow distribution pattern in the center channel.

Fuel assembly spacer

International Nuclear Information System (INIS)

Shirakawa, Ken-etsu.

1988-01-01

Purpose: To reduce the pressure loss of coolants by fuel assembly spacers. Constitution: Spacers for supporting a fuel assembly are attached by means of a plurality of wires to an outer frame. The outer frame is made of shape memory alloy such that the wires are caused to slacken at normal temperature and the slacking of the wires is eliminated in excess of the transition temperature. Since the wires slacken at the normal temperature, fuel rods can be inserted easily. After the insertion of the fuel rods, when the entire portion or the outer frame is heated by water or gas at a predetermined temperature, the outer frame resumes its previously memorized shape to tighten the wires and, accordingly, the fuel rods can be supported firmly. In this way, since the fuel rods are inserted in the slacken state of the wires and, after the assembling, the outer frame resumes its memorized shape, the assembling work can be conducted efficiently. (Kamimura, M.)

Oligonucleotide Therapy for Obstructive and Restrictive Respiratory Diseases

Directory of Open Access Journals (Sweden)

Wupeng Liao

2017-01-01

Full Text Available Inhaled oligonucleotide is an emerging therapeutic modality for various common respiratory diseases, including obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD and restrictive airway diseases like idiopathic pulmonary fibrosis (IPF. The advantage of direct accessibility for oligonucleotide molecules to the lung target sites, bypassing systemic administration, makes this therapeutic approach promising with minimized potential systemic side effects. Asthma, COPD, and IPF are common chronic respiratory diseases, characterized by persistent airway inflammation and dysregulated tissue repair and remodeling, although each individual disease has its unique etiology. Corticosteroids have been widely prescribed for the treatment of asthma, COPD, and IPF. However, the effectiveness of corticosteroids as an anti-inflammatory drug is limited by steroid resistance in severe asthma, the majority of COPD cases, and pulmonary fibrosis. There is an urgent medical need to develop target-specific drugs for the treatment of these respiratory conditions. Oligonucleotide therapies, including antisense oligonucleotide (ASO, small interfering RNA (siRNA, and microRNA (miRNA are now being evaluated both pre-clinically and clinically as potential therapeutics. The mechanisms of action of ASO and siRNA are highly target mRNA specific, ultimately leading to target protein knockdown. miRNA has both biomarker and therapeutic values, and its knockdown by a miRNA antagonist (antagomir has a broader but potentially more non-specific biological outcome. This review will compile the current findings of oligonucleotide therapeutic targets, verified in various respiratory disease models and in clinical trials, and evaluate different chemical modification approaches to improve the stability and potency of oligonucleotides for the treatment of respiratory diseases.

Spacer grid for fuel elements

International Nuclear Information System (INIS)

Hensolt, T.; Huenner, M.; Rau, P.; Veca, A.

1978-01-01

The spacer grid for fuel elements of a gas-cooled fast breeder reactor (but also for PWRs and BWRs) consists of a lattice field with dodecagonal meshes. These meshes are formed by three each adjacent hexagons grouped arround a central axis. The pairs of legs extending into the dodecagon and being staggered by 120 0 are designed as knubs with inclined abutting surfaces for the fuel rods. By this means there is formed a three-point bearing for centering the fuel rods. The spacer grid mentioned above is rough-worked from a single disc- resp. plate-shaped body (unfinished piece). (DG) [de

Spacer grid for fuel elements

International Nuclear Information System (INIS)

Hensolt, T.; Huenner, M.; Rau, P.; Veca, A.

1980-01-01

The spacer grid for fuel elements of a gas-cooled fast breeder reactor (but also for PWRs and BWRs) consists of a lattice field with dodecagonal meshes. These meshes are formed by three each adjacent hexagons grouped arround a central axis. The pairs of legs extending into the dodecagon and being staggered by 120 are designed as knubs with inclined abutting surfaces for the fuel rods. By this means there is formed a three-point bearing for centering the fuel rods. The spacer grid mentioned above is rough-worked from a single disc- resp. plate-shaped body (unfinished piece). (orig.)

Differential detection of type II methanotrophic bacteria in acidic peatlands using newly developed 16S rRNA-targeted fluorescent oligonucleotide probes.

Science.gov (United States)

Dedysh, Svetlana N; Dunfield, Peter F; Derakshani, Manigee; Stubner, Stephan; Heyer, Jürgen; Liesack, Werner

2003-04-01

Abstract Based on an extensive 16S rRNA sequence database for type II methanotrophic bacteria, a set of 16S rRNA-targeted oligonucleotide probes was developed for differential detection of specific phylogenetic groups of these bacteria by fluorescence in situ hybridisation (FISH). This set of oligonucleotides included a genus-specific probe for Methylocystis (Mcyst-1432) and three species-specific probes for Methylosinus sporium (Msins-647), Methylosinus trichosporium (Msint-1268) and the recently described acidophilic methanotroph Methylocapsa acidiphila (Mcaps-1032). These novel probes were applied to further characterise the type II methanotroph community that was detected in an acidic Sphagnum peat from West Siberia in a previous study (Dedysh et al. (2001) Appl. Environ. Microbiol. 67, 4850-4857). The largest detectable population of indigenous methanotrophs simultaneously hybridised with a group-specific probe targeting all currently known Methylosinus/Methylocystis spp. (M-450), with a genus-specific probe for Methylocystis spp. (Mcyst-1432), and with an additional probe (Mcyst-1261) that had been designed to target a defined phylogenetic subgroup of Methylocystis spp. The same subgroup of Methylocystis was also detected in acidic peat sampled from Sphagnum-dominated wetland in northern Germany. The population size of this peat-inhabiting Methylocystis subgroup was 2.0+/-0.1x10(6) cells g(-1) (wet weight) of peat from Siberia and 5.5+/-0.5x10(6) cells g(-1) of peat from northern Germany. This represented 60 and 95%, respectively, of the total number of methanotroph cells detected by FISH in these two wetland sites. Other major methanotroph populations were M. acidiphila and Methylocella palustris. Type I methanotrophs accounted for not more than 1% of total methanotroph cells. Neither M. trichosporium nor M. sporium were detected in acidic Sphagnum peat.

Differentiation of the seven major lyssavirus species by oligonucleotide microarray.

Science.gov (United States)

Xi, Jin; Guo, Huancheng; Feng, Ye; Xu, Yunbin; Shao, Mingfu; Su, Nan; Wan, Jiayu; Li, Jiping; Tu, Changchun

2012-03-01

An oligonucleotide microarray, LyssaChip, has been developed and verified as a highly specific diagnostic tool for differentiation of the 7 major lyssavirus species. As with conventional typing microarray methods, the LyssaChip relies on sequence differences in the 371-nucleotide region coding for the nucleoprotein. This region was amplified using nested reverse transcription-PCR primers that bind to the 7 major lyssaviruses. The LyssaChip includes 57 pairs of species typing and corresponding control oligonucleotide probes (oligoprobes) immobilized on glass slides, and it can analyze 12 samples on a single slide within 8 h. Analysis of 111 clinical brain specimens (65 from animals with suspected rabies submitted to the laboratory and 46 of butchered dog brain tissues collected from restaurants) showed that the chip method was 100% sensitive and highly consistent with the "gold standard," a fluorescent antibody test (FAT). The chip method could detect rabies virus in highly decayed brain tissues, whereas the FAT did not, and therefore the chip test may be more applicable to highly decayed brain tissues than the FAT. LyssaChip may provide a convenient and inexpensive alternative for diagnosis and differentiation of rabies and rabies-related diseases.

Procedure for vibration test of the fuel rod supported by spacer grids

International Nuclear Information System (INIS)

Choi, Myoung Hwan; Kang, Heung Seok; Yoon, Kyung Ho; Kim, Hyung Kyu; Song, Kee Nam

2002-07-01

One of the methods that are used to compare and verify the supporting performance of the spacer grids developed is the vibration characteristic test. In this report there are two aims. One is of the understand of the experimental method and procedure performing the modal testing using I-DEAS TDAS module. The other is the investigation of the vibration behaviors of a dummy fuel rod supported by 8 optimized H type spacer grids. This report describes the method and procedure of modal testing to obtain the vibration characteristics such as amplitudes, natural frequencies and mode shapes of the fuel rod using a shaker, a non-contact gap sensor and an accelerometer. This report provides a test procedure in detail so that anyone can be easily understood and use the I-DEAS TDAS program. The I-DEAS TDAS program related to the modal testing has several tasks including the Modal analysis, Signal Processing et al.. This report includes model preparation to prepare the geometrical model, Signal Processing (Sine/Standard measurement) to acquire the signal, Modal analysis to obtain the frequencies and mode shapes, Correlation to analyze the relation between the test and FE analysis and Post Processing tasks. In addition, this report contains the actual test and analysis data of a dummy fuel rod in length 3847mm supported by 8 optimized H type spacer grids

PCR-Internal Transcribed Spacer (ITS) genes sequencing and ...

African Journals Online (AJOL)

Methods: DNA extraction, purification, amplification and sequencing of Internal Transcribed Spacer (ITS) genes were per- formed using ... Keywords: Internal transcribed spacer genes, phylogenetic, genetic relationship, clinical and environmental fungi, HIV-TB. ... Nigeria. An Ethical clearance was obtained from the Eth-.

Surface-Tethered Iterative Carbohydrate Synthesis (STICS): A spacer study

Science.gov (United States)

Ganesh, N. Vijaya; Fujikawa, Kohki; Tan, Yih Horng; Nigudkar, Swati S.

2013-01-01

Comparative study of STICS using HPLC-assisted experimental set-up clearly demonstrated benefits of using longer spacer-anchoring systems. The use of mixed self-assembled monolayers helps to provide the required space for glycosylation reaction around the immobilized glycosyl acceptor. Both extension of the spacer length and using mixed self-assembled monolayers help to promote reaction and the beneficial effects may include moving the glycosyl acceptor further out into solution and providing additional conformational flexibility. It is possible that surface-immobilized glycosyl acceptors with a longer spacer (C8-O-C8)-lipoic acid have a higher tendency to mimic a solution-phase reaction environment than that of acceptors with shorter spacers. PMID:23822088

Therapeutic Oligonucleotides Targeting Liver Disease: TTR Amyloidosis

Directory of Open Access Journals (Sweden)

Christoph Niemietz

2015-09-01

Full Text Available The liver has become an increasingly interesting target for oligonucleotide therapy. Mutations of the gene encoding transthyretin (TTR, expressed in vast amounts by the liver, result in a complex degenerative disease, termed familial amyloid polyneuropathy (FAP. Misfolded variants of TTR are linked to the establishment of extracellular protein deposition in various tissues, including the heart and the peripheral nervous system. Recent progress in the chemistry and formulation of antisense (ASO and small interfering RNA (siRNA designed for a knockdown of TTR mRNA in the liver has allowed to address the issue of gene-specific molecular therapy in a clinical setting of FAP. The two therapeutic oligonucleotides bind to RNA in a sequence specific manner but exploit different mechanisms. Here we describe major developments that have led to the advent of therapeutic oligonucleotides for treatment of TTR-related disease.

Targeting DMPK with Antisense Oligonucleotide Improves Muscle Strength in Myotonic Dystrophy Type 1 Mice

Directory of Open Access Journals (Sweden)

Dominic Jauvin

2017-06-01

Full Text Available Myotonic dystrophy type 1 (DM1, a dominant hereditary muscular dystrophy, is caused by an abnormal expansion of a (CTGn trinucleotide repeat in the 3′ UTR of the human dystrophia myotonica protein kinase (DMPK gene. As a consequence, mutant transcripts containing expanded CUG repeats are retained in nuclear foci and alter the function of splicing regulatory factors members of the MBNL and CELF families, resulting in alternative splicing misregulation of specific transcripts in affected DM1 tissues. In the present study, we treated DMSXL mice systemically with a 2′-4′-constrained, ethyl-modified (ISIS 486178 antisense oligonucleotide (ASO targeted to the 3′ UTR of the DMPK gene, which led to a 70% reduction in CUGexp RNA abundance and foci in different skeletal muscles and a 30% reduction in the heart. Furthermore, treatment with ISIS 486178 ASO improved body weight, muscle strength, and muscle histology, whereas no overt toxicity was detected. This is evidence that the reduction of CUGexp RNA improves muscle strength in DM1, suggesting that muscle weakness in DM1 patients may be improved following elimination of toxic RNAs.

Targeting DMPK with Antisense Oligonucleotide Improves Muscle Strength in Myotonic Dystrophy Type 1 Mice.

Science.gov (United States)

Jauvin, Dominic; Chrétien, Jessina; Pandey, Sanjay K; Martineau, Laurie; Revillod, Lucille; Bassez, Guillaume; Lachon, Aline; MacLeod, A Robert; Gourdon, Geneviève; Wheeler, Thurman M; Thornton, Charles A; Bennett, C Frank; Puymirat, Jack

2017-06-16

Myotonic dystrophy type 1 (DM1), a dominant hereditary muscular dystrophy, is caused by an abnormal expansion of a (CTG) n trinucleotide repeat in the 3' UTR of the human dystrophia myotonica protein kinase (DMPK) gene. As a consequence, mutant transcripts containing expanded CUG repeats are retained in nuclear foci and alter the function of splicing regulatory factors members of the MBNL and CELF families, resulting in alternative splicing misregulation of specific transcripts in affected DM1 tissues. In the present study, we treated DMSXL mice systemically with a 2'-4'-constrained, ethyl-modified (ISIS 486178) antisense oligonucleotide (ASO) targeted to the 3' UTR of the DMPK gene, which led to a 70% reduction in CUG exp RNA abundance and foci in different skeletal muscles and a 30% reduction in the heart. Furthermore, treatment with ISIS 486178 ASO improved body weight, muscle strength, and muscle histology, whereas no overt toxicity was detected. This is evidence that the reduction of CUG exp RNA improves muscle strength in DM1, suggesting that muscle weakness in DM1 patients may be improved following elimination of toxic RNAs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Membrane with integrated spacer

NARCIS (Netherlands)

Balster, J.H.; Stamatialis, Dimitrios; Wessling, Matthias

2010-01-01

Many membrane processes are severely influenced by concentration polarisation. Turbulence promoting spacers placed in between the membranes can reduce the diffusional resistance of concentration polarisation by inducing additional mixing. Electrodialysis (ED) used for desalination suffers from

A Study on Structural Strength of Irradiated Spacer Grid for PWR Fuel

Energy Technology Data Exchange (ETDEWEB)

Jin, Y. G.; Baek, S. J.; Kim, D. S.; Yoo, B. O.; Ahn, S. B.; Chun, Y. B. [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, J. I.; Kim, Y. H.; Lee, J. J. [KEPCO NF, Daejeon (Korea, Republic of)

2014-10-15

A fuel assembly consists of an array of fuel rods, spacer grids, guide thimbles, instrumentation tubes, and top and bottom nozzles. In PWR (Pressurized light Water Reactor) fuel assemblies, the spacer grids support the fuel rods by the friction forces between the fuel rods and springs/dimples. Under irradiation, the spacer grids supporting the fuel rods absorb vibration impacts due to the reactor coolant flow, and also bear static and dynamic loads during operation inside the nuclear reactor and transportation for spent fuel storage. Thus, it is important to understand the characteristics of deformation behavior and the change in structural strength of an irradiated spacer grid.. In the present study, the static compression test of a spacer grid was conducted to investigate the structural strength of the irradiated spacer grid in a hot cell at IMEF (Irradiated Materials Examination Facility) of KAERI. To evaluate the structural strength of an irradiated spacer grid, hot cell tests were carried out at IMEF of KAERI. The fuel assembly was dismantled and the irradiated spacer grid was obtained for the compression test. The apparatus for measuring the compression strength of the irradiated spacer grid was developed and installed successfully in the hot cell.

Effect of spacer grid mixing vanes on coolant outlet temperature distribution

Energy Technology Data Exchange (ETDEWEB)

Raemae, Tommi; Lahtinen, Tuukka; Brandt, Tellervo; Toppila, Timo [Fortum Power and Heat, Fortum (Finland). Nuclear Competence Center

2012-08-15

In Loviisa VVER-440-type NPP the coolant outlet temperature of the hot subchannel is constantly monitored during the operation. According to the authority requirement the maximum subchannel outlet temperature must not exceed the saturation temperature. Coolant temperature distribution inside the fuel assembly is affected by the efficiency of the coolant mixing. In order to enhance the coolant mixing the fuel manufacturer is introducing the additional mixing vanes on the fuel bundle spacer grids. In the paper the effect of the different mixing vane modifications is studied with computational fluid dynamics (CFD) simulation. Goal of the modelling is to find vane modifications with which sufficient mixing is reached with acceptable increase in the spacer grid pressure loss. The results of the studies are discussed in the paper. (orig.)

Ribosomal DNA intergenic spacer sequence in foxtail millet, Setaria italica (L.) P. Beauv. and its characterization and application to typing of foxtail millet landraces.

Science.gov (United States)

Fukunaga, Kenji; Ichitani, Katsuyuki; Taura, Satoru; Sato, Muneharu; Kawase, Makoto

2005-02-01

We determined the sequence of ribosomal DNA (rDNA) intergenic spacer (IGS) of foxtail millet isolated in our previous study, and identified subrepeats in the polymorphic region. We also developed a PCR-based method for identifying rDNA types based on sequence information and assessed 153 accessions of foxtail millet. Results were congruent with our previous works. This study provides new findings regarding the geographical distribution of rDNA variants. This new method facilitates analyses of numerous foxtail millet accessions. It is helpful for typing of foxtail millet germplasms and elucidating the evolution of this millet.

Diagnosis Of Persistent Infection In Prosthetic Two-Stage Exchange: PCR analysis of Sonication fluid From Bone Cement Spacers.

Science.gov (United States)

Mariaux, Sandrine; Tafin, Ulrika Furustrand; Borens, Olivier

2017-01-01

Introduction: When treating periprosthetic joint infections with a two-stage procedure, antibiotic-impregnated spacers are used in the interval between removal of prosthesis and reimplantation. According to our experience, cultures of sonicated spacers are most often negative. The objective of our study was to investigate whether PCR analysis would improve the detection of bacteria in the spacer sonication fluid. Methods: A prospective monocentric study was performed from September 2014 to January 2016. Inclusion criteria were two-stage procedure for prosthetic infection and agreement of the patient to participate in the study. Beside tissues samples and sonication, broad range bacterial PCRs, specific S. aureus PCRs and Unyvero-multiplex PCRs were performed on the sonicated spacer fluid. Results: 30 patients were identified (15 hip, 14 knee and 1 ankle replacements). At reimplantation, cultures of tissue samples and spacer sonication fluid were all negative. Broad range PCRs were all negative. Specific S. aureus PCRs were positive in 5 cases. We had two persistent infections and four cases of infection recurrence were observed, with bacteria different than for the initial infection in three cases. Conclusion: The three different types of PCRs did not detect any bacteria in spacer sonication fluid that was culture-negative. In our study, PCR did not improve the bacterial detection and did not help to predict whether the patient will present a persistent or recurrent infection. Prosthetic 2-stage exchange with short interval and antibiotic-impregnated spacer is an efficient treatment to eradicate infection as both culture- and molecular-based methods were unable to detect bacteria in spacer sonication fluid after reimplantation.

Identification and distribution of three serologically undetected alleles of HLA-DR by oligonucleotide x DNA typing analysis

International Nuclear Information System (INIS)

Tiercy, J.M.; Gorski, J.; Jeannet, M.; Mach, B.

1988-01-01

Recent progress in the molecular biology of human major histocompatibility complex class II genes (HLA-DP, -DQ, -DR) have shown that the genetic complexity and allelic polymorphism are greater than expected. In the case of HLA-DR, three DR β-chain loci have been identified and linked, two of which (DR βI and DR βIII, now assigned names HLA-DR1B and HLA-DR3B) are functional. The authors have shown that the HLA micropolymorphism detected at the DNA sequence level can easily be analyzed by hybridization with allele-specific oligonucleotides (HLA oligotyping). In the case of the HLA DRw52 supertypic specificity, which includes the DR3, DR5, DRw6, and DRw8 haplotypes, three alleles, referred to as DRw52a, DRw52b, and DRw52c, have recently been identified at the HLA-DR3B locus by DNA sequencing. Hybridization with locus- and allele-specific oligonucleotide probes (designated 52a, 52b, and 52c) has been performed on DNA from normal individuals forming a panel of 82 haplotypes to establish the distribution of these three alleles. Individuals of the DR3 haplotype had either the DRw52a or DRw52b allele, and individuals of extended haplotype HLA-A1,B8,DR3 had only the DRw52a allele. DR5 individuals all had the DRw52b allele, while individuals of DRw6 haplotype had the DRw52a, -52b, or -52c allele. None of these three alleles are found in DRw8 individuals. Analysis of this micropolymorphism, undetectable by common typing procedures, is therefore now operational for more accurate HLA matching for transplantation and for improving correlations between HLA and disease susceptibility

In vitro microbiologic evaluation of PTFE and cotton as spacer materials.

Science.gov (United States)

Paranjpe, Avina; Jain, Sumita; Alibhai, Karim J; Wadhwani, Chandur P; Darveau, Richard P; Johnson, James D

2012-09-01

To microbiologically evaluate the efficacy of cotton and polytetrafluoroethylene (PTFE) tape used as spacer materials. Twenty-six extracted human molars were restored using either cotton or PTFE tape as spacers under a standardized provisional restorative material (Cavit). The teeth were incubated for 7 days in a culture of Streptococcus gordonii or in liquid media alone. The spacers were removed and tested for bacterial contamination. The access cavities were also evaluated for bacterial contamination. Nine of 10 teeth with cotton spacers and one of 10 teeth with PTFE spacers were positive for S gordonii growth. The nine teeth in the cotton group also showed contamination of the access cavities. Even under optimal conditions, cotton spacers may cause leakage into the access cavities. Cotton fibers may serve as a route for bacterial contamination of the access cavities and root canal space. In contrast, PTFE tape did not provide an avenue for bacterial contamination.

Molecular profiling of microbial communities from contaminated sources: Use of subtractive cloning methods and rDNA spacer sequences. 1998 annual progress report

International Nuclear Information System (INIS)

Robb, F.T.

1998-01-01

'The major objective of the research is to provide appropriate sequences and to assemble a high-density DNA array of oligonucleotides that can be used for rapid profiling of microbial populations from polluted areas. The sequences to be assigned to the DNA array are chosen from from cloned genomic DNA sequences (the ribosomal operon, described below) from groundwater at DOE sites containing organic solvents. The sites, Hanford Nuclear Plant and Lawrence Livermore Site 300, have well characterized pollutant histories, which have been provided by the collaborators. At this mid-point of the project, over 60 unique sequence classes of intergenic spacer region have been identified from the first sample site. The use of these sequences as hybridization probes, and their frequency of occurrence, allow a clear distinction between bacterial communities before and after remediation by acetate/nitrate pumping. The authors have developed the hybridization conditions for identifying PCR products in a 96 well format, a versatile alignment and visualization program (acronym: MALIGN) developed by Dr. Dennis Maeder, has been used to align the ISRs, which are variable in length and sometimes in position of the tRNAs. Finally, in collaboration with Dr. W. Chen and Dr. J. Zhou at ORNL, they have significant evidence that mass spectrometer analysis can be used to determine the lengths of PCR amplified intergenic spacer DNA.'

The CRISPR Spacer Space Is Dominated by Sequences from Species-Specific Mobilomes.

Science.gov (United States)

Shmakov, Sergey A; Sitnik, Vassilii; Makarova, Kira S; Wolf, Yuri I; Severinov, Konstantin V; Koonin, Eugene V

2017-09-19

Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein (CRISPR-Cas) systems store the memory of past encounters with foreign DNA in unique spacers that are inserted between direct repeats in CRISPR arrays. For only a small fraction of the spacers, homologous sequences, called protospacers, are detectable in viral, plasmid, and microbial genomes. The rest of the spacers remain the CRISPR "dark matter." We performed a comprehensive analysis of the spacers from all CRISPR- cas loci identified in bacterial and archaeal genomes, and we found that, depending on the CRISPR-Cas subtype and the prokaryotic phylum, protospacers were detectable for 1% to about 19% of the spacers (~7% global average). Among the detected protospacers, the majority, typically 80 to 90%, originated from viral genomes, including proviruses, and among the rest, the most common source was genes that are integrated into microbial chromosomes but are involved in plasmid conjugation or replication. Thus, almost all spacers with identifiable protospacers target mobile genetic elements (MGE). The GC content, as well as dinucleotide and tetranucleotide compositions, of microbial genomes, their spacer complements, and the cognate viral genomes showed a nearly perfect correlation and were almost identical. Given the near absence of self-targeting spacers, these findings are most compatible with the possibility that the spacers, including the dark matter, are derived almost completely from the species-specific microbial mobilomes. IMPORTANCE The principal function of CRISPR-Cas systems is thought to be protection of bacteria and archaea against viruses and other parasitic genetic elements. The CRISPR defense function is mediated by sequences from parasitic elements, known as spacers, that are inserted into CRISPR arrays and then transcribed and employed as guides to identify and inactivate the cognate parasitic genomes. However, only a small fraction of the CRISPR spacers

Eddy current monitoring of spacers in coolant channel assemblies of nuclear reactor

International Nuclear Information System (INIS)

Bhole, V.M.; Rastogi, P.K.; Kulkarni, P.G.; Vijayaraghavan, R.

1993-01-01

An eddy current testing method has been standardised for monitoring spacer springs which are used in coolant channel assemblies of pressurised heavy water nuclear reactors (PHWRs). The standard bobbin coil probe used for monitoring the spacer spring detects only the location but does not monitor the tilt orientation and tilt angle of a tilted spacer spring. The knowledge of location along with the tilt orientation of the spacer spring greatly improves the performance of repositioning methods. A modified probe with angular windings has been developed in laboratory tests for monitoring the location as well as the tilt orientation of the spacer springs. Experimental results are presented showing excellent performance of the modified probe in monitoring the exact location as well as tilt orientation of a spacer spring. The modified probe has also been used successfully in the field during repositioning of spacer springs in PHWRs before commissioning. (Author)

Molecular Profiling of Microbial Communities from Contaminated Sources: Use of Subtractive Cloning Methods and rDNA Spacer Sequences; FINAL

International Nuclear Information System (INIS)

Robb, Frank T.

2001-01-01

The major objective of this research was to provide appropriate sequences and assemble a DNA array of oligonucleotides to be used for rapid profiling of microbial populations from polluted areas and other areas of interest. The sequences to be assigned to the DNA array were chosen from cloned genomic DNA taken from groundwater sites having well characterized pollutant histories at Hanford Nuclear Plant and Lawrence Livermore Site 300. Glass-slide arrays were made and tested; and a new multiplexed, bead-based method was developed that uses nucleic acid hybridization on the surface of microscopic polystyrene spheres to identify specific sequences in heterogeneous mixtures of DNA sequences. The test data revealed considerable strain variation between sample sites showing a striking distribution of sequences. It also suggests that diversity varies greatly with bioremediation, and that there are many bacterial intergenic spacer region sequences that can indicate its effects. The bead method exhibited superior sequence discrimination and has features for easier and more accurate measurement

Antibiotic-impregnated articulating cement spacer for infected total knee arthroplasty

Directory of Open Access Journals (Sweden)

Parag Garg

2011-01-01

Full Text Available Background : Standard treatment of chronic infected total knee arthroplasty (TKA is a two-stage revision, the first step being placement of an antibiotic-impregnated cement spacer. Here we describe the results of a new technique (modification of the Goldstien′s technique for intraoperative manufacture of a customized articulating spacer at minimal cost and with relatively good conformity and longevity. Materials and Methods : Thirty-six infected knees underwent this procedure from June 2002 to May 2007. The technique consists of using the freshened femur and tibia interface as molds wrapped in a tin foil for manufacturing the two components of the spacer with antibiotic-impregnated methyl methycrylate cement. We used the spacer and the femoral component of the trial set of a TKA system to mold them to perfect articulation. We also reinforced the spacer with a K-wire scaffold to prevent fracture of the cement mantle in the last 21 cases. Results : All 36 knees showed excellent results in terms of infection control, mobility, and stability. There was significant improvement in the WOMAC and Knee Society Scores (20 and 39 points respectively. There were two fractures of the spacers in the initial 15 cases that did not have K-wire scaffolding but none in the last 21 that had reinforcement. Conclusion : This technique provides a more conforming spacer, with good range of motion and stability. The reinforcement helps in preventing the fracture of the cement mantle and is cost effective.

Development of oligonucleotide microarrays for simultaneous multi-species identification of Phellinus tree-pathogenic fungi.

Science.gov (United States)

Tzean, Yuh; Shu, Po-Yao; Liou, Ruey-Fen; Tzean, Shean-Shong

2016-03-01

Polyporoid Phellinus fungi are ubiquitously present in the environment and play an important role in shaping forest ecology. Several species of Phellinus are notorious pathogens that can affect a broad variety of tree species in forest, plantation, orchard and urban habitats; however, current detection methods are overly complex and lack the sensitivity required to identify these pathogens at the species level in a timely fashion for effective infestation control. Here, we describe eight oligonucleotide microarray platforms for the simultaneous and specific detection of 17 important Phellinus species, using probes generated from the internal transcribed spacer regions unique to each species. The sensitivity, robustness and efficiency of this Phellinus microarray system was subsequently confirmed against template DNA from two key Phellinus species, as well as field samples collected from tree roots, trunks and surrounding soil. This system can provide early, specific and convenient detection of Phellinus species for forestry, arboriculture and quarantine inspection, and could potentially help to mitigate the environmental and economic impact of Phellinus-related diseases. © 2015 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Development and characterization of 3D-printed feed spacers for spiral wound membrane systems

KAUST Repository

Siddiqui, Amber

2016-01-02

Feed spacers are important for the impact of biofouling on the performance of spiral-wound reverse osmosis (RO) and nanofiltration (NF) membrane systems. The objective of this study was to propose a strategy for developing, characterizing, and testing of feed spacers by numerical modeling, three-dimensional (3D) printing of feed spacers and experimental membrane fouling simulator (MFS) studies. The results of numerical modeling on the hydraulic behavior of various feed spacer geometries suggested that the impact of spacers on hydraulics and biofouling can be improved. A good agreement was found for the modeled and measured relationship between linear flow velocity and pressure drop for feed spacers with the same geometry, indicating that modeling can serve as first step in spacer characterization. An experimental comparison study of a feed spacer currently applied in practice and a 3D printed feed spacer with the same geometry showed (i) similar hydraulic behavior, (ii) similar pressure drop development with time and (iii) similar biomass accumulation during MFS biofouling studies, indicating that 3D printing technology is an alternative strategy for development of thin feed spacers with a complex geometry. Based on the numerical modeling results, a modified feed spacer with low pressure drop was selected for 3D printing. The comparison study of the feed spacer from practice and the modified geometry 3D printed feed spacer established that the 3D printed spacer had (i) a lower pressure drop during hydraulic testing, (ii) a lower pressure drop increase in time with the same accumulated biomass amount, indicating that modifying feed spacer geometries can reduce the impact of accumulated biomass on membrane performance. The combination of numerical modeling of feed spacers and experimental testing of 3D printed feed spacers is a promising strategy (rapid, low cost and representative) to develop advanced feed spacers aiming to reduce the impact of biofilm formation on

(ISSR) and internal transcribed spacer

African Journals Online (AJOL)

Cladistic relationships within the genus Cinnamomum (Lauraceae) in Taiwan based on analysis of leaf morphology and inter-simple sequence repeat (ISSR) and internal transcribed spacer (ITS) molecular markers.

Optical Characterization of Oligonucleotide DNA Influenced by Magnetic Fields

Directory of Open Access Journals (Sweden)

Seyedeh Maryam Banihashemian

2013-09-01

Full Text Available UV-VIS spectroscopic analysis of oligonucleotide DNA exposed to different magnetic fields was performed in order to investigate the relationship between DNA extinction coefficients and optical parameters according to magnetic-field strength. The results with the oligonucleotides adenine-thymine 100 mer (AT-100 DNA and cytosine-guanine 100 mer (CG-100 DNA indicate that the magnetic field influences DNA molar extinction coefficients and refractive indexes. The imaginary parts of the refractive index and molar extinction coefficients of the AT-100 and CG-100 DNA decreased after exposure to a magnetic field of 750 mT due to cleavage of the DNA oligonucleotides into smaller segments.

Orthognathic model surgery with LEGO key-spacer.

Science.gov (United States)

Tsang, Alfred Chee-Ching; Lee, Alfred Siu Hong; Li, Wai Keung

2013-12-01

A new technique of model surgery using LEGO plates as key-spacers is described. This technique requires less time to set up compared with the conventional plaster model method. It also retains the preoperative setup with the same set of models. Movement of the segments can be measured and examined in detail with LEGO key-spacers. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Staged Custom, Intramedullary Antibiotic Spacers for Severe Segmental Bone Loss in Infected Total Hip Arthroplasty

Directory of Open Access Journals (Sweden)

Atul F. Kamath

2011-01-01

Full Text Available Introduction. Total hip arthroplasty (THA infections with severe bone loss pose significant reconstructive challenges. We present our experience with two-stage hip reimplantation using an intramedullary, antibiotic-impregnated nail. Methods. Three patients with infected THA with severe proximal femoral bone loss (Mallory type IIIB or greater were treated using a custom antibiotic spacer. Clinical outcomes and any complications were recorded. Average followup was 49 months from final reimplantation. Results. Mean age at spacer placement (stage 1 was 53 years. The mean Harris Hip Score at final followup was 80. Two patients had asymptomatic heterotopic ossification, and one patient had a 2 cm leg-length discrepancy. Conclusions. A custom intramedullary nail antibiotic spacer is a reliable option in the staged management of the infected THA with severe proximal femoral bone loss. Benefits of this technique include limb salvage with maintenance of leg length, soft tissue tension, and functional status.

Anti-vibration method for wind-induced vibration in cable arrays of cable-stayed bridges. Part 2. Experimental study on the efficiency of spacers as vibration dampers; Shachokyo heiretsu cable no taifu seishin taisaku. 2. Shushu no jokenka ni okeru masatsugata gensui kinotsuki spacer no yukosei

Energy Technology Data Exchange (ETDEWEB)

Nomura, T.; Fujiwara, A.; Ito, M. [Obayashi Corp., Tokyo (Japan)

1997-07-10

The present study has performed a two-dimensional sprint supporting experiment on effects imposed on vibration damping efficiency of spacers by variation in cable interval, vibration frequency, weight and diameter of parallel cables used in cable-stayed bridges. The experiment indicated phenomena varying in such a way that a characteristic having an unstable limit cycle is shown at cable intervals smaller than SH = 3.05 D, while a soft type characteristic is shown at cable intervals greater than 4.0 D. The onset velocity for wake galloping (WG) to appear increases in proportion to mass and attenuation parameters. Its increasing rate agrees nearly well with the manual type gradient. The appearance of WG can be suppressed easily when the cable intervals are greater than 4 D. The lower the cable vibration frequency, the higher the damping capability can be raised by using friction force. Because the damping performance of spacers decreases relatively when cable weight increases, the suppression effect decreases contrarily to a case of using no spacers. The wind velocity for the WG to appear when spacers are used can be evaluated by using the damping gradient. 5 refs., 20 figs., 1 tab.

Fully automated parallel oligonucleotide synthesizer

Czech Academy of Sciences Publication Activity Database

Lebl, M.; Burger, Ch.; Ellman, B.; Heiner, D.; Ibrahim, G.; Jones, A.; Nibbe, M.; Thompson, J.; Mudra, Petr; Pokorný, Vít; Poncar, Pavel; Ženíšek, Karel

2001-01-01

Roč. 66, č. 8 (2001), s. 1299-1314 ISSN 0010-0765 Institutional research plan: CEZ:AV0Z4055905 Keywords : automated oligonucleotide synthesizer Subject RIV: CC - Organic Chemistry Impact factor: 0.778, year: 2001

System for measuring spacer pin pitch in a nuclear fuel assembly

International Nuclear Information System (INIS)

Isono, Kenji; Tateishi, Yoshinori; Mano, Tadashi.

1975-01-01

Object: To reduce the period for discriminating whether or not spacer pin pitch is satisfactory by simultaneously inserting a number of reference rods into a nuclear fuel assembly spacer ring element of a reactor and arranging them such that they can be simultaneously withdrawn to simplify the withdrawing operation. Structure: A spacer provided with a ring element which clamps a nuclear fuel element is supported on a spacer support with a rod secured to the support as a guide and is secured to the support by securing means. A vertically movable structure with a reference rod provided upright and thru-holes formed in two support plates provided in the same row as the spacer ring element is operated by a fluid pressure mechanism to simultaneously insert the reference rod into the spacer ring element. The reference rod is mounted in support plates via ball bearings such that it is slightly movable in the horizontal direction, and it is aligned with respect to the core of the ring element. The intercore distance of the reference rod is measured with the reference rod inserted in the ring element, thereby measuring the space pin pitch. From the results of measurement, discrimination as to whether the spacer is satisfactory or not is made. (Kamimura, M.)

Hydrogel Spacer Prospective Multicenter Randomized Controlled Pivotal Trial: Dosimetric and Clinical Effects of Perirectal Spacer Application in Men Undergoing Prostate Image Guided Intensity Modulated Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Mariados, Neil, E-mail: nmariados@ampofny.com [Associated Medical Professionals of New York, Syracuse, New York (United States); Sylvester, John [21st Century Oncology, East Bradenton, Florida (United States); Shah, Dhiren [Western New York Urology Associates, Cancer Care of WNY, Cheektowaga, New York (United States); Karsh, Lawrence [The Urology Center of Colorado, Denver, Colorado (United States); Hudes, Richard [Chesapeake Urology Research Associates, The Prostate Center, Owings Mills, Maryland (United States); Beyer, David [Arizona Oncology Services Foundation, Phoenix, Arizona (United States); Kurtzman, Steven [Urological Surgeons of Northern California, Campbell, California (United States); Bogart, Jeffrey [The Research Foundation of State University of New York, SUNY Upstate Medical University, Syracuse, New York (United States); Hsi, R. Alex [Peninsula Cancer Center, Poulsbo, Washington (United States); Kos, Michael [Urology Nevada, Reno, Nevada (United States); Ellis, Rodney [University Hospitals Case Medical Center, Cleveland, Ohio (United States); Logsdon, Mark [Sutter Health Sacramento Sierra Region, Sutter Institute for Medical Research, Sacramento, California (United States); Zimberg, Shawn [Advanced Radiation Centers of New York, Lake Success, New York (United States); Forsythe, Kevin [Oregon Urology Institute, Springfield, Oregon (United States); Zhang, Hong [University of Rochester, Rochester, New York (United States); Soffen, Edward [CentraState Medical Center, Freehold, New Jersey (United States); Francke, Patrick [Carolina Regional Cancer Center, 21st Century Oncology, Myrtle Beach, South Carolina (United States); Mantz, Constantine [21st Century Oncology, Fort Meyers, Florida (United States); Rossi, Peter [Emory University, Atlanta, Georgia (United States); DeWeese, Theodore [The Johns Hopkins University, Baltimore, Maryland (United States); and others

2015-08-01

Purpose: Perirectal spacing, whereby biomaterials are placed between the prostate and rectum, shows promise in reducing rectal dose during prostate cancer radiation therapy. A prospective multicenter randomized controlled pivotal trial was performed to assess outcomes following absorbable spacer (SpaceOAR system) implantation. Methods and Materials: Overall, 222 patients with clinical stage T1 or T2 prostate cancer underwent computed tomography (CT) and magnetic resonance imaging (MRI) scans for treatment planning, followed with fiducial marker placement, and were randomized to receive spacer injection or no injection (control). Patients received postprocedure CT and MRI planning scans and underwent image guided intensity modulated radiation therapy (79.2 Gy in 1.8-Gy fractions). Spacer safety and impact on rectal irradiation, toxicity, and quality of life were assessed throughout 15 months. Results: Spacer application was rated as “easy” or “very easy” 98.7% of the time, with a 99% hydrogel placement success rate. Perirectal spaces were 12.6 ± 3.9 mm and 1.6 ± 2.0 mm in the spacer and control groups, respectively. There were no device-related adverse events, rectal perforations, serious bleeding, or infections within either group. Pre-to postspacer plans had a significant reduction in mean rectal V70 (12.4% to 3.3%, P<.0001). Overall acute rectal adverse event rates were similar between groups, with fewer spacer patients experiencing rectal pain (P=.02). A significant reduction in late (3-15 months) rectal toxicity severity in the spacer group was observed (P=.04), with a 2.0% and 7.0% late rectal toxicity incidence in the spacer and control groups, respectively. There was no late rectal toxicity greater than grade 1 in the spacer group. At 15 months 11.6% and 21.4% of spacer and control patients, respectively, experienced 10-point declines in bowel quality of life. MRI scans at 12 months verified spacer absorption. Conclusions: Spacer

Multispacer sequence typing relapsing fever Borreliae in Africa.

Directory of Open Access Journals (Sweden)

Haitham Elbir

Full Text Available BACKGROUND: In Africa, relapsing fevers are neglected arthropod-borne infections caused by closely related Borrelia species. They cause mild to deadly undifferentiated fever particularly severe in pregnant women. Lack of a tool to genotype these Borrelia organisms limits knowledge regarding their reservoirs and their epidemiology. METHODOLOGY/PRINCIPAL FINDINGS: Genome sequence analysis of Borrelia crocidurae, Borrelia duttonii and Borrelia recurrentis yielded 5 intergenic spacers scattered between 10 chromosomal genes that were incorporated into a multispacer sequence typing (MST approach. Sequencing these spacers directly from human blood specimens previously found to be infected by B. recurrentis (30 specimens, B. duttonii (17 specimens and B. crocidurae (13 specimens resolved these 60 strains and the 3 type strains into 13 species-specific spacer types in the presence of negative controls. B. crocidurae comprised of 8 spacer types, B. duttonii of 3 spacer types and B. recurrentis of 2 spacer types. CONCLUSIONS/SIGNIFICANCE: Phylogenetic analyses of MST data suggested that B. duttonii, B. crocidurae and B. recurrentis are variants of a unique ancestral Borrelia species. MST proved to be a suitable approach for identifying and genotyping relapsing fever borreliae in Africa. It could be applied to both vectors and clinical specimens.

Biofouling Control in Spiral-Wound Membrane Systems: Impact of Feed Spacer Modification and Biocides

KAUST Repository

Siddiqui, Amber

2016-12-01

High-quality drinking water can be produced with membrane-based filtration processes like reverse osmosis and nanofiltration. One of the major problems in these membrane systems is biofouling that reduces the membrane performance, increasing operational costs. Current biofouling control strategies such as pre-treatment, membrane modification, and chemical cleaning are not sufficient in all cases. Feed spacers are thin (0.8 mm), complex geometry meshes that separate membranes in a module. The main objective of this research was to evaluate whether feed spacer modification is a suitable strategy to control biofouling. Membrane fouling simulator studies with six feed spacers showed differences in biofouled spacer performance, concluding that (i) spacer geometry influences biofouling impact and (ii) biofouling studies are essential for evaluation of spacer biofouling impact. Computed tomography (CT) was found as a suitable technique to obtain three-dimensional (3D) measurements of spacers, enabling more representative mathematical modeling of hydraulic behavior of spacers in membrane systems. A strategy for developing, characterizing, and testing of spacers by numerical modeling, 3D printing of spacers and experimental membrane fouling simulator studies was developed. The combination of modeling and experimental testing of 3D printed spacers is a promising strategy to develop advanced spacers aiming to reduce the impact of biofilm formation on membrane performance and to improve the cleanability of spiral-wound membrane systems.

Synthesis of 3'-, or 5'-, or internal methacrylamido-modified oligonucleotides

Science.gov (United States)

Golova, Julia B.; Chernov, Boris K.

2010-04-27

New modifiers were synthesized for incorporation of a methacrylic function in 3'-, 5'- and internal positions of oligonucleotides during solid phase synthesis. A modifier was used for synthesis of 5'-methacrylated oligonucleotides for preparation of microarrays by a co-polymerization method.

Experimental investigation of turbulent flow through spacer grids in fuel rod bundles

International Nuclear Information System (INIS)

Caraghiaur, Diana; Anglart, Henryk; Frid, Wiktor

2009-01-01

This paper contains experimental data of pressure, velocity and turbulence intensity in a 24-rod fuel bundle with spacer grids. Detailed pressure measurements inside the spacer grid have been obtained by use of a sliding pressure-sensing rod. Laser Doppler Velocimetry technique was used to measure the local axial velocity and its fluctuating component upstream and downstream of the spacer grid in sub-channels with different blockage ratios. The measurements show a changing pattern in function of radial position in the cross-section of the fuel bundle. For sub-channels close to the box wall, the turbulence intensity suddenly increases just downstream of the spacer and then gradually decays. In inner sub-channels, however, the turbulence intensity downstream of the spacer decreases below its upstream value and then gradually increases until it reaches the maximum value at approximately two spacer heights. The present study reveals that spacer effects, such as local pressure distribution and turbulence intensity enhancement, not only depend exclusively on the local geometry details, but also on the location in the cross-section of the rod bundle.

Experimental investigation of turbulent flow through spacer grids in fuel rod bundles

Energy Technology Data Exchange (ETDEWEB)

Caraghiaur, Diana [Royal Institute of Technology, Division of Nuclear Reactor Technology, Department of Physics, School of Engineering Sciences, AlbaNova University Center, SE-106 91 Stockholm (Sweden)], E-mail: dianac@kth.se; Anglart, Henryk [Royal Institute of Technology, Division of Nuclear Reactor Technology, Department of Physics, School of Engineering Sciences, AlbaNova University Center, SE-106 91 Stockholm (Sweden); Frid, Wiktor [Swedish Radiation Safety Authority, Reactor Technology and Structural Integrity, SE-171 16 Stockholm (Sweden)

2009-10-15

This paper contains experimental data of pressure, velocity and turbulence intensity in a 24-rod fuel bundle with spacer grids. Detailed pressure measurements inside the spacer grid have been obtained by use of a sliding pressure-sensing rod. Laser Doppler Velocimetry technique was used to measure the local axial velocity and its fluctuating component upstream and downstream of the spacer grid in sub-channels with different blockage ratios. The measurements show a changing pattern in function of radial position in the cross-section of the fuel bundle. For sub-channels close to the box wall, the turbulence intensity suddenly increases just downstream of the spacer and then gradually decays. In inner sub-channels, however, the turbulence intensity downstream of the spacer decreases below its upstream value and then gradually increases until it reaches the maximum value at approximately two spacer heights. The present study reveals that spacer effects, such as local pressure distribution and turbulence intensity enhancement, not only depend exclusively on the local geometry details, but also on the location in the cross-section of the rod bundle.

Degradation product characterization of therapeutic oligonucleotides using liquid chromatography mass spectrometry.

Science.gov (United States)

Elzahar, N M; Magdy, N; El-Kosasy, Amira M; Bartlett, Michael G

2018-05-01

Synthetic antisense phosphorothioate oligonucleotides (PS) have undergone rapid development as novel therapeutic agents. The increasing significance of this class of drugs requires significant investment in the development of quality control methods. The determination of the many degradation pathways of such complex molecules presents a significant challenge. However, an understanding of the potential impurities that may arise is necessary to continue to advance these powerful new therapeutics. In this study, four different antisense oligonucleotides representing several generations of oligonucleotide therapeutic agents were evaluated under various stress conditions (pH, thermal, and oxidative stress) using ion-pairing reversed-phase liquid chromatography tandem mass spectrometry (IP-RPLC-MS/MS) to provide in-depth characterization and identification of the degradation products. The oligonucleotide samples were stressed under different pH values at 45 and 90 °C. The main degradation products were observed to be losses of nucleotide moieties from the 3'- and 5'-terminus, depurination, formation of terminal phosphorothioates, and production of ribose, ribophosphorothioates (Rp), and phosphoribophosphorothioates (pRp). Moreover, the effects of different concentrations of hydrogen peroxide were studied resulting in primarily extensive desulfurization and subsequent oxidation of the phosphorothioate linkage to produce the corresponding phosphodiester. The reaction kinetics for the degradation of the oligonucleotides under the different stress conditions were studied and were found to follow pseudo-first-order kinetics. Differences in rates exist even for oligonucleotides of similar length but consisting of different sequences. Graphical abstract Identification of degradation products across several generations of oligonucleotide therapeutics using LC-MS.

Grid spacers for use in a nuclear fuel assembly

International Nuclear Information System (INIS)

Kuwako, Akira.

1987-01-01

Purpose: To obtain spacers capable of reducing the pressure loss by enlarging coolant flow channels when the fuel temperature is high, while capable of reliably maintaining the fuel pins with no vibrations when the fuel temperature is low. Constitution: This invention concerns grid spacers for constituting fuel assemblies for use in water cooled reactors. Memory shape alloys are disposed at least a portion of a spacer element that takes such a shape as urging the pin when the fuel temperature is low, while enlarging the coolant flow channel to reduce the pressure loss when the fuel temperature is high. (Ikeda, J.)

Computer-Aided Design Method of Warp-Knitted Jacquard Spacer Fabrics

Directory of Open Access Journals (Sweden)

Li Xinxin

2016-06-01

Full Text Available Based on a further study on knitting and jacquard principles, this paper presents a mathematical design model to make computer-aided design of warp-knitted jacquard spacer fabrics more efficient. The mathematical model with matrix method employs three essential elements of chain notation, threading and Jacquard designing. With this model, the processing to design warp-knitted jacquard spacer fabrics with CAD software is also introduced. In this study, the sports shoes which have separated functional areas according to the feet structure and characteristics of movement are analysed. The results show the different patterns on Jacquard spacer fabrics that are seamlessly stitched with jacquard technics. The computer-aided design method of warp-knitted jacquard spacer fabrics is efficient and simple.

The influence of the preliminary garter spring spacer simulator clamping force in the pressure tube spacer -calandria tube hook-up simulator aging behaviour

International Nuclear Information System (INIS)

Gyongyosi, T.; Deloreanu, G.; Puiu, D.; Corbescu, B.; Anghel, N.; Dinu, E.

2016-01-01

The garter spring spacer is a specially constructed torsion spring used to fit-out the CANDU 6 fuel channel. The pressure tube ageing decreases the gap to the calandria tube. Continuous gap decrease directly affects the garter spring spacers behavior during fuel channel assembly operation. The preliminary clamping force value of the garter spring spacer assembly is important for its ageing behavior. This paper briefly describes the experimental technological facilities used for conducted the experiments and highlights some of the important moments during an experiment carried out in laboratory conditions, without using pressurized boiled water and irradiation working conditions. The results analysis and some conclusions are outlined at the end, pointing out that a garter spring spacer preliminary clamping force increase reduces the vibration response signal amplitude, and does not lead to its relaxation. The paper is dedicated to specialists working in research and technological engineering. (authors)

Design and analysis of effects of triplet repeat oligonucleotides in cell models for myotonic dystrophy

NARCIS (Netherlands)

Gonzalez-Barriga, A.; Mulders, S.A.M.; Giessen, J. van der; Hooijer, J.D.; Bijl, S.; Kessel, I.D.G. van; Beers, J. van; Deutekom, J.C. van; Fransen, J.A.M.; Wieringa, B.; Wansink, D.G.

2013-01-01

Myotonic dystrophy type 1 (DM1) is caused by DM protein kinase (DMPK) transcripts containing an expanded (CUG)n repeat. Antisense oligonucleotide (AON)-mediated suppression of these mutant RNAs is considered a promising therapeutic strategy for this severe disorder. Earlier, we identified a

Preliminary analysis of the effect of the grid spacers on the reflood heat transfer

International Nuclear Information System (INIS)

Sugimoto, Jun; Murao, Yoshio

1982-02-01

The results are described about the preliminary analysis of the effect of the grid spacers on the heat transfer during reflood phase of a PWR LOCA. Experiments at JAERI and other facilities showed substantial heat transfer enhancement near the grid spacers. The heat transfer enhancement decreases with the distance from the grid spacers in the downstream region of the grid spacers. Several mechanisms are discussed about the heat transfer enhancement near the grid spacers. A model of a coalescence of the water droplets downstream the spacers is proposed based on the review of the experimental data. The heat transfer correlation for the saturated film boiling is utilized to quantify the heat transfer augmentation by the grid spacers. (author)

Polymerase-endonuclease amplification reaction (PEAR for large-scale enzymatic production of antisense oligonucleotides.

