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Sample records for ring pmo antisense

  1. Antisense PMO found in dystrophic dog model was effective in cells from exon 7-deleted DMD patient.

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    Takashi Saito

    Full Text Available BACKGROUND: Antisense oligonucleotide-induced exon skipping is a promising approach for treatment of Duchenne muscular dystrophy (DMD. We have systemically administered an antisense phosphorodiamidate morpholino oligomer (PMO targeting dystrophin exons 6 and 8 to a dog with canine X-linked muscular dystrophy in Japan (CXMD(J lacking exon 7 and achieved recovery of dystrophin in skeletal muscle. To date, however, antisense chemical compounds used in DMD animal models have not been directly applied to a DMD patient having the same type of exon deletion. We recently identified a DMD patient with an exon 7 deletion and tried direct translation of the antisense PMO used in dog models to the DMD patient's cells. METHODOLOGY/PRINCIPAL FINDINGS: We converted fibroblasts of CXMD(J and the DMD patient to myotubes by FACS-aided MyoD transduction. Antisense PMOs targeting identical regions of dog and human dystrophin exons 6 and 8 were designed. These antisense PMOs were mixed and administered as a cocktail to either dog or human cells in vitro. In the CXMD(J and human DMD cells, we observed a similar efficacy of skipping of exons 6 and 8 and a similar extent of dystrophin protein recovery. The accompanying skipping of exon 9, which did not alter the reading frame, was different between cells of these two species. CONCLUSION/SIGNIFICANCE: Antisense PMOs, the effectiveness of which has been demonstrated in a dog model, achieved multi-exon skipping of dystrophin gene on the FACS-aided MyoD-transduced fibroblasts from an exon 7-deleted DMD patient, suggesting the feasibility of systemic multi-exon skipping in humans.

  2. Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds

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    Yuchen Nan

    2018-04-01

    Full Text Available Phosphorodiamidate morpholino oligomers (PMO are short single-stranded DNA analogs that are built upon a backbone of morpholine rings connected by phosphorodiamidate linkages. As uncharged nucleic acid analogs, PMO bind to complementary sequences of target mRNA by Watson–Crick base pairing to block protein translation through steric blockade. PMO interference of viral protein translation operates independently of RNase H. Meanwhile, PMO are resistant to a variety of enzymes present in biologic fluids, a characteristic that makes them highly suitable for in vivo applications. Notably, PMO-based therapy for Duchenne muscular dystrophy (DMD has been approved by the United States Food and Drug Administration which is now a hallmark for PMO-based antisense therapy. In this review, the development history of PMO, delivery methods for improving cellular uptake of neutrally charged PMO molecules, past studies of PMO antagonism against RNA and DNA viruses, PMO target selection, and remaining questions of PMO antiviral strategies are discussed in detail and new insights are provided.

  3. PMO Delivery System Using Bubble Liposomes and Ultrasound Exposure for Duchenne Muscular Dystrophy Treatment.

    Science.gov (United States)

    Negishi, Yoichi; Ishii, Yuko; Nirasawa, Kei; Sasaki, Eri; Endo-Takahashi, Yoko; Suzuki, Ryo; Maruyama, Kazuo

    2018-01-01

    Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration, caused by nonsense or frameshift mutations in the dystrophin (DMD) gene. Antisense oligonucleotides can be used to induce specific exon skipping; recently, a phosphorodiamidate morpholino oligomer (PMO) has been approved for clinical use in DMD. However, an efficient PMO delivery strategy is required to improve the therapeutic efficacy in DMD patients. We previously developed polyethylene glycol (PEG)-modified liposomes containing ultrasound contrast gas, "Bubble liposomes" (BLs), and found that the combination of BLs with ultrasound exposure is a useful gene delivery tool. Here, we describe an efficient PMO delivery strategy using the combination of BLs and ultrasound exposure to treat muscles in a DMD mouse model (mdx). This ultrasound-mediated BL technique can increase the PMO-mediated exon-skipping efficiency, leading to significantly increased dystrophin expression. Thus, the combination of BLs and ultrasound exposure may be a feasible PMO delivery method to improve therapeutic efficacy and reduce the PMO dosage for DMD treatment.

  4. Poly(ester amine Composed of Polyethylenimine and Pluronic Enhance Delivery of Antisense Oligonucleotides In Vitro and in Dystrophic mdx Mice

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    Mingxing Wang

    2016-01-01

    Full Text Available A series of poly(esteramines (PEAs constructed from low molecular weight polyethyleneimine (LPEI and Pluronic were evaluated for the delivery of antisense oligonuclotides (AOs, 2′-O-methyl phosphorothioate RNA (2′-OMePS and phosphorodiamidate morpholino oligomer (PMO in cell culture and dystrophic mdx mice. Improved exon-skipping efficiency of both 2′-OMePS and PMO was observed in the C2C12E50 cell line with all PEA polymers compared with PEI 25k or LF-2k. The degree of efficiency was found in the order of PEA 01, PEA 04 > PEA 05 > others. The in vivo study in mdx mice demonstrated enhanced exon-skipping of 2′-OMePS with the order of PEA 06 > PEA 04, PEA 07 > PEA 03 > PEA 01 > others, and much higher than PEI 25k formulated 2′-OMePS. Exon-skipping efficiency of PMO in formulation with the PEAs were significantly enhanced in the order of PEA 02 > PEA 10 > PEA 01, PEA 03 > PEA 05, PEA 07, PEA 08 > others, with PEA 02 reaching fourfold of Endo-porter formulated PMO. PEAs improve PMO delivery more effectively than 2′-OMePS delivery in vivo, and the systemic delivery evaluation further highlight the efficiency of PEA for PMO delivery in all skeletal muscle. The results suggest that the flexibility of PEA polymers could be explored for delivery of different AO chemistries, especially for antisense therapy.

  5. Functional rescue of dystrophin-deficient mdx mice by a chimeric peptide-PMO.

    Science.gov (United States)

    Yin, Haifang; Moulton, Hong M; Betts, Corinne; Merritt, Thomas; Seow, Yiqi; Ashraf, Shirin; Wang, Qingsong; Boutilier, Jordan; Wood, Matthew Ja

    2010-10-01

    Splice modulation using antisense oligonucleotides (AOs) has been shown to yield targeted exon exclusion to restore the open reading frame and generate truncated but partially functional dystrophin protein. This has been successfully demonstrated in dystrophin-deficient mdx mice and in Duchenne muscular dystrophy (DMD) patients. However, DMD is a systemic disease; successful therapeutic exploitation of this approach will therefore depend on effective systemic delivery of AOs to all affected tissues. We have previously shown the potential of a muscle-specific/arginine-rich chimeric peptide-phosphorodiamidate morpholino (PMO) conjugate, but its long-term activity, optimized dosing regimen, capacity for functional correction and safety profile remain to be established. Here, we report the results of this chimeric peptide-PMO conjugate in the mdx mouse using low doses (3 and 6 mg/kg) administered via a 6 biweekly systemic intravenous injection protocol. We show 100% dystrophin-positive fibers and near complete correction of the dystrophin transcript defect in all peripheral muscle groups, with restoration of 50% dystrophin protein over 12 weeks, leading to correction of the DMD pathological phenotype and restoration of muscle function in the absence of detectable toxicity or immune response. Chimeric muscle-specific/cell-penetrating peptides therefore represent highly promising agents for systemic delivery of splice-correcting PMO oligomers for DMD therapy.

  6. Chemical modifications of antisense morpholino oligomers enhance their efficacy against Ebola virus infection.

    Science.gov (United States)

    Swenson, Dana L; Warfield, Kelly L; Warren, Travis K; Lovejoy, Candace; Hassinger, Jed N; Ruthel, Gordon; Blouch, Robert E; Moulton, Hong M; Weller, Dwight D; Iversen, Patrick L; Bavari, Sina

    2009-05-01

    Phosphorodiamidate morpholino oligomers (PMOs) are uncharged nucleic acid-like molecules designed to inactivate the expression of specific genes via the antisense-based steric hindrance of mRNA translation. PMOs have been successful at knocking out viral gene expression and replication in the case of acute viral infections in animal models and have been well tolerated in human clinical trials. We propose that antisense PMOs represent a promising class of therapeutic agents that may be useful for combating filoviral infections. We have previously shown that mice treated with a PMO whose sequence is complementary to a region spanning the start codon of VP24 mRNA were protected against lethal Ebola virus challenge. In the present study, we report on the abilities of two additional VP24-specific PMOs to reduce the cell-free translation of a VP24 reporter, to inhibit the in vitro replication of Ebola virus, and to protect mice against lethal challenge when the PMOs are delivered prior to infection. Additionally, structure-activity relationship evaluations were conducted to assess the enhancement of antiviral efficacy associated with PMO chemical modifications that included conjugation with peptides of various lengths and compositions, positioning of conjugated peptides to either the 5' or the 3' terminus, and the conferring of charge modifications by the addition of piperazine moieties. Conjugation with arginine-rich peptides greatly enhanced the antiviral efficacy of VP24-specific PMOs in infected cells and mice during lethal Ebola virus challenge.

  7. Translational inhibition of CTX M extended spectrum β-lactamase in clinical strains of Escherichia coli by synthetic antisense oligonucleotides partially restores sensitivity to cefotaxime.

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    John Benedict Readman

    2016-03-01

    Full Text Available Synthetic antisense oligomers are DNA mimics that can specifically inhibit gene expression at the translational level by ribosomal steric hindrance. They bind to their mRNA targets by Watson Crick base pairing and are resistant to degradation by both nucleases and proteases. A 25 mer phosphorodiamidate morpholino oligomer (PMO and a 13 mer polyamide (peptide nucleic acid (PNA were designed to target mRNA (positions -4 to +21, and –17 to –5 respectively close to the translational initiation site of the extended spectrum β lactamase resistance genes of CTX M group 1. These antisense oligonucleotides were found to inhibit β lactamase activity by up to 96% in a cell free translation transcription coupled system using an expression vector carrying a blaCTX-M-15 gene cloned from a clinical isolate. Despite evidence for up regulation of CTX-M gene expression, they were both found to significantly restore sensitivity to cefotaxime in E. coli AS19, an atypical cell wall permeable mutant, in a dose dependant manner (0 - 40 nM. The PMO and PNA were covalently bound to the cell penetrating peptide (KFF3K and both significantly (P<0.05 increased sensitivity to cefotaxime in a dose dependent manner (0 - 40 nM in field isolates harbouring CTX-M group 1 β-lactamases. Antisense oligonucleotides targeted to the translational initiation site and Shine Dalgarno region of blaCTX-M-15 inhibited gene expression, and when conjugated to a cell penetrating delivery vehicle, partially restored antibiotic sensitivity to both field and clinical isolates.

  8. Biomolecules Electrochemical Sensing Properties of a PMo11V@N-Doped Few Layer Graphene Nanocomposite

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    Diana M. Fernandes

    2015-05-01

    Full Text Available A novel hybrid nanocomposite, PMo11V@N-doped few layer graphene, was prepared by a one-step protocol through direct immobilization of the tetrabutylammonium salt of a vanadium-substituted phosphomolybdate (PMo11V onto N-doped few layer graphene (N-FLG. The nanocomposite characterization by FTIR and XPS confirmed its successful synthesis. Glassy carbon modified electrodes with PMo11V and PMo11V@N-FLG showed cyclic voltammograms consistent with surface-confined redox processes attributed to Mo-centred reductions (MoVI→MoV and a vanadium reduction (VV→VIV. Furthermore, PMo11V@N-FLG modified electrodes showed good stability and well-resolved redox peaks with high current intensities. The observed enhancement of PMo11V electrochemical properties is a consequence of a strong electronic communication between the POM and the N-doped few layer graphene. Additionally, the electro-catalytic and sensing properties towards acetaminophen (AC and theophylline (TP were evaluated by voltammetric techniques using a glassy carbon electrode modified with PMo11V@N-FLG. Under the conditions used, the square wave voltammetric peak current increased linearly with AC concentration in the presence of TP, but showing two linear ranges: 1.2 × 10−6 to 1.2 × 10−4 and 1.2 × 10−4 to 4.8 × 10−4 mol dm−3, with different AC sensitivity values, 0.022 A/mol dm−3 and 0.035 A/mol dm−3, respectively (detection limit, DL = 7.5 × 10−7 mol dm−3.

  9. Oxidative desulfurization of diesel by potato based-carbon as green support for H5PMo10V2O40: Efficient composite nanorod catalyst

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    Ezzat Rafiee

    2017-07-01

    Full Text Available The C@POM (carbon@polyoxometalate containing H3PMo12O40 (PMo12, H5PMo10V2O40 (PMo10V2, H6PMo9V3O40 (PMo9V3, H7PMo8V4O40 (PMo8V4, H3PW12O40 (PW, and H4SiW12O40 (SiW were prepared from natural potato as green, and cheap catalyst support source. The C@PMo10V2 was found to be a unique, effective, and eco-friendly catalyst for selective oxidation of sulfides, using 30% aq. H2O2. C@PMo10V2 composite was characterized by X-ray diffraction spectroscopy (XRD, energy dispersive X-ray spectroscopy (EDX, scanning electron microscopy (SEM, thermal gravimetric analysis (TGA, Fourier transform infrared (FT-IR spectrophotometry, zeta sizer, and zeta potential. The XRD results show that during immobilization PMo10V2 on the carbon catalyst support (CCS, the crystallite structure of PMo10V2 and CCS was not changed. The SEM results show that PMo10V2 crystals deposited on the surface CCS rods as composite nanorod structure. A variety of sulfides, sulfur-containing model and real oil were oxidized with the C@PMo10V2/H2O2 at room temperature. Recovered catalyst show excellent activity for at least four repeating cycles.

  10. 49 CFR 633.13 - Initiation of PMO services.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Initiation of PMO services. 633.13 Section 633.13 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION... engineering phase of the project. However, consistent with other provisions in this part, the Administrator...

  11. Sandy PMO Disaster Relief Appropriations Act of 2013 Financial Data

    Data.gov (United States)

    Department of Homeland Security — Sandy PMO: Disaster Relief Appropriations Act of 2013 (Sandy Supplemental Bill) Financial Data. This is the Sandy Supplemental Quarterly Financial Datasets that are...

  12. Facile Electrodeposition of Flower-Like PMo12-Pt/rGO Composite with Enhanced Electrocatalytic Activity towards Methanol Oxidation

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    Xiaoying Wang

    2015-07-01

    Full Text Available A facile, rapid and green method based on potentiostatic electrodeposition is developed to synthesize a novel H3PMo12O40-Pt/reduced graphene oxide (denoted as PMo12-Pt/rGO composite. The as-prepared PMo12-Pt/rGO is characterized by X-ray diffraction (XRD, scanning electron microscopy (SEM and X-ray photoelectron spectroscopy (XPS. The results reveal that graphene oxide (GO is reduced to the rGO by electrochemical method and POMs clusters are successfully located on the rGO as the modifier. Furthermore, the PMo12-Pt/rGO composite shows higher electrocatalytic activity, better tolerance towards CO and better stability than the conventional pure Pt catalyst.

  13. Directional gene expression and antisense transcripts in sexual and asexual stages of Plasmodium falciparum

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    López-Barragán María J

    2011-11-01

    Full Text Available Abstract Background It has been shown that nearly a quarter of the initial predicted gene models in the Plasmodium falciparum genome contain errors. Although there have been efforts to obtain complete cDNA sequences to correct the errors, the coverage of cDNA sequences on the predicted genes is still incomplete, and many gene models for those expressed in sexual or mosquito stages have not been validated. Antisense transcripts have widely been reported in P. falciparum; however, the extent and pattern of antisense transcripts in different developmental stages remain largely unknown. Results We have sequenced seven bidirectional libraries from ring, early and late trophozoite, schizont, gametocyte II, gametocyte V, and ookinete, and four strand-specific libraries from late trophozoite, schizont, gametocyte II, and gametocyte V of the 3D7 parasites. Alignment of the cDNA sequences to the 3D7 reference genome revealed stage-specific antisense transcripts and novel intron-exon splicing junctions. Sequencing of strand-specific cDNA libraries suggested that more genes are expressed in one direction in gametocyte than in schizont. Alternatively spliced genes, antisense transcripts, and stage-specific expressed genes were also characterized. Conclusions It is necessary to continue to sequence cDNA from different developmental stages, particularly those of non-erythrocytic stages. The presence of antisense transcripts in some gametocyte and ookinete genes suggests that these antisense RNA may play an important role in gene expression regulation and parasite development. Future gene expression studies should make use of directional cDNA libraries. Antisense transcripts may partly explain the observed discrepancy between levels of mRNA and protein expression.

  14. study on the serum levels of E2, IL-6 and IGF-I in patients with post-menopausal osteoporosis (PMO)

    International Nuclear Information System (INIS)

    Lv Kuan; Liu Chunyu; Lu Yingju

    2006-01-01

    Objective: To study the changes of serum levels of E 2 , IL-6, IGF-I in patients with post-menopausal osteoporosis (PMO). Methods: Serum levels of E 2 (with CLIA), IL-6, IGF-I, BGP (with RIA) were measured in the following subjects: (1) 32 patients with PMO (2) 32 post-menopausal women without PMO and (3) 30 pre-menopausal controls. Serum P, Ca and AKP levels were also determined. Results: As a whole, serum levels of IL -6 in postmenopausal women were higher than those in controls. Levels in subjects with PMO were significantly higher than those without PMO (P 2 and BMD index (r=-0. 587, - 0. 438 respectively, P 2 and BMD index (r=0.569, 0.433 respectively, P 2 levels will in someway promote the expression of IL-6 ( osteoclastic) and reduce the expression of IGF-I (osteoclastic), resulting in lessening of bone mass. HRT, despite of the controversy over cardio-vascalar safety, is beneficial for osteoporosis. (authors)

  15. 41 CFR 128-1.5006-2 - Property management officer (PMO).

    Science.gov (United States)

    2010-07-01

    ... leadership, guidance, and operating procedures for personal property management functions. (b) Ensuring... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Property management officer (PMO). 128-1.5006-2 Section 128-1.5006-2 Public Contracts and Property Management Federal Property...

  16. Identification of a Peptide for Systemic Brain Delivery of a Morpholino Oligonucleotide in Mouse Models of Spinal Muscular Atrophy

    Science.gov (United States)

    Shabanpoor, Fazel; Hammond, Suzan M; Abendroth, Frank; Hazell, Gareth; Wood, Matthew J.A.

    2017-01-01

    Splice-switching antisense oligonucleotides are emerging treatments for neuromuscular diseases, with several splice-switching oligonucleotides (SSOs) currently undergoing clinical trials such as for Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA). However, the development of systemically delivered antisense therapeutics has been hampered by poor tissue penetration and cellular uptake, including crossing of the blood–brain barrier (BBB) to reach targets in the central nervous system (CNS). For SMA application, we have investigated the ability of various BBB-crossing peptides for CNS delivery of a splice-switching phosphorodiamidate morpholino oligonucleotide (PMO) targeting survival motor neuron 2 (SMN2) exon 7 inclusion. We identified a branched derivative of the well-known ApoE (141–150) peptide, which as a PMO conjugate was capable of exon inclusion in the CNS following systemic administration, leading to an increase in the level of full-length SMN2 transcript. Treatment of newborn SMA mice with this peptide-PMO (P-PMO) conjugate resulted in a significant increase in the average lifespan and gains in weight, muscle strength, and righting reflexes. Systemic treatment of adult SMA mice with this newly identified P-PMO also resulted in small but significant increases in the levels of SMN2 pre-messenger RNA (mRNA) exon inclusion in the CNS and peripheral tissues. This work provides proof of principle for the ability to select new peptide paradigms to enhance CNS delivery and activity of a PMO SSO through use of a peptide-based delivery platform for the treatment of SMA potentially extending to other neuromuscular and neurodegenerative diseases. PMID:28118087

  17. Identification of sequence motifs significantly associated with antisense activity

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    Peek Andrew S

    2007-06-01

    Full Text Available Abstract Background Predicting the suppression activity of antisense oligonucleotide sequences is the main goal of the rational design of nucleic acids. To create an effective predictive model, it is important to know what properties of an oligonucleotide sequence associate significantly with antisense activity. Also, for the model to be efficient we must know what properties do not associate significantly and can be omitted from the model. This paper will discuss the results of a randomization procedure to find motifs that associate significantly with either high or low antisense suppression activity, analysis of their properties, as well as the results of support vector machine modelling using these significant motifs as features. Results We discovered 155 motifs that associate significantly with high antisense suppression activity and 202 motifs that associate significantly with low suppression activity. The motifs range in length from 2 to 5 bases, contain several motifs that have been previously discovered as associating highly with antisense activity, and have thermodynamic properties consistent with previous work associating thermodynamic properties of sequences with their antisense activity. Statistical analysis revealed no correlation between a motif's position within an antisense sequence and that sequences antisense activity. Also, many significant motifs existed as subwords of other significant motifs. Support vector regression experiments indicated that the feature set of significant motifs increased correlation compared to all possible motifs as well as several subsets of the significant motifs. Conclusion The thermodynamic properties of the significantly associated motifs support existing data correlating the thermodynamic properties of the antisense oligonucleotide with antisense efficiency, reinforcing our hypothesis that antisense suppression is strongly associated with probe/target thermodynamics, as there are no enzymatic

  18. Preparation and characterization of Keggin-type heteropolysalts, CoxPMo12O40 (x = 0–1.5

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    Mazari T.

    2013-09-01

    Full Text Available Polyoxometalates (POMs, based transition-metal oxide clusters, have received much attention in various fields such as catalysis, photochemistry, nonlinear optics, biology and medicine [1]. Their physico-chemical, acidic and oxidative properties can be adjusted according with the nature of constituent elements [2]. In the field of catalysis, the most studied POMs are those with the Keggin. They were tested in wide variety of reactions in homogeneous and heterogeneous phases. In the redox processes, the nature of counter- cation in the [PMo12O40]3− system can play a significant role. Thus, it has been shown that using Fe(III, vanadyl(VO2+, antimony (Sb3+ or cobalt (Co2+ counter-cation develop a more favourable distribution of both reduced Mo(V and oxidized Mo(VI sites [3]. In the present work we report the synthesis and characterization using several techniques of Keggin-type heteropolysalts of composition H3−2xCoxPMo12O40(x = 0 − 1.5 denoted as CoxPMo12.

  19. Polyethylenimine-modified Pluronics (PCMs) Improve Morpholino Oligomer Delivery in Cell Culture and Dystrophic mdx Mice

    OpenAIRE

    Wang, Mingxing; Wu, Bo; Lu, Peijuan; Cloer, Caryn; Tucker, Jay D; Lu, Qilong

    2012-01-01

    We investigated a series of small-sized polyethylenimine (PEI, 0.8/1.2 k)-conjugated pluronic copolymers (PCMs) for their potential to enhance delivery of an antisense phosphorodiamidate morpholino oligomer (PMO) in vitro and in dystrophic mdx mice. PCM polymers containing pluronics of molecular weight (Mw) ranging 2–6 k, with hydrophilic-lipophilic balance (HLB) 7–23, significantly enhanced PMO-induced exon-skipping in a green fluorescent protein (GFP) reporter-based myoblast culture system....

  20. Pyrrole PMOs, incorporating new N-heterocyclic compounds on an ethene-PMO through Diels–Alder reactions

    International Nuclear Information System (INIS)

    Esquivel, Dolores; De Canck, Els; Jiménez-Sanchidrián, César; Romero-Salguero, Francisco J.; Van Der Voort, Pascal

    2014-01-01

    The ethenylene bridges on the walls of an ethenylene-bridged periodic mesoporous organosilica were successfully modified with a variety of pyrrole derivatives – pyrrole, methylpyrrole, dimethylpyrrole, trimethylpyrrole and 1-phenylpyrrole – through Diels–Alder reactions. X-ray diffraction measurements and N 2 adsorption–desorption analysis confirmed the preservation of the ordering and mesoporosity of the parent material as well as the decoration of the pores with the surface Diels–Alder adducts. Moreover, other techniques such as DRIFT, 13 C and 29 Si nuclear magnetic resonances revealed the formation of the surface N-heterocyclic compounds at the parent ethenylene sites. - Highlights: • Chemical modification of the double bonds on an ethene-PMO through the Diels–Alder reaction. • A family of pyrrole derivatives act as dienes in the Diels–Alder reaction. • Well-ordering and mesoporosity are retained after the post-functionalization. • N-containing compounds on the surface of ethene-PMO are present after the Diels–Alder reaction

  1. Pyrrole PMOs, incorporating new N-heterocyclic compounds on an ethene-PMO through Diels–Alder reactions

    Energy Technology Data Exchange (ETDEWEB)

    Esquivel, Dolores; De Canck, Els [Center for Ordered Materials, Organometallics and Catalysis, Department of Inorganic and Physical Chemistry, Ghent University, Krijgslaan 281-S3, 9000 Ghent (Belgium); Jiménez-Sanchidrián, César [Department of Organic Chemistry, Nanochemistry and Fine Chemistry Research Institute (IUIQFN), Faculty of Sciences, University of Córdoba, Campus de Rabanales, Marie Curie Building, Ctra. Nnal. IV, km 396, 14071 Córdoba (Spain); Romero-Salguero, Francisco J., E-mail: qo2rosaf@uco.es [Department of Organic Chemistry, Nanochemistry and Fine Chemistry Research Institute (IUIQFN), Faculty of Sciences, University of Córdoba, Campus de Rabanales, Marie Curie Building, Ctra. Nnal. IV, km 396, 14071 Córdoba (Spain); Van Der Voort, Pascal, E-mail: pascal.vandervoort@ugent.be [Center for Ordered Materials, Organometallics and Catalysis, Department of Inorganic and Physical Chemistry, Ghent University, Krijgslaan 281-S3, 9000 Ghent (Belgium)

    2014-11-14

    The ethenylene bridges on the walls of an ethenylene-bridged periodic mesoporous organosilica were successfully modified with a variety of pyrrole derivatives – pyrrole, methylpyrrole, dimethylpyrrole, trimethylpyrrole and 1-phenylpyrrole – through Diels–Alder reactions. X-ray diffraction measurements and N{sub 2} adsorption–desorption analysis confirmed the preservation of the ordering and mesoporosity of the parent material as well as the decoration of the pores with the surface Diels–Alder adducts. Moreover, other techniques such as DRIFT, {sup 13}C and {sup 29}Si nuclear magnetic resonances revealed the formation of the surface N-heterocyclic compounds at the parent ethenylene sites. - Highlights: • Chemical modification of the double bonds on an ethene-PMO through the Diels–Alder reaction. • A family of pyrrole derivatives act as dienes in the Diels–Alder reaction. • Well-ordering and mesoporosity are retained after the post-functionalization. • N-containing compounds on the surface of ethene-PMO are present after the Diels–Alder reaction.

  2. Efficient removal of H2S at high temperature using the ionic liquid solutions of [C4mim]3PMo12O40-An organic polyoxometalate.

    Science.gov (United States)

    Ma, Yunqian; Liu, Xinpeng; Wang, Rui

    2017-06-05

    An innovative approach to H 2 S capture and sulfur recovery via liquid redox at high temperature has been developed using [C 4 mim] 3 PMo 12 O 40 at temperatures ranging from 80 to 180°C, which is superior to the conventional water-based system with an upper limit of working temperature normally below 60°C. The ionic liquids used as solvents include [C 4 mim]Cl, [C 4 mim]BF 4 , [C 4 mim]PF 6 and [C 4 mim]NTf 2 . Microscopic observation and turbidity measurement were used to investigate the dissolution of [C 4 mim] 3 PMo 12 O 40 in the ionic liquids. Stabilization energy between H 2 S and the anion of ionic liquid as well as H 2 O was calculated to illustrate the interaction between H 2 S and the solvents. The cavity theory can be adopted to illustrate the mechanism for H 2 S absorption: the Cl - ion with small radius can be incorporated into the cavities of [C 4 mim] 3 PMo 12 O 40 , and interact with H 2 S strongly. The underlying mechanism for sulfur formation is the redox reaction between H 2 S and PMo 12 O 40 3- . H 2 S can be oxidized to elemental sulfur and Mo 6+ is partly reduced during absorption, according to UV-vis and FTIR spectra. The [C 4 mim] 3 PMo 12 O 40 -[C 4 mim]Cl after reaction can be readily regenerated by air and thus enabling its efficient and repeatitive use. The absorbent of [C 4 mim] 3 PMo 12 O 40 -ionic liquid system provides a new approach for wet oxidation desulfurization at high temperature. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Antisense downregulation of mutant huntingtin in a cell model

    DEFF Research Database (Denmark)

    Hasholt, L.; Abell, K.; Norremolle, A.

    2003-01-01

    or by addition to the culture medium. Results Expression of the fusion protein containing the mutant huntingtin fragment resulted in diffuse green fluorescence in the cytoplasm and formation of aggregates in some of the NT2 cells and NT2-N neurons. We obtained antisense sequence-specific inhibition of expression...... of the fusion protein and/or suppression of the aggregate formation in both cell types. In the NT2 cells the antisense effect was dependent on the way of administration of the oligo. Conclusions The PS-antisense oligo is effective in downregulation of mutant huntingtin, and the reduction of aggregate formation...... is a sensitive biological marker. The findings suggest that antisense knockdown of huntingtin could be a useful strategy for treatment of HD, and could also be suitable for studies of the normal and pathological function of huntingtin in different cellular model systems....

  4. Peptide nucleic acid (PNA) antisense effects in Escherichia coli

    DEFF Research Database (Denmark)

    Good, L; Nielsen, P E

    1999-01-01

    Antisense peptide nucleic acid (PNA) can be used to control cell growth, gene expression and growth phenotypes in the bacteria Escherichia coli. PNAs targeted to the RNA components of the ribosome can inhibit translation and cell growth, and PNAs targeted to mRNA can limit gene expression with gene...... and sequence specificity. In an E. coli cell extract, efficient inhibition is observed when using PNA concentrations in the nanomolar range, whereas micromolar concentrations are required for inhibition in growing cells. A mutant strain of E. coli that is more permeable to antibiotics also is more susceptible...... to antisense PNAs than the wild type. This chapter details methods for testing the antisense activities of PNA in E. coli. As an example of the specific antisense inhibition possible, we show the effects of an anti-beta-galactosidase PNA in comparison to control PNAs. With improvements in cell uptake...

  5. Advancements of antisense oligonucleotides in treatment of breast cancer

    Institute of Scientific and Technical Information of China (English)

    YANGShuan-Ping; SONGSan-Tai; 等

    2003-01-01

    Breast cancer is one kind of multi-gene related malignancy.Overexpression of some oncogenes such as HER-2(c-erbB-2,Neu),bcl-2/bcl-xL,protein kinase A(PKA),and transferrin receptor gene(TfR gene),etc significantly affect the prognosis of breast cancer.It was shown that specific suppression of the overexpressed genes above resulted in the improvement of the therapy of breast cancer.Antisense interference.one of useful tools for inhibiting the overexpression of specific oncogenes,was involved in the therapy of breast cancer in recent years. Data indicated that antisense oligonucleotides(ON)could inhibit specially the expression of the target genes on mRNA or protein levels in most of cases;some ON candidates showed encouraging therapeutic effects in vitro and in vivo on breast cancer cell lines or xenografts.Furthermore,the combination use of the antisense ON and normal chemotherapeutic agents indicated synergistic antitumor effects,which was probably the best utilization of antisense ON in the treatment of breast cancer.

  6. Downstream Antisense Transcription Predicts Genomic Features That Define the Specific Chromatin Environment at Mammalian Promoters.

    Directory of Open Access Journals (Sweden)

    Christopher A Lavender

    2016-08-01

    Full Text Available Antisense transcription is a prevalent feature at mammalian promoters. Previous studies have primarily focused on antisense transcription initiating upstream of genes. Here, we characterize promoter-proximal antisense transcription downstream of gene transcription starts sites in human breast cancer cells, investigating the genomic context of downstream antisense transcription. We find extensive correlations between antisense transcription and features associated with the chromatin environment at gene promoters. Antisense transcription downstream of promoters is widespread, with antisense transcription initiation observed within 2 kb of 28% of gene transcription start sites. Antisense transcription initiates between nucleosomes regularly positioned downstream of these promoters. The nucleosomes between gene and downstream antisense transcription start sites carry histone modifications associated with active promoters, such as H3K4me3 and H3K27ac. This region is bound by chromatin remodeling and histone modifying complexes including SWI/SNF subunits and HDACs, suggesting that antisense transcription or resulting RNA transcripts contribute to the creation and maintenance of a promoter-associated chromatin environment. Downstream antisense transcription overlays additional regulatory features, such as transcription factor binding, DNA accessibility, and the downstream edge of promoter-associated CpG islands. These features suggest an important role for antisense transcription in the regulation of gene expression and the maintenance of a promoter-associated chromatin environment.

  7. Antiviral effects of herpes simplex virus specific anti-sense nucleic acids.

    Science.gov (United States)

    Cantin, E M; Podsakoff, G; Willey, D E; Openshaw, H

    1992-01-01

    We have targeted mRNA sequences encompassing the translation initiation codon of the essential herpes simplex virus type 1 (HSV-1) IE3 gene with three kinds of anti-sense molecule. Addition of a 15mer oligodeoxyribonucleoside methylphosphonate to tissue culture cells resulted in suppression of viral replication. HSV-1 replication was also inhibited in cultured cells containing anti-sense vectors expressing transcripts complementary to the IE3 mRNA. We have also constructed a ribozyme which upon base pairing with the target IE3 mRNA induces cleavage at the predicted GUC site. A major obstacle to anti-sense studies in animals is drug delivery of preformed antisense molecules to ganglionic neurons, the site of HSV latency and reactivation. We speculate as to how this may be accomplished through carrier compounds which are taken up by nerve terminals and transported by retrograde axoplasmic flow. By the same route, HSV itself may be used as an anti-sense vector.

  8. Antisense Treatments for Biothreat Agents

    National Research Council Canada - National Science Library

    Warfield, Kelly L; Panchal, Rekha G; Aman, M J; Bavari, Sina

    2006-01-01

    ... a variety of pathogens in cell culture studies and nonhuman primate models of infection. For these reasons, antisense technologies are being pursued as treatments against biothreat agents such as Ebola virus, dengue virus and Bacillus anthracis...

  9. Research and Grant Management: The Role of the Project Management Office (PMO) in a European Research Consortium Context

    Science.gov (United States)

    Wedekind, Gerben Kristian; Philbin, Simon Patrick

    2018-01-01

    This paper illustrates how a university-based project management office (PMO) can provide focused support across the entire grant project lifecycle within a European research context. In recent years, EU (European Union) research and innovation grant programs have increasingly shifted to support multidisciplinary consortia composed of industry,…

  10. Dyslipidemia, sense, antisense or nonsense?

    NARCIS (Netherlands)

    Visser, M.E.

    2011-01-01

    Maartje Visser onderzocht het remmen van de synthese van apoB met behulp van antisense - een nieuwe farmacologische techniek. Dit blijkt het slechte LDL-cholesterol op een effectieve manier te verlagen. Bij sommige proefpersonen resulteerde dit in leververvetting. Of dit op de lange termijn

  11. Identification of antisense long noncoding RNAs that function as SINEUPs in human cells.

    Science.gov (United States)

    Schein, Aleks; Zucchelli, Silvia; Kauppinen, Sakari; Gustincich, Stefano; Carninci, Piero

    2016-09-20

    Mammalian genomes encode numerous natural antisense long noncoding RNAs (lncRNAs) that regulate gene expression. Recently, an antisense lncRNA to mouse Ubiquitin carboxyl-terminal hydrolase L1 (Uchl1) was reported to increase UCHL1 protein synthesis, representing a new functional class of lncRNAs, designated as SINEUPs, for SINE element-containing translation UP-regulators. Here, we show that an antisense lncRNA to the human protein phosphatase 1 regulatory subunit 12A (PPP1R12A), named as R12A-AS1, which overlaps with the 5' UTR and first coding exon of the PPP1R12A mRNA, functions as a SINEUP, increasing PPP1R12A protein translation in human cells. The SINEUP activity depends on the aforementioned sense-antisense interaction and a free right Alu monomer repeat element at the 3' end of R12A-AS1. In addition, we identify another human antisense lncRNA with SINEUP activity. Our results demonstrate for the first time that human natural antisense lncRNAs can up-regulate protein translation, suggesting that endogenous SINEUPs may be widespread and present in many mammalian species.

  12. Scintigraphic imaging of oncogenes with antisense probes: does it make sense?

    International Nuclear Information System (INIS)

    Urbain, J.L.C.; Shore, S.K.; Vekemans, M.C.; Cosenza, S.C.; DeRiel, K.; Patel, G.V.; Charkes, N.D.; Malmud, L.S.; Reddy, E.P.

    1995-01-01

    The aim of this study was to demonstrate that cells which are expressing a particular mRNA transcript do preferentially and specifically retain the antisense probe targeting that mRNA. Using a mouse plasmacytoma cell line (MOPC315) which produces high levels of IgA heavy chain mRNA, a control mouse pre B cell line (7OZ/3B), a human mammary cell line (MCF7) which expresses the erbB2 or neu oncogene, MOPC315 cells as neu-negative controls, and antisense DNA oligonucleotides complementary to the 5' region of the mRNAs and the sense sequence, we have shown that there is a preferential, specific retention of the IgA and neu antisense sequence in MOPC315 and MCF7 cells, respectively. We have further demonstrated that this retention is time and concentration dependent with a maximum at 24 h. We conclude that cancer cells which express a particular oncogene are suitable targets for radiolabeled antisense deoxyoligonucleotides directed toward the oncogene transcript. (orig.)

  13. Bcl-2 antisense therapy in B-cell malignancies.

    Science.gov (United States)

    Chanan-Khan, Asher

    2005-07-01

    Bcl-2 is an apoptosis regulating protein, overexpression of which is associated with chemotherapy resistant disease, aggressive clinical course, and poor survival in patients with B-cell lymphoproliferative disorders. Overexpression of Bcl-2 protein results in an aberrant intrinsic apoptotic pathway that confers a protective effect on malignant cells against a death signal (e.g., chemotherapy or radiotherapy). Downregulation of this oncoprotein, thus, represents a possible new way to target clinically aggressive disease. Preclinical studies have shown that this oncoprotein can be effectively decreased by Bcl-2 antisense in malignant lymphoid cells and can reverse chemotherapy resistance, as well as enhance the anti-apoptotic potential of both chemotherapeutic and biologic agents. Ongoing clinical trials are exploring the role of Bcl-2 downregulation with oblimersen (Bcl-2 antisense) in patients with non-Hodgkin's lymphoma, chronic lymphocytic leukemia and multiple myeloma. Early results from these studies are promising and support the proof of the principle. As these studies are completed and mature data emerges, the role of Bcl-2 antisense therapy in the treatment of B-cell malignancies will become clearer.

  14. Down-regulation of Survivin by Antisense Oligonucleotides Increases Apoptosis, Inhibits Cytokinesis and Anchorage-Independent Growth

    Directory of Open Access Journals (Sweden)

    Jun Chen

    2000-05-01

    Full Text Available Survivin, a member of the inhibitor of apoptosis protein (IAP family, is detected in most common human cancers but not in adjacent normal cells. Previous studies suggest that survivin associates with the mitotic spindle and directly inhibits caspase activity. To further investigate the function of survivin, we used a survivin antisense (AS oligonucleotide to downregulate survivin expression in normal and cancer cells. We found that inhibition of survivin expression increased apoptosis and polyploidy while decreasing colony formation in soft agar. Immunohistochemistry showed that cells without survivin can initiate the cleavage furrow and contractile ring, but cannot complete cytokinesis, thus resulting in multinucleated cells. These findings indicate that survivin plays important roles in a late stage of cytokinesis, as well as in apoptosis.

  15. Developmental transitions in Arabidopsis are regulated by antisense RNAs resulting from bidirectionally transcribed genes.

    Science.gov (United States)

    Krzyczmonik, Katarzyna; Wroblewska-Swiniarska, Agata; Swiezewski, Szymon

    2017-07-03

    Transcription terminators are DNA elements located at the 3' end of genes that ensure efficient cleavage of nascent RNA generating the 3' end of mRNA, as well as facilitating disengagement of elongating DNA-dependent RNA polymerase II. Surprisingly, terminators are also a potent source of antisense transcription. We have recently described an Arabidopsis antisense transcript originating from the 3' end of a master regulator of Arabidopsis thaliana seed dormancy DOG1. In this review, we discuss the broader implications of our discovery in light of recent developments in yeast and Arabidopsis. We show that, surprisingly, the key features of terminators that give rise to antisense transcription are preserved between Arabidopsis and yeast, suggesting a conserved mechanism. We also compare our discovery to known antisense-based regulatory mechanisms, highlighting the link between antisense-based gene expression regulation and major developmental transitions in plants.

  16. 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

  17. Large-scale analysis of antisense transcription in wheat using the Affymetrix GeneChip Wheat Genome Array

    Directory of Open Access Journals (Sweden)

    Settles Matthew L

    2009-05-01

    Full Text Available Abstract Background Natural antisense transcripts (NATs are transcripts of the opposite DNA strand to the sense-strand either at the same locus (cis-encoded or a different locus (trans-encoded. They can affect gene expression at multiple stages including transcription, RNA processing and transport, and translation. NATs give rise to sense-antisense transcript pairs and the number of these identified has escalated greatly with the availability of DNA sequencing resources and public databases. Traditionally, NATs were identified by the alignment of full-length cDNAs or expressed sequence tags to genome sequences, but an alternative method for large-scale detection of sense-antisense transcript pairs involves the use of microarrays. In this study we developed a novel protocol to assay sense- and antisense-strand transcription on the 55 K Affymetrix GeneChip Wheat Genome Array, which is a 3' in vitro transcription (3'IVT expression array. We selected five different tissue types for assay to enable maximum discovery, and used the 'Chinese Spring' wheat genotype because most of the wheat GeneChip probe sequences were based on its genomic sequence. This study is the first report of using a 3'IVT expression array to discover the expression of natural sense-antisense transcript pairs, and may be considered as proof-of-concept. Results By using alternative target preparation schemes, both the sense- and antisense-strand derived transcripts were labeled and hybridized to the Wheat GeneChip. Quality assurance verified that successful hybridization did occur in the antisense-strand assay. A stringent threshold for positive hybridization was applied, which resulted in the identification of 110 sense-antisense transcript pairs, as well as 80 potentially antisense-specific transcripts. Strand-specific RT-PCR validated the microarray observations, and showed that antisense transcription is likely to be tissue specific. For the annotated sense-antisense

  18. Human Immunodeficiency Virus-Type 1 LTR DNA contains an intrinsic gene producing antisense RNA and protein products

    Directory of Open Access Journals (Sweden)

    Hsiao Chiu-Bin

    2006-11-01

    Full Text Available Abstract Background While viruses have long been shown to capitalize on their limited genomic size by utilizing both strands of DNA or complementary DNA/RNA intermediates to code for viral proteins, it has been assumed that human retroviruses have all their major proteins translated only from the plus or sense strand of RNA, despite their requirement for a dsDNA proviral intermediate. Several studies, however, have suggested the presence of antisense transcription for both HIV-1 and HTLV-1. More recently an antisense transcript responsible for the HTLV-1 bZIP factor (HBZ protein has been described. In this study we investigated the possibility of an antisense gene contained within the human immunodeficiency virus type 1 (HIV-1 long terminal repeat (LTR. Results Inspection of published sequences revealed a potential transcription initiator element (INR situated downstream of, and in reverse orientation to, the usual HIV-1 promoter and transcription start site. This antisense initiator (HIVaINR suggested the possibility of an antisense gene responsible for RNA and protein production. We show that antisense transcripts are generated, in vitro and in vivo, originating from the TAR DNA of the HIV-1 LTR. To test the possibility that protein(s could be translated from this novel HIV-1 antisense RNA, recombinant HIV antisense gene-FLAG vectors were designed. Recombinant protein(s were produced and isolated utilizing carboxy-terminal FLAG epitope (DYKDDDDK sequences. In addition, affinity-purified antisera to an internal peptide derived from the HIV antisense protein (HAP sequences identified HAPs from HIV+ human peripheral blood lymphocytes. Conclusion HIV-1 contains an antisense gene in the U3-R regions of the LTR responsible for both an antisense RNA transcript and proteins. This antisense transcript has tremendous potential for intrinsic RNA regulation because of its overlap with the beginning of all HIV-1 sense RNA transcripts by 25 nucleotides. The

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

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  20. Bcl-2 antisense therapy in B-cell malignant proliferative disorders.

    Science.gov (United States)

    Chanan-Khan, Asher; Czuczman, Myron S

    2004-08-01

    Overexpression of Bcl-2 oncogene has been clinically associated with an aggressive clinical course, chemotherapy and radiotherapy resistance, and poor survival in patients with malignant B-cell disorders. Patients with relapsed or refractory chronic lymphocytic leukemia, multiple myeloma, or non-Hodgkin's lymphoma have limited therapeutic options. Preclinical and early clinical data have shown that Bcl-2 oncoprotein can be decreased by Bcl-2 antisense therapy. Also, downregulation of Bcl-2 protein can result in reversal of chemotherapy resistance and improved antitumor activity of biologic agents. Various clinical trials are evaluating the role of targeting Bcl-2 as a mechanism to enhance the antitumor potential of chemotherapy and immunotherapy. Early results from these clinical studies are encouraging and confirm the proof of principle for antisense therapy. As current data mature, these trials will hopefully validate preliminary results and establish Bcl-2 antisense as an important addition to the current armamentarium used in the treatment of patients with B-cell neoplasms.

  1. ANALYSIS OF THE POSSIBILITY FOR ESTABLISHING PROJECT MANAGEMENT OFFICE (PMO IN COMPANIES IN SERBIA

    Directory of Open Access Journals (Sweden)

    Dragana Milin

    2012-09-01

    Full Text Available Project Management Office (PMO is an organizational unit established to help project managers, project teams and the various levels of management in carrying out the principles of project management. The research was carried out in Serbia, in 2011, with the aim to establish which methodologies and techniques are used for project m anagement, and which of them are used the most frequently. Furthermore, the need for establishment of PMOs in Serbia is discussed. These offices should help in establishing a standardized methodology (at the organization level and thus overcome the obviou s poor use of any project management methodology at all.

  2. PMO-immobilized Au(I)-NHC complexes: Heterogeneous catalysts for sustainable processes

    KAUST Repository

    van der Voort, Pascal

    2017-11-08

    A stable Periodic Mesoporous Organosilica (PMO) with accessible sulfonic acid functionalities is prepared via a one-pot-synthesis and is used as solid support for highly active catalysts, consisting of gold(I)-N-heterocyclic carbene (NHC) complexes. The gold complexes are successfully immobilized on the nanoporous hybrid material via a straightforward acid-base reaction with the corresponding [Au(OH)(NHC)] synthon. This catalyst design strategy results in a boomerang-type catalyst, allowing the active species to detach from the surface to perform the catalysis and then to recombine with the solid after all the starting material is consumed. This boomerang behavior is assessed in the hydration of alkynes. The tested catalysts were found to be active in the latter reaction, and after an acidic work-up, the IPr*-based gold catalyst can be recovered and then reused several times without any loss in efficiency

  3. Discovery and early development of AVI-7537 and AVI-7288 for the treatment of Ebola virus and Marburg virus infections.

    Science.gov (United States)

    Iversen, Patrick L; Warren, Travis K; Wells, Jay B; Garza, Nicole L; Mourich, Dan V; Welch, Lisa S; Panchal, Rekha G; Bavari, Sina

    2012-11-06

    There are no currently approved treatments for filovirus infections. In this study we report the discovery process which led to the development of antisense Phosphorodiamidate Morpholino Oligomers (PMOs) AVI-6002 (composed of AVI-7357 and AVI-7539) and AVI-6003 (composed of AVI-7287 and AVI-7288) targeting Ebola virus and Marburg virus respectively. The discovery process involved identification of optimal transcript binding sites for PMO based RNA-therapeutics followed by screening for effective viral gene target in mouse and guinea pig models utilizing adapted viral isolates. An evolution of chemical modifications were tested, beginning with simple Phosphorodiamidate Morpholino Oligomers (PMO) transitioning to cell penetrating peptide conjugated PMOs (PPMO) and ending with PMOplus containing a limited number of positively charged linkages in the PMO structure. The initial lead compounds were combinations of two agents targeting separate genes. In the final analysis, a single agent for treatment of each virus was selected, AVI-7537 targeting the VP24 gene of Ebola virus and AVI-7288 targeting NP of Marburg virus, and are now progressing into late stage clinical development as the optimal therapeutic candidates.

  4. Antisense oligodeoxynucleotide inhibition as a potent diagnostic tool for gene function in plant biology

    Energy Technology Data Exchange (ETDEWEB)

    Jansson, Christer; Sun, Chuanxin; Ghebramedhin, Haile; Hoglund, Anna-Stina; Jansson, Christer

    2008-01-15

    Antisense oligodeoxynucleotide (ODN) inhibition emerges as an effective means for probing gene function in plant cells. Employing this method we have established the importance of the SUSIBA2 transcription factor for regulation of starch synthesis in barley endosperm, and arrived at a model for the role of the SUSIBAs in sugar signaling and source-sink commutation during cereal endosperm development. In this addendum we provide additional data demonstrating the suitability of the antisense ODN technology in studies on starch branching enzyme activities in barley leaves. We also comment on the mechanism for ODN uptake in plant cells. Antisense ODNs are short (12-25 nt-long) stretches of single-stranded ODNs that hybridize to the cognate mRNA in a sequence-specific manner, thereby inhibiting gene expression. They are naturally occurring in both prokaryotes and eukaryotes where they partake in gene regulation and defense against viral infection. The mechanisms for antisense ODN inhibition are not fully understood but it is generally considered that the ODN either sterically interferes with translation or promotes transcript degradation by RNase H activation. The earliest indication of the usefulness of antisense ODN technology for the purposes of molecular biology and medical therapy was the demonstration in 1978 that synthetic ODNs complementary to Raos sarcoma virus could inhibit virus replication in tissue cultures of chick embryo fibroblasts. Since then the antisense ODN technology has been widely used in animal sciences and as an important emerging therapeutic approach in clinical medicine. However, antisense ODN inhibition has been an under-exploited strategy for plant tissues, although the prospects for plant cells in suspension cultures to take up single-stranded ODNs was reported over a decade ago. In 2001, two reports from Malho and coworker demonstrated the use of cationic-complexed antisense ODNs to suppress expression of genes encoding pollen

  5. Repression of Meiotic Genes by Antisense Transcription and by Fkh2 Transcription Factor in Schizosaccharomyces pombe

    OpenAIRE

    Chen, Huei-Mei; Rosebrock, Adam P.; Khan, Sohail R.; Futcher, Bruce; Leatherwood, Janet K.

    2012-01-01

    In S. pombe, about 5% of genes are meiosis-specific and accumulate little or no mRNA during vegetative growth. Here we use Affymetrix tiling arrays to characterize transcripts in vegetative and meiotic cells. In vegetative cells, many meiotic genes, especially those induced in mid-meiosis, have abundant antisense transcripts. Disruption of the antisense transcription of three of these mid-meiotic genes allowed vegetative sense transcription. These results suggest that antisense transcription ...

  6. Modulation of lipoprotein metabolism by antisense technology: preclinical drug discovery methodology.

    Science.gov (United States)

    Crooke, Rosanne M; Graham, Mark J

    2013-01-01

    Antisense oligonucleotides (ASOs) are a new class of specific therapeutic agents that alter the intermediary metabolism of mRNA, resulting in the suppression of disease-associated gene products. ASOs exert their pharmacological effects after hybridizing, via Watson-Crick base pairing, to a specific target RNA. If appropriately designed, this event results in the recruitment of RNase H, the degradation of targeted mRNA or pre-mRNA, and subsequent inhibition of the synthesis of a specific protein. A key advantage of the technology is the ability to selectively inhibit targets that cannot be modulated by traditional therapeutics such as structural proteins, transcription factors, and, of topical interest, lipoproteins. In this chapter, we will first provide an overview of antisense technology, then more specifically describe the status of lipoprotein-related genes that have been studied using the antisense platform, and finally, outline the general methodology required to design and evaluate the in vitro and in vivo efficacy of those drugs.

  7. Nanoparticle for delivery of antisense γPNA oligomers targeting CCR5.

    Science.gov (United States)

    Bahal, Raman; McNeer, Nicole Ali; Ly, Danith H; Saltzman, W Mark; Glazer, Peter M

    2013-01-01

    The development of a new class of peptide nucleic acids (PNAs), i.e., gamma PNAs (γPNAs), creates the need for a general and effective method for its delivery into cells for regulating gene expression in mammalian cells. Here we report the antisense activity of a recently developed hydrophilic and biocompatible diethylene glycol (miniPEG)-based gamma peptide nucleic acid called MPγPNAs via its delivery by poly(lactide-co-glycolide) (PLGA)-based nanoparticle system. We show that MPγPNA oligomers designed to bind to the selective region of chemokine receptor 5 (CC R5) transcript, induce potent and sequence-specific antisense effects as compared with regular PNA oligomers. In addition, PLGA nanoparticle delivery of MPγPNAs is not toxic to the cells. The findings reported in this study provide a combination of γPNA technology and PLGA-based nanoparticle delivery method for regulating gene expression in live cells via the antisense mechanism.

  8. A Simple Three-Step Method for Design and Affinity Testing of New Antisense Peptides: An Example of Erythropoietin

    Directory of Open Access Journals (Sweden)

    Nikola Štambuk

    2014-05-01

    Full Text Available Antisense peptide technology is a valuable tool for deriving new biologically active molecules and performing peptide–receptor modulation. It is based on the fact that peptides specified by the complementary (antisense nucleotide sequences often bind to each other with a higher specificity and efficacy. We tested the validity of this concept on the example of human erythropoietin, a well-characterized and pharmacologically relevant hematopoietic growth factor. The purpose of the work was to present and test simple and efficient three-step procedure for the design of an antisense peptide targeting receptor-binding site of human erythropoietin. Firstly, we selected the carboxyl-terminal receptor binding region of the molecule (epitope as a template for the antisense peptide modeling; Secondly, we designed an antisense peptide using mRNA transcription of the epitope sequence in the 3'→5' direction and computational screening of potential paratope structures with BLAST; Thirdly, we evaluated sense–antisense (epitope–paratope peptide binding and affinity by means of fluorescence spectroscopy and microscale thermophoresis. Both methods showed similar Kd values of 850 and 816 µM, respectively. The advantages of the methods were: fast screening with a small quantity of the sample needed, and measurements done within the range of physicochemical parameters resembling physiological conditions. Antisense peptides targeting specific erythropoietin region(s could be used for the development of new immunochemical methods. Selected antisense peptides with optimal affinity are potential lead compounds for the development of novel diagnostic substances, biopharmaceuticals and vaccines.

  9. Functional comparison of antisense proteins of HTLV-1 and HTLV-2 in viral pathogenesis

    Directory of Open Access Journals (Sweden)

    Benoit eBarbeau

    2013-08-01

    Full Text Available The production of antisense transcripts from the 3’ long terminal repeat (LTR in human T-lymphotropic retroviruses has now been clearly demonstrated. After the identification of the antisense strand-encoded HTLV-1 bZIP (HBZ factor, we reported that HBZ could interact with CREB transcription factors and consequently turn off the important activating potential of the viral Tax protein on HTLV-1 5’ LTR promoter activity. We have recently accumulated new results demonstrating that antisense transcripts also exist in HTLV-2, -3 and -4. Furthermore, our data have confirmed the existence of encoded proteins from these antisense transcripts (termed antisense proteins of HTLVs or APHs. APHs are also involved in the down-regulation of Tax-dependent viral transcription. In this review, we will focus on the different molecular mechanisms used by HBZ and APH-2 to control viral expression. While HBZ interacts with CREB through its basic zipper domain, APH-2 binds to this cellular factor through a five amino acid motif localized in its carboxyl terminus. Moreover, unlike APH-2, HBZ possesses an N-terminal activation domain that also contributes to the inhibition of the viral transcription by interacting with the KIX domain of p300/CBP. On the other hand, HBZ was found to induce T-cell proliferation while APH-2 was unable to promote such proliferation. Interestingly, HTLV-2 has not been causally linked to human T-cell leukemia, while HTLV-1 is responsible for the development of the Adult T-cell Leukemia/Lymphoma (ATLL. We will further discuss the possible role played by antisense proteins in the establishment of pathologies induced by viral infection.

  10. Mismatched single stranded antisense oligonucleotides can induce efficient dystrophin splice switching

    Directory of Open Access Journals (Sweden)

    Kole Ryszard

    2011-10-01

    Full Text Available Abstract Background Antisense oligomer induced exon skipping aims to reduce the severity of Duchenne muscular dystrophy by redirecting splicing during pre-RNA processing such that the causative mutation is by-passed and a shorter but partially functional Becker muscular dystrophy-like dystrophin isoform is produced. Normal exons are generally targeted to restore the dystrophin reading frame however, an appreciable subset of dystrophin mutations are intra-exonic and therefore have the potential to compromise oligomer efficiency, necessitating personalised oligomer design for some patients. Although antisense oligomers are easily personalised, it remains unclear whether all patient polymorphisms within antisense oligomer target sequences will require the costly process of producing and validating patient specific compounds. Methods Here we report preclinical testing of a panel of splice switching antisense oligomers, designed to excise exon 25 from the dystrophin transcript, in normal and dystrophic patient cells. These patient cells harbour a single base insertion in exon 25 that lies within the target sequence of an oligomer shown to be effective at removing exon 25. Results It was anticipated that such a mutation would compromise oligomer binding and efficiency. However, we show that, despite the mismatch an oligomer, designed and optimised to excise exon 25 from the normal dystrophin mRNA, removes the mutated exon 25 more efficiently than the mutation-specific oligomer. Conclusion This raises the possibility that mismatched AOs could still be therapeutically applicable in some cases, negating the necessity to produce patient-specific compounds.

  11. Tumor delivery of antisense oligomer using trastuzumab within a streptavidin nanoparticle

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yi [University of Massachusetts Medical School, Division of Nuclear Medicine, Department of Radiology, Worcester, MA (United States); Yale University, Yale PET Center, Department of Diagnostic Radiology, New Haven, CT (United States); Liu, Xinrong; Chen, Ling; Cheng, Dengfeng; Rusckowski, Mary [University of Massachusetts Medical School, Division of Nuclear Medicine, Department of Radiology, Worcester, MA (United States); Hnatowich, Donald J. [University of Massachusetts Medical School, Division of Nuclear Medicine, Department of Radiology, Worcester, MA (United States); Umass Medical School, Department of Radiology, Worcester, MA (United States)

    2009-12-15

    Trastuzumab (Herceptin trademark) is often internalized following binding to Her2+ tumor cells. The objective of this study was to investigate whether trastuzumab can be used as a specific carrier to deliver antisense oligomers into Her2+ tumor cells both in vitro and in vivo. A biotinylated MORF oligomer antisense to RhoC mRNA and its biotinylated sense control were labeled with either lissamine for fluorescence detection or {sup 99m}Tc for radioactivity detection and were linked to biotinylated trastuzumab via streptavidin. The nanoparticles were studied in SUM190 (RhoC+, Her2+) study and SUM149 (RhoC+, Her2-) control cells in culture and as xenografts in mice. As evidence of unimpaired Her2+ binding of trastuzumab within the nanoparticle, accumulations were clearly higher in SUM190 compared to SUM149 cells and, by whole-body imaging, targeting of SUM190 tumor was similar to that expected for a radiolabeled trastuzumab. As evidence of internalization, fluorescence microscopy images of cells grown in culture and obtained from xenografts showed uniform cytoplasm distribution of the lissamine-MORF. An invasion assay showed decreased RhoC expression in SUM190 cells when incubated with the antisense MORF nanoparticles at only 100 nM. Both in cell culture and in animals, the nanoparticle with trastuzumab as specific carrier greatly improved tumor delivery of the antisense oligomer against RhoC mRNA into tumor cells overexpressing Her2 and may be of general utility. (orig.)

  12. Repression of meiotic genes by antisense transcription and by Fkh2 transcription factor in Schizosaccharomyces pombe.

    Science.gov (United States)

    Chen, Huei-Mei; Rosebrock, Adam P; Khan, Sohail R; Futcher, Bruce; Leatherwood, Janet K

    2012-01-01

    In S. pombe, about 5% of genes are meiosis-specific and accumulate little or no mRNA during vegetative growth. Here we use Affymetrix tiling arrays to characterize transcripts in vegetative and meiotic cells. In vegetative cells, many meiotic genes, especially those induced in mid-meiosis, have abundant antisense transcripts. Disruption of the antisense transcription of three of these mid-meiotic genes allowed vegetative sense transcription. These results suggest that antisense transcription represses sense transcription of meiotic genes in vegetative cells. Although the mechanism(s) of antisense mediated transcription repression need to be further explored, our data indicates that RNAi machinery is not required for repression. Previously, we and others used non-strand specific methods to study splicing regulation of meiotic genes and concluded that 28 mid-meiotic genes are spliced only in meiosis. We now demonstrate that the "unspliced" signal in vegetative cells comes from the antisense RNA, not from unspliced sense RNA, and we argue against the idea that splicing regulates these mid-meiotic genes. Most of these mid-meiotic genes are induced in mid-meiosis by the forkhead transcription factor Mei4. Interestingly, deletion of a different forkhead transcription factor, Fkh2, allows low levels of sense expression of some mid-meiotic genes in vegetative cells. We propose that vegetative expression of mid-meiotic genes is repressed at least two independent ways: antisense transcription and Fkh2 repression.

  13. Sense-antisense (complementary) peptide interactions and the proteomic code; potential opportunities in biology and pharmaceutical science.

    Science.gov (United States)

    Miller, Andrew D

    2015-02-01

    A sense peptide can be defined as a peptide whose sequence is coded by the nucleotide sequence (read 5' → 3') of the sense (positive) strand of DNA. Conversely, an antisense (complementary) peptide is coded by the corresponding nucleotide sequence (read 5' → 3') of the antisense (negative) strand of DNA. Research has been accumulating steadily to suggest that sense peptides are capable of specific interactions with their corresponding antisense peptides. Unfortunately, although more and more examples of specific sense-antisense peptide interactions are emerging, the very idea of such interactions does not conform to standard biology dogma and so there remains a sizeable challenge to lift this concept from being perceived as a peripheral phenomenon if not worse, into becoming part of the scientific mainstream. Specific interactions have now been exploited for the inhibition of number of widely different protein-protein and protein-receptor interactions in vitro and in vivo. Further, antisense peptides have also been used to induce the production of antibodies targeted to specific receptors or else the production of anti-idiotypic antibodies targeted against auto-antibodies. Such illustrations of utility would seem to suggest that observed sense-antisense peptide interactions are not just the consequence of a sequence of coincidental 'lucky-hits'. Indeed, at the very least, one might conclude that sense-antisense peptide interactions represent a potentially new and different source of leads for drug discovery. But could there be more to come from studies in this area? Studies on the potential mechanism of sense-antisense peptide interactions suggest that interactions may be driven by amino acid residue interactions specified from the genetic code. If so, such specified amino acid residue interactions could form the basis for an even wider amino acid residue interaction code (proteomic code) that links gene sequences to actual protein structure and function, even

  14. Re-sensitizing drug-resistant bacteria to antibiotics by designing Antisense Therapeutics

    Science.gov (United States)

    Courtney, Colleen; Chatterjee, Anushree

    2014-03-01

    ``Super-bugs'' or ``multi-drug resistant organisms'' are a serious international health problem, with devastating consequences to patient health care. The Center for Disease Control has identified antibiotic resistance as one of the world's most pressing public health problems as a significant fraction of bacterial infections contracted are drug resistant. Typically, antibiotic resistance is encoded by ``resistance-genes'' which express proteins that carryout the resistance causing functions inside the bacterium. We present a RNA based therapeutic strategy for designing antimicrobials capable of re-sensitizing resistant bacteria to antibiotics by targeting labile regions of messenger RNAs encoding for resistance-causing proteins. We perform in silico RNA secondary structure modeling to identify labile target regions in an mRNA of interest. A synthetic biology approach is then used to administer antisense nucleic acids to our model system of ampicillin resistant Escherichia coli. Our results show a prolonged lag phase and decrease in viability of drug-resistant E. colitreated with antisense molecules. The antisense strategy can be applied to alter expression of other genes in antibiotic resistance pathways or other pathways of interest.

  15. Repression of Meiotic Genes by Antisense Transcription and by Fkh2 Transcription Factor in Schizosaccharomyces pombe

    Science.gov (United States)

    Chen, Huei-Mei; Rosebrock, Adam P.; Khan, Sohail R.; Futcher, Bruce; Leatherwood, Janet K.

    2012-01-01

    In S. pombe, about 5% of genes are meiosis-specific and accumulate little or no mRNA during vegetative growth. Here we use Affymetrix tiling arrays to characterize transcripts in vegetative and meiotic cells. In vegetative cells, many meiotic genes, especially those induced in mid-meiosis, have abundant antisense transcripts. Disruption of the antisense transcription of three of these mid-meiotic genes allowed vegetative sense transcription. These results suggest that antisense transcription represses sense transcription of meiotic genes in vegetative cells. Although the mechanism(s) of antisense mediated transcription repression need to be further explored, our data indicates that RNAi machinery is not required for repression. Previously, we and others used non-strand specific methods to study splicing regulation of meiotic genes and concluded that 28 mid-meiotic genes are spliced only in meiosis. We now demonstrate that the “unspliced” signal in vegetative cells comes from the antisense RNA, not from unspliced sense RNA, and we argue against the idea that splicing regulates these mid-meiotic genes. Most of these mid-meiotic genes are induced in mid-meiosis by the forkhead transcription factor Mei4. Interestingly, deletion of a different forkhead transcription factor, Fkh2, allows low levels of sense expression of some mid-meiotic genes in vegetative cells. We propose that vegetative expression of mid-meiotic genes is repressed at least two independent ways: antisense transcription and Fkh2 repression. PMID:22238674

  16. Repression of meiotic genes by antisense transcription and by Fkh2 transcription factor in Schizosaccharomyces pombe.

    Directory of Open Access Journals (Sweden)

    Huei-Mei Chen

    Full Text Available In S. pombe, about 5% of genes are meiosis-specific and accumulate little or no mRNA during vegetative growth. Here we use Affymetrix tiling arrays to characterize transcripts in vegetative and meiotic cells. In vegetative cells, many meiotic genes, especially those induced in mid-meiosis, have abundant antisense transcripts. Disruption of the antisense transcription of three of these mid-meiotic genes allowed vegetative sense transcription. These results suggest that antisense transcription represses sense transcription of meiotic genes in vegetative cells. Although the mechanism(s of antisense mediated transcription repression need to be further explored, our data indicates that RNAi machinery is not required for repression. Previously, we and others used non-strand specific methods to study splicing regulation of meiotic genes and concluded that 28 mid-meiotic genes are spliced only in meiosis. We now demonstrate that the "unspliced" signal in vegetative cells comes from the antisense RNA, not from unspliced sense RNA, and we argue against the idea that splicing regulates these mid-meiotic genes. Most of these mid-meiotic genes are induced in mid-meiosis by the forkhead transcription factor Mei4. Interestingly, deletion of a different forkhead transcription factor, Fkh2, allows low levels of sense expression of some mid-meiotic genes in vegetative cells. We propose that vegetative expression of mid-meiotic genes is repressed at least two independent ways: antisense transcription and Fkh2 repression.

  17. Lysine metabolism in antisense C-hordein barley grains

    DEFF Research Database (Denmark)

    Schmidt, Daiana; Rizzi, Vanessa; Gaziola, Salete A

    2015-01-01

    The grain proteins of barley are deficient in lysine and threonine due to their low concentrations in the major storage protein class, the hordeins, especially in the C-hordein subgroup. Previously produced antisense C-hordein transgenic barley lines have an improved amino acid composition, with ...

