WorldWideScience

Sample records for assemble spliced alignments

  1. Faster exon assembly by sparse spliced alignment

    CERN Document Server

    Tiskin, Alexander

    2007-01-01

    Assembling a gene from candidate exons is an important problem in computational biology. Among the most successful approaches to this problem is \\emph{spliced alignment}, proposed by Gelfand et al., which scores different candidate exon chains within a DNA sequence of length $m$ by comparing them to a known related gene sequence of length n, $m = \\Theta(n)$. Gelfand et al.\\ gave an algorithm for spliced alignment running in time O(n^3). Kent et al.\\ considered sparse spliced alignment, where the number of candidate exons is O(n), and proposed an algorithm for this problem running in time O(n^{2.5}). We improve on this result, by proposing an algorithm for sparse spliced alignment running in time O(n^{2.25}). Our approach is based on a new framework of \\emph{quasi-local string comparison}.

  2. Automated Eukaryotic Gene Structure Annotation Using EVidenceModeler and the Program to Assemble Spliced Alignments

    Energy Technology Data Exchange (ETDEWEB)

    Haas, B J; Salzberg, S L; Zhu, W; Pertea, M; Allen, J E; Orvis, J; White, O; Buell, C R; Wortman, J R

    2007-12-10

    EVidenceModeler (EVM) is presented as an automated eukaryotic gene structure annotation tool that reports eukaryotic gene structures as a weighted consensus of all available evidence. EVM, when combined with the Program to Assemble Spliced Alignments (PASA), yields a comprehensive, configurable annotation system that predicts protein-coding genes and alternatively spliced isoforms. Our experiments on both rice and human genome sequences demonstrate that EVM produces automated gene structure annotation approaching the quality of manual curation.

  3. SPA: a probabilistic algorithm for spliced alignment.

    OpenAIRE

    Erik van Nimwegen; Nicodeme Paul; Robert Sheridan; Mihaela Zavolan

    2006-01-01

    Recent large-scale cDNA sequencing efforts show that elaborate patterns of splice variation are responsible for much of the proteome diversity in higher eukaryotes. To obtain an accurate account of the repertoire of splice variants, and to gain insight into the mechanisms of alternative splicing, it is essential that cDNAs are very accurately mapped to their respective genomes. Currently available algorithms for cDNA-to-genome alignment do not reach the necessary level of accuracy because the...

  4. BBMap: A Fast, Accurate, Splice-Aware Aligner

    Energy Technology Data Exchange (ETDEWEB)

    Bushnell, Brian

    2014-03-17

    Alignment of reads is one of the primary computational tasks in bioinformatics. Of paramount importance to resequencing, alignment is also crucial to other areas - quality control, scaffolding, string-graph assembly, homology detection, assembly evaluation, error-correction, expression quantification, and even as a tool to evaluate other tools. An optimal aligner would greatly improve virtually any sequencing process, but optimal alignment is prohibitively expensive for gigabases of data. Here, we will present BBMap [1], a fast splice-aware aligner for short and long reads. We will demonstrate that BBMap has superior speed, sensitivity, and specificity to alternative high-throughput aligners bowtie2 [2], bwa [3], smalt, [4] GSNAP [5], and BLASR [6].

  5. SPA: a probabilistic algorithm for spliced alignment.

    Directory of Open Access Journals (Sweden)

    Erik van Nimwegen

    2006-04-01

    Full Text Available Recent large-scale cDNA sequencing efforts show that elaborate patterns of splice variation are responsible for much of the proteome diversity in higher eukaryotes. To obtain an accurate account of the repertoire of splice variants, and to gain insight into the mechanisms of alternative splicing, it is essential that cDNAs are very accurately mapped to their respective genomes. Currently available algorithms for cDNA-to-genome alignment do not reach the necessary level of accuracy because they use ad hoc scoring models that cannot correctly trade off the likelihoods of various sequencing errors against the probabilities of different gene structures. Here we develop a Bayesian probabilistic approach to cDNA-to-genome alignment. Gene structures are assigned prior probabilities based on the lengths of their introns and exons, and based on the sequences at their splice boundaries. A likelihood model for sequencing errors takes into account the rates at which misincorporation, as well as insertions and deletions of different lengths, occurs during sequencing. The parameters of both the prior and likelihood model can be automatically estimated from a set of cDNAs, thus enabling our method to adapt itself to different organisms and experimental procedures. We implemented our method in a fast cDNA-to-genome alignment program, SPA, and applied it to the FANTOM3 dataset of over 100,000 full-length mouse cDNAs and a dataset of over 20,000 full-length human cDNAs. Comparison with the results of four other mapping programs shows that SPA produces alignments of significantly higher quality. In particular, the quality of the SPA alignments near splice boundaries and SPA's mapping of the 5' and 3' ends of the cDNAs are highly improved, allowing for more accurate identification of transcript starts and ends, and accurate identification of subtle splice variations. Finally, our splice boundary analysis on the human dataset suggests the existence of a novel non

  6. SPA: A Probabilistic Algorithm for Spliced Alignment

    Science.gov (United States)

    van Nimwegen, Erik; Paul, Nicodeme; Sheridan, Robert; Zavolan, Mihaela

    2006-01-01

    Recent large-scale cDNA sequencing efforts show that elaborate patterns of splice variation are responsible for much of the proteome diversity in higher eukaryotes. To obtain an accurate account of the repertoire of splice variants, and to gain insight into the mechanisms of alternative splicing, it is essential that cDNAs are very accurately mapped to their respective genomes. Currently available algorithms for cDNA-to-genome alignment do not reach the necessary level of accuracy because they use ad hoc scoring models that cannot correctly trade off the likelihoods of various sequencing errors against the probabilities of different gene structures. Here we develop a Bayesian probabilistic approach to cDNA-to-genome alignment. Gene structures are assigned prior probabilities based on the lengths of their introns and exons, and based on the sequences at their splice boundaries. A likelihood model for sequencing errors takes into account the rates at which misincorporation, as well as insertions and deletions of different lengths, occurs during sequencing. The parameters of both the prior and likelihood model can be automatically estimated from a set of cDNAs, thus enabling our method to adapt itself to different organisms and experimental procedures. We implemented our method in a fast cDNA-to-genome alignment program, SPA, and applied it to the FANTOM3 dataset of over 100,000 full-length mouse cDNAs and a dataset of over 20,000 full-length human cDNAs. Comparison with the results of four other mapping programs shows that SPA produces alignments of significantly higher quality. In particular, the quality of the SPA alignments near splice boundaries and SPA's mapping of the 5′ and 3′ ends of the cDNAs are highly improved, allowing for more accurate identification of transcript starts and ends, and accurate identification of subtle splice variations. Finally, our splice boundary analysis on the human dataset suggests the existence of a novel non-canonical splice

  7. FineSplice, enhanced splice junction detection and quantification: a novel pipeline based on the assessment of diverse RNA-Seq alignment solutions.

    Science.gov (United States)

    Gatto, Alberto; Torroja-Fungairiño, Carlos; Mazzarotto, Francesco; Cook, Stuart A; Barton, Paul J R; Sánchez-Cabo, Fátima; Lara-Pezzi, Enrique

    2014-04-01

    Alternative splicing is the main mechanism governing protein diversity. The recent developments in RNA-Seq technology have enabled the study of the global impact and regulation of this biological process. However, the lack of standardized protocols constitutes a major bottleneck in the analysis of alternative splicing. This is particularly important for the identification of exon-exon junctions, which is a critical step in any analysis workflow. Here we performed a systematic benchmarking of alignment tools to dissect the impact of design and method on the mapping, detection and quantification of splice junctions from multi-exon reads. Accordingly, we devised a novel pipeline based on TopHat2 combined with a splice junction detection algorithm, which we have named FineSplice. FineSplice allows effective elimination of spurious junction hits arising from artefactual alignments, achieving up to 99% precision in both real and simulated data sets and yielding superior F1 scores under most tested conditions. The proposed strategy conjugates an efficient mapping solution with a semi-supervised anomaly detection scheme to filter out false positives and allows reliable estimation of expressed junctions from the alignment output. Ultimately this provides more accurate information to identify meaningful splicing patterns. FineSplice is freely available at https://sourceforge.net/p/finesplice/. PMID:24574529

  8. The proper splicing of RNAi factors is critical for pericentric heterochromatin assembly in fission yeast.

    Directory of Open Access Journals (Sweden)

    Scott P Kallgren

    Full Text Available Heterochromatin preferentially assembles at repetitive DNA elements, playing roles in transcriptional silencing, recombination suppression, and chromosome segregation. The RNAi machinery is required for heterochromatin assembly in a diverse range of organisms. In fission yeast, RNA splicing factors are also required for pericentric heterochromatin assembly, and a prevailing model is that splicing factors provide a platform for siRNA generation independently of their splicing activity. Here, by screening the fission yeast deletion library, we discovered four novel splicing factors that are required for pericentric heterochromatin assembly. Sequencing total cellular RNAs from the strongest of these mutants, cwf14Δ, showed intron retention in mRNAs of several RNAi factors. Moreover, introducing cDNA versions of RNAi factors significantly restored pericentric heterochromatin in splicing mutants. We also found that mutations of splicing factors resulted in defective telomeric heterochromatin assembly and mis-splicing the mRNA of shelterin component Tpz1, and that replacement of tpz1+ with its cDNA partially rescued heterochromatin defects at telomeres in splicing mutants. Thus, proper splicing of RNAi and shelterin factors contributes to heterochromatin assembly at pericentric regions and telomeres.

  9. Nanoplasmonic probes of RNA folding and assembly during pre-mRNA splicing

    Science.gov (United States)

    Nguyen, Anh H.; Lee, Jong Uk; Sim, Sang Jun

    2016-02-01

    RNA splicing plays important roles in transcriptome and proteome diversity. Herein, we describe the use of a nanoplasmonic system that unveils RNA folding and assembly during pre-mRNA splicing wherein the quantification of mRNA splice variants is not taken into account. With a couple of SERS-probes and plasmonic probes binding at the boundary sites of exon-2/intron-2 and intron-2/exon-3 of the pre-mature RNA of the β-globin gene, the splicing process brings the probes into the plasmonic bands. For plasmonic probes, a plasmon shift increase of ~29 nm, corresponding to intron removal and exon-2 and exon-3 connection to form the mRNA molecule, is measured by plasmonic coupling. The increased scattering intensity and surface-enhanced Raman scattering (SERS) fingerprinting reveal the clear dynamics of pre-mRNA splicing. Moreover, a time-resolved experiment of individual RNA molecules exhibited a successful splicing and an inhibited splicing event by 33 μM biflavonoid isoginkgetin, a general inhibitor of RNA splicing. The results suggest that the RNA splicing is successfully monitored with the nanoplasmonic system. Thus, this platform can be useful for studying RNA nanotechnology, biomolecular folding, alternative splicing, and maturation of microRNA.

  10. Assembly of splicing complexes on exon 11 of the human insulin receptor gene does not correlate with splicing efficiency in-vitro

    Directory of Open Access Journals (Sweden)

    Caples Matt

    2004-07-01

    Full Text Available Abstract Background Incorporation of exon 11 of the insulin receptor gene is both developmentally and hormonally-regulated. Previously, we have shown the presence of enhancer and silencer elements that modulate the incorporation of the small 36-nucleotide exon. In this study, we investigated the role of inherent splice site strength in the alternative splicing decision and whether recognition of the splice sites is the major determinant of exon incorporation. Results We found that mutation of the flanking sub-optimal splice sites to consensus sequences caused the exon to be constitutively spliced in-vivo. These findings are consistent with the exon-definition model for splicing. In-vitro splicing of RNA templates containing exon 11 and portions of the upstream intron recapitulated the regulation seen in-vivo. Unexpectedly, we found that the splice sites are occupied and spliceosomal complex A was assembled on all templates in-vitro irrespective of splicing efficiency. Conclusion These findings demonstrate that the exon-definition model explains alternative splicing of exon 11 in the IR gene in-vivo but not in-vitro. The in-vitro results suggest that the regulation occurs at a later step in spliceosome assembly on this exon.

  11. Primary mirror alignment and assembly for a multispectral space telescope

    Science.gov (United States)

    Lin, Wei-Cheng; Chang, Shenq-Tsong; Chang, Sheng-Hsiung; Chang, Chen-Peng; Lin, Yu-Chuan; Huang, Po-Hsuan; Tsay, Ho-Lin; Chin, Chi-Chieh; Pan, Hsu-Pin; Huang, Ting-Ming

    2013-10-01

    For a currently developing multispectral space Cassegrain telescope, the primary mirror with 450 mm clear aperture is made of Zerodur and lightweighted at a ratio about 50 % to meet both thermal and mass requirement. For this mirror, it is critical to reduce the astigmatism caused from the gravity effect, bonding process and the deformation from the mounting to the main structure of the telescope (main plate). In this article, the primary mirror alignment, MGSE, assembly process and the optical performance test for the primary mirror assembly are presented. The mechanical shim is the interface between the iso-static mount and main plate. It is used to compensate the manufacture errors of components and differences of local co-planarity errors to prevent the stress while iso-static mount (ISM) is screwed to main plate. After primary mirror assembly, an optical performance test method called bench test with novel algorithm is used to analyze the astigmatism caused from the gravity effect and the deformation from the mounting or supporter. In an effort to achieve the requirement for the tolerance in primary mirror assembly, the astigmatism caused from the gravity and deformation by the mounting force could be less than P-V 0.02λ at 633 nm. The consequence of these demonstrations indicates that the designed mechanical ground supported equipment (MGSE) for the alignment and assembly processes meet the critical requirements for primary mirror assembly of the telescope.

  12. Waferscale assembly of Field-Aligned nanotube Networks (FANs)

    DEFF Research Database (Denmark)

    Dimaki, Maria; Bøggild, Peter

    2006-01-01

    We demonstrate the integration of nanotube networks on 512 individual devices on a full 4-inch wafer in less than 60 seconds with a roughly 80% yield using dielectrophoresis. We present here investigations of the morphology and electrical resistance of such field aligned networks for different...... frequencies of the electrical field used to attract the nanotubes to the electrodes. Preliminary data of response to visible light irradiation as well as changes in the humidity indicate that the field aligned networks could be used as sensor components that may well integrate with CMOS due to mild assembly...

  13. The Alignment and Assembly for EAST Tokamak Device

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    EAST (HT-7U) is a large fusion experimental device. It is a full superconducting tokamak with 1 MA of plasma current, 1000 s of plasma duration, high elongation and triangularity. It mainly consists of superconducting magnets of poloidal and toroidal field (PF& TF),vacuum vessel (VV), thermal radiation shield (TRS) and cryostat vessel (CV). The significant difficulty for assembly of EAST is tight installation tolerances, which are in the order of several tenth of a millimeter. In particular, the alignment of plasma facing components to the magnetic axis of the device is less than ± 0.5 mm.At present, a reasonable assembly process of EAST has been defined, and based on it, the alignment method for EAST, including the survey control network, the location of the main components in different directions, the magnetic axis determination and the accurate positioning of the plasma facing components inside of the vacuum vessel and so on, has been defined by using the sophisticated optical metrology system (SOMS).This paper describes the assembly procedure of EAST and the installation tolerances associated with the main components. Meanwhile, how to establish the assembly survey control network,magnetic axis determination methods, are introduced in detail.

  14. A novel posture alignment system for aircraft wing assembly

    Institute of Scientific and Technical Information of China (English)

    Bin ZHANG; Bao-guo YAO; Ying-lin KE

    2009-01-01

    A novel 6-degree of freedom (DOF) posture alignment system, based on 3-DOF positioners, is presented for the assembly of aircraft wings. Each positioner is connected with the wing through a rotational and adsorptive half-ball shaped end-effector, and the positioners together with the wing are considered as a 3-PPPS (P denotes a prismatic joint and S denotes a spherical joint) redundantly actuated parallel mechanism. The kinematic model of this system is established and a trajectory planning method is introduced. A complete analysis of inverse dynamics is carried out with the Newton-Euler algorithm, which is used to find the desired actuating torque in the design and path planning phase. Simulation analysis of the displacement and actuating torque of each joint of the positioners based on inverse kinematics and dynamics is conducted, and the results show that the system is feasible for the posture alignment of aircraft wings.

  15. The exosome controls alternative splicing by mediating the gene expression and assembly of the spliceosome complex

    OpenAIRE

    Lin Zhang; Yufeng Wan; Guobin Huang; Dongni Wang; Xinyang Yu; Guocun Huang; Jinhu Guo

    2015-01-01

    The exosome is a complex with exoribonuclease activity that regulates RNA surveillance and turnover. The exosome also plays a role in regulating the degradation of precursor mRNAs to maintain the expression of splicing variants. In Neurospora, the silencing of rrp44, which encodes the catalytic subunit of the exosome, changed the expression of a set of spliceosomal snRNA, snRNP genes and SR protein related genes. The knockdown of rrp44 also affected the assembly of the spliceosome. RNA-seq an...

  16. Aligned nanowires and nanodots by directed block copolymer assembly

    Energy Technology Data Exchange (ETDEWEB)

    Xiao Shuaigang; Yang Xiaomin; Lee, Kim Y; Ver der Veerdonk, Rene J M; Kuo, David [Seagate Technology, 47010 Kato Road, Fremont, CA 94538 (United States); Russell, Thomas P, E-mail: shuaigang.xiao@seagate.com [Department of Polymer Science and Engineering, University of Massachusetts, 120 Governors Drive, Amherst, MA 01003 (United States)

    2011-07-29

    The directed self-assembly of block copolymers (BCPs) is a promising route to generate highly ordered arrays of sub-10 nm features. Ultradense arrays of a monolayer of spherical microdomains or cylindrical microdomains oriented parallel to the surface have been produced where the lateral ordering is guided by surface patterning and the lattice defined by the patterning can be commensurate or incommensurate with the natural period of the BCP. Commensurability between the two can be used to elegantly manipulate the lateral ordering and orientation of the BCP microdomains so as to form well-aligned arrays of 1D nanowires or 2D addressable nanodots. No modification of the substrate surface, aside from the patterning, was used, making the influence of lattice mismatch and pattern amplification on the size, shape and pitch of the BCP microdomains more transparent. A skew angle between incommensurate lattices, defining a stretching or compression of the BCP chains to compensate for the lattice mismatch, is presented.

  17. Aligned nanowires and nanodots by directed block copolymer assembly

    International Nuclear Information System (INIS)

    The directed self-assembly of block copolymers (BCPs) is a promising route to generate highly ordered arrays of sub-10 nm features. Ultradense arrays of a monolayer of spherical microdomains or cylindrical microdomains oriented parallel to the surface have been produced where the lateral ordering is guided by surface patterning and the lattice defined by the patterning can be commensurate or incommensurate with the natural period of the BCP. Commensurability between the two can be used to elegantly manipulate the lateral ordering and orientation of the BCP microdomains so as to form well-aligned arrays of 1D nanowires or 2D addressable nanodots. No modification of the substrate surface, aside from the patterning, was used, making the influence of lattice mismatch and pattern amplification on the size, shape and pitch of the BCP microdomains more transparent. A skew angle between incommensurate lattices, defining a stretching or compression of the BCP chains to compensate for the lattice mismatch, is presented.

  18. Assembly Test of Elastic Averaging Technique to Improve Mechanical Alignment for Accelerating Structure Assemblies in CLIC

    CERN Document Server

    Huopana, J

    2010-01-01

    The CLIC (Compact LInear Collider) is being studied at CERN as a potential multi-TeV e+e- collider [1]. The manufacturing and assembly tolerances for the required RF-components are important for the final efficiency and for the operation of CLIC. The proper function of an accelerating structure is very sensitive to errors in shape and location of the accelerating cavity. This causes considerable issues in the field of mechanical design and manufacturing. Currently the design of the accelerating structures is a disk design. Alternatively it is possible to create the accelerating assembly from quadrants, which favour the mass manufacturing. The functional shape inside of the accelerating structure remains the same and a single assembly uses less parts. The alignment of these quadrants has been previously made kinematic by using steel pins or spheres to align the pieces together. This method proved to be a quite tedious and time consuming method of assembly. To limit the number of different error sources, a meth...

  19. Aligning self-assembled gelators by drying under shear.

    Science.gov (United States)

    Draper, Emily R; Mykhaylyk, Oleksandr O; Adams, Dave J

    2016-05-25

    We show how drying under shear can be used to prepare aligned fibres and worm-like micelles from low molecular weight gelators. Shearing followed by drying leads to the dealignment before the water can be removed; continuous shear whilst drying is required to maintain the alignment. Combining a slow pH change with continuous shear allows alignment of the gelling fibres, which can then be dried. PMID:27146964

  20. The Alignment Test System for AXAF-I's High Resolution Mirror Assembly

    Science.gov (United States)

    Waldman, Mark

    1995-01-01

    The AXAF-1 High Resolution Mirror Assembly (HRMA) consists of four nested mirror pairs of Wolter Type-1 grazing incidence optics. The HRMA assembly and alignment will take place in a vibration-isolated, cleanliness class 100, 18 meter high tower at an Eastman Kodak Company facility in Rochester, NY. Each mirror pair must be aligned such that its image is coma-free, and the four pairs must be aligned such that their images are coincident. In addition, both the HRMA optical axis and focal point must be precisely known with respect to physical references on the HRMA. The alignment of the HRMA mirrors is measured by the HRMA Alignment Test System (HATS), which is an integral part of the tower facility. The HATS is configured as a double-pass, autocollimating Hartmann test where each mirror aperture is scanned to determine the state of alignment. This paper will describe the design and operation of the HATS.

  1. Television alignment of mast assembly in refueling of nuclear reactor

    International Nuclear Information System (INIS)

    This patent describes the refueling of a nuclear reactor having component assemblies of at least one type and being disposed in a pit in a containment under water, the refueling being carried out with a mast movable axially and circumferentially for raising and lowering the component assemblies, a mechanism, connected to an end of the mast, cooperative with the mast, for engaging a component assembly to be raised by the mast, a television camera, and a television monitor having an image-reference indication, the mechanism being connected to the mast movable with the mast; the method of positioning the mechanism to engage the component assembly appropriately for raising and lowering. It comprises: mounting the camera on the mechanism movable therewith, suspending the mast in the water of the pit with the mechanism extending from the end of the mast in the pit in position to engage the component assembly

  2. Testing to evaluate synergistic effects from LOCA environments. Test IX. Simultaneous mode; cables, splice assemblies, and electrical insulation samples

    International Nuclear Information System (INIS)

    This test was conducted to complement Test VIII which was a sequential test of cables, cable splices, and insulation samples. In this test, the generic LOCA environments (radiation, temperature, pressure, chemical spray) were simulated and simultaneously applied to the test items. There were no failures of any assemblies and all were able to function at rated current and voltage throughout the entire test. An additional parameter, dissipation factor, was monitored in this test and when used in conjunction with capacitance, provided a better indication of insulation degradation

  3. Pre-mRNA splicing within an assembled yeast spliceosome requires an RNA-dependent ATPase and ATP hydrolysis.

    OpenAIRE

    Kim, S. H.; Lin, R J

    1993-01-01

    Unlike autocatalyzed self-splicing of group I or group II introns, the removal of pre-mRNA introns in vitro occurs in the spliceosome. The spliceosome is a multicomponent complex composed of pre-mRNA, small nuclear ribonucleoprotein particles, and protein factors. ATP is required for the assembly of the spliceosome and both transesterification reactions. An RNA-dependent ATPase, the product of the yeast PRP2 gene, has been shown to be involved in the first transesterification of pre-mRNA spli...

  4. Magnetic Self-Assembly with Unique Rotational Alignment

    NARCIS (Netherlands)

    Kuran, E.E.

    2015-01-01

    The majority of flexible electronics applications require integration of thin chips on low-cost polymer substrates, with a high volume manufacturing fashion. However, handling thin parts (below< 100μm) with contact-based micro-assembly techniques is challenging due to the strong adhesion forces at m

  5. Aligning 3D nanofibrous networks from self-assembled phenylalanine nanofibers†

    OpenAIRE

    Wang, Xianfeng; CHEN, YI CHARLIE; Li, Bingyun

    2014-01-01

    Self-assembled synthetic materials are typically disordered, and controlling the alignment of such materials at the nanometer scale may be important for a variety of biological applications. In this study, we have applied directional freeze-drying, for the first time, to develop well aligned three dimensional (3D) nanofibrous materials using amino acid like L-phenylalanine (Phe). 3D free-standing Phe nanofibrous monoliths have been successfully prepared using directional freeze-drying, and ha...

  6. Assembly of splicing complexes on exon 11 of the human insulin receptor gene does not correlate with splicing efficiency in-vitro

    OpenAIRE

    Caples Matt; Evans Lui-Guojing; Webster Nicholas JG; Erker Laura; Chew Shern L

    2004-01-01

    Abstract Background Incorporation of exon 11 of the insulin receptor gene is both developmentally and hormonally-regulated. Previously, we have shown the presence of enhancer and silencer elements that modulate the incorporation of the small 36-nucleotide exon. In this study, we investigated the role of inherent splice site strength in the alternative splicing decision and whether recognition of the splice sites is the major determinant of exon incorporation. Results We found that mutation of...

  7. Installation and Alignment of Neutron Guides for In-pile Plug Assembly and Primary Shutter

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Jin Won; Cho, Yeong Garp [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2008-12-15

    The HANARO will be equipped with a neutron guide system, in order to transport cold neutrons from the neutron source to the neutron scattering instruments in the neutron guide hall near the reactor building. The neutron guide system of HANARO consists of the in-pile plug assembly with in-pile guides, the primary shutter with in-shutter guides, the neutron guides in the guide shielding room with dedicated secondary shutters, and the neutron guides connected to the instruments in the neutron guide hall. Neutron guides have rectangular shapes of glass which is specially coated inside by Ni and Ti. It is very important to align neutron guides accurately in order to minimize a loss of cold neutrons which are transferred to scattering instruments. The alignment is one of significant factors together with a reflectivity and a manufacturing accuracy, which decide the performance of neutron guides. So it is necessary to develop special alignment tools and techniques to align neutron guides successfully. There is some limit of accessibility and workability to use optical measurement while aligning neutron guides of the in-pile plug assembly and the primary shutter because of a high radiation level at the CN beam port. So we adopted a laser tracker as the measurement system to align neutron guides accurately in a radiation environment. The laser tracker enables to measure coordinates of neutron guides at far and offset positions of the beam port. This report describes a method of neutron guides alignment for the in-pile plug assembly and the primary shutter using a laser tracker. The result of the installation and the alignment of neutron guides is also presented.

  8. Alignment of neutron guides for the in-pile plug assembly and the primary shutter

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Jin Won; Cho, Yeong Garp; Cho, Sang Jin; Lee, Jung Hee [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2009-05-15

    KAERI has been developing a neutron guide system for cold neutron research facilities in HANARO since 2003. The neutron guide system plays an important role in transporting cold neutrons from the cold neutron source to the neutron scattering instruments in the neutron guide hall. A beam port assigned for the cold neutron (CN) has been used for an 8-m SANS without neutron guides until early 2008. The old instrument at the CN beam port was removed and a completely new system has been installed, which is composed of an in-pile plug assembly with in-plug guides, a primary shutter with in-shutter guides, removable shielding blocks, and a vacuum system. It is very important to align the neutron guides accurately in order to minimize a loss of cold neutrons which are transferred to scattering instruments. The alignment is one of significant factors together with a reflectivity and a manufacturing accuracy, which decide the performance of neutron guides. So it is necessary to develop special alignment tools and techniques to align the neutron guides successfully. There exist some limits of accessibility and workability to use conventional optical measurements while aligning the neutron guides for the in-pile plug assembly and the primary shutter because of a high radiation level at the CN beam port. So we adopted a laser tracker as a measurement system to align the neutron guides in a radiation environment. The accurate alignment of neutron guides was safely achieved by a laser tracker through measuring the coordinates of neutron guides at far and offset positions of the beam port. This paper presents the successful result of the installation and alignment of neutron guides for the in pile plug assembly and the primary shutter using a laser tracker.

  9. Aligning 3D nanofibrous networks from self-assembled phenylalanine nanofibers†

    Science.gov (United States)

    Wang, Xianfeng; Chen, Yi Charlie

    2015-01-01

    Self-assembled synthetic materials are typically disordered, and controlling the alignment of such materials at the nanometer scale may be important for a variety of biological applications. In this study, we have applied directional freeze-drying, for the first time, to develop well aligned three dimensional (3D) nanofibrous materials using amino acid like L-phenylalanine (Phe). 3D free-standing Phe nanofibrous monoliths have been successfully prepared using directional freeze-drying, and have presented a unique hierarchical structure with well-aligned nanofibers at the nanometer scale and an ordered compartmental architecture at the micrometer scale. We have found that the physical properties (e.g. nanofiber density and alignment) of the nanofibrous materials could be tuned by controlling the concentration and pH of the Phe solution and the freezing temperature. Moreover, the same strategy (i.e. directional freeze-drying) has been successfully applied to assemble peptide nanofibrous materials using a dipeptide (i.e. diphenylalanine), and to assemble Phe-based nanofibrous composites using polyethylenimine and poly(vinyl alcohol). The tunability of the nanofibrous structures together with the biocompatibility of Phe may make these 3D nanofibrous materials suitable for a variety of applications, including biosensor templates, tissue scaffolds, filtration membranes, and absorbents. The strategy reported here is likely applicable to create aligned nanofibrous structures using other amino acids, peptides, and polymers. PMID:25621167

  10. Single Mode Fiber Optic Connectors And Splices

    Science.gov (United States)

    Woods, John G.

    1984-08-01

    There is a trend toward increasing use of single mode transmission, particularly in telecommunications where high data bit rates are transmitted for long distances. Inter-connections of multimode fibers can be made in a number of ways, using ferrules, v-grooves, elastomeric splices, etc. However, the connection of single mode fibers, which have core diameters of 4 to 13 μm, requires more precise alignment than do the multimode fibers having core diameters of 50 μm or more. At TRW, we have adapted the four rod alignment guide concept for single mode fiber inter-connections. The principle of this OPTAGUIDE* alignment guide is presented. The single mode connectors and splices use the four rod scheme with an index matching material to eliminate or reduce the losses incurred through fiber end roughness or angularity. We are able to produce demountable connectors for 80/4.4 pm fibers having typical insertion losses of 1.0dB. The main factors in obtaining this result are the naturally precise fiber alignment provided by the alignment guide, and the ability of several manufacturers to maintain tight diametral and core offset tolerances. The single mode OPTALIGN* SM Connectors have been subjected to performance and environmental tests including repeated matings, temperature cycle and vibration. The results of these tests are described in this paper. A feature of the OPTALIGN* SM Connectors is the relative ease and speed of attachment to fiber optic cable in the field, without the use of epoxy or polishing procedures. The alignment guide concept has also been applied to permanent single mode splices. The splicing procedure is simple to perform in the field without expensive or delicate equipment. Construction and assembly procedures of the demountable connectors and permanent splices will be described with the aid of diagrams and photographs.

  11. Self-Assembly of Semiconducting Single-Walled Carbon Nanotubes into Dense, Aligned Rafts

    CERN Document Server

    Wu, Justin; Antaris, Alexander; Choi, Charina L; Xie, Liming; Wu, Yingpeng; Diao, Shuo; Chen, Changxin; Chen, Yongsheng; Dai, Hongjie

    2013-01-01

    Single-walled carbon nanotubes are promising nanoelectronic materials but face long-standing challenges including production of pure semiconducting SWNTs and integration into ordered structures. Here, highly pure semiconducting single-walled carbon nanotubes are separated from bulk materials and self-assembled into densely aligned rafts driven by depletion attraction forces. Microscopy and spectroscopy revealed a high degree of alignment and a high packing density of ~100 tubes/micron within SWNT rafts. Field-effect transistors made from aligned SWNT rafts afforded short channel (~150 nm long) devices comprised of tens of purely semiconducting SWNTs derived from chemical separation within a < 1 micron channel width, achieving unprecedented high on-currents (up to ~120 microamperes per device) with high on/off ratios. The average on-current was ~ 3-4 microamperes per tube. The results demonstrated densely aligned high quality semiconducting SWNTs for integration into high performance nanoelectronics.

  12. Alignment and assembly process for primary mirror subsystem of a spaceborne telescope

    Science.gov (United States)

    Lin, Wei-Cheng; Chang, Shenq-Tsong; Chang, Sheng-Hsiung; Chang, Chen-Peng; Lin, Yu-Chuan; Chin, Chi-Chieh; Pan, Hsu-Pin; Huang, Ting-Ming

    2015-11-01

    In this study, a multispectral spaceborne Cassegrain telescope was developed. The telescope was equipped with a primary mirror with a 450-mm clear aperture composed of Zerodur and lightweighted at a ratio of approximately 50% to meet both thermal and mass requirements. Reducing the astigmatism was critical for this mirror. The astigmatism is caused by gravity effects, the bonding process, and deformation from mounting the main structure of the telescope (main plate). This article presents the primary mirror alignment, mechanical ground-supported equipment (MGSE), assembly process, and optical performance test used to assemble the primary mirror. A mechanical compensated shim is used as the interface between the bipod flexure and main plate. The shim was used to compensate for manufacturer errors found in components and differences between local coplanarity errors to prevent stress while the bipod flexure was screwed to the main plate. After primary mirror assembly, an optical performance test method called a bench test with an algorithm was used to analyze the astigmatism caused by the gravity effect and deformation from the mounting or supporter. The tolerance conditions for the primary mirror assembly require the astigmatism caused by gravity and mounting force deformation to be less than P-V 0.02 λ at 632.8 nm. The results demonstrated that the designed MGSE used in the alignment and assembly processes met the critical requirements for the primary mirror assembly of the telescope.

  13. EMPTY PERICARP16 is required for mitochondrial nad2 intron 4 cis-splicing, complex I assembly and seed development in maize.

    Science.gov (United States)

    Xiu, Zhihui; Sun, Feng; Shen, Yun; Zhang, Xiaoyan; Jiang, Ruicheng; Bonnard, Géraldine; Zhang, Jianhua; Tan, Bao-Cai

    2016-02-01

    In higher plants, chloroplast and mitochondrial transcripts contain a number of group II introns that need to be precisely spliced before translation into functional proteins. However, the mechanism of splicing and the factors involved in this process are not well understood. By analysing a seed mutant in maize, we report here the identification of Empty pericarp16 (Emp16) that is required for splicing of nad2 intron 4 in mitochondria. Disruption of Emp16 function causes developmental arrest in the embryo and endosperm, giving rise to an empty pericarp phenotype in maize. Differentiation of the basal endosperm transfer layer cells is severely affected. Molecular cloning indicates that Emp16 encodes a P-type pentatricopeptide repeat (PPR) protein with 11 PPR motifs and is localized in the mitochondrion. Transcript analysis revealed that mitochondrial nad2 intron 4 splicing is abolished in the emp16 mutants, leading to severely reduced assembly and activity of complex I. In response, the mutant dramatically increases the accumulation of mitochondrial complex III and the expression of alternative oxidase AOX2. These results imply that EMP16 is specifically required for mitochondrial nad2 intron 4 cis-splicing and is essential for complex I assembly and embryogenesis and development endosperm in maize. PMID:26764126

  14. Fully automated hybrid diode laser assembly using high precision active alignment

    Science.gov (United States)

    Böttger, Gunnar; Weber, Daniel; Scholz, Friedemann; Schröder, Henning; Schneider-Ramelow, Martin; Lang, Klaus-Dieter

    2016-03-01

    Fraunhofer IZM, Technische Universität Berlin and eagleyard Photonics present various implementations of current micro-optical assemblies for high quality free space laser beam forming and efficient fiber coupling. The laser modules shown are optimized for fast and automated assembly in small form factor packages via state-of-the-art active alignment machinery, using alignment and joining processes that have been developed and established in various industrial research projects. Operational wavelengths and optical powers ranging from 600 to 1600 nm and from 1 mW to several W respectively are addressed, for application in high-resolution laser spectroscopy, telecom and optical sensors, up to the optical powers needed in industrial and medical laser treatment.

  15. Effect of the Ortho Alkylation of Perylene Bisimides on the Alignment and Self-Assembly Properties

    OpenAIRE

    2014-01-01

    The effect of the ortho alkylation of perylene bisimides on the alignment and self-assembly properties has been studied. It was found that the dichroic properties of perylene bisimides in a liquid crystal host can be reversed with a single synthetic step by ortho alkylation. Furthermore, a solvent-induced growth of ultralong organic n-type semiconducting fibrils from non-ortho-alkylated perylene bisimide was observed. Ortho substitution of the perylene bisimide core alters the mode of fibrill...

  16. Laser micro-machining of hydrophobic-hydrophilic patterns for fluid driven self-alignment in micro-assembly

    OpenAIRE

    Römer, Gert-Willem; Jorritsma, Mark; Arnaldo del Cerro, Daniel; Chang, Bo; Liimatainen, Ville; Zhou, Quan; Huis in 't Veld, Bert

    2011-01-01

    Fluid driven self-alignment is a low cost alternative to fast but relatively inaccurate robotic pickand-place assembly of micro-fabricated components. This fluidic self-alignment technique relies on a hydrophobic-hydrophilic pattern on the surface of the receiving substrate, which confines a fluid to a receptor site. When a micro-component is dropped on the fluid capillary forces drive the assembly process, resulting in accurate positioning of the part relative to the site. This paper demonst...

  17. Laser micro-machining of hydrophobic-hydrophilic patterns for fluid driven self-alignment in micro-assembly

    NARCIS (Netherlands)

    Römer, G.R.B.E.; Jorritsma, M.M.J.; Del Cerro, D.A.; Chang, B.; Liimatainen, V.; Zhou, Q.; Huis in 't Veld, A.J.