Directory of Open Access Journals (Sweden)

Xiaolong Wang

Full Text Available Antisense oligonucleotides targeting microRNAs or their mRNA targets prove to be powerful tools for molecular biology research and may eventually emerge as new therapeutic agents. Synthetic oligonucleotides are often contaminated with highly homologous failure sequences. Synthesis of a certain oligonucleotide is difficult to scale up because it requires expensive equipment, hazardous chemicals and a tedious purification process. Here we report a novel thermocyclic reaction, polymerase-endonuclease amplification reaction (PEAR, for the amplification of oligonucleotides. A target oligonucleotide and a tandem repeated antisense probe are subjected to repeated cycles of denaturing, annealing, elongation and cleaving, in which thermostable DNA polymerase elongation and strand slipping generate duplex tandem repeats, and thermostable endonuclease (PspGI cleavage releases monomeric duplex oligonucleotides. Each round of PEAR achieves over 100-fold amplification. The product can be used in one more round of PEAR directly, and the process can be further repeated. In addition to avoiding dangerous materials and improved product purity, this reaction is easy to scale up and amenable to full automation. PEAR has the potential to be a useful tool for large-scale production of antisense oligonucleotide drugs.

BWR fuel assembly having fuel rod spacers axially positioned by exterior springs

International Nuclear Information System (INIS)

Taleyarkhan, R.P.

1988-01-01

In a fuel assembly having spaced fuel rods, an outer hollow tubular flow channel surrounding the fuel rods so as to direct flow of coolant/moderator fluid there-along, and at least one spacer being disposed along the channel and about the fuel rods so as to maintain them in side-by-side spaced relationship, an arrangement for disposing the spacer in a desired axial position along the fuel rods is described comprising: yieldably resilient springs disposed between an interior side of the outer channel and an exterior side of the spacer. The springs have an inherent spring bias directed away from the exterior sides of the spacers and toward the interior side of the channel such that by contact with the channel and spacer the springs assume states in which they are deflected away from the channel interior side so as to exert sufficient compressive contacting force thereon to maintain the spacer substantially stationary in the desired axial position along the fuel rods

Biominetic High Density Lipoproteins for the Delivery of Therapeutic Oligonucleotides

Science.gov (United States)

Tripathy, Sushant

Advances in nanotechnology have brought about novel inorganic and hybrid nanoparticles with unique physico-chemical properties that make them suitable for a broad range of applications---from nano-circuitry to drug delivery. A significant part of those advancements have led to ground-breaking discoveries that have changed the approaches to formulation of therapeutics against diseases, such as cancer. Now-a-days the focus does not lie solely on finding a candidate small-molecule therapeutic with minimal adverse effects, but researchers are looking up to nanoparticles to improve biodistribution and biocompatibility profile of clinically proven therapeutics. The plethora of conjugation chemistries offered by currently extant inorganic nanoparticles have, in recent years, led to great leaps in the field of biomimicry---a modality that promises high biocompatibility. Further, in the pursuit of highly specific therapeutic molecules, researchers have turned to silencing oligonucleotides and some have already brought together the strengths of nanoparticles and silencing oligonucleotides in search of an efficacious therapy for cancer with minimal adverse effects. This dissertation work focuses on such a biomimetic platform---a gold nanoparticle based high density lipoprotein biomimetic (HDL NP), for the delivery of therapeutic oligonucleotides. The first chapter of this body of work introduces the molecular target of the silencing oligonucleotides---VEGFR2, and its role in the progression of solid tumor cancers. The background information also covers important aspects of natural high density lipoproteins (HDL), especially their innate capacity to bind and deliver exogenous and endogenous silencing oligonucleotides to tissues that express their high affinity receptor SRB1. We subsequently describe the synthesis of the biomimetic HDL NP and its oligonucleotide conjugates, and establish their biocompatibility. Further on, experimental data demonstrate the efficacy of silencing

Oligonucleotide-based biosensors for in vitro diagnostics and environmental hazard detection.

Science.gov (United States)

Jung, Il Young; Lee, Eun Hee; Suh, Ah Young; Lee, Seung Jin; Lee, Hyukjin

2016-04-01

Oligonucleotide-based biosensors have drawn much attention because of their broad applications in in vitro diagnostics and environmental hazard detection. They are particularly of interest to many researchers because of their high specificity as well as excellent sensitivity. Recently, oligonucleotide-based biosensors have been used to achieve not only genetic detection of targets but also the detection of small molecules, peptides, and proteins. This has further broadened the applications of these sensors in the medical and health care industry. In this review, we highlight various examples of oligonucleotide-based biosensors for the detection of diseases, drugs, and environmentally hazardous chemicals. Each example is provided with detailed schematics of the detection mechanism in addition to the supporting experimental results. Furthermore, future perspectives and new challenges in oligonucleotide-based biosensors are discussed.

Analyses of the Collapse Behavior of a Spacer Grid

International Nuclear Information System (INIS)

Jang, Myung-Geun; Na, Geum Ju; Jag, Yeon-Hui; Kim, Hee Cheol; Kim, Jong-Bong; Kim, Jaeyoug

2016-01-01

In order to investigate the protection capability of a spacer grid assembly for impact load, a hammer impact test has been carried out. The crush strength is measured in the hammer impact test. Song et al. carried out the experiment and finite element analysis for the hammer impact test for various weld line depth. Park et al. designed the spacer grid shape to get required crush strength via finite element analysis. Song et al. also optimized the spacer grid shape to maximize the crush strength, and carried out the finite element analysis for the hammer impact test considering the weld properties. Kim et al. carried out finite element analysis for various guide tube hole shape and compared the crush shape and crush strength. In this study, the effect of shape defect on the crush behavior in the hammer impact test is investigated. The spacer grid cannot be exactly the square. Therefore a lateral displacement (imperfection) is imposed to square spacer grid and then hammer impact is carried out. The effect of the lateral imperfection on the crush strength is investigated. The effect of the shape defect on the crushing behavior in the hammer impact test is investigated by finite element analysis. It is shown that the collapse become severe as the lateral imperfection displacement increases, especially when the imperfection is greater than or equal to 0.7 mm

Impact of spacer thickness on biofouling in forward osmosis

KAUST Repository

Valladares Linares, Rodrigo

2014-06-01

Forward osmosis (FO) indirect desalination systems integrate wastewater recovery with seawater desalination. Niche applications for FO systems have been reported recently, due to the demonstrated advantages compared to conventional high-pressure membrane processes such as nanofiltration (NF) and reverse osmosis (RO). Among them, wastewater recovery has been identified to be particularly suitable for practical applications. However, biofouling in FO membranes has rarely been studied in applications involving wastewater effluents. Feed spacers separating the membrane sheets in cross-flow systems play an important role in biofilm formation. The objective of this study was to determine the influence of feed spacer thickness (28, 31 and 46mil) on biofouling development and membrane performance in a FO system, using identical cross-flow cells in parallel studies. Flux development, biomass accumulation, fouling localization and composition were determined and analyzed. For all spacer thicknesses, operated at the same feed flow and the same run time, the same amount of biomass was found, while the flux reduction decreased with thicker spacers. These observations are in good agreement with biofouling studies for RO systems, considering the key differences between FO and RO. Our findings contradict previous cross-flow studies on particulate/colloidal fouling, where higher cross-flow velocities improved system performance. Thicker spacers reduced the impact of biofouling on FO membrane flux. © 2014 Elsevier Ltd.

Impact of spacer thickness on biofouling in forward osmosis.

Science.gov (United States)

Valladares Linares, R; Bucs, Sz S; Li, Z; AbuGhdeeb, M; Amy, G; Vrouwenvelder, J S

2014-06-15

Forward osmosis (FO) indirect desalination systems integrate wastewater recovery with seawater desalination. Niche applications for FO systems have been reported recently, due to the demonstrated advantages compared to conventional high-pressure membrane processes such as nanofiltration (NF) and reverse osmosis (RO). Among them, wastewater recovery has been identified to be particularly suitable for practical applications. However, biofouling in FO membranes has rarely been studied in applications involving wastewater effluents. Feed spacers separating the membrane sheets in cross-flow systems play an important role in biofilm formation. The objective of this study was to determine the influence of feed spacer thickness (28, 31 and 46 mil) on biofouling development and membrane performance in a FO system, using identical cross-flow cells in parallel studies. Flux development, biomass accumulation, fouling localization and composition were determined and analyzed. For all spacer thicknesses, operated at the same feed flow and the same run time, the same amount of biomass was found, while the flux reduction decreased with thicker spacers. These observations are in good agreement with biofouling studies for RO systems, considering the key differences between FO and RO. Our findings contradict previous cross-flow studies on particulate/colloidal fouling, where higher cross-flow velocities improved system performance. Thicker spacers reduced the impact of biofouling on FO membrane flux. Copyright © 2014 Elsevier Ltd. All rights reserved.

Impact of spacer thickness on biofouling in forward osmosis

KAUST Repository

Valladares Linares, Rodrigo; Bucs, Szilard; Li, Z.; AbuGhdeeb, M.; Amy, Gary L.; Vrouwenvelder, Johannes S.

2014-01-01

Forward osmosis (FO) indirect desalination systems integrate wastewater recovery with seawater desalination. Niche applications for FO systems have been reported recently, due to the demonstrated advantages compared to conventional high-pressure membrane processes such as nanofiltration (NF) and reverse osmosis (RO). Among them, wastewater recovery has been identified to be particularly suitable for practical applications. However, biofouling in FO membranes has rarely been studied in applications involving wastewater effluents. Feed spacers separating the membrane sheets in cross-flow systems play an important role in biofilm formation. The objective of this study was to determine the influence of feed spacer thickness (28, 31 and 46mil) on biofouling development and membrane performance in a FO system, using identical cross-flow cells in parallel studies. Flux development, biomass accumulation, fouling localization and composition were determined and analyzed. For all spacer thicknesses, operated at the same feed flow and the same run time, the same amount of biomass was found, while the flux reduction decreased with thicker spacers. These observations are in good agreement with biofouling studies for RO systems, considering the key differences between FO and RO. Our findings contradict previous cross-flow studies on particulate/colloidal fouling, where higher cross-flow velocities improved system performance. Thicker spacers reduced the impact of biofouling on FO membrane flux. © 2014 Elsevier Ltd.

Abundant and diverse clustered regularly interspaced short palindromic repeat spacers in Clostridium difficile strains and prophages target multiple phage types within this pathogen.

Science.gov (United States)

Hargreaves, Katherine R; Flores, Cesar O; Lawley, Trevor D; Clokie, Martha R J

2014-08-26

Clostridium difficile is an important human-pathogenic bacterium causing antibiotic-associated nosocomial infections worldwide. Mobile genetic elements and bacteriophages have helped shape C. difficile genome evolution. In many bacteria, phage infection may be controlled by a form of bacterial immunity called the clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR/Cas) system. This uses acquired short nucleotide sequences (spacers) to target homologous sequences (protospacers) in phage genomes. C. difficile carries multiple CRISPR arrays, and in this paper we examine the relationships between the host- and phage-carried elements of the system. We detected multiple matches between spacers and regions in 31 C. difficile phage and prophage genomes. A subset of the spacers was located in prophage-carried CRISPR arrays. The CRISPR spacer profiles generated suggest that related phages would have similar host ranges. Furthermore, we show that C. difficile strains of the same ribotype could either have similar or divergent CRISPR contents. Both synonymous and nonsynonymous mutations in the protospacer sequences were identified, as well as differences in the protospacer adjacent motif (PAM), which could explain how phages escape this system. This paper illustrates how the distribution and diversity of CRISPR spacers in C. difficile, and its prophages, could modulate phage predation for this pathogen and impact upon its evolution and pathogenicity. Clostridium difficile is a significant bacterial human pathogen which undergoes continual genome evolution, resulting in the emergence of new virulent strains. Phages are major facilitators of genome evolution in other bacterial species, and we use sequence analysis-based approaches in order to examine whether the CRISPR/Cas system could control these interactions across divergent C. difficile strains. The presence of spacer sequences in prophages that are homologous to phage genomes raises an

Optimized Design of Spacer in Electrodialyzer Using CFD Simulation Method

Science.gov (United States)

Jia, Yuxiang; Yan, Chunsheng; Chen, Lijun; Hu, Yangdong

2018-06-01

In this study, the effects of length-width ratio and diversion trench of the spacer on the fluid flow behavior in an electrodialyzer have been investigated through CFD simulation method. The relevant information, including the pressure drop, velocity vector distribution and shear stress distribution, demonstrates the importance of optimized design of the spacer in an electrodialysis process. The results show width of the diversion trench has a great effect on the fluid flow compared with length. Increase of the diversion trench width could strength the fluid flow, but also increase the pressure drop. Secondly, the dead zone of the fluid flow decreases with increase of length-width ratio of the spacer, but the pressure drop increases with the increase of length-width ratio of the spacer. So the appropriate length-width ratio of the space should be moderate.

Design of oligonucleotides for microarrays and perspectives for design of multi-transcriptome arrays

DEFF Research Database (Denmark)

Nielsen, Henrik Bjørn; Wernersson, Rasmus; Knudsen, Steen

2003-01-01

with an overview of these parameters. We present here a flexible tool named OligoWiz for designing oligonucleotides for multiple purposes. OligoWiz presents a set of parameter scores in a graphical interface to facilitate an overview for the user. Additional custom parameter scores can easily be added......Optimal design of oligonucleotides for microarrays involves tedious and laborious work evaluating potential oligonucleotides relative to a series of parameters. The currently available tools for this purpose are limited in their flexibility and do not present the oligonucleotide designer...... to the program to extend the default parameters: homology, DeltaTm, low-complexity, position and GATC-only. Furthermore we present an analysis of the limitations in designing oligonucleotide sets that can detect transcripts from multiple organisms. OligoWiz is available at www.cbs.dtu.dk/services/OligoWiz/....

Flow visualization on a natural circulation inter-wrapper flow. Experimental and numerical results under a geometric condition of button type spacer pads

Energy Technology Data Exchange (ETDEWEB)

Yasuda, A.; Miyakoshi, H.; Hayashi, K.; Nishimura, M.; Kamide, H.; Hishida, K. [Japan Nuclear Cycle Development Inst., Oarai, Ibaraki (Japan). Oarai Engineering Center

1999-04-01

Investigations on the inter-wrapper flow (IWF) in a liquid metal cooled fast breeder reactor core have been carried out. The IWF is a natural circulation flow between wrapper tubes in the core barrel where cold fluid is coming from a direct heat exchanger (DHX) in the upper plenum. It was shown by the sodium experiment using 7-subassembly core model that the IWF can cool the subassemblies. To clarify thermal-hydraulic characteristics of the IWF in the core, the water experiment was performed using the flow visualization technique. The test rig for IWF (TRIF) has the core simulating the fuel subassemblies and radial reflectors. The subassemblies are constructed featuring transparent heater to enable both Joule heating and flow visualization. The transparent heater was made of glass with thin conductor film coating of tin oxide, and the glass heater was embedded on the wall of modeled wrapper tube made of acrylic plexiglass. In the present experiment, influences of peripheral geometric parameters such as flow holes of core formers on the thermal-hydraulic field were investigated with the button type spacer pads of the wrapper tube. Through the water tests, flow patterns of the IWF were revealed and velocity fields were quantitatively measured with a particle image velocimetry (PIV). Also, no substantial influence of peripheral geometry was found on the temperature field of the IWF, as far as the button type spacer pad was applied. Numerical simulation was applied to the experimental analysis of IWF by using multidimensional code with porous body model. The numerical results reproduced the flow patterns within TRIF and agreed well to experimental temperature distributions, showing capability of predicting IWF with porous body model. (author)

A Study on Cell Size of Irradiated Spacer Grid for PWR Fuel

International Nuclear Information System (INIS)

Jin, Y. G.; Kim, G. S.; Ryu, W. S. and others

2014-01-01

The spacer grids supporting the fuel rods absorb vibration impacts due to the reactor coolant flow, and grid spring force decreases under irradiation. This reduction of contact force might cause grid-to-rod fretting wear. The fretting failure of the fuel rod is one of the recent significant issues in the nuclear industry from an economical as well as a safety concern. Thus, it is important to understand the characteristics of cell spring behavior and the change in size of grid cells for an irradiated spacer grid. In the present study, the dimensional measurement of a spacer grid was conducted to investigate the cell size of an irradiated spacer grid in a hot cell at IMEF (Irradiated Materials Examination Facility) of KAERI. To evaluate the fretting wear performance of an irradiated spacer grid, hot cell tests were carried out at IMEF of KAERI. Hot cell examinations include dimensional measurements for the irradiated spacer grid. The change of cell sizes was dependent on the direction of the spacer grids, leading to significant gap variations. It was found that the change in size of the cell springs due to irradiation-induced stress relaxation and creep during the fuel residency in the reactor core affect the contact behavior between the fuel rod and the cell spring

Thermodynamics of Oligonucleotide Duplex Melting

Science.gov (United States)

Schreiber-Gosche, Sherrie; Edwards, Robert A.

2009-01-01

Melting temperatures of oligonucleotides are useful for a number of molecular biology applications, such as the polymerase chain reaction (PCR). Although melting temperatures are often calculated with simplistic empirical equations, application of thermodynamics provides more accurate melting temperatures and an opportunity for students to apply…

Antisense Oligonucleotides Internally Labeled with Peptides Show Improved Target Recognition and Stability to Enzymatic Degradation

DEFF Research Database (Denmark)

Taskova, Maria; Madsen, Charlotte S.; Jensen, Knud J.

2017-01-01

Specific target binding and stability in diverse biological media is of crucial importance for applications of synthetic oligonucleotides as diagnostic and therapeutic tools. So far, these issues have been addressed by chemical modification of oligonucleotides and by conjugation with a peptide, m...... and makes internally labeled POCs an exciting object of study, i.e., showing high target specificity and simultaneous stability in biological media.......Specific target binding and stability in diverse biological media is of crucial importance for applications of synthetic oligonucleotides as diagnostic and therapeutic tools. So far, these issues have been addressed by chemical modification of oligonucleotides and by conjugation with a peptide......, most often at the terminal position of the oligonucleotide. Herein, we for the first time systematically investigate the influence of internally attached short peptides on the properties of antisense oligonucleotides. We report the synthesis and internal double labeling of 21-mer oligonucleotides...

Influence of the spacer dielectric processes on PMOS junction properties

International Nuclear Information System (INIS)

Morin, Pierre; Wacquant, Francois; Juhel, Marc; Laviron, Cyrille; Lenoble, D.

2005-01-01

In this paper, the interaction observed in PMOS transistor between the boron lightly doped drain (LDD) extensions and the spacer oxide and nitride dielectrics have been studied, with a simple experimental methodology. Low thermal budget oxide obtained by sub-atmospheric chemical vapor deposition (SACVD) and nitride deposited by plasma process have been evaluated as spacer layers. The influence of the oxide liner hydrogen content is shown to be critical for the p type shallow junction. Indeed, during the activation anneal, hydrogen content increases the boron out diffusion from the extension into the oxide liner and yield to a significant dose loss in this area. Nitride porosity has also been studied. A lower boron dose loss is observed with a porous layer because hydrogen can degas out significantly from the oxide, during anneal, through the porous nitride film. These results confirm the model of boron out diffusion based on oxide hydrogen content proposed by Kohli. Finally, a boron diffusion mechanism driven by chemistry and enhanced by hydrogen defects is proposed

ATLAS barrel hadron tile calorimeter: spacers plates mass production

International Nuclear Information System (INIS)

Artikov, A.M.; Budagov, Yu.A.; Khubua, J.

1999-01-01

In this article we expose the main problems of the mass production of the so-called 'spacer plates' for the ATLAS Barrel Hadron Tile Calorimeter. We describe all practical solutions of these problems. Particularly we present the measurement procedures and calculation schemes we used for the spacers dimensions determination. The results of the calculations are presented

On the impact analysis of a PWR spacer grid

International Nuclear Information System (INIS)

Song, Kee Nam; Lee, S. H.

2012-01-01

A spacer grid, which is an interconnected array of slotted grid straps and is welded at the intersections to form an egg crate structure, is one of the most important structural components in a PWR fuel assembly. From a structural point of view, the spacer grid is required to have sufficient crush strength under lateral loads so that nuclear fuel rods are maintained in a cool able geometry, and that control rods can be inserted. The capacity of a spacer grid to resist lateral loads is usually characterized in terms of its crush strength, and it was reported that the lateral crush strength of the spacer grid is closely related with welding quality of the spacer grid. Microstructures in the weld zone, including a heat affected zone (HAZ), are different from that in a parent material. Consequently, the mechanical properties in the weld zone are different from those in the parent material to some extent. When a welded structure is loaded, the mechanical behavior of the welded structure might be different from the case of a structure with homogeneous mechanical properties. Nonetheless, mechanical properties in the welded structure have been neglected in many structural analyses of the spacer grid due to a lack of mechanical properties in the weld zone. When the weld zone is very narrow and the interfaces are not clear, it is difficult to take tensile test specimens in the weld zone. The reason for this is that the mechanical properties in the parent material are usually used in the structural analyses in the welded structure. As an aside, it has been recently determined that the ball indentation technique has the potential to be an excellent substitute for a standard tensile test, particularly in the case of small specimens or property gradient materials such as welds. In this study, to investigate the effect on the mechanical behavior of the spacer grid when using weld mechanical properties, strength analyses considering the weld mechanical properties recently obtained

Oligonucleotide-based pharmaceuticals: Non-clinical and clinical safety signals and non-clinical testing strategies.

Science.gov (United States)

Mustonen, Enni-Kaisa; Palomäki, Tiina; Pasanen, Markku

2017-11-01

Antisense oligonucleotides, short interfering RNAs (siRNAs) and aptamers are oligonucleotide-based pharmaceuticals with a promising role in targeted therapies. Currently, five oligonucleotide-based pharmaceuticals have achieved marketing authorization in Europe or USA and many more are undergoing clinical testing. However, several safety concerns have been raised in non-clinical and clinical studies. Oligonucleotides share properties with both chemical and biological pharmaceuticals and therefore they pose challenges also from the regulatory point of view. We have analyzed the safety data of oligonucleotides and evaluated the applicability of current non-clinical toxicological guidelines for assessing the safety of oligonucleotide-based pharmaceuticals. Oligonucleotide-based pharmaceuticals display a similar toxicological profile, exerting adverse effects on liver and kidney, evoking hematological alterations, as well as causing immunostimulation and prolonging the coagulation time. It is possible to extrapolate some of these effects from non-clinical studies to humans. However, evaluation strategies for genotoxicity testing of "non-natural" oligonucleotides should be revised. Additionally, the selective use of surrogates and prediction of clinical endpoints for non-clinically observed immunostimulation is complicated by its multiple potential manifestations, demanding improvements in the testing strategies. Utilizing more relevant and mechanistic-based approaches and taking better account of species differences, could possibly improve the prediction of relevant immunological/proinflammatory effects in humans. Copyright © 2017 Elsevier Inc. All rights reserved.

Static magnetic field reduced exogenous oligonucleotide uptake by spermatozoa using magnetic nanoparticle gene delivery system

Science.gov (United States)

Katebi, Samira; Esmaeili, Abolghasem; Ghaedi, Kamran

2016-03-01

Spermatozoa could introduce exogenous oligonucleotides of interest to the oocyte. The most important reason of low efficiency of sperm mediated gene transfer (SMGT) is low uptake of exogenous DNA by spermatozoa. The aim of this study was to evaluate the effects of static magnetic field on exogenous oligonucleotide uptake of spermatozoa using magnetofection method. Magnetic nanoparticles (MNPs) associated with the labeled oligonucleotides were used to increase the efficiency of exogenous oligonucleotide uptake by rooster spermatozoa. We used high-field/high-gradient magnet (NdFeB) to enhance and accelerate exogenous DNA sedimentation at the spermatozoa surface. Flow cytometry analysis was performed to measure viability and percentage of exogenous oligonucleotide uptake by sperm. Flow cytometry analysis showed a significant increase in exogenous oligonucleotide uptake by rooster spermatozoa (Prooster spermatozoa; however unlike others studies, static magnetic field, was not only ineffective to enhance exogenous oligonucleotide uptake by rooster spermatozoa but also led to reduction in efficiency of magnetic nanoparticles in gene transfer.

Effects of grid spacer with mixing vane on entrainments and depositions in two-phase annular flows

Directory of Open Access Journals (Sweden)

Akimaro Kawahara

2015-06-01

Full Text Available The effects of mixing vanes (MVs attached to a grid spacer on the characteristics of air–water annular flows were experimentally investigated. To know the effects, a grid spacer with or without MV was inserted in a vertical circular pipe of 16-mm internal diameter. For three cases (i.e., no spacer, spacer without MV, and spacer with MV, the liquid film thickness, liquid entrainment fraction, and deposition rate were measured by the constant current method, single liquid film extraction method, and double liquid film extraction method, respectively. The MVs significantly promote the re-deposition of liquid droplets in the gas core flow into the liquid film on the channel walls. The deposition mass transfer coefficient is three times higher for the spacer with MV than for the spacer without MV, even for cases 0.3-m downstream from the spacer. The liquid film thickness becomes thicker upstream and downstream for the spacer with MV, compared with the thickness for the spacer without MV and for the case with no spacer.

Quantitation of ultraviolet-induced single-strand breaks using oligonucleotide chip

International Nuclear Information System (INIS)

Pal, Sukdeb; Kim, Min Jung; Choo, Jaebum; Kang, Seong Ho; Lee, Kyeong-Hee; Song, Joon Myong

2008-01-01

A simple, accurate and robust methodology was established for the direct quantification of ultraviolet (UV)-induced single-strand break (SSB) using oligonucleotide chip. Oligonucleotide chips were fabricated by covalently anchoring the fluorescent-labeled ssDNAs onto silicon dioxide chip surfaces. Assuming that the possibility of more than one UV-induced SSB to be generated in a small oligonucleotide is extremely low, SSB formation was investigated quantifying the endpoint probe density by fluorescence measurement upon UV irradiation. The SSB yields obtained based on the highly sensitive laser-induced fluorometric determination of fluorophore-labeled oligonucleotides were found to coincide well with that predicted from a theoretical extrapolation of the results obtained for plasmid DNAs using conventional agarose gel electrophoresis. The developed method has the potential to serve as a high throughput, sample-thrifty, and time saving tool to realize more realistic, and direct quantification of radiation and chemical-induced strand breaks. It will be especially useful for determining the frequency of SSBs or lesions convertible to SSBs by specific cleaving reagents or enzymes

Polyetheretherketone (PEEK) Spacers for Anterior Cervical Fusion: A Retrospective Comparative Effectiveness Clinical Trial.

Science.gov (United States)

Lemcke, Johannes; Al-Zain, Ferass; Meier, Ullrich; Suess, Olaf

2011-01-01

Anterior cervical decompression and fusion (ACDF) is the standard surgical treatment for radiculopathy and myelopathy. Polyetheretherketone (PEEK) has an elasticity similar to bone and thus appears well suited for use as the implant in ACDF procedures. The aim of this study is to examine the clinical and radiographic outcome of patients treated with standing alone PEEK spacers without bone morphogenic protein (BMP) or plating and to examine the influence of the different design of the two spacers on the rate of subsidence and dislocation. This retrospective comparative study reviewed 335 patients treated by ACDF in a specialized urban hospital for radiculopathy or myelopathy due to degenerative pathologies. The Intromed PEEK spacer was used in 181 patients from 3/2002 to 11/2004, and the AMT SHELL spacer was implanted in 154 patients from 4/2004 to 12/2007. The follow-up rate was 100% at three months post-op and 82.7% (277 patients) at one year. The patients were assessed with the Japanese Orthopedic Association (JOA) questionnaire and radiographically. At the one-year follow-up there were 118/277 patients with an excellent clinical outcome on the JOA, 112/277 with a good outcome, 20/277 with a fair outcome, and 27/277 with a poor outcome. Subsidence was observed in 13.3% of patients with the Intromed spacer vs 8.4% of the patients with the AMT SHELL. Dislocation of the spacer was observed in 10 of the 181 patients with Intromed spacers but in none of the 154 patients with Shell spacers. The study demonstrates that ACDF with standing alone PEEK cages leads to excellent and good clinical outcomes. The differences we observed in the subsidence rate between the two spacers were not significant and cannot be related to a single design feature of the spacers.

Measurement and CFD calculation of spacer loss coefficient for a tight-lattice fuel bundle

International Nuclear Information System (INIS)

In, Wang Kee; Shin, Chang Hwan; Kwack, Young Kyun; Lee, Chi Young

2015-01-01

Highlights: • Experiment and CFD analysis evaluated the pressure drop in a spacer grid. • The measurement and CFD errors for the spacer loss coefficient were estimated. • The spacer loss coefficient for the dual-cooled annular fuel bundle was determined. • The CFD prediction agrees with the measured spacer loss coefficient within 8%. - Abstract: An experiment and computational fluid dynamics (CFD) analysis were performed to evaluate the pressure drop in a spacer grid for a dual-cooled annular fuel (DCAF) bundle. The DCAF bundle for the Korean optimum power reactor (OPR1000) is a 12 × 12 tight-lattice rod array with a pitch-to-diameter ratio of 1.08 owing to a larger outer diameter of the annular fuel rod. An experiment was conducted to measure the pressure drop in spacer grid for the DCAF bundle. The test bundle is a full-size 12 × 12 rod bundle with 11 spacer grid. The test condition covers a Reynolds number range of 2 × 10 4 –2 × 10 5 by changing the temperature and flow rate of water. A CFD analysis was also performed to predict the pressure drop through a spacer grid using the full-size and partial bundle models. The pressure drop and loss coefficient of a spacer grid were predicted and compared with the experimental results. The CFD predictions of spacer pressure drop and loss coefficient agree with the measured values within 8%. The spacer loss coefficient for the DCAF bundle is estimated to be approximately 1.50 at a nominal operating condition of OPR1000, i.e., Re = 4 × 10 5

Separator-spacer for electrochemical systems

Science.gov (United States)

Grimes, Patrick G.; Einstein, Harry; Newby, Kenneth R.; Bellows, Richard J.

1983-08-02

An electrochemical cell construction features a novel co-extruded plastic electrode in an interleaved construction with a novel integral separator-spacer. Also featured is a leak and impact resistant construction for preventing the spill of corrosive materials in the event of rupture.

Experimental study of mechanical properties on spacer in NHR

International Nuclear Information System (INIS)

Jiang Yueyuan; Shi Jibing; Xu Yong

2007-01-01

The spacer of NHR-200 is composed mainly of the inner, outer and cornual strips which are ranged in egg-crate of 12 x 12-3. First, the pre-distortion of three kinds of three-arc springs on reactor working condition and their related clipping-force ranges are analyzed in this paper. Secondly, the mechanical experiments of 1:1 prototype, such as the load-distortion experiments, which the load and distortion are respectively measured by strain gauge and displacement sensor, of three kinds of springs, rigid supports and the spacers in two different directions are carried out on a special experimental facility. The experimental results show that the spacer can completely meet the design demands of mechanical properties of the fuel assemblies in NHR-200. (authors)

Folding Topology of a Short Coiled-Coil Peptide Structure Templated by an Oligonucleotide Triplex

DEFF Research Database (Denmark)

Lou, Chenguang; Christensen, Niels Johan; Martos Maldonado, Manuel Cristo

2017-01-01

by oligonucleotide duplex and triplex formation. POC synthesis was achieved by copper-free alkyne-azide cycloaddition between three oligonucleotides and a 23-mer peptide, which by itself exhibited multiple oligomeric states in solution. The oligonucleotide domain was designed to furnish a stable parallel triplex......, small-angle X-ray scattering (SAXS), and molecular modeling. Stabilizing cooperativity was observed between the trimeric peptide and the oligonucleotide triplex domains, and the overall molecular size (ca. 12nm) in solution was revealed to be independent of concentration. The topological folding...

Solution-processed organic tandem solar cells with embedded optical spacers

NARCIS (Netherlands)

Hadipour, Afshin; de Boer, Bert; Blom, Paul W. M.

2007-01-01

We demonstrate a solution-processed polymer tandem solar cell in which the two photoactive single cells are separated by an optical spacer. The use of an optical spacer allows for an independent optimization of both the electronic and optical properties of the tandem cell. The optical transmission

3-D flow analyses for design of nuclear fuel spacer

Energy Technology Data Exchange (ETDEWEB)

Karouta, Z. [ABB Combustion Engineering, Windsor, CT (United States); GU, Chun-Yuan [ABB Corporate Research, Vaesteras (Sweden); Schoelin, B. [ABB Atom AB, Vaesteras (Sweden)

1995-09-01

The Computational Fluid Dynamics (CFD) code, CFDS-FLOW3D, was used to develop improved fuel designs for PWR cores. It was used primarily to understand the fluid dynamics of grid spacers, the mass transfer between subchannels caused by spacers and in the long term to develop two-phase models which enable prediction of critical heat flux in PWR fuel. A single subchannel of one grid span was modeled. In this model different spacer designs with mixing devices were analyzed. A special treatment of the boundary condition was developed making use of flow symmetry to model the mass transfer between different subchannels and minimize the size of the computational model. This reduced the computational model to a fraction of a subchannel using traditional periodic boundary conditions. The Navier-Stokes equation was solved for the liquid and the flow turbulence was modeled by k-{xi} turbulence model. The spacer and mixing device were treated as infinite thin surfaces in the model and a zero velocity condition and turbulent wall function were applied on each side of the thin surfaces. This approach simulated the swirl from the mixing devices well, but had the drawback of not predicting pressure drop accurately since the wake behind the plates and the acceleration effect of the spacers were ignored. CFDS-FLOW3D models with mixing devices were applied in the single-phase flow regime. Velocity profiles from the CFDS-FLOW3D models were compared to Laser Doppler Velocimeter measurements taken from the flow field downstream of spaces in a full scale, cold water test loop. The predicted axial and lateral velocity profiles were in good agreement with the measurements. The evaluation of the performance of different spacer devices was made by comparing the swirl ratio downstream of the grid spacers. It is planned to evaluate heat transfer coefficient downstream of the spaces, to implement two-phase flow models, and to model the superheated boundary layer on the surface of the fuel rod.

Porosity of spacer-filled channels in spiral-wound membrane systems: Quantification methods and impact on hydraulic characterization

KAUST Repository

Siddiqui, Amber

2017-04-13

The porosity of spacer-filled feed channels influences the hydrodynamics of spiral-wound membrane systems and impacts the overall performance of the system. Therefore, an exact measurement and a detailed understanding of the impact of the feed channel porosity is required to understand and improve the hydrodynamics of spiral-wound membrane systems applied for desalination and wastewater reuse. The objectives of this study were to assess the accuracy of porosity measurement techniques for feed spacers differing in geometry and thickness and the consequences of using an inaccurate method on hydrodynamic predictions, which may affect permeate production. Six techniques were applied to measure the porosity namely, three volumetric calculations based on spacer strand count together with cuboidal (SC), cylindrical (VCC) and ellipsoidal volume calculation (VCE) and three independent techniques based on volume displacement (VD), weight and density (WD) and computed tomography scanning (CT). The CT method was introduced as an alternative for the other five already existing and applied methods in practice.Six feed spacers used for the porosity measurement differed in filament thickness, angle between the filaments and mesh-size. The results of the studies showed differences between the porosities, measured by the six methods. The results of the microscopic techniques SC, VCC and VCE deviated significantly from measurements by VD, WD and CT, which showed similar porosity values for all spacer types.Depending on the maximum deviation of the porosity measurement techniques from –6% to +6%, (i) the linear velocity deviations were −5.6% and +6.4% respectively and (ii) the pressure drop deviations were –31% and +43% respectively, illustrating the importance of an accurate porosity measurement. Because of the accuracy and standard deviation, the VD and WD method should be applied for the porosity determination of spacer-filled channels, while the CT method is recommended for

Spacer geometry and particle deposition in spiral wound membrane feed channels

KAUST Repository

Radu, A.I.

2014-11-01

Deposition of microspheres mimicking bacterial cells was studied experimentally and with a numerical model in feed spacer membrane channels, as used in spiral wound nanofiltration (NF) and reverse osmosis (RO) membrane systems. In-situ microscopic observations in membrane fouling simulators revealed formation of specific particle deposition patterns for different diamond and ladder feed spacer orientations. A three-dimensional numerical model combining fluid flow with a Lagrangian approach for particle trajectory calculations could describe very well the in-situ observations on particle deposition in flow cells. Feed spacer geometry, positioning and cross-flow velocity sensitively influenced the particle transport and deposition patterns. The deposition patterns were not influenced by permeate production. This combined experimental-modeling approach could be used for feed spacer geometry optimization studies for reduced (bio)fouling. © 2014 Elsevier Ltd.

Thermal Stability of Modified i-Motif Oligonucleotides with Naphthalimide Intercalating Nucleic Acids

DEFF Research Database (Denmark)

El-Sayed, Ahmed Ali; Pedersen, Erik B.; Khaireldin, Nahid Y.

2016-01-01

In continuation of our investigation of characteristics and thermodynamic properties of the i-motif 5′-d[(CCCTAA)3CCCT)] upon insertion of intercalating nucleotides into the cytosine-rich oligonucleotide, this article evaluates the stabilities of i-motif oligonucleotides upon insertion of naphtha......In continuation of our investigation of characteristics and thermodynamic properties of the i-motif 5′-d[(CCCTAA)3CCCT)] upon insertion of intercalating nucleotides into the cytosine-rich oligonucleotide, this article evaluates the stabilities of i-motif oligonucleotides upon insertion...... of naphthalimide (1H-benzo[de]isoquinoline-1,3(2H)-dione) as the intercalating nucleic acid. The stabilities of i-motif structures with inserted naphthalimide intercalating nucleotides were studied using UV melting temperatures (Tm) and circular dichroism spectra at different pH values and conditions (crowding...

Cellular Internalization of Therapeutic Oligonucleotides by Peptide Amphiphile Nanofibers and Nanospheres.

Science.gov (United States)

Mumcuoglu, Didem; Sardan Ekiz, Melis; Gunay, Gokhan; Tekinay, Turgay; Tekinay, Ayse B; Guler, Mustafa O

2016-05-11

Oligonucleotides are promising drug candidates due to the exceptionally high specificity they exhibit toward their target DNA and RNA sequences. However, their poor pharmacokinetic and pharmacodynamic properties, in conjunction with problems associated with their internalization by cells, necessitates their delivery through specialized carrier systems for efficient therapy. Here, we investigate the effects of carrier morphology on the cellular internalization mechanisms of oligonucleotides by using self-assembled fibrous or spherical peptide nanostructures. Size and geometry were both found to be important parameters for the oligonucleotide internalization process; direct penetration was determined to be the major mechanism for the internalization of nanosphere carriers, whereas nanofibers were internalized by clathrin- and dynamin-dependent endocytosis pathways. We further showed that glucose conjugation to carrier nanosystems improved cellular internalization in cancer cells due to the enhanced glucose metabolism associated with oncogenesis, and the internalization of the glucose-conjugated peptide/oligonucleotide complexes was found to be dependent on glucose transporters present on the surface of the cell membrane.

Stereospecificity of oligonucleotide interactions revisited: no evidence for heterochiral hybridization and ribozyme/DNAzyme activity.

Directory of Open Access Journals (Sweden)

Kai Hoehlig

Full Text Available A major challenge for the application of RNA- or DNA-oligonucleotides in biotechnology and molecular medicine is their susceptibility to abundant nucleases. One intriguing possibility to tackle this problem is the use of mirror-image (l-oligonucleotides. For aptamers, this concept has successfully been applied to even develop therapeutic agents, so-called Spiegelmers. However, for technologies depending on RNA/RNA or RNA/DNA hybridization, like antisense or RNA interference, it has not been possible to use mirror-image oligonucleotides because Watson-Crick base pairing of complementary strands is (thought to be stereospecific. Many scientists consider this a general principle if not a dogma. A recent publication proposing heterochiral Watson-Crick base pairing and sequence-specific hydrolysis of natural RNA by mirror-image ribozymes or DNAzymes (and vice versa prompted us to systematically revisit the stereospecificity of oligonucleotides hybridization and catalytic activity. Using hyperchromicity measurements we demonstrate that hybridization only occurs among homochiral anti-parallel complementary oligonucleotide strands. As expected, achiral PNA hybridizes to RNA and DNA irrespective of their chirality. In functional assays we could not confirm an alleged heterochiral hydrolytic activity of ribozymes or DNAzymes. Our results confirm a strict stereospecificity of oligonucleotide hybridization and clearly argue against the possibility to use mirror-image oligonucleotides for gene silencing or antisense applications.

Rapid and accurate synthesis of TALE genes from synthetic oligonucleotides.

Science.gov (United States)

Wang, Fenghua; Zhang, Hefei; Gao, Jingxia; Chen, Fengjiao; Chen, Sijie; Zhang, Cuizhen; Peng, Gang

2016-01-01

Custom synthesis of transcription activator-like effector (TALE) genes has relied upon plasmid libraries of pre-fabricated TALE-repeat monomers or oligomers. Here we describe a novel synthesis method that directly incorporates annealed synthetic oligonucleotides into the TALE-repeat units. Our approach utilizes iterative sets of oligonucleotides and a translational frame check strategy to ensure the high efficiency and accuracy of TALE-gene synthesis. TALE arrays of more than 20 repeats can be constructed, and the majority of the synthesized constructs have perfect sequences. In addition, this novel oligonucleotide-based method can readily accommodate design changes to the TALE repeats. We demonstrated an increased gene targeting efficiency against a genomic site containing a potentially methylated cytosine by incorporating non-conventional repeat variable di-residue (RVD) sequences.

Oligonucleotide assisted light-emitting Alq3 microrods: energy transfer effect with fluorescent dyes.

Science.gov (United States)

Cui, Chunzhi; Park, Dong Hyuk; Kim, Jeongyong; Joo, Jinsoo; Ahn, Dong June

2013-06-14

Oligonucleotide assisted tri(8-hydroxyquinoline) aluminium (Alq3) microrods were prepared for the first time. When hybridized with oligonucleotide labeled by Cy3 fluorescent dye, a significant photoluminescence variation of the Alq3 microrods was observed due to Förster resonance energy transfer, unlike when Cy5-oligonucleotide was used. Versatile nucleotide manipulation would open up wider applications of Alq3-based materials, based on this fundamental observation.

Type III CRISPR-Cas systems can provide redundancy to counteract viral escape from type I systems.

Science.gov (United States)

Silas, Sukrit; Lucas-Elio, Patricia; Jackson, Simon A; Aroca-Crevillén, Alejandra; Hansen, Loren L; Fineran, Peter C; Fire, Andrew Z; Sánchez-Amat, Antonio

2017-08-17

CRISPR-Cas-mediated defense utilizes information stored as spacers in CRISPR arrays to defend against genetic invaders. We define the mode of target interference and role in antiviral defense for two CRISPR-Cas systems in Marinomonas mediterranea . One system (type I-F) targets DNA. A second system (type III-B) is broadly capable of acquiring spacers in either orientation from RNA and DNA, and exhibits transcription-dependent DNA interference. Examining resistance to phages isolated from Mediterranean seagrass meadows, we found that the type III-B machinery co-opts type I-F CRISPR-RNAs. Sequencing and infectivity assessments of related bacterial and phage strains suggests an 'arms race' in which phage escape from the type I-F system can be overcome through use of type I-F spacers by a horizontally-acquired type III-B system. We propose that the phage-host arms race can drive selection for horizontal uptake and maintenance of promiscuous type III interference modules that supplement existing host type I CRISPR-Cas systems.

Dielectric properties of DNA oligonucleotides on the surface of silicon nanostructures

Energy Technology Data Exchange (ETDEWEB)

Bagraev, N. T., E-mail: bagraev@mail.ioffe.ru [St. Petersburg Polytechnic University (Russian Federation); Chernev, A. L. [Russian Academy of Sciences, St. Petersburg Academic University—Nanotechnology Research and Education Center (Russian Federation); Klyachkin, L. E. [St. Petersburg Polytechnic University (Russian Federation); Malyarenko, A. M. [Russian Academy of Sciences, Ioffe Physical–Technical Institute (Russian Federation); Emel’yanov, A. K.; Dubina, M. V. [Russian Academy of Sciences, St. Petersburg Academic University—Nanotechnology Research and Education Center (Russian Federation)

2016-10-15

Planar silicon nanostructures that are formed as a very narrow silicon quantum well confined by δ barriers heavily doped with boron are used to study the dielectric properties of DNA oligonucleotides deposited onto the surface of the nanostructures. The capacitance characteristics of the silicon nanostructures with oligonucleotides deposited onto their surface are determined by recording the local tunneling current–voltage characteristics by means of scanning tunneling microscopy. The results show the possibility of identifying the local dielectric properties of DNA oligonucleotide segments consisting of repeating G–C pairs. These properties apparently give grounds to correlate the segments with polymer molecules exhibiting the properties of multiferroics.

Numerical simulation of bubble motion about a grid spacer in a rod bundle

International Nuclear Information System (INIS)

Zhang, Zheng; Hosokawa, Shigeo; Hayashi, Kosuke; Tomiyama, Akio

2009-01-01

Numerical simulations based on a three-dimensional two-way bubble tracking method are carried out to predict bubble motions in a square duct with an obstacle and in a two-by-three rod bundle with a grid spacer. Comparisons between measured and predicted bubble motions demonstrate that the two-way bubble tracking method gives good predictions for trajectories of small bubbles in the upstream side of the grid spacer in the rod bundle geometry. The predicted bubble trajectories clearly show that bubbles are apt to migrate toward the rod surface in the vicinity of the bottom of the grid spacer. Analysis of forces acting on the bubbles confirms that pressure gradient force induced by the presence of the spacer is the main cause of the bubble lateral migration toward the rod surface. Motions of steam bubbles at a nominal operating condition of a pressurized water reactor (PWR) are also predicted by using the bubble tracking method, which indicates that steam bubbles also migrate toward the rod surface at the upstream side of the spacer due to the spacer-induced pressure gradient force. (author)

Multi-Scaled Modeling the Mechanical Properties of Tubular Composites Reinforced with Innovated 3D Weft Knitted Spacer Fabrics

Science.gov (United States)

Omrani, Elahe; Hasani, Hossein; Dibajian, Sayed Houssain

2018-02-01

Textile composites of 3D integrated spacer configurations have been recently focused by several researchers all over the world. In the present study, newly-designed tubular composites reinforced with 3D spacer weft knitted fabrics were considered and the effects of their structural parameters on some applicable mechanical properties were investigated. For this purpose, two different samples of 3D spacer weft knitted textile types in tubular form were produced on an electronic flat knitting machine, using glass/nylon hybrid yarns. Thermoset tubular-shaped composite parts were manufactured via vacuum infusion molding process using epoxy resin. The mechanical properties of the produced knitted composites in term of external static and internal hydrostatic pressures were evaluated. Resistance of the produced composites against the external static and internal hydrostatic pressures was numerically simulated using multi-scale modeling method. The finding revealed that there is acceptable correlation between experimental and theoretical results.

Modeling the effect of spacers and biofouling on forward osmosis performance

KAUST Repository

Mosqueira Santillá n, Marí a José

2014-01-01

and operational conditions. For this, a two dimensional numerical model for FO systems was developed using computational fluid dynamics (CFD). This model allowed the evaluation of the impact of (i) spacers and (ii) biofilm, and (iii) the combined impact of spacers

Articulating spacers used in two-stage revision of infected hip and knee prostheses abrade with time.

Science.gov (United States)

Fink, Bernd; Rechtenbach, Annett; Büchner, Hubert; Vogt, Sebastian; Hahn, Michael

2011-04-01

Articulating spacers used in two-stage revision surgery of infected prostheses have the potential to abrade and subsequently induce third-body wear of the new prosthesis. We asked whether particulate material abraded from spacers could be detected in the synovial membrane 6 weeks after implantation when the spacers were removed for the second stage of the revision. Sixteen hip spacers (cemented prosthesis stem articulating with a cement cup) and four knee spacers (customized mobile cement spacers) were explanted 6 weeks after implantation and the synovial membranes were removed at the same time. The membranes were examined by xray fluorescence spectroscopy, xray diffraction for the presence of abraded particles originating from the spacer material, and analyzed in a semiquantitative manner by inductively coupled plasma mass spectrometry. Histologic analyses also were performed. We found zirconium dioxide in substantial amounts in all samples, and in the specimens of the hip synovial lining, we detected particles that originated from the metal heads of the spacers. Histologically, zirconium oxide particles were seen in the synovial membrane of every spacer and bone cement particles in one knee and two hip spacers. The observations suggest cement spacers do abrade within 6 weeks. Given the presence of abrasion debris, we recommend total synovectomy and extensive lavage during the second-stage reimplantation surgery to minimize the number of abraded particles and any retained bacteria.

Deformation behavior of cell spring of an irradiated spacer grid

International Nuclear Information System (INIS)

Jin, Y. G.; Baek, S. J.; Ryu, W. S.; Kim, G. S.; Yoo, B. O.; Kim, D. S.; Ahn, S. B.; Chun, Y. B.; Choo, Y. S.

2012-01-01

Mechanical properties of a space grid of a fuel assembly are of great importance for fuel operation reliability in extended fuel burnup and duration of fuel life. The spacer grid with inner and outer straps has cell spring and dimples, which are in contact with the fuel rod. The spacer grids supporting the fuel rods absorb vibration impacts due to the reactor coolant flow and also grid spring force is decreasing under irradiation. This reduction of contact force might cause the grid to rod fretting wear. The fretting failure of the fuel rod is one of the significant issues recently in the nuclear industry from an economical as well as a safety concern. Thus, it is important to understand the characteristics of cell spring behavior for an irradiated spacer grid. In the present study, the stiffness test and dimensional measurement of cell springs were conducted to investigate the deformation behavior of cell springs of an irradiated spacer grid in a hot cell at IMEF (irradiated materials examination facility) of KAERI

Implementation of spacer therapy for acute asthma in children.

LENUS (Irish Health Repository)

Vandeleur, M

2009-09-01

The aim was to develop and implement an evidence based guideline for the treatment of acute asthma using a metered dose inhaler and spacer combination. Children admitted to Cork University Hospital Paediatric Department with acute asthma were identified during two identical 2 month seasonal periods before (2005) and after (2006) implementation of the new guidelines in September 2006. Pre-intervention and post-intervention audits by case note review were performed to determine the impact of and compliance with this evidence-based guideline emphasising patient assessment, spacer delivered bronchodilator and specific discharge criteria. Patients had similar characteristics during the two study periods. There was a raised threshold for admission after guideline implementation with 11\\/52 patients having mild exacerbations in 2006, compared to 21\\/36 in 2005. Duration of admission was less in the post-implementation group for equivalent exacerbation severity e.g. for moderate severity; 28 hours in 2005, 23 hours in 2006. Duration of bronchodilator therapy was shorter in 2006 and more likely to be given by spacer device earlier for equivalent levels of severity e.g. for moderate exacerbations, in 2006 the average length of salbutamol therapy was 18 hours with 12 hours by spacer device, in 2005 the average length of therapy was 25 hours with 3 hours by spacer. There was earlier initiation of oral corticosteroids; the average time to administration was 56 minutes in 2006 and 227 minutes in 2005. There was an improved documentation of asthma education in 2006 e.g. inhaler technique was reviewed in 37\\/52 in 2006, 21\\/35 in 2005 and better use of written action plans.

Effect of spacer grids on CHF in tube bundles

International Nuclear Information System (INIS)

Jayanti, Sreenivas; Valette, Michel

2004-01-01

Spacers grids are used to support tube bundles in steam generators and in nuclear reactor fuel assemblies. These grids interface with the flow and heat transfer in a number of ways and their effect has been studied by a number of researchers. It is known that generally they have a beneficial effect on critical heat flux (CHF) in typical nuclear reactor assemblies. However, the enhancement obtained depends on the geometric characteristics of the spacer grids as well as on the parameter range in terms of pressure, local mass velocity and quality. In the present study, the problem is approached in the context of a one-dimensional three-field model. Unlike in previous approaches, no specific modeling of the constitutive laws is made to account for spacer effects and only the geometric details such as the reduction in the cross-sectional area and the hydraulic diameter are included in the calculation which is otherwise the same as that for flow through a single tube. It is shown by comparison with literature data that this approach leads to satisfactory prediction of the thermal-hydraulic effects of spacers and that the beneficial effects of spacers on dry out can be manifested only when the entrainment rate is neither too high nor too low. Their effect on reducing the post-dry out wall temperature is also limited to certain cases. The present work has been performed as part of the EDF-CEA Neptune project also supported by the Institut de Radioprotection et de Surete Nucleaire (IRSN, France) and FRAMATOME-ANP. NEPTUNE is a new set of two phase thermalhydraulic computer codes devoted to safety analysis of nuclear power plants. (author)

Effect of a spacer moiety on radiometal labelled Neurotensin derivatives

Energy Technology Data Exchange (ETDEWEB)

Mascarin, A.; Valverde, I.E.; Mindt, T.L. [Univ. of Basel Hospital (Switzerland). Div. of Radiopharmaceutical Chemistry

2013-07-01

The binding sequence of the regulatory peptide Neurotensin, NT(8-13), represents a promising tumour-specific vector for the development of radiopeptides useful in nuclear oncology for the diagnosis (imaging) and therapy of cancer. A number of radiometal-labelled NT(8-13) derivatives have been reported, however, the effect of the spacer which connects the vector with the radiometal complex has yet not been investigated systematically. Because a spacer moiety can influence potentially important biological characteristics of radiopeptides, we synthesized three [DOTA({sup 177}Lu)]-X-NT(8-13) derivatives and evaluated the effect of a spacer (X) on the physico-chemical properties of the conjugate including lipophilicity, stability, and in vitro receptor affinity and cell internalization. (orig.)