  18. Tye7 regulates yeast Ty1 retrotransposon sense and antisense transcription in response to adenylic nucleotides stress.

    Science.gov (United States)

    Servant, Géraldine; Pinson, Benoit; Tchalikian-Cosson, Aurélie; Coulpier, Fanny; Lemoine, Sophie; Pennetier, Carole; Bridier-Nahmias, Antoine; Todeschini, Anne Laure; Fayol, Hélène; Daignan-Fornier, Bertrand; Lesage, Pascale

    2012-07-01

    Transposable elements play a fundamental role in genome evolution. It is proposed that their mobility, activated under stress, induces mutations that could confer advantages to the host organism. Transcription of the Ty1 LTR-retrotransposon of Saccharomyces cerevisiae is activated in response to a severe deficiency in adenylic nucleotides. Here, we show that Ty2 and Ty3 are also stimulated under these stress conditions, revealing the simultaneous activation of three active Ty retrotransposon families. We demonstrate that Ty1 activation in response to adenylic nucleotide depletion requires the DNA-binding transcription factor Tye7. Ty1 is transcribed in both sense and antisense directions. We identify three Tye7 potential binding sites in the region of Ty1 DNA sequence where antisense transcription starts. We show that Tye7 binds to Ty1 DNA and regulates Ty1 antisense transcription. Altogether, our data suggest that, in response to adenylic nucleotide reduction, TYE7 is induced and activates Ty1 mRNA transcription, possibly by controlling Ty1 antisense transcription. We also provide the first evidence that Ty1 antisense transcription can be regulated by environmental stress conditions, pointing to a new level of control of Ty1 activity by stress, as Ty1 antisense RNAs play an important role in regulating Ty1 mobility at both the transcriptional and post-transcriptional stages.

  19. Discovery and Early Development of AVI-7537 and AVI-7288 for the Treatment of Ebola Virus and Marburg Virus Infections

    Directory of Open Access Journals (Sweden)

    Sina Bavari

    2012-11-01

    Full Text Available There are no currently approved treatments for filovirus infections. In this study we report the discovery process which led to the development of antisense Phosphorodiamidate Morpholino Oligomers (PMOs AVI-6002 (composed of AVI-7357 and AVI-7539 and AVI-6003 (composed of AVI-7287 and AVI-7288 targeting Ebola virus and Marburg virus respectively. The discovery process involved identification of optimal transcript binding sites for PMO based RNA-therapeutics followed by screening for effective viral gene target in mouse and guinea pig models utilizing adapted viral isolates. An evolution of chemical modifications were tested, beginning with simple Phosphorodiamidate Morpholino Oligomers (PMO transitioning to cell penetrating peptide conjugated PMOs (PPMO and ending with PMOplus containing a limited number of positively charged linkages in the PMO structure. The initial lead compounds were combinations of two agents targeting separate genes. In the final analysis, a single agent for treatment of each virus was selected, AVI-7537 targeting the VP24 gene of Ebola virus and AVI-7288 targeting NP of Marburg virus, and are now progressing into late stage clinical development as the optimal therapeutic candidates.

  20. Diseño de una oficina de dirección de proyectos (PMO) para la empresa OILEC

    OpenAIRE

    Quishpe Fuertes, Santiago Stalin

    2017-01-01

    El presente trabajo está enfocado a diseñar una oficina de dirección de proyectos (PMO) para la empresa OILEC, la misma que tendrá el propósito de convertirse en un área estratégica para la organización en lo que respecta a la dirección de proyectos. La empresa se desenvuelve dentro de mercado altamente competitivo, como son los sectores de energía, minería e hidrocarburos, en donde el desarrollo de proyectos requiere del cumplimiento de exigentes estándares y una planificación exhaustiva, ta...

  1. Peptide nucleic acid (PNA) cell penetrating peptide (CPP) conjugates as carriers for cellular delivery of antisense oligomers

    DEFF Research Database (Denmark)

    Shiraishi, Takehiko; Nielsen, Peter E

    2012-01-01

    We have explored the merits of a novel delivery strategy for the antisense oligomers based on cell penetrating peptide (CPP) conjugated to a carrier PNA with sequence complementary to part of the antisense oligomer. The effect of these carrier CPP-PNAs was evaluated by using antisense PNA targeting......-PNA (cPNA1(7)-(D-Arg)8) and hexamer carrier decanoyl-CPP-PNA (Deca-cPNA1(6)-(D-Arg)8), respectively, without showing significant additional cellular toxicity. Most interestingly, the activity reached the same level obtained by enhancement with endosomolytic chloroquine (CQ) treatment, suggesting...... that the carrier might facilitate endosomal escape. Furthermore, 50% downregulation of luciferase expression at 60 nM siRNA was obtained using this carrier CPP-PNA delivery strategy (with CQ co-treatment) for a single stranded antisense RNA targeting normal luciferase mRNA. These results indicated that CPP...

  2. Transfection of mouse cytotoxic T lymphocyte with an antisense granzyme A vector reduces lytic activity.

    Science.gov (United States)

    Talento, A; Nguyen, M; Law, S; Wu, J K; Poe, M; Blake, J T; Patel, M; Wu, T J; Manyak, C L; Silberklang, M

    1992-12-15

    Murine CTL have seven serine proteases, known as granzymes, in their lytic granules. Despite considerable effort, convincing evidence that these enzymes play an obligatory role in the lytic process has not been presented. To investigate the function of one of these proteases, granzyme A (GA), we utilized an antisense expression vector to lower the level of the enzyme in the cells. An expression vector containing antisense cDNA for GA and the gene for hygromycin B resistance was constructed and electroporated into the murine CTL line, AR1. Transfectants were selected based on resistance to hygromycin B, and a number of stable lines were developed. One of the antisense lines had greatly reduced levels of GA mRNA, when compared to the parental cells or to control lines transfected with the vector lacking the antisense DNA. The message levels for two other CTL granule proteins, granzyme B and perforin, were unaffected by the antisense vector. The amount of GA, as measured by enzymatic activity, was 3- to 10-fold lower in the transfectant. Most significantly, this line also consistently showed 50 to 70% lower ability to lyse nucleated target cells and to degrade their DNA. Furthermore, it exhibited 90 to 95% lower lytic activity to anti-CD3-coated SRBC. Conjugate formation with target cells, however, was normal. These data provide strong evidence that GA plays an important role in the cytolytic cycle, and that the quantity of enzyme is a limiting factor in these cytolytic cells.

  3. 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.

  4. Dopamine-induced apoptosis in human neuronal cells: inhibition by nucleic acides antisense to the dopamine transporter

    International Nuclear Information System (INIS)

    Porat, S.; Gabbay, M.; Tauber, M.; Ratovitski, T.; Blinder, E.; Simantov, R.

    1996-01-01

    Human neuroblastoma NMB cells take up [ 3 H]dopamine in a selective manner indicating that dopamine transporters are responsible for this uptake. These cells were therefore used as a model to study dopamine neurotoxicity, and to elucidate the role of dopamine transporters in controlling cell death. Treatment with 0.05-0.4 mM dopamine changed cells' morphology within 4 h, accompanied by retraction of processes, shrinkage, apoptosis-like atrophy, accumulation of apoptotic particles, DNA fragmentation and cell death. Cycloheximide inhibited dopamine's effect, suggesting that induction of apoptosis by dopamine was dependent upon protein synthesis. Dopamine cytotoxicity, monitored morphologically by flow cytometric analysis, and by lactate dehydrogenase released, was blocked by cocaine but not by the noradrenaline and serotonin uptake blockers desimipramine and imipramine, respectively. Attempting to inhibit dopamine transport and toxicity in a drug-free and highly selective way, three 18-mer dopamine transporter antisense phosphorothioate oligonucleotides (numbers 1, 2 and 3) and a new plasmid vector expressing the entire rat dopamine transporter complementary DNA in the antisense orientation were prepared and tested. Antisense phosphorothioate oligonucleotide 3 inhibited [ 3 H]dopamine uptake in a time- and dose-dependent manner. Likewise, transient transfection of NMB cells with the plasmid expressing dopamine transporter complementary DNA in the antisense orientation partially blocked [ 3 H]dopamine uptake. Antisense phosphorothioate oligonucleotide 3 also decreased, dose-dependently, the toxic effect of dopamine and 6-hydroxydopamine. Western blot analysis with newly prepared anti-human dopamine transporter antibodies showed that antisense phosphorothioate oligonucleotide 3 decreased the transporter protein level. These studies contribute to better understand the mechanism of dopamine-induced apoptosis and neurotoxicity. (Copyright (c) 1996 Elsevier Science B

  5. 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

  6. 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

  7. Analysis of antisense expression by whole genome tiling microarrays and siRNAs suggests mis-annotation of Arabidopsis orphan protein-coding genes.

    Directory of Open Access Journals (Sweden)

    Casey R Richardson

    2010-05-01

    Full Text Available MicroRNAs (miRNAs and trans-acting small-interfering RNAs (tasi-RNAs are small (20-22 nt long RNAs (smRNAs generated from hairpin secondary structures or antisense transcripts, respectively, that regulate gene expression by Watson-Crick pairing to a target mRNA and altering expression by mechanisms related to RNA interference. The high sequence homology of plant miRNAs to their targets has been the mainstay of miRNA prediction algorithms, which are limited in their predictive power for other kingdoms because miRNA complementarity is less conserved yet transitive processes (production of antisense smRNAs are active in eukaryotes. We hypothesize that antisense transcription and associated smRNAs are biomarkers which can be computationally modeled for gene discovery.We explored rice (Oryza sativa sense and antisense gene expression in publicly available whole genome tiling array transcriptome data and sequenced smRNA libraries (as well as C. elegans and found evidence of transitivity of MIRNA genes similar to that found in Arabidopsis. Statistical analysis of antisense transcript abundances, presence of antisense ESTs, and association with smRNAs suggests several hundred Arabidopsis 'orphan' hypothetical genes are non-coding RNAs. Consistent with this hypothesis, we found novel Arabidopsis homologues of some MIRNA genes on the antisense strand of previously annotated protein-coding genes. A Support Vector Machine (SVM was applied using thermodynamic energy of binding plus novel expression features of sense/antisense transcription topology and siRNA abundances to build a prediction model of miRNA targets. The SVM when trained on targets could predict the "ancient" (deeply conserved class of validated Arabidopsis MIRNA genes with an accuracy of 84%, and 76% for "new" rapidly-evolving MIRNA genes.Antisense and smRNA expression features and computational methods may identify novel MIRNA genes and other non-coding RNAs in plants and potentially other

  8. Suppression of cell division by pKi-67 antisense-RNA and recombinant protein.

    Science.gov (United States)

    Duchrow, M; Schmidt, M H; Zingler, M; Anemüller, S; Bruch, H P; Broll, R

    2001-01-01

    The human antigen defined by the monoclonal antibody Ki-67 (pKi-67) is a human nuclear protein strongly associated with cell proliferation and found in all tissues studied. It is widely used as a marker of proliferating cells, yet its function is unknown. To investigate its function we suppressed pKi-67 expression by antisense RNA and overexpressed a partial structure of pKi-67 in HeLa cells. A BrdU-incorporation assay showed a significant decrease in DNA synthesis after antisense inhibition. Cell cycle analysis indicated a higher proportion of cells in G1 phase and a lower proportion of cells in S phase while the number of G(2)/M phase cells remained constant. Overexpression of a recombinant protein encoding three of the repetitive elements from exon 13 of pKi-67 had a similar effect to that obtained by antisense inhibition. The similarity of the effect of expressing 'Ki-67 repeats' and pKi-67 antisense RNA could be explained by a negative effect on the folding of the endogenous protein in the endoplasmatic reticulum. Furthermore excessive self-association of pKi-67 via the repeat structure could inhibit its nuclear transport, preventing it from getting to its presumptive site of action. We conclude that the Ki-67 protein has an important role in the regulation of the cell cycle, which is mediated in part by its repetitive elements. Copyright 2001 S. Karger AG, Basel

  9. Fabrication of self-assembled ultrathin photochromic films containing mixed-addenda polyoxometalates H5[PMo10V2O40] and 1,10-decanediamine

    International Nuclear Information System (INIS)

    Wang Zhongliang; Ma Ying; Zhang Ruili; Xu Da; Fu Hongbing; Yao Jiannian

    2009-01-01

    A layered phosphovanadomolybdate/1,10-decanediamine (1,10-DAD) self-assembled ultrathin film was fabricated by means of alternating adsorption of mixed-addenda polyoxometalates (POMs) (phosphovanadomolybdate, H 5 [PMo 10 V 2 O 40 ]) and 1,10-DAD, and its photochromic properties were investigated. It is found that the self-assembled multilayer (SAM) film shows high-photochromic response, excellent photochromic stability and reversibility. The photochromic behavior of the SAM is closely related to the reduction potentials of addenda atoms in mixed-addenda POMs. In the case of photo-reduced mixed-addenda POMs, the electron is localized on the more reducible atom, and the addenda atoms with higher reduction potentials show prior photochromism compared with those with lower reduction potentials. The coloration speed is improved after introduction of V into molybdenum POM. The well-ordered lamellar structure of the film was well maintained during the coloration. - Graphical abstract: An ordered H 5 [PMo 10 V 2 O 40 ]/1,10-decanediamine ultrathin film was fabricated by a self-assembled technique. The hybrid film displays good photochromism closely related to the reduction potentials of addenda atoms.

  10. Implementation of a Project Management Office (PMO)--experiences from year 1.

    Science.gov (United States)

    Isola, Miriam; Polikaitis, Audrius; Laureto, Rose Ann

    2006-01-01

    Recognized as an early leader in clinical information systems, the University of Illinois Medical Center was challenged to meet the ever-increasing demand for information systems. Interviews with key stakeholders revealed unfavorable attitudes toward the Information Services department. Reasons given were that projects often are not aligned with business strategy, projects are delayed, IS itself is a barrier to progress, and a lack of proactive planning precipitates crises. Under the leadership of a new CIO, IS began developing a Project Management Office, or PMO, to better meet medical center business objectives and to more effectively manage technology projects. Successes during the first year included comprehensive IT strategic planning. Collaborative relationships were established with departmental leaders for planning, prioritizing, budgeting, and executing projects. A formal Web-based process for requesting IS projects was implemented, project management training was provided, and elements of standard project management methodology were implemented. While a framework for effective project management was created, significant effort is still required to firmly root these new processes within the organizational culture. Project management office goals for the second year include implementing a project portfolio management tool, refining the benefits methodology, and continuing the advancement of the project management methodology.

  11. Antisense long noncoding RNAs regulate var gene activation in the malaria parasite Plasmodium falciparum.

    Science.gov (United States)

    Amit-Avraham, Inbar; Pozner, Guy; Eshar, Shiri; Fastman, Yair; Kolevzon, Netanel; Yavin, Eylon; Dzikowski, Ron

    2015-03-03

    The virulence of Plasmodium falciparum, the causative agent of the deadliest form of human malaria, is attributed to its ability to evade human immunity through antigenic variation. These parasites alternate between expression of variable antigens, encoded by members of a multicopy gene family named var. Immune evasion through antigenic variation depends on tight regulation of var gene expression, ensuring that only a single var gene is expressed at a time while the rest of the family is maintained transcriptionally silent. Understanding how a single gene is chosen for activation is critical for understanding mutually exclusive expression but remains a mystery. Here, we show that antisense long noncoding RNAs (lncRNAs) initiating from var introns are associated with the single active var gene at the time in the cell cycle when the single var upstream promoter is active. We demonstrate that these antisense transcripts are incorporated into chromatin, and that expression of these antisense lncRNAs in trans triggers activation of a silent var gene in a sequence- and dose-dependent manner. On the other hand, interference with these lncRNAs using complement peptide nucleic acid molecules down-regulated the active var gene, erased the epigenetic memory, and induced expression switching. Altogether, our data provide evidence that these antisense lncRNAs play a key role in regulating var gene activation and mutually exclusive expression.

  12. Alteration of rice growth and development via antisense expression ...

    African Journals Online (AJOL)

    user

    OsGA20ox2 in regulating plant growth and development, we used reverse genomic approach to ... pathways. Similarly, Carmen et al. (2007) suggested that. Carrizo citrange plants have produced antisense ... universal SP6 and T7 primers to conform their reality (Sangon, ..... Optimising the tissue culture conditions for.

  13. 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.

  14. Cellular delivery and antisense effects of peptide nucleic acid conjugated to polyethyleneimine via disulfide linkers

    DEFF Research Database (Denmark)

    Berthold, Peter R; Shiraishi, Takehiko; Nielsen, Peter E

    2010-01-01

    Peptide nucleic acid (PNA) is potentially an attractive antisense and antigene agent for which more efficient cellular delivery systems are still warranted. The cationic polymer polyethylenimine (PEI) is commonly used for cellular transfection of DNA and RNA complexes, but is not readily applicable...... moiety) and further reacted this with a cysteine PNA. The level of modification was determined spectrophotometrically with high accuracy, and the PNA transfection efficiency of the conjugates was evaluated in an antisense luciferase splice-correction assay using HeLa pLuc705 cells. We find that PEI...... is an efficient vector for PNA delivery yielding significantly higher (up to 10-fold) antisense activity than an analogous PNA-octaarginine conjugate, even in the presence of chloroquine, which only slightly enhances the PEI-PNA activity. The PEI-PEG conjugates are preferred due to lower acute cellular toxicity...

  15. Cocaine alters Homer1 natural antisense transcript in the nucleus accumbens.

    Science.gov (United States)

    Sartor, Gregory C; Powell, Samuel K; Velmeshev, Dmitry; Lin, David Y; Magistri, Marco; Wiedner, Hannah J; Malvezzi, Andrea M; Andrade, Nadja S; Faghihi, Mohammad A; Wahlestedt, Claes

    2017-12-01

    Natural antisense transcripts (NATs) are an abundant class of long noncoding RNAs that have recently been shown to be key regulators of chromatin dynamics and gene expression in nervous system development and neurological disorders. However, it is currently unclear if NAT-based mechanisms also play a role in drug-induced neuroadaptations. Aberrant regulation of gene expression is one critical factor underlying the long-lasting behavioral abnormalities that characterize substance use disorder, and it is possible that some drug-induced transcriptional responses are mediated, in part, by perturbations in NAT activity. To test this hypothesis, we used an automated algorithm that mines the NCBI AceView transcriptomics database to identify NAT overlapping genes linked to addiction. We found that 22% of the genes examined contain NATs and that expression of Homer1 natural antisense transcript (Homer1-AS) was altered in the nucleus accumbens (NAc) of mice 2h and 10days following repeated cocaine administration. In in vitro studies, depletion of Homer1-AS lead to an increase in the corresponding sense gene expression, indicating a potential regulatory mechanisms of Homer1 expression by its corresponding antisense transcript. Future in vivo studies are needed to definitely determine a role for Homer1-AS in cocaine-induced behavioral and molecular adaptations. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Role of natural antisense transcripts pertaining to tumor suppressor genes in human carcinomas

    International Nuclear Information System (INIS)

    Pelicci, G.; Pierotti, M.

    2009-01-01

    Overlapping transcripts in opposite orientations can potentially form perfect sense-antisense duplex RNA. Recently, several studies have revealed the extent of natural antisense transcripts (NATs) and their role in important biological phenomena also in higher organisms. In order to test the hypothesis that the function of NATs in man might represent an essential element in the regulation of gene expression, especially at transcriptional level, in this study we planned to look for, systematically examine, and characterize NATs belonging in the human genome to the tumour suppressor class of genes, so to identify physiological (and potentially pathological) modulators in this gene class

  17. Antisense RNA: a genetic approach to cell resistance against Parvovirus; RNA antisentido: una aproximacion de resistencia genetica a Parvovirus

    Energy Technology Data Exchange (ETDEWEB)

    Ramirez Martinez, J.C.

    1992-12-31

    The Minute Virus of Mice (MVMp), an autonomous Parvovirus that replicates cytolytically in the A9 mouse fibroblast cell line, was interfered by constitutive expression of an antisense RNA targeted against the major non-structural NS-1 protein. Permanently transfected A9 clones expressing NS-1 antisense, showed increased proliferative capacity upon virus infection, and likewise cultures infected at low multiplicity by MVMp reached confluence overcoming virus growth. Correspondingly, an inhibition in virus multiplication was demonstrated by a significant lower virus production and plaque forming ability in clones expressing antisense RNa. At the molecular level, several fold reduction in viral DNA, RNA and proteins was quantitated by respective analysis of Southern, RNase protection and bidimensional gels. Remarkably, the accumulation of all three viral messengers(R1,R2,R3) was decreased both in the cytoplasm and in the nucleus, suggesting that antisense-mediated inhibition is primarily exerted at the level of viral transcription or nuclear post-transcriptional events. Thus, this system illustrates the possibility to create an antisense-mediated protective stage to highly cytotoxic viruses in permissive cells, by down-modulation the expression of a transactivator of virus genes. (author)180 refs., 25 figs.

  18. Antisense RNA: a genetic approach to cell resistance against Parvovirus. RNA antisentido: una aproximacion de resistencia genetica a Parvovirus

    Energy Technology Data Exchange (ETDEWEB)

    Ramirez Martinez, J.C.

    1992-01-01

    The Minute Virus of Mice (MVMp), an autonomous Parvovirus that replicates cytolytically in the A9 mouse fibroblast cell line, was interfered by constitutive expression of an antisense RNA targeted against the major non-structural NS-1 protein. Permanently transfected A9 clones expressing NS-1 antisense, showed increased proliferative capacity upon virus infection, and likewise cultures infected at low multiplicity by MVMp reached confluence overcoming virus growth. Correspondingly, an inhibition in virus multiplication was demonstrated by a significant lower virus production and plaque forming ability in clones expressing antisense RNa. At the molecular level, several fold reduction in viral DNA, RNA and proteins was quantitated by respective analysis of Southern, RNase protection and bidimensional gels. Remarkably, the accumulation of all three viral messengers(R1,R2,R3) was decreased both in the cytoplasm and in the nucleus, suggesting that antisense-mediated inhibition is primarily exerted at the level of viral transcription or nuclear post-transcriptional events. Thus, this system illustrates the possibility to create an antisense-mediated protective stage to highly cytotoxic viruses in permissive cells, by down-modulation the expression of a transactivator of virus genes. (author)180 refs., 25 figs.

  19. Encapsulation of c-myc antisense oligodeoxynucleotides in lipid particles improves antitumoral efficacy in vivo in a human melanoma line.

    Science.gov (United States)

    Leonetti, C; Biroccio, A; Benassi, B; Stringaro, A; Stoppacciaro, A; Semple, S C; Zupi, G

    2001-06-01

    Phosphorothioate c-myc antisense oligodeoxynucleotides [S]ODNs (free INX-6295) were encapsulated in a new liposome formulation and the antitumor activity was compared to the unencapsulated antisense in a human melanoma xenograft. The systemic administration of INX-6295 encapsulated in stabilized antisense lipid particles (SALP INX-6295) improved plasma AUC (area under the plasma concentration-time curve) and initial half-life of free INX-6295, resulting in a significant enhancement in tumor accumulation and improvement in tumor distribution of antisense oligodeoxynucleotides. Animals treated with SALP INX-6295 exhibited a prolonged reduction of c-myc expression, reduced tumor growth and increased mice survival. When administered in combination with cisplatin (DDP), SALP INX-6295 produced a complete tumor regression in approximately 30% of treated mice, which persisted for at least 60 days following the first cycle of treatment. Finally, the median survival of mice treated with DDP/SALP INX-6295 increased by 105% compared to 84% for animals treated with the combination DDP/free INX-6295. These data indicate that the biological activity and the therapeutic efficacy of c-myc antisense therapy may be improved when these agents are administered in lipid-based delivery systems.

  20. Avaliação para implantar PMO em pequena empresa de projetos de drenagem urbana - Distrito Federal: estudo de caso

    OpenAIRE

    Silva, Marcelo Augusto Sales da; Silva, Venine de Cássia Sales da

    2014-01-01

    Objetiva-se com esse artigo realizar um estudo para implantar o Escritório de Projetos (Project Management Office – PMO) em uma empresa projetista de pequeno porte, que atua na área de drenagem urbana no Distrito Federal. A metodologia utilizada pautou-se em: caracterizar o objeto de estudo; avaliar a posição estragégica em relação ao mercado na área de atuação (Matriz SWOT); mapear os principais processos relativos aos projetos de drenagem elaborados no DF; estudar e propor uma estrutura org...

  1. Antisense silencing of the creA gene in Aspergillus nidulans

    DEFF Research Database (Denmark)

    Bautista, L. F.; Aleksenko, Alexei Y.; Hentzer, Morten

    2000-01-01

    Antisense expression of a portion of the gene encoding the major carbon catabolite repressor CREA in Aspergillus nidulans resulted in a substantial increase in the levels of glucose-repressible enzymes, both endogenous and heterologous, in the presence of glucose. The derepression effect was appr...

  2. Antisense mediated exon skipping therapy for duchenne muscular dystrophy (DMD)

    DEFF Research Database (Denmark)

    Brolin, Camilla; Shiraishi, Takehiko

    2011-01-01

    Duchenne Muscular Dystrophy (DMD) is a lethal disease caused by mutations in the dystrophin gene (DMD) that result in the absence of essential muscle protein dystrophin. Among many different approaches for DMD treatment, exon skipping, mediated by antisense oligonucleotides, is one of the most...

  3. 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.

  4. BC047440 antisense eukaryotic expression vectors inhibited HepG2 cell proliferation and suppressed xenograft tumorigenicity

    International Nuclear Information System (INIS)

    Lu, Zheng; Ping, Liang; JianBo, Zhou; XiaoBing, Huang; Yu, Wen; Zheng, Wang; Jing, Li

    2012-01-01

    The biological functions of the BC047440 gene highly expressed by hepatocellular carcinoma (HCC) are unknown. The objective of this study was to reconstruct antisense eukaryotic expression vectors of the gene for inhibiting HepG 2 cell proliferation and suppressing their xenograft tumorigenicity. The full-length BC047440 cDNA was cloned from human primary HCC by RT-PCR. BC047440 gene fragments were ligated with pMD18-T simple vectors and subsequent pcDNA3.1(+) plasmids to construct the recombinant antisense eukaryotic vector pcDNA3.1(+)BC047440AS. The endogenous BC047440 mRNA abundance in target gene-transfected, vector-transfected and naive HepG 2 cells was semiquantitatively analyzed by RT-PCR and cell proliferation was measured by the MTT assay. Cell cycle distribution and apoptosis were profiled by flow cytometry. The in vivo xenograft experiment was performed on nude mice to examine the effects of antisense vector on tumorigenicity. BC047440 cDNA fragments were reversely inserted into pcDNA3.1(+) plasmids. The antisense vector significantly reduced the endogenous BC047440 mRNA abundance by 41% in HepG 2 cells and inhibited their proliferation in vitro (P < 0.01). More cells were arrested by the antisense vector at the G 1 phase in an apoptosis-independent manner (P = 0.014). Additionally, transfection with pcDNA3.1(+) BC047440AS significantly reduced the xenograft tumorigenicity in nude mice. As a novel cell cycle regulator associated with HCC, the BC047440 gene was involved in cell proliferation in vitro and xenograft tumorigenicity in vivo through apoptosis-independent mechanisms

  5. Inhibition of B cell proliferation by antisense DNA to both alpha and beta forms of Fc epsilon R II.

    Science.gov (United States)

    Bhatti, L; Behle, K; Stevens, R H

    1992-10-01

    Epstein-Barr Virus (EBV) infection activates B lymphocyte proliferation through partially understood mechanisms, resulting in phenotypic changes, including the appearance of new antigens. One such antigen is Fc epsilon R II/CD-23 which may be relevant for B cell proliferation. We have used anti-sense oligonucleotides to study the importance of the two forms of this molecule for proliferation in the EBV-transformed, Fc epsilon R II +ve lymphoblastoid B cell line, RPMI 8866. Anti-sense oligodeoxynucleotides were generated to the two forms of Fc epsilon R II; Fc epsilon R IIa (alpha) and IIb (beta) which differ only in their intracytoplasmic domains. Addition of increasing concentrations of anti-sense oligonucleotides, ranging from 1 to 30 microM, significantly decreased cellular proliferation as measured by the incorporation of [3H]thymidine (inhibition range 8-88%). Optimum inhibition of cellular proliferation was apparent at 15 microM concentration of both anti-sense Fc epsilon R IIa and IIb (Fc epsilon R IIa, mean +/- SE = 75 +/- 7% inhibition, p less than 0.001; Fc epsilon R IIb, mean +/- SE = 71 +/- 7% inhibition, p less than 0.001). Anti-sense oligonucleotides complementary to the common part of Fc epsilon R II resulted in a similar inhibition of proliferation. Sense oligonucleotides did not induce significant inhibition. Preincubation of sense and anti-sense oligonucleotides resulted in an abrogation of proliferation inhibition. Moreover, none of these oligonucleotides had any effect on a Fc epsilon R II -ve cell line. Incubation with both anti-sense IIa and IIb resulted in additive, but not synergistic inhibition of proliferation. Addition of soluble Fc epsilon R II did not reverse inhibition of proliferation, suggesting that membrane-bound or intracellular rather than soluble Fc epsilon R II was important for the induced proliferation. Analysis of cell surface expression for Fc epsilon II indicated that while there was a pronounced effect on cell number

  6. Oxacillin sensitization of methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus pseudintermedius by antisense peptide nucleic acids in vitro.

    Science.gov (United States)

    Goh, Shan; Loeffler, Anette; Lloyd, David H; Nair, Sean P; Good, Liam

    2015-11-11

    Antibiotic resistance genes can be targeted by antisense agents, which can reduce their expression and thus restore cellular susceptibility to existing antibiotics. Antisense inhibitors can be gene and pathogen specific, or designed to inhibit a group of bacteria having conserved sequences within resistance genes. Here, we aimed to develop antisense peptide nucleic acids (PNAs) that could be used to effectively restore susceptibility to β-lactams in methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus pseudintermedius (MRSP). Antisense PNAs specific for conserved regions of the mobilisable gene mecA, and the growth essential gene, ftsZ, were designed. Clinical MRSA and MRSP strains of high oxacillin resistance were treated with PNAs and assayed for reduction in colony forming units on oxacillin plates, reduction in target gene mRNA levels, and cell size. Anti-mecA PNA at 7.5 and 2.5 μM reduced mecA mRNA in MRSA and MRSP (p resistance in staphylococci. Further studies are warranted as clinical treatment alternatives are needed.

  7. Effect of injection of antisense oligodeoxynucleotides of GAD isozymes into rat ventromedial hypothalamus on food intake and locomotor activity.

    Science.gov (United States)

    Bannai, M; Ichikawa, M; Nishihara, M; Takahashi, M

    1998-02-16

    In the ventromedial hypothalamus (VMH), gamma-aminobutyric acid (GABA) plays a role in regulating feeding and running behaviors. The GABA synthetic enzyme, glutamic acid decarboxylase (GAD), consists of two isozymes, GAD65 and GAD67. In the present study, the phosphorothioated antisense oligodeoxynucleotides (ODNs) of each GAD isozyme were injected bilaterally into the VMH of male rats, and food intake, body weight and locomotor activity were monitored. ODNs were incorporated in the water-absorbent polymer (WAP, 0.2 nmol/microliter) so that ODNs were retained at the injection site. Each antisense ODN of GAD65 or GAD67 tended to reduce food intake on day 1 (day of injection=day 0) though not significantly. An injection combining both antisense ODNs significantly decreased food intake only on day 1, but body weight remained significantly lower than the control for 5 days. This suppression of body weight gain could be attributed to a significant increase in locomotor activity between days 3 and 5. Individual treatment with either ODNs did not change locomotor activity. The increase in daily locomotor activity in the group receiving the combined antisense ODNs occurred mainly during the light phase. Neither vehicle (WAP) nor control ODN affected food intake, body weight and locomotor activity. Histological studies indicated that antisense ODN distributed within 800 micron from the edge of the area where WAP was located 24 h after the injection gradually disappeared within days, but still remained within 300 micron m distance even 7 days after the injection. Antisense ODN was effectively incorporated by all the cell types examined, i.e., neurons, astrocytes and microglias. Further, HPLC analysis revealed that antisense ODNs of GAD isozymes, either alone or combined, decreased the content of GABA by 50% in VMH 24 h after the injection. These results indicate that suppression of GABA synthesis by either of the GAD isozymes is synergistically involved in suppressing food

  8. Complex community of nitrite-dependent anaerobic methane oxidation bacteria in coastal sediments of the Mai Po wetland by PCR amplification of both 16S rRNA and pmoA genes.

    Science.gov (United States)

    Chen, Jing; Zhou, Zhichao; Gu, Ji-Dong

    2015-02-01

    In the present work, both 16S rRNA and pmoA gene-based PCR primers were employed successfully to study the diversity and distribution of n-damo bacteria in the surface and lower layer sediments at the coastal Mai Po wetland. The occurrence of n-damo bacteria in both the surface and subsurface sediments with high diversity was confirmed in this study. Unlike the two other known n-damo communities from coastal areas, the pmoA gene-amplified sequences in the present work clustered not only with some freshwater subclusters but also within three newly erected marine subclusters mostly, indicating the unique niche specificity of n-damo bacteria in this wetland. Results suggested vegetation affected the distribution and community structures of n-damo bacteria in the sediments and n-damo could coexist with sulfate-reducing methanotrophs in the coastal ecosystem. Community structures of the Mai Po n-damo bacteria based on 16S rRNA gene were different from those of either the freshwater or the marine. In contrast, structures of the Mai Po n-damo communities based on pmoA gene grouped with the marine ones and were clearly distinguished from the freshwater ones. The abundance of n-damo bacteria at this wetland was quantified using 16S rRNA gene PCR primers to be 2.65-6.71 × 10(5) copies/g dry sediment. Ammonium and nitrite strongly affected the community structures and distribution of n-damo bacteria in the coastal Mai Po wetland sediments.

  9. Preparation and quality test of superparamagnetic iron oxide labeled antisense oligodeoxynucleotide probe: a preliminary study.

    Science.gov (United States)

    Wen, Ming; Li, Bibo; Ouyang, Yu; Luo, Yi; Li, Shaolin

    2009-06-01

    Molecular imaging of tumor antisense gene techniques have been applied to the study of magnetic resonance (MR) gene imaging associated with malignant tumors. In this study, we designed, synthesized, and tested a novel molecular probe, in which the antisense oligodeoxynucleotide (ASODN) was labeled with superparamagnetic iron oxide (SPIO), and its efficiency was examined by in vitro MR imaging after SK-Br-3 mammary carcinoma cell lines (oncocytes) transfection. The SPIO-labeled ASODN probe was prepared through SPIO conjugated to ASODN using a chemical cross linking method. Its morphology and size were detected by atomic force microscope, size distribution were detected by laser granulometer, the conjugating rate and biological activity were determined by high performance liquid chromatography, and the stability was determined by polyacrylamide gel electrophoresis. After that, the probes were transfected into the SK-Br-3 oncocytes, cellular iron uptake was analyzed qualitatively at light and electron microscopy and was quantified at atomic absorption spectrometry, and the signal change of the transfected cells was observed and measured using MR imaging. The morphology of the SPIO-labeled ASODN probe was mostly spherical with well-distributed scattering, and the diameters were between 25 and 40 nm (95%) by atomic force microscope and laser granulometer, the conjugating rate of the probe was 99%. Moreover, this probe kept its activity under physiological conditions and could conjugate with antisense oligodeoxynucleotide. In addition, light microscopy revealed an intracellular uptake of iron oxides in the cytosol and electron microscopic studies revealed a lysosomal deposition of iron oxides in the transfected SK-Br-3 oncocytes by antisense probes, some of them gathered stacks, and the iron content of the group of transfected SK-Br-3 oncocytes by antisense probe is significantly higher (18.37 +/- 0.42 pg) than other contrast groups, the MR imaging showed that

  10. Small RNAs and the regulation of cis-natural antisense transcripts in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Lonardi Stefano

    2008-01-01

    Full Text Available Abstract Background In spite of large intergenic spaces in plant and animal genomes, 7% to 30% of genes in the genomes encode overlapping cis-natural antisense transcripts (cis-NATs. The widespread occurrence of cis-NATs suggests an evolutionary advantage for this type of genomic arrangement. Experimental evidence for the regulation of two cis-NAT gene pairs by natural antisense transcripts-generated small interfering RNAs (nat-siRNAs via the RNA interference (RNAi pathway has been reported in Arabidopsis. However, the extent of siRNA-mediated regulation of cis-NAT genes is still unclear in any genome. Results The hallmarks of RNAi regulation of NATs are 1 inverse regulation of two genes in a cis-NAT pair by environmental and developmental cues and 2 generation of siRNAs by cis-NAT genes. We examined Arabidopsis transcript profiling data from public microarray databases to identify cis-NAT pairs whose sense and antisense transcripts show opposite expression changes. A subset of the cis-NAT genes displayed negatively correlated expression profiles as well as inverse differential expression changes under at least one of the examined developmental stages or treatment conditions. By searching the Arabidopsis Small RNA Project (ASRP and Massively Parallel Signature Sequencing (MPSS small RNA databases as well as our stress-treated small RNA dataset, we found small RNAs that matched at least one gene in 646 pairs out of 1008 (64% protein-coding cis-NAT pairs, which suggests that siRNAs may regulate the expression of many cis-NAT genes. 209 putative siRNAs have the potential to target more than one gene and half of these small RNAs could target multiple members of a gene family. Furthermore, the majority of the putative siRNAs within the overlapping regions tend to target only one transcript of a given NAT pair, which is consistent with our previous finding on salt- and bacteria-induced nat-siRNAs. In addition, we found that genes encoding plastid- or

  11. Peripheral administration of antisense oligonucleotides targeting the amyloid-β protein precursor reverses AβPP and LRP-1 overexpression in the aged SAMP8 mouse brain.

    Science.gov (United States)

    Erickson, Michelle A; Niehoff, Michael L; Farr, Susan A; Morley, John E; Dillman, Lucy A; Lynch, Kristin M; Banks, William A

    2012-01-01

    The senescence accelerated mouse-prone 8 (SAMP8) mouse model of Alzheimer's disease has a natural mutation leading to age-related increases in the amyloid-β protein precursor (AβPP) and amyloid-β (Aβ) in the brain, memory impairment, and deficits in Aβ removal from the brain. Previous studies show that centrally administered antisense oligonucleotide directed against AβPP can decrease AβPP expression and Aβ production in the brains of aged SAMP8 mice, and improve memory. The same antisense crosses the blood-brain barrier and reverses memory deficits when injected intravenously. Here, we give 6 μg of AβPP or control antisense 3 times over 2 week intervals to 12 month old SAMP8 mice. Object recognition test was done 48 hours later, followed by removal of whole brains for immunoblot analysis of AβPP, low-density lipoprotein-related protein-1 (LRP-1), p-glycoprotein (Pgp), receptor for advanced glycation endproducts (RAGE), or ELISA of soluble Aβ(40). Our results show that AβPP antisense completely reverses a 30% age-associated increase in AβPP signal (p < 0.05 versus untreated 4 month old SAMP8). Soluble Aβ(40) increased with age, but was not reversed by antisense. LRP-1 large and small subunits increased significantly with age (147.7%, p < 0.01 and 123.7%, p < 0.05 respectively), and AβPP antisense completely reversed these increases (p < 0.05). Pgp and RAGE were not significantly altered with age or antisense. Antisense also caused improvements in memory (p < 0.001). Together, these data support the therapeutic potential of AβPP antisense and show a unique association between AβPP and LRP-1 expression in the SAMP8 mouse.

  12. Central and peripheral administration of antisense oligonucleotide targeting amyloid-β protein precursor improves learning and memory and reduces neuroinflammatory cytokines in Tg2576 (AβPPswe) mice.

    Science.gov (United States)

    Farr, Susan A; Erickson, Michelle A; Niehoff, Michael L; Banks, William A; Morley, John E

    2014-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease. Currently, there are no therapies to stop or reverse the symptoms of AD. We have developed an antisense oligonucleotide (OL-1) against the amyloid-β protein precursor (AβPP) that can decrease AβPP expression and amyloid-β protein (Aβ) production. This antisense rapidly crosses the blood-brain barrier, reverses learning and memory impairments, reduces oxidative stress, and restores brain-to-blood efflux of Aβ in SAMP8 mice. Here, we examined the effects of this AβPP antisense in the Tg2576 mouse model of AD. We administered the OL-1 antisense into the lateral ventricle 3 times at 2week intervals. Seventy-two hours after the third injection, we tested learning and memory in T-maze foot shock avoidance. In the second study, we injected the mice with OL-1 antisense 3 times at 2-week intervals via the tail vein. Seventy-two hours later, we tested learning and memory T-maze, novel object recognition, and elevated plus maze. At the end of behavioral testing, brain tissue was collected. OL-1 antisense administered centrally improved acquisition and retention of T-maze foot shock avoidance. OL-1 antisense administered via tail vein improved learning and memory in both T-maze foot shock avoidance and novel object-place recognition. In the elevated plus maze, the mice which received OL-1 antisense spent less time in the open arms and had fewer entries into the open arms indicating reduced disinhibitation. Biochemical analyses reveal significant reduction of AβPP signal and a reduction of measures of neuroinflammation. The current findings support the therapeutic potential of OL-1 AβPP antisense.

  13. Respirable antisense oligonucleotides: a new drug class for respiratory disease

    Directory of Open Access Journals (Sweden)

    Tanaka Makoto

    2000-12-01

    Full Text Available Abstract Respirable antisense oligonucleotides (RASONs, which attenuate specific disease-associated mRNAs, represent a new class of respiratory therapeutics with considerable potential. RASONs overcome previous obstacles that have impeded the development of antisense therapeutics targeting diseases in other organ systems. RASONs are delivered directly to the target tissue via inhalation; their uptake seems to be enhanced by cationic properties inherent in pulmonary surfactant, and, because of the markedly different target properties of mRNA and proteins, they can have very long durations of effect compared with traditional drugs targeting the protein of the same gene. RASONs contain chemical modifications that decrease their degradation by cellular nucleases. However, total insensitivity to nucleases is probably not an optimal design criterion for RASONs, because moderate nuclease sensitivity can prevent their systemic delivery, decreasing the potential for systemic toxicity. EPI-2010 is a 21-mer phosphorothioate RASON that attenuates bronchoconstriction, inflammation and surfactant depletion in preclinical models of human asthma, has a duration of effect of seven days, and seems to undergo minimal systemic delivery.

  14. Dual-Specificity Anti-HER-2/neu Antisense DNA Agents for Breast Cancer Therapy

    National Research Council Canada - National Science Library

    Stein, Stanley

    2001-01-01

    .... To achieve high avidity and specificity, we designed chimeric antisense molecules consisting of a short active DNA fused to a short "anchor" 2'-0-methyl RNA complementary to non-contiguous single...

  15. Comparison of three techniques for generation of tolerogenic dendritic cells: siRNA, oligonucleotide antisense, and antibody blocking.

    Science.gov (United States)

    Karimi, Mohammad Hossein; Ebadi, Padideh; Pourfathollah, Ali Akbar; Moazzeni, Mohammad; Soheili, Zahra Soheila; Samiee, Shahram

    2010-12-01

    In recent years, a new view of dendritic cells (DCs) as a main regulator of immunity to induce and maintain tolerance has been established. In vitro manipulation of their development and maturation is a topic of DC therapeutic application, which utilizes their inherent tolerogenicity. In this field, the therapeutic potential of antisense, siRNA, and blocking antibody are an interesting goal. In the present study, the efficiency of these three methods--siRNA, antisense, and blocking antibody--against CD40 molecule and its function in DCs and BCL1 cell line are compared. DCs were separated from mouse spleen and then cultured in vitro using Lipofectamine 2000 to deliver both silencers; the efficacy of transfection was estimated by flow cytometry. mRNA expression and protein synthesis were assessed by real time-PCR and flow cytometry, respectively. By Annexin V and propidium iodine staining, we could evaluate the viability of transfected cells. Knocking down the CD40 gene into separate groups of DCs by siRNA, antisense, and blocking antibody treated DCs can cause an increase in IL-4, decrease in IL-12, IFN-γ production, and allostimulation activity. Our results indicated that, in comparison to antisense and blocking antibody, siRNAs appear to be quantitatively more efficient in CD40 downregulation and their differences are significant.

  16. Technetium-99m labeled antisense probes uptake in vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Zhang, Y.X.; Qin, G.M.; An, R.; Cao, G.X.; Cao, W.; Gao, Z.R.

    2002-01-01

    In the arterial wall, smooth muscle cells (SMC) normally exist in a quiescent, differentiated state, representing the contractile phenotype. During the development of atherosclerosis SMC change towards the synthetic phenotype going along with proliferation, chemotactic response and increased monocyte binding. The Fas/Fas ligand/caspase death-signaling pathway, Bcl-2 protein family/mitochondria, the tumor suppressive gene p53, and the proto-oncogene c-myc may be activated in atherosclerotic lesions, and mediates vascular apoptosis during the development of atherosclerosis. The atherosclerotic plaques contained 3-4 fold more c-myc mRNA than those in the normal aortic arteries, while increased Bax and Bak coupled with lack/paucity of Bcl-2 and Bcl-xL are associated with SMC apoptosis in advanced lesions. 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. Cell uptake studies: 99m Tc- MAG 3 -DNA radioactivity incorporation into porcine coronary smooth muscle cells in the log and plateau phases, respectively, was determined after different times of incubation at 37. The influence of extracellular 99m Tc- MAG 3 -DNA concentration on SMC uptake was also analyzed. [Results] Essentially complete conjugation was achieved by reverse-phase Sep-Pak C18 chromatography analysis. The MAG 3 -DNA was labeled with 99m Tc at room temperature and neutral pH, with a mean labeling efficiency of 80.11%(s.d=2.96%,n=4). The labeled antisense DNA still remained the ability to hybridize with its complementary DNA. After labeling, the stability of the DNA in saline or serum was retained as determined by reverse-phase Sep-Pak C18 chromatography analysis, except a shift at 30 min in serum incubation that suggesting a short time serum protein binding. 99m Tc-MAG 3 -c-myc uptake plateaued at 60 min and was directly proportional to the

  17. Calcium ions effectively enhance the effect of antisense peptide nucleic acids conjugated to cationic tat and oligoarginine peptides

    DEFF Research Database (Denmark)

    Shiraishi, Takehiko; Pankratova, Stanislava; Nielsen, Peter E

    2005-01-01

    Cell-penetrating peptides have been widely used to improve cellular delivery of a variety of proteins and antisense agents. However, recent studies indicate that such cationic peptides are predominantly entering cells via an endosomal pathway. We now show that the nuclear antisense effect in He......La cells of a variety of peptide nucleic acid (PNA) peptide conjugates is significantly enhanced by addition of 6 mM Ca(2+) (as well as by the lysosomotrophic agent chloroquine). In particular, the antisense activities of Tat(48-60) and heptaarginine-conjugated PNAs were increased 44-fold and 8.5-fold......, respectively. Evidence is presented that the mechanism involves endosomal release. The present results show that Ca(2+) can be used as an effective enhancer for in vitro cellular delivery of cationic peptide-conjugated PNA oligomers, and also emphasize the significance of the endosomal escape route...

  18. Antisense expression of a gene encoding a calcium-binding protein ...

    Indian Academy of Sciences (India)

    PRAKASH

    using the transgenic approach. The transformation of ... methods using EhCaBP or AtCaM3 gene-specific primers in ... acetone) was added, mixed and incubated for 15–18 h in the dark at .... as expected from the design of the AtCaM3 antisense construct .... Thus, there seems to be a positive qualitative correlation between ...

  19. A Simple Three-Step Method for Design and Affinity Testing of New Antisense Peptides: An Example of Erythropoietin

    OpenAIRE

    Štambuk, Nikola; Manojlović, Zoran; Turčić, Petra; Martinić, Roko; Konjevoda, Paško; Weitner, Tin; Wardega, Piotr; Gabričević, Mario

    2014-01-01

    Antisense peptide technology is a valuable tool for deriving new biologically active molecules and performing peptide–receptor modulation. It is based on the fact that peptides specified by the complementary (antisense) nucleotide sequences often bind to each other with a higher specificity and efficacy. We tested the validity of this concept on the example of human erythropoietin, a well-characterized and pharmacologically relevant hematopoietic growth factor. The purpose of the work was to ...

  20. Antisense repression of sucrose phosphate synthase in transgenic muskmelon alters plant growth and fruit development

    International Nuclear Information System (INIS)

    Tian, Hongmei; Ma, Leyuan; Zhao, Cong; Hao, Hui; Gong, Biao; Yu, Xiyan; Wang, Xiufeng

    2010-01-01

    To unravel the roles of sucrose phosphate synthase (SPS) in muskmelon (Cucumis melo L.), we reduced its activity in transgenic muskmelon plants by an antisense approach. For this purpose, an 830 bp cDNA fragment of muskmelon sucrose phosphate synthase was expressed in antisense orientation behind the 35S promoter of the cauliflower mosaic virus. The phenotype of the antisense plants clearly differed from that of control plants. The transgenic plant leaves were markedly smaller, and the plant height and stem diameter were obviously shorter and thinner. Transmission electron microscope observation revealed that the membrane degradation of chloroplast happened in transgenic leaves and the numbers of grana and grana lamella in the chloroplast were significantly less, suggesting that the slow growth and weaker phenotype of transgenic plants may be due to the damage of the chloroplast ultrastructure, which in turn results in the decrease of the net photosynthetic rate. The sucrose concentration and levels of sucrose phosphate synthase decreased in transgenic mature fruit, and the fruit size was smaller than the control fruit. Together, our results suggest that sucrose phosphate synthase may play an important role in regulating the muskmelon plant growth and fruit development.

  1. Antisense repression of sucrose phosphate synthase in transgenic muskmelon alters plant growth and fruit development

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Hongmei; Ma, Leyuan; Zhao, Cong; Hao, Hui; Gong, Biao [College of Horticulture Science and Engineering, State Key Laboratory of Crop Biology, Shandong Agricultural University, Tai' an, Shandong 271018 (China); Yu, Xiyan, E-mail: yuxiyan@sdau.edu.cn [College of Horticulture Science and Engineering, State Key Laboratory of Crop Biology, Shandong Agricultural University, Tai' an, Shandong 271018 (China); Wang, Xiufeng, E-mail: xfwang@sdau.edu.cn [College of Horticulture Science and Engineering, State Key Laboratory of Crop Biology, Shandong Agricultural University, Tai' an, Shandong 271018 (China)

    2010-03-12

    To unravel the roles of sucrose phosphate synthase (SPS) in muskmelon (Cucumis melo L.), we reduced its activity in transgenic muskmelon plants by an antisense approach. For this purpose, an 830 bp cDNA fragment of muskmelon sucrose phosphate synthase was expressed in antisense orientation behind the 35S promoter of the cauliflower mosaic virus. The phenotype of the antisense plants clearly differed from that of control plants. The transgenic plant leaves were markedly smaller, and the plant height and stem diameter were obviously shorter and thinner. Transmission electron microscope observation revealed that the membrane degradation of chloroplast happened in transgenic leaves and the numbers of grana and grana lamella in the chloroplast were significantly less, suggesting that the slow growth and weaker phenotype of transgenic plants may be due to the damage of the chloroplast ultrastructure, which in turn results in the decrease of the net photosynthetic rate. The sucrose concentration and levels of sucrose phosphate synthase decreased in transgenic mature fruit, and the fruit size was smaller than the control fruit. Together, our results suggest that sucrose phosphate synthase may play an important role in regulating the muskmelon plant growth and fruit development.

  2. Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humans.

    Science.gov (United States)

    Graham, Mark J; Lee, Richard G; Bell, Thomas A; Fu, Wuxia; Mullick, Adam E; Alexander, Veronica J; Singleton, Walter; Viney, Nick; Geary, Richard; Su, John; Baker, Brenda F; Burkey, Jennifer; Crooke, Stanley T; Crooke, Rosanne M

    2013-05-24

    Elevated plasma triglyceride levels have been recognized as a risk factor for the development of coronary heart disease. Apolipoprotein C-III (apoC-III) represents both an independent risk factor and a key regulatory factor of plasma triglyceride concentrations. Furthermore, elevated apoC-III levels have been associated with metabolic syndrome and type 2 diabetes mellitus. To date, no selective apoC-III therapeutic agent has been evaluated in the clinic. To test the hypothesis that selective inhibition of apoC-III with antisense drugs in preclinical models and in healthy volunteers would reduce plasma apoC-III and triglyceride levels. Rodent- and human-specific second-generation antisense oligonucleotides were identified and evaluated in preclinical models, including rats, mice, human apoC-III transgenic mice, and nonhuman primates. We demonstrated the selective reduction of both apoC-III and triglyceride in all preclinical pharmacological evaluations. We also showed that inhibition of apoC-III was well tolerated and not associated with increased liver triglyceride deposition or hepatotoxicity. A double-blind, placebo-controlled, phase I clinical study was performed in healthy subjects. Administration of the human apoC-III antisense drug resulted in dose-dependent reductions in plasma apoC-III, concomitant lowering of triglyceride levels, and produced no clinically meaningful signals in the safety evaluations. Antisense inhibition of apoC-III in preclinical models and in a phase I clinical trial with healthy subjects produced potent, selective reductions in plasma apoC-III and triglyceride, 2 known risk factors for cardiovascular disease. This compelling pharmacological profile supports further clinical investigations in hypertriglyceridemic subjects.

  3. Extensive polycistronism and antisense transcription in the mammalian Hox clusters.

    Directory of Open Access Journals (Sweden)

    Gaëll Mainguy

    Full Text Available The Hox clusters play a crucial role in body patterning during animal development. They encode both Hox transcription factor and micro-RNA genes that are activated in a precise temporal and spatial sequence that follows their chromosomal order. These remarkable collinear properties confer functional unit status for Hox clusters. We developed the TranscriptView platform to establish high resolution transcriptional profiling and report here that transcription in the Hox clusters is far more complex than previously described in both human and mouse. Unannotated transcripts can represent up to 60% of the total transcriptional output of a cluster. In particular, we identified 14 non-coding Transcriptional Units antisense to Hox genes, 10 of which (70% have a detectable mouse homolog. Most of these Transcriptional Units in both human and mouse present conserved sizeable sequences (>40 bp overlapping Hox transcripts, suggesting that these Hox antisense transcripts are functional. Hox clusters also display at least seven polycistronic clusters, i.e., different genes being co-transcribed on long isoforms (up to 30 kb. This work provides a reevaluated framework for understanding Hox gene function and dys-function. Such extensive transcriptions may provide a structural explanation for Hox clustering.

  4. Novel Oxidative Desulfurization of a Model Fuel with H2O2 Catalyzed by AlPMo12O40 under Phase Transfer Catalyst-Free Conditions

    OpenAIRE

    José da Silva, Márcio; Faria dos Santos, Lidiane

    2013-01-01

    A novel process was developed for oxidative desulfurization (ODS) in the absence of a phase transfer catalyst (PTC) using only Keggin heteropolyacids and their aluminum salts as catalysts. Reactions were performed in biphasic mixtures of isooctane/acetonitrile, with dibenzothiophene (DBT) as a model sulfur compound and hydrogen peroxide as the oxidant. Remarkably, only the AlPMo12O40-catalyzed reactions resulted in complete oxidation of DBT into DBT sulfone, which was totally extracted by ace...

  5. Potent Antibacterial Antisense Peptide-Peptide Nucleic Acid Conjugates Against Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Ghosal, Anubrata; Nielsen, Peter E

    2012-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen causing severe infections in hospital settings, especially with immune compromised patients, and the increasing prevalence of multidrug resistant strains urges search for new drugs with novel mechanisms of action. In this study we introduce...... significantly reduced bacterial survival. These results open the possibility of development of antisense antibacterials for treatment of Pseudomonas infections....

  6. Antisense-mediated suppression of C-hordein biosynthesis in the barley grain results in correlated changes in the transcriptome, protein profile, and amino acid composition

    DEFF Research Database (Denmark)

    Hansen, Mette; Lange, Marianne; Friis, Carsten

    2007-01-01

    Antisense- or RNAi-mediated suppression of the biosynthesis of nutritionally inferior storage proteins is a promising strategy for improving the amino acid profile of seeds. However, the potential pleiotropic effects of this on interconnected pathways and the agronomic quality traits need...... to be addressed. In the current study, a transcriptomic analysis of an antisense C-hordein line of barley was performed, using a grain-specific cDNA array. The C-hordein antisense line is characterized by marked changes in storage protein and amino acid profiles, while the seed weight is within the normal range...... and no external morphological irregularities were observed. The results of the transcriptome analysis showed excellent correlation with data on changes in the relative proportions of storage proteins and amino acid composition. The antisense line had a lower C-hordein level and down-regulated transcript encoding...

  7. Effective Liquid-phase Nitration of Benzene Catalyzed by a Stable Solid Acid Catalyst: Silica Supported Cs{sub 2.5}H{sub 0.5}PMo{sub 12}O{sub 40}

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Shu-wen; Liu, Li-jun; Zhang, Qian; Wang, Liang-yin [Liaocheng University, Liaocheng (China)

    2012-04-15

    Silica supported Cs{sub 2.5}H{sub 0.5}PMo{sub 12}O{sub 40} catalyst was prepared through sol-gel method with ethyl silicate-40 as silicon resource and characterized by X-ray diffraction, infrared spectroscopy, scanning electron microscopy, nitrogen adsorption-desorption and potentiometric titration methods. The Cs{sub 2.5}H{sub 0.5}PMo{sub 12}O{sub 40} particles with Keggin-type structure well dispersed on the surface of silica, and the catalyst exhibited high surface area and acidity. The catalytic performance of the catalysts for benzene liquid-phase nitration was examined with 65% nitric acid as nitrating agent, and the effects of various parameters were tested, which including temperature, time and amount of catalyst, reactants ratio, especially the recycle of catalyst was emphasized. Benzene was effectively nitrated to mononitro-benzene with high conversion (95%) in optimized conditions. Most importantly, the supported catalyst was proved has excellent stability in the nitration progress, and there were no any other organic solvent and sulfuric acid were used in the reaction system, so the liquid-phase nitration of benzene that we developed was an eco-friendly and attractive alternative for the commercial technology

  8. 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...

  9. 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.

  10. Cell number and transfection volume dependent peptide nucleic acid antisense activity by cationic delivery methods

    DEFF Research Database (Denmark)

    Llovera Nadal, Laia; Berthold, Peter; Nielsen, Peter E

    2012-01-01

    have now quantitatively compared the cellular activity (in the pLuc705 HeLa cell splice correction system) of PNA antisense oligomers using lipoplex delivery of cholesterol- and bisphosphonate-PNA conjugates, polyplex delivery via a PNA-polyethyleneimine conjugate and CPP delivery via a PNA......Efficient intracellular delivery is essential for high activity of nucleic acids based therapeutics, including antisense agents. Several strategies have been developed and practically all rely on auxiliary transfection reagents such as cationic lipids, cationic polymers and cell penetrating...... peptides as complexing agents and carriers of the nucleic acids. However, uptake mechanisms remain rather poorly understood, and protocols always require optimization of transfection parameters. Considering that cationic transfection complexes bind to and thus may up-concentrate on the cell surface, we...

  11. Thiolated carboxymethyl dextran as a nanocarrier for colon delivery of hSET1 antisense: In vitro stability and efficiency study

    Energy Technology Data Exchange (ETDEWEB)

    Kiani, Melika, E-mail: Melika.kiani@gmail.com [Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran (Iran, Islamic Republic of); Mirzazadeh Tekie, Farnaz Sadat, E-mail: mirzazadehf@yahoo.com [Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran (Iran, Islamic Republic of); Dinarvand, Meshkat, E-mail: mdinarvand@hotmail.com [Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran (Iran, Islamic Republic of); Soleimani, Masoud, E-mail: soleim_m@modares.ac.ir [Stem Cell Technology Research Centre, P.O. Box 14155-3174, Tehran (Iran, Islamic Republic of); Department of Hematology, School of Medical Sciences, Tarbiat Modares University, P.O. Box: 14115-111, Tehran (Iran, Islamic Republic of); Dinarvand, Rassoul, E-mail: dinarvand@tums.ac.ir [Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran (Iran, Islamic Republic of); Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Atyabi, Fatemeh, E-mail: atyabifa@tums.ac.ir [Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran (Iran, Islamic Republic of); Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2016-05-01

    Gene therapy is an optimistic approach in cancer treatment. However, for efficient delivery of gene materials, designing an appropriate vector is necessary. Polyelectrolyte complexes (PECs) of chitosan and dextran could be considered a proper nanoparticulate carrier for sensitive biomaterials. In this study, PECs of chitosan and thiolated dextran were used as either an injectable or oral gene delivery system. hSET1 antisense was loaded into the PECs to suppress proliferation of colon cancer cell line. The prepared nanoparticles have ~ 115 nm diameter size and positive zeta potential with high mucoadhesion properties. They are able to protect antisense from degradation in serum and biorelevant fluids (FaSSIF and FaSSGF). Furthermore, prepared nanoparticles demonstrated superior cellular penetration and inhibitory effect on SW480 colon cancer cell proliferation. All nanoparticles significantly down regulated hSET1 in comparison with naked antisense. It can be concluded that thiolated PECs have potential use for injectable or oral delivery of nucleic acids such as antisense. - Highlights: • Formation of stable nanoparticle with dextran and chitosan derivatives for oral and intravenous gene delivery. • Satifactory cellular uptake of nanoparticles and approximately complete suppression of hSET1 expression in SW480 cell lines • Prolonged stability of nanoparticles against biorelevent media with desirable release rate.

  12. Thiolated carboxymethyl dextran as a nanocarrier for colon delivery of hSET1 antisense: In vitro stability and efficiency study

    International Nuclear Information System (INIS)

    Kiani, Melika; Mirzazadeh Tekie, Farnaz Sadat; Dinarvand, Meshkat; Soleimani, Masoud; Dinarvand, Rassoul; Atyabi, Fatemeh

    2016-01-01

    Gene therapy is an optimistic approach in cancer treatment. However, for efficient delivery of gene materials, designing an appropriate vector is necessary. Polyelectrolyte complexes (PECs) of chitosan and dextran could be considered a proper nanoparticulate carrier for sensitive biomaterials. In this study, PECs of chitosan and thiolated dextran were used as either an injectable or oral gene delivery system. hSET1 antisense was loaded into the PECs to suppress proliferation of colon cancer cell line. The prepared nanoparticles have ~ 115 nm diameter size and positive zeta potential with high mucoadhesion properties. They are able to protect antisense from degradation in serum and biorelevant fluids (FaSSIF and FaSSGF). Furthermore, prepared nanoparticles demonstrated superior cellular penetration and inhibitory effect on SW480 colon cancer cell proliferation. All nanoparticles significantly down regulated hSET1 in comparison with naked antisense. It can be concluded that thiolated PECs have potential use for injectable or oral delivery of nucleic acids such as antisense. - Highlights: • Formation of stable nanoparticle with dextran and chitosan derivatives for oral and intravenous gene delivery. • Satifactory cellular uptake of nanoparticles and approximately complete suppression of hSET1 expression in SW480 cell lines • Prolonged stability of nanoparticles against biorelevent media with desirable release rate.

  13. Molecular characterization of a stable antisense chalcone synthase phenotype in strawberry (Fragaria ananassa)

    NARCIS (Netherlands)

    Lunkenbein, S.; Coiner, H.; Vos, de C.H.; Schaart, J.G.; Boone, M.J.; Krens, F.A.; Schwab, W.; Salentijn, E.M.J.

    2006-01-01

    An octaploid (Fragaria × ananassa cv. Calypso) genotype of strawberry was transformed with an antisense chalcone synthase (CHS) gene construct using a ripening related CHS cDNA from Fragaria × ananassa cv. Elsanta under the control of the constitutive CaMV 35S promoter via Agrobacterium tumefaciens.

  14. Functional Analysis of Polyphenol Oxidases by Antisense/Sense Technology

    Directory of Open Access Journals (Sweden)

    Jutharat Attajarusit

    2007-07-01

    Full Text Available Polyphenol oxidases (PPOs catalyze the oxidation of phenolics to quinones, the secondary reactions of which lead to oxidative browning and postharvest losses of many fruits and vegetables. PPOs are ubiquitous in angiosperms, are inducible by both biotic and abiotic stresses, and have been implicated in several physiological processes including plant defense against pathogens and insects, the Mehler reaction, photoreduction of molecular oxygen by PSI, regulation of plastidic oxygen levels, aurone biosynthesis and the phenylpropanoid pathway. Here we review experiments in which the roles of PPO in disease and insect resistance as well as in the Mehler reaction were investigated using transgenic tomato (Lycopersicon esculentum plants with modified PPO expression levels (suppressed PPO and overexpressing PPO. These transgenic plants showed normal growth, development and reproduction under laboratory, growth chamber and greenhouse conditions. Antisense PPO expression dramatically increased susceptibility while PPO overexpression increased resistance of tomato plants to Pseudomonas syringae. Similarly, PPO-overexpressing transgenic plants showed an increase in resistance to various insects, including common cutworm (Spodoptera litura (F., cotton bollworm (Helicoverpa armigera (Hübner and beet army worm (Spodoptera exigua (Hübner, whereas larvae feeding on plants with suppressed PPO activity had higher larval growth rates and consumed more foliage. Similar increases in weight gain, foliage consumption, and survival were also observed with Colorado potato beetles (Leptinotarsa decemlineata (Say feeding on antisense PPO transgenic tomatoes. The putative defensive mechanisms conferred by PPO and its interaction with other defense proteins are discussed. In addition, transgenic plants with suppressed PPO exhibited more favorable water relations and decreased photoinhibition compared to nontransformed controls and transgenic plants

  15. Sense and antisense transcripts of the developmentally regulated murine hsp70.2 gene are expressed in distinct and only partially overlapping areas in the adult brain

    Science.gov (United States)

    Murashov, A. K.; Wolgemuth, D. J.

    1996-01-01

    We have examined the spatial pattern of expression of a member of the hsp70 gene family, hsp70.2, in the mouse central nervous system. Surprisingly, RNA blot analysis and in situ hybridization revealed abundant expression of an 'antisense' hsp70.2 transcript in several areas of adult mouse brain. Two different transcripts recognized by sense and antisense riboprobes for the hsp70.2 gene were expressed in distinct and only partially overlapping neuronal populations. RNA blot analysis revealed low levels of the 2.7 kb transcript of hsp70.2 in several areas of the brain, with highest signal in the hippocampus. Abundant expression of a slightly larger (approximately 2.8 kb) 'antisense' transcript was detected in several brain regions, notably in the brainstem, cerebellum, mesencephalic tectum, thalamus, cortex, and hippocampus. In situ hybridization revealed that the sense and antisense transcripts were both predominantly neuronal and localized to the same cell types in the granular layer of the cerebellum, trapezoid nucleus of the superior olivary complex, locus coeruleus and hippocampus. The hsp70.2 antisense transcripts were particularly abundant in the frontal cortex, dentate gyrus, subthalamic nucleus, zona incerta, superior and inferior colliculi, central gray, brainstem, and cerebellar Purkinje cells. Our findings have revealed a distinct cellular and spatial localization of both sense and antisense transcripts, demonstrating a new level of complexity in the function of the heat shock genes.

  16. Anti-sense suppression of epidermal growth factor receptor expression alters cellular proliferation, cell-adhesion and tumorigenicity in ovarian cancer cells.