    2011-01-01

    Fluid driven self-alignment is a low cost alternative to fast but relatively inaccurate robotic pickand- place assembly of micro-fabricated components. This fluidic self-alignment technique relies on a hydrophobic-hydrophilic pattern on the surface of the receiving substrate, which confines a fluid

  18. Laser micro-machining of hydrophobic-hydrophilic patterns for fluid driven self-alignment in micro-assembly

    NARCIS (Netherlands)

    Römer, Gert-Willem; Jorritsma, Mark; Arnaldo del Cerro, Daniel; Chang, Bo; Liimatainen, Ville; Zhou, Quan; Huis in 't Veld, Bert

    2011-01-01

    Fluid driven self-alignment is a low cost alternative to fast but relatively inaccurate robotic pickand-place assembly of micro-fabricated components. This fluidic self-alignment technique relies on a hydrophobic-hydrophilic pattern on the surface of the receiving substrate, which confines a fluid t

  19. Alignment and Use of Self-Assembled Peptide Nanotubes as Dry-Etching Mask

    Science.gov (United States)

    Andersen, Karsten B.; Castillo-León, Jaime; Bakmand, Tanya; Svendsen, Winnie E.

    2012-06-01

    Self-assembled diphenylalanine peptide nanotubes provide a means of achieving nanostructured materials in a very simple and fast way. Recent discoveries have shown that this unique material, in addition to remaining stable under dry conditions, rapidly dissolves in water making it a promising candidate for controlled nanofabrication without organic solvents. The present work demonstrates how this unique structure can be aligned, manipulated and used as both an etching mask in a dry etching procedure and as a lift-off material. As a further demonstration of the potential of this technique, the peptide nanotubes were utilized to fabricate silicon nanowire devices and gold nanoslits in a rapid manner.

  20. Genome-wide survey of Alternative Splicing in Sorghum Bicolor.

    Science.gov (United States)

    Panahi, Bahman; Abbaszadeh, Bahram; Taghizadeghan, Mehdi; Ebrahimie, Esmaeil

    2014-07-01

    Sorghum bicolor is a member of grass family which is an attractive model plant for genome study due to interesting genome features like low genome size. In this research, we performed comprehensive investigation of Alternative Splicing and ontology aspects of genes those have undergone these events in sorghum bicolor. We used homology based alignments between gene rich transcripts, represented by tentative consensus (TC) transcript sequences, and genomic scaffolds to deduce the structure of genes and identify alternatively spliced transcripts in sorghum. Using homology mapping of assembled expressed sequence tags with genomics data, we identified 2,137 Alternative Splicing events in S. bicolor. Our study showed that complex events and intron retention are the main types of Alternative Splicing events in S. bicolor and highlights the prevalence of splicing site recognition for definition of introns in this plant. Annotations of the alternatively spliced genes revealed that they represent diverse biological process and molecular functions, suggesting a fundamental role for Alternative Splicing in affecting the development and physiology of S. bicolor. PMID:25049459

  1. Magnetic field aligned assembly of nonmagnetic composite dumbbells in nanoparticle-based aqueous ferrofluid.

    Science.gov (United States)

    Takahashi, Hayato; Nagao, Daisuke; Watanabe, Kanako; Ishii, Haruyuki; Konno, Mikio

    2015-05-26

    Monodisperse, nonmagnetic, asymmetrical composite dumbbells in a suspension of magnetic nanoparticles (ferrofluid) were aligned by application of an external magnetic field to the ferrofluid. The asymmetrical composite dumbbells were prepared by two-step soap-free emulsion polymerization consisting of the first polymerization to coat spherical silica cores with cross-linked poly(methyl methacrylate) (PMMA) shell and the second polymerization to protrude a polystyrene (PSt) lobe from the core-shell particles. A chain structure of nonmagnetic dumbbells oriented to the applied magnetic field was observed at nanoparticle content of 2.0 vol % and field strengths higher than 1.0 mT. A similar chain structure of the dumbbells was observed under application of alternating electric field at strengths higher than 50 V/mm. Parallel and orthogonally combined applications of the electric and magnetic fields were also conducted to examine independence of the electric and magnetic applications as operational factors in the dumbbell assembling. Dumbbell chains stiffer than those in a single application of external field were formed in the parallel combined application of electric and magnetic fields. The orthogonal combination of the different applied fields could form a magnetically aligned chain structure of the nonmagnetic dumbbells oriented to the electric field. The present work experimentally indicated that the employment of inverse magnetorheological effect for nonmagnetic, anisotropic particles can be a useful method for the simultaneous controls over the orientation and the positon of anisotropic particles in their assembling. PMID:25927488

  2. Assembly of vorticity-aligned hard-sphere colloidal strings in a simple shear flow

    KAUST Repository

    Cheng, X.

    2011-12-23

    Colloidal suspensions self-assemble into equilibrium structures ranging from face- and body-centered cubic crystals to binary ionic crystals, and even kagome lattices. When driven out of equilibrium by hydrodynamic interactions, even more diverse structures can be accessed. However, mechanisms underlying out-of-equilibrium assembly are much less understood, though such processes are clearly relevant in many natural and industrial systems. Even in the simple case of hard-sphere colloidal particles under shear, there are conflicting predictions about whether particles link up into string-like structures along the shear flow direction. Here, using confocal microscopy, we measure the shear-induced suspension structure. Surprisingly, rather than flow-aligned strings, we observe log-rolling strings of particles normal to the plane of shear. By employing Stokesian dynamics simulations, we address the mechanism leading to this out-of-equilibrium structure and show that it emerges from a delicate balance between hydrodynamic and interparticle interactions. These results demonstrate a method for assembling large-scale particle structures using shear flows.

  3. MapSplice: accurate mapping of RNA-seq reads for splice junction discovery.

    Science.gov (United States)

    Wang, Kai; Singh, Darshan; Zeng, Zheng; Coleman, Stephen J; Huang, Yan; Savich, Gleb L; He, Xiaping; Mieczkowski, Piotr; Grimm, Sara A; Perou, Charles M; MacLeod, James N; Chiang, Derek Y; Prins, Jan F; Liu, Jinze

    2010-10-01

    The accurate mapping of reads that span splice junctions is a critical component of all analytic techniques that work with RNA-seq data. We introduce a second generation splice detection algorithm, MapSplice, whose focus is high sensitivity and specificity in the detection of splices as well as CPU and memory efficiency. MapSplice can be applied to both short (<75 bp) and long reads (≥ 75 bp). MapSplice is not dependent on splice site features or intron length, consequently it can detect novel canonical as well as non-canonical splices. MapSplice leverages the quality and diversity of read alignments of a given splice to increase accuracy. We demonstrate that MapSplice achieves higher sensitivity and specificity than TopHat and SpliceMap on a set of simulated RNA-seq data. Experimental studies also support the accuracy of the algorithm. Splice junctions derived from eight breast cancer RNA-seq datasets recapitulated the extensiveness of alternative splicing on a global level as well as the differences between molecular subtypes of breast cancer. These combined results indicate that MapSplice is a highly accurate algorithm for the alignment of RNA-seq reads to splice junctions. Software download URL: http://www.netlab.uky.edu/p/bioinfo/MapSplice. PMID:20802226

  4. Fabrication of a Mono-Domain Alignment Ferroelectric Liquid Crystal Device Using a Polar Self-Assembled Monolayer

    Institute of Scientific and Technical Information of China (English)

    ZOU Zhong-Fei; YAO Li-Shuang; TANG Xian-Zhu; JI Xin-Jian; XUAN Li

    2008-01-01

    A mono-domain ferroelectric liquid crystal device (FLCD) is fabricated using a novel method. The cell used in this method is an asymmetric cell, typically the combination of a polar self-assembled monolayer (SAM) for one substrate and a rubbed polyimide for the other substrate. A defect-free alignment of ferroelectric liquid crystal is fabricated without applying a dc voltage to remove degeneracy in the layer structure. The contact angles of self-assembled monolayer and PI-2942 are measured and the polarity of SAM is higher than the PI alignment. It is found that the polarity of self-assembled monolayer is a key factor in the formation of mono-domain alignment of FLC.

  5. Investigation of the growth and spontaneous alignment of lanthanum gallate self-assembled microdots on Si(111) surface

    International Nuclear Information System (INIS)

    Full text: The formation of self-assembled Quantum Dots (QDs) on semiconductor surfaces is well-known. We have used RF sputtering to produce self-assembled islands of doped Lanthanum Gallate on Si(III) substrate that are several orders of magnitude larger than the QDs. These microdots, however, share many features with Quantum Dots, such as the ability for spontaneous alignment. We present our Scanning Electron Microscopy (SEM) and Energy Dispersive Spectrometry (EDS) results, and put forward explanations of the formation and alignment by reference to the Stranski-Krastanov (SK) Growth Mechanism. Copyright (2005) Australian Institute of Physics

  6. Vertically aligned self-assembled gold nanorods as low turn-on, stable field emitters

    Science.gov (United States)

    Apte, Amey; Joshi, Padmashree; Bhaskar, Prashant; Joag, Dilip; Kulkarni, Sulabha

    2015-11-01

    In this work we have investigated field emission from self-assembled, vertically aligned, gold nanorod arrays, which were synthesized via a colloidal growth method. A field emission current density of ∼1 mA/cm2 was measured for these gold nanorod arrays using an anode-cathode separation of ∼3.5 mm. The field emission investigation of these gold nanorod arrays was carried out at a base pressure of ∼10-8 mbar. The turn on field, defined as the electric field required to obtain a current density of 1 μA/cm2, is observed to be 1.9 V/μm. Assuming a work function value of 5.3 eV, the field enhancement factor β is estimated to be ∼2931, which is higher than the reported values for other gold nanostructures/arrays.

  7. Fuel assembly alignment pins, development of a new hard faced design

    International Nuclear Information System (INIS)

    Ni-base alloys for fuel assembly alignment pins showed corrosion behaviour which was not satisfactory for service conditions in PWR's. For future applications a new material design was established. Determined by the operating requirements a solution with austenitic stainless steel and a thin hardfacing layer by detonation-gun coating technique was developed. For qualification purposes several system properties as application process, corrosion resistance, bond strength, thermal fatigue behaviour, wear resistance and irradiation behaviour were investigated. The coating process was specified, a quality assurance program was established. Corrosion resistance was examined by autoclave corrosion tests. The wear mechanism, wear rates and surface roughening were determined in both, high and room temperature wear tests. Also results of irradiation exposed specimens for material changes and embrittlement are reported. The test procedures and test results are described and lead to an acceptable and reliable design. The application feed back proves the qualification results. (authors). 6 figs

  8. Satellite Alignment: I. Distribution of Substructures and Their Dependence On Assembly History From N-Body Simulations

    CERN Document Server

    Wang, Yang Ocean; Kang, Xi; Dutton, Aaron; Yu, Yu; Macciò, Andrea V

    2014-01-01

    Observations have shown that the spatial distribution of satellite galaxies is not random, but aligned with the major axes of central galaxies. This alignment is dependent on galaxy properties, such that red satellites are more strongly aligned than blue satellites. Theoretical work done to interpret this phenomena has found that it is due to the non-spherical nature of dark matter halos. However, most studies over-predict the alignment signal under the assumption that the central galaxy shape follows the shape of the host halo. It is also not clear whether the color dependence of alignment is due to an assembly bias or an evolution effect. In this paper we study these problems using a cosmological N-body simulation. Subhalos are used to trace the positions of satellite galaxies. It is found that the shape of dark matter halos are mis-aligned at different radii. If the central galaxy shares the same shape as the inner host halo, then the alignment effect is weaker and agrees with observational data. However, ...

  9. Comprehensive analysis of alternative splicing in rice and comparative analyses with Arabidopsis

    Directory of Open Access Journals (Sweden)

    Mount Stephen M

    2006-12-01

    Full Text Available Abstract Background Recently, genomic sequencing efforts were finished for Oryza sativa (cultivated rice and Arabidopsis thaliana (Arabidopsis. Additionally, these two plant species have extensive cDNA and expressed sequence tag (EST libraries. We employed the Program to Assemble Spliced Alignments (PASA to identify and analyze alternatively spliced isoforms in both species. Results A comprehensive analysis of alternative splicing was performed in rice that started with >1.1 million publicly available spliced ESTs and over 30,000 full length cDNAs in conjunction with the newly enhanced PASA software. A parallel analysis was performed with Arabidopsis to compare and ascertain potential differences between monocots and dicots. Alternative splicing is a widespread phenomenon (observed in greater than 30% of the loci with transcript support and we have described nine alternative splicing variations. While alternative splicing has the potential to create many RNA isoforms from a single locus, the majority of loci generate only two or three isoforms and transcript support indicates that these isoforms are generally not rare events. For the alternate donor (AD and acceptor (AA classes, the distance between the splice sites for the majority of events was found to be less than 50 basepairs (bp. In both species, the most frequent distance between AA is 3 bp, consistent with reports in mammalian systems. Conversely, the most frequent distance between AD is 4 bp in both plant species, as previously observed in mouse. Most alternative splicing variations are localized to the protein coding sequence and are predicted to significantly alter the coding sequence. Conclusion Alternative splicing is widespread in both rice and Arabidopsis and these species share many common features. Interestingly, alternative splicing may play a role beyond creating novel combinations of transcripts that expand the proteome. Many isoforms will presumably have negative

  10. Novel surface treatment materials for aligning block-co-polymer in directed self-assembly processes

    Science.gov (United States)

    Someya, Yasunobu; Wakayama, Hiroyuki; Endo, Takafumi; Sakamoto, Rikimaru

    2014-03-01

    Directed Self-Assembly (DSA) process is one of the attractive processes for creating the very fine pitch pattern. Especially, the contact hole shrink processes with block-co-polymer (BCP) or polymer blend materials were attractive processes for creating very small size hole patterns with better CD uniformity compare to general photo-lithography patterning. In general contact hole shrink process, the pattern of Spin-on Carbon Hardmask (SOC) or the photo Resist pattern created by Negative-Tone Development (NTD) process were selected for guide patterns. Since the alignment property of BCP was affected by the surface of these guide materials, it is important to control the surface condition of guide in order to obtain good shrunk contact hole patterns. In this study, we will report the surface treatment materials to control the surface condition of guide patterns such as SOC or NTD resist to achieve the better contact hole shrink performance. These materials were attached to guide pattern surface and controlled the surface energy.

  11. Satellite alignment. I. Distribution of substructures and their dependence on assembly history from n-body simulations

    International Nuclear Information System (INIS)

    Observations have shown that the spatial distribution of satellite galaxies is not random, but aligned with the major axes of central galaxies. This alignment is dependent on galaxy properties, such that red satellites are more strongly aligned than blue satellites. Theoretical work conducted to interpret this phenomenon has found that it is due to the non-spherical nature of dark matter halos. However, most studies overpredict the alignment signal under the assumption that the central galaxy shape follows the shape of the host halo. It is also not clear whether the color dependence of alignment is due to an assembly bias or an evolution effect. In this paper we study these problems using a cosmological N-body simulation. Subhalos are used to trace the positions of satellite galaxies. It is found that the shapes of dark matter halos are mis-aligned at different radii. If the central galaxy shares the same shape as the inner host halo, then the alignment effect is weaker and agrees with observational data. However, it predicts almost no dependence of alignment on the color of satellite galaxies, though the late accreted subhalos show stronger alignment with the outer layer of the host halo than their early accreted counterparts. We find that this is due to the limitation of pure N-body simulations where satellite galaxies without associated subhalos ('orphan galaxies') are not resolved. These orphan (mostly red) satellites often reside in the inner region of host halos and should follow the shape of the host halo in the inner region.

  12. Satellite alignment. I. Distribution of substructures and their dependence on assembly history from n-body simulations

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yang Ocean; Lin, W. P.; Yu, Yu [Key Laboratory for Research in Galaxies and Cosmology, Shanghai Astronomical Observatory, Chinese Academy of Science, 80 Nandan Road, Shanghai 200030 (China); Kang, X. [The Partner Group of MPI for Astronomy, Purple Mountain Observatory, 2 West Beijing Road, Nanjing 210008 (China); Dutton, Aaron; Macciò, Andrea V., E-mail: wangyang@shao.ac.cn, E-mail: linwp@shao.ac.cn [Max-Planck-Institute für Astronomie, Königstuhl 17, D-69117 Heidelberg (Germany)

    2014-05-01

    Observations have shown that the spatial distribution of satellite galaxies is not random, but aligned with the major axes of central galaxies. This alignment is dependent on galaxy properties, such that red satellites are more strongly aligned than blue satellites. Theoretical work conducted to interpret this phenomenon has found that it is due to the non-spherical nature of dark matter halos. However, most studies overpredict the alignment signal under the assumption that the central galaxy shape follows the shape of the host halo. It is also not clear whether the color dependence of alignment is due to an assembly bias or an evolution effect. In this paper we study these problems using a cosmological N-body simulation. Subhalos are used to trace the positions of satellite galaxies. It is found that the shapes of dark matter halos are mis-aligned at different radii. If the central galaxy shares the same shape as the inner host halo, then the alignment effect is weaker and agrees with observational data. However, it predicts almost no dependence of alignment on the color of satellite galaxies, though the late accreted subhalos show stronger alignment with the outer layer of the host halo than their early accreted counterparts. We find that this is due to the limitation of pure N-body simulations where satellite galaxies without associated subhalos ('orphan galaxies') are not resolved. These orphan (mostly red) satellites often reside in the inner region of host halos and should follow the shape of the host halo in the inner region.

  13. A pseudo 3D glass microprobe array: glass microprobe with embedded silicon for alignment and electrical interconnection during assembly

    International Nuclear Information System (INIS)

    This study presents a process for the assembling of a pseudo 3D glass microprobe array. A glass microprobe with embedded silicon (ES) is batch fabricated by a glass reflow process. The silicon fixture and carrier for the assembly are also batch fabricated by silicon micromachining processes. First, the chips with a glass microprobe array are bonded by parylene-C to form the pseudo 3D glass microprobe array. The pseudo 3D microprobe array is then mounted on the silicon carrier. ES is employed for alignment during the assembly, and also acts as the electrical routing for signal recording. In application, the impedance of this glass microprobe is measured, and at 1 kHz it is 1.1 MΩ. Action potentials from rat brain cortex are also successfully recorded.

  14. Control of Alternative Splicing by Signal-dependent Degradation of Splicing-regulatory Proteins*S⃞

    OpenAIRE

    Katzenberger, Rebeccah J.; Marengo, Matthew S.; Wassarman, David A.

    2009-01-01

    Alternative pre-mRNA splicing is a major gene expression regulatory mechanism in metazoan organisms. Proteins that bind pre-mRNA elements and control assembly of splicing complexes regulate utilization of pre-mRNA alternative splice sites. To understand how signaling pathways impact this mechanism, an RNA interference screen in Drosophila S2 cells was used to identify proteins that regulate TAF1 (TBP-associated factor 1) alternative splicing in response to activation o...

  15. Large-scale submicron horizontally aligned single-walled carbon nanotube surface arrays on various substrates produced by a fluidic assembly method

    International Nuclear Information System (INIS)

    Single-walled carbon nanotube (CNT) arrays have been assembled on various substrates over mm-scale surface areas by combining fluidic alignment with soft lithography (micropatterning in capillaries) techniques. The feature size of the nanotube patterns reaches down to submicrometre scale. To this end, tailored substrate surface modification and pre-alignment of chopped CNTs in suspension are highly critical

  16. Large-scale submicron horizontally aligned single-walled carbon nanotube surface arrays on various substrates produced by a fluidic assembly method.

    Science.gov (United States)

    Yan, Y H; Li, S; Chen, L Q; Chan-Park, M B; Zhang, Qing

    2006-11-28

    Single-walled carbon nanotube (CNT) arrays have been assembled on various substrates over mm-scale surface areas by combining fluidic alignment with soft lithography (micropatterning in capillaries) techniques. The feature size of the nanotube patterns reaches down to submicrometre scale. To this end, tailored substrate surface modification and pre-alignment of chopped CNTs in suspension are highly critical. PMID:21727344

  17. SplicingTypesAnno: annotating and quantifying alternative splicing events for RNA-Seq data.

    Science.gov (United States)

    Sun, Xiaoyong; Zuo, Fenghua; Ru, Yuanbin; Guo, Jiqiang; Yan, Xiaoyan; Sablok, Gaurav

    2015-04-01

    Alternative splicing plays a key role in the regulation of the central dogma. Four major types of alternative splicing have been classified as intron retention, exon skipping, alternative 5 splice sites or alternative donor sites, and alternative 3 splice sites or alternative acceptor sites. A few algorithms have been developed to detect splice junctions from RNA-Seq reads. However, there are few tools targeting at the major alternative splicing types at the exon/intron level. This type of analysis may reveal subtle, yet important events of alternative splicing, and thus help gain deeper understanding of the mechanism of alternative splicing. This paper describes a user-friendly R package, extracting, annotating and analyzing alternative splicing types for sequence alignment files from RNA-Seq. SplicingTypesAnno can: (1) provide annotation for major alternative splicing at exon/intron level. By comparing the annotation from GTF/GFF file, it identifies the novel alternative splicing sites; (2) offer a convenient two-level analysis: genome-scale annotation for users with high performance computing environment, and gene-scale annotation for users with personal computers; (3) generate a user-friendly web report and additional BED files for IGV visualization. SplicingTypesAnno is a user-friendly R package for extracting, annotating and analyzing alternative splicing types at exon/intron level for sequence alignment files from RNA-Seq. It is publically available at https://sourceforge.net/projects/splicingtypes/files/ or http://genome.sdau.edu.cn/research/software/SplicingTypesAnno.html. PMID:25720307

  18. Alignment and Use of Self-Assembled Peptide Nanotubes as Dry-Etching Mask

    DEFF Research Database (Denmark)

    Andersen, Karsten Brandt; Castillo, Jaime; Bakmand, Tanya;

    2012-01-01

    Self-assembled diphenylalanine peptide nanotubes provide a means of achieving nanostructured materials in a very simple and fast way. Recent discoveries have shown that this unique material, in addition to remaining stable under dry conditions, rapidly dissolves in water making it a promising...

  19. Self-formation of highly aligned metallic, semiconducting and single chiral single-walled carbon nanotubes assemblies via a crystal template method

    Energy Technology Data Exchange (ETDEWEB)

    Kawai, Hideki; Hasegawa, Kai; Yanagi, Kazuhiro, E-mail: yanagi-kazuhiro@tmu.ac.jp [Department of Physics, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397 (Japan); Oyane, Ayako [Nanosystem Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8562 (Japan); Naitoh, Yasuhisa [Nanosystem Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8564 (Japan)

    2014-09-01

    The fabrication of an aligned array of single-walled carbon nanotubes (SWCNTs) with a single chiral state has been a significant challenge for SWCNT applications as well as for basic science research. Here, we developed a simple, unique technique to produce assemblies in which metallic, semiconducting, and single chiral state SWCNTs were densely and highly aligned. We utilized a crystal of surfactant as a template on which mono-dispersed SWCNTs in solution self-assembled. Micro-Raman measurements and scanning electron microscopy measurements clearly showed that the SWCNTs were highly and densely aligned parallel to the crystal axis, indicating that approximately 70% of the SWCNTs were within 7° of being parallel. Moreover, the assemblies exhibited good field effect transistor characteristics with an on/off ratio of 1.3 × 10{sup 5}.

  20. Self-formation of highly aligned metallic, semiconducting and single chiral single-walled carbon nanotubes assemblies via a crystal template method

    International Nuclear Information System (INIS)

    The fabrication of an aligned array of single-walled carbon nanotubes (SWCNTs) with a single chiral state has been a significant challenge for SWCNT applications as well as for basic science research. Here, we developed a simple, unique technique to produce assemblies in which metallic, semiconducting, and single chiral state SWCNTs were densely and highly aligned. We utilized a crystal of surfactant as a template on which mono-dispersed SWCNTs in solution self-assembled. Micro-Raman measurements and scanning electron microscopy measurements clearly showed that the SWCNTs were highly and densely aligned parallel to the crystal axis, indicating that approximately 70% of the SWCNTs were within 7° of being parallel. Moreover, the assemblies exhibited good field effect transistor characteristics with an on/off ratio of 1.3 × 105.

  1. Alignment of human cardiomyocytes on laser patterned biphasic core/shell nanowire assemblies

    International Nuclear Information System (INIS)

    The management of end stage heart failure patients is only possible by heart transplantation or by the implantation of artificial hearts as a bridge for later transplantation. However, these therapeutic strategies are limited by a lack of donor hearts and by the associated complications, such as coagulation and infection, due to the used artificial mechanical circulatory assist devices. Therefore, new strategies for myocardial regenerative approaches are under extensive research to produce contractile myocardial tissue in the future to replace non-contractile myocardial ischemic and scarred tissue. Different approaches, such as cell transplantation, have been studied intensively. Although successful approaches have been observed, there are still limitations to the application. It is envisaged that myocardial tissue engineering can be used to help replace infarcted non-contractile tissue. The developed tissue should later mimic the aligned fibrillar structure of the extracellular matrix and provide important guidance cues for the survival, function and the needed orientation of cardiomyocytes. Nanostructured surfaces have been tested to provide a guided direction that cells can follow. In the present study, the cellular adhesion/alignment of human cardiomyocytes and the biocompatibility have been investigated after cultivation on different laser-patterned nanowires compared with unmodified nanowires. As a result, the nanostructured surfaces possessed good biocompatibility before and after laser modification. The laser-induced scalability of the pattern enabled the growth and orientation of the adhered myocardial tissue. Such approaches may be used to modify the surface of potential scaffolds to develop myocardial contractile tissue in the future. (paper)

  2. Tuning molecular level alignment and work function modification through self-assembled monolayers on noble metals: theoretical perspectives

    International Nuclear Information System (INIS)

    Full text: There is currently significant interest in highly-ordered, self-assembled monolayers (SAMs) on (noble) metal surfaces, inspired both by the emergence of the field of molecular electronics alongside the high potential for SAMs to improve the properties of more conventional device structures. SAMs are also used to control surface reactivity and for chemical sensing applications. In order to tune the interface properties and to endow the self-assembled systems with functionality suitable for use in either macroscopic or nanoscale devices, the use of π-conjugated systems is highly promising and the focus of intense, multidisciplinary research. The goal of the present study is to provide an in-depth description of the electronic structure of the interface between metallic substrates and covalently bound conjugated molecules. In this way, we expect to devise strategies to tune the interaction and thus the properties of the investigated systems and eventually to gain a full understanding of the processes governing the electronics of metal/organic interfaces. Here, we describe a first step in that direction: we study conjugated SAMs consisting of molecules with widely varied molecular ionization potentials, different conjugated backbones with different polarizabilities, and monolayers with varying degrees of coverage. We consider noble metals with varying work functions such as Au, Ag, and Pt, different molecule docking groups and investigate the effects of mechanical stress on the organic system. Using DFT band-structure-type methods, the details of the interface morphology, charge transfer between the metal and the molecules, interface dipoles, molecular layer depolarization, and work function modifications as well as the alignment between metallic and molecular levels are described. Our thorough analysis provides results that are sometimes a priori unexpected, like the finding that by properly tuning the molecular structure, the level alignment between the

  3. Quick synthesis of highly aligned or randomly oriented nanofibrous structures composed of C60 molecules via self-assembly

    Science.gov (United States)

    Kurosu, Shunji; Fukuda, Takahiro; Maekawa, Toru

    2013-06-01

    Assemblies, which are composed of nanoparticles such as nanofibres, have been intensively studied in recent years. This has particularly been the case in the field of biomedicine, where the aim is to develop efficient methodologies for capturing and separating target biomolecules and cells and/or encouraging bio-chemical reactions, utilizing the extremely high surface area to volume ratio of assemblies. There is an urgent need for the development of a quick synthesis method of forming nanofibrous structures on the surface of biomedical microchips and devices for the investigation of the interactions between biomolecules/cells and the nanostructures. Here, we produce nanofibrous structures composed of C60 molecules, which are aligned in one direction or randomly oriented, by dissolving C60 molecules and sulphur in benzene and evaporating a droplet of the solution on a glass substrate under appropriate conditions. The synthesis time is as short as 30 s. Sulphur is extracted and nanofibres are crystallized by leaving them in supercritical carbon dioxide.

  4. Self-assembly of designed precursors: A route to crystallographically aligned new materials with controlled nanoarchitecture

    Science.gov (United States)

    Westover, Richard; Atkins, Ryan A.; Falmbigl, Matthias; Ditto, Jeffrey J.; Johnson, David C.

    2016-04-01

    Modulated elemental reactants is a method by which new and complex intergrowth compounds can be synthesized by the self-assembly of designed precursors prepared by physical vapor deposition. Careful calibration of the composition and thickness of the precursors ensures the formation of the desired product by precise control of local composition and diffusion lengths. Superstructures of increasing complexity can be realized using binary and ternary systems as starting points. The synthesis of systems based on three different binary compounds, either alloyed together or separated into distinct layers, expands the number of possible superstructures that can be formed using this technique, but provides analytical challenges. The synthesis of [(SnSe)1.15]1([TaxV1-x]Se2)1[(SnSe)1.15]1([VyTa1-y]Se2)1 compound is used to illustrate the preparation of precursors and the challenges in both measuring and limiting the interdiffusion of layers during self-assembly. Systematic changes in the electrical properties of (SnSe)1+δ(TaxV1-x)Se2 alloys are observed as x is varied. The electrical resistivity of [(SnSe)1.15]1([TaxV1-x]Se2)1[(SnSe)1.15]1([VyTa1-y]Se2)1 can be modeled as the two constituent layers in parallel.

  5. Cotranscriptional splicing efficiency differs dramatically between Drosophila and mouse

    OpenAIRE

    Khodor, Yevgenia L.; Menet, Jerome S; Tolan, Michael; Rosbash, Michael

    2012-01-01

    Spliceosome assembly and/or splicing of a nascent transcript may be crucial for proper isoform expression and gene regulation in higher eukaryotes. It has been shown that cotranscriptional splicing occurs efficiently in Drosophila, but there are not comparable genome-wide nascent splicing data from mammals. To provide this comparison, the authors analyzed a recently generated, high-throughput sequencing data set of mouse liver nascent RNA. Cotranscriptional splicing is approximately twofold l...

  6. High electrocatalytic activity of Pt-Pd binary spherocrystals chemically assembled in vertically aligned TiO2 nanotubes.

    Science.gov (United States)

    Lei, Yanzhu; Zhao, Guohua; Tong, Xili; Liu, Meichuan; Li, Dongming; Geng, Rong

    2010-01-18

    To obtain noble metal catalysts with high efficiency, long-term stability, and poison resistance, Pt and Pd are assembled in highly ordered and vertically aligned TiO(2) nanotubes (NTs) by means of the pulsed-current deposition (PCD) method with assistance of ultrasonication (UC). Here, Pd serves as a dispersant which prevents agglomeration of Pt. Thus Pt-Pd binary catalysts are embed into TiO(2) NTs array under UC in sunken patterns of composite spherocrystals (Sps). Owing to this synthesis method and restriction by the NTs, the these catalysts show improved dispersion, more catalytically active sites, and higher surface area. This nanotubular metallic support material with good physical and chemical stability prevents catalyst loss and poisoning. Compared with monometallic Pt and Pd, the sunken-structured Pt-Pd spherocrystal catalyst exhibits better catalytic activity and poison resistance in electrocatalytic methanol oxidation because of its excellent dispersion. The catalytic current density is enhanced by about 15 and 310 times relative to monometallic Pt and Pd, respectively. The poison resistance of the Pt-Pd catalyst was 1.5 times higher than that of Pt and Pd, and they show high electrochemical stability with a stable current enduring for more than 2100 s. Thus, the TiO(2) NTs on a Ti substrate serve as an excellent support material for the loading and dispersion of noble metal catalysts. PMID:19924757

  7. ScanIndel: a hybrid framework for indel detection via gapped alignment, split reads and de novo assembly.

    Science.gov (United States)

    Yang, Rendong; Nelson, Andrew C; Henzler, Christine; Thyagarajan, Bharat; Silverstein, Kevin A T

    2015-01-01

    Comprehensive identification of insertions/deletions (indels) across the full size spectrum from second generation sequencing is challenging due to the relatively short read length inherent in the technology. Different indel calling methods exist but are limited in detection to specific sizes with varying accuracy and resolution. We present ScanIndel, an integrated framework for detecting indels with multiple heuristics including gapped alignment, split reads and de novo assembly. Using simulation data, we demonstrate ScanIndel's superior sensitivity and specificity relative to several state-of-the-art indel callers across various coverage levels and indel sizes. ScanIndel yields higher predictive accuracy with lower computational cost compared with existing tools for both targeted resequencing data from tumor specimens and high coverage whole-genome sequencing data from the human NIST standard NA12878. Thus, we anticipate ScanIndel will improve indel analysis in both clinical and research settings. ScanIndel is implemented in Python, and is freely available for academic use at https://github.com/cauyrd/ScanIndel. PMID:26643039

  8. Splicing Programs and Cancer

    OpenAIRE

    Sophie Germann; Lise Gratadou; Martin Dutertre; Didier Auboeuf

    2012-01-01

    Numerous studies report splicing alterations in a multitude of cancers by using gene-by-gene analysis. However, understanding of the role of alternative splicing in cancer is now reaching a new level, thanks to the use of novel technologies allowing the analysis of splicing at a large-scale level. Genome-wide analyses of alternative splicing...

  9. Choice of reference sequence and assembler for alignment of Listeria monocytogenes short-read sequence data greatly influences rates of error in SNP analyses.

    Science.gov (United States)

    Pightling, Arthur W; Petronella, Nicholas; Pagotto, Franco

    2014-01-01

    The wide availability of whole-genome sequencing (WGS) and an abundance of open-source software have made detection of single-nucleotide polymorphisms (SNPs) in bacterial genomes an increasingly accessible and effective tool for comparative analyses. Thus, ensuring that real nucleotide differences between genomes (i.e., true SNPs) are detected at high rates and that the influences of errors (such as false positive SNPs, ambiguously called sites, and gaps) are mitigated is of utmost importance. The choices researchers make regarding the generation and analysis of WGS data can greatly influence the accuracy of short-read sequence alignments and, therefore, the efficacy of such experiments. We studied the effects of some of these choices, including: i) depth of sequencing coverage, ii) choice of reference-guided short-read sequence assembler, iii) choice of reference genome, and iv) whether to perform read-quality filtering and trimming, on our ability to detect true SNPs and on the frequencies of errors. We performed benchmarking experiments, during which we assembled simulated and real Listeria monocytogenes strain 08-5578 short-read sequence datasets of varying quality with four commonly used assemblers (BWA, MOSAIK, Novoalign, and SMALT), using reference genomes of varying genetic distances, and with or without read pre-processing (i.e., quality filtering and trimming). We found that assemblies of at least 50-fold coverage provided the most accurate results. In addition, MOSAIK yielded the fewest errors when reads were aligned to a nearly identical reference genome, while using SMALT to align reads against a reference sequence that is ∼0.82% distant from 08-5578 at the nucleotide level resulted in the detection of the greatest numbers of true SNPs and the fewest errors. Finally, we show that whether read pre-processing improves SNP detection depends upon the choice of reference sequence and assembler. In total, this study demonstrates that researchers should

  10. Choice of reference sequence and assembler for alignment of Listeria monocytogenes short-read sequence data greatly influences rates of error in SNP analyses.

    Directory of Open Access Journals (Sweden)

    Arthur W Pightling

    Full Text Available The wide availability of whole-genome sequencing (WGS and an abundance of open-source software have made detection of single-nucleotide polymorphisms (SNPs in bacterial genomes an increasingly accessible and effective tool for comparative analyses. Thus, ensuring that real nucleotide differences between genomes (i.e., true SNPs are detected at high rates and that the influences of errors (such as false positive SNPs, ambiguously called sites, and gaps are mitigated is of utmost importance. The choices researchers make regarding the generation and analysis of WGS data can greatly influence the accuracy of short-read sequence alignments and, therefore, the efficacy of such experiments. We studied the effects of some of these choices, including: i depth of sequencing coverage, ii choice of reference-guided short-read sequence assembler, iii choice of reference genome, and iv whether to perform read-quality filtering and trimming, on our ability to detect true SNPs and on the frequencies of errors. We performed benchmarking experiments, during which we assembled simulated and real Listeria monocytogenes strain 08-5578 short-read sequence datasets of varying quality with four commonly used assemblers (BWA, MOSAIK, Novoalign, and SMALT, using reference genomes of varying genetic distances, and with or without read pre-processing (i.e., quality filtering and trimming. We found that assemblies of at least 50-fold coverage provided the most accurate results. In addition, MOSAIK yielded the fewest errors when reads were aligned to a nearly identical reference genome, while using SMALT to align reads against a reference sequence that is ∼0.82% distant from 08-5578 at the nucleotide level resulted in the detection of the greatest numbers of true SNPs and the fewest errors. Finally, we show that whether read pre-processing improves SNP detection depends upon the choice of reference sequence and assembler. In total, this study demonstrates that researchers

  11. Embracing the complexity of pre-mRNA splicing

    Institute of Scientific and Technical Information of China (English)

    Peter J Shepard; Klemens J Hertel

    2010-01-01

    @@ Pre-mRNA splicing is a fundamental process required for the expression of most metazoan genes. It is carried out by the spliceosome, which catalyzes the removal of non-coding intronic sequences to assemble exons into mature mRNAs prior to export and translation.Defects in splicing lead to many human genetic diseases [1], and splicing mutations in a number of genes involved in growth control have been implicated in multiple types of cancer.