G-Quadruplex Forming Oligonucleotides as Anti-HIV Agents.

Science.gov (United States)

Musumeci, Domenica; Riccardi, Claudia; Montesarchio, Daniela

2015-09-22

Though a variety of different non-canonical nucleic acids conformations have been recognized, G-quadruplex structures are probably the structural motifs most commonly found within known oligonucleotide-based aptamers. This could be ascribed to several factors, as their large conformational diversity, marked responsiveness of their folding/unfolding processes to external stimuli, high structural compactness and chemo-enzymatic and thermodynamic stability. A number of G-quadruplex-forming oligonucleotides having relevant in vitro anti-HIV activity have been discovered in the last two decades through either SELEX or rational design approaches. Improved aptamers have been obtained by chemical modifications of natural oligonucleotides, as terminal conjugations with large hydrophobic groups, replacement of phosphodiester linkages with phosphorothioate bonds or other surrogates, insertion of base-modified monomers, etc. In turn, detailed structural studies have elucidated the peculiar architectures adopted by many G-quadruplex-based aptamers and provided insight into their mechanism of action. An overview of the state-of-the-art knowledge of the relevance of putative G-quadruplex forming sequences within the viral genome and of the most studied G-quadruplex-forming aptamers, selectively targeting HIV proteins, is here presented.

Manipulation of recombination zone by utilizing the donor of electroplex as a spacer

Energy Technology Data Exchange (ETDEWEB)

Lü, Zhaoyue, E-mail: lvzhaoyue@ecust.edu.cn [Department of Physics, School of Science, East China University of Science & Technology, Shanghai 200237 (China); Yin, Yuehong [Department of Applied Physics, Institute of Physical Chemistry, Henan Polytechnic University, Jiaozuo, Henan Province 454000 (China); Xiao, Jing [Physics and Electronic Engineering College, Taishan University, Shandong Province 271021,China (China)

2016-11-15

The emission of electroplex is varied with applied voltages, leading to poor color stability of devices. In this work, the recombination region was investigated in organic light-emitting diodes (OLEDs) based on the electroplex between N,N’-diphenyl-N,N’-bis(1-naphthyl-phenyl)-1,1′-biphenyl-4,4′-diamine(NPB) and 2-(4-biphenylyl)-5-(4-tert-butylphenyl)-1,2,4-oxadiazole (PBD). Color stability was manipulated by introducing the donor of electroplex as a spacer, which plays an important role of recombination zone for electroplex-based OLEDs. The 5-nm-spacer-device brought out a tolerable chromaticity coordinate shift of less than 0.01 for both x- and y-value. White light emission with CIE coordinates of (0.37,0.28) and (0.33,0.26) at 12 V was achieved when the thickness of spacer was 7 and 10 nm, respectively. The 7-nm-spacer-device exhibited better color stability than the 10-nm-spacer-device. This proves that adjusting spacer thickness is a simple and efficient method to control recombination region and can be useful for fulfilling color-stable electroplex-based white emission.

Manipulation of recombination zone by utilizing the donor of electroplex as a spacer

International Nuclear Information System (INIS)

Lü, Zhaoyue; Yin, Yuehong; Xiao, Jing

2016-01-01

The emission of electroplex is varied with applied voltages, leading to poor color stability of devices. In this work, the recombination region was investigated in organic light-emitting diodes (OLEDs) based on the electroplex between N,N’-diphenyl-N,N’-bis(1-naphthyl-phenyl)-1,1′-biphenyl-4,4′-diamine(NPB) and 2-(4-biphenylyl)-5-(4-tert-butylphenyl)-1,2,4-oxadiazole (PBD). Color stability was manipulated by introducing the donor of electroplex as a spacer, which plays an important role of recombination zone for electroplex-based OLEDs. The 5-nm-spacer-device brought out a tolerable chromaticity coordinate shift of less than 0.01 for both x- and y-value. White light emission with CIE coordinates of (0.37,0.28) and (0.33,0.26) at 12 V was achieved when the thickness of spacer was 7 and 10 nm, respectively. The 7-nm-spacer-device exhibited better color stability than the 10-nm-spacer-device. This proves that adjusting spacer thickness is a simple and efficient method to control recombination region and can be useful for fulfilling color-stable electroplex-based white emission.

Effect of the spacer group nature on the optical and electrical properties of confined poly( p-phenylene vinylene) derivatives

Science.gov (United States)

Benzarti-Ghédira, Maha; Zahou, Imen; Hrichi, Haikel; Jaballah, Nejmeddine; Ben Chaâbane, Rafik; Majdoub, Mustapha; Ben Ouada, Hafedh

2015-09-01

This study is an investigation about the effect of chemical modification on the morphological, optical and electrical properties of semiconducting organic thin films. Two confined poly( p-phenylene vinylene) (PPV)-type polymers containing different spacer groups were studied: P1 has an isopropylidene spacer group and P2 with hexafluoroisopropylidene spacer. The UV-Vis absorption and PL analysis showed a stronger π- π interaction in the P1 film; in P2, the π-stacking is limited by the introduction of a bulky trifluoromethyl (CF3) groups on the spacer units. The P2 exhibits a better film quality as illustrated by the atomic force microscopy. The HOMO and LUMO energy levels and electrochemical band gap of the polymers were determinate by the cyclic voltammetry. The electrical properties of ITO/PPV derivative/Al diodes were investigated by means of current-voltage and show a space-charge-limited current conduction mechanism with higher mobility in the P2 thin layer. The impedance spectra of the devices can be discussed in terms of an equivalent circuit model designed as a parallel resistance ( R p) and capacitance ( C p) network in series with a resistance.

A functional analysis of the spacer of V(DJ recombination signal sequences.

Directory of Open Access Journals (Sweden)

Alfred Ian Lee

2003-10-01

Full Text Available During lymphocyte development, V(DJ recombination assembles antigen receptor genes from component V, D, and J gene segments. These gene segments are flanked by a recombination signal sequence (RSS, which serves as the binding site for the recombination machinery. The murine Jbeta2.6 gene segment is a recombinationally inactive pseudogene, but examination of its RSS reveals no obvious reason for its failure to recombine. Mutagenesis of the Jbeta2.6 RSS demonstrates that the sequences of the heptamer, nonamer, and spacer are all important. Strikingly, changes solely in the spacer sequence can result in dramatic differences in the level of recombination. The subsequent analysis of a library of more than 4,000 spacer variants revealed that spacer residues of particular functional importance are correlated with their degree of conservation. Biochemical assays indicate distinct cooperation between the spacer and heptamer/nonamer along each step of the reaction pathway. The results suggest that the spacer serves not only to ensure the appropriate distance between the heptamer and nonamer but also regulates RSS activity by providing additional RAG:RSS interaction surfaces. We conclude that while RSSs are defined by a "digital" requirement for absolutely conserved nucleotides, the quality of RSS function is determined in an "analog" manner by numerous complex interactions between the RAG proteins and the less-well conserved nucleotides in the heptamer, the nonamer, and, importantly, the spacer. Those modulatory effects are accurately predicted by a new computational algorithm for "RSS information content." The interplay between such binary and multiplicative modes of interactions provides a general model for analyzing protein-DNA interactions in various biological systems.

How to use an inhaler - no spacer

Science.gov (United States)

... MDI) administration - no spacer; Bronchial nebulizer; Wheezing - nebulizer; Reactive airway - nebulizer; COPD - ... 66. National Asthma Education and Prevention Program website. How to use a metered-dose inhaler. ...

Characterization of feed channel spacer performance using geometries obtained by X-ray computed tomography

KAUST Repository

Haaksman, Viktor A.

2016-09-09

Spiral-wound membrane modules used in water treatment for water reuse and desalination make use of spacer meshes for keeping the membrane leaves apart and for enhancing the mass transfer. Computational fluid dynamics (CFD) has gained importance in the design of new spacers with optimized hydrodynamic characteristics, but this requires a precise description of the spacer geometry. This study developed a method to obtain accurate three-dimensional (3-D) geometry representations for any given spacer design from X-ray computed tomography (CT) scans. The method revealed that the filaments of industrial spacers have a highly variable cross-section size and shape, which impact the flow characteristics in the feed channel. The pressure drop and friction factors were calculated from numerical simulations on five commercially available feed spacers used in practice. Model solutions compared well to experimental data measured using a flow cell for average velocities up to 0.2 m/s, as used in industrial reverse osmosis and nanofiltration membrane operations. A newly-proposed spacer geometry with alternating strand thickness was tested, which was found to yield a lower pressure drop while being highly efficient in converting the pumping power into membrane shear. Numerical model solutions using CFD with geometries from CT scans were closer to measurements than those obtained using the traditional circular cross-section strand simplification, indicating that CT scans are very well suitable to approximate real feed spacer geometries. By providing detailed insight on the spacer filament shape, CT scans allow better quantification of local distribution of velocity and shear, possibly leading to more accurate estimations of fouling and concentration polarization. © 2016 Elsevier B.V.

Effect of spacer layer on the magnetization dynamics of permalloy/rare-earth/permalloy trilayers

International Nuclear Information System (INIS)

Luo, Chen; Yin, Yuli; Zhang, Dong; Jiang, Sheng; Yue, Jinjin; Zhai, Ya; Du, Jun; Zhai, Hongru

2015-01-01

The permalloy/rare-earth/permalloy trilayers with different types (Gd and Nd) and thicknesses of spacer layer are investigated using frequency dependence of ferromagnetic resonance (FMR) measurements at room temperature, which shows different behaviors with different rare earth spacer layers. By fitting the frequency dependence of the FMR resonance field and linewidth, we find that the in-plane uniaxial anisotropy retains its value for all samples, the perpendicular anisotropy remains almost unchanged for different thickness of Gd layer but the values are tailored by different thicknesses of Nd layer. The Gilbert damping is almost unchanged with different thicknesses of Gd; however, the Gilbert damping is significantly enhanced from 8.4×10 −3 to 20.1×10 −3 with 6 nm of Nd and then flatten out when the Nd thickness rises above 6 nm

Intrinsically Labeled Fluorescent Oligonucleotide Probes on Quantum Dots for Transduction of Nucleic Acid Hybridization.

Science.gov (United States)

Shahmuradyan, Anna; Krull, Ulrich J

2016-03-15

Quantum dots (QDs) have been widely used in chemical and biosensing due to their unique photoelectrical properties and are well suited as donors in fluorescence resonance energy transfer (FRET). Selective hybridization interactions of oligonucleotides on QDs have been determined by FRET. Typically, the QD-FRET constructs have made use of labeled targets or have implemented labeled sandwich format assays to introduce dyes in proximity to the QDs for the FRET process. The intention of this new work is to explore a method to incorporate the acceptor dye into the probe molecule. Thiazole orange (TO) derivatives are fluorescent intercalating dyes that have been used for detection of double-stranded nucleic acids. One such dye system has been reported in which single-stranded oligonucleotide probes were doubly labeled with adjacent thiazole orange derivatives. In the absence of the fully complementary (FC) oligonucleotide target, the dyes form an H-aggregate, which results in quenching of fluorescence emission due to excitonic interactions between the dyes. The hybridization of the FC target to the probe provides for dissociation of the aggregate as the dyes intercalate into the double stranded duplex, resulting in increased fluorescence. This work reports investigation of the dependence of the ratiometric signal on the type of linkage used to conjugate the dyes to the probe, the location of the dye along the length of the probe, and the distance between adjacent dye molecules. The limit of detection for 34mer and 90mer targets was found to be identical and was 10 nM (2 pmol), similar to analogous QD-FRET using labeled oligonucleotide target. The detection system could discriminate a one base pair mismatch (1BPM) target and was functional without substantial compromise of the signal in 75% serum. The 1BPM was found to reduce background signal, indicating that the structure of the mismatch affected the environment of the intercalating dyes.

Enhancement of nuclear heat transfer in a typical pressurized water reactor by new spacer grids

International Nuclear Information System (INIS)

Nazifi, M.; Nematollahi, M.

2007-01-01

The fuel element geometry typically used in nuclear reactor is rod bundle whose rod-to-rod clearance is maintained by grid spacer. The heat generated in the rod by nuclear reaction is removed by coolant, usually in turbulent flow. The coolant moves axially through the subchannels. Fuel spacer grid affects the coolant flow distribution in a fuel rod bundle, and so spacer geometry has a strong influence on a bundle's thermal-hydraulic characteristics such as critical heat flux and pressure drop. An understanding of the detailed structure of the turbulent flow and heat transfer in the rod bundle, used especially as nuclear fuel elements, is of major interest to the nuclear power industry for their safe and reliable operation. The flow mixing devices on grid spacer would enhance the mixing rate between sub-channels and promote the turbulence in subchannel. The present study evaluates the effects of mixing vane shape on flow structure and heat transfer downstream of mixing vane in a sub-channel of fuel assembly, by obtaining velocity and pressure fields, turbulent intensity, flow mixing factors, heat transfer coefficient and friction factor using three-dimensional RANS analysis. Six new shapes mixing vane designed by the authors, are simulated numerically to evaluate the performance in enhancing the heat transfer, in comparison with commercialized split vane. Standard K-epsilon model are used as a turbulence closure model and periodic and symmetry condition are set as boundary conditions. The capability of the model to predict the coolant flow distribution inside rod bundles is shown and discussed on the base of comparison with experimental data for a variety of geometrical and Reynolds number conditions. It is conformed that the turbulence in the sub-channel was significantly promoted by spacer and mixing devices but rapidly decreased to a fully developed level approximately 10 time of hydraulic diameter downstream of the top of spacer. Ring type mixer showed a high

Effect of plastic spacer handling on salbutamol lung deposition in asthmatic children

DEFF Research Database (Denmark)

Lipworth, Brian J; Lee, Daniel K C; Anhøj, Jacob

2002-01-01

AIMS: To study the effects of electrostatics in a plastic spacer on the lung deposition of salbutamol in asthmatic children. METHODS: Twenty-five children (5-12 years) with mild asthma were given salbutamol hydrofluoroalkane pressurized metered dose inhaler 400 micro g via a 750 ml plastic spacer...... on separate days. Blood samples were taken for plasma salbutamol at 5, 10, 15 and 20 min after inhalation to measure lung bioavailability as a surrogate for relative lung dose. With immediate inhalation following actuation, a new rinsed spacer (NewRinsed ) was compared with a used spacer after repeated daily...... log transformed and expressed as geometric mean fold difference for the average plasma salbutamol concentration (Cav) over 20 min. RESULTS: There were significant differences (P NewRinsed 1.92 fold (95% CI 1.15, 3...

Optimized spacer layer thickness for plasmonic-induced enhancement of photocurrent in a-Si:H

Energy Technology Data Exchange (ETDEWEB)

Saleh, Z. M., E-mail: zaki.saleh@aauj.edu, E-mail: zakimsaleh@yahoo.com; Nasser, H.; Özkol, E.; Günöven, M.; Abak, K. [Middle East Technical University, Center for Solar Energy Research and Applications (GÜNAM) (Turkey); Canli, S. [Middle East Technical University, Central Laboratory (Turkey); Bek, A.; Turan, R. [Middle East Technical University, Center for Solar Energy Research and Applications (GÜNAM) (Turkey)

2015-10-15

Plasmonic interfaces consisting of silver nanoparticles of different sizes (50–100 nm) have been processed by the self-assembled dewetting technique and integrated to hydrogenated amorphous silicon (a-Si:H) using SiNx spacer layers to investigate the dependence of optical trapping enhancement on spacer layer thickness through the enhancements in photocurrent. Samples illuminated from the a-Si:H side exhibit a localized surface plasmon resonance (LSPR) that is red-shifted with the increasing particle size and broadened into the red with the increasing spacer layer thickness. The photocurrent measured in a-Si:H is not only consistent with the red-shift and broadening of the LSPR, but exhibits critical dependence on the spacer layer thickness also. The samples with plasmonic interfaces and a SiNx spacer layer exhibit appreciable enhancement of photocurrent compared with flat a-Si:H reference depending on the size of the Ag nanoparticle. Simulations conducted on one-dimensional square structures exhibit electric fields that are localized near the plasmonic structures but extend appreciably into the higher refractive index a-Si:H. These simulations produce a clear red-shift and broadening of extinction spectra for all spacer layer thicknesses and predict an enhancement in photocurrent in agreement with experimental results. The spectral dependence of photocurrent for six plasmonic interfaces with different Ag nanoparticle sizes and spacer layer thicknesses are correlated with the optical spectra and compared with the simulations to predict an optimal spacer layer thickness.

[Oligonucleotide derivatives in the nucleic acid hybridization analysis. III. Synthesis and investigation of properties of oligonucleotides, bearing bifunctional non-nucleotide insert].

Science.gov (United States)

Kupriushkin, M S; Pyshnyĭ, D V

2012-01-01

Non-nucleotide phosporamidites were synthetized, having branched backbone with different position of functional groups. Obtained phosphoramidite monomers contain intercalator moiety--6-chloro-2-methoxyacridine, and additional hydroxyl residue protected with dimethoxytrityl group or with tert-butyldimethylsilyl group for post-synthetic modification. Synthesized oligothymidilates contain one or more modified units in different positions of sequence. Melting temperature and thermodynamic parameters of formation of complementary duplexes formed by modified oligonucleotides was defined (change in enthalpy and entropy). The introduction of intercalating residue causes a significant stabilization of DNA duplexes. It is shown that the efficiency of the fluorescence of acridine residue in the oligonucleotide conjugate significantly changes upon hybridization with DNA.

Cold-neutron tomography of annular flow and functional spacer performance in a model of a boiling water reactor fuel rod bundle

International Nuclear Information System (INIS)

Zboray, Robert; Kickhofel, John; Damsohn, Manuel; Prasser, Horst-Michael

2011-01-01

Highlights: → Annular flows w/wo functional spacers are investigated by cold neutron imaging. → Liquid film thickness distribution on fuel pins and on spacer vanes is measured. → The influence of the spacers on the liquid film distributions has been quantified. → The cross-sectional averaged liquid hold-up significantly affected by the spacers. → The sapers affect the fraction of the entrained liquid hold up in the gas core. - Abstract: Dryout of the coolant liquid film at the upper part of the fuel pins of a boiling water reactor (BWR) core constitutes the type of heat transfer crisis relevant for the conditions of high void fractions. It is both a safety concern and a limiting factor in the thermal power and thus for the economy of BWRs. We have investigated adiabatic, air-water annular flows in a scaled-up model of two neighboring subchannels as found in BWR fuel assemblies using cold-neutron tomography. The imaging of the double suchannel has been performed at the ICON beamline at the neutron spallation source SINQ at the Paul Scherrer Institute, Switzerland. Cold-neutron tomography is shown here to be an excellent tool for investigating air-water annular flows and the influence of functional spacers of different geometries on such flows. The high-resolution, high-contrast measurements provide the spatial distributions of the coolant liquid film thickness on the fuel pin surfaces as well as on the surfaces of the spacer vanes. The axial variations of the cross-section averaged liquid hold-up and its fraction in the gas core shows the effect of the spacers on the redistribution of the two phases.

Triplex-forming ability of modified oligonucleotides

DEFF Research Database (Denmark)

Højland, Torben; Babu, Bolle Ravindra; Bryld, Torsten

2007-01-01

We present our studies on the ability of several different nucleotide analogs as triplex-forming oligonucleotides. The modifications tested include 4'-C-hydroxymethyl, LNA, 2'-amino-LNA and N2'-functionalized 2'-amino-LNA. Triplexes containing monomers of N2'-glycyl-functionalized 2'-amino-LNA ar...

Preliminary results for validation of Computational Fluid Dynamics for prediction of flow through a split vane spacer grid

International Nuclear Information System (INIS)

Rashkovan, A.; Novog, D.R.

2012-01-01

This paper presents the results of the CFD simulations of turbulent flow past spacer grid with mixing vanes. This study summarizes the first stage of the ongoing numerical blind exercise organized by OECD-NEA. McMaster University along with other participants plan to submit a numerical prediction of the detailed flow field and turbulence characteristics of the flow past 5x5 rod bundle with a spacer grid equipped with two types of mixing vanes. The results will be compared with blind experimental measurements performed in Korea. Due to the fact that a number of the modeling strategies are suggested in literature for such types of flows, we have performed a series of tests to assess the mesh requirements, flow steadiness, turbulence modeling and wall treatment effects. Results of these studies are reported in the present paper. (author)

Shelf life of pie caps with biodegradable films as spacers

Directory of Open Access Journals (Sweden)

Daniela Verónica Escobar Gianni

2013-01-01

Full Text Available Commonly pie caps at market use polyethylene films as spacers between them. This paper studies the conventional spacers replacement with edible and biodegradable films made with whey protein isolate (WPI and potassium sorbate as a preservative. Besides facilitating the separation of pie caps, with this application is intended to increase their shelf life. The films made by the compression molding method were used as spacers in pie caps without preservative in their formula (A and with preservative (B and they were compared with conventional polyethylene spacers (C. During four months, monthly sensory, microbiological and physicochemical (humidity evaluations were done on the pie caps, together with humidity and solubility evaluations of the films. None of the samples showed microbiological or sensory deterioration. The sensory attributes showed no or slight difference in study time. Between samples the differences were minor: the best scores were for sample A in color, sample C in flavor, and samples B and C in texture and overall liking. The edible films have an interesting potential for this application, although studies in disguise the flavor of serum should be done.

Knitting Technologies And Tensile Properties Of A Novel Curved Flat-Knitted Three-Dimensional Spacer Fabrics

Directory of Open Access Journals (Sweden)

Li Xiaoying

2015-09-01

Full Text Available This paper introduces a knitting technique for making innovative curved three-dimensional (3D spacer fabrics by the computer flat-knitting machine. During manufacturing, a number of reinforcement yarns made of aramid fibres are inserted into 3D spacer fabrics along the weft direction to enhance the fabric tensile properties. Curved, flat-knitted 3D spacer fabrics with different angles (in the warp direction were also developed. Tensile tests were carried out in the weft and warp directions for the two spacer fabrics (with and without reinforcement yarns, and their stress–strain curves were compared. The results showed that the reinforcement yarns can reduce the fabric deformation and improve tensile stress and dimensional stability of 3D spacer fabrics. This research can help the further study of 3D spacer fabric when applied to composites.

Pros and cons of symmetrical dual-k spacer technology in hybrid FinFETs

Science.gov (United States)

Pradhan, K. P.; Andrade, M. G. C.; Sahu, P. K.

2016-12-01

The symmetrical dual-k spacer technology in hybrid FinFETs has been widely explored for better electrostatic control of the fin-based devices in nanoscale region. Since, high-k tangible spacer materials are broadly became a matter of study due to their better immunity to the short channel effects (SCEs) in nano devices. However, the only cause that restricts the circuit designers from using high-k spacer is the unreasonable increasing fringing capacitances. This work quantitatively analyzed the benefits and drawbacks of considering two different dielectric spacer materials symmetrically in either sides of the channel for the hybrid device. From the demonstrated results, the inclusion of high-k spacer predicts an effective reduction in off-state leakage along with an improvement in drive current. However, these devices have paid the cost in terms of a high total gate-to-gate capacitance (Cgg) that consequently results poor cutoff frequency (fT) and delay.

Using cathode spacers to minimize reactor size in air cathode microbial fuel cells

KAUST Repository

Yang, Qiao

2012-04-01

Scaling up microbial fuel cells (MFCs) will require more compact reactor designs. Spacers can be used to minimize the reactor size without adversely affecting performance. A single 1.5mm expanded plastic spacer (S1.5) produced a maximum power density (973±26mWm -2) that was similar to that of an MFC with the cathode exposed directly to air (no spacer). However, a very thin spacer (1.3mm) reduced power by 33%. Completely covering the air cathode with a solid plate did not eliminate power generation, indicating oxygen leakage into the reactor. The S1.5 spacer slightly increased columbic efficiencies (from 20% to 24%) as a result of reduced oxygen transfer into the system. Based on operating conditions (1000ς, CE=20%), it was estimated that 0.9Lh -1 of air would be needed for 1m 2 of cathode area suggesting active air flow may be needed for larger scale MFCs. © 2012 Elsevier Ltd.

Systematic validation and atomic force microscopy of non-covalent short oligonucleotide barcode microarrays.

Directory of Open Access Journals (Sweden)

Michael A Cook

Full Text Available BACKGROUND: Molecular barcode arrays provide a powerful means to analyze cellular phenotypes in parallel through detection of short (20-60 base unique sequence tags, or "barcodes", associated with each strain or clone in a collection. However, costs of current methods for microarray construction, whether by in situ oligonucleotide synthesis or ex situ coupling of modified oligonucleotides to the slide surface are often prohibitive to large-scale analyses. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that unmodified 20mer oligonucleotide probes printed on conventional surfaces show comparable hybridization signals to covalently linked 5'-amino-modified probes. As a test case, we undertook systematic cell size analysis of the budding yeast Saccharomyces cerevisiae genome-wide deletion collection by size separation of the deletion pool followed by determination of strain abundance in size fractions by barcode arrays. We demonstrate that the properties of a 13K unique feature spotted 20 mer oligonucleotide barcode microarray compare favorably with an analogous covalently-linked oligonucleotide array. Further, cell size profiles obtained with the size selection/barcode array approach recapitulate previous cell size measurements of individual deletion strains. Finally, through atomic force microscopy (AFM, we characterize the mechanism of hybridization to unmodified barcode probes on the slide surface. CONCLUSIONS/SIGNIFICANCE: These studies push the lower limit of probe size in genome-scale unmodified oligonucleotide microarray construction and demonstrate a versatile, cost-effective and reliable method for molecular barcode analysis.

Nuclear reactor fuel assembly spacer grids

International Nuclear Information System (INIS)

Jabsen, F.S.

1977-01-01

Designs of nuclear reactor fuel assembly spacer grids for supporting and spacing fuel elements are described which do not utilize resilient grid plate protrusions in the peripheral band but retain the advantages inherent in the combination resilient and rigid protrusion cells. (U.K.)

Binding of Dumbbell Oligonucleotides to MoMuLV Reverse Transcriptase: Inhibitory Properties of RNase H Activity

Directory of Open Access Journals (Sweden)

Ajay Kumar

2010-01-01

Full Text Available Dumbbell oligonucleotides with loops of various chemistry were synthesized. Incubation of dumbbell oligonucleotides containing phosphorothioate bonds or trimethylene phosphate linkages in loops with S1 nuclease did not result in significant cleavage under conditions which led to the degradation of dumbbell oligonucleotide containing phophodiester bonds in the loops. The binding of reverse transcriptase of Moloney Murine Leukemia Virus (MoMuLV was evaluated with all the five oligonucleotides. The protein binds to all the dumbbell oligonucleotides with similar affinity. The dissociation constants evaluated using PAGE band mobility shift assays were of the order of 10-7. The inhibitory properties of the retroviral RNase H activity was evaluated using 3H –UTP-labeled RNA:RNA-DNA hybrid. It was found that the best dumbbell oligonucleotide, inhibitor contained phosphorothioate residues in both the loops. Our value studies demonstrated that this particularly designed oligonucleotide displays an IC50 of 18 nM in its inhibition on the reverse transcriptase RNase H activity, a magnitude lower than that of first nucleotide reverse transcriptase of HIV-1, tenofovir, introduced by Gilead Science in the market.

Suppression of subthreshold characteristics variation for junctionless multigate transistors using high-k spacers

International Nuclear Information System (INIS)

Lou, Haijun; Zhang, Baili; Li, Dan; Lin, Xinnan; He, Jin; Chan, Mansun

2015-01-01

In this work, the high-k spacer is proposed to suppress the subthreshold characteristics variation of junctionless multigate transistor (JMT) with non-ideal sidewall angle for the first time. It is demonstrated that the variation of subthreshold characteristics induced by the changing sidewall angle is efficiently suppressed by high-k spacers due to the enhanced corner effect through the fringe capacitance, and the electrostatic integrity of JMTs is also improved at sub-22 nm gate length. Two key parameters of high-k spacer, the thickness and length, have been optimized in terms of the suppression of subthreshold characteristics variation. Then their optimal values are proposed. The benefit of high-k spacer makes JMTs more scalable. (paper)

Associating Oligonucleotides with Positively Charged Liposomes

Czech Academy of Sciences Publication Activity Database

Jurkiewicz, P.; Okruszek, A.; Hof, Martin; Langner, M.

2003-01-01

Roč. 8, č. 1 (2003), s. 77-84 ISSN 1425-8153 R&D Projects: GA MŠk LN00A032 Institutional research plan: CEZ:AV0Z4040901 Keywords : oligonucleotides * fluorescence correlation spectroscopy * DOTAP Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 0.455, year: 2003

Disturbance Elimination for Partial Discharge Detection in the Spacer of Gas-Insulated Switchgears

Directory of Open Access Journals (Sweden)

Guoming Wang

2017-11-01

Full Text Available With the increasing demand for precise condition monitoring and diagnosis of gas-insulated switchgears (GISs, it has become a challenge to improve the detection sensitivity of partial discharge (PD induced in the GIS spacer. This paper deals with the elimination of the capacitive component from the phase-resolved partial discharge (PRPD signal generated in GIS spacers based on discrete wavelet transform (WT. Three types of typical insulation defects were simulated using PD cells. The single PD pulses were detected and were further used to determine the optimal mother wavelet. As a result, the bior6.8 was selected to decompose the PD signal into 8 levels and the signal energy at each level was calculated. The decomposed components related with capacitive disturbance were discarded, whereas those associated with PD were de-noised by a threshold and a thresholding function. Finally, the PRPD signals were reconstructed using the de-noised components.

THERAPEUTIC ANTISENSE OLIGONUCLEOTIDES AGAINST CANCER: HURDLING TO THE CLINIC

Directory of Open Access Journals (Sweden)

Pedro Miguel Duarte Moreno

2014-10-01

Full Text Available Under clinical development since the early 90’s and with two successfully approved drugs (Fomivirsen and Mipomersen, oligonucleotide-based therapeutics have not yet delivered a clinical drug to the market in the cancer field. Whilst many pre-clinical data has been generated, a lack of understanding still exists on how to efficiently tackle all the different challenges presented for cancer targeting in a clinical setting. Namely, effective drug vectorization, careful choice of target gene or synergistic multi-gene targeting are surely decisive, while caution must be exerted to avoid potential toxic, often misleading off-target-effects. Here a brief overview will be given on the nucleic acid chemistry advances that established oligonucleotide technologies as a promising therapeutic alternative and ongoing cancer related clinical trials. Special attention will be given towards a perspective on the hurdles encountered specifically in the cancer field by this class of therapeutic oligonucleotides and a view on possible avenues for success is presented, with particular focus on the contribution from nanotechnology to the field.

Peroxide-mediated desulfurization of phosphorothioate oligonucleotides and its prevention.

Science.gov (United States)

Krotz, Achim H; Mehta, Rahul C; Hardee, Gregory E

2005-02-01

Desulfurization at the internucleotide phosphorothioate linkage of antisense oligonucleotides (ASOs) in dermatological formulations has been investigated using strong ion exchange chromatography and mass spectroscopy. The formation of phosphate diester linkages appeared to arise from a reaction between the phosphorothioate oligonucleotide and a potent oxidizing agent. Screening of excipients used in the formulation indicated that the cause of desulfurization was related to the presence of polyethylene glycol-derived nonionic surfactants MYRJ 52 or BRIJ 58. Autoxidation of the polyethylene glycol chain is suggested as the probable origin for the observed incompatibility. The ability of various antioxidants to prevent oxidative degradation of ASO-1 in simple test systems and in oil-in-water emulsions is described. It is found that in test systems both lipophilic and hydrophilic antioxidants are effective. However, in cream formulation (oil-in-water emulsions) of ASO-1 the addition of hydrophilic antioxidants L-cysteine or DL-alpha-lipoic acid has been shown to be superior in protecting the oligonucleotide from desulfurization upon storage. Copyright 2004 Wiley-Liss, Inc.

A Kinetic Model Explains Why Shorter and Less Affine Enzyme-recruiting Oligonucleotides Can Be More Potent

Directory of Open Access Journals (Sweden)

Lykke Pedersen

2014-01-01

Full Text Available Antisense oligonucleotides complementary to RNA targets promise generality and ease of drug design. The first systemically administered antisense drug was recently approved for treatment and others are in clinical development. Chemical modifications that increase the hybridization affinity of oligonucleotides are reasoned to confer higher potency, i.e., modified oligonucleotides can be dosed at lower concentrations to achieve the same effect. Surprisingly, shorter and less affine oligonucleotides sometimes display increased potency. To explain this apparent contradiction, increased uptake or decreased propensity to form structures have been suggested as possible mechanisms. Here, we provide an alternative explanation that invokes only the kinetics behind oligonucleotide-mediated cleavage of RNA targets. A model based on the law of mass action predicts, and experiments support, the existence of an optimal binding affinity. Exaggerated affinity, and not length per se, is detrimental to potency. This finding clarifies how to optimally apply high-affinity modifications in the discovery of potent antisense oligonucleotide drugs.

BWR fuel assembly with improved spacer and fuel bundle design for enhanced thermal-hydraulic performance

International Nuclear Information System (INIS)

Mildrum, C.M.; Taleyarkhan, R.P.

1987-01-01

In a fuel assembly having a bundle of elongated fuel rods disposed in side-by-side relationship so as to form an array of spaced fuel rods, an outer tubular flow channel surrounding the fuel rods so as to direct flow of coolant/moderator fluid along the fuel rods, a hollow water cross extending centrally through and interconnected with the outer flow channel so as to divide the channel into separate compartments and the bundle of fuelrods into a plurality of mini-bundles thereof being disposed in the compartments, and spacers axially displaced along the fuel rods in each of the mini-bundles thereof. Each spacer is composed of inner and outer means which together define spacer cells at corner, side and interior locations of the spacer and have respective protrusions formed thereon which extend into cells so as to maintain the fuel rods received through the spacer cells in laterally spaced relationships. The improvement is described which comprises: (a) a generally uniform poison coating within at least a majority of the fuel rods; (b) a predetermined pattern of fuel enrichment with respect to the fuel rods of each mini-bundle thereof which together with the uniform poison coating within the fuel rods ensures that the packing powers of the fuel rods in the corner and side cells of the spacers are less than the peaking power of a leading one of the fuel rods in the interior cells of the spacers; and (c) each of the fuel rods being received through the cells of each spacer having a diametric size smaller than that of each of the fuel rods received through the side and interior cells of each spacer, the diametric sizes of each of the fuel rods received through the side and interior cells of each spacer being generally equal

Versatile functionalization of nanoelectrodes by oligonucleotides via pyrrole electrochemistry.

Science.gov (United States)

Descamps, Emeline; Nguyen, Khoa; Bouchain-Gautier, Christelle; Filoramo, Arianna; Goux-Capes, Laurence; Goffman, Marcello; Bourgoin, Jean-Philippe; Mailley, Pascal; Livache, Thierry

2010-11-15

Surface modification at the nanometer scale is a challenge for the future of molecular electronics. In particular, the precise anchoring and electrical addressing of biological scaffolds such as complex DNA nanonetworks is of importance for generating bio-directed assemblies of nano-objects for nanocircuit purposes. Herein, we consider the individual modification of nanoelectrodes with different oligonucleotide sequences by an electrochemically driven co-polymerization process of pyrrole and modified oligonucleotide sequences bearing pyrrole monomers. We demonstrate that this one-step technique presents the advantages of simplicity, localization of surface modification, mechanical, biological and chemical stability of the coatings, and high lateral resolution.

Numerical investigation on practicability of reducing MCST by using grid spacer in a tight rod bundle

International Nuclear Information System (INIS)

Zhu, Xiaojing; Morooka, Shinichi; Oka, Yoshiaki

2014-01-01

Highlights: • Standard grid spacer design causes decreased heat transfer in a tight rod bundle. • Heat transfer is greatly enhanced by flow-enhancing features. • Swirling flow adversely affects the heat transfer downstream of grid spacer. • Enhanced heat transfer by existing grid spacer is limited in a short region. • Improved grid spacer can effectively reduce MCST. - Abstract: The numerical investigation was carried out to reveal the practicability of reducing the maximum cladding surface temperature (MCST) within the inner sub-channel of a tight, hexagon rod bundle using commercial CFD code STAR CCM+ 6.04. The special heat transfer and pressure drop characteristics caused by four existing grid spacer designs were discussed in detail by analyzing the effects of grid strap length, different flow enhancing features and different Reynolds numbers. It was found that the local heat transfer within the grid strap is greatly enhanced due to the raised flow velocity. Both the standard grid spacer and the grid spacer with split-vanes cause decreased heat transfer in the downstream region. The friction drag is very influential in the tight rod bundle and can eliminate the positive effect of flow blockage on the heat transfer performance. The grid spacer with flow blockage discs induces relatively good heat transfer performance and higher pressure drop within sub-channels, indicating a tradeoff between the heat transfer augmentation and the pressure drop. The combination of multiple existing grid spacers can reduce the MCST to a certain level, but the corresponding disadvantages cannot be ignored. The improved grid spacer design was proposed based on the overall considerations of heat transfer and pressure drop characteristics and has been proved more suitable to widely reduce MCST for SCWR than any other grid spacer designs involved in present study

Spacer grid for a nuclear reactor fuel assembly

International Nuclear Information System (INIS)

Jabsen, F.S.

1978-01-01

The spacer grid consists of pairs of plates forming rectangular cells and enclosing the cylindrical fuel assemblies. They have got rigid as well as elastic projections extending into the cells and holding the fuel assemblies. Additional pairs of plates are arranged in about the center of the grid of plates. They have got only elastic projections extending on both sides of the plates into one cell each. This spacer grid may be used for reactor cores with and without fuel channels. By the combination of spring-elastic and rigid projections there is obtained a reinforced outer tie. Hydraulic pressure losses, parasitic neutron capture, and hot spots are essentially reduced. (DG) [de

Detection of DNA oligonucleotides with base mutations by terahertz spectroscopy and microstructures.

Directory of Open Access Journals (Sweden)

Mingjie Tang

Full Text Available DNA oligonucleotides with a 5-base mutation at the 3'-terminus were investigated by terahertz (THz spectroscopy in a marker-free manner. The four single-stranded oligonucleotides with 17nt have been detected with specificity on a microfluidic chip, and corroborated by spectral measurements with split-ring resonators. The number of hydrogen bonds formed between the oligonucleotide and its surrounding water molecules, deemed a key contribution to the THz absorption of biological solutions, was explored by molecular dynamics simulations to explain the experimental findings. Our work underlies the feasibility of THz spectroscopy combined with microstructures for marker-free detection of DNA, which may form the basis of a prospective diagnostic tool for studying genic mutation.

Biofouling patterns in spacer filled channels: High resolution imaging for characterization of heterogeneous biofilms

KAUST Repository

Staal, Marc

2017-08-15

Biofilms develop in heterogeneous patterns at a µm scale up to a cm scale, and patterns become more pronounced when biofilms develop under complex hydrodynamic flow regimes. Spatially heterogeneous biofilms are especially known in spiral wound reverse osmosis (RO) and nanofiltration (NF) membrane filtration systems used for desalination and wastewater reuse to produce high quality (drinking) water. These spiral wound membrane modules contain mesh-like spacer structures used to create an intermembrane space and improve water mixing. Spacers create inhomogeneous water flow patterns resulting in zones favouring biofilm growth, possibly leading to biofouling thus hampering water production. Oxygen sensing planar optodes were used to visualize variations in oxygen decrease rates (ODR). ODR is an indication of biofilm activity. In this study, ODR images of multiple repetitive spacer areas in a membrane fouling simulator were averaged to produce high resolution, low noise ODR images. Averaging 40 individual spacer areas improved the ODR distribution image significantly and allowed comparison of biofilm patterning over a spacer structure at different positions in an RO filter. This method clearly showed that most active biofilm accumulated on and in direct vicinity of the spacer. The averaging method was also used to calculate the deviation of ODR patterning from individual spacer areas to the average ODR pattern, proposing a new approach to determine biofilm spatial heterogeneity. This study showed that the averaging method can be applied and that the improved, averaged ODR images can be used as an analytical, in-situ, non-destructive method to assess and quantify the effect of membrane installation operational parameters or different spacer geometries on biofilm development in spiral wound membrane systems characterized by complex hydrodynamic conditions.

Complementarily addressed modification and cleavage of a single-stranded fragment of DNA with the aid of alkylating derivatives of oligonucleotides

International Nuclear Information System (INIS)

Brosalina, E.B.; Vlasov, V.V.; Kutyavin, I.V.; Mamaev, S.V.; Pletnev, A.G.; Podyminogin, M.A.

1986-01-01

The chemical modification of a 303-nucleotide single-stranded fragment of DNA by alkylating oligonucleotide derivatives bearing 4-[N-methyl-N-(2-chloroethyl)amino]benzyl groups in the 5'-terminal phosphate of the 3'-terminal ribose residue has been investigated. It has been shown that under the conditions of the formation of a complex with the DNA fragment both types of derivatives specifically alkylate nucleotides of the DNA fragments that are located directly adjacent to the sections complementary to the oligonucleotides bearing the reactive groups. Alkylation takes place with a high efficiency, and the DNA fragment can be cleaved specifically at the position of the alkylated nucleotides

5 X 5 rod bundle flow field measurements downstream a PWR spacer grid

Energy Technology Data Exchange (ETDEWEB)

Castro, Higor F.P.; Silva, Vitor V A.; Santos, André A.C.; Veloso, Maria A.F., E-mail: higorfabiano@gmail.com, E-mail: mdora@nuclear.ufmg.br, E-mail: vitors@cdtn.br, E-mail: aacs@cdtn.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil); Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

2017-07-01

The spacer grids are structures present in nuclear fuel assembly of Pressurized Water Reactors (PWR). They play an important structural role and also assist in heat removal through the assembly by promoting increased turbulence of the flow. Understanding the flow dynamics downstream the spacer grid is paramount for fuel element design and analysis. This paper presents water flow velocity profiles measurements downstream a spacer grid in a 5 x 5 rod bundle test rig with the objective of highlighting important fluid dynamic behavior near the grid and supplying data for CFD simulation validation. These velocity profiles were obtained at two different heights downstream the spacer grid using a LDV (Laser Doppler Velocimetry) through the top of test rig. The turbulence intensities and patterns of the swirl and cross flow were evaluated. The tests were conducted for Reynolds numbers ranging from 1.8 x 10{sup 4} to 5.4 x 10{sup 4}. This experimental research was carried out in thermo-hydraulics laboratory of Nuclear Technology Development Center – CDTN. Results show great repeatability and low uncertainties (< 1.24 %). Details of the flow field show how the mixture and turbulence induced by the spacer grid quickly decays downstream the spacer grid. It is shown that the developed methodology can supply high resolution low uncertainty results that can be used for validation of CFD simulations. (author)

5 X 5 rod bundle flow field measurements downstream a PWR spacer grid

International Nuclear Information System (INIS)

Castro, Higor F.P.; Silva, Vitor V A.; Santos, André A.C.; Veloso, Maria A.F.

2017-01-01

The spacer grids are structures present in nuclear fuel assembly of Pressurized Water Reactors (PWR). They play an important structural role and also assist in heat removal through the assembly by promoting increased turbulence of the flow. Understanding the flow dynamics downstream the spacer grid is paramount for fuel element design and analysis. This paper presents water flow velocity profiles measurements downstream a spacer grid in a 5 x 5 rod bundle test rig with the objective of highlighting important fluid dynamic behavior near the grid and supplying data for CFD simulation validation. These velocity profiles were obtained at two different heights downstream the spacer grid using a LDV (Laser Doppler Velocimetry) through the top of test rig. The turbulence intensities and patterns of the swirl and cross flow were evaluated. The tests were conducted for Reynolds numbers ranging from 1.8 x 10"4 to 5.4 x 10"4. This experimental research was carried out in thermo-hydraulics laboratory of Nuclear Technology Development Center – CDTN. Results show great repeatability and low uncertainties (< 1.24 %). Details of the flow field show how the mixture and turbulence induced by the spacer grid quickly decays downstream the spacer grid. It is shown that the developed methodology can supply high resolution low uncertainty results that can be used for validation of CFD simulations. (author)

Research report on development of spacer grid strap for AFA 3G fuel assembly

International Nuclear Information System (INIS)

Ye Yuandong

2004-11-01

The current development and tendency for fuel assemblies being of low leakage, high burn-up and long cycle fuel reload in the world are presented, and the necessity and feasibility to develop the spacer grid for high burn-up fuel assembly are elaborated. Considering all the activities in implementing of spacer grid and the technical difficulties in machining of tools, the major technological processes are introduced; the research program and the approaches to develop the spacer grid while research targets and overall schedule are defined and some key technical points and applicable practices are discussed. Finally the requirements and the conditions necessary for developing of spacer grid are proposed. (authors)

A functional analysis of the spacer of V(D)J recombination signal sequences.

Science.gov (United States)

Lee, Alfred Ian; Fugmann, Sebastian D; Cowell, Lindsay G; Ptaszek, Leon M; Kelsoe, Garnett; Schatz, David G

2003-10-01

During lymphocyte development, V(D)J recombination assembles antigen receptor genes from component V, D, and J gene segments. These gene segments are flanked by a recombination signal sequence (RSS), which serves as the binding site for the recombination machinery. The murine Jbeta2.6 gene segment is a recombinationally inactive pseudogene, but examination of its RSS reveals no obvious reason for its failure to recombine. Mutagenesis of the Jbeta2.6 RSS demonstrates that the sequences of the heptamer, nonamer, and spacer are all important. Strikingly, changes solely in the spacer sequence can result in dramatic differences in the level of recombination. The subsequent analysis of a library of more than 4,000 spacer variants revealed that spacer residues of particular functional importance are correlated with their degree of conservation. Biochemical assays indicate distinct cooperation between the spacer and heptamer/nonamer along each step of the reaction pathway. The results suggest that the spacer serves not only to ensure the appropriate distance between the heptamer and nonamer but also regulates RSS activity by providing additional RAG:RSS interaction surfaces. We conclude that while RSSs are defined by a "digital" requirement for absolutely conserved nucleotides, the quality of RSS function is determined in an "analog" manner by numerous complex interactions between the RAG proteins and the less-well conserved nucleotides in the heptamer, the nonamer, and, importantly, the spacer. Those modulatory effects are accurately predicted by a new computational algorithm for "RSS information content." The interplay between such binary and multiplicative modes of interactions provides a general model for analyzing protein-DNA interactions in various biological systems.

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A-T phosphoramidite building blocks.

Science.gov (United States)

Schmidtgall, Boris; Höbartner, Claudia; Ducho, Christian

2015-01-01

Modifications of the nucleic acid backbone are essential for the development of oligonucleotide-derived bioactive agents. The NAA-modification represents a novel artificial internucleotide linkage which enables the site-specific introduction of positive charges into the otherwise polyanionic backbone of DNA oligonucleotides. Following initial studies with the introduction of the NAA-linkage at T-T sites, it is now envisioned to prepare NAA-modified oligonucleotides bearing the modification at X-T motifs (X = A, C, G). We have therefore developed the efficient and stereoselective synthesis of NAA-linked 'dimeric' A-T phosphoramidite building blocks for automated DNA synthesis. Both the (S)- and the (R)-configured NAA-motifs were constructed with high diastereoselectivities to furnish two different phosphoramidite reagents, which were employed for the solid phase-supported automated synthesis of two NAA-modified DNA oligonucleotides. This represents a significant step to further establish the NAA-linkage as a useful addition to the existing 'toolbox' of backbone modifications for the design of bioactive oligonucleotide analogues.

Nucleobase-modified antisense oligonucleotides containing 5-(phenyltriazol)-2′-deoxyuridine nucleotides induce exon-skipping

DEFF Research Database (Denmark)

Le, Bao T.; Hornum, Mick; Sharma, Pawan K.

2017-01-01

Chemically-modified antisense oligonucleotide-mediated exon-skipping has been validated as a therapeutic strategy for tackling several disease pathologies, particularly duchenne muscular dystrophy. To date, only sugar-modified and internucleotide linkage-modified oligonucleotide chemistries have...

Suppression of human immunodeficiency virus type 1 activity in vitro by oligonucleotides which form intramolecular tetrads.

Science.gov (United States)

Rando, R F; Ojwang, J; Elbaggari, A; Reyes, G R; Tinder, R; McGrath, M S; Hogan, M E

1995-01-27

An oligonucleotide (I100-15) composed of only deoxyguanosine and thymidine was able to inhibit human immunodeficiency virus type-1 (HIV-1) in culture assay systems. I100-15 did not block virus entry into cells but did reduce viral-specific transcripts. As assessed by NMR and polyacrylamide gel methods, I100-15 appears to form a structure in which two stacked guanosine tetrads are connected by three two-base long loops. Structure/activity experiments indicated that formation of intramolecular guanosine tetrads was necessary to achieve maximum antiviral activity. The single deoxyguanosine nucleotide present in each loop was found to be extremely important for the overall antiviral activity. The toxicity of I100-15 was determined to be well above the 50% effective dose (ED50) in culture which yielded a high therapeutic index (> 100). The addition of a cholesterol moiety to the 3' terminus of I100-15 (I100-23) reduced the ED50 value to less than 50 nM (from 0.12 microM for I100-15) and increased the duration of viral suppression to greater than 21 days (versus 7-10 days for I100-15) after removal of the drug from infected cell cultures. The favorable therapeutic index of such molecules coupled with the prolonged suppression of HIV-1, suggest that such compounds further warrant investigation as potential therapeutic agents.

Campylobacter jejuni acquire new host-derived CRISPR spacers when in association with bacteriophages harbouring a CRISPR-like Cas4 protein

Directory of Open Access Journals (Sweden)

Ian F. Connerton

2015-01-01

Full Text Available Campylobacter jejuni is a worldwide cause of human diarrhoeal disease. Clustered Repetitively Interspaced Palindromic Repeats (CRISPRs and associated proteins allow Bacteria and Archaea to evade bacteriophage and plasmid infection. Type II CRISPR systems are found in association with combinations of genes encoding the CRISPR-associated Cas1, Cas2, Cas4 or Csn2, and Cas9 proteins. C. jejuni possesses a minimal subtype II-C CRISPR system containing cas1, cas2, and cas9 genes whilst cas4 is notably absent. Cas4 proteins possess 5ʹ-3ʹ exonuclease activity to create recombinogenic-ends for spacer acquisition. Here we report a conserved Cas4-like protein in Campylobacter bacteriophages that creates a novel split arrangement between the bacteriophage and host that represents a new twist in the bacteriophage/host co-evolutionary arms race. The continuous association of bacteriophage and host in the carrier state life cycle of C. jejuni provided an opportunity to study spacer acquisition in this species. Remarkably all the spacer sequences observed were of host origin. We hypothesise that Campylobacter bacteriophages can use Cas4-like protein to activate spacer acquisition to use host DNA as an effective decoy to bacteriophage DNA. Bacteria that acquire self-spacers and escape phage infection must overcome CRISPR-mediated autoimmunity either by loss of the interference functions leaving them susceptible to foreign DNA incursion or tolerate changes in gene regulation.

Transcriptome changes in STSV2-infected Sulfolobus islandicus REY15A undergoing continuous CRISPR spacer acquisition

DEFF Research Database (Denmark)

León-Sobrino, Carlos; Kot, Witold P; Garrett, Roger A

2016-01-01

A transcriptome study was performed on Sulfolobus islandicus REY15A actively undergoing CRISPR spacer acquisition from the crenarchaeal monocaudavirus STSV2 in rich and basal media over a 6 day period. Spacer acquisition preceded strong host growth retardation, altered transcriptional activity...... of four different CRISPR-Cas modules and changes in viral copy numbers, and with significant differences in the two media. Transcript levels of proteins involved in the cell cycle were reduced, while those of DNA replication, DNA repair, transcriptional regulation, and some antitoxin-toxin pairs...... and transposases were unchanged or enhanced. Antisense RNAs were implicated in the transcriptional regulation of adaptation and interference modules of the type I-A CRISPR-Cas system and evidence was found for the occurrence of functional coordination between the single CRISPR-Cas adaptation module...

Effect of plastic spacer handling on salbutamol lung deposition in asthmatic children

DEFF Research Database (Denmark)

Lipworth, Brian J; Lee, Daniel K C; Anhøj, Jacob

2002-01-01

AIMS: To study the effects of electrostatics in a plastic spacer on the lung deposition of salbutamol in asthmatic children. METHODS: Twenty-five children (5-12 years) with mild asthma were given salbutamol hydrofluoroalkane pressurized metered dose inhaler 400 micro g via a 750 ml plastic spacer...

The detection and differentiation of canine respiratory pathogens using oligonucleotide microarrays.