    Science.gov (United States)

    Alper, O; De Santis, M L; Stromberg, K; Hacker, N F; Cho-Chung, Y S; Salomon, D S

    2000-11-15

    Over-expression of epidermal growth factor receptor (EGFR) in ovarian cancer has been well documented. Human NIH:OVCAR-8 ovarian carcinoma cells were transfected with an expression vector containing the anti-sense orientation of truncated human EGFR cDNA. EGFR anti-sense over-expression resulted in decreased EGFR protein and mRNA expression, cell proliferation and tumor formation in nude mice. In accordance with the reduced levels of EGFR in EGFR anti-sense-expressing cells, tyrosine phosphorylation of EGFR was decreased compared to untransfected parental cells treated with EGF. In EGFR anti-sense-transfected cells, expression of erbB-3, but not erbB-2, was increased. In addition, basal and heregulin-beta 1-stimulated tyrosine phosphorylation of erbB-3 was higher in EGFR anti-sense vector-transfected cells. A morphological alteration in EGFR anti-sense gene-expressing cells was correlated with a decrease in the expression of E-cadherin, alpha-catenin and, to a lesser extent, beta-catenin. Changes in the expression of these proteins were associated with a reduction in complex formation among E-cadherin, beta-catenin and alpha-catenin and between beta-catenin and EGFR in EGFR anti-sense-expressing cells compared to sense-transfected control cells. These results demonstrate that EGFR expression in ovarian carcinoma cells regulates expression of cell adhesion proteins that may enhance cell growth and invasiveness. Copyright 2000 Wiley-Liss, Inc.

  17. Preliminary studies on gene therapy with TGF β1 antisense gene/liposome complexes and adenovirus transfer vector in RPF rats

    International Nuclear Information System (INIS)

    Liu Chunjie; Wang Dewen; Zhang Zhaoshan; Gao Yabing; Xiong Chengqi; Long Jianyin; Wang Huixin; Peng Ruiyun; Cui Xuemei

    2001-01-01

    Objective: To observed the efficiency of gene therapy with TGF β1 antisense gene/liposome complexes and adenovirus transfer vector in RPF rats. Methods: TGFβ1 sense and antisense gene expression vectors and adenovirus transfer vector were introduced into rat bronchus by way of intratracheal instillation. Results: At day 1.5 after TGFβ1 sense and antisense gene transfer, PCR amplification using neo gene-specific primer from lung tissue DNA was all positive. After day 5.5, 67% (2/3) of lung tissue DNA was positive. RNA dot blot hybridization indicated that TGFβ1 mRNA content of lung tissue transfected with pMAMneo-antiTGFβ1 gene decreased. Detection of lung hydroxyproline (Hyp) content after day 35 of gene transfer showed that even in lung of rats received pMAMneo-AntiTGFβ1 lipid complexes it raised remarkably (P 9 pfu/ml were instilled into bronchus at 0.5 ml per rat. After day 2 day 6, the lung tissues of all six rats (three per each group )expressed the transfected luciferase gene by luminometer. Conclusion: Cationic lipid-mediated TGFβ1 antisense gene therapy was a simple and easy method. It can slow down the course of pathogenesis of lung fibrosis. Replication-deficient recombinant adenovirus-mediated gene therapy of lung diseases is a good and efficient method

  18. Combination of vascular endothelial growth factor antisense oligonucleotide therapy and radiotherapy increases the curative effects against maxillofacial VX2 tumors in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Zheng Linfeng, E-mail: zhenglinfeng04@yahoo.com.cn [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Li Yujie, E-mail: yujieli01@yahoo.com.cn [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Wang Han, E-mail: bingowh@hotmail.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Zhao Jinglong, E-mail: jinglongz@yahoo.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Wang Xifu, E-mail: wangxiechen001@163.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Hu Yunsheng, E-mail: springmorninghu@163.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Zhang Guixiang, E-mail: guixiangzhang@sina.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China)

    2011-05-15

    Purpose: To study the effects of combination of vascular endothelial growth factor (VEGF) antisense oligonucleotide therapy and radiotherapy on maxillofacial VX2 tumors in rabbits. Methods: We used 24 New Zealand white rabbits as a model to induce maxillofacial VX2 tumor. The rabbits were randomly divided into the following 4 groups: radiotherapy group (group A), treated with 16 Gy of radiotherapy; VEGF antisense oligonucleotide treatment group (group B), treated with an injection of 150 {mu}g of VEGF antisense oligonucleotide into the local tumor; VEGF antisense oligonucleotide combined with radiotherapy group (group C), treated with an injection of 150 {mu}g of VEGF antisense oligonucleotide into the local tumor immediately after 16 Gy of radiotherapy; and control group (group D), treated with an injection of 300 {mu}l 5% aqueous glucose solution into the local tumor. On days 3 and 14 after treatment, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed to calculate maximal enhancement ratio (MER), slope of enhancement (SLE), and tumor volume change. Rabbits were killed on day 14 to obtain samples for pathological examination and immunohistochemical staining for VEGF. Results: In group C, tumor volume was significantly reduced on day 14 after treatment, and the difference was statistically different as compared to that before treatment, on day 3 after treatment and other groups (P < 0.01). Values of both MER and SLE after treatment were significantly lower than the values before treatment (P < 0.05). Pathological specimen revealed tumor cell edema, bleeding, necrosis, vascular wall thickening and occlusion, and decreased VEGF expression. The immunohistochemical score (IHS) of group C was significantly different from groups A and D respectively (P < 0.05). Conclusion: Injecting the tumor with VEGF antisense oligonucleotide immediately after radiotherapy can enhance the curative effect on rabbit maxillofacial VX2 tumor, and DCE-MRI can serve

  19. Metabolite profiling of Arabidopsis thaliana (L.) plants transformed with an antisense chalcone synthase gene

    DEFF Research Database (Denmark)

    Le Gall, G.; Metzdorff, Stine Broeng; Pedersen, Jan W.

    2005-01-01

    A metabolite profiling study has been carried out on Arabidopsis thaliana (L.) Heynh. ecotype Wassilewskija and a series of transgenic lines of the ecotype transformed with a CHS (chalcone synthase) antisense construct. Compound identifications by LC/MS and H-1 NMR are discussed. The glucosinolate...

  20. Morpholino oligomer-mediated exon skipping averts the onset of dystrophic pathology in the mdx mouse.

    Science.gov (United States)

    Fletcher, Sue; Honeyman, Kaite; Fall, Abbie M; Harding, Penny L; Johnsen, Russell D; Steinhaus, Joshua P; Moulton, Hong M; Iversen, Patrick L; Wilton, Stephen D

    2007-09-01

    Duchenne and Becker muscular dystrophies are allelic disorders arising from mutations in the dystrophin gene. Duchenne muscular dystrophy is characterized by an absence of functional protein, whereas Becker muscular dystrophy, commonly caused by in-frame deletions, shows synthesis of partially functional protein. Anti-sense oligonucleotides can induce specific exon removal during processing of the dystrophin primary transcript, while maintaining or restoring the reading frame, and thereby overcome protein-truncating mutations. The mdx mouse has a non-sense mutation in exon 23 of the dystrophin gene that precludes functional dystrophin production, and this model has been used in the development of treatment strategies for dystrophinopathies. A phosphorodiamidate morpholino oligomer (PMO) has previously been shown to exclude exon 23 from the dystrophin gene transcript and induce dystrophin expression in the mdxmouse, in vivo and in vitro. In this report, a cell-penetrating peptide (CPP)-conjugated oligomer targeted to the mouse dystrophin exon 23 donor splice site was administered to mdxmice by intraperitoneal injection. We demonstrate dystrophin expression and near-normal muscle architecture in all muscles examined, except for cardiac muscle. The CPP greatly enhanced uptake of the PMO, resulting in widespread dystrophin expression.

  1. Inhaled ENaC antisense oligonucleotide ameliorates cystic fibrosis-like lung disease in mice.

    Science.gov (United States)

    Crosby, Jeff R; Zhao, Chenguang; Jiang, Chong; Bai, Dong; Katz, Melanie; Greenlee, Sarah; Kawabe, Hiroshi; McCaleb, Michael; Rotin, Daniela; Guo, Shuling; Monia, Brett P

    2017-11-01

    Epithelial sodium channel (ENaC, Scnn1) hyperactivity in the lung leads to airway surface dehydration and mucus accumulation in cystic fibrosis (CF) patients and in mice with CF-like lung disease. We identified several potent ENaC specific antisense oligonucleotides (ASOs) and tested them by inhalation in mouse models of CF-like lung disease. The inhaled ASOs distributed into lung airway epithelial cells and decreased ENaC expression by inducing RNase H1-dependent degradation of the targeted Scnn1a mRNA. Aerosol delivered ENaC ASO down-regulated mucus marker expression and ameliorated goblet cell metaplasia, inflammation, and airway hyper-responsiveness. Lack of systemic activity of ASOs delivered via the aerosol route ensures the safety of this approach. Our results demonstrate that antisense inhibition of ENaC in airway epithelial cells could be an effective and safe approach for the prevention and reversal of lung symptoms in CF and potentially other inflammatory diseases of the lung. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  2. Conserved alternative and antisense transcripts at the programmed cell death 2 locus

    Czech Academy of Sciences Publication Activity Database

    Mihola, Ondřej; Forejt, Jiří; Trachtulec, Zdeněk

    2007-01-01

    Roč. 8, - (2007), s. 20 ISSN 1471-2164 R&D Projects: GA ČR(CZ) GA204/01/0997; GA ČR GA301/05/0738; GA AV ČR IAA5052406; GA MŠk(CZ) 1M0520 Institutional research plan: CEZ:AV0Z50520514 Keywords : Pdcd2 * antisense * alternative transcript * imprinting Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.180, year: 2007

  3. G3139, a Bcl-2 antisense oligodeoxynucleotide, induces clinical responses in VAD refractory myeloma

    NARCIS (Netherlands)

    van de Donk, N. W. C. J.; de Weerdt, O.; Veth, G.; Eurelings, M.; van Stralen, E.; Frankel, S. R.; Hagenbeek, A.; Bloem, A. C.; Lokhorst, H. M.

    2004-01-01

    Expression of Bcl-2 in multiple myeloma is associated with resistance to chemotherapeutic drugs. Conversely, suppression of Bcl-2 enhanced the chemosensitivity of myeloma cells in vitro. G3139 is an antisense oligodeoxynucleotide targeted to the first six codons of the Bcl-2 mRNA open reading frame.

  4. Physicochemical and biological properties of self-assembled antisense/poly(amidoamine dendrimer nanoparticles: the effect of dendrimer generation and charge ratio

    Directory of Open Access Journals (Sweden)

    Alireza Nomani

    2010-05-01

    Full Text Available Alireza Nomani1,6, Ismaeil Haririan1,5, Ramin Rahimnia2,4, Shamileh Fouladdel2, Tarane Gazori1, Rassoul Dinarvand1, Yadollah Omidi3, Ebrahim Azizi2,41Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 2Molecular Research Lab, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 3Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; 4Department of Medical Biotechnology, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran; 5Biomaterials Research Center (BRC Tehran, Iran; 6Department of Pharmaceutics, Faculty of Pharmacy, Zanjan University of Medical Sciences, Zanjan, IranAbstract: To gain a deeper understanding of the physicochemical phenomenon of self-assembled nanoparticles of different generations and ratios of poly (amidoamine dendrimer (PAMAM dendrimer and a short-stranded DNA (antisense oligonucleotide, multiple methods were used to characterize these nanoparticles including photon correlation spectroscopy (PCS; zeta potential measurement; and atomic force microscopy (AFM. PCS and AFM results revealed that, in contrast to larger molecules of DNA, smaller molecules produce more heterodisperse and large nanoparticles when they are condensed with a cationic dendrimer. AFM images also showed that such nanoparticles were spherical. The stability of the antisense content of the nanoparticles was investigated over different charge ratios using polyacrylamide gel electrophoresis. It was clear from such analyses that much more than charge neutrality point was required to obtain stable nanoparticles. For cell uptake, self-assembled nanoparticles were prepared with PAMAM G5 and 5’-FITC labeled antisense and the uptake experiment was carried out in T47D cell culture. This investigation also shows that the cytotoxicity of the nanoparticles was

  5. Antisense to the glucocorticoid receptor in hippocampal dentate gyrus reduces immobility in forced swim test

    NARCIS (Netherlands)

    Korte, S.M.; de Kloet, E.R.; Buwalda, B; Bouman, S.D.; Bohus, B

    1996-01-01

    Immobility time of rats in the forced swim test was reduced after bilateral infusion of an 18-mer antisense phosphorothioate oligodeoxynucleotide targeted to the glucocorticoid receptor mRNA into the dentate gyrus of the hippocampus. Vehicle-, sense- and scrambled sequence-treated animals spent

  6. Nanoparticle for delivery of antisense γPNA oligomers targeting CCR5

    OpenAIRE

    Bahal, Raman; McNeer, Nicole Ali; Ly, Danith H.; Saltzman, W. Mark; Glazer, Peter M.

    2013-01-01

    The development of a new class of peptide nucleic acids (PNAs), i.e., gamma PNAs (γPNAs), creates the need for a general and effective method for its delivery into cells for regulating gene expression in mammalian cells. Here we report the antisense activity of a recently developed hydrophilic and biocompatible diethylene glycol (miniPEG)-based gamma peptide nucleic acid called MPγPNAs via its delivery by poly(lactide-co-glycolide) (PLGA)-based nanoparticle system. We show that MPγPNA oligome...

  7. Diversity of antisense and other non-coding RNAs in Archaea revealed by comparative small RNA sequencing in four Pyrobaculum species

    Directory of Open Access Journals (Sweden)

    David L Bernick

    2012-07-01

    Full Text Available A great diversity of small, non-coding RNA molecules with roles in gene regulation and RNA processing have been intensely studied in eukaryotic and bacterial model organisms, yet our knowledge of possible parallel roles for small RNAs in archaea is limited. We employed RNA-seq to identify novel small RNA across multiple species of the hyperthermophilic genus Pyrobaculum, known for unusual RNA gene characteristics. By comparing transcriptional data collected in parallel among four species, we were able to identify conserved RNA genes fitting into known and novel families. Among our findings, we highlight three novel cis-antisense small RNAs encoded opposite to key regulatory (ferric uptake regulator, metabolic (triose-phosphate isomerase, and core transcriptional apparatus genes (transcription factor B. We also found a large increase in the number of conserved C/D box small RNA genes over what had been previously recognized; many of these genes are encoded antisense to protein coding genes. The conserved opposition to orthologous genes across the Pyrobaculum genus suggests similarities to other cis-antisense regulatory systems. Furthermore, the genus-specific nature of these small RNAs indicates they are relatively recent, stable adaptations.

  8. Ring Theory

    CERN Document Server

    Jara, Pascual; Torrecillas, Blas

    1988-01-01

    The papers in this proceedings volume are selected research papers in different areas of ring theory, including graded rings, differential operator rings, K-theory of noetherian rings, torsion theory, regular rings, cohomology of algebras, local cohomology of noncommutative rings. The book will be important for mathematicians active in research in ring theory.

  9. Rapid blockade of telomerase activity and tumor cell growth by the DPL lipofection of ribbon antisense to hTR.

    Science.gov (United States)

    Bajpai, Arun K; Park, Jeong-Hoh; Moon, Ik-Jae; Kang, Hyungu; Lee, Yun-Han; Doh, Kyung-Oh; Suh, Seong-Il; Chang, Byeong-Churl; Park, Jong-Gu

    2005-09-29

    Ribbon antisense (RiAS) to the hTR RNA, a component of the telomerase complex, was employed to inhibit telomerase activity and cancer cell growth. The antisense molecule, hTR-RiAS, combined with enhanced cellular uptake was shown to effectively inhibit telomerase activity and cause rapid cell death in various cancer cell lines. When cancer cells were treated with hTR-RiAS, the level of hTR RNA was reduced by more than 90% accompanied with reduction in telomerase activity. When checked for cancer cell viability, cancer cell lines treated with hTR-RiAS using DNA+Peptide+Lipid complex showed 70-80% growth inhibition in 3 days. The reduced cell viability was due to apoptosis as the percentage of cells exhibiting the sub-G0 arrest and DNA fragmentation increased after antisense treatment. Further, when subcutaneous tumors of a colon cancer cell line (SW480) were treated intratumorally with hTR-RiAS, tumor growth was markedly suppressed with almost total ablation of hTR RNA in the tumor tissue. Cells in the tumor tissue were also found to undergo apoptosis after hTR-RiAS treatment. These results suggest that hTR-RiAS is an effective anticancer reagent, with a potential for broad efficacy to diverse malignant tumors.

  10. Report of the eRHIC Ring-Ring Working Group

    Energy Technology Data Exchange (ETDEWEB)

    Aschenauer, E. C. [Brookhaven National Lab. (BNL), Upton, NY (United States); Berg, S. [Brookhaven National Lab. (BNL), Upton, NY (United States); Blaskiewicz, M. [Brookhaven National Lab. (BNL), Upton, NY (United States); Brennan, M. [Brookhaven National Lab. (BNL), Upton, NY (United States); Fedotov, A. [Brookhaven National Lab. (BNL), Upton, NY (United States); Fischer, W. [Brookhaven National Lab. (BNL), Upton, NY (United States); Litvinenko, V. [Brookhaven National Lab. (BNL), Upton, NY (United States); Montag, C. [Brookhaven National Lab. (BNL), Upton, NY (United States); Palmer, R. [Brookhaven National Lab. (BNL), Upton, NY (United States); Parker, B. [Brookhaven National Lab. (BNL), Upton, NY (United States); Peggs, S. [Brookhaven National Lab. (BNL), Upton, NY (United States); Ptitsyn, V. [Brookhaven National Lab. (BNL), Upton, NY (United States); Ranjbar, V. [Brookhaven National Lab. (BNL), Upton, NY (United States); Tepikian, S. [Brookhaven National Lab. (BNL), Upton, NY (United States); Trbojevic, D. [Brookhaven National Lab. (BNL), Upton, NY (United States); Willeke, F. [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2015-10-13

    This report evaluates the ring-ring option for eRHIC as a lower risk alternative to the linac-ring option. The reduced risk goes along with a reduced initial luminosity performance. However, a luminosity upgrade path is kept open. This upgrade path consists of two branches, with the ultimate upgrade being either a ring-ring or a linac-ring scheme. The linac-ring upgrade could be almost identical to the proposed linac-ring scheme, which is based on an ERL in the RHIC tunnel. This linac-ring version has been studied in great detail over the past ten years, and its significant risks are known. On the other hand, no detailed work on an ultimate performance ring-ring scenario has been performed yet, other than the development of a consistent parameter set. Pursuing the ring-ring upgrade path introduces high risks and requires significant design work that is beyond the scope of this report.

  11. Influence of different chelators (HYNIC, MAG3 and DTPA) on tumor cell accumulation and mouse biodistribution of technetium-99m labeled to antisense DNA

    International Nuclear Information System (INIS)

    Zhang, Y.M.; Liu, N.; Zhu, Z.-H.; Rusckowski, M.; Hnatowich, D.J.

    2000-01-01

    We have shown recently that cell accumulation in culture of antisense DNA is strongly influenced by the presence of a 99m Tc-MAG 3 group for radiolabeling. We have now compared the in vitro and mouse in vivo behavior of 99m Tc when radiolabeled to one antisense phosphorothioate DNA by three different methods. The 18-mer antisense DNA against the RIα subunit of PKA was conjugated via a primary amine on the 5'-end with the NHS esters of HYNIC and MAG 3 and by the cyclic anhydride of DTPA. Surface plasmon resonance measurements revealed that the association rate constant for hybridization was unchanged for all three chelators as compared with that of the native DNA. Size exclusion HPLC showed rapid and quantitative protein binding for all three chelators upon incubation of labeled DNAs in 37 C serum and cell culture medium. However, in each case, radiolabeled and intact oligonucleotide was still detectable after 24 h. Cellular uptake was tested in an RIα mRNA-positive cancer cell line. The order of cellular accumulation of 99m Tc was DTPA>HYNIC(tricine)>MAG 3 , with the differences increasing with time between 4 and 24 h. The rate of 99m Tc egress from cells was found to be MAG 3 >HYNIC>DTPA, which may explain the order of cellular accumulation. The biodistribution in normal mice was heavily influenced by the labeling method and followed a pattern similar to that seen previously by us for peptides labeled with the same chelators. In conclusion, although these studies concerned only one antisense DNA in one cell line, the results suggest that the success of antisense imaging may depend, in part, on the method of radiolabeling. (orig.)

  12. Study on biodistribution and imaging of radioiodinated antisense oligonucleotides in nude mice bearing human lymphoma

    International Nuclear Information System (INIS)

    Wang, R.F.; Shen, J.; Zhang, C.L.; Liu, M.; Guo, F.Q.

    2005-01-01

    The incidence of sporadic lymphoma has risen due to an increase in immunosuppressed patients, particularly those with human immunodeficiency virus (HIV) infection. Sometimes suspect lymphoma has an undetectable location and we can not get the pathological specimen. Management of lymphoma is also difficult because the persistence of a significant number of residual tumor cells after intensive treatment. These relative failures can be attributed to make us choose this study for opening a new diagnostic and therapeutic field of lymphoma from molecular level. Immunoglobulin (Ig) heavy chain framework region (FR) of V1 family have been verified to be a major determinant of malignant phenotype of V1 family B-cell lymphoma. Most of targets for tumor antisense therapy study are protooncogenes, such as c-myc, bc1-2, which are broad -spectrum tumor imaging agents. The aim of this study was to investigate the possibility of using radioiodine labeled FR antisense oligonucleotides (ASONs) as an imaging agent or antisense therapeutic radiopharmaceutical in lymphoma. A 18-mer partial phosphorothioate oligonucleotide sequence was synthesized and grafted in 5 ' with a tyramine group which was further labeled with 125 I or 131 I using the chloramine T method. Normal CD-1 mice were injected via a tail vein with 148 kBq of 125 I-FR-ASON (2∼3 μ g). Animals were sacrificed at 1, 2, 4 and 24 h and tissue samples were studied. Liposome-mediated 3.33 MBq of 131 I-FR-ASON (7 ∼ 9μ g) was injected intratumorally into tumor-bearing BALB/c mice (6 weeks after inoculation of 10 7 Namalwa cells) meanwhile liposome-mediated 131 I labeled sense oligonucleotides served as controls. Biodistribution was monitored by sequential scintigraphy and organ radioactivity measurement 24 h after injection. The percentage of the injected dose per gram (%ID/g) of tumor and tumor/ non-tumor tissue ratios (T/NT) were calculated for each group of mice and the difference between two groups was assessed. The 5

  13. Novel interactions between the HTLV antisense proteins HBZ and APH-2 and the NFAR protein family: Implications for the HTLV lifecycles

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, Jane; Hall, William W. [Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4 (Ireland); Ratner, Lee [Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Saint Louis, Missouri, United States of America (United States); Sheehy, Noreen [Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4 (Ireland)

    2016-07-15

    The human T-cell leukaemia virus type 1 and type 2 (HTLV-1/HTLV-2) antisense proteins HBZ and APH-2 play key roles in the HTLV lifecycles and persistence in the host. Nuclear Factors Associated with double-stranded RNA (NFAR) proteins NF90/110 function in the lifecycles of several viruses and participate in host innate immunity against infection and oncogenesis. Using GST pulldown and co-immunoprecipitation assays we demonstrate specific novel interactions between HBZ/APH-2 and NF90/110 and characterised the protein domains involved. Moreover we show that NF90/110 significantly enhance Tax mediated LTR activation, an effect that was abolished by HBZ but enhanced by APH-2. Additionally we found that HBZ and APH-2 modulate the promoter activity of survivin and are capable of antagonising NF110-mediated survivin activation. Thus interactions between HTLV antisense proteins and the NFAR protein family have an overall positive impact on HTLV infection. Hence NFARs may represent potential therapeutic targets in HTLV infected cells. - Highlights: • This study demonstrates for the first time interactions between NF90/110 and the HTLV antisense proteins HBZ and APH-2. • We show that NF90/110 significantly enhance LTR activation by the HTLV Tax protein, an effect that is abolished by HBZ but enhanced by APH-2. • The study shows that even though the HTLV antisense proteins activate survivin expression they antagonize the ability of NF90/110 to do so. • Overall we found that NF90/110 positively regulate HTLV infection and as such might represent a therapeutic target in infected cells.

  14. Novel interactions between the HTLV antisense proteins HBZ and APH-2 and the NFAR protein family: Implications for the HTLV lifecycles

    International Nuclear Information System (INIS)

    Murphy, Jane; Hall, William W.; Ratner, Lee; Sheehy, Noreen

    2016-01-01

    The human T-cell leukaemia virus type 1 and type 2 (HTLV-1/HTLV-2) antisense proteins HBZ and APH-2 play key roles in the HTLV lifecycles and persistence in the host. Nuclear Factors Associated with double-stranded RNA (NFAR) proteins NF90/110 function in the lifecycles of several viruses and participate in host innate immunity against infection and oncogenesis. Using GST pulldown and co-immunoprecipitation assays we demonstrate specific novel interactions between HBZ/APH-2 and NF90/110 and characterised the protein domains involved. Moreover we show that NF90/110 significantly enhance Tax mediated LTR activation, an effect that was abolished by HBZ but enhanced by APH-2. Additionally we found that HBZ and APH-2 modulate the promoter activity of survivin and are capable of antagonising NF110-mediated survivin activation. Thus interactions between HTLV antisense proteins and the NFAR protein family have an overall positive impact on HTLV infection. Hence NFARs may represent potential therapeutic targets in HTLV infected cells. - Highlights: • This study demonstrates for the first time interactions between NF90/110 and the HTLV antisense proteins HBZ and APH-2. • We show that NF90/110 significantly enhance LTR activation by the HTLV Tax protein, an effect that is abolished by HBZ but enhanced by APH-2. • The study shows that even though the HTLV antisense proteins activate survivin expression they antagonize the ability of NF90/110 to do so. • Overall we found that NF90/110 positively regulate HTLV infection and as such might represent a therapeutic target in infected cells.

  15. 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.

  16. ASSOCIATIVE RINGS SOLVED AS LIE RINGS

    Directory of Open Access Journals (Sweden)

    M. B. Smirnov

    2011-01-01

    Full Text Available The paper has proved that an associative ring which is solvable of a n- class as a Lie ring has a nilpotent ideal of the nilpotent class not more than 3×10n–2  and a corresponding quotient ring satisfies an identity [[x1, x2, [x3, x4

  17. Antisense-induced exon skipping for duplications in Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    van Ommen Gert-Jan B

    2007-07-01

    Full Text Available Abstract Background Antisense-mediated exon skipping is currently one of the most promising therapeutic approaches for Duchenne muscular dystrophy (DMD. Using antisense oligonucleotides (AONs targeting specific exons the DMD reading frame is restored and partially functional dystrophins are produced. Following proof of concept in cultured muscle cells from patients with various deletions and point mutations, we now focus on single and multiple exon duplications. These mutations are in principle ideal targets for this approach since the specific skipping of duplicated exons would generate original, full-length transcripts. Methods Cultured muscle cells from DMD patients carrying duplications were transfected with AONs targeting the duplicated exons, and the dystrophin RNA and protein were analyzed. Results For two brothers with an exon 44 duplication, skipping was, even at suboptimal transfection conditions, so efficient that both exons 44 were skipped, thus generating, once more, an out-of-frame transcript. In such cases, one may resort to multi-exon skipping to restore the reading frame, as is shown here by inducing skipping of exon 43 and both exons 44. By contrast, in cells from a patient with an exon 45 duplication we were able to induce single exon 45 skipping, which allowed restoration of wild type dystrophin. The correction of a larger duplication (involving exons 52 to 62, by combinations of AONs targeting the outer exons, appeared problematic due to inefficient skipping and mistargeting of original instead of duplicated exons. Conclusion The correction of DMD duplications by exon skipping depends on the specific exons targeted. Its options vary from the ideal one, restoring for the first time the true, wild type dystrophin, to requiring more 'classical' skipping strategies, while the correction of multi-exon deletions may need the design of tailored approaches.

  18. In depth analysis of the Sox4 gene locus that consists of sense and natural antisense transcripts

    Science.gov (United States)

    Ling, King-Hwa; Brautigan, Peter J.; Moore, Sarah; Fraser, Rachel; Leong, Melody Pui-Yee; Leong, Jia-Wen; Zainal Abidin, Shahidee; Lee, Han-Chung; Cheah, Pike-See; Raison, Joy M.; Babic, Milena; Lee, Young Kyung; Daish, Tasman; Mattiske, Deidre M.; Mann, Jeffrey R.; Adelson, David L.; Thomas, Paul Q.; Hahn, Christopher N.; Scott, Hamish S.

    2016-01-01

    SRY (Sex Determining Region Y)-Box 4 or Sox4 is an important regulator of the pan-neuronal gene expression during post-mitotic cell differentiation within the mammalian brain. Sox4 gene locus has been previously characterized with multiple sense and overlapping natural antisense transcripts [1], [2]. Here we provide accompanying data on various analyses performed and described in Ling et al. [2]. The data include a detail description of various features found at Sox4 gene locus, additional experimental data derived from RNA-Fluorescence in situ Hybridization (RNA-FISH), Western blotting, strand-specific reverse-transcription quantitative polymerase chain reaction (RT-qPCR), gain-of-function and in situ hybridization (ISH) experiments. All the additional data provided here support the existence of an endogenous small interfering- or PIWI interacting-like small RNA known as Sox4_sir3, which origin was found within the overlapping region consisting of a sense and a natural antisense transcript known as Sox4ot1. PMID:26958646

  19. Asymmetric localization of natural antisense RNA of neuropeptide sensorin in Aplysia sensory neurons during aging and activity.

    Science.gov (United States)

    Kadakkuzha, Beena M; Liu, Xin-An; Narvaez, Maria; Kaye, Alexandra; Akhmedov, Komolitdin; Puthanveettil, Sathyanarayanan V

    2014-01-01

    Despite the advances in our understanding of transcriptome, regulation and function of its non-coding components continue to be poorly understood. Here we searched for natural antisense transcript for sensorin (NAT-SRN), a neuropeptide expressed in the presynaptic sensory neurons of gill-withdrawal reflex of the marine snail Aplysia californica. Sensorin (SRN) has a key role in learning and long-term memory storage in Aplysia. We have now identified NAT-SRN in the central nervous system (CNS) and have confirmed its expression by northern blotting and fluorescent RNA in situ hybridization. Quantitative analysis of NAT-SRN in micro-dissected cell bodies and processes of sensory neurons suggest that NAT-SRN is present in the distal neuronal processes along with sense transcripts. Importantly, aging is associated with reduction in levels of NAT-SRN in sensory neuron processes. Furthermore, we find that forskolin, an activator of CREB signaling, differentially alters the distribution of SRN and NAT-SRN. These studies reveal novel insights into physiological regulation of natural antisense RNAs.

  20. In depth analysis of the Sox4 gene locus that consists of sense and natural antisense transcripts

    Directory of Open Access Journals (Sweden)

    King-Hwa Ling

    2016-06-01

    Full Text Available SRY (Sex Determining Region Y-Box 4 or Sox4 is an important regulator of the pan-neuronal gene expression during post-mitotic cell differentiation within the mammalian brain. Sox4 gene locus has been previously characterized with multiple sense and overlapping natural antisense transcripts [1,2]. Here we provide accompanying data on various analyses performed and described in Ling et al. [2]. The data include a detail description of various features found at Sox4 gene locus, additional experimental data derived from RNA-Fluorescence in situ Hybridization (RNA-FISH, Western blotting, strand-specific reverse-transcription quantitative polymerase chain reaction (RT-qPCR, gain-of-function and in situ hybridization (ISH experiments. All the additional data provided here support the existence of an endogenous small interfering- or PIWI interacting-like small RNA known as Sox4_sir3, which origin was found within the overlapping region consisting of a sense and a natural antisense transcript known as Sox4ot1.

  1. Asymmetric localization of natural antisense RNA of neuropeptide sensorin in Aplysia sensory neurons during aging and activity

    Directory of Open Access Journals (Sweden)

    Beena eKadakkuzha

    2014-04-01

    Full Text Available Despite the advances in our understanding of transcriptome, regulation and function of its noncoding components continue to be poorly understood. Here we searched for natural antisense transcript for sensorin (NAT-SRN, a neuropeptide expressed in the presynaptic sensory neurons of gill-withdrawal reflex of the marine snail Aplysia californica. Sensorin (SRN has a key role in learning and long-term memory storage in Aplysia. We have identified NAT-SRN in the central nervous system (CNS and have confirmed its expression by northern blotting and fluorescent RNA in situ hybridization. Quantitative analysis of NAT-SRN in micro dissected cell bodies and processes of sensory neurons suggest that NAT-SRN is present in the distal neuronal processes along with sense transcripts. Importantly, aging is associated with reduced levels of NAT-SRN in sensory neuron processes. Furthermore, we find that forskolin, an activator of CREB signaling, differentially alters the distribution of SRN and NAT-SRN. These studies reveal novel insights into physiological regulation of natural antisense RNAs.

  2. Retroviral gene transfer of an antisense construct against membrane type 1 matrix metalloproteinase reduces the invasiveness of rheumatoid arthritis synovial fibroblasts.

    Science.gov (United States)

    Rutkauskaite, Edita; Volkmer, Dagmar; Shigeyama, Yukio; Schedel, Jörg; Pap, Geza; Müller-Ladner, Ulf; Meinecke, Ingmar; Alexander, Dorothea; Gay, Renate E; Drynda, Susanne; Neumann, Wolfram; Michel, Beat A; Aicher, Wilhelm K; Gay, Steffen; Pap, Thomas

    2005-07-01

    Membrane type 1 matrix metalloproteinase (MT1-MMP) is expressed prominently in rheumatoid arthritis synovial fibroblasts (RASFs), but the specific contribution of MT1-MMP to fibroblast-mediated destruction of articular cartilage is incompletely understood. This study used gene transfer of an antisense expression construct to assess the effects of MT1-MMP inhibition on the invasiveness of RASFs. Retroviral gene transfer of a pLXIN vector-based antisense RNA expression construct (MT1-MMPalphaS) to MT1-MMP was used to stably transduce RASFs. Levels of MT1-MMP RNA and protein were determined by quantitative polymerase chain reaction, Western blotting, and immunocytochemistry in MT1-MMPalphaS-transduced RASFs as well as in control cells, with monitoring for 60 days. The effects of MT1-MMPalphaS on the invasiveness of RASFs were analyzed in the SCID mouse co-implantation model of RA. MT1-MMPalphaS-transduced RASFs produced high levels of antisense RNA that exceeded endogenous levels of MT1-MMP messenger RNA by 15-fold and resulted in a down-regulation of MT1-MMP at the protein level. Inhibition of MT1-MMP production was maintained for 60 days and significantly reduced the invasiveness of RASFs in the SCID mouse model. Whereas prominent invasion into cartilage by non-transduced and mock-transduced RASFs was observed (mean invasion scores 3.0 and 3.1, respectively), MT1-MMPalphaS-transduced cells showed only moderate invasiveness (mean invasion score 1.8; P < 0.05). The data demonstrate that an antisense RNA expression construct against MT1-MMP can be generated and expressed in RASFs for at least 60 days. Inhibition of MT1-MMP significantly reduces the cartilage degradation by RASFs.

  3. Expression of antisense small RNAs in response to stress in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Gómez Lozano, María; Marvig, Rasmus Lykke; Tulstrup, Monica Vera-Lise

    2014-01-01

    Background: RNA sequencing technologies reveal that bacteria express RNA molecules other than mRNA, rRNA or tRNA. During the last years genome-wide bacterial transcriptomes have been shown to comprise intergenic RNA, antisense RNA, and untranslated regions, all capable of performing diverse...... that the extent of overlap between the studies is very limited. Conclusions: RNA-seq experiments are revealing hundreds of novel transcripts in all bacterial genomes investigated. The comparison between independent studies that used RNA-seq to detect novel asRNAs in P. aeruginosa shows that the overlap between...

  4. Mapping Ring Particle Cooling across Saturn's Rings with Cassini CIRS

    Science.gov (United States)

    Brooks, Shawn M.; Spilker, L. J.; Edgington, S. G.; Pilorz, S. H.; Deau, E.

    2010-10-01

    Previous studies have shown that the rings' thermal inertia, a measure of their response to changes in the thermal environment, varies from ring to ring. Thermal inertia can provide insight into the physical structure of Saturn's ring particles and their regoliths. Low thermal inertia and quick temperature responses are suggestive of ring particles that have more porous or fluffy regoliths or that are riddled with cracks. Solid, coherent particles can be expected to have higher thermal inertias (Ferrari et al. 2005). Cassini's Composite Infrared Spectrometer has recorded millions of spectra of Saturn's rings since its arrival at Saturn in 2004 (personal communication, M. Segura). CIRS records far infrared radiation between 10 and 600 cm-1 (16.7 and 1000 µm) at focal plane 1 (FP1), which has a field of view of 3.9 mrad. Thermal emission from Saturn's rings peaks in this wavelength range. FP1 spectra can be used to infer ring temperatures. By tracking how ring temperatures vary, we can determine the thermal inertia of the rings. In this work we focus on CIRS observations of the shadowed portion of Saturn's rings. The thermal budget of the rings is dominated by the solar radiation absorbed by its constituent particles. When ring particles enter Saturn's shadow this source of energy is abruptly cut off. As a result, ring particles cool as they traverse Saturn's shadow. From these shadow observations we can create cooling curves at specific locations across the rings. We will show that the rings' cooling curves and thus their thermal inertia vary not only from ring to ring, but by location within the individual rings. This research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under contract with NASA. Copyright 2010 California Institute of Technology. Government sponsorship acknowledged.

  5. Quantitative Antisense Screening and Optimization for Exon 51 Skipping in Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Echigoya, Yusuke; Lim, Kenji Rowel Q; Trieu, Nhu; Bao, Bo; Miskew Nichols, Bailey; Vila, Maria Candida; Novak, James S; Hara, Yuko; Lee, Joshua; Touznik, Aleksander; Mamchaoui, Kamel; Aoki, Yoshitsugu; Takeda, Shin'ichi; Nagaraju, Kanneboyina; Mouly, Vincent; Maruyama, Rika; Duddy, William; Yokota, Toshifumi

    2017-11-01

    Duchenne muscular dystrophy (DMD), the most common lethal genetic disorder, is caused by mutations in the dystrophin (DMD) gene. Exon skipping is a therapeutic approach that uses antisense oligonucleotides (AOs) to modulate splicing and restore the reading frame, leading to truncated, yet functional protein expression. In 2016, the US Food and Drug Administration (FDA) conditionally approved the first phosphorodiamidate morpholino oligomer (morpholino)-based AO drug, eteplirsen, developed for DMD exon 51 skipping. Eteplirsen remains controversial with insufficient evidence of its therapeutic effect in patients. We recently developed an in silico tool to design antisense morpholino sequences for exon skipping. Here, we designed morpholino AOs targeting DMD exon 51 using the in silico tool and quantitatively evaluated the effects in immortalized DMD muscle cells in vitro. To our surprise, most of the newly designed morpholinos induced exon 51 skipping more efficiently compared with the eteplirsen sequence. The efficacy of exon 51 skipping and rescue of dystrophin protein expression were increased by up to more than 12-fold and 7-fold, respectively, compared with the eteplirsen sequence. Significant in vivo efficacy of the most effective morpholino, determined in vitro, was confirmed in mice carrying the human DMD gene. These findings underscore the importance of AO sequence optimization for exon skipping. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  6. Search for antisense copies of beta-globin mRNA in anemic mouse spleen

    Directory of Open Access Journals (Sweden)

    Taylor John M

    2001-03-01

    Full Text Available Abstract Background Previous studies by Volloch and coworkers have reported that during the expression of high levels of β-globin mRNA in the spleen of anemic mice, they could also detect small but significant levels of an antisense (AS globin RNA species, which they postulated might have somehow arisen by RNA-directed RNA synthesis. For two reasons we undertook to confirm and possibly extend these studies. First, previous studies in our lab have focussed on what is an unequivocal example of host RNA-directed RNA polymerase activity on the RNA genome of human hepatitis delta virus. Second, if AS globin species do exist they could in turn form double-stranded RNA species which might induce post-transcriptional gene silencing, a phenomenon somehow provoked in eukaryotic cells by AS RNA sequences. Results We reexamined critical aspects of the previous globin studies. We used intraperitoneal injections of phenylhydrazine to induce anemia in mice, as demonstrated by the appearance and ultimate disappearance of splenomegaly. While a 30-fold increase in globin mRNA was detected in the spleen, the relative amount of putative AS RNA could be no more than 0.004%. Conclusions Contrary to earlier reports, induction of a major increase in globin transcripts in the mouse spleen was not associated with a detectable level of antisense RNA to globin mRNA.

  7. Effect of antisense c-raf-1 on tumorigenicity and radiation sensitivity of a human squamous carcinoma

    International Nuclear Information System (INIS)

    Kasid, U.; Pfeifer, A.; Brennan, T.; Beckett, M.; Weichselbaum, R.R.; Dritschilo, A.; Mark, G.E.

    1989-01-01

    Antisense RNA-mediated inhibition of gene expression was used to investigate the biological function of the c-raf-1 gene in a radiation-resistant human squamous carcinoma cell line, SQ-20B. S1 nuclease protection assays revealed that transfection of full-length raf complementary DNA in the antisense orientation (AS) leads to a specific reduction (greater than tenfold) of steady-state levels of the endogenous c-raf-1 sense (S) transcript in SQ-20B cells. In nude mice, the malignant potential of SQ-20B cells transfected with raf (S) was significantly increased relative to that of SQ-20B cells transfected with raf (AS). SQ-20B cells containing transfected raf (S) maintained a radiation-resistant phenotype as compared to those cells harboring the AS version, which appeared to have enhanced radiation sensitivity. These data indicate that the reduced expression of endogenous c-raf-1 is sufficient to modulate the tumorigenicity and the radiation-resistant phenotype of SQ-20B cells, thus implicating c-raf-1 in a pathway important to the genesis of this type of cancer

  8. The endogenous retroviral insertion in the human complement C4 gene modulates the expression of homologous genes by antisense inhibition.

    Science.gov (United States)

    Schneider, P M; Witzel-Schlömp, K; Rittner, C; Zhang, L

    2001-02-01

    Intron 9 contains the complete endogenous retrovirus HERV-K(C4) as a 6.4-kb insertion in 60% of human C4 genes. The retroviral insertion is in reverse orientation to the C4 coding sequence. Therefore, expression of C4 could lead to the transcription of an antisense RNA, which might protect against exogenous retroviral infections. To test this hypothesis, open reading frames from the HERV sequence were subcloned in sense orientiation into a vector allowing expression of a beta-galactosidase fusion protein. Mouse L cells which had been stably transfected with either the human C4A or C4B gene both carrying the HERV insertion (LC4 cells), and L(Tk-) cells without the C4 gene were transiently transfected either with a retroviral construct or with the wild-type vector. Expression was monitored using an enzymatic assay. We demonstrated that (1) HERV-K(C4) antisense mRNA transcripts are present in cells constitutively expressing C4, (2) expression of retroviral-like constructs is significantly downregulated in cells expressing C4, and (3) this downregulation is further modulated in a dose-dependent fashion following interferon-gamma stimulation of C4 expression. These results support the hypothesis of a genomic antisense strategy mediated by the HERV-K(C4) insertion as a possible defense mechanism against exogenous retroviral infections.

  9. Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors.

    Science.gov (United States)

    Lobos-González, Lorena; Silva, Verónica; Araya, Mariela; Restovic, Franko; Echenique, Javiera; Oliveira-Cruz, Luciana; Fitzpatrick, Christopher; Briones, Macarena; Villegas, Jaime; Villota, Claudio; Vidaurre, Soledad; Borgna, Vincenzo; Socias, Miguel; Valenzuela, Sebastián; Lopez, Constanza; Socias, Teresa; Varas, Manuel; Díaz, Jorge; Burzio, Luis O; Burzio, Verónica A

    2016-09-06

    We reported that knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptotic death of several human tumor cell lines, but not normal cells, suggesting this approach for selective therapy against different types of cancer. In order to translate these results to a preclinical scenario, we characterized the murine noncoding mitochondrial RNAs (ncmtRNAs) and performed in vivo knockdown in syngeneic murine melanoma models. Mouse ncmtRNAs display structures similar to the human counterparts, including long double-stranded regions arising from the presence of inverted repeats. Knockdown of ASncmtRNAs with specific antisense oligonucleotides (ASO) reduces murine melanoma B16F10 cell proliferation and induces apoptosis in vitro through downregulation of pro-survival and metastasis markers, particularly survivin. For in vivo studies, subcutaneous B16F10 melanoma tumors in C57BL/6 mice were treated systemically with specific and control antisense oligonucleotides (ASO). For metastasis studies, tumors were resected, followed by systemic administration of ASOs and the presence of metastatic nodules in lungs and liver was assessed. Treatment with specific ASO inhibited tumor growth and metastasis after primary tumor resection. In a metastasis-only assay, mice inoculated intravenously with cells and treated with the same ASO displayed reduced number and size of melanoma nodules in the lungs, compared to controls. Our results suggest that ASncmtRNAs could be potent targets for melanoma therapy. To our knowledge, the ASncmtRNAs are the first potential non-nuclear targets for melanoma therapy.

  10. Improved cellular uptake of antisense Peptide nucleic acids by conjugation to a cell-penetrating Peptide and a lipid domain

    DEFF Research Database (Denmark)

    Shiraishi, Takehiko; Nielsen, Peter E

    2011-01-01

    based on a splicing correction of a mutated luciferase gene in HeLa pLuc705 cells by targeting antisense oligonucleotides to a cryptic splice site. Further improvement in the delivery of CatLip-PNA conjugates is achieved by using auxiliary agents/treatments (e.g., chloroquine, calcium ions......Unaided cellular uptake of RNA interference agents such as antisense oligonucleotides and siRNA is extremely poor, and in vivo bioavailability is also limited. Thus, effective delivery strategies for such potential drugs are in high demand. Recently, a novel approach using a class of short cationic....... We have found, however, that this low -bioavailability can be significantly improved by chemical conjugation to a lipid domain ("Lip," such as a fatty acid), thereby creating "CatLip"-conjugates. The cellular uptake of these conjugates is conveniently evaluated using a sensitive cellular assay system...

  11. PLGA-PEG-PLGA microspheres as a delivery vehicle for antisense oligonucleotides to CTGF: Implications on post-surgical peritoneal adhesion prevention

    Science.gov (United States)

    Azeke, John Imuetinyan-Jesu, Jr.

    Abdominal adhesions are the aberrant result of peritoneal wound healing commonly associated with surgery and inflammation. A subject of a large number of studies since the first half of the last century, peritoneal adhesion prevention has, for the most part, evaded the scientific community and continues to cost Americans an estimated $2-4 billion annually. It is known that transforming growth factor-beta (TGF-beta) plays a key role in the wound healing cascade; however, suppression of this multifunctional growth factor's activity may have more harmful consequences than can be tolerated. As a result, much attention has fallen on connective tissue growth factor (CTGF), a downstream mediator of TGF-beta's fibrotic action. It has been demonstrated in several in vitro models, that the suppression of CTGF hinders fibroblast proliferation, a necessary condition for fibrosis. Furthermore, antisense oligonucleotides (antisense oligos, AO) to CTGF have been shown to knock down CTGF mRNA levels by specifically hindering the translation of CTGF protein. Antisense technologies have met with a great deal of excitement as a viable means of preventing diseases such as adhesions by hindering protein translation at the mRNA level. However, the great challenge associated with the use of these drugs lies in the short circulation time when administered "naked". Viral delivery systems, although excellent platforms in metabolic studies, are not ideal for diagnostic use because of the inherent danger associated with viral vectors. Microparticles made of biodegradable polymers have therefore presented themselves as a viable means of delivering these drugs to target cells over extended periods. Herein, we present two in vivo studies confirming the up-regulation of TGF-beta protein and CTGF mRNA following injury to the uterine tissues of female rats. We were able to selectively knockdown post-operative CTGF protein levels following surgery, however, our observations led us to conclude that

  12. Black rings

    International Nuclear Information System (INIS)

    Emparan, Roberto; Reall, Harvey S

    2006-01-01

    A black ring is a five-dimensional black hole with an event horizon of topology S 1 x S 2 . We provide an introduction to the description of black rings in general relativity and string theory. Novel aspects of the presentation include a new approach to constructing black ring coordinates and a critical review of black ring microscopics. (topical review)

  13. Subnanomolar antisense activity of phosphonate-peptide nucleic acid (PNA) conjugates delivered by cationic lipids to HeLa cells

    DEFF Research Database (Denmark)

    Shiraishi, Takehiko; Hamzavi, Ramin; Nielsen, Peter E

    2008-01-01

    oligomer. This modification of the PNA does not interfere with the nucleic acid target binding affinity based on thermal stability of the PNA/RNA duplexes. When delivered to cultured HeLa pLuc705 cells by Lipofectamine, the PNAs showed dose-dependent nuclear antisense activity in the nanomolar range...

  14. Polyoxometalate grafting onto silica: stability diagrams of H3PMo12O40 on {001}, {101}, and {111} β-cristobalite surfaces analyzed by DFT

    KAUST Repository

    Rozanska, Xavier; Sautet, Philippe; Delbecq, Franoise; Lefebvre, Fré dé ric; Borshch, Sergei; Chermette, Henri; Basset, Jean-Marie; Grinenval, Eva

    2011-01-01

    The process of grafting H3PMo12O40 onto silica surfaces is studied using periodic density functional theory methods. For surfaces with a high hydroxyl coverage, the hydroxyl groups are consumed by the polyoxometalate protons, resulting in water formation and the creation of a covalent bond between the polyoxometalate and the surface, and mostly no remaining acidic proton on the polyoxometalate. When the surfaces are partially dehydroxylated and more hydrophobic, after temperature pretreatment, less covalent and hydrogen bonds are formed and the polyoxometalate tends to retain surface hydroxyl groups, while at least one acidic proton remains. Hence the hydroxylation of the surface has a great impact on the chemical properties of the grafted polyoxometalate. In return, the polyoxometalate species affects the compared stability of the partially hydroxylated silica surfaces in comparison with the bare silica case. © 2011 the Owner Societies.

  15. Antisense RNA Controls LRP1 Sense Transcript Expression through Interaction with a Chromatin-Associated Protein, HMGB2

    Directory of Open Access Journals (Sweden)

    Yasunari Yamanaka

    2015-05-01

    Full Text Available Long non-coding RNAs (lncRNAs, including natural antisense transcripts (NATs, are expressed more extensively than previously anticipated and have widespread roles in regulating gene expression. Nevertheless, the molecular mechanisms of action of the majority of NATs remain largely unknown. Here, we identify a NAT of low-density lipoprotein receptor-related protein 1 (Lrp1, referred to as Lrp1-AS, that negatively regulates Lrp1 expression. We show that Lrp1-AS directly binds to high-mobility group box 2 (Hmgb2 and inhibits the activity of Hmgb2 to enhance Srebp1a-dependent transcription of Lrp1. Short oligonucleotides targeting Lrp1-AS inhibit the interaction of antisense transcript and Hmgb2 protein and increase Lrp1 expression by enhancing Hmgb2 activity. Quantitative RT-PCR analysis of brain tissue samples from Alzheimer’s disease patients and aged-matched controls revealed upregulation of LRP1-AS and downregulation of LRP1. Our data suggest a regulatory mechanism whereby a NAT interacts with a ubiquitous chromatin-associated protein to modulate its activity in a locus-specific fashion.

  16. Efficient encapsulation of antisense oligonucleotides in lipid vesicles using ionizable aminolipids: formation of novel small multilamellar vesicle structures.

    Science.gov (United States)

    Semple, S C; Klimuk, S K; Harasym, T O; Dos Santos, N; Ansell, S M; Wong, K F; Maurer, N; Stark, H; Cullis, P R; Hope, M J; Scherrer, P

    2001-02-09

    Typical methods used for encapsulating antisense oligodeoxynucleotides (ODN) and plasmid DNA in lipid vesicles result in very low encapsulation efficiencies or employ cationic lipids that exhibit unfavorable pharmacokinetic and toxicity characteristics when administered intravenously. In this study, we describe and characterize a novel formulation process that utilizes an ionizable aminolipid (1,2-dioleoyl-3-dimethylammonium propane, DODAP) and an ethanol-containing buffer system for encapsulating large quantities (0.15--0.25 g ODN/g lipid) of polyanionic ODN in lipid vesicles. This process requires the presence of up to 40% ethanol (v/v) and initial formulation at acidic pH values where the DODAP is positively charged. In addition, the presence of a poly(ethylene glycol)-lipid was required during the formulation process to prevent aggregation. The 'stabilized antisense-lipid particles' (SALP) formed are stable on adjustment of the external pH to neutral pH values and the formulation process allows encapsulation efficiencies of up to 70%. ODN encapsulation was confirmed by nuclease protection assays and (31)P NMR measurements. Cryo-electron microscopy indicated that the final particles consisted of a mixed population of unilamellar and small multilamellar vesicles (80--140 nm diameter), the relative proportion of which was dependent on the initial ODN to lipid ratio. Finally, SALP exhibited significantly enhanced circulation lifetimes in mice relative to free antisense ODN, cationic lipid/ODN complexes and SALP prepared with quaternary aminolipids. Given the small particle sizes and improved encapsulation efficiency, ODN to lipid ratios, and circulation times of this formulation compared to others, we believe SALP represent a viable candidate for systemic applications involving nucleic acid therapeutics.

  17. Variations in Ring Particle Cooling across Saturn's Rings with Cassini CIRS

    Science.gov (United States)

    Brooks, S. M.; Spilker, L. J.; Pilorz, S.; Edgington, S. G.; Déau, E.; Altobelli, N.

    2010-12-01

    Cassini's Composite Infrared Spectrometer has recorded over two million of spectra of Saturn's rings in the far infrared since arriving at Saturn in 2004. CIRS records far infrared radiation between 10 and 600 cm-1 ( 16.7 and 1000 μ {m} ) at focal plane 1 (FP1), which has a field of view of 3.9 mrad. Thermal emission from Saturn’s rings peaks in this wavelength range. Ring temperatures can be inferred from FP1 data. By tracking how ring temperatures vary, we can determine the thermal inertia of the rings. Previous studies have shown that the rings' thermal inertia, a measure of their response to changes in the thermal environment, varies from ring to ring. Thermal inertia can provide insight into the physical structure of Saturn's ring particles and their regoliths. Low thermal inertia and rapidly changing temperatures are suggestive of ring particles that have more porous or fluffy regoliths or that are riddled with cracks. Solid particles can be expected to have higher thermal inertias. Ferrari et al. (2005) fit thermal inertia values of 5218 {Jm)-2 {K}-1 {s}-1/2 to their B ring data and 6412 {Jm)-2 {K}-1 {s}-1/2 to their C ring data. In this work we focus on CIRS observations of the shadowed portion of Saturn's rings. The rings’ thermal budget is dominated by its absorption of solar radiation. As a result, ring particles abruptly cool as they traverse Saturn's shadow. From these shadow observations we can create cooling curves at specific locations across the rings. We will show that the rings' cooling curves and thus their thermal inertia vary not only from ring to ring, but by location within the individual rings. This research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under contract with NASA. Copyright 2010 California Institute of Technology. Government sponsorship acknowledged.

  18. Antisense imaging of epidermal growth factor-induced p21{sup WAF-1/CIP-1} gene expression in MDA-MB-468 human breast cancer xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Judy; Chen, Paul; Mrkobrada, Marko [Leslie Dan Faculty of Pharmacy, University of Toronto, 19 Russell Street, M5S 2S2, Toronto, Ontario (Canada); Hu, Meiduo [Leslie Dan Faculty of Pharmacy, University of Toronto, 19 Russell Street, M5S 2S2, Toronto, Ontario (Canada); Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario (Canada); Vallis, Katherine A. [Department of Radiation Oncology, Princess Margaret Hospital, University Health Network, 610 University Avenue, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Reilly, Raymond M. [Department of Medical Imaging, University of Toronto, Toronto, Ontario (Canada)

    2003-09-01

    Molecular imaging of the expression of key genes which determine the response to DNA damage following cancer treatment may predict the effectiveness of a particular treatment strategy. A prominent early response gene for DNA damage is the gene encoding p21{sup WAF-1/CIP-1}, a cyclin-dependent kinase inhibitor that regulates progression through the cell cycle. In this study, we explored the feasibility of imaging p21{sup WAF-1/CIP-1} gene expression at the mRNA level using an 18-mer phosphorothioated antisense oligodeoxynucleotide (ODN) labeled with {sup 111}In. The known induction of the p21{sup WAF-1/CIP-1} gene in MDA-MB-468 human breast cancer cells following exposure to epidermal growth factor (EGF) was used as an experimental tool. Treatment of MDA-MB-468 cells in vitro with EGF (20 nM) increased the ratio of p21{sup WAF-1/CIP-1} mRNA/{beta}-actin mRNA threefold within 2 h as measured by the reverse transcription polymerase chain reaction (RT-PCR). A concentration-dependent inhibition of EGF-induced p21{sup WAF-1/CIP-1} protein expression was achieved in MDA-MB-468 cells by treatment with antisense ODNs with up to a tenfold decrease observed at 1 {mu}M. There was a fourfold lower inhibition of p21{sup WAF-1/CIP-1} protein expression by control sense or random sequence ODNs. Intratumoral injections of EGF (15 {mu}g/day x 3 days) were employed to induce p21{sup WAF-1/CIP-1} gene expression in MDA-MB-468 xenografts implanted subcutaneously into athymic mice. RT-PCR of explanted tumors showed a threefold increased level of p21{sup WAF-1/CIP-1} mRNA compared with normal saline-treated tumors. Successful imaging of EGF-induced p21{sup WAF-1/CIP-1} gene expression in MDA-MB-468 xenografts was achieved at 48 h post injection of {sup 111}In-labeled antisense ODNs (3.7 MBq; 2 {mu}g). Tumors displaying basal levels of p21{sup WAF-1/CIP-1} gene expression in the absence of EGF treatment could not be visualized. Biodistribution studies showed a significantly higher tumor

  19. Nanomolar Cellular Antisense Activity of Peptide Nucleic Acid (PNA) Cholic Acid ("Umbrella") and Cholesterol Conjugates Delivered by Cationic Lipids

    DEFF Research Database (Denmark)

    Shiraishi, Takehiko; Nielsen, Peter E

    2012-01-01

    of cholesterol and cholic acid ("umbrella") derivatives of splice correction antisense PNA oligomers. While the conjugates alone were practically inactive up to 1 µM, their activity was dramatically improved when delivered by a cationic lipid transfection agent (LipofectAMINE2000). In particular, PNAs...

  20. Alternative loop rings

    CERN Document Server

    Goodaire, EG; Polcino Milies, C

    1996-01-01

    For the past ten years, alternative loop rings have intrigued mathematicians from a wide cross-section of modern algebra. As a consequence, the theory of alternative loop rings has grown tremendously. One of the main developments is the complete characterization of loops which have an alternative but not associative, loop ring. Furthermore, there is a very close relationship between the algebraic structures of loop rings and of group rings over 2-groups. Another major topic of research is the study of the unit loop of the integral loop ring. Here the interaction between loop rings and group ri

  1. Primitivity and weak distributivity in near rings and matrix near rings

    International Nuclear Information System (INIS)

    Abbasi, S.J.

    1993-08-01

    This paper shows the structure of matrix near ring constructed over a weakly distributive and primative near ring. It is proved that a weakly distributive primitive near ring is a ring and the matrix near rings constructed over it is also a bag. (author). 14 refs

  2. Feasibility of SPECT-CT imaging to study the pharmacokinetics of antisense oligonucleotides in a mouse model of Duchenne muscular dystrophy

    NARCIS (Netherlands)

    Steeg, E. van de; Läppchen, T.; Aguilera, B.; Jansen, H.T.; Muilwijk, D.; Vermue, R.; Hoorn, J.W. van der; Donato, K.; Rossin, R.; Visser, P.C. de; Vlaming, M.L.H.

    2017-01-01

    Antisense oligonucleotides (AONs) are promising candidates for treatment of Duchenne muscular dystrophy (DMD), a severe and progressive disease resulting in premature death. However, more knowledge on the pharmacokinetics of new AON drug candidates is desired for effective application in the clinic.

  3. SINEUPs are modular antisense long-non coding RNAs that increase synthesis of target proteins in cells

    Directory of Open Access Journals (Sweden)

    Silvia eZucchelli

    2015-05-01

    Full Text Available Despite recent efforts in discovering novel long non-coding RNAs (lncRNAs and unveiling their functions in a wide range of biological processes their applications as biotechnological or therapeutic tools are still at their infancy. We have recently shown that AS Uchl1, a natural lncRNA antisense to the Parkinson’s disease-associated gene Ubiquitin carboxyl-terminal esterase L1 (Uchl1, is able to increase UchL1 protein synthesis at post-transcriptional level. Its activity requires two RNA elements: an embedded inverted SINEB2 sequence to increase translation and the overlapping region to target its sense mRNA. This functional organization is shared with several mouse lncRNAs antisense to protein coding genes. The potential use of AS Uchl1-derived lncRNAs as enhancers of target mRNA translation remains unexplored. Here we define AS Uchl1 as the representative member of a new functional class of natural and synthetic antisense lncRNAs that activate translation. We named this class of RNAs SINEUPs for their requirement of the inverted SINEB2 sequence to UP-regulate translation in a gene-specific manner. The overlapping region is indicated as the Binding Doman (BD while the embedded inverted SINEB2 element is the Effector Domain (ED. By swapping BD, synthetic SINEUPs are designed targeting mRNAs of interest. SINEUPs function in an array of cell lines and can be efficiently directed towards N-terminally tagged proteins. Their biological activity is retained in a miniaturized version within the range of small RNAs length. Its modular structure was exploited to successfully design synthetic SINEUPs targeting endogenous Parkinson’s disease-associated DJ-1 and proved to be active in different neuronal cell lines.In summary, SINEUPs represent the first scalable tool to increase synthesis of proteins of interest. We propose SINEUPs as reagents for molecular biology experiments, in protein manufacturing as well as in therapy of haploinsufficiencies.

  4. Os DNA sintéticos anti-sentido Antisense Synthtetic DNA

    Directory of Open Access Journals (Sweden)

    Alfredo Cravador

    1998-07-01

    Full Text Available One old dream of the chemist in the field of the drug research is to create molecules capable of reaching their target with the precision of a missile. To accomplish it these molecules must have the propriety of distinguishing qualitative differences between healthy and diseased cells. A therapy based on this principle, able of eradicating specifically defective cells, or cells affected by a pathogen has an enormous advantage with the regard to the classical approach in which the cytotoxic drugs merely exploit quantitative biochemical and kinetic differences between abnormal and normal cells. We present in this article a review on the chemical synthesis of analogues of desoxyribonucleotides and on results obtained on the specific and irreversible inhibition of undesired genetic expression using the antisense principle.

  5. Interaction of ring dark solitons with ring impurities in Bose-Einstein condensates

    International Nuclear Information System (INIS)

    Xue Jukui

    2005-01-01

    The interaction of ring dark solitons/vortexes with the ring-shaped repulsive and attractive impurities in two-dimensional Bose-Einstein condensates is investigated numerically. Very rich interaction phenomena are obtained, i.e., not only the interaction between the ring soliton and the impurity, but also the interaction between vortexes and the impurity. The interaction characters, i.e., snaking of ring soliton, quasitrapping or reflection of ring soliton and vortexes by the impurity, strongly depend on initial ring soliton velocity, impurity strength, initial position of ring soliton and impurity. The numerical results also reveal that ring dark solitons/vortexes can be trapped and dragged by an adiabatically moving attractive ring impurity

  6. Storage Rings

    International Nuclear Information System (INIS)

    Fischer, W.

    2010-01-01

    Storage rings are circular machines that store particle beams at a constant energy. Beams are stored in rings without acceleration for a number of reasons (Tab. 1). Storage rings are used in high-energy, nuclear, atomic, and molecular physics, as well as for experiments in chemistry, material and life sciences. Parameters for storage rings such as particle species, energy, beam intensity, beam size, and store time vary widely depending on the application. The beam must be injected into a storage ring but may not be extracted (Fig. 1). Accelerator rings such as synchrotrons are used as storage rings before and after acceleration. Particles stored in rings include electrons and positrons; muons; protons and anti-protons; neutrons; light and heavy, positive and negative, atomic ions of various charge states; molecular and cluster ions, and neutral polar molecules. Spin polarized beams of electrons, positrons, and protons were stored. The kinetic energy of the stored particles ranges from 10 -6 eV to 3.5 x 10 12 eV (LHC, 7 x 10 12 eV planned), the number of stored particles from one (ESR) to 1015 (ISR). To store beam in rings requires bending (dipoles) and transverse focusing (quadrupoles). Higher order multipoles are used to correct chromatic aberrations, to suppress instabilities, and to compensate for nonlinear field errors of dipoles and quadrupoles. Magnetic multipole functions can be combined in magnets. Beams are stored bunched with radio frequency systems, and unbunched. The magnetic lattice and radio frequency system are designed to ensure the stability of transverse and longitudinal motion. New technologies allow for better storage rings. With strong focusing the beam pipe dimensions became much smaller than previously possible. For a given circumference superconducting magnets make higher energies possible, and superconducting radio frequency systems allow for efficient replenishment of synchrotron radiation losses of large current electron or positron beams

  7. Strand-specific RNA-seq reveals widespread occurrence of novel cis-natural antisense transcripts in rice

    Directory of Open Access Journals (Sweden)

    Lu Tingting

    2012-12-01

    Full Text Available Abstract Background Cis-natural antisense transcripts (cis-NATs are RNAs transcribed from the antisense strand of a gene locus, and are complementary to the RNA transcribed from the sense strand. Common techniques including microarray approach and analysis of transcriptome databases are the major ways to globally identify cis-NATs in various eukaryotic organisms. Genome-wide in silico analysis has identified a large number of cis-NATs that may generate endogenous short interfering RNAs (nat-siRNAs, which participate in important biogenesis mechanisms for transcriptional and post-transcriptional regulation in rice. However, the transcriptomes are yet to be deeply sequenced to comprehensively investigate cis-NATs. Results We applied high-throughput strand-specific complementary DNA sequencing technology (ssRNA-seq to deeply sequence mRNA for assessing sense and antisense transcripts that were derived under salt, drought and cold stresses, and normal conditions, in the model plant rice (Oryza sativa. Combined with RAP-DB genome annotation (the Rice Annotation Project Database build-5 data set, 76,013 transcripts corresponding to 45,844 unique gene loci were assembled, in which 4873 gene loci were newly identified. Of 3819 putative rice cis-NATs, 2292 were detected as expressed and giving rise to small RNAs from their overlapping regions through integrated analysis of ssRNA-seq data and small RNA data. Among them, 503 cis-NATs seemed to be associated with specific conditions. The deep sequence data from isolated epidermal cells of rice seedlings further showed that 54.0% of cis-NATs were expressed simultaneously in a population of homogenous cells. Nearly 9.7% of rice transcripts were involved in one-to-one or many-to-many cis-NATs formation. Furthermore, only 17.4-34.7% of 223 many-to-many cis-NAT groups were all expressed and generated nat-siRNAs, indicating that only some cis-NAT groups may be involved in complex regulatory networks. Conclusions

  8. Electroporation increases antitumoral efficacy of the bcl-2 antisense G3139 and chemotherapy in a human melanoma xenograft

    Directory of Open Access Journals (Sweden)

    Baldi Alfonso

    2011-07-01

    Full Text Available Abstract Background Nucleic acids designed to modulate the expression of target proteins remain a promising therapeutic strategy in several diseases, including cancer. However, clinical success is limited by the lack of efficient intracellular delivery. In this study we evaluated whether electroporation could increase the delivery of antisense oligodeoxynucleotides against bcl-2 (G3139 as well as the efficacy of combination chemotherapy in human melanoma xenografts. Methods Melanoma-bearing nude mice were treated i.v. with G3139 and/or cisplatin (DDP followed by the application of trains of electric pulses to tumors. Western blot, immunohistochemistry and real-time PCR were performed to analyze protein and mRNA expression. The effect of electroporation on muscles was determined by histology, while tumor apoptosis and the proliferation index were analyzed by immunohistochemistry. Antisense oligodeoxynucleotides tumor accumulation was measured by FACS and confocal microscopy. Results The G3139/Electroporation combined therapy produced a significant inhibition of tumor growth (TWI, more than 50% accompanied by a marked tumor re-growth delay (TRD, about 20 days. The efficacy of this treatment was due to the higher G3139 uptake in tumor cells which led to a marked down-regulation of bcl-2 protein expression. Moreover, the G3139/EP combination treatment resulted in an enhanced apoptotic index and a decreased proliferation rate of tumors. Finally, an increased tumor response was observed after treatment with the triple combination G3139/DDP/EP, showing a TWI of about 75% and TRD of 30 days. Conclusions These results demonstrate that electroporation is an effective strategy to improve the delivery of antisense oligodeoxynucleotides within tumor cells in vivo and it may be instrumental in optimizing the response of melanoma to chemotherapy. The high response rate observed in this study suggest to apply this strategy for the treatment of melanoma patients.