  12. Self-alignment of RFID dies on four-pad patterns with water droplet for sparse self-assembly

    International Nuclear Information System (INIS)

    This paper reports an in-depth study of a water-droplet-assisted self-alignment technique that self-aligns radio frequency identification (RFID) dies on four-pad patterns. The segmented structure of four hydrophilic pads on a hydrophobic substrate brings freedom to the design of the electrical functionality and the surface functionality. The paper investigates the influence of the key parameters that may affect the self-alignment in theory and experiment. The theoretical model justifies that RFID dies can be reliably aligned on the segmented four-pad pattern even when the initial placement error is as large as 50% of the size of the die and the gap between the four pads is about 10% of the size of the die. A method has been introduced to estimate the sufficient droplet volume for self-alignment. A series of experiments have been carried out to verify the results of the model. The experiments indicate that the self-alignment between the 730 × 730 µm RFID dies and the pattern occurs reliably when the releasing bias between the RFID die and antenna is less than 400 µm for patterns with 50 and 100 µm gaps, and successful self-alignment is possible even with greater bias of 500 µm

  13. Self-Assembly of Chip-Size Components with Cavity Structures: High-Precision Alignment and Direct Bonding without Thermal Compression for Hetero Integration

    Directory of Open Access Journals (Sweden)

    Mitsumasa Koyanagi

    2011-02-01

    Full Text Available New surface mounting and packaging technologies, using self-assembly with chips having cavity structures, were investigated for three-dimensional (3D and hetero integration of complementary metal-oxide semiconductors (CMOS and microelectromechanical systems (MEMS. By the surface tension of small droplets of 0.5 wt% hydrogen fluoride (HF aqueous solution, the cavity chips, with a side length of 3 mm, were precisely aligned to hydrophilic bonding regions on the surface of plateaus formed on Si substrates. The plateaus have micro-channels to readily evaporate and fully remove the liquid from the cavities. The average alignment accuracy of the chips with a 1 mm square cavity was found to be 0.4 mm. The alignment accuracy depends, not only on the area of the bonding regions on the substrates and the length of chip periphery without the widths of channels in the plateaus, but also the area wetted by the liquid on the bonding regions. The precisely aligned chips were then directly bonded to the substrates at room temperature without thermal compression, resulting in a high shear bonding strength of more than 10 MPa.

  14. Complex Alternative Splicing

    OpenAIRE

    Park, Jung Woo; Graveley, Brenton R.

    2007-01-01

    Alternative splicing is a powerful means of controlling gene expression and increasing protein diversity. Most genes express a limited number of mRNA isoforms, but there are several examples of genes that use alternative splicing to generate hundreds, thousands, and even tens of thousands of isoforms. Collectively such genes are considered to undergo complex alternative splicing. The best example is the Drosophila Down syndrome cell adhesion molecule (Dscam) gene, which can generate 38,016 is...

  15. Where splicing joins chromatin

    OpenAIRE

    Hnilicová, Jarmila; Staněk, David

    2011-01-01

    There are numerous data suggesting that two key steps in gene expression—transcription and splicing influence each other closely. For a long time it was known that chromatin modifications regulate transcription, but only recently it was shown that chromatin and histone modifications play a significant role in pre-mRNA splicing. Here we summarize interactions between splicing machinery and chromatin and discuss their potential functional significance. We focus mainly on histone acetylation and...

  16. spliceR

    DEFF Research Database (Denmark)

    Vitting-Seerup, Kristoffer; Porse, Bo Torben; Sandelin, Albin;

    2014-01-01

    RNA-seq data is currently underutilized, in part because it is difficult to predict the functional impact of alternate transcription events. Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing...

  17. A study of alternative splicing in the pig

    Directory of Open Access Journals (Sweden)

    Jørgensen Claus B

    2010-05-01

    Full Text Available Abstract Background Since at least half of the genes in mammalian genomes are subjected to alternative splicing, alternative pre-mRNA splicing plays an important contribution to the complexity of the mammalian proteome. Expressed sequence tags (ESTs provide evidence of a great number of possible alternative isoforms. With the EST resource for the domestic pig now containing more than one million porcine ESTs, it is possible to identify alternative splice forms of the individual transcripts in this species from the EST data with some confidence. Results The pig EST data generated by the Sino-Danish Pig Genome project has been assembled with publicly available ESTs and made available in the PigEST database. Using the Distiller package 2,515 EST clusters with candidate alternative isoforms were identified in the EST data with high confidence. In agreement with general observations in human and mouse, we find putative splice variants in about 30% of the contigs with more than 50 ESTs. Based on the criteria that a minimum of two EST sequences confirmed each splice event, a list of 100 genes with the most distinct tissue-specific alternative splice events was generated from the list of candidates. To confirm the tissue specificity of the splice events, 10 genes with functional annotation were randomly selected from which 16 individual splice events were chosen for experimental verification by quantitative PCR (qPCR. Six genes were shown to have tissue specific alternatively spliced transcripts with expression patterns matching those of the EST data. The remaining four genes had tissue-restricted expression of alternative spliced transcripts. Five out of the 16 splice events that were experimentally verified were found to be putative pig specific. Conclusions In accordance with human and rodent studies we estimate that approximately 30% of the porcine genes undergo alternative splicing. We found a good correlation between EST predicted tissue

  18. Synthesis, transfer printing, electrical and optical properties, and applications of materials composed of self-assembled, aligned single-walled carbon nanotubes

    Science.gov (United States)

    Pint, Cary L.

    Super growth of single-walled carbon nanotubes (SWNTs) has emerged as a unique method for synthesizing self-assembled, pristine, aligned SWNT materials composed of ultra-long (millimeter-long) nanotubes. This thesis focuses on novel routes of synthesizing such self-assembled SWNTs and the challenges that arise in integrating this material into next-generation applications. First of all, this work provides unique insight into growth termination of aligned SWNTs, emphasizing the mechanism that inhibits the growth of infinitely long nanotubes. Exhaustive real-time growth studies, combined with ex-situ and in-situ TEM characterization emphasizes that Ostwald ripening and subsurface diffusion of catalyst particles play a key role in growth termination. As a result, rational steps to solving this problem can enhance growth, and may ultimately lead to the meter or kilometer-long SWNTs that are necessary for a number of applications. In addition, other novel synthesis routes are discussed, such as the ability to form macroscopic fibrils of SWNTs, called "flying carpets" from 40 nm thick substrates, and the ability to achieve supergrowth of SWNTs that are controllably doped with nitrogen. In the latter case, molecular heterojunctions of doped and undoped sections in a single strand of ultralong SWNTs are demonstrated Secondly, as supergrowth is conducted on alumina coated SiO2 substrates, any applications will require that one can transfer the SWNTs to host surfaces with minimal processing. This work demonstrates a unique contact transfer route by which both patterned arrays of SWNTs, or homogenous SWNT carpets, can be transferred to any host surface. In the first case, the SWNTs are grown vertically aligned, and transferred in patterns of horizontally aligned SWNT. This transfer process relies on simple water-vapor etching of amorphous carbons at the catalyst following growth, and strong van der Waals adhesion of the high surface-area SWNT to host surfaces (gecko effect

  19. Efficient Photocatalytic Degradation of Rhodamine B Dye by Aligned Arrays of Self-Assembled Hydrogen Titanate Nanotubes

    Directory of Open Access Journals (Sweden)

    Sriparna Chatterjee

    2014-01-01

    Full Text Available We show that an aligned array of hydrothermally grown, multiwalled hydrogen titanate (H2Ti3O7 nanotubes—anchored to both faces of a metallic Ti foil—acts as an efficient photocatalyst. We studied the degradation of rhodamine B dye in the presence of the nanostructured photocatalyst under UV irradiation, by monitoring the optical absorption of the dye. Rhodamine B was chosen as a representative—and particularly harmful—industrial pollutant dye. The inner and outer diameters of the H2Ti3O7 nanotubes were 5 nm and 10 nm, respectively. The nanotube array catalyst is recyclable and structurally stable. Most importantly, it shows comparable or higher photodecomposition rate constant than those of both H2Ti3O7 nanotube powder and P-25 (Degussa. The enhanced photocatalytic performance may be ascribed to the nanotube array having a superhydrophilic surface with a high accessible surface area.

  20. Genome-wide analysis of alternative splicing in Chlamydomonas reinhardtii

    Directory of Open Access Journals (Sweden)

    Thomas Julie

    2010-02-01

    Full Text Available Abstract Background Genome-wide computational analysis of alternative splicing (AS in several flowering plants has revealed that pre-mRNAs from about 30% of genes undergo AS. Chlamydomonas, a simple unicellular green alga, is part of the lineage that includes land plants. However, it diverged from land plants about one billion years ago. Hence, it serves as a good model system to study alternative splicing in early photosynthetic eukaryotes, to obtain insights into the evolution of this process in plants, and to compare splicing in simple unicellular photosynthetic and non-photosynthetic eukaryotes. We performed a global analysis of alternative splicing in Chlamydomonas reinhardtii using its recently completed genome sequence and all available ESTs and cDNAs. Results Our analysis of AS using BLAT and a modified version of the Sircah tool revealed AS of 498 transcriptional units with 611 events, representing about 3% of the total number of genes. As in land plants, intron retention is the most prevalent form of AS. Retained introns and skipped exons tend to be shorter than their counterparts in constitutively spliced genes. The splice site signals in all types of AS events are weaker than those in constitutively spliced genes. Furthermore, in alternatively spliced genes, the prevalent splice form has a stronger splice site signal than the non-prevalent form. Analysis of constitutively spliced introns revealed an over-abundance of motifs with simple repetitive elements in comparison to introns involved in intron retention. In almost all cases, AS results in a truncated ORF, leading to a coding sequence that is around 50% shorter than the prevalent splice form. Using RT-PCR we verified AS of two genes and show that they produce more isoforms than indicated by EST data. All cDNA/EST alignments and splice graphs are provided in a website at http://combi.cs.colostate.edu/as/chlamy. Conclusions The extent of AS in Chlamydomonas that we observed is much

  1. Hydrodynamic alignment and assembly of nano-fibrillated cellulose in the laminar extensional flow: Effects of solidifying agents

    Science.gov (United States)

    Mittal, Nitesh; Lundell, Fredrik; Soderberg, Daniel

    2015-11-01

    There are several fiber production technologies that are based on wet-spinning processes. Many such processes rely on the transformation of a liquid solution into a solid filament. The kinetics of solidification depends largely on the diffusion of the solvents, additives and polymer molecules, which make such systems quite complex and differ from a system to another as a function of the specific chemical, physical and structural features of the used material components. Moreover, tuning the orientation of the polymers in the liquid suspensions makes it further possible to control their structure, which in turn can lead to materials having improved properties. By keeping in mind the facts mentioned above, the aim of the current study is to utilize benefits of a flow focusing approach to align carboxymethylated cellulose nanofibrils (CNF), as a colloidal dispersion, with the help of a laminar elongational flow-field followed by the solidification using different solidifying agents or molecules (with dissimilar diffusion behavior based on their size and charges) to synthesize fibers with enhanced mechanical properties. CNF are charged elongated particles obtained from woods with diameter of 4-10 nm and length of 1-1.5 μm, and they are completely biodegradable.

  2. Cross-kingdom patterns of alternative splicing and splice recognition

    OpenAIRE

    Pearson, Matthew D.; McGuire, Abigail M; Neafsey, Daniel Edward; Galagan, James E.

    2007-01-01

    Background: Variations in transcript splicing can reveal how eukaryotes recognize intronic splice sites. Retained introns (RIs) commonly appear when the intron definition (ID) mechanism of splice site recognition inconsistently identifies intron-exon boundaries, and cassette exons (CEs) are often caused by variable recognition of splice junctions by the exon definition (ED) mechanism. We have performed a comprehensive survey of alternative splicing across 42 eukaryotes to gain ins...

  3. SpliceDisease database: linking RNA splicing and disease

    OpenAIRE

    WANG, Juan; Jie ZHANG; Li, Kaibo; Zhao, Wei; Cui, Qinghua

    2011-01-01

    RNA splicing is an important aspect of gene regulation in many organisms. Splicing of RNA is regulated by complicated mechanisms involving numerous RNA-binding proteins and the intricate network of interactions among them. Mutations in cis-acting splicing elements or its regulatory proteins have been shown to be involved in human diseases. Defects in pre-mRNA splicing process have emerged as a common disease-causing mechanism. Therefore, a database integrating RNA splicing and disease associa...

  4. Splicing regulators: targets and drugs

    OpenAIRE

    Yeo, Gene Wei-Ming

    2005-01-01

    Silencing of splicing regulators by RNA interference, combined with splicing-specific microarrays, has revealed a complex network of distinct alternative splicing events in Drosophila, while a high-throughput screen of more than 6,000 compounds has identified drugs that interfere specifically and directly with one class of splicing regulators in human cells.

  5. Horizontal carbon nanotube alignment.

    Science.gov (United States)

    Cole, Matthew T; Cientanni, Vito; Milne, William I

    2016-09-21

    The production of horizontally aligned carbon nanotubes offers a rapid means of realizing a myriad of self-assembled near-atom-scale technologies - from novel photonic crystals to nanoscale transistors. The ability to reproducibly align anisotropic nanostructures has huge technological value. Here we review the present state-of-the-art in horizontal carbon nanotube alignment. For both in and ex situ approaches, we quantitatively assess the reported linear packing densities alongside the degree of alignment possible for each of these core methodologies. PMID:27546174

  6. Optical Fiber Fusion Splicing

    CERN Document Server

    Yablon, Andrew D

    2005-01-01

    This book is an up-to-date treatment of optical fiber fusion splicing incorporating all the recent innovations in the field. It provides a toolbox of general strategies and specific techniques that the reader can apply when optimizing fusion splices between novel fibers. It specifically addresses considerations important for fusion splicing of contemporary specialty fibers including dispersion compensating fiber, erbium-doped gain fiber, polarization maintaining fiber, and microstructured fiber. Finally, it discusses the future of optical fiber fusion splicing including silica and non-silica based optical fibers as well as the trend toward increasing automation. Whilst serving as a self-contained reference work, abundant citations from the technical literature will enable readers to readily locate primary sources.

  7. Superconducting current transformer for testing Nb3Sn cable splicing technique

    International Nuclear Information System (INIS)

    To provide a quick feedback on different approaches to superconducting cable splicing design and assembly techniques, a superconducting current transformer that can deliver more than 20 kA for testing splice samples has been designed and fabricated. The existing infrastructure of the Short Sample Test Facility at Fermilab, including its cryostat, power supply, and data acquisition system, was used for housing and operating the transformer. This report presents the design features of the transformer and the main results of cable splice tests

  8. Detecting chimeric 5′/3′UTRs with cross-chromosomal splicing by bioinformatics

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhihua; ZHANG Yong; SHI Baochen; DENG Wei; ZHAO Yi; CHEN Runsheng

    2004-01-01

    The 5′/3′ UTRs of mRNA are crucial in translational regulation, and several serious diseases are believed to be associated with abnormal splicing of these parts of the mRNA sequence. In this work a novel method which uses sequence alignment database searching for detecting chimeric 5′3′ UTRs with cross-chromosomal splicing is reported. Eight highly credible instances of cross-chromosomal splicing have been found using this method, representing additional confirmation of the existence of cross-chromosomal splicing events provided by bioinformatics tools. Since no conserved motif has been found in any of the eight instances, and at the same time current prediction algorithms produce only trivial secondary structures at the "splicing sites", it is not possible to identify any specific signal leading to the splicing.

  9. Alternative splicing and muscular dystrophy

    OpenAIRE

    Pistoni, Mariaelena; Ghigna, Claudia; Gabellini, Davide

    2010-01-01

    Alternative splicing of pre-mRNAs is a major contributor to proteomic diversity and to the control of gene expression in higher eukaryotic cells. For this reasons, alternative splicing is tightly regulated in different tissues and developmental stages and its disruption can lead to a wide range of human disorders. The aim of this review is to focus on the relevance of alternative splicing for muscle function and muscle disease. We begin by giving a brief overview of alternative splicing, musc...

  10. Designing oligo libraries taking alternative splicing into account

    Science.gov (United States)

    Shoshan, Avi; Grebinskiy, Vladimir; Magen, Avner; Scolnicov, Ariel; Fink, Eyal; Lehavi, David; Wasserman, Alon

    2001-06-01

    We have designed sequences for DNA microarrays and oligo libraries, taking alternative splicing into account. Alternative splicing is a common phenomenon, occurring in more than 25% of the human genes. In many cases, different splice variants have different functions, are expressed in different tissues or may indicate different stages of disease. When designing sequences for DNA microarrays or oligo libraries, it is very important to take into account the sequence information of all the mRNA transcripts. Therefore, when a gene has more than one transcript (as a result of alternative splicing, alternative promoter sites or alternative poly-adenylation sites), it is very important to take all of them into account in the design. We have used the LEADS transcriptome prediction system to cluster and assemble the human sequences in GenBank and design optimal oligonucleotides for all the human genes with a known mRNA sequence based on the LEADS predictions.

  11. No statistical support for correlation between the positions of protein interaction sites and alternatively spliced regions

    Directory of Open Access Journals (Sweden)

    Gelfand Mikhail S

    2004-04-01

    Full Text Available Abstract Background Alternative splicing is an efficient mechanism for increasing the variety of functions fulfilled by proteins in a living cell. It has been previously demonstrated that alternatively spliced regions often comprise functionally important and conserved sequence motifs. The objective of this work was to test the hypothesis that alternative splicing is correlated with contact regions of protein-protein interactions. Results Protein sequence spans involved in contacts with an interaction partner were delineated from atomic structures of transient interaction complexes and juxtaposed with the location of alternatively spliced regions detected by comparative genome analysis and spliced alignment. The total of 42 alternatively spliced isoforms were identified in 21 amino acid chains involved in biomolecular interactions. Using this limited dataset and a variety of sophisticated counting procedures we were not able to establish a statistically significant correlation between the positions of protein interaction sites and alternatively spliced regions. Conclusions This finding contradicts a naïve hypothesis that alternatively spliced regions would correlate with points of contact. One possible explanation for that could be that all alternative splicing events change the spatial structure of the interacting domain to a sufficient degree to preclude interaction. This is indirectly supported by the observed lack of difference in the behaviour of relatively short regions affected by alternative splicing and cases when large portions of proteins are removed. More structural data on complexes of interacting proteins, including structures of alternative isoforms, are needed to test this conjecture.

  12. Where splicing joins chromatin

    Czech Academy of Sciences Publication Activity Database

    Hnilicová, Jarmila; Staněk, David

    2011-01-01

    Roč. 2, č. 3 (2011), s. 182-188. ISSN 1949-1034 R&D Projects: GA ČR GAP305/10/0424; GA AV ČR KAN200520801 Institutional research plan: CEZ:AV0Z50520514 Keywords : chromatin * exon * alternative splicing * transcription * snRNP Subject RIV: EB - Genetics ; Molecular Biology

  13. High-power fused assemblies enabled by advances in fiber-processing technologies

    Science.gov (United States)

    Wiley, Robert; Clark, Brett

    2011-02-01

    The power handling capabilities of fiber lasers are limited by the technologies available to fabricate and assemble the key optical system components. Previous tools for the assembly, tapering, and fusion of fiber laser elements have had drawbacks with regard to temperature range, alignment capability, assembly flexibility and surface contamination. To provide expanded capabilities for fiber laser assembly, a wide-area electrical plasma heat source was used in conjunction with an optimized image analysis method and a flexible alignment system, integrated according to mechatronic principles. High-resolution imaging and vision-based measurement provided feedback to adjust assembly, fusion, and tapering process parameters. The system was used to perform assembly steps including dissimilar-fiber splicing, tapering, bundling, capillary bundling, and fusion of fibers to bulk optic devices up to several mm in diameter. A wide range of fiber types and diameters were tested, including extremely large diameters and photonic crystal fibers. The assemblies were evaluated for conformation to optical and mechanical design criteria, such as taper geometry and splice loss. The completed assemblies met the performance targets and exhibited reduced surface contamination compared to assemblies prepared on previously existing equipment. The imaging system and image analysis algorithms provided in situ fiber geometry measurement data that agreed well with external measurement. The ability to adjust operating parameters dynamically based on imaging was shown to provide substantial performance benefits, particularly in the tapering of fibers and bundles. The integrated design approach was shown to provide sufficient flexibility to perform all required operations with a minimum of reconfiguration.

  14. Spliced leader trans-splicing in the nematode Trichinella spiralis uses highly polymorphic, noncanonical spliced leaders

    OpenAIRE

    Pettitt, Jonathan; Müller, Berndt; Stansfield, Ian; Connolly, Bernadette

    2008-01-01

    The trans-splicing of short spliced leader (SL) RNAs onto the 5′ ends of mRNAs occurs in a diverse range of taxa. In nematodes, all species so far characterized utilize a characteristic, conserved spliced leader, SL1, as well as variants that are employed in the resolution of operons. Here we report the identification of spliced leader trans-splicing in the basal nematode Trichinella spiralis, and show that this nematode does not possess a canonical SL1, but rather has at least 15 distinct sp...

  15. Differential connectivity of splicing activators and repressors to the human spliceosome

    OpenAIRE

    Akerman, Martin; Fregoso, Oliver I.; Das, Shipra; Ruse, Cristian; Jensen, Mads A.; Pappin, Darryl J.; Zhang, Michael Q.; Krainer, Adrian R.

    2015-01-01

    Background During spliceosome assembly, protein-protein interactions (PPI) are sequentially formed and disrupted to accommodate the spatial requirements of pre-mRNA substrate recognition and catalysis. Splicing activators and repressors, such as SR proteins and hnRNPs, modulate spliceosome assembly and regulate alternative splicing. However, it remains unclear how they differentially interact with the core spliceosome to perform their functions. Results Here, we investigate the protein connec...

  16. Towards understanding pre-mRNA splicing mechanisms and the role of SR proteins.

    Science.gov (United States)

    Sahebi, Mahbod; Hanafi, Mohamed M; van Wijnen, Andre J; Azizi, Parisa; Abiri, Rambod; Ashkani, Sadegh; Taheri, Sima

    2016-08-10

    Alternative pre-mRNA splicing provides a source of vast protein diversity by removing non-coding sequences (introns) and accurately linking different exonic regions in the correct reading frame. The regulation of alternative splicing is essential for various cellular functions in both pathological and physiological conditions. In eukaryotic cells, this process is commonly used to increase proteomic diversity and to control gene expression either co- or post-transcriptionally. Alternative splicing occurs within a megadalton-sized, multi-component machine consisting of RNA and proteins; during the splicing process, this complex undergoes dynamic changes via RNA-RNA, protein-protein and RNA-protein interactions. Co-transcriptional splicing functionally integrates the transcriptional machinery, thereby enabling the two processes to influence one another, whereas post-transcriptional splicing facilitates the coupling of RNA splicing with post-splicing events. This review addresses the structural aspects of spliceosomes and the mechanistic implications of their stepwise assembly on the regulation of pre-mRNA splicing. Moreover, the role of phosphorylation-based, signal-induced changes in the regulation of the splicing process is demonstrated. PMID:27154819

  17. Towards a Consolidation of LHC Superconducting Splices for 7 TeV Operation

    CERN Document Server

    Bertinelli, F; Fessia, P; Garion, C; Mathot, S; Perin, A; Scheuerlein, C; Sgobba, S; ten Kat, H; Tock, J P; Verweij, A; Willering, G

    2010-01-01

    Following the analysis of the September 2008 LHC incident, the assembly process and the quality assurance of the main 13 kA interconnection splices were improved, with new measurement and diagnostics methods introduced. During the 2008-2009 shutdown ~5% of these 10 000 splices were newly assembled with these improvements implemented, but essentially maintaining the original design. It is known today that a limiting factor towards 7 TeV operation is the normal conducting resistance of ~15% of the original main 13 kA interconnection splices, associated to the electrical continuity of the copper stabiliser. A “Splices Task Force” has been set up at CERN to evaluate the need for, develop and test design improvements and prepare the implementation of a consolidation campaign. Important issues of splice design, process choice, resources and time requirements are considered.

  18. Nuclear reactor internals alignment configuration

    Science.gov (United States)

    Gilmore, Charles B.; Singleton, Norman R.

    2009-11-10

    An alignment system that employs jacking block assemblies and alignment posts around the periphery of the top plate of a nuclear reactor lower internals core shroud to align an upper core plate with the lower internals and the core shroud with the core barrel. The distal ends of the alignment posts are chamfered and are closely received within notches machined in the upper core plate at spaced locations around the outer circumference of the upper core plate. The jacking block assemblies are used to center the core shroud in the core barrel and the alignment posts assure the proper orientation of the upper core plate. The alignment posts may alternately be formed in the upper core plate and the notches may be formed in top plate.

  19. Exon definition may facilitate splice site selection in RNAs with multiple exons.

    OpenAIRE

    Robberson, B L; Cote, G J; Berget, S M

    1990-01-01

    Interactions at the 3' end of the intron initiate spliceosome assembly and splice site selection in vertebrate pre-mRNAs. Multiple factors, including U1 small nuclear ribonucleoproteins (snRNPs), are involved in initial recognition at the 3' end of the intron. Experiments were designed to test the possibility that U1 snRNP interaction at the 3' end of the intron during early assembly functions to recognize and define the downstream exon and its resident 5' splice site. Splicing precursor RNAs...

  20. Aligned Layers of Silver Nano-Fibers

    OpenAIRE

    Golovin, Andrii B.; Liubov Kreminska; Jeremy Stromer

    2012-01-01

    We describe a new dichroic polarizers made by ordering silver nano-fibers to aligned layers. The aligned layers consist of nano-fibers and self-assembled molecular aggregates of lyotropic liquid crystals. Unidirectional alignment of the layers is achieved by means of mechanical shearing. Aligned layers of silver nano-fibers are partially transparent to a linearly polarized electromagnetic radiation. The unidirectional alignment and density of the silver nano-fibers determine degree of polariz...

  1. The neurogenetics of alternative splicing

    OpenAIRE

    Vuong, CK; Black, DL; S. Zheng

    2016-01-01

    Alternative precursor-mRNA splicing is a key mechanism for regulating gene expression in mammals and is controlled by specialized RNA-binding proteins. The misregulation of splicing is implicated in multiple neurological disorders. We describe recent mouse genetic studies of alternative splicing that reveal its critical role in both neuronal development and the function of mature neurons. We discuss the challenges in understanding the extensive genetic programmes controlled by proteins that r...

  2. Fusion splicing of silicon optical fibres

    OpenAIRE

    Xiao, L.M.; Healy, N; Gibson, U.; Hawkins, T.; Jones, M.; Ballato, J; A. C. Peacock

    2015-01-01

    The first splicing experiments between silicon optical fibres (SOFs) and conventional fibres are investigated. An optimized fusion splicing approach for a polycrystalline SOF is demonstrated and the material properties after splicing are characterized.

  3. Method of predicting Splice Sites based on signal interactions

    Directory of Open Access Journals (Sweden)

    Deogun Jitender S

    2006-04-01

    Full Text Available Abstract Background Predicting and proper ranking of canonical splice sites (SSs is a challenging problem in bioinformatics and machine learning communities. Any progress in SSs recognition will lead to better understanding of splicing mechanism. We introduce several new approaches of combining a priori knowledge for improved SS detection. First, we design our new Bayesian SS sensor based on oligonucleotide counting. To further enhance prediction quality, we applied our new de novo motif detection tool MHMMotif to intronic ends and exons. We combine elements found with sensor information using Naive Bayesian Network, as implemented in our new tool SpliceScan. Results According to our tests, the Bayesian sensor outperforms the contemporary Maximum Entropy sensor for 5' SS detection. We report a number of putative Exonic (ESE and Intronic (ISE Splicing Enhancers found by MHMMotif tool. T-test statistics on mouse/rat intronic alignments indicates, that detected elements are on average more conserved as compared to other oligos, which supports our assumption of their functional importance. The tool has been shown to outperform the SpliceView, GeneSplicer, NNSplice, Genio and NetUTR tools for the test set of human genes. SpliceScan outperforms all contemporary ab initio gene structural prediction tools on the set of 5' UTR gene fragments. Conclusion Designed methods have many attractive properties, compared to existing approaches. Bayesian sensor, MHMMotif program and SpliceScan tools are freely available on our web site. Reviewers This article was reviewed by Manyuan Long, Arcady Mushegian and Mikhail Gelfand.

  4. Inverse splicing of a group II intron.

    OpenAIRE

    Jarrell, K A

    1993-01-01

    I describe the self-splicing of an RNA that consists of exon sequences flanked by group II intron sequences. I find that this RNA undergoes accurate splicing in vitro, yielding an excised exon circle. This splicing reaction involves the joining of the 5' splice site at the end of an exon to the 3' splice site at the beginning of the same exon; thus, I term it inverse splicing. Inverse splicing provides a potential mechanism for exon scrambling, for exon deletion in alternative splicing pathwa...

  5. Beam alignment system for laser welding system

    International Nuclear Information System (INIS)

    The patent describes a beam alignment system for laser welding work pieces, such as fuel rod grids for nuclear fuel assemblies. The apparatus for performing various laser-machining comprises a beam alignment system including alignment target means, as well as means for emitting, directing and focusing the laser beam. (U.K.)

  6. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    S. Szillasi

    2013-01-01

    The CMS detector has been gradually opened and whenever a wheel became exposed the first operation was the removal of the MABs, the sensor structures of the Hardware Barrel Alignment System. By the last days of June all 36 MABs have arrived at the Alignment Lab at the ISR where, as part of the Alignment Upgrade Project, they are refurbished with new Survey target holders. Their electronic checkout is on the way and finally they will be recalibrated. During LS1 the alignment system will be upgraded in order to allow more precise reconstruction of the MB4 chambers in Sector 10 and Sector 4. This requires new sensor components, so called MiniMABs (pictured below), that have already been assembled and calibrated. Image 6: Calibrated MiniMABs are ready for installation For the track-based alignment, the systematic uncertainties of the algorithm are under scrutiny: this study will enable the production of an improved Monte Carlo misalignment scenario and to update alignment position errors eventually, crucial...

  7. Pupil Alignment Measuring Technique and Alignment Reference for Instruments or Optical Systems

    Science.gov (United States)

    Hagopian, John G.

    2010-01-01

    A technique was created to measure the pupil alignment of instruments in situ by measuring calibrated pupil alignment references (PARs) in instruments. The PAR can also be measured using an alignment telescope or an imaging system. PAR allows the verification of the science instrument (SI) pupil alignment at the integrated science instrument module (ISIM) level of assembly at ambient and cryogenic operating temperature. This will allow verification of the ISIM+SI alignment, and provide feedback to realign the SI if necessary.

  8. Alignment validation

    CERN Document Server

    Golling, T

    2007-01-01

    The four experiments, ALICE, ATLAS, CMS and LHCb are currently under construction at CERN. They will study the products of proton-proton collisions at the Large Hadron Collider. All experiments are equipped with sophisticated tracking systems, unprecedented in size and complexity. Full exploitation of both the inner detector and the muon system requires an accurate alignment of all detector elements. Alignment information is deduced from dedicated hardware alignment systems and the reconstruction of charged particles. However, the system is degenerate which means the data is insufficient to constrain all alignment degrees of freedom, so the techniques are prone to converging on wrong geometries. This deficiency necessitates validation and monitoring of the alignment. An exhaustive discussion of means to validate is subject to this document, including examples and plans from all four LHC experiments, as well as other high energy experiments.

  9. Analysis of a splice array experiment elucidates roles of chromatin elongation factor Spt4-5 in splicing.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Xiao

    2005-09-01

    Full Text Available Splicing is an important process for regulation of gene expression in eukaryotes, and it has important functional links to other steps of gene expression. Two examples of these linkages include Ceg1, a component of the mRNA capping enzyme, and the chromatin elongation factors Spt4-5, both of which have recently been shown to play a role in the normal splicing of several genes in the yeast Saccharomyces cerevisiae. Using a genomic approach to characterize the roles of Spt4-5 in splicing, we used splicing-sensitive DNA microarrays to identify specific sets of genes that are mis-spliced in ceg1, spt4, and spt5 mutants. In the context of a complex, nested, experimental design featuring 22 dye-swap array hybridizations, comprising both biological and technical replicates, we applied five appropriate statistical models for assessing differential expression between wild-type and the mutants. To refine selection of differential expression genes, we then used a robust model-synthesizing approach, Differential Expression via Distance Synthesis, to integrate all five models. The resultant list of differentially expressed genes was then further analyzed with regard to select attributes: we found that highly transcribed genes with long introns were most sensitive to spt mutations. QPCR confirmation of differential expression was established for the limited number of genes evaluated. In this paper, we showcase splicing array technology, as well as powerful, yet general, statistical methodology for assessing differential expression, in the context of a real, complex experimental design. Our results suggest that the Spt4-Spt5 complex may help coordinate splicing with transcription under conditions that present kinetic challenges to spliceosome assembly or function.

  10. Intronic Alus influence alternative splicing.

    Directory of Open Access Journals (Sweden)

    Galit Lev-Maor

    Full Text Available Examination of the human transcriptome reveals higher levels of RNA editing than in any other organism tested to date. This is indicative of extensive double-stranded RNA (dsRNA formation within the human transcriptome. Most of the editing sites are located in the primate-specific retrotransposed element called Alu. A large fraction of Alus are found in intronic sequences, implying extensive Alu-Alu dsRNA formation in mRNA precursors. Yet, the effect of these intronic Alus on splicing of the flanking exons is largely unknown. Here, we show that more Alus flank alternatively spliced exons than constitutively spliced ones; this is especially notable for those exons that have changed their mode of splicing from constitutive to alternative during human evolution. This implies that Alu insertions may change the mode of splicing of the flanking exons. Indeed, we demonstrate experimentally that two Alu elements that were inserted into an intron in opposite orientation undergo base-pairing, as evident by RNA editing, and affect the splicing patterns of a downstream exon, shifting it from constitutive to alternative. Our results indicate the importance of intronic Alus in influencing the splicing of flanking exons, further emphasizing the role of Alus in shaping of the human transcriptome.

  11. MapSplice: Accurate mapping of RNA-seq reads for splice junction discovery

    OpenAIRE

    Kai WANG; Singh, Darshan; Zeng, Zheng; Coleman, Stephen J.; Huang, Yan; Savich, Gleb L.; He, Xiaping; Mieczkowski, Piotr; Grimm, Sara A; Perou, Charles M; MacLeod, James N; Chiang, Derek Y.; Prins, Jan F.; Liu, Jinze

    2010-01-01

    The accurate mapping of reads that span splice junctions is a critical component of all analytic techniques that work with RNA-seq data. We introduce a second generation splice detection algorithm, MapSplice, whose focus is high sensitivity and specificity in the detection of splices as well as CPU and memory efficiency. MapSplice can be applied to both short (

  12. MUSE optical alignment procedure

    Science.gov (United States)

    Laurent, Florence; Renault, Edgard; Loupias, Magali; Kosmalski, Johan; Anwand, Heiko; Bacon, Roland; Boudon, Didier; Caillier, Patrick; Daguisé, Eric; Dubois, Jean-Pierre; Dupuy, Christophe; Kelz, Andreas; Lizon, Jean-Louis; Nicklas, Harald; Parès, Laurent; Remillieux, Alban; Seifert, Walter; Valentin, Hervé; Xu, Wenli

    2012-09-01

    MUSE (Multi Unit Spectroscopic Explorer) is a second generation VLT integral field spectrograph (1x1arcmin² Field of View) developed for the European Southern Observatory (ESO), operating in the visible wavelength range (0.465-0.93 μm). A consortium of seven institutes is currently assembling and testing MUSE in the Integration Hall of the Observatoire de Lyon for the Preliminary Acceptance in Europe, scheduled for 2013. MUSE is composed of several subsystems which are under the responsibility of each institute. The Fore Optics derotates and anamorphoses the image at the focal plane. A Splitting and Relay Optics feed the 24 identical Integral Field Units (IFU), that are mounted within a large monolithic instrument mechanical structure. Each IFU incorporates an image slicer, a fully refractive spectrograph with VPH-grating and a detector system connected to a global vacuum and cryogenic system. During 2011, all MUSE subsystems were integrated, aligned and tested independently in each institute. After validations, the systems were shipped to the P.I. institute at Lyon and were assembled in the Integration Hall This paper describes the end-to-end optical alignment procedure of the MUSE instrument. The design strategy, mixing an optical alignment by manufacturing (plug and play approach) and few adjustments on key components, is presented. We depict the alignment method for identifying the optical axis using several references located in pupil and image planes. All tools required to perform the global alignment between each subsystem are described. The success of this alignment approach is demonstrated by the good results for the MUSE image quality. MUSE commissioning at the VLT (Very Large Telescope) is planned for 2013.

  13. Suspended photonic waveguide arrays for submicrometer alignment

    OpenAIRE

    Peters, T. J.; Tichem, M.; Staufer, U.

    2014-01-01

    This paper presents a new alignment concept for the alignment of multichannel photonic intergrated circuits (PICs) using flexible photonic waveguides on one of the PICs that are positionable by integrated micro electro mechanical system (MEMS) actuators. The concept aims for high precision and high degree of assembly process automation. The proposed concept includes pre-alignment of both PICs on a common substrate followed by fine-alignment using the on-chip flexible waveguides and MEMS funct...

  14. Conserved RNA secondary structures promote alternative splicing

    OpenAIRE

    Shepard, PJ; Hertel, KJ

    2008-01-01

    Pre-mRNA splicing is carried out by the spliceosome, which identifies exons and removes intervening introns. Alternative splicing in higher eukaryotes results in the generation of multiple protein isoforms from gene transcripts. The extensive alternative splicing observed implies a flexibility of the spliceosome to identify exons within a given pre-mRNA. To reach this flexibility, splice-site selection in higher eukaryotes has evolved to depend on multiple parameters such as splice-site stren...

  15. Engineering splicing factors with designed specificities

    OpenAIRE

    Wang, Yang; Cheong, Cheom-Gil; Hall, Traci M Tanaka; Wang, Zefeng

    2009-01-01

    Alternative splicing is generally regulated by trans-acting factors that specifically bind pre-mRNA to activate or inhibit the splicing reaction. This regulation is critical for normal gene expression, and dysregulation of splicing is closely associated with human diseases. Here we engineer artificial splicing factors by combining sequence-specific RNA-binding domains of human Pumilio1 with functional domains that regulate splicing. We applied these factors to modulate different types of alte...