Science.gov (United States)

Wang, Lih-Chiann; Kuo, Ya-Ting; Chueh, Ling-Ling; Huang, Dean; Lin, Jiunn-Horng

2017-05-01

Canine respiratory diseases are commonly seen in dogs along with co-infections with multiple respiratory pathogens, including viruses and bacteria. Virus infections in even vaccinated dogs were also reported. The clinical signs caused by different respiratory etiological agents are similar, which makes differential diagnosis imperative. An oligonucleotide microarray system was developed in this study. The wild type and vaccine strains of canine distemper virus (CDV), influenza virus, canine herpesvirus (CHV), Bordetella bronchiseptica and Mycoplasma cynos were detected and differentiated simultaneously on a microarray chip. The detection limit is 10, 10, 100, 50 and 50 copy numbers for CDV, influenza virus, CHV, B. bronchiseptica and M. cynos, respectively. The clinical test results of nasal swab samples showed that the microarray had remarkably better efficacy than the multiplex PCR-agarose gel method. The positive detection rate of microarray and agarose gel was 59.0% (n=33) and 41.1% (n=23) among the 56 samples, respectively. CDV vaccine strain and pathogen co-infections were further demonstrated by the microarray but not by the multiplex PCR-agarose gel. The oligonucleotide microarray provides a highly efficient diagnosis alternative that could be applied to clinical usage, greatly assisting in disease therapy and control. Copyright © 2017 Elsevier B.V. All rights reserved.

Bimetallic spacer means for a nuclear fuel assembly

International Nuclear Information System (INIS)

Anthony, A.J.

1981-01-01

A bimetallic spacer means designed to be cooperatively associated with a nuclear fuel assembly and operative to resist the occurrence of in-reactor bowing of the nuclear fuel assembly. The subject bimetallic spacer means in accord with one embodiment of the invention includes a member formed, at least principally, of Zircaloy to which are attached a plurality of stainless steel strips. The latter stainless steel strips are located on the external surface of the Zircaloy member and with the major axis of each of the plurality of stainless steel strips extending substantially perpendicular to the major axis of the Zircaloy member. In accord with another embodiment of the invention, the subject bimetallic spacer means includes a member formed at least principally of Zircaloy to which a plurality of stainless steel strips are attached so as to be positioned thereon externally thereof and with the major axis of each of the plurality of stainless steel strips extending substantially parallel to the major axis of the Zircaloy member. In accord with a further embodiment of the invention, the stainless steel strips are attached to preselected members, each embodying at least a cladding of Zircaloy, which are located in the rows of fuel rods that define the perimeter of the fuel matrix of the nuclear fuel assembly. In each of the embodiments, the stainless steel strips during power production expand outwardly to a greater extent than do the members to which the stainless steel strips are attached, thereby forming stiff springs which abut against like bimetallic spacer means with which the other nuclear fuel assemblies are provided in a given nuclear reactor core to thus prevent the occurrence of in-reactor bowing of the nuclear fuel assemblies. Namely, the stainless steel strips expand laterally relative to the fuel assembly and thereby occupy the space adjacent to the external surface of the fuel assembly

Functional regulation of RNA-induced silencing complex by photoreactive oligonucleotides.

Science.gov (United States)

Matsuyama, Yohei; Yamayoshi, Asako; Kobori, Akio; Murakami, Akira

2014-02-01

We developed a novel method for regulation of RISC function by photoreactive oligonucleotides (Ps-Oligo) containing 2'-O-psoralenylmethoxyethyl adenosine (Aps). We observed that inhibitory effects of Ps-Oligos on RISC function were enhanced by UV-irradiation compared with 2'-O-methyl-oligonucleotide without Aps. These results suggest Ps-Oligo inhibited RISC function by cross-linking effect, and we propose that the concept described in this report may be promising and applicable one to regulate the small RNA-mediated post-transcriptional regulation. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Application of a hydrogel spacer for postoperative salvage radiotherapy of prostate cancer

International Nuclear Information System (INIS)

Pinkawa, Michael; Schubert, Carolin; Escobar-Corral, Nuria; Holy, Richard; Eble, Michael J.

2015-01-01

In contrast to primary radiotherapy, no reports are available for a hydrogel spacer application in postoperative salvage radiotherapy for prostate cancer. A 77-year-old patient presented 20 years after radical prostatectomy with a digitally palpable local recurrence at the urethrovesical anastomosis (PSA 5.5 ng/ml). The hydrogel spacer (10 ml, SpaceOAR trademark) was injected between the local recurrence and rectal wall under transrectal ultrasound guidance. Treatment planning was performed with an intensity-modulated technique up to a total dose of 76 Gy in 2-Gy fractions. The same planning was performed based on computed tomography before spacer injection for comparison. The local recurrence, initially directly on the rectal wall, could be displaced more than 1 cm from the rectal wall after hydrogel injection. With a mean total dose of 76 Gy to the planning target volume, rectal wall volumes included in the 70 Gy, 60 Gy, 50 Gy isodoses were 0 cm 3 , 0 cm 3 , and 0.4 cm 3 with a spacer and 2.9 cm 3 , 4.5 cm 3 , and 6.2 cm 3 without a spacer, respectively. The patient reported rectal urgency during radiotherapy, completely resolving after the end of treatment. The PSA level was 5.4 ng/ml a week before the end of radiotherapy and dropped to 0.9 ng/ml 5 months after radiotherapy. A hydrogel spacer was successfully applied for dose-escalated radiotherapy in a patient with macroscopic local prostate cancer recurrence at the urethrovesical anastomosis to decrease the dose at the rectal wall. This option can be considered in specifically selected patients. (orig.) [de

Mechanical test for fuel assembly spacer grid

International Nuclear Information System (INIS)

Kang, Heung Seok; Jeong, Yeon Ho; Song, Kee Nam; Kim, Hyung Kyu; Yoon, Kyung Ho; Bang, Je Keun.

1997-06-01

In order to propose some tests for a new spacer grid, the grid mechanical tests performed by ABB-CE, KWU and Westinghouse have been investigated. It is known that a static compression test, a dynamic impact test, and a grid spring characteristic test were commonly carried out by the vendors when a prototype spacer grid was developed. The static compression test is to measure the stresses on the strips as well as to obtain the grid stiffness. The dynamic impact test is to get some basic data for accident analysis such as impact stiffness, impact strength, and coefficient of restitution. Since each fuel vendor has his theory on an accident analysis, every vendor employs his particular method for the dynamic impact test. The dynamic impact test can be divided into two in accordance with the number of impact face, and the duration of impact pulse. One is an one-sided impact test and the other is an through-gird impact test. The duration of the impact pulse for the former is considerably shorter than the latter. Therefore, the grid can endure much higher load under the one-sided impact condition than under the through-grid impact condition. The grid spring characteristic test is to obtain a force versus deflection curve. This curve is very important in designing the spacer grid to provide fuel rods with a sound supports in core. (author). 18 tabs., 26 figs

Experimental investigations of turbulent flows in rod bundles with and without spacer grids

International Nuclear Information System (INIS)

Trippe, G.

1979-07-01

In the thermofluiddynamic design of liquid metal cooled reactor fuel elements the lack of experimentally confirmed knowledge of the three-dimensional flow events in rod bundles provided with spacer grids has appeared as a significant problem. To close this gap of knowledge, detailed measurements of the local velocities were made on a 19-rod bundle model. The Pitot method of differential pressure measurements was used as the measuring system. In the first part of the work the fully developed flow regime not influenced by spacers was investigated. A simple relation was derived for distributing the mass flow among the subchannels of a rod bundle; it is but slightly dependent on the Reynolds number. This relation allows a quick, coarse calculation of the distribution of the undisturbed, fully developed mass flow in bundles with similar geometries. By evaluation of further experiments known from the literature, empirical relationships were found for the local velocity distribution within the subchannels of such bundles. In the second part the effect of grid shaped spacers was investigated. The three-dimensional flow events caused by the spacers were completely recorded and interpreted physically. The deeper understanding of these flow processes can now serve to improve the model concept used in the present design computer programs. Single results of the investigations which take primary importance are the quantitative relations existing between the changes of mass flow in the bundle boundary zone, caused by a spacer, and the geometry of this spacer. The transferability to other bundle geometries was discussed and delimited. Moreover, it was shown that the mass flow in the bundle boundary zone can be successively reduced by spacers placed one behind the other in the bundle. A noticeable dependence of flow events on the Reynolds number was not found for the range relevant in practical application (30.000 [de

The independent loss model with ordered insertions for the evolution of CRISPR spacers.

Science.gov (United States)

Baumdicker, F; Huebner, A M I; Pfaffelhuber, P

2018-02-01

Today, the CRISPR (clustered regularly interspaced short palindromic repeats) region within bacterial and archaeal genomes is known to encode an adaptive immune system. We rely on previous results on the evolution of the CRISPR arrays, which led to the ordered independent loss model, introduced by Kupczok and Bollback (2013). When focusing on the spacers (between the repeats), new elements enter a CRISPR array at rate θ at the leader end of the array, while all spacers present are lost at rate ρ along the phylogeny relating the sample. Within this model, we compute the distribution of distances of spacers which are present in all arrays in a sample of size n. We use these results to estimate the loss rate ρ from spacer array data for n=2 and n=3. Copyright © 2017 Elsevier Inc. All rights reserved.

Technology of electron beam welding for Zr-4 alloy spacer grid

International Nuclear Information System (INIS)

Pei Qiusheng; Wu Xueyi; Yang Qishun

1989-10-01

The welding technology for Zr-4 alloy spacer grid by using vacuum electron beam was studied. Through a series of welding technological experiments, metallographic examinations of seam structure and detecting tests for welding defect by X-ray defectoscopy, a good welding technology was selected to meet the requirements. The experimental results indicated that the Zr-4 alloy spacer grid welded by vacuum electron beam welding is feasible

A PCR method targeting internal transcribed spacers: the simultaneous detection of Babesia bigemina and Babesia bovis in cattle.

Science.gov (United States)

Liu, Junlong; Guan, Guiquan; Liu, Aihong; Li, Youquan; Yin, Hong; Luo, Jianxun

2014-03-01

In this study, two pairs of oligonucleotide primers were designed according to the nucleotide sequence of the internal transcribed spacers (ITSs) of Babesia bigemina and B. bovis isolates from China. The primers were used in a multiplex PCR to detect parasite DNA in blood samples from cattle. There was no cross reactions with B. ovata, B. major, B. sp. Kashi, Theileria annulata, T. sergenti, T. sinensis or normal bovine DNA. The sensitivity of multiplex PCR assay was 1 pg and 10 pg DNA for B. bigemina and B. bovis, respectively. A total of 260 field blood samples collected from cattle in five provinces of China were analyzed by multiplex PCR and light microscopy. PCR testing revealed that 7.3% (19/260) and 5.8% (15/260) of cattle were positive for B. bigemina and B. bovis and 1.2% (3/260) of cattle were co-infected with B. bigemina and B. bovis. Using light microscopy, 2.3% (6/260) and 1.5% (4/260) of cattle were infected by B. bigemina and B. bovis, respectively, and no co-infection was found. The results showed that the multiplex PCR developed in the present study could be an alternative diagnostic tool for the detection of B. bovis and B. bigemina infection in cattle.

Short G-rich oligonucleotides as a potential therapeutic for Huntington's Disease

Directory of Open Access Journals (Sweden)

Parekh-Olmedo Hetal

2006-10-01

Full Text Available Abstract Background Huntington's Disease (HD is an inherited autosomal dominant genetic disorder in which neuronal tissue degenerates. The pathogenesis of the disease appears to center on the development of protein aggregates that arise initially from the misfolding of the mutant HD protein. Mutant huntingtin (Htt is produced by HD genes that contain an increased number of glutamine codons within the first exon and this expansion leads to the production of a protein that misfolds. Recent studies suggest that mutant Htt can nucleate protein aggregation and interfere with a multitude of normal cellular functions. Results As such, efforts to find a therapy for HD have focused on agents that disrupt or block the mutant Htt aggregation pathway. Here, we report that short guanosine monotonic oligonucleotides capable of adopting a G-quartet structure, are effective inhibitors of aggregation. By utilizing a biochemical/immunoblotting assay as an initial screen, we identified a 20-mer, all G-oligonucleotide (HDG as an active molecule. Subsequent testing in a cell-based assay revealed that HDG was an effective inhibitor of aggregation of a fusion protein, comprised of a mutant Htt fragment and green fluorescent protein (eGFP. Taken together, our results suggest that a monotonic G-oligonucleotide, capable of adopting a G-quartet conformation is an effective inhibitor of aggregation. This oligonucleotide can also enable cell survival in PC12 cells overexpressing a mutant Htt fragment fusion gene. Conclusion Single-stranded DNA oligonucleotides capable of forming stable G-quartets can inhibit aggregation of the mutant Htt fragment protein. This activity maybe an important part of the pathogenecity of Huntington's Disease. Our results reveal a new class of agents that could be developed as a therapeutic approach for Huntington's Disease.

In vitro performance of three combinations of spacers and pressurized metered dose inhalers for treatment in children

DEFF Research Database (Denmark)

Berg, E; Madsen, J; Bisgaard, H

1998-01-01

The performance of pressurized metered dose inhalers (pMDIs) and spacers in correct dose recommendations is important, but limited information on dose delivery and fine-particle dose from different combinations of spacers and pMDIs is available. In this study, three combinations of spacers and p...... and spacers, with the NebuChamber giving the highest dose, both as delivered dose and in droplets account for these differences....

Modulation of 5' splice site selection using tailed oligonucleotides carrying splicing signals

Directory of Open Access Journals (Sweden)

Elela Sherif

2006-01-01

Full Text Available Abstract Background We previously described the use of tailed oligonucleotides as a means of reprogramming alternative pre-mRNA splicing in vitro and in vivo. The tailed oligonucleotides that were used interfere with splicing because they contain a portion complementary to sequences immediately upstream of the target 5' splice site combined with a non-hybridizing 5' tail carrying binding sites for the hnRNP A1/A2 proteins. In the present study, we have tested the inhibitory activity of RNA oligonucleotides carrying different tail structures. Results We show that an oligonucleotide with a 5' tail containing the human β-globin branch site sequence inhibits the use of the 5' splice site of Bcl-xL, albeit less efficiently than a tail containing binding sites for the hnRNP A1/A2 proteins. A branch site-containing tail positioned at the 3' end of the oligonucleotide also elicited splicing inhibition but not as efficiently as a 5' tail. The interfering activity of a 3' tail was improved by adding a 5' splice site sequence next to the branch site sequence. A 3' tail carrying a Y-shaped branch structure promoted similar splicing interference. The inclusion of branch site or 5' splice site sequences in the Y-shaped 3' tail further improved splicing inhibition. Conclusion Our in vitro results indicate that a variety of tail architectures can be used to elicit splicing interference at low nanomolar concentrations, thereby broadening the scope and the potential impact of this antisense technology.

On possible contribution of standing wave like spacer dynamics in polymer liquid crystals to quasi-elastic cold neutron scattering spectra

International Nuclear Information System (INIS)

Jecl, R.; Cvikl, B.

1998-01-01

The quasi-elastic cold neutron incoherent scattering law, QNS, for the assumed case of transversal standing wave type of motion of the linear chain a spacer-of the polyacrylate polymer liquid crystal, based upon the random walk of the particle between two perfectly potential barriers, is derived. The spacer protons are taken to vibrate (within the stationary plane) transversely to the line joining the oxygen atoms in a way where they are all simultaneously displaced in the same direction with amplitudes of the standing wave fundamental mode of the vibration excited. The calculated relevant incoherent scattering law is found to be a non-distinct function of the scattering vector Q, in the sense that the postulated dynamical effect of the spacer protons causes the peak value of the calculated incoherent scattering law, S(Q,ω), to remain constant throughout the experimentally accessible range of the scattering vector Q. It appears that, when the experimental resolution broadening effects is taken into account, the contribution of the postulated dynamical behavior to the measured QNS spectra might be small, particularly so, if dome additional motion of the scatters is present, and consequently the standing wave like spacer dynamics in polymer liquid crystals will be very difficult to be identified uniquely in the quasielastic neutron scattering experiments.(author)

Procedure on the Impact Characteristic Test for the One-sided and Thru-grid Spacer Grid

International Nuclear Information System (INIS)

Yoon, Kyung Ho; Kim, Jae Yong; Lee, Kang Hee; Song, Kee Nam

2006-09-01

In order to perform the one-sided and the through-grid impact tests for a new developed spacer grid, the drop type impact test machines were established. The dynamic impact test is to get some basic data for accident analysis such as impact strength, stiffness, and coefficient of the restitution. Furthermore, these developed test methods and procedures will be qualified standard for increasing the reliability of the test results. Chapter 2 provides an introduction to the test facilities and instrumentations. Chapter 3 describes on how spacer grid and the single span fuel assembly specimen will be prepared. In addition to this, how to set up these testing machines. Chapter 4 illustrates detail test procedure on how to acquire impact signal of the two kinds of the specimen. Chapter 5 deals with signal processing and analysis for the test data. Finally, chapter 6 summarise the overall test procedure and the test method

Selective Detection of Peptide-Oligonucleotide Heteroconjugates Utilizing Capillary HPLC-ICPMS

Science.gov (United States)

Catron, Brittany; Caruso, Joseph A.; Limbach, Patrick A.

2012-06-01

A method for the selective detection and quantification of peptide:oligonucleotide heteroconjugates, such as those generated by protein:nucleic acid cross-links, using capillary reversed-phase high performance liquid chromatography (cap-RPHPLC) coupled with inductively coupled plasma mass spectrometry detection (ICPMS) is described. The selective detection of phosphorus as 31P+, the only natural isotope, in peptide-oligonucleotide heteroconjugates is enabled by the elemental detection capabilities of the ICPMS. Mobile phase conditions that allow separation of heteroconjugates while maintaining ICPMS compatibility were investigated. We found that trifluoroacetic acid (TFA) mobile phases, used in conventional peptide separations, and hexafluoroisopropanol/triethylamine (HFIP/TEA) mobile phases, used in conventional oligonucleotide separations, both are compatible with ICPMS and enable heteroconjugate separation. The TFA-based separations yielded limits of detection (LOD) of ~40 ppb phosphorus, which is nearly seven times lower than the LOD for HFIP/TEA-based separations. Using the TFA mobile phase, 1-2 pmol of a model heteroconjugate were routinely separated and detected by this optimized capLC-ICPMS method.

i-Genome: A database to summarize oligonucleotide data in genomes

Directory of Open Access Journals (Sweden)

Chang Yu-Chung

2004-10-01

Full Text Available Abstract Background Information on the occurrence of sequence features in genomes is crucial to comparative genomics, evolutionary analysis, the analyses of regulatory sequences and the quantitative evaluation of sequences. Computing the frequencies and the occurrences of a pattern in complete genomes is time-consuming. Results The proposed database provides information about sequence features generated by exhaustively computing the sequences of the complete genome. The repetitive elements in the eukaryotic genomes, such as LINEs, SINEs, Alu and LTR, are obtained from Repbase. The database supports various complete genomes including human, yeast, worm, and 128 microbial genomes. Conclusions This investigation presents and implements an efficiently computational approach to accumulate the occurrences of the oligonucleotides or patterns in complete genomes. A database is established to maintain the information of the sequence features, including the distributions of oligonucleotide, the gene distribution, the distribution of repetitive elements in genomes and the occurrences of the oligonucleotides. The database can provide more effective and efficient way to access the repetitive features in genomes.

In vitro transcription in the presence of DNA oligonucleotides can generate strong anomalous initiation sites.

Science.gov (United States)

Chow, C W; Clark, M P; Rinaldo, J E; Chalkley, R

1996-03-01

In the present study, we have explored an unexpected observation in transcription initiation that is mediated by single-stranded oligonucleotides. Initially, our goal was to understand the function of different upstream regulatory elements/initiation sites in the rat xanthine dehydrogenase/oxidase (XDH/XO) promoter. We performed in vitro transcription with HeLa nuclear extracts in the presence of different double-stranded oligonucleotides against upstream elements as competitors. A new and unusual transcription initiation site was detected by primer extension. This new initiation site maps to the downstream region of the corresponding competitor. Subsequent analyses have indicated that the induction of a new transcription initiation site is anomalous which is due to the presence of a small amount of single-stranded oligonucleotide in the competitor. We found that this anomalous initiation site is insensitive to the orientation of the promoter and requires only a small amount of single-stranded oligonucleotide (< 2-fold molar excess relative to template). We surmise that a complementary interaction between the single-stranded oligonucleotide and transiently denatured promoter template may be responsible for this sequence-specific transcription initiation artifact. To study the regulation of transcription initiation by in vitro transcription approaches, we propose that one should probe the effect of removing transacting factors by adding an excess of a cognate oligonucleotide which does not bear exact sequence identity to the template.

A simulation methodology of spacer grid residual spring deflection for predictive and interpretative purposes

International Nuclear Information System (INIS)

Kim, K. T.; Kim, H. K.; Yoon, K. H.

1994-01-01

The in-reactor fuel rod support conditions against the fretting wear-induced damage can be evaluated by spacer grid residual spring deflection. In order to predict the spacer grid residual spring deflection as a function of burnup for various spring designs, a simulation methodology of spacer grid residual spring deflection has been developed and implemented in the GRIDFORCE program. The simulation methodology takes into account cladding creep rate, initial spring deflection, initial spring force, and spring force relaxation rate as the key parameters affecting the residual spring deflection. The simulation methodology developed in this study can be utilized as an effective tool in evaluating the capability of a newly designed spacer grid spring to prevent the fretting wear-induced damage

Non linear fe analysis on the static buckling behavior of the spacer grid structures

International Nuclear Information System (INIS)

Song, K.N.; Yoon, K.H.

2001-01-01

In this study considered is the static buckling behavior of spacer grids in the fuel assembly, which are required to have a sufficient strength against an accident like earthquake. Special attention is given to the finite element modeling of the spot-welding and the constraints between the spacer strips assembled together: it is found that a proper treatment of the constraints is critical for accurate assessment of the buckling behavior including strain localization at the point of spot welding. The buckling strength of the 17 x 17 spacer grid, which is difficult to analyze due to a large number of degrees of freedom, is estimated from analysis for the smaller models 3 x 3, 5 x 5, 7 x 7, and 9 x 9 spacer grids. (authors)

Nuclear reactor spring strip grid spacer

International Nuclear Information System (INIS)

Patterson, J.F.; Flora, B.S.

1978-01-01

A bimetallic grid spacer is described comprising a grid structure of zircaloy formed by intersecting striplike members which define fuel element openings for receiving fuel elements and spring strips made of Inconel positioned within the grid structure for cooperating with the fuel elements to maintain them in their desired position. A plurality of these spring strips extend longitudinally between sides of the grid structure, being locked in position by the grid retaining strips. The fuel rods, which are disposed in the fuel openings formed in the grid structure, are positioned by means of the springs associated with the spring strips and a plurality of dimples which extend from the zircaloy grid structure into the openings. In one embodiment the strips are disposed in a plurality of arrays with those spring strip arrays situated in opposing diagonal quadrants of the grid structure extending in the same direction and adjacent spring strip arrays in each half of the spacer extending in relatively perpendicular directions. Other variations of the spring strip arrangements for a particular fuel design are disclosed herein

A study on the characteristics of the spacer spring by finite element method

Energy Technology Data Exchange (ETDEWEB)

Park, Sung Keun; Kim, Hyung Kyu; Kim, Kyu Tae [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

1995-06-01

The mechanical integrity of spacer springs in KOFA was certified through the mechanical tests by KWU. In this report, the spacer spring characteristics were obtained by using a commercial FEM code ANSYS, and the calculated results were compared with the mechanical test results. It has been found that the analytical results from ANSYS were in good agreement with the test results in the actual working range of the spacer springs even though some errors occurred in the range of initial spring deflection. The errors were thought to occur due to the simplified boundary conditions and the nominal dimensions which are used in calculations rather than the as-fabricated dimensions. Though the results from ANSYS are not fully satisfied, the analytical method in this report has been verified to be used as a method for investigating the characteristic of spacer springs roughly before conducting mechanical tests. 8 tabs., 25 figs (Author) .new.

Solid-phase synthesis of 2{sup '}-O-methoxyethyl oligonucleotides using dimeric phosphoramidate blocks

Energy Technology Data Exchange (ETDEWEB)

Yu, Gi Weon; Kang, Yong Han [Dept. of Applied Chemistry, Hanyang University, Ansan (Korea, Republic of)

2016-11-15

This research focused on the method of using dimeric phosphoramidite blocks to synthesize oligonucleotides for development as oligonucleotide drugs. A 16-mer oligonucleotide with the randomly selected sequence of C*C*T*C*G*C *T*C*T*C*G*C*C* C*G*C was synthesized using CC, GC, and TC dimers, a combination of monomers and dimers, or only monomers as building blocks. Using dimer blocks in this synthetic method provided a significant decrease in critical impurities that had similar properties to the main product, which was confirmed by LC-MS and HPLC analysis.

Technical aspects of typing for HLA-DP alleles using allele-specific DNA in vitro amplification and sequence-specific oligonucleotide probes. Detection of single base mismatches

DEFF Research Database (Denmark)

Fugger, L; Morling, N; Ryder, L P

1990-01-01

The polymerase chain reaction (PCR) is an effective method for in vitro DNA amplification which combined with probing with synthetic oligonucleotides can be used for, e.g., HLA-typing. We have studied the technical aspects of HLA-DP typing with the technique. DNA from mononuclear nucleated cells...... was extracted with either a simple salting out method or phenol/chloroform. Both DNAs could be readily used for PCR. The MgC2 concentration of the PCR buffer and the annealing temperature of the thermal cycle of the PCR were the two most important variables. The MgCl2 concentration and the temperature must...... be carefully titrated for each primer pair in the PCR. The influence of mismatches between the primer and the DNA template were studied and we found that, by using primers differing only from each other at the 3' end, cross-amplification of closely homologous alleles could be avoided. Thus, single base...

Photodynamic antisense regulation of mRNA having a point mutation with psoralen-conjugated oligonucleotide.

Science.gov (United States)

Higuchi, Maiko; Yamayoshi, Asako; Kobori, Akio; Murakami, Akira

2008-01-01

Nucleic acid-based drugs, such as antisense oligonucleotide, ribozyme, and small interfering RNA, are specific compounds that inhibit gene expression at the post-transcriptional level. To develop more effective nucleic acid-based drugs, we focused on photo-reactive antisense oligonucleotides. We have optimized the structure of psoralen-conjugated oligonucleotide to improve their sequence selectivity and photo-crosslinking efficiency. Previously, we reported that photo reactive oligonucleotides containing 2'-O-psoralenyl-methoxyethyl adenosine (2'-Ps-eom) showed drastic photo-reactivity with a strictly sequence specific manner in vitro. In this report, we evaluated the binding ability toward intracellular target mRNA. The 2'-Ps-eom selectively photo-cross-linked to the target mRNA extracted from cells. The 2'-Ps-eom also cross-linked to target mRNA in cells. Furthermore, 2'-Ps-eom did not cross-link to mRNA having a mismatch base. These results suggest that 2'-Ps-eom is a powerful antisense molecule to inhibit the expression of mRNA having a point mutation.

Predicting the impact of feed spacer modification on biofouling by hydraulic characterization and biofouling studies in membrane fouling simulators

KAUST Repository

Siddiqui, Amber

2016-12-22

Feed spacers are an essential part of spiral-wound reverse osmosis (RO) and nanofiltration (NF) membrane modules. Geometric modification of feed spacers is a potential option to reduce the impact of biofouling on the performance of membrane systems. The objective of this study was to evaluate the biofouling potential of two commercially available reference feed spacers and four modified feed spacers. The spacers were compared on hydraulic characterization and in biofouling studies with membrane fouling simulators (MFSs). The virgin feed spacer was characterized hydraulically by their resistance, measured in terms of feed channel pressure drop, performed by operating MFSs at varying feed water flow rates. Short-term (9 days) biofouling studies were carried out with nutrient dosage to the MFS feed water to accelerate the biofouling rate. Long-term (96 days) biofouling studies were done without nutrient dosage to the MFS feed water. Feed channel pressure drop was monitored and accumulation of active biomass was quantified by adenosine tri phosphate (ATP) determination. The six feed spacers were ranked on pressure drop (hydraulic characterization) and on biofouling impact (biofouling studies). Significantly different trends in hydraulic resistance and biofouling impact for the six feed spacers were observed. The same ranking for biofouling impact on the feed spacers was found for the (i) short-term biofouling study with nutrient dosage and the (ii) long-term biofouling study without nutrient dosage. The ranking for hydraulic resistance for six virgin feed spacers differed significantly from the ranking of the biofouling impact, indicating that hydraulic resistance of clean feed spacers does not predict the hydraulic resistance of biofouled feed spacers. Better geometric design of feed spacers can be a suitable approach to minimize impact of biofouling in spiral wound membrane systems.

USE OF ANTIBIOTIC CEMENT SPACERS/BEADS IN TREATMENT ...

African Journals Online (AJOL)

ABSTRACT. Background: Chronic musculoskeletal infection involving bone present a big challenge to orthopaedic surgeons. ... Current data has demonstrated that the use of .... Antibiotic spacers are effective and add value in the treament of ...

Ion therapy of prostate cancer: daily rectal dose reduction by application of spacer gel

International Nuclear Information System (INIS)

Rucinski, Antoni; Brons, Stephan; Richter, Daniel; Habl, Gregor; Debus, Jürgen; Bert, Christoph; Haberer, Thomas; Jäkel, Oliver

2015-01-01

Ion beam therapy represents a promising approach to treat prostate cancer, mainly due to its high conformity and radiobiological effectiveness. However, the presence of prostate motion, patient positioning and range uncertainties may deteriorate target dose and increase exposure of organs at risk. Spacer gel injected between prostate and rectum may increase the safety of prostate cancer (PC) radiation therapy by separating the rectum from the target dose field. The dosimetric impact of the application of spacer gel for scanned carbon ion therapy of PC has been analyzed at Heidelberg Ion-Beam Therapy Center (HIT). The robustness of ion therapy treatment plans was investigated by comparison of two data sets of patients treated with and without spacer gel. A research treatment planning system for ion therapy was used for treatment plan optimization and calculation of daily dose distributions on 2 to 9 Computed Tomography (CT) studies available for each of the 19 patients. Planning and daily dose distributions were analyzed with respect to target coverage, maximal dose to the rectum (excluding 1 ml of the greatest dose; Dmax-1 ml) and the rectal volume receiving dose greater than 90% of prescribed target dose (V90 Rectum ), respectively. The application of spacer gel did substantially diminish rectum dose. Dmax-1 ml on the treatment planning CT was on average reduced from 100.0 ± 1.0% to 90.2 ± 4.8%, when spacer gel was applied. The robustness analysis performed with daily CT studies demonstrated for all analyzed patient cases that application of spacer gel results in a decrease of the daily V90 Rectum index, which calculated over all patient cases and CT studies was 10.2 ± 10.4 [ml] and 1.1 ± 2.1 [ml] for patients without and with spacer gel, respectively. The dosimetric benefit of increasing the distance between prostate and rectum using spacer gel for PC treatment with carbon ion beams has been quantified. Application of spacer gel substantially reduced rectal

The effect of endoskeleton on antibiotic impregnated cement spacer for treating deep hip infection

Directory of Open Access Journals (Sweden)

Hsu Wei-Hsiu

2011-01-01

Full Text Available Abstract Backgrounds A two-stage revision arthroplasty was suggested optimal treatment for deep infections in hip joint. The effect of endoskeleton of cement spacers on the interim function and infection control remains unclear. Methods From Jan. 2004 to Dec. 2007, we collected a prospective cohort of consecutive 34 patients who treated with two-stage revision total hip arthroplasty for deep infection of hip joint. In group 1, fifteen patients were treated by a novel design augmented with hip compression screw while nineteen patients were treated by traditional design in group 2. Results No fracture of cement spacer occurred in group 1 while 6 cases developed spacer failure in group 2. (p Conclusions Patients being treated for deep infection of hip joint using cement spacer augmented with stronger endoskeleton have lower pain levels and better joint function between stages.

Surface modification of plasmonic nanostructured materials with thiolated oligonucleotides in 10 seconds using selective microwave heating

International Nuclear Information System (INIS)

Abel, B.; Aslan, K.

2012-01-01

This study demonstrates the proof-of-principle of rapid surface modification of plasmonic nanostructured materials with oligonucleotides using low power microwave heating. Due to their interesting optical and electronic properties, silver nanoparticle films (SNFs, 2 nm thick) deposited onto glass slides were used as the model plasmonic nanostructured materials. Rapid surface modification of SNFs with oligonucleotides was carried out using two strategies (1) Strategy 1: for ss-oligonucleotides, surface hybridization and (2) Strategy 2: for ds-oligonucleotides, solution hybridization, where the samples were exposed to 10, 15, 30 and 60 seconds microwave heating. To assess the efficacy of our new rapid surface modification technique, identical experiments carried out without the microwave heating (i.e., conventional method), which requires 24 hours for the completion of the identical steps. It was found that SNFs can be modified with ss- and ds-oligonucleotides in 10 seconds, which typically requires several hours of incubation time for the chemisorption of thiol groups on to the planar metal surface using conventional techniques. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

An Active Type I-E CRISPR-Cas System Identified in Streptomyces avermitilis.

Directory of Open Access Journals (Sweden)

Yi Qiu

Full Text Available CRISPR-Cas systems, the small RNA-dependent immune systems, are widely distributed in prokaryotes. However, only a small proportion of CRISPR-Cas systems have been identified to be active in bacteria. In this work, a naturally active type I-E CRISPR-Cas system was found in Streptomyces avermitilis. The system shares many common genetic features with the type I-E system of Escherichia coli, and meanwhile shows unique characteristics. It not only degrades plasmid DNA with target protospacers, but also acquires new spacers from the target plasmid DNA. The naive features of spacer acquisition in the type I-E system of S. avermitilis were investigated and a completely conserved PAM 5'-AAG-3' was identified. Spacer acquisition displayed differential strand bias upstream and downstream of the priming spacer, and irregular integrations of new spacers were observed. In addition, introduction of this system into host conferred phage resistance to some extent. This study will give new insights into adaptation mechanism of the type I-E systems in vivo, and meanwhile provide theoretical foundation for applying this system on the genetic modification of S. avermitilis.

Development and characterization of 3D-printed feed spacers for spiral wound membrane systems

KAUST Repository

Siddiqui, Amber; Farhat, Nadia; Bucs, Szilard; Valladares Linares, Rodrigo; Picioreanu, Cristian; Kruithof, Joop C.; van Loosdrecht, Mark C.M.; Kidwell, James; Vrouwenvelder, Johannes S.

2016-01-01

suggested that the impact of spacers on hydraulics and biofouling can be improved. A good agreement was found for the modeled and measured relationship between linear flow velocity and pressure drop for feed spacers with the same geometry, indicating

Methods for the preparation of large quantities of complex single-stranded oligonucleotide libraries.

Science.gov (United States)

Murgha, Yusuf E; Rouillard, Jean-Marie; Gulari, Erdogan

2014-01-01

Custom-defined oligonucleotide collections have a broad range of applications in fields of synthetic biology, targeted sequencing, and cytogenetics. Also, they are used to encode information for technologies like RNA interference, protein engineering and DNA-encoded libraries. High-throughput parallel DNA synthesis technologies developed for the manufacture of DNA microarrays can produce libraries of large numbers of different oligonucleotides, but in very limited amounts. Here, we compare three approaches to prepare large quantities of single-stranded oligonucleotide libraries derived from microarray synthesized collections. The first approach, alkaline melting of double-stranded PCR amplified libraries with a biotinylated strand captured on streptavidin coated magnetic beads results in little or no non-biotinylated ssDNA. The second method wherein the phosphorylated strand of PCR amplified libraries is nucleolyticaly hydrolyzed is recommended when small amounts of libraries are needed. The third method combining in vitro transcription of PCR amplified libraries to reverse transcription of the RNA product into single-stranded cDNA is our recommended method to produce large amounts of oligonucleotide libraries. Finally, we propose a method to remove any primer binding sequences introduced during library amplification.

Biofouling Control in Spiral-Wound Membrane Systems: Impact of Feed Spacer Modification and Biocides

KAUST Repository

Siddiqui, Amber

2016-01-01

was developed. The combination of modeling and experimental testing of 3D printed spacers is a promising strategy to develop advanced spacers aiming to reduce the impact of biofilm formation on membrane performance and to improve the cleanability of spiral

Simulation study of transfer characteristics for spacer-filled membrane distillation desalination modules

International Nuclear Information System (INIS)

Chang, Hsuan; Hsu, Jian-An; Chang, Cheng-Liang; Ho, Chii-Dong; Cheng, Tung-Wen

2017-01-01

Highlights: • A 3D CFD model takes in transmembrane heat and mass transfer developed. • DCMD modules using spacer-filled and empty channels for desalination simulated. • Fluid flow, heat transfer and mass transfer profiles revealed. • Correlations of friction factor and Nusselt number developed. - Abstract: Membrane distillation (MD) is an emerging and promising membrane separation process, which can directly utilize renewable thermal energy or low-grade waste heat, for applications in water or wastewater treatment and food industry. However, a major drawback of MD process is its low energy efficiency. Spacer is the most suggested and studied eddy promoter to enhance the heat and mass transfer, which further improves both the separation and the energy utilization performance, of MD processes. This paper presents the results of a 3D computational fluid dynamics (CFD) simulation of DCMD (direct contact membrane distillation) modules using channels with and without spacers for desalination application. The model employs permeable wall boundary condition to take into account the transmembrane heat and mass transfer and simulates the entire module length. The simulation reveals similar fluctuating distributions of temperature polarization coefficient, transmembrane heat and mass fluxes as well as the shear stress on the membrane surface along the entire module length. Correlations have been developed for friction factor and average Nusselt number. These correlations are useful for the analysis and design of DCMD modules. The extent of heat transfer enhancement by spacers depends on the geometry of spacers and the Reynolds number of fluid.

Microbiologic Evaluation of Cotton and Polytetrafluoroethylene (PTFE) Tape as Endodontic Spacer Materials in Primary Molars An in Vivo Study.

Science.gov (United States)

Prabhakar, Attiguppe Ramasetty; Dixit, Kratika; Raju, O S

PTFE tape, which is commonly used as plumber's tape is an inorganic, non-fibrous, ribbon like material. The aim of this study was to evaluate PTFE tape as endodontic spacer material and to compare it with commonly used spacer material that is cotton, in primary teeth. Seventeen children undergoing pulpectomy of lower second primary molar bilaterally were included in the study. Cotton and PTFE tape were placed as spacers on each side randomly. Samples were taken from the access cavity at baseline and after seven days to check for microbial leakage. Spacer materials were also checked for microbial contamination. The results revealed that there was a significant increase in the bacterial colony count after seven days in cotton group. The access cavities were also positive for microbial leakage in the cotton group where the spacers showed positive growth. In PTFE group only two samples showed microbial contamination of spacer and out of two only one sample showed contamination of access cavity along with spacer. Within the limitations of this study, it can be concluded that PTFE tape performed better than cotton as endodontic spacer material. Thus, PTFE tape can be recommended as an endodontic spacer material as an alternative to cotton in primary teeth.

18F-labelling of oligonucleotides using succinimido 4-[18F]fluorobenzoat

International Nuclear Information System (INIS)

Hedberg, Elisabeth; Laangstroem, Bengt

1998-01-01

A general method for the labelling of oligodeoxynucleotide and oligonucleoside phosphorothioates in the 5'-position with the positron-emitting radionuclide 18 F (t 1/2 = 110 min) is described. The label was incorporated by the reaction of succinimido 4 -[ 18 F]fluorobenzoate 4 with oligonucleotides (18- and 20-mers) modified in the 5'-position with a hexylamine linker. Oligodeoxynucleotides 5'-GCT,AAG,CGA,TGC,CTC,CGT-3' (MTCa) and 5'-GAA,CCT,CTG,AGA,GTT,CAT,CT-3' (CROa) were labelled in 20±3 % (MTCa) and 13±3 % (CROa) radiochemical yields (non-isolated, decay-corrected and based on 4). Oligonucleoside phosphorotioates MTCa (S-MTCa) and CROa (S-CROa) were labelled in 9 and 7% isolated radiochemical yield, respectively (decay-corrected and based on 4). Labelled oligonucleotides and phosphorothioate analogues were separated from their unlabelled counterparts using reversed-phase perfusion chromatography. The molecular mass of a labelled oligonucleotide CROa was determined by ESI-MS after a mixed 18 F/ 19 F fluorobenzoate labelling experiment and corresponded with the expected structure. (au)

Spacers for fuel rod clusters

International Nuclear Information System (INIS)

Jabsen, F.S.

1978-01-01

The proposition deals with the fixing of nuclear fuel element rods in a grid which consists of a number of crossed Zy-plates which form cells. The rectangular cells have projections which serve as spacers for the fuel rods. According to the invention there are additional butt straps which can be moved in such a way that insertion and extraction of the fuel rods can be done without obstruction and they can be spring-loaded hold in their final position. (UWI) [de

Organic light-emitting diodes with a spacer enhanced exciplex emission

Science.gov (United States)

Yan, Fei; Chen, Rui; Sun, Handong; Wei Sun, Xiao

2014-04-01

By introducing a spacer molecule into the blended exciplex emissive layer, the performance of the bulk heterojunction exciplex organic light-emitting diodes (OLEDs) was improved dramatically; the maximum luminous efficiency was enhanced by about 22% from 7.9 cd/A to 9.7 cd/A, and the luminous efficiency drop was reduced by 28% at 400 mA/cm2. Besides the suppressed annihilation of exciton, the time-resolved photoluminescence measurements indicated that the spacer enhanced the delayed fluorescence through increasing the backward intersystem crossing rate from the triplet to singlet exciplex state. This method is useful for developing high performance exciplex OLEDs.

Effect of Weld Properties on the Crush Strength of the PWR Spacer Grid

Directory of Open Access Journals (Sweden)

Kee-nam Song

2012-01-01

Full Text Available Mechanical properties in a weld zone are different from those in the base material because of different microstructures. A spacer grid in PWR fuel is a structural component with an interconnected and welded array of slotted grid straps. Previous research on the strength analyses of the spacer grid was performed using base material properties owing to a lack of mechanical properties in the weld zone. In this study, based on the mechanical properties in the weld zone of the spacer grid recently obtained by an instrumented indentation technique, the strength analyses considering the mechanical properties in the weld zone were performed, and the analysis results were compared with the previous research.

Barriers and supports to implementation of MDI/spacer use in nine Canadian pediatric emergency departments: a qualitative study

Directory of Open Access Journals (Sweden)

Graham Ian D

2009-10-01

Full Text Available Abstract Background Despite recent research supporting the use of metered dose inhalers with spacer devices (MDI/spacers in pediatric emergency departments (PEDs for acute exacerbations of asthma, uptake of this practice has been slow. The objectives of this study were to determine the barriers and supports to implementing MDI/spacer research and to identify factors associated with early and late adoption of MDI/spacers in Canadian PEDs. Methods Using a comparative case study design, we classified nine tertiary care pediatric hospital PEDs based on their stage of implementation. Data were collected using focus group interviews with physicians, registered nurses (RNs, and respiratory therapists (RTs, and individual interviews with both patient care and medical directors at each site. Initial coding was based on the Ottawa Model of Research Use (OMRU categories of elements known to influence the uptake of innovations. Results One hundred and fifty healthcare professionals from nine different healthcare institutions participated in this study. Lack of leadership in the form of a research champion, a lack of consensus about the benefits of MDI/spacers among staff, perceived resistance from patients/parents, and perceived increased cost and workload associated with MDI/spacer use were the most prevalent barriers to the adoption of the MDI/spacer. Common strategies used by early-adopting sites included the active participation of all professional groups in the adoption process in addition to a well-planned and executed educational component for staff, patients, and families. Early adopter sites were also more likely to have the MDI/spacer included in a clinical protocol/pathway. Conclusion Potential barriers and supports to implementation have been identified that will help EDs adopt MDI/spacer use. Future interventions intended to increase MDI/spacer use in PEDs will need to be sensitive to the barriers identified in this study.

Prediction of droplet deposition around BWR fuel spacer by FEM flow analysis

International Nuclear Information System (INIS)

Yamamoto, Yasushi; Morooka, Shinichi

1997-01-01

The critical power of the BWR fuel assembly has been remarkably increased. That increase mainly depends on the improvement of the spacer which keeps fixed gaps between fuel rods. So far, these improvements have been carried out on the basis of what developers consider to be appropriate and the results of mockup tests of the BWR fuel assembly. However, continued reliance on these approaches for the development of a higher performance fuel assembly will prove time-consuming and costly. Therefore, it is hoped that the spacer effects for the critical power can be investigated by computer simulation, and it is significantly important to develop the critical power prediction method. Direct calculation of the two-phase flow in a BWR fuel channel s still difficult. Accordingly, a new method for predicting the critical power was proposed. Our method consists of CFD (computer fluid dynamics) code based on the single-phase flow analysis method and the subchannel analysis code. To verify our method, the critical power predictions for various spacer geometries were performed. The predicted results of the critical power were compared with the experimental data. The result of the comparison showed a good agreement and the applicability of our method for various spacer geometries. (author)

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

DEFF Research Database (Denmark)

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'...

In Silico Study of Spacer Arm Length Influence on Drug Vectorization by Fullerene C60

Directory of Open Access Journals (Sweden)

Haifa Khemir

2015-01-01

Full Text Available This work studies theoretically the effect of spacer arm lengths on the characteristics of a fullerene C60-based nanovector. The spacer arm is constituted of a carbon chain including a variable number of methylene groups (n = 2–11. To improve the ability of the fullerene carriage, two arms are presented simultaneously through a malonyl bridge. Then the evolution of selected physicochemical parameters is monitored as a function of the spacer arm length and the angle between the two arms. We show here that while the studied characteristics are almost independent of the spacer arm length or vary monotonically with it, the dipole moment and its orientation vary periodically with the parity of the number of carbon atoms. This periodicity is related to both modules and orientations of dipole moments of the spacer arms. In the field of chemical synthesis, these results highlight the importance of theoretical calculations for the optimization of operating conditions. In the field of drug discovery, they show that theoretical calculations of the chemical properties of a drug candidate can help predict its in vivo behaviour, notably its bioavailability and biodistribution, which are known to be tightly dependent of its polarity.

A high-performance channel engineered charge-plasma-based MOSFET with high-κ spacer

Science.gov (United States)

Shan, Chan; Wang, Ying; Luo, Xin; Bao, Meng-tian; Yu, Cheng-hao; Cao, Fei

2017-12-01

In this paper, the performance of graded channel double-gate MOSFET (GC-DGFET) that utilizes the charge-plasma concept and a high-κ spacer is investigated through 2-D device simulations. The results demonstrate that GC-DGFET with high-κ spacer can effectively improve the ON-state driving current (ION) and reduce the OFF-leakage current (IOFF). We find that reduction of the initial energy barrier between the source and channel is the origin of this ION enhancement. The reason for the IOFF reduction is identified to be the extension of the effective channel length owing to the fringing field via high-κ spacers. Consequently, these devices offer enhanced performance by reducing the total gate-to-gate capacitance (Cgg) and decreasing the intrinsic delay (τ).

Geometric effects of spacer grid in an annulus flow channel during reflooding period

International Nuclear Information System (INIS)

Cho, S.; Chun, S. Y.; Kim, B. D.; Park, J. K.; Yun, Y. J.; Baek, W. P.

2004-01-01

A number of studies on the reflooding phase were actively carried out from the early 70's due to its importance for the safety of the nuclear reactor. (Martini et al., 1973; Henry, 1974; Chung, 1978;) However, few studies have presented the spacer grid effect during the reflooding period. Since the grid is an obstruction in the flow passage, it causes an increased pressure drop due to form and skin friction losses. On the other hand, the spacer grid tends to increase the local wall heat transfer. The present work has been performed in a vertical annulus flow channel with various flow conditions. The objective of this paper is to evaluate the effects of a swirl-vane spacer grid on the rewetting phenomena during the reflooding phase

Lower end fitting debris collector and end cap spacer grid

International Nuclear Information System (INIS)

Bryan, W.J.

1990-01-01

This patent describes a nuclear reactor having fuel assemblies including an upper end fitting and spaced nuclear fuel rod spacer grids for supporting and spacing a plurality of elongated nuclear fuel rods. Each includes a hollow active portion of nuclear fuel filled cladding intermediate the rod ends and tapering end cap of solid material with a circumferential groove on the rod end which first encounters reactor coolant flow, a lower end filtering debris collector and end cap spacer grid for capturing and retaining deleterious debris carried by reactor coolant before it enters the active region of a fuel assembly and creates fuel rod cladding damage

Intravitreal Injection of Splice-switching Oligonucleotides to Manipulate Splicing in Retinal Cells

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Xavier Gérard

2015-01-01

Full Text Available Leber congenital amaurosis is a severe hereditary retinal dystrophy responsible for neonatal blindness. The most common disease-causing mutation (c.2991+1655A>G; 10–15% creates a strong splice donor site that leads to insertion of a cryptic exon encoding a premature stop codon. Recently, we reported that splice-switching oligonucleotides (SSO allow skipping of the mutant cryptic exon and the restoration of ciliation in fibroblasts of affected patients, supporting the feasibility of a SSO-mediated exon skipping strategy to correct the aberrant splicing. Here, we present data in the wild-type mouse, which demonstrate that intravitreal administration of 2’-OMePS-SSO allows selective alteration of Cep290 splicing in retinal cells, including photoreceptors as shown by successful alteration of Abca4 splicing using the same approach. We show that both SSOs and Cep290 skipped mRNA were detectable for at least 1 month and that intravitreal administration of oligonucleotides did not provoke any serious adverse event. These data suggest that intravitreal injections of SSO should be considered to bypass protein truncation resulting from the c.2991+1655A>G mutation as well as other truncating mutations in genes which like CEP290 or ABCA4 have a mRNA size that exceed cargo capacities of US Food and Drug Administration (FDA-approved adeno-associated virus (AAV-vectors, thus hampering gene augmentation therapy.

Some considerations on special spacers with damping device for suppressing wake galloping in tandem cables of cable-stayed bridges; Heiretsu cable yo gensui kino tsuki supesa no gensui fuka tokusei ni kansuru 2,3 no kosatsu

Energy Technology Data Exchange (ETDEWEB)

Yoneda, M. [Kinki Univ., Higashi-Osaka, Osaka (Japan). Faculty of Science and Technology] Setouchi, H. [Kawada Industries Inc., Osaka (Japan)

1998-03-20

Cable vibration called wake galloping appears on cable-stayed bridges with parallel arranged cables and its suppression is an important problem. Various methods have been proposed for spacers with damping device for suppressing wake galloping in tandem cables of cable-stayed bridges. But, comparison of damping performances of various methods have not been discussed sufficiently. This paper deals with a type in which dampers are equipped on the midway of the tandem cables through the spacer jig and a type in which dampers are equipped on each surface of the tandem cables to generate shear deformation between them and circular spacer jig moiety and complex eigenvalue analyses are carried out on the two types with changing center spacing and diameters of the cables. The results clarify the relation between the structural damping characteristics and the cable spacing and the effect of torsional rigidity of the cables and also clarify of damping characteristics of the two types. 16 refs., 14 figs., 4 tabs.

Effect of electrostatic charge in plastic spacers on the lung delivery of HFA-salbutamol in children

DEFF Research Database (Denmark)

Anhøj, J; Bisgaard, H; Lipworth, B J

1999-01-01

delivered a significantly (Pplastic spacers reduces lung dose in children by more than two-fold. This is clinically significant and the use of potentially electrostatically charged......AIMS: The effect of the electrostatic charge in plastic spacers in vivo on drug delivery to the lung of hydrofluoroalkane (HFA) salbutamol spray was studied in children. METHODS: Five children, aged 7-12 years, were included in a 3-way crossover randomised single-blind trial. Salbutamol HFA spray...... was delivered on 3 different study days from plastic spacers with mouthpiece. Pre-treatment of the spacers differed between study days: (a) Non-electrostatic 350 ml Babyhaler (coated with benzalkonium chloride) (b) New 350 ml Babyhaler (rinsed in water), and (c) New 145 ml AeroChamber (rinsed in water). Plasma...

Spacer Thickness-Dependent Electron Transport Performance of Titanium Dioxide Thick Film for Dye-Sensitized Solar Cells

Directory of Open Access Journals (Sweden)

Reda E. El-Shater

2015-01-01

Full Text Available A titanium dioxide (P25 film was deposited by cast coating as conductive photoelectrode and subsequently immersed in dye solution (N719 to fabricate the photoanode of dye-sensitized solar cells (DSSCs. A plastic spacer was used as a separation and sealant layer between the photoanode and the counter electrode. The effect of the thickness of this spacer on the transfer of electrons in the liquid electrolyte of the DSSCs was studied by means of both IV curves and electrochemical impedance. Using a spacer thickness range of 20 μm to 50 μm, efficiency ranges from 3.73% to 7.22%. The highest efficiency of 7.22% was obtained with an optimal spacer thickness of 40 μm.

Exploring backbone-cation alkyl spacers for multi-cation side chain anion exchange membranes

Science.gov (United States)

Zhu, Liang; Yu, Xuedi; Hickner, Michael A.