  9. Intravenous administration of stabilized antisense lipid particles (SALP) leads to activation and expansion of liver natural killer cells.

    Science.gov (United States)

    Bramson, J L; Bodner, C A; Johnson, J; Semple, S; Hope, M J

    2000-06-01

    Stabilized antisense lipid particles (SALP) have been developed for the systemic delivery of oligonucleotides. The impact of intravenous SALP administration was measured with respect to activation of natural killer (NK) and NK1.1+ T (NKT) cells in the livers of immunocompetent mice. Treatment with a SALP containing a highly mitogenic oligonucleotide (INX-6295) generated an increase in NK cytolytic activity and cell number within the liver but did not appear to affect the number of hepatic NKT cells or their cytolytic activity. The same results were observed after intravenous administration of the mitogenic oligonucleotide alone. Interestingly, treatment with a SALP containing a weakly mitogenic oligonucleotide (INX-6300) also activated the liver NK cells, whereas the oligonucleotide alone was unable to elicit these effects. The NK stimulatory activity of a SALP containing INX-6300 required both lipid and oligonucleotide components. These results demonstrate that in addition to modifying the pharmacokinetics and biodistribution of intravenously administered oligonucleotides, SALP possess immunostimulatory activity independent of oligonucleotide mitogenicity, which can serve as an adjuvant to antisense therapies for cancer.

  10. Modulation of splicing of the preceding intron by antisense oligonucleotide complementary to intra-exon sequence deleted in dystrophin Kobe

    Energy Technology Data Exchange (ETDEWEB)

    Takeshima, Y.; Matuso, M.; Sakamoto, H.; Nishio, H. [Kobe Univ. School of Medicine and Science (Japan)

    1994-09-01

    Molecular analysis of dystrophin Kobe showed that exon 19 of the dystrophin gene bearing a 52 bp deletion was skipped during splicing, although the known consensus sequences at the 5{prime} and 3{prime} splice site of exon 19 were maintained. These data suggest that the deleted sequence of exon 19 may function as a cis-acting factor for exact splicing for the upstream intron. To investigate this potential role, an in vitro splicing system using dystrophin precursors was established. A two-exon precursor containing exon 18, truncated intron 18, and exon 19 was accurately spliced. However, splicing of intron 18 was dramatically inhibited when wild exon 19 was replaced with mutated exon 19. Even though the length of exon 19 was restored to normal by replacing the deleted sequence with other sequence, splicing of intron 18 was not fully reactivated. Characteristically, splicing of intron 18 was inactivated more markedly when the replaced sequence contained less polypurine stretches. These data suggested that modification of the exon sequence would result in a splicing abnormality. Antisense 31 mer 2`-O-methyl ribonucleotide was targeted against 5{prime} end of deleted region of exon 19 to modulate splicing of the mRNA precursor. Splicing of intron 18 was inhibited in a dose- and time-dependent manner. This is the first in vitro evidence to show splicing of dystrophin pre-mRNA can be managed by antisense oligonucleotides. These experiments represent an approach in which antisense oligonucleotides are used to restore the function of a defective dystrophin gene in Duchenne muscular dystrophy by inducing skipping of certain exons during splicing.

  11. Rings in drugs.

    Science.gov (United States)

    Taylor, Richard D; MacCoss, Malcolm; Lawson, Alastair D G

    2014-07-24

    We have analyzed the rings, ring systems, and frameworks in drugs listed in the FDA Orange Book to understand the frequency, timelines, molecular property space, and the application of these rings in different therapeutic areas and target classes. This analysis shows that there are only 351 ring systems and 1197 frameworks in drugs that came onto the market before 2013. Furthermore, on average six new ring systems enter drug space each year and approximately 28% of new drugs contain a new ring system. Moreover, it is very unusual for a drug to contain more than one new ring system and the majority of the most frequently used ring systems (83%) were first used in drugs developed prior to 1983. These observations give insight into the chemical novelty of drugs and potentially efficient ways to assess compound libraries and develop compounds from hit identification to lead optimization and beyond.

  12. Regulation of Peripheral Myelination through Transcriptional Buffering of Egr2 by an Antisense Long Non-coding RNA

    Directory of Open Access Journals (Sweden)

    Margot Martinez-Moreno

    2017-08-01

    Full Text Available Precise regulation of Egr2 transcription is fundamentally important to the control of peripheral myelination. Here, we describe a long non-coding RNA antisense to the promoter of Egr2 (Egr2-AS-RNA. During peripheral nerve injury, the expression of Egr2-AS-RNA is increased and correlates with decreased Egr2 transcript and protein levels. Ectopic expression of Egr2-AS-RNA in dorsal root ganglion (DRG cultures inhibits the expression of Egr2 mRNA and induces demyelination. In vivo inhibition of Egr2-AS-RNA using oligonucleotide GapMers released from a biodegradable hydrogel following sciatic nerve injury reverts the EGR2-mediated gene expression profile and significantly delays demyelination. Egr2-AS-RNA gradually recruits H3K27ME3, AGO1, AGO2, and EZH2 on the Egr2 promoter following sciatic nerve injury. Furthermore, expression of Egr2-AS-RNA is regulated through ERK1/2 signaling to YY1, while loss of Ser184 of YY1 regulates binding to Egr2-AS-RNA. In conclusion, we describe functional exploration of an antisense long non-coding RNA in peripheral nervous system (PNS biology.

  13. Efficacy and Safety Profile of Tricyclo-DNA Antisense Oligonucleotides in Duchenne Muscular Dystrophy Mouse Model

    Directory of Open Access Journals (Sweden)

    Karima Relizani

    2017-09-01

    Full Text Available Antisense oligonucleotides (AONs hold promise for therapeutic splice-switching correction in many genetic diseases. However, despite advances in AON chemistry and design, systemic use of AONs is limited due to poor tissue uptake and sufficient therapeutic efficacy is still difficult to achieve. A novel class of AONs made of tricyclo-DNA (tcDNA is considered very promising for the treatment of Duchenne muscular dystrophy (DMD, a neuromuscular disease typically caused by frameshifting deletions or nonsense mutations in the gene-encoding dystrophin and characterized by progressive muscle weakness, cardiomyopathy, and respiratory failure in addition to cognitive impairment. Herein, we report the efficacy and toxicology profile of a 13-mer tcDNA in mdx mice. We show that systemic delivery of 13-mer tcDNA allows restoration of dystrophin in skeletal muscles and to a lower extent in the brain, leading to muscle function improvement and correction of behavioral features linked to the emotional/cognitive deficiency. More importantly, tcDNA treatment was generally limited to minimal glomerular changes and few cell necroses in proximal tubules, with only slight variation in serum and urinary kidney toxicity biomarker levels. These results demonstrate an encouraging safety profile for tcDNA, albeit typical of phosphorothiate AONs, and confirm its therapeutic potential for the systemic treatment of DMD patients. Keywords: antisense oligonucleotides, Duchenne muscular dystrophy, preclinical, splice switching, tcDNA-AONs

  14. Biodegradable polymer nanocarriers for therapeutic antisense microRNA delivery in living animals

    Science.gov (United States)

    Paulmurugan, Ramasamy; Sekar, Narayana M.; Sekar, Thillai V.

    2012-03-01

    MicroRNAs are endogenous regulators of gene expression, deregulated in several cellular diseases including cancer. Altering the cellular microenvironment by modulating the microRNAs functions can regulate different genes involved in major cellular processes, and this approach is now being investigated as a promising new generation of molecularly targeted anti-cancer therapies. AntagomiRs (Antisense-miRNAs) are a novel class of chemically modified stable oligonucleotides used for blocking the functions of endogenous microRNAs, which are overexpressed. A key challenge in achieving effective microRNAbased therapeutics lies in the development of an efficient delivery system capable of specifically delivering antisense oligonucleotides and target cancer cells in living animals. We are now developing an effective delivery system designed to selectively deliver antagomiR- 21 and antagomiR-10b to triple negative breast cancer cells, and to revert tumor cell metastasis and invasiveness. The FDA-approved biodegradable PLGA-nanoparticles were selected as a carrier for antagomiRs delivery. Chemically modified antagomiRs (antagomiR-21 and antagomiR-10b) were co-encapsulated in PEGylated-PLGA-nanoparticles by using the double-emulsification (W/O/W) solvent evaporation method, and the resulting average particle size of 150-200nm was used for different in vitro and in vivo experiments. The antagomiR encapsulated PLGA-nanoparticles were evaluated for their in vitro antagomiRs delivery, intracellular release profile, and antagomiRs functional effects, by measuring the endogenous cellular targets, and the cell growth and metastasis. The xenografts of tumor cells in living mice were used for evaluating the anti-metastatic and anti-invasive properties of cells. The results showed that the use of PLGA for antagomiR delivery is not only efficient in crossing cell membrane, but can also maintain functional intracellular antagomiRs level for a extended period of time and achieve

  15. The cellular uptake of antisense oligonucleotid of E6 mRNA into cervical cancer cells by DOPE-modified hydroxyapatite nanoparticles

    Directory of Open Access Journals (Sweden)

    Negin Saffarzadeh

    2014-10-01

    Full Text Available Objective(s: Although several chemical and physical methods for gene delivery have been introduced, their cytotoxicity, non-specific immune responses and the lack of biodegradability remain the main issues. In this study, hydroxyapatite nanoparticles (NPs and 1,2-dioleoyl-sn-glycero-3-phosphoethanol​amine (DOPE-modified hydroxyapatite NPs was coated with antisense oligonucleotide of E6 mRNA, and their uptakes into the cervical cancer cell line were evaluated. Materials and Methods: Calcium nitrate and diammonium phosphate were used for the synthesis of the hydroxyapatite nanoparticle. Thus, they were coated with polyethylene glycol (PEG, DOPE and antisense oligonucleotide of E6 mRNA using a cross-linker. Then, hydroxyapatite NPs and DOPE-modified hydroxyapatite NPs were incubated 48 hours with cervical cancer cells and their uptakes were evaluated by fluorescent microscopy. Results: The hydroxyapatite NPs had different shapes and some agglomeration with average size of 100 nm. The results showed DOPE-modified hydroxyapatite NPs had higher uptake than hydroxyapatite NPs (P

  16. White Ring; White ring

    Energy Technology Data Exchange (ETDEWEB)

    Aoki, H.; Yuzawa, H. [Nikken Sekkei Ltd., Osaka (Japan)

    1998-01-05

    White Ring is a citizen`s gymnasium used for figure skating and short track speed skating games of 18th Winter Olympic Games in 1998. White Ring is composed of a main-arena and a sub-arena. For the main-arena with an area 41mtimes66m, an ice link can be made by disengaging the potable floor and by flowing brine in the bridged polystyrene pipes embedded in the concrete floor. Due to the fortunate groundwater in this site, well water is used for the outside air treatment energy in 63% during heating and in 35% during cooling. Ammonia is used as a cooling medium for refrigerating facility. For the heating of audience area in the large space, heat load from the outside is reduced by enhancing the heat insulation performance of the roof of arena. The audience seats are locally heated using heaters. For the White Ring, high quality environment is realized for games through various functions of the large-scale roof of the large space. Success of the big event was expected. 15 figs., 4 tabs.

  17. Token Ring Project

    Directory of Open Access Journals (Sweden)

    Adela Ionescu

    2007-01-01

    Full Text Available Ring topology is a simple configuration used to connect processes that communicate among themselves. A number of network standards such as token ring, token bus, and FDDI are based on the ring connectivity. This article will develop an implementation of a ring of processes that communicate among themselves via pipe links. The processes are nodes in the ring. Each process reads from its standard input and writes in its standard output. N-1 process redirects the its standard output to a standard input of the process through a pipe. When the ring-structure is designed, the project can be extended to simulate networks or to implement algorithms for mutual exclusion

  18. Semi-algebraic function rings and reflectors of partially ordered rings

    CERN Document Server

    Schwartz, Niels

    1999-01-01

    The book lays algebraic foundations for real geometry through a systematic investigation of partially ordered rings of semi-algebraic functions. Real spectra serve as primary geometric objects, the maps between them are determined by rings of functions associated with the spectra. The many different possible choices for these rings of functions are studied via reflections of partially ordered rings. Readers should feel comfortable using basic algebraic and categorical concepts. As motivational background some familiarity with real geometry will be helpful. The book aims at researchers and graduate students with an interest in real algebra and geometry, ordered algebraic structures, topology and rings of continuous functions.

  19. Rotating ring-ring electrode theory and experiment

    NARCIS (Netherlands)

    Kuiken, H.K.; Bakkers, E.P.A.M.; Ligthart, H.; Kellyb, J.J.

    2000-01-01

    A model is presented for the rotating ring-ring electrode. Although the electrode is defined by four characteristic lengths, it is shown that the collection efficiency depends on only two dimensionless parameters. A simple relationship between these and the corresponding parameters for the rotating

  20. Peripheral reduction of FGFR4 with antisense oligonucleotides increases metabolic rate and lowers adiposity in diet-induced obese mice.

    Directory of Open Access Journals (Sweden)

    Xing Xian Yu

    Full Text Available Obesity is a primary risk factor for multiple metabolic disorders. Many drugs for the treatment of obesity, which mainly act through CNS as appetite suppressants, have failed during development or been removed from the market due to unacceptable adverse effects. Thus, there are very few efficacious drugs available and remains a great unmet medical need for anti-obesity drugs that increase energy expenditure by acting on peripheral tissues without severe side effects. Here, we report a novel approach involving antisense inhibition of fibroblast growth factor receptor 4 (FGFR4 in peripheral tissues. Treatment of diet-induce obese (DIO mice with FGFR4 antisense oligonucleotides (ASO specifically reduced liver FGFR4 expression that not only resulted in decrease in body weight (BW and adiposity in free-feeding conditions, but also lowered BW and adiposity under caloric restriction. In addition, combination treatment with FGFR4 ASO and rimonabant showed additive reduction in BW and adiposity. FGFR4 ASO treatment increased basal metabolic rate during free-feeding conditions and, more importantly, prevented adaptive decreases of metabolic rate induced by caloric restriction. The treatment increased fatty acid oxidation while decreased lipogenesis in both liver and fat. Mechanistic studies indicated that anti-obesity effect of FGFR4 ASO was mediated at least in part through an induction of plasma FGF15 level resulted from reduction of hepatic FGFR4 expression. The anti-obesity effect was accompanied by improvement in plasma glycemia, whole body insulin sensitivity, plasma lipid levels and liver steatosis. Therefore, FGFR4 could be a potential novel target and antisense reduction of hepatic FGFR4 expression could be an efficacious therapy as an adjunct to diet restriction or to an appetite suppressant for the treatment of obesity and related metabolic disorders.

  1. Peripheral reduction of FGFR4 with antisense oligonucleotides increases metabolic rate and lowers adiposity in diet-induced obese mice.

    Science.gov (United States)

    Yu, Xing Xian; Watts, Lynnetta M; Manchem, Vara Prasad; Chakravarty, Kaushik; Monia, Brett P; McCaleb, Michael L; Bhanot, Sanjay

    2013-01-01

    Obesity is a primary risk factor for multiple metabolic disorders. Many drugs for the treatment of obesity, which mainly act through CNS as appetite suppressants, have failed during development or been removed from the market due to unacceptable adverse effects. Thus, there are very few efficacious drugs available and remains a great unmet medical need for anti-obesity drugs that increase energy expenditure by acting on peripheral tissues without severe side effects. Here, we report a novel approach involving antisense inhibition of fibroblast growth factor receptor 4 (FGFR4) in peripheral tissues. Treatment of diet-induce obese (DIO) mice with FGFR4 antisense oligonucleotides (ASO) specifically reduced liver FGFR4 expression that not only resulted in decrease in body weight (BW) and adiposity in free-feeding conditions, but also lowered BW and adiposity under caloric restriction. In addition, combination treatment with FGFR4 ASO and rimonabant showed additive reduction in BW and adiposity. FGFR4 ASO treatment increased basal metabolic rate during free-feeding conditions and, more importantly, prevented adaptive decreases of metabolic rate induced by caloric restriction. The treatment increased fatty acid oxidation while decreased lipogenesis in both liver and fat. Mechanistic studies indicated that anti-obesity effect of FGFR4 ASO was mediated at least in part through an induction of plasma FGF15 level resulted from reduction of hepatic FGFR4 expression. The anti-obesity effect was accompanied by improvement in plasma glycemia, whole body insulin sensitivity, plasma lipid levels and liver steatosis. Therefore, FGFR4 could be a potential novel target and antisense reduction of hepatic FGFR4 expression could be an efficacious therapy as an adjunct to diet restriction or to an appetite suppressant for the treatment of obesity and related metabolic disorders.

  2. The human PINK1 locus is regulated in vivo by a non-coding natural antisense RNA during modulation of mitochondrial function

    Directory of Open Access Journals (Sweden)

    Wahlestedt Claes

    2007-03-01

    Full Text Available Abstract Background Mutations in the PTEN induced putative kinase 1 (PINK1 are implicated in early-onset Parkinson's disease. PINK1 is expressed abundantly in mitochondria rich tissues, such as skeletal muscle, where it plays a critical role determining mitochondrial structural integrity in Drosophila. Results Herein we characterize a novel splice variant of PINK1 (svPINK1 that is homologous to the C-terminus regulatory domain of the protein kinase. Naturally occurring non-coding antisense provides sophisticated mechanisms for diversifying genomes and we describe a human specific non-coding antisense expressed at the PINK1 locus (naPINK1. We further demonstrate that PINK1 varies in vivo when human skeletal muscle mitochondrial content is enhanced, supporting the idea that PINK1 has a physiological role in mitochondrion. The observation of concordant regulation of svPINK1 and naPINK1 during in vivo mitochondrial biogenesis was confirmed using RNAi, where selective targeting of naPINK1 results in loss of the PINK1 splice variant in neuronal cell lines. Conclusion Our data presents the first direct observation that a mammalian non-coding antisense molecule can positively influence the abundance of a cis-transcribed mRNA under physiological abundance conditions. While our analysis implies a possible human specific and dsRNA-mediated mechanism for stabilizing the expression of svPINK1, it also points to a broader genomic strategy for regulating a human disease locus and increases the complexity through which alterations in the regulation of the PINK1 locus could occur.

  3. Topological ring currents in the "empty" ring of benzo-annelated perylenes.

    Science.gov (United States)

    Dickens, Timothy K; Mallion, Roger B

    2011-01-27

    Cyclic conjugation in benzo-annelated perylenes is examined by means of the topological π-electron ring currents calculated for each of their constituent rings, in a study that is an exact analogy of a recent investigation by Gutman et al. based on energy-effect values for the corresponding rings in each of these structures. "Classical" approaches, such as Kekulé structures, Clar "sextet" formulas, and circuits of conjugation, predict that the central ring in perylene is "empty" and thus contributes negligibly to cyclic conjugation. However, conclusions from the present calculations of topological ring currents agree remarkably with those arising from the earlier study involving energy-effect values in that, contrary to what would be predicted from the classical approaches, rings annelated in an angular fashion relative to the central ring of these perylene structures materially increase the extent of that ring's involvement in cyclic conjugation. It is suggested that such close quantitative agreement between the predictions of these two superficially very different indices (energy effect and topological ring current) might be due to the fact that, ultimately, both depend, albeit in ostensibly quite different ways, only on an adjacency matrix that contains information about the carbon-carbon connectivity of the conjugated system in question.

  4. Reversible antisense inhibition of Shaker-like Kv1.1 potassium channel expression impairs associative memory in mouse and rat

    Science.gov (United States)

    Meiri, Noam; Ghelardini, Carla; Tesco, Giuseppina; Galeotti, Nicoletta; Dahl, Dennis; Tomsic, Daniel; Cavallaro, Sebastiano; Quattrone, Alessandro; Capaccioli, Sergio; Bartolini, Alessandro; Alkon, Daniel L.

    1997-01-01

    Long-term memory is thought to be subserved by functional remodeling of neuronal circuits. Changes in the weights of existing synapses in networks might depend on voltage-gated potassium currents. We therefore studied the physiological role of potassium channels in memory, concentrating on the Shaker-like Kv1.1, a late rectifying potassium channel that is highly localized within dendrites of hippocampal CA3 pyramidal and dentate gyrus granular cells. Repeated intracerebroventricular injection of antisense oligodeoxyribonucleotide to Kv1.1 reduces expression of its particular intracellular mRNA target, decreases late rectifying K+ current(s) in dentate granule cells, and impairs memory but not other motor or sensory behaviors, in two different learning paradigms, mouse passive avoidance and rat spatial memory. The latter, hippocampal-dependent memory loss occurred in the absence of long-term potentiation changes recorded both from the dentate gyrus or CA1. The specificity of the reversible antisense targeting of mRNA in adult animal brains may avoid irreversible developmental and genetic background effects that accompany transgenic “knockouts”. PMID:9114006

  5. Reversible antisense inhibition of Shaker-like Kv1.1 potassium channel expression impairs associative memory in mouse and rat.

    Science.gov (United States)

    Meiri, N; Ghelardini, C; Tesco, G; Galeotti, N; Dahl, D; Tomsic, D; Cavallaro, S; Quattrone, A; Capaccioli, S; Bartolini, A; Alkon, D L

    1997-04-29

    Long-term memory is thought to be subserved by functional remodeling of neuronal circuits. Changes in the weights of existing synapses in networks might depend on voltage-gated potassium currents. We therefore studied the physiological role of potassium channels in memory, concentrating on the Shaker-like Kv1.1, a late rectifying potassium channel that is highly localized within dendrites of hippocampal CA3 pyramidal and dentate gyrus granular cells. Repeated intracerebroventricular injection of antisense oligodeoxyribonucleotide to Kv1.1 reduces expression of its particular intracellular mRNA target, decreases late rectifying K+ current(s) in dentate granule cells, and impairs memory but not other motor or sensory behaviors, in two different learning paradigms, mouse passive avoidance and rat spatial memory. The latter, hippocampal-dependent memory loss occurred in the absence of long-term potentiation changes recorded both from the dentate gyrus or CA1. The specificity of the reversible antisense targeting of mRNA in adult animal brains may avoid irreversible developmental and genetic background effects that accompany transgenic "knockouts".

  6. Kayser-Fleischer Rings

    Science.gov (United States)

    ... Support Contacts Lab Tracker/Copper Calculator Stories Programs & Research ... About Everything you need to know about Wilson Disease Kayser-Fleischer Rings Definition Kayser-Fleischer Ring: Clinical sign. Brownish-yellow ring visible around the corneo- ...

  7. Planetary Rings

    Science.gov (United States)

    Nicholson, P. D.

    2001-11-01

    A revolution in the studies in planetary rings studies occurred in the period 1977--1981, with the serendipitous discovery of the narrow, dark rings of Uranus, the first Voyager images of the tenuous jovian ring system, and the many spectacular images returned during the twin Voyager flybys of Saturn. In subsequent years, ground-based stellar occultations, HST observations, and the Voyager flybys of Uranus (1986) and Neptune (1989), as well as a handful of Galileo images, provided much additional information. Along with the completely unsuspected wealth of detail these observations revealed came an unwelcome problem: are the rings ancient or are we privileged to live at a special time in history? The answer to this still-vexing question may lie in the complex gravitational interactions recent studies have revealed between the rings and their retinues of attendant satellites. Among the four known ring systems, we see elegant examples of Lindblad and corotation resonances (first invoked in the context of galactic disks), electromagnetic resonances, spiral density waves and bending waves, narrow ringlets which exhibit internal modes due to collective instabilities, sharp-edged gaps maintained via tidal torques from embedded moonlets, and tenuous dust belts created by meteoroid impact onto parent bodies. Perhaps most puzzling is Saturn's multi-stranded, clumpy F ring, which continues to defy a simple explanation 20 years after it was first glimpsed in grainy images taken by Pioneer 11. Voyager and HST images reveal a complex, probably chaotic, dynamical interaction between unseen parent bodies within this ring and its two shepherd satellites, Pandora and Prometheus. The work described here reflects contributions by Joe Burns, Jeff Cuzzi, Luke Dones, Dick French, Peter Goldreich, Colleen McGhee, Carolyn Porco, Mark Showalter, and Bruno Sicardy, as well as those of the author. This research has been supported by NASA's Planetary Geology and Geophysics program and the

  8. Quantitative Analysis of Survivin Protein Expression and Its Therapeutic Depletion by an Antisense Oligonucleotide in Human Lung Tumors

    Directory of Open Access Journals (Sweden)

    Anna L Olsen

    2012-01-01

    Full Text Available RNA-directed antisense and interference therapeutics are a promising treatment option for cancer. The demonstration of depletion of target proteins within human tumors in vivo using validated methodology will be a key to the application of this technology. Here, we present a flow cytometric-based approach to quantitatively determine protein levels in solid tumor material derived by fiber optic brushing (FOB of non-small cell lung cancer (NSCLC patients. Focusing upon the survivin protein, and its depletion by an antisense oligonucleotide (ASO (LY2181308, we show that we can robustly identify a subpopulation of survivin positive tumor cells in FOB samples, and, moreover, detect survivin depletion in tumor samples from a patient treated with LY2181308. Survivin depletion appears to be a result of treatment with this ASO, because a tumor treated with conventional cytotoxic chemotherapy did not exhibit a decreased percentage of survivin positive cells. Our approach is likely to be broadly applicable to, and useful for, the quantification of protein levels in tumor samples obtained as part of clinical trials and studies, facilitating the proof-of-principle testing of novel targeted therapies.

  9. Preparation for electron ring - plasma ring merging experiments in RECE-MERGE

    International Nuclear Information System (INIS)

    Taggart, D.; Sekiguchi, A.; Fleischmann, H.H.

    1986-01-01

    The formation of a mixed-CT using relativistic electron rings and gun-produced plasma rings by MERGE-ing them axially is simulated. This process is similar to the axial stacking of relativistic electron rings in RECE-Christa. The results of their first plasm production experiment are reported here. After study of the gun-produced plasma's properties is completed, the gun will be mounted at the downstream end of the vacuum tank and the source of relativistic electron rings will be at the upstream end. The two rings, formed at opposite ends of the tank, will be translated axially and merged

  10. Widespread anti-sense transcription in apple is correlated with siRNA production and indicates a large potential for transcriptional and/or post-transcriptional control.

    Science.gov (United States)

    Celton, Jean-Marc; Gaillard, Sylvain; Bruneau, Maryline; Pelletier, Sandra; Aubourg, Sébastien; Martin-Magniette, Marie-Laure; Navarro, Lionel; Laurens, François; Renou, Jean-Pierre

    2014-07-01

    Characterizing the transcriptome of eukaryotic organisms is essential for studying gene regulation and its impact on phenotype. The realization that anti-sense (AS) and noncoding RNA transcription is pervasive in many genomes has emphasized our limited understanding of gene transcription and post-transcriptional regulation. Numerous mechanisms including convergent transcription, anti-correlated expression of sense and AS transcripts, and RNAi remain ill-defined. Here, we have combined microarray analysis and high-throughput sequencing of small RNAs (sRNAs) to unravel the complexity of transcriptional and potential post-transcriptional regulation in eight organs of apple (Malus × domestica). The percentage of AS transcript expression is higher than that identified in annual plants such as rice and Arabidopsis thaliana. Furthermore, we show that a majority of AS transcripts are transcribed beyond 3'UTR regions, and may cover a significant portion of the predicted sense transcripts. Finally we demonstrate at a genome-wide scale that anti-sense transcript expression is correlated with the presence of both short (21-23 nt) and long (> 30 nt) siRNAs, and that the sRNA coverage depth varies with the level of AS transcript expression. Our study provides a new insight on the functional role of anti-sense transcripts at the genome-wide level, and a new basis for the understanding of sRNA biogenesis in plants. © 2014 INRA. New Phytologist © 2014 New Phytologist Trust.

  11. Long-term Exon Skipping Studies With 2′-O-Methyl Phosphorothioate Antisense Oligonucleotides in Dystrophic Mouse Models

    Directory of Open Access Journals (Sweden)

    Christa L Tanganyika-de Winter

    2012-01-01

    Full Text Available Antisense-mediated exon skipping for Duchenne muscular dystrophy (DMD is currently tested in phase 3 clinical trials. The aim of this approach is to modulate splicing by skipping a specific exon to reframe disrupted dystrophin transcripts, allowing the synthesis of a partly functional dystrophin protein. Studies in animal models allow detailed analysis of the pharmacokinetic and pharmacodynamic profile of antisense oligonucleotides (AONs. Here, we tested the safety and efficacy of subcutaneously administered 2′-O-methyl phosphorothioate AON at 200 mg/kg/week for up to 6 months in mouse models with varying levels of disease severity: mdx mice (mild phenotype and mdx mice with one utrophin allele (mdx/utrn+/−; more severe phenotype. Long-term treatment was well tolerated and exon skipping and dystrophin restoration confirmed for all animals. Notably, in the more severely affected mdx/utrn+/− mice the therapeutic effect was larger: creatine kinase (CK levels were more decreased and rotarod running time was more increased. This suggests that the mdx/utrn+/− model may be a more suitable model to test potential therapies than the regular mdx mouse. Our results also indicate that long-term subcutaneous treatment in dystrophic mouse models with these AONs is safe and beneficial.

  12. Divergently overlapping cis-encoded antisense RNA regulating toxin-antitoxin systems from E. coli: hok/sok, ldr/rdl, symE/symR.

    Science.gov (United States)

    Kawano, Mitsuoki

    2012-12-01

    Toxin-antitoxin (TA) systems are categorized into three classes based on the type of antitoxin. In type I TA systems, the antitoxin is a small antisense RNA that inhibits translation of small toxic proteins by binding to the corresponding mRNAs. Those type I TA systems were originally identified as plasmid stabilization modules rendering a post-segregational killing (PSK) effect on the host cells. The type I TA loci also exist on the Escherichia coli chromosome but their biological functions are less clear. Genetic organization and regulatory elements of hok/sok and ldr/rdl families are very similar and the toxins are predicted to contain a transmembrane domain, but otherwise share no detectable sequence similarity. This review will give an overview of the type I TA modules of E. coli K-12, especially hok/sok, ldr/rdl and SOS-inducible symE/symR systems, which are regulated by divergently overlapping cis-encoded antisense RNAs.

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

    DEFF Research Database (Denmark)

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

    2018-01-01

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

  14. Ring faults and ring dikes around the Orientale basin on the Moon.

    Science.gov (United States)

    Andrews-Hanna, Jeffrey C; Head, James W; Johnson, Brandon; Keane, James T; Kiefer, Walter S; McGovern, Patrick J; Neumann, Gregory A; Wieczorek, Mark A; Zuber, Maria T

    2018-08-01

    The Orientale basin is the youngest and best-preserved multiring impact basin on the Moon, having experienced only modest modification by subsequent impacts and volcanism. Orientale is often treated as the type example of a multiring basin, with three prominent rings outside of the inner depression: the Inner Rook Montes, the Outer Rook Montes, and the Cordillera. Here we use gravity data from NASA's Gravity Recovery and Interior Laboratory (GRAIL) mission to reveal the subsurface structure of Orientale and its ring system. Gradients of the gravity data reveal a continuous ring dike intruded into the Outer Rook along the plane of the fault associated with the ring scarp. The volume of this ring dike is ~18 times greater than the volume of all extrusive mare deposits associated with the basin. The gravity gradient signature of the Cordillera ring indicates an offset along the fault across a shallow density interface, interpreted to be the base of the low-density ejecta blanket. Both gravity gradients and crustal thickness models indicate that the edge of the central cavity is shifted inward relative to the equivalent Inner Rook ring at the surface. Models of the deep basin structure show inflections along the crust-mantle interface at both the Outer Rook and Cordillera rings, indicating that the basin ring faults extend from the surface to at least the base of the crust. Fault dips range from 13-22° for the Cordillera fault in the northeastern quadrant, to 90° for the Outer Rook in the northwestern quadrant. The fault dips for both outer rings are lowest in the northeast, possibly due to the effects of either the direction of projectile motion or regional gradients in pre-impact crustal thickness. Similar ring dikes and ring faults are observed around the majority of lunar basins.

  15. Groups, rings, modules

    CERN Document Server

    Auslander, Maurice

    2014-01-01

    This classic monograph is geared toward advanced undergraduates and graduate students. The treatment presupposes some familiarity with sets, groups, rings, and vector spaces. The four-part approach begins with examinations of sets and maps, monoids and groups, categories, and rings. The second part explores unique factorization domains, general module theory, semisimple rings and modules, and Artinian rings. Part three's topics include localization and tensor products, principal ideal domains, and applications of fundamental theorem. The fourth and final part covers algebraic field extensions

  16. Saturn's Rings Edge-on

    Science.gov (United States)

    1995-01-01

    In one of nature's most dramatic examples of 'now-you see-them, now-you-don't', NASA's Hubble Space Telescope captured Saturn on May 22, 1995 as the planet's magnificent ring system turned edge-on. This ring-plane crossing occurs approximately every 15 years when the Earth passes through Saturn's ring plane.For comparison, the top picture was taken by Hubble on December 1, 1994 and shows the rings in a more familiar configuration for Earth observers.The bottom picture was taken shortly before the ring plane crossing. The rings do not disappear completely because the edge of the rings reflects sunlight. The dark band across the middle of Saturn is the shadow of the rings cast on the planet (the Sun is almost 3 degrees above the ring plane.) The bright stripe directly above the ring shadow is caused by sunlight reflected off the rings onto Saturn's atmosphere. Two of Saturn's icy moons are visible as tiny starlike objects in or near the ring plane. They are, from left to right, Tethys (slightly above the ring plane) and Dione.This observation will be used to determine the time of ring-plane crossing and the thickness of the main rings and to search for as yet undiscovered satellites. Knowledge of the exact time of ring-plane crossing will lead to an improved determination of the rate at which Saturn 'wobbles' about its axis (polar precession).Both pictures were taken with Hubble's Wide Field Planetary Camera 2. The top image was taken in visible light. Saturn's disk appears different in the bottom image because a narrowband filter (which only lets through light that is not absorbed by methane gas in Saturn's atmosphere) was used to reduce the bright glare of the planet. Though Saturn is approximately 900 million miles away, Hubble can see details as small as 450 miles across.The Wide Field/Planetary Camera 2 was developed by the Jet Propulsion Laboratory and managed by the Goddard Spaced Flight Center for NASA's Office of Space Science.This image and other images and

  17. Antisense oligonucleotides suppress cell-volume-induced activation of chloride channels.

    Science.gov (United States)

    Gschwentner, M; Nagl, U O; Wöll, E; Schmarda, A; Ritter, M; Paulmichl, M

    1995-08-01

    Cell volume regulation is an essential feature of most cells. After swelling in hypotonic media, the simultaneous activation of potassium and chloride channels is believed to be the initial, time-determining step in cell volume regulation. The activation of both pathways is functionally linked and enables the cells to lose ions and water, subsequently leading to cell shrinkage and readjustment of the initial volume. NIH 3T3 fibroblasts efficiently regulate their volume after swelling and bear chloride channels that are activated by decreasing extracellular osmolarity. The chloride current elicited in these cells after swelling is reminiscent of the current found in oocytes expressing an outwardly rectifying chloride current termed ICln. Introduction of antisense oligodeoxynucleotides complementary to the first 30 nucleotides of the coding region of the ICln channel into NIH 3T3 fibroblasts suppresses the activation of the swelling-induced chloride current. The experiments directly demonstrate an unambiguous link between a volume-activated chloride current and a cloned protein involved in chloride transport.

  18. 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

  19. The Rotating Ring-Ring Electrode. Theory and Experiment

    NARCIS (Netherlands)

    Kuiken, H.K.; Bakkers, E.P.A.M.; Ligthart, H.; Kelly, J.J.

    2000-01-01

    A model is presented for the rotating ring-ring electrode. Although the electrode is defined by four characteristic lengths, it is shown that the collection efficiency depends on only two dimensionless parameters. A simple relationship between these and the corresponding parameters for the rotating

  20. Wear Analysis of Top Piston Ring to Reduce Top Ring Reversal Bore Wear

    Directory of Open Access Journals (Sweden)

    P. Ilanthirayan

    2017-12-01

    Full Text Available The piston rings are the most important part in engine which controls the lubricating oil consumption and blowby of the gases. The lubricating film of oil is provided to seal of gases towards crankcase and also to give smooth friction free translatory motion between rings and liner. Of the three rings present top ring is more crucial as it does the main work of restricting gases downwards the crankcase. Boundary lubrication is present at the Top dead centre (TDC and Bottom dead centre (BDC of the liner surface. In addition to this, top ring is exposed to high temperature gases which makes the oil present near the top ring to get evaporated and decreasing its viscosity, making metal-metal contact most of the time. Due to this at TDC, excess wear happens on the liner which is termed as Top ring reversal bore wear. The wear rate depends upon many parameters such as lubrication condition, viscosity index, contact type, normal forces acting on ring, geometry of ring face, surface roughness, material property. The present work explores the wear depth for different geometries of barrel ring using Finite Element model with the help of Archard wear law and the same is validated through experimentation. The study reveals that Asymmetric barrel rings have less contact pressure which in turn reduces the wear at Top dead centre.

  1. PREFACE: Special section on vortex rings Special section on vortex rings

    Science.gov (United States)

    Fukumoto, Yasuhide

    2009-10-01

    This special section of Fluid Dynamics Research includes five articles on vortex rings in both classical and quantum fluids. The leading scientists of the field describe the trends in and the state-of-the-art development of experiments, theories and numerical simulations of vortex rings. The year 2008 was the 150th anniversary of 'vortex motion' since Hermann von Helmholtz opened up this field. In 1858, Helmholtz published a paper in Crelle's Journal which put forward the concept of 'vorticity' and made the first analysis of vortex motion. Fluid mechanics before that was limited to irrotational motion. In the absence of vorticity, the motion of an incompressible homogeneous fluid is virtually equivalent to a rigid-body motion in the sense that the fluid motion is determined once the boundary configuration is specified. Helmholtz proved, among other things, that, without viscosity, a vortex line is frozen into the fluid. This Helmholtz's law immediately implies the preservation of knots and links of vortex lines and its implication is enormous. One of the major trends of fluid mechanics since the latter half of the 20th century is to clarify the topological meaning of Helmholtz's law and to exploit it to develop theoretical and numerical methods to find the solutions of the Euler equations and to develop experimental techniques to gain an insight into fluid motion. Vortex rings are prominent coherent structures in a variety of fluid motions from the microscopic scale, through human and mesoscale to astrophysical scales, and have attracted people's interest. The late professor Philip G Saffman (1981) emphasized the significance of studies on vortex rings. One particular motion exemplifies the whole range of problems of vortex motion and is also a commonly known phenomenon, namely the vortex ring or smoke ring. Vortex rings are easily produced by dropping drops of one liquid into another, or by puffing fluid out of a hole, or by exhaling smoke if one has the skill

  2. Vortex rings

    CERN Document Server

    Akhmetov, D G

    2009-01-01

    This text on vortex rings covers their theoretical foundation, systematic investigations, and practical applications such as the extinction of fires at gushing oil wells. It pays special attention to the formation and motion of turbulent vortex rings.

  3. An antisense oligodeoxynucleotide targeted against the type IIβ regulatory subunit mRNA of protein kinase inhibits cAMP-induced differentiation in HL-60 leukemia cells without affecting phorbol ester effects

    International Nuclear Information System (INIS)

    Tortora, G.; Clair, T.; Cho-Chung, Y.S.

    1990-01-01

    The type II β regulatory subunit of cAMP-dependent protein kinase (RII β ) has been hypothesized to play an important role in the growth inhibition and differentiation induced by site-selective cAMP analogs in human cancer cells, but direct proof of this function has been lacking. To address this tissue, HL-60 human promyelocytic leukemia cells were exposed to RII β antisense synthetic oligodeoxynucleotide, and the effects on cAMP-induced growth regulation were examined. Exposure of these cells to RII β antisense oligodeoxynucleotide resulted in a decrease in cAMP analog-induced growth inhibition and differentiation without apparent effect on differentiation induced by phorbol esters. This loss in cAMP growth regulatory function correlated with a decrease in basal and induced levels of RII β protein. Exposure to RII β sense, RI α and RII α antisense, or irrelevant oligodeoxynucleotides had no such effect. These results show that the RII β regulatory subunit of protein kinase plays a critical role in the cAMP-induced growth regulation of HL-60 leukemia cells

  4. FUZZY RINGS AND ITS PROPERTIES

    Directory of Open Access Journals (Sweden)

    Karyati Karyati

    2017-01-01

      One of algebraic structure that involves a binary operation is a group that is defined  an un empty set (classical with an associative binary operation, it has identity elements and each element has an inverse. In the structure of the group known as the term subgroup, normal subgroup, subgroup and factor group homomorphism and its properties. Classical algebraic structure is developed to algebraic structure fuzzy by the researchers as an example semi group fuzzy and fuzzy group after fuzzy sets is introduced by L. A. Zadeh at 1965. It is inspired of writing about semi group fuzzy and group of fuzzy, a research on the algebraic structure of the ring is held with reviewing ring fuzzy, ideal ring fuzzy, homomorphism ring fuzzy and quotient ring fuzzy with its properties. The results of this study are obtained fuzzy properties of the ring, ring ideal properties fuzzy, properties of fuzzy ring homomorphism and properties of fuzzy quotient ring by utilizing a subset of a subset level  and strong level  as well as image and pre-image homomorphism fuzzy ring.   Keywords: fuzzy ring, subset level, homomorphism fuzzy ring, fuzzy quotient ring

  5. Polarization Insensitivity in Double-Split Ring and Triple-Split Ring Terahertz Resonators

    International Nuclear Information System (INIS)

    Wu Qian-Nan; Lan Feng; Tang Xiao-Pin; Yang Zi-Qiang

    2015-01-01

    A modified double-split ring resonator and a modified triple-split ring resonator, which offer polarization-insensitive performance, are investigated, designed and fabricated. By displacing the two gaps of the conventional double-split ring resonator away from the center, the second resonant frequency for the 0° polarized wave and the resonant frequency for the 90° polarized wave become increasingly close to each other until they are finally identical. Theoretical and experimental results show that the modified double-split ring resonator and the modified triple-split ring resonator are insensitive to different polarized waves and show strong resonant frequency dips near 433 and 444 GHz, respectively. The results of this work suggest new opportunities for the investigation and design of polarization-dependent terahertz devices based on split ring resonators. (paper)

  6. REM sleep enhancement and behavioral cataplexy following orexin (hypocretin)-II receptor antisense perfusion in the pontine reticular formation.

    Science.gov (United States)

    Thakkar, M M; Ramesh, V; Cape, E G; Winston, S; Strecker, R E; McCarley, R W

    1999-01-01

    Orexin (hypocretin)-containing neurons of the hypothalamus project to brainstem sites that are involved in the neural control of REM sleep, including the locus coeruleus, the dorsal raphe nucleus, the cholinergic zone of the mesopontine tegmentum, and the pontine reticular formation (PRF). Orexin knockout mice exhibit narcolepsy/cataplexy, and a mutant and defective gene for the orexin type II receptor is present in dogs with an inherited form of narcolepsy/cataplexy. However, the physiological systems mediating these effects have not been described. We reasoned that, since the effector neurons for the majority of REM sleep signs, including muscle atonia, were located in the PRF, this region was likely implicated in the production of these orexin-related abnormalities. To test this possibility, we used microdialysis perfusion of orexin type II receptor antisense in the PRF of rats. Ten to 24 hours after antisense perfusion, REM sleep increased two- to three-fold during both the light period (quiescent phase) and the dark period (active phase), and infrared video showed episodes of behavioral cataplexy. Moreover, preliminary data indicated no REM-related effects following perfusion with nonsense DNA, or when perfusion sites were outside the PRF. More work is needed to provide precise localization of the most effective site of orexin-induced inhibition of REM sleep phenomena.

  7. Rescue of peripheral vestibular function in Usher syndrome mice using a splice-switching antisense oligonucleotide.

    Science.gov (United States)

    Vijayakumar, Sarath; Depreux, Frederic F; Jodelka, Francine M; Lentz, Jennifer J; Rigo, Frank; Jones, Timothy A; Hastings, Michelle L

    2017-09-15

    Usher syndrome type 1C (USH1C/harmonin) is associated with profound retinal, auditory and vestibular dysfunction. We have previously reported on an antisense oligonucleotide (ASO-29) that dramatically improves auditory function and balance behavior in mice homozygous for the harmonin mutation Ush1c c.216G > A following a single systemic administration. The findings were suggestive of improved vestibular function; however, no direct vestibular assessment was made. Here, we measured vestibular sensory evoked potentials (VsEPs) to directly assess vestibular function in Usher mice. We report that VsEPs are absent or abnormal in Usher mice, indicating profound loss of vestibular function. Strikingly, Usher mice receiving ASO-29 treatment have normal or elevated vestibular response thresholds when treated during a critical period between postnatal day 1 and 5, respectively. In contrast, treatment of mice with ASO-29 treatment at P15 was minimally effective at rescuing vestibular function. Interestingly, ASO-29 treatment at P1, P5 or P15 resulted in sufficient vestibular recovery to support normal balance behaviors, suggesting a therapeutic benefit to balance with ASO-29 treatment at P15 despite the profound vestibular functional deficits that persist with treatment at this later time. These findings provide the first direct evidence of an effective treatment of peripheral vestibular function in a mouse model of USH1C and reveal the potential for using antisense technology to treat vestibular dysfunction. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Specific RNP capture with antisense LNA/DNA mixmers.

    Science.gov (United States)

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

    2017-08-01

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

  9. RINGED ACCRETION DISKS: EQUILIBRIUM CONFIGURATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Pugliese, D.; Stuchlík, Z., E-mail: d.pugliese.physics@gmail.com, E-mail: zdenek.stuchlik@physics.cz [Institute of Physics and Research Centre of Theoretical Physics and Astrophysics, Faculty of Philosophy and Science, Silesian University in Opava, Bezručovo náměstí 13, CZ-74601 Opava (Czech Republic)

    2015-12-15

    We investigate a model of a ringed accretion disk, made up by several rings rotating around a supermassive Kerr black hole attractor. Each toroid of the ringed disk is governed by the general relativity hydrodynamic Boyer condition of equilibrium configurations of rotating perfect fluids. Properties of the tori can then be determined by an appropriately defined effective potential reflecting the background Kerr geometry and the centrifugal effects. The ringed disks could be created in various regimes during the evolution of matter configurations around supermassive black holes. Therefore, both corotating and counterrotating rings have to be considered as being a constituent of the ringed disk. We provide constraints on the model parameters for the existence and stability of various ringed configurations and discuss occurrence of accretion onto the Kerr black hole and possible launching of jets from the ringed disk. We demonstrate that various ringed disks can be characterized by a maximum number of rings. We present also a perturbation analysis based on evolution of the oscillating components of the ringed disk. The dynamics of the unstable phases of the ringed disk evolution seems to be promising in relation to high-energy phenomena demonstrated in active galactic nuclei.

  10. Stirling engine piston ring

    Science.gov (United States)

    Howarth, Roy B.

    1983-01-01

    A piston ring design for a Stirling engine wherein the contact pressure between the piston and the cylinder is maintained at a uniform level, independent of engine conditions through a balancing of the pressure exerted upon the ring's surface and thereby allowing the contact pressure on the ring to be predetermined through the use of a preloaded expander ring.

  11. Physics of quantum rings

    International Nuclear Information System (INIS)

    Fomin, Vladimir M.

    2014-01-01

    Presents the new class of materials of quantum rings. Provides an elemental basis for low-cost high-performance devices promising for electronics, optoelectronics, spintronics and quantum information processing. Explains the physical properties of quantum rings to cover a gap in scientific literature. Presents the application of most advanced nanoengineering and nanocharacterization techniques. This book deals with a new class of materials, quantum rings. Innovative recent advances in experimental and theoretical physics of quantum rings are based on the most advanced state-of-the-art fabrication and characterization techniques as well as theoretical methods. The experimental efforts allow to obtain a new class of semiconductor quantum rings formed by capping self-organized quantum dots grown by molecular beam epitaxy. Novel optical and magnetic properties of quantum rings are associated with non-trivial topologies at the nanoscale. An adequate characterization of quantum rings is possible on the basis of modern characterization methods of nanostructures, such as Scanning Tunneling Microscopy. A high level of complexity is demonstrated to be needed for a dedicated theoretical model to adequately represent the specific features of quantum rings. The findings presented in this book contribute to develop low-cost high-performance electronic, spintronic, optoelectronic and information processing devices based on quantum rings.

  12. How does the blue-ringed octopus (Hapalochlaena lunulata) flash its blue rings?

    Science.gov (United States)

    Mäthger, Lydia M; Bell, George R R; Kuzirian, Alan M; Allen, Justine J; Hanlon, Roger T

    2012-11-01

    The blue-ringed octopus (Hapalochlaena lunulata), one of the world's most venomous animals, has long captivated and endangered a large audience: children playing at the beach, divers turning over rocks, and biologists researching neurotoxins. These small animals spend much of their time in hiding, showing effective camouflage patterns. When disturbed, the octopus will flash around 60 iridescent blue rings and, when strongly harassed, bite and deliver a neurotoxin that can kill a human. Here, we describe the flashing mechanism and optical properties of these rings. The rings contain physiologically inert multilayer reflectors, arranged to reflect blue-green light in a broad viewing direction. Dark pigmented chromatophores are found beneath and around each ring to enhance contrast. No chromatophores are above the ring; this is unusual for cephalopods, which typically use chromatophores to cover or spectrally modify iridescence. The fast flashes are achieved using muscles under direct neural control. The ring is hidden by contraction of muscles above the iridophores; relaxation of these muscles and contraction of muscles outside the ring expose the iridescence. This mechanism of producing iridescent signals has not previously been reported in cephalopods and we suggest that it is an exceptionally effective way to create a fast and conspicuous warning display.

  13. α-Skew π-McCoy Rings

    Directory of Open Access Journals (Sweden)

    Areej M. Abduldaim

    2013-01-01

    Full Text Available As a generalization of α-skew McCoy rings, we introduce the concept of α-skew π-McCoy rings, and we study the relationships with another two new generalizations, α-skew π1-McCoy rings and α-skew π2-McCoy rings, observing the relations with α-skew McCoy rings, π-McCoy rings, α-skew Armendariz rings, π-regular rings, and other kinds of rings. Also, we investigate conditions such that α-skew π1-McCoy rings imply α-skew π-McCoy rings and α-skew π2-McCoy rings. We show that in the case where R is a nonreduced ring, if R is 2-primal, then R is an α-skew π-McCoy ring. And, let R be a weak (α,δ-compatible ring; if R is an α-skew π1-McCoy ring, then R is α-skew π2-McCoy.

  14. The antisense RNA As1_flv4 in the Cyanobacterium Synechocystis sp. PCC 6803 prevents premature expression of the flv4-2 operon upon shift in inorganic carbon supply.

    Science.gov (United States)

    Eisenhut, Marion; Georg, Jens; Klähn, Stephan; Sakurai, Isamu; Mustila, Henna; Zhang, Pengpeng; Hess, Wolfgang R; Aro, Eva-Mari

    2012-09-28

    The functional relevance of natural cis-antisense transcripts is mostly unknown. Here we have characterized the association of three antisense RNAs and one intergenically encoded noncoding RNA with an operon that plays a crucial role in photoprotection of photosystem II under low carbon conditions in the cyanobacterium Synechocystis sp. PCC 6803. Cyanobacteria show strong gene expression dynamics in response to a shift of cells from high carbon to low levels of inorganic carbon (C(i)), but the regulatory mechanisms are poorly understood. Among the most up-regulated genes in Synechocystis are flv4, sll0218, and flv2, which are organized in the flv4-2 operon. The flavodiiron proteins encoded by this operon open up an alternative electron transfer route, likely starting from the Q(B) site in photosystem II, under photooxidative stress conditions. Our expression analysis of cells shifted from high carbon to low carbon demonstrated an inversely correlated transcript accumulation of the flv4-2 operon mRNA and one antisense RNA to flv4, designated as As1_flv4. Overexpression of As1_flv4 led to a decrease in flv4-2 mRNA. The promoter activity of as1_flv4 was transiently stimulated by C(i) limitation and negatively regulated by the AbrB-like transcription regulator Sll0822, whereas the flv4-2 operon was positively regulated by the transcription factor NdhR. The results indicate that the tightly regulated antisense RNA As1_flv4 establishes a transient threshold for flv4-2 expression in the early phase after a change in C(i) conditions. Thus, it prevents unfavorable synthesis of the proteins from the flv4-2 operon.

  15. The Antisense RNA As1_flv4 in the Cyanobacterium Synechocystis sp. PCC 6803 Prevents Premature Expression of the flv4-2 Operon upon Shift in Inorganic Carbon Supply*

    Science.gov (United States)

    Eisenhut, Marion; Georg, Jens; Klähn, Stephan; Sakurai, Isamu; Mustila, Henna; Zhang, Pengpeng; Hess, Wolfgang R.; Aro, Eva-Mari

    2012-01-01

    The functional relevance of natural cis-antisense transcripts is mostly unknown. Here we have characterized the association of three antisense RNAs and one intergenically encoded noncoding RNA with an operon that plays a crucial role in photoprotection of photosystem II under low carbon conditions in the cyanobacterium Synechocystis sp. PCC 6803. Cyanobacteria show strong gene expression dynamics in response to a shift of cells from high carbon to low levels of inorganic carbon (Ci), but the regulatory mechanisms are poorly understood. Among the most up-regulated genes in Synechocystis are flv4, sll0218, and flv2, which are organized in the flv4-2 operon. The flavodiiron proteins encoded by this operon open up an alternative electron transfer route, likely starting from the QB site in photosystem II, under photooxidative stress conditions. Our expression analysis of cells shifted from high carbon to low carbon demonstrated an inversely correlated transcript accumulation of the flv4-2 operon mRNA and one antisense RNA to flv4, designated as As1_flv4. Overexpression of As1_flv4 led to a decrease in flv4-2 mRNA. The promoter activity of as1_flv4 was transiently stimulated by Ci limitation and negatively regulated by the AbrB-like transcription regulator Sll0822, whereas the flv4-2 operon was positively regulated by the transcription factor NdhR. The results indicate that the tightly regulated antisense RNA As1_flv4 establishes a transient threshold for flv4-2 expression in the early phase after a change in Ci conditions. Thus, it prevents unfavorable synthesis of the proteins from the flv4-2 operon. PMID:22854963

  16. Simultaneous Expression from Both the Sense and Antisense Strand of the Erythropoietin Receptor Gene Mitigates Acute Lung Injury

    Science.gov (United States)

    2017-09-01

    concept efficacy that increasing EpoR or RopE expression by cDNA delivery to lung cells in vitro enhances cytoprotection against hyperoxia-induced injury...oxidative damage, cell culture, rodent model, inhalation cDNA delivery, sense and antisense erythropoietin receptor transcripts 16. SECURITY...prevention of acute lung injury. 1-6 50% Subtask 1: Prepare plasmid cDNA of EpoR and RopE in nanoparticle formulation. 1 Completed 06.2017 Subtask 2

  17. Inhibiting the growth of methicillin-resistant Staphylococcus aureus in vitro with antisense peptide nucleic acid conjugates targeting the ftsZ gene

    Directory of Open Access Journals (Sweden)

    Shumei Liang

    2015-01-01

    Conclusion: Our results demonstrate that the potent effects of PNAs on bacterial growth and cell viability were mediated by the down-regulation or even knock-out of ftsZ gene expression. This highlights the utility of ftsZ as a promising target for the development of new antisense antibacterial agents to treat MRSA infections.

  18. VUV optical ring resonator for Duke storage ring free electron laser

    Energy Technology Data Exchange (ETDEWEB)

    Park, S.H.; Litvinenko, V.N.; Madey, J.M.J. [Duke Univ., Durham, NC (United States)] [and others

    1995-12-31

    The conceptual design of the multifaceted-mirror ring resonator for Duke storage ring VUV FEL is presented. The expected performance of the OK-4 FEL with ring resonator is described. We discuss in this paper our plans to study reflectivity of VUV mirrors and their resistivity to soft X-ray spontaneous radiation from OK-4 undulator.

  19. Interaction Region Design for a Ring-Ring LHeC

    CERN Document Server

    Thompson, L N S; Bernard, N R; Fitterer, M; Holzer, B; Klein, M; Kostka, P

    2011-01-01

    tively low energy and moderately high intensity provides high luminosity TeV-scale e-p collisions at one of the LHC interaction points, running simultaneously with existing experiments. Two designs are studied; an electron ring situated in the LHC tunnel, and an electron linac. The focus of this paper is on the ring design. Designing an e-p machine presents interesting accelerator physics and design challenges, particularly when considering the interaction region. These include coupled optics, beam separation and unconventional mini-beta focusing schemes. Designs are constrained by an array of interdependent factors, including beam-beam interaction, detector dimensions and acceptance, luminosity and synchrotron radiation. Methods of addressing these complex issues are discussed. The current designs for the LHeC Ring-Ring interaction region and long straight section are presented and discussed, in the context of the project goals and design challenges encountered. Future developments and work are also discusse...

  20. Uniquely Strongly Clean Group Rings

    Institute of Scientific and Technical Information of China (English)

    WANG XIU-LAN

    2012-01-01

    A ring R is called clean if every element is the sum of an idempotent and a unit,and R is called uniquely strongly clean (USC for short) if every element is uniquely the sum of an idempotent and a unit that commute.In this article,some conditions on a ring R and a group G such that RG is clean are given.It is also shown that if G is a locally finite group,then the group ring RG is USC if and only if R is USC,and G is a 2-group.The left uniquely exchange group ring,as a middle ring of the uniquely clean ring and the USC ring,does not possess this property,and so does the uniquely exchange group ring.

  1. Influence of ring growth rate on damage development in hot ring rolling

    NARCIS (Netherlands)

    Wang, C.; Geijselaers, H. J.M.; Omerspahic, E.; Recina, V.; van den Boogaard, A. H.

    2015-01-01

    As an incremental forming process of bulk metal, ring rolling provides a cost effective process route to manufacture seamless rings. In the production of hot rolled rings, defects such as porosity can sometimes be found in high alloyed steel, manufactured from ingots having macro-segregation. For

  2. Ring rotational speed trend analysis by FEM approach in a Ring Rolling process

    Science.gov (United States)

    Allegri, G.; Giorleo, L.; Ceretti, E.

    2018-05-01

    Ring Rolling is an advanced local incremental forming technology to fabricate directly precise seamless ring-shape parts with various dimensions and materials. In this process two different deformations occur in order to reduce the width and the height of a preform hollow ring; as results a diameter expansion is obtained. In order to guarantee a uniform deformation, the preform is forced toward the Driver Roll whose aim is to transmit the rotation to the ring. The ring rotational speed selection is fundamental because the higher is the speed the higher will be the axial symmetry of the deformation process. However, it is important to underline that the rotational speed will affect not only the final ring geometry but also the loads and energy needed to produce it. Despite this importance in industrial environment, usually, a constant value for the Driver Roll angular velocity is set so to result in a decreasing trend law for the ring rotational speed. The main risk due to this approach is not fulfilling the axial symmetric constrain (due to the diameter expansion) and to generate a high localized ring section deformation. In order to improve the knowledge about this topic in the present paper three different ring rotational speed trends (constant, linearly increasing and linearly decreasing) were investigated by FEM approach. Results were compared in terms of geometrical and dimensional analysis, loads and energies required.

  3. Mechanical improvement of metal reinforcement rings for a finite ring-shaped superconducting bulk

    Science.gov (United States)

    Huang, Chen-Guang; Zhou, You-He

    2018-03-01

    As a key technique, reinforcement of type-II superconducting bulks with metal rings can efficiently improve their mechanical properties to enhance the maximum trapped field. In this paper, we study the magnetostrictive and fracture behaviors of a finite superconducting ring bulk reinforced by three typical reinforcing structures composed of metal rings during the magnetizing process by means of the minimization of magnetic energy and the finite element method. After a field-dependent critical current density is adopted, the magnetostriction, pinning-induced stress, and crack tip stress intensity factor are calculated considering the demagnetization effects. The results show that the mechanical properties of the ring bulk are strongly dependent on the reinforcing structure and the material and geometrical parameters of the metal rings. Introducing the metal ring can significantly reduce the hoop stress, and the reduction effect by internal reinforcement is much improved relative to external reinforcement. By comparison, bilateral reinforcement seems to be the best candidate structure. Only when the metal rings have particular Young's modulus and radial thickness will they contribute to improve the mechanical properties the most. In addition, if an edge crack is pre-existing in the ring bulk, the presence of metal rings can effectively avoid crack propagation since it reduces the crack tip stress intensity factor by nearly one order of magnitude.

  4. Ring correlations in random networks.

    Science.gov (United States)

    Sadjadi, Mahdi; Thorpe, M F

    2016-12-01

    We examine the correlations between rings in random network glasses in two dimensions as a function of their separation. Initially, we use the topological separation (measured by the number of intervening rings), but this leads to pseudo-long-range correlations due to a lack of topological charge neutrality in the shells surrounding a central ring. This effect is associated with the noncircular nature of the shells. It is, therefore, necessary to use the geometrical distance between ring centers. Hence we find a generalization of the Aboav-Weaire law out to larger distances, with the correlations between rings decaying away when two rings are more than about three rings apart.

  5. Growth inhibition of human pancreatic cancer cells by lipofection mediated IGF-1R antisense oligodeoxynucletides in combination with ionizing radiation

    International Nuclear Information System (INIS)

    Pan Yaozhen; Sun Chengyi; Wang Yuzhi

    2004-01-01

    Objective: To study the growth inhibition of human pancreatic cancer cells (PC-3) by lipofection-mediated and ionizing radiation improving transfection of IGF-1R antisense oligodeoxynucletides (ASON) in vitro. Methods: Colonigenicity of PC-3 cells in vitro after 60 Co γ-radiation was observed for ascertaining their radiosensitivity and optimal radiation dose was selected according to the radiation sensitivity. PC-3 cells were transfected by two ways: 1) by lipofection-mediated IGF-1R ASON combined with ionizing radiation. 2) by lipo-ASON alone without ionizing radiation. Cell growth was assessed by MTT method. The expression of IGF-1R at mRNA level was examined by RT-PCR. Flow cytometry was used to demonstrate apoptotic changes in lipo-ASON-treated cells. Results: The inhibitory efficiency of lipo-ASON combined with ionizing radiation was higher than that without ionizing radiation (P < 0.05). The apoptotic efficiency and the decreased level of IGF-1R at mRNA were significantly improved (P < 0.05). Conclusion: Lipofection-mediated and ionizing radiation-promoted transfection of IGF-1R antisense oligodeoxynucletides (ASON) significantly decreases IGF-1R at mRNA level and induces apoptosis of human pancreatic cancer cells in vitro

  6. Alpha - Skew Pi - Armendariz Rings

    Directory of Open Access Journals (Sweden)

    Areej M Abduldaim

    2018-03-01

    Full Text Available In this article we introduce a new concept called Alpha-skew Pi-Armendariz rings (Alpha - S Pi - ARas a generalization of the notion of Alpha-skew Armendariz rings.Another important goal behind studying this class of rings is to employ it in order to design a modern algorithm of an identification scheme according to the evolution of using modern algebra in the applications of the field of cryptography.We investigate general properties of this concept and give examples for illustration. Furthermore, this paperstudy the relationship between this concept and some previous notions related to Alpha-skew Armendariz rings. It clearly presents that every weak Alpha-skew Armendariz ring is Alpha-skew Pi-Armendariz (Alpha-S Pi-AR. Also, thisarticle showsthat the concepts of Alpha-skew Armendariz rings and Alpha-skew Pi- Armendariz rings are equivalent in case R is 2-primal and semiprime ring.Moreover, this paper proves for a semicommutative Alpha-compatible ringR that if R[x;Alpha] is nil-Armendariz, thenR is an Alpha-S Pi-AR. In addition, if R is an Alpha - S Pi -AR, 2-primal and semiprime ring, then N(R[x;Alpha]=N(R[x;Alpha]. Finally, we look forwardthat Alpha-skew Pi-Armendariz rings (Alpha-S Pi-ARbe more effect (due to their properties in the field of cryptography than Pi-Armendariz rings, weak Armendariz rings and others.For these properties and characterizations of the introduced concept Alpha-S Pi-AR, we aspire to design a novel algorithm of an identification scheme.

  7. Regulation of an antisense RNA with the transition of neonatal to IIb myosin heavy chain during postnatal development and hypothyroidism in rat skeletal muscle.

    Science.gov (United States)

    Pandorf, Clay E; Jiang, Weihua; Qin, Anqi X; Bodell, Paul W; Baldwin, Kenneth M; Haddad, Fadia

    2012-04-01

    Postnatal development of fast skeletal muscle is characterized by a transition in expression of myosin heavy chain (MHC) isoforms, from primarily neonatal MHC at birth to primarily IIb MHC in adults, in a tightly coordinated manner. These isoforms are encoded by distinct genes, which are separated by ∼17 kb on rat chromosome 10. The neonatal-to-IIb MHC transition is inhibited by a hypothyroid state. We examined RNA products [mRNA, pre-mRNA, and natural antisense transcript (NAT)] of developmental and adult-expressed MHC genes (embryonic, neonatal, I, IIa, IIx, and IIb) at 2, 10, 20, and 40 days after birth in normal and thyroid-deficient rat neonates treated with propylthiouracil. We found that a long noncoding antisense-oriented RNA transcript, termed bII NAT, is transcribed from a site within the IIb-Neo intergenic region and across most of the IIb MHC gene. NATs have previously been shown to mediate transcriptional repression of sense-oriented counterparts. The bII NAT is transcriptionally regulated during postnatal development and in response to hypothyroidism. Evidence for a regulatory mechanism is suggested by an inverse relationship between IIb MHC and bII NAT in normal and hypothyroid-treated muscle. Neonatal MHC transcription is coordinately expressed with bII NAT. A comparative phylogenetic analysis also suggests that bII NAT-mediated regulation has been a conserved trait of placental mammals for most of the eutherian evolutionary history. The evidence in support of the regulatory model implicates long noncoding antisense RNA as a mechanism to coordinate the transition between neonatal and IIb MHC during postnatal development.

  8. Plasma-ring, fast-opening switch

    International Nuclear Information System (INIS)

    Hartman, C.W.; Eddleman, J.; Hammer, J.H.