  16. Alternative Splicing and Expression Profile Analysis of Expressed Sequence Tags in Domestic Pig

    Institute of Scientific and Technical Information of China (English)

    Liang Zhang; Lin Tao; Lin Ye; Ling He; Yuan-Zhong Zhu; Yue-Dong Zhu; Yan Zhou

    2007-01-01

    Domestic pig (Sus scrofa domestica) is one of the most important mammals to humans. Alternative splicing is a cellular mechanism in eukaryotes that greatly increases the diversity of gene products. Expression sequence tags (ESTs) have been widely used for gene discovery, expression profile analysis, and alternative splicing detection. In this study, a total of 712,905 ESTs extracted from 101 different nonnormalized EST libraries of the domestic pig were analyzed. These EST libraries cover the nervous system, digestive system, immune system, and meat production related tissues from embryo, newborn, and adult pigs, making contributions to the analysis of alternative splicing variants as well as expression profiles in various stages of tissues. A modified approach was designed to cluster and assemble large EST datasets, aiming to detect alternative splicing together with EST abundance of each splicing variant. Much efforts were made to classify alternative splicing into different types and apply different filters to each type to get more reliable results. Finally, a total of 1,223 genes with average 2.8 splicing variants were detected among 16,540 unique genes. The overview of expression profiles would change when we take alternative splicing into account.

  17. Alignment telescope for Antares

    International Nuclear Information System (INIS)

    The Antares Automatic Alignment System employs a specially designed telescope for alignment of its laser beamlines. There are two telescopes in the system, and since each telescope is a primary alignment reference, stringent boresight accuracy and stability over the focus range were required. Optical and mechanical designs, which meet this requirement as well as that of image quality over a wide wavelength band, are described. Special test techniques for initial assembly and alignment of the telescope are also presented. The telescope, which has a 180-mm aperture FK51-KZF2 type glass doublet objective, requires a boresight accuracy of 2.8 μrad at two focal lengths, and object distances between 11 meters and infinity. Travel of a smaller secondary doublet provides focus from 11 m to infinity with approximately 7.8 m effective focal length. By flipping in a third doublet, the effective focal length is reduced to 2.5 m. Telescope alignment was accomplished by using a rotary air bearing to establish an axis in front of the system and placing the focus of a Laser Unequal Path Interferometer (LUPI) at the image plane

  18. Integrating many co-splicing networks to reconstruct splicing regulatory modules

    OpenAIRE

    Dai Chao; Li Wenyuan; Liu Juan; Zhou Xianghong

    2012-01-01

    Abstract Background Alternative splicing is a ubiquitous gene regulatory mechanism that dramatically increases the complexity of the proteome. However, the mechanism for regulating alternative splicing is poorly understood, and study of coordinated splicing regulation has been limited to individual cases. To study genome-wide splicing regulation, we integrate many human RNA-seq datasets to identify splicing module, which we define as a set of cassette exons co-regulated by the same splicing f...

  19. Alternative Splicing Regulation During C. elegans Development: Splicing Factors as Regulated Targets

    OpenAIRE

    Sergio Barberan-Soler; Zahler, Alan M.

    2008-01-01

    Alternative splicing generates protein diversity and allows for post-transcriptional gene regulation. Estimates suggest that 10% of the genes in Caenorhabditis elegans undergo alternative splicing. We constructed a splicing-sensitive microarray to detect alternative splicing for 352 cassette exons and tested for changes in alternative splicing of these genes during development. We found that the microarray data predicted that 62/352 (approximately 18%) of the alternative splicing events studi...

  20. Design of a Split Intein with Exceptional Protein Splicing Activity.

    Science.gov (United States)

    Stevens, Adam J; Brown, Zachary Z; Shah, Neel H; Sekar, Giridhar; Cowburn, David; Muir, Tom W

    2016-02-24

    Protein trans-splicing (PTS) by split inteins has found widespread use in chemical biology and biotechnology. Herein, we describe the use of a consensus design approach to engineer a split intein with enhanced stability and activity that make it more robust than any known PTS system. Using batch mutagenesis, we first conduct a detailed analysis of the difference in splicing rates between the Npu (fast) and Ssp (slow) split inteins of the DnaE family and find that most impactful residues lie on the second shell of the protein, directly adjacent to the active site. These residues are then used to generate an alignment of 73 naturally occurring DnaE inteins that are predicted to be fast. The consensus sequence from this alignment (Cfa) demonstrates both rapid protein splicing and unprecedented thermal and chaotropic stability. Moreover, when fused to various proteins including antibody heavy chains, the N-terminal fragment of Cfa exhibits increased expression levels relative to other N-intein fusions. The durability and efficiency of Cfa should improve current intein based technologies and may provide a platform for the development of new protein chemistry techniques. PMID:26854538

  1. Splicing changes in SMA mouse motoneurons and SMN-depleted neuroblastoma cells: evidence for involvement of splicing regulatory proteins.

    OpenAIRE

    Huo, Qing; Kayikci, Melis; Odermatt, Philipp; Meyer, Kathrin; Michels, Olivia; Saxena, Smita; Ule, Jernej; Schümperli, Daniel

    2014-01-01

    Spinal Muscular Atrophy (SMA) is caused by deletions or mutations in the Survival Motor Neuron 1 (SMN1) gene. The second gene copy, SMN2, produces some, but not enough, functional SMN protein. SMN is essential to assemble small nuclear ribonucleoproteins (snRNPs) that form the spliceosome. However, it is not clear whether SMA is caused by defects in this function that could lead to splicing changes in all tissues, or by the impairment of an additional, less well characterized, but motoneuron-...

  2. Spliced-leader trans-splicing in freshwater planarians.

    Science.gov (United States)

    Zayas, Ricardo M; Bold, Tyler D; Newmark, Phillip A

    2005-10-01

    trans-Splicing, in which a spliced-leader (SL) RNA is appended to the most 5' exon of independently transcribed pre-mRNAs, has been described in a wide range of eukaryotes, from protozoans to chordates. Here we describe trans-splicing in the freshwater planarian Schmidtea mediterranea, a free-living member of the phylum Platyhelminthes. Analysis of an expressed sequence tag (EST) collection from this organism showed that over 300 transcripts shared one of two approximately 35-base sequences (Smed SL-1 and SL-2) at their 5' ends. Examination of genomic sequences encoding representatives of these transcripts revealed that these shared sequences were transcribed elsewhere in the genome. RNA blot analysis, 5' and 3' rapid amplification of cDNA ends, as well as genomic sequence data showed that 42-nt SL sequences were derived from small RNAs of approximately 110 nt. Similar sequences were also found at the 5' ends of ESTs from the planarian Dugesia japonica. trans-Splicing has already been described in numerous representatives of the phylum Platyhelminthes (trematodes, cestodes, and polyclads); its presence in two representatives of the triclads supports the hypothesis that this mode of RNA processing is ancestral within this group. The upcoming complete genome sequence of S. mediterranea, combined with this animal's experimental accessibility and susceptibility to RNAi, provide another model organism in which to study the function of the still-enigmatic trans-splicing. PMID:15972844

  3. Strategies for active alignment of lenses

    Science.gov (United States)

    Langehanenberg, Patrik; Heinisch, Josef; Wilde, Chrisitan; Hahne, Felix; Lüerß, Bernd

    2015-10-01

    Today's optical systems require up-to-date assembly and joining technology. The trend of keeping dimensions as small as possible while maintaining or increasing optical imaging performance leaves little to no room for mechanical lens adjustment equipment that may remain in the final product. In this context active alignment of optical elements opens up possibilities for the fast and cost-economic manufacturing of lenses and lens assemblies with highest optical performance. Active alignment for lens manufacturing is the precise alignment of the optical axis of a lens with respect to an optical or mechanical reference axis (e.g. housing) including subsequent fixation by glue. In this contribution we will describe different approaches for active alignment and outline strengths and limitations of the different methods. Using the SmartAlign principle, highest quality cemented lenses can be manufactured without the need for high precision prealignment, while the reduction to a single alignment step greatly reduces the cycle time. The same strategies can also be applied to bonding processes. Lenses and lens groups can be aligned to both mechanical and optical axes to maximize the optical performance of a given assembly. In hybrid assemblies using both mechanical tolerances and active alignment, SmartAlign can be used to align critical lens elements anywhere inside the system for optimized total performance. Since all geometrical parameters are re-measured before each alignment, this process is especially suited for complex and time-consuming production processes where the stability of the reference axis would otherwise be critical. For highest performance, lenses can be actively aligned using up to five degrees of freedom. In this way, SmartAlign enables the production of ultra-precise mounted lenses with an alignment precision below 1 μm.

  4. Binary Mixtures of SH- and CH3-Terminated Self-Assembled Monolayers to Control the Average Spacing Between Aligned Gold Nanoparticles

    Directory of Open Access Journals (Sweden)

    Pavelka Laura

    2009-01-01

    Full Text Available Abstract This paper presents a method to control the average spacing between organometallic chemical vapor deposition (OMCVD grown gold nanoparticles (Au NPs in a line. Focused ion beam patterned CH3-terminated self-assembled monolayers are refilled systematically with different mixtures of SH- and CH3-terminated silanes. The average spacing between OMCVD Au NPs is demonstrated systematically to decrease by increasing the v/v% ratio of the thiols in the binary silane mixtures with SH- and CH3-terminated groups.

  5. Beyond Alignment

    DEFF Research Database (Denmark)

    Beyond Alignment: Applying Systems Thinking to Architecting Enterprises is a comprehensive reader about how enterprises can apply systems thinking in their enterprise architecture practice, for business transformation and for strategic execution. The book's contributors find that systems thinking...... is a valuable way of thinking about the viable enterprise and how to architect it....

  6. Microstructure and superconducting properties of YBa2Cu3O7−δ thin films incorporated with a self-assembled magnetic vertically aligned nanocomposite

    International Nuclear Information System (INIS)

    A thin layer of a vertically aligned nanocomposite (VAN) with separated phases of ferromagnetic Fe2O3 and non-magnetic CeO2, arranged as alternating nanopillars, is introduced in YBa2Cu3O7−δ (YBCO) thin films as either a cap or a buffer layer using a pulsed laser deposition method. Detailed microstructural characterization including XRD, high resolution XTEM and STEM is conducted and correlated with the superconducting properties to investigate the flux pinning properties introduced by the magnetic VAN layers. The Tc values of both doped samples are above 89 K and the Jcsf measured at 65 K increased to 150% of that of the reference YBCO prepared under the same conditions. As the measurement temperature decreases, the magnetic pinning effect increases and the field dependent Jc(H ∥ c) is further improved to more than 200% of the Jc value of the reference YBCO sample. This suggests that the Fe2O3:CeO2 VAN can provide both ordered magnetic pillars and controlled defect density. Furthermore, the magnetic pillars are very effective pinning centers especially in the high field and low temperature regime. (paper)

  7. EASI—enrichment of alternatively spliced isoforms

    OpenAIRE

    Julian P Venables; Burn, John

    2006-01-01

    Alternative splicing produces more than one protein from the majority of genes and the rarer forms can have dominant functions. Instability of alternative transcripts can also hinder the study of regulation of gene expression by alternative splicing. To investigate the true extent of alternative splicing we have developed a simple method of enriching alternatively spliced isoforms (EASI) from PCRs using beads charged with Thermus aquaticus single-stranded DNA-binding protein (T.Aq ssb). This ...

  8. Mechano-Regulation of Alternative Splicing

    OpenAIRE

    Liu, Huan; Tang, Liling

    2013-01-01

    Alternative splicing contributes to the complexity of proteome by producing multiple mRNAs from a single gene. Affymetrix exon arrays and experiments in vivo or in vitro demonstrated that alternative splicing was regulated by mechanical stress. Expression of mechano-growth factor (MGF) which is the splicing isoform of insulin-like growth factor 1(IGF-1) and vascular endothelial growth factor (VEGF) splicing variants such as VEGF121, VEGF165, VEGF206, VEGF189, VEGF165 and VEGF145 are regulated...

  9. ASD: a bioinformatics resource on alternative splicing

    OpenAIRE

    Stamm, Stefan; Riethoven, Jean-Jack; Le Texier, Vincent; Gopalakrishnan, Chellappa; Kumanduri, Vasudev; Tang, Yesheng; Barbosa-Morais, Nuno L.; Thanaraj, Thangavel Alphonse

    2005-01-01

    Alternative splicing is an important regulatory mechanism of mammalian gene expression. The alternative splicing database (ASD) consortium is systematically collecting and annotating data on alternative splicing. We present the continuation and upgrade of the ASD [T. A. Thanaraj, S. Stamm, F. Clark, J. J. Riethoven, V. Le Texier, J. Muilu (2004) Nucleic Acids Res. 32, D64–D69] that consists of computationally and manually generated data. Its largest parts are AltSplice, a value-added database...

  10. Targeting RNA Splicing for Disease Therapy

    OpenAIRE

    Havens, Mallory A.; Duelli, Dominik M.; Hastings, Michelle L.

    2013-01-01

    Splicing of pre-messenger RNA into mature messenger RNA is an essential step for expression of most genes in higher eukaryotes. Defects in this process typically affect cellular function and can have pathological consequences. Many human genetic diseases are caused by mutations that cause splicing defects. Furthermore, a number of diseases are associated with splicing defects that are not attributed to overt mutations. Targeting splicing directly to correct disease-associated aberrant splicin...

  11. Evolution of alternative splicing after gene duplication

    OpenAIRE

    Su, Zhixi; Wang, Jianmin; Yu, Jun; Huang, Xiaoqiu; Gu, Xun

    2006-01-01

    Alternative splicing and gene duplication are two major sources of proteomic function diversity. Here, we study the evolutionary trend of alternative splicing after gene duplication by analyzing the alternative splicing differences between duplicate genes. We observed that duplicate genes have fewer alternative splice (AS) forms than single-copy genes, and that a negative correlation exists between the mean number of AS forms and the gene family size. Interestingly, we found that the loss of ...

  12. Fr-TM-align: a new protein structural alignment method based on fragment alignments and the TM-score

    Directory of Open Access Journals (Sweden)

    Skolnick Jeffrey

    2008-12-01

    Full Text Available Abstract Background Protein tertiary structure comparisons are employed in various fields of contemporary structural biology. Most structure comparison methods involve generation of an initial seed alignment, which is extended and/or refined to provide the best structural superposition between a pair of protein structures as assessed by a structure comparison metric. One such metric, the TM-score, was recently introduced to provide a combined structure quality measure of the coordinate root mean square deviation between a pair of structures and coverage. Using the TM-score, the TM-align structure alignment algorithm was developed that was often found to have better accuracy and coverage than the most commonly used structural alignment programs; however, there were a number of situations when this was not true. Results To further improve structure alignment quality, the Fr-TM-align algorithm has been developed where aligned fragment pairs are used to generate the initial seed alignments that are then refined using dynamic programming to maximize the TM-score. For the assessment of the structural alignment quality from Fr-TM-align in comparison to other programs such as CE and TM-align, we examined various alignment quality assessment scores such as PSI and TM-score. The assessment showed that the structural alignment quality from Fr-TM-align is better in comparison to both CE and TM-align. On average, the structural alignments generated using Fr-TM-align have a higher TM-score (~9% and coverage (~7% in comparison to those generated by TM-align. Fr-TM-align uses an exhaustive procedure to generate initial seed alignments. Hence, the algorithm is computationally more expensive than TM-align. Conclusion Fr-TM-align, a new algorithm that employs fragment alignment and assembly provides better structural alignments in comparison to TM-align. The source code and executables of Fr-TM-align are freely downloadable at: http://cssb.biology.gatech.edu/skolnick/files/FrTMalign/.

  13. The Integrity of ACSR Full Tension Single-Stage Splice Connector at Higher Operation Temperature

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jy-An John [ORNL; Lara-Curzio, Edgar [ORNL; King Jr, Thomas J [ORNL

    2008-10-01

    Due to increases in power demand and limited investment in new infrastructure, existing overhead power transmission lines often need to operate at temperatures higher than those used for the original design criteria. This has led to the accelerated aging and degradation of splice connectors. It is manifested by the formation of hot-spots that have been revealed by infrared imaging during inspection. The implications of connector aging is two-fold: (1) significant increases in resistivity of the splice connector (i.e., less efficient transmission of electricity) and (2) significant reductions in the connector clamping strength, which could ultimately result in separation of the power transmission line at the joint. Therefore, the splice connector appears to be the weakest link in electric power transmission lines. This report presents a protocol for integrating analytical and experimental approaches to evaluate the integrity of full tension single-stage splice connector assemblies and the associated effective lifetime at high operating temperature.

  14. The RRR of the Cu components of the LHC main bus bar splices

    CERN Document Server

    Heck, S; Fessia, P; Principe, R; CERN. Geneva. TE Department

    2010-01-01

    The different LHC main bus bar splice components (bus bar cable, splice U-piece and wedge and bus bar stabilizer) are subjected to different heat treatments (HTs) during bus bar assembly and splice soldering. The influence of soldering HTs on the RRR of the LHC main bus bar cable strands has been determined. The RRR of several splice U-pieces and wedges dismounted from the LHC has been measured. A correlation between the Vickers hardness and the RRR of the high purity Cu profiles has been established. All U-pieces tested that were produced before 2009 have a RRR>200, while the RRR of all wedges and of U-pieces of 2009 production have a much lower RRR. All tests of LHC main bus bar samples performed so far in the laboratory indicate a RRR of approximately 200 or higher.

  15. SAW: A Method to Identify Splicing Events from RNA-Seq Data Based on Splicing Fingerprints

    OpenAIRE

    Kang Ning; Damian Fermin

    2010-01-01

    Splicing event identification is one of the most important issues in the comprehensive analysis of transcription profile. Recent development of next-generation sequencing technology has generated an extensive profile of alternative splicing. However, while many of these splicing events are between exons that are relatively close on genome sequences, reads generated by RNA-Seq are not limited to alternative splicing between close exons but occur in virtually all splicing events. In this work, ...

  16. Alternative splicing and trans-splicing events revealed by analysis of the Bombyx mori transcriptome

    OpenAIRE

    Shao, Wei; Zhao, Qiong-Yi; Wang, Xiu-Ye; Xu, Xin-Yan; Tang, Qing; Li, Muwang; Li, Xuan; Xu, Yong-Zhen

    2012-01-01

    Alternative splicing and trans-splicing events have not been systematically studied in the silkworm Bombyx mori. Here, the silkworm transcriptome was analyzed by RNA-seq. The authors identified 320 novel genes, modified 1140 gene models, and found thousands of alternative splicing and 58 trans-splicing events. Studies of three SR proteins show that both their alternative splicing patterns and mRNA products are conserved from insect to human, and one isoform of Srsf6 with a retained intron is ...

  17. HMMSplicer: a tool for efficient and sensitive discovery of known and novel splice junctions in RNA-Seq data.

    Directory of Open Access Journals (Sweden)

    Michelle T Dimon

    Full Text Available BACKGROUND: High-throughput sequencing of an organism's transcriptome, or RNA-Seq, is a valuable and versatile new strategy for capturing snapshots of gene expression. However, transcriptome sequencing creates a new class of alignment problem: mapping short reads that span exon-exon junctions back to the reference genome, especially in the case where a splice junction is previously unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we introduce HMMSplicer, an accurate and efficient algorithm for discovering canonical and non-canonical splice junctions in short read datasets. HMMSplicer identifies more splice junctions than currently available algorithms when tested on publicly available A. thaliana, P. falciparum, and H. sapiens datasets without a reduction in specificity. CONCLUSIONS/SIGNIFICANCE: HMMSplicer was found to perform especially well in compact genomes and on genes with low expression levels, alternative splice isoforms, or non-canonical splice junctions. Because HHMSplicer does not rely on pre-built gene models, the products of inexact splicing are also detected. For H. sapiens, we find 3.6% of 3' splice sites and 1.4% of 5' splice sites are inexact, typically differing by 3 bases in either direction. In addition, HMMSplicer provides a score for every predicted junction allowing the user to set a threshold to tune false positive rates depending on the needs of the experiment. HMMSplicer is implemented in Python. Code and documentation are freely available at http://derisilab.ucsf.edu/software/hmmsplicer.

  18. Image alignment

    Science.gov (United States)

    Dowell, Larry Jonathan

    2014-04-22

    Disclosed is a method and device for aligning at least two digital images. An embodiment may use frequency-domain transforms of small tiles created from each image to identify substantially similar, "distinguishing" features within each of the images, and then align the images together based on the location of the distinguishing features. To accomplish this, an embodiment may create equal sized tile sub-images for each image. A "key" for each tile may be created by performing a frequency-domain transform calculation on each tile. A information-distance difference between each possible pair of tiles on each image may be calculated to identify distinguishing features. From analysis of the information-distance differences of the pairs of tiles, a subset of tiles with high discrimination metrics in relation to other tiles may be located for each image. The subset of distinguishing tiles for each image may then be compared to locate tiles with substantially similar keys and/or information-distance metrics to other tiles of other images. Once similar tiles are located for each image, the images may be aligned in relation to the identified similar tiles.

  19. Heterojunction bipolar assembly with CrxTi1-xO2 thin films and vertically aligned ZnO nanorods

    International Nuclear Information System (INIS)

    Polycrystalline and homogeneous CrxTi1-xO2 thin films were deposited on silicon (Si) substrates and on indium doped tin oxide (ITO) coated glass substrates by spin coating technique. We report the p-type conductivity in CrxTi1-xO2 thin films (x = 0.005, 0.05, 0.1, 0.15, 0.2) and variable turn-on voltages (VO) in heterojunction ZnO-nanorod/CrxTi1-xO2/ITO bipolar device. Results showed that VO varies substantially from ∼0.8 V (x = 0.005) to ∼0.53 (x = 0.2) for the bipolar assembly. X-ray photoelectron spectroscopy (XPS) showed that chemical state of Ti is the +4 valence state and Cr remains in three different oxidation states of +3. XPS in the valence band region showed a shift in the binding energy towards the lower energy side with increasing Cr intake confirming more p-type conductivity in CrxTi1-xO2 thin films.

  20. COMMUNICATION: Alternative splicing and genomic stability

    Science.gov (United States)

    Cahill, Kevin

    2004-06-01

    Alternative splicing allows an organism to make different proteins in different cells at different times, all from the same gene. In a cell that uses alternative splicing, the total length of all the exons is much shorter than in a cell that encodes the same set of proteins without alternative splicing. This economical use of exons makes genes more stable during reproduction and development because a genome with a shorter exon length is more resistant to harmful mutations. Genomic stability may be the reason why higher vertebrates splice alternatively. For a broad class of alternatively spliced genes, a formula is given for the increase in their stability.

  1. GC content around splice sites affects splicing through pre-mRNA secondary structures

    Directory of Open Access Journals (Sweden)

    Chen Liang

    2011-01-01

    Full Text Available Abstract Background Alternative splicing increases protein diversity by generating multiple transcript isoforms from a single gene through different combinations of exons or through different selections of splice sites. It has been reported that RNA secondary structures are involved in alternative splicing. Here we perform a genomic study of RNA secondary structures around splice sites in humans (Homo sapiens, mice (Mus musculus, fruit flies (Drosophila melanogaster, and nematodes (Caenorhabditis elegans to further investigate this phenomenon. Results We observe that GC content around splice sites is closely associated with the splice site usage in multiple species. RNA secondary structure is the possible explanation, because the structural stability difference among alternative splice sites, constitutive splice sites, and skipped splice sites can be explained by the GC content difference. Alternative splice sites tend to be GC-enriched and exhibit more stable RNA secondary structures in all of the considered species. In humans and mice, splice sites of first exons and long exons tend to be GC-enriched and hence form more stable structures, indicating the special role of RNA secondary structures in promoter proximal splicing events and the splicing of long exons. In addition, GC-enriched exon-intron junctions tend to be overrepresented in tissue-specific alternative splice sites, indicating the functional consequence of the GC effect. Compared with regions far from splice sites and decoy splice sites, real splice sites are GC-enriched. We also found that the GC-content effect is much stronger than the nucleotide-order effect to form stable secondary structures. Conclusion All of these results indicate that GC content is related to splice site usage and it may mediate the splicing process through RNA secondary structures.

  2. Titin Diversity—Alternative Splicing Gone Wild

    Directory of Open Access Journals (Sweden)

    Wei Guo

    2010-01-01

    Full Text Available Titin is an extremely large protein found in highest concentrations in heart and skeletal muscle. The single mammalian gene is expressed in multiple isoforms as a result of alternative splicing. Although titin isoform expression is controlled developmentally and in a tissue specific manner, the vast number of potential splicing pathways far exceeds those described in any other alternatively spliced gene. Over 1 million human splice pathways for a single individual can be potentially derived from the PEVK region alone. A new splicing pattern for the human cardiac N2BA isoform type has been found in which the PEVK region includes only the N2B type exons. The alterations in splicing and titin isoform expression in human heart disease provide impetus for future detailed study of the splicing mechanisms for this giant protein.

  3. Production and Quality Assurance of Main Busbar Interconnection Splices during the LHC 2008-2009 Shutdown.

    CERN Document Server

    Bertinelli, F; Dalin, J-M; Fessia, P; Flora, R H; Heck, S; Pfeffer, H; Prin, H; Scheuerlein, C; Thonet, P; Tock, J-P; Williams, L

    2011-01-01

    The main busbar interconnection splices of the Large Hadron Collider are assembled by inductive soldering of the Rutherford type cables and the copper profiles of the stabilizer. Following the September 2008 incident, the assembly process and the quality assurance have been improved, with new measurement and diagnostics methods introduced. In the 2008-2009 shutdown the resistance both in the superconducting and in the normal conducting states have been the focus for improvements. The introduction of gamma radiography has allowed the visualization of voids between cable and stabilizer. It is now known that during the standard soldering heating cycle solder is lost from the busbar extremities adjacent to the splice profiles, leaving parts of the cable in poor contact with the stabilizer. A room temperature resistance measurement has been introduced as a simple, non-destructive test to measure the electrical continuity of the splice in its normal conducting state. An ultrasonic test has been performed systematic...

  4. Extending reference assembly models

    DEFF Research Database (Denmark)

    Church, Deanna M.; Schneider, Valerie A.; Steinberg, Karyn Meltz;

    2015-01-01

    The human genome reference assembly is crucial for aligning and analyzing sequence data, and for genome annotation, among other roles. However, the models and analysis assumptions that underlie the current assembly need revising to fully represent human sequence diversity. Improved analysis tools...

  5. Microstructure, magnetic, and low-field magnetotransport properties of self-assembled (La0.7Sr0.3MnO3)0.5:(CeO2)0.5 vertically aligned nanocomposite thin films

    International Nuclear Information System (INIS)

    Two-phase (La0.7Sr0.3MnO3)0.5:(CeO2)0.5 (LSMO:CeO2) heteroepitaxial nanocomposite films were grown on SrTiO3 (STO) (001) by pulsed laser deposition (PLD). X-ray diffraction (XRD) and transmission electron microscopy (TEM) results show that LSMO:CeO2 films epitaxially grow on STO as self-assembled vertically aligned nanocomposite (VAN). Magnetic and magnetotransport measurements demonstrate that the LSMO phase in the VAN structure behaves differently from its epitaxial single-phase counterpart, e.g. greatly enhanced coercivity (HC) and low-field magnetoresistance (LFMR). The enhanced properties in the VAN system are attributed to the interaction between the perovskite and the secondary phase or phase boundary. The results suggest that the growth of functional oxide in another oxide matrix with vertical heteroepitaxial form is a promising approach to achieve new functionality that may not be easily realized in the single epitaxial phase.

  6. Spliced leader RNA trans-splicing discovered in copepods

    Science.gov (United States)

    Yang, Feifei; Xu, Donghui; Zhuang, Yunyun; Yi, Xiaoyan; Huang, Yousong; Chen, Hongju; Lin, Senjie; Campbell, David A.; Sturm, Nancy R.; Liu, Guangxing; Zhang, Huan

    2015-12-01

    Copepods are one of the most abundant metazoans in the marine ecosystem, constituting a critical link in aquatic food webs and contributing significantly to the global carbon budget, yet molecular mechanisms of their gene expression are not well understood. Here we report the detection of spliced leader (SL) trans-splicing in calanoid copepods. We have examined nine species of wild-caught copepods from Jiaozhou Bay, China that represent the major families of the calanoids. All these species contained a common 46-nt SL (CopepodSL). We further determined the size of CopepodSL precursor RNA (slRNA; 108-158 nt) through genomic analysis and 3‧-RACE technique, which was confirmed by RNA blot analysis. Structure modeling showed that the copepod slRNA folded into typical slRNA secondary structures. Using a CopepodSL-based primer set, we selectively enriched and sequenced copepod full-length cDNAs, which led to the characterization of copepod transcripts and the cataloging of the complete set of 79 eukaryotic cytoplasmic ribosomal proteins (cRPs) for a single copepod species. We uncovered the SL trans-splicing in copepod natural populations, and demonstrated that CopepodSL was a sensitive and specific tool for copepod transcriptomic studies at both the individual and population levels and that it would be useful for metatranscriptomic analysis of copepods.

  7. SpliceProt: a protein sequence repository of predicted human splice variants.

    Science.gov (United States)

    Tavares, Raphael; de Miranda Scherer, Nicole; Pauletti, Bianca Alves; Araújo, Elói; Folador, Edson Luiz; Espindola, Gabriel; Ferreira, Carlos Gil; Paes Leme, Adriana Franco; de Oliveira, Paulo Sergio Lopes; Passetti, Fabio

    2014-02-01

    The mechanism of alternative splicing in the transcriptome may increase the proteome diversity in eukaryotes. In proteomics, several studies aim to use protein sequence repositories to annotate MS experiments or to detect differentially expressed proteins. However, the available protein sequence repositories are not designed to fully detect protein isoforms derived from mRNA splice variants. To foster knowledge for the field, here we introduce SpliceProt, a new protein sequence repository of transcriptome experimental data used to investigate for putative splice variants in human proteomes. Current version of SpliceProt contains 159 719 non-redundant putative polypeptide sequences. The assessment of the potential of SpliceProt in detecting new protein isoforms resulting from alternative splicing was performed by using publicly available proteomics data. We detected 173 peptides hypothetically derived from splice variants, which 54 of them are not present in UniprotKB/TrEMBL sequence repository. In comparison to other protein sequence repositories, SpliceProt contains a greater number of unique peptides and is able to detect more splice variants. Therefore, SpliceProt provides a solution for the annotation of proteomics experiments regarding splice isofoms. The repository files containing the translated sequences of the predicted splice variants and a visualization tool are freely available at http://lbbc.inca.gov.br/spliceprot. PMID:24273012

  8. Linking splicing to Pol II transcription stabilizes pre-mRNAs and influences splicing patterns.

    OpenAIRE

    Hicks, Martin J; Chin-Rang Yang; Matthew V Kotlajich; Hertel, Klemens J.

    2006-01-01

    RNA processing is carried out in close proximity to the site of transcription, suggesting a regulatory link between transcription and pre-mRNA splicing. Using an in vitro transcription/splicing assay, we demonstrate that an association of RNA polymerase II ( Pol II) transcription and pre-mRNA splicing is required for efficient gene expression. Pol II-synthesized RNAs containing functional splice sites are protected from nuclear degradation, presumably because the local concentration of the sp...

  9. Competition between Pre-mRNAs for the splicing machinery drives global regulation of splicing

    OpenAIRE

    Munding, EM; Shiue, L; Katzman, S.; Donohue, J; Ares, M

    2013-01-01

    During meiosis in yeast, global splicing efficiency increases and then decreases. Here we provide evidence that splicing improves due to reduced competition for the splicing machinery. The timing of this regulation corresponds to repression and reactivation of ribosomal protein genes (RPGs) during meiosis. In vegetative cells, RPG repression by rapamycin treatment also increases splicing efficiency. Downregulation of the RPG-dedicated transcription factor gene IFH1 genetically suppresses two ...

  10. Regulation of Splicing Factors by Alternative Splicing and NMD Is Conserved between Kingdoms Yet Evolutionarily Flexible

    OpenAIRE

    Liana F Lareau; Brenner, Steven E.

    2015-01-01

    Ultraconserved elements, unusually long regions of perfect sequence identity, are found in genes encoding numerous RNA-binding proteins including arginine-serine rich (SR) splicing factors. Expression of these genes is regulated via alternative splicing of the ultraconserved regions to yield mRNAs that are degraded by nonsense-mediated mRNA decay (NMD), a process termed unproductive splicing (Lareau et al. 2007; Ni et al. 2007). As all human SR genes are affected by alternative splicing and N...

  11. Evolutionary conservation of alternative splicing in chicken

    OpenAIRE

    Katyal, S.; Gao, Z.; Liu, R.-Z.; R Godbout

    2007-01-01

    Alternative splicing represents a source of great diversity for regulating protein expression and function. It has been estimated that one-third to two-thirds of mammalian genes are alternatively spliced. With the sequencing of the chicken genome and analysis of transcripts expressed in chicken tissues, we are now in a position to address evolutionary conservation of alternative splicing events in chicken and mammals. Here, we compare chicken and mammalian transcript sequences of 41 alternati...

  12. Recursive splicing in long vertebrate genes.

    Science.gov (United States)

    Sibley, Christopher R; Emmett, Warren; Blazquez, Lorea; Faro, Ana; Haberman, Nejc; Briese, Michael; Trabzuni, Daniah; Ryten, Mina; Weale, Michael E; Hardy, John; Modic, Miha; Curk, Tomaž; Wilson, Stephen W; Plagnol, Vincent; Ule, Jernej

    2015-05-21

    It is generally believed that splicing removes introns as single units from precursor messenger RNA transcripts. However, some long Drosophila melanogaster introns contain a cryptic site, known as a recursive splice site (RS-site), that enables a multi-step process of intron removal termed recursive splicing. The extent to which recursive splicing occurs in other species and its mechanistic basis have not been examined. Here we identify highly conserved RS-sites in genes expressed in the mammalian brain that encode proteins functioning in neuronal development. Moreover, the RS-sites are found in some of the longest introns across vertebrates. We find that vertebrate recursive splicing requires initial definition of an 'RS-exon' that follows the RS-site. The RS-exon is then excluded from the dominant mRNA isoform owing to competition with a reconstituted 5' splice site formed at the RS-site after the first splicing step. Conversely, the RS-exon is included when preceded by cryptic promoters or exons that fail to reconstitute an efficient 5' splice site. Most RS-exons contain a premature stop codon such that their inclusion can decrease mRNA stability. Thus, by establishing a binary splicing switch, RS-sites demarcate different mRNA isoforms emerging from long genes by coupling cryptic elements with inclusion of RS-exons. PMID:25970246

  13. Angular interpolations and splice options for three-dimensional transport computations

    International Nuclear Information System (INIS)

    New, accurate and mathematically rigorous angular Interpolation strategies are presented. These strategies preserve flow and directionality separately over each octant of the unit sphere, and are based on a combination of spherical harmonics expansions and least squares algorithms. Details of a three-dimensional to three-dimensional (3-D to 3-D) splice method which utilizes the new angular interpolations are summarized. The method has been implemented in a multidimensional discrete ordinates transport computer program. Various features of the splice option are illustrated by several applications to a benchmark Dog-Legged Void Neutron (DLVN) streaming and transport experimental assembly

  14. The Effective Lifetime of ACSR Full Tension Splice Connector Operated at Higher Temperature

    International Nuclear Information System (INIS)

    This paper is to address the issues related to integrity of ACSR full tension splice connectors operated at high temperatures. A protocol of integrating analytical and experimental approaches to evaluate the integrity of a full tension single-stage splice connector (SSC) assembly during service at high operating temperature was developed. Based on the developed protocol the effective lifetime evaluation was demonstrated with ACSR Drake conductor SSC systems. The investigation indicates that thermal cycling temperature and frequency, conductor cable tension loading, and the compressive residual stress field within a SSC system have significant impact on the SSC integrity and the associated effective lifetime

  15. Method of loading fuel assembly

    International Nuclear Information System (INIS)

    Purpose: To shorten the fuel assembly loading time by loading fuel assembly group as one body into the reactor core. Method: A fuel assembly is fed from an auxiliary reactor building via a pit crane into the reactor container, and is stood from lateral position to vertical position. Further, the fuel assemblies are moved laterallyiin a pool of the container, and every four assembly groups are formed by an aligning jig. These assembly groups are associated into one body and loaded into the container. Thus, the round trip time of the crane in the fuel assembly loading work can be shortened. (Yoshihara, H.)

  16. Alternative mRNA Splicing: Control by Combination

    OpenAIRE

    Mabon, Stephen A; Tom Misteli

    2005-01-01

    Alternative splicing in mammalian cells has been suggested to be largely controlled by combinatorial binding of basal splicing factors to pre-mRNA templates. This model predicts that distinct sets of pre-mRNA splicing factors are associated with alternatively spliced transcripts. However, no experimental evidence for differential recruitment of splicing factors to transcripts with distinct splicing fates is available. Here we have used quantitative single-cell imaging to test this key predict...

  17. Large-scale comparative analysis of splicing signals and their corresponding splicing factors in eukaryotes

    OpenAIRE

    Schwartz, Schraga; Silva, João(CFTP, Departamento de Física, Instituto Superior Técnico, Universidade de Lisboa, Avenida Rovisco Pais 1, 1049, Lisboa, Portugal); Burstein, David; Pupko, Tal; Eyras, Eduardo; Ast, Gil

    2008-01-01

    Introns are among the hallmarks of eukaryotic genes. Splicing of introns is directed by three main splicing signals: the 5′ splice site (5′ss), the branch site (BS), and the polypyrimdine tract/3′splice site (PPT-3′ss). To study the evolution of these splicing signals, we have conducted a systematic comparative analysis of these signals in over 1.2 million introns from 22 eukaryotes. Our analyses suggest that all these signals have dramatically evolved: The PPT is weak among most fungi, inter...