2018-01-01

In order to systematically study how the arrangement of cations on the side chain and length of alkyl spacers between cations impact the performance of multi-cation AEMs for alkaline fuel cells, a series of polyphenylene oxide (PPO)-based AEMs with different cationic side chains were synthesized. This work resulted in samples with two or three cations in a side chain pendant to the PPO backbone. More importantly, the length of the spacer between cations varied from 3 methylene (-CH2-) (C3) groups to 8 methylene (C8) groups. The highest conductivity, up to 99 mS/cm in liquid water at room temperature, was observed for the triple-cation side chain AEM with pentyl (C5) or hexyl (C6) spacers. The multi-cation AEMs were found to have decreased water uptake and ionic conductivity when the spacer chains between cations were lengthened from pentyl (C5) or hexyl (C6) to octyl (C8) linking groups. The triple-cation membranes with pentyl (C5) or hexyl (C6) groups between cations showed greatest stability after immersion in 1 M NaOH at 80 °C for 500 h.

The Dynamics of Compound, Transcript, and Protein Effects After Treatment With 2OMePS Antisense Oligonucleotides in mdx Mice

Directory of Open Access Journals (Sweden)

Ingrid E C Verhaart

2014-01-01

Full Text Available Antisense-mediated exon skipping is currently in clinical development for Duchenne muscular dystrophy (DMD to amend the consequences of the underlying genetic defect and restore dystrophin expression. Due to turnover of compound, transcript, and protein, chronic treatment with effector molecules (antisense oligonucleotides will be required. To investigate the dynamics and persistence of antisense 2′-O-methyl phosphorothioate oligonucleotides, exon skipping, and dystrophin expression after dosing was concluded, mdx mice were treated subcutaneously for 8 weeks with 100 mg/kg oligonucleotides twice weekly. Thereafter, mice were sacrificed at different time points after the final injection (36 hours–24 weeks. Oligonucleotide half-life was longer in heart (~65 days compared with that in skeletal muscle, liver, and kidney (~35 days. Exon skipping half-lives varied between 33 and 53 days, whereas dystrophin protein showed a long half-life (>100 days. Oligonucleotide and exon-skipping levels peaked in the first week and declined thereafter. By contrast, dystrophin expression peaked after 3–8 weeks and then slowly declined, remaining detectable after 24 weeks. Concordance between levels of oligonucleotides, exon skipping, and proteins was observed, except in heart, wherein high oligonucleotide levels but low exon skipping and dystrophin expression were seen. Overall, these results enhance our understanding of the pharmacokinetics and pharmacodynamics of 2′-O-methyl phosphorothioate oligos used for the treatment of DMD.

Measurement and model development of the droplet diameter in rod bundles with spacer grids in the reactor core

Energy Technology Data Exchange (ETDEWEB)

No, Hee Cheon; Lee, Eo Hwak; Yoo, Seung Hun; Jin, Hyung Gon; Kim, In Hun [KAIST, Daejeon (Korea, Republic of)

2010-05-15

To understand and to predict the heat transfer between superheated steam and droplets properly during reflood phase of LBLOCA of APR1400, it is very important to measure broken droplet sizes by spacer grids. A study, therefore, has been performed to investigate droplet size in rod bundles with spacer grids and to develop a spacer grid droplet size model for safety analysis codes. Experiments were conducted with liquid droplets (SMD of 300{approx}700 {mu}m) impacting on various spacer grids at air superficial velocity of 10 and 20 m/s based on FLECHT SEASET. The test channel and the grids were heated to 150 .deg. C to prevent the formation of liquid film during tests. The spacer grids were designed refer to the Korean fuel rod bundles (Korean Standard Fuel, Plus 7) of APR1400 with various blockage area ratio and grid geometries (strap thickness, mixing vane) and about 15,000 droplets were measured at upstream and downstream of the grids in 16 tests. As a result, the measurement of broken droplet size by spacer grids with photography method is presented and the droplet size model related to spacer grids as a function of blockage area ratio is suggested in this report

Streptavidin-coated gold nanoparticles: critical role of oligonucleotides on stability and fractal aggregation

Directory of Open Access Journals (Sweden)

Roberta D'Agata

2017-01-01

Full Text Available Gold nanoparticles (AuNPs exhibit unique properties that can be modulated through a tailored surface functionalization, enabling their targeted use in biochemical sensing and medical diagnostics. In particular, streptavidin-modified AuNPs are increasingly used for biosensing purposes. We report here a study of AuNPs surface-functionalized with streptavidin-biotinylated oligonucleotide, focussing on the role played by the oligonucleotide probes in the stabilization/destabilization of the functionalized nanoparticle dispersion. The behaviour of the modified AuNP dispersion as a consequence of the competitive displacement of the biotinylated oligonucleotide has been investigated and the critical role of displaced oligonucletides in triggering the quasi one-dimensional aggregation of nanoparticles is demonstrated for the first time. The thorough understanding of the fundamental properties of bioconjugated AuNPs is of great importance for the design of highly sensitive and reliable functionalized AuNP-based assays.

Reentrainment of droplet from grid spacer in mist flow portion of LOCA reflood of PWR

International Nuclear Information System (INIS)

Lee, S.L.; Cho, S.K.; Sheen, H.J.

1983-01-01

An investigation is made on the influence of a quenched grid spacer on the greatly enhanced heat transfer from heated fuel rods during the mist flow phase of emergency reflood of loss of coolant accident (LOCA) of a pressurized water reactor (PWR). The situation for the case of a dry grid spacer before its quenching has not been covered in this study. The experimental technique used is a relatively simple optical scheme which combines the reference-mode laser-Doppler anemometry making use of the scattering of a light beam from a droplet. The results reveal that the large droplets in the mist flow, which are intercepted by the grid spacer, are responsible for the creation of a large number of smaller droplets. These small droplets, due to their large surface area to mass ratios, can serve as superb evaporative cooling agents to heat transfer downstream of the grid spacer

Efficient and colour-stable hybrid white organic light-emitting diodes utilizing electron-hole balanced spacers

International Nuclear Information System (INIS)

Leem, Dong-Seok; Kim, Ji Whan; Kim, Jang-Joo; Jung, Sung Ouk; Kim, Seul-Ong; Kwon, Soon-Ki; Kim, Se Hoon; Kim, Kee Young; Kim, Yun-Hi

2010-01-01

High-efficiency two-colour white organic light-emitting diodes (WOLEDs) comprising a newly synthesized iridium complex orange phosphor ((impy) 2 Ir(acac)) and a blue fluorophor (BD012) have been realized by placing several kinds of thin spacers between two emitters. Hybrid WOLEDs with a spacer composed of a hole-transporting N,N-dicarbazolyl-3,5-benzene (mCP) and an electron-transporting 4,7-diphenyl-1,10-phenanthroline (Bphen) exhibit a high external quantum efficiency (EQE) of up to 8.4% and a negligible colour change (the colour coordinate of (0.39, 0.41) at 1000 cd m -2 ) with increasing brightness, whereas the device using a hole-transporting mCP spacer shows a relatively low EQE of 6.2% and a large shift of emitting colour with increasing brightness. Device performance is further characterized based on the charge transport behaviour of the spacers inserted between the two emitters.

Similar Results in Children with Asthma for Steady State Pharmacokinetic Parameters of Ciclesonide Inhaled with or without Spacer

Directory of Open Access Journals (Sweden)

H. Boss

2010-01-01

Full Text Available Background Ciclesonide is an inhaled corticosteroid administered by a metered dose inhaler (MDI to treat bronchial asthma. After inhalation, the inactive ciclesonide is converted by esterases in the airways to active metabolite desisobutyryl-ciclesonide (des-CIC. Aim To compare the pharmacokinetic (PK parameters of des-CIC in children after administration of therapeutic dose of ciclesonide with and without spacer (AeroChamber Plus™. Methods Open-label, 3 period, cross over, repeated dose, PK study in 37 children with mild to moderate stable asthma (age: 6–11 y; body weight: 20–53 kg. During each 7-day treatment period, ciclesonide was inhaled once in the morning: A 160 μg MDI with spacer, B 80 μg MDI with spacer, and C 160 μg MDI without spacer. Serum PK parameters of ciclesonide and des-CIC were determined on Day 7 of each period. The primary PK parameters were the AUC τ and C max for des-CIC. Results Inhaling ciclesonide with spacer led to a dose proportional systemic exposure (AUC τ of des-CIC (0.316 μg*h/L for 80 μg and 0.663 μg*h/L for 160 μg. The dose-normalized systemic exposure for des-CIC (based on AUC τ was 27% higher after inhalation of ciclesonide 80 μg or 160 μg with spacer than without spacer; the corresponding C max values for des-CIC were, respectively, 63% and 55% higher with spacer. No clinically relevant abnormalities or adverse drug reactions were observed. Conclusions Inhalation of therapeutic ciclesonide dose with spacer led to a slight increase in the systemic exposure of des-CIC, which does not warrant dose adjustment.

Experimental benchmark data for PWR rod bundle with spacer-grids

International Nuclear Information System (INIS)

Dominguez-Ontiveros, Elvis E.; Hassan, Yassin A.; Conner, Michael E.; Karoutas, Zeses

2012-01-01

In numerical simulations of fuel rod bundle flow fields, the unsteady Navier–Stokes equations have to be solved in order to determine the time (phase) dependent characteristics of the flow. In order to validate the simulations results, detailed comparison with experimental data must be done. Experiments investigating complex flows in rod bundles with spacer grids that have mixing devices (such as flow mixing vanes) have mostly been performed using single-point measurements. In order to obtain more details and insight on the discrepancies between experimental and numerical data as well as to obtain a global understanding of the causes of these discrepancies, comparisons of the distributions of complete phase-averaged velocity and turbulence fields for various locations near spacer-grids should be performed. The experimental technique Particle Image Velocimetry (PIV) is capable of providing such benchmark data. This paper describes an experimental database obtained using two-dimensional Time Resolved Particle Image Velocimetry (TR-PIV) measurements within a 5 × 5 PWR rod bundle with spacer-grids that have flow mixing vanes. One of the unique characteristic of this set-up is the use of the Matched Index of Refraction technique employed in this investigation to allow complete optical access to the rod bundle. This unique feature allows flow visualization and measurement within the bundle without rod obstruction. This approach also allows the use of high temporal and spatial non-intrusive dynamic measurement techniques namely TR-PIV to investigate the flow evolution below and immediately above the spacer. The experimental data presented in this paper includes explanation of the various cases tested such as test rig dimensions, measurement zones, the test equipment and the boundary conditions in order to provide appropriate data for comparison with Computational Fluid Dynamics (CFD) simulations. Turbulence parameters of the obtained data are presented in order to gain

The illusion of specific capture: surface and solution studies of suboptimal oligonucleotide hybridization

Science.gov (United States)

2013-01-01

Background Hybridization based assays and capture systems depend on the specificity of hybridization between a probe and its intended target. A common guideline in the construction of DNA microarrays, for instance, is that avoiding complementary stretches of more than 15 nucleic acids in a 50 or 60-mer probe will eliminate sequence specific cross-hybridization reactions. Here we present a study of the behavior of partially matched oligonucleotide pairs with complementary stretches starting well below this threshold complementarity length – in silico, in solution, and at the microarray surface. The modeled behavior of pairs of oligonucleotide probes and their targets suggests that even a complementary stretch of sequence 12 nt in length would give rise to specific cross-hybridization. We designed a set of binding partners to a 50-mer oligonucleotide containing complementary stretches from 6 nt to 21 nt in length. Results Solution melting experiments demonstrate that stable partial duplexes can form when only 12 bp of complementary sequence are present; surface hybridization experiments confirm that a signal close in magnitude to full-strength signal can be obtained from hybridization of a 12 bp duplex within a 50mer oligonucleotide. Conclusions Microarray and other molecular capture strategies that rely on a 15 nt lower complementarity bound for eliminating specific cross-hybridization may not be sufficiently conservative. PMID:23445545

DETECTING LOW-LEVEL SYNTHESIS IMPURITIES IN MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES USING LIQUID CHROMATOGRAPHY – HIGH RESOLUTION MASS SPECTROMETRY

Science.gov (United States)

Nikcevic, Irena; Wyrzykiewicz, Tadeusz K.; Limbach, Patrick A.

2010-01-01

Summary An LC-MS method based on the use of high resolution Fourier transform ion cyclotron resonance mass spectrometry (FTIRCMS) for profiling oligonucleotides synthesis impurities is described. Oligonucleotide phosphorothioatediesters (phosphorothioate oligonucleotides), in which one of the non-bridging oxygen atoms at each phosphorus center is replaced by a sulfur atom, are now one of the most popular oligonucleotide modifications due to their ease of chemical synthesis and advantageous pharmacokinetic properties. Despite significant progress in the solid-phase oligomerization chemistry used in the manufacturing of these oligonucleotides, multiple classes of low-level impurities always accompany synthetic oligonucleotides. Liquid chromatography-mass spectrometry has emerged as a powerful technique for the identification of these synthesis impurities. However, impurity profiling, where the entire complement of low-level synthetic impurities is identified in a single analysis, is more challenging. Here we present an LC-MS method based the use of high resolution-mass spectrometry, specifically Fourier transform ion cyclotron resonance mass spectrometry (FTIRCMS or FTMS). The optimal LC-FTMS conditions, including the stationary phase and mobile phases for the separation and identification of phosphorothioate oligonucleotides, were found. The characteristics of FTMS enable charge state determination from single m/z values of low-level impurities. Charge state information then enables more accurate modeling of the detected isotopic distribution for identification of the chemical composition of the detected impurity. Using this approach, a number of phosphorothioate impurities can be detected by LC-FTMS including failure sequences carrying 3′-terminal phosphate monoester and 3′-terminal phosphorothioate monoester, incomplete backbone sulfurization and desulfurization products, high molecular weight impurities, and chloral, isobutyryl, and N3 (2-cyanoethyl) adducts

Structural properties of oligonucleotide monolayers on gold surfaces probed by fluorescence investigations.

Science.gov (United States)

Rant, Ulrich; Arinaga, Kenji; Fujita, Shozo; Yokoyama, Naoki; Abstreiter, Gerhard; Tornow, Marc

2004-11-09

We present optical investigations on the conformation of oligonucleotide layers on Au surfaces. Our studies concentrate on the effect of varying surface coverage densities on the structural properties of layers of 12- and 24mer single-stranded DNA, tethered to the Au surface at one end while being labeled with a fluorescent marker at the opposing end. The distance-dependent energy transfer from the marker dye to the metal surface, which causes quenching of the observed fluorescence, is used to provide information on the orientation of the DNA strands relative to the surface. Variations in the oligonucleotide coverage density, as determined from electrochemical quantification, over 2 orders of magnitude are achieved by employing different preparation conditions. The observed enhancement in fluorescence intensity with increasing DNA coverage can be related to a model involving mutual steric interactions of oligonucleotides on the surface, as well as fluorescence quenching theory. Finally, the applicability of the presented concepts for investigations of heterogeneous monolayers is demonstrated by means of studying the coadsorption of mercaptohexanol onto DNA-modified Au surfaces.

Experimental investigation of effect of spacer on two phase turbulent mixing rate in subchannels of pressure tube type BWR

Energy Technology Data Exchange (ETDEWEB)

Verma, Shashi Kant; Sinha, S.L. [National Institute of Technology, Raipur (India). Mechanical Engineering Dept.; Chandraker, D.K. [Bhabha Atomic Research Centre, Mumbai (India). Reactor Design and Development Group

2017-11-15

Turbulent mixing rate between adjacent subchannels in a two-phase flow has been known to be strongly dependent on the flow pattern. The most important aspect of turbulent motion is that the velocity and pressure at a fixed point do not remain constant with time even in steady state but go through very irregular high frequency fluctuations. These fluctuations influence the diffusion of scalar and vector quantities. The Advanced Heavy Water Reactor (AHWR) is a vertical pressure tube type, heavy water moderated and boiling light water cooled natural circulation based reactor. The fuel bundle of AHWR contains 54 fuel rods set in three concentric rings of 12, 18 and 24 fuel rods. This fuel bundle is divided into number of imaginary interacting flow channel called subchannels. Alteration from single phase to two phase flow situation occurs in reactor rod bundle with raise in power. The two phase flow regimes like bubbly, slug-churn, and annular flow are generally encountered in reactor rod bundle. Prediction of thermal margin of the reactor has necessitated the investigation of turbulent mixing rate of coolant between these subchannels under these flow regimes. Thus, it is fundamental to estimate the effect of spacer grids on turbulent mixing between subchannels of AHWR rod bundle.

Factor XI Antisense Oligonucleotide for Prevention of Venous Thrombosis

NARCIS (Netherlands)

Büller, Harry R.; Bethune, Claudette; Bhanot, Sanjay; Gailani, David; Monia, Brett P.; Raskob, Gary E.; Segers, Annelise; Verhamme, Peter; Weitz, Jeffrey I.; Weitz, Jeffrey; Prins, Martin; Beenen, Ludo; Otten, Hans-Martin; Roos, Yvo; Slagboom, Ton; Vandenbriele, Christophe; Vanassche, Thomas; Dani, Vidhi; Schulz, Dan; Shapiro, Cara; Kwoh, Katherine; Jung, Bill; Gawinek-Samelczak, Agata; Kaemmer, Christina; Angelov, S.; Stavrev, V.; Kinov, P.; Dessouki, E.; Abuzgaya, F.; Baurovskis, A.; Peredistijs, A.; Petronis, S.; Danilyak, V.; Driagin, V.; Kuropatkin, G.; Parfeev, S.; Safronov, A.; Ankin, M.; Korzh, M.; Olinichenko, G.; Polivoda, A.; Shevchenko, V.; Sulyma, V.

2015-01-01

Background Experimental data indicate that reducing factor XI levels attenuates thrombosis without causing bleeding, but the role of factor XI in the prevention of postoperative venous thrombosis in humans is unknown. FXI-ASO (ISIS 416858) is a second-generation antisense oligonucleotide that

Impact of feed spacer and membrane modification by hydrophilic, bactericidal and biocidal coating on biofouling control

KAUST Repository

Araú jo, Paula A.; Miller, Daniel J.; Correia, Patrí cia B.; van Loosdrecht, Mark C.M.; Kruithof, Joop C.; Freeman, Benny Dean; Paul, Donald; Vrouwenvelder, Johannes S.

2012-01-01

surface modification agents expected to resist protein and bacterial adhesion, while copper feed spacer coatings and biocides infused in feed spacers are expected to restrict biological growth. Our studies showed that polydopamine and polydopamine-. g

Cervical interfacet spacers and maintenance of cervical lordosis.

Science.gov (United States)

Tan, Lee A; Straus, David C; Traynelis, Vincent C

2015-05-01

OBJECT The cervical interfacet spacer (CIS) is a relatively new technology that can increase foraminal height and area by facet distraction. These offer the potential to provide indirect neuroforaminal decompression while simultaneously enhancing fusion potential due to the relatively large osteoconductive surface area and compressive forces exerted on the grafts. These potential benefits, along with the relative ease of implantation during posterior cervical fusion procedures, make the CIS an attractive adjuvant in the management of cervical pathology. One concern with the use of interfacet spacers is the theoretical risk of inducing iatrogenic kyphosis. This work tests the hypothesis that interfacet spacers are associated with loss of cervical lordosis. METHODS Records from patients undergoing posterior cervical fusion at Rush University Medical Center between March 2011 and December 2012 were reviewed. The FacetLift CISs were used in all patients. Preoperative and postoperative radiographic data were reviewed and the Ishihara indices and cervical lordotic angles were measured and recorded. Statistical analyses were performed using STATA software. RESULTS A total of 64 patients were identified in whom 154 cervical levels were implanted with machined allograft interfacet spacers. Of these, 15 patients underwent anterior-posterior fusions, 4 underwent anterior-posterior-anterior fusions, and the remaining 45 patients underwent posterior-only fusions. In the 45 patients with posterior-only fusions, a total of 110 levels were treated with spacers. There were 14 patients (31%) with a single level treated, 16 patients (36%) with two levels treated, 5 patients (11%) with three levels treated, 5 patients (11%) with four levels treated, 1 patient (2%) with five levels treated, and 4 patients (9%) with six levels treated. Complete radiographic data were available in 38 of 45 patients (84%). On average, radiographic follow-up was obtained at 256.9 days (range 48-524 days

[Oligonucleotide derivatives in the nucleic acid hybridization analysis. I. Covalent immobilization of oligonucleotide probes onto the nylon].

Science.gov (United States)

Dmitrienko, E V; Pyshnaia, I A; Pyshnyĭ, D V

2010-01-01

The features of UV-induced immobilization of oligonucleotides on a nylon membranes and the effectiveness of enzymatic labeling of immobilized probes at heterophase detection of nucleic acids are studied. Short terminal oligothymidilate (up to 10 nt) sequences are suggested to attach to the probe via a flexible ethylene glycol based linker. The presence of such fragment enhances the intensity of immobilization and reduces UV-dependent degradation of the targeted (sequence-specific) part of the probe by reducing the dose needed for the immobilization of DNA. The optimum dose of UV-irradiation is determined to be ~0.4 J/cm(2) at the wavelength 254 nm. This dose provides high level of hybridization signal for immobilized probes with various nucleotide composition of the sequence specific moiety. The amide groups of the polyamide are shown to play the key role in the photoinduced immobilization of nucleic acids, whereas the primary amino groups in the structure of PA is not the center responsible for the covalent binding of DNA by UV-irradiation, as previously believed. Various additives in the soaking solution during the membrane of UV-dependent immobilization of probes are shown to influence its effectiveness. The use of alternative to UV-irradiation system of radical generation are shown to provide the immobilization of oligonucleotides onto the nylon membrane.

Efficient and colour-stable hybrid white organic light-emitting diodes utilizing electron-hole balanced spacers

Energy Technology Data Exchange (ETDEWEB)

Leem, Dong-Seok; Kim, Ji Whan; Kim, Jang-Joo [Department of Materials Science and Engineering, and OLED Center, Seoul National University, Seoul 151-744 (Korea, Republic of); Jung, Sung Ouk; Kim, Seul-Ong; Kwon, Soon-Ki [School of Materials Science and Engineering, and Engineering Research Institute (ERI), Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Kim, Se Hoon; Kim, Kee Young [Dongwoo Fine-Chem Co., Ltd, Pyeongtaek 451-822 (Korea, Republic of); Kim, Yun-Hi, E-mail: jjkim@snu.ac.k, E-mail: skwon@gnu.ac.k [Department of Chemistry and RINS, Gyeongsang National University, Jinju 660-701 (Korea, Republic of)

2010-10-13

High-efficiency two-colour white organic light-emitting diodes (WOLEDs) comprising a newly synthesized iridium complex orange phosphor ((impy){sub 2}Ir(acac)) and a blue fluorophor (BD012) have been realized by placing several kinds of thin spacers between two emitters. Hybrid WOLEDs with a spacer composed of a hole-transporting N,N-dicarbazolyl-3,5-benzene (mCP) and an electron-transporting 4,7-diphenyl-1,10-phenanthroline (Bphen) exhibit a high external quantum efficiency (EQE) of up to 8.4% and a negligible colour change (the colour coordinate of (0.39, 0.41) at 1000 cd m{sup -2}) with increasing brightness, whereas the device using a hole-transporting mCP spacer shows a relatively low EQE of 6.2% and a large shift of emitting colour with increasing brightness. Device performance is further characterized based on the charge transport behaviour of the spacers inserted between the two emitters.

Oligonucleotide Aptamers: New Tools for Targeted Cancer Therapy

Directory of Open Access Journals (Sweden)

Hongguang Sun

2014-01-01

Full Text Available Aptamers are a class of small nucleic acid ligands that are composed of RNA or single-stranded DNA oligonucleotides and have high specificity and affinity for their targets. Similar to antibodies, aptamers interact with their targets by recognizing a specific three-dimensional structure and are thus termed “chemical antibodies.” In contrast to protein antibodies, aptamers offer unique chemical and biological characteristics based on their oligonucleotide properties. Hence, they are more suitable for the development of novel clinical applications. Aptamer technology has been widely investigated in various biomedical fields for biomarker discovery, in vitro diagnosis, in vivo imaging, and targeted therapy. This review will discuss the potential applications of aptamer technology as a new tool for targeted cancer therapy with emphasis on the development of aptamers that are able to specifically target cell surface biomarkers. Additionally, we will describe several approaches for the use of aptamers in targeted therapeutics, including aptamer-drug conjugation, aptamer-nanoparticle conjugation, aptamer-mediated targeted gene therapy, aptamer-mediated immunotherapy, and aptamer-mediated biotherapy.

Experimental and numerical characterization of the water flow in spacer-filled channels of spiral-wound membranes

KAUST Repository

Bucs, Szilard; Valladares Linares, Rodrigo; Marston, Jeremy O.; Radu, Andrea I.; Vrouwenvelder, Johannes S.; Picioreanu, Cristian

2015-01-01

Micro-scale flow distribution in spacer-filled flow channels of spiral-wound membrane modules was determined with a particle image velocimetry system (PIV), aiming to elucidate the flow behaviour in spacer-filled flow channels. Two-dimensional water

Identifying members of the domain Archaea with rRNA-targeted oligonucleotide probes.

Science.gov (United States)

Burggraf, S; Mayer, T; Amann, R; Schadhauser, S; Woese, C R; Stetter, K O

1994-09-01

Two 16S rRNA-targeted oligonucleotide probes were designed for the archaeal kingdoms Euryachaeota and Crenarchaeota. Probe specificities were evaluated by nonradioactive dot blot hybridization against selected reference organisms. The successful application of fluorescent-probe derivatives for whole-cell hybridization required organism-specific optimizations of fixation and hybridization conditions to assure probe penetration and morphological integrity of the cells. The probes allowed preliminary grouping of three new hyperthermophilic isolates. Together with other group-specific rRNA-targeted oligonucleotide probes, these probes will facilitate rapid in situ monitoring of the populations present in hydrothermal systems and support cultivation attempts.

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...

Reliability and applications of statistical methods based on oligonucleotide frequencies in bacterial and archaeal genomes

DEFF Research Database (Denmark)

Bohlin, J; Skjerve, E; Ussery, David

2008-01-01

with here are mainly used to examine similarities between archaeal and bacterial DNA from different genomes. These methods compare observed genomic frequencies of fixed-sized oligonucleotides with expected values, which can be determined by genomic nucleotide content, smaller oligonucleotide frequencies......, or be based on specific statistical distributions. Advantages with these statistical methods include measurements of phylogenetic relationship with relatively small pieces of DNA sampled from almost anywhere within genomes, detection of foreign/conserved DNA, and homology searches. Our aim was to explore...... the reliability and best suited applications for some popular methods, which include relative oligonucleotide frequencies (ROF), di- to hexanucleotide zero'th order Markov methods (ZOM) and 2.order Markov chain Method (MCM). Tests were performed on distant homology searches with large DNA sequences, detection...

Custom-made hinged spacers in revision knee surgery for patients with infection, bone loss and instability.

Science.gov (United States)

Macmull, S; Bartlett, W; Miles, J; Blunn, G W; Pollock, R C; Carrington, R W J; Skinner, J A; Cannon, S R; Briggs, T W R

2010-12-01

Polymethyl methacrylate spacers are commonly used during staged revision knee arthroplasty for infection. In cases with extensive bone loss and ligament instability, such spacers may not preserve limb length, joint stability and motion. We report a retrospective case series of 19 consecutive patients using a custom-made cobalt chrome hinged spacer with antibiotic-loaded cement. The "SMILES spacer" was used at first-stage revision knee arthroplasty for chronic infection associated with a significant bone loss due to failed revision total knee replacement in 11 patients (58%), tumour endoprosthesis in four patients (21%), primary knee replacement in two patients (11%) and infected metalwork following fracture or osteotomy in a further two patients (11%). Mean follow-up was 38 months (range 24-70). In 12 (63%) patients, infection was eradicated, three patients (16%) had persistent infection and four (21%) developed further infection after initially successful second-stage surgery. Above knee amputation for persistent infection was performed in two patients. In this particularly difficult to treat population, the SMILES spacer two-stage technique has demonstrated encouraging results and presents an attractive alternative to arthrodesis or amputation. Copyright © 2009 Elsevier B.V. All rights reserved.

Highly Efficient White Organic Light-Emitting Diodes with Ultrathin Emissive Layers and a Spacer-Free Structure

Science.gov (United States)

Wu, Shengfan; Li, Sihua; Sun, Qi; Huang, Chenchao; Fung, Man-Keung

2016-05-01

Ultrathin emissive layers (UEMLs) of phosphorescent materials with a layer thickness of less than 0.3 nm were introduced for high-efficiency organic light-emitting diodes (OLEDs). All the UEMLs for white OLEDs can be prepared without the use of interlayers or spacers. Compared with devices fabricated with interlayers inserted in-between the UEMLs, our spacer-free structure not only significantly improves device efficiency, but also simplifies the fabrication process, thus it has a great potential in lowering the cost of OLED panels. In addition, its spacer-free structure decreases the number of interfaces which often introduce unnecessary energy barriers in these devices. In the present work, UEMLs of red, green and blue-emitting phosphorescent materials and yellow and blue phosphorescent emitters are utilized for the demonstration of spacer-free white OLEDs. Upon optimization of the device structure, we demonstrated spacer-free and simple-structured white-emitting OLEDs with a good device performance. The current and power efficiencies of our white-emitting devices are as high as 56.0 cd/A and 55.5 lm/W, respectively. These efficiencies are the highest ever reported for OLEDs fabricated with the UEML approach.

Spacer Facial Artery Musculomucosal Flap: Simultaneous Closure of Oronasal Fistulas and Palatal Lengthening.

Science.gov (United States)

Lee, Jonathan Y; Alizadeh, Kaveh

2016-01-01

In this series, the authors describe a modification of the facial artery musculomucosal flap for oronasal fistula repair. The spacer facial artery musculomucosal flap technique is characterized by a pedicle inset into the retromolar trigone and palate, obviating a second operative stage. This was performed in 14 patients with a 5.2-cm mean fistula size. Average follow-up was 4.3 years, with one partial flap necrosis but no recurrent oronasal fistula. There was a mean decrease of 18 percent in the distance between the velum and the posterior pharyngeal wall. The spacer facial artery musculomucosal flap provides a single-stage reconstruction of oronasal fistula while lengthening the palate through a pushback mechanism. Although further study of velopharyngeal function is needed, the spacer facial artery musculomucosal flap may be beneficial for patients with a short velum and an oronasal fistula. Therapeutic, IV.

AA stacking, tribological and electronic properties of double-layer graphene with krypton spacer.

Science.gov (United States)

Popov, Andrey M; Lebedeva, Irina V; Knizhnik, Andrey A; Lozovik, Yurii E; Potapkin, Boris V; Poklonski, Nikolai A; Siahlo, Andrei I; Vyrko, Sergey A

2013-10-21

Structural, energetic, and tribological characteristics of double-layer graphene with commensurate and incommensurate krypton spacers of nearly monolayer coverage are studied within the van der Waals-corrected density functional theory. It is shown that when the spacer is in the commensurate phase, the graphene layers have the AA stacking. For this phase, the barriers to relative in-plane translational and rotational motion and the shear mode frequency of the graphene layers are calculated. For the incommensurate phase, both of the barriers are found to be negligibly small. A considerable change of tunneling conductance between the graphene layers separated by the commensurate krypton spacer at their relative subangstrom displacement is revealed by the use of the Bardeen method. The possibility of nanoelectromechanical systems based on the studied tribological and electronic properties of the considered heterostructures is discussed.

Characterization of rat brain NCAM mRNA using DNA oligonucleotide probes

DEFF Research Database (Denmark)

Andersson, A M; Gaardsvoll, H; Giladi, E

1990-01-01

A number of different isoforms of the neural cell adhesion molecule (NCAM) have been identified. The difference between these is due to alternative splicing of a single NCAM gene. In rat brain NCAM mRNAs with sizes of 7.4, 6.7, 5.2, 4.3 and 2.9 kb have been reported. We have synthesized six DNA...... oligonucleotides, that hybridize to different exons in the NCAM gene. Furthermore we have constructed three oligonucleotides, that exclusively hybridize to mRNAs lacking certain exons, by letting them consist of sequences adjacent to both sides of the splice sites. By means of these probes we have characterized...... the five NCAM mRNAs in rat brain....

Development, characterization and experimental validation of a cultivated sunflower (Helianthus annuus L.) gene expression oligonucleotide microarray.

Science.gov (United States)

Fernandez, Paula; Soria, Marcelo; Blesa, David; DiRienzo, Julio; Moschen, Sebastian; Rivarola, Maximo; Clavijo, Bernardo Jose; Gonzalez, Sergio; Peluffo, Lucila; Príncipi, Dario; Dosio, Guillermo; Aguirrezabal, Luis; García-García, Francisco; Conesa, Ana; Hopp, Esteban; Dopazo, Joaquín; Heinz, Ruth Amelia; Paniego, Norma

2012-01-01

Oligonucleotide-based microarrays with accurate gene coverage represent a key strategy for transcriptional studies in orphan species such as sunflower, H. annuus L., which lacks full genome sequences. The goal of this study was the development and functional annotation of a comprehensive sunflower unigene collection and the design and validation of a custom sunflower oligonucleotide-based microarray. A large scale EST (>130,000 ESTs) curation, assembly and sequence annotation was performed using Blast2GO (www.blast2go.de). The EST assembly comprises 41,013 putative transcripts (12,924 contigs and 28,089 singletons). The resulting Sunflower Unigen Resource (SUR version 1.0) was used to design an oligonucleotide-based Agilent microarray for cultivated sunflower. This microarray includes a total of 42,326 features: 1,417 Agilent controls, 74 control probes for sunflower replicated 10 times (740 controls) and 40,169 different non-control probes. Microarray performance was validated using a model experiment examining the induction of senescence by water deficit. Pre-processing and differential expression analysis of Agilent microarrays was performed using the Bioconductor limma package. The analyses based on p-values calculated by eBayes (psunflower unigene collection, and a custom, validated sunflower oligonucleotide-based microarray using Agilent technology. Both the curated unigene collection and the validated oligonucleotide microarray provide key resources for sunflower genome analysis, transcriptional studies, and molecular breeding for crop improvement.

Two pion correlation from SPACER

International Nuclear Information System (INIS)

Csoergoe, T.; Zimanyi, J.; Pratt, S.

1989-12-01

The correlation function for neutral and negative pions produced in ultrarelativistic heavy ion collisions was calculated without free parameters based on a space-time version of the LUND model, called SPACER: Simulation of Phase space distribution of Atomic nuclear Collisions in Energetic Reactions. This method includes the effect of Bose correlations for the emitted pion pair. Effects arising from correlations between space-time and momentum space distributions are investigated. The results are compared to the data of two different experiments. The role and interpretation of the chaocity parameter are discussed. (D.G.) 14 refs.; 4 figs

Ribosomal DNA internal transcribed spacer 1 and internal ...

African Journals Online (AJOL)

USER

2010-07-26

Jul 26, 2010 ... in some East Asian countries such as China, Korea and. *Corresponding author. E-mail: soonkwan@kangwon.ac.kr. Tel: +82 33 250 6476. Fax: +82 33 250 6470. Abbreviations: nrDNA, Nuclear ribosomal DNA; ITS, internal transcribed spacer; PCR, polymerase chain reaction; BLAST, basic local alignment ...

Preclinical investigations towards the first spacer gel application in prostate cancer treatment during particle therapy at HIT

International Nuclear Information System (INIS)

Ruciński, Antoni; Parodi, Katia; Jäkel, Oliver; Haberer, Thomas; Bauer, Julia; Campbell, Patrick; Brons, Stephan; Unholtz, Daniel; Habl, Gregor; Herfarth, Klaus; Debus, Jürgen; Bert, Christoph

2013-01-01

The application of spacer gel represents a promising approach to reliably spare the rectal frontal wall during particle therapy (IJROBP 76:1251-1258, 2010). In order to qualify the spacer gel for the clinical use in particle therapy, a variety of measurements were performed in order to ensure the biological compatibility of the gel, its physical stability during and after the irradiation, and a proper definition of the gel in terms of the Hounsfield Unit (HU) values for the treatment planning system. The potential for the use of the spacer gel for particle therapy monitoring with off-line Positron Emission Tomography (PET) was also investigated. The spacer gel implanted to the prostate patient in direct neighbourhood to the clinical target volume does not interfere with the particle therapy treatment planning procedure applied at Heidelberg Ion Beam Therapy Centre (HIT). The performed measurements show that Bragg-peak position of the particles can be properly predicted on the basis of computed tomography imaging with the treatment planning system used at HIT (measured water equivalent path length of 1.011 ±0.011 (2σ), measured Hounsfield Unit of 28.9 ±6.1 (2σ)). The spacer gel samples remain physically unchanged after irradiation with a dose exceeding the therapeutic dose level. The independently measured Bragg-Peak position does not change within the time interval of 10 weeks. As a result of the presented experiments, the first clinical application of spacer gel implant during prostate cancer treatment with carbon ions and protons was possible at HIT in 2012. The reported pre-clinical investigations demonstrate that use of spacer gel is safe in particle therapy in presence of therapy target motion and patient positioning induced particle range variations. The spacer gel injected between prostate and rectum enlarge the distance between both organs, which is expected to clinically significantly decrease the undesirable exposure of the most critical organ at risk

Development of Multiexon Skipping Antisense Oligonucleotide Therapy for Duchenne Muscular Dystrophy

Science.gov (United States)

Yokota, Toshifumi; Wood, Matthew J. A.

2013-01-01

Duchenne muscular dystrophy (DMD) is an incurable, X-linked progressive muscle degenerative disorder that results from the absence of dystrophin protein and leads to premature death in affected individuals due to respiratory and/or cardiac failure typically by age of 30. Very recently the exciting prospect of an effective oligonucleotide therapy has emerged which restores dystrophin protein expression to affected tissues in DMD patients with highly promising data from a series of clinical trials. This therapeutic approach is highly mutation specific and thus is personalised. Therefore DMD has emerged as a model genetic disorder for understanding and overcoming of the challenges of developing personalised genetic medicines. One of the greatest weaknesses of the current oligonucleotide approach is that it is a mutation-specific therapy. To address this limitation, we have recently demonstrated that exons 45–55 skipping therapy has the potential to treat clusters of mutations that cause DMD, which could significantly reduce the number of compounds that would need to be developed in order to successfully treat all DMD patients. Here we discuss and review the latest preclinical work in this area as well as a variety of accompanying issues, including efficacy and potential toxicity of antisense oligonucleotides, prior to human clinical trials. PMID:23984357

Effects of spacer orientations on the cake formation during membrane fouling: Quantitative analysis based on 3D OCT imaging.

Science.gov (United States)

Liu, Xin; Li, Weiyi; Chong, Tzyy Haur; Fane, Anthony G

2017-03-01

Spacer design plays an important role in improving the performance of membrane processes for water/wastewater treatment. This work focused on a fundamental issue of spacer design, i.e., investigating the effects of spacer orientations on the fouling behavior during a membrane process. A series of fouling experiments with different spacer orientation were carried out to in situ characterize the formation of a cake layer in a spacer unit cell via 3D optical coherence tomography (OCT) imaging. The cake layers formed at different times were digitalized for quantitatively analyzing the variation in the cake morphology as a function of time. In particular, the local deposition rates were evaluated to determine the active regions where the instantaneous changes in deposit thickness were significant. The characterization results indicate that varying the spacer orientation could substantially change the evolution of membrane fouling by particulate foulants and thereby result in a cake layer with various morphologies; the competition between growth and erosion at different locations would instantaneously respond to the micro-hydrodynamic environment that might change with time. This work confirms that the OCT-based characterization method is a powerful tool for exploring novel spacer design. Copyright © 2016 Elsevier Ltd. All rights reserved.

CFD analysis of pressure drop across grid spacers in rod bundles compared to correlations and heavy liquid metal experimental data

Energy Technology Data Exchange (ETDEWEB)

Batta, A., E-mail: batta@kit.edu; Class, A.G., E-mail: class@kit.edu

2017-02-15

Early studies of the flow in rod bundles with spacer grids suggest that the pressure drop can be decomposed in contributions due to flow area variations by spacer grids and frictional losses along the rods. For these shape and frictional losses simple correlations based on theoretical and experimental data have been proposed. In the OECD benchmark study LACANES it was observed that correlations could well describe the flow behavior of the heavy liquid metal loop including a rod bundle with the exception of the core region, where different experts chose different pressure-loss correlations for the losses due to spacer grids. Here, RANS–CFD simulations provided very good data compared to the experimental data. It was observed that the most commonly applied Rehme correlation underestimated the shape losses. The available correlations relate the pressure drop across a grid spacer to the relative plugging of the spacer i.e. solidity e{sub max}. More sophisticated correlations distinct between spacer grids with round or sharp leading edge shape. The purpose of this study is to (i) show that CFD is suitable to predict pressure drop across spacer grids and (ii) to access the generality of pressure drop correlations. By verification and validation of CFD results against experimental data obtained in KALLA we show (i). The generality (ii) is challenged by considering three cases which yield identical pressure drop in the correlations. First we test the effect of surface roughness, a parameter not present in the correlations. Here we compare a simulation assuming a typical surface roughness representing the experimental situation to a perfectly smooth spacer surface. Second we reverse the flow direction for the spacer grid employed in the experiments which is asymmetric. The flow direction reversal is chosen for convenience, since an asymmetric spacer grid with given blockage ratio, may result in different flow situations depending on flow direction. Obviously blockage

Lipid-modified G4-decoy oligonucleotide anchored to nanoparticles

DEFF Research Database (Denmark)

Cogoi, S; Jakobsen, U; Pedersen, E B

2016-01-01

KRAS is mutated in >90% of pancreatic ductal adenocarcinomas. As its inactivation leads to tumour regression, mutant KRAS is considered an attractive target for anticancer drugs. In this study we report a new delivery strategy for a G4-decoy oligonucleotide that sequesters MAZ, a transcription fa...

Time spans and spacers : Molecular phylogenetic explorations in the Cladophora complex (Chlorophyta) from the perspective of rDNA gene and spacer sequences

NARCIS (Netherlands)

Bakker, Frederik Theodoor

1995-01-01

In this study, phylogenetic relationships among genera, species and biogeographic representatives of single Cladophora species within the Cladophorales were analyzed using rDNA gene and spacer sequences. Based on phylogenetic analysis of 18S rRNA gene sequences, the Cladophora complex is shown to be

Single-Stage Treatment of Osteomyelitis for Digital Salvage by Using an Antibiotic-Eluting, Methylmethacrylate Joint-Spanning Spacer.

Science.gov (United States)

Aimé, Victoria L; Kidwell, John T; Webb, Leland H

2017-06-01

Osteomyelitis of the digit is a challenging problem that can result in amputation. We describe 13 cases of osteomyelitis involving bones of the hand managed with a novel technique. We reviewed records of 12 patients (13 digits) who had joint-spanning, antibiotic-eluting (tobramycin or vancomycin), methylmethacrylate spacers placed as definitive, single-stage treatment for digital osteomyelitis. The primary outcome was digit salvage. Secondary outcomes were infection eradication (no recurrence at 3 months) and spacer removal. Patients were followed up until the infection resolved (ie, no cutaneous signs of infection, including pain, erythema, or swelling). At a mean of 24 months, 10 of 13 infections had successful one-stage treatment. One patient required a second operation to revise a soft tissue flap but the spacer remained in place. Two spacers were removed because of malalignment. An antibiotic-eluting methylmethacrylate spacer is an innovative treatment for digital osteomyelitis. In 12 consecutive patients (13 digits), we successfully salvaged the digit. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Assessing the Interplay between the Physicochemical Parameters of Ion-Pairing Reagents and the Analyte Sequence on the Electrospray Desorption Process for Oligonucleotides

Science.gov (United States)

Basiri, Babak; Murph, Mandi M.; Bartlett, Michael G.

2017-08-01

Alkylamines are widely used as ion-pairing agents during LC-MS of oligonucleotides. In addition to a better chromatographic separation, they also assist with the desorption of oligonucleotide ions into the gas phase, cause charge state reduction, and decrease cation adduction. However, the choice of such ion-pairing agents has considerable influence on the MS signal intensity of oligonucleotides as they can also cause significant ion suppression. Interestingly, optimal ion-pairing agents should be selected on a case by case basis as their choice is strongly influenced by the sequence of the oligonucleotide under investigation. Despite imposing major practical difficulties to analytical method development, such a highly variable system that responds very strongly to the nuances of the electrospray composition provides an excellent opportunity for a fundamental study of the electrospray ionization process. Our investigations using this system quantitatively revealed the major factors that influenced the ESI ionization efficiency of oligonucleotides. Parameters such as boiling point, proton affinity, partition coefficient, water solubility, and Henry's law constants for the ion-pairing reagents and the hydrophobic thymine content of the oligonucleotides were found to be the most significant contributors. Identification of these parameters also allowed for the development of a statistical predictive algorithm that can assist with the choice of an optimum IP agent for each particular oligonucleotide sequence. We believe that research in the field of oligonucleotide bioanalysis will significantly benefit from this algorithm (included in Supplementary Material) as it advocates for the use of lesser-known but more suitable ion-pair alternatives to TEA for many oligonucleotide sequences.

Spacer length impacts the efficacy of targeted docetaxel conjugates in prostate-specific membrane antigen expressing prostate cancer.

Science.gov (United States)

Peng, Zheng-Hong; Sima, Monika; Salama, Mohamed E; Kopečková, Pavla; Kopeček, Jindřich

2013-12-01

Combination of targeted delivery and controlled release is a powerful technique for cancer treatment. In this paper, we describe the design, synthesis, structure validation and biological properties of targeted and non-targeted N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-docetaxel conjugates. Docetaxel (DTX) was conjugated to HPMA copolymer via a tetrapeptide spacer (-GFLG-). 3-(1,3-dicarboxypropyl)-ureido]pentanedioic acid (DUPA) was used as the targeting moiety to actively deliver DTX for treatment of Prostate-Specific Membrane Antigen (PSMA) expressing prostate cancer. Short and long spacer DUPA monomers were prepared, and four HPMA copolymer--DTX conjugates (non-targeted, two targeted with short spacer of different molecular weight and targeted with long spacer) were prepared via Reversible Addition-Fragmentation Chain Transfer (RAFT) copolymerization. Following confirmation of PSMA expression on C4-2 cell line, the DTX conjugates' in vitro cytotoxicity was tested against C4-2 tumor cells and their anticancer efficacies were assessed in nude mice bearing s.c. human prostate adenocarcinoma C4-2 xenografts. The in vivo results show that the spacer length between targeting moieties and HPMA copolymer backbone can significantly affect the treatment efficacy of DTX conjugates against C4-2 tumor bearing nu/nu mice. Moreover, histological analysis indicated that the DUPA-targeted DTX conjugate with longer spacer had no toxicity in major organs of treated mice.

Inhibition of cyclic AMP response element-directed transcription by decoy oligonucleotides enhances tumor-specific radiosensitivity

Energy Technology Data Exchange (ETDEWEB)

Park, Serk In, E-mail: serkin@korea.edu [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of); The BK21 Plus Program for Biomedical Sciences, Korea University College of Medicine, Seoul (Korea, Republic of); Department of Medicine and Center for Bone Biology, Vanderbilt University School of Medicine, Nashville, TN (United States); Park, Sung-Jun [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of); Laboratory of Obesity and Aging Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Lee, Junghan; Kim, Hye Eun; Park, Su Jin; Sohn, Jeong-Won [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of); Park, Yun Gyu, E-mail: parkyg@korea.ac.kr [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of)

2016-01-15

The radiation stress induces cytotoxic responses of cell death as well as cytoprotective responses of cell survival. Understanding exact cellular mechanism and signal transduction pathways is important in improving cancer radiotherapy. Increasing evidence suggests that cyclic AMP response element binding protein (CREB)/activating transcription factor (ATF) family proteins act as a survival factor and a signaling molecule in response to stress. We postulated that CREB inhibition via CRE decoy oligonucleotide increases tumor cell sensitization to γ-irradiation-induced cytotoxic stress. In the present study, we demonstrate that CREB phosphorylation and CREB DNA-protein complex formation increased in time- and radiation dose-dependent manners, while there was no significant change in total protein level of CREB. In addition, CREB was phosphorylated in response to γ-irradiation through p38 MAPK pathway. Further investigation revealed that CREB blockade by decoy oligonucleotides functionally inhibited transactivation of CREB, and significantly increased radiosensitivity of multiple human cancer cell lines including TP53- and/or RB-mutated cells with minimal effects on normal cells. We also demonstrate that tumor cells ectopically expressing dominant negative mutant CREB (KCREB) and the cells treated with p38 MAPK inhibitors were more sensitive to γ-irradiation than wild type parental cells or control-treated cells. Taken together, we conclude that CREB protects tumor cells from γ-irradiation, and combination of CREB inhibition plus ionizing radiation will be a promising radiotherapeutic approach. - Highlights: • γ-Irradiation induced CREB phosphorylation and CRE-directed transcription in tumor. • γ-Irradiation-induced transcriptional activation of CREB was via p38 MAPK pathway. • CRE blockade increased radiosensitivity of tumor cells but not of normal cells. • CRE decoy oligonucleotides or p38 MAPK inhibitors can be used as radiosensitizers.

Inhibition of cyclic AMP response element-directed transcription by decoy oligonucleotides enhances tumor-specific radiosensitivity

International Nuclear Information System (INIS)

Park, Serk In; Park, Sung-Jun; Lee, Junghan; Kim, Hye Eun; Park, Su Jin; Sohn, Jeong-Won; Park, Yun Gyu

2016-01-01

The radiation stress induces cytotoxic responses of cell death as well as cytoprotective responses of cell survival. Understanding exact cellular mechanism and signal transduction pathways is important in improving cancer radiotherapy. Increasing evidence suggests that cyclic AMP response element binding protein (CREB)/activating transcription factor (ATF) family proteins act as a survival factor and a signaling molecule in response to stress. We postulated that CREB inhibition via CRE decoy oligonucleotide increases tumor cell sensitization to γ-irradiation-induced cytotoxic stress. In the present study, we demonstrate that CREB phosphorylation and CREB DNA-protein complex formation increased in time- and radiation dose-dependent manners, while there was no significant change in total protein level of CREB. In addition, CREB was phosphorylated in response to γ-irradiation through p38 MAPK pathway. Further investigation revealed that CREB blockade by decoy oligonucleotides functionally inhibited transactivation of CREB, and significantly increased radiosensitivity of multiple human cancer cell lines including TP53- and/or RB-mutated cells with minimal effects on normal cells. We also demonstrate that tumor cells ectopically expressing dominant negative mutant CREB (KCREB) and the cells treated with p38 MAPK inhibitors were more sensitive to γ-irradiation than wild type parental cells or control-treated cells. Taken together, we conclude that CREB protects tumor cells from γ-irradiation, and combination of CREB inhibition plus ionizing radiation will be a promising radiotherapeutic approach. - Highlights: • γ-Irradiation induced CREB phosphorylation and CRE-directed transcription in tumor. • γ-Irradiation-induced transcriptional activation of CREB was via p38 MAPK pathway. • CRE blockade increased radiosensitivity of tumor cells but not of normal cells. • CRE decoy oligonucleotides or p38 MAPK inhibitors can be used as radiosensitizers.