    1986-01-01

    The authors discuss a fast-opening switch concept based on magnetically confined plasma rings, PROS (for Plasma Ring Opening Switch). In PROS, the plasma ring, confined by Bθ /sub and B/poloidal /sub fields of a compact torus, provide a low mass, localized conduction path between coaxial electrodes. To operate the switch, driver current is passed across the electrodes through the ring, storing inductive energy in external inductance and between the electrodes on the driver side of the ring. The ring is accelerated away from the driver by the field of the driver current and passes over a load gap transferring the current to the load. The authors distinguish two configurations in PROS, straight PROS where the electrodes are coaxial cylinders, and cone PROS with conical electrodes. In straight PROS ring acceleration takes place during the inductive store period as in foil switches, but with the localized ring providing the current path. Increased performance is predicted for the cone PROS (see figure) which employs compression of the ring in the cone during the inductive store period. Here, the B/θ /sub field of the driver forces the ring towards the apex of the cone but the force is in near balance with the opposing component of the radial equilibrium force of the ring along the cone. As a result, the ring undergoes a slow, quasistatic compression limited only by resistive decay of the ring field. Slow compression allows inductive storage with low-power drivers (homopoloar, magneto cumulative generators, high C-low V capacitor banks, etc.). Near the apex of the cone, near peak compression, the ring is allowed to enter a straight coaxial section where, because of low-mass, it rapidly accelerates to high velocity and crosses the load gap

  9. Fusion Rings for Quantum Groups

    DEFF Research Database (Denmark)

    Andersen, Henning Haahr; Stroppel, Catharina

    2014-01-01

    We study the fusion rings of tilting modules for a quantum group at a root of unity modulo the tensor ideal of negligible tilting modules. We identify them in type A with the combinatorial rings from Korff, C., Stroppel, C.: The sl(ˆn)k-WZNW fusion ring: a combinato-rial construction...... and a realisation as quotient of quantum cohomology. Adv. Math. 225(1), 200–268, (2010) and give a similar description of the sp2n-fusion ring in terms of non-commutative symmetric functions. Moreover we give a presentation of all fusion rings in classical types as quotients of polynomial rings. Finally we also...... compute the fusion rings for type G2....

  10. The LSU Electron Storage Ring, the first commercially-built storage ring

    International Nuclear Information System (INIS)

    Sah, R.

    1990-01-01

    The Brobeck Division of Maxwell Laboratories, Inc., is building the first industrially-produced storage ring. It will be located at Louisiana State University (LSU) at the Center for Advanced Microstructures and Devices (CAMD) in Baton Rouge. The purpose of this electron storage ring is to provide intense beams of x-rays to advance the state-of-the-art in lithography and to permit research in a broad area. This facility consists of a 1.2 GeV, 400 mA electron storage ring with a 200 MeV linac injector. The magnet lattice is a Chasman-Green design (double-bend achromat), and the ring circumference is 55.2 meters. There are four 3.0 meter, dispersion-free straight sections, one for injection, one for the 500 MHz RF cavity, and two for possible future insertion devices. The storge ring construction project is in the detailed-design stage, and many systems are in the initial stages of fabrication. 4 figs., 1 tab

  11. Fusion rings and fusion ideals

    DEFF Research Database (Denmark)

    Andersen, Troels Bak

    by the so-called fusion ideals. The fusion rings of Wess-Zumino-Witten models have been widely studied and are well understood in terms of precise combinatorial descriptions and explicit generating sets of the fusion ideals. They also appear in another, more general, setting via tilting modules for quantum......This dissertation investigates fusion rings, which are Grothendieck groups of rigid, monoidal, semisimple, abelian categories. Special interest is in rational fusion rings, i.e., fusion rings which admit a finite basis, for as commutative rings they may be presented as quotients of polynomial rings...

  12. Physicochemical and biological properties of self-assembled antisense/poly(amidoamine) dendrimer nanoparticles: the effect of dendrimer generation and charge ratio

    OpenAIRE

    Nomani, Alireza; Haririan, Ismaeil; Rahimnia, Ramin; Fouladdel, Shamileh; Gazori, Tarane; Dinarvand, Rassoul; Omidi, Yadollah; Azizi, Ebrahim

    2010-01-01

    To gain a deeper understanding of the physicochemical phenomenon of self-assembled nanoparticles of different generations and ratios of poly (amidoamine) dendrimer (PAMAM) dendrimer and a short-stranded DNA (antisense oligonucleotide), multiple methods were used to characterize these nanoparticles including photon correlation spectroscopy (PCS); zeta potential measurement; and atomic force microscopy (AFM). PCS and AFM results revealed that, in contrast to larger molecules of DNA, smaller mol...

  13. 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.

  14. Evaluation of ring impedance of the Photon Factory storage ring

    International Nuclear Information System (INIS)

    Kiuchi, T.; Izawa, M.; Tokumoto, S.; Hori, Y.; Sakanaka, S.; Kobayashi, M.; Kobayakawa, H.

    1992-05-01

    The loss parameters of the ducts in the Photon Factory (PF) storage ring were evaluated using the wire method and the code TBCI. Both the measurement and the calculation were done for a different bunch length (σ) ranging from 23 to 80 ps. The PF ring impedance was estimated to be |Z/n|=3.2 Ω using the broadband impedance model. The major contribution to the impedance comes from the bellows and the gate valve sections. Improvements of these components will lower the ring impedance by half. (author)

  15. Materiales híbridos moleculares orgánicos-inorgánicos: síntesis y aplicación como electrodos en baterías recargables de litio

    Directory of Open Access Journals (Sweden)

    Torres-Gómez, G.

    2000-06-01

    Full Text Available A novel family of molecular hybrid materials based on electroactive inorganic species dispersed in conducting organic polymers is reported as electrodes for energy storage or conversion. Polyaniline and polypyrrole are effectively doped with electroactive polyoxometalates ([PMo12O40]3- or ferricyanide ([(FeCN6]3- anions as the only doping species. The high charge and size of these anions prevents their deintercalation during reduction in most cases. The synthesis of these hybrids can be made by chemical (bulk powders and electrochemical (films methods. For [PMo12O40]3-, nine aniline/pyrrole rings by anion are found in each case and the anion stays in the polymer matrix even after reduction at -0.4V (vs Ag/AgCl, 2.6V vs Li. In the case of Polypyrrole-FeCN6 hybrid the pyrrole-ring/Fe(CN6 ratio was around 10-12 depending on the temperature of synthesis. Temperature also affects the electrical conductivity, with the best values around 60Scm-1 (sample prepared at 0ºC. Fe(CN6 stays in the polymer matrix when the hybrid material is reduced in organic media. PMo12 hybrids intercalate up to 5.3 h+ during discharge (52 Ah/Kg whereas the hybrid with Fe(CN6 intercalates 2.7 lithium ions per formula unit (69Ah/Kg.

    Se describe la síntesis y aplicación como electrodos para el almacenamiento o conversión de energía de materiales híbridos basados en la dispersión de especies inorgánicas electroactivas en el seno de polímeros orgánicos conductores. Polianilina y polipirrol son dopados con polioxometalatos electroactivos ([PMo12O40]3- o aniones ferricianuro ([(FeCN6]3- como únicas especies dopantes. La elevada carga y tamaño de estos aniones evitan, en la mayoría de los casos, su desintercalación durante la reducción. Estos híbridos se han sintetizado por métodos químicos y electroquímicos, siendo la relación anillos de anilina o de pirrol por anión de [PMo12O40]3- de nueve, de manera que el anión permanece en el interior de la matriz

  16. Context Dependent Effects of Chimeric Peptide Morpholino Conjugates Contribute to Dystrophin Exon-skipping Efficiency.

    Science.gov (United States)

    Yin, Haifang; Boisguerin, Prisca; Moulton, Hong M; Betts, Corinne; Seow, Yiqi; Boutilier, Jordan; Wang, Qingsong; Walsh, Anthony; Lebleu, Bernard; Wood, Matthew Ja

    2013-09-24

    We have recently reported that cell-penetrating peptides (CPPs) and novel chimeric peptides containing CPP (referred as B peptide) and muscle-targeting peptide (referred as MSP) motifs significantly improve the systemic exon-skipping activity of morpholino phosphorodiamidate oligomers (PMOs) in dystrophin-deficient mdx mice. In the present study, the general mechanistic significance of the chimeric peptide configuration on the activity and tissue uptake of peptide conjugated PMOs in vivo was investigated. Four additional chimeric peptide-PMO conjugates including newly identified peptide 9 (B-9-PMO and 9-B-PMO) and control peptide 3 (B-3-PMO and 3-B-PMO) were tested in mdx mice. Immunohistochemical staining, RT-PCR and western blot results indicated that B-9-PMO induced significantly higher level of exon skipping and dystrophin restoration than its counterpart (9-B-PMO), further corroborating the notion that the activity of chimeric peptide-PMO conjugates is dependent on relative position of the tissue-targeting peptide motif within the chimeric peptide with respect to PMOs. Subsequent mechanistic studies showed that enhanced cellular uptake of B-MSP-PMO into muscle cells leads to increased exon-skipping activity in comparison with MSP-B-PMO. Surprisingly, further evidence showed that the uptake of chimeric peptide-PMO conjugates of both orientations (B-MSP-PMO and MSP-B-PMO) was ATP- and temperature-dependent and also partially mediated by heparan sulfate proteoglycans (HSPG), indicating that endocytosis is likely the main uptake pathway for both chimeric peptide-PMO conjugates. Collectively, our data demonstrate that peptide orientation in chimeric peptides is an important parameter that determines cellular uptake and activity when conjugated directly to oligonucleotides. These observations provide insight into the design of improved cell targeting compounds for future therapeutics studies.Molecular Therapy-Nucleic Acids (2013) 2, e124; doi:10.1038/mtna.2013

  17. Context Dependent Effects of Chimeric Peptide Morpholino Conjugates Contribute to Dystrophin Exon-skipping Efficiency

    Directory of Open Access Journals (Sweden)

    HaiFang Yin

    2013-01-01

    Full Text Available We have recently reported that cell-penetrating peptides (CPPs and novel chimeric peptides containing CPP (referred as B peptide and muscle-targeting peptide (referred as MSP motifs significantly improve the systemic exon-skipping activity of morpholino phosphorodiamidate oligomers (PMOs in dystrophin-deficient mdx mice. In the present study, the general mechanistic significance of the chimeric peptide configuration on the activity and tissue uptake of peptide conjugated PMOs in vivo was investigated. Four additional chimeric peptide-PMO conjugates including newly identified peptide 9 (B-9-PMO and 9-B-PMO and control peptide 3 (B-3-PMO and 3-B-PMO were tested in mdx mice. Immunohistochemical staining, RT-PCR and western blot results indicated that B-9-PMO induced significantly higher level of exon skipping and dystrophin restoration than its counterpart (9-B-PMO, further corroborating the notion that the activity of chimeric peptide-PMO conjugates is dependent on relative position of the tissue-targeting peptide motif within the chimeric peptide with respect to PMOs. Subsequent mechanistic studies showed that enhanced cellular uptake of B-MSP-PMO into muscle cells leads to increased exon-skipping activity in comparison with MSP-B-PMO. Surprisingly, further evidence showed that the uptake of chimeric peptide-PMO conjugates of both orientations (B-MSP-PMO and MSP-B-PMO was ATP- and temperature-dependent and also partially mediated by heparan sulfate proteoglycans (HSPG, indicating that endocytosis is likely the main uptake pathway for both chimeric peptide-PMO conjugates. Collectively, our data demonstrate that peptide orientation in chimeric peptides is an important parameter that determines cellular uptake and activity when conjugated directly to oligonucleotides. These observations provide insight into the design of improved cell targeting compounds for future therapeutics studies.

  18. Increased cell survival by inhibition of BRCA1 using an antisense approach in an estrogen responsive ovarian carcinoma cell line

    International Nuclear Information System (INIS)

    Annab, Lois A; Hawkins, Rebecca E; Solomon, Greg; Barrett, J Carl; Afshari, Cynthia A

    2000-01-01

    We tested the hypothesis that BRCA1 may play a role in the regulation of ovarian tumor cell death as well as the inhibition of ovarian cell proliferation. Introduction of BRCA1 antisense retroviral constructs into BG-1 estrogen-dependent ovarian adenocarcinoma cells resulted in reduced BRCA1 expression. BRCA1 antisense pooled populations and derived subclones were able to proliferate in monolayer culture without estrogen, whereas control cells began to die after 10 days of estrogen deprivation. In addition, both populations and subclones of BRCA1 antisense infected cells demonstrated a growth advantage in monolayer culture in the presence of estrogen and were able to proliferate in monolayer culture without estrogen, while control cells did not. Furthermore, clonal studies demonstrated that reduced levels of BRCA1 protein correlated with growth in soft agar and greater tumor formation in nude mice in the absence of estrogen. These data suggest that reduction of BRCA1 protein in BG-1 ovarian adenocarcinoma cells may have an effect on cell survival during estrogen deprivation both in vitro and in vivo. Germline mutations in the breast and ovarian cancer susceptibility gene BRCA1, which is located on chromosome 17q21, are associated with a predisposition to the development of cancer in these organs [1,2]. No mutations in the BRCA1 gene have been detected in sporadic breast cancer cases, but mutations have been detected in sporadic cases of ovarian cancer [3,4]. Although there is debate regarding the level of cancer risk associated with mutations in BRCA1 and the significance of the lack of mutations in sporadic tumors, it is possible that alterations in the function of BRCA1 may occur by mechanisms other than mutation, leading to an underestimation of risk when it is calculated solely on the basis of mutational analysis. Such alterations cannot be identified until the function and regulation of BRCA1 are better understood. The BRCA1 gene encodes a 220-kDa nuclear

  19. Tree Rings: Timekeepers of the Past.

    Science.gov (United States)

    Phipps, R. L.; McGowan, J.

    One of a series of general interest publications on science issues, this booklet describes the uses of tree rings in historical and biological recordkeeping. Separate sections cover the following topics: dating of tree rings, dating with tree rings, tree ring formation, tree ring identification, sample collections, tree ring cross dating, tree…

  20. Data in support of transcriptional regulation and function of Fas-antisense long noncoding RNA during human erythropoiesis

    Directory of Open Access Journals (Sweden)

    Olga Villamizar

    2016-06-01

    Full Text Available This paper describes data related to a research article titled, “Fas-antisense long noncoding RNA is differentially expressed during maturation of human erythrocytes and confers resistance to Fas-mediated cell death” [1]. Long noncoding RNAs (lncRNAs are increasingly appreciated for their capacity to regulate many steps of gene expression. While recent studies suggest that many lncRNAs are functional, the scope of their actions throughout human biology is largely undefined including human red blood cell development (erythropoiesis. Here we include expression data for 82 lncRNAs during early, intermediate and late stages of human erythropoiesis using a commercial qPCR Array. From these data, we identified lncRNA Fas-antisense 1 (Fas-AS1 or Saf described in the research article. Also included are 5′ untranslated sequences (UTR for lncRNA Saf with transcription factor target sequences identified. Quantitative RT-PCR data demonstrate relative levels of critical erythroid transcription factors, GATA-1 and KLF1, in K562 human erythroleukemia cells and maturing erythroblasts derived from human CD34+ cells. End point and quantitative RT-PCR data for cDNA prepared using random hexamers versus oligo(dT18 revealed that lncRNA Saf is not effectively polyadenylated. Finally, we include flow cytometry histograms demonstrating Fas levels on maturing erythroblasts derived from human CD34+ cells transduced using mock conditions or with lentivirus particles encoding for Saf.

  1. Antisense targeting of 3' end elements involved in DUX4 mRNA processing is an efficient therapeutic strategy for facioscapulohumeral dystrophy: a new gene-silencing approach.

    Science.gov (United States)

    Marsollier, Anne-Charlotte; Ciszewski, Lukasz; Mariot, Virginie; Popplewell, Linda; Voit, Thomas; Dickson, George; Dumonceaux, Julie

    2016-04-15

    Defects in mRNA 3'end formation have been described to alter transcription termination, transport of the mRNA from the nucleus to the cytoplasm, stability of the mRNA and translation efficiency. Therefore, inhibition of polyadenylation may lead to gene silencing. Here, we choose facioscapulohumeral dystrophy (FSHD) as a model to determine whether or not targeting key 3' end elements involved in mRNA processing using antisense oligonucleotide drugs can be used as a strategy for gene silencing within a potentially therapeutic context. FSHD is a gain-of-function disease characterized by the aberrant expression of the Double homeobox 4 (DUX4) transcription factor leading to altered pathogenic deregulation of multiple genes in muscles. Here, we demonstrate that targeting either the mRNA polyadenylation signal and/or cleavage site is an efficient strategy to down-regulate DUX4 expression and to decrease the abnormally high-pathological expression of genes downstream of DUX4. We conclude that targeting key functional 3' end elements involved in pre-mRNA to mRNA maturation with antisense drugs can lead to efficient gene silencing and is thus a potentially effective therapeutic strategy for at least FSHD. Moreover, polyadenylation is a crucial step in the maturation of almost all eukaryotic mRNAs, and thus all mRNAs are virtually eligible for this antisense-mediated knockdown strategy. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Some Aspects of Ring Theory

    CERN Document Server

    Herstein, IN

    2011-01-01

    S. Amitsur: Associative rings with identities.- I.N. Herstein: Topics in ring theory.- N. Jacobson: Representation theory of Jordan algebras.- I. Kaplansky: The theory of homological dimension.- D. Buchsbaum: Complexes in local ring theory.- P.H. Cohn: Two topics in ring theory.- A.W. Goldie: Non-commutative localisation.

  3. Improving the Accuracy of Laplacian Estimation with Novel Variable Inter-Ring Distances Concentric Ring Electrodes

    Directory of Open Access Journals (Sweden)

    Oleksandr Makeyev

    2016-06-01

    Full Text Available Noninvasive concentric ring electrodes are a promising alternative to conventional disc electrodes. Currently, the superiority of tripolar concentric ring electrodes over disc electrodes, in particular, in accuracy of Laplacian estimation, has been demonstrated in a range of applications. In our recent work, we have shown that accuracy of Laplacian estimation can be improved with multipolar concentric ring electrodes using a general approach to estimation of the Laplacian for an (n + 1-polar electrode with n rings using the (4n + 1-point method for n ≥ 2. This paper takes the next step toward further improving the Laplacian estimate by proposing novel variable inter-ring distances concentric ring electrodes. Derived using a modified (4n + 1-point method, linearly increasing and decreasing inter-ring distances tripolar (n = 2 and quadripolar (n = 3 electrode configurations are compared to their constant inter-ring distances counterparts. Finite element method modeling and analytic results are consistent and suggest that increasing inter-ring distances electrode configurations may decrease the truncation error resulting in more accurate Laplacian estimates compared to respective constant inter-ring distances configurations. For currently used tripolar electrode configuration, the truncation error may be decreased more than two-fold, while for the quadripolar configuration more than a six-fold decrease is expected.

  4. Improving the Accuracy of Laplacian Estimation with Novel Variable Inter-Ring Distances Concentric Ring Electrodes

    Science.gov (United States)

    Makeyev, Oleksandr; Besio, Walter G.

    2016-01-01

    Noninvasive concentric ring electrodes are a promising alternative to conventional disc electrodes. Currently, the superiority of tripolar concentric ring electrodes over disc electrodes, in particular, in accuracy of Laplacian estimation, has been demonstrated in a range of applications. In our recent work, we have shown that accuracy of Laplacian estimation can be improved with multipolar concentric ring electrodes using a general approach to estimation of the Laplacian for an (n + 1)-polar electrode with n rings using the (4n + 1)-point method for n ≥ 2. This paper takes the next step toward further improving the Laplacian estimate by proposing novel variable inter-ring distances concentric ring electrodes. Derived using a modified (4n + 1)-point method, linearly increasing and decreasing inter-ring distances tripolar (n = 2) and quadripolar (n = 3) electrode configurations are compared to their constant inter-ring distances counterparts. Finite element method modeling and analytic results are consistent and suggest that increasing inter-ring distances electrode configurations may decrease the truncation error resulting in more accurate Laplacian estimates compared to respective constant inter-ring distances configurations. For currently used tripolar electrode configuration, the truncation error may be decreased more than two-fold, while for the quadripolar configuration more than a six-fold decrease is expected. PMID:27294933

  5. Antitumor effects of radioiodinated antisense oligonucleotide mediated by VIP receptor

    International Nuclear Information System (INIS)

    Ou Xiaohong; Tan Tianzhi; Li Yunchun; Kuang Anren

    2004-01-01

    Purpose: we had constructed a targeting delivery system based on intestinal peptide (VIP) for antisense oligonucleotide (ASON) transfer into VIP receptor-positive cells in previous study. The aims of present studies are to observe the antitumor effect of VIP-131I-ASON in HT29 human colon adenocarcinoma xenografts. Methods: A 15-met phosphorothioate ASON, which was complementary to the translation start region of the C-myc oncogene mRNA, was labeled with 131I and the labelled compound was linked to the VIP bound covalently 'to a polylysine chain so as to deliver oligonucleotide into tumor cells. Distribution experiments for evaluating the radiolabeled antisense complexe uptake in tumor tissue were performed in BALB/c nude mice bearing with HT29 tumor xenografts. Nude mice beating HT29 tumor xenografts were adminstered VIP-131I-ASON (3.7,7.4 MBq) or 131I-ASON (3.7 MBq), 131I labeled control sense and nosense DNA (3.7 MBq), or saline. Antitumor effects were assessed using endpoints of tumor growth delay. C-myc-encoded protein expression of tumor was measured by immunocytohistochemical staining. Results: Distribution experiment performed with athymic mice bearing human colon tumor xenografts revealed maximal accumulation of conjugated ASON in the tumor tissue 2 h after administration and significantly higher than that in nude mice injected unconjngated ASON [(5.89±1.03)%ID/g and(1.56±0.31)%ID/g, respectively; t=7.7954 P<0.001]. The radioratio of tumor to muscle was peaked 4h after administration. VIP-131I-ASON exhibited strong antitumor effects against HT29 xenografts, decreasing their growth rate 7-fold compare with that in saline-treated mice(tumor growth delay, 25.4±0.89 day). The antitumor effects of unconjugated 131I-ASON were much less profound than VIP-131I-ASON (tumor growth delay, 3.2±1.3 and 25.4±0.89 day, respectively; q=51.4126 P<0.01). Sense, nosense control ON with VIP carder caused no therapeutic effect. There was no progressive weight loss or

  6. Radar imaging of Saturn's rings

    Science.gov (United States)

    Nicholson, Philip D.; French, Richard G.; Campbell, Donald B.; Margot, Jean-Luc; Nolan, Michael C.; Black, Gregory J.; Salo, Heikki J.

    2005-09-01

    We present delay-Doppler images of Saturn's rings based on radar observations made at Arecibo Observatory between 1999 and 2003, at a wavelength of 12.6 cm and at ring opening angles of 20.1°⩽|B|⩽26.7°. The average radar cross-section of the A ring is ˜77% relative to that of the B ring, while a stringent upper limit of 3% is placed on the cross-section of the C ring and 9% on that of the Cassini Division. These results are consistent with those obtained by Ostro et al. [1982, Icarus 49, 367-381] from radar observations at |B|=21.4°, but provide higher resolution maps of the rings' reflectivity profile. The average cross-section of the A and B rings, normalized by their projected unblocked area, is found to have decreased from 1.25±0.31 to 0.74±0.19 as the rings have opened up, while the circular polarization ratio has increased from 0.64±0.06 to 0.77±0.06. The steep decrease in cross-section is at variance with previous radar measurements [Ostro et al., 1980, Icarus 41, 381-388], and neither this nor the polarization variations are easily understood within the framework of either classical, many-particle-thick or monolayer ring models. One possible explanation involves vertical size segregation in the rings, whereby observations at larger elevation angles which see deeper into the rings preferentially see the larger particles concentrated near the rings' mid-plane. These larger particles may be less reflective and/or rougher and thus more depolarizing than the smaller ones. Images from all four years show a strong m=2 azimuthal asymmetry in the reflectivity of the A ring, with an amplitude of ±20% and minima at longitudes of 67±4° and 247±4° from the sub-Earth point. We attribute the asymmetry to the presence of gravitational wakes in the A ring as invoked by Colombo et al. [1976, Nature 264, 344-345] to explain the similar asymmetry long seen at optical wavelengths. A simple radiative transfer model suggests that the enhancement of the azimuthal

  7. Study of improvement in 1st ring`s gas-seal; Top ring no gas seal seino kojo no kento

    Energy Technology Data Exchange (ETDEWEB)

    Ando, H; Tateishi, Y; Fujimura, K; Hitosugi, H [Nippon Piston Ring Co. Ltd., Tokyo (Japan)

    1997-10-01

    The authors studied the effect of an angle of 1st ring twist on the amount of blow-by concerning higher speed/higher output engines for motorcycles. As a result, the authors found the twist made the ring restrained in a ring groove of piston , and confirmed its suitable range for blow-by. By means of the developed optimization method, the authors have achieved significant reduction in blow-by at high engine speed. 1 ref., 9 figs., 2 tabs.

  8. Viscosity of ring polymer melts

    KAUST Repository

    Pasquino, Rossana

    2013-10-15

    We have measured the linear rheology of critically purified ring polyisoprenes, polystyrenes, and polyethyleneoxides of different molar masses. The ratio of the zero-shear viscosities of linear polymer melts η0,linear to their ring counterparts η0,ring at isofrictional conditions is discussed as a function of the number of entanglements Z. In the unentangled regime η0,linear/η 0,ring is virtually constant, consistent with the earlier data, atomistic simulations, and the theoretical expectation η0,linear/ η0,ring = 2. In the entanglement regime, the Z-dependence of ring viscosity is much weaker than that of linear polymers, in qualitative agreement with predictions from scaling theory and simulations. The power-law extracted from the available experimental data in the rather limited range 1 < Z < 20, η0,linear/η0,ring ∼ Z 1.2±0.3, is weaker than the scaling prediction (η0,linear/η0,ring ∼ Z 1.6±0.3) and the simulations (η0,linear/ η0,ring ∼ Z2.0±0.3). Nevertheless, the present collection of state-of-the-art experimental data unambiguously demonstrates that rings exhibit a universal trend clearly departing from that of their linear counterparts, and hence it represents a major step toward resolving a 30-year-old problem. © 2013 American Chemical Society.

  9. Viscosity of ring polymer melts

    KAUST Repository

    Pasquino, Rossana; Vasilakopoulos, Thodoris C.; Jeong, Youncheol; Lee, Hyojoon; Rogers, Simon A.; Sakellariou, Georgios; Allgaier, Jü rgen B.; Takano, Atsushi; Brá s, Ana Rita E; Chang, Taihyun; Gooß en, Sebastian; Pyckhout-Hintzen, Wim; Wischnewski, Andreas; Hadjichristidis, Nikolaos; Richter, Dieter R.; Rubinstein, Michael H.; Vlassopoulos, Dimitris

    2013-01-01

    We have measured the linear rheology of critically purified ring polyisoprenes, polystyrenes, and polyethyleneoxides of different molar masses. The ratio of the zero-shear viscosities of linear polymer melts η0,linear to their ring counterparts η0,ring at isofrictional conditions is discussed as a function of the number of entanglements Z. In the unentangled regime η0,linear/η 0,ring is virtually constant, consistent with the earlier data, atomistic simulations, and the theoretical expectation η0,linear/ η0,ring = 2. In the entanglement regime, the Z-dependence of ring viscosity is much weaker than that of linear polymers, in qualitative agreement with predictions from scaling theory and simulations. The power-law extracted from the available experimental data in the rather limited range 1 < Z < 20, η0,linear/η0,ring ∼ Z 1.2±0.3, is weaker than the scaling prediction (η0,linear/η0,ring ∼ Z 1.6±0.3) and the simulations (η0,linear/ η0,ring ∼ Z2.0±0.3). Nevertheless, the present collection of state-of-the-art experimental data unambiguously demonstrates that rings exhibit a universal trend clearly departing from that of their linear counterparts, and hence it represents a major step toward resolving a 30-year-old problem. © 2013 American Chemical Society.

  10. ring og refleksion

    DEFF Research Database (Denmark)

    Wahlgren, B.; Rattleff, Pernille; Høyrup, S.

    State of the art inden for forskning om læring på arbejdspladsen samt gennemgang af læringsteori og refleksionsbegrebet hos Dewey, Dreyfus, Schön, Argyris, Kolb, Jarvis, Mezirow og Brookfield. Afsluttes med diskussion af syntetiseret model for læring på arbejdspladsen.......State of the art inden for forskning om læring på arbejdspladsen samt gennemgang af læringsteori og refleksionsbegrebet hos Dewey, Dreyfus, Schön, Argyris, Kolb, Jarvis, Mezirow og Brookfield. Afsluttes med diskussion af syntetiseret model for læring på arbejdspladsen....

  11. Birth Control Ring

    Science.gov (United States)

    ... Health Food & Fitness Diseases & Conditions Infections Drugs & Alcohol School & Jobs Sports Expert Answers (Q&A) Staying Safe Videos for Educators Search English Español Birth Control Ring KidsHealth / For Teens / Birth Control Ring What's ...

  12. From coffee ring to spherulites ring of poly(ethylene oxide) film from drying droplet

    Science.gov (United States)

    Hu, Yinchun; Zhang, Xuerong; Qiu, Maibo; Wei, Yan; Zhou, Qiong; Huang, Di

    2018-03-01

    We discuss how the "spherulites ring" morphology and "coffee ring" profile of PEO film formed by the drying droplet at glass substrate with different heating rate. Upon increasing the heating rate of substrate, it is found that deposited PEO film from drying droplet shows the unusually observed "coffee ring" profile and "spherulites ring" morphology. The main mechanism for this phenomenon is proposed to be an enhanced Marangoni convection which is induced by the increased solute concentration gradient and reduced viscous force above 70 °C. A simple formation mechanism of the unusually observed "coffee ring" profile and "spherulites ring" morphology is proposed. These findings can be exploited to trace the center of Marangoni convection, with potential applications in designing the spherulite patterns of crystalline polymer films in ink-jet printing and self-assembly fields.

  13. Systematic Search for Rings around Kepler Planet Candidates: Constraints on Ring Size and Occurrence Rate

    Science.gov (United States)

    Aizawa, Masataka; Masuda, Kento; Kawahara, Hajime; Suto, Yasushi

    2018-05-01

    We perform a systematic search for rings around 168 Kepler planet candidates with sufficient signal-to-noise ratios that are selected from all of the short-cadence data. We fit ringed and ringless models to their light curves and compare the fitting results to search for the signatures of planetary rings. First, we identify 29 tentative systems, for which the ringed models exhibit statistically significant improvement over the ringless models. The light curves of those systems are individually examined, but we are not able to identify any candidate that indicates evidence for rings. In turn, we find several mechanisms of false positives that would produce ringlike signals, and the null detection enables us to place upper limits on the size of the rings. Furthermore, assuming the tidal alignment between axes of the planetary rings and orbits, we conclude that the occurrence rate of rings larger than twice the planetary radius is less than 15%. Even though the majority of our targets are short-period planets, our null detection provides statistical and quantitative constraints on largely uncertain theoretical models of the origin, formation, and evolution of planetary rings.

  14. Plant 7SL RNA and tRNA(Tyr) genes with inserted antisense sequences are efficiently expressed in an in vitro transcription system from Nicotiana tabacum cells

    Czech Academy of Sciences Publication Activity Database

    Yukawa, Y.; Matoušek, Jaroslav; Grimm, M.; Vrba, Lukáš; Steger, G.; Sugiura, M.; Beier, H.

    2002-01-01

    Roč. 50, - (2002), s. 713-723 ISSN 0167-4412 R&D Projects: GA ČR GA521/99/1591; GA MŠk ME 463 Keywords : antisense RNA Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.529, year: 2002

  15. Structure and dynamics of ringed galaxies

    International Nuclear Information System (INIS)

    Buta, R.J.

    1984-01-01

    In many spiral and SO galaxies, single or multiple ring structures are visible in the disk. These inner rings (r), outer rings (R), and nuclear rings (nr) were investigated by means of morphology, photometry, and spectroscopy in order to provide basic data on a long neglected phenomenon. The metric properties of each ring are investigated and found to correlate with the structure of the parent galaxy. When properly calibrated, inner rings in barred (SB) systems can be used as geometric extragalactic distance indicators to distances in excess of 100 Mpc. Other statistics are presented that confirm previous indications that the rings have preferred shapes, relative sizes, and orientations with respect to bars. A survey is made of the less homogeneous non-barred (SA) ringed systems, and the causes of the inhomogeneity are isolated. It is shown that rings can be identified in multiple-ring SA systems that are exactly analogous to those in barred spirals

  16. Multiplicative Structure and Hecke Rings of Generator Matrices for Codes over Quotient Rings of Euclidean Domains

    Directory of Open Access Journals (Sweden)

    Hajime Matsui

    2017-12-01

    Full Text Available In this study, we consider codes over Euclidean domains modulo their ideals. In the first half of the study, we deal with arbitrary Euclidean domains. We show that the product of generator matrices of codes over the rings mod a and mod b produces generator matrices of all codes over the ring mod a b , i.e., this correspondence is onto. Moreover, we show that if a and b are coprime, then this correspondence is one-to-one, i.e., there exist unique codes over the rings mod a and mod b that produce any given code over the ring mod a b through the product of their generator matrices. In the second half of the study, we focus on the typical Euclidean domains such as the rational integer ring, one-variable polynomial rings, rings of Gaussian and Eisenstein integers, p-adic integer rings and rings of one-variable formal power series. We define the reduced generator matrices of codes over Euclidean domains modulo their ideals and show their uniqueness. Finally, we apply our theory of reduced generator matrices to the Hecke rings of matrices over these Euclidean domains.

  17. An Approach to Detect and Study DNA Double-Strand Break Repair by Transcript RNA Using a Spliced-Antisense RNA Template.

    Science.gov (United States)

    Keskin, Havva; Storici, Francesca

    2018-01-01

    A double-strand break (DSB) is one of the most dangerous DNA lesion, and its repair is crucial for genome stability. Homologous recombination is considered the safest way to repair a DNA DSB and requires an identical or nearly identical DNA template, such as a sister chromatid or a homologous chromosome for accurate repair. Can transcript RNA serve as donor template for DSB repair? Here, we describe an approach that we developed to detect and study DNA repair by transcript RNA. Key features of the method are: (i) use of antisense (noncoding) RNA as template for DSB repair by RNA, (ii) use of intron splicing to distinguish the sequence of the RNA template from that of the DNA that generates the RNA template, and (iii) use of a trans and cis system to study how RNA repairs a DSB in homologous but distant DNA or in its own DNA, respectively. This chapter provides details on how to use a spliced-antisense RNA template to detect and study DSB repair by RNA in trans or cis in yeast cells. Our approach for detection of DSB repair by RNA in cells can be applied to cell types other than yeast, such as bacteria, mammalian cells, or other eukaryotic cells. © 2018 Elsevier Inc. All rights reserved.

  18. Binomial Rings: Axiomatisation, Transfer and Classification

    OpenAIRE

    Xantcha, Qimh Richey

    2011-01-01

    Hall's binomial rings, rings with binomial coefficients, are given an axiomatisation and proved identical to the numerical rings studied by Ekedahl. The Binomial Transfer Principle is established, enabling combinatorial proofs of algebraical identities. The finitely generated binomial rings are completely classified. An application to modules over binomial rings is given.

  19. AN N-BODY INTEGRATOR FOR GRAVITATING PLANETARY RINGS, AND THE OUTER EDGE OF SATURN'S B RING

    International Nuclear Information System (INIS)

    Hahn, Joseph M.; Spitale, Joseph N.

    2013-01-01

    A new symplectic N-body integrator is introduced, one designed to calculate the global 360° evolution of a self-gravitating planetary ring that is in orbit about an oblate planet. This freely available code is called epi i nt, and it is distinct from other such codes in its use of streamlines to calculate the effects of ring self-gravity. The great advantage of this approach is that the perturbing forces arise from smooth wires of ring matter rather than discreet particles, so there is very little gravitational scattering and so only a modest number of particles are needed to simulate, say, the scalloped edge of a resonantly confined ring or the propagation of spiral density waves. The code is applied to the outer edge of Saturn's B ring, and a comparison of Cassini measurements of the ring's forced response to simulations of Mimas's resonant perturbations reveals that the B ring's surface density at its outer edge is σ 0 = 195 ± 60 g cm –2 , which, if the same everywhere across the ring, would mean that the B ring's mass is about 90% of Mimas's mass. Cassini observations show that the B ring-edge has several free normal modes, which are long-lived disturbances of the ring-edge that are not driven by any known satellite resonances. Although the mechanism that excites or sustains these normal modes is unknown, we can plant such a disturbance at a simulated ring's edge and find that these modes persist without any damping for more than ∼10 5 orbits or ∼100 yr despite the simulated ring's viscosity ν s = 100 cm 2 s –1 . These simulations also indicate that impulsive disturbances at a ring can excite long-lived normal modes, which suggests that an impact in the recent past by perhaps a cloud of cometary debris might have excited these disturbances, which are quite common to many of Saturn's sharp-edged rings

  20. Galactic rings revisited - I. CVRHS classifications of 3962 ringed galaxies from the Galaxy Zoo 2 Database

    Science.gov (United States)

    Buta, Ronald J.

    2017-11-01

    Rings are important and characteristic features of disc-shaped galaxies. This paper is the first in a series that re-visits galactic rings with the goals of further understanding the nature of the features and for examining their role in the secular evolution of galaxy structure. The series begins with a new sample of 3962 galaxies drawn from the Galaxy Zoo 2 citizen science data base, selected because zoo volunteers recognized a ring-shaped pattern in the morphology as seen in Sloan Digital Sky Survey colour images. The galaxies are classified within the framework of the Comprehensive de Vaucouleurs revised Hubble-Sandage system. It is found that zoo volunteers cued on the same kinds of ring-like features that were recognized in the 1995 Catalogue of Southern Ringed Galaxies. This paper presents the full catalogue of morphological classifications, comparisons with other sources of classifications and some histograms designed mainly to highlight the content of the catalogue. The advantages of the sample are its large size and the generally good quality of the images; the main disadvantage is the low physical resolution that limits the detectability of linearly small rings such as nuclear rings. The catalogue includes mainly inner and outer disc rings and lenses. Cataclysmic (`encounter-driven') rings (such as ring and polar ring galaxies) are recognized in less than 1 per cent of the sample.

  1. Quantum Fourier Transform Over Galois Rings

    OpenAIRE

    Zhang, Yong

    2009-01-01

    Galois rings are regarded as "building blocks" of a finite commutative ring with identity. There have been many papers on classical error correction codes over Galois rings published. As an important warm-up before exploring quantum algorithms and quantum error correction codes over Galois rings, we study the quantum Fourier transform (QFT) over Galois rings and prove it can be efficiently preformed on a quantum computer. The properties of the QFT over Galois rings lead to the quantum algorit...

  2. The cellular uptake of antisense oligonucleotid of E6 mRNA into cervical cancer cells by DOPE-modified hydroxyapatite nanoparticles

    OpenAIRE

    Negin Saffarzadeh; Seyed Mehdi Kalantar; Ali Jebali; Seyed Hossein Hekmatimoghaddam; Mohammad Hassan Sheikhha; Ehsan Farashahi

    2014-01-01

    Objective(s): Although several chemical and physical methods for gene delivery have been introduced, their cytotoxicity, non-specific immune responses and the lack of biodegradability remain the main issues. In this study, hydroxyapatite nanoparticles (NPs) and 1,2-dioleoyl-sn-glycero-3-phosphoethanol​amine (DOPE)-modified hydroxyapatite NPs was coated with antisense oligonucleotide of E6 mRNA, and their uptakes into the cervical cancer cell line were evaluated. Materials and Methods: Calcium...

  3. Novel manifestations of the Aharonov-Bohm effect in quantum rings and Moebius rings

    International Nuclear Information System (INIS)

    Fomin, Vladimir M.

    2013-01-01

    - An overview is given on the recent experimental and theoretical advancements in studies of novel manifestations of the Aharonov-Bohm quantum-interference effect for excitons confined to self assembled quantum rings and other semiconductor nanostructures with ring-like states of charge carriers as well as for electrons in Moebius rings at the micro- and nanoscale. The exciton Aharonov-Bohm effect can be effectively controlled by an out-of-plane magnetic field, a vertical electric field, a spin disorder. A 'delocalization-to-localization' transition for the electron ground state occurs in a Moebius ring as it is made more inhomogeneous. (authors)

  4. Ring closure in actin polymers

    Energy Technology Data Exchange (ETDEWEB)

    Sinha, Supurna, E-mail: supurna@rri.res.in [Raman Research Institute, Bangalore 560080 (India); Chattopadhyay, Sebanti [Doon University, Dehradun 248001 (India)

    2017-03-18

    We present an analysis for the ring closure probability of semiflexible polymers within the pure bend Worm Like Chain (WLC) model. The ring closure probability predicted from our analysis can be tested against fluorescent actin cyclization experiments. We also discuss the effect of ring closure on bend angle fluctuations in actin polymers. - Highlights: • Ring closure of biopolymers. • Worm like chain model. • Predictions for experiments.

  5. On P-coherent endomorphism rings

    Indian Academy of Sciences (India)

    A ring is called right -coherent if every principal right ideal is finitely presented. Let M R be a right -module. We study the -coherence of the endomorphism ring of M R . It is shown that is a right -coherent ring if and only if every endomorphism of M R has a pseudokernel in add M R ; S is a left -coherent ring if and ...

  6. 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.

  7. Antisense-MDM2 Sensitizes LNCaP Prostate Cancer Cells to Androgen Deprivation, Radiation, and the Combination In Vivo

    International Nuclear Information System (INIS)

    Stoyanova, Radka; Hachem, Paul; Hensley, Harvey; Khor, L.-Y.; Mu Zhaomei; Hammond, M. Elizabeth H.; Agrawal, Sudhir; Pollack, Alan

    2007-01-01

    Purpose: To test the effects of antisense (AS)-MDM2 alone and with androgen deprivation (AD), radiotherapy (RT), and AD + RT on wild-type LNCaP cells in an orthotopic in vivo model. Methods: Androgen-sensitive LNCaP cells were grown in the prostates of nude mice. Magnetic resonance imaging-based tumor volume and serum prostate-specific antigen (PSA) measurements were used to assess effects on tumor response. Tumor response was measured by biochemical and tumor volume failure definitions and doubling time estimates from fitted PSA and tumor volume growth curves. Expression of MDM2, p53, p21, and Ki-67 was quantified using immunohistochemical staining and image analysis of formalin-fixed tissue, analogous to methods used clinically. Results: Antisense-MDM2 significantly inhibited the growth of LNCaP tumors over the mismatch controls. The most significant increase in tumor growth delay and tumor doubling time was from AS-MDM2 + AD + RT, although the effect of AS-MDM2 + AD was substantial. Expression of MDM2 was significantly reduced by AS-MDM2 in the setting of RT. Conclusions: This is the first in vivo investigation of the effects of AS-MDM2 in an orthotopic model and the first to demonstrate incremental sensitization when added to AD and AD + RT. The results with AD underscore the potential to affect micrometastatic disease, which is probably responsible for treatment failure in 30-40% of men with high-risk disease

  8. Faithfully quadratic rings

    CERN Document Server

    Dickmann, M

    2015-01-01

    In this monograph the authors extend the classical algebraic theory of quadratic forms over fields to diagonal quadratic forms with invertible entries over broad classes of commutative, unitary rings where -1 is not a sum of squares and 2 is invertible. They accomplish this by: (1) Extending the classical notion of matrix isometry of forms to a suitable notion of T-isometry, where T is a preorder of the given ring, A, or T = A^2. (2) Introducing in this context three axioms expressing simple properties of (value) representation of elements of the ring by quadratic forms, well-known to hold in

  9. BERKELEY: ALS ring

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1993-06-15

    Everybody at Lawrence Berkeley Laboratory's Center for Beam Physics is pleased with the rapid progress in commissioning LBL's Advanced Light Source (ALS) electron storage ring, the foundation for this third-generation synchrotron radiation facility. Designed for a maximum current of 400 mA, the ALS storage ring reached 407 mA just 24 days after storing the first beam on 16 March. ALS construction as a US Department of Energy (DOE) national user facility to provide high-brightness vacuum ultra-violet and soft x-ray radiation began in October 1987. One technical requirement marking project completion was to accumulate a 50-mA current in the storage ring. The ALS passed this milestone on 24 March, a week ahead of the official deadline. Once injected, the electron beam decays quasi-exponentially primarily because of interactions with residual gas molecules in the storage-ring vacuum chamber. Eventually, when the pressure in the vacuum chamber with beam decreases toward the expected operating level of 1 nano Torr, it will only be necessary to refill the storage ring at intervals of four to eight hours. At present the vacuum is improving rapidly as surfaces are irradiated (scrubbed) by the synchrotron radiation itself. At 100 mA, beam lifetime was about one hour (9 April)

  10. Compressible Vortex Ring

    Science.gov (United States)

    Elavarasan, Ramasamy; Arakeri, Jayawant; Krothapalli, Anjaneyulu

    1999-11-01

    The interaction of a high-speed vortex ring with a shock wave is one of the fundamental issues as it is a source of sound in supersonic jets. The complex flow field induced by the vortex alters the propagation of the shock wave greatly. In order to understand the process, a compressible vortex ring is studied in detail using Particle Image Velocimetry (PIV) and shadowgraphic techniques. The high-speed vortex ring is generated from a shock tube and the shock wave, which precedes the vortex, is reflected back by a plate and made to interact with the vortex. The shadowgraph images indicate that the reflected shock front is influenced by the non-uniform flow induced by the vortex and is decelerated while passing through the vortex. It appears that after the interaction the shock is "split" into two. The PIV measurements provided clear picture about the evolution of the vortex at different time interval. The centerline velocity traces show the maximum velocity to be around 350 m/s. The velocity field, unlike in incompressible rings, contains contributions from both the shock and the vortex ring. The velocity distribution across the vortex core, core diameter and circulation are also calculated from the PIV data.

  11. BERKELEY: ALS ring

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    Everybody at Lawrence Berkeley Laboratory's Center for Beam Physics is pleased with the rapid progress in commissioning LBL's Advanced Light Source (ALS) electron storage ring, the foundation for this third-generation synchrotron radiation facility. Designed for a maximum current of 400 mA, the ALS storage ring reached 407 mA just 24 days after storing the first beam on 16 March. ALS construction as a US Department of Energy (DOE) national user facility to provide high-brightness vacuum ultra-violet and soft x-ray radiation began in October 1987. One technical requirement marking project completion was to accumulate a 50-mA current in the storage ring. The ALS passed this milestone on 24 March, a week ahead of the official deadline. Once injected, the electron beam decays quasi-exponentially primarily because of interactions with residual gas molecules in the storage-ring vacuum chamber. Eventually, when the pressure in the vacuum chamber with beam decreases toward the expected operating level of 1 nano Torr, it will only be necessary to refill the storage ring at intervals of four to eight hours. At present the vacuum is improving rapidly as surfaces are irradiated (scrubbed) by the synchrotron radiation itself. At 100 mA, beam lifetime was about one hour (9 April)

  12. Accidental ingestion of BiTine ring and a note on inefficient ring separation forceps

    Directory of Open Access Journals (Sweden)

    Baghele ON

    2011-05-01

    Full Text Available Om Nemichand Baghele1, Mangala Om Baghele21Department of Periodontology, SMBT Dental College and Hospital, Sangamner, Ahmednagar, Maharashtra, India; 2Private General Dental Practice, Mumbai, IndiaBackground: Accidental ingestion of medium-to-large instruments is relatively uncommon during dental treatment but can be potentially dangerous. A case of BiTine ring ingestion is presented with a note on inefficient ring separation forceps.Case description: A 28-year-old male patient accidentally ingested the BiTine ring (2 cm diameter, 0.5 cm outward projections while it was being applied to a distoproximal cavity in tooth # 19. The ring placement forceps were excessively flexible; bending of the beaks towards the ring combined with a poor no-slippage mechanism led to sudden disengagement of the ring and accelerated movement towards the pharynx. We followed the patient with bulk forming agents and radiographs. Fortunately the ring passed out without any complications.Clinical implications: Checking equipment and methods is as important as taking precautions against any preventable medical emergency. It is the responsibility of the clinician to check, verify and then use any instrument/equipment.Keywords: foreign bodies/radiography, foreign bodies/complications, equipment failure, dental instrument, accidental ingestion

  13. On the Laurent polynomial rings

    International Nuclear Information System (INIS)

    Stefanescu, D.

    1985-02-01

    We describe some properties of the Laurent polynomial rings in a finite number of indeterminates over a commutative unitary ring. We study some subrings of the Laurent polynomial rings. We finally obtain two cancellation properties. (author)

  14. The Hi-Ring DCN Architecture

    DEFF Research Database (Denmark)

    Galili, Michael; Kamchevska, Valerija; Ding, Yunhong

    2016-01-01

    We will review recent work on the proposed hierarchical ring-based architecture (HiRing) proposed for data center networks. We will discuss the architecture and initial demonstrations of optical switching performance and time-domain synchronization......We will review recent work on the proposed hierarchical ring-based architecture (HiRing) proposed for data center networks. We will discuss the architecture and initial demonstrations of optical switching performance and time-domain synchronization...

  15. EBT ring physics

    International Nuclear Information System (INIS)

    Uckan, N.A.

    1980-04-01

    This workshop attempted to evaluate the status of the current experimental and theoretical understanding of hot electron ring properties. The dominant physical processes that influence ring formation, scaling, and their optimal behavior are also studied. Separate abstracts were prepared for each of the 27 included papers

  16. PlantNATsDB: a comprehensive database of plant natural antisense transcripts.

    Science.gov (United States)

    Chen, Dijun; Yuan, Chunhui; Zhang, Jian; Zhang, Zhao; Bai, Lin; Meng, Yijun; Chen, Ling-Ling; Chen, Ming

    2012-01-01

    Natural antisense transcripts (NATs), as one type of regulatory RNAs, occur prevalently in plant genomes and play significant roles in physiological and pathological processes. Although their important biological functions have been reported widely, a comprehensive database is lacking up to now. Consequently, we constructed a plant NAT database (PlantNATsDB) involving approximately 2 million NAT pairs in 69 plant species. GO annotation and high-throughput small RNA sequencing data currently available were integrated to investigate the biological function of NATs. PlantNATsDB provides various user-friendly web interfaces to facilitate the presentation of NATs and an integrated, graphical network browser to display the complex networks formed by different NATs. Moreover, a 'Gene Set Analysis' module based on GO annotation was designed to dig out the statistical significantly overrepresented GO categories from the specific NAT network. PlantNATsDB is currently the most comprehensive resource of NATs in the plant kingdom, which can serve as a reference database to investigate the regulatory function of NATs. The PlantNATsDB is freely available at http://bis.zju.edu.cn/pnatdb/.

  17. The successes and future prospects of the linear antisense RNA amplification methodology.

    Science.gov (United States)

    Li, Jifen; Eberwine, James

    2018-05-01

    It has been over a quarter of a century since the introduction of the linear RNA amplification methodology known as antisense RNA (aRNA) amplification. Whereas most molecular biology techniques are rapidly replaced owing to the fast-moving nature of development in the field, the aRNA procedure has become a base that can be built upon through varied uses of the technology. The technique was originally developed to assess RNA populations from small amounts of starting material, including single cells, but over time its use has evolved to include the detection of various cellular entities such as proteins, RNA-binding-protein-associated cargoes, and genomic DNA. In this Perspective we detail the linear aRNA amplification procedure and its use in assessing various components of a cell's chemical phenotype. This procedure is particularly useful in efforts to multiplex the simultaneous detection of various cellular processes. These efforts are necessary to identify the quantitative chemical phenotype of cells that underlies cellular function.

  18. Ground Movement in SSRL Ring

    International Nuclear Information System (INIS)

    Sunikumar, Nikita

    2011-01-01

    Users of the Stanford Synchrotron Radiation Lightsource (SSRL) are being affected by diurnal motion of the synchrotron's storage ring, which undergoes structural changes due to outdoor temperature fluctuations. In order to minimize the effects of diurnal temperature fluctuations, especially on the vertical motion of the ring floor, scientists at SSRL tried three approaches: painting the storage ring white, covering the asphalt in the middle of the ring with highly reflective Mylar and installing Mylar on a portion of the ring roof and walls. Vertical motion in the storage ring is measured by a Hydrostatic Leveling System (HLS), which calculates the relative height of water in a pipe that extends around the ring. The 24-hr amplitude of the floor motion was determined using spectral analysis of HLS data, and the ratio of this amplitude before and after each experiment was used to quantitatively determine the efficacy of each approach. The results of this analysis showed that the Mylar did not have any significant effect on floor motion, although the whitewash project did yield a reduction in overall HLS variation of 15 percent. However, further analysis showed that the reduction can largely be attributed to a few local changes rather than an overall reduction in floor motion around the ring. Future work will consist of identifying and selectively insulating these local regions in order to find the driving force behind diurnal floor motion in the storage ring.

  19. Token ring technology report

    CERN Document Server

    2013-01-01

    Please note this is a Short Discount publication. This report provides an overview of the IBM Token-Ring technology and products built by IBM and compatible vendors. It consists of two sections: 1. A summary of the design trade-offs for the IBM Token-Ring. 2. A summary of the products of the major token-ring compatible vendors broken down by adapters and components, wiring systems, testing, and new chip technology.

  20. Prototype moving-ring reactor

    International Nuclear Information System (INIS)

    Smith, A.C. Jr.; Ashworth, C.P.; Abreu, K.E.

    1982-01-01

    We have completed a design of the Prototype Moving-Ring Reactor. The fusion fuel is confined in current-carrying rings of magnetically-field-reversed plasma (Compact Toroids). The plasma rings, formed by a coaxial plasma gun, undergo adiabatic magnetic compression to ignition temperature while they are being injected into the reactor's burner section. The cylindrical burner chamber is divided into three burn stations. Separator coils and a slight axial guide field gradient are used to shuttle the ignited toroids rapidly from one burn station to the next, pausing for 1/3 of the total burn time at each station. D-T- 3 He ice pellets refuel the rings at a rate which maintains constant radiated power

  1. Polycomb Group Proteins RING1A and RING1B Regulate the Vegetative Phase Transition in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Jian Li

    2017-05-01

    Full Text Available Polycomb group (PcG protein-mediated gene silencing is a major regulatory mechanism in higher eukaryotes that affects gene expression at the transcriptional level. Here, we report that two conserved homologous PcG proteins, RING1A and RING1B (RING1A/B, are required for global H2A monoubiquitination (H2Aub in Arabidopsis. The mutation of RING1A/B increased the expression of members of the SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL gene family and caused an early vegetative phase transition. The early vegetative phase transition observed in ring1a ring1b double mutant plants was dependent on an SPL family gene, and the H2Aub status of the chromatin at SPL locus was dependent on RING1A/B. Moreover, mutation in RING1A/B affected the miRNA156a-mediated vegetative phase transition, and RING1A/B and the AGO7-miR390-TAS3 pathway were found to additively regulate this transition in Arabidopsis. Together, our results demonstrate that RING1A/B regulates the vegetative phase transition in Arabidopsis through the repression of SPL family genes.

  2. Effects of CD49d-targeted antisense-oligonucleotide on α4 integrin expression and function of acute lymphoblastic leukemia cells: Results of in vitro and in vivo studies.

    Directory of Open Access Journals (Sweden)

    Yann Duchartre

    Full Text Available We recently demonstrated the effectiveness of blocking CD49d with anti-functional antibodies or small molecule inhibitors as a rational targeted approach to the treatment of acute leukemia in combination with chemotherapy. Antisense oligonucleotide promises to be no less specific than antibodies and inhibitors, but more interesting for pharmacokinetics and pharmacodynamics. We addressed this using the published CD49d antisense drug ATL1102. In vitro, we incubated/nucleofected the ALL cell line Kasumi-2 with ATL1102. In vivo, immunodeficient hosts were engrafted with primary ALL cells and treated with ATL1102. Changes in expression of CD49d mRNA and CD49d protein, and of cooperating gene products, including ß1 integrin and CXCR4, as well as survival in the mouse experiments were quantified. We observed dose-dependent down-regulation of CD49d mRNA and protein levels and its partner integrin ß1 cell surface protein level and, up-regulation of CXCR4 surface expression. The suppression was more pronounced after nucleofection than after incubation, where down-regulation was significant only at the higher doses. In vivo effects of ATL1102 were not sufficient to translate into "clinical" benefit in the leukemia model. In summary, antisense oligonucleotides are successful tools for specifically modulating gene expression but sufficient delivery to down-regulate CD49d in vivo may be difficult to achieve.

  3. Researches on the Piston Ring

    Science.gov (United States)

    Ehihara, Keikiti

    1944-01-01

    In internal combustion engines, steam engines, air compressors, and so forth, the piston ring plays an important role. Especially, the recent development of Diesel engines which require a high compression pressure for their working, makes, nowadays, the packing action of the piston ring far more important than ever. Though a number of papers have been published in regard to researches on the problem of the piston ring, none has yet dealt with an exact measurement of pressure exerted on the cylinder wall at any given point of the ring. The only paper that can be traced on this subject so far is Mr. Nakagawa's report on the determination of the relative distribution of pressure on the cylinder wall, but the measuring method adopted therein appears to need further consideration. No exact idea has yet been obtained as to how the obturation of gas between the piston and cylinder, the frictional resistance of the piston, and the wear of the cylinder wall are affected by the intensity and the distribution of the radial pressure of the piston ring. Consequently, the author has endeavored, by employing an apparatus of his own invention, to get an exact determination of the pressure distribution of the piston ring. By means of a newly devised ring tester, to which piezoelectricity of quartz was applied, the distribution of the radial pressure of many sample rings on the market was accurately determined. Since many famous piston rings show very irregular pressure distribution, the author investigated and achieved a manufacturing process of the piston ring which will exert uniform pressure on the cylinder wall. Temperature effects on the configuration and on the mean spring power have also been studied. Further, the tests were performed to ascertain how the gas tightness of the piston ring may be affected by the number or spring power. The researches as to the frictional resistance between the piston ring and the cylinder wall were carried out, too. The procedure of study, and

  4. Generation of stable mixed-compact-toroid rings by inducing plasma currents in strong E rings

    International Nuclear Information System (INIS)

    Jayakumar, R.; Taggart, D.P.; Parker, M.R.; Fleischmann, H.H.

    1989-01-01

    In the RECE-Christa device, hybrid-type compact toroid rings are generated by inducing large toroidal plasma currents I rho in strong electron rings using a thin induction coil positioned along the ring axis. Starting from field-reversal values δ ο = 50 - 120 percent of the original pure fast-electron ring, the induced plasma current I rho raises δ to a maximum value of up to 240 percent with I rho contributing more than 50 percent of the total ring current. Quite interestingly, the generated hybrid compact toroid configurations appear gross-stable during the full I rho pulse length (half-amplitude width about 100 μs)

  5. Magnetization of two coupled rings

    International Nuclear Information System (INIS)

    Avishai, Y; Luck, J M

    2009-01-01

    We investigate the persistent currents and magnetization of a mesoscopic system consisting of two clean metallic rings sharing a single contact point in a magnetic field. Many novel features with respect to the single-ring geometry are underlined, including the explicit dependence of wavefunctions on the Aharonov-Bohm fluxes, the complex pattern of two-fold and three-fold degeneracies, the key role of length and flux commensurability, and in the case of commensurate ring lengths the occurrence of idle levels which do not carry any current. Spin-orbit interactions, induced by the electric fields of charged wires threading the rings, give rise to a peculiar version of the Aharonov-Casher effect where, unlike for a single ring, spin is not conserved. Remarkably enough, this can only be realized when the Aharonov-Bohm fluxes in both rings are neither integer nor half-integer multiples of the flux quantum

  6. Antisense myb inhibition of purified erythroid progenitors in development and differentiation is linked to cycling activity and expression of DNA polymerase alpha

    International Nuclear Information System (INIS)

    Valtieri, M.; Venturelli, D.; Care, A.; Fossati, C.; Pelosi, E.; Labbaye, C.; Mattia, G.; Gewirtz, A.M.; Calabretta, B.; Peschle, C.

    1991-01-01

    These studies aimed to determine the expression and functional role of c-myb in erythroid progenitors with different cycling activities. In the first series of experiments the erythroid burst-forming unit (BFU-E) and colony-forming unit (CFU-E) populations from adult peripheral blood (PB), bone marrow (BM), and embryonic-fetal liver (FL) were treated with either c-myb antisense oligomers or 3H-thymidine (3H-TdR). A direct correlation was always observed between the inhibitory effect of anti-myb oligomers and the level of cycling activity. Thus, the inhibitory effect of antisense c-myb on the number of BFU-E colonies was 28.3% +/- 15.8% in PB, 53.4% +/- 9.3% in BM, and 68.2% +/- 24.5% in FL. Both adult and embryonic CFU-E were markedly inhibited. Using purified PB progenitors, we observed a similar pattern, although with slightly lower inhibitory effects. In the 3H-TdR suicide assay the killing index of BFU-E was 8.9% +/- 4.2% in PB, 29.4% +/- 6.5% in BM, and 40.1% +/- 9.6% in FL. The values for adult and embryonic CFU-E were 55.7% +/- 7.9% and 60.98% +/- 6.6%, respectively. We then investigated the kinetics of c-myb mRNA level during the erythroid differentiation of purified adult PB and FL BFU-E, as evaluated in liquid-phase culture by reverse transcription-polymerase chain reaction. Adult erythroid precursors showed a gradual increase of c-myb mRNA from day 4 through day 8 of culture and a sharp decrease at later times, whereas the expression of c-myb mRNA and protein in differentiation embryonic precursors peaked 2 days earlier. In both cases, c-myb mRNA level peaked at the CFU-E stage of differentiation. Finally, highly purified adult PB BFU-E were stimulated into cycling by a 3-day treatment with interleukin-3 in liquid phase: both the sensitivity to c-myb antisense oligomers and the 3H-TdR suicide index showed a gradual, strictly parallel increase

  7. Radioactive gold ring dermatitis

    International Nuclear Information System (INIS)

    Miller, R.A.; Aldrich, J.E.

    1990-01-01

    A superficial squamous cell carcinoma developed in a woman who wore a radioactive gold ring for more than 30 years. Only part of the ring was radioactive. Radiation dose measurements indicated that the dose to basal skin layer was 2.4 Gy (240 rad) per week. If it is assumed that the woman continually wore her wedding ring for 37 years since purchase, she would have received a maximum dose of approximately 4600 Gy

  8. Barriers to Effective Postmenopausal Osteoporosis Treatment: A Qualitative Study of Patients’ and Practitioners’ Views

    Science.gov (United States)

    2016-01-01

    Background Only a minority of patients at high risk for osteoporotic fracture receive treatment. Objective Study patients’ and physicians’ views regarding postmenopausal osteoporosis (PMO) to identify impediments to good care. Methods A qualitative study involving 18 physicians and 37 women (age 57–87) with PMO. Results All women interviewed considered PMO to be somewhat normal wear-and-tear associated with old age. The women identified a large number of "causes" for osteoporosis but finally viewed it as chance. They all described its progression as slow. Three representations of PMO severity were identified: some women tended to interpreted it as benign (21), others tended to dramatize it (11), and the rest were uncertain (5). These representations did not appear linked to age or fracture. Even the women who associated fracture and PMO were uncertain of the link between them. Fractures were considered to be random events, independent of osteoporosis. Women received general life-style recommendations from their physicians positively, but did not connect them specifically to osteoporosis. Indeed, these recommendations, along with the fear of side effects, the absence of tangible results of treatments, the view of PMO as a natural process, and the representations of PMO severity are factors that may deter treatments and impact compliance. As for the physicians, they identified eight risk factors, recognizing menopause as central to PMO and recognized the link between risk of fracture and PMO. However, some considered the impact of fractures to be limited in time, and viewed PMO as a "benign" disease. Seeing the progression of PMO as slow and inevitable reduced their urgency to diagnose and treat it as compared to other diseases. Some physicians acknowledged limited mastery of the existing therapeutic arsenal and unsuccessful handling of patient compliance. Conclusion Women’s and physicians’ perspectives on PMO converged to trivialize postmenopausal

  9. Analytical model for double split ring resonators with arbitrary ring width

    DEFF Research Database (Denmark)

    Zhurbenko, Vitaliy; Jensen, Thomas; Krozer, Viktor

    2008-01-01

    For the first time, the analytical model for a double split ring resonator with unequal width rings is developed. The proposed models for the resonators with equal and unequal widths are based on an impedance matrix representation and provide the prediction of performance in a wide frequency range...

  10. Pure subrings of the rings

    International Nuclear Information System (INIS)

    Tsarev, Andrei V

    2009-01-01

    Pure subrings of finite rank in the Z-adic completion of the ring of integers and in its homomorphic images are considered. Certain properties of these rings are studied (existence of an identity element, decomposability into a direct sum of essentially indecomposable ideals, condition for embeddability into a csp-ring, etc.). Additive groups of these rings and conditions under which these rings are subrings of algebraic number fields are described. Bibliography: 12 titles.

  11. Ring accelerators

    International Nuclear Information System (INIS)

    Gisler, G.; Faehl, R.

    1983-01-01

    We present two-dimensional simulations in (r-z) and r-theta) cylinderical geometries of imploding-liner-driven accelerators of rings of charged particles. We address issues of azimuthal and longitudinal stability of the rings. We discuss self-trapping designs in which beam injection and extraction is aided by means of external cusp fields. Our simulations are done with the 2-1/2-D particle-in-cell plasma simulation code CLINER, which combines collisionless, electromagnetic PIC capabilities with a quasi-MHD finite element package

  12. Manipulation of vortex rings for flow control

    International Nuclear Information System (INIS)

    Toyoda, Kuniaki; Hiramoto, Riho

    2009-01-01

    This paper reviews the dynamics of vortex rings and the control of flow by the manipulation of vortex rings. Vortex rings play key roles in many flows; hence, the understanding of the dynamics of vortex rings is crucial for scientists and engineers dealing with flow phenomena. We describe the structures and motions of vortex rings in circular and noncircular jets, which are typical examples of flows evolving into vortex rings. For circular jets the mechanism of evolving, merging and breakdown of vortex rings is described, and for noncircular jets the dynamics of three-dimensional deformation and interaction of noncircular vortex rings under the effect of self- and mutual induction is discussed. The application of vortex-ring manipulation to the control of various flows is reviewed with successful examples, based on the relationship between the vortex ring dynamics and the flow properties. (invited paper)

  13. The Rings of Saturn

    Science.gov (United States)

    Cuzzi, J. N.; Filacchione, G.; Marouf, E. A.

    2018-03-01

    One could become an expert on Saturn's iconic rings pretty easily in the early 1970s, as very little was known about them beyond the distinction between the A, B, and C rings, and the Cassini Division or "gap" between rings A and B (Alexander, 1962; Bobrov, 1970). Water ice was discovered spectroscopically on the ring particle surfaces, and radar and microwave emission observations proved that the particles must be centimeters to meters in size, consisting primarily, not just superficially, of water ice (Pollack, 1975). While a 2:1 orbital resonance with Mimas had long been suspected of having something to do with the Cassini Division, computers of the time were unable to model the subtle dynamical effects that we now know to dominate ring structure. This innocent state of affairs was exploded by the Voyager 1 and 2 encounters in 1980 and 1981. Spectacular images revealed filigree structure and odd regional color variations, and exquisitely detailed radial profiles of fluctuating particle abundance were obtained from the first stellar and radio occultations, having resolution almost at the scale of single particles. Voyager-era understanding was reviewed by Cuzzi et al. (1984) and Esposito et al. (1984). While the Voyager data kept ring scientists busy for decades, planning which led to the monumentally successful NASA-ESA-ASI Cassini mission, which arrived in 2004, had been under way even before Voyager got to Saturn. A review of pre-Cassini knowledge of Saturn's Rings can be found in Orton et al. (2009). This chapter will build on recent topical and process-specific reviews that treat the gamut of ring phenomena and its underlying physics in considerable detail (Colwell et al., 2009; Cuzzi et al., 2009; Horányi et al., 2009; Schmidt et al., 2009; Esposito, 2010; Tiscareno, 2013b; Esposito, 2014). We will follow and extend the general organization of Cuzzi et al. (2010), the most recent general discussion of Saturn's rings. For brevity and the benefit of the

  14. Examination techniques for non-magnetic rings

    International Nuclear Information System (INIS)

    Metala, M.J.; Kilpatrick, N.L.; Frank, W.W.