  18. DNA Align Editor: DNA Alignment Editor Tool

    Science.gov (United States)

    The SNPAlignEditor is a DNA sequence alignment editor that runs on Windows platforms. The purpose of the program is to provide an intuitive, user-friendly tool for manual editing of multiple sequence alignments by providing functions for input, editing, and output of nucleotide sequence alignments....

  19. Precision alignment of permanent magnet drift tubes

    International Nuclear Information System (INIS)

    The Lawrence Berkeley National Laboratory (LBNL) technique of drift-tube alignment has been resurrected at Los Alamos for the precision alignment of 1-cm-core drift tubes that carry high gradient rare-earth-cobalt quadrupoles. Because the quadrupoles cannot be switched off, this technique is not applicable to a drift-tube assembly, but tests indicate that individual magnetic centers can be detected with a precision of +/-0.003 mm. Methods of transferring this information to machined alignment flats on the sides of the drift-tube body are discussed. With measurements of drift tubes designed for a 100-mA, 425-MHz drift-tube linac, offsets between the geometric and magnetic axes of up to +/-0.05 mm were detected following final assembly and welding. This degree of offset is serious if not accommodated, because it represents the entire alignment tolerance for the 40-cell tank. The measurement equipment and technique are described

  20. Alignments between galaxies, satellite systems and haloes

    OpenAIRE

    Shao, Shi; Cautun, Marius; Frenk, Carlos S.; Gao, Liang; Crain, Robert A.; Schaller, Matthieu; Schaye, Joop; Theuns, Tom

    2016-01-01

    The spatial distribution of the satellite populations of the Milky Way and Andromeda are puzzling in that they are nearly perpendicular to the disks of their central galaxies. To understand the origin of such configurations we study the alignment of the central galaxy, satellite system and dark matter halo in the largest of the "Evolution and Assembly of GaLaxies and their Environments" (EAGLE) simulation. We find that centrals and their satellite systems tend to be well aligned with their ha...

  1. Spliced

    DEFF Research Database (Denmark)

    Addison, Courtney Page

    2016-01-01

    Human gene therapy (HGT) aims to cure disease by inserting or editing the DNA of patients with genetic conditions. Since foundational genetic techniques came into use in the 1970s, the field has developed to the point that now three therapies have market approval, and over 1800 clinical trials have......-work stretches out from science to enlist diverse publics, social formations and the natural world in the pursuit of legitimacy....

  2. Alternative splicing regulation during C. elegans development: splicing factors as regulated targets.

    Directory of Open Access Journals (Sweden)

    Sergio Barberan-Soler

    2008-02-01

    Full Text Available Alternative splicing generates protein diversity and allows for post-transcriptional gene regulation. Estimates suggest that 10% of the genes in Caenorhabditis elegans undergo alternative splicing. We constructed a splicing-sensitive microarray to detect alternative splicing for 352 cassette exons and tested for changes in alternative splicing of these genes during development. We found that the microarray data predicted that 62/352 (approximately 18% of the alternative splicing events studied show a strong change in the relative levels of the spliced isoforms (>4-fold during development. Confirmation of the microarray data by RT-PCR was obtained for 70% of randomly selected genes tested. Among the genes with the most developmentally regulated alternatively splicing was the hnRNP F/H splicing factor homolog, W02D3.11 - now named hrpf-1. For the cassette exon of hrpf-1, the inclusion isoform comprises 65% of hrpf-1 steady state messages in embryos but only 0.1% in the first larval stage. This dramatic change in the alternative splicing of an alternative splicing factor suggests a complex cascade of splicing regulation during development. We analyzed splicing in embryos from a strain with a mutation in the splicing factor sym-2, another hnRNP F/H homolog. We found that approximately half of the genes with large alternative splicing changes between the embryo and L1 stages are regulated by sym-2 in embryos. An analysis of the role of nonsense-mediated decay in regulating steady-state alternative mRNA isoforms was performed. We found that 8% of the 352 events studied have alternative isoforms whose relative steady-state levels in embryos change more than 4-fold in a nonsense-mediated decay mutant, including hrpf-1. Strikingly, 53% of these alternative splicing events that are affected by NMD in our experiment are not obvious substrates for NMD based on the presence of premature termination codons. This suggests that the targeting of splicing factors

  3. Position dependence of the rous sarcoma virus negative regulator of splicing element reflects proximity to a 5' splice site

    International Nuclear Information System (INIS)

    Rous sarcoma virus (RSV) requires incomplete splicing of its viral transcripts to maintain efficient replication. A splicing inhibitor element, the negative regulator of splicing (NRS), is located near the 5' end of the RNA but the significance of this positioning is not known. In a heterologous intron the NRS functions optimally when positioned close to the authentic 5' splice site. This observation led us to investigate the basis of the position dependence. Four explanations were put forth and stressed the role of three major elements involved in splicing, the 3' splice site, the 5' splice site, and the 5' end cap structure. NRS function was unrelated to its position relative to the 3' splice site or the cap structure and appeared to depend on its position relative to the authentic 5' splice site. We conclude that position dependence may reflect distance constraints necessary for competition of the NRS with the authentic 5' splice site for pairing with the 3' splice sites

  4. Microbial and Natural Metabolites That Inhibit Splicing: A Powerful Alternative for Cancer Treatment.

    Science.gov (United States)

    Martínez-Montiel, Nancy; Rosas-Murrieta, Nora Hilda; Martínez-Montiel, Mónica; Gaspariano-Cholula, Mayra Patricia; Martínez-Contreras, Rebeca D

    2016-01-01

    In eukaryotes, genes are frequently interrupted with noncoding sequences named introns. Alternative splicing is a nuclear mechanism by which these introns are removed and flanking coding regions named exons are joined together to generate a message that will be translated in the cytoplasm. This mechanism is catalyzed by a complex machinery known as the spliceosome, which is conformed by more than 300 proteins and ribonucleoproteins that activate and regulate the precision of gene expression when assembled. It has been proposed that several genetic diseases are related to defects in the splicing process, including cancer. For this reason, natural products that show the ability to regulate splicing have attracted enormous attention due to its potential use for cancer treatment. Some microbial metabolites have shown the ability to inhibit gene splicing and the molecular mechanism responsible for this inhibition is being studied for future applications. Here, we summarize the main types of natural products that have been characterized as splicing inhibitors, the recent advances regarding molecular and cellular effects related to these molecules, and the applications reported so far in cancer therapeutics. PMID:27610372

  5. Strategies and tools for whole genome alignments

    Energy Technology Data Exchange (ETDEWEB)

    Couronne, Olivier; Poliakov, Alexander; Bray, Nicolas; Ishkhanov,Tigran; Ryaboy, Dmitriy; Rubin, Edward; Pachter, Lior; Dubchak, Inna

    2002-11-25

    The availability of the assembled mouse genome makespossible, for the first time, an alignment and comparison of two largevertebrate genomes. We have investigated different strategies ofalignment for the subsequent analysis of conservation of genomes that areeffective for different quality assemblies. These strategies were appliedto the comparison of the working draft of the human genome with the MouseGenome Sequencing Consortium assembly, as well as other intermediatemouse assemblies. Our methods are fast and the resulting alignmentsexhibit a high degree of sensitivity, covering more than 90 percent ofknown coding exons in the human genome. We have obtained such coveragewhile preserving specificity. With a view towards the end user, we havedeveloped a suite of tools and websites for automatically aligning, andsubsequently browsing and working with whole genome comparisons. Wedescribe the use of these tools to identify conserved non-coding regionsbetween the human and mouse genomes, some of which have not beenidentified by other methods.

  6. Optical fiber alignment using cleaved-edge diffracted light

    Science.gov (United States)

    Brun, Louis C.; Bergeron, Patrick; Duguay, Michel A.; Ouellette, Francois; Tetu, Michel

    1993-08-01

    We describe a simple technique for aligning optical fibers prior to fusion splicing. The technique relies on the fact that well-cleaved fiber ends have extremely sharp edges. By making the narrow pencil of light emerging from one fiber scan laterally over the entrance face of a second fiber, and by monitoring the light diffracted past its sharp edges, we can locate precisely the geometric center of the output fiber. With this technique, we have aligned fiber cores with a mean lateral offset of 0.81 micrometers , the major part of this offset caused by the eccentricity of the core relative to the cladding's circular perimeter.

  7. Aberrant splicing and drug resistance in AML.

    Science.gov (United States)

    de Necochea-Campion, Rosalia; Shouse, Geoffrey P; Zhou, Qi; Mirshahidi, Saied; Chen, Chien-Shing

    2016-01-01

    The advent of next-generation sequencing technologies has unveiled a new window into the heterogeneity of acute myeloid leukemia (AML). In particular, recurrent mutations in spliceosome machinery and genome-wide aberrant splicing events have been recognized as a prominent component of this disease. This review will focus on how these factors influence drug resistance through altered splicing of tumor suppressor and oncogenes and dysregulation of the apoptotic signaling network. A better understanding of these factors in disease progression is necessary to design appropriate therapeutic strategies recognizing specific alternatively spliced or mutated oncogenic targets. PMID:27613060

  8. ASDB: database of alternatively spliced genes

    OpenAIRE

    Dralyuk, I; Brudno, M.; Gelfand, M S; Zorn, M.; Dubchak, I.

    2000-01-01

    Version 2.1 of ASDB (Alternative Splicing Data Base) contains 1922 protein and 2486 DNA sequences. The protein entries from SWISS-PROT are joined into clusters corresponding to alternatively spliced variants of one gene. The DNA division consists of complete genes with alternative splicing mentioned or annotated in GenBank. The search engine allows one to search over SWISS-PROT and GenBank fields and then follow the links to all variants. The database can be assessed at the URL http://cbcg.ne...

  9. Regulation of Alternative Splicing in Vivo by Overexpression of Antagonistic Splicing Factors

    Science.gov (United States)

    Caceres, Javier F.; Stamm, Stefan; Helfman, David M.; Krainer, Adrian R.

    1994-09-01

    The opposing effects of SF2/ASF and heterogeneous nuclear ribonucleoprotein (hnRNP) A1 influence alternative splicing in vitro. SF2/ASF or hnRNP A1 complementary DNAs were transiently overexpressed in HeLa cells, and the effect on alternative splicing of several cotransfected reporter genes was measured. Increased expression of SF2/ASF activated proximal 5' splice sites, promoted inclusion of a neuron-specific exon, and prevented abnormal exon skipping. Increased expression of hnRNP A1 activated distal 5' splice sites. Therefore, variations in the intracellular levels of antagonistic splicing factors influence different modes of alternative splicing in vivo and may be a natural mechanism for tissue-specific or developmental regulation of gene expression.

  10. Product-internal assembly functions: a novel micro-assembly concept applied to optical interconnects

    OpenAIRE

    Henneken, V.A.

    2008-01-01

    In this project, the technical feasibility of a novel assembly concept was explored, in which microsystem-based self-assembly functionality is added to an existing product. The case considered is the accurate alignment of an optical fibre relative to a telecommunication laser source. In the most demanding cases this requires alignment accuracies down to 0.1 µm to achieve adequate optical coupling. This is very difficult to achieve using conventional assembly, making the assembly cost up ...

  11. Analysis of differential splicing suggests different modes of short-term splicing regulation

    OpenAIRE

    Topa, Hande; Honkela, Antti

    2016-01-01

    Motivation: Alternative splicing is an important mechanism in which the regions of pre-mRNAs are differentially joined in order to form different transcript isoforms. Alternative splicing is involved in the regulation of normal physiological functions but also linked to the development of diseases such as cancer. We analyse differential expression and splicing using RNA-sequencing time series in three different settings: overall gene expression levels, absolute transcript expression levels an...

  12. Hollywood: a comparative relational database of alternative splicing

    OpenAIRE

    Holste, Dirk; Huo, George; Tung, Vivian; Burge, Christopher B.

    2005-01-01

    RNA splicing is an essential step in gene expression, and is often variable, giving rise to multiple alternatively spliced mRNA and protein isoforms from a single gene locus. The design of effective databases to support experimental and computational investigations of alternative splicing (AS) is a significant challenge. In an effort to integrate accurate exon and splice site annotation with current knowledge about splicing regulatory elements and predicted AS events, and to link information ...

  13. HIV-1 Vpr: A Novel Role in Regulating RNA Splicing

    OpenAIRE

    Zhang, Xianfeng; Aida, Yoko

    2009-01-01

    Pre-mRNA splicing is a critical step in gene expression for metazoans. Several viral proteins regulate the splicing of pre-mRNAs through complex interactions between the virus and the host cell RNA splicing machinery. Here, we focus on a novel function of HIV-1 Vpr, that selectively inhibit cellular and viral pre-mRNA splicing, via interactions with components of functional spliceosomal complexes. This review discusses our current knowledge of how RNA splicing regulation is accomplished by Vp...

  14. Control of Pre-mRNA Splicing by the General Splicing Factors PUF60 and U2AF65

    OpenAIRE

    Hastings, Michelle L.; Eric Allemand; Duelli, Dominik M.; Michael P Myers; Krainer, Adrian R.

    2007-01-01

    Pre-mRNA splicing is a crucial step in gene expression, and accurate recognition of splice sites is an essential part of this process. Splice sites with weak matches to the consensus sequences are common, though it is not clear how such sites are efficiently utilized. Using an in vitro splicing-complementation approach, we identified PUF60 as a factor that promotes splicing of an intron with a weak 3' splice-site. PUF60 has homology to U2AF(65), a general splicing factor that facilitates 3' s...

  15. A Novel Type of Splicing Enhancer Regulating Adenovirus Pre-mRNA Splicing

    OpenAIRE

    Mühlemann, Oliver; Yue, Bai-Gong; Petersen-Mahrt, Svend; Akusjärvi, Göran

    2000-01-01

    Splicing of the adenovirus IIIa pre-mRNA is subjected to a temporal regulation, such that efficient IIIa 3′ splice site usage is confined to the late phase of the infectious cycle. Here we show that IIIa pre-mRNA splicing is activated more than 200-fold in nuclear extracts prepared from late adenovirus-infected cells (Ad-NE) compared to uninfected HeLa cell nuclear extracts (HeLa-NE). In contrast, splicing of the β-globin pre-mRNA is repressed in Ad-NE. We constructed hybrid pre-mRNAs between...

  16. Competition between pre-mRNAs for the splicing machinery drives global regulation of splicing.

    Science.gov (United States)

    Munding, Elizabeth M; Shiue, Lily; Katzman, Sol; Donohue, John Paul; Ares, Manuel

    2013-08-01

    During meiosis in yeast, global splicing efficiency increases and then decreases. Here we provide evidence that splicing improves due to reduced competition for the splicing machinery. The timing of this regulation corresponds to repression and reactivation of ribosomal protein genes (RPGs) during meiosis. In vegetative cells, RPG repression by rapamycin treatment also increases splicing efficiency. Downregulation of the RPG-dedicated transcription factor gene IFH1 genetically suppresses two spliceosome mutations, prp11-1 and prp4-1, and globally restores splicing efficiency in prp4-1 cells. We conclude that the splicing apparatus is limiting and that pre-messenger RNAs compete. Splicing efficiency of a pre-mRNA therefore depends not just on its own concentration and affinity for limiting splicing factor(s), but also on those of competing pre-mRNAs. Competition between RNAs for limiting processing factors appears to be a general condition in eukaryotes for a variety of posttranscriptional control mechanisms including microRNA (miRNA) repression, polyadenylation, and splicing. PMID:23891561

  17. Group II Intron Self-Splicing.

    Science.gov (United States)

    Pyle, Anna Marie

    2016-07-01

    Group II introns are large, autocatalytic ribozymes that catalyze RNA splicing and retrotransposition. Splicing by group II introns plays a major role in the metabolism of plants, fungi, and yeast and contributes to genetic variation in many bacteria. Group II introns have played a major role in genome evolution, as they are likely progenitors of spliceosomal introns, retroelements, and other machinery that controls genetic variation and stability. The structure and catalytic mechanism of group II introns have recently been elucidated through a combination of genetics, chemical biology, solution biochemistry, and crystallography. These studies reveal a dynamic machine that cycles progressively through multiple conformations as it stimulates the various stages of splicing. A central active site, containing a reactive metal ion cluster, catalyzes both steps of self-splicing. These studies provide insights into RNA structure, folding, and catalysis, as they raise new questions about the behavior of RNA machines. PMID:27391926

  18. Protein splicing and its evolution in eukaryotes

    Directory of Open Access Journals (Sweden)

    Starokadomskyy P. L.

    2010-02-01

    Full Text Available Inteins, or protein introns, are parts of protein sequences that are post-translationally excised, their flanking regions (exteins being spliced together. This process was called protein splicing. Originally inteins were found in prokaryotic or unicellular eukaryotic organisms. But the general principles of post-translation protein rearrangement are evolving yielding different post-translation modification of proteins in multicellular organisms. For clarity, these non-intein mediated events call either protein rearrangements or protein editing. The most intriguing example of protein editing is proteasome-mediated splicing of antigens in vertebrates that may play important role in antigen presentation. Other examples of protein rearrangements are maturation of Hg-proteins (critical receptors in embryogenesis as well as maturation of several metabolic enzymes. Despite a lack of experimental data we try to analyze some intriguing examples of protein splicing evolution.

  19. Tau exon 10 alternative splicing and tauopathies

    OpenAIRE

    Liu Fei; Gong Cheng-Xin

    2008-01-01

    Abstract Abnormalities of microtubule-associated protein tau play a central role in neurofibrillary degeneration in several neurodegenerative disorders that collectively called tauopathies. Six isoforms of tau are expressed in adult human brain, which result from alternative splicing of pre-mRNA generated from a single tau gene. Alternative splicing of tau exon 10 results in tau isoforms containing either three or four microtubule-binding repeats (3R-tau and 4R-tau, respectively). Approximate...

  20. Splice Junction Map of Simian Parvovirus Transcripts

    OpenAIRE

    Vashisht, Kapil; Faaberg, Kay S.; Aber, Amanda L.; Brown, Kevin E.; O’Sullivan, M. Gerard

    2004-01-01

    The transcription map of simian parvovirus (SPV), an Erythrovirus similar to Parvovirus B19, was investigated. RNA was extracted from tissues of experimentally infected cynomolgus macaques and subjected to reverse transcription-PCR with SPV-specific primers. The PCR products were cloned and sequenced to identify splice junctions. A total of 14 distinct sequences were identified as putative partial transcripts. Of these, 13 were spliced; a single unspliced transcript putatively encoded NS1. Se...

  1. Alcoholism and Alternative Splicing of Candidate Genes

    OpenAIRE

    Toshikazu Sasabe; Shoichi Ishiura

    2010-01-01

    Gene expression studies have shown that expression patterns of several genes have changed during the development of alcoholism. Gene expression is regulated not only at the level of transcription but also through alternative splicing of pre-mRNA. In this review, we discuss some of the evidence suggesting that alternative splicing of candidate genes such as DRD2 (encoding dopamine D2 receptor) may form the basis of the mechanisms underlying the pathophysiology of alcoholism. These reports sugg...

  2. Automatic alignment of multiple magnets into Halbach cylinders

    International Nuclear Information System (INIS)

    Halbach cylinders have found various applications for their ability to produce strong and homogenous magnetostatic fields. Contrary to their conventional manual fabrication, we introduce a novel approach to automatically align multiple permanent magnets into a Halbach cylinder. The approach uses the magnetic field distribution from a diametrically magnetized cylindrical magnet to simultaneously align multiple magnets. The extent to which the automatic assembly can approximate a Halbach cylinder was analyzed using 3D Finite Element Modeling. Prototypes were built that demonstrated automatic alignment of eight magnets into Halbach cylinders. Automatic alignment eliminates the complexity of manually aligning Halbach cylinders. - Highlights: • A new method for fabricating cylindrical Halbach array. • Simultaneously alignment of multiple magnets into Halbach cylinders. • Automatic alignment eliminates the complexity of manually aligning Halbach cylinders

  3. iAssembler: a package for de novo assembly of Roche-454/Sanger transcriptome sequences

    Directory of Open Access Journals (Sweden)

    Zheng Yi

    2011-11-01

    Full Text Available Abstract Background Expressed Sequence Tags (ESTs have played significant roles in gene discovery and gene functional analysis, especially for non-model organisms. For organisms with no full genome sequences available, ESTs are normally assembled into longer consensus sequences for further downstream analysis. However current de novo EST assembly programs often generate large number of assembly errors that will negatively affect the downstream analysis. In order to generate more accurate consensus sequences from ESTs, tools are needed to reduce or eliminate errors from de novo assemblies. Results We present iAssembler, a pipeline that can assemble large-scale ESTs into consensus sequences with significantly higher accuracy than current existing assemblers. iAssembler employs MIRA and CAP3 assemblers to generate initial assemblies, followed by identifying and correcting two common types of transcriptome assembly errors: 1 ESTs from different transcripts (mainly alternatively spliced transcripts or paralogs are incorrectly assembled into same contigs; and 2 ESTs from same transcripts fail to be assembled together. iAssembler can be used to assemble ESTs generated using the traditional Sanger method and/or the Roche-454 massive parallel pyrosequencing technology. Conclusion We compared performances of iAssembler and several other de novo EST assembly programs using both Roche-454 and Sanger EST datasets. It demonstrated that iAssembler generated significantly more accurate consensus sequences than other assembly programs.

  4. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G.Gomez.

    Since June of 2009, the muon alignment group has focused on providing new alignment constants and on finalizing the hardware alignment reconstruction. Alignment constants for DTs and CSCs were provided for CRAFT09 data reprocessing. For DT chambers, the track-based alignment was repeated using CRAFT09 cosmic ray muons and validated using segment extrapolation and split cosmic tools. One difference with respect to the previous alignment is that only five degrees of freedom were aligned, leaving the rotation around the local x-axis to be better determined by the hardware system. Similarly, DT chambers poorly aligned by tracks (due to limited statistics) were aligned by a combination of photogrammetry and hardware-based alignment. For the CSC chambers, the hardware system provided alignment in global z and rotations about local x. Entire muon endcap rings were further corrected in the transverse plane (global x and y) by the track-based alignment. Single chamber track-based alignment suffers from poor statistic...

  5. Evolution of alternative splicing regulation: changes in predicted exonic splicing regulators are not associated with changes in alternative splicing levels in primates

    OpenAIRE

    Manuel Irimia; Jakob Lewin Rukov; Scott William Roy

    2009-01-01

    Alternative splicing is tightly regulated in a spatio-temporal and quantitative manner. This regulation is achieved by a complex interplay between spliceosomal (trans) factors that bind to different sequence (cis) elements. cis-elements reside in both introns and exons and may either enhance or silence splicing. Differential combinations of cis-elements allows for a huge diversity of overall splicing signals, together comprising a complex ‘splicing code’. Many cis-elements have been identifie...

  6. Desktop aligner for fabrication of multilayer microfluidic devices

    Science.gov (United States)

    Li, Xiang; Yu, Zeta Tak For; Geraldo, Dalton; Weng, Shinuo; Alve, Nitesh; Dun, Wu; Kini, Akshay; Patel, Karan; Shu, Roberto; Zhang, Feng; Li, Gang; Jin, Qinghui; Fu, Jianping

    2015-07-01

    Multilayer assembly is a commonly used technique to construct multilayer polydimethylsiloxane (PDMS)-based microfluidic devices with complex 3D architecture and connectivity for large-scale microfluidic integration. Accurate alignment of structure features on different PDMS layers before their permanent bonding is critical in determining the yield and quality of assembled multilayer microfluidic devices. Herein, we report a custom-built desktop aligner capable of both local and global alignments of PDMS layers covering a broad size range. Two digital microscopes were incorporated into the aligner design to allow accurate global alignment of PDMS structures up to 4 in. in diameter. Both local and global alignment accuracies of the desktop aligner were determined to be about 20 μm cm-1. To demonstrate its utility for fabrication of integrated multilayer PDMS microfluidic devices, we applied the desktop aligner to achieve accurate alignment of different functional PDMS layers in multilayer microfluidics including an organs-on-chips device as well as a microfluidic device integrated with vertical passages connecting channels located in different PDMS layers. Owing to its convenient operation, high accuracy, low cost, light weight, and portability, the desktop aligner is useful for microfluidic researchers to achieve rapid and accurate alignment for generating multilayer PDMS microfluidic devices.

  7. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G. Gomez and J. Pivarski

    2011-01-01

    Alignment efforts in the first few months of 2011 have shifted away from providing alignment constants (now a well established procedure) and focussed on some critical remaining issues. The single most important task left was to understand the systematic differences observed between the track-based (TB) and hardware-based (HW) barrel alignments: a systematic difference in r-φ and in z, which grew as a function of z, and which amounted to ~4-5 mm differences going from one end of the barrel to the other. This difference is now understood to be caused by the tracker alignment. The systematic differences disappear when the track-based barrel alignment is performed using the new “twist-free” tracker alignment. This removes the largest remaining source of systematic uncertainty. Since the barrel alignment is based on hardware, it does not suffer from the tracker twist. However, untwisting the tracker causes endcap disks (which are aligned ...

  8. Splicing therapy for neuromuscular disease.

    Science.gov (United States)

    Douglas, Andrew G L; Wood, Matthew J A

    2013-09-01

    Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) are two of the most common inherited neuromuscular diseases in humans. Both conditions are fatal and no clinically available treatments are able to significantly alter disease course in either case. However, by manipulation of pre-mRNA splicing using antisense oligonucleotides, defective transcripts from the DMD gene and from the SMN2 gene in SMA can be modified to once again produce protein and restore function. A large number of in vitro and in vivo studies have validated the applicability of this approach and an increasing number of preliminary clinical trials have either been completed or are under way. Several different oligonucleotide chemistries can be used for this purpose and various strategies are being developed to facilitate increased delivery efficiency and prolonged therapeutic effect. As these novel therapeutic compounds start to enter the clinical arena, attention must also be drawn to the question of how best to facilitate the clinical development of such personalised genetic therapies and how best to implement their provision. PMID:23631896

  9. Alternative Splice in Alternative Lice.

    Science.gov (United States)

    Tovar-Corona, Jaime M; Castillo-Morales, Atahualpa; Chen, Lu; Olds, Brett P; Clark, John M; Reynolds, Stuart E; Pittendrigh, Barry R; Feil, Edward J; Urrutia, Araxi O

    2015-10-01

    Genomic and transcriptomics analyses have revealed human head and body lice to be almost genetically identical; although con-specific, they nevertheless occupy distinct ecological niches and have differing feeding patterns. Most importantly, while head lice are not known to be vector competent, body lice can transmit three serious bacterial diseases; epidemictyphus, trench fever, and relapsing fever. In order to gain insights into the molecular bases for these differences, we analyzed alternative splicing (AS) using next-generation sequencing data for one strain of head lice and one strain of body lice. We identified a total of 3,598 AS events which were head or body lice specific. Exon skipping AS events were overrepresented among both head and body lice, whereas intron retention events were underrepresented in both. However, both the enrichment of exon skipping and the underrepresentation of intron retention are significantly stronger in body lice compared with head lice. Genes containing body louse-specific AS events were found to be significantly enriched for functions associated with development of the nervous system, salivary gland, trachea, and ovarian follicle cells, as well as regulation of transcription. In contrast, no functional categories were overrepresented among genes with head louse-specific AS events. Together, our results constitute the first evidence for transcript pool differences in head and body lice, providing insights into molecular adaptations that enabled human lice to adapt to clothing, and representing a powerful illustration of the pivotal role AS can play in functional adaptation. PMID:26169943

  10. Spliced leader trapping reveals widespread alternative splicing patterns in the highly dynamic transcriptome of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Daniel Nilsson

    Full Text Available Trans-splicing of leader sequences onto the 5'ends of mRNAs is a widespread phenomenon in protozoa, nematodes and some chordates. Using parallel sequencing we have developed a method to simultaneously map 5'splice sites and analyze the corresponding gene expression profile, that we term spliced leader trapping (SLT. The method can be applied to any organism with a sequenced genome and trans-splicing of a conserved leader sequence. We analyzed the expression profiles and splicing patterns of bloodstream and insect forms of the parasite Trypanosoma brucei. We detected the 5' splice sites of 85% of the annotated protein-coding genes and, contrary to previous reports, found up to 40% of transcripts to be differentially expressed. Furthermore, we discovered more than 2500 alternative splicing events, many of which appear to be stage-regulated. Based on our findings we hypothesize that alternatively spliced transcripts present a new means of regulating gene expression and could potentially contribute to protein diversity in the parasite. The entire dataset can be accessed online at TriTrypDB or through: http://splicer.unibe.ch/.

  11. Optical interconnect assembly

    Science.gov (United States)

    Laughlin, Daric; Abel, Philip

    2015-06-09

    An optical assembly includes a substrate with a first row of apertures and a second row of apertures. A first optical die includes a first plurality of optical transducer elements and is mounted on the substrate such that an optical signal interface of each transducer element is aligned with an aperture of the first row of optical apertures. A second optical die includes a second plurality of optical transducer elements and is mounted on the substrate such that an optical signal interface of each of the second plurality of optical transducer elements is aligned with an aperture of the second row of optical apertures. A connector configured to mate with the optical assembly supports a plurality of optical fibers. A terminal end of each optical fiber protrudes from the connector and extends into one of the apertures when the connector is coupled with the optical assembly.

  12. Fast statistical alignment.

    Directory of Open Access Journals (Sweden)

    Robert K Bradley

    2009-05-01

    Full Text Available We describe a new program for the alignment of multiple biological sequences that is both statistically motivated and fast enough for problem sizes that arise in practice. Our Fast Statistical Alignment program is based on pair hidden Markov models which approximate an insertion/deletion process on a tree and uses a sequence annealing algorithm to combine the posterior probabilities estimated from these models into a multiple alignment. FSA uses its explicit statistical model to produce multiple alignments which are accompanied by estimates of the alignment accuracy and uncertainty for every column and character of the alignment--previously available only with alignment programs which use computationally-expensive Markov Chain Monte Carlo approaches--yet can align thousands of long sequences. Moreover, FSA utilizes an unsupervised query-specific learning procedure for parameter estimation which leads to improved accuracy on benchmark reference alignments in comparison to existing programs. The centroid alignment approach taken by FSA, in combination with its learning procedure, drastically reduces the amount of false-positive alignment on biological data in comparison to that given by other methods. The FSA program and a companion visualization tool for exploring uncertainty in alignments can be used via a web interface at http://orangutan.math.berkeley.edu/fsa/, and the source code is available at http://fsa.sourceforge.net/.

  13. Fast statistical alignment.

    Science.gov (United States)

    Bradley, Robert K; Roberts, Adam; Smoot, Michael; Juvekar, Sudeep; Do, Jaeyoung; Dewey, Colin; Holmes, Ian; Pachter, Lior

    2009-05-01

    We describe a new program for the alignment of multiple biological sequences that is both statistically motivated and fast enough for problem sizes that arise in practice. Our Fast Statistical Alignment program is based on pair hidden Markov models which approximate an insertion/deletion process on a tree and uses a sequence annealing algorithm to combine the posterior probabilities estimated from these models into a multiple alignment. FSA uses its explicit statistical model to produce multiple alignments which are accompanied by estimates of the alignment accuracy and uncertainty for every column and character of the alignment--previously available only with alignment programs which use computationally-expensive Markov Chain Monte Carlo approaches--yet can align thousands of long sequences. Moreover, FSA utilizes an unsupervised query-specific learning procedure for parameter estimation which leads to improved accuracy on benchmark reference alignments in comparison to existing programs. The centroid alignment approach taken by FSA, in combination with its learning procedure, drastically reduces the amount of false-positive alignment on biological data in comparison to that given by other methods. The FSA program and a companion visualization tool for exploring uncertainty in alignments can be used via a web interface at http://orangutan.math.berkeley.edu/fsa/, and the source code is available at http://fsa.sourceforge.net/. PMID:19478997

  14. A global analysis of C. elegans trans-splicing

    OpenAIRE

    Allen, Mary Ann; Hillier, LaDeana W.; Waterston, Robert H.; Blumenthal, Thomas

    2011-01-01

    Trans-splicing of one of two short leader RNAs, SL1 or SL2, occurs at the 5′ ends of pre-mRNAs of many C. elegans genes. We have exploited RNA-sequencing data from the modENCODE project to analyze the transcriptome of C. elegans for patterns of trans-splicing. Transcripts of ∼70% of genes are trans-spliced, similar to earlier estimates based on analysis of far fewer genes. The mRNAs of most trans-spliced genes are spliced to either SL1 or SL2, but most genes are not trans-spliced to both, ind...

  15. Alignment of the NOMAD-STAR detector

    CERN Document Server

    Cervera-Villanueva, A

    2000-01-01

    This note describes the alignment of the NOMAD-STAR detector. This is the B/sub 4/C-silicon target installed in the NOMAD spectrometer in 1997. NOMAD-STAR is composed of modules of 12 silicon detectors each giving a total length of 72 cm. Ten of these modules (called ladders) are assembled to form a layer. There are five layers interleaved with passive boron carbide plates. The total surface of silicon is 1.14 m /sup 2/. Energetic muons from the flat-top of the CERN SPS cycle provide the necessary information to perform a very precise software alignment. This alignment is needed to ensure that the impact parameter measurement needed for the identification of taus in a detector like NOMAD-STAR will not be limited by the error in the alignment. (15 refs).

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

    Directory of Open Access Journals (Sweden)

    Elela Sherif

    2006-01-01

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

  17. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G.Gomez

    2010-01-01

    The main developments in muon alignment since March 2010 have been the production, approval and deployment of alignment constants for the ICHEP data reprocessing. In the barrel, a new geometry, combining information from both hardware and track-based alignment systems, has been developed for the first time. The hardware alignment provides an initial DT geometry, which is then anchored as a rigid solid, using the link alignment system, to a reference frame common to the tracker. The “GlobalPositionRecords” for both the Tracker and Muon systems are being used for the first time, and the initial tracker-muon relative positioning, based on the link alignment, yields good results within the photogrammetry uncertainties of the Tracker and alignment ring positions. For the first time, the optical and track-based alignments show good agreement between them; the optical alignment being refined by the track-based alignment. The resulting geometry is the most complete to date, aligning all 250 DTs, ...

  18. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    Z. Szillasi and G. Gomez.

    2013-01-01

    When CMS is opened up, major components of the Link and Barrel Alignment systems will be removed. This operation, besides allowing for maintenance of the detector underneath, is needed for making interventions that will reinforce the alignment measurements and make the operation of the alignment system more reliable. For that purpose and also for their general maintenance and recalibration, the alignment components will be transferred to the Alignment Lab situated in the ISR area. For the track-based alignment, attention is focused on the determination of systematic uncertainties, which have become dominant, since now there is a large statistics of muon tracks. This will allow for an improved Monte Carlo misalignment scenario and updated alignment position errors, crucial for high-momentum muon analysis such as Z′ searches.

  19. Discovery of Novel Splice Variants and Regulatory Mechanisms for Microsomal Triglyceride Transfer Protein in Human Tissues.

    Science.gov (United States)

    Suzuki, Takashi; Swift, Larry L

    2016-01-01

    Microsomal triglyceride transfer protein (MTP) is a unique lipid transfer protein essential for the assembly of triglyceride-rich lipoproteins by the liver and intestine. Previous studies in mice identified a splice variant of MTP with an alternate first exon. Splice variants of human MTP have not been reported. Using PCR approaches we have identified two splice variants in human tissues, which we have named MTP-B and MTP-C. MTP-B has a unique first exon (Ex1B) located 10.5 kb upstream of the first exon (Ex1A) for canonical MTP (MTP-A); MTP-C contains both first exons for MTP-A and MTP-B. MTP-B was found in a number of tissues, whereas MTP-C was prominent in brain and testis. MTP-B does not encode a protein; MTP-C encodes the same protein encoded by MTP-A, although MTP-C translation is strongly inhibited by regulatory elements within its 5'-UTR. Using luciferase assays, we demonstrate that the promoter region upstream of exon 1B is quite adequate to drive expression of MTP. We conclude that alternate splicing plays a key role in regulating cellular MTP levels by introducing distinct promoter regions and unique 5'-UTRs, which contain elements that alter translation efficiency, enabling the cell to optimize MTP activity. PMID:27256115

  20. Alternative splicing of RyR1 alters the efficacy of skeletal EC coupling

    Science.gov (United States)

    Kimura, Takashi; Lueck, John D.; Harvey, Peta J.; Pace, Suzy M.; Ikemoto, Noriaki; Casarotto, Marco G.; Dirksen, Robert T.; Dulhunty, Angela F.

    2009-01-01

    Summary Alternative splicing of ASI residues (Ala3481-Gln3485) in the skeletal muscle ryanodine receptor (RyR1) is developmentally regulated: the residues are present in adult ASI(+)RyR1, but absent in the juvenile ASI(-)RyR1 which is over-expressed in adult myotonic dystrophy type 1 (DM1). Although this splicing switch may influence RyR1 function in developing muscle and DM1, little is known about the properties of the splice variants. We examined excitation-contraction (EC) coupling and the structure and interactions of the ASI domain (Thr3471-Gly3500) in the splice variants. Depolarisation-dependent Ca2+ release was enhanced by >50% in myotubes expressing ASI(-)RyR1 compared with ASI(+)RyR1, although DHPR L-type currents and SR Ca2+ content were unaltered, while ASI(-)RyR1 channel function was actually depressed. The effect on EC coupling did not depend on changes in ASI domain secondary structure. Probing RyR1 function with peptides possessing the ASI domain sequence indicated that the domain contributes to an inhibitory module in RyR1. The action of the peptide depended on a sequence of basic residues and their alignment in an α-helix adjacent to the ASI splice site. This is the first evidence that the ASI residues contribute to an inhibitory module in RyR1 that influences EC coupling. Implications for development and DM1 are discussed. PMID:19131108

  1. Functional and evolutionary analysis of alternatively spliced genes is consistent with an early eukaryotic origin of alternative splicing

    Directory of Open Access Journals (Sweden)

    Penny David

    2007-10-01

    Full Text Available Abstract Background Alternative splicing has been reported in various eukaryotic groups including plants, apicomplexans, diatoms, amoebae, animals and fungi. However, whether widespread alternative splicing has evolved independently in the different eukaryotic groups or was inherited from their last common ancestor, and may therefore predate multicellularity, is still unknown. To better understand the origin and evolution of alternative splicing and its usage in diverse organisms, we studied alternative splicing in 12 eukaryotic species, comparing rates of alternative splicing across genes of different functional classes, cellular locations, intron/exon structures and evolutionary origins. Results For each species, we find that genes from most functional categories are alternatively spliced. Ancient genes (shared between animals, fungi and plants show high levels of alternative splicing. Genes with products expressed in the nucleus or plasma membrane are generally more alternatively spliced while those expressed in extracellular location show less alternative splicing. We find a clear correspondence between incidence of alternative splicing and intron number per gene both within and between genomes. In general, we find several similarities in patterns of alternative splicing across these diverse eukaryotes. Conclusion Along with previous studies indicating intron-rich genes with weak intron boundary consensus and complex spliceosomes in ancestral organisms, our results suggest that at least a simple form of alternative splicing may already have been present in the unicellular ancestor of plants, fungi and animals. A role for alternative splicing in the evolution of multicellularity then would largely have arisen by co-opting the preexisting process.