MO-AB-BRA-02: Modeling Nanoparticle-Eluting Spacer Degradation During Brachytherapy Application with in Situ Dose-Painting

Energy Technology Data Exchange (ETDEWEB)

Boateng, F [University of Massachusetts Lowell, Lowell, Massachusetts (United States); Ngwa, W [University of Massachusetts Lowell, Lowell, Massachusetts (United States); Harvard Medical School, Boston, MA (United States)

2016-06-15

Purpose: Brachytherapy application with in situ dose-painting using gold nanoparticles (GNP) released from GNP-loaded brachytherapy spacers has been proposed as an innovative approach to increase therapeutic efficacy during brachytherapy. This work investigates the dosimetric impact of slow versus burst release of GNP from next generation biodegradable spacers. Methods: Mathematical models were developed based on experimental data to study the release of GNP from a spacer designed with FDA approved poly(lactic-co-glycolic acid) (PLGA) polymer. The diffusion controlled released process and PLGA polymer degradation kinetics was incorporated in the calculations for the first time. An in vivo determined diffusion coefficient was used for determining the concentration profiles and corresponding dose enhancement based on initial GNP-loading concentrations of 7 mg/g. Results: The results showed that there is significant delay before the concentration profile of GNP diffusion in the tumor is similar to that when burst release is assumed as in previous studies. For example, in the case of burst release after spacer administration, it took up to 25 days for all the GNP to be released from the spacer using diffusion controlled release process only. However, it took up to 45 days when a combined model for both diffusion and polymer degradation processes was used. Based on the tumor concentration profiles, a significant dose enhancement factor (DEF >20%), could be attained at a tumor distances of 5 mm from a spacer loaded with 10 nm GNP sizes. Conclusion: The results highlight the need to take the slow release of GNP from spacers and factors such as biodegradation of polymers into account in research development of GNP-eluting spacers for brachytherapy applications with in-situ dose-painting using gold nanoparticles. The findings suggest that I-125 may be the more appropriate for such applications given the relatively longer half-live compared to other radioisotopes like Pd-103

Phage annealing proteins promote oligonucleotide-directed mutagenesis in Escherichia coli and mouse ES cells

Directory of Open Access Journals (Sweden)

Muyrers Joep PP

2003-01-01

Full Text Available Abstract Background The phage protein pairs, RecE/RecT from Rac or Redα/Redβ from λ, initiate efficient double strand break repair (DSBR in Escherichia coli that has proven very useful for DNA engineering. These phage pairs initiate DSBR either by annealing or by another mechanism that is not defined. Results Here we report that these proteins also mediate single strand oligonucleotide repair (ssOR at high efficiencies. The ssOR activity, unlike DSBR, does not require a phage exonuclease (RecE or Redα but only requires a phage annealing protein (RecT or Redβ. Notably, the P22 phage annealing protein Erf, which does not mediate the same DSBR reactions, also delivers ssOR activity. By altering aspects of the oligonucleotides, we document length and design parameters that affect ssOR efficiency to show a simple relationship to homologies either side of the repair site. Notably, ssOR shows strand bias. Oligonucleotides that can prime lagging strand replication deliver more ssOR than their leading complements. This suggests a model in which the annealing proteins hybridize the oligonucleotides to single stranded regions near the replication fork. We also show that ssOR is a highly efficient way to engineer BACs and can be detected in a eukaryotic cell upon expression of a phage annealing protein. Conclusion Phage annealing proteins can initiate the recombination of single stranded oligonucleotides into endogenous targets in Escherichia coli at very high efficiencies. This expands the repertoire of useful DNA engineering strategies, shows promise for applications in eukaryotic cells, and has implications for the unanswered questions regarding DSBR mediated by RecE/RecT and Redα/Redβ.

Ultramild protein-mediated click chemistry creates efficient oligonucleotide probes for targeting and detecting nucleic acids

DEFF Research Database (Denmark)

Nåbo, Lina J.; Madsen, Charlotte S.; Jensen, Knud J.

2015-01-01

Functionalized synthetic oligonucleotides are finding growing applications in research, clinical studies, and therapy. However, it is not easy to prepare them in a biocompatible and highly efficient manner. We report a new strategy to synthesize oligonucleotides with promising nucleic acid...... targeting and detection properties. We focus in particular on the pH sensitivity of these new probes and their high target specificity. For the first time, human copper(I)-binding chaperon Cox17 was applied to effectively catalyze click labeling of oligonucleotides. This was performed under ultramild...... conditions with fluorophore, peptide, and carbohydrate azide derivatives. In thermal denaturation studies, the modified probes showed specific binding to complementary DNA and RNA targets. Finally, we demonstrated the pH sensitivity of the new rhodamine-based fluorescent probes in vitro and rationalize our...

Oligonucleotide aptamers against tyrosine kinase receptors: Prospect for anticancer applications.

Science.gov (United States)

Camorani, Simona; Crescenzi, Elvira; Fedele, Monica; Cerchia, Laura

2018-04-01

Transmembrane receptor tyrosine kinases (RTKs) play crucial roles in cancer cell proliferation, survival, migration and differentiation. Area of intense research is searching for effective anticancer therapies targeting these receptors and, to date, several monoclonal antibodies and small-molecule tyrosine kinase inhibitors have entered the clinic. However, some of these drugs show limited efficacy and give rise to acquired resistance. Emerging highly selective compounds for anticancer therapy are oligonucleotide aptamers that interact with their targets by recognizing a specific three-dimensional structure. Because of their nucleic acid nature, the rational design of advanced strategies to manipulate aptamers for both diagnostic and therapeutic applications is greatly simplified over antibodies. In this manuscript, we will provide a comprehensive overview of oligonucleotide aptamers as next generation strategies to efficiently target RTKs in human cancers. Copyright © 2018 Elsevier B.V. All rights reserved.

A numerical approach to the simulation of one-phase and two phase reactor coolant flow around nuclear fuel spacers

International Nuclear Information System (INIS)

Stosic, Z.V.; Stevanovic, V.D.

2001-01-01

A methodology for the simulation and analysis of one-phase and two-phase coolant flows around one or a row of spacers is presented. It is based on the multidimensional two-fluid mass, momentum and energy balance equations and application of adequate turbulence models. Necessary closure laws for interfacial transfer processes are presented. The stated general approach enables simulation and analyses of reactor coolant flow around spacers on different scale levels of the rod bundle geometry: detailed modelling of coolant flow around spacers and investigation of the influence of spacer's geometry on the coolant thermal-hydraulics, as well as prediction of global thermal-hydraulic parameters within the whole rod bundle with the investigation of the influence of rows of spacers on the bulk thermal-hydraulic processes. Sample problems are included illustrating these different modelling approaches. (author)

Effect of different commercial feed spacers on biofouling of reverse osmosis membrane systems: A numerical study

KAUST Repository

Bucs, Szilard

2014-06-01

Feed spacers and hydrodynamics have been found relevant for the impact of biofouling on performance in reverse osmosis (RO) and nanofiltration (NF) membrane systems.The objectives of this study on biofouling development were to determine the impact of (i) linear flow velocity and bacterial cell load, (ii) biomass location and (iii) various feed spacer geometries as applied in practice as well as a modified geometry spacer.A three-dimensional mathematical model for biofouling of feed spacer channels including hydrodynamics, solute mass transport and biofilm formation was developed in COMSOL Multiphysics and MATLAB software.Results of this study indicate that the feed channel pressure drop increase caused by biofilm formation can be reduced by using thicker and/or modified feed spacer geometry and/or a lower flow rate in the feed channel. The increase of feed channel pressure drop by biomass accumulation is shown to be strongly influenced by the location of biomass. Results of numerical simulations are in satisfactory agreement with experimental data, indicating that this micro-scale mechanistic model is representative for practice. The developed model can help to understand better the biofouling process of spiral-wound RO and NF membrane systems and to develop strategies to reduce and control biofouling. © 2013 Elsevier B.V.

Effect of different commercial feed spacers on biofouling of reverse osmosis membrane systems: A numerical study

KAUST Repository

Bucs, Szilard; Radu, Andrea I.; Lavric, Vasile; Vrouwenvelder, Johannes S.; Picioreanu, Cristian

2014-01-01

Feed spacers and hydrodynamics have been found relevant for the impact of biofouling on performance in reverse osmosis (RO) and nanofiltration (NF) membrane systems.The objectives of this study on biofouling development were to determine the impact of (i) linear flow velocity and bacterial cell load, (ii) biomass location and (iii) various feed spacer geometries as applied in practice as well as a modified geometry spacer.A three-dimensional mathematical model for biofouling of feed spacer channels including hydrodynamics, solute mass transport and biofilm formation was developed in COMSOL Multiphysics and MATLAB software.Results of this study indicate that the feed channel pressure drop increase caused by biofilm formation can be reduced by using thicker and/or modified feed spacer geometry and/or a lower flow rate in the feed channel. The increase of feed channel pressure drop by biomass accumulation is shown to be strongly influenced by the location of biomass. Results of numerical simulations are in satisfactory agreement with experimental data, indicating that this micro-scale mechanistic model is representative for practice. The developed model can help to understand better the biofouling process of spiral-wound RO and NF membrane systems and to develop strategies to reduce and control biofouling. © 2013 Elsevier B.V.

Single-electron transistors fabricated with sidewall spacer patterning

Science.gov (United States)

Park, Byung-Gook; Kim, Dae Hwan; Kim, Kyung Rok; Song, Ki-Whan; Lee, Jong Duk

2003-09-01

We have implemented a sidewall spacer patterning method for novel dual-gate single-electron transistor (DGSET) and metal-oxide-semiconductor-based SET (MOSET) based on the uniform SOI wire, using conventional lithography and processing technology. A 30 nm wide silicon quantum wire is defined by a sidewall spacer patterning method, and depletion gates for two tunnel junctions of the DGSET are formed by the doped polycrystalline silicon sidewall. The fabricated DGSET and MOSET show clear single-electron tunneling phenomena at liquid nitrogen temperature and insensitivity of the Coulomb oscillation period to gate bias conditions. On the basis of the phase control capability of the sidewall depletion gates, we have proposed a complementary self-biasing method, which enables the SET/CMOS hybrid multi-valued logic (MVL) to operate perfectly well at high temperature, where the peak-to-valley current ratio of Coulomb oscillation severely decreases. The suggested scheme is evaluated by SPICE simulation with an analytical DGSET model, and it is confirmed that even DGSETs with a large Si island can be utilized efficiently in the multi-valued logic.

Resolving prokaryotic taxonomy without rRNA: longer oligonucleotide word lengths improve genome and metagenome taxonomic classification.

Science.gov (United States)

Alsop, Eric B; Raymond, Jason

2013-01-01

Oligonucleotide signatures, especially tetranucleotide signatures, have been used as method for homology binning by exploiting an organism's inherent biases towards the use of specific oligonucleotide words. Tetranucleotide signatures have been especially useful in environmental metagenomics samples as many of these samples contain organisms from poorly classified phyla which cannot be easily identified using traditional homology methods, including NCBI BLAST. This study examines oligonucleotide signatures across 1,424 completed genomes from across the tree of life, substantially expanding upon previous work. A comprehensive analysis of mononucleotide through nonanucleotide word lengths suggests that longer word lengths substantially improve the classification of DNA fragments across a range of sizes of relevance to high throughput sequencing. We find that, at present, heptanucleotide signatures represent an optimal balance between prediction accuracy and computational time for resolving taxonomy using both genomic and metagenomic fragments. We directly compare the ability of tetranucleotide and heptanucleotide world lengths (tetranucleotide signatures are the current standard for oligonucleotide word usage analyses) for taxonomic binning of metagenome reads. We present evidence that heptanucleotide word lengths consistently provide more taxonomic resolving power, particularly in distinguishing between closely related organisms that are often present in metagenomic samples. This implies that longer oligonucleotide word lengths should replace tetranucleotide signatures for most analyses. Finally, we show that the application of longer word lengths to metagenomic datasets leads to more accurate taxonomic binning of DNA scaffolds and have the potential to substantially improve taxonomic assignment and assembly of metagenomic data.

Resolving prokaryotic taxonomy without rRNA: longer oligonucleotide word lengths improve genome and metagenome taxonomic classification.

Directory of Open Access Journals (Sweden)

Eric B Alsop

Full Text Available Oligonucleotide signatures, especially tetranucleotide signatures, have been used as method for homology binning by exploiting an organism's inherent biases towards the use of specific oligonucleotide words. Tetranucleotide signatures have been especially useful in environmental metagenomics samples as many of these samples contain organisms from poorly classified phyla which cannot be easily identified using traditional homology methods, including NCBI BLAST. This study examines oligonucleotide signatures across 1,424 completed genomes from across the tree of life, substantially expanding upon previous work. A comprehensive analysis of mononucleotide through nonanucleotide word lengths suggests that longer word lengths substantially improve the classification of DNA fragments across a range of sizes of relevance to high throughput sequencing. We find that, at present, heptanucleotide signatures represent an optimal balance between prediction accuracy and computational time for resolving taxonomy using both genomic and metagenomic fragments. We directly compare the ability of tetranucleotide and heptanucleotide world lengths (tetranucleotide signatures are the current standard for oligonucleotide word usage analyses for taxonomic binning of metagenome reads. We present evidence that heptanucleotide word lengths consistently provide more taxonomic resolving power, particularly in distinguishing between closely related organisms that are often present in metagenomic samples. This implies that longer oligonucleotide word lengths should replace tetranucleotide signatures for most analyses. Finally, we show that the application of longer word lengths to metagenomic datasets leads to more accurate taxonomic binning of DNA scaffolds and have the potential to substantially improve taxonomic assignment and assembly of metagenomic data.

Introduction on Using the FastPCR Software and the Related Java Web Tools for PCR and Oligonucleotide Assembly and Analysis.

Science.gov (United States)

Kalendar, Ruslan; Tselykh, Timofey V; Khassenov, Bekbolat; Ramanculov, Erlan M

2017-01-01

This chapter introduces the FastPCR software as an integrated tool environment for PCR primer and probe design, which predicts properties of oligonucleotides based on experimental studies of the PCR efficiency. The software provides comprehensive facilities for designing primers for most PCR applications and their combinations. These include the standard PCR as well as the multiplex, long-distance, inverse, real-time, group-specific, unique, overlap extension PCR for multi-fragments assembling cloning and loop-mediated isothermal amplification (LAMP). It also contains a built-in program to design oligonucleotide sets both for long sequence assembly by ligase chain reaction and for design of amplicons that tile across a region(s) of interest. The software calculates the melting temperature for the standard and degenerate oligonucleotides including locked nucleic acid (LNA) and other modifications. It also provides analyses for a set of primers with the prediction of oligonucleotide properties, dimer and G/C-quadruplex detection, linguistic complexity as well as a primer dilution and resuspension calculator. The program consists of various bioinformatical tools for analysis of sequences with the GC or AT skew, CG% and GA% content, and the purine-pyrimidine skew. It also analyzes the linguistic sequence complexity and performs generation of random DNA sequence as well as restriction endonucleases analysis. The program allows to find or create restriction enzyme recognition sites for coding sequences and supports the clustering of sequences. It performs efficient and complete detection of various repeat types with visual display. The FastPCR software allows the sequence file batch processing that is essential for automation. The program is available for download at http://primerdigital.com/fastpcr.html , and its online version is located at http://primerdigital.com/tools/pcr.html .

Pharmacokinetics on a microscale: visualizing Cy5-labeled oligonucleotide release from poly(n-butylcyanoacrylate nanocapsules in cells

Directory of Open Access Journals (Sweden)

Tomcin S

2014-11-01

Full Text Available Stephanie Tomcin,1 Grit Baier,1 Katharina Landfester,1 Volker Mailänder1,21Max Planck Institute for Polymer Research, 2University Medical Center of the Johannes Gutenberg University, III Medical Clinic, Mainz, GermanyAbstract: For successful design of a nanoparticulate drug delivery system, the fate of the carrier and cargo need to be followed. In this work, we fluorescently labeled poly(n-butylcyanoacrylate (PBCA nanocapsules as a shell and separately an oligonucleotide (20 mer as a payload. The nanocapsules were formed by interfacial anionic polymerization on aqueous droplets generated by an inverse miniemulsion process. After uptake, the PBCA capsules were shown to be round-shaped, endosomal structures and the payload was successfully released. Cy5-labeled oligonucleotides accumulated at the mitochondrial membrane due to a combination of the high mitochondrial membrane potential and the specific molecular structure of Cy5. The specificity of this accumulation at the mitochondria was shown as the uncoupler dinitrophenol rapidly diminished the accumulation of the Cy5-labeled oligonucleotide. Importantly, a fluorescence resonance energy transfer investigation showed that the dye-labeled cargo (Cy3/Cy5-labeled oligonucleotides reached its target site without degradation during escape from an endosomal compartment to the cytoplasm. The time course of accumulation of fluorescent signals at the mitochondria was determined by evaluating the colocalization of Cy5-labeled oligonucleotides and mitochondrial markers for up to 48 hours. As oligonucleotides are an ideal model system for small interfering RNA PBCA nanocapsules demonstrate to be a versatile delivery platform for small interfering RNA to treat a variety of diseases.Keywords: drug delivery, mitochondria, miniemulsion, colocalization

Preliminary Investigation on Turbulent Flow in Tight-lattice Rod Bundle with Twist-mixing Vane Spacer Grid

International Nuclear Information System (INIS)

Lee, Chiyoung; Kwack, Youngkyun; Park, Juyong; Shin, Changhwan; In, Wangkee

2013-01-01

Our research group has investigated the effect of P/D difference on the behavior of turbulent rod bundle flow without the mixing vane spacer grid, using PIV (Particle Image Velocimetry) and MIR (Matching Index of Refraction) techniques for tight lattice fuel rod bundle application. In this work, using the tight-lattice rod bundle with a twist-mixing vane spacer grid, the turbulent rod bundle flow is preliminarily examined to validate the PIV measurement and CFD (Computational Fluid Dynamics) simulation. The turbulent flow in the tight-lattice rod bundle with a twist-mixing vane spacer grid was preliminarily examined to validate the PIV measurement and CFD simulation. Both were in agreement with each other within a reasonable degree of accuracy. Using PIV measurement and CFD simulation tested in this work, the detailed investigations on the behavior of turbulent rod bundle flow with the twist-mixing vane spacer grid will be performed at various conditions, and reported in the near future

Spatially Defined Oligonucleotide Arrays. Technical Report for Phase II; FINAL

International Nuclear Information System (INIS)

None

2000-01-01

The goal of the Human Genome Project is to sequence all 3 billion base pairs of the human genome. Progress in this has been rapid; GenBank(reg s ign) finished 1994 with 286 million bases of sequence and grew by 2470 in the first quarter of 1995. The challenge to the scientific community is to understand the biological relevance of this genetic information. In most cases the sequence being generated for any single region of the genome represents the genotype of a single individual. A complete understanding of the function of specific genes and other regions of the genome and their role in human disease and development will only become apparent when the sequence of many more individuals is known. Access to genetic information is ultimately limited by the ability to screen DNA sequence. Although the pioneering sequencing methods of Sanger et al. (15) and Maxam and Gilbert (11) have become standard in virtually all molecular biology laboratories, the basic protocols remain largely unchanged. The throughput of this sequencing technology is now becoming the rate-limiting step in both large-scale sequencing projects such as the Human Genome Project and the subsequent efforts to understand genetic diversity. This has inspired the development of advanced DNA sequencing technologies (9), Incremental improvements to Sanger sequencing have been made in DNA labeling and detection. High-speed electrophoresis methods using ultrathin gels or capillary arrays are now being more widely employed. However, these methods are throughput-limited by their sequential nature and the speed and resolution of separations. This limitation will become more pronounced as the need to rapidly screen newly discovered genes for biologically relevant polymorphisms increases. An alternative to gel-based sequencing is to use high-density oligonucleotide probe arrays. Oligonucleotide probe arrays display specific oligonucleotide probes at precise locations in a high density, information-rich format (5

WE-FG-BRA-02: Docetaxel Eluting Brachytherapy Spacers for Local Chemo-Radiation Therapy in Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Belz, J [Northeastern University, Boston, MA (United States); Kumar, R; Sridhar, S [Northeastern University & Dana Farber Cancer Institute, Boston, MA (United States); Makrigiorgos, G; Nguyen, P [Dana Farber Cancer Institute, Boston, MA (United States); D’Amico, A [Brigham & Women’s Hospital, Boston, MA (United States); Cormack, R [Harvard Medical School, Boston, MA (United States)

2016-06-15

Purpose: We propose an innovative combinatorial treatment strategy of Local ChemoRadiation Therapy (LCRT) using a sustained drug delivery platform in the form of a spacer to locally radio-sensitize the prostate with Docetaxel (DTX) enabling a synergistic cure with the use of lower radiation doses. These biodegradable spacers are physically similar to the inert spacers routinely used in prostate brachytherapy but are now loaded with formulations of DTX. Methods: Spacers were loaded with ∼500µg Docetaxel (DTX) for prostate cancer studies. The implants were characterized in vitro using SEM and HPLC. The release kinetic studies were carried out in buffer (pH 6.0) at 37°C. Subcutaneous PC3 tumors were xenografted in nude mice. Prostate cancer studies were done with and without radiation using SARRP at 5Gy, 10Gy, and 15Gy. Drug-loaded implants were injected once intratumorally using an 18G brachytherapy needle. Results: The release study in vitro showed a highly sustained release for multiple weeks at therapeutically relevant doses. The monotherapy with local DTX spacer showed sustained tumor inhibition compared to empty implants and an equivalent DTX dose given systemically. At 40 days, 89% survival was observed for mice treated with DTX implants compared with 0% in all other treatment groups. The combined treatment with local DTX spacer and radiation (10Gy) showed the highest degree of tumor suppression (significant tumor growth inhibition by day 90). The control mice showed continuous tumor growth and were scarified by day 56. Groups of mice treated with DTX-spacer or radiation alone showed initial tumor suppression but growth continued after day 60. A larger experiment is ongoing. Conclusion: This approach provides localized delivery of the chemotherapeutic sensitizer directly to the tumor and avoids the toxicities associated with both brachytherapy and current systemic delivery of docetaxel. Sustained release of DTX is an effective chemotherapy option alone or

Spacer grid corner gusset

International Nuclear Information System (INIS)

Larson, J.G.

1984-01-01

There is provided a spacer grid for a bundle of longitudinally extending rods in spaced generally parallel relationship comprising spacing means for holding the rods in spaced generally parallel relationship; the spacing means includes at least one exterior grid strip circumscribing the bundle of rods along the periphery thereof; with at least one exterior grid strip having a first edge defining the boundary of the strip in one longitudinal direction and a second edge defining the boundary of the strip in the other longitudinal direction; with at least one exterior grid strip having at least one band formed therein parallel to the longitudinal direction; a plurality of corner gussets truncating each of a plurality of corners formed by at least one band and the first edge and the second edge

Combining gene expression data from different generations of oligonucleotide arrays

Directory of Open Access Journals (Sweden)

Kong Sek

2004-10-01

Full Text Available Abstract Background One of the important challenges in microarray analysis is to take full advantage of previously accumulated data, both from one's own laboratory and from public repositories. Through a comparative analysis on a variety of datasets, a more comprehensive view of the underlying mechanism or structure can be obtained. However, as we discover in this work, continual changes in genomic sequence annotations and probe design criteria make it difficult to compare gene expression data even from different generations of the same microarray platform. Results We first describe the extent of discordance between the results derived from two generations of Affymetrix oligonucleotide arrays, as revealed in cluster analysis and in identification of differentially expressed genes. We then propose a method for increasing comparability. The dataset we use consists of a set of 14 human muscle biopsy samples from patients with inflammatory myopathies that were hybridized on both HG-U95Av2 and HG-U133A human arrays. We find that the use of the probe set matching table for comparative analysis provided by Affymetrix produces better results than matching by UniGene or LocusLink identifiers but still remains inadequate. Rescaling of expression values for each gene across samples and data filtering by expression values enhance comparability but only for few specific analyses. As a generic method for improving comparability, we select a subset of probes with overlapping sequence segments in the two array types and recalculate expression values based only on the selected probes. We show that this filtering of probes significantly improves the comparability while retaining a sufficient number of probe sets for further analysis. Conclusions Compatibility between high-density oligonucleotide arrays is significantly affected by probe-level sequence information. With a careful filtering of the probes based on their sequence overlaps, data from different

An oral oligonucleotide delivery system based on a thiolated polymer: Development and in vitro evaluation.

Science.gov (United States)

Martien, Ronny; Hoyer, Herbert; Perera, Glen; Schnürch, Andreas Bernkop

2011-08-01

The purpose of this study was to develop and evaluate an oral oligonucleotide delivery system based on a thiolated polymer/reduced glutathione (GSH) system providing a protective effect toward nucleases and permeation enhancement. A polycarbophil-cysteine conjugate (PCP-Cys) was synthesized. Enzymatic degradation of a model oligonucleotide by DNase I and within freshly collected intestinal fluid was investigated in the absence and presence of PCP-Cys. Permeation studies with PCP-Cys/GSH versus control were performed in vitro on Caco-2 cell monolayers and ex vivo on rat intestinal mucosa. PCP-Cys displayed 223 ± 13.8 μmol thiol groups per gram polymer. After 4h, 61% of the free oligonucleotides were degraded by DNase I and 80% within intestinal fluid. In contrast, less than 41% (DNase I) and 60% (intestinal fluid) were degraded in the presence of 0.02% (m/v) PCP-Cys. Permeation studies revealed an 8-fold (Caco-2) and 10-fold (intestinal mucosa) increase in apparent permeability compared to buffer control. Hence, this PCP-Cys/GSH system might be a promising tool for the oral administration of oligonucleotides as it allows a significant protection toward degrading enzymes and facilitates their transport across intestinal membranes. Copyright © 2011 Elsevier B.V. All rights reserved.

Spacers for use in nuclear fuel assembly

International Nuclear Information System (INIS)

Shiohata, Hironori; Nakamura, Shozo; Hasegawa, Kunio; Higuchi, Shigeo; Nagashima, Hideaki; Kawada, Yoshishige.

1987-01-01

Purpose: To prevent liquid film breakage at the surface of a fuel rod due to swirlings of steam flow generated at the upstream of a contact portion between the fuel rod and a spacer leaf spring, that is, below the contact portion. Constitution: Steam-hot water 2-phase streams flowing from the lower to the upper portions of a fuel assembly is hindered by leaf springs, thereby forming swirlings in the steam flow at the upstream of a contact portion between the fuel rod and the leaf springs, that is, below the contact portion. The horseshoe-like swirlings shed the liquid films at the surface of the fuel rod to remarkably decrease the heat cooling performance, by which the surface temperature of a fuel can is temporarily increased thereby possibly causing failures due to so-called burnout in view of the above, steps are formed to the spacer leaf spring for use in the fuel assembly, to reduce the pressure difference between the leaf spring and the fuel rod at the upstream of the springs relative to the 2-phase coolant stream. In this way, formation of the swirlings is moderated to prevent the liquid film breakage and improve the critical heat power. (Kamimura, M.)

Advances in Antisense Oligonucleotide Development for Target Identification, Validation, and as Novel Therapeutics

Directory of Open Access Journals (Sweden)

Moizza Mansoor

2008-01-01

Full Text Available Antisense oligonucleotides (As-ODNs are single stranded, synthetically prepared strands of deoxynucleotide sequences, usually 18–21 nucleotides in length, complementary to the mRNA sequence of the target gene. As-ODNs are able to selectively bind cognate mRNA sequences by sequence-specific hybridization. This results in cleavage or disablement of the mRNA and, thus, inhibits the expression of the target gene. The specificity of the As approach is based on the probability that, in the human genome, any sequence longer than a minimal number of nucleotides (nt, 13 for RNA and 17 for DNA, normally occurs only once. The potential applications of As-ODNs are numerous because mRNA is ubiquitous and is more accessible to manipulation than DNA. With the publication of the human genome sequence, it has become theoretically possible to inhibit mRNA of almost any gene by As-ODNs, in order to get a better understanding of gene function, investigate its role in disease pathology and to study novel therapeutic targets for the diseases caused by dysregulated gene expression. The conceptual simplicity, the availability of gene sequence information from the human genome, the inexpensive availability of synthetic oligonucleotides and the possibility of rational drug design makes As-ODNs powerful tools for target identification, validation and therapeutic intervention. In this review we discuss the latest developments in antisense oligonucleotide design, delivery, pharmacokinetics and potential side effects, as well as its uses in target identification and validation, and finally focus on the current developments of antisense oligonucleotides in therapeutic intervention in various diseases.

An examination of the influence of spacers on burnout in an annulus cooled by the upflow of Freon-12

International Nuclear Information System (INIS)

Ilic, V.

1975-04-01

To evaluate the spacer influence on burnout, tests were carried out in Freon-12 at 1.04 MPa (abs.) test section inlet pressure with an internally heated annulus 2743 mm long by 14.4 mm heater diameter, the outer tube (shroud) having a bore of 22.1 mm. The inner rod (heater) was located centrally to the shroud by spacers and their configuration was changed for each test. Comparison of the results with those obtained with a test section having no spacers indicated that spacers can increase burnout power up to 75 per cent, decrease it, or show no effect at all, depending on the combination of the inlet temperature and mass velocity. If the spacers were streamlined, removed from the upstream portion of the heater or relocated farther upstream from the downstream end of the heater, there was a considerably reduced effect on the test section performance. (author)

Sequence-Dependent Mechanism of DNA Oligonucleotide Dehybridization Resolved through Infrared Spectroscopy.

Science.gov (United States)

Sanstead, Paul J; Stevenson, Paul; Tokmakoff, Andrei

2016-09-14

Despite its important role in biology and nanotechnology, many questions remain regarding the molecular mechanism and dynamics by which oligonucleotides recognize and hybridize to their complementary sequence. The thermodynamics and kinetics of DNA oligonucleotide hybridization and dehybridization are often assumed to involve an all-or-nothing two-state dissociation pathway, but deviations from this behavior can be considerable even for short sequences. We introduce a new strategy to characterize the base-pair-specific thermal dissociation mechanism of DNA oligonucleotides through steady-state and time-resolved infrared spectroscopy. Experiments are interpreted with a lattice model to provide a structure-specific interpretation. This method is applied to a model set of self-complementary 10-base-pair sequences in which the placement of GC base pairs is varied in an otherwise AT strand. Through a combination of Fourier transform infrared and two-dimensional infrared spectroscopy, experiments reveal varying degrees of deviation from simple two-state behavior. As the temperature is increased, duplexes dissociate through a path in which the terminal bases fray, without any significant contribution from loop configurations. Transient temperature jump experiments reveal time scales of 70-100 ns for fraying and 10-30 μs for complete dissociation near the melting temperature. Whether or not frayed states are metastable intermediates or short-lived configurations during the full dissociation of the duplex is dictated by the nucleobase sequence.

The use of ZnO as optical spacer in polymer solar cells : theoretical and experimental study

NARCIS (Netherlands)

Gilot, J.; Barbu, I.; Wienk, M.M.; Janssen, R.A.J.

2007-01-01

For org. solar cells, insertion of an optical spacer between the active layer and the reflective electrode results in a redistribution of the optical elec. field. In this paper, theor. calcns. using optical modeling are compared with exptl. results for devices with ZnO as optical spacer. An

Development of an Efficient G-Quadruplex-Stabilised Thrombin-Binding Aptamer Containing a Three-Carbon Spacer Molecule

DEFF Research Database (Denmark)

Aaldering, Lukas J.; Poongavanam, Vasanthanathan; Langkjær, Niels

2017-01-01

The thrombin-binding aptamer (TBA), which shows anticoagulant properties, is one of the most studied G-quadruplex-forming aptamers. In this study, we investigated the impact of different chemical modifications such as a three-carbon spacer (spacer-C3), unlocked nucleic acid (UNA) and 3′-amino-mod...

Hammerhead ribozyme activity and oligonucleotide duplex stability in mixed solutions of water and organic compounds

Directory of Open Access Journals (Sweden)

Shu-ichi Nakano

2014-01-01

Full Text Available Nucleic acids are useful for biomedical targeting and sensing applications in which the molecular environment is different from that of a dilute aqueous solution. In this study, the influence of various types of mixed solutions of water and water-soluble organic compounds on RNA was investigated by measuring the catalytic activity of the hammerhead ribozyme and the thermodynamic stability of an oligonucleotide duplex. The compounds with a net neutral charge, such as poly(ethylene glycol, small primary alcohols, amide compounds, and aprotic solvent molecules, added at high concentrations changed the ribozyme-catalyzed RNA cleavage rate, with the magnitude of the effect dependent on the NaCl concentration. These compounds also changed the thermodynamic stability of RNA base pairs of an oligonucleotide duplex and its dependence on the NaCl concentration. Specific interactions with RNA molecules and reduced water activity could account for the inhibiting effects on the ribozyme catalysis and destabilizing effects on the duplex stability. The salt concentration dependence data correlated with the dielectric constant, but not with water activity, viscosity, and the size of organic compounds. This observation suggests the significance of the dielectric constant effects on the RNA reactions under molecular crowding conditions created by organic compounds.

Investigation on effect of methylene spacer in holographic grating formation in eosin containing polymethacrylates

Energy Technology Data Exchange (ETDEWEB)

Manickasundaram, S. [Department of Chemistry, Anna University, Sardar Vallabai Patel Road, Chennai 600025 (India); Kannan, P. [Department of Chemistry, Anna University, Sardar Vallabai Patel Road, Chennai 600025 (India)]. E-mail: pakannan@annauniv.edu; Deepa, S. [Centre for Laser Technology, Department of Physics, Anna University, Chennai 600025 (India); Palanisamy, P.K. [Centre for Laser Technology, Department of Physics, Anna University, Chennai 600025 (India)

2007-01-15

A new series of eosin dye based poly(alkyloxymethacrylate)s was synthesized with an even number of side-chain methylene spacers by a free radical addition polymerization method for holographic optical data storage applications. These polymers were characterized by UV, IR and {sup 1}H NMR spectroscopy. The glass transition temperature and thermal stability of the polymers were investigated by DSC and TGA, respectively. As the spacer length increases in the side-chain, Tg, Tm and thermal stability of the polymers decrease, while a reverse trend was observed with film forming ability of the polymers. The optical characterization of the polymers was investigated by forming holographic grating using an Argon ion laser. The grating diffraction efficiency was found to depend not only on the concentration of polymeric film but also on the spacer length of the polymers.

Investigation on effect of methylene spacer in holographic grating formation in eosin containing polymethacrylates

International Nuclear Information System (INIS)

Manickasundaram, S.; Kannan, P.; Deepa, S.; Palanisamy, P.K.

2007-01-01

A new series of eosin dye based poly(alkyloxymethacrylate)s was synthesized with an even number of side-chain methylene spacers by a free radical addition polymerization method for holographic optical data storage applications. These polymers were characterized by UV, IR and 1 H NMR spectroscopy. The glass transition temperature and thermal stability of the polymers were investigated by DSC and TGA, respectively. As the spacer length increases in the side-chain, Tg, Tm and thermal stability of the polymers decrease, while a reverse trend was observed with film forming ability of the polymers. The optical characterization of the polymers was investigated by forming holographic grating using an Argon ion laser. The grating diffraction efficiency was found to depend not only on the concentration of polymeric film but also on the spacer length of the polymers

Interaction between zircaloy tube and inconel spacer grid at high temperature

International Nuclear Information System (INIS)

Nagase, Fumihisa; Otomo, Takashi; Uetsuka, Hiroshi; Furuta, Teruo

1990-09-01

In order to investigate the interaction between fuel cladding and spacer grid of the pressurized water reactor during a severe accident, isothermal reaction tests were performed at the temperature range from 1248 to 1673K. A specimen consisted of a short Zircaloy-4 cladding tube and a piece of spacer grid of Inconel-718. In the tests in an argon atmosphere, eutectic reaction between Zircaloy and Inconel was observed at the contact points at 1248K. Rapid reaction was observed at higher test temperatures. For example, in the test at 1373K for 300s, Zircaloy reacted with Inconel over the entire thickness (0.62mm) of the tube in the vicinity of the contact point. In the present tests, Zircaloy which has higher melting point than Inconel was dissolved preferentially due to eutectic formation. In the tests in an oxygen atmosphere, no eutectic reaction was observed at temperatures below 1437K. A trace of interaction was found at the contact point of specimen heated at 1573 and 1623K. However, decrease in Zircaloy thickness was not measured. The possibility of eutectic reaction between Zircaloy cladding and Inconel spacer grid seems to be quite limited when sufficient oxygen is supplied. (author)

Quantification of Different Eubacterium spp. in Human Fecal Samples with Species-Specific 16S rRNA-Targeted Oligonucleotide Probes

OpenAIRE

Schwiertz, Andreas; Le Blay, Gwenaelle; Blaut, Michael

2000-01-01

Species-specific 16S rRNA-targeted, Cy3 (indocarbocyanine)-labeled oligonucleotide probes were designed and validated to quantify different Eubacterium species in human fecal samples. Probes were directed at Eubacterium barkeri, E. biforme, E. contortum, E. cylindroides (two probes), E. dolichum, E. hadrum, E. lentum, E. limosum, E. moniliforme, and E. ventriosum. The specificity of the probes was tested with the type strains and a range of common intestinal bacteria. With one exception, none...

[Cervical adaptation of complete cast crowns of various metal alloys, with and without die spacers].

Science.gov (United States)

Stephano, C B; Roselino, R F; Roselino, R B; Campos, G M

1989-01-01

A metallic replica from a dental preparation for crown was used to make 8 class-IV stone dies. The wax patterns for the casting of the crowns were obtained in two conditions: a) from the stone die with no spacer; and b) from the stone die with an acrylic spacer. Thus, 64 metallic crowns were casted, using 4 different alloys: DURACAST (Cu-Al), NICROCAST (Ni-Cr) and DURABOND (Ni-Cr), and gold. The casted crowns were fitted in the metallic replica and measured as to the cervical discrepance of fitting. The results showed that the use of die spacers decreases the clinical discrepancies of fitting of the casted crowns (in a statistically significant level), no matter the metallic alloy employed.

Recent advances in antisense oligonucleotide therapy in genetic neuromuscular diseases

Directory of Open Access Journals (Sweden)

Ashok Verma

2018-01-01

Full Text Available Genetic neuromuscular diseases are caused by defective expression of nuclear or mitochondrial genes. Mutant genes may reduce expression of wild-type proteins, and strategies to activate expression of the wild-type proteins might provide therapeutic benefits. Also, a toxic mutant protein may cause cell death, and strategies that reduce mutant gene expression may provide therapeutic benefit. Synthetic antisense oligonucleotide (ASO can recognize cellular RNA and control gene expression. In recent years, advances in ASO chemistry, creation of designer ASO molecules to enhance their safety and target delivery, and scientific controlled clinical trials to ascertain their therapeutic safety and efficacy have led to an era of plausible application of ASO technology to treat currently incurable neuromuscular diseases. Over the past 1 year, for the first time, the United States Food and Drug Administration has approved two ASO therapies in genetic neuromuscular diseases. This overview summarizes the recent advances in ASO technology, evolution and use of synthetic ASOs as a therapeutic platform, and the mechanism of ASO action by exon-skipping in Duchenne muscular dystrophy and exon-inclusion in spinal muscular atrophy, with comments on their advantages and limitations.

Conjugation of a 3-(1H-phenanthro[9,10-d]imidazol-2-yl)-1H-indole intercalator to a triplex oligonucleotide and to a three-way junction

DEFF Research Database (Denmark)

Fatthalla, Maha I.; Elkholy, Yehya M; Abbas, Nermeen S

2012-01-01

a phenanthroimidazole moiety linked to the indole ring. Insertion of the new intercalator as a bulge into a Triplex Forming Oligonucleotide resulted in good thermal stability of the corresponding Hoogsteen-type triplexes. Molecular modeling supports the possible intercalating ability of M. Hybridisation properties...

Peri-Prosthetic Knee Infection Management: Spacers Loaded with Two or Three Antibiotic Agents.

Science.gov (United States)

Ortola, David Joaquin; Fenga, Domenico; Marcellino, Sandra; Rosi, Massimiliano; Centofanti, Francesco; Rosa, Michele Attilio

2017-07-01

The purpose of this work was to compare pre-made antibiotic-loaded spacers with two commercially available antibiotic agents and custom-made cements with three antibiotic agents added. We evaluated: (a) the validity of our procedures, (b) the control of the rate of infection in the long term, (c) complications, and (d) quality of life and patient satisfaction. A retrospective cohort study was performed on 112 consecutively treated patients between January 2010 and December 2013; 56 patients were treated with a pre-formed cement spacer (clindamycin + gentamicin), and 56 patients were treated with a spacer loaded with three antibiotic agents (clindamycin + gentamicin + vancomycin). Demographic data were collected: Classification of infection according to criteria of Cierny-Mader; microbiologic results; number of previous operations; and years of disease. Infection control or relapse after at least 18 months of follow-up was evaluated. Complications were recorded. Every patient completed the SF-36 test and Oxford Knee Score. With a follow-up of 32.87 months (standard deviation 12.04), at the end of treatment, amputation occurred in three of 112 patients because of recurrence of infection, and one patient died from other causes not related to the infection. The study population presented a rate of recurrence of infection of 2.70%. Our results suggest that a two stage re-implant with three antibiotic agents added to the spacer should be considered to avoid rescue procedures, especially in patients with multi-resistant micro-organism infections.

Hydration-dependent dynamics of human telomeric oligonucleotides in the picosecond timescale: A neutron scattering study

Energy Technology Data Exchange (ETDEWEB)

Sebastiani, F.; Comez, L.; Sacchetti, F. [Dipartimento di Fisica e Geologia, Università degli Studi di Perugia, Via A. Pascoli, 06123 Perugia (Italy); CNR, Istituto Officina dei Materiali, Unità di Perugia, c/o Dipartimento di Fisica e Geologia, Università di Perugia, 06123 Perugia (Italy); Longo, M. [Dipartimento di Fisica e Geologia, Università degli Studi di Perugia, Via A. Pascoli, 06123 Perugia (Italy); Elettra—Sincrotrone Trieste, 34149 Basovizza, Trieste (Italy); Orecchini, A.; Petrillo, C.; Paciaroni, A., E-mail: alessandro.paciaroni@fisica.unipg.it [Dipartimento di Fisica e Geologia, Università degli Studi di Perugia, Via A. Pascoli, 06123 Perugia (Italy); De Francesco, A. [CNR-IOM OGG c/o Institut Laue-Langevin, 71 Avenue des Martyrs, CS20156, 38042 Grenoble Cedex 9 (France); Muthmann, M. [Jülich Centre for Neutron Science, Forschungszentrum Jülich GmbH, Outstation at Heinz Maier-Leibnitz Zentrum, Lichtenbergstrasse 1, 85747 Garching (Germany); Teixeira, S. C. M. [EPSAM, Keele University, Staffordshire ST5 5BG (United Kingdom); Institut Laue–Langevin, 71 Avenue des Martyrs, CS20156, 38042 Grenoble Cedex 9 (France)

2015-07-07

The dynamics of the human oligonucleotide AG{sub 3}(T{sub 2}AG{sub 3}){sub 3} has been investigated by incoherent neutron scattering in the sub-nanosecond timescale. A hydration-dependent dynamical activation of thermal fluctuations in weakly hydrated samples was found, similar to that of protein powders. The amplitudes of such thermal fluctuations were evaluated in two different exchanged wave-vector ranges, so as to single out the different contributions from intra- and inter-nucleotide dynamics. The activation energy was calculated from the temperature-dependent characteristic times of the corresponding dynamical processes. The trends of both amplitudes and activation energies support a picture where oligonucleotides possess a larger conformational flexibility than long DNA sequences. This additional flexibility, which likely results from a significant relative chain-end contribution to the average chain dynamics, could be related to the strong structural polymorphism of the investigated oligonucleotides.

Polynucleotides. XXXII. Further studies on the synthesis of oligonucleotides containing 8,2'-S-cycloadenosine.

Science.gov (United States)

Ikehara, M; Tezuka, T

1975-01-01

A dinucleoside monophosphate, 8,2'-anhydro-8-mercapto-9-beta-D-arabinofuranosyladenine phosphoryl-(3'-5')-inosine (AspI) was synthesized by the condensation of protected 8-mercapto-adenosine 2',3'-cyclic phosphate and 2',3'-isopropylideneinosine with diphenylphosphorochloridate. 8-Mercaptoadenosine 2',3'-cyclic phosphate was polymerized by using tetraphenyl pyrophosphate as the condensing reagent. As oligonucleotides, thus obtained, contained some uncyclized 8-mercaptoadenosine residues and were cleaved at these sites with 0.3N KOH. As 5'-phosphate was synthesized and polymerized with DCC to give oligonucleotides with chain lengths 2 to 9. PMID:170595

Comparative study of the contribution of various PWR spacer grid components to hydrodynamic and wall pressure characteristics

Energy Technology Data Exchange (ETDEWEB)

Bhattacharjee, Saptarshi, E-mail: saptarshi.bhattacharjee@outlook.com [Alternative Energies and Atomic Energy Commission (CEA) – Cadarache, DEN/DTN/STCP/LHC, 13108 Saint Paul lez Durance Cedex (France); Laboratoire de Mécanique, Modélisation et Procédés Propres (M2P2), UMR7340 CNRS, Aix-Marseille Université, Centrale Marseille, 13451 Marseille Cedex (France); Ricciardi, Guillaume [Alternative Energies and Atomic Energy Commission (CEA) – Cadarache, DEN/DTN/STCP/LHC, 13108 Saint Paul lez Durance Cedex (France); Viazzo, Stéphane [Laboratoire de Mécanique, Modélisation et Procédés Propres (M2P2), UMR7340 CNRS, Aix-Marseille Université, Centrale Marseille, 13451 Marseille Cedex (France)

2017-06-15

Highlights: • Complex geometry inside a PWR fuel assembly is simulated using simplified 3D models. • Structured meshes are generated as far as possible. • Fluctuating hydrodynamic and wall pressure field are analyzed using LES. • Comparative studies between square spacer grid, circular spacer grid and mixing vanes are presented. • Simulations are compared with experimental data. - Abstract: Flow-induced vibrations in a pressurized water reactor (PWR) core can cause fretting wear in fuel rods. These vibrations can compromise safety of a nuclear reactor. So, it is necessary to know the random fluctuating forces acting on the rods which cause these vibrations. In this paper, simplified 3D models like square spacer grid, circular spacer grid and symmetric mixing vanes have been used inside an annular pipe. Hydrodynamic and wall pressure characteristics are evaluated using large eddy simulations (LES). Structured meshes are generated as far as possible. Simulations are compared with an experiment. Results show that the grid and vanes have a combined effect: grid accelerates the flow whereas the vanes contribute to the swirl structures. Spectral analysis of the simulations illustrate vortex shedding phenomenon in the wake of spacer grids. This initial study opens up interesting perspectives towards improving the modeling strategy and understanding the complex phenomenon inside a PWR core.

Comparative study of the contribution of various PWR spacer grid components to hydrodynamic and wall pressure characteristics

International Nuclear Information System (INIS)

Bhattacharjee, Saptarshi; Ricciardi, Guillaume; Viazzo, Stéphane

2017-01-01

Highlights: • Complex geometry inside a PWR fuel assembly is simulated using simplified 3D models. • Structured meshes are generated as far as possible. • Fluctuating hydrodynamic and wall pressure field are analyzed using LES. • Comparative studies between square spacer grid, circular spacer grid and mixing vanes are presented. • Simulations are compared with experimental data. - Abstract: Flow-induced vibrations in a pressurized water reactor (PWR) core can cause fretting wear in fuel rods. These vibrations can compromise safety of a nuclear reactor. So, it is necessary to know the random fluctuating forces acting on the rods which cause these vibrations. In this paper, simplified 3D models like square spacer grid, circular spacer grid and symmetric mixing vanes have been used inside an annular pipe. Hydrodynamic and wall pressure characteristics are evaluated using large eddy simulations (LES). Structured meshes are generated as far as possible. Simulations are compared with an experiment. Results show that the grid and vanes have a combined effect: grid accelerates the flow whereas the vanes contribute to the swirl structures. Spectral analysis of the simulations illustrate vortex shedding phenomenon in the wake of spacer grids. This initial study opens up interesting perspectives towards improving the modeling strategy and understanding the complex phenomenon inside a PWR core.

Measurement of droplet dynamics across grid spacer in mist cooling of subchannel of PWR

International Nuclear Information System (INIS)

Lee, S.L.; Sheen, H.J.; Cho, S.K.; Issapour, I.

1984-01-01

An experiment was conducted of the dynamics and heat transfer of a droplet-vapor mist flow across a test grid spacer in a flow channel of 2 x 2 electrically heated simulation fuel rods. Embedded thermocouples were used to measure the rod cladding temperature and an unshielded Chromel-Alumel thermocouple was transversed in the center of the subchannel to measure the temperature of the water and steam coolant phases at various axial locations. Thermocouples were also embedded in the test grid spacer. Optical measurements of the size and velocity distributions of droplets and the velocity distribution of the superheated steam were made by special laser-Doppler anemometry techniques through quartz glass windows immediately upstream and downstream of the test grid spacer. Experiments over a range of steam and injected water flow rates and rod heat flux have been performed and some representative results and discussions are presented

Antisense oligonucleotide therapy rescues disruptions in organization of exploratory movements associated with Usher syndrome type 1C in mice.

Science.gov (United States)

Donaldson, Tia N; Jennings, Kelsey T; Cherep, Lucia A; McNeela, Adam M; Depreux, Frederic F; Jodelka, Francine M; Hastings, Michelle L; Wallace, Douglas G

2018-02-15

Usher syndrome, Type 1C (USH1C) is an autosomal recessive inherited disorder in which a mutation in the gene encoding harmonin is associated with multi-sensory deficits (i.e., auditory, vestibular, and visual). USH1C (Usher) mice, engineered with a human USH1C mutation, exhibit these multi-sensory deficits by circling behavior and lack of response to sound. Administration of an antisense oligonucleotide (ASO) therapeutic that corrects expression of the mutated USH1C gene, has been shown to increase harmonin levels, reduce circling behavior, and improve vestibular and auditory function. The current study evaluates the organization of exploratory movements to assess spatial organization in Usher mice and determine the efficacy of ASO therapy in attenuating any such deficits. Usher and heterozygous mice received the therapeutic ASO, ASO-29, or a control, non-specific ASO treatment at postnatal day five. Organization of exploratory movements was assessed under dark and light conditions at two and six-months of age. Disruptions in exploratory movement organization observed in control-treated Usher mice were consistent with impaired use of self-movement and environmental cues. In general, ASO-29 treatment rescued organization of exploratory movements at two and six-month testing points. These observations are consistent with ASO-29 rescuing processing of multiple sources of information and demonstrate the potential of ASO therapies to ameliorate topographical disorientation associated with other genetic disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Immobilization of oligonucleotide probes on silicon surfaces using biotin–streptavidin system examined with microscopic and spectroscopic techniques

Energy Technology Data Exchange (ETDEWEB)

Awsiuk, K., E-mail: kamil.awsiuk@uj.edu.pl [M. Smoluchowski Institute of Physics, Jagiellonian University, Reymonta 4, Kraków 30-059 (Poland); Rysz, J. [M. Smoluchowski Institute of Physics, Jagiellonian University, Reymonta 4, Kraków 30-059 (Poland); Petrou, P. [Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety, NCSR “Demokritos”, End Patriarchou Gregoriou Str., Aghia Paraskevi 15310 (Greece); Budkowski, A. [M. Smoluchowski Institute of Physics, Jagiellonian University, Reymonta 4, Kraków 30-059 (Poland); Bernasik, A. [Faculty of Physics and Applied Computer Science, AGH-University of Science and Technology, Al. Mickiewicza 30, Kraków 30-059 (Poland); Kakabakos, S. [Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety, NCSR “Demokritos”, End Patriarchou Gregoriou Str., Aghia Paraskevi 15310 (Greece); Marzec, M.M. [Faculty of Physics and Applied Computer Science, AGH-University of Science and Technology, Al. Mickiewicza 30, Kraków 30-059 (Poland); Raptis, I. [Institute for Advanced Materials, Physicochemical Processes, Nanotechnology and Microsystems, NCSR “Demokritos”, End Patriarchou Gregoriou Str., Aghia Paraskevi 15310 (Greece)

2014-01-30

To immobilize effectively oligonucleotide probes on SiO{sub 2} modified with (3-aminopropyl)triethoxysilane, four procedures based on streptavidin–biotin system are compared with Atomic Force Microscopy, Angle-Resolved X-ray Photoelectron Spectroscopy and Time-of-Flight Secondary Ion Mass Spectrometry. The first approach involves: adsorption of biotinylated Bovine Serum Albumin, blocking free surface sites with BSA, binding of streptavidin and biotinylated oligonucleotide (b-oligo). Final steps are exchanged in the second procedure with immobilization of preformed streptavidin–b-oligo conjugate. The third approach consists of streptavidin adsorption, blocking with BSA and b-oligo binding. Finally, streptavidin–b-oligo conjugate is immobilized directly within the fourth method. Surface coverage with biomolecules, determined from ARXPS, accords with average AFM height, and is anti-correlated with the intensity of Si+ ions. Higher biomolecular coverage was achieved during the last steps of the first (2.45(±0.38) mg/m{sup 2}) and second (1.31(±0.22) mg/m{sup 2}) approach, as compared to lower surface density resulting from the third (0.58(±0.20) mg/m{sup 2}) and fourth (0.41(±0.11) mg/m{sup 2}) method. Phosphorus atomic concentration indicates effectiveness of oligonucleotide immobilization. Secondary ions intensities, characteristic for oligonucleotides, streptavidin, BSA, and proteins, allow additional insight into overlayer composition. These measurements verify the ARXPS results and show the superiority of the first two immobilization approaches in terms of streptavidin and oligonucleotide density achieved onto the surface.

Immobilization of oligonucleotide probes on silicon surfaces using biotin–streptavidin system examined with microscopic and spectroscopic techniques

International Nuclear Information System (INIS)

Awsiuk, K.; Rysz, J.; Petrou, P.; Budkowski, A.; Bernasik, A.; Kakabakos, S.; Marzec, M.M.; Raptis, I.