    1990-01-01

    Until the introduction of 18Mn18Cr rings a few years ago, most non-magnetic steel rings for generator rotors were made from 18Mn5Cr alloy steel, which is highly susceptible to stress corrosion cracking in the presence of water. This, the latest in a series of papers on the subject of non-magnetic rings by the authors' company, provides a discussion of nondestructive examination of 18Mn5Cr rings for stress corrosion distress. With rings on the rotor, fluorescent penetrant, ultrasonic and special visual techniques are applied. With rings off the rotor, the fluorescent penetrant technique is used, with and without stress enhancement

  15. Dose-Dependent Lowering of Mutant Huntingtin Using Antisense Oligonucleotides in Huntington Disease Patients.

    Science.gov (United States)

    van Roon-Mom, Willeke M C; Roos, Raymund A C; de Bot, Susanne T

    2018-04-01

    On December 11 of 2017, Ionis Pharmaceuticals published a press release announcing dose-dependent reductions of mutant huntingtin protein in their HTTRx Phase 1/2a study in Huntington disease (HD) patients. The results from this Ionis trial have gained much attention from the patient community and the oligonucleotide therapeutics field, since it is the first trial targeting the cause of HD, namely the mutant huntingtin protein, using antisense oligonucleotides (ASOs). The press release also states that the primary endpoints of the study (safety and tolerability) were met, but does not contain data. This news follows the approval of another therapeutic ASO nusinersen (trade name Spinraza) for a neurological disease, spinal muscular atrophy, by the U.S. Food and Drug Administration and European Medicines Agency, in 2016 and 2017, respectively. Combined, this offers hope for the development of the HTTRx therapy for HD patients.

  16. Ionization cooling ring for muons

    Directory of Open Access Journals (Sweden)

    R. Palmer

    2005-06-01

    Full Text Available Practical ionization cooling rings could lead to lower cost or improved performance in neutrino factory or muon collider designs. The ring modeled here uses realistic three-dimensional fields. The performance of the ring compares favorably with the linear cooling channel used in the second U.S. Neutrino Factory Study. The normalized 6D emittance of an ideal ring is decreased by a factor of approximately 240, compared with a factor of only 15 for the linear channel. We also examine such real-world effects as windows on the absorbers and rf cavities and leaving empty lattice cells for injection and extraction. For realistic conditions the ring decreases the normalized 6D emittance by a factor of 49.

  17. HTLV Deregulation of the NF-κB Pathway: An Update on Tax and Antisense Proteins Role

    Science.gov (United States)

    Fochi, Stefania; Mutascio, Simona; Bertazzoni, Umberto; Zipeto, Donato; Romanelli, Maria G.

    2018-01-01

    Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive CD4+/CD25+ T-cell malignancy and of a severe neurodegenerative disease, HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The chronic activation or deregulation of the canonical and non-canonical nuclear factor kappa B (NF-κB) pathways play a crucial role in tumorigenesis. The HTLV-1 Tax-1 oncoprotein is a potent activator of the NF-κB transcription factors and the NF-κB response is required for promoting the development of HTLV-1 transformed cell lines. The homologous retrovirus HTLV-2, which also expresses a Tax-2 transforming protein, is not associated with ATL. In this review, we provide an updated synopsis of the role of Tax-1 in the deregulation of the NF-κB pathway, highlighting the differences with the homologous Tax-2. Special emphasis is directed toward the understanding of the molecular mechanisms involved in NF-κB activation resulting from Tax interaction with host factors affecting several cellular processes, such as cell cycle, apoptosis, senescence, cell proliferation, autophagy, and post-translational modifications. We also discuss the current knowledge on the role of the antisense viral protein HBZ in down-regulating the NF-κB activation induced by Tax, and its implication in cellular senescence. In addition, we review the recent studies on the mechanism of HBZ-mediated inhibition of NF-κB activity as compared to that exerted by the HTLV-2 antisense protein, APH-2. Finally, we discuss recent advances aimed at understanding the role exerted in the development of ATL by the perturbation of NF-κB pathway by viral regulatory proteins. PMID:29515558

  18. HTLV Deregulation of the NF-κB Pathway: An Update on Tax and Antisense Proteins Role.

    Science.gov (United States)

    Fochi, Stefania; Mutascio, Simona; Bertazzoni, Umberto; Zipeto, Donato; Romanelli, Maria G

    2018-01-01

    Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive CD4 + /CD25 + T-cell malignancy and of a severe neurodegenerative disease, HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The chronic activation or deregulation of the canonical and non-canonical nuclear factor kappa B (NF-κB) pathways play a crucial role in tumorigenesis. The HTLV-1 Tax-1 oncoprotein is a potent activator of the NF-κB transcription factors and the NF-κB response is required for promoting the development of HTLV-1 transformed cell lines. The homologous retrovirus HTLV-2, which also expresses a Tax-2 transforming protein, is not associated with ATL. In this review, we provide an updated synopsis of the role of Tax-1 in the deregulation of the NF-κB pathway, highlighting the differences with the homologous Tax-2. Special emphasis is directed toward the understanding of the molecular mechanisms involved in NF-κB activation resulting from Tax interaction with host factors affecting several cellular processes, such as cell cycle, apoptosis, senescence, cell proliferation, autophagy, and post-translational modifications. We also discuss the current knowledge on the role of the antisense viral protein HBZ in down-regulating the NF-κB activation induced by Tax, and its implication in cellular senescence. In addition, we review the recent studies on the mechanism of HBZ-mediated inhibition of NF-κB activity as compared to that exerted by the HTLV-2 antisense protein, APH-2. Finally, we discuss recent advances aimed at understanding the role exerted in the development of ATL by the perturbation of NF-κB pathway by viral regulatory proteins.

  19. Self-gravitation in Saturn's rings

    International Nuclear Information System (INIS)

    Salo, H.; Lukkari, J.

    1982-01-01

    In a ring-shaped collisional system self-gravitation reduces the equilibrium values of the geometric and optical thickness. In Saturn's rings both effects are appreciable. The previously found discrepancy between the calculated profile and the observed profile of the rings is chiefly caused by the omission of self-gravitation. (Auth.)

  20. Saturn’s ring temperatures at equinox

    Science.gov (United States)

    Spilker, Linda J.; Ferrari, C.; Morishima, R.

    2013-10-01

    Modeling the thermal emission of Saturn's rings is challenging due to the numerous heating sources as well as the structural properties of the disk and of the particles that are closely related. At equinox, however, the main rings are externally heated by Saturn alone and the problem is somewhat simplified. We test the abilities of our current models to reproduce the temperatures observed with the Cassini CIRS instrument around equinox in August 2009. A simple semi-analytic model which includes mutual shadowing effects can mostly explain the radial profile of the equinox ring temperatures, except the model predicts lower temperatures than those observed for the A ring. The temperature variation at a given saturnocentric radius is primarily caused by observational geometry variations relative to Saturn. The observed temperature increases with decreasing Saturn-ring-observer angle. In addition, we found evidence that the leading hemispheres of particles are warmer than the trailing hemispheres at least for the C ring and probably for the A and B rings as well. This is explained if some fraction of particles has spin rates lower than the synchronous rotation rate as predicted by N-body simulations. The spin model for a monolayer ring (Ferrari, C., Leyrat, C., 2006, Astron. Astrophys. 447, 745-760) can fit the temperature variations with spacecraft longitude observed in the C ring with currently known thermal properties and a mixing of slow and fast rotators. The multilayer model (Morishima, R., Salo, H., Ohtsuki, K., 2009, Icarus 201, 634-654) can reproduce the temperatures of the B and C rings but gives A ring temperatures that are significantly lower than those observed as does the simple semi-analytic model. More advanced models which take into account self-gravity wakes may explain the A ring temperature behavior.

  1. NATpipe: an integrative pipeline for systematical discovery of natural antisense transcripts (NATs) and phase-distributed nat-siRNAs from de novo assembled transcriptomes

    Science.gov (United States)

    Yu, Dongliang; Meng, Yijun; Zuo, Ziwei; Xue, Jie; Wang, Huizhong

    2016-01-01

    Nat-siRNAs (small interfering RNAs originated from natural antisense transcripts) are a class of functional small RNA (sRNA) species discovered in both plants and animals. These siRNAs are highly enriched within the annealed regions of the NAT (natural antisense transcript) pairs. To date, great research efforts have been taken for systematical identification of the NATs in various organisms. However, developing a freely available and easy-to-use program for NAT prediction is strongly demanded by researchers. Here, we proposed an integrative pipeline named NATpipe for systematical discovery of NATs from de novo assembled transcriptomes. By utilizing sRNA sequencing data, the pipeline also allowed users to search for phase-distributed nat-siRNAs within the perfectly annealed regions of the NAT pairs. Additionally, more reliable nat-siRNA loci could be identified based on degradome sequencing data. A case study on the non-model plant Dendrobium officinale was performed to illustrate the utility of NATpipe. Finally, we hope that NATpipe would be a useful tool for NAT prediction, nat-siRNA discovery, and related functional studies. NATpipe is available at www.bioinfolab.cn/NATpipe/NATpipe.zip. PMID:26858106

  2. Split ring containment attachment device

    International Nuclear Information System (INIS)

    Sammel, A.G.

    1996-01-01

    A containment attachment device is described for operatively connecting a glovebag to plastic sheeting covering hazardous material. The device includes an inner split ring member connected on one end to a middle ring member wherein the free end of the split ring member is inserted through a slit in the plastic sheeting to captively engage a generally circular portion of the plastic sheeting. A collar potion having an outer ring portion is provided with fastening means for securing the device together wherein the glovebag is operatively connected to the collar portion. 5 figs

  3. An N-body Integrator for Planetary Rings

    Science.gov (United States)

    Hahn, Joseph M.

    2011-04-01

    A planetary ring that is disturbed by a satellite's resonant perturbation can respond in an organized way. When the resonance lies in the ring's interior, the ring responds via an m-armed spiral wave, while a ring whose edge is confined by the resonance exhibits an m-lobed scalloping along the ring-edge. The amplitude of these disturbances are sensitive to ring surface density and viscosity, so modelling these phenomena can provide estimates of the ring's properties. However a brute force attempt to simulate a ring's full azimuthal extent with an N-body code will likely fail because of the large number of particles needed to resolve the ring's behavior. Another impediment is the gravitational stirring that occurs among the simulated particles, which can wash out the ring's organized response. However it is possible to adapt an N-body integrator so that it can simulate a ring's collective response to resonant perturbations. The code developed here uses a few thousand massless particles to trace streamlines within the ring. Particles are close in a radial sense to these streamlines, which allows streamlines to be treated as straight wires of constant linear density. Consequently, gravity due to these streamline is a simple function of the particle's radial distance to all streamlines. And because particles are responding to smooth gravitating streamlines, rather than discrete particles, this method eliminates the stirring that ordinarily occurs in brute force N-body calculations. Note also that ring surface density is now a simple function of streamline separations, so effects due to ring pressure and viscosity are easily accounted for, too. A poster will describe this N-body method in greater detail. Simulations of spiral density waves and scalloped ring-edges are executed in typically ten minutes on a desktop PC, and results for Saturn's A and B rings will be presented at conference time.

  4. Minimal Gromov-Witten rings

    International Nuclear Information System (INIS)

    Przyjalkowski, V V

    2008-01-01

    We construct an abstract theory of Gromov-Witten invariants of genus 0 for quantum minimal Fano varieties (a minimal class of varieties which is natural from the quantum cohomological viewpoint). Namely, we consider the minimal Gromov-Witten ring: a commutative algebra whose generators and relations are of the form used in the Gromov-Witten theory of Fano varieties (of unspecified dimension). The Gromov-Witten theory of any quantum minimal variety is a homomorphism from this ring to C. We prove an abstract reconstruction theorem which says that this ring is isomorphic to the free commutative ring generated by 'prime two-pointed invariants'. We also find solutions of the differential equation of type DN for a Fano variety of dimension N in terms of the generating series of one-pointed Gromov-Witten invariants

  5. Effective photo-enhancement of cellular activity of fluorophore-octaarginine antisense PNA conjugates correlates with singlet oxygen formation, endosomal escape and chromophore lipophilicity

    DEFF Research Database (Denmark)

    Yarani, Reza; Shiraishi, Takehiko; Nielsen, Peter E.

    2018-01-01

    Photochemical internalization (PCI) is a cellular drug delivery method based on the generation of light-induced reactive oxygen species (ROS) causing damage to the endosomal membrane and thereby resulting in drug release to the cytoplasm. In our study a series of antisense fluorophore octaarginin...... indicate that efficient photodynamic endosomal escape is strongly dependent on the quantum yield for photochemical singlet oxygen formation, photostability as well as the lipophilicity of the chromophore....

  6. A small molecule for a big transformation: Topical application of a 20-nucleotide-long antisense fragment of the DIAP-2 gene inhibits the development of Drosophila melanogaster female imagos

    Directory of Open Access Journals (Sweden)

    Nyadar Palmah M.

    2018-01-01

    Full Text Available Several genes have been identified to play important roles associated with sex selection in Drosophila melanogaster. An essential part is attributed to the sex-lethal gene that depends on the expression of the X:A (number of chromosomes to autosomes ratio signal controlling both sex selection and dosage compensation processes in D. melanogaster. Interestingly, for sex selection in D. melanogaster there are no documented data addressing the role of the inhibitor of apoptosis (IAP genes and their signaling influence on this biological process. In this study, we found that topical application of a 20-nucleotide-long antisense DNA fragment (oligoDIAP-2 from the death-associated inhibitor of apoptosis (DIAP-2 gene interferes with D. melanogaster development and significantly decreases the number of female imagos and their biomass. We show that the applied antisense oligoDIAP-2 fragment downregulates the target DIAP-2 gene whose normal concentration is necessary for the development of female D. melanogaster. These data correspond to the results on downregulation of the target host IAP-Z gene of Lymantria dispar L. female imagos after topical treatment with an 18-nucleotide-long antisense DNA fragment from the L. dispar multicapsid nuclear polyhedrosis virus IAP-3 gene at the larval stage. The observed novel phenomenon linking the downregulation of insect IAP genes and the low rate of female imago development could have practical application, especially in insect pest control and molecular pathology.

  7. Electro-optical hybrid slip ring

    Science.gov (United States)

    Hong, En

    2005-11-01

    The slip ring is a rotary electrical interface, collector, swivel or rotary joint. It is a physical system that can perform continuous data transfer and data exchange between a stationary and a rotating structure. A slip ring is generally used to transfer data or power from an unrestrained, continuously rotating electro-mechanical system in real-time, thereby simplifying operations and eliminating damage-prone wires dangling from moving joints. Slip rings are widely used for testing, evaluating, developing and improving various technical equipment and facilities with rotating parts. They are widely used in industry, especially in manufacturing industries employing turbo machinery, as in aviation, shipbuilding, aerospace, defense, and in precise facilities having rotating parts such as medical Computerized Tomography (CT) and MRI scanners and so forth. Therefore, any improvement in slip ring technology can impact large markets. Research and development in this field will have broad prospects long into the future. The goal in developing the current slip ring technology is to improve and increase the reliability, stability, anti-interference, and high data fidelity between rotating and stationary structures. Up to now, there have been numerous approaches used for signal and data transfer utilizing a slip ring such as metal contacts, wires, radio transmission, and even liquid media. However, all suffer from drawbacks such as data transfer speed limitations, reliability, stability, electro-magnetic interference and durability. The purpose of the current research is to break through these basic limitations using an optical solution, thereby improving performance in current slip ring applications. This dissertation introduces a novel Electro-Optical Hybrid Slip Ring technology, which makes "through the air" digital-optical communication between stationary and rotating systems a reality with high data transfer speed, better reliability and low interference susceptibility

  8. Double acting stirling engine piston ring

    Science.gov (United States)

    Howarth, Roy B.

    1986-01-01

    A piston ring design for a Stirling engine wherein the contact pressure between the piston and the cylinder is maintained at a uniform level, independent of engine conditions through a balancing of the pressure exerted upon the ring's surface and thereby allowing the contact pressure on the ring to be predetermined through the use of a preloaded expander ring.

  9. Structure and expression of two nuclear receptor genes in marsupials: insights into the evolution of the antisense overlap between the α-thyroid hormone receptor and Rev-erbα

    Directory of Open Access Journals (Sweden)

    Brown M Scott

    2010-12-01

    Full Text Available Abstract Background Alternative processing of α-thyroid hormone receptor (TRα, NR1A1 mRNAs gives rise to two functionally antagonistic nuclear receptors: TRα1, the α-type receptor, and TRα2, a non-hormone binding variant that is found only in mammals. TRα2 shares an unusual antisense coding overlap with mRNA for Rev-erbα (NR1D1, another nuclear receptor protein. In this study we examine the structure and expression of these genes in the gray short-tailed opossum, Monodelphis domestica, in comparison with that of eutherian mammals and three other marsupial species, Didelphis virginiana, Potorous tridactylus and Macropus eugenii, in order to understand the evolution and regulatory role of this antisense overlap. Results The sequence, expression and genomic organization of mRNAs encoding TRα1 and Rev-erbα are very similar in the opossum and eutherian mammals. However, the sequence corresponding to the TRα2 coding region appears truncated by almost 100 amino acids. While expression of TRα1 and Rev-erbα was readily detected in all tissues of M. domestica ages 0 days to 18 weeks, TRα2 mRNA was not detected in any tissue or stage examined. These results contrast with the widespread and abundant expression of TRα2 in rodents and other eutherian mammals. To examine requirements for alternative splicing of TRα mRNAs, a series of chimeric minigenes was constructed. Results show that the opossum TRα2-specific 5' splice site sequence is fully competent for splicing but the sequence homologous to the TRα2 3' splice site is not, even though the marsupial sequences are remarkably similar to core splice site elements in rat. Conclusions Our results strongly suggest that the variant nuclear receptor isoform, TRα2, is not expressed in marsupials and that the antisense overlap between TRα and Rev-erbα thus is unique to eutherian mammals. Further investigation of the TRα and Rev-erbα genes in marsupial and eutherian species promises to yield

  10. Structure and expression of two nuclear receptor genes in marsupials: insights into the evolution of the antisense overlap between the α-thyroid hormone receptor and Rev-erbα

    Science.gov (United States)

    2010-01-01

    Background Alternative processing of α-thyroid hormone receptor (TRα, NR1A1) mRNAs gives rise to two functionally antagonistic nuclear receptors: TRα1, the α-type receptor, and TRα2, a non-hormone binding variant that is found only in mammals. TRα2 shares an unusual antisense coding overlap with mRNA for Rev-erbα (NR1D1), another nuclear receptor protein. In this study we examine the structure and expression of these genes in the gray short-tailed opossum, Monodelphis domestica, in comparison with that of eutherian mammals and three other marsupial species, Didelphis virginiana, Potorous tridactylus and Macropus eugenii, in order to understand the evolution and regulatory role of this antisense overlap. Results The sequence, expression and genomic organization of mRNAs encoding TRα1 and Rev-erbα are very similar in the opossum and eutherian mammals. However, the sequence corresponding to the TRα2 coding region appears truncated by almost 100 amino acids. While expression of TRα1 and Rev-erbα was readily detected in all tissues of M. domestica ages 0 days to 18 weeks, TRα2 mRNA was not detected in any tissue or stage examined. These results contrast with the widespread and abundant expression of TRα2 in rodents and other eutherian mammals. To examine requirements for alternative splicing of TRα mRNAs, a series of chimeric minigenes was constructed. Results show that the opossum TRα2-specific 5' splice site sequence is fully competent for splicing but the sequence homologous to the TRα2 3' splice site is not, even though the marsupial sequences are remarkably similar to core splice site elements in rat. Conclusions Our results strongly suggest that the variant nuclear receptor isoform, TRα2, is not expressed in marsupials and that the antisense overlap between TRα and Rev-erbα thus is unique to eutherian mammals. Further investigation of the TRα and Rev-erbα genes in marsupial and eutherian species promises to yield additional insight into the

  11. Fusion Rings for Quantum Groups

    DEFF Research Database (Denmark)

    Andersen, Henning Haahr; Stroppel, Catharina

    2012-01-01

    We study the fusion rings of tilting modules for a quantum group at a root of unity modulo the tensor ideal of negligible tilting modules. We identify them in type A with the combinatorial rings from [12] and give a similar description of the sp2n-fusion ring in terms of noncommutative symmetric...

  12. Topological rings

    CERN Document Server

    Warner, S

    1993-01-01

    This text brings the reader to the frontiers of current research in topological rings. The exercises illustrate many results and theorems while a comprehensive bibliography is also included. The book is aimed at those readers acquainted with some very basic point-set topology and algebra, as normally presented in semester courses at the beginning graduate level or even at the advanced undergraduate level. Familiarity with Hausdorff, metric, compact and locally compact spaces and basic properties of continuous functions, also with groups, rings, fields, vector spaces and modules, and with Zorn''s Lemma, is also expected.

  13. Energy spectra of quantum rings.

    Science.gov (United States)

    Fuhrer, A; Lüscher, S; Ihn, T; Heinzel, T; Ensslin, K; Wegscheider, W; Bichler, M

    2001-10-25

    Quantum mechanical experiments in ring geometries have long fascinated physicists. Open rings connected to leads, for example, allow the observation of the Aharonov-Bohm effect, one of the best examples of quantum mechanical phase coherence. The phase coherence of electrons travelling through a quantum dot embedded in one arm of an open ring has also been demonstrated. The energy spectra of closed rings have only recently been studied by optical spectroscopy. The prediction that they allow persistent current has been explored in various experiments. Here we report magnetotransport experiments on closed rings in the Coulomb blockade regime. Our experiments show that a microscopic understanding of energy levels, so far limited to few-electron quantum dots, can be extended to a many-electron system. A semiclassical interpretation of our results indicates that electron motion in the rings is governed by regular rather than chaotic motion, an unexplored regime in many-electron quantum dots. This opens a way to experiments where even more complex structures can be investigated at a quantum mechanical level.

  14. Forandringslæring med autismediagnoser?

    DEFF Research Database (Denmark)

    Gustafson, Kari Ingrid; Mørck, Line Lerche

    2013-01-01

    Artiklen drøfter en række aktuelle spørgsmål omkring læring hos børn og unge med autisme-spektrum-forstyrrelses diagnoser. Der introduceres til en social praksisteoretisk forståelse af forandringslæring, der diskuterer forandring ikke kun i relation til en persons identitet, men også aktuelle og...... potentielle forandringer, når det gælder overskridelse af binær logik i autisme versus normalitet, samt i relation til at overskride individualiserede og dualistiske problem-forståelser af fejl og mangler ved det autistiske barn. Det illustreres, hvordan disse former for dualistisk tænkning er forankret i et...... Rasmus’ ændringer i læring, selvforståelse og tilhørsforhold perspektiveres med andre ASF-diagnostiseredes læring udforsket bl.a. gennem gruppeinterviews i regi af Asperger-foreningen. Artiklen byder således på et alternativ i form af at forstå forandringslæring som overskridende læring, med langt større...

  15. Antisense pre-treatment increases gene therapy efficacy in dystrophic muscles.

    Science.gov (United States)

    Peccate, Cécile; Mollard, Amédée; Le Hir, Maëva; Julien, Laura; McClorey, Graham; Jarmin, Susan; Le Heron, Anita; Dickson, George; Benkhelifa-Ziyyat, Sofia; Piétri-Rouxel, France; Wood, Matthew J; Voit, Thomas; Lorain, Stéphanie

    2016-08-15

    In preclinical models for Duchenne muscular dystrophy, dystrophin restoration during adeno-associated virus (AAV)-U7-mediated exon-skipping therapy was shown to decrease drastically after six months in treated muscles. This decline in efficacy is strongly correlated with the loss of the therapeutic AAV genomes, probably due to alterations of the dystrophic myofiber membranes. To improve the membrane integrity of the dystrophic myofibers at the time of AAV-U7 injection, mdx muscles were pre-treated with a single dose of the peptide-phosphorodiamidate morpholino (PPMO) antisense oligonucleotides that induced temporary dystrophin expression at the sarcolemma. The PPMO pre-treatment allowed efficient maintenance of AAV genomes in mdx muscles and enhanced the AAV-U7 therapy effect with a ten-fold increase of the protein level after 6 months. PPMO pre-treatment was also beneficial to AAV-mediated gene therapy with transfer of micro-dystrophin cDNA into muscles. Therefore, avoiding vector genome loss after AAV injection by PPMO pre-treatment would allow efficient long-term restoration of dystrophin and the use of lower and thus safer vector doses for Duchenne patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Changes of Tc-99m sestamibi uptake in P-glycoprotein expressing leukaemia cells treated in vivo with antisense oligodeoxynucleotide complementary to mdr1 mRNA

    International Nuclear Information System (INIS)

    Kinuya, S.; Yokoyama, K; Fukuoka, M.; Michigishi, T.; Tonami, N.; Shiba, K.; Mori, H.; Watanabe, N.; Shuke, N.

    2006-01-01

    We examined the feasibility of Tc-99m sestamibi to monitor changes of mRNA expression of MDRl/P-glycoprotein (Pgp) following antisense oligodeoxynucleotide (AS-ODN) treatment in vivo. Three days after the intraperitoneal inoculation of murine leukaemia P388/R cells expressing MDR1/P-gp in CDFI mice, 15-mer phosphorothioate ASODN to the initiation codon of mouse mdr1 mRNA was administered intraperitoneally at 10 mg/kg daily for 3 or 4 days. Cells collected from ascites were suspended in medium for Tc-99m sestamibi uptake studies. To know the duration of antisense effects, cells were harvested 2 days later after the 3-day treatment. AS-ODN treatment increased Tc-99m sestamibi uptake. Effects of 3-day treatment and 4-day treatment were the same. Treatment effects were not detected when uptake was observed 2 days after 3-day treatment. Based on the results it was concluded that in vivo treatment with AS-ODN specific to the coding portion of mdr1 mRNA increased Tc-99m sestamibi uptake in leukaemia cells possessing MDR function. (author)

  17. The Lord of Rings - the mysterious case of the stolen rings: a critical analysis

    Science.gov (United States)

    Sandrelli, S.

    The Lord of Rings - the mysterious case of the stolen rings: a critical analysis S. Sandrelli INAF - Osservatorio Astronomico di Brera, Milano, Italy (stefano.sandrelli@brera.inaf.it / Fax: 02 72001600 / Phone: +39 02 72320337) "The Lord of Rings - the mysterious case of the stolen rings" is a live astronomical role-playing game for kids aged 10 -13. Its goal is to introduce them to some of the main topics of the Solar System: a) the role of gravity; b) the distribution of mass & light; c) the effects of rotation; d) the distribution of water. The game was held both at the Perugia (2004) and the Genova Science Festival (2005), obtaining great success. Teams of about 6-8 members are introduced to Mr Schioppanelli, the astro-detective of the town (the name is a pun: it reminds Schiaparelli, the famous italian astronomer, and it is a slang expression meaning "ring-breaker"). Mr Schioppanelli has his office in an "gastronomical astronomical observatory", known as The Red Giant Pizzeria. Schioppanelli informs the kids that a mysterious Centaur succeded in stealing the rings of Saturn. The partecipants are appointed astro-detectives in-charge and asked to find the rings by browsing around the Solar System, which is scaled so as to fit the town historical centre or a pedestrian area, going from the Sun to Saturn or beyond, depending on the actual area at disposal. Great care must be taken allowing children playing only in a car-free area of the town. At the right scaled distances, the partecipants meet characters playing as the various planets. The kids can talk to them after solving a riddle, obtaining useful informations. A special characters play as a comet, timely going in and out of the inner solar system. The teams can also talk to some shepherd-moons of the rings. They easily discover that the rings were totally destroyed by the Centaur: a real disaster! They are also suggested to gather the necessary ingredients (gravity, light, rotation, inclination, dust and

  18. Vortex rings in classical and quantum systems

    International Nuclear Information System (INIS)

    Barenghi, C F; Donnelly, R J

    2009-01-01

    The study of vortex rings has been pursued for decades and is a particularly difficult subject. However, the discovery of quantized vortex rings in superfluid helium has greatly increased interest in vortex rings with very thin cores. While rapid progress has been made in the simulation of quantized vortex rings, there has not been comparable progress in laboratory studies of vortex rings in a viscous fluid such as water. This article overviews the history and current frontiers of classical and quantum vortex rings. After introducing the classical results, this review discusses thin-cored vortex rings in superfluid helium in section 2, and recent progress in understanding vortex rings of very thin cores propagating in water in section 3. (invited paper)

  19. Laparoscopic appendicectomy using endo-ring applicator and fallope rings

    International Nuclear Information System (INIS)

    Ali, Iyoob V; Maliekkal, Joji I

    2009-01-01

    Wider adoption of laparoscopic appendicectomy (LA) is limited by problems in securing the appendiceal base as well as the cost and the duration compared with the open procedure. The objective of this study was to assess the feasibility and efficacy of a new method for securing the appendiceal base in LA, so as to make the entire procedure simpler and cheaper, and hence, more popular. Twenty-five patients who were candidates for appendicectomy (emergency as well as elective) and willing for the laparoscopic procedure were selected for this study. Ports used were 10 mm at the umbilicus, 5 mm at the lower right iliac fossa, and 10 mm at the left iliac fossa. Extremely friable, ruptured, or turgid organs of diameters larger than 8 mm were excluded from the study. The mesoappendix was divided close to the appendix by diathermy. Fallope rings were applied to the appendiceal base using a special ring applicator, and the appendix was divided and extracted through the lumen of the applicator. The procedure was successful in 23 (92%) cases, and the mean duration of the procedure was 20 minutes (15-32 minutes). There were no procedural complications seen during a median follow-up of two weeks. The equipment and rings were cheaper when compared with that of the standard methods of securing the base of the appendix. LA using fallope rings is a safe, simple, easy-to-learn, and economically viable method. (author)

  20. Novel composite material polyoxovanadate@MIL-101(Cr): a highly efficient electrocatalyst for ascorbic acid oxidation.

    Science.gov (United States)

    Fernandes, Diana M; Barbosa, André D S; Pires, João; Balula, Salete S; Cunha-Silva, Luís; Freire, Cristina

    2013-12-26

    A novel hybrid composite material, PMo10V2@MIL-101 was prepared by the encapsulation of the tetra-butylammonium (TBA) salt of the vanadium-substituted phosphomolybdate [PMo10V2O40](5-) (PMo10V2) into the porous metal-organic framework (MOF) MIL-101(Cr). The materials characterization by powder X-ray diffraction, Fourier transform infrared spectra and scanning electron microscopy confirmed the preparation of the composite material without disruption of the MOF porous structure. Pyrolytic graphite electrodes modified with the original components (MIL-101(Cr), PMo10V2), and the composite material PMo10V2@MIL-101 were prepared and their electrochemical responses were studied by cyclic voltammetry. Surface confined redox processes were observed for all the immobilized materials. MIL-101(Cr) showed one-electron reduction process due to chromium centers (Cr(III) → Cr(II)), while PMo10V2 presented five reduction processes: the peak at more positive potentials is attributed to two superimposed 1-electron vanadium reduction processes (V(V) → V(IV)) and the other four peaks to Mo-centred two-electron reduction processes (Mo(VI) → Mo(V)). The electrochemical behavior of the composite material PMo10V2@MIL-101 showed both MIL-101(Cr) and PMo10V2 redox features, although with the splitting of the two vanadium processes and the shift of the Mo- and Cr- centered processes to more negative potentials. Finally, PMo10V2@MIL-101 modified electrode showed outstanding enhanced vanadium-based electrocatalytic properties towards ascorbic acid oxidation, in comparison with the free PMo10V2, as a result of its immobilization into the porous structure of the MOF. Furthermore, PMo10V2@MIL-101 modified electrode showed successful simultaneous detection of ascorbic acid and dopamine.

  1. SMARANDACHE NON-ASSOCIATIVE RINGS

    OpenAIRE

    Vasantha, Kandasamy

    2002-01-01

    An associative ring is just realized or built using reals or complex; finite or infinite by defining two binary operations on it. But on the contrary when we want to define or study or even introduce a non-associative ring we need two separate algebraic structures say a commutative ring with 1 (or a field) together with a loop or a groupoid or a vector space or a linear algebra. The two non-associative well-known algebras viz. Lie algebras and Jordan algebras are mainly built using a vecto...

  2. Heavy ion storage rings

    International Nuclear Information System (INIS)

    Schuch, R.

    1987-01-01

    A brief overview of synchrotron storage rings for heavy ions, which are presently under construction in different accelerator laboratories is given. Ions ranging from protons up to uranium ions at MeV/nucleon energies will be injected into these rings using multiturn injection from the accelerators available or being built in these laboratories. After injection, it is planned to cool the phase space distribution of the ions by merging them with cold electron beams or laser beams, or by using stochastic cooling. Some atomic physics experiments planned for these rings are presented. 35 refs

  3. Moving ring reactor 'Karin-1'

    International Nuclear Information System (INIS)

    1983-12-01

    The conceptual design of a moving ring reactor ''Karin-1'' has been carried out to advance fusion system design, to clarify the research and development problems, and to decide their priority. In order to attain these objectives, a D-T reactor with tritium breeding blanket is designed, a commercial reactor with net power output of 500 MWe is designed, the compatibility of plasma physics with fusion engineering is demonstrated, and some other guideline is indicated. A moving ring reactor is composed mainly of three parts. In the first formation section, a plasma ring is formed and heated up to ignition temperature. The plasma ring of compact torus is transported from the formation section through the next burning section to generate fusion power. Then the plasma ring moves into the last recovery section, and the energy and particles of the plasma ring are recovered. The outline of a moving ring reactor ''Karin-1'' is described. As a candidate material for the first wall, SiC was adopted to reduce the MHD effect and to minimize the interaction with neutrons and charged particles. The thin metal lining was applied to the SiC surface to solve the problem of the compatibility with lithium blanket. Plasma physics, the engineering aspect and the items of research and development are described. (Kako, I.)

  4. Tinkering at the main-ring lattice

    Energy Technology Data Exchange (ETDEWEB)

    Ohnuma, S.

    1982-08-23

    To improve production of usable antiprotons using the proton beam from the main ring and the lossless injection of cooled antiprotons into the main ring, modifications of the main ring lattice are recommended.

  5. The ring plus project: safety and acceptability of vaginal rings that protect women from unintended pregnancy

    OpenAIRE

    Schurmans, C?line; De Baetselier, Irith; Kestelyn, Evelyne; Jespers, Vicky; Delvaux, Th?r?se; Agaba, Stephen K; van Loen, Harry; Menten, Joris; van de Wijgert, Janneke; Crucitti, Tania

    2015-01-01

    Background Research is ongoing to develop multipurpose vaginal rings to be used continuously for contraception and to prevent Human Immunodeficiency Virus (HIV) infection. Contraceptive vaginal rings (CVRs) are available in a number of countries and are most of the time used intermittently i.e. three weeks out of a 4-week cycle. Efficacy trials with a dapivirine-containing vaginal ring for HIV prevention are ongoing and plans to develop multi-purpose vaginal rings for prevention of both HIV a...

  6. Pyrimidine-pyridine ring interconversion

    NARCIS (Netherlands)

    Plas, van der H.C.

    2003-01-01

    This chapter discusses the pyrimidine-to-pyridine ring transformation and pyridine-to-pyrimidine ring transformation. In nucleophile-induced pyrimidine-to-pyridine rearrangements, two types of reactions can be distinguished depending on the structure of the nucleophile: (1) reactions in which the

  7. Electron beam cooling at a magnetic storage ring, TARN II, and an electrostatic storage ring

    International Nuclear Information System (INIS)

    Tanabe, Tetsumi

    2006-01-01

    At the High Energy Accelerator Research Organization (KEK), a magnetic storage ring, TARN II, with an electron cooler was operated from 1989 to 1999, while an electrostatic storage ring with a small electron cooler has been operational since 2000. In this paper, the electron cooling at TARN II and the electrostatic storage ring is described. (author)

  8. Leapfrogging of multiple coaxial viscous vortex rings

    International Nuclear Information System (INIS)

    Cheng, M.; Lou, J.; Lim, T. T.

    2015-01-01

    A recent theoretical study [Borisov, Kilin, and Mamaev, “The dynamics of vortex rings: Leapfrogging, choreographies and the stability problem,” Regular Chaotic Dyn. 18, 33 (2013); Borisov et al., “The dynamics of vortex rings: Leapfrogging in an ideal and viscous fluid,” Fluid Dyn. Res. 46, 031415 (2014)] shows that when three coaxial vortex rings travel in the same direction in an incompressible ideal fluid, each of the vortex rings alternately slips through (or leapfrogs) the other two ahead. Here, we use a lattice Boltzmann method to simulate viscous vortex rings with an identical initial circulation, radius, and separation distance with the aim of studying how viscous effect influences the outcomes of the leapfrogging process. For the case of two identical vortex rings, our computation shows that leapfrogging can be achieved only under certain favorable conditions, which depend on Reynolds number, vortex core size, and initial separation distance between the two rings. For the case of three coaxial vortex rings, the result differs from the inviscid model and shows that the second vortex ring always slips through the leading ring first, followed by the third ring slipping through the other two ahead. A simple physical model is proposed to explain the observed behavior

  9. Anti-sense expression of a metallopeptidase gene enhances nuclear entry of HBV-DNA

    International Nuclear Information System (INIS)

    Yeh, C.-T.; Lai, H.-Y.; Chu, S.-P.; Tseng, I-Chu

    2004-01-01

    Although several putative hepatitis B virus (HBV) receptors have been identified, none of them is capable of initiating HBV replication in a non-permissive human cell line. Using an Epstein-Barr virus-based extrachromosomal replication system, we have screened through a human liver cDNA library and successfully identified a clone capable of facilitating nuclear transport of HBV-DNA during the early phase of HBV infection. This clone contained a cDNA encoding a metallopeptidase-like protein in anti-sense orientation. Pretreatment of naive HepG2 cells with 1,10-phenanthroline, an inhibitor for liver metallopeptidases, led to nuclear entry of HBV-DNA after HBV infection. However, cccDNA was still undetectable in the nuclei, indicating other cellular factors required to complete the replication cycle were still missing. Our present data suggest that in the initial stage of HBV infection, liver metallopeptidase constitutes a barrier for effective nuclear entry of HBV genomic DNA. Attenuation of metallopeptidase activity may facilitate HBV infection

  10. A long natural-antisense RNA is accumulated in the conidia of Aspergillus oryzae.

    Science.gov (United States)

    Tsujii, Masaru; Okuda, Satoshi; Ishi, Kazutomo; Madokoro, Kana; Takeuchi, Michio; Yamagata, Youhei

    2016-01-01

    Analysis of expressed sequence tag libraries from various culture conditions revealed the existence of conidia-specific transcripts assembled to putative conidiation-specific reductase gene (csrA) in Aspergillus oryzae. However, the all transcripts were transcribed with opposite direction to the gene csrA. The sequence analysis of the transcript revealed that the RNA overlapped mRNA of csrA with 3'-end, and did not code protein longer than 60 amino acid residues. We designated the transcript Conidia Specific Long Natural-antisense RNA (CSLNR). The real-time PCR analysis demonstrated that the CSLNR is conidia-specific transcript, which cannot be transcribed in the absence of brlA, and the amount of CSLNR was much more than that of the transcript from csrA in conidia. Furthermore, the csrA deletion, also lacking coding region of CSLNR in A. oryzae reduced the number of conidia. Overexpression of CsrA demonstrated the inhibition of growth and conidiation, while CSLNR did not affect conidiation.

  11. Redox shuttles having an aromatic ring fused to a 1,1,4,4-tetrasubstituted cyclohexane ring

    Science.gov (United States)

    Weng, Wei; Zhang, Zhengcheng; Amine, Khalil

    2015-12-01

    An electrolyte includes an alkali metal salt; an aprotic solvent; and a redox shuttle additive including an aromatic compound having at least one aromatic ring fused with at least one non-aromatic ring, the aromatic ring having two or more oxygen or phosphorus-containing substituents.

  12. Molecular imaging of atherosclerotic plaques with technetium-99m-labelled antisense oligonucleotides

    International Nuclear Information System (INIS)

    Qin Guangming; Zhang Yongxue; Cao Wei; An Rui; Gao Zairong; Xu Wendai; Zhang Kaijun; Li Guiling; Li Shuren

    2005-01-01

    The purpose of this study was to visualise experimental atherosclerotic lesions using radiolabelled antisense oligonucleotides (ASONs). Atherosclerosis was induced in New Zealand White rabbits fed 1% cholesterol for approximately 60 days. In vivo and ex vivo imaging was performed in atherosclerotic rabbits and normal control rabbits after i.v. injection of 92.5±18.5 MBq 99m Tc-labelled ASON or 99m Tc-labelled sense oligonucleotides. Immediately after the in vivo imaging, the animals were sacrificed and ex vivo imaging of the aortic specimens was performed. Biodistribution of radiolabelled c-mycASON was evaluated in vivo in atherosclerotic rabbits. Planar imaging revealed accumulation of 99m Tc-labelled c-mycASON in atherosclerotic lesions along the artery wall. Ex vivo imaging further demonstrated that the area of activity accumulation matched the area of atherosclerotic lesions. In contrast, no atherosclerotic lesions were found in the vessel wall and no positive imaging results were obtained in animals of the control group. This molecular imaging approach has potential for non-invasive imaging of atherosclerotic plaques at an early stage. (orig.)

  13. Interaction of Vortex Ring with Cutting Plate

    Science.gov (United States)

    Musta, Mustafa

    2015-11-01

    The interaction of a vortex ring impinging on a thin cutting plate was made experimentally using Volumetric 3-component Velocitmetry (v3v) technique. The vortex rings were generated with piston-cylinder vortex ring generator using piston stroke-to-diameter ratios and Re at 2-3 and 1500 - 3000, respectively. The cutting of vortex rings below center line leads to the formation of secondary vortices on each side of the plate which is look like two vortex rings, and a third vortex ring propagates further downstream in the direction of the initial vortex ring, which is previously showed by flow visualization study of Weigand (1993) and called ``trifurcation''. Trifurcation is very sensitive to the initial Reynolds number and the position of the plate with respect to the vortex ring generator pipe. The present work seeks more detailed investigation on the trifurcation using V3V technique. Conditions for the formation of trifurcation is analyzed and compared with Weigand (1993). The formed secondary vortex rings and the propagation of initial vortex ring in the downstream of the plate are analyzed by calculating their circulation, energy and trajectories.

  14. Magnetic ring for stripping enhancement

    International Nuclear Information System (INIS)

    Selph, F.

    1992-10-01

    A ring designed to recycle ions through a stripping medium offers the possibility for increasing output of the desired charge state by up to 4x. This could be a very important component of a Radioactive Nuclear Beam Facility. In order for such a ring to work effectively it must satisfy certain design conditions. These include achromaticity at the stripper, a dispersed region for an extraction magnet, and a number of first and higher order optics constraints which are necessary to insure that the beam emittance is not degraded unduly by the ring. An example is given of a candidate design of a stripping ring

  15. Acceleration of magnetized plasma rings

    International Nuclear Information System (INIS)

    Hartman, D.; Eddleman, J.; Hammer, J.H.

    1982-01-01

    One scheme is considered, acceleration of a ring between coaxial electrodes by a B/sub theta/ field as in a coaxial rail-gun. If the electrodes are conical, a ring accelerated towards the apex of the cone undergoes self-similar compression (focussing) during acceleration. Because the allowable acceleration force F/sub a/ = kappa U/sub m//R (kappa - 2 , the accelerating distance for conical electrodes is considerably shortened over that required for coaxial electrodes. In either case however, since the accelerating flux can expand as the ring moves, most of the accelerating field energy can be converted into kinetic energy of the ring leading to high efficiency

  16. A first course in noncommutative rings

    CERN Document Server

    Lam, T Y

    2001-01-01

    A First Course in Noncommutative Rings, an outgrowth of the author's lectures at the University of California at Berkeley, is intended as a textbook for a one-semester course in basic ring theory. The material covered includes the Wedderburn-Artin theory of semisimple rings, Jacobson's theory of the radical, representation theory of groups and algebras, prime and semiprime rings, local and semilocal rings, perfect and semiperfect rings, etc. By aiming the level of writing at the novice rather than the connoisseur and by stressing th the role of examples and motivation, the author has produced a text that is suitable not only for use in a graduate course, but also for self- study in the subject by interested graduate students. More than 400 exercises testing the understanding of the general theory in the text are included in this new edition.

  17. Delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA as a cancer therapeutic: a proof-of-concept study

    Directory of Open Access Journals (Sweden)

    Lin KY

    2016-05-01

    Full Text Available Kun-Yuan Lin,1 Siao Muk Cheng,2 Shing-Ling Tsai,2 Ju-Ya Tsai,1 Chun-Hui Lin,1 Chun Hei Antonio Cheung1,2 1Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC; 2Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC Abstract: Survivin is a member of the inhibitor-of-apoptosis proteins family. It is overexpressed in many different cancer types but not in the differentiated normal tissue. In addition, overexpression of survivin promotes cancer cell survival and induces chemotherapeutic drug resistance, making it an attractive target for new anticancer interventions. Despite survivin being a promising molecular target for anticancer treatment, it is widely accepted that survivin is only a “semi-druggable” target. Therefore, it is important to develop a new strategy to target survivin for anticancer treatment. In this study, we constructed a novel survivin promoter-driven full-length antisense survivin (pSur/AS-Sur expression plasmid DNA. Promoter activity assay revealed that the activity of the survivin promoter of pSur/AS-Sur correlated with the endogenous expression of survivin at the transcriptional level in the transfected A549, MDA-MB-231, and PANC-1 cancer cells. Western blot analysis showed that liposomal delivery of pSur/AS-Sur successfully downregulated the expression of survivin in A549, MBA-MB-231, and PANC-1 cells in vitro. In addition, delivery of pSur/AS-Sur induced autophagy, caspase-dependent apoptosis, and caspase-independent apoptosis as indicated by the increased LC3B-II conversion, autophagosome formation, caspase-9/-3 and poly(ADP-ribose polymerase-1 cleavage, and apoptosis-inducing factor nuclear translocation in A549, MBA-MB-231, and PANC-1 cells. Importantly, liposomal delivery of pSur/AS-Sur was also capable of decreasing the proliferation of the survivin/MDR1 coexpressing multidrug-resistant KB-TAX50 cancer cells and

  18. Design of Piston Ring Friction Tester Apparatus

    DEFF Research Database (Denmark)

    Klit, Peder

    2006-01-01

    One of the major prerequisites for calculating piston ring friction is a good description of the tribological situation. Piston rings operate in three different lubrication regimes and the theoretical models should be capable to describe this. A very important condition for describing the frictio......One of the major prerequisites for calculating piston ring friction is a good description of the tribological situation. Piston rings operate in three different lubrication regimes and the theoretical models should be capable to describe this. A very important condition for describing...... the frictional behavior of a piston ring correctly is knowledge about the amount of lubricant present. For piston rings the external load may be established by measuring the pressure distribution, i.e. the pressure drop in the piston ring package. Speed and temperature may also be established. The amount...... available is reflected in the friction absorbed in the bearing. The following properties will be measured: Oil fillm thickness - along liner (axial variation), oil film thickness - along piston ring (circumferential variation), piston tilt, temperature of piston rings and liner, pressure at piston lands...

  19. Study for ILC Damping Ring at KEKB

    Energy Technology Data Exchange (ETDEWEB)

    Flanagan, J.W.; Fukuma, H.; Kanazawa, K.I.; Koiso, H.; Masuzawa, M.; Ohmi, Kazuhito; Ohnishi, Y.; Oide, Katsunobu; Suetsugu, Y.; Tobiyama, M.; /KEK, Tsukuba; Pivi, M.; /SLAC

    2011-11-04

    ILC damping ring consists of very low emittance electron and positron storage rings. It is necessary for ILC damping ring to study electron cloud effects in such low emittance positron ring. We propose a low emittance operation of KEKB to study the effects.

  20. Planetary ring systems properties, structures, and evolution

    CERN Document Server

    Murray, Carl D

    2018-01-01

    Planetary rings are among the most intriguing structures of our solar system and have fascinated generations of astronomers. Collating emerging knowledge in the field, this volume reviews our current understanding of ring systems with reference to the rings of Saturn, Uranus, Neptune, and more. Written by leading experts, the history of ring research and the basics of ring–particle orbits is followed by a review of the known planetary ring systems. All aspects of ring system science are described in detail, including specific dynamical processes, types of structures, thermal properties and their origins, and investigations using computer simulations and laboratory experiments. The concluding chapters discuss the prospects of future missions to planetary rings, the ways in which ring science informs and is informed by the study of other astrophysical disks, and a perspective on the field's future. Researchers of all levels will benefit from this thorough and engaging presentation.

  1. Longitudinal beam instability due to the ring impedance at KEK's accelerator test facility damping ring

    International Nuclear Information System (INIS)

    Kim, Eun-San

    2003-01-01

    This paper shows the results of a numerical study of the impedance in the Accelerator Test Facility damping ring. The longitudinal impedance in the damping ring is shown to be inductive. It is shown that the total impedance |Z || /n| is 0.23 Ω and the inductance is L = 14 nH. In the extremely low emittance beam of the damping ring, bunch lengthening is caused by both the effects of potential-well distortion and intra-beam scattering. In this paper, the bunch-lengthening due to the ring impedance is numerically investigated, and the result shows qualitative agreement with the result of an analysis performed using the bunch-length measurement. With the calculated longitudinal impedance, the instability threshold in the damping ring is estimated to be a bunch population of 3.3 x 10 10 by using both a Vlasov equation approach and a multi-particle tracking method.

  2. Periodic Mesoporous Organosilica Nanoparticles with Controlled Morphologies and High Drug/Dye Loadings for Multicargo Delivery in Cancer Cells

    KAUST Repository

    Croissant, Jonas G.

    2016-06-01

    Despite the worldwide interest generated by periodic mesoporous organosilica (PMO) bulk materials, the design of PMO nanomaterials with controlled morphology remains largely unexplored and their properties unknown. In this work, we describe the first study of PMO nanoparticles (NPs) based on meta-phenylene bridges, and we conducted a comparative structure–property relationship investigation with para-phenylene-bridged PMO NPs. Our findings indicate that the change of the isomer drastically affects the structure, morphology, size, porosity and thermal stability of PMO materials. We observed a much higher porosity and thermal stability of the para-based PMO which was likely due to a higher molecular periodicity. Additionally, the para isomer could generate multipodal NPs at very low stirring speed and upon this discovery we designed a phenylene–ethylene bridged PMO with a controlled Janus morphology. Unprecedentedly high payloads could be obtained from 40 to 110 wt % regardless of the organic bridge of PMOs. Finally, we demonstrate for the first time the co-delivery of two cargos by PMO NPs. Importantly, the cargo stability in PMOs did not require the capping of the pores, unlike pure silica, and the delivery could be autonomously triggered in cancer cells by acidic pH with nearly 70 % cell killing. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

  3. The antisense expression of AhPEPC1 increases seed oil production in peanuts (Arachis hypogaea L.)

    Energy Technology Data Exchange (ETDEWEB)

    Pan, L.; Zhang, J.; Chi, X.; Chen, N.; Chen, M.; Wang, M.; Wang, T.; Yang, Z.; Zhang, Z.; Wan, Y.; Yu, S.; Liu, F.

    2016-07-01

    Although phosphoenolpyruvate carboxylases (PEPCs) are reported to be involved in fatty acid accumulation, nitrogen assimilation, and salt and drought stresses, knowledge regarding PEPC gene functions is still limited, particularly in peanuts (Arachis hypogaea L.). In this study, the antisense expression of the peanut PEPC isoform 1 (AhPEPC1) gene increased the lipid content by 5.7%–10.3%. This indicated that AhPEPC1 might be related to plant lipid accumulation. The transgenic plants underwent more root elongation than the wild-type under salinity stress. Additionally, the specific down regulation of the AhPEPC1 gene improved the salt tolerance in peanuts. This is the first report on the role of PEPC in lipid accumulation and salt tolerance in peanuts.

  4. Formulation and drug-content assay of microencapsulated antisense oligonucleotide to NF-κB using ATR-FTIR

    International Nuclear Information System (INIS)

    Siwale, Rodney; Meadows, Fred; Mody, Vicky V; Shah, Samit

    2013-01-01

    Antisense oligonucleotide to NF-κB sequence: 5′-GGA AAC ACA TCC TCC ATG-3′, was microencapsulated in an albumin matrix by the method of spray drying TM . Spectral analysis was performed on varying drug loading formulations of both drugs by mid-IR attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). An out of plane O–H bending vibration at 948 cm −1 , unique to both the native and microencapsulated drugs was identified. The calculated peak areas corresponded to the drug loadings in the microsphere formulations. A standard curve could then be used to determine the drug content of an unknown microsphere formulation. Accuracy and precision were determined to be comparable to other analytical techniques such as HPLC. (paper)

  5. Acceleration effect of alcohols on ion association of molbdophosphate with malachite green and its use to the sensitive flow-injection determination of phosphate. Molybdo rinsan ion-malachite green ion kaigotai seisei ni oyobosu alcohol no hanno sokushinkoka to sore wo riyosuru rin no kokando flow injection bunseki

    Energy Technology Data Exchange (ETDEWEB)

    Motomizu, S; Yasuda, Y; Oshima, M [Okayama Univ., Okayama (Japan). Faculty of Science

    1991-12-10

    Molibdophosphoric acid (PMo) reacts with malachite green (MG{sup +}) to form a colored ion associate (MG{sup +}- PMo) in an acidic solution according to the formula : HMG{sup 2+}+H{sub 3}PMo{sub 12}O{sub 40}{yields}(MG{sup +})H{sub 2}PMo{sub 12}O{sub 40}+2H{sup +}. A protonated form HMG{sup 2+} is yellow (the absorption mximum at 446 nm), whereas the ion associate MG{sup +} is blue green (the absorption maximum at 650 nm). MG{sup +} is found to accelerate the formation of PMo. Water-miscible organic solvents such as methanol,ethanol and propanol also accelerate the formation of PMo as well as the formation of MG sup + - PMo. Some anionic surfactants decelerate the reaction, however, contribute to the suppression of the baseline drift in a flow injection analysis (FIA). By the use of the proposed reaction accelerator and surfactant. a highly sensitive FIA system is established for,orthophosphate up to the range of several ppb. 16 figs.. 11 refs.

  6. Syntheses and applications of periodic mesoporous organosilica nanoparticles

    KAUST Repository

    Croissant, Jonas G.

    2015-11-06

    Periodic Mesoporous Organosilica (PMO) nanomaterials are envisioned to be one of the most prolific subjects of research in the next decade. Similar to mesoporous silica nanoparticles (MSN), PMO nanoparticles (NPs) prepared from organo-bridged alkoxysilanes have tunable mesopores that could be utilized for many applications such as gas and molecule adsorption, catalysis, drug and gene delivery, electronics, and sensing; but unlike MSN, the diversity in chemical nature of the pore walls of such nanomaterials is theoretically unlimited. Thus, we expect that PMO NPs will attract considerable interest over the next decade. In this review, we will present a comprehensive overview of the synthetic strategies for the preparation of nanoscaled PMO materials, and then describe their applications in catalysis and nanomedicine. The remarkable assets of the PMO structure are also detailed, and insights are provided for the preparation of more complex PMO nanoplatforms.

  7. Accretion in Saturn's F Ring

    Science.gov (United States)

    Meinke, B. K.; Esposito, L. W.; Stewart, G.

    2012-12-01

    Saturn's F ring is the solar system's principal natural laboratory for direct observation of accretion and disruption processes. The ring resides in the Roche zone, where tidal disruption competes with self-gravity, which allows us to observe the lifecycle of moonlets. Just as nearby moons create structure at the B ring edge (Esposito et al. 2012) and the Keeler gap (Murray 2007), the F ring "shepherding" moons Prometheus and Pandora stir up ring material and create observably changing structures on timescales of days to decades. In fact, Beurle et al (2010) show that Prometheus makes it possible for "distended, yet gravitationally coherent clumps" to form in the F ring, and Barbara and Esposito (2002) predicted a population of ~1 km bodies in the ring. In addition to the observations over the last three decades, the Cassini Ultraviolet Imaging Spectrograph (UVIS) has detected 27 statistically significant features in 101 occultations by Saturn's F ring since July 2004. Seventeen of those 27 features are associated with clumps of ring material. Two features are opaque in occultation, which makes them candidates for solid objects, which we refer to as Moonlets. The 15 other features partially block stellar signal for 22 m to just over 3.7 km along the radial expanse of the occultation. Upon visual inspection of the occultation profile, these features resemble Icicles, thus we will refer to them as such here. The density enhancements responsible for such signal attenuations are likely due to transient clumping of material, evidence that aggregations of material are ubiquitous in the F ring. Our lengthy observing campaign reveals that Icicles are likely transient clumps, while Moonlets are possible solid objects. Optical depth is an indicator of clumping because more-densely aggregated material blocks more light; therefore, it is natural to imagine moonlets as later evolutionary stage of icicle, when looser clumps of material compact to form a feature that appears

  8. Latency of Epstein-Barr virus is stabilized by antisense-mediated control of the viral immediate-early gene BZLF-1.

    Science.gov (United States)

    Prang, N; Wolf, H; Schwarzmann, F

    1999-12-01

    The ability of the Epstein-Barr virus (EBV) to avoid lytic replication and to establish a latent infection in B-lymphocytes is fundamental for its lifelong persistence and the pathogenesis of various EBV-associated diseases. The viral immediate-early gene BZLF-1 plays a key role for the induction of lytic replication and its activity is strictly regulated on different levels of gene expression. Recently, it was demonstrated that BZLF-1 is also controlled by a posttranscriptional mechanism. Transient synthesis of a mutated competitor RNA saturated this mechanism and caused both expression of the BZLF-1 protein and the induction of lytic viral replication. Using short overlapping fragments of the competitor, it is shown that this control acts on the unspliced primary transcript. RT-PCR demonstrated unspliced BZLF-1 RNA in latently infected B-lymphocytes in the absence of BZLF-1 protein. Due to the complementarity of the gene BZLF-1 and the latency-associated gene EBNA-1 on the opposite strand of the genome, we propose an antisense-mediated mechanism. RNase protection assays demonstrated transcripts in antisense orientation to the BZLF-1 transcript during latency, which comprise a comparable constellation to other herpesviruses. A combined RNAse protection/RT-PCR assay detected the double-stranded hybrid RNA, consisting of the unspliced BZLF-1 transcript and a noncoding intron of the EBNA-1 gene. Binding of BZLF-1 transcripts is suggested to be an important backup control mechanism in addition to transcriptional regulation, stabilizing latency and preventing inappropriate lytic viral replication in vivo. Copyright 1999 Wiley-Liss, Inc.

  9. Nonlinear analysis of ring oscillator circuits

    KAUST Repository

    Ge, Xiaoqing

    2010-06-01

    Using nonlinear systems techniques, we analyze the stability properties and synchronization conditions for ring oscillator circuits, which are essential building blocks in digital systems. By making use of its cyclic structure, we investigate local and global stability properties of an n-stage ring oscillator. We present a sufficient condition for global asymptotic stability of the origin and obtain necessity if the ring oscillator consists of identical inverter elements. We then give a synchronization condition for identical interconnected ring oscillators.

  10. Nonlinear analysis of ring oscillator circuits

    KAUST Repository

    Ge, Xiaoqing; Arcak, Murat; Salama, Khaled N.

    2010-01-01

    Using nonlinear systems techniques, we analyze the stability properties and synchronization conditions for ring oscillator circuits, which are essential building blocks in digital systems. By making use of its cyclic structure, we investigate local and global stability properties of an n-stage ring oscillator. We present a sufficient condition for global asymptotic stability of the origin and obtain necessity if the ring oscillator consists of identical inverter elements. We then give a synchronization condition for identical interconnected ring oscillators.

  11. Quality Assurance Project Plan for Verification of Sediment Ecotoxicity Assessment Ring(SEA Ring)

    Science.gov (United States)

    The objective of the verification is to test the efficacy and ability of the Sediment Ecotoxicity Assessment Ring (SEA Ring) to evaluate the toxicity of contaminants in the sediment, at the sediment-water interface, and WC to organisms that live in those respective environments.

  12. Dynamical Evolution of Ring-Satellite Systems

    Science.gov (United States)

    Ohtsuki, Keiji

    2005-01-01

    The goal of this research was to understand dynamical processes related to the evolution of size distribution of particles in planetary rings and application of theoretical results to explain features in the present rings of giant planets. We studied velocity evolution and accretion rates of ring particles in the Roche zone. We developed a new numerical code for the evolution of ring particle size distribution, which takes into account the above results for particle velocity evolution and accretion rates. We also studied radial diffusion rate of ring particles due to inelastic collisions and gravitational encounters. Many of these results can be also applied to dynamical evolution of a planetesimal disk. Finally, we studied rotation rates of moonlets and particles in planetary rings, which would influence the accretional evolution of these bodies. We describe our key accomplishments during the past three years in more detail in the following.

  13. Propellers in Saturn's rings

    Science.gov (United States)

    Sremcevic, M.; Stewart, G. R.; Albers, N.; Esposito, L. W.

    2013-12-01

    Theoretical studies and simulations have demonstrated the effects caused by objects embedded in planetary rings. Even if the objects are too small to be directly observed, each creates a much larger gravitational imprint on the surrounding ring material. These strongly depend on the mass of the object and range from "S" like propeller-shaped structures for about 100m-sized icy bodies to the opening of circumferential gaps as in the case of the embedded moons Pan and Daphnis and their corresponding Encke and Keeler Gaps. Since the beginning of the Cassini mission many of these smaller objects (~data from Cassini Ultraviolet Imaging Spectrograph (UVIS) and Imaging Science Subsystem (ISS) experiments. We show evidence that B ring seems to harbor two distinct populations of propellers: "big" propellers covering tens of degrees in azimuth situated in the densest part of B ring, and "small" propellers in less dense inner B ring that are similar in size and shape to known A ring propellers. The population of "big" propellers is exemplified with a single object which is observed for 5 years of Cassini data. The object is seen as a very elongated bright stripe (40 degrees wide) in unlit Cassini images, and dark stripe in lit geometries. In total we report observing the feature in images at 18 different epochs between 2005 and 2010. In UVIS occultations we observe this feature as an optical depth depletion in 14 out of 93 occultation cuts at corrotating longitudes compatible with imaging data. Combining the available Cassini data we infer that the object is a partial gap located at r=112,921km embedded in the high optical depth region of the B ring. The gap moves at Kepler speed appropriate for its radial location. Radial offsets of the gap locations in UVIS occultations are consistent with an asymmetric propeller shape. The asymmetry of the observed shape is most likely a consequence of the strong surface mass density gradient, as the feature is located at an edge between

  14. Cosmic rings from colliding galaxies

    Energy Technology Data Exchange (ETDEWEB)

    Mitton, S

    1976-11-18

    Research on two ring galaxies has led to the proposal of an interaction model to account for the rings. It is envisaged that this class of galaxy is created when a compact galaxy crashes through the disc of a spiral galaxy. The results of a spectroscopic investigation of the galaxy known as the Cartwheel and of another ring galaxy 11 NZ 4 are discussed. The general picture of ring galaxies which emerges from these studies of a massive starry nucleus with a necklace of emitting gas and some spokes and along the spin axis of the wheel a small companion galaxy that is devoid of interstellar gas. An explanation of these properties is considered.

  15. [Subchronic toxicity test of genetically modified rice with double antisense starch-branching enzyme gene].

    Science.gov (United States)

    Li, Min; Piao, Jianhua; Yang, Xiaoguang

    2010-07-01

    To observe the sub-chronic toxic effects of the genetically modified rice with double antisense SBE gene. Based on gender and weight, weanling Wistar rats were randomly sorted into five groups: non-genetically modified rice group (group A), genetically modified rice group (group B), half genetically modified rice group (group C), quarter genetically modified rice group (group D) and AIN-93G normal diet group (group E). Indicators were the followings: body weight, food consumption, blood routine, blood biochemical test, organ weight, bone density and pathological examination of organs. At the middle of the experiment, the percentage of monocyte of female group B was less than that of group E (P 0.05), and no notable abnormity in the pathological examination of main organs (P > 0.05). There were no enough evidence to confirm the sub-chronic toxicity of genetically modified rice on rats.

  16. Attenuation of alpha2A-adrenergic receptor expression in neonatal rat brain by RNA interference or antisense oligonucleotide reduced anxiety in adulthood.

    Science.gov (United States)

    Shishkina, G T; Kalinina, T S; Dygalo, N N

    2004-01-01

    Brain alpha2-adrenergic receptors (alpha2-ARs) have been implicated in the regulation of anxiety, which is associated with stress. Environmental treatments during neonatal development could modulate the level of brain alpha2-AR expression and alter anxiety in adults, suggesting possible involvement of these receptors in early-life programming of anxiety state. The present study was undertaken to determine whether the reduction of the expression of A subtype of these receptors most abundant in the neonatal brain affects anxiety-related behavior in adulthood. We attenuated the expression of alpha2A-ARs during neonatal life by two different sequence specific approaches, antisense technology and RNA interference. Treatment of rats with the antisense oligodeoxynucleotide or short interfering RNA (siRNA) against alpha2A-ARs on the days 2-4 of their life, produced a marked acute decrease in the levels of both alpha2A-AR mRNA and [3H]RX821002 binding sites in the brainstem into which drugs were injected. The decrease of alpha2A-AR expression in the neonatal brainstem influenced the development of this receptor system in the brain regions as evidenced by the increased number of [3H]RX821002 binding sites in the hypothalamus of adult animals with both neonatal alpha2A-AR knockdown treatments; also in the frontal cortex of antisense-treated, and in the hippocampus of siRNA-treated adult rats. These adult animals also demonstrated a decreased anxiety in the elevated plus-maze as evidenced by an increased number of the open arm entries, greater proportion of time spent in the open arms, and more than a two-fold increase in the number of exploratory head dips. The results provide the first evidence that the reduction in the brain expression of a gene encoding for alpha2A-AR during neonatal life led to the long-term neurochemical and behavioral alterations. The data suggests that alterations in the expression of the receptor-specific gene during critical periods of brain

  17. Endogenous Msx1 antisense transcript: In vivo and in vitro evidences, structure, and potential involvement in skeleton development in mammals

    OpenAIRE

    Blin-Wakkach, C.; Lezot, F.; Ghoul-Mazgar, S.; Hotton, D.; Monteiro, S.; Teillaud, C.; Pibouin, L.; Orestes-Cardoso, S.; Papagerakis, P.; Macdougall, M.; Robert, B.; Berdal, A.

    2001-01-01

    Msx1 is a key factor for the development of tooth and craniofacial skeleton and has been proposed to play a pivotal role in terminal cell differentiation. In this paper, we demonstrated the presence of an endogenous Msx1 antisense RNA (Msx1-AS RNA) in mice, rats, and humans. In situ analysis revealed that this RNA is expressed only in differentiated dental and bone cells with an inverse correlation with Msx1 protein. These in vivo data and overexpression of Msx1 sense and AS RNA in an odontob...