  2. Regulation of mammalian pre-mRNA splicing

    Institute of Scientific and Technical Information of China (English)

    HUI JingYi

    2009-01-01

    In eukaryotes, most protein-coding genes contain introns which are removed by precursor messenger RNA (pre-mRNA) splicing. Alternative splicing is a process by which multiple messenger RNAs (mRNAs) are generated from a single pre-mRNA, resulting in functionally distinct proteins. Recent genome-wide analyses of alternative splicing indicated that in higher eukaryotes alternative splicing is an important mechanism that generates proteomic complexity and regulates gene expression. Mis-regulation of splicing causes a wide range of human diseases. This review describes the current understanding of pre-mRNA splicing and the mechanisms that regulate mammalian pre-mRNA splicing. It also discusses emerging directions in the field of alternative splicing.

  3. Altered PLP1 splicing causes hypomyelination of early myelinating structures

    DEFF Research Database (Denmark)

    Kevelam, Sietske H; Taube, Jennifer R; van Spaendonk, Rosalina M L;

    2015-01-01

    causal mutations. In silico analysis of effects of the mutations on splicing and RNA folding was performed. In vitro gene splicing was examined in RNA from patients' fibroblasts and an immortalized immature oligodendrocyte cell line after transfection with mutant minigene splicing constructs. RESULTS......: All patients had unusual hemizygous mutations of PLP1 located in exon 3B (one deletion, one missense and two silent), which is spliced out in isoform DM20, or in intron 3 (five mutations). The deletion led to truncation of PLP1, but not DM20. Four mutations were predicted to affect PLP1/DM20...... alternative splicing by creating exonic splicing silencer motifs or new splice donor sites or by affecting the local RNA structure of the PLP1 splice donor site. Four deep intronic mutations were predicted to destabilize a long-distance interaction structure in the secondary PLP1 RNA fragment involved in...

  4. Regulation of mammalian pre-mRNA splicing

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    In eukaryotes,most protein-coding genes contain introns which are removed by precursor messenger RNA(pre-mRNA) splicing.Alternative splicing is a process by which multiple messenger RNAs(mRNAs) are generated from a single pre-mRNA,resulting in functionally distinct proteins.Recent genome-wide analyses of alternative splicing indicated that in higher eukaryotes alternative splicing is an important mechanism that generates proteomic complexity and regulates gene expression.Mis-regulation of splicing causes a wide range of human diseases.This review describes the current understanding of pre-mRNA splicing and the mechanisms that regulate mammalian pre-mRNA splicing.It also discusses emerging directions in the field of alternative splicing.

  5. Quality control of cadweld (mechanical) splices

    International Nuclear Information System (INIS)

    Test data for cadweld splicing of reinforcing steel collected during a study of quality assurance practices on nine nuclear power plant construction projects are presented and evaluated. These data lead to an important hypothesis that the visual inspection identifies procedural deficiencies, and the tensile test identifies material defects. It is also suggested that a material testing program and the visual inspection will detect essentially all substandard cadwell splices. This would permit the deletion of the expensive tensile testing program. Accordingly, most quality control programs require overtesting and overdocumentation of cadweld splices; and furthermore, these programs fail to recognize material defects. The project specifications and quality control requirements for the nine projects are compared. Where possible, these are evaluated against the industry standards and Federal regulations. It is shown that there are a number of deficiencies in these standards, and that in most cases, the testing requirements are not commensurate with the quality that is being achieved in the field

  6. Splicing variants of porcine synphilin-1

    DEFF Research Database (Denmark)

    Larsen, Knud Erik; Madsen, Lone Bruhn; Farajzadeh, Leila;

    2015-01-01

    (90%) and to mouse (84%) synphilin-1. Three shorter transcript variants of the synphilin-1 gene were identified, all lacking one or more exons. SNCAIP transcripts were detected in most examined organs and tissues and the highest expression was found in brain tissues and lung. Conserved splicing......RNA was investigated by RNAseq. The presented work reports the molecular cloning and characterization of the porcine (Sus scrofa) synphilin-1 cDNA (SNCAIP) and three splice variants hereof. The porcine SNCAIP cDNA codes for a protein (synphilin-1) of 919 amino acids which shows a high similarity to human...... variants and a novel splice form of synhilin-1 were found in this study. All synphilin-1 isoforms encoded by the identified transcript variants lack functional domains important for protein degradation....

  7. Regulation of alternative splice site selection by reversible protein phosphorylation

    OpenAIRE

    Novoyatleva, Tatyana

    2007-01-01

    Splicing is the process that removes introns and joins exons from pre-mesenger RNA (pre-mRNA). It is an essential step in pre-mRNA processing that form the mature RNA. Microarray data indicates that approximately 75% of human genes produce transcripts that are alternatively spliced. Alternative splicing is one of the major mechanisms that ultimately generate high number of protein isoforms from a limited number of genes. The proper catalysis and regulation of alternative splice site selection...

  8. Progress toward therapy with antisense-mediated splicing modulation

    OpenAIRE

    Du, Liutao; Gatti, Richard A.

    2009-01-01

    Antisense oligonucleotides (AO) or antisense RNA can complementarily bind to a target site in pre-mRNA and regulate gene splicing, either to restore gene function by reprogramming gene splicing or to inhibit gene expression by disrupting splicing. These two applications represent novel therapeutic strategies for several types of diseases such as genetic disorders, cancers and infectious diseases. In this review, the recent developments and applications of antisense-mediated splicing modulatio...

  9. Alternative splicing of DNA damage response genes and gastrointestinal cancers

    OpenAIRE

    Rahmutulla, Bahityar; Matsushita, Kazuyuki; Nomura, Fumio

    2014-01-01

    Alternative splicing, which is a common phenomenon in mammalian genomes, is a fundamental process of gene regulation and contributes to great protein diversity. Alternative splicing events not only occur in the normal gene regulation process but are also closely related to certain diseases including cancer. In this review, we briefly demonstrate the concept of alternative splicing and DNA damage and describe the association of alternative splicing and cancer pathogenesis, focusing on the pote...

  10. RNA structure and the mechanisms of alternative splicing

    OpenAIRE

    McManus, C. Joel; Graveley, Brenton R.

    2011-01-01

    Alternative splicing is a widespread means of increasing protein diversity and regulating gene expression in eukaryotes. Much progress has been made in understanding the proteins involved in regulating alternative splicing, the sequences they bind to, and how these interactions lead to changes in splicing patterns. However, several recent studies have identified other players involved in regulating alternative splicing. A major theme emerging from these studies is that RNA secondary structure...

  11. Evolution of alternative splicing in primate brain transcriptomes

    OpenAIRE

    Lin, Lan; Shen, Shihao; Jiang, Peng; Sato, Seiko; Davidson, Beverly L.; Xing, Yi

    2010-01-01

    Alternative splicing is a predominant form of gene regulation in higher eukaryotes. The evolution of alternative splicing provides an important mechanism for the acquisition of novel gene functions. In this work, we carried out a genome-wide phylogenetic survey of lineage-specific splicing patterns in the primate brain, via high-density exon junction array profiling of brain transcriptomes of humans, chimpanzees and rhesus macaques. We identified 509 genes showing splicing differences among t...

  12. Functional and evolutionary analysis of alternatively spliced genes is consistent with an early eukaryotic origin of alternative splicing

    DEFF Research Database (Denmark)

    Irimia, Manuel; Rukov, Jakob Lewin; Penny, David;

    2007-01-01

    , and may therefore predate multicellularity, is still unknown. To better understand the origin and evolution of alternative splicing and its usage in diverse organisms, we studied alternative splicing in 12 eukaryotic species, comparing rates of alternative splicing across genes of different functional...... classes, cellular locations, intron/exon structures and evolutionary origins. RESULTS: For each species, we find that genes from most functional categories are alternatively spliced. Ancient genes (shared between animals, fungi and plants) show high levels of alternative splicing. Genes with products...... expressed in the nucleus or plasma membrane are generally more alternatively spliced while those expressed in extracellular location show less alternative splicing. We find a clear correspondence between incidence of alternative splicing and intron number per gene both within and between genomes. In general...

  13. Fast Statistical Alignment

    OpenAIRE

    Bradley, Robert K.; Adam Roberts; Michael Smoot; Sudeep Juvekar; Jaeyoung Do; Colin Dewey; Ian Holmes; Lior Pachter

    2009-01-01

    We describe a new program for the alignment of multiple biological sequences that is both statistically motivated and fast enough for problem sizes that arise in practice. Our Fast Statistical Alignment program is based on pair hidden Markov models which approximate an insertion/deletion process on a tree and uses a sequence annealing algorithm to combine the posterior probabilities estimated from these models into a multiple alignment. FSA uses its explicit statistical model to produce multi...

  14. SpliceMiner: a high-throughput database implementation of the NCBI Evidence Viewer for microarray splice variant analysis

    OpenAIRE

    Liu Hongfang; Ryan Michael C; Kahn Ari B; Zeeberg Barry R; Jamison D Curtis; Weinstein John N

    2007-01-01

    Abstract Background There are many fewer genes in the human genome than there are expressed transcripts. Alternative splicing is the reason. Alternatively spliced transcripts are often specific to tissue type, developmental stage, environmental condition, or disease state. Accurate analysis of microarray expression data and design of new arrays for alternative splicing require assessment of probes at the sequence and exon levels. Description SpliceMiner is a web interface for querying Evidenc...

  15. The epithelial splicing factors ESRP1 and ESRP2 positively and negatively regulate diverse types of alternative splicing events

    OpenAIRE

    Warzecha, Claude C.; Shen, Shihao; Xing, Yi; Carstens, Russ P.

    2009-01-01

    Cell-type and tissue-specific alternative splicing events are regulated by combinatorial control involving both abundant RNA binding proteins as well as those with more discrete expression and specialized functions. Epithelial Splicing Regulatory Proteins 1 and 2 (ESRP1 and ESRP2) are recently discovered epithelial-specific RNA binding proteins that promote splicing of the epithelial variant of the FGFR2, ENAH, CD44 and CTNND1 transcripts. To catalogue a larger set of splicing events under th...

  16. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G.Gomez

    2010-01-01

    Most of the work in muon alignment since December 2009 has focused on the geometry reconstruction from the optical systems and improvements in the internal alignment of the DT chambers. The barrel optical alignment system has progressively evolved from reconstruction of single active planes to super-planes (December 09) to a new, full barrel reconstruction. Initial validation studies comparing this full barrel alignment at 0T with photogrammetry provide promising results. In addition, the method has been applied to CRAFT09 data, and the resulting alignment at 3.8T yields residuals from tracks (extrapolated from the tracker) which look smooth, suggesting a good internal barrel alignment with a small overall offset with respect to the tracker. This is a significant improvement, which should allow the optical system to provide a start-up alignment for 2010. The end-cap optical alignment has made considerable progress in the analysis of transfer line data. The next set of alignment constants for CSCs will there...

  17. Orthodontics and Aligners

    Science.gov (United States)

    ... Repairing Chipped Teeth Teeth Whitening Tooth-Colored Fillings Orthodontics and Aligners Straighten teeth for a healthier smile. Orthodontics When consumers think about orthodontics, braces are the ...

  18. Auxiliary splice factor U2AF26 and transcription factor Gfi1 cooperate directly in regulating CD45 alternative splicing.

    NARCIS (Netherlands)

    Heyd, F.; Dam, G.B. ten; Moroy, T.

    2006-01-01

    By alternative splicing, different isoforms of the transmembrane tyrosine phosphatase CD45 are generated that either enhance or limit T cell receptor signaling. We report here that CD45 alternative splicing is regulated by cooperative action of the splice factor U2AF26 and the transcription factor G

  19. Age-related nuclear translocation of P2X6 subunit modifies splicing activity interacting with splicing factor 3A1.

    Directory of Open Access Journals (Sweden)

    Juan Ignacio Díaz-Hernández

    Full Text Available P2X receptors are ligand-gated ion channels sensitive to extracellular nucleotides formed by the assembling of three equal or different P2X subunits. In this work we report, for the first time, the accumulation of the P2X6 subunit inside the nucleus of hippocampal neurons in an age-dependent way. This location is favored by its anchorage to endoplasmic reticulum through its N-terminal domain. The extracellular domain of P2X6 subunit is the key to reach the nucleus, where it presents a speckled distribution pattern and is retained by interaction with the nuclear envelope protein spectrin α2. The in vivo results showed that, once inside the nucleus, P2X6 subunit interacts with the splicing factor 3A1, which ultimately results in a reduction of the mRNA splicing activity. Our data provide new insights into post-transcriptional regulation of mRNA splicing, describing a novel mechanism that could explain why this process is sensitive to changes that occur with age.

  20. Alignments between galaxies, satellite systems and haloes

    CERN Document Server

    Shao, Shi; Frenk, Carlos S; Gao, Liang; Crain, Robert A; Schaller, Matthieu; Schaye, Joop; Theuns, Tom

    2016-01-01

    The spatial distribution of the satellite populations of the Milky Way and Andromeda are puzzling in that they are nearly perpendicular to the disks of their central galaxies. To understand the origin of such configurations we study the alignment of the central galaxy, satellite system and dark matter halo in the largest of the "Evolution and Assembly of GaLaxies and their Environments" (EAGLE) simulation. We find that centrals and their satellite systems tend to be well aligned with their haloes, with a median misalignment angle of $33^{\\circ}$ in both cases. While the centrals are better aligned with the inner $10$ kpc halo, the satellite systems are better aligned with the entire halo indicating that satellites preferentially trace the outer halo. The central - satellite alignment is weak (median misalignment angle of $52^{\\circ}$) and we find that around $20\\%$ of systems have a misalignment angle larger than $78^{\\circ}$, which is the value for the Milky Way. The central - satellite alignment is a conseq...

  1. Capillary Electrophoresis Analysis of Conventional Splicing Assays

    DEFF Research Database (Denmark)

    de Garibay, Gorka Ruiz; Acedo, Alberto; García-Casado, Zaida;

    2014-01-01

    Rare sequence variants in "high-risk" disease genes, often referred as unclassified variants (UVs), pose a serious challenge to genetic testing. However, UVs resulting in splicing alterations can be readily assessed by in vitro assays. Unfortunately, analytical and clinical interpretation of thes...

  2. Alternative-splicing-mediated gene expression

    Science.gov (United States)

    Wang, Qianliang; Zhou, Tianshou

    2014-01-01

    Alternative splicing (AS) is a fundamental process during gene expression and has been found to be ubiquitous in eukaryotes. However, how AS impacts gene expression levels both quantitatively and qualitatively remains to be fully explored. Here, we analyze two common models of gene expression, each incorporating a simple splice mechanism that a pre-mRNA is spliced into two mature mRNA isoforms in a probabilistic manner. In the constitutive expression case, we show that the steady-state molecular numbers of two mature mRNA isoforms follow mutually independent Poisson distributions. In the bursting expression case, we demonstrate that the tail decay of the steady-state distribution for both mature mRNA isoforms that in general are not mutually independent can be characterized by the product of mean burst size and splicing probability. In both cases, we find that AS can efficiently modulate both the variability (measured by variance) and the noise level of the total mature mRNA, and in particular, the latter is always lower than the noise level of the pre-mRNA, implying that AS always reduces the noise. These results altogether reveal that AS is a mechanism of efficiently controlling the gene expression noise.

  3. Approaches to link RNA secondary structures with splicing regulation

    DEFF Research Database (Denmark)

    Plass, Mireya; Eyras, Eduardo

    2014-01-01

    facilitating or hindering the interaction with factors and small nuclear ribonucleoproteins (snRNPs) that regulate splicing. Moreover, the secondary structure could play a fundamental role in the splicing of yeast species, which lack many of the regulatory splicing factors present in metazoans. This chapter......In higher eukaryotes, alternative splicing is usually regulated by protein factors, which bind to the pre-mRNA and affect the recognition of splicing signals. There is recent evidence that the secondary structure of the pre-mRNA may also play an important role in this process, either by...

  4. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    Gervasio Gomez

    The main progress of the muon alignment group since March has been in the refinement of both the track-based alignment for the DTs and the hardware-based alignment for the CSCs. For DT track-based alignment, there has been significant improvement in the internal alignment of the superlayers inside the DTs. In particular, the distance between superlayers is now corrected, eliminating the residual dependence on track impact angles, and good agreement is found between survey and track-based corrections. The new internal geometry has been approved to be included in the forthcoming reprocessing of CRAFT samples. The alignment of DTs with respect to the tracker using global tracks has also improved significantly, since the algorithms use the latest B-field mapping, better run selection criteria, optimized momentum cuts, and an alignment is now obtained for all six degrees of freedom (three spatial coordinates and three rotations) of the aligned DTs. This work is ongoing and at a stage where we are trying to unders...

  5. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G.Gomez

    2011-01-01

    The Muon Alignment work now focuses on producing a new track-based alignment with higher track statistics, making systematic studies between the results of the hardware and track-based alignment methods and aligning the barrel using standalone muon tracks. Currently, the muon track reconstruction software uses a hardware-based alignment in the barrel (DT) and a track-based alignment in the endcaps (CSC). An important task is to assess the muon momentum resolution that can be achieved using the current muon alignment, especially for highly energetic muons. For this purpose, cosmic ray muons are used, since the rate of high-energy muons from collisions is very low and the event statistics are still limited. Cosmics have the advantage of higher statistics in the pT region above 100 GeV/c, but they have the disadvantage of having a mostly vertical topology, resulting in a very few global endcap muons. Only the barrel alignment has therefore been tested so far. Cosmic muons traversing CMS from top to bottom are s...

  6. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G. Gomez

    Since December, the muon alignment community has focused on analyzing the data recorded so far in order to produce new DT and CSC Alignment Records for the second reprocessing of CRAFT data. Two independent algorithms were developed which align the DT chambers using global tracks, thus providing, for the first time, a relative alignment of the barrel with respect to the tracker. These results are an important ingredient for the second CRAFT reprocessing and allow, for example, a more detailed study of any possible mis-modelling of the magnetic field in the muon spectrometer. Both algorithms are constructed in such a way that the resulting alignment constants are not affected, to first order, by any such mis-modelling. The CSC chambers have not yet been included in this global track-based alignment due to a lack of statistics, since only a few cosmics go through the tracker and the CSCs. A strategy exists to align the CSCs using the barrel as a reference until collision tracks become available. Aligning the ...

  7. Discovery of a Splicing Regulator Required for Cell Cycle Progression

    Energy Technology Data Exchange (ETDEWEB)

    Suvorova, Elena S.; Croken, Matthew; Kratzer, Stella; Ting, Li-Min; Conde de Felipe, Magnolia; Balu, Bharath; Markillie, Lye Meng; Weiss, Louis M.; Kim, Kami; White, Michael W.

    2013-02-01

    In the G1 phase of the cell division cycle, eukaryotic cells prepare many of the resources necessary for a new round of growth including renewal of the transcriptional and protein synthetic capacities and building the machinery for chromosome replication. The function of G1 has an early evolutionary origin and is preserved in single and multicellular organisms, although the regulatory mechanisms conducting G1 specific functions are only understood in a few model eukaryotes. Here we describe a new G1 mutant from an ancient family of apicomplexan protozoans. Toxoplasma gondii temperature-sensitive mutant 12-109C6 conditionally arrests in the G1 phase due to a single point mutation in a novel protein containing a single RNA-recognition-motif (TgRRM1). The resulting tyrosine to asparagine amino acid change in TgRRM1 causes severe temperature instability that generates an effective null phenotype for this protein when the mutant is shifted to the restrictive temperature. Orthologs of TgRRM1 are widely conserved in diverse eukaryote lineages, and the human counterpart (RBM42) can functionally replace the missing Toxoplasma factor. Transcriptome studies demonstrate that gene expression is downregulated in the mutant at the restrictive temperature due to a severe defect in splicing that affects both cell cycle and constitutively expressed mRNAs. The interaction of TgRRM1 with factors of the tri-SNP complex (U4/U6 & U5 snRNPs) indicate this factor may be required to assemble an active spliceosome. Thus, the TgRRM1 family of proteins is an unrecognized and evolutionarily conserved class of splicing regulators. This study demonstrates investigations into diverse unicellular eukaryotes, like the Apicomplexa, have the potential to yield new insights into important mechanisms conserved across modern eukaryotic kingdoms.

  8. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G. Gomez

    2011-01-01

    A new set of muon alignment constants was approved in August. The relative position between muon chambers is essentially unchanged, indicating good detector stability. The main changes concern the global positioning of the barrel and of the endcap rings to match the new Tracker geometry. Detailed studies of the differences between track-based and optical alignment of DTs have proven to be a valuable tool for constraining Tracker alignment weak modes, and this information is now being used as part of the alignment procedure. In addition to the “split-cosmic” analysis used to investigate the muon momentum resolution at high momentum, a new procedure based on reconstructing the invariant mass of di-muons from boosted Zs is under development. Both procedures show an improvement in the momentum precision of Global Muons with respect to Tracker-only Muons. Recent developments in track-based alignment include a better treatment of the tails of residual distributions and accounting for correla...

  9. Real Interference Alignment

    CERN Document Server

    Motahari, Abolfazl Seyed; Maddah-Ali, Mohammad-Ali; Khandani, Amir Keyvan

    2010-01-01

    In this paper, we show that the total Degrees-Of-Freedoms (DOF) of the $K$-user Gaussian Interference Channel (GIC) can be achieved by incorporating a new alignment technique known as \\emph{real interference alignment}. This technique compared to its ancestor \\emph{vector interference alignment} performs on a single real line and exploits the properties of real numbers to provide optimal signaling. The real interference alignment relies on a new coding scheme in which several data streams having fractional multiplexing gains are sent by transmitters and interfering streams are aligned at receivers. The coding scheme is backed up by a recent result in the field of Diophantine approximation, which states that the convergence part of the Khintchine-Groshev theorem holds for points on non-degenerate manifolds.

  10. Homeotropic alignment of lyotropic chromonic liquid crystals using noncovalent interactions.

    Science.gov (United States)

    Jeong, Joonwoo; Han, Ganghee; Johnson, A T Charlie; Collings, Peter J; Lubensky, Tom C; Yodh, Arjun G

    2014-03-18

    We report on the homeotropic alignment of lyotropic chromonic liquid crystals (LCLCs). Homeotropic anchoring of LCLCs is difficult to achieve, and this challenge has limited development of applications for LCLCs. In this work, homeotropic alignment is achieved using noncovalent interactions between the LCLC molecules and various alignment layers including graphene, parylene films, poly(methyl methacrylate) films, and fluoropolymer films. The LCLC molecules are unique in that they self-assemble via noncovalent interactions in water into elongated aggregates which, in turn, form nematic and columnar liquid crystal (LC) phases. Here we exploit these same noncovalent interactions to induce homeotropic anchoring of the nematic LCLC. Homeotropic alignment is confirmed by polarized optical microscopy and conoscopy. We also report on novel transient stripe textures that occur when an initial flow-induced planar alignment transforms into the equilibrium homeotropic alignment required by boundary conditions. An understanding of this behavior could be important for switching applications. PMID:24559290

  11. Scintillation counter: photomultiplier tube alignment

    International Nuclear Information System (INIS)

    A scintillation counter, particularly for counting gamma ray photons, includes a massive lead radiation shield surrounding a sample-receiving zone. The shield is disassembleable into a plurality of segments to allow facile installation and removal of a photomultiplier tube assembly, the segments being so constructed as to prevent straight-line access of external radiation through the shield into the sample receiving zone. Provisions are made for accurately aligning the photomultiplier tube with respect to one or more sample-transmitting bores extending through the shield to the sample receiving zone. A sample elevator, used in transporting samples into the zone, is designed to provide a maximum gamma-receiving aspect to maximize the gamma detecting efficiency. (auth)

  12. Coding exon-structure aware realigner (CESAR) utilizes genome alignments for accurate comparative gene annotation.

    Science.gov (United States)

    Sharma, Virag; Elghafari, Anas; Hiller, Michael

    2016-06-20

    Identifying coding genes is an essential step in genome annotation. Here, we utilize existing whole genome alignments to detect conserved coding exons and then map gene annotations from one genome to many aligned genomes. We show that genome alignments contain thousands of spurious frameshifts and splice site mutations in exons that are truly conserved. To overcome these limitations, we have developed CESAR (Coding Exon-Structure Aware Realigner) that realigns coding exons, while considering reading frame and splice sites of each exon. CESAR effectively avoids spurious frameshifts in conserved genes and detects 91% of shifted splice sites. This results in the identification of thousands of additional conserved exons and 99% of the exons that lack inactivating mutations match real exons. Finally, to demonstrate the potential of using CESAR for comparative gene annotation, we applied it to 188 788 exons of 19 865 human genes to annotate human genes in 99 other vertebrates. These comparative gene annotations are available as a resource (http://bds.mpi-cbg.de/hillerlab/CESAR/). CESAR (https://github.com/hillerlab/CESAR/) can readily be applied to other alignments to accurately annotate coding genes in many other vertebrate and invertebrate genomes. PMID:27016733

  13. Surface Dipole Control of Liquid Crystal Alignment.

    Science.gov (United States)

    Schwartz, Jeffrey J; Mendoza, Alexandra M; Wattanatorn, Natcha; Zhao, Yuxi; Nguyen, Vinh T; Spokoyny, Alexander M; Mirkin, Chad A; Baše, Tomáš; Weiss, Paul S

    2016-05-11

    Detailed understanding and control of the intermolecular forces that govern molecular assembly are necessary to engineer structure and function at the nanoscale. Liquid crystal (LC) assembly is exceptionally sensitive to surface properties, capable of transducing nanoscale intermolecular interactions into a macroscopic optical readout. Self-assembled monolayers (SAMs) modify surface interactions and are known to influence LC alignment. Here, we exploit the different dipole magnitudes and orientations of carboranethiol and -dithiol positional isomers to deconvolve the influence of SAM-LC dipolar coupling from variations in molecular geometry, tilt, and order. Director orientations and anchoring energies are measured for LC cells employing various carboranethiol and -dithiol isomer alignment layers. The normal component of the molecular dipole in the SAM, toward or away from the underlying substrate, was found to determine the in-plane LC director orientation relative to the anisotropy axis of the surface. By using LC alignment as a probe of interaction strength, we elucidate the role of dipolar coupling of molecular monolayers to their environment in determining molecular orientations. We apply this understanding to advance the engineering of molecular interactions at the nanoscale. PMID:27090503

  14. Dielectrophoresis in particle confinement: Aligned carbon particles in polymer matrix below percolation threshold

    Science.gov (United States)

    Knaapila, M.; Høyer, H.; Helgesen, G.

    2014-09-01

    We review preparation and properties of confined, aligned string-like particle assemblies formed by dielectrophoresis under alternating electric fields. Particular attention is placed on carbon particles aligned in the oligomer matrix. In these systems the particle fraction is low, below the isotropic percolation threshold. The matrix is polymerized after alignment, which locks the aligned strings in place. Application examples are discussed including particle separation, conductivity enhancement and piezoresistive sensors.

  15. SpliceMiner: a high-throughput database implementation of the NCBI Evidence Viewer for microarray splice variant analysis

    Directory of Open Access Journals (Sweden)

    Liu Hongfang

    2007-03-01

    Full Text Available Abstract Background There are many fewer genes in the human genome than there are expressed transcripts. Alternative splicing is the reason. Alternatively spliced transcripts are often specific to tissue type, developmental stage, environmental condition, or disease state. Accurate analysis of microarray expression data and design of new arrays for alternative splicing require assessment of probes at the sequence and exon levels. Description SpliceMiner is a web interface for querying Evidence Viewer Database (EVDB. EVDB is a comprehensive, non-redundant compendium of splice variant data for human genes. We constructed EVDB as a queryable implementation of the NCBI Evidence Viewer (EV. EVDB is based on data obtained from NCBI Entrez Gene and EV. The automated EVDB build process uses only complete coding sequences, which may or may not include partial or complete 5' and 3' UTRs, and filters redundant splice variants. Unlike EV, which supports only one-at-a-time queries, SpliceMiner supports high-throughput batch queries and provides results in an easily parsable format. SpliceMiner maps probes to splice variants, effectively delineating the variants identified by a probe. Conclusion EVDB can be queried by gene symbol, genomic coordinates, or probe sequence via a user-friendly web-based tool we call SpliceMiner (http://discover.nci.nih.gov/spliceminer. The EVDB/SpliceMiner combination provides an interface with human splice variant information and, going beyond the very valuable NCBI Evidence Viewer, supports fluent, high-throughput analysis. Integration of EVDB information into microarray analysis and design pipelines has the potential to improve the analysis and bioinformatic interpretation of gene expression data, for both batch and interactive processing. For example, whenever a gene expression value is recognized as important or appears anomalous in a microarray experiment, the interactive mode of SpliceMiner can be used quickly and easily to

  16. Coexistence of type-I and type-II band alignments in In0.46Al0.54As/Ga0.46Al0.54As self-assembled quantum dots

    International Nuclear Information System (INIS)

    Optical properties of In0.46Al0.54As/Ga0.46Al0.54As quantum dots (QDs) have been investigated by photoluminescence (PL). At a low temperature of 8 K, the PL peak energy blue-shifts 44 meV and the linewidth broadens by 21 meV as the excitation intensity increases by four orders of magnitude. As the temperature increases, the QD spectra demonstrate a fast redshift and narrowing from ∼35 K. These observations have been explained by the type-II nature of QDs and the lateral carrier transfer due to electronic coupling between neighboring QDs. A special double exponential decay behavior indicates the coexistence of type-I and type-II band alignment in this QD sample

  17. Alignment for CSR

    International Nuclear Information System (INIS)

    Cooled Storage Ring of Heavy Ion Research Facility in Lanzhou (HIRFL-CSR) belongs to China great scientific project in China. The alignment for it is very difficult because of very large area and very high accuracy. For the special case in HIRFL-CSR, some new methods and new instruments are used, including the construction of survey control network, the usage of laser tracker, and CSR alignment database system with applications developed to store and analyze data. The author describes the whole procedure of CSR alignment

  18. Galaxy alignments: An overview

    CERN Document Server

    Joachimi, Benjamin; Kitching, Thomas D; Leonard, Adrienne; Mandelbaum, Rachel; Schäfer, Björn Malte; Sifón, Cristóbal; Hoekstra, Henk; Kiessling, Alina; Kirk, Donnacha; Rassat, Anais

    2015-01-01

    The alignments between galaxies, their underlying matter structures, and the cosmic web constitute vital ingredients for a comprehensive understanding of gravity, the nature of matter, and structure formation in the Universe. We provide an overview on the state of the art in the study of these alignment processes and their observational signatures, aimed at a non-specialist audience. The development of the field over the past one hundred years is briefly reviewed. We also discuss the impact of galaxy alignments on measurements of weak gravitational lensing, and discuss avenues for making theoretical and observational progress over the coming decade.

  19. Evolution of alternative splicing regulation: changes in predicted exonic splicing regulators are not associated with changes in alternative splicing levels in primates.

    Directory of Open Access Journals (Sweden)

    Manuel Irimia

    Full Text Available Alternative splicing is tightly regulated in a spatio-temporal and quantitative manner. This regulation is achieved by a complex interplay between spliceosomal (trans factors that bind to different sequence (cis elements. cis-elements reside in both introns and exons and may either enhance or silence splicing. Differential combinations of cis-elements allows for a huge diversity of overall splicing signals, together comprising a complex 'splicing code'. Many cis-elements have been identified, and their effects on exon inclusion levels demonstrated in reporter systems. However, the impact of interspecific differences in these elements on the evolution of alternative splicing levels has not yet been investigated at genomic level. Here we study the effect of interspecific differences in predicted exonic splicing regulators (ESRs on exon inclusion levels in human and chimpanzee. For this purpose, we compiled and studied comprehensive datasets of predicted ESRs, identified by several computational and experimental approaches, as well as microarray data for changes in alternative splicing levels between human and chimpanzee. Surprisingly, we found no association between changes in predicted ESRs and changes in alternative splicing levels. This observation holds across different ESR exon positions, exon lengths, and 5' splice site strengths. We suggest that this lack of association is mainly due to the great importance of context for ESR functionality: many ESR-like motifs in primates may have little or no effect on splicing, and thus interspecific changes at short-time scales may primarily occur in these effectively neutral ESRs. These results underscore the difficulties of using current computational ESR prediction algorithms to identify truly functionally important motifs, and provide a cautionary tale for studies of the effect of SNPs on splicing in human disease.

  20. Evolution of alternative splicing regulation: changes in predicted exonic splicing regulators are not associated with changes in alternative splicing levels in primates.

    Science.gov (United States)

    Irimia, Manuel; Rukov, Jakob Lewin; Roy, Scott William

    2009-01-01

    Alternative splicing is tightly regulated in a spatio-temporal and quantitative manner. This regulation is achieved by a complex interplay between spliceosomal (trans) factors that bind to different sequence (cis) elements. cis-elements reside in both introns and exons and may either enhance or silence splicing. Differential combinations of cis-elements allows for a huge diversity of overall splicing signals, together comprising a complex 'splicing code'. Many cis-elements have been identified, and their effects on exon inclusion levels demonstrated in reporter systems. However, the impact of interspecific differences in these elements on the evolution of alternative splicing levels has not yet been investigated at genomic level. Here we study the effect of interspecific differences in predicted exonic splicing regulators (ESRs) on exon inclusion levels in human and chimpanzee. For this purpose, we compiled and studied comprehensive datasets of predicted ESRs, identified by several computational and experimental approaches, as well as microarray data for changes in alternative splicing levels between human and chimpanzee. Surprisingly, we found no association between changes in predicted ESRs and changes in alternative splicing levels. This observation holds across different ESR exon positions, exon lengths, and 5' splice site strengths. We suggest that this lack of association is mainly due to the great importance of context for ESR functionality: many ESR-like motifs in primates may have little or no effect on splicing, and thus interspecific changes at short-time scales may primarily occur in these effectively neutral ESRs. These results underscore the difficulties of using current computational ESR prediction algorithms to identify truly functionally important motifs, and provide a cautionary tale for studies of the effect of SNPs on splicing in human disease. PMID:19495418

  1. Human Aldehyde Dehydrogenase Genes: Alternatively-Spliced Transcriptional Variants and Their Suggested Nomenclature

    Science.gov (United States)

    Black, William J.; Stagos, Dimitrios; Marchitti, Satori A.; Nebert, Daniel W.; Tipton, Keith F.; Bairoch, Amos; Vasiliou, Vasilis

    2011-01-01

    OBJECTIVE The human aldehyde dehydrogenase (ALDH) gene superfamily consists of 19 genes encoding enzymes critical for NAD(P)+-dependent oxidation of endogenous and exogenous aldehydes, including drugs and environmental toxicants. Mutations in ALDH genes are the molecular basis of several disease states (e.g. Sjögren-Larsson syndrome, pyridoxine-dependent seizures, and type II hyperprolinemia) and may contribute to the etiology of complex diseases such as cancer and Alzheimer’s disease. The aim of this nomenclature update was to identify splice transcriptional variants principally for the human ALDH genes. METHODS Data-mining methods were used to retrieve all human ALDH sequences. Alternatively-spliced transcriptional variants were determined based upon: a) criteria for sequence integrity and genomic alignment; b) evidence of multiple independent cDNA sequences corresponding to a variant sequence; and c) if available, empirical evidence of variants from the literature. RESULTS AND CONCLUSION Alternatively-spliced transcriptional variants and their encoded proteins exist for most of the human ALDH genes; however, their function and significance remain to be established. When compared with the human genome, rat and mouse include an additional gene, Aldh1a7, in the ALDH1A subfamily. In order to avoid confusion when identifying splice variants in various genomes, nomenclature guidelines for the naming of such alternative transcriptional variants and proteins are recommended herein. In addition, a web database (www.aldh.org) has been developed to provide up-to-date information and nomenclature guidelines for the ALDH superfamily. PMID:19823103

  2. GAP: A computer program for gene assembly

    Energy Technology Data Exchange (ETDEWEB)

    Eisnstein, J.R.; Uberbacher, E.C.; Guan, X.; Mural, R.J.; Mann, R.C.

    1991-09-01

    A computer program, GAP (Gene Assembly Program), has been written to assemble and score hypothetical genes, given a DNA sequence containing the gene, and the outputs of several other programs which analyze the sequence. These programs include the codign-recognition and splice-junction-recognition modules developed in this laboratory. GAP is a prototype of a planned system in which it will be integrated with an expert system and rule base. Initial tests of GAP have been carried out with four sequences, the exons of which have been determined by biochemcial methods. The highest-scoring hypothetical genes for each of the four sequences had percent correct splice junctions ranging from 50 to 100% (average 81%) and percent correct bases ranging from 92 to 100% (average 96%). 9 refs., 1 tab.