2014-01-01

To immobilize effectively oligonucleotide probes on SiO 2 modified with (3-aminopropyl)triethoxysilane, four procedures based on streptavidin–biotin system are compared with Atomic Force Microscopy, Angle-Resolved X-ray Photoelectron Spectroscopy and Time-of-Flight Secondary Ion Mass Spectrometry. The first approach involves: adsorption of biotinylated Bovine Serum Albumin, blocking free surface sites with BSA, binding of streptavidin and biotinylated oligonucleotide (b-oligo). Final steps are exchanged in the second procedure with immobilization of preformed streptavidin–b-oligo conjugate. The third approach consists of streptavidin adsorption, blocking with BSA and b-oligo binding. Finally, streptavidin–b-oligo conjugate is immobilized directly within the fourth method. Surface coverage with biomolecules, determined from ARXPS, accords with average AFM height, and is anti-correlated with the intensity of Si+ ions. Higher biomolecular coverage was achieved during the last steps of the first (2.45(±0.38) mg/m 2 ) and second (1.31(±0.22) mg/m 2 ) approach, as compared to lower surface density resulting from the third (0.58(±0.20) mg/m 2 ) and fourth (0.41(±0.11) mg/m 2 ) method. Phosphorus atomic concentration indicates effectiveness of oligonucleotide immobilization. Secondary ions intensities, characteristic for oligonucleotides, streptavidin, BSA, and proteins, allow additional insight into overlayer composition. These measurements verify the ARXPS results and show the superiority of the first two immobilization approaches in terms of streptavidin and oligonucleotide density achieved onto the surface.

Tandem Oligonucleotide Probe Annealing and Elongation To Discriminate Viral Sequence

DEFF Research Database (Denmark)

Taskova, Maria; Uhd, Jesper; Miotke, Laura

2017-01-01

opportunities in transcriptome analysis, virology, and other fields. Herein, we report for the first time a "click" chemistry approach to oligonucleotide probe elongation as a novel approach to specifically detect a viral sequence. We hybridized a library of short, terminally labeled probes to Ebola virus RNA...

Genome dynamics of short oligonucleotides: the example of bacterial DNA uptake enhancing sequences.

Directory of Open Access Journals (Sweden)

Mohammed Bakkali

Full Text Available Among the many bacteria naturally competent for transformation by DNA uptake-a phenomenon with significant clinical and financial implications- Pasteurellaceae and Neisseriaceae species preferentially take up DNA containing specific short sequences. The genomic overrepresentation of these DNA uptake enhancing sequences (DUES causes preferential uptake of conspecific DNA, but the function(s behind this overrepresentation and its evolution are still a matter for discovery. Here I analyze DUES genome dynamics and evolution and test the validity of the results to other selectively constrained oligonucleotides. I use statistical methods and computer simulations to examine DUESs accumulation in Haemophilus influenzae and Neisseria gonorrhoeae genomes. I analyze DUESs sequence and nucleotide frequencies, as well as those of all their mismatched forms, and prove the dependence of DUESs genomic overrepresentation on their preferential uptake by quantifying and correlating both characteristics. I then argue that mutation, uptake bias, and weak selection against DUESs in less constrained parts of the genome combined are sufficient enough to cause DUESs accumulation in susceptible parts of the genome with no need for other DUES function. The distribution of overrepresentation values across sequences with different mismatch loads compared to the DUES suggests a gradual yet not linear molecular drive of DNA sequences depending on their similarity to the DUES. Other genomically overrepresented sequences, both pro- and eukaryotic, show similar distribution of frequencies suggesting that the molecular drive reported above applies to other frequent oligonucleotides. Rare oligonucleotides, however, seem to be gradually drawn to genomic underrepresentation, thus, suggesting a molecular drag. To my knowledge this work provides the first clear evidence of the gradual evolution of selectively constrained oligonucleotides, including repeated, palindromic and protein

Response of an electrostatic probe for a right cylindrical spacer

DEFF Research Database (Denmark)

Rerup, T; Crichton, George C; McAllister, Iain Wilson

1994-01-01

During the last decade many experimental studies of surface charge phenomena have been undertaken employing right cylindrical spacers. Measurement of the surface charge was performed using small electrostatic field probes to scan across the dielectric surface. Charges are electrostatically induced...

Application of a cholesterol stationary phase in the analysis of phosphorothioate oligonucleotides by means of ion pair chromatography coupled with tandem mass spectrometry.

Science.gov (United States)

Studzińska, Sylwia; Krzemińska, Katarzyna; Szumski, Michał; Buszewski, Bogusław

2016-07-01

The main aim of this study was the investigation of the influence of several ion pair reagents towards both the retention and the mass spectrometry sensitivity of phosphorothioate oligonucleotides. A cholesterol stationary phase was applied for the first time in the analysis of this group of compounds. The mobile phase composition was modified by changing the concentration and the type of amines and acetates or 1,1,1,3,3,3-hexafluoroisopropanol. It has been shown that the increase of amines concentration results in the retention factor increase for each oligonucleotide, on each adsorbent. The only exception was the mobile phase composed of triethylamine and 1,1,1,3,3,3-hexafluoroisopropanol. This is a consequence of interactions taking place between a cholesterol molecule and an alcohol. This effect was convenient when the mass spectrometry detection was applied, since it allowed an increase in the sensitivity. Moreover, optimization of the mobile phase composition and its impact on the efficiency of ionization process and on the sensitivity in mass spectrometry were also presented. The optimization of this new method, based on cholesterol stationary phase coupled with mass spectrometry detection, was finally applied for the determination of phosphorothioate oligonucleotides impurity in a real sample. Copyright © 2016 Elsevier B.V. All rights reserved.

Measurements of the Effects of Spacers on the Burnout Conditions for Flow of Boiling Water in a Vertical Annulus and a Vertical 7-Rod Cluster

International Nuclear Information System (INIS)

Becker, Kurt M.; Hernborg, G.

1964-11-01

The present report deals with measurements of the effects of spacers on the burnout conditions in a vertical annulus and a vertical 7-rod cluster. The following ranges of variables were studied and 162 burnout measurements were obtained. Pressure p = 31 kg/cm; Inlet sub-cooling 35 sub 2 ; Mass velocity 94 2 /s; Burnout steam quality 0.10 BO < 0.56. The experimental results showed that the type of spacers employed during the present investigation had negligible effects on the burnout conditions and that the measured burnout heat fluxes could be predicted within ± 5 per cent by means of the correlation by Becker et al for flow in smooth channels

Enhanced current-perpendicular-to-plane giant magnetoresistance effect in half-metallic NiMnSb based nanojunctions with multiple Ag spacers

Energy Technology Data Exchange (ETDEWEB)

Wen, Zhenchao; Yamamoto, Tatsuya [Institute for Materials Research, Tohoku University, Sendai 980-8577 (Japan); Kubota, Takahide; Takanashi, Koki [Institute for Materials Research, Tohoku University, Sendai 980-8577 (Japan); Center for Spintronics Research Network (CSRN), Tohoku University, Sendai 980-8577 (Japan)

2016-06-06

Current-perpendicular-to-plane giant magnetoresistance (CPP-GMR) heterostructure devices using half-metallic NiMnSb Heusler alloy electrodes with single, dual, and triple Ag spacers were fabricated. The NiMnSb alloy films and Ag spacers show (001) epitaxial growth in all CPP-GMR multilayer structures. The dual-spacer CPP-GMR nanojunction exhibited an enhanced CPP-GMR ratio of 11% (a change in the resistance-area product, ΔRA, of 3.9 mΩ μm{sup 2}) at room temperature, which is approximately twice (thrice) of 6% (1.3 mΩ μm{sup 2}) in the single-spacer device. The enhancement of the CPP-GMR effects in the dual-spacer devices could be attributed to improved interfacial spin asymmetry. Moreover, it was observed that the CPP-GMR ratios increased monotonically as the temperatures decreased. At 4.2 K, a CPP-GMR ratio of 41% (ΔRA = 10.5 mΩ μm{sup 2}) was achieved in the dual-spacer CPP-GMR device. This work indicates that multispacer structures provide an efficient enhancement of CPP-GMR effects in half-metallic material-based CPP-GMR systems.

Triple helix-forming oligonucleotide corresponding to the polypyrimidine sequence in the rat alpha 1(I) collagen promoter specifically inhibits factor binding and transcription.

Science.gov (United States)

Kovacs, A; Kandala, J C; Weber, K T; Guntaka, R V

1996-01-19

Type I and III fibrillar collagens are the major structural proteins of the extracellular matrix found in various organs including the myocardium. Abnormal and progressive accumulation of fibrillar type I collagen in the interstitial spaces compromises organ function and therefore, the study of transcriptional regulation of this gene and specific targeting of its expression is of major interest. Transient transfection of adult cardiac fibroblasts indicate that the polypurine-polypyrimidine sequence of alpha 1(I) collagen promoter between nucleotides - 200 and -140 represents an overall positive regulatory element. DNase I footprinting and electrophoretic mobility shift assays suggest that multiple factors bind to different elements of this promoter region. We further demonstrate that the unique polypyrimidine sequence between -172 and -138 of the promoter represents a suitable target for a single-stranded polypurine oligonucleotide (TFO) to form a triple helix DNA structure. Modified electrophoretic mobility shift assays show that this TFO specifically inhibits the protein-DNA interaction within the target region. In vitro transcription assays and transient transfection experiments demonstrate that the transcriptional activity of the promoter is inhibited by this oligonucleotide. We propose that TFOs represent a therapeutic potential to specifically influence the expression of alpha 1(I) collagen gene in various disease states where abnormal type I collagen accumulation is known to occur.

Molecular Strain Typing of Clinical Isolates, Trichophyton rubrum using Non Transcribed Spacer (NTS) Region as a Molecular Marker.

Science.gov (United States)

Ramaraj, Vijayakumar; Vijayaraman, Rajyoganandh S; Elavarashi, Elangovan; Rangarajan, Sudha; Kindo, Anupma Jyoti

2017-05-01

Dermatophytes are a group of fungi which infect keratinized tissues and causes superficial mycoses in humans and animals. The group comprises of three major genera, Trichophyton , Microsporum and Epidermophyton . Among them Trichophyton rubrum is a predominant anthropophilic fungi which causes chronic infections. Although, the infection is superficial and treatable, reinfection/coinfection causes inflation in the treatment cost. Identifying the source and mode of transmission is essential to prevent its transmission. Accurate discrimination is required to understand the clinical (relapse or reinfection) and epidemiological implications of the genetic heterogeneity of this species. Polymorphism in the Non Transcribed Spacer (NTS) region of ribosomal DNA (rDNA) clusters renders an effective way to discriminate strains among T. rubrum . To carry out the strain typing of the clinical isolates, Trichophyton rubrum using NTS as a molecular marker. Seventy T.rubrum clinical isolates obtained from April-2011-March 2013, from Sri Ramachandra Medical Centre, Chennai, Tamil Nadu, India, were identified by conventional phenotypic methods and included in this prospective study. The isolates were then subjected to Polymerase Chain Reaction (PCR) targeting two subrepeat elements (SREs), TRS-1 and TRS-2 of the NTS region. Strain-specific polymorphism was observed in both subrepeat loci. Total, nine different strains were obtained on combining both TRS-1 and TRS-2, SREs. The outcome has given a strong representation for using NTS region amplification in discriminating the T. rubrum clinical isolates. The method can be adapted as a tool for conducting epidemiology and population based study in T. rubrum infections. This will help in future exploration of the epidemiology of T. rubrum .

Heated oligonucleotide ligation assay (HOLA): an affordable single nucleotide polymorphism assay.

Science.gov (United States)

Black, W C; Gorrochotegui-Escalante, N; Duteau, N M

2006-03-01

Most single nucleotide polymorphism (SNP) detection requires expensive equipment and reagents. The oligonucleotide ligation assay (OLA) is an inexpensive SNP assay that detects ligation between a biotinylated "allele-specific detector" and a 3' fluorescein-labeled "reporter" oligonucleotide. No ligation occurs unless the 3' detector nucleotide is complementary to the SNP nucleotide. The original OLA used chemical denaturation and neutralization. Heated OLA (HOLA) instead uses a thermal stable ligase and cycles of denaturing and hybridization for ligation and SNP detection. The cost per genotype is approximately US$1.25 with two-allele SNPs or approximately US$1.75 with three-allele SNPs. We illustrate the development of HOLA for SNP detection in the Early Trypsin and Abundant Trypsin loci in the mosquito Aedes aegypti (L.) and at the a-glycerophosphate dehydrogenase locus in the mosquito Anopheles gambiae s.s.

Higher order structure of short immunostimulatory oligonucleotides studied by atomic force microscopy

International Nuclear Information System (INIS)

Klein, Dionne C.G.; Latz, Eicke; Espevik, Terje; Stokke, Bjorn T.

2010-01-01

Immunostimulatory CpG-DNA activates the innate immune system by binding to Toll-like receptor 9. Structurally different CpG-containing oligonucleotides trigger a different type of immune response while activating the same receptor. We therefore investigated the higher order structure of two different classes of immunostimulatory CpG-DNA. Class A, which contains a partly self-complementary sequence and poly-G ends, forms duplexes and nanoparticles in salt solution, while class B, which does not contain these features and is purely linear, does not form a duplex or nanoparticles. Results obtained here by high-resolution atomic force microscopy of classes A and B CpG-DNA, reflect these differences in secondary structure. Detailed structural analysis of the atomic force microscopy topographs is presented for two different sample preparation methods.

Higher order structure of short immunostimulatory oligonucleotides studied by atomic force microscopy

Energy Technology Data Exchange (ETDEWEB)

Klein, Dionne C.G., E-mail: dionne.c.g.klein@ntnu.no [Department of Physics, Norwegian University of Science and Technology, N-7491, Trondheim (Norway); Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, N-7489, Trondheim (Norway); Latz, Eicke [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, N-7489, Trondheim (Norway); Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605 (United States); Institute of Innate Immunity, University Hospitals, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn (Germany); Espevik, Terje [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, N-7489, Trondheim (Norway); Stokke, Bjorn T. [Department of Physics, Norwegian University of Science and Technology, N-7491, Trondheim (Norway)

2010-05-15

Immunostimulatory CpG-DNA activates the innate immune system by binding to Toll-like receptor 9. Structurally different CpG-containing oligonucleotides trigger a different type of immune response while activating the same receptor. We therefore investigated the higher order structure of two different classes of immunostimulatory CpG-DNA. Class A, which contains a partly self-complementary sequence and poly-G ends, forms duplexes and nanoparticles in salt solution, while class B, which does not contain these features and is purely linear, does not form a duplex or nanoparticles. Results obtained here by high-resolution atomic force microscopy of classes A and B CpG-DNA, reflect these differences in secondary structure. Detailed structural analysis of the atomic force microscopy topographs is presented for two different sample preparation methods.

Single-Labeled Oligonucleotides Showing Fluorescence Changes upon Hybridization with Target Nucleic Acids

Directory of Open Access Journals (Sweden)

Gil Tae Hwang

2018-01-01

Full Text Available Sequence-specific detection of nucleic acids has been intensively studied in the field of molecular diagnostics. In particular, the detection and analysis of single-nucleotide polymorphisms (SNPs is crucial for the identification of disease-causing genes and diagnosis of diseases. Sequence-specific hybridization probes, such as molecular beacons bearing the fluorophore and quencher at both ends of the stem, have been developed to enable DNA mutation detection. Interestingly, DNA mutations can be detected using fluorescently labeled oligonucleotide probes with only one fluorophore. This review summarizes recent research on single-labeled oligonucleotide probes that exhibit fluorescence changes after encountering target nucleic acids, such as guanine-quenching probes, cyanine-containing probes, probes containing a fluorophore-labeled base, and microenvironment-sensitive probes.

Development, characterization and experimental validation of a cultivated sunflower (Helianthus annuus L. gene expression oligonucleotide microarray.

Directory of Open Access Journals (Sweden)

Paula Fernandez

Full Text Available Oligonucleotide-based microarrays with accurate gene coverage represent a key strategy for transcriptional studies in orphan species such as sunflower, H. annuus L., which lacks full genome sequences. The goal of this study was the development and functional annotation of a comprehensive sunflower unigene collection and the design and validation of a custom sunflower oligonucleotide-based microarray. A large scale EST (>130,000 ESTs curation, assembly and sequence annotation was performed using Blast2GO (www.blast2go.de. The EST assembly comprises 41,013 putative transcripts (12,924 contigs and 28,089 singletons. The resulting Sunflower Unigen Resource (SUR version 1.0 was used to design an oligonucleotide-based Agilent microarray for cultivated sunflower. This microarray includes a total of 42,326 features: 1,417 Agilent controls, 74 control probes for sunflower replicated 10 times (740 controls and 40,169 different non-control probes. Microarray performance was validated using a model experiment examining the induction of senescence by water deficit. Pre-processing and differential expression analysis of Agilent microarrays was performed using the Bioconductor limma package. The analyses based on p-values calculated by eBayes (p<0.01 allowed the detection of 558 differentially expressed genes between water stress and control conditions; from these, ten genes were further validated by qPCR. Over-represented ontologies were identified using FatiScan in the Babelomics suite. This work generated a curated and trustable sunflower unigene collection, and a custom, validated sunflower oligonucleotide-based microarray using Agilent technology. Both the curated unigene collection and the validated oligonucleotide microarray provide key resources for sunflower genome analysis, transcriptional studies, and molecular breeding for crop improvement.

Correlating In Vitro Splice Switching Activity With Systemic In Vivo Delivery Using Novel ZEN-modified Oligonucleotides

Directory of Open Access Journals (Sweden)

Suzan M Hammond

2014-01-01

Full Text Available Splice switching oligonucleotides (SSOs induce alternative splicing of pre-mRNA and typically employ chemical modifications to increase nuclease resistance and binding affinity to target pre-mRNA. Here we describe a new SSO non-base modifier (a naphthyl-azo group, “ZEN™” to direct exon exclusion in mutant dystrophin pre-mRNA to generate functional dystrophin protein. The ZEN modifier is placed near the ends of a 2′-O-methyl (2′OMe oligonucleotide, increasing melting temperature and potency over unmodified 2′OMe oligonucleotides. In cultured H2K cells, a ZEN-modified 2′OMe phosphorothioate (PS oligonucleotide delivered by lipid transfection greatly enhanced dystrophin exon skipping over the same 2′OMePS SSO lacking ZEN. However, when tested using free gymnotic uptake in vitro and following systemic delivery in vivo in dystrophin deficient mdx mice, the same ZEN-modified SSO failed to enhance potency. Importantly, we show for the first time that in vivo activity of anionic SSOs is modelled in vitro only when using gymnotic delivery. ZEN is thus a novel modifier that enhances activity of SSOs in vitro but will require improved delivery methods before its in vivo clinical potential can be realized.

Nuclear reactor fuel assembly spacer grid

International Nuclear Information System (INIS)

Jabsen, F.S.

1977-01-01

A spacer grid for a nuclear fuel assembly is comprised of a lattice of grid plates forming multiple cells that are penetrated by fuel elements. Resilient protrusions and rigid protrusions projecting into the cells from the plates bear against the fuel element to effect proper support and spacing. Pairs of intersecting grid plates, disposed in a longitudinally spaced relationship, cooperate with other plates to form a lattice wherein each cell contains adjacent panels having resilient protrusions arranged opposite adjacent panels having rigid protrusions. The peripheral band bounding the lattice is provided solely with rigid protrusions projecting into the peripheral cells. (Auth.)

Spectroscopic (UV/VIS, Raman) and Electrophoresis Study of Cytosine-Guanine Oligonucleotide DNA Influenced by Magnetic Field.

Science.gov (United States)

Banihashemian, Seyedeh Maryam; Periasamy, Vengadesh; Boon Tong, Goh; Abdul Rahman, Saadah

2016-01-01

Studying the effect of a magnetic field on oligonucleotide DNA can provide a novel DNA manipulation technique for potential application in bioengineering and medicine. In this work, the optical and electrochemical response of a 100 bases oligonucleotides DNA, cytosine-guanine (CG100), is investigated via exposure to different magnetic fields (250, 500, 750, and 1000 mT). As a result of the optical response of CG100 to the magnetic field, the ultra-violet-visible spectrum indicated a slight variation in the band gap of CG100 of about 0.3 eV. Raman spectroscopy showed a significant deviation in hydrogen and phosphate bonds' vibration after exposure to the magnetic field. Oligonucleotide DNA mobility was investigated in the external electric field using the gel electrophoresis technique, which revealed a small decrease in the migration of CG100 after exposure to the magnetic field.

Sub-15 nm nano-pattern generation by spacer width control for high density precisely positioned self-assembled device nanomanufacturing

KAUST Repository

Rojas, Jhonathan Prieto; Hussain, Muhammad Mustafa

2012-01-01

We present a conventional micro-fabrication based thin film vertical sidewall (spacer) width controlled nano-gap fabrication process to create arrays of nanopatterns for high density precisely positioned self-assembled nanoelectronics device integration. We have used conventional optical lithography to create base structures and then silicon nitride (Si 3N4) based spacer formation via reactive ion etching. Control of Si3N4 thickness provides accurate control of vertical sidewall (spacer) besides the base structures. Nano-gaps are fabricated between two adjacent spacers whereas the width of the gap depends on the gap between two adjacent base structures minus width of adjacent spacers. We demonstrate the process using a 32 nm node complementary metal oxide semiconductor (CMOS) platform to show its compatibility for very large scale heterogeneous integration of top-down and bottom-up fabrication as well as conventional and selfassembled nanodevices. This process opens up clear opportunity to overcome the decade long challenge of high density integration of self-assembled devices with precise position control. © 2012 IEEE.

Sub-15 nm nano-pattern generation by spacer width control for high density precisely positioned self-assembled device nanomanufacturing

KAUST Repository

Rojas, Jhonathan Prieto

2012-08-01

We present a conventional micro-fabrication based thin film vertical sidewall (spacer) width controlled nano-gap fabrication process to create arrays of nanopatterns for high density precisely positioned self-assembled nanoelectronics device integration. We have used conventional optical lithography to create base structures and then silicon nitride (Si 3N4) based spacer formation via reactive ion etching. Control of Si3N4 thickness provides accurate control of vertical sidewall (spacer) besides the base structures. Nano-gaps are fabricated between two adjacent spacers whereas the width of the gap depends on the gap between two adjacent base structures minus width of adjacent spacers. We demonstrate the process using a 32 nm node complementary metal oxide semiconductor (CMOS) platform to show its compatibility for very large scale heterogeneous integration of top-down and bottom-up fabrication as well as conventional and selfassembled nanodevices. This process opens up clear opportunity to overcome the decade long challenge of high density integration of self-assembled devices with precise position control. © 2012 IEEE.

Internal Transcribed Spacer 1 (ITS1 based sequence typing reveals phylogenetically distinct Ascaris population

Directory of Open Access Journals (Sweden)

Koushik Das

2015-01-01

Full Text Available Taxonomic differentiation among morphologically identical Ascaris species is a debatable scientific issue in the context of Ascariasis epidemiology. To explain the disease epidemiology and also the taxonomic position of different Ascaris species, genome information of infecting strains from endemic areas throughout the world is certainly crucial. Ascaris population from human has been genetically characterized based on the widely used genetic marker, internal transcribed spacer1 (ITS1. Along with previously reported and prevalent genotype G1, 8 new sequence variants of ITS1 have been identified. Genotype G1 was significantly present among female patients aged between 10 to 15 years. Intragenic linkage disequilibrium (LD analysis at target locus within our study population has identified an incomplete LD value with potential recombination events. A separate cluster of Indian isolates with high bootstrap value indicate their distinct phylogenetic position in comparison to the global Ascaris population. Genetic shuffling through recombination could be a possible reason for high population diversity and frequent emergence of new sequence variants, identified in present and other previous studies. This study explores the genetic organization of Indian Ascaris population for the first time which certainly includes some fundamental information on the molecular epidemiology of Ascariasis.

Characterization of peptide-oligonucleotide heteroconjugates by mass spectrometry.

OpenAIRE

Jensen, O N; Kulkarni, S; Aldrich, J V; Barofsky, D F

1996-01-01

Two peptide-oligothymidylic acids, prepared by joining an 11 residue synthetic peptide containing one internal carboxyl group (Asp side chain) to amino-linker-5'pdT6 and amino-linker-5'pdT10 oligonucleotides, were analyzed by matrix-assisted laser desorption/ionization (MALDI) on a linear time-of-flight mass spectrometer and by electrospray ionization (ESI) on a triple-quadrupole system. These synthetic compounds model peptide-nucleic acid heteroconjugates encountered in antisense research an...

Detection and genotyping of Entamoeba histolytica, Entamoeba dispar, Giardia lamblia, and Cryptosporidium parvum by oligonucleotide microarray.

Science.gov (United States)

Wang, Zheng; Vora, Gary J; Stenger, David A

2004-07-01

Entamoeba histolytica, Giardia lamblia, and Cryptosporidium parvum are the most frequently identified protozoan parasites causing waterborne disease outbreaks. The morbidity and mortality associated with these intestinal parasitic infections warrant the development of rapid and accurate detection and genotyping methods to aid public health efforts aimed at preventing and controlling outbreaks. In this study, we describe the development of an oligonucleotide microarray capable of detecting and discriminating between E. histolytica, Entamoeba dispar, G. lamblia assemblages A and B, and C. parvum types 1 and 2 in a single assay. Unique hybridization patterns for each selected protozoan were generated by amplifying six to eight diagnostic sequences/organism by multiplex PCR; fluorescent labeling of the amplicons via primer extension; and subsequent hybridization to a set of genus-, species-, and subtype-specific covalently immobilized oligonucleotide probes. The profile-based specificity of this methodology not only permitted for the unequivocal identification of the six targeted species and subtypes, but also demonstrated its potential in identifying related species such as Cryptosporidium meleagridis and Cryptosporidium muris. In addition, sensitivity assays demonstrated lower detection limits of five trophozoites of G. lamblia. Taken together, the specificity and sensitivity of the microarray-based approach suggest that this methodology may provide a promising tool to detect and genotype protozoa from clinical and environmental samples.

Direct Mutagenesis of Thousands of Genomic Targets using Microarray-derived Oligonucleotides

DEFF Research Database (Denmark)

Bonde, Mads; Kosuri, Sriram; Genee, Hans Jasper

2015-01-01

Multiplex Automated Genome Engineering (MAGE) allows simultaneous mutagenesis of multiple target sites in bacterial genomes using short oligonucleotides. However, large-scale mutagenesis requires hundreds to thousands of unique oligos, which are costly to synthesize and impossible to scale-up by ...

PairWise Neighbours database: overlaps and spacers among prokaryote genomes

Directory of Open Access Journals (Sweden)

Garcia-Vallvé Santiago

2009-06-01

Full Text Available Abstract Background Although prokaryotes live in a variety of habitats and possess different metabolic and genomic complexity, they have several genomic architectural features in common. The overlapping genes are a common feature of the prokaryote genomes. The overlapping lengths tend to be short because as the overlaps become longer they have more risk of deleterious mutations. The spacers between genes tend to be short too because of the tendency to reduce the non coding DNA among prokaryotes. However they must be long enough to maintain essential regulatory signals such as the Shine-Dalgarno (SD sequence, which is responsible of an efficient translation. Description PairWise Neighbours is an interactive and intuitive database used for retrieving information about the spacers and overlapping genes among bacterial and archaeal genomes. It contains 1,956,294 gene pairs from 678 fully sequenced prokaryote genomes and is freely available at the URL http://genomes.urv.cat/pwneigh. This database provides information about the overlaps and their conservation across species. Furthermore, it allows the wide analysis of the intergenic regions providing useful information such as the location and strength of the SD sequence. Conclusion There are experiments and bioinformatic analysis that rely on correct annotations of the initiation site. Therefore, a database that studies the overlaps and spacers among prokaryotes appears to be desirable. PairWise Neighbours database permits the reliability analysis of the overlapping structures and the study of the SD presence and location among the adjacent genes, which may help to check the annotation of the initiation sites.

Rapid Induction of Protective Immunity Against Biothreat Agents Using CPG-Based Oligonucleotides

National Research Council Canada - National Science Library

Klinman, Dennis

2003-01-01

This research project examines the ability of synthetic oligonucleotides (ODN) containing immunostimulatory "CpG motifs' to trigger the innate immune system, thereby improving the host's ability to survive infection by biowarfare agents...

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....

Experimental studies of the effect of functional spacers to annular flow in subchannels of a BWR fuel element

Energy Technology Data Exchange (ETDEWEB)

Damsohn, M., E-mail: damsohn@lke.mavt.ethz.c [ETH Zurich, Department of Mechanical and Process Engineering, Sonneggstrasse 3, 8092 Zuerich (Switzerland); Prasser, H.-M. [ETH Zurich, Department of Mechanical and Process Engineering, Sonneggstrasse 3, 8092 Zuerich (Switzerland)

2010-10-15

For the prediction of dryout in fuel elements of boiling water reactors, the dynamic behavior of the water film covering the fuel rod has to be understood. This paper provides high resolved experimental data of the liquid film and gives insight into the dynamic film behavior. The experiments of this work were conducted in a vertical channel representing a pair of neighboring subchannels of a BWR fuel rod bundle. Air and water at ambient pressure and temperature are used as model fluids, creating an annular flow in the test section. The influence of different functional spacer shapes on the liquid film has been studied. The heart of the instrumentation is a liquid film sensor (LFS), which measures the film thickness distribution around a half cylinder with a matrix of 64 x 16 measuring points with a time resolution of 10,000 frames per second and a spatial resolution of 2 mm x 2 mm. The high resolution allows for a visualization of the dynamic liquid film as a movie animation. Principals of the dynamic behavior of the liquid film are observed. The time-averaged film thickness distributions show that the spacers structure the liquid film significantly. The gaseous phase is accelerated due to the cross-section blockage caused by the spacer. This leads to a local thinning of the liquid film downstream of the spacer. Two statistical evaluation methods are presented to determine different dynamic wave properties: The wave velocity as function of the wave height, the traveling path of the waves and the location of wave separation and merge events. The first evaluation method shows that big waves move generally faster than small waves. The analysis further shows wave acceleration in close proximity of the spacer with subsequent deceleration further downstream. Analyzing the wave as a two-dimensional entity it can be seen that the wave paths are clearly structured by the spacer and hence do not travel circumferentially around the fuel rod. Wave separation and merge has a

Experimental studies of the effect of functional spacers to annular flow in subchannels of a BWR fuel element

International Nuclear Information System (INIS)

Damsohn, M.; Prasser, H.-M.

2010-01-01

For the prediction of dryout in fuel elements of boiling water reactors, the dynamic behavior of the water film covering the fuel rod has to be understood. This paper provides high resolved experimental data of the liquid film and gives insight into the dynamic film behavior. The experiments of this work were conducted in a vertical channel representing a pair of neighboring subchannels of a BWR fuel rod bundle. Air and water at ambient pressure and temperature are used as model fluids, creating an annular flow in the test section. The influence of different functional spacer shapes on the liquid film has been studied. The heart of the instrumentation is a liquid film sensor (LFS), which measures the film thickness distribution around a half cylinder with a matrix of 64 x 16 measuring points with a time resolution of 10,000 frames per second and a spatial resolution of 2 mm x 2 mm. The high resolution allows for a visualization of the dynamic liquid film as a movie animation. Principals of the dynamic behavior of the liquid film are observed. The time-averaged film thickness distributions show that the spacers structure the liquid film significantly. The gaseous phase is accelerated due to the cross-section blockage caused by the spacer. This leads to a local thinning of the liquid film downstream of the spacer. Two statistical evaluation methods are presented to determine different dynamic wave properties: The wave velocity as function of the wave height, the traveling path of the waves and the location of wave separation and merge events. The first evaluation method shows that big waves move generally faster than small waves. The analysis further shows wave acceleration in close proximity of the spacer with subsequent deceleration further downstream. Analyzing the wave as a two-dimensional entity it can be seen that the wave paths are clearly structured by the spacer and hence do not travel circumferentially around the fuel rod. Wave separation and merge has a

Technetium-99m labeled antisense oligonucleotide-noninvasive tumor imaging in mice

International Nuclear Information System (INIS)

Qin, G.M.; Zhang, Y.X.; An, R.; Gao, Z.R.; Cao, W.; Cao, G.X.; Hnatowich, D.J.

2002-01-01

Single-stranded RNA and DNA oligonucleotides may be useful as radiopharmaceuticals for antisense and other in vivo applications if convenient methods for stably attaching radionuclides such as 99m Tc can be developed. The c-myc oncogene works in cooperation with other oncogenes in a variety of malignant tumors. The concentration of c-myc messenger RNA increases rapidly 30 to 50 fold during DNA synthesis, thus making it a suitable target for following the progression of malignancy by noninvasive imaging with radiolabeled antisense oligonucleotide probes. Methods: 1 Oligonucleotide Conjugation: A solution of single stranded amine-derivatized DNA (100-1000μg) was prepared at a concentration of 2 mg/ml in 0.25M sodium bicarbonate, 1 M sodium chloride, 1mM EDTA, pH8.5. 2 Oligonucleotide Labeling: A fresh 50mg/ml solution of sodium tartrate was prepared in sterile 0.5 M ammonium The ability of the labeled DNA to hybridize to its complement was analyzed by Sep-Pak column chromatography before and after the addition of the complementary DNA. 3 Biodistribution and Tumor Imaging Studies: A colony of KM mice (15-20g) were inoculated with 1x10 6 Ehrlich carcinoma tumor cells in the right thigh, and the tumors were allowed to grow for 6-7 days to a size of 1.0-1.5 cm in diameter. Biodistribution studies were performed in 32 KM mice after 50 μCi per mouse of 99m Tc-labeled oncogene probes were injected intravenously. A total of 8 mice were injected intravenously in the tail vein with 1-2 mCi of 99m Tc-labeled sense or antisense probes, immobilized with ketamine hydrochloride and imaged periodically from 0.5hr to 24hr with a gamma camera. Results: Essentially complete conjugation was achieved by reverse-phase Sep-Pak C18 chromatography analysis. The labeled antisense DNA still remained the ability to hybridize with its complementary DNA. The highest accumulation of label was in the liver first, with the kidney and small bowel next. The injected activity localized in the lesion

Detection and enumeration of methanotrophs in acidic Sphagnum peat by 16S rRNA fluorescence in situ hybridization, including the use of newly developed oligonucleotide probes for Methylocella palustris.

Science.gov (United States)

Dedysh, S N; Derakshani, M; Liesack, W

2001-10-01

Two 16S rRNA-targeted oligonucleotide probes, Mcell-1026 and Mcell-181, were developed for specific detection of the acidophilic methanotroph Methylocella palustris using fluorescence in situ hybridization (FISH). The fluorescence signal of probe Mcell-181 was enhanced by its combined application with the oligonucleotide helper probe H158. Mcell-1026 and Mcell-181, as well as 16S rRNA oligonucleotide probes with reported group specificity for either type I methanotrophs (probes M-84 and M-705) or the Methylosinus/Methylocystis group of type II methanotrophs (probes MA-221 and M-450), were used in FISH to determine the abundance of distinct methanotroph groups in a Sphagnum peat sample of pH 4.2. M. palustris was enumerated at greater than 10(6) cells per g of peat (wet weight), while the detectable population size of type I methanotrophs was three orders of magnitude below the population level of M. palustris. The cell counts with probe MA-221 suggested that only 10(4) type II methanotrophs per g of peat (wet weight) were present, while the use of probe M-450 revealed more than 10(6) type II methanotroph cells per g of the same samples. This discrepancy was due to the fact that probe M-450 targets almost all currently known strains of Methylosinus and Methylocystis, whereas probe MA-221, originally described as group specific, does not detect a large proportion of Methylocystis strains. The total number of methanotrophic bacteria detected by FISH was 3.0 (+/-0.2) x 10(6) cells per g (wet weight) of peat. This was about 0.8% of the total bacterial cell number. Thus, our study clearly suggests that M. palustris and a defined population of Methylocystis spp. were the predominant methanotrophs detectable by FISH in an acidic Sphagnum peat bog.

An evaluation of oligonucleotide-based therapeutic strategies for polyQ diseases

Directory of Open Access Journals (Sweden)

Fiszer Agnieszka

2012-03-01

Full Text Available Abstract Background RNA interference (RNAi and antisense strategies provide experimental therapeutic agents for numerous diseases, including polyglutamine (polyQ disorders caused by CAG repeat expansion. We compared the potential of different oligonucleotide-based strategies for silencing the genes responsible for several polyQ diseases, including Huntington's disease and two spinocerebellar ataxias, type 1 and type 3. The strategies included nonallele-selective gene silencing, gene replacement, allele-selective SNP targeting and CAG repeat targeting. Results Using the patient-derived cell culture models of polyQ diseases, we tested various siRNAs, and antisense reagents and assessed their silencing efficiency and allele selectivity. We showed considerable allele discrimination by several SNP targeting siRNAs based on a weak G-G or G-U pairing with normal allele and strong G-C pairing with mutant allele at the site of RISC-induced cleavage. Among the CAG repeat targeting reagents the strongest allele discrimination is achieved by miRNA-like functioning reagents that bind to their targets and inhibit their translation without substantial target cleavage. Also, morpholino analog performs well in mutant and normal allele discrimination but its efficient delivery to cells at low effective concentration still remains a challenge. Conclusions Using three cellular models of polyQ diseases and the same experimental setup we directly compared the performance of different oligonucleotide-based treatment strategies that are currently under development. Based on the results obtained by us and others we discussed the advantages and drawbacks of these strategies considering them from several different perspectives. The strategy aimed at nonallele-selective inhibiting of causative gene expression by targeting specific sequence of the implicated gene is the easiest to implement but relevant benefits are still uncertain. The gene replacement strategy that

Spacer geometry and particle deposition in spiral wound membrane feed channels

KAUST Repository

Radu, A.I.; van Steen, M.S.H.; Vrouwenvelder, Johannes S.; van Loosdrecht, Mark C.M.; Picioreanu, C.

2014-01-01

Deposition of microspheres mimicking bacterial cells was studied experimentally and with a numerical model in feed spacer membrane channels, as used in spiral wound nanofiltration (NF) and reverse osmosis (RO) membrane systems. In-situ microscopic

Novel approaches to study low-energy electron-induced damage to DNA oligonucleotides

International Nuclear Information System (INIS)

Rackwitz, Jenny; Bald, Ilko; Ranković, Miloš Lj; Milosavljević, Aleksandar R

2015-01-01

The novel approach of DNA origami structures as templates for precise quantification of various well- defined oligonucleotides provides the opportunity to determine the sensitivity of complex DNA sequences towards low-energy electrons. (paper)

Synthesis of modified oligonucleotides for repair and replication studies of single and double radio-induced DNA lesions

International Nuclear Information System (INIS)

Muller, E.

2002-01-01

Several oxidative processes induce the formation of DNA lesions. In order to evaluate the biological and structural significance of such damage, several DNA lesions were inserted into synthetic oligonucleotides at defined sites. The research work aimed at describing the preparation of oligonucleotides t hat contained DNA damage and the evaluation of the biological properties of the lesions. A first part described the incorporation of radiation-induced lesions, namely (5'S,6S)-5',6-cyclo-5,6-dihydro-2'-deoxyuridine and (5'S,5S,6S)-5',6-cyclo-5-hydroxy-5,6-dihydro-2'-desoxyuridine into oligonucleotides. The modified DNA fragments were characterised by several spectroscopic and biochemical analyses including ESI MS, MALDI-TOF MS, CLHP and enzymatic digestions. During in vitro DNA synthesis by Taq DNA polymerase and Klenow exo fragment, the pyrimidine cyclo-nucleosides were found to block the progression of the enzymes. Then, repair studies by ADN N glycosylases, operating in the base excision repair pathway, have shown that the anhydro-nucleoside lesions were not recognised nor excised by Fpg, endo III, endo VIII, yNtg1 yNtg2 and yOgg1. Interestingly, the Latococcus lactis Fpg protein recognises (formation of a non covalent complex) but do not excise the damage. The incorporation into oligonucleotides of the (5R*) and (5S*) diastereoisomers of 1-[2-deoxy-β-D-erythro-pentofuranosyl]-5-hydroxy-hydantoin, generated by several oxidative processes was then described. In vitro DNA replication assays using modified oligonucleotides matrix showed a lethal potential of the latter base damage. Repair studies by ADN N-glycosylases showed that the damage was substrate for Fpg, endo III, endo VIII, Ntg1, Ntg2 and Fpg-L1. The rates of excision as inferred from the determination of the Michaelis kinetics constants were found to be affected by the presence of the damage. MALDI-TOF MS was used in order to gain insights into mechanistic aspects of oligonucleotides cleavage by the

Automated synthesis of an {sup 18}F-labelled pyridine-based alkylating agent for high yield oligonucleotide conjugation

Energy Technology Data Exchange (ETDEWEB)

Guggenberg, Elisabeth von; Sader, Jayden A.; Wilson, John S.; Shahhosseini, Soraya; Koslowsky, Ingrid; Wuest, Frank [Edmonton PET Centre, Division of Oncologic Imaging, Department of Oncology, Cross Cancer Institute, 11560 University Ave, Edmonton, AB, T6G 1Z2 (Canada); Mercer, John R. [Edmonton PET Centre, Division of Oncologic Imaging, Department of Oncology, Cross Cancer Institute, 11560 University Ave, Edmonton, AB, T6G 1Z2 (Canada)], E-mail: johnmerc@cancerboard.ab.ca

2009-09-15

Alkylating agents have been shown to be very promising for the radiolabelling of oligonucleotides with fluorine-18. In this report we describe the fully automated synthesis of 2-bromo-N-[3-(2-[{sup 18}F]fluoropyridin-3-yloxy)propyl]acetamide ([{sup 18}F]FPyBrA) utilizing a modular synthesis unit. Reaction conditions for the coupling of this pyridine-based alkylating agent at the 5' end of a fully phosphorothioated random 20-mer DNA sequence were optimized to achieve very high radiochemical yields (>90%) and a maximum specific activity of 5-6 GBq/{mu}moL. The potential for rapid purification by solid phase extraction without need of chromatographic isolation of the radiolabelled oligonucleotide presents an overall benefit for the application of oligonucleotides in preclinical studies and potential clinical applications.

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...

Spectroscopic (UV/VIS, Raman and Electrophoresis Study of Cytosine-Guanine Oligonucleotide DNA Influenced by Magnetic Field.

Directory of Open Access Journals (Sweden)

Seyedeh Maryam Banihashemian

Full Text Available Studying the effect of a magnetic field on oligonucleotide DNA can provide a novel DNA manipulation technique for potential application in bioengineering and medicine. In this work, the optical and electrochemical response of a 100 bases oligonucleotides DNA, cytosine-guanine (CG100, is investigated via exposure to different magnetic fields (250, 500, 750, and 1000 mT. As a result of the optical response of CG100 to the magnetic field, the ultra-violet-visible spectrum indicated a slight variation in the band gap of CG100 of about 0.3 eV. Raman spectroscopy showed a significant deviation in hydrogen and phosphate bonds' vibration after exposure to the magnetic field. Oligonucleotide DNA mobility was investigated in the external electric field using the gel electrophoresis technique, which revealed a small decrease in the migration of CG100 after exposure to the magnetic field.

Experimental and numerical characterization of the water flow in spacer-filled channels of spiral-wound membranes

KAUST Repository

Bucs, Szilard

2015-09-25

Micro-scale flow distribution in spacer-filled flow channels of spiral-wound membrane modules was determined with a particle image velocimetry system (PIV), aiming to elucidate the flow behaviour in spacer-filled flow channels. Two-dimensional water velocity fields were measured in a flow cell (representing the feed spacer-filled flow channel of a spiral wound reverse osmosis membrane module without permeate production) at several planes throughout the channel height. At linear flow velocities (volumetric flow rate per cross-section of the flow channel considering the channel porosity, also described as crossflow velocities) used in practice (0.074 and 0.163 m∙s-1) the recorded flow was laminar with only slight unsteadiness in the upper velocity limit. At higher linear flow velocity (0.3 m∙s-1) the flow was observed to be unsteady and with recirculation zones. Measurements made at different locations in the flow cell exhibited very similar flow patterns within all feed spacer mesh elements, thus revealing the same hydrodynamic conditions along the length of the flow channel. Three-dimensional (3-D) computational fluid dynamics simulations were performed using the same geometries and flow parameters as the experiments, based on steady laminar flow assumption. The numerical results were in good agreement (0.85-0.95 Bray-Curtis similarity) with the measured flow fields at linear velocities of 0.074 and 0.163 m∙s-1, thus supporting the use of model-based studies in the optimization of feed spacer geometries and operational conditions of spiral wound membrane systems.

Experimental and numerical characterization of the water flow in spacer-filled channels of spiral-wound membranes.

Science.gov (United States)

Bucs, Szilard S; Linares, Rodrigo Valladares; Marston, Jeremy O; Radu, Andrea I; Vrouwenvelder, Johannes S; Picioreanu, Cristian

2015-12-15

Micro-scale flow distribution in spacer-filled flow channels of spiral-wound membrane modules was determined with a particle image velocimetry system (PIV), aiming to elucidate the flow behaviour in spacer-filled flow channels. Two-dimensional water velocity fields were measured in a flow cell (representing the feed spacer-filled flow channel of a spiral wound reverse osmosis membrane module without permeate production) at several planes throughout the channel height. At linear flow velocities (volumetric flow rate per cross-section of the flow channel considering the channel porosity, also described as crossflow velocities) used in practice (0.074 and 0.163 m·s(-1)) the recorded flow was laminar with only slight unsteadiness in the upper velocity limit. At higher linear flow velocity (0.3 m·s(-1)) the flow was observed to be unsteady and with recirculation zones. Measurements made at different locations in the flow cell exhibited very similar flow patterns within all feed spacer mesh elements, thus revealing the same hydrodynamic conditions along the length of the flow channel. Three-dimensional (3-D) computational fluid dynamics simulations were performed using the same geometries and flow parameters as the experiments, based on steady laminar flow assumption. The numerical results were in good agreement (0.85-0.95 Bray-Curtis similarity) with the measured flow fields at linear velocities of 0.074 and 0.163 m·s(-1), thus supporting the use of model-based studies in the optimization of feed spacer geometries and operational conditions of spiral wound membrane systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

Knowledge of spacer device, peak flow meter and inhaler technique ...

African Journals Online (AJOL)

Background: Metered dose inhalers are cornerstone in effective management of bronchial asthma when correctly used. Most studies hitherto have focused on assessing patient's knowledge of inhaler technique. We sought to assess the knowledge of inhaler technique, spacer device and peak flow meter among doctors and ...

Influence of spacer length on heparin coupling efficiency and fibrinogen adsorption of modified titanium surfaces

Directory of Open Access Journals (Sweden)

Gbureck Uwe

2007-07-01

Full Text Available Abstract Background Chemical bonding of the drug onto surfaces by means of spacer molecules is accompanied with a reduction of the biological activity of the drug due to a constricted mobility since normally only short spacer molecule like aminopropyltrimethoxysilane (APMS are used for drug coupling. This work aimed to study covalent attachment of heparin to titanium(oxide surfaces by varying the length of the silane coupling agent, which should affect the biological potency of the drug due to a higher mobility with longer spacer chains. Methods Covalent attachment of heparin to titanium metal and TiO2 powder was carried out using the coupling agents 3-(Trimethoxysilyl-propylamine (APMS, N- [3-(Trimethoxysilylpropyl]ethylenediamine (Diamino-APMS and N1- [3-(Trimethoxy-silyl-propyl]diethylenetriamine (Triamino-APMS. The amount of bound coupling agent and heparin was quantified photometrically by the ninhydrin reaction and the tolidine-blue test. The biological potency of heparin was determined photometrically by the chromogenic substrate Chromozym TH and fibrinogen adsorption to the modified surfaces was researched using the QCM-D (Quartz Crystal Microbalance with Dissipation Monitoring technique. Results Zeta-potential measurements confirmed the successful coupling reaction; the potential of the unmodified anatase surface (approx. -26 mV shifted into the positive range (> + 40 mV after silanisation. Binding of heparin results in a strongly negatively charged surface with zeta-potentials of approx. -39 mV. The retaining biological activity of heparin was highest for the spacer molecule Triamino-APMS. QCM-D measurements showed a lower viscosity for adsorbed fibrinogen films on heparinised surfaces by means of Triamino-APMS. Conclusion The remaining activity of heparin was found to be highest for the covalent attachment with Triamino-APMS as coupling agent due to the long chain of this spacer molecule and therefore the highest mobility of the drug

Study of special spacer with damping device for suppressing wake galloping in tandem cables of cable-stayed bridges and its application to full scale bridge; Nendanseitai wo riyoshita heiretsu cable yo gensui kinotsuki spacer to sono jikkyo cable eno tekiyo ni kansuru kenkyu

Energy Technology Data Exchange (ETDEWEB)

Yoneda, M.; Setouchi, H.; Yoshioka, A. [Kawada Industries Inc., Tokyo (Japan); Shimoda, I.; Kawahara, S. [Oiles Corp., Tokyo (Japan)

1996-12-20

Cable vibration called wake galloping occurs in a cable-stayed bridge, in which cables are arranged tandem, and suppression of the vibration is an extremely important discussion item. This paper describes a complex eigen value analysis performed on tandem cables having lengths of 200 m and 100 m. The analysis revealed that damping characteristics added by a spacer system with a damping device (a type to install a visco-elastic body at about middle of the tandem cables via a jig) depend largely on torsional rigidity of the cables; and the characteristics may vary with difference in intervals between cable centers and that in cable diameters. A visco-elastic damping material of an asphalt system and a spacer with a damping device used as a spring material were fabricated and applied to a full scale bridge to identify quantitatively the damping addition characteristics of this system. Furthermore, the results of tests on the full scale bridge were compared with the result of the complex eigen value analysis, from which findings useful for actual works were obtained. 18 refs., 17 figs., 6 tabs.

Measurement of grid spacer's enhanced droplet cooling under reflood condition in a PWR by LDA

International Nuclear Information System (INIS)

Lee, S.L.; Sheen, H.J.; Cho, S.K.; Issapour, I.; Hua, S.Q.

1984-01-01

Reported is an experiment designed for the measurements of grid spacer's enhanced droplet cooling under reflood condition at elevated temperatures in a steam environment. The flow channel consists of a simulated 1.60m-long pressurized water reactor (PWR) fuel rod bundle of 2 x 2 electrically heated rods. Embedded thermocouples are used to measure the rod cladding temperature at various axial levels and an unshielded Chromel-Alumel thermocouple sheathed by a small Inconel tube is traversed in the center of the subchannel to measure the temperatures of the water and steam coolant phases at various levels. The droplet dynamics across the grid spacer is directly obtained by a special laser-Doppler anemometry technique for the in situ simultaneous measurement of velocity and size of droplets through two observation windows on the test channel, one immediately before and one immediately after the grid spacer. Some results are presented and analyzed

A Facile Technique to Make Articulating Spacers for Infected Total Knee Arthroplasty

Directory of Open Access Journals (Sweden)

Yu-Ping Su

2009-03-01

Conclusion: Treating infected total knee arthroplasty with these self-made articulating spacers eradicates infection effectively, improves the life quality before reimplantation and provides good final results without significant complications.

Spacer stability and prostate position variability during radiotherapy for prostate cancer applying a hydrogel to protect the rectal wall

International Nuclear Information System (INIS)

Pinkawa, Michael; Piroth, Marc D.; Holy, Richard; Escobar-Corral, Nuria; Caffaro, Mariana; Djukic, Victoria; Klotz, Jens; Eble, Michael J.

2013-01-01

Background and purpose: The aim was to evaluate the spacer dimensions and prostate position variability during the course of radiotherapy for prostate cancer. Materials and methods: CT scans were performed in a group of 15 patients (G1) after the 10 ml injection of a hydrogel spacer (SpaceOAR™) and 30 patients without a spacer (G2) before the beginning of treatment (CT1) and in the last treatment week, 10–12 weeks following spacer implantation (CT2). Spacer dimensions and displacements were determined and prostate displacements compared. Results: Mean volume of the hydrogel increased slightly (17%; p 2 cm 3 . The average displacement of the hydrogel center of mass was 0.6 mm (87% ⩽ 2.2 mm), −0.6 mm (100% ⩽ 2.2 mm) and 1.4 mm (87% ⩽ 4.3 mm) in the x-, y- and z-axes (not significant). The average distance between prostate and anterior rectal wall before/at the end of radiotherapy was 1.6 cm/1.5 cm, 1.2 cm/1.3 cm and 1.0 cm/1.1 cm at the level of the base, middle and apex (G1). Prostate position variations were similar comparing G1 and G2, but significant systematic posterior displacements were only found in G2. Conclusions: A stable distance between the prostate and anterior rectal wall results during the radiotherapy course after injection of the spacer before treatment planning. Larger posterior prostate displacements could be reduced

Predicting the impact of feed spacer modification on biofouling by hydraulic characterization and biofouling studies in membrane fouling simulators

KAUST Repository

Siddiqui, Amber; Lehmann, S.; Bucs, Szilard; Fresquet, M.; Fel, L.; Prest, E.I.E.C.; Ogier, J.; Schellenberg, C.; van Loosdrecht, M.C.M.; Kruithof, J.C.; Vrouwenvelder, Johannes S.