  18. On Semiprime Noetherian PI-Rings

    OpenAIRE

    Chiba, Katsuo

    2000-01-01

    Let R be a semiprime Noetherian PI-ring and Q(R) the semisimple Artinian ring of fractions of R. We shall prove the following conditions are equivalent: (1) the Krull dimention of R is at most one, (2) Any ring between R and Q(R) is again right Noetherian, (3) Let a, b be central regular elements of Q(R). Then the subring R + aR[b] of Q(R) is right Noetherian.

  19. On zero divisor graph of unique product monoid rings over Noetherian reversible ring

    Directory of Open Access Journals (Sweden)

    Ebrahim Hashemi

    2016-02-01

    Full Text Available Let $R$ be an associative ring with identity and $Z^*(R$ be its set of non-zero zero divisors.  The zero-divisor graph of $R$, denoted by $Gamma(R$, is the graph whose vertices are the non-zero  zero-divisors of  $R$, and two distinct vertices $r$ and $s$ are adjacent if and only if $rs=0$ or $sr=0$.  In this paper, we bring some results about undirected zero-divisor graph of a monoid ring over reversible right (or left Noetherian ring $R$. We essentially classify the diameter-structure of this graph and show that $0leq mbox{diam}(Gamma(Rleq mbox{diam}(Gamma(R[M]leq 3$. Moreover, we give a characterization for the possible diam$(Gamma(R$ and diam$(Gamma(R[M]$, when $R$ is a reversible Noetherian ring and $M$ is a u.p.-monoid. Also, we study relations between the girth of $Gamma(R$ and that of $Gamma(R[M]$.

  20. Imidazolopiperazines (IPZ) kill both rings and dormant rings in wild type and K13 artemisinin resistant Plasmodium falciparum in vitro.

    Science.gov (United States)

    Dembele, Laurent; Gupta, Devendra Kumar; Lim, Michelle Yi-Xiu; Ang, Xiaoman; Selva, Jeremy J; Chotivanich, Kesinee; Nguon, Chea; Dondorp, Arjen M; Bonamy, Ghislain M C; Diagana, Thierry T; Bifani, Pablo

    2018-03-12

    Artemisinin (ART) resistance has spread through Southeast Asia, posing serious threat to the control and elimination of malaria. ART resistance has been associated with mutations in the Plasmodium falciparum kelch-13 ( Pfk13 ) propeller domain. Phenotypically, ART resistance is defined as delayed parasite clearance in patients' due to the reduced susceptibility of early ring-stage parasites to the active metabolite of ART dihydroartemisinin (DHA). Early rings can enter a state of quiescence upon DHA exposure and resume growth in its absence. These quiescent rings are referred to as dormant rings or DHA-pretreated rings (called here dormant rings). The imidazolopiperazine (IPZ) is a novel class of antimalarial drugs, which has demonstrated efficacy in early clinical trials. Here, we characterized the stage of action of IPZ GNF179 and evaluated its activity against rings and dormant rings in wild type and ART resistant parasites. Unlike DHA, GNF179 does not induce dormancy. We show that GNF179 is more rapidly cidal against schizonts than ring and trophozoite stages. However, with 12 hours exposure, the compound effectively kills rings and dormant rings of both susceptible and ART resistant parasites within 72 hours. We further demonstrate that in combination with ART, GNF179 effectively prevent recrudescence of dormant rings including those bearing pfk13 propeller mutations. Copyright © 2018 Dembele et al.

  1. Complete snake and rotator schemes for spin polarization in proton rings and large electron rings

    International Nuclear Information System (INIS)

    Steffen, K.

    1983-11-01

    In order to maintain spin polarization in proton rings and large electron rings, some generalized Siberian Snake scheme may be required to make the spin tune almost independent of energy and thus avoid depolarizing resonances. The practical problem of finding such schemes that, at reasonable technical effort, can be made to work over large energy ranges has been addressed before and is here revisited in a broadened view and with added new suggestions. As a result, possibly optimum schemes for electron rings (LEP) and proton rings are described. In the proposed LEP scheme, spin rotation is devised such that, at the interaction points, the spin direction is longitudinal as required for experiments. (orig.)

  2. Koffka's Ring Effect Depends on Thickness, Not Continuity

    OpenAIRE

    Abigail E. Huang; Alice J. Hon; Eric L. Altschuler

    2007-01-01

    More than 70 years ago Gestalt psychologist Kurt Koffka described a fascinating effect1,2: When a contiguous grey ring is placed on a background half of one shade of grey (different from the ring) and half of another shade of grey, the ring appears to be a homogenous. However, if the ring is slightly divided, now the two halves of the ring appear different shades of grey with the half of the ring on the darker background appearing lighter than the half of the ring on the darker background. Th...

  3. Almost ring theory

    CERN Document Server

    2003-01-01

    This book develops thorough and complete foundations for the method of almost etale extensions, which is at the basis of Faltings' approach to p-adic Hodge theory. The central notion is that of an "almost ring". Almost rings are the commutative unitary monoids in a tensor category obtained as a quotient V-Mod/S of the category V-Mod of modules over a fixed ring V; the subcategory S consists of all modules annihilated by a fixed ideal m of V, satisfying certain natural conditions. The reader is assumed to be familiar with general categorical notions, some basic commutative algebra and some advanced homological algebra (derived categories, simplicial methods). Apart from these general prerequisites, the text is as self-contained as possible. One novel feature of the book - compared with Faltings' earlier treatment - is the systematic exploitation of the cotangent complex, especially for the study of deformations of almost algebras.

  4. IAG ring test animal proteins 2014

    NARCIS (Netherlands)

    Raamsdonk, van L.W.D.; Pinckaers, V.G.Z.; Scholtens-Toma, I.M.J.; Prins, T.W.; Voet, van der H.; Vliege, J.J.M.

    2014-01-01

    A ring test was organized for the detection of animal proteins in animal feed by microscopy in the framework of the annual ring tests of the IAG – International Association for Feeding stuff Analysis, Section Feeding stuff Microscopy. The aim of the ring study was to provide the participants

  5. IAG ring test animal proteins 2015

    NARCIS (Netherlands)

    Raamsdonk, van L.W.D.; Rhee, van de N.E.; Scholtens-Toma, I.M.J.; Prins, T.W.; Vliege, J.J.M.; Pinckaers, V.G.Z.

    2015-01-01

    A ring test was organized for the detection of animal proteins in animal feed by microscopy in the framework of the annual ring tests of the IAG - International Association for Feeding stuff Analysis, Section Feeding stuff Microscopy. The organizer of the ring test was RIKILT - Wageningen UR, The

  6. IAG ring test animal proteins 2013

    NARCIS (Netherlands)

    Raamsdonk, van L.W.D.; Pinckaers, V.G.Z.; Scholtens-Toma, I.M.J.; Prins, T.W.; Vliege, J.J.M.

    2013-01-01

    A ring test was organized for the detection of animal proteins in animal feed by microscopy in the framework of the annual ring tests of the IAG - International Association for Feeding stuff Analysis, Section Feeding stuff Microscopy. The organizer of the the ring study was to provide the

  7. Cooling rings for TeV colliders

    International Nuclear Information System (INIS)

    Palmer, R.B.

    1985-02-01

    Consideration is given to quantum fluctuations, intra beam scattering, cooling rates, and ring acceptance in order to see if one can obtain a normalized emittance of 10 -8 in any plausible cooling ring. It is concluded that only a small gain is obtained by varying the partition functions, but a very significant gain is made by using higher bending fields. The ring is found to get bigger if the magnet apertures are increased. The ring diameter is found to increase if the momentum spread of the beam is reduced. It is shown that the power can be reduced by allowing a high beamstrahlung energy loss resulting in higher current in the cooling ring. Parameters are also given for a 10 -7 m radian emittance case

  8. Dipole Magnets for the LHeC Ring-Ring Option

    CERN Document Server

    Tommasini, D; Chritin, R

    2012-01-01

    The Ring-Ring option of a Large Hadron electron Collider (LHeC) requires 3080 bending magnets, 5.35-meter-long each providing a magnetic field ranging from 0.0127 T at 10 GeV to 0.0763 T at 60 GeV. Main issues in the design of these magnets are the very low injection field, constituting a challenge in achieving a satisfactory field reproducibility from cycle to cycle, and the required compactness to fit in the existing LHC tunnel. This paper describes and discusses a design meeting these requirements, together with its experimental validation by the manufacture and measurement of a 400-mm-long magnet model.

  9. The multi-bend achromat storage rings

    Energy Technology Data Exchange (ETDEWEB)

    Eriksson, Mikael [MAX IV Laboratory Ole Römers v. 1 22100 Lund Sweden (Sweden)

    2016-07-27

    Not very long ago, the 3{sup rd} generation storage ring technology was judged as mature. Most of the 3{sup rd} generation storage rings used the Double-Bend Achromat (DBA) or Triple-Bend Achromat (TBA) concepts. It was however a well-known fact that increasing the number of magnet cells in the rings is a powerful way of decreasing the electron beam emittance and thus the source brilliance, but at the penalty of increasing the size and cost of the rings. Preserving the Dynamic Aperture (DA) in the rings became also an issue when increasing the number of magnet cells. The Multi-Bend Achromat (MBA) concept, including a miniaturization of the ring elements, has now drastically changed the picture. The MBA rings, now in construction or being planned, offer orders of magnitudes higher brilliance than rings of conventional designs. Several light sources around the world are now implementing or planning to implement this MBA concept. This article touches on the science drivers for higher brilliance. We will then describe the MBA concept with its advantages as well as its challenges. A short survey of the MBA activity around the world will also be presented. The author apologies for focusing on the MAX IV project regarding technical solutions. This is motivated by that MAX IV is the facility he knows best and it might be regarded as a fore-runner for the MBA concept.

  10. The multi-bend achromat storage rings

    International Nuclear Information System (INIS)

    Eriksson, Mikael

    2016-01-01

    Not very long ago, the 3"r"d generation storage ring technology was judged as mature. Most of the 3"r"d generation storage rings used the Double-Bend Achromat (DBA) or Triple-Bend Achromat (TBA) concepts. It was however a well-known fact that increasing the number of magnet cells in the rings is a powerful way of decreasing the electron beam emittance and thus the source brilliance, but at the penalty of increasing the size and cost of the rings. Preserving the Dynamic Aperture (DA) in the rings became also an issue when increasing the number of magnet cells. The Multi-Bend Achromat (MBA) concept, including a miniaturization of the ring elements, has now drastically changed the picture. The MBA rings, now in construction or being planned, offer orders of magnitudes higher brilliance than rings of conventional designs. Several light sources around the world are now implementing or planning to implement this MBA concept. This article touches on the science drivers for higher brilliance. We will then describe the MBA concept with its advantages as well as its challenges. A short survey of the MBA activity around the world will also be presented. The author apologies for focusing on the MAX IV project regarding technical solutions. This is motivated by that MAX IV is the facility he knows best and it might be regarded as a fore-runner for the MBA concept.

  11. Ring wormholes via duality rotations

    Directory of Open Access Journals (Sweden)

    Gary W. Gibbons

    2016-09-01

    Full Text Available We apply duality rotations and complex transformations to the Schwarzschild metric to obtain wormhole geometries with two asymptotically flat regions connected by a throat. In the simplest case these are the well-known wormholes supported by phantom scalar field. Further duality rotations remove the scalar field to yield less well known vacuum metrics of the oblate Zipoy–Voorhees–Weyl class, which describe ring wormholes. The ring encircles the wormhole throat and can have any radius, whereas its tension is always negative and should be less than −c4/4G. If the tension reaches the maximal value, the geometry becomes exactly flat, but the topology remains non-trivial and corresponds to two copies of Minkowski space glued together along the disk encircled by the ring. The geodesics are straight lines, and those which traverse the ring get to the other universe. The ring therefore literally produces a hole in space. Such wormholes could perhaps be created by negative energies concentrated in toroidal volumes, for example by vacuum fluctuations.

  12. Evidence for Quantisation in Planetary Ring Systems

    OpenAIRE

    WAYTE, RICHARD

    2017-01-01

    Absolute radial positions of the main features in Saturn's ring system have been calculated by adapting the quantum theory of atomic spectra. Fine rings superimposed upon broad rings are found to be covered by a harmonic series of the form N α A(r)1/2, where N and A are integers. Fourier analysis of the ring system shows that the spectral amplitude fits a response profile which is characteristic of a resonant system. Rings of Jupiter, Uranus and Neptune also obey the same rules. Involvement o...

  13. Phosphomolybdic acid functionalized graphene loading copper nanoparticles modified electrodes for non-enzymatic electrochemical sensing of glucose

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Jiaoyan; Cao, Xiyue [College of Chemistry and Chemical Engineering, Shandong Sino-Japanese Center for Collaborative Research of Carbon Nanomaterials, Collaborative Innovation Center for Marine Biomass Fiber Materials and Textiles, Laboratory of Fiber Materials and Modern Textile, The Growing Base for State Key Laboratory, Qingdao University, Qingdao 266071 (China); Xia, Jianfei, E-mail: xiajianfei@126.com [College of Chemistry and Chemical Engineering, Shandong Sino-Japanese Center for Collaborative Research of Carbon Nanomaterials, Collaborative Innovation Center for Marine Biomass Fiber Materials and Textiles, Laboratory of Fiber Materials and Modern Textile, The Growing Base for State Key Laboratory, Qingdao University, Qingdao 266071 (China); Gong, Shida [College of Chemistry and Chemical Engineering, Shandong Sino-Japanese Center for Collaborative Research of Carbon Nanomaterials, Collaborative Innovation Center for Marine Biomass Fiber Materials and Textiles, Laboratory of Fiber Materials and Modern Textile, The Growing Base for State Key Laboratory, Qingdao University, Qingdao 266071 (China); Wang, Zonghua, E-mail: wangzonghua@qdu.edu.cn [College of Chemistry and Chemical Engineering, Shandong Sino-Japanese Center for Collaborative Research of Carbon Nanomaterials, Collaborative Innovation Center for Marine Biomass Fiber Materials and Textiles, Laboratory of Fiber Materials and Modern Textile, The Growing Base for State Key Laboratory, Qingdao University, Qingdao 266071 (China); Lu, Lin [College of Chemistry and Chemical Engineering, Shandong Sino-Japanese Center for Collaborative Research of Carbon Nanomaterials, Collaborative Innovation Center for Marine Biomass Fiber Materials and Textiles, Laboratory of Fiber Materials and Modern Textile, The Growing Base for State Key Laboratory, Qingdao University, Qingdao 266071 (China); Zibo Normal College, Zibo, Shandong 255100 (China)

    2016-08-31

    A sensitive non-enzymatic glucose electrochemical biosensor (Cu/PMo{sub 12}-GR/GCE) was developed based on the combination of copper nanoparticles (CuNPs) and phosphomolybdic acid functionalized graphene (PMo{sub 12}-GR). PMo{sub 12}-GR films were modified on the surface of glassy carbon electrode (GCE) through electrostatic self-assembly with the aid of poly diallyl dimethyl ammonium chloride (PDDA). Then CuNPs were successfully decorated onto the PMo{sub 12}-GR modified GCE through electrodeposition. The morphology of Cu/PMo{sub 12}-GR/GCE was characterized by scanning electron microscope (SEM). Cyclic voltammetry (CV) and chronoamperometry were used to investigate the electrochemical performances of the biosensor. The results indicated that the modified electrode displayed a synergistic effect of PMo{sub 12}-GR sheets and CuNPs towards the electro-oxidation of glucose in the alkaline solution. At the optimal detection potential of 0.50 V, the response towards glucose presented a linear response ranging from 0.10 μM to 1.0 mM with a detection limit of 3.0 × 10{sup −2} μM (S/N = 3). In addition, Cu/PMo{sub 12}-GR/GCE possessed a high selectivity, good reproducibility, excellent stability and acceptable recovery, which indicating the potential application in clinical field. - Highlights: • Cu/PMo{sub 12}-GR/GCE as a non-enzymatic glucose electrochemical sensor. • PMo{sub 12} is efficient for the uniform growth of Cu-NPs and electron transport. • The sensor exhibits good sensitivity and specificity towards glucose.

  14. Multiplication modules over non-commutative rings

    International Nuclear Information System (INIS)

    Tuganbaev, A A

    2003-01-01

    It is proved that each submodule of a multiplication module over a regular ring is a multiplicative module. If A is a ring with commutative multiplication of right ideals, then each projective right ideal is a multiplicative module, and a finitely generated A-module M is a multiplicative module if and only if all its localizations with respect to maximal right ideals of A are cyclic modules over the corresponding localizations of A. In addition, several known results on multiplication modules over commutative rings are extended to modules over not necessarily commutative rings

  15. Status of the SLC damping rings

    International Nuclear Information System (INIS)

    Hutton, A.M.; Davies-White, W.A.; Delahaye, J.P.

    1985-06-01

    Electron beams of full design energy 1.21 GeV and nearly full design intensity 4 x 10 10 particles/pulse (design 5 x 10 10 ) have been extracted from the Stanford Linac and successfully stored in the electron damping ring. Beams of less intensity have been extracted from the ring and reinjected into the Linac. The present intensity limits are not thought to be fundamental. The operating experience with the electron ring and the status of the construction of the positron ring will be discussed. 11 refs., 1 fig., 2 tabs

  16. Characterization of heterocyclic rings through quantum chemical topology.

    Science.gov (United States)

    Griffiths, Mark Z; Popelier, Paul L A

    2013-07-22

    Five-membered rings are found in a myriad of molecules important in a wide range of areas such as catalysis, nutrition, and drug and agrochemical design. Systematic insight into their largely unexplored chemical space benefits from first principle calculations presented here. This study comprehensively investigates a grand total of 764 different rings, all geometry optimized at the B3LYP/6-311+G(2d,p) level, from the perspective of Quantum Chemical Topology (QCT). For the first time, a 3D space of local topological properties was introduced, in order to characterize rings compactly. This space is called RCP space, after the so-called ring critical point. This space is analogous to BCP space, named after the bond critical point, which compactly and successfully characterizes a chemical bond. The relative positions of the rings in RCP space are determined by the nature of the ring scaffold, such as the heteroatoms within the ring or the number of π-bonds. The summed atomic QCT charges of the five ring atoms revealed five features (number and type of heteroatom, number of π-bonds, substituent and substitution site) that dictate a ring's net charge. Each feature independently contributes toward a ring's net charge. Each substituent has its own distinct and systematic effect on the ring's net charge, irrespective of the ring scaffold. Therefore, this work proves the possibility of designing a ring with specific properties by fine-tuning it through manipulation of these five features.

  17. Single photon emission and quantum ring-cavity coupling in InAs/GaAs quantum rings

    International Nuclear Information System (INIS)

    Gallardo, E; Nowak, A K; Sanvitto, D; Meulen, H P van der; Calleja, J M; MartInez, L J; Prieto, I; Alija, A R; Granados, D; Taboada, A G; GarcIa, J M; Postigo, P A; Sarkar, D

    2010-01-01

    Different InAs/GaAs quantum rings embedded in a photonic crystal microcavity are studied by quantum correlation measurements. Single photon emission, with g (2) (0) values around 0.3, is demonstrated for a quantum ring not coupled to the microcavity. Characteristic rise-times are found to be longer for excitons than for biexcitons, resulting in the time asymmetry of the exciton-biexciton cross-correlation. No antibunching is observed in another quantum ring weakly coupled to the microcavity.

  18. Powder metallurgy ferrous synchronizer ring with brass-based friction layer; Tetsu-do niso shoketsu synchronize ring no kaihatsu

    Energy Technology Data Exchange (ETDEWEB)

    Okajima, H; Yoshikawa, K; Miyajima, K; Sugiyama, M [Toyota Motor Corp., Aichi (Japan); Nakamura, M; Ito, M [Japan Powder Metallurgy Co. Ltd., Tokyo (Japan)

    1997-10-01

    Synchronizer rings for manual transmissions are generally made of brass or molybdenum coated brass. Powder metallurgy (PM) synchronizer ring was developed for the purpose of high performance and cost reduction. This synchronizer ring consists of the high strength PM ferrous ring that needs neither special densification nor heat treatment, and it has the brass-based friction layer. New joining technique was required because of that shape and two different materials. Powder of copper-phosphorus alloy are admixed with the friction material. While sintering, that melt and migrate to the interface. Then the friction layer and the ferrous ring are joined tightly. 7 refs., 9 figs., 6 tabs.

  19. Vliv hipokampální aplikace Nr1/Nr2 antisense oligodeoxynukleotidů na expresi proteinů postsynaptické denzity a na prepulzní inhibici

    Czech Academy of Sciences Publication Activity Database

    Vrajová, M.; Klaschka, Jan; Tejkalová, H.; Bubeníková-Valešová, V.

    2011-01-01

    Roč. 15, Suppl. 2 (2011), s. 11-14 ISSN 1211-7579 R&D Projects: GA MŠk(CZ) 1M0517 Institutional research plan: CEZ:AV0Z10300504 Keywords : NMDA receptor * PSD proteins * antisense oligodeoxynucleotides for NMDA-NR1/NR2 subunits * prepulse inhibition Subject RIV: FL - Psychiatry, Sexuology http://www.tigis.cz/images/stories/psychiatrie/2011/s2/03_vrajova_cns_2-11.pdf

  20. A Health Care Project Management Office's Strategies for Continual Change and Continuous Improvement.

    Science.gov (United States)

    Lavoie-Tremblay, Mélanie; Aubry, Monique; Richer, Marie-Claire; Cyr, Guylaine

    Health care organizations need project and change management support in order to achieve successful transformations. A project management office (PMO) helps support the organizations through their transformations along with increasing their capabilities in project and change management. The aim of the present study was to extend understanding of the continuous improvement mechanisms used by PMOs and to describe PMO's strategies for continual change and continuous improvement in the context of major transformation in health care. This study is a descriptive case study design with interviews conducted from October to December 2015 with PMO's members (3 managers and 1 director) and 3 clients working with the PMO after a major redevelopment project ended (transition to the new facility). Participants suggested a number of elements including carefully selecting the members of the PMO, having a clear mandate for the PMO, having a method and a discipline at the same time as allowing openness and flexibility, clearly prioritizing projects, optimizing collaboration, planning for everything the PMO will need, not overlooking organizational culture, and retaining the existing support model. This study presents a number of factors ensuring the sustainability of changes.

  1. 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

  2. Vortex Ring Dynamics in Radially Confined Domains

    Science.gov (United States)

    Stewart, Kelley; Niebel, Casandra; Jung, Sunghwan; Vlachos, Pavlos

    2010-11-01

    Vortex ring dynamics have been studied extensively in semi-infinite quiescent volumes. However, very little is known about vortex-ring formation in wall-bounded domains where vortex wall interaction will affect both the vortex ring pinch-off and propagation velocity. This study addresses this limitation and studies vortex formation in radially confined domains to analyze the affect of vortex-ring wall interaction on the formation and propagation of the vortex ring. Vortex rings were produced using a pneumatically driven piston cylinder arrangement and were ejected into a long cylindrical tube which defined the confined downstream domain. A range of confinement domains were studied with varying confinement diameters Velocity field measurements were performed using planar Time Resolved Digital Particle Image Velocimetry (TRDPIV) and were processed using an in-house developed cross-correlation PIV algorithm. The experimental analysis was used to facilitate the development of a theoretical model to predict the variations in vortex ring circulation over time within confined domains.

  3. Effects of Antisense Oligonucleotides against C-Reactive Protein on the Development of Atherosclerosis in WHHL Rabbits

    Directory of Open Access Journals (Sweden)

    Qi Yu

    2014-01-01

    Full Text Available Increased plasma levels of C-reactive protein (CRP are closely associated with cardiovascular diseases, but whether CRP is directly involved in the pathogenesis of atherosclerosis is still under debate. Many controversial and contradictory results using transgenic mice and rabbits have been published but it is also unclear whether CRP lowering can be used for the treatment of atherosclerosis. In the current study, we examined the effects of the rabbit CRP antisense oligonucleotides (ASO on the development of atherosclerosis in WHHL rabbits. CRP ASO treatment led to a significant reduction of plasma CRP levels; however, both aortic and coronary atherosclerotic lesions were not significantly changed compared to those of control WHHL rabbits. These results suggest that inhibition of plasma CRP does not affect the development of atherosclerosis in WHHL rabbits.

  4. The Conversion of Wiswesser Line Notations to Ring Codes. I. The Conversion of Ring Systems

    Science.gov (United States)

    Granito, Charles E.; And Others

    1972-01-01

    The computerized conversion of Wiswesser Line Notations to Ring Codes, using a two-part approach, and the set of computer programs generated for the conversion of ring systems are described. (9 references) (Author)

  5. Phosphomolybdic acid and ferric iron as efficient electron mediators for coupling biomass pretreatment to produce bioethanol and electricity generation from wheat straw

    Science.gov (United States)

    Yi Ding; Bo Du; Xuebing Zhao; J.Y. Zhu; Dehua Liu

    2017-01-01

    Phosphomolybdic acid (PMo12) was used as an electron mediator and proton carrier to mediate biomass pretreatment for ethanol production and electricity generation from wheat straw. In the pretreatment, lignin was oxidized anaerobically by PMo12 with solubilization of a fraction of hemicelluloses, and the PMo12...

  6. The Saturnian rings

    International Nuclear Information System (INIS)

    Alfven, H.

    1975-09-01

    The structure of the Saturnian rings is traditionally believed to be due to resonances caused by Mimas (and possibly other satellites). It is shown that both theoretical and observational evidence rule out this interpretation. The increased observational accuracy on one hand and the increased understanding of the cosmogonic processes on the other makes it possible to explain the structure of the ring system as a product of condensation from a partially corotating plasma. In certain respects the agreement between theory and observations is about 1%. (Auth.)

  7. Hubble again views Saturn's Rings Edge-on

    Science.gov (United States)

    1995-01-01

    Saturn's magnificent ring system is seen tilted edge-on -- for the second time this year -- in this NASA Hubble Space Telescope picture taken on August 10, 1995, when the planet was 895 million miles (1,440 million kilometers) away. Hubble snapped the image as Earth sped back across Saturn's ring plane to the sunlit side of the rings. Last May 22, Earth dipped below the ring plane, giving observers a brief look at the backlit side of the rings. Ring-plane crossing events occur approximately every 15 years. Earthbound observers won't have as good a view until the year 2038. Several of Saturn's icy moons are visible as tiny starlike objects in or near the ring plane. They are from left to right, Enceladus, Tethys, Dione and Mimas. 'The Hubble data shows numerous faint satellites close to the bright rings, but it will take a couple of months to precisely identify them,' according to Steve Larson (University of Arizona). During the May ring plane crossing, Hubble detected two, and possibly four, new moons orbiting Saturn. These new observations also provide a better view of the faint E ring, 'to help determine the size of particles and whether they will pose a collision hazard to the Cassini spacecraft,' said Larson. The picture was taken with Hubble's Wide Field Planetary Camera 2 in wide field mode. This image is a composite view, where a long exposure of the faint rings has been combined with a shorter exposure of Saturn's disk to bring out more detail. When viewed edge-on, the rings are so dim they almost disappear because they are very thin -- probably less than a mile thick.The Wide Field/Planetary Camera 2 was developed by the Jet Propulsion Laboratory and managed by the Goddard Spaced Flight Center for NASA's Office of Space Science.This image and other images and data received from the Hubble Space Telescope are posted on the World Wide Web on the Space Telescope Science Institute home page at URL http://oposite.stsci.edu/pubinfo/

  8. Vaginal rings for delivery of HIV microbicides.

    Science.gov (United States)

    Malcolm, R Karl; Fetherston, Susan M; McCoy, Clare F; Boyd, Peter; Major, Ian

    2012-01-01

    Following the successful development of long-acting steroid-releasing vaginal ring devices for the treatment of menopausal symptoms and contraception, there is now considerable interest in applying similar devices to the controlled release of microbicides against HIV. In this review article, the vaginal ring concept is first considered within the wider context of the early advances in controlled-release technology, before describing the various types of ring device available today. The remainder of the article highlights the key developments in HIV microbicide-releasing vaginal rings, with a particular focus on the dapivirine ring that is presently in late-stage clinical testing.

  9. The ring plus project: safety and acceptability of vaginal rings that protect women from unintended pregnancy.

    Science.gov (United States)

    Schurmans, Céline; De Baetselier, Irith; Kestelyn, Evelyne; Jespers, Vicky; Delvaux, Thérèse; Agaba, Stephen K; van Loen, Harry; Menten, Joris; van de Wijgert, Janneke; Crucitti, Tania

    2015-04-10

    Research is ongoing to develop multipurpose vaginal rings to be used continuously for contraception and to prevent Human Immunodeficiency Virus (HIV) infection. Contraceptive vaginal rings (CVRs) are available in a number of countries and are most of the time used intermittently i.e. three weeks out of a 4-week cycle. Efficacy trials with a dapivirine-containing vaginal ring for HIV prevention are ongoing and plans to develop multi-purpose vaginal rings for prevention of both HIV and pregnancy have been elaborated. In contrast with the CVRs, multi-purpose vaginal rings will have to be used continuously. Women who continuously use a CVR will no longer have menses. Furthermore, some safety aspects of CVR use have never been studied in-depth in the past, such as the impact of the vaginal ring on the vaginal microbiota, biofilm formation and induction of inflammation. We studied acceptability and these novel aspects of safety in Rwandan women. Although significant progress has been made over the past decade, Rwanda still has a high unmet need for contraception (with 47% unplanned births) and a generalized HIV epidemic, and CVRs are not yet available. We will conduct an open label, single centre, randomized controlled trial. A total of 120 HIV-negative women will be randomized to intermittent CVR use (to allow menstruation) or continuous CVR use. Women will be followed for a maximum of 14 weeks. In parallel, we will conduct a qualitative study using in-depth interview and focus group discussion methodology. In addition to evaluating the safety and acceptability of intermittent and continuous CVR use in Rwandan women, we hope that our findings will inform the development of future multipurpose vaginal rings, will prepare Rwandan study populations for future clinical trials of multipurpose vaginal rings, and will pave the way for introduction of CVRs on African markets. Clinicaltrials.gov NCT01796613 . Registered 14 February 2013.

  10. Common pass decentered annular ring resonator

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, D. A.; Waite, T. R.

    1985-04-30

    An optical resonator having an annular cylindrical gain region for use in a chemical laser or the like in which two ring-shaped mirrors having substantially conical reflecting surfaces are spaced apart along a common axis of revolution of the respective conical surfaces. A central conical mirror reflects incident light directed along said axis radially outwardly to the reflecting surface of a first one of the ring-shaped mirrors. The radial light rays are reflected by the first ring mirror to the second ring mirror within an annular cylindrical volume concentric with said common axis and forming a gain region. Light rays impinging on the second ring mirror are reflected to diametrically opposite points on the same conical mirror surfaces and back to the first ring mirror through the same annular cylindrical volume. The return rays are then reflected by the conical mirror surface of the first ring mirror back to the central conical mirror. The mirror surfaces are angled such that the return rays are reflected back along the common axis by the central mirror in a concentric annular cylindrical volume. A scraper mirror having a central opening centered on said axis and an offset opening reflects all but the rays passing through the two openings in an output beam. The rays passing through the second opening are reflected back through the first opening to provide feedback.

  11. Tritium concentrations in tree ring cellulose

    International Nuclear Information System (INIS)

    Kaji, Toshio; Momoshima, Noriyuki; Takashima, Yoshimasa.

    1989-01-01

    Measurements of tritium (tissue bound tritium; TBT) concentration in tree rings are presented and discussed. Such measurement is expected to provide a useful means of estimating the tritium level in the environment in the past. The concentration of tritium bound in the tissue (TBT) in a tree ring considered to reflect the environmental tritium level in the area at the time of the formation of the ring, while the concentration of tritium in the free water in the tissue represents the current environmental tritium level. First, tritium concentration in tree ring cellulose sampled from a cedar tree grown in a typical environment in Fukuoka Prefecture is compared with the tritium concentration in precipitation in Tokyo. Results show that the year-to-year variations in the tritium concentration in the tree rings agree well with those in precipitation. The maximum concentration, which occurred in 1963, is attibuted to atmospheric nuclear testing which was performed frequently during the 1961 - 1963 period. Measurement is also made of the tritium concentration in tree ring cellulose sampled from a pine tree grown near the Isotope Center of Kyushu University (Fukuoka). Results indicate that the background level is higher probably due to the release of tritium from the facilities around the pine tree. Thus, measurement of tritium in tree ring cellulose clearly shows the year-to-year variation in the tritium concentration in the atmosphere. (N.K.)

  12. Inorganic glass ceramic slip rings

    Science.gov (United States)

    Glossbrenner, E. W.; Cole, S. R.

    1972-01-01

    Prototypes of slip rings have been fabricated from ceramic glass, a material which is highly resistant to deterioration due to high temperature. Slip ring assemblies were not structurally damaged by mechanical tests and performed statisfactorily for 200 hours.

  13. Translational velocity oscillations of piston generated vortex rings

    Science.gov (United States)

    Kumar, Manoj; Arakeri, J. H.; Shankar, P. N.

    1995-11-01

    Experimental results are presented that show that the translational velocities of piston generated vortex rings often undergo oscillations, similar to those recently discovered for drop generated rings. An attempt has been made to minimize uncertainties by utilizing both dye and hydrogen bubbles for visualization and carefully repeating measurements on the same ring and on different realizations under the same nominal piston conditions. The results unambiguously show that under most conditions, both for laminar and turbulent rings and for rings generated from pipes and orifices, the oscillations are present. The present results, together with the earlier results on drop generated rings, give support to the view that translational velocity oscillations are probably an inherent feature of translating vortex ring fields.

  14. Seco-B-Ring Steroidal Dienynes with Aromatic D Ring: Design, Synthesis and Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Marcin Szybinski

    2017-10-01

    Full Text Available Continuing our structure-activity studies on the vitamin D analogs with the altered intercyclic seco-B-ring fragment, we designed compounds possessing dienyne system conjugated with the benzene D ring. Analysis of the literature data and the docking experiments seemed to indicate that the target compounds could mimic the ligands with a good affinity to the vitamin D receptor (VDR. Multi-step synthesis of the C/D-ring building block of the tetralone structure was achieved and its enol triflate was coupled with the known A-ring fragments, possessing conjugated enyne moiety, using Sonogashira protocol. The structures of the final products were confirmed by NMR, UV and mass spectroscopy. Their binding affinities for the full-length human VDR were determined and it was established that compound substituted at C-2 with exomethylene group showed significant binding to the receptor. This analog was also able to induce monocytic differentiation of HL-60 cells.

  15. Saturn's Ring: Pre-Cassini Status and Mission Goals

    Science.gov (United States)

    Cuzzi, Jeff N.; DeVincenzi, Donald L. (Technical Monitor)

    1999-01-01

    In November 1980, and again in August 1981, identical Voyager spacecraft flew through the Saturn system, changing forever the way we think about planetary rings. Although Saturn's rings had been the only known ring system for three centuries, a ring system around Uranus had been discovered by stellar occultations from Earth in 1977, and the nearly transparent ring of Jupiter was imaged by Voyager in 1979 (the presence of material there had been inferred from charged particle experiments on Pioneer 10 and 11 several years earlier). While Saturn had thus temporarily lost its uniqueness as having the only ring system, with Voyager it handily recaptured the role of having the most fascinating one. The Voyager breakthroughs included spiral density and bending waves such as cause galactic structure; ubiquitous fine-scale radial 'irregular' structure, with the appearance of record-grooves; regional and local variations in particle color; complex, azimuthally variable ring structure; empty gaps in the rings, some containing very regular, sharp-edged, elliptical rings and one containing both a small moonlet and incomplete arcs of dusty material; and shadowy 'spokes' that flicker across the main rings. One of the paradigm shifts of this period was the realization that many aspects of planetary rings, and even the ring systems themselves, could be 'recent' on geological timescales. These early results are reviewed and summarized in the Arizona Space Science series volumes 'Saturn'. (An excellent review of ring dynamics at a formative stage is by Goldreich and Tremaine.) From the mid 1980's to the time of this writing, progress has been steady, while at a less heady pace, and some of the novel ring properties revealed by Voyager 1 and 2 are beginning to be better understood. It is clearly impossible to cite, much less review, every advance over the last decade; however, below we summarize the main advances in understanding of Saturn's rings since the mid 1980's, in the context

  16. Rings Related to Special Atoms | France-Jackson | Quaestiones ...

    African Journals Online (AJOL)

    Abstract unavailable at this time... Mathematics Subject Classification (1991): 16A21, 16A12 Keywords: ring, special atoms, atoms, *k-ring, prime ring, *-ring, Jacobson, artinia, essential extension, homomorphic image, ideals. Quaestiones Mathematicae 24(1) 2001, 105–109 ...

  17. Using Ring Strain to Control 4π-Electrocyclization Reactions: Torquoselectivity in Ring Closing of Medium-Ring Dienes and Ring Opening of Bicyclic Cyclobutenes.

    Science.gov (United States)

    Boon, Byron A; Green, Aaron G; Liu, Peng; Houk, K N; Merlic, Craig A

    2017-05-05

    Syntheses of strained cyclic dienes were accomplished via palladium(II)-catalyzed oxidative cyclizations of terminal bis(vinylboronate esters). The reactions generate strained (E,E)-1,3-dienes that undergo spontaneous 4π-electrocyclizations to form bicyclic cyclobutenes. Formation of the cyclobutenes is driven by the strain in the medium-ring (E,E)-1,3-diene intermediate. Thermal ring openings of the cyclobutenes give (Z,Z)-1,3-diene products, again for thermodynamic reasons. DFT calculations verified the thermodynamic versus kinetic control of the reactions, and kinetic studies are in excellent agreement with the calculated energy changes. An extension of the tandem coupling/4π-electrocyclization pathway was demonstrated by a palladium(II)-catalyzed oxidative homocoupling/8π-electrocyclization cascade.

  18. Ring Avulsion Injuries: A Systematic Review.

    Science.gov (United States)

    Bamba, Ravinder; Malhotra, Gautam; Bueno, Reuben A; Thayer, Wesley P; Shack, R Bruce

    2018-01-01

    Ring avulsion injuries can range from soft tissue injury to complete amputation. Grading systems have been developed to guide treatment, but there is controversy with high-grade injuries. Traditionally, advanced ring injuries have been treated with completion amputation, but there is evidence that severe ring injuries can be salvaged. The purpose of this systematic review was to pool the current published data on ring injuries. A systematic review of the English literature published from 1980 to 2015 in PubMed and MEDLINE databases was conducted to identify patients who underwent treatment for ring avulsion injuries. Twenty studies of ring avulsion injuries met the inclusion criteria. There were a total of 572 patients reported with ring avulsion injuries. The Urbaniak class breakdown was class I (54 patients), class II (204 patients), and class III (314 patients). The average total arc of motion (TAM) for patients with a class I injury was 201.25 (n = 40). The average 2-point discrimination was 5.6 (n = 10). The average TAM for patients with a class II injury undergoing microsurgical revascularization was 187.0 (n = 114), and the average 2-point discrimination was 8.3 (n = 40). The average TAM for patients with a class III injury undergoing microsurgical revascularization was 168.2 (n = 170), and the average 2-point discrimination was 10.5 (n = 97). Ring avulsion injuries are commonly classified with the Urbaniak class system. Outcomes are superior for class I and II injuries, and there are select class III injuries that can be treated with replantation. Shared decision making with patients is imperative to determine whether replantation is appropriate.

  19. Investigation of piston ring – cylinder liner dry wear using a block-on-ring test rig

    DEFF Research Database (Denmark)

    Bihlet, Uffe; Klit, Peder; Felter, Christian L.

    Characterization of the wear of piston rings and cylinder liner is an important aspect of large two stroke diesel engine design. Two major wear mechanisms exist; corrosive wear and mechanical wear. This paper deals with the most aggressive form of the latter, which is known as scuffing. Different...... that ceramic coating on the piston ring decreases the dry wear rate of both piston ring and liner, while the coefficient of friction is increased....

  20. Novel Fiber-Optic Ring Acoustic Emission Sensor.

    Science.gov (United States)

    Wei, Peng; Han, Xiaole; Xia, Dong; Liu, Taolin; Lang, Hao

    2018-01-13

    Acoustic emission technology has been applied to many fields for many years. However, the conventional piezoelectric acoustic emission sensors cannot be used in extreme environments, such as those with heavy electromagnetic interference, high pressure, or strong corrosion. In this paper, a novel fiber-optic ring acoustic emission sensor is proposed. The sensor exhibits high sensitivity, anti-electromagnetic interference, and corrosion resistance. First, the principle of a novel fiber-optic ring sensor is introduced. Different from piezoelectric and other fiber acoustic emission sensors, this novel sensor includes both a sensing skeleton and a sensing fiber. Second, a heterodyne interferometric demodulating method is presented. In addition, a fiber-optic ring sensor acoustic emission system is built based on this method. Finally, fiber-optic ring acoustic emission experiments are performed. The novel fiber-optic ring sensor is glued onto the surface of an aluminum plate. The 150 kHz standard continuous sinusoidal signals and broken lead signals are successfully detected by the novel fiber-optic ring acoustic emission sensor. In addition, comparison to the piezoelectric acoustic emission sensor is performed, which shows the availability and reliability of the novel fiber-optic ring acoustic emission sensor. In the future, this novel fiber-optic ring acoustic emission sensor will provide a new route to acoustic emission detection in harsh environments.

  1. Nilradicals of skew Hurwitz series of rings

    Directory of Open Access Journals (Sweden)

    Morteza Ahmadi

    2015-05-01

    Full Text Available ‎For a ring endomorphism α of a ring R, ‎Krempa called α a rigid endomorphism if aα(a=0 implies a = 0 for a in R. ‎A ring R is called rigid if there exists a rigid endomorphism of R. ‎In this paper‎, ‎we extend the α-rigid property of a ring R to the upper nilradical N_r(R of R. ‎For an endomorphism α and the upper nilradical N_r(R of a ring R, ‎we introduce the condition (*: ‎N_r(R is a α-ideal of R and aα(a in N_r(R implies a in N_r(R for a in R. ‎We study characterizations of a ring R with an endomorphism α satisfying the condition (*, ‎and we investigate their related properties‎. ‎The connections between the upper nilradical of R and the upper nilradical of the skew Hurwitz series ring (HR,α of R are also investigated‎.

  2. Spin transitions in semiconductor quantum rings

    International Nuclear Information System (INIS)

    Baxevanis, Benjamin; Pfannkuche, Daniela

    2010-01-01

    We adopt the path integral Monte Carlo method to accurately resolve the total spin of the ground state of electrons confined in a quantum ring with different geometries. Using this method, an evaluation of the ground state of three electrons in a ring shows a spin transition to the fully polarized state by increasing the radius and thereby enhancing the Coulomb interaction. The total spin of the ground state is determined by the mutual interplay of confinement and electron-electron interaction. An analysis of the four-electron ring demonstrates that in this case no spin transitions take place. Furthermore, the effect of geometric distortion of the ring on its ground state has been investigated. Elliptically deforming the ring breaks the symmetry of the system and leads to the removal of orbital degeneracy. For strong distortion the splitting between hybridized states is sufficient to overcome the exchange-energy saving associated with a higher spin state. We have found that this effect removes the polarization of three electrons. Even in a four-electron ring the ground state is forced by the distortion to be unpolarized and thus suppressing the Hund's rule ground state.

  3. INJECTION EFFICIENCY IN COMPTON RING NESTOR

    Directory of Open Access Journals (Sweden)

    P. I. Gladkikh

    2017-12-01

    Full Text Available NESTOR is the hard X-ray source that is under commissioning at NSC KIPT. NESTOR based on the Compton scattering of laser photons on relativistic electrons. The structure of the facility can be represented as the following components: a linear accelerator, a transport channel, a storage ring, and a laser-optical system. Electrons are stored in the storage ring for energy of 40-200 MeV. Inevitable alignment errors of magnetic elements are strongly effect on the beam dynamics in the storage ring. These errors lead to a shift of the equilibrium orbit relative to the ideal one. Significant shift of the equilibrium orbit could lead to loss of the beam on physical apertures. Transverse sizes of electron and laser beams are only few tens of microns at the interaction point. The shift of electron beam at the interaction point could greatly complicate the operation adjustment of storage ring without sufficient beam position diagnostic system. This article presents the simulation results of the efficiency of electron beam accumulation in the NESTOR storage ring. Also, this article is devoted to electron beam dynamics due to alignment errors of magnetic element in the ring.

  4. Control of ring lasers by means of coupled cavities

    DEFF Research Database (Denmark)

    Buchhave, Preben; Abitan, Haim; Tidemand-Lichtenberg, Peter

    2000-01-01

    Variable phase coupling to an external ring is used to control a unidirectional ring laser. The observed behavior of the coupled rings is explained theoretically. We have found experimentally that by quickly changing the phase of the feedback from the external ring it is possible to Q......-switch the ring laser. Also, at certain values of the phase of the feedback in the external ring, instabilities in the total system occur and oscillations arise in the ring laser....

  5. Moving-ring field-reversed mirror reactor

    International Nuclear Information System (INIS)

    Smith, A.C. Jr.; Ashworth, C.P.; Abreu, K.E.

    1981-01-01

    We describe a first prototype fusion reactor design of the Moving-Ring Field-Reversed Mirror Reactor. The fusion fuel is confined in current-carrying rings of magnetically-field-reversed plasma. The plamsa rings, formed by a coaxial plasma gun, are magnetically compressed to ignition temperature while they are being injected into the reactor's burner section. DT ice pellets refuel the rings during the burn at a rate which maintains constant fusion power. A steady train of plasma rings moves at constant speed through the reactor under the influence of a slightly diverging magnetic field. The aluminum first wall and breeding zone structure minimize induced radioactivity; hands-on maintenance is possible on reactor components outside the breeding blanket. Helium removes the heat from the Li 2 O tritium breeding blanket and is used to generate steam. The reactor produces a constant, net power of 376 MW

  6. Artificial light harvesting by dimerized Möbius ring

    Science.gov (United States)

    Xu, Lei; Gong, Z. R.; Tao, Ming-Jie; Ai, Qing

    2018-04-01

    We theoretically study artificial light harvesting by a Möbius ring. When the donors in the ring are dimerized, the energies of the donor ring are split into two subbands. Because of the nontrivial Möbius boundary condition, both the photon and acceptor are coupled to all collective-excitation modes in the donor ring. Therefore, the quantum dynamics in the light harvesting is subtly influenced by dimerization in the Möbius ring. It is discovered that energy transfer is more efficient in a dimerized ring than that in an equally spaced ring. This discovery is also confirmed by a calculation with the perturbation theory, which is equivalent to the Wigner-Weisskopf approximation. Our findings may be beneficial to the optimal design of artificial light harvesting.

  7. ring system

    African Journals Online (AJOL)

    1,3,2-DIAZABORACYCLOALKANE. RING SYSTEM. Negussie Retta" and Robert H. Neilson. 'Department of Chemistry, Addis Ababa University, P.O. Box 1176, Addis Ababa, Ethiopia. Department of Chemistry, Texas Christian University.

  8. 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...

  9. Ring cavity for a Raman capillary waveguide amplifier

    Science.gov (United States)

    Kurnit, N.A.

    1981-01-27

    A regenerative ring amplifier and regenerative ring oscillator are described which function to feed back a portion of the Stokes signal to complete the ring cavity. The ring cavity configuration allows the CO/sub 2/ laser pump signal and Stokes signal to copropagate through the Raman capillary waveguide amplifier. A Raman capillary waveguide amplifier is also provided in the return leg of the ring cavity to increase gain without increasing the round trip time. Additionally, the ring cavity can be designed such that the amplified Stokes signal is synchronous with the mode-locked spikes of the incoming CO/sub 2/ laser pump signal.

  10. Ring cavity for a Raman capillary waveguide amplifir

    Science.gov (United States)

    Kurnit, N.A.

    1981-01-27

    A regenerative ring amplifier and regenerative ring oscillator are described which function to feed back a portion of the Stokes signal to complete the ring cavity. The ring cavity configuration allows the CO/sub 2/ laser pump signal and Stokes signal to copropagate through the Raman capillary waveguide amplifier. A Raman capillary waveguide amplifier is also provided in the return leg of the ring cavity to increase gain without increasing the round trip time. Additionally, the ring cavity can be designed such that the amplified Stokes signal is synchronous with the mode-locked spikes of the incoming CO/sub 2/ laser pump signal.

  11. Experimental Study of Shock Generated Compressible Vortex Ring

    Science.gov (United States)

    Das, Debopam; Arakeri, Jaywant H.; Krothapalli, Anjaneyulu

    2000-11-01

    Formation of a compressible vortex ring and generation of sound associated with it is studied experimentally. Impulse of a shock wave is used to generate a vortex ring from the open end of a shock-tube. Vortex ring formation process has been studied in details using particle image Velocimetry (PIV). As the shock wave exits the tube it diffracts and expands. A circular vortex sheet forms at the edge and rolls up into a vortex ring. Far field microphone measurement shows that the acoustic pressure consists of a spike due to shock wave followed by a low frequency pressure wave of decaying nature, superimposed with high frequency pressure wave. Acoustic waves consist of waves due to expansion, waves formed in the tube during diaphragm breakage and waves associated with the vortex ring and shear-layer vortices. Unsteady evolution of the vortex ring and shear-layer vortices in the jet behind the ring is studied by measuring the velocity field using PIV. Corresponding vorticity field, circulation around the vortex core and growth rate of the vortex core is calculated from the measured velocity field. The velocity field in a compressible vortex ring differs from that of an incompressible ring due to the contribution from both shock and vortex ring.

  12. [Liesegang's rings resembling helminthiasis].

    Science.gov (United States)

    Zámecník, M; Riedl, I

    1996-12-01

    So called Liesegang's rings are lamellar corpuscles which develop after periodical precipitation of oversaturated solutions in gel medium. They can occur in cysts, closed cavities, inflammatory exudates and necroses. They resemble parasitic eggs, larvae or adult forms. A case of 28-year-old woman is presented with many Liesegang's rings in a stuff from dilated renal calyx. Their preliminary evaluation considered helminths, especially Dioctophyma renale.

  13. Synlig læring

    DEFF Research Database (Denmark)

    Brandsen, Mads

    2017-01-01

    Introduktionen af John Hatties synlig læring i den danske skoleverden møder stadig meget kritik. Mange lærere og pædagoger oplever synlig læring som en tornado, der vil opsuge og ødelægge deres særlige danske udgave af den kontinentale dannelsestænkning, didaktik og pædagogik. Spørgsmålet er om...

  14. Effect of bcl-2 antisense oligodexynucleotides on chemotherapy efficacy of Vp-16 on human small cell lung cancer cell line NCI-H69

    International Nuclear Information System (INIS)

    He Wenqian; Liu Zhonghua

    2007-01-01

    Objective: To study the effect of bcl-2 antisense oligodexynucleotides on chemotherapy efficacy of Vp-16 on human small cell lung cancer cell line NCI-H69. Methods: Cultured NCI-H69 cells were derided into 4 groups: bcl-2 antisense oligodexynucleotides (ASODN) added, sense oligodexynucleotides (SODN) added, nonsense oligodexynucleotides (NSODN) added and control (no nucleotides added), the oligodexynucleotides were transfected into the cultured cells with oligofectamine. The cellular expression of Bcl-2 protein 72h later was examined with Western-Blot. The four different groups of cultured tumor cells were treated with etopside(Vp-16) at different concentrations (0, 0.25, 0.5, 1.0, 2.0 and 4.0 μg/ml) for 48hr then the cell survival fraction was assessed with MTY test. Results: The apoptotic rate of cells in the ASODN group was significantly higher than that of the control group, also, the survival fraction of cells in ASODN group was significantly lower than that of the control group. The Bcl-2 protein expression in ASODN group was significantly lower than that in the control group, but no inhibition was observed in SODN and NSODN groups. Conclusion: The bcl-2 ASODN could enhance the sensitivity to chemotherapy with Vp-16 in small cell lung cancer cell line NCI-H69 by effectively blocking bcl-2 gene expression. (authors)

  15. How Jupiter's Ring Was Discovered.

    Science.gov (United States)

    Elliot, James; Kerr, Richard

    1985-01-01

    "Rings" (by astronomer James Elliot and science writer Richard Kerr) is a nontechnical book about the discovery and exploration of ring systems from the time of Galileo to the era of the Voyager spacecraft. One of this book's chapters is presented. (JN)

  16. Adiabatic compression of ion rings

    International Nuclear Information System (INIS)

    Larrabee, D.A.; Lovelace, R.V.

    1982-01-01

    A study has been made of the compression of collisionless ion rings in an increasing external magnetic field, B/sub e/ = zB/sub e/(t), by numerically implementing a previously developed kinetic theory of ring compression. The theory is general in that there is no limitation on the ring geometry or the compression ratio, lambdaequivalentB/sub e/ (final)/B/sub e/ (initial)> or =1. However, the motion of a single particle in an equilibrium is assumed to be completely characterized by its energy H and canonical angular momentum P/sub theta/ with the absence of a third constant of the motion. The present computational work assumes that plasma currents are negligible, as is appropriate for a low-temperature collisional plasma. For a variety of initial ring geometries and initial distribution functions (having a single value of P/sub theta/), it is found that the parameters for ''fat'', small aspect ratio rings follow general scaling laws over a large range of compression ratios, 1 3 : The ring radius varies as lambda/sup -1/2/; the average single particle energy as lambda/sup 0.72/; the root mean square energy spread as lambda/sup 1.1/; and the total current as lambda/sup 0.79/. The field reversal parameter is found to saturate at values typically between 2 and 3. For large compression ratios the current density is found to ''hollow out''. This hollowing tends to improve the interchange stability of an embedded low β plasma. The implications of these scaling laws for fusion reactor systems are discussed

  17. Vortex Ring Interaction With a Coaxially Aligned Cylinderical Rod

    Science.gov (United States)

    Arakeri, Jaywant H.; Rajmanoharan, P.; Koochesfahani, Manoochehr

    1998-11-01

    We present results of experiments of a fully developed vortex ring interacting with a cylinderical rod, having a rounded nose, placed coaxially in line with the motion of the ring. The pressure field of the translating ring causes unsteady boundary layer separation and results in the formation of one or more ( secondary ) vortex rings, that subsequently interact. The nature and strength of the interaction depends on the ratio of the cylinder diameter to the ring diameter. For the larger diameter cylinders the vortex ring travels a few ring diameters before it breaks up. For the smaller diameter cylinders the vortex ring speed decreases slowly and, simultaneously, its diameter increases.

  18. A study of the outermost ring of Saturn

    International Nuclear Information System (INIS)

    Bobrov, M.S.

    1974-01-01

    The attention is called to the fact that the discovery by Feibelman (1967) of the rarefied outer ring of Saturn is confirmed by the observations of Kuiper (1972). It is proposed to designate this object as E-ring (exterior) in order to avoid confusion with the innermost, also rarefied, D-ring observed by Guerin (1970) and earlier by Barabashov and Semejkin (1933). The effects of the interaction of E-ring with inner Saturn's satellites are briefly discussed. The conclusion is drawn that in cosmogonic time scale these effects are small. It is also shown that the optical thickness of E-ring is lower than 1/20000; the available photometric estimations of the geometric thickness of A- and B-rings need not be corrected for the light scattering and absorption by E-ring. (Auth.)

  19. Cytoplasmic tethering of a RING protein RBCK1 by its splice variant lacking the RING domain

    International Nuclear Information System (INIS)

    Yoshimoto, Nobuo; Tatematsu, Kenji; Koyanagi, Tomoyoshi; Okajima, Toshihide; Tanizawa, Katsuyuki; Kuroda, Shun'ichi

    2005-01-01

    RBCC protein interacting with PKC 1 (RBCK1) is a transcription factor belonging to the RING-IBR protein family and has been shown to shuttle between the nucleus and cytoplasm, possessing both the nuclear export and localization signals within its amino acid sequence. RBCK2, lacking the C-terminal half of RBCK1 including the RING-IBR domain, has also been identified as an alternative splice variant of RBCK1. RBCK2 shows no transcriptional activity and instead it represses the transcriptional activity of RBCK1. Here, we show that RBCK2 is present usually in the cytoplasm containing two Leu-rich regions that presumably serve as a nuclear export signal (NES). Moreover, an NES-disrupted RBCK1 that is mostly localized within the nucleus is translocated to the cytoplasm when coexpressed with RBCK2, suggesting that RBCK2 serves as a cytoplasmic tethering protein for RBCK1. We propose a novel and general function of RING-lacking splice variants of RING proteins to control the intracellular localization and functions of the parental RING proteins by forming a hetero-oligomeric complex

  20. Minimizing guard ring dead space in silicon detectors with an n-type guard ring at the edge of the detector

    International Nuclear Information System (INIS)

    Palviainen, Tanja; Tuuva, Tuure; Leinonen, Kari

    2007-01-01

    Detectors with n-type silicon with an n + -type guard ring were investigated. In the present work, a new p + /n/n + detector structure with an n + guard ring is described. The guard ring is placed at the edge of the detector. The detector depletion region extends also sideways, allowing for signal collection very close to the n-guard ring. In this kind of detector structure, the dead space of the detector is minimized to be only below the guard ring. This is proved by simulations done using Silvaco/ATLAS software

  1. Minimizing guard ring dead space in silicon detectors with an n-type guard ring at the edge of the detector

    Energy Technology Data Exchange (ETDEWEB)

    Palviainen, Tanja [Lappeenranta University of Technology, P.O. Box 20, FIN-53851 Lappeenranta (Finland)]. E-mail: tanja.palviainen@lut.fi; Tuuva, Tuure [Lappeenranta University of Technology, P.O. Box 20, FIN-53851 Lappeenranta (Finland); Leinonen, Kari [Lappeenranta University of Technology, P.O. Box 20, FIN-53851 Lappeenranta (Finland)

    2007-04-01

    Detectors with n-type silicon with an n{sup +}-type guard ring were investigated. In the present work, a new p{sup +}/n/n{sup +} detector structure with an n{sup +} guard ring is described. The guard ring is placed at the edge of the detector. The detector depletion region extends also sideways, allowing for signal collection very close to the n-guard ring. In this kind of detector structure, the dead space of the detector is minimized to be only below the guard ring. This is proved by simulations done using Silvaco/ATLAS software.

  2. Soft Congruence Relations over Rings

    Science.gov (United States)

    Xin, Xiaolong; Li, Wenting

    2014-01-01

    Molodtsov introduced the concept of soft sets, which can be seen as a new mathematical tool for dealing with uncertainty. In this paper, we initiate the study of soft congruence relations by using the soft set theory. The notions of soft quotient rings, generalized soft ideals and generalized soft quotient rings, are introduced, and several related properties are investigated. Also, we obtain a one-to-one correspondence between soft congruence relations and idealistic soft rings and a one-to-one correspondence between soft congruence relations and soft ideals. In particular, the first, second, and third soft isomorphism theorems are established, respectively. PMID:24949493

  3. Distributively generated matrix near rings

    International Nuclear Information System (INIS)

    Abbasi, S.J.

    1993-04-01

    It is known that if R is a near ring with identity then (I,+) is abelian if (I + ,+) is abelian and (I,+) is abelian if (I*,+) is abelian [S.J. Abbasi, J.D.P. Meldrum, 1991]. This paper extends these results. We show that if R is a distributively generated near ring with identity then (I,+) is included in Z(R), the center of R, if (I + ,+) is included in Z(M n (R)), the center of matrix near ring M n (R). Furthermore (I,+) is included in Z(R) if (I*,+) is included in Z(M n (R)). (author). 5 refs

  4. Storage rings, internal targets and PEP

    International Nuclear Information System (INIS)

    Spencer, J.E.

    1986-11-01

    Storage rings with internal targets are described, using PEP as an example. The difference between electrons and heavier particles such as protons, antiprotons, and heavy ions is also discussed because it raises possibilities of bypass insertions for more exotic experiments. PEP is compared to other rings in various contexts to verify the assertion that it is an ideal ring for many fundamental and practical applications that can be carried on simultaneously

  5. MOLYBDENUM CATALYZED ACID PEROXIDE BLEACHING OF EUCALYPTUS KRAFT PULP

    Directory of Open Access Journals (Sweden)

    Marcos S. Rabelo

    2008-08-01

    Full Text Available Molybdenum catalyzed peroxide bleaching (PMo Stage consists of pulp treatment with hydrogen peroxide under acidic conditions in the presence of a molybdenum catalyst. Molybdenum is applied in catalytic doses (50-200 mg/kg pulp and may originate from various sources, including (NH46Mo7O24.4H2O, Na2MoO4.2H2O, siliconmolybdate, etc. This work is aimed at optimizing the PMo stage and evaluating its industrial application in the OAZDP sequence. Optimum PMo stage conditions for bleaching eucalyptus pulp were 90 ºC, pH 3.5, 2 h, 0.1 kg/adt Mo and 5 kg/adt H2O2. The PMo stage was more efficient to remove pulp hexenuronic acids than lignin. Its efficiency decreased with increasing pH in the range of 1.5-5.5, while it increased with increasing temperature and peroxide and molybdenum doses. The application of the PMo stage as replacement for the A-stage of the AZDP sequence significantly decreased chlorine dioxide demand. The PMo stage caused a decrease of 20-30% in the generation of organically bound chlorine. The quality parameters of the pulp produced during the PMo stage mill trial were comparable to those obtained with the reference A-stage.

  6. Novel Fiber-Optic Ring Acoustic Emission Sensor

    Directory of Open Access Journals (Sweden)

    Peng Wei

    2018-01-01

    Full Text Available Acoustic emission technology has been applied to many fields for many years. However, the conventional piezoelectric acoustic emission sensors cannot be used in extreme environments, such as those with heavy electromagnetic interference, high pressure, or strong corrosion. In this paper, a novel fiber-optic ring acoustic emission sensor is proposed. The sensor exhibits high sensitivity, anti-electromagnetic interference, and corrosion resistance. First, the principle of a novel fiber-optic ring sensor is introduced. Different from piezoelectric and other fiber acoustic emission sensors, this novel sensor includes both a sensing skeleton and a sensing fiber. Second, a heterodyne interferometric demodulating method is presented. In addition, a fiber-optic ring sensor acoustic emission system is built based on this method. Finally, fiber-optic ring acoustic emission experiments are performed. The novel fiber-optic ring sensor is glued onto the surface of an aluminum plate. The 150 kHz standard continuous sinusoidal signals and broken lead signals are successfully detected by the novel fiber-optic ring acoustic emission sensor. In addition, comparison to the piezoelectric acoustic emission sensor is performed, which shows the availability and reliability of the novel fiber-optic ring acoustic emission sensor. In the future, this novel fiber-optic ring acoustic emission sensor will provide a new route to acoustic emission detection in harsh environments.

  7. The rings of Uranus

    Science.gov (United States)

    Elliot, J. L.; Dunham, E.; Mink, D.

    1977-01-01

    A description is given of the observation of five brief occultations of the star SAO 158687 which occurred both before and after its occultation by Uranus on March 10, 1977. The events were observed with a three-channel occultation photometer, attached to a 91-cm telescope. The observations indicate that at least five rings encircle the planet Uranus. Possible reasons for the narrowness of the Uranus rings are discussed.

  8. Vortex Ring Interaction with a Heated Screen

    Science.gov (United States)

    Smith, Jason; Krueger, Paul S.

    2008-11-01

    Previous examinations of vortex rings impinging on porous screens has shown the reformation of the vortex ring with a lower velocity after passing through the screen, the creation of secondary vortices, and mixing. A heated screen could, in principle, alter the vortex-screen interaction by changing the local liquid viscosity and density. In the present investigation, a mechanical piston-cylinder vortex ring generator was used to create vortex rings in an aqueous sucrose solution. The rings impinged on a screen of horizontal wires that were heated using electrical current. The flow was visualized with food color and video imaging. Tests with and without heat were conducted at a piston stroke-to-jet diameter ratio of 4 and a jet Reynolds number (Re) of 1000. The vortex rings slowed after passing through the screen, but in tests with heat, they maintained a higher fraction of their before-screen velocity due to reduction in fluid viscosity near the wires. In addition, small ``fingers'' that developed on the front of the vortex rings as they passed through the screen exhibited positive buoyancy effects in the heated case.

  9. Achieving Translationally Invariant Trapped Ion Rings

    Science.gov (United States)

    Urban, Erik; Li, Hao-Kun; Noel, Crystal; Hemmerling, Boerge; Zhang, Xiang; Haeffner, Hartmut

    2017-04-01

    We present the design and implementation of a novel surface ion trap design in a ring configuration. By eliminating the need for wire bonds through the use of electrical vias and using a rotationally invariant electrode configuration, we have realized a trap that is able to trap up to 20 ions in a ring geometry 45um in diameter, 400um above the trap surface. This large trapping height to ring diameter ratio allows for global addressing of the ring with both lasers and electric fields in the chamber, thereby increasing our ability to control the ring as a whole. Applying compensating electric fields, we measure very low tangential trap frequencies (less than 20kHz) corresponding to rotational barriers down to 4mK. This measurement is currently limited by the temperature of the ions but extrapolation indicates the barrier can be reduced much further with more advanced cooling techniques. Finally, we show that we are able to reduce this energy barrier sufficiently such that the ions are able to overcome it either through thermal motion or rotational motion and delocalize over the full extent of the ring. This work was funded by the Keck Foundation and the NSF.

  10. On Learning Ring-Sum-Expansions

    DEFF Research Database (Denmark)

    Fischer, Paul; Simon, H. -U.

    1992-01-01

    The problem of learning ring-sum-expansions from examples is studied. Ring-sum-expansions (RSE) are representations of Boolean functions over the base {#123;small infinum, (+), 1}#125;, which reflect arithmetic operations in GF(2). k-RSE is the class of ring-sum-expansions containing only monomials...... of length at most k:. term-RSE is the class of ring-sum-expansions having at most I: monomials. It is shown that k-RSE, k>or=1, is learnable while k-term-RSE, k>2, is not learnable if RPnot=NP. Without using a complexity-theoretical hypothesis, it is proven that k-RSE, k>or=1, and k-term-RSE, k>or=2 cannot...... be learned from positive (negative) examples alone. However, if the restriction that the hypothesis which is output by the learning algorithm is also a k-RSE is suspended, then k-RSE is learnable from positive (negative) examples only. Moreover, it is proved that 2-term-RSE is learnable by a conjunction...

  11. Computerspil og læring

    Directory of Open Access Journals (Sweden)

    Lasse Juel Larsen

    2015-02-01

    Full Text Available Game-based learning og gamification er ord, der ofte optræder i forbindelse med computerspil og læring. Denne artikel vil analytisk undersøge, hvordan computerspil og læring går i forbindelse med hinanden. Artikel tager afsæt i Gregory Batesons læringsteori og læser denne igennem det kommercielle computerspil StarCraft 2 fra Blizzard Intertainment. Batesons læringsteori vil ikke alene blive gennemgået, men også udvidet og perspektiveret.  Formålet med denne indsats er at skabe et afsæt, der kan demonstrere, hvordan læring foregår i computerspil. Herefter vil afsættet blive anvendt til at destillere et læringsteoretisk udkast. Artiklen falder således i to dele, hvor den første analytisk adresserer, hvordan læring i computerspil foregår, mens den anden er teoriproducerende på baggrund af resultaterne fra første del.

  12. On rings generating supernilpotent and special atoms | France ...

    African Journals Online (AJOL)

    We study prime rings which generate supernilpotent (respectively special) atoms, that is, atoms of the lattice of all supernilpotent (respectively special) radicals. A prime ring A is called a **-ring if the smallest special class containing A is closed under semiprime homomorphic images of A. A semiprime ring A whose every ...