  3. Entropic contributions to the splicing process

    International Nuclear Information System (INIS)

    It has been recently argued that depletion attraction may play an important role in different aspects of cellular organization, ranging from the organization of transcriptional activity in transcription factories to the formation of nuclear bodies. In this paper, we suggest a new application of these ideas in the context of the splicing process, a crucial step of messenger RNA maturation in eukaryotes. We shall show that entropy effects and the resulting depletion attraction may explain the relevance of the aspecific intron length variable in the choice of splice-site recognition modality. On top of that, some qualitative features of the genome architecture of higher eukaryotes can find evolutionary realistic motivation in the light of our model

  4. The Exon Junction Complex Controls the Efficient and Faithful Splicing of a Subset of Transcripts Involved in Mitotic Cell-Cycle Progression.

    Science.gov (United States)

    Fukumura, Kazuhiro; Wakabayashi, Shunichi; Kataoka, Naoyuki; Sakamoto, Hiroshi; Suzuki, Yutaka; Nakai, Kenta; Mayeda, Akila; Inoue, Kunio

    2016-01-01

    The exon junction complex (EJC) that is deposited onto spliced mRNAs upstream of exon-exon junctions plays important roles in multiple post-splicing gene expression events, such as mRNA export, surveillance, localization, and translation. However, a direct role for the human EJC in pre-mRNA splicing has not been fully understood. Using HeLa cells, we depleted one of the EJC core components, Y14, and the resulting transcriptome was analyzed by deep sequencing (RNA-Seq) and confirmed by RT-PCR. We found that Y14 is required for efficient and faithful splicing of a group of transcripts that is enriched in short intron-containing genes involved in mitotic cell-cycle progression. Tethering of EJC core components (Y14, eIF4AIII or MAGOH) to a model reporter pre-mRNA harboring a short intron showed that these core components are prerequisites for the splicing activation. Taken together, we conclude that the EJC core assembled on pre-mRNA is critical for efficient and faithful splicing of a specific subset of short introns in mitotic cell cycle-related genes. PMID:27490541

  5. Tidal alignment of galaxies

    CERN Document Server

    Blazek, Jonathan; Seljak, Uroš

    2015-01-01

    We develop an analytic model for galaxy intrinsic alignments (IA) based on the theory of tidal alignment. We calculate all relevant nonlinear corrections at one-loop order, including effects from nonlinear density evolution, galaxy biasing, and source density weighting. Contributions from density weighting are found to be particularly important and lead to bias dependence of the IA amplitude, even on large scales. This effect may be responsible for much of the luminosity dependence in IA observations. The increase in IA amplitude for more highly biased galaxies reflects their locations in regions with large tidal fields. We also consider the impact of smoothing the tidal field on halo scales. We compare the performance of this consistent nonlinear model in describing the observed alignment of luminous red galaxies with the linear model as well as the frequently used "nonlinear alignment model," finding a significant improvement on small and intermediate scales. We also show that the cross-correlation between ...

  6. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G.Gomez

    Since September, the muon alignment system shifted from a mode of hardware installation and commissioning to operation and data taking. All three optical subsystems (Barrel, Endcap and Link alignment) have recorded data before, during and after CRAFT, at different magnetic fields and during ramps of the magnet. This first data taking experience has several interesting goals: •    study detector deformations and movements under the influence of the huge magnetic forces; •    study the stability of detector structures and of the alignment system over long periods, •    study geometry reproducibility at equal fields (specially at 0T and 3.8T); •    reconstruct B=0T geometry and compare to nominal/survey geometries; •    reconstruct B=3.8T geometry and provide DT and CSC alignment records for CMSSW. However, the main goal is to recons...

  7. Splicing therapy for neuromuscular disease ☆

    OpenAIRE

    Andrew G. L. Douglas; Wood, Matthew J. A.

    2013-01-01

    Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) are two of the most common inherited neuromuscular diseases in humans. Both conditions are fatal and no clinically available treatments are able to significantly alter disease course in either case. However, by manipulation of pre-mRNA splicing using antisense oligonucleotides, defective transcripts from the DMD gene and from the SMN2 gene in SMA can be modified to once again produce protein and restore function. A large numb...

  8. Resolving deconvolution ambiguity in gene alternative splicing

    Directory of Open Access Journals (Sweden)

    Hubbell Earl

    2009-08-01

    Full Text Available Abstract Background For many gene structures it is impossible to resolve intensity data uniquely to establish abundances of splice variants. This was empirically noted by Wang et al. in which it was called a "degeneracy problem". The ambiguity results from an ill-posed problem where additional information is needed in order to obtain an unique answer in splice variant deconvolution. Results In this paper, we analyze the situations under which the problem occurs and perform a rigorous mathematical study which gives necessary and sufficient conditions on how many and what type of constraints are needed to resolve all ambiguity. This analysis is generally applicable to matrix models of splice variants. We explore the proposal that probe sequence information may provide sufficient additional constraints to resolve real-world instances. However, probe behavior cannot be predicted with sufficient accuracy by any existing probe sequence model, and so we present a Bayesian framework for estimating variant abundances by incorporating the prediction uncertainty from the micro-model of probe responsiveness into the macro-model of probe intensities. Conclusion The matrix analysis of constraints provides a tool for detecting real-world instances in which additional constraints may be necessary to resolve splice variants. While purely mathematical constraints can be stated without error, real-world constraints may themselves be poorly resolved. Our Bayesian framework provides a generic solution to the problem of uniquely estimating transcript abundances given additional constraints that themselves may be uncertain, such as regression fit to probe sequence models. We demonstrate the efficacy of it by extensive simulations as well as various biological data.

  9. Alternative Splicing Programs in Prostate Cancer

    OpenAIRE

    Claudio Sette

    2013-01-01

    Prostate cancer (PCa) remains one of the most frequent causes of death for cancer in the male population. Although the initial antiandrogenic therapies are efficacious, PCa often evolves into a hormone-resistant, incurable disease. The genetic and phenotypic heterogeneity of this type of cancer renders its diagnosis and cure particularly challenging. Mounting evidence indicates that alternative splicing, the process that allows production of multiple mRNA variants from each gene, contributes ...

  10. Splicing variants of porcine synphilin-1

    Directory of Open Access Journals (Sweden)

    Knud Larsen

    2015-09-01

    Full Text Available Parkinson's disease (PD, idiopathic and familial, is characterized by degradation of dopaminergic neurons and the presence of Lewy bodies (LB in the substantia nigra. LBs contain aggregated proteins of which α-synuclein is the major component. The protein synphilin-1 interacts and colocalizes with α-synuclein in LBs. The aim of this study was to isolate and characterize porcine synphilin-1 and isoforms hereof with the future perspective to use the pig as a model for Parkinson's disease. The porcine SNCAIP cDNA was cloned by reverse transcriptase PCR. The spatial expression of SNCAIP mRNA was investigated by RNAseq. The presented work reports the molecular cloning and characterization of the porcine (Sus scrofa synphilin-1 cDNA (SNCAIP and three splice variants hereof. The porcine SNCAIP cDNA codes for a protein (synphilin-1 of 919 amino acids which shows a high similarity to human (90% and to mouse (84% synphilin-1. Three shorter transcript variants of the synphilin-1 gene were identified, all lacking one or more exons. SNCAIP transcripts were detected in most examined organs and tissues and the highest expression was found in brain tissues and lung. Conserved splicing variants and a novel splice form of synhilin-1 were found in this study. All synphilin-1 isoforms encoded by the identified transcript variants lack functional domains important for protein degradation.

  11. A new method for splice site prediction based on the sequence patterns of splicing signals and regulatory elements

    Institute of Scientific and Technical Information of China (English)

    SUN ZongXiao; SANG LingJie; JU LiNing; ZHU HuaiQiu

    2008-01-01

    It is of significance for splice site prediction to develop novel algorithms that combine the sequence patterns of regulatory elements such as enhancers and silencers with the patterns of splicing signals. In this paper, a statistical model of splicing signals was built based on the entropy density profile (EDP) method, weight array method (WAM) and κ test; moreover, the model of splicing regulatory elements was developed by an unsupervised self-learning method to detect motifs associated with regulatory elements. With two models incorporated, a multi-level support vector machine (SVM) system was de-vised to perform ab initio prediction for splice sites originating from DNA sequence in eukaryotic ge-home. Results of large scale tests on human genomic splice sites show that the new method achieves a comparative high performance in splice site prediction. The method is demonstrated to be with at least the same level of performance and usually better performance than the existing SpliceScan method based on modeling regulatory elements, and shown to have higher accuracies than the traditional methods with modeling splicing signals such as the GeneSplicer. In particular, the method has evident advantage over splice site prediction for the genes with lower GC content.

  12. ATLAS Muon Endcap Alignment

    CERN Document Server

    Bensinger, J R

    2005-01-01

    To align the endcap muon chambers of the ATLAS experiment, an optical grid is set up between aluminum “alignment bars” nested in each layer of chambers. Optical lines are made of laser diodes and CCD cameras that form an alignment grid. The alignment bars are self-aligning. They are then carefully measured using a large coordinate measuring machine (CMM). The subsequent shape changes of the bar are determined by calculations that are corrected by the readings of the internal monitors. The relationship between the bars is then established by a network of sensors that measure the bearing angle of light sources on the other parts of the system. The system is over-determined and the location and orientation of each bar is determined using a fitting program. Chambers are then referenced to the alignment grid using proximity sensors. This information is used to provide corrections to the nominal chamber positions before calculating track momentum. The performance of the system has been validated in a test beam ...

  13. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G. Gomez

    2012-01-01

      A new muon alignment has been produced for 2012 A+B data reconstruction. It uses the latest Tracker alignment and single-muon data samples to align both DTs and CSCs. Physics validation has been performed and shows a modest improvement in stand-alone muon momentum resolution in the barrel, where the alignment is essentially unchanged from the previous version. The reference-target track-based algorithm using only collision muons is employed for the first time to align the CSCs, and a substantial improvement in resolution is observed in the endcap and overlap regions for stand-alone muons. This new alignment is undergoing the approval process and is expected to be deployed as part of a new global tag in the beginning of December. The pT dependence of the φ-bias in curvature observed in Monte Carlo was traced to a relative vertical misalignment between the Tracker and barrel muon systems. Moving the barrel as a whole to match the Tracker cures this pT dependence, leaving only the &phi...

  14. IWR-solution for the ITER vacuum vessel assembly

    International Nuclear Information System (INIS)

    The assembly of ITER vacuum vessel (VV) is still a very big challenge as the process can only be done from inside the VV. The welding of the VV assembly is carried out using the dedicated robotic systems. The main functions of the robots are: (i) measuring the actual space between every two sectors, (ii) positioning of the 150 kg splice plates between the sector shells, (iii) welding the splice plates to the sector shells, (iv) NDT of the welds, (v) repairing, including machining of the welds, (vi) He-leak tests of the welds, and (vii) the non-planned functions that may turn out. This paper presents a reasonable method to assemble the ITER VV. In this article, one parallel mobile robot, running on the track rail fixed on the wall inside the VV, is designed and tested. The assembling process, carried out by the mobile robot together with the welding robot, is presented.

  15. Splicing modulation therapy in the treatment of genetic diseases

    Directory of Open Access Journals (Sweden)

    Arechavala-Gomeza V

    2014-12-01

    Full Text Available Virginia Arechavala-Gomeza,1 Bernard Khoo,2 Annemieke Aartsma-Rus3 1Neuromuscular Disorders Group, BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain; 2Endocrinology, Division of Medicine, University College London, London, UK; 3Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands All authors contributed equally to this manuscript Abstract: Antisense-mediated splicing modulation is a tool that can be exploited in several ways to provide a potential therapy for rare genetic diseases. This approach is currently being tested in clinical trials for Duchenne muscular dystrophy and spinal muscular atrophy. The present review outlines the versatility of the approach to correct cryptic splicing, modulate alternative splicing, restore the open reading frame, and induce protein knockdown, providing examples of each. Finally, we outline a possible path forward toward the clinical application of this approach for a wide variety of inherited rare diseases. Keywords: splicing, therapy, antisense oligonucleotides, cryptic splicing, alternative splicing

  16. Accumulation of GC donor splice signals in mammals

    Directory of Open Access Journals (Sweden)

    Koonin Eugene V

    2008-07-01

    Full Text Available Abstract The GT dinucleotide in the first two intron positions is the most conserved element of the U2 donor splice signals. However, in a small fraction of donor sites, GT is replaced by GC. A substantial enrichment of GC in donor sites of alternatively spliced genes has been observed previously in human, nematode and Arabidopsis, suggesting that GC signals are important for regulation of alternative splicing. We used parsimony analysis to reconstruct evolution of donor splice sites and inferred 298 GT > GC conversion events compared to 40 GC > GT conversion events in primate and rodent genomes. Thus, there was substantive accumulation of GC donor splice sites during the evolution of mammals. Accumulation of GC sites might have been driven by selection for alternative splicing. Reviewers This article was reviewed by Jerzy Jurka and Anton Nekrutenko. For the full reviews, please go to the Reviewers' Reports section.

  17. The implications of alternative splicing in the ENCODE protein complement

    DEFF Research Database (Denmark)

    Tress, Michael L.; Martelli, Pier Luigi; Frankish, Adam;

    2007-01-01

    Alternative premessenger RNA splicing enables genes to generate more than one gene product. Splicing events that occur within protein coding regions have the potential to alter the biological function of the expressed protein and even to create new protein functions. Alternative splicing has been...... suggested as one explanation for the discrepancy between the number of human genes and functional complexity. Here, we carry out a detailed study of the alternatively spliced gene products annotated in the ENCODE pilot project. We find that alternative splicing in human genes is more frequent than has...... commonly been suggested, and we demonstrate that many of the potential alternative gene products will have markedly different structure and function from their constitutively spliced counterparts. For the vast majority of these alternative isoforms, little evidence exists to suggest they have a role as...

  18. Splicing remodels messenger ribonucleoprotein architecture via eIF4A3-dependent and -independent recruitment of exon junction complex components.

    Science.gov (United States)

    Zhang, Zuo; Krainer, Adrian R

    2007-07-10

    Pre-mRNA splicing not only removes introns and joins exons to generate spliced mRNA but also results in remodeling of the spliced messenger ribonucleoprotein, influencing various downstream events. This remodeling includes the loading of an exon-exon junction complex (EJC). It is unclear how the spliceosome recruits the EJC onto the mRNA and whether EJC formation or EJC components are required for pre-mRNA splicing. Here we immunodepleted the EJC core component eIF4A3 from HeLa cell nuclear extract and found that eIF4A3 is dispensable for pre-mRNA splicing in vitro. However, eIF4A3 is required for the splicing-dependent loading of the Y14/Magoh heterodimer onto mRNA, and this activity of human eIF4A3 is also present in the Drosophila ortholog. Surprisingly, the loading of six other EJC components was not affected by eIF4A3 depletion, suggesting that their binding to mRNA involves different or redundant pathways. Finally, we found that the assembly of the EJC onto mRNA occurs at the late stages of the splicing reaction and requires the second-step splicing and mRNA-release factor HRH1/hPrp22. The EJC-dependent and -independent recruitment of RNA-binding proteins onto mRNA suggests a role for the EJC in messenger ribonucleoprotein remodeling involving interactions with other proteins already bound to the pre-mRNA, which has implications for nonsense-mediated mRNA decay and other mRNA transactions. PMID:17606899

  19. Tissue-specific splicing factor gene expression signatures

    OpenAIRE

    Grosso, A. R.; Gomes, Anita; Barbosa-Morais, Nuno; Caldeira, Sandra; Thorne, Natalie; Grech, Godfrey; Lindern, Marieke; Carmo-Fonseca, Maria

    2008-01-01

    textabstractThe alternative splicing code that controls and coordinates the transcriptome in complex multicellular organisms remains poorly understood. It has long been argued that regulation of alternative splicing relies on combinatorial interactions between multiple proteins, and that tissue-specific splicing decisions most likely result from differences in the concentration and/or activity of these proteins. However, large-scale data to systematically address this issue have just recently...

  20. Alternative Splicing and Its Impact as a Cancer Diagnostic Marker

    OpenAIRE

    Kim, Yun-Ji; Kim, Heui-Soo

    2012-01-01

    Most genes are processed by alternative splicing for gene expression, resulting in the complexity of the transcriptome in eukaryotes. It allows a limited number of genes to encode various proteins with intricate functions. Alternative splicing is regulated by genetic mutations in cis-regulatory factors and epigenetic events. Furthermore, splicing events occur differently according to cell type, developmental stage, and various diseases, including cancer. Genome instability and flexible proteo...

  1. Pre-mRNA splicing in disease and therapeutics

    OpenAIRE

    Singh, Ravi K.; Cooper, Thomas A.

    2012-01-01

    In metazoans, alternative splicing of genes is essential for regulating gene expression and contributing to functional complexity. Computational predictions, comparative genomics, and transcriptome profiling of normal and diseased tissues indicate an unexpectedly high fraction of diseases are caused by mutations that alter splicing. Mutations in cis elements cause mis-splicing of genes that alter gene function and contribute to disease pathology. Mutations of core spliceosomal factors are ass...

  2. Phosphorylation-Mediated Regulation of Alternative Splicing in Cancer

    OpenAIRE

    Chiara Naro; Claudio Sette

    2013-01-01

    Alternative splicing (AS) is one of the key processes involved in the regulation of gene expression in eukaryotic cells. AS catalyzes the removal of intronic sequences and the joining of selected exons, thus ensuring the correct processing of the primary transcript into the mature mRNA. The combinatorial nature of AS allows a great expansion of the genome coding potential, as multiple splice-variants encoding for different proteins may arise from a single gene. Splicing is mediated by a large...

  3. Curriculum Alignment Research Suggests that Alignment Can Improve Student Achievement

    Science.gov (United States)

    Squires, David

    2012-01-01

    Curriculum alignment research has developed showing the relationship among three alignment categories: the taught curriculum, the tested curriculum and the written curriculum. Each pair (for example, the taught and the written curriculum) shows a positive impact for aligning those results. Following this, alignment results from the Third…

  4. DNA splice site sequences clustering method for conservativeness analysis

    Institute of Scientific and Technical Information of China (English)

    Quanwei Zhang; Qinke Peng; Tao Xu

    2009-01-01

    DNA sequences that are near to splice sites have remarkable conservativeness,and many researchers have contributed to the prediction of splice site.In order to mine the underlying biological knowledge,we analyze the conservativeness of DNA splice site adjacent sequences by clustering.Firstly,we propose a kind of DNA splice site sequences clustering method which is based on DBSCAN,and use four kinds of dissimilarity calculating methods.Then,we analyze the conservative feature of the clustering results and the experimental data set.

  5. Adenosine to Inosine editing frequency controlled by splicing efficiency.

    Science.gov (United States)

    Licht, Konstantin; Kapoor, Utkarsh; Mayrhofer, Elisa; Jantsch, Michael F

    2016-07-27

    Alternative splicing and adenosine to inosine (A to I) RNA-editing are major factors leading to co- and post-transcriptional modification of genetic information. Both, A to I editing and splicing occur in the nucleus. As editing sites are frequently defined by exon-intron basepairing, mRNA splicing efficiency should affect editing levels. Moreover, splicing rates affect nuclear retention and will therefore also influence the exposure of pre-mRNAs to the editing-competent nuclear environment. Here, we systematically test the influence of splice rates on RNA-editing using reporter genes but also endogenous substrates. We demonstrate for the first time that the extent of editing is controlled by splicing kinetics when editing is guided by intronic elements. In contrast, editing sites that are exclusively defined by exonic structures are almost unaffected by the splicing efficiency of nearby introns. In addition, we show that editing levels in pre- and mature mRNAs do not match. This phenomenon can in part be explained by the editing state of an RNA influencing its splicing rate but also by the binding of the editing enzyme ADAR that interferes with splicing. PMID:27112566

  6. Functional roles of alternative splicing factors in human disease.

    Science.gov (United States)

    Cieply, Benjamin; Carstens, Russ P

    2015-01-01

    Alternative splicing (AS) is an important mechanism used to generate greater transcriptomic and proteomic diversity from a finite genome. Nearly all human gene transcripts are alternatively spliced and can produce protein isoforms with divergent and even antagonistic properties that impact cell functions. Many AS events are tightly regulated in a cell-type or tissue-specific manner, and at different developmental stages. AS is regulated by RNA-binding proteins, including cell- or tissue-specific splicing factors. In the past few years, technological advances have defined genome-wide programs of AS regulated by increasing numbers of splicing factors. These splicing regulatory networks (SRNs) consist of transcripts that encode proteins that function in coordinated and related processes that impact the development and phenotypes of different cell types. As such, it is increasingly recognized that disruption of normal programs of splicing regulated by different splicing factors can lead to human diseases. We will summarize examples of diseases in which altered expression or function of splicing regulatory proteins has been implicated in human disease pathophysiology. As the role of AS continues to be unveiled in human disease and disease risk, it is hoped that further investigations into the functions of numerous splicing factors and their regulated targets will enable the development of novel therapies that are directed at specific AS events as well as the biological pathways they impact. PMID:25630614

  7. The deterministic optical alignment of the HERMES spectrograph

    Science.gov (United States)

    Gers, Luke; Staszak, Nicholas

    2014-07-01

    The High Efficiency and Resolution Multi Element Spectrograph (HERMES) is a four channel, VPH-grating spectrograph fed by two 400 fiber slit assemblies whose construction and commissioning has now been completed at the Anglo Australian Telescope (AAT). The size, weight, complexity, and scheduling constraints of the system necessitated that a fully integrated, deterministic, opto-mechanical alignment system be designed into the spectrograph before it was manufactured. This paper presents the principles about which the system was assembled and aligned, including the equipment and the metrology methods employed to complete the spectrograph integration.

  8. MaxAlign: maximizing usable data in an alignment

    OpenAIRE

    Pedersen Anders G; Sackett Peter W; Gouveia-Oliveira Rodrigo

    2007-01-01

    Abstract Background The presence of gaps in an alignment of nucleotide or protein sequences is often an inconvenience for bioinformatical studies. In phylogenetic and other analyses, for instance, gapped columns are often discarded entirely from the alignment. Results MaxAlign is a program that optimizes the alignment prior to such analyses. Specifically, it maximizes the number of nucleotide (or amino acid) symbols that are present in gap-free columns – the alignment area – by selecting the ...

  9. Study and Development of a Laser Based Alignment System

    CERN Multimedia

    Stern, G

    2014-01-01

    CLIC (Compact Linear Collider) has tight requirements regarding pre-alignment of beam related components: 10 µm accuracy over a sliding window of 200 m along the 20 km of linac. To perform such an alignment, a new system is proposed combining laser beam as straight line reference and camera/shutter assemblies as sensors. The poster describes the alignment system and shows results regarding laser pointing stability with respect to time, shutter type, distance and environment. These results give a frame for future building and calibrating of sensors.

  10. Robust Adhesive Precision Bonding in Automated Assembly Cells

    OpenAIRE

    Müller, Tobias; Haag, Sebastian; Bastuck, Thomas; Gisler, Thomas; Moser, Hansruedi; Uusimaa, Petteri; Axt, Christoph; Brecher, Christian

    2014-01-01

    The assembly of optical components goes along with highest requirements regarding assembly precision. Laser products have become an integral part of many industrial, medical, and consumer applications and their relevance will increase significantly in the years to come. Still economic challenges remain. Assembly costs are driven by the demanding requirements regarding alignment and adhesive bonding. Especially challenging in precision bonding are the interdependencies between alignment and bo...

  11. Ergodic Secret Alignment

    CERN Document Server

    Bassily, Raef

    2010-01-01

    In this paper, we introduce two new achievable schemes for the fading multiple access wiretap channel (MAC-WT). In the model that we consider, we assume that perfect knowledge of the state of all channels is available at all the nodes in a causal fashion. Our schemes use this knowledge together with the time varying nature of the channel model to align the interference from different users at the eavesdropper perfectly in a one-dimensional space while creating a higher dimensionality space for the interfering signals at the legitimate receiver hence allowing for better chance of recovery. While we achieve this alignment through signal scaling at the transmitters in our first scheme (scaling based alignment (SBA)), we let nature provide this alignment through the ergodicity of the channel coefficients in the second scheme (ergodic secret alignment (ESA)). For each scheme, we obtain the resulting achievable secrecy rate region. We show that the secrecy rates achieved by both schemes scale with SNR as 1/2log(SNR...

  12. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G. Gomez

    2010-01-01

    For the last three months, the Muon Alignment group has focussed on providing a new, improved set of alignment constants for the end-of-year data reprocessing. These constants were delivered on time and approved by the CMS physics validation team on November 17. The new alignment incorporates several improvements over the previous one from March for nearly all sub-systems. Motivated by the loss of information from a hardware failure in May (an entire MAB was lost), the optical barrel alignment has moved from a modular, super-plane reconstruction, to a full, single loop calculation of the entire geometry for all DTs in stations 1, 2 and 3. This makes better use of the system redundancy, mitigating the effect of the information loss. Station 4 is factorised and added afterwards to make the system smaller (and therefore faster to run), and also because the MAB calibration at the MB4 zone is less precise. This new alignment procedure was tested at 0 T against photogrammetry resulting in precisions of the order...

  13. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    Gervasio Gomez

    2012-01-01

      The new alignment for the DT chambers has been successfully used in physics analysis starting with the 52X Global Tag. The remaining main areas of development over the next few months will be preparing a new track-based CSC alignment and producing realistic APEs (alignment position errors) and MC misalignment scenarios to match the latest muon alignment constants. Work on these items has been delayed from the intended timeline, mostly due to a large involvement of the muon alignment man-power in physics analyses over the first half of this year. As CMS keeps probing higher and higher energies, special attention must be paid to the reconstruction of very-high-energy muons. Recent muon POG reports from mid-June show a φ-dependence in curvature bias in Monte Carlo samples. This bias is observed already at the tracker level, where it is constant with muon pT, while it grows with pT as muon chamber information is added to the tracks. Similar studies show a much smaller effect in data, at le...

  14. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    M. Dallavalle

    2013-01-01

    A new Muon misalignment scenario for 2011 (7 TeV) Monte Carlo re-processing was re-leased. The scenario is based on running of standard track-based reference-target algorithm (exactly as in data) using single-muon simulated sample (with the transverse-momentum spectrum matching data). It used statistics similar to what was used for alignment with 2011 data, starting from an initially misaligned Muon geometry from uncertainties of hardware measurements and using the latest Tracker misalignment geometry. Validation of the scenario (with muons from Z decay and high-pT simulated muons) shows that it describes data well. The study of systematic uncertainties (dominant by now due to huge amount of data collected by CMS and used for muon alignment) is finalised. Realistic alignment position errors are being obtained from the estimated uncertainties and are expected to improve the muon reconstruction performance. Concerning the Hardware Alignment System, the upgrade of the Barrel Alignment is in progress. By now, d...

  15. Ultraconserved elements are associated with homeostatic control of splicing regulators by alternative splicing and nonsense-mediated decay

    OpenAIRE

    Ni, Julie Z.; Grate, Leslie; Donohue, John Paul; Preston, Christine; Nobida, Naomi; O’Brien, Georgeann; Shiue, Lily; Clark, Tyson A.; Blume, John E; Ares, Manuel

    2007-01-01

    Many alternative splicing events create RNAs with premature stop codons, suggesting that alternative splicing coupled with nonsense-mediated decay (AS-NMD) may regulate gene expression post-transcriptionally. We tested this idea in mice by blocking NMD and measuring changes in isoform representation using splicing-sensitive microarrays. We found a striking class of highly conserved stop codon-containing exons whose inclusion renders the transcript sensitive to NMD. A genomic search for additi...

  16. The CMS Tracker Alignment Strategy

    CERN Document Server

    Weber, Martin

    2006-01-01

    CMS silicon Tracker alignment consists of three key components: Survey during tracker construction, measurements with the Laser Alignment System during operation and track based alignment. Methods and results are explained in detail, with a special focus on track based alignment due to its enormous complexity and numerical challenges.

  17. RNA Structural Alignments, Part I

    DEFF Research Database (Denmark)

    Havgaard, Jakob Hull; Gorodkin, Jan

    Simultaneous alignment and secondary structure prediction of RNA sequences is often referred to as "RNA structural alignment." A class of the methods for structural alignment is based on the principles proposed by Sankoff more than 25 years ago. The Sankoff algorithm simultaneously folds and aligns...

  18. hnRNP H Is a Component of a Splicing Enhancer Complex That Activates a c-src Alternative Exon in Neuronal Cells

    OpenAIRE

    Chou, Min-Yuan; Rooke, Nanette; Turck, Christoph W.; Black, Douglas L.

    1999-01-01

    The regulation of the c-src N1 exon is mediated by an intronic splicing enhancer downstream of the N1 5′ splice site. Previous experiments showed that a set of proteins assembles onto the most conserved core of this enhancer sequence specifically in neuronal WERI-1 cell extracts. The most prominent components of this enhancer complex are the proteins hnRNP F, KSRP, and an unidentified protein of 58 kDa (p58). This p58 protein was purified from the WERI-1 cell nuclear extract by ammonium sulfa...

  19. Pre-mRNA Splicing in Plants: In Vivo Functions of RNA-Binding Proteins Implicated in the Splicing Process

    Directory of Open Access Journals (Sweden)

    Katja Meyer

    2015-07-01

    Full Text Available Alternative pre-messenger RNA splicing in higher plants emerges as an important layer of regulation upon exposure to exogenous and endogenous cues. Accordingly, mutants defective in RNA-binding proteins predicted to function in the splicing process show severe phenotypic alterations. Among those are developmental defects, impaired responses to pathogen threat or abiotic stress factors, and misregulation of the circadian timing system. A suite of splicing factors has been identified in the model plant Arabidopsis thaliana. Here we summarize recent insights on how defects in these splicing factors impair plant performance.

  20. Genetic Variation of Pre-mRNA Alternative Splicing in Human Populations

    OpenAIRE

    Lu, Zhi-xiang; Jiang, Peng; Xing, Yi

    2011-01-01

    The precise splicing outcome of a transcribed gene is controlled by complex interactions between cis regulatory splicing signals and trans-acting regulators. In higher eukaryotes, alternative splicing is a prevalent mechanism for generating transcriptome and proteome diversity. Alternative splicing can modulate gene function, affect organismal phenotype and cause disease. Common genetic variation that affects splicing regulation can lead to differences in alternative splicing between human in...

  1. The Caenorhabditis elegans Gene mfap-1 Encodes a Nuclear Protein That Affects Alternative Splicing

    OpenAIRE

    Long Ma; Xiaoyang Gao; Jintao Luo; Liange Huang; Yanling Teng; H Robert Horvitz

    2012-01-01

    RNA splicing is a major regulatory mechanism for controlling eukaryotic gene expression. By generating various splice isoforms from a single pre-mRNA, alternative splicing plays a key role in promoting the evolving complexity of metazoans. Numerous splicing factors have been identified. However, the in vivo functions of many splicing factors remain to be understood. In vivo studies are essential for understanding the molecular mechanisms of RNA splicing and the biology of numerous RNA splicin...

  2. Small-molecule inhibition of HIV pre-mRNA splicing as a novel antiretroviral therapy to overcome drug resistance.

    Directory of Open Access Journals (Sweden)

    Nadia Bakkour

    2007-10-01

    Full Text Available The development of multidrug-resistant viruses compromises antiretroviral therapy efficacy and limits therapeutic options. Therefore, it is an ongoing task to identify new targets for antiretroviral therapy and to develop new drugs. Here, we show that an indole derivative (IDC16 that interferes with exonic splicing enhancer activity of the SR protein splicing factor SF2/ASF suppresses the production of key viral proteins, thereby compromising subsequent synthesis of full-length HIV-1 pre-mRNA and assembly of infectious particles. IDC16 inhibits replication of macrophage- and T cell-tropic laboratory strains, clinical isolates, and strains with high-level resistance to inhibitors of viral protease and reverse transcriptase. Importantly, drug treatment of primary blood cells did not alter splicing profiles of endogenous genes involved in cell cycle transition and apoptosis. Thus, human splicing factors represent novel and promising drug targets for the development of antiretroviral therapies, particularly for the inhibition of multidrug-resistant viruses.

  3. Altered PLP1 splicing causes hypomyelination of early myelinating structures

    Science.gov (United States)

    Kevelam, Sietske H; Taube, Jennifer R; van Spaendonk, Rosalina M L; Bertini, Enrico; Sperle, Karen; Tarnopolsky, Mark; Tonduti, Davide; Valente, Enza Maria; Travaglini, Lorena; Sistermans, Erik A; Bernard, Geneviève; Catsman-Berrevoets, Coriene E; van Karnebeek, Clara D M; Østergaard, John R; Friederich, Richard L; Fawzi Elsaid, Mahmoud; Schieving, Jolanda H; Tarailo-Graovac, Maja; Orcesi, Simona; Steenweg, Marjan E; van Berkel, Carola G M; Waisfisz, Quinten; Abbink, Truus E M; van der Knaap, Marjo S; Hobson, Grace M; Wolf, Nicole I

    2015-01-01

    Objective The objective of this study was to investigate the genetic etiology of the X-linked disorder “Hypomyelination of Early Myelinating Structures” (HEMS). Methods We included 16 patients from 10 families diagnosed with HEMS by brain MRI criteria. Exome sequencing was used to search for causal mutations. In silico analysis of effects of the mutations on splicing and RNA folding was performed. In vitro gene splicing was examined in RNA from patients’ fibroblasts and an immortalized immature oligodendrocyte cell line after transfection with mutant minigene splicing constructs. Results All patients had unusual hemizygous mutations of PLP1 located in exon 3B (one deletion, one missense and two silent), which is spliced out in isoform DM20, or in intron 3 (five mutations). The deletion led to truncation of PLP1, but not DM20. Four mutations were predicted to affect PLP1/DM20 alternative splicing by creating exonic splicing silencer motifs or new splice donor sites or by affecting the local RNA structure of the PLP1 splice donor site. Four deep intronic mutations were predicted to destabilize a long-distance interaction structure in the secondary PLP1 RNA fragment involved in regulating PLP1/DM20 alternative splicing. Splicing studies in fibroblasts and transfected cells confirmed a decreased PLP1/DM20 ratio. Interpretation Brain structures that normally myelinate early are poorly myelinated in HEMS, while they are the best myelinated structures in Pelizaeus–Merzbacher disease, also caused by PLP1 alterations. Our data extend the phenotypic spectrum of PLP1-related disorders indicating that normal PLP1/DM20 alternative splicing is essential for early myelination and support the need to include intron 3 in diagnostic sequencing. PMID:26125040

  4. Improving Multiple Sequence Alignments by Revising Sequence Families with Alignment Scoring Approaches

    OpenAIRE

    Levchuk, Aleksandr O.

    2011-01-01

    Characterizing the functional, structural, and evolutionary relationships of biological sequences is an important task in modern genomics and computational biology. Most of these applications involve the assembly of sequence families by similarity searching, subsequent formation of multiple sequence alignments (MSAs) and downstream phylogenetic analyses. Especially, MSAs play a central role in this modeling workflow. Thus, the quality of the MSAs is of critical importance for its success. In ...

  5. The conserved splicing factor SUA controls alternative splicing of the developmental regulator ABI3 in Arabidopsis.

    NARCIS (Netherlands)

    Sugliani, M.; Brambilla, V.; Clerkx, E.J.M.; Koornneef, M.; Soppe, W.J.J.

    2010-01-01

    ABSCISIC ACID INSENSITIVE3 (ABI3) is a major regulator of seed maturation in Arabidopsis thaliana. We detected two ABI3 transcripts, ABI3- and ABI3-ß, which encode full-length and truncated proteins, respectively. Alternative splicing of ABI3 is developmentally regulated, and the ABI3-ß transcript a

  6. Strategic Alignment of Business Intelligence

    OpenAIRE

    Cederberg, Niclas

    2010-01-01

    This thesis is about the concept of strategic alignment of business intelligence. It is based on a theoretical foundation that is used to define and explain business intelligence, data warehousing and strategic alignment. By combining a number of different methods for strategic alignment a framework for alignment of business intelligence is suggested. This framework addresses all different aspects of business intelligence identified as relevant for strategic alignment of business intelligence...

  7. RHIC survey and alignment

    International Nuclear Information System (INIS)

    The Relativistic Heavy Ion Collider consists of two interlaced plane rings, a pair of mirror-symmetric beam injection arcs, a spatially curved beam transfer line from the Alternating Gradient Synchrotron, and a collection of precisely positioned and aligned magnets, on appropriately positioned support stands, threaded on those arcs. RHIC geometry is defined by six beam crossing points exactly in a plane, lying precisely at the vertices of a regular hexagon of specified size position and orientation of this hexagon are defined geodetically. Survey control and alignment procedures, currently in use to construct RHIC, are described

  8. Splice connector with internal heat transfer jacket

    Science.gov (United States)

    Silva, Frank A.; Mayer, Robert W.

    1977-01-01

    A heat transfer jacket is placed over the terminal portions of the conductors of a pair of high voltage cables which are connected in a splice connection wherein a housing surrounds the connected conductor portions, the heat transfer jacket extending longitudinally between the confronting ends of a pair of adaptor sleeves placed upon the insulation of the cables to engage and locate the adaptor sleeves relative to one another, and laterally between the conductors and the housing to provide a path of relatively high thermal conductivity between the connected conductor portions and the housing.