2016-01-01

Feed spacers are an essential part of spiral-wound reverse osmosis (RO) and nanofiltration (NF) membrane modules. Geometric modification of feed spacers is a potential option to reduce the impact of biofouling on the performance of membrane systems

Visible light dynamical diffraction in a 1-D photonic crystal-based interferometer with an extremely thin spacer layer

International Nuclear Information System (INIS)

Prudnikov, I.R.

2016-01-01

Properties of light diffraction in a Fabry–Pérot-like interferometer composed of two 1-D photonic crystals and a nanometer-thick spacer layer are analytically investigated. It is shown that the resonant enhancement of light wave intensity in such a layer is possible because of light dynamical diffraction from the photonic crystals of the interferometer. Numerical simulations of (i) light reflectivity and transmittance curves of the interferometer having an ultra-thin spacer layer (its thickness changes from less than 1 nm to about 10 nm) and (ii) the resonant distribution of the light wave intensity in the vicinity of the layer are performed. Based on the numerical simulations, potentialities for the determination of the structural parameters (e.g., thicknesses and refraction indexes) of ultra-thin spacer films are discussed. A difference is found to appear in resonant intensity enhancements inside the ultra-thin spacer layers between s- and p-polarized light waves.

Splice-correcting oligonucleotides restore BTK function in X-linked agammaglobulinemia model

DEFF Research Database (Denmark)

Bestas, Burcu; Moreno, Pedro M D; Blomberg, K Emelie M

2014-01-01

, splice-correcting oligonucleotides (SCOs) targeting mutated BTK transcripts for treating XLA. Both the SCO structural design and chemical properties were optimized using 2'-O-methyl, locked nucleic acid, or phosphorodiamidate morpholino backbones. In order to have access to an animal model of XLA, we...

Eddy current detection of spacers in the fuel channels of CANDU nuclear reactors

International Nuclear Information System (INIS)

Krause, T.W.; Schankula, J.; Sullivan, S.P.

2002-01-01

Garter Spring (GS) spacers in the fuel channels of CANDU nuclear reactors maintain separation between the hot pressure tube and surrounding moderator cooled calandria tube. Eddy current detection of the four GSs provides assurance that spacers are at or close to design positions and are performing their intended function of maintaining a non-zero gap between pressure tube and calandria tube. Pressure tube constrictions, resulting from relatively less diametral creep at end-of-fuel bundle locations, also produce large eddy current signals. Large constrictions, present in higher service pressure tubes, can produce signals that are 10 times larger than GS signals, reducing GS detectability to 30% in standard GS-detect probes. The introduction of field-focussing elements into the design of the standard GS detection eddy current probe has been used to recover the detectability of GS spacers by increasing the signal amplitude obtained from GSs relative to that from constrictions by a factor of 10. The work presented here compares laboratory, modelling and in-reactor measurements of GS and constriction signals obtained from the standard probe with that obtained from field-focussed eddy current probe designs. (author)

PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice

Science.gov (United States)

Zinker, Bradley A.; Rondinone, Cristina M.; Trevillyan, James M.; Gum, Rebecca J.; Clampit, Jill E.; Waring, Jeffrey F.; Xie, Nancy; Wilcox, Denise; Jacobson, Peer; Frost, Leigh; Kroeger, Paul E.; Reilly, Regina M.; Koterski, Sandra; Opgenorth, Terry J.; Ulrich, Roger G.; Crosby, Seth; Butler, Madeline; Murray, Susan F.; McKay, Robert A.; Bhanot, Sanjay; Monia, Brett P.; Jirousek, Michael R.

2002-01-01

The role of protein-tyrosine phosphatase 1B (PTP1B) in diabetes was investigated using an antisense oligonucleotide in ob/ob and db/db mice. PTP1B antisense oligonucleotide treatment normalized plasma glucose levels, postprandial glucose excursion, and HbA1C. Hyperinsulinemia was also reduced with improved insulin sensitivity. PTP1B protein and mRNA were reduced in liver and fat with no effect in skeletal muscle. Insulin signaling proteins, insulin receptor substrate 2 and phosphatidylinositol 3 (PI3)-kinase regulatory subunit p50α, were increased and PI3-kinase p85α expression was decreased in liver and fat. These changes in protein expression correlated with increased insulin-stimulated protein kinase B phosphorylation. The expression of liver gluconeogenic enzymes, phosphoenolpyruvate carboxykinase, and fructose-1,6-bisphosphatase was also down-regulated. These findings suggest that PTP1B modulates insulin signaling in liver and fat, and that therapeutic modalities targeting PTP1B inhibition may have clinical benefit in type 2 diabetes. PMID:12169659

Diagnosis of Persistent Infection in Prosthetic Two-Stage Exchange: Evaluation of the Effect of Sonication on Antibiotic Release from Bone Cement Spacers.

Science.gov (United States)

Mariaux, Sandrine; Furustrand Tafin, Ulrika; Borens, Olivier

2018-01-01

Introduction : When treating periprosthetic joint infection with a two-stage procedure, antibiotic-impregnated spacers can be used in the interval between prosthetic removal and reimplantation. In our experience, cultures of sonicated spacers are most often negative. The objective of the study was to assess whether that sonication causes an elution of antibiotics, leading to elevated antibiotic concentrations in the sonication fluid inhibiting bacterial growth and thus causing false-negative cultures. Methods : A prospective monocentric study was performed from September 2014 to March 2016. Inclusion criteria were a two-stage procedure for prosthetic infection and agreement of the patient to participate in the study. Spacers were made of gentamicin-containing cement to which tobramycin and vancomycin were added. Antibiotic concentrations in the sonication fluid were determined by mass-spectometry (LC-MS). Results : 30 patients were identified (15 hip and 14 knee and 1 ankle arthroplasties). No cases of culture positive sonicated spacer fluid were observed in our serie. In the sonication fluid median concentrations of 13.2µg/ml, 392 µg/ml and 16.6 µg/ml were detected for vancomycin, tobramycin and gentamicin, respectively. According to the European Committee on antimicrobial susceptibility testing (EUCAST), these concentrations released from cement spacer during sonication are higher than the minimal inhibitory concentrations (MICs) for most bacteria relevant in prosthetic joint infections. Conclusion: Spacer sonication cultures remained sterile in all of our cases. Elevated concentrations of antibiotics released during sonication could explain partly negative-cultured sonicated spacers. Indeed, the absence of antibiotic free interval during the two-stages can also contribute to false-negative spacers sonicated cultures.

Time spans and spacers: Molecular phylogenetic explorations in the Cladophora complex (Chlorophyta) from the perspective of rDNA gene and spacer sequences

OpenAIRE

Bakker, Frederik Theodoor

1995-01-01

In this study, phylogenetic relationships among genera, species and biogeographic representatives of single Cladophora species within the Cladophorales were analyzed using rDNA gene and spacer sequences. Based on phylogenetic analysis of 18S rRNA gene sequences, the Cladophora complex is shown to be paraphyletic with respect to Cladophora species and includes several genera shich werde traditionally ascribed to the Siphonocladales (Chapter 3). ... Zie: Summary/Samenvatting

Diamond cubic phase of monoolein and water as an amphiphilic matrix for electrophoresis of oligonucleotides.

Science.gov (United States)

Carlsson, Nils; Winge, Ann-Sofie; Engström, Sven; Akerman, Björn

2005-10-06

We used a cubic liquid crystal formed by the nonionic monoglyceride monoolein and water as a porous matrix for the electrophoresis of oligonucleotides. The diamond cubic phase is thermodynamically stable when in contact with a water-rich phase, which we exploit to run the electrophoresis in the useful submarine mode. Oligonucleotides are separated according to size and secondary structure by migration through the space-filling aqueous nanometer pores of the regular liquid crystal, but the comparatively slow migration means the cubic phase will not be a replacement for the conventional DNA gels. However, our demonstration that the cubic phase can be used in submarine electrophoresis opens up the possibility for a new matrix for electrophoresis of amphiphilic molecules. From this perspective, the results on the oligonucleotides show that water-soluble particles of nanometer size, typical for the hydrophilic parts of membrane-bound proteins, may be a useful separation motif. A charged contamination in the commercial sample of monoolein, most likely oleic acid that arises from its hydrolysis, restricts useful buffer conditions to a pH below 5.6.

Aerosol delivery from spacers in wheezy infants: a daily life study

NARCIS (Netherlands)

H.M. Janssens (Hettie); E.M. Heijnen; V.M. de Jong; W.C.J. Hop (Wim); W.P. Holland (Wim); J.C. de Jongste (Johan); H.A.W.M. Tiddens (Harm)

2000-01-01

textabstractThe aims of this study were to assess and compare dose delivery and dose variability of pressurized metered dose inhalers (pMDI)/spacers in wheezy infants in daily life and to investigate factors influencing aerosol delivery. In an open randomized

Accurate and rapid modeling of iron-bleomycin-induced DNA damage using tethered duplex oligonucleotides and electrospray ionization ion trap mass spectrometric analysis.

Science.gov (United States)

Harsch, A; Marzilli, L A; Bunt, R C; Stubbe, J; Vouros, P

2000-05-01

Bleomycin B(2)(BLM) in the presence of iron [Fe(II)] and O(2)catalyzes single-stranded (ss) and double-stranded (ds) cleavage of DNA. Electrospray ionization ion trap mass spectrometry was used to monitor these cleavage processes. Two duplex oligonucleotides containing an ethylene oxide tether between both strands were used in this investigation, allowing facile monitoring of all ss and ds cleavage events. A sequence for site-specific binding and cleavage by Fe-BLM was incorporated into each analyte. One of these core sequences, GTAC, is a known hot-spot for ds cleavage, while the other sequence, GGCC, is a hot-spot for ss cleavage. Incubation of each oligo-nucleotide under anaerobic conditions with Fe(II)-BLM allowed detection of the non-covalent ternary Fe-BLM/oligonucleotide complex in the gas phase. Cleavage studies were then performed utilizing O(2)-activated Fe(II)-BLM. No work-up or separation steps were required and direct MS and MS/MS analyses of the crude reaction mixtures confirmed sequence-specific Fe-BLM-induced cleavage. Comparison of the cleavage patterns for both oligonucleotides revealed sequence-dependent preferences for ss and ds cleavages in accordance with previously established gel electrophoresis analysis of hairpin oligonucleotides. This novel methodology allowed direct, rapid and accurate determination of cleavage profiles of model duplex oligonucleotides after exposure to activated Fe-BLM.

Antisense Oligonucleotide-mediated Exon Skipping as a Systemic Therapeutic Approach for Recessive Dystrophic Epidermolysis Bullosa.

Science.gov (United States)

Bremer, Jeroen; Bornert, Olivier; Nyström, Alexander; Gostynski, Antoni; Jonkman, Marcel F; Aartsma-Rus, Annemieke; van den Akker, Peter C; Pasmooij, Anna Mg

2016-10-18

The "generalized severe" form of recessive dystrophic epidermolysis bullosa (RDEB-gen sev) is caused by bi-allelic null mutations in COL7A1, encoding type VII collagen. The absence of type VII collagen leads to blistering of the skin and mucous membranes upon the slightest trauma. Because most patients carry exonic point mutations or small insertions/deletions, most exons of COL7A1 are in-frame, and low levels of type VII collagen already drastically improve the disease phenotype, this gene seems a perfect candidate for antisense oligonucleotide (AON)-mediated exon skipping. In this study, we examined the feasibility of AON-mediated exon skipping in vitro in primary cultured keratinocytes and fibroblasts, and systemically in vivo using a human skin-graft mouse model. We show that treatment with AONs designed against exon 105 leads to in-frame exon 105 skipping at the RNA level and restores type VII collagen protein production in vitro. Moreover, we demonstrate that systemic delivery in vivo induces de novo expression of type VII collagen in skin grafts generated from patient cells. Our data demonstrate strong proof-of-concept for AON-mediated exon skipping as a systemic therapeutic strategy for RDEB.

Intensity Modulated Proton and Photon Therapy for Early Prostate Cancer With or Without Transperineal Injection of a Polyethylen Glycol Spacer: A Treatment Planning Comparison Study

Energy Technology Data Exchange (ETDEWEB)

Weber, Damien C., E-mail: damien.weber@unige.ch [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Zilli, Thomas [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Vallee, Jean Paul [Department of Diagnostic Radiology, Geneva University Hospital, Geneva (Switzerland); Rouzaud, Michel; Miralbell, Raymond [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Cozzi, Luca [Oncology Institute of Southern Switzerland, Medical Physics Unit, Bellinzona (Switzerland)

2012-11-01

Purpose: Rectal toxicity is a serious adverse effect in early-stage prostate cancer patients treated with curative radiation therapy (RT). Injecting a spacer between Denonvilliers' fascia increases the distance between the prostate and the anterior rectal wall and may thus decrease the rectal radiation-induced toxicity. We assessed the dosimetric impact of this spacer with advanced delivery RT techniques, including intensity modulated RT (IMRT), volumetric modulated arc therapy (VMAT), and intensity modulated proton beam RT (IMPT). Methods and Materials: Eight prostate cancer patients were simulated for RT with or without spacer. Plans were computed for IMRT, VMAT, and IMPT using the Eclipse treatment planning system using both computed tomography spacer+ and spacer- data sets. Prostate {+-} seminal vesicle planning target volume [PTV] and organs at risk (OARs) dose-volume histograms were calculated. The results were analyzed using dose and volume metrics for comparative planning. Results: Regardless of the radiation technique, spacer injection decreased significantly the rectal dose in the 60- to 70-Gy range. Mean V{sub 70Gy} and V{sub 60Gy} with IMRT, VMAT, and IMPT planning were 5.3 {+-} 3.3%/13.9 {+-} 10.0%, 3.9 {+-} 3.2%/9.7 {+-} 5.7%, and 5.0 {+-} 3.5%/9.5 {+-} 4.7% after spacer injection. Before spacer administration, the corresponding values were 9.8 {+-} 5.4% (P=.012)/24.8 {+-} 7.8% (P=.012), 10.1 {+-} 3.0% (P=.002)/17.9 {+-} 3.9% (P=.003), and 9.7 {+-} 2.6% (P=.003)/14.7% {+-} 2.7% (P=.003). Importantly, spacer injection usually improved the PTV coverage for IMRT. With this technique, mean V{sub 70.2Gy} (P=.07) and V{sub 74.1Gy} (P=0.03) were 100 {+-} 0% to 99.8 {+-} 0.2% and 99.1 {+-} 1.2% to 95.8 {+-} 4.6% with and without Spacer, respectively. As a result of spacer injection, bladder doses were usually higher but not significantly so. Only IMPT managed to decrease the rectal dose after spacer injection for all dose levels, generally with no

Influence of an interpositional spacer on the behaviour of the tibiofemoral joint: a finite element study.

Science.gov (United States)

Checa, S; Taylor, M; New, A

2008-10-01

Interpositional arthroplasty is considered by many surgeons for the treatment of isolated medial compartment osteoarthritis of the knee. In this procedure, an interpositional spacer is inserted into the medial compartment of the joint with no bone resection and no mechanical fixation. Major problems such as implant dislocation, severe pain or need for revision have been reported post-operatively. In this study, the kinematics of a knee implanted with an interpositional spacer made of either polyurethane or cobalt-chrome during walking, stair ascent and squatting cycles have been predicted and compared to the normal knee using finite element analysis. In addition, articular cartilage stress histories have been examined to obtain distributions of cumulative stress, a measure of the likelihood of articular cartilage degeneration. The insertion of a polyurethane interpositional spacer in the medial side of the knee did not affect knee kinematics as compared to the normal knee, but caused an increase of articular cartilage cumulative contact stress exposures in the medial compartment of the joint. The knee implanted with the Co-Cr spacer exhibited similar trends in knee kinematics, however significantly different ranges of motion were observed during some periods of the activity cycles, specifically during the first half of the walking cycle where lower ranges of motion were predicted. In addition, higher articular cartilage cumulative contact stress exposures were observed in both compartments of the knee. In both cases, cumulative contact stress exposures of the tibial articular cartilage were more affected than those of the femoral articular cartilage. These results suggest implant material as an important parameter in the design phase of interpositional spacers.

A facile one-step fluorescence method for the quantitation of low-content single base deamination impurity in synthetic oligonucleotides.

Science.gov (United States)

Su, Xiaoye; Liang, Ruiting; Stolee, Jessica A

2018-06-05

Oligonucleotides are being researched and developed as potential drug candidates for the treatment of a broad spectrum of diseases. The characterization of antisense oligonucleotide (ASO) impurities caused by base mutations (e.g. deamination) which are closely related to the target ASO is a significant analytical challenge. Herein, we describe a novel one-step method, utilizing a strategy that combines fluorescence-ON detection with competitive hybridization, to achieve single base mutation quantitation in extensively modified synthetic ASOs. Given that this method is highly specific and sensitive (LoQ = 4 nM), we envision that it will find utility for screening other impurities as well as sequencing modified oligonucleotides. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of a laser multi-layer cladding technology for damage mitigation of fuel spacers in Hanaro reactor

International Nuclear Information System (INIS)

Kim, J. S.; Lee, D. H.; Hwang, S. S.; Suh, J. H.

2002-01-01

A laser multi-layer cladding technology was developed to mitigate the fretting wear damages occurred at fuel spacers in Hanaro reactor. The detailed experimental results are as follows. 1) Analyses of fretting wear damages and fabrication process of fuel spacers 2) Development and analysis of spherical Al 6061 T-6 alloy powders for the laser cladding 3) Analysis of parameter effects on laser cladding process for clad bids, and optimization of laser cladding process 4) Analysis on the changes of cladding layers due to overlapping factor change 5) Microstructural observation and phase analysis 6) Characterization of materials properties (hardness and wear tests) 7) Manufacture of prototype fuel spacers 8) Development of a vision system and revision of its related softwares

Finite element analysis of the contact between fuel rod and spacer grid

Energy Technology Data Exchange (ETDEWEB)

Kim, Hyung Kyu; Kim, Young Koon; Kang, Heung Seok; Yoon, Kyung Ho; Song, Kee Nam [Korea Atomic Energy Research Institute, Taejon (Korea)

1999-01-01

For the research on the fretting failure problem of nuclear fuel, the contact length and normal stress field are evaluated for the contact between fuel rod and spacer grid by using the Finite Element Method (FEM). An assumption of semi-infiniteness is necessary for applying the Contact Mechanics which is based on the classical theory of elasticity to the present problem. For the contact problem of fuel fretting, the contact mechanical solutions could be utilized well with sufficient accuracy if the contact bodies (i.e., the cladding tube and the spacer grid) can be assumed as semi-infinite bodies. To this end, the contact length evaluated by FEM is discussed together with the relevant research which concerned the effect of dimension for the validity of the assumption of semi-infiniteness. Normal stress profile on the contact is also studied through comparing the theoretical and the FE results. For the analysis of contact problem by FEM, ANSYS code (Version 5.3) is utilized and the geometry is chosen to be the Hertzian (cylinder-to-cylinder), the strip-to-cylinder and the fuel rod/spacer grid contact (strip-to-tube). Present research will be utilized for accessing the fuel fretting problem by FEM together with the theoretical (i.e., contact mechanical) analysis which has been published as KAERI/TR-1113/98. (author). 15 refs., 44 figs., 4 tabs.

Heat Transfer Enhancement Studies in a Circular Tube Fitted with Right-Left Helical Inserts with Spacer

OpenAIRE

P. K. Nagarajan; P. Sivashanmugam

2011-01-01

Experimental investigation of heat transfer and friction factor characteristics of circular tube fitted with 300 right-left helical screw inserts with 100 mm spacer of different twist ratio has been presented for laminar and turbulent flow.. The experimental data obtained were compared with those obtained from plain tube published data. The heat transfer coefficient enhancement for 300 RL inserts with 100 mm spacer is quite comparable with for 300 R-L inserts. Performance evalu...

Fluorinated Nucleotide Modifications Modulate Allele Selectivity of SNP-Targeting Antisense Oligonucleotides

Directory of Open Access Journals (Sweden)

Michael E. Østergaard

2017-06-01

Full Text Available Antisense oligonucleotides (ASOs have the potential to discriminate between subtle RNA mismatches such as SNPs. Certain mismatches, however, allow ASOs to bind at physiological conditions and result in RNA cleavage mediated by RNase H. We showed that replacing DNA nucleotides in the gap region of an ASO with other chemical modification can improve allele selectivity. Herein, we systematically substitute every position in the gap region of an ASO targeting huntingtin gene (HTT with fluorinated nucleotides. Potency is determined in cell culture against mutant HTT (mtHTT and wild-type HTT (wtHTT mRNA and RNase H cleavage intensities, and patterns are investigated. This study profiled five different fluorinated nucleotides and showed them to have predictable, site-specific effects on RNase H cleavage, and the cleavage patterns were rationalized from a published X-ray structure of human RNase H1. The results herein can be used as a guide for future projects where ASO discrimination of SNPs is important.

The Construction of Chimeric T-Cell Receptor with Spacer Base of Modeling Study of VHH and MUC1 Interaction

Directory of Open Access Journals (Sweden)

Nazanin Pirooznia

2011-01-01

Full Text Available Adaptive cell immunotherapy with the use of chimeric receptors leads to the best and most specific response against tumors. Chimeric receptors consist of a signaling fragment, extracellular spacer, costimulating domain, and an antibody. Antibodies cause immunogenicity; therefore, VHH is a good replacement for ScFv in chimeric receptors. Since peptide sequences have an influence on chimeric receptors, the effect of peptide domains on each other's conformation were investigated. CD3Zeta, CD28, VHH and CD8α, and FcgIIα are used as signaling moieties, costimulating domain, antibody, and spacers, respectively. To investigate the influence of the ligation of spacers on the conformational structure of VHH, models of VHH were constructed. Molecular dynamics simulation was run to study the influence of the presence of spacers on the conformational changes in the binding sites of VHH. Root mean square deviation and root mean square fluctuation of critical segments in the binding site showed no noticeable differences with those in the native VHH. Results from molecular docking revealed that the presence of spacer FcgIIα causes an increasing effect on VHH with MUC1 interaction. Each of the constructs was transformed into the Jurkat E6.1. Expression analysis and evaluation of their functions were examined. The results showed good expression and function.

Effective intracellular delivery of oligonucleotides in order to make sense of antisense

NARCIS (Netherlands)

Shi, FX; Hoekstra, D

2004-01-01

For more than two decades, antisense oligonucleotides (ODNs) have been used to modulate gene expression for the purpose of applications in cell biology and for development of novel sophisticated medical therapeutics. Conceptually, the antisense approach represents an elegant strategy, involving the

Nuclear reactor fuel element assembly spacer grid and method of making

International Nuclear Information System (INIS)

Chetter, J.

1975-01-01

A cellular fuel element assembly spacer grid is described which provides for resilient bracing of fuel pins in the cells of the grid by bow spring locating members projecting inside the cells of the grid to hold the fuel pins against opposed rigid stops also projecting inside the cells of the grid. The grid comprises two tiers each formed from intersecting strip members defining cells which are penetrated by the fuel pins and arranged parallel to one another but spaced apart. The bow spring locating members extend longitudinally between the two tiers and have end ferrules which are a sliding fit on locating members which extend longitudinally from the facing inner edges of the strip members forming the two tiers. The grid tiers are fabricated individually by heat bonding the intersecting strip members prior to assembling the tiers into the spacer grid. (U.S.)

Specificity tests of an oligonucleotide probe against food-outbreak salmonella for biosensor detection

Science.gov (United States)

Chen, I.-H.; Horikawa, S.; Xi, J.; Wikle, H. C.; Barbaree, J. M.; Chin, B. A.

2017-05-01

Phage based magneto-elastic (ME) biosensors have been shown to be able to rapidly detect Salmonella in various food systems to serve food pathogen monitoring purposes. In this ME biosensor platform, the free-standing strip-shaped magneto-elastic sensor is the transducer and the phage probe that recognizes Salmonella in food serves as the bio-recognition element. According to Sorokulova et al. at 2005, a developed oligonucleotide probe E2 was reported to have high specificity to Salmonella enterica Typhimurium. In the report, the specificity tests were focused in most of Enterobacterace groups outside of Salmonella family. Here, to understand the specificity of phage E2 to different Salmonella enterica serotypes within Salmonella Family, we further tested the specificity of the phage probe to thirty-two Salmonella serotypes that were present in the major foodborne outbreaks during the past ten years (according to Centers for Disease Control and Prevention). The tests were conducted through an Enzyme linked Immunosorbent Assay (ELISA) format. This assay can mimic probe immobilized conditions on the magnetoelastic biosensor platform and also enable to study the binding specificity of oligonucleotide probes toward different Salmonella while avoiding phage/ sensor lot variations. Test results confirmed that this oligonucleotide probe E2 was high specific to Salmonella Typhimurium cells but showed cross reactivity to Salmonella Tennessee and four other serotypes among the thirty-two tested Salmonella serotypes.

Ultrasensitive Detection of Ebola Virus Oligonucleotide Based on Upconversion Nanoprobe/Nanoporous Membrane System.

Science.gov (United States)

Tsang, Ming-Kiu; Ye, WeiWei; Wang, Guojing; Li, Jingming; Yang, Mo; Hao, Jianhua

2016-01-26

Ebola outbreaks are currently of great concern, and therefore, development of effective diagnosis methods is urgently needed. The key for lethal virus detection is high sensitivity, since early-stage detection of virus may increase the probability of survival. Here, we propose a luminescence scheme of assay consisting of BaGdF5:Yb/Er upconversion nanoparticles (UCNPs) conjugated with oligonucleotide probe and gold nanoparticles (AuNPs) linked with target Ebola virus oligonucleotide. As a proof of concept, a homogeneous assay was fabricated and tested, yielding a detection limit at picomolar level. The luminescence resonance energy transfer is ascribed to the spectral overlapping of upconversion luminescence and the absorption characteristics of AuNPs. Moreover, we anchored the UCNPs and AuNPs on a nanoporous alumina (NAAO) membrane to form a heterogeneous assay. Importantly, the detection limit was greatly improved, exhibiting a remarkable value at the femtomolar level. The enhancement is attributed to the increased light-matter interaction throughout the nanopore walls of the NAAO membrane. The specificity test suggested that the nanoprobes were specific to Ebola virus oligonucleotides. The strategy combining UCNPs, AuNPs, and NAAO membrane provides new insight into low-cost, rapid, and ultrasensitive detection of different diseases. Furthermore, we explored the feasibility of clinical application by using inactivated Ebola virus samples. The detection results showed great potential of our heterogeneous design for practical application.

CRISPR Spacer Arrays for Detection of Viral Signatures from Acidic Hot Springs

Science.gov (United States)

Snyder, J. C.; Bateson, M. M.; Suciu, D.; Young, M. J.

2010-04-01

Viruses are the most abundant life-like entities on the planet Earth. Using CRISPR spacer sequences, we have developed a microarray-based approach to detecting viral signatures in the acidic hot springs of Yellowstone.

Measurements of the Effects of Spacers on the Burnout Conditions for Flow of Boiling Water in a Vertical Annulus and a Vertical 7-Rod Cluster

Energy Technology Data Exchange (ETDEWEB)

Becker, Kurt M; Hernborg, G

1964-11-15

The present report deals with measurements of the effects of spacers on the burnout conditions in a vertical annulus and a vertical 7-rod cluster. The following ranges of variables were studied and 162 burnout measurements were obtained. Pressure p = 31 kg/cm; Inlet sub-cooling 35 < {delta}t{sub sub} < 174 deg C; Surface heat flux 89 < q/A < 305 W/cm{sup 2}; Mass velocity 94 < m'/F < 900 kg/m{sup 2}/s; Burnout steam quality 0.10 < x{sub BO} < 0.56. The experimental results showed that the type of spacers employed during the present investigation had negligible effects on the burnout conditions and that the measured burnout heat fluxes could be predicted within {+-} 5 per cent by means of the correlation by Becker et al for flow in smooth channels.

The effect of spacer grid critical component on pressure drop under both single and two phase flow conditions

International Nuclear Information System (INIS)

Han, B.; Yang, B.W.; Zhang, H.; Mao, H.; Zha, Y.

2016-01-01

As pressure drop is one of the most critical thermal hydraulic parameters for spacer grids the accurate estimation of it is the key to the design and development of spacer grids. Most of the available correlations for pressure drop do not contain any real geometrical parameters that characterize the grid effect. The main functions for spacer grid are structural support and flow mixing. Once the boundary sublayer near the rod bundle is disturbed, the liquid forms swirls or flow separation that affect pressure drop. However, under two phase flow conditions, due to the existence of steam bubble, the complexity for spacer grid are multiplied and pressure drop calculation becomes much more challenging. The influence of the dimple location, distance of mixing vane to the nearest strip, and the effect of inter-subchannel mixing among neighboring subchannels on pressure drop and downstream flow fields are analyzed in this paper. Based on this study, more detailed space grid geometry parameters are recommended for adding into the correlation when predicting pressure drop.

A simulation study on the variation of virtual NMR signals by winding, bobbin, spacer error of HTS magnet

Energy Technology Data Exchange (ETDEWEB)

Kim, Jun Seong; Lee, Woo Seung; Kim, Jin Sub; Song, Seung Hyun; Nam, Seok Ho; Jeon, Hae Ryong; Beak, Geon Woo; Ko, Tae Kuk [Yonsei University, Seoul (Korea, Republic of)

2016-09-15

Recently, production technique and property of the High-Temperature Superconductor (HTS) tape have been improved. Thus, the study on applying an HTS magnet to the high magnetic field application is rapidly increased. A Nuclear Magnetic Resonance (NMR) spectrometer requires high magnitude and homogeneous of central magnetic field. However, the HTS magnet has fabrication errors because shape of HTS is tape and HTS magnet is manufactured by winding HTS tape to the bobbin. The fabrication errors are winding error, bobbin diameter error, spacer thickness error and so on. The winding error occurs when HTS tape is departed from the arranged position on the bobbin. The bobbin diameter and spacer thickness error occur since the diameter of bobbin and spacer are inaccurate. These errors lead magnitude and homogeneity of central magnetic field to be different from its ideal design. The purpose of this paper is to investigate the effect of winding error, bobbin diameter error and spacer thickness error on the central field and field homogeneity of HTS magnet using the virtual NMR signals in MATLAB simulation.

Correction of Spatial Bias in Oligonucleotide Array Data

Directory of Open Access Journals (Sweden)

Philippe Serhal

2013-01-01

Full Text Available Background. Oligonucleotide microarrays allow for high-throughput gene expression profiling assays. The technology relies on the fundamental assumption that observed hybridization signal intensities (HSIs for each intended target, on average, correlate with their target’s true concentration in the sample. However, systematic, nonbiological variation from several sources undermines this hypothesis. Background hybridization signal has been previously identified as one such important source, one manifestation of which appears in the form of spatial autocorrelation. Results. We propose an algorithm, pyn, for the elimination of spatial autocorrelation in HSIs, exploiting the duality of desirable mutual information shared by probes in a common probe set and undesirable mutual information shared by spatially proximate probes. We show that this correction procedure reduces spatial autocorrelation in HSIs; increases HSI reproducibility across replicate arrays; increases differentially expressed gene detection power; and performs better than previously published methods. Conclusions. The proposed algorithm increases both precision and accuracy, while requiring virtually no changes to users’ current analysis pipelines: the correction consists merely of a transformation of raw HSIs (e.g., CEL files for Affymetrix arrays. A free, open-source implementation is provided as an R package, compatible with standard Bioconductor tools. The approach may also be tailored to other platform types and other sources of bias.

Correction of Spatial Bias in Oligonucleotide Array Data

Science.gov (United States)

Lemieux, Sébastien

2013-01-01

Background. Oligonucleotide microarrays allow for high-throughput gene expression profiling assays. The technology relies on the fundamental assumption that observed hybridization signal intensities (HSIs) for each intended target, on average, correlate with their target's true concentration in the sample. However, systematic, nonbiological variation from several sources undermines this hypothesis. Background hybridization signal has been previously identified as one such important source, one manifestation of which appears in the form of spatial autocorrelation. Results. We propose an algorithm, pyn, for the elimination of spatial autocorrelation in HSIs, exploiting the duality of desirable mutual information shared by probes in a common probe set and undesirable mutual information shared by spatially proximate probes. We show that this correction procedure reduces spatial autocorrelation in HSIs; increases HSI reproducibility across replicate arrays; increases differentially expressed gene detection power; and performs better than previously published methods. Conclusions. The proposed algorithm increases both precision and accuracy, while requiring virtually no changes to users' current analysis pipelines: the correction consists merely of a transformation of raw HSIs (e.g., CEL files for Affymetrix arrays). A free, open-source implementation is provided as an R package, compatible with standard Bioconductor tools. The approach may also be tailored to other platform types and other sources of bias. PMID:23573083

Efficient thermal diode with ballistic spacer

Science.gov (United States)

Chen, Shunda; Donadio, Davide; Benenti, Giuliano; Casati, Giulio

2018-03-01

Thermal rectification is of importance not only for fundamental physics, but also for potential applications in thermal manipulations and thermal management. However, thermal rectification effect usually decays rapidly with system size. Here, we show that a mass-graded system, with two diffusive leads separated by a ballistic spacer, can exhibit large thermal rectification effect, with the rectification factor independent of system size. The underlying mechanism is explained in terms of the effective size-independent thermal gradient and the match or mismatch of the phonon bands. We also show the robustness of the thermal diode upon variation of the model's parameters. Our finding suggests a promising way for designing realistic efficient thermal diodes.

Dependency of Tunneling-Magnetoresistance Ratio on Nanoscale Spacer Thickness and Material for Double MgO Based Perpendicular-Magnetic-Tunneling-Junction

Science.gov (United States)

Lee, Du-Yeong; Hong, Song-Hwa; Lee, Seung-Eun; Park, Jea-Gun

2016-12-01

It was found that in double MgO based perpendicular magnetic tunneling junction spin-valves ex-situ annealed at 400 °C, the tunneling magnetoresistance ratio was extremely sensitive to the material and thickness of the nanoscale spacer: it peaked at a specific thickness (0.40~0.53 nm), and the TMR ratio for W spacers (~134%) was higher than that for Ta spacers (~98%). This dependency on the spacer material and thickness was associated with the (100) body-centered-cubic crystallinity of the MgO layers: the strain enhanced diffusion length in the MgO layers of W atoms (~1.40 nm) was much shorter than that of Ta atoms (~2.85 nm) and the shorter diffusion length led to the MgO layers having better (100) body-centered-cubic crystallinity.

Hetero-oligonucleotide Nanoscale Tiles Capable of Two-Dimensional Lattice Formation as Testbeds for a Rapid, Affordable Purification Methodology

Science.gov (United States)

2013-01-01

devices; however, DNA is not the only polymer that can take advantage of the specicity of the Watson – Crick base-pair to achieve these goals. Central to...14. ABSTRACT 16. SECURITY CLASSIFICATION OF: New nanoscale hetero-oligonucleotide tiles are assembled from DNA , RNA and morpholino oligos and...purified using size exclusion filtration. Homo-oligonucleotide tiles assembled from RP-cartridge processed DNA oligos are purified by nondenaturing gel

Response of an annular electrostatic probe for a right cylindrical spacer

DEFF Research Database (Denmark)

Johansson, Torben; MacAllister, I. W.

2002-01-01

The response of an annular electrostatic probe mounted in an electrode is examined with reference to a right cylindrical spacer. The study involves using the probe λ function to derive characteristic parameters. These parameters enable the response of the probe to different charge distributions...

Thermoplastic polymers surfaces for Dip-Pen Nanolithography of oligonucleotides

International Nuclear Information System (INIS)

Suriano, Raffaella; Biella, Serena; Cesura, Federico; Levi, Marinella; Turri, Stefano

2013-01-01

Different thermoplastic polymers were spin-coated to prepare smooth surfaces for the direct deposition of end-group modified oligonucleotides by Dip-Pen Nanolithography. A study of the diffusion process was done in order to investigate the dependence of calibration coefficient and quality of deposited features on environmental parameters (temperature, relative humidity) and ink's molecular weight and functionality. The optimization of the process parameters led to the realization of high quality and density nanoarrays on plastics.

Feasibility Study of Interactive Game Technologies to Improve Experience with Inhaler Spacer Devices in Young Children

OpenAIRE

Aslam, Tariq; Shakir, Savana; Murray, Clare

2016-01-01

IntroductionThe correct use of inhaler devices with facemasks and spacers in young children can be difficult for both children and parents, resulting in distress for both, poor adherence and ineffective drug delivery. The aim of this study was to develop and assess the utility and impact of an interactive electronic game designed to improve the experience of spacer devices in young asthmatic children.MethodsThe Respiratory Aid For Inhaler (RAFIhaler) technology consists of a smartphone mounte...

Drop drying on surfaces determines chemical reactivity - the specific case of immobilization of oligonucleotides on microarrays

Science.gov (United States)

2013-01-01

Background Drop drying is a key factor in a wide range of technical applications, including spotted microarrays. The applied nL liquid volume provides specific reaction conditions for the immobilization of probe molecules to a chemically modified surface. Results We investigated the influence of nL and μL liquid drop volumes on the process of probe immobilization and compare the results obtained to the situation in liquid solution. In our data, we observe a strong relationship between drop drying effects on immobilization and surface chemistry. In this work, we present results on the immobilization of dye labeled 20mer oligonucleotides with and without an activating 5′-aminoheptyl linker onto a 2D epoxysilane and a 3D NHS activated hydrogel surface. Conclusions Our experiments identified two basic processes determining immobilization. First, the rate of drop drying that depends on the drop volume and the ambient relative humidity. Oligonucleotides in a dried spot react unspecifically with the surface and long reaction times are needed. 3D hydrogel surfaces allow for immobilization in a liquid environment under diffusive conditions. Here, oligonucleotide immobilization is much faster and a specific reaction with the reactive linker group is observed. Second, the effect of increasing probe concentration as a result of drop drying. On a 3D hydrogel, the increasing concentration of probe molecules in nL spotting volumes accelerates immobilization dramatically. In case of μL volumes, immobilization depends on whether the drop is allowed to dry completely. At non-drying conditions, very limited immobilization is observed due to the low oligonucleotide concentration used in microarray spotting solutions. The results of our study provide a general guideline for microarray assay development. They allow for the initial definition and further optimization of reaction conditions for the immobilization of oligonucleotides and other probe molecule classes to different

Detection and identification of intestinal pathogenic bacteria by hybridization to oligonucleotide microarrays

Science.gov (United States)

Jin, Lian-Qun; Li, Jun-Wen; Wang, Sheng-Qi; Chao, Fu-Huan; Wang, Xin-Wei; Yuan, Zheng-Quan

2005-01-01

AIM: To detect the common intestinal pathogenic bacteria quickly and accurately. METHODS: A rapid (<3 h) experimental procedure was set up based upon the gene chip technology. Target genes were amplified and hybridized by oligonucleotide microarrays. RESULTS: One hundred and seventy strains of bacteria in pure culture belonging to 11 genera were successfully discriminated under comparatively same conditions, and a series of specific hybridization maps corresponding to each kind of bacteria were obtained. When this method was applied to 26 divided cultures, 25 (96.2%) were identified. CONCLUSION: Salmonella sp., Escherichia coli, Shigella sp., Listeria monocytogenes, Vibrio parahaemolyticus, Staphylococcus aureus, Proteus sp., Bacillus cereus, Vibrio cholerae, Enterococcus faecalis, Yersinia enterocolitica, and Campylobacter jejuni can be detected and identified by our microarrays. The accuracy, range, and discrimination power of this assay can be continually improved by adding further oligonucleotides to the arrays without any significant increase of complexity or cost. PMID:16437687

Bronchodilator Effect of Tiotropium via Respimat®Administered with a Spacer in Patients with Chronic Obstructive Pulmonary Disease (COPD).

Science.gov (United States)

Ogasawara, Takashi; Sakata, Jun; Aoshima, Yoichiro; Tanaka, Kazuki; Yano, Toshiaki; Kasamatsu, Norio

2017-09-15

Objective Among elderly patients with chronic obstructive pulmonary disease (COPD), there are some patients who cannot inhale tiotropium via Respimat ® due to poor hand-lung coordination. This study aimed to examine whether or not tiotropium inhalation therapy using Respimat ® with a spacer increased the forced expiratory volume in 1 s (FEV 1 ) in patients with COPD. Methods A randomized, crossover, single-center study was conducted in 18 patients with stable COPD. Tiotropium (5 μg) via Respimat ® with or without a spacer (AeroChamber ® ) was administered for 2 weeks. Following a 2-week washout period using a transdermal tulobuterol patch (2 mg per day), participants were then crossed over to the other inhalation therapy with respect to spacer use. The trough FEV 1 was measured at every visit using a spirometer. A questionnaire regarding inhalation therapy was administered to patients at the final visit. Results The administration of tiotropium via Respimat ® both with and without a spacer significantly increased the trough FEV 1 from baseline during each treatment period, with mean differences of 115.0±169.6 mL and 92.8±128.1 mL, respectively. There was no significant difference in the change in the trough FEV 1 between the 2 procedures (p=0.66). A total of 86% of patients reported that inhalation using a spacer was not difficult, and more than half also rated both the usage and maintenance of the AeroChamber ® as easy. Conclusion Tiotropium inhalation therapy administered via Respimat ® using a spacer exerted a bronchodilatory effect similar to that observed with tiotropium Respimat ® alone.

An experimental investigation of supercritical heat transfer in a three-rod bundle equipped with wire-wrap and grid spacers and cooled by carbon dioxide

Energy Technology Data Exchange (ETDEWEB)

Eter, Ahmad, E-mail: eng.eter@yahoo.com; Groeneveld, Dé, E-mail: degroeneveld@gmail.com; Tavoularis, Stavros, E-mail: stavros.tavoularis@uottawa.ca

2016-07-15

tube at similar conditions and with predictions of a supercritical heat transfer correlation. Heat transfer was observed to deteriorate near the start of the heated section of the rod bundle equipped with either type of spacers as well as in a circular tube for mass fluxes between 200 and 700 kg m{sup −2} s{sup −1}. The onset of deterioration occurred at a higher heat flux for the wire-wrapped bundle than for the one with grid spacers, and at the lowest heat flux for the tube. Normal heat transfer in either of the rod bundles behaved similarly to the one in the tube and was also compatible with the predictions of the correlation of Jackson. The grid spacers introduced a strong local enhancement, but their effects disappeared only about 10 rod diameters downstream.

Models for the cross flow and the turbulent eddy diffusivity in bundles of rods with helical spacers

International Nuclear Information System (INIS)

Fernandez y Fernandez, E.; Carajilescov, P.

1985-01-01

The fuel elements of a LMFBR type reactor consist of a bundle of rods wrapped by helical wires that work as spacers. The bundle of rods is surrounded by an hexagonal duct. Models for the channel cross flow and for the turbulent eddy diffusivity were developed. In conjunction with these models, the flow redistribution factors permit to estabish a determinist method to calculate the temperature distribution. The obtained results are compared with experimental data available in the literature and with results given by other codes. Although these codes are based on much more complex models, the comparison was very satisfactory. (Author) [pt

Coronal microleakage of four temporary restorative materials in Class II-type endodontic access preparations

Directory of Open Access Journals (Sweden)

Sang-Mi Yun

2012-02-01

Full Text Available Objectives The purpose of this study was to evaluate the microleakage of 4 temporary materials in teeth with Class II-type endodontic access preparations by using a glucose penetration model. Materials and Methods Glucose reaction test was performed to rule out the presence of any reaction between glucose and temporary material. Class II-type endodontic access preparations were made in extracted human premolars with a single root (n = 10. Each experimental group was restored with Caviton (GC, Spacer (Vericom, IRM (Dentsply-Caulk, or Fuji II(GC. Microleakage of four materials used as temporary restorative materials was evaluated by using a glucose penetration model. Data were analyzed by the one-way analysis of variance followed by a multiple-comparison Tukey test. The interface between materials and tooth were examined under a scanning electron microscope (SEM. Results There was no significant reaction between glucose and temporary materials used in this study. Microleakage was significantly lower for Caviton and Spacer than for Fuji II and IRM. SEM observation showed more intimate adaptation of tooth-restoration interfaces in Caviton and Spacer than in IRM and Fuji II. Conclusions Compared to IRM and Fuji II, Caviton and Spacer can be considered better temporary sealing materials in Class II-type endodontic access cavities.

PCR amplification on microarrays of gel immobilized oligonucleotides

Science.gov (United States)

Strizhkov, Boris; Tillib, Sergei; Mikhailovich, Vladimir; Mirzabekov, Andrei

2003-11-04

The invention relates two general methods for performing PCR amplification, combined with the detection and analysis of the PCR products on a microchip. In the first method, the amplification occurs both outside and within a plurality of gel pads on a microchip, with at least one oligonucleotide primer immobilized in a gel pad. In the second method, PCR amplification also takes place within gel pads on a microchip, but the pads are surrounded by a hydrophobic liquid such as that which separates the individual gel pads into environments which resemble micro-miniaturized test tubes.

INTERSPINOUS SPACER IN PERSISTENT DISCOGENIC PAIN: PERCUTANEOUS APPROACH OR OPEN TECHNIQUE

Directory of Open Access Journals (Sweden)

José Antonio Cruz Ricardez

Full Text Available ABSTRACT Objective: To compare the postoperative clinical course of placement of interspinous spacer with open technique (ISO with percutaneous interspinous spacer (PIS. Methods: Quasi-experimental, longitudinal study of 42 patients with discogenic pain uncontrolled with analgesics, aged 35-55 years old, 21 women, and 21 men. Clinical history, location of pain, VAS scale before and after surgery, Oswestry Disability Index and Macnab modified scale at 6 months were used. Results: When performing quantitative analysis statistical significance (p = 0.0478, 0.0466, 0.0399 was demonstrated with Student's t test between the results according to VAS scale; in the qualitative analysis with the Oswestry index and Macnab modified scale it was demonstrated the hypothesis that the results is dependent of the surgical technique. Conclusions: According to the results, we can conclude that there is a statistically significant difference depending on the surgical technique used with respect to the rate of disability and functionality in daily life as well as in the improvement of pain symptoms.

Family- and genus-level 16S rRNA-targeted oligonucleotide probes for ecological studies of methanotrophic bacteria.

Science.gov (United States)

Gulledge, J; Ahmad, A; Steudler, P A; Pomerantz, W J; Cavanaugh, C M

2001-10-01

Methanotrophic bacteria play a major role in the global carbon cycle, degrade xenobiotic pollutants, and have the potential for a variety of biotechnological applications. To facilitate ecological studies of these important organisms, we developed a suite of oligonucleotide probes for quantitative analysis of methanotroph-specific 16S rRNA from environmental samples. Two probes target methanotrophs in the family Methylocystaceae (type II methanotrophs) as a group. No oligonucleotide signatures that distinguish between the two genera in this family, Methylocystis and Methylosinus, were identified. Two other probes target, as a single group, a majority of the known methanotrophs belonging to the family Methylococcaceae (type I/X methanotrophs). The remaining probes target members of individual genera of the Methylococcaceae, including Methylobacter, Methylomonas, Methylomicrobium, Methylococcus, and Methylocaldum. One of the family-level probes also covers all methanotrophic endosymbionts of marine mollusks for which 16S rRNA sequences have been published. The two known species of the newly described genus Methylosarcina gen. nov. are covered by a probe that otherwise targets only members of the closely related genus Methylomicrobium. None of the probes covers strains of the newly proposed genera Methylocella and "Methylothermus," which are polyphyletic with respect to the recognized methanotrophic families. Empirically determined midpoint dissociation temperatures were 49 to 57 degrees C for all probes. In dot blot screening against RNA from positive- and negative-control strains, the probes were specific to their intended targets. The broad coverage and high degree of specificity of this new suite of probes will provide more detailed, quantitative information about the community structure of methanotrophs in environmental samples than was previously available.

Impact of a Protective Vest and Spacer Garment on Exercise-Heat Strain

National Research Council Canada - National Science Library

Cheuvront, Samuel N; Goodman, Daniel A; Kenefick, Robert W; Montain, Scott J; Sawka, Michael N

2008-01-01

...). Volunteers wore the US Army battle dress uniform (trial B), B + protective vest (trial P), and B + P + spacer garment (trial S). Biophysical clothing properties were determined and found similar to many law enforcement, industry, and sports ensembles...

[Identification of medicinal plant Dendrobium based on the chloroplast psbK-psbI intergenic spacer].

Science.gov (United States)

Yao, Hui; Yang, Pei; Zhou, Hong; Ma, Shuang-jiao; Song, Jing-yuan; Chen, Shi-lin

2015-06-01

In this paper, the chloroplast psbK-psbI intergenic spacers of 18 species of Dendrobium and their adulterants were amplified and sequenced, and then the sequence characteristics were analyzed. The sequence lengths of chloroplast psbK-psbI regions of Dendrobium ranged from 474 to 513 bp and the GC contents were 25.4%-27.6%. The variable sites were 71 while the informative sites were 46. The inter-specific genetic distances calculated by Kimura 2-parameter (K2P) of Dendrobium were 0.006 1-0.058 1, with an average of 0.028 4. The K2P genetic distances between Dendrobium species and Bulbophyllum odoratissimum were 0.093 2-0.120 4. The NJ tree showed that the Dendrobium species can be easily differentiated from each other and 6 samples of the inspected Dendrobium species were identified successfully through sequencing the psbK-psbI intergenic spacer. Therefore, the chloroplast psbK-psbI intergenic spacer can be used as a candidate marker to identify Dendrobium species and its adulterants.

Analysis of oligonucleotide array experiments with repeated measures using mixed models

Directory of Open Access Journals (Sweden)

Getchell Thomas V

2004-12-01

Full Text Available Abstract Background Two or more factor mixed factorial experiments are becoming increasingly common in microarray data analysis. In this case study, the two factors are presence (Patients with Alzheimer's disease or absence (Control of the disease, and brain regions including olfactory bulb (OB or cerebellum (CER. In the design considered in this manuscript, OB and CER are repeated measurements from the same subject and, hence, are correlated. It is critical to identify sources of variability in the analysis of oligonucleotide array experiments with repeated measures and correlations among data points have to be considered. In addition, multiple testing problems are more complicated in experiments with multi-level treatments or treatment combinations. Results In this study we adopted a linear mixed model to analyze oligonucleotide array experiments with repeated measures. We first construct a generalized F test to select differentially expressed genes. The Benjamini and Hochberg (BH procedure of controlling false discovery rate (FDR at 5% was applied to the P values of the generalized F test. For those genes with significant generalized F test, we then categorize them based on whether the interaction terms were significant or not at the α-level (αnew = 0.0033 determined by the FDR procedure. Since simple effects may be examined for the genes with significant interaction effect, we adopt the protected Fisher's least significant difference test (LSD procedure at the level of αnew to control the family-wise error rate (FWER for each gene examined. Conclusions A linear mixed model is appropriate for analysis of oligonucleotide array experiments with repeated measures. We constructed a generalized F test to select differentially expressed genes, and then applied a specific sequence of tests to identify factorial effects. This sequence of tests applied was designed to control for gene based FWER.

Thermoplastic polymers surfaces for Dip-Pen Nanolithography of oligonucleotides

Energy Technology Data Exchange (ETDEWEB)

Suriano, Raffaella [Dipartimento di Chimica, Materiali e Ingegneria Chimica “Giulio Natta”, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy); Biella, Serena, E-mail: serena.biella@polimi.it [Dipartimento di Chimica, Materiali e Ingegneria Chimica “Giulio Natta”, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy); Cesura, Federico; Levi, Marinella; Turri, Stefano [Dipartimento di Chimica, Materiali e Ingegneria Chimica “Giulio Natta”, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy)

2013-05-15

Different thermoplastic polymers were spin-coated to prepare smooth surfaces for the direct deposition of end-group modified oligonucleotides by Dip-Pen Nanolithography. A study of the diffusion process was done in order to investigate the dependence of calibration coefficient and quality of deposited features on environmental parameters (temperature, relative humidity) and ink's molecular weight and functionality. The optimization of the process parameters led to the realization of high quality and density nanoarrays on plastics.

Rehme correlation for spacer pressure drop compared to XT-ADS rod bundle simulations and water experiment

International Nuclear Information System (INIS)

Batta, A.; Class, A.; Litfin, K.; Wetzel, T.

2011-01-01

The Rehme correlation is the most common formula to estimate the pressure drop of spacers in the design phase of new bundle geometries. It is based on considerations of momentum losses and takes into account the obstruction of the flow cross section but it ignores the geometric details of the spacer design. Within the framework of accelerator driven sub-critical reactor systems (ADS), heavy-liquid-metal (HLM) cooled fuel assemblies are considered. At the KArlsruhe Liquid metal LAboratory (KALLA) of the Karlsruhe Institute of Technology a series of experiments to quantify both pressure losses and heat transfer in HLM-cooled rod bundles are performed. The present study compares simulation results obtained with the commercial CFD code Star-CCM to experiments and the Rehme correlation. It can be shown that the Rehme correlation, simulations and experiments all yield similar trends, but quantitative predictions can only be delivered by the CFD which takes into account the full geometric details of the spacer geometry. (orig.)