  13. Identification of a novel antisense long non-coding RNA PLA2G16-AS that regulates the expression of PLA2G16 in pigs.

    Science.gov (United States)

    Liu, Pengliang; Jin, Long; Zhao, Lirui; Long, Keren; Song, Yang; Tang, Qianzi; Ma, Jideng; Wang, Xun; Tang, Guoqing; Jiang, Yanzhi; Zhu, Li; Li, Xuewei; Li, Mingzhou

    2018-05-31

    Natural antisense transcripts (NATs) are widely present in mammalian genomes and act as pivotal regulator molecules to control gene expression. However, studies on the NATs of pigs are relatively rare. Here, we identified a novel antisense transcript, designated PLA2G16-AS, transcribed from the phospholipase A2 group XVI locus (PLA2G16) in the porcine genome, which is a well-known regulatory molecule of fat deposition. PLA2G16-AS and PLA2G16 were dominantly expressed in porcine adipose tissue, and were differentially expressed between Tibetan pigs and Rongchang pigs. In addition, PLA2G16-AS has a weak sequence conservation among different vertebrates. PLA2G16-AS was also shown to form an RNA-RNA duplex with PLA2G16, and to regulate PLA2G16 expression at the mRNA level. Moreover, the overexpression of PLA2G16-AS increased the stability of PLA2G16 mRNA in porcine cells. We envision that our findings of a NAT for a regulatory gene associated with lipolysis might further our understanding of the molecular regulation of fat deposition. Copyright © 2017. Published by Elsevier B.V.

  14. Lamb shift of energy levels in quantum rings

    International Nuclear Information System (INIS)

    Kryuchkyan, G Yu; Kyriienko, O; Shelykh, I A

    2015-01-01

    We study the vacuum radiative corrections to energy levels of a confined electron in quantum rings. The calculations are provided for the Lamb shift of energy levels in a low-momentum region of virtual photons and for both one-dimensional and two-dimensional quantum rings. We show that contrary to the well known case of a hydrogen atom the value of the Lamb shift increases with the magnetic momentum quantum number m. We also investigate the dependence of the Lamb shift on magnetic flux piercing the ring and demonstrate a presence of magnetic-flux-dependent oscillations. For a one-dimensional ring the value of the shift strongly depends on the radius of the ring. It is small for semiconductor rings but can attain measurable quantities in natural organic ring-shape molecules, such as benzene, cycloalcanes and porphyrins. (paper)

  15. Phase behaviour of polyethylene knotted ring chains

    International Nuclear Information System (INIS)

    Wen Xiao-Hui; Xia A-Gen; Chen Hong-Ping; Zhang Lin-Xi

    2011-01-01

    The phase behaviour of polyethylene knotted ring chains is investigated by using molecular dynamics simulations. In this paper, we focus on the collapse of the polyethylene knotted ring chain, and also present the results of linear and ring chains for comparison. At high temperatures, a fully extensive knot structure is observed. The mean-square radius of gyration per bond (S 2 )/(Nb 2 ) and the shape factor (δ*) depend on not only the chain length but also the knot type. With temperature decreasing, chain collapse is observed, and the collapse temperature decreases with the chain length increasing. The actual collapse transition can be determined by the specific heat capacity C v , and the knotted ring chain undergoes gas—liquid—solid-like transition directly. The phase transition of a knotted ring chain is only one-stage collapse, which is different from the polyethylene linear and ring chains. This investigation can provide some insights into the statistical properties of knotted polymer chains. (condensed matter: structural, mechanical, and thermal properties)

  16. Foundations of commutative rings and their modules

    CERN Document Server

    Wang, Fanggui

    2016-01-01

    This book provides an introduction to the basics and recent developments of commutative algebra. A glance at the contents of the first five chapters shows that the topics covered are ones that usually are included in any commutative algebra text. However, the contents of this book differ significantly from most commutative algebra texts: namely, its treatment of the Dedekind–Mertens formula, the (small) finitistic dimension of a ring, Gorenstein rings, valuation overrings and the valuative dimension, and Nagata rings. Going further, Chapter 6 presents w-modules over commutative rings as they can be most commonly used by torsion theory and multiplicative ideal theory. Chapter 7 deals with multiplicative ideal theory over integral domains. Chapter 8 collects various results of the pullbacks, especially Milnor squares and D+M constructions, which are probably the most important example-generating machines. In Chapter 9, coherent rings with finite weak global dimensions are probed, and the local ring of weak gl...

  17. SXLS storage ring design

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    X-ray lithography has emerged as a strong candidate to meet the demands of ever finer linewidths on integrated circuits, particularly for linewidths less than .25 microns. Proximity printing X-ray lithography makes use of soft X-rays to shadow print an image of a mask onto a semiconductor wafer to produce integrated circuits. To generate the required X-rays in sufficient quantities to make commercial production viable, electron storage rings have been proposed as the soft X-ray sources. Existing storage rings have been used to do the initial development work and the success of these efforts has led the lithographers to request that new rings be constructed that are dedicated to X-ray lithography. As a result of a series of workshops held at BNL [10.3] which were attended by both semiconductor and accelerator scientists, the following set of zeroth order specifications' on the light and electron beam of a storage ring for X-ray lithography were developed: critical wavelength of light: λ c = 6 to 10 angstroms, white light power: P = 0.25 to 2.5 watts/mrad, horizontal collection angle per port: θ = 10 to 50 mrad, electron beam sizes: σ x ∼ σ y y ' < 1 mrad

  18. The Storage Ring Proton EDM Experiment

    Science.gov (United States)

    Semertzidis, Yannis; Storage Ring Proton EDM Collaboration

    2014-09-01

    The storage ring pEDM experiment utilizes an all-electric storage ring to store ~1011 longitudinally polarized protons simultaneously in clock-wise and counter-clock-wise directions for 103 seconds. The radial E-field acts on the proton EDM for the duration of the storage time to precess its spin in the vertical plane. The ring lattice is optimized to reduce intra-beam scattering, increase the statistical sensitivity and reduce the systematic errors of the method. The main systematic error is a net radial B-field integrated around the ring causing an EDM-like vertical spin precession. The counter-rotating beams sense this integrated field and are vertically shifted by an amount, which depends on the strength of the vertical focusing in the ring, thus creating a radial B-field. Modulating the vertical focusing at 10 kHz makes possible the detection of this radial B-field by a SQUID-magnetometer (SQUID-based BPM). For a total number of n SQUID-based BPMs distributed around the ring the effectiveness of the method is limited to the N = n /2 harmonic of the background radial B-field due to the Nyquist sampling theorem limit. This limitation establishes the requirement to reduce the maximum radial B-field to 0.1-1 nT everywhere around the ring by layers of mu-metal and aluminum vacuum tube. The metho's sensitivity is 10-29 e .cm , more than three orders of magnitude better than the present neutron EDM experimental limit, making it sensitive to SUSY-like new physics mass scale up to 300 TeV.

  19. Open-ring enhancement sign in diagnosing demyelinating pseudotumor

    International Nuclear Information System (INIS)

    Fang Liting; Wang Zhiping; Wang Linyou

    2010-01-01

    Objective: To describe open-ring enhancement sign on MRI of demyelinating pseudotumor. Methods: Contrast-enhanced MRI of histologically confirmed demyelinating pseudotumors (14 patients) and astrocytomas (21) was reviewed. Results: Of the 14 cases of demyelinating pseudotumor, open-ring enhancement pattern was observed in 6; closed ring enhancement in 2; nodular enhancement in 3; patchy enhancement in 1; slight enhancement in 1; and no enhancement in 1. Of the 21 cases of astrocytoma, there was complete ring or lace-like enhancement in 13, no contrast enhancement in 6, patchy enhancement in 2, and none with open-ring enhancement pattern. Conclusion: Open-ring enhancement is a valuable sign in differential diagnosis between demyelinating pseudotumor and astrocytoma. (authors)

  20. 21 CFR 870.3800 - Annuloplasty ring.

    Science.gov (United States)

    2010-04-01

    ...) Identification. An annuloplasty ring is a rigid or flexible ring implanted around the mitral or tricuspid heart valve for reconstructive treatment of valvular insufficiency. (b) Classification. Class II (special...

  1. Tree rings and radiocarbon calibration

    International Nuclear Information System (INIS)

    Barbetti, M.

    1999-01-01

    Only a few kinds of trees in Australia and Southeast Asia are known to have growth rings that are both distinct and annual. Those that do are therefore extremely important to climatic and isotope studies. In western Tasmania, extensive work with Huon pine (Lagarostrobos franklinii) has shown that many living trees are more than 1,000 years old, and that their ring widths are sensitive to temperature, rainfall and cloud cover (Buckley et al. 1997). At the Stanley River there is a forest of living (and recently felled) trees which we have sampled and measured. There are also thousands of subfossil Huon pine logs, buried at depths less than 5 metres in an area of floodplain extending over a distance of more than a kilometre with a width of tens of metres. Some of these logs have been buried for 50,000 years or more, but most of them belong to the period between 15,000 years and the present. In previous expeditions in the 1980s and 1990s, we excavated and sampled about 350 logs (Barbetti et al. 1995; Nanson et al. 1995). By measuring the ring-width patterns, and matching them between logs and living trees, we have constructed a tree-ring dated chronology from 571 BC to AD 1992. We have also built a 4254-ring floating chronology (placed by radiocarbon at ca. 3580 to 7830 years ago), and an earlier 1268-ring chronology (ca. 7,580 to 8,850 years ago). There are many individuals, or pairs of logs which match and together span several centuries, at 9,000 years ago and beyond

  2. Bimodality and the formation of Saturn's ring particles

    International Nuclear Information System (INIS)

    Gehrels, T.

    1980-01-01

    The F ring appears to have an outer and an inner rim, with only the latter observed by the imaging photopolarimeter (IPP) on the Pioneer Saturn spacecraft. The inside of the G ring, near 2.49 R/sub S/, may also be seen in the optical data. 1979S1 is red as well as dark. The light scattered through the B ring is noticeably red. The A ring has a dense outer rim. The Cassini Division and the French Division (Dollfus Division) have a dark gap near their centers. The C ring becomes weaker toward the center such that outer, middle, and inner C rings can be recognized. The Pioneer and earth-based observations are explained with a model for the B and A rings to some extent of a bimodal size distributions of particles; the larger ones may be original accretions, while small debris diffuses inward through the Cassini Division and the C ring. During the formation of the ring system, differential gravitation allowed only silicaceous grains of higher density (rho> or approx. =3 g cm -3 ) to coagulate. These serve as interstitial cores for snowy carbonaceous grains, between the times of accretion from interplanetary cometary grains and liberation by collision followed by diffusion inward to Saturn and final evaporation

  3. Mechanical seal having a double-tier mating ring

    Science.gov (United States)

    Khonsari, Michael M.; Somanchi, Anoop K.

    2005-09-13

    An apparatus and method to enhance the overall performance of mechanical seals in one of the following ways: by reducing seal face wear, by reducing the contact surface temperature, or by increasing the life span of mechanical seals. The apparatus is a mechanical seal (e.g., single mechanical seals, double mechanical seals, tandem mechanical seals, bellows, pusher mechanical seals, and all types of rotating and reciprocating machines) comprising a rotating ring and a double-tier mating ring. In a preferred embodiment, the double-tier mating ring comprises a first and a second stationary ring that together form an agitation-inducing, guided flow channel to allow for the removal of heat generated at the seal face of the mating ring by channeling a coolant entering the mating ring to a position adjacent to and in close proximity with the interior surface area of the seal face of the mating ring.

  4. Polarized particles in storage rings

    International Nuclear Information System (INIS)

    Derbenev, Ya.S.; Kondratenko, A.M.; Serednyakov, S.I.; Skrinskij, A.N.; Tumajkin, G.M.; Shatunov, Yu.M.

    1977-01-01

    Experiments with polarized beams on the VEPP-2M and SPEAK storage rings are described. Possible methods of producing polarized particle beams in storage rings as well as method of polarization monitoring are counted. Considered are the processes of radiation polarization of electrons and positrons. It is shown, that to preserve radiation polarization the introduction of regions with a strong sign-variable magnetic field is recommended. Methods of polarization measurement are counted. It is suggested for high energies to use dependence of synchrotron radiation power on transverse polarization of electrons and positrons. Examples of using polarizability of colliding beams in storage rings are presented

  5. Saturn Rings Origin: Quantum Trapping of Superconducting Iced Particles and Meissner Effect Lead to the Stable Rings System

    Science.gov (United States)

    Viktorovich Tchernyi, Vladimir

    2018-06-01

    Saturn Rings Origin: Quantum Trapping of Superconducting Iced Particles and Meissner Effect Lead to the Stable Rings System Vladimir V. Tchernyi (Cherny), Andrew Yu. Pospelov Modern Science Institute, SAIBR, Moscow, Russia. E-mail: chernyv@bk.ruAbstractIt is demonstrated how superconducting iced particles of the protoplanetary cloud of Saturn are coming to magnetic equator plane and create the stable enough rings disk. There are two steps. First, after appearance of the Saturn magnetic field due to Meissner phenomenon all particles orbits are moving to the magnetic equator plane. Finally they become distributed as rings and gaps like iron particles around magnet on laboratory table. And they are separated from each other by the magnetic field expelled from them. It takes up to few tens of thousands years with ten meters rings disk thickness. Second, due to their quantum trapping all particles become to be trapped within magnetic well at the magnetic equator plane due to Abrikosov vortex for superconductor. It works even when particles have small fraction of superconductor. During the rings evolution some contribution to the disk also could come from the collision-generated debris of the current moon and from the geysers like it happened due to magnetic coupling of Saturn and Enceladus. The rings are relict of the early days of the magnetic field of Saturn system.

  6. On the evolution of vortex rings with swirl

    International Nuclear Information System (INIS)

    Naitoh, Takashi; Okura, Nobuyuki; Gotoh, Toshiyuki; Kato, Yusuke

    2014-01-01

    A laminar vortex ring with swirl, which has the meridional velocity component inside the vortex core, was experimentally generated by the brief fluid ejection from a rotating outlet. The evolution of the vortex ring was investigated with flow visualizations and particle image velocimetry measurements in order to find the influence of swirling flow in particular upon the transition to turbulence. Immediately after the formation of a vortex ring with swirl, a columnar strong vortex along the symmetric axis is observed in all cases of the present experiment. Then the characteristic fluid discharging from a vortex ring with swirl referred to as “peeling off” appears. The amount of discharging fluid due to the “peeling off” increases with the angular velocity of the rotating outlet. We conjectured that the mechanism generating the “peeling off” is related to the columnar strong vortex by close observations of the spatio-temporal development of the vorticity distribution and the cutting 3D images constructed from the successive cross sections of a vortex ring. While a laminar vortex ring without swirl may develop azimuthal waves around its circumference at some later time and the ring structure subsequently breaks, the swirling flow in a vortex ring core reduces the amplification rate of the azimuthal wavy deformation and preserved its ring structure. Then the traveling distance of a vortex ring can be extended using the swirl flow under certain conditions

  7. On the evolution of vortex rings with swirl

    Energy Technology Data Exchange (ETDEWEB)

    Naitoh, Takashi, E-mail: naitoh.takashi@nitech.ac.jp [Department of Engineering Physics, Electronics and Mechanics, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555 (Japan); Okura, Nobuyuki, E-mail: ohkura@meijo-u.ac.jp [Department of Vehicle and Mechanical Engineering, Meijo University, 1-501 Shiogamaguchi Tempaku-ku, Nagoya 468-8502 (Japan); Gotoh, Toshiyuki, E-mail: gotoh.toshiyuki@nitech.ac.jp [Department of Scientific and Engineering Simulation, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555 (Japan); Kato, Yusuke [Controller Business Unit Engineering Division 1, Engineering Department 3, Denso Wave Incorporated, 1 Yoshiike Kusagi Agui-cho, Chita-gun Aichi 470-2297 (Japan)

    2014-06-15

    A laminar vortex ring with swirl, which has the meridional velocity component inside the vortex core, was experimentally generated by the brief fluid ejection from a rotating outlet. The evolution of the vortex ring was investigated with flow visualizations and particle image velocimetry measurements in order to find the influence of swirling flow in particular upon the transition to turbulence. Immediately after the formation of a vortex ring with swirl, a columnar strong vortex along the symmetric axis is observed in all cases of the present experiment. Then the characteristic fluid discharging from a vortex ring with swirl referred to as “peeling off” appears. The amount of discharging fluid due to the “peeling off” increases with the angular velocity of the rotating outlet. We conjectured that the mechanism generating the “peeling off” is related to the columnar strong vortex by close observations of the spatio-temporal development of the vorticity distribution and the cutting 3D images constructed from the successive cross sections of a vortex ring. While a laminar vortex ring without swirl may develop azimuthal waves around its circumference at some later time and the ring structure subsequently breaks, the swirling flow in a vortex ring core reduces the amplification rate of the azimuthal wavy deformation and preserved its ring structure. Then the traveling distance of a vortex ring can be extended using the swirl flow under certain conditions.

  8. Beam dynamic issues in TESLA damping ring

    International Nuclear Information System (INIS)

    Shiltsev, V.

    1996-05-01

    In this paper we study general requirements on impedances of the linear collider TESLA damping ring design. Quantitative consideration is performed for 17-km long ''dog-bone'' ring. Beam dynamics in alternative options of 6.3 and 2.3-km long damping rings is briefly discussed. 5 refs., 2 tabs

  9. New graft sizing rings for aortic valve reimplantation procedures.

    Science.gov (United States)

    Jelenc, Matija; Jelenc, Blaž; Kneževic, Ivan; Klokocovnik, Tomislav

    2018-01-01

    The objective was to design sizing rings that would enable proper sizing of the graft in reimplantation procedures and to perform leaflet repair before graft implantation. The rings were designed in Autodesk Fusion 360 (San Rafael, CA, USA) and 3D printed using a commercial online 3D printing service. We designed incomplete rings with a low profile and complete rings with a high profile. The complete rings are best suited for reimplantation procedures, whereas low profile C rings are intended for isolated aortic valve repair, where the ascending aorta is not transected. The rings come in sizes corresponding to Vascutek Gelweave graft sizes (Vascutek Terumo, Renfrewshire, Scotland). The ring internal diameters are 5% larger than the designated ring sizes and account for the 5% stretch of the grafts when pressurized. Blades of the rings are placed at 20° intervals. The slits between the blades are designed in such a way that the commissural U-sutures, when put in place and under tension, will lock the ring in position. The rings were successfully used in 10 of our latest reimplantation procedures. After dissection of the aortic root, the commissures were suspended with U-stitches and then the ring was seated onto them. Complete leaflet repair with plication to achieve adequate effective height was then performed, followed by graft implantation. No additional leaflet repair was needed. The newly designed sizing rings enable proper sizing of the graft in reimplantation procedures and enable complete leaflet repair before graft implantation. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  10. HYPERAUTOFLUORESCENT RING IN AUTOIMMUNE RETINOPATHY

    Science.gov (United States)

    LIMA, LUIZ H.; GREENBERG, JONATHAN P.; GREENSTEIN, VIVIENNE C.; SMITH, R. THEODORE; SALLUM, JULIANA M. F.; THIRKILL, CHARLES; YANNUZZI, LAWRENCE A.; TSANG, STEPHEN H.

    2015-01-01

    Purpose To report the presence of a hyperautofluorescent ring and corresponding spectral-domain optical coherence tomography (SD-OCT) features seen in patients with autoimmune retinopathy. Methods All eyes were evaluated by funduscopic examination, full-fleld electroretinography, fundus autofluorescence, and SD-OCT. Further confirmation of the diagnosis was obtained with immunoblot and immunohistochemistry testing of the patient’s serum. Humphrey visual fields and microperimetry were also performed. Results Funduscopic examination showed atrophic retinal pigment epithelium (RPE) associated with retinal artery narrowing but without pigment deposits. The scotopic and photopic full-field electroretinograms were nondetectable in three patients and showed a cone–rod pattern of dysfunction in one patient. Fundus autofluorescence revealed a hyperautofluorescent ring in the parafoveal region, and the corresponding SD-OCT demonstrated loss of the photoreceptor inner segment–outer segment junction with thinning of the outer nuclear layer from the region of the hyperautofluorescent ring toward the retinal periphery. The retinal layers were generally intact within the hyperautofluorescent ring, although the inner segment–outer segment junction was disrupted, and the outer nuclear layer and photoreceptor outer segment layer were thinned. Conclusion This case series revealed the structure of the hyperautofluorescent ring in autoimmune retinopathy using SD-OCT. Fundus autofluorescence and SD-OCT may aid in the diagnosis of autoimmune retinopathy and may serve as a tool to monitor its progression. PMID:22218149

  11. RING STAR FORMATION RATES IN BARRED AND NONBARRED GALAXIES

    International Nuclear Information System (INIS)

    Grouchy, R. D.; Buta, R. J.; Salo, H.; Laurikainen, E.

    2010-01-01

    Nonbarred ringed galaxies are relatively normal galaxies showing bright rings of star formation in spite of lacking a strong bar. This morphology is interesting because it is generally accepted that a typical galactic disk ring forms when material collects near a resonance, set up by the pattern speed of a bar or bar-like perturbation. Our goal in this paper is to examine whether the star formation properties of rings are related to the strength of a bar or, in the absence of a bar, to the non-axisymmetric gravity potential in general. For this purpose, we obtained Hα emission line images and calculated the line fluxes and star formation rates (SFRs) for 16 nonbarred SA galaxies and four weakly barred SAB galaxies with rings. For comparison, we combine our new observations with a re-analysis of previously published data on five SA, seven SAB, and 15 SB galaxies with rings, three of which are duplicates from our sample. With these data, we examine what role a bar may play in the star formation process in rings. Compared to barred ringed galaxies, we find that the inner ring SFRs and Hα+[N II] equivalent widths in nonbarred ringed galaxies show a similar range and trend with absolute blue magnitude, revised Hubble type, and other parameters. On the whole, the star formation properties of inner rings, excluding the distribution of H II regions, are independent of the ring shapes and the bar strength in our small samples. We confirm that the deprojected axis ratios of inner rings correlate with maximum relative gravitational force Q g ; however, if we consider all rings, a better correlation is found when a local bar forcing at the radius of the ring, Q r , is used. Individual cases are described and other correlations are discussed. By studying the physical properties of these galaxies, we hope to gain a better understanding of their placement in the scheme of the Hubble sequence and how they formed rings without the driving force of a bar.

  12. On (m, n)-absorbing ideals of commutative rings

    Indian Academy of Sciences (India)

    with respect to various ring theoretic constructions and study (m, n)-absorbing ideals in several commutative rings. For example, in a Bézout ring or a Boolean ring, an ideal is an (m, n)-absorbing ideal if and only if it is an n-absorbing ideal, and in an almost. Dedekind domain every (m, n)-absorbing ideal is a product of at ...

  13. Remnants of black rings from gravity’s rainbow

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Ahmed Farag [Center for Fundamental Physics, Zewail City of Science and Technology,6th of October City, Giza 12588 (Egypt); Department of Physics, Faculty of Science, Benha University,Benha 13518 (Egypt); Faizal, Mir [Department of Physics and Astronomy, University of Waterloo,Waterloo, Ontario, N2L 3G1 (Canada); Khalil, Mohammed M. [Department of Electrical Engineering, Alexandria University,El-Horreya Rd., Alexandria 12544 (Egypt)

    2014-12-29

    In this paper, we investigate a spinning black ring and a charged black ring in the context of gravity’s rainbow. By incorporating rainbow functions proposed by Amelino-Camelia, et al. in http://dx.doi.org/10.1142/S0217751X97000566 http://dx.doi.org/10.12942/lrr-2013-5 in the metric of the black rings, a considerable modification happens to their thermodynamical properties. We calculate corrections to the temperature, entropy and heat capacity of the black rings. These calculations demonstrate that the behavior of Hawking radiation changes considerably near the Planck scale in gravity’s rainbow, where it is shown that black rings do not evaporate completely and a remnant is left as the black rings evaporate down to Planck scale.

  14. Beam Instrumentation for the Spallation Neutron Source Ring

    International Nuclear Information System (INIS)

    Witkover, R. L.; Cameron, P. R.; Shea, T. J.; Connolly, R. C.; Kesselman, M.

    1999-01-01

    The Spallation Neutron Source (SNS) will be constructed by a multi-laboratory collaboration with BNL responsible for the transfer lines and ring. The 1 MW beam power necessitates careful monitoring to minimize un-controlled loss. This high beam power will influence the design of the monitors in the high energy beam transport line (HEBT) from linac to ring, in the ring, and in the ring-to-target transfer line (RTBT). The ring instrumentation must cover a 3-decade range of beam intensity during accumulation. Beam loss monitoring will be especially critical since un-controlled beam loss must be kept below 10 -4 . A Beam-In-Gap (BIG) monitor is being designed to assure out-of-bucket beam will not be lost in the ring

  15. Atomic-phase interference devices based on ring-shaped Bose-Einstein condensates: Two-ring case

    International Nuclear Information System (INIS)

    Anderson, B.P.; Dholakia, K.; Wright, E.M.

    2003-01-01

    We theoretically investigate the ground-state properties and quantum dynamics of a pair of adjacent ring-shaped Bose-Einstein condensates that are coupled via tunneling. This device, which is the analog of a symmetric superconducting quantum interference device, is the simplest version of what we term an atomic-phase interference device (APHID). The two-ring APHID is shown to be sensitive to rotation

  16. NANOGRAIN DENSITY OUTSIDE SATURN’S A RING

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Robert E. [Engineering Physics, University of Virginia, Charlottesville, VA 22902 (United States); Tseng, Wei-Ling [National Taiwan Normal University, No. 88, Sec. 4, Tingzhou Road, Wenshan District, Taipei 11677, Taiwan (China); Elrod, M. K. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Persoon, A. M., E-mail: rej@virginia.edu, E-mail: wltseng@ntnu.edu.tw, E-mail: meredith.k.elrod@nasa.gov, E-mail: ann-persoon@uiowa.edu [Department of Physics and Astronomy, University of Iowa, Iowa City, IA 52242 (United States)

    2017-01-01

    The observed disparity between the radial dependence of the ion and electron densities measured by the Cassini plasma (CAPS) and radio (RPWS) science instruments are used to show that the region between the outer edge of Saturn’s main rings and its tenuous G ring is permeated with small charged grains (nanograins). These grains emanate from the edge of the A ring and from the tenuous F and G rings. This is a region of Saturn’s magnetosphere that is relatively unexplored, but will be a focus of Cassini ’s F ring orbits prior to the end of mission in 2017 September. Confirmation of the grain densities predicted here will enhance our ability to describe the formation and destruction of material in this important region of Saturn’s magnetosphere.

  17. Passive scalar transport mediated by laminar vortex rings

    Energy Technology Data Exchange (ETDEWEB)

    Hernández, R H; Rodríguez, G, E-mail: rohernan@ing.uchile.cl [LEAF-NL, Depto. Ingeniería Civil Mecánica, Universidad de Chile, Casilla 2777, Santiago (Chile)

    2017-04-15

    Numerical simulations were used to study the dynamics of a passive conserved scalar quantity entrained by a self-propelling viscous vortex ring. The transport and mixing process of the passive scalar variable were studied considering two initial scalar distributions: (i) The scalar substance was introduced into the ring during its formation, further focusing in the shedding into the wake of the ring; (ii) A disk-like scalar layer was placed in the ring’s path where the entrainment of the scalar substance into the ring bubble was studied as a function of the ring strength. In both cases, the scalar concentration inside the vortex bubble exhibits a steady decay with time. In the second case, it was shown that the entrained scalar mass grows with both the Reynolds number of the ring and the thickness of the scalar layer in the propagation direction. The ring can be viewed as a mechanism for scalar transportation along important distances. (paper)

  18. Virtual Exploration of the Ring Systems Chemical Universe.

    Science.gov (United States)

    Visini, Ricardo; Arús-Pous, Josep; Awale, Mahendra; Reymond, Jean-Louis

    2017-11-27

    Here, we explore the chemical space of all virtually possible organic molecules focusing on ring systems, which represent the cyclic cores of organic molecules obtained by removing all acyclic bonds and converting all remaining atoms to carbon. This approach circumvents the combinatorial explosion encountered when enumerating the molecules themselves. We report the chemical universe database GDB4c containing 916 130 ring systems up to four saturated or aromatic rings and maximum ring size of 14 atoms and GDB4c3D containing the corresponding 6 555 929 stereoisomers. Almost all (98.6%) of these ring systems are unknown and represent chiral 3D-shaped macrocycles containing small rings and quaternary centers reminiscent of polycyclic natural products. We envision that GDB4c can serve to select new ring systems from which to design analogs of such natural products. The database is available for download at www.gdb.unibe.ch together with interactive visualization and search tools as a resource for molecular design.

  19. Cellular Internalization and Biocompatibility of Periodic Mesoporous Organosilica Nanoparticles with Tunable Morphologies: From Nanospheres to Nanowires

    KAUST Repository

    Fatieiev, Yevhen

    2017-01-10

    This work describes the sol-gel syntheses of para-substituted phenylene-bridged periodic mesoporous organosilica (PMO) nanoparticles (NPs) with tunable morphologies ranging from nanowires to nanospheres. The findings show the key role of the addition of organic co-solvents in the aqueous templates on the final morphologies of PMO NPs. Other factors such as the temperature, the stirring speed, and the amount of organic solvents also influence the shape of PMO NPs. The tuning of the shape of the PMO nanomaterials made it possible to study the influence of the particle morphology on the cellular internalization and biocompatibility.

  20. International Tree Ring Data Bank (ITRDB)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Tree ring data from the International Tree Ring Data Bank and World Data Center for Paleoclimatology archives. Data include raw treering measurements (most are...

  1. Self-assembly of concentric quantum double rings.

    Science.gov (United States)

    Mano, Takaaki; Kuroda, Takashi; Sanguinetti, Stefano; Ochiai, Tetsuyuki; Tateno, Takahiro; Kim, Jongsu; Noda, Takeshi; Kawabe, Mitsuo; Sakoda, Kazuaki; Kido, Giyuu; Koguchi, Nobuyuki

    2005-03-01

    We demonstrate the self-assembled formation of concentric quantum double rings with high uniformity and excellent rotational symmetry using the droplet epitaxy technique. Varying the growth process conditions can control each ring's size. Photoluminescence spectra emitted from an individual quantum ring complex show peculiar quantized levels that are specified by the carriers' orbital trajectories.

  2. Ring-Interferometric Sol-Gel Bio-Sensor

    Science.gov (United States)

    Bearman, Gregory (Inventor); Cohen, David (Inventor)

    2006-01-01

    A biosensor embodying the invention includes a sensing volume having an array of pores sized for immobilizing a first biological entity tending to bind to a second biological entity in such a manner as to change an index of refraction of the sensing volume. The biosensor further includes a ring interferometer, one volumetric section of the ring interferometer being the sensing volume, a laser for supplying light to the ring interferometer, and a photodetector for receiving light from the interferometer.

  3. Evaluation of radiation-induced degradation of silicon '0' ring

    International Nuclear Information System (INIS)

    Ikeshima, Yoshiaki; Shiraishi; Tadao; Sato, Ryuichi; Tanaka, Isao; Ichihashi, Yoshinori; Ito, Masayuki.

    1990-12-01

    Currently there is too few available data on mechanical properties of an 'O' ring made of organic material, which is used over an extensive period of time under actual Nuclear Reactor environmental conditions. The 'O' rings which were evaluated were made of Silicon Rubber, and are used to provide water tightness. The 'O' rings also served as a pressure boundary within the nozzle of the in-reactor tube in the Water Loop-2 (OWL-2) at the JMTR in Oarai, Ibaraki. The 'O' rings were subjected to a constant penetrating radiation (up to 3.46 kGy) over a period of thirteen (13) years. The effects on the mechanical properties of a Silicon Rubber 'O' Ring were evaluated after having been used over an extensive period of time in an actual in-reactor tube within a radiation environment; a full thirteen years in durations. In making comparison of the properties of other Silicon Rubber 'O' Rings. It was also found that these other 'O' rings were subject to Gamma Rays for a shorter period, but with the same amount of radiation as the 'O' rings in the reactor were supposedly to have received. The evaluation showed that a Silicon Rubber 'O' Ring could have been used for a period, as much as forty (40) years even with a (absorbed) dose of about 300 kGy, before the life expectancy of such an 'O' ring is fully met. It was also discovered that the mechanical properties of an Ethylene Propylene 'O' Rings (currently used in the new OWL-2 in-reactor tube) were much superior to those of the Silicon Rubber 'O' Rings. The Ethylene Propylene 'O' Rings had a live expectancy which was about three times that of a Silicon Rubber 'O' Rings. (author)

  4. The "g-2" Muon Storage Ring

    CERN Multimedia

    CERN PhotoLab

    1974-01-01

    The "g-2" muon storage ring, shortly before completion in June 1974. Bursts of pions (from a target, hit by a proton beam from the 26 GeV PS) are injected and polarized muons from their decay are captured on a stable orbit. When the muons decay too, their precession in the magnetic field of the storage ring causes a modulation of the decay-electron counting rate, from which the muon's anomalous magnetic moment can be determined. In 1977, the "g-2" magnets were modified to build ICE (Initial Cooling Experiment), a proton and antiproton storage ring for testing stochastic and electron cooling. Later on, the magnets had a 3rd life, when the ion storage ring CELSIUS was built from them in Uppsala. For later use as ICE, see 7711282, 7802099, 7809081,7908242.

  5. Airpower, Chaos, and Infrastructure: Lords of the Rings

    National Research Council Canada - National Science Library

    Felker, Edward

    1998-01-01

    .... It focuses on the third ring (infrastructure) of John A. Warden III's theory of five strategic rings, which the author argues is often neglected in the debate over the importance of leadership (first ring...

  6. CMB lensing and giant rings

    Energy Technology Data Exchange (ETDEWEB)

    Rathaus, Ben; Itzhaki, Nissan, E-mail: nitzhaki@post.tau.ac.il, E-mail: ben.rathaus@gmail.com [Raymond and Beverly Sackler Faculty of Exact Sciences, School of Physics and Astronomy, Tel-Aviv University, Ramat-Aviv, 69978 (Israel)

    2012-05-01

    We study the CMB lensing signature of a pre-inationary particle (PIP), assuming it is responsible for the giant rings anomaly that was found recently in the WMAP data. Simulating Planck-like data we find that generically the CMB lensing signal to noise ratio associated with such a PIP is quite small and it would be difficult to cross correlate the temperature giant rings with the CMB lensing signal. However, if the pre-inationary particle is also responsible for the bulk flow measured from the local large scale structure, which happens to point roughly at the same direction as the giant rings, then the CMB lensing signal to noise ratio is fairly significant.

  7. Damping Ring R&D at CESR-TA

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, David L. [Cornell Univ., Ithaca, NY (United States). Dept. of Physics

    2015-01-23

    Accelerators that collide high energy beams of matter and anti-matter are essential tools for the investigation of the fundamental constituents of matter, and the search for new forms of matter and energy. A “Linear Collider” is a machine that would bring high energy and very compact bunches of electrons and positrons (anti-electrons) into head-on collision. Such a machine would produce (among many other things) the newly discovered Higgs particle, enabling a detailed study of its properties. Among the most critical and challenging components of a linear collider are the damping rings that produce the very compact and intense beams of electrons and positrons that are to be accelerated into collision. Hot dilute particle beams are injected into the damping rings, where they are compressed and cooled. The size of the positron beam must be reduced more than a thousand fold in the damping ring, and this compression must be accomplished in a fraction of a second. The cold compact beams are then extracted from the damping ring and accelerated into collision at high energy. The proposed International Linear Collider (ILC), would require damping rings that routinely produce such cold, compact and intense beams. The goal of the Cornell study was a credible design for the damping rings for the ILC. Among the technical challenges of the damping rings; the development of instrumentation that can measure the properties of the very small beams in a very narrow window of time, and mitigation of the forces that can destabilize the beams and prevent adequate cooling, or worse lead to beam loss. One of the most pernicious destabilizing forces is due to the formation of clouds of electrons in the beam pipe. The electron cloud effect is a phenomenon in particle accelerators in which a high density of low energy electrons, build up inside the vacuum chamber. At the outset of the study, it was anticipated that electron cloud effects would limit the intensity of the positron ring

  8. Influence of topology in a quantum ring

    International Nuclear Information System (INIS)

    Netto, A.L. Silva; Chesman, C.; Furtado, C.

    2008-01-01

    In this Letter we study the quantum rings in the presence of a topological defect. We use geometric theory of defects to describe one and two-dimensional quantum rings in the presence of a single screw dislocation. In addition we consider some potential in a two dimensional ring and calculate their energy spectrum. It is shown that the energy spectrum depend on the parabolic way on the burgers vectors of the screw dislocation. We also show that the presence of a topological defect introduces a new contribution for the Aharonov-Bohm effect in the quantum ring

  9. Topological matter, integrable models and fusion rings

    International Nuclear Information System (INIS)

    Nemeschansky, D.; Warner, N.P.

    1992-01-01

    We show how topological G k /G k models can be embedded into the topological matter models that are obtained by perturbing the twisted N = 2 supersymmetric, hermitian symmetric, coset models. In particular, this leads to an embedding of the fusion ring of G as a sub-ring of the perturbed, chiral primary ring. The perturbation of the twisted N = 2 model that leads to the fusion ring is also shown to lead to an integrable N = 2 supersymmetric field theory when the untwisted N = 2 superconformal field theory is perturbed by the same operator and its hermitian conjugate. (orig.)

  10. Ring distributions leading to species formation: a global topographic analysis of geographic barriers associated with ring species.

    Science.gov (United States)

    Monahan, William B; Pereira, Ricardo J; Wake, David B

    2012-03-12

    In the mid 20th century, Ernst Mayr and Theodosius Dobzhansky championed the significance of circular overlaps or ring species as the perfect demonstration of speciation, yet in the over 50 years since, only a handful of such taxa are known. We developed a topographic model to evaluate whether the geographic barriers that favor processes leading to ring species are common or rare, and to predict where other candidate ring barriers might be found. Of the 952,147 geographic barriers identified on the planet, only about 1% are topographically similar to barriers associated with known ring taxa, with most of the likely candidates occurring in under-studied parts of the world (for example, marine environments, tropical latitudes). Predicted barriers separate into two distinct categories: (i) single cohesive barriers (barriers - formed by groups of barriers (each 184,000 to 1.7 million km2) in close geographic proximity (totaling 1.9 to 2.3 million km2) - associated with taxa that differentiate at larger spatial scales (birds: Phylloscopus trochiloides and Larus (sp. argentatus and fuscus)). When evaluated globally, we find a large number of cohesive barriers that are topographically similar to those associated with known ring taxa. Yet, compared to cohesive barriers, an order of magnitude fewer composite barriers are similar to those that favor ring divergence in species with higher dispersal. While these findings confirm that the topographic conditions that favor evolutionary processes leading to ring speciation are, in fact, rare, they also suggest that many understudied natural systems could provide valuable demonstrations of continuous divergence towards the formation of new species. Distinct advantages of the model are that it (i) requires no a priori information on the relative importance of features that define barriers, (ii) can be replicated using any kind of continuously distributed environmental variable, and (iii) generates spatially explicit hypotheses of

  11. Ring power balance observing plasma stability constraints

    International Nuclear Information System (INIS)

    Campbell, R.B.; Logan, B.G.

    1982-01-01

    Ring power balance is performed for an E-ring stabilized tandem mirror reactor, taking into account constraints imposed by plasma stability. The two most important criteria are the stability of the core interchange and hot electron interchange modes. The former determines the ring thickness, the latter determines the minimum hot electron temperature; both quantities are important for power balance. The combination of the hot electron interchange constraint and the fact that the barrier density is low places the operating point on the synchrotron dominated branch of power balance. The reference case considered here requires a reasonable 34 MW of heating power deposited in the rings. We also have examined the sensitivity of the required ring power on uncertainties in the numerical coefficients of the stability constraints. We have found that the heating power is strongly affected

  12. Vaginal rings for delivery of HIV microbicides

    Directory of Open Access Journals (Sweden)

    McCoy CF

    2012-11-01

    Full Text Available R Karl Malcolm, Susan M Fetherston, Clare F McCoy, Peter Boyd, Ian MajorSchool of Pharmacy, Queen's University Belfast, Belfast, UKAbstract: Following the successful development of long-acting steroid-releasing vaginal ring devices for the treatment of menopausal symptoms and contraception, there is now considerable interest in applying similar devices to the controlled release of microbicides against HIV. In this review article, the vaginal ring concept is first considered within the wider context of the early advances in controlled-release technology, before describing the various types of ring device available today. The remainder of the article highlights the key developments in HIV microbicide-releasing vaginal rings, with a particular focus on the dapivirine ring that is presently in late-stage clinical testing.Keywords: controlled release, sustained release, antiretroviral, dapivirine, SILCS diaphragm, silicone elastomer, thermoplastic

  13. Computerspil og læring

    DEFF Research Database (Denmark)

    Larsen, Lasse Juel

    2015-01-01

    Game-based learning og gamification er ord, der ofte optræder i forbindelse med computerspil og læring. Denne artikel vil analytisk undersøge, hvordan computerspil og læring går i forbindelse med hinanden. Artikel tager afsæt i Gregory Batesons læringsteori og læser denne igennem det kommercielle...

  14. Flux qubits on semiconducting quantum ring

    International Nuclear Information System (INIS)

    Szopa, M; Zipper, E

    2010-01-01

    The ability to control the quantum state of a single electrons in a quantum ring made of a semiconductor is at the heart of recent developments towards a scalable quantum computer. A peculiar dispersion relation of quantum rings allows to steer the ground state properties by the magnetic flux and offers spin and orbital degrees of freedom for quantum manipulations. We show that such ring can be effectively reduced to the two-state system forming a qubit on orbital or spin degrees of freedom.

  15. Storage ring group summary

    International Nuclear Information System (INIS)

    King, N.M.

    1980-01-01

    The Storage Ring Group set out to identify and pursue salient problems in accelerator physics for heavy ion fusion, divorced from any particular reference design concept. However, it became apparent that some basic parameter framework was required to correlate the different study topics. As the Workshop progressed, ring parameters were modified and updated. Consequently, the accompanying papers on individual topics will be found to refer to slightly varied parameters, according to the stage at which the different problems were tackled

  16. Comparison of disposable sutureless silicone ring and traditional metal ring in 23-gauge vitrectomy combined with cataract surgery

    Directory of Open Access Journals (Sweden)

    Li X-R

    2011-06-01

    Full Text Available Jian-Guo Wu, Rui-Hua Wei, Ai-Hua Liu, Xiao-Xu Zhou, Guo-Ling Sun, Xiao-Rong LiTianjin Medical University Eye Center, Tianjin, ChinaBackground: The purpose of this prospective, interventional, comparative case series was to evaluate the efficiency and feasibility of a disposable sutureless silicone lens ring for corneal contact lens stabilization during combined 23-gauge vitrectomy and cataract surgery.Methods: We developed a ring consisting of a single silicone component with three footplates along the ring margin to fit cannulae for holding conventional contact lenses. Thirty eyes from 30 patients with cataract and vitreoretinal disease were included, and divided into two matched groups according to disease type and ring used. In Group A, we used a 23-gauge transconjunctival vitrectomy system and a disposable sutureless silicone lens ring (n = 15. In Group B, we used a 23-gauge transconjunctival vitrectomy system and a conventional metal lens ring (n = 15. The main outcome measures were: time required for vitrectomy preparation, rate of intraoperative corneal limbus bleeding, and limbus scar rate at the final follow-up visit.Results: Thirty cases were successfully completed. The average vitrectomy preparation time was less in Group A than in Group B (P < 0.01, and the average preparation time saved was 3.94 minutes. None of the Group A patients had intraoperative bleeding or postoperative scarring, whereas all 15 Group B cases had bleeding and five had scarring. There was a statistically significant difference between Group A and Group B for these complications (P ≤ 0.05.Conclusion: This report demonstrates the advantages of using a sutureless silicone ring during combined 23-gauge vitrectomy and cataract surgery. Using this method could allow extra time for the surgeon to pay more attention to complex vitreoretinal procedures.Keywords: pars plana vitrectomy, contact lens, silicone ring, cataract surgery

  17. Periodic mesoporous organosilica-doped nanocomposite membranes and systems including same

    KAUST Repository

    Hammami, Mohamed Amen

    2017-12-28

    A periodic mesoporous organosilica (PMO) nanoparticle functionalized nanocomposite membrane (NCM) for membrane distillation, the NCM including: polymer fibers such as polyetherimide fibers aggregated into a matrix; and hydrophobic PMO nanoparticles disposed on the polymer fibers. The PMO nanoparticles include a framework connected by organic groups and pentafluorophenyl groups. Good membrane flux and anti-fouling was demonstrated. Membranes can be prepared by electrospinning.

  18. Periodic mesoporous organosilica-doped nanocomposite membranes and systems including same

    KAUST Repository

    Hammami, Mohamed Amen; Francis, Lijo; Croissant, Jonas; Ghaffour, NorEddine; Alsaiari, Shahad; Khashab, Niveen M.

    2017-01-01

    A periodic mesoporous organosilica (PMO) nanoparticle functionalized nanocomposite membrane (NCM) for membrane distillation, the NCM including: polymer fibers such as polyetherimide fibers aggregated into a matrix; and hydrophobic PMO nanoparticles disposed on the polymer fibers. The PMO nanoparticles include a framework connected by organic groups and pentafluorophenyl groups. Good membrane flux and anti-fouling was demonstrated. Membranes can be prepared by electrospinning.

  19. A dystrophic Duchenne mouse model for testing human antisense oligonucleotides.

    Directory of Open Access Journals (Sweden)

    Marcel Veltrop

    Full Text Available Duchenne muscular dystrophy (DMD is a severe muscle-wasting disease generally caused by reading frame disrupting mutations in the DMD gene resulting in loss of functional dystrophin protein. The reading frame can be restored by antisense oligonucleotide (AON-mediated exon skipping, allowing production of internally deleted, but partially functional dystrophin proteins as found in the less severe Becker muscular dystrophy. Due to genetic variation between species, mouse models with mutations in the murine genes are of limited use to test and further optimize human specific AONs in vivo. To address this we have generated the del52hDMD/mdx mouse. This model carries both murine and human DMD genes. However, mouse dystrophin expression is abolished due to a stop mutation in exon 23, while the expression of human dystrophin is abolished due to a deletion of exon 52. The del52hDMD/mdx model, like mdx, shows signs of muscle dystrophy on a histological level and phenotypically mild functional impairment. Local administration of human specific vivo morpholinos induces exon skipping and dystrophin restoration in these mice. Depending on the number of mismatches, occasional skipping of the murine Dmd gene, albeit at low levels, could be observed. Unlike previous models, the del52hDMD/mdx model enables the in vivo analysis of human specific AONs targeting exon 51 or exon 53 on RNA and protein level and muscle quality and function. Therefore, it will be a valuable tool for optimizing human specific AONs and genome editing approaches for DMD.

  20. Analysis of axial behavior of three piece oil control ring; Kumiawase oil ring no jikuhoko kyodo no kaiseki

    Energy Technology Data Exchange (ETDEWEB)

    Tateishi, Y; Fujimura, K; Hitosugi, H [Nippon Piston Ring Co. Ltd., Tokyo (Japan)

    1997-10-01

    It is considered that the reduction of oil control ring tension is a major problem in reducing the friction-loss of internal combustion engines. The authors have successfully developed a calculating method for the axial behavior prediction of a three piece type oil control ring as a method used in reduction of lube-oil consumption when lower tension ring is used. By means of the method, the authors found that the effect in reduction of lube-oil consumption was able to be expected by optimizing design parameters of the oil ring, the tension and the seating tab angle of expander-spacer, and the gas pressure on the 3rd land. 3 refs., 14 figs.

  1. O-Ring sealing arrangements for ultra-high vacuum systems

    Science.gov (United States)

    Kim, Chang-Kyo; Flaherty, Robert

    1981-01-01

    An all metal reusable O-ring sealing arrangement for sealing two concentric tubes in an ultra-high vacuum system. An O-ring of a heat recoverable alloy such as Nitinol is concentrically positioned between protruding sealing rings of the concentric tubes. The O-ring is installed between the tubes while in a stressed martensitic state and is made to undergo a thermally induced transformation to an austenitic state. During the transformation the O-ring expands outwardly and contracts inwardly toward a previously sized austenitic configuration, thereby sealing against the protruding sealing rings of the concentric tubes.

  2. Light-Ring Stability for Ultracompact Objects

    Science.gov (United States)

    Cunha, Pedro V. P.; Berti, Emanuele; Herdeiro, Carlos A. R.

    2017-12-01

    We prove the following theorem: axisymmetric, stationary solutions of the Einstein field equations formed from classical gravitational collapse of matter obeying the null energy condition, that are everywhere smooth and ultracompact (i.e., they have a light ring) must have at least two light rings, and one of them is stable. It has been argued that stable light rings generally lead to nonlinear spacetime instabilities. Our result implies that smooth, physically and dynamically reasonable ultracompact objects are not viable as observational alternatives to black holes whenever these instabilities occur on astrophysically short time scales. The proof of the theorem has two parts: (i) We show that light rings always come in pairs, one being a saddle point and the other a local extremum of an effective potential. This result follows from a topological argument based on the Brouwer degree of a continuous map, with no assumptions on the spacetime dynamics, and, hence, it is applicable to any metric gravity theory where photons follow null geodesics. (ii) Assuming Einstein's equations, we show that the extremum is a local minimum of the potential (i.e., a stable light ring) if the energy-momentum tensor satisfies the null energy condition.

  3. Wavepacket revivals in monolayer and bilayer graphene rings.

    Science.gov (United States)

    García, Trinidad; Rodríguez-Bolívar, Salvador; Cordero, Nicolás A; Romera, Elvira

    2013-06-12

    We have studied the existence of quantum revivals in graphene quantum rings within a simplified model. The time evolution of a Gaussian-populated wavepacket shows revivals in monolayer and bilayer graphene rings. We have also studied this behavior for quantum rings in a perpendicular magnetic field. We have found that revival time is an observable that shows different values for monolayer and bilayer graphene quantum rings. In addition, the revival time shows valley degeneracy breaking.

  4. Corneal iron ring after conductive keratoplasty.

    Science.gov (United States)

    Kymionis, George D; Naoumidi, Tatiana L; Aslanides, Ioannis M; Pallikaris, Ioannis G

    2003-08-01

    To report formation of corneal iron ring deposits after conductive keratoplasty. Observational case report. Case report. A 54-year-old woman underwent conductive keratoplasty for hyperopia. One year after conductive keratoplasty, iron ring pattern pigmentation was detected at the corneal epithelium of both eyes. This is the first report of the appearance of corneal iron ring deposits following conductive keratoplasty treatment in a patient. It is suggested that alterations in tear film stability, resulting from conductive keratoplasty-induced changes in corneal curvature, constitute the contributory factor for these deposits.

  5. Injection envelope matching in storage rings

    International Nuclear Information System (INIS)

    Minty, M.G.; Spence, W.L.

    1995-05-01

    The shape and size of the transverse phase space injected into a storage ring can be deduced from turn-by-turn measurements of the transient behavior of the beam envelope in the ring. Envelope oscillations at 2 x the β-tron frequency indicate the presence of a β-mismatch, while envelope oscillations at the β-tron frequency are the signature of a dispersion function mismatch. Experiments in injection optimization using synchrotron radiation imaging of the beam and a fast-gated camera at the SLC damping rings are reported

  6. Device for monitoring electron-ion ring parameters

    International Nuclear Information System (INIS)

    Tyutyunnikov, S.I.; Shalyapin, V.N.

    1982-01-01

    The invention is classified as the method of collective ion acceleration. The device for electron-ion ring parameters monitoring is described. The invention is aimed at increasing functional possibilities of the device at the expense of the enchance in the number of the ring controlled parameters. The device comprises three similar plane mirrors installed over accelerating tube circumference and a mirror manufactured in the form of prism and located in the tube centre, as well as the system of synchrotron radiation recording and processing. Two plane mirrors are installed at an angle of 45 deg to the vertical axis. The angle of the third plane mirror 3 α and that of prismatic mirror 2 α to the vertical axis depend on geometric parameters of the ring and accelerating tube and they are determined by the expression α=arc sin R K /2(R T -L), where R K - ring radius, R T - accelerating tube radius, L - the height of segment, formed by the mirror and inner surface of the accelerating tube. The device suggested permits to determine longitudinal dimensions of the ring, its velocity and the number of electrons and ions in the ring

  7. Ring current proton decay by charge exchange

    Science.gov (United States)

    Smith, P. H.; Hoffman, R. A.; Fritz, T.

    1975-01-01

    Explorer 45 measurements during the recovery phase of a moderate magnetic storm have confirmed that the charge exchange decay mechanism can account for the decay of the storm-time proton ring current. Data from the moderate magnetic storm of 24 February 1972 was selected for study since a symmetrical ring current had developed and effects due to asymmetric ring current losses could be eliminated. It was found that after the initial rapid decay of the proton flux, the equatorially mirroring protons in the energy range 5 to 30 keV decayed throughout the L-value range of 3.5 to 5.0 at the charge exchange decay rate calculated by Liemohn. After several days of decay, the proton fluxes reached a lower limit where an apparent equilibrium was maintained, between weak particle source mechanisms and the loss mechanisms, until fresh protons were injected into the ring current region during substorms. While other proton loss mechanisms may also be operating, the results indicate that charge exchange can entirely account for the storm-time proton ring current decay, and that this mechanism must be considered in all studies involving the loss of proton ring current particles.

  8. Profiled support vector machines for antisense oligonucleotide efficacy prediction

    Directory of Open Access Journals (Sweden)

    Martín-Guerrero José D

    2004-09-01

    Full Text Available Abstract Background This paper presents the use of Support Vector Machines (SVMs for prediction and analysis of antisense oligonucleotide (AO efficacy. The collected database comprises 315 AO molecules including 68 features each, inducing a problem well-suited to SVMs. The task of feature selection is crucial given the presence of noisy or redundant features, and the well-known problem of the curse of dimensionality. We propose a two-stage strategy to develop an optimal model: (1 feature selection using correlation analysis, mutual information, and SVM-based recursive feature elimination (SVM-RFE, and (2 AO prediction using standard and profiled SVM formulations. A profiled SVM gives different weights to different parts of the training data to focus the training on the most important regions. Results In the first stage, the SVM-RFE technique was most efficient and robust in the presence of low number of samples and high input space dimension. This method yielded an optimal subset of 14 representative features, which were all related to energy and sequence motifs. The second stage evaluated the performance of the predictors (overall correlation coefficient between observed and predicted efficacy, r; mean error, ME; and root-mean-square-error, RMSE using 8-fold and minus-one-RNA cross-validation methods. The profiled SVM produced the best results (r = 0.44, ME = 0.022, and RMSE= 0.278 and predicted high (>75% inhibition of gene expression and low efficacy (http://aosvm.cgb.ki.se/. Conclusions The SVM approach is well suited to the AO prediction problem, and yields a prediction accuracy superior to previous methods. The profiled SVM was found to perform better than the standard SVM, suggesting that it could lead to improvements in other prediction problems as well.

  9. Ring rolling of AW5083 large rings for the external cylinder of CMS

    CERN Multimedia

    S. Sgobba / EST

    2001-01-01

    Picture 1: The forged cylinder is engaged in the ring rolling plant. Picture 2: Vertical rolls allow for the reduction in the axial direction. Rolling is carried out at approx. 400 degrees C. Horizontal rolls (not shown) allow for the reduction in the radial direction. Picture 3: Handling of the ring, rolled at the internal diameter of approx. 7m, and transfer to the quenching both. All pictures have been taken during the visit of Mr. Sgobba at Dembiermont, Mobeuge (Bruxelles).

  10. Bernstein instability driven by thermal ring distribution

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Peter H., E-mail: yoonp@umd.edu [Institute for Physical Science and Technology, University of Maryland, College Park, Maryland 20742 (United States); School of Space Research, Kyung Hee University, Yongin-Si, Gyeonggi-Do 446-701 (Korea, Republic of); Hadi, Fazal; Qamar, Anisa [Institute of Physics and Electronics, University of Peshawar, Peshawar 25000 (Pakistan)

    2014-07-15

    The classic Bernstein waves may be intimately related to banded emissions detected in laboratory plasmas, terrestrial, and other planetary magnetospheres. However, the customary discussion of the Bernstein wave is based upon isotropic thermal velocity distribution function. In order to understand how such waves can be excited, one needs an emission mechanism, i.e., an instability. In non-relativistic collision-less plasmas, the only known Bernstein wave instability is that associated with a cold perpendicular velocity ring distribution function. However, cold ring distribution is highly idealized. The present Brief Communication generalizes the cold ring distribution model to include thermal spread, so that the Bernstein-ring instability is described by a more realistic electron distribution function, with which the stabilization by thermal spread associated with the ring distribution is demonstrated. The present findings imply that the excitation of Bernstein waves requires a sufficiently high perpendicular velocity gradient associated with the electron distribution function.

  11. Bernstein instability driven by thermal ring distribution

    International Nuclear Information System (INIS)

    Yoon, Peter H.; Hadi, Fazal; Qamar, Anisa

    2014-01-01

    The classic Bernstein waves may be intimately related to banded emissions detected in laboratory plasmas, terrestrial, and other planetary magnetospheres. However, the customary discussion of the Bernstein wave is based upon isotropic thermal velocity distribution function. In order to understand how such waves can be excited, one needs an emission mechanism, i.e., an instability. In non-relativistic collision-less plasmas, the only known Bernstein wave instability is that associated with a cold perpendicular velocity ring distribution function. However, cold ring distribution is highly idealized. The present Brief Communication generalizes the cold ring distribution model to include thermal spread, so that the Bernstein-ring instability is described by a more realistic electron distribution function, with which the stabilization by thermal spread associated with the ring distribution is demonstrated. The present findings imply that the excitation of Bernstein waves requires a sufficiently high perpendicular velocity gradient associated with the electron distribution function

  12. Conceptual design of a moving-ring reactor

    International Nuclear Information System (INIS)

    Smith, A.C.; Carlson, G.A.; Ashworth, C.P.

    1986-01-01

    A design of a prototype moving-ring reactor was completed, and a development plan for a pilot reactor is outlined. The fusion fuel is confined in current-carrying rings of magnetically field-reversed plasma (''compact toroids''). The plasma rings, formed by a coaxial plasma gun, undergo adiabatic magnetic compression to ignition temperature while they are being injected into the reactor's burner section. The cylindrical burner chamber is divided into three ''burn stations.'' Separator coils and a slight axial guide field gradient are used to shuttle the ignited toroids rapidly from one burn station to the next, pausing for one-third of the total burn time at each station. Deuterium-tritium- 3 He ice pellets refuel the rings at a rate that maintains constant radiated power. The fusion power per ring is approx. =105.5 MW. The burn time to reach a fusion energy gain of Q = 30 is 5.9 s

  13. Corneal iron ring after hyperopic photorefractive keratectomy.

    Science.gov (United States)

    Bilgihan, K; Akata, F; Gürelik, G; Adigüzel, U; Akpinar, M; Hasanreisoğlu, B

    1999-05-01

    To report the incidence and course of corneal iron deposition after hyperopic photorefractive keratectomy (PRK). Gazi University, Medical School, Department of Ophthalmology, Ankara, Turkey. Between January 1995 and December 1997, 62 eyes had PRK to correct hyperopia. Nine eyes developed corneal iron ring 5 to 8 months (mean 6.25 months +/- 1.3 [SD]) after PRK for hyperopia. The rings persisted during the mean follow-up of 19 +/- 11.09 months. The ring-shaped iron deposition after PRK for hyperopia must be differentiated from the Fleischer ring. Our results suggest that the slitlamp findings of peripheral corneal iron deposition in hyperopic PRK patients correlate with achieved correction.

  14. Comparison of disposable sutureless silicone ring and traditional metal ring in 23-gauge vitrectomy combined with cataract surgery.

    Science.gov (United States)

    Wu, Jian-Guo; Wei, Rui-Hua; Liu, Ai-Hua; Zhou, Xiao-Xu; Sun, Guo-Ling; Li, Xiao-Rong

    2011-01-01

    The purpose of this prospective, interventional, comparative case series was to evaluate the efficiency and feasibility of a disposable sutureless silicone lens ring for corneal contact lens stabilization during combined 23-gauge vitrectomy and cataract surgery. We developed a ring consisting of a single silicone component with three footplates along the ring margin to fit cannulae for holding conventional contact lenses. Thirty eyes from 30 patients with cataract and vitreoretinal disease were included, and divided into two matched groups according to disease type and ring used. In Group A, we used a 23-gauge transconjunctival vitrectomy system and a disposable sutureless silicone lens ring (n = 15). In Group B, we used a 23-gauge transconjunctival vitrectomy system and a conventional metal lens ring (n = 15). The main outcome measures were: time required for vitrectomy preparation, rate of intraoperative corneal limbus bleeding, and limbus scar rate at the final follow-up visit. Thirty cases were successfully completed. The average vitrectomy preparation time was less in Group A than in Group B (P < 0.01), and the average preparation time saved was 3.94 minutes. None of the Group A patients had intraoperative bleeding or postoperative scarring, whereas all 15 Group B cases had bleeding and five had scarring. There was a statistically significant difference between Group A and Group B for these complications (P ≤ 0.05). This report demonstrates the advantages of using a sutureless silicone ring during combined 23-gauge vitrectomy and cataract surgery. Using this method could allow extra time for the surgeon to pay more attention to complex vitreoretinal procedures.

  15. The covariant chiral ring

    Energy Technology Data Exchange (ETDEWEB)

    Bourget, Antoine; Troost, Jan [Laboratoire de Physique Théorique, École Normale Supérieure, 24 rue Lhomond, 75005 Paris (France)

    2016-03-23

    We construct a covariant generating function for the spectrum of chiral primaries of symmetric orbifold conformal field theories with N=(4,4) supersymmetry in two dimensions. For seed target spaces K3 and T{sup 4}, the generating functions capture the SO(21) and SO(5) representation theoretic content of the chiral ring respectively. Via string dualities, we relate the transformation properties of the chiral ring under these isometries of the moduli space to the Lorentz covariance of perturbative string partition functions in flat space.

  16. A muon storage ring for neutrino beams

    International Nuclear Information System (INIS)

    Lee, W.; Neuffer, D.

    1988-01-01

    A muon storage ring can provide electron and muon neutrino beams of precisely knowable flux. Constraints on muon collection and storage-ring design are discussed. Sample muon storage rings are presented and muon and neutrino intensities are estimated. Experimental use of the ν-beams, detector properties, and possible variations are described. Future directions for conceptual designs are outlined. 11 refs., 4 figs., 3 tabs

  17. Acceptability of the vaginal contraceptive ring among adolescent women.

    Science.gov (United States)

    Terrell, Lekeisha R; Tanner, Amanda E; Hensel, Devon J; Blythe, Margaret J; Fortenberry, J Dennis

    2011-08-01

    Although underutilized, the vaginal contraceptive ring has several advantages over other contraceptive methods that could benefit adolescents. We examined factors that may influence willingness to try the vaginal ring including: sexual and contraceptive history, genital comfort, and vaginal ring characteristics. Cross sectional Midwestern adolescent health clinics Adolescent women (N = 200; 14-18 years; 89% African-American) INTERVENTIONS/MAIN OUTCOME MEASURES: All participants received education about the vaginal ring and viewed pictures demonstrating insertion; they then completed a visual/audio computer-assisted self interview. The primary outcome variable, willingness to try the vaginal ring, was a single Likert-scale item. Over half the participants reported knowledge of the vaginal ring with healthcare providers identified as the most important source of contraceptive information. Comfort with one's genitals, insertion and removal, using alternative methods of insertion, and knowing positive method characteristics were significantly associated with willingness to try the vaginal ring. A decreased willingness to try the vaginal ring was related to concerns of the ring getting lost inside or falling out of the vagina. Willingness to try the ring was associated with positive feelings about genitals (e.g., comfort with appearance, hygiene, function). Thus, to increase willingness to try the vaginal ring among adolescents, providers should make it common practice to discuss basic female reproductive anatomy, raise awareness about female genital health and address concerns about their genitals. Providers can offer alternative insertion techniques (e.g., gloves) to make use more accessible. These strategies may increase vaginal ring use among adolescents. 2011 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  18. Ring-Expansion/Contraction Radical Crossover Reactions of Cyclic Alkoxyamines: A Mechanism for Ring Expansion-Controlled Radical Polymerization

    Directory of Open Access Journals (Sweden)

    Atsushi Narumi

    2018-06-01

    Full Text Available Macrocyclic polymers present an important class of macromolecules, displaying the reduced radius of gyration or impossibility to entangle. A rare approach for their synthesis is the ring expansion-controlled radical “vinyl” polymerization, starting from a cyclic alkoxyamine. We here describe ring-expansion radical crossover reactions of cyclic alkoxyamines which run in parallel to chain-propagation reactions in the polymerization system. The radical crossover reactions extensively occurred at 105–125 °C, eventually producing high molecular weight polymers with multiple inherent dynamic covalent bonds (NOC bonds. A subsequent ring-contraction radical crossover reaction and the second ring-expansion radical crossover reaction are also described. The major products for the respective three stages were shown to possess cyclic morphologies by the molecular weight profiles and the residual ratios for the NOC bonds (φ in %. In particular, the high φ values ranging from ca. 80% to 98% were achieved for this cyclic alkoxyamine system. This result verifies the high availability of this system as a tool demonstrating the ring-expansion “vinyl” polymerization that allows them to produce macrocyclic polymers via a one-step vinyl polymerization.

  19. Formation of ring-patterned nanoclusters by laser–plume interaction

    International Nuclear Information System (INIS)

    Sivayoganathan, Mugunthan; Tan Bo; Venkatakrishnan, Krishnan

    2013-01-01

    This article reports for the first time a unique study performed to regulate the ring diameter of nanoclusters fabricated during femtosecond laser ablation of solids and a mechanism is proposed for the formation of those ring clusters. The ring nanoclusters are made out of nanoparticles with a range of 10–30 nm. Our experimental studies showed the synthesis of ring nanoclusters with random diameter distribution on metals, nonmetals, and semiconductors, such as titanium, aluminum, glasses, ceramics, graphite, and silicon. To regulate the ring size, the effects of laser parameters, such as wavelength, pulse duration, pulse energy, and repetition rate on the ring diameter are analyzed. The influence of ablated materials and the background gas on ring size is also elaborated in this article. The motion of plume species under the influence of ponderomotive force on free electrons possibly played a key role in the formation of the ring-patterned nanoclusters. This study could help to understand the fundamentals in laser ablative nanosynthesis as well as to produce nanostructures with organized ring diameter that controls the density and porosity of those 3D nanostructures.

  20. Ring Confidential Transactions

    Directory of Open Access Journals (Sweden)

    Shen Noether

    2016-12-01

    Full Text Available This article introduces a method of hiding transaction amounts in the strongly decentralized anonymous cryptocurrency Monero. Similar to Bitcoin, Monero is a cryptocurrency which is distributed through a proof-of-work “mining” process having no central party or trusted setup. The original Monero protocol was based on CryptoNote, which uses ring signatures and one-time keys to hide the destination and origin of transactions. Recently the technique of using a commitment scheme to hide the amount of a transaction has been discussed and implemented by Bitcoin Core developer Gregory Maxwell. In this article, a new type of ring signature, A Multilayered Linkable Spontaneous Anonymous Group signature is described which allows one to include a Pedersen Commitment in a ring signature. This construction results in a digital currency with hidden amounts, origins and destinations of transactions with reasonable efficiency and verifiable, trustless coin generation. The author would like to note that early drafts of this were publicized in the Monero Community and on the #bitcoin-wizards IRC channel. Blockchain hashed drafts are available showing that this work was started in Summer 2015, and completed in early October 2015. An eprint is also available at http://eprint.iacr.org/2015/1098.