  9. Alignment of the MSGC barrel support structure

    International Nuclear Information System (INIS)

    The MSGC barrel is a sub-part of the tracking system of the CMS experiment at the LHC. The mechanical support structure of the MSGC barrel consists of ladder-like support beams carrying the detector modules and of four disks supporting the ladders. The required alignment precision of the modules, a few tens of micrometers, is designed to be obtained by precise part manufacture and by careful measurement of the alignment during the assembly of the structure. In the paper the use of digital photogrammetry for the measurement of the alignment of the disks and for the structural verification is presented. Digital photogrammetry was chosen from a number of potential methods after a careful evaluation. The use of photogrammetry for the structural verification of a prototype is presented. The displacements were measured both of unloaded and loaded disk by using photogrammetry and linear displacement transducers for verification. The displacements obtained from the two measurement methods corresponded well, not only to each other, but also to the results given by finite element analysis. The structural verification will be done and the alignment procedure will be tested with a full-sized prototype of a half of the MSGC barrel. Preparations for the photogrammetry measurements are presented and the design of the required supplementary equipment is shown. (authors)

  10. Exon Expression and Alternatively Spliced Genes in Tourette Syndrome

    NARCIS (Netherlands)

    Tian, Yingfang; Liao, Isaac H.; Zhan, Xinhua; Gunther, Joan R.; Ander, Bradley P.; Liu, Dazhi; Lit, Lisa; Jickling, Glen C.; Corbett, Blythe A.; Bos-Veneman, Netty G. P.; Hoekstra, Pieter J.; Sharp, Frank R.

    2011-01-01

    Tourette Syndrome (TS) is diagnosed based upon clinical criteria including motor and vocal tics. We hypothesized that differences in exon expression and splicing might be useful for pathophysiology and diagnosis. To demonstrate exon expression and alternatively spliced gene differences in blood of i

  11. A study of alternative splicing in the pig

    DEFF Research Database (Denmark)

    Hillig, Ann-Britt Nygaard; Cirera Salicio, Susanna; Gilchrist, Michael J.;

    2010-01-01

    BACKGROUND: Since at least half of the genes in mammalian genomes are subjected to alternative splicing, alternative pre-mRNA splicing plays an important contribution to the complexity of the mammalian proteome. Expressed sequence tags (ESTs) provide evidence of a great number of possible alterna...

  12. Synaptic signaling and aberrant RNA splicing in autism spectrum disorders

    OpenAIRE

    Ryan M Smith; Wolfgang eSadee

    2011-01-01

    Interactions between presynaptic and postsynaptic cellular adhesion molecules drive synapse maturation during development. These trans-synaptic interactions are regulated by alternative splicing of cellular adhesion molecule RNAs, which ultimately determines neurotransmitter phenotype. The diverse assortment of RNAs produced by alternative splicing generates countless protein isoforms necessary for guiding specialized cell-to-cell connectivity. Failure to generate the appropriate synaptic ...

  13. Minor class splicing shapes the zebrafish transcriptome during development

    DEFF Research Database (Denmark)

    Markmiller, Sebastian; Cloonan, Nicole; Lardelli, Rea M;

    2014-01-01

    Minor class or U12-type splicing is a highly conserved process required to remove a minute fraction of introns from human pre-mRNAs. Defects in this splicing pathway have recently been linked to human disease, including a severe developmental disorder encompassing brain and skeletal abnormalities...

  14. Synaptic Signaling and Aberrant RNA Splicing in Autism Spectrum Disorders

    OpenAIRE

    Smith, Ryan M; Sadee, Wolfgang

    2011-01-01

    Interactions between presynaptic and postsynaptic cellular adhesion molecules (CAMs) drive synapse maturation during development. These trans-synaptic interactions are regulated by alternative splicing of CAM RNAs, which ultimately determines neurotransmitter phenotype. The diverse assortment of RNAs produced by alternative splicing generates countless protein isoforms necessary for guiding specialized cell-to-cell connectivity. Failure to generate the appropriate synaptic adhesion proteins i...

  15. Quantitative regulation of alternative splicing in evolution and development

    DEFF Research Database (Denmark)

    Irimia, Manuel; Rukov, Jakob L; Roy, Scott W;

    2009-01-01

    Alternative splicing (AS) is a widespread mechanism with an important role in increasing transcriptome and proteome diversity by generating multiple different products from the same gene. Evolutionary studies of AS have focused primarily on the conservation of alternatively spliced sequences or of...... additional layer in complex gene regulatory networks and in the emergence of genetic novelties....

  16. Tissue-specific splicing factor gene expression signatures

    NARCIS (Netherlands)

    A.R. Grosso; A.Q. Gomes (Anita); N.L. Barbosa-Morais (Nuno); S. Caldeira (Sandra); N.P. Thorne (Natalie); G. Grech (Godfrey); M.M. von Lindern (Marieke); M. Carmo-Fonseca (Maria)

    2008-01-01

    textabstractThe alternative splicing code that controls and coordinates the transcriptome in complex multicellular organisms remains poorly understood. It has long been argued that regulation of alternative splicing relies on combinatorial interactions between multiple proteins, and that tissue-spec

  17. Kluyveromyces lactis maintains Saccharomyces cerevisiae intron-encoded splicing signals.

    OpenAIRE

    Deshler, J O; Larson, G P; Rossi, J J

    1989-01-01

    The actin (ACT) gene from the budding yeast Kluyveromyces lactis was cloned, and the nucleotide sequence was determined. The gene had a single intron 778 nucleotides in length which possessed the highly conserved splicing signals found in Saccharomyces cerevisiae introns. We demonstrated splicing of heterologous ACT transcripts in both K. lactis and S. cerevisiae.

  18. Discriminative Shape Alignment

    DEFF Research Database (Denmark)

    Loog, M.; de Bruijne, M.

    taking into account that eventually the shapes are to be assigned to two or more different classes. This work introduces a discriminative variation to well-known Procrustes alignment and demonstrates its benefit over this classical method in shape classification tasks. The focus is on two...

  19. MUON DETECTORS: ALIGNMENT

    CERN Multimedia

    G. Gomez and Y. Pakhotin

    2012-01-01

      A new track-based alignment for the DT chambers is ready for deployment: an offline tag has already been produced which will become part of the 52X Global Tag. This alignment was validated within the muon alignment group both at low and high momentum using a W/Z skim sample. It shows an improved mass resolution for pairs of stand-alone muons, improved curvature resolution at high momentum, and improved DT segment extrapolation residuals. The validation workflow for high-momentum muons used to depend solely on the “split cosmics” method, looking at the curvature difference between muon tracks reconstructed in the upper or lower half of CMS. The validation has now been extended to include energetic muons decaying from heavily boosted Zs: the di-muon invariant mass for global and stand-alone muons is reconstructed, and the invariant mass resolution is compared for different alignments. The main areas of development over the next few months will be preparing a new track-based C...

  20. Aligning Mental Representations

    DEFF Research Database (Denmark)

    Kano Glückstad, Fumiko

    2013-01-01

    This work introduces a framework that implements asymmetric communication theory proposed by Sperber and Wilson [1]. The framework applies a generalization model known as the Bayesian model of generalization (BMG) [2] for aligning knowledge possessed by two communicating parties. The work focuses...

  1. The surveyors' quest for perfect alignment

    CERN Multimedia

    2003-01-01

    Photogrammetry of a CMS endcap and part of the hadronic calorimeter.The structure was covered with targets photographed by digital cameras. Perfect alignment.... Although CERN's surveyors do not claim to achieve it, they are constantly striving for it and deploy all necessary means to come as close as they can. In their highly specialised field of large-scale metrology, the solution lies in geodesy and photogrammetry, both of which are based on increasingly sophisticated instruments and systems. In civil engineering, these techniques are used for non-destructive inspection of bridges, dams and other structures, while industrial applications include dimensional verification and deformation measurement in large mechanical assemblies. The same techniques also come into play for the metrology of research tools such as large telescopes and of course, particle accelerators. Particle physics laboratories are especially demanding customers, and CERN has often asked for the impossible. As a result, the alignment metro...

  2. Splice Site Mutations in the ATP7A Gene

    DEFF Research Database (Denmark)

    Skjørringe, Tina; Tümer, Zeynep; Møller, Lisbeth Birk

    2011-01-01

    Menkes disease (MD) is caused by mutations in the ATP7A gene. We describe 33 novel splice site mutations detected in patients with MD or the milder phenotypic form, Occipital Horn Syndrome. We review these 33 mutations together with 28 previously published splice site mutations. We investigate 12...... mutations for their effect on the mRNA transcript in vivo. Transcriptional data from another 16 mutations were collected from the literature. The theoretical consequences of splice site mutations, predicted with the bioinformatics tool Human Splice Finder, were investigated and evaluated in relation to in...... vivo results. Ninety-six percent of the mutations identified in 45 patients with classical MD were predicted to have a significant effect on splicing, which concurs with the absence of any detectable wild-type transcript in all 19 patients investigated in vivo. Sixty-seven percent of the mutations...

  3. Comparative Analysis of Splice Site Regions by Information Content

    Institute of Scientific and Technical Information of China (English)

    T. Shashi Rekha; Chanchal K. Mitra

    2006-01-01

    We have applied concepts from information theory for a comparative analysis of donor (gt) and acceptor (ag) splice site regions in the genes of five different organisms by calculating their mutual information content (relative entropy) over a selected block of nucleotides. A similar pattern that the information content decreases as the block size increases was observed for both regions in all the organisms studied. This result suggests that the information required for splicing might be contained in the consensus of ~6-8 nt at both regions. We assume from our study that even though the nucleotides are showing some degrees of conservation in the flanking regions of the splice sites, certain level of variability is still tolerated,which leads the splicing process to occur normally even if the extent of base pairing is not fully satisfied. We also suggest that this variability can be compensated by recognizing different splice sites with different spliceosomal factors.

  4. Evolution of alternative splicing regulation: changes in predicted exonic splicing regulators are not associated with changes in alternative splicing levels in primates

    DEFF Research Database (Denmark)

    Irimia, Manuel; Rukov, Jakob Lewin; Roy, Scott William

    2009-01-01

    interspecific differences in these elements on the evolution of alternative splicing levels has not yet been investigated at genomic level. Here we study the effect of interspecific differences in predicted exonic splicing regulators (ESRs) on exon inclusion levels in human and chimpanzee. For this purpose, we...... compiled and studied comprehensive datasets of predicted ESRs, identified by several computational and experimental approaches, as well as microarray data for changes in alternative splicing levels between human and chimpanzee. Surprisingly, we found no association between changes in predicted ESRs and...... or no effect on splicing, and thus interspecific changes at short-time scales may primarily occur in these effectively neutral ESRs. These results underscore the difficulties of using current computational ESR prediction algorithms to identify truly functionally important motifs, and provide a...

  5. Fast global sequence alignment technique

    KAUST Repository

    Bonny, Mohamed Talal

    2011-11-01

    Bioinformatics database is growing exponentially in size. Processing these large amount of data may take hours of time even if super computers are used. One of the most important processing tool in Bioinformatics is sequence alignment. We introduce fast alignment algorithm, called \\'Alignment By Scanning\\' (ABS), to provide an approximate alignment of two DNA sequences. We compare our algorithm with the wellknown sequence alignment algorithms, the \\'GAP\\' (which is heuristic) and the \\'Needleman-Wunsch\\' (which is optimal). The proposed algorithm achieves up to 51% enhancement in alignment score when it is compared with the GAP Algorithm. The evaluations are conducted using different lengths of DNA sequences. © 2011 IEEE.

  6. ABS: Sequence alignment by scanning

    KAUST Repository

    Bonny, Mohamed Talal

    2011-08-01

    Sequence alignment is an essential tool in almost any computational biology research. It processes large database sequences and considered to be high consumers of computation time. Heuristic algorithms are used to get approximate but fast results. We introduce fast alignment algorithm, called Alignment By Scanning (ABS), to provide an approximate alignment of two DNA sequences. We compare our algorithm with the well-known alignment algorithms, the FASTA (which is heuristic) and the \\'Needleman-Wunsch\\' (which is optimal). The proposed algorithm achieves up to 76% enhancement in alignment score when it is compared with the FASTA Algorithm. The evaluations are conducted using different lengths of DNA sequences. © 2011 IEEE.

  7. Comprehensive splicing graph analysis of alternative splicing patterns in chicken, compared to human and mouse

    Directory of Open Access Journals (Sweden)

    Ranganathan Shoba

    2009-07-01

    Full Text Available Abstract Background Alternative transcript diversity manifests itself as a prime cause of complexity in higher eukaryotes. Recently, transcript diversity studies have suggested that 60–80% of human genes are alternatively spliced. We have used a splicing pattern approach for the bioinformatics analysis of Alternative Splicing (AS in chicken, human and mouse. Exons involved in splicing are subdivided into distinct and variant exons, based on the prevalence of the exons across the transcripts. Four possible permutations of these two different groups of exons were categorised as class I (distinct-variant, class II (distinct-variant, class III (variant-distinct and class IV (variant-variant. This classification quantifies the variation in transcript diversity in the three species. Results In all, 3901 chicken AS genes have been compared with 16,715 human and 16,491 mouse AS genes, with 23% of chicken genes being alternatively spliced, compared to 68% in humans and 57% in mice. To minimize any gene structure bias in the input data, comparative genome analysis has been carried out on the orthologous subset of AS genes for the three species. Gene-level analysis suggested that chicken genes show fewer AS events compared to human and mouse. An event-level analysis showed that the percentage of AS events in chicken is similar to that of human, which implies that a smaller number of chicken genes show greater transcript diversity. Overall, chicken genes were found to have fewer transcripts per gene and shorter introns than human and mouse genes. Conclusion In chicken, the majority of genes generate only two or three isoforms, compared to almost eight in human and six in mouse. We observed that intron definition is expressed strongly when compared to exon definition for chicken genome, based on 3% intron retention in chicken, compared to 2% in human and mouse. Splicing patterns with variant exons account for 33% of AS chicken orthologous genes compared to

  8. Product-internal assembly functions: a novel micro-assembly concept applied to optical interconnects

    NARCIS (Netherlands)

    Henneken, V.A.

    2008-01-01

    In this project, the technical feasibility of a novel assembly concept was explored, in which microsystem-based self-assembly functionality is added to an existing product. The case considered is the accurate alignment of an optical fibre relative to a telecommunication laser source. In the most dem

  9. MaxAlign: maximizing usable data in an alignment

    Directory of Open Access Journals (Sweden)

    Pedersen Anders G

    2007-08-01

    Full Text Available Abstract Background The presence of gaps in an alignment of nucleotide or protein sequences is often an inconvenience for bioinformatical studies. In phylogenetic and other analyses, for instance, gapped columns are often discarded entirely from the alignment. Results MaxAlign is a program that optimizes the alignment prior to such analyses. Specifically, it maximizes the number of nucleotide (or amino acid symbols that are present in gap-free columns – the alignment area – by selecting the optimal subset of sequences to exclude from the alignment. MaxAlign can be used prior to phylogenetic and bioinformatical analyses as well as in other situations where this form of alignment improvement is useful. In this work we test MaxAlign's performance in these tasks and compare the accuracy of phylogenetic estimates including and excluding gapped columns from the analysis, with and without processing with MaxAlign. In this paper we also introduce a new simple measure of tree similarity, Normalized Symmetric Similarity (NSS that we consider useful for comparing tree topologies. Conclusion We demonstrate how MaxAlign is helpful in detecting misaligned or defective sequences without requiring manual inspection. We also show that it is not advisable to exclude gapped columns from phylogenetic analyses unless MaxAlign is used first. Finally, we find that the sequences removed by MaxAlign from an alignment tend to be those that would otherwise be associated with low phylogenetic accuracy, and that the presence of gaps in any given sequence does not seem to disturb the phylogenetic estimates of other sequences. The MaxAlign web-server is freely available online at http://www.cbs.dtu.dk/services/MaxAlign where supplementary information can also be found. The program is also freely available as a Perl stand-alone package.

  10. WT1 interacts with the splicing protein RBM4 and regulates its ability to modulate alternative splicing in vivo

    International Nuclear Information System (INIS)

    Wilm's tumor protein 1 (WT1), a protein implicated in various cancers and developmental disorders, consists of two major isoforms: WT1(-KTS), a transcription factor, and WT1(+KTS), a post-transcriptional regulator that binds to RNA and can interact with splicing components. Here we show that WT1 interacts with the novel splicing regulator RBM4. Each protein was found to colocalize in nuclear speckles and to cosediment with supraspliceosomes in glycerol gradients. RBM4 conferred dose-dependent and cell-specific regulation of alternative splicing of pre-mRNAs transcribed from several reporter genes. We found that overexpressed WT1(+KTS) abrogated this effect of RBM4 on splice-site selection, whereas WT1(-KTS) did not. We conclude that the (+KTS) form of WT1 is able to inhibit the effect of RBM4 on alternative splicing

  11. Microstructure, magnetic, and low-field magnetotransport properties of self-assembled (La{sub 0.7}Sr{sub 0.3}MnO{sub 3}){sub 0.5}:(CeO{sub 2}){sub 0.5} vertically aligned nanocomposite thin films

    Energy Technology Data Exchange (ETDEWEB)

    Chen Aiping; Bi Zhenxing; Hazariwala, Harshad; Su Qing; Chen Li; Wang Haiyan [Department of Electrical and Computer Engineering, Texas A and M University, College Station, TX 77843 (United States); Zhang Xinghang [Department of Mechanical Engineering, Texas A and M University, College Station, TX 77843 (United States); Jia Quanxi [Center for Integrated Nanotechnologies (CINT), Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); MacManus-Driscoll, Judith L, E-mail: wangh@ece.tamu.edu [Department of Materials Science and Metallurgy, University of Cambridge, Pembroke Street, Cambridge, CB2 3QZ (United Kingdom)

    2011-08-05

    Two-phase (La{sub 0.7}Sr{sub 0.3}MnO{sub 3}){sub 0.5}:(CeO{sub 2}){sub 0.5} (LSMO:CeO{sub 2}) heteroepitaxial nanocomposite films were grown on SrTiO{sub 3} (STO) (001) by pulsed laser deposition (PLD). X-ray diffraction (XRD) and transmission electron microscopy (TEM) results show that LSMO:CeO{sub 2} films epitaxially grow on STO as self-assembled vertically aligned nanocomposite (VAN). Magnetic and magnetotransport measurements demonstrate that the LSMO phase in the VAN structure behaves differently from its epitaxial single-phase counterpart, e.g. greatly enhanced coercivity (H{sub C}) and low-field magnetoresistance (LFMR). The enhanced properties in the VAN system are attributed to the interaction between the perovskite and the secondary phase or phase boundary. The results suggest that the growth of functional oxide in another oxide matrix with vertical heteroepitaxial form is a promising approach to achieve new functionality that may not be easily realized in the single epitaxial phase.

  12. Vacuum mechatronic laser alignment system on the Nova laser

    International Nuclear Information System (INIS)

    The experiments conducted on NOVA are done to investigate inertially confined laser fusion reactions. To this end, the ten beams of the laser are aligned to within 30mm. The target chamber employs a vacuum mechatronic based reticle/target positioning system to accomplish this. It is a five degree-of-freedom chamber resident system, known as the Alignment Aids Positioner or AAP. The AAP aids in beam and diagnostic alignment by accurately positioning a reticle at target chamber center to with 7mm. The AAP system increases target positioning and alignment flexibility and accuracy through the use of a computer controlled multi degree-of-freedom stage assembly. This device uses microstepping DC stepper motors with encoders to achieve closed loop control in a 10-6 torr vacuum. The AAP has two positioning regimes to move the alignment reticle and do beam alignment. One is course positioning in the Y-Z plane that moves a high resolution stage assembly to target chamber center. The other regime is high resolution movement in the X,Y,Z and q directions. 5 refs., 9 figs

  13. Sequence assembly

    DEFF Research Database (Denmark)

    Scheibye-Alsing, Karsten; Hoffmann, S.; Frankel, Annett Maria;

    2009-01-01

    Despite the rapidly increasing number of sequenced and re-sequenced genomes, many issues regarding the computational assembly of large-scale sequencing data have remain unresolved. Computational assembly is crucial in large genome projects as well for the evolving high-throughput technologies and...... plays an important role in processing the information generated by these methods. Here, we provide a comprehensive overview of the current publicly available sequence assembly programs. We describe the basic principles of computational assembly along with the main concerns, such as repetitive sequences...... in genomic DNA, highly expressed genes and alternative transcripts in EST sequences. We summarize existing comparisons of different assemblers and provide a detailed descriptions and directions for download of assembly programs at: http://genome.ku.dk/resources/assembly/methods.html....

  14. Fuel nozzle assembly

    Science.gov (United States)

    Johnson, Thomas Edward; Ziminsky, Willy Steve; Lacey, Benjamin Paul; York, William David; Stevenson, Christian Xavier

    2011-08-30

    A fuel nozzle assembly is provided. The assembly includes an outer nozzle body having a first end and a second end and at least one inner nozzle tube having a first end and a second end. One of the nozzle body or nozzle tube includes a fuel plenum and a fuel passage extending therefrom, while the other of the nozzle body or nozzle tube includes a fuel injection hole slidably aligned with the fuel passage to form a fuel flow path therebetween at an interface between the body and the tube. The nozzle body and the nozzle tube are fixed against relative movement at the first ends of the nozzle body and nozzle tube, enabling the fuel flow path to close at the interface due to thermal growth after a flame enters the nozzle tube.

  15. Jet activity versus alignment

    CERN Document Server

    Lokhtin, I P; Sarycheva, L I; Snigirev, A M

    2005-01-01

    The hypothesis about the relation between the observed alignment of spots in the x-ray film in cosmic ray emulsion experiments and the features of events in which jets prevail at super high energies is tested. Due to strong correlation between jet axis directions and that between momenta (almost collinearity) of jet particles, the evaluated degree of alignment is considerably larger than that at randomly selected chaoticly located spots in the x-ray film. It appears comparable with experimental data provided that the height of primary interaction, the collision energy and the total energy of selected clusters meet certain conditions. The Monte Carlo generator PYTHIA, which basically well describes jet events in hadron-hadron interactions, was used for the analysis.

  16. Inflation by alignment

    Energy Technology Data Exchange (ETDEWEB)

    Burgess, C.P. [PH -TH Division, CERN,CH-1211, Genève 23 (Switzerland); Department of Physics & Astronomy, McMaster University,1280 Main Street West, Hamilton ON (Canada); Perimeter Institute for Theoretical Physics,31 Caroline Street North, Waterloo ON (Canada); Roest, Diederik [Van Swinderen Institute for Particle Physics and Gravity, University of Groningen,Nijenborgh 4, 9747 AG Groningen (Netherlands)

    2015-06-08

    Pseudo-Goldstone bosons (pGBs) can provide technically natural inflatons, as has been comparatively well-explored in the simplest axion examples. Although inflationary success requires trans-Planckian decay constants, f≳M{sub p}, several mechanisms have been proposed to obtain this, relying on (mis-)alignments between potential and kinetic energies in multiple-field models. We extend these mechanisms to a broader class of inflationary models, including in particular the exponential potentials that arise for pGB potentials based on noncompact groups (and so which might apply to moduli in an extra-dimensional setting). The resulting potentials provide natural large-field inflationary models and can predict a larger primordial tensor signal than is true for simpler single-field versions of these models. In so doing we provide a unified treatment of several alignment mechanisms, showing how each emerges as a limit of the more general setup.

  17. Alignments of RNA structures.

    Science.gov (United States)

    Blin, Guillaume; Denise, Alain; Dulucq, Serge; Herrbach, Claire; Touzet, Hélène

    2010-01-01

    We describe a theoretical unifying framework to express the comparison of RNA structures, which we call alignment hierarchy. This framework relies on the definition of common supersequences for arc-annotated sequences and encompasses the main existing models for RNA structure comparison based on trees and arc-annotated sequences with a variety of edit operations. It also gives rise to edit models that have not been studied yet. We provide a thorough analysis of the alignment hierarchy, including a new polynomial-time algorithm and an NP-completeness proof. The polynomial-time algorithm involves biologically relevant edit operations such as pairing or unpairing nucleotides. It has been implemented in a software, called gardenia, which is available at the Web server http://bioinfo.lifl.fr/RNA/gardenia. PMID:20431150

  18. In vitro Splicing of Influenza Viral NS1 mRNA and NS1-β -globin Chimeras: Possible Mechanisms for the Control of Viral mRNA Splicing

    Science.gov (United States)

    Plotch, Stephen J.; Krug, Robert M.

    1986-08-01

    In influenza virus-infected cells, the splicing of the viral NS1 mRNA catalyzed by host nuclear enzymes is controlled so that the steady-state amount of the spliced NS2 mRNA is only 5-10% of that of the unspliced NS1 mRNA. Here we examine the splicing of NS1 mRNA in vitro, using nuclear extracts from HeLa cells. We show that in addition to its consensus 5' and 3' splice sites, NS1 mRNA has an intron branch-point adenosine residue that was functional in lariat formation. Nonetheless, this RNA was not detectably spliced in vitro under conditions in which a human β -globin precursor was efficiently spliced. Using chimeric RNA precursors containing both NS1 and β -globin sequences, we show that the NS1 5' splice site was effectively utilized by the β -globin branch-point sequence and 3' splice site to form a spliced RNA, whereas the NS1 3' splice site did not function in detectable splicing in vitro, even in the presence of the β -globin branch-point sequence or in the presence of both the branch-point sequence and 5' exon and splice site from β -globin With the chimeric precursors that were not detectably spliced, as with NS1 mRNA itself, a low level of a lariat structure containing only intron and not 3' exon sequences was formed. The inability of the consensus 3' splice site of NS1 mRNA to function effectively in in vitro splicing suggests that this site is structurally inaccessible to components of the splicing machinery. Based on these results, we propose two mechanisms whereby NS1 mRNA splicing in infected cells is controlled via the accessibility of its 3' splice site.

  19. Alignment of concerns

    DEFF Research Database (Denmark)

    Andersen, Tariq Osman; Bansler, Jørgen P.; Kensing, Finn; Moll, Jonas; Nielsen, Karen Dam

    E-health promises to enable and support active patient participation in chronic care. However, these fairly recent innovations are complicated matters and emphasize significant challenges, such as patients’ and clinicians’ different ways of conceptualizing disease and illness. Informed by insights...... from medical phenomenology and our own empirical work in telemonitoring and medical care of heart patients, we propose a design rationale for e-health systems conceptualized as the ‘alignment of concerns’....

  20. Nuclear reactor alignment plate configuration

    Science.gov (United States)

    Altman, David A; Forsyth, David R; Smith, Richard E; Singleton, Norman R

    2014-01-28

    An alignment plate that is attached to a core barrel of a pressurized water reactor and fits within slots within a top plate of a lower core shroud and upper core plate to maintain lateral alignment of the reactor internals. The alignment plate is connected to the core barrel through two vertically-spaced dowel pins that extend from the outside surface of the core barrel through a reinforcement pad and into corresponding holes in the alignment plate. Additionally, threaded fasteners are inserted around the perimeter of the reinforcement pad and into the alignment plate to further secure the alignment plate to the core barrel. A fillet weld also is deposited around the perimeter of the reinforcement pad. To accomodate thermal growth between the alignment plate and the core barrel, a gap is left above, below and at both sides of one of the dowel pins in the alignment plate holes through with the dowel pins pass.

  1. Stable assembly of HIV-1 export complexes occurs cotranscriptionally

    DEFF Research Database (Denmark)

    Nawroth, Isabel; Mueller, Florian; Basyuk, Eugenia;

    2014-01-01

    The HIV-1 Rev protein mediates export of unspliced and singly spliced viral transcripts by binding to the Rev response element (RRE) and recruiting the cellular export factor CRM1. Here, we investigated the recruitment of Rev to the transcription sites of HIV-1 reporters that splice either post- or...... cotranscriptionally. In both cases, we observed that Rev localized to the transcription sites of the reporters and recruited CRM1. Rev and CRM1 remained at the reporter transcription sites when cells were treated with the splicing inhibitor Spliceostatin A (SSA), showing that the proteins associate with RNA prior to...... or during early spliceosome assembly. Fluorescence recovery after photobleaching (FRAP) revealed that Rev and CRM1 have similar kinetics as the HIV-1 RNA, indicating that Rev, CRM1, and RRE-containing RNAs are released from the site of transcription in one single export complex. These results suggest...

  2. Automated alignment of optical components for high-power diode lasers

    Science.gov (United States)

    Brecher, C.; Pyschny, N.; Haag, S.; Guerrero Lule, V.

    2012-03-01

    Despite major progress in developing brilliant laser sources a huge potential for cost reductions can be found in simpler setups and automated assembly processes, especially for large volume applications. In this presentation, a concept for flexible automation in optics assembly is presented which is based on standard micro assembly systems with relatively large workspace and modular micromanipulators to enhance the system with additional degrees of freedom and a very high motion resolution. The core component is a compact flexure-based micromanipulator especially designed for the alignment of micro optical components which will be described in detail. The manipulator has been applied in different scenarios to develop and investigate automated alignment processes. This paper focuses on the automated alignment of fast axis collimation (FAC) lenses which is a crucial step during the production of diode lasers. The handling and positioning system, the measuring arrangement for process feedback during active alignment as well as the alignment strategy will be described. The fine alignment of the FAC lens is performed with the micromanipulator under concurrent analysis of the far and the near field intensity distribution. An optimization of the image processing chains for the alignment of a FAC in front of a diode bar led to cycle times of less than 30 seconds. An outlook on other applications and future work regarding the development of automated assembly processes as well as new ideas for flexible assembly systems with desktop robots will close the talk.

  3. Seeking the perfect alignment

    CERN Multimedia

    2002-01-01

    The first full-scale tests of the ATLAS Muon Spectrometer are about to begin in Prévessin. The set-up includes several layers of Monitored Drift Tubes Chambers (MDTs) and will allow tests of the performance of the detectors and of their highly accurate alignment system.   Monitored Drift Chambers in Building 887 in Prévessin, where they are just about to be tested. Muon chambers are keeping the ATLAS Muon Spectrometer team quite busy this summer. Now that most people go on holiday, the beam and alignment tests for these chambers are just starting. These chambers will measure with high accuracy the momentum of high-energy muons, and this implies very demanding requirements for their alignment. The MDT chambers consist of drift tubes, which are gas-filled metal tubes, 3 cm in diameter, with wires running down their axes. With high voltage between the wire and the tube wall, the ionisation due to traversing muons is detected as electrical pulses. With careful timing of the pulses, the position of the muon t...

  4. Alignment at the ESRF

    International Nuclear Information System (INIS)

    The ESRF Survey and Alignment group is responsible for the installation, control and periodic realignment of the accelerators and experiments which produce high quality x-rays used by scientists from Europe and around the world. Alignment tolerances are typically less than one millimetre and often in the order of several micrometers. The group is composed of one engineer, five highly trained survey technicians, one electronic and one computer technician. This team is fortified during peak periods by technicians from an external survey company. First an overview and comparative study of the main large-scale survey instrumentation and methods used by the group is made. Secondly a discussion of long term deformation on the ESRF site is presented. This is followed by presentation of the methods used in the realignment of the various machines. Two important aspects of our work, beamline and front-end alignment, and the so-called machine exotic devices are briefly discussed. Finally, the ESRF calibration bench is presented. (authors)

  5. Semiautomated improvement of RNA alignments

    DEFF Research Database (Denmark)

    Andersen, Ebbe Sloth; Lind-Thomsen, Allan; Knudsen, Bjarne;

    2007-01-01

    We have developed a semiautomated RNA sequence editor (SARSE) that integrates tools for analyzing RNA alignments. The editor highlights different properties of the alignment by color, and its integrated analysis tools prevent the introduction of errors when doing alignment editing. SARSE readily...... the SARSE editor makes it a flexible tool to improve all RNA alignments with relatively little human intervention. Online documentation and software are available at (http://sarse.ku.dk)....

  6. Splicing Express: a software suite for alternative splicing analysis using next-generation sequencing data

    OpenAIRE

    Kroll, Jose E.; Kim, JiHoon; Ohno-Machado, Lucila; de Souza, Sandro J.

    2015-01-01

    Motivation. Alternative splicing events (ASEs) are prevalent in the transcriptome of eukaryotic species and are known to influence many biological phenomena. The identification and quantification of these events are crucial for a better understanding of biological processes. Next-generation DNA sequencing technologies have allowed deep characterization of transcriptomes and made it possible to address these issues. ASEs analysis, however, represents a challenging task especially when many dif...

  7. Alignment as a Teacher Variable

    Science.gov (United States)

    Porter, Andrew C.; Smithson, John; Blank, Rolf; Zeidner, Timothy

    2007-01-01

    With the exception of the procedures developed by Porter and colleagues (Porter, 2002), other methods of defining and measuring alignment are essentially limited to alignment between tests and standards. Porter's procedures have been generalized to investigating the alignment between content standards, tests, textbooks, and even classroom…

  8. Assisted Assembly: How to Improve a De Novo Genome Assembly By Using Related Species

    OpenAIRE

    Gnerre, Sante; Lindblad-Toh, Kerstin; Jaffe, David B; Lander, Eric Steven

    2009-01-01

    We describe a new assembly algorithm, where a genome assembly with low sequence coverage, either throughout the genome or locally, due to cloning bias, is considerably improved through an assisting process via a related genome. We show that the information provided by aligning the whole-genome shotgun reads of the target against a reference genome can be used to substantially improve the quality of the resulting assembly.

  9. Using Sorting by Reversal: Breakpoint Graph for Gene Assembly in Ciliates

    Science.gov (United States)

    Brijder, Robert; Jan Hoogeboom, Hendrik

    2007-09-01

    The theory of gene assembly in ciliates has much in common with the theory of sorting by reversal. Both model processes that are based on splicing, and have a fixed begin and end product. The main difference is the type of splicing operations used to obtain the end product from the begin product. In this overview paper we show that the concept of breakpoint graph, known from the theory of sorting by reversal, has many uses in the theory of gene assembly. Our aim is to present the material in an intuitive and informal manner to allow for an efficient introduction into the subject.

  10. SSC dipole magnet measurement and alignment using laser technology

    Energy Technology Data Exchange (ETDEWEB)

    Lipski, A.; Carson, J.A.; Robotham, W.F.

    1990-06-01

    Advancing into the prototype production stage of the SSC dipole magnets has introduced the need for a reliable, readily available, accurate alignment measuring system which gives results in real time. Components and subassemblies such as the cold mass and vacuum vessel are being measured for various geometric conditions such as straightness and twist. Variations from nominal dimensions are also being recorded so they can be compensated for during the final assembly process. Precision laser alignment takes specific advantages of the greatest accuracy. When combined with an optically produced perpendicular plane, this results in a system of geometric references of unparalleled accuracy. This paper describes the geometric requirements for SSC dipole magnet components, sub and final assemblies as well as the use of laser technology for surveying as part of the assembly process.

  11. SSC dipole magnet measurement and alignment using laser technology

    International Nuclear Information System (INIS)

    Advancing into the prototype production stage of the SSC dipole magnets has introduced the need for a reliable, readily available, accurate alignment measuring system which gives results in real time. Components and subassemblies such as the cold mass and vacuum vessel are being measured for various geometric conditions such as straightness and twist. Variations from nominal dimensions are also being recorded so they can be compensated for during the final assembly process. Precision laser alignment takes specific advantages of the greatest accuracy. When combined with an optically produced perpendicular plane, this results in a system of geometric references of unparalleled accuracy. This paper describes the geometric requirements for SSC dipole magnet components, sub and final assemblies as well as the use of laser technology for surveying as part of the assembly process

  12. GPCODON ALIGNMENT: A GLOBAL PAIRWISE CODON BASED SEQUENCE ALIGNMENT APPROACH

    Directory of Open Access Journals (Sweden)

    Zeinab A. Fareed

    2016-02-01

    Full Text Available The alignment of two DNA sequences is a basic step in the analysis of biological data. Sequencing a long DNA sequence is one of the most interesting problems in bioinformatics. Several techniques have been developed to solve this sequence alignment problem like dynamic programming and heuristic algorithms. In this paper, we introduce (GPCodon alignment a pairwise DNA-DNA method for global sequence alignment that improves the accuracy of pairwise sequence alignment. We use a new scoring matrix to produce the final alignment called the empirical codon substitution matrix. Using this matrix in our technique enabled the discovery of new relationships between sequences that could not be discovered using traditional matrices. In addition, we present experimental results that show the performance of the proposed technique over eleven datasets of average length of 2967 bps. We compared the efficiency and accuracy of our techniques against a comparable tool called “Pairwise Align Codons” [1].

  13. Chemical strategies for die/wafer submicron alignment and bonding.

    Energy Technology Data Exchange (ETDEWEB)

    Martin, James Ellis; Baca, Alicia I.; Chu, Dahwey; Rohwer, Lauren Elizabeth Shea

    2010-09-01

    This late-start LDRD explores chemical strategies that will enable sub-micron alignment accuracy of dies and wafers by exploiting the interfacial energies of chemical ligands. We have micropatterned commensurate features, such as 2-d arrays of micron-sized gold lines on the die to be bonded. Each gold line is functionalized with alkanethiol ligands before the die are brought into contact. The ligand interfacial energy is minimized when the lines on the die are brought into registration, due to favorable interactions between the complementary ligand tails. After registration is achieved, standard bonding techniques are used to create precision permanent bonds. We have computed the alignment forces and torque between two surfaces patterned with arrays of lines or square pads to illustrate how best to maximize the tendency to align. We also discuss complex, aperiodic patterns such as rectilinear pad assemblies, concentric circles, and spirals that point the way towards extremely precise alignment.

  14. Proximity-dependent and proximity-independent trans-splicing in mammalian cells

    OpenAIRE

    Viles, Kristi D.; Sullenger, Bruce A

    2008-01-01

    Most human pre-mRNAs are cis-spliced, removing introns and joining flanking exons of the same RNA molecule. However, splicing of exons present on separate pre-mRNA molecules can also occur. This trans-splicing reaction can be exploited by pre-trans-splicing molecules (PTMs), which are incapable of cis-splicing. PTM-mediated trans-splicing has been utilized to repair mutant RNAs as a novel approach to gene therapy. Herein we explore how the site of PTM expression influences trans-splicing acti...

  15. Alternative splicing of SMPD1 in human sepsis.

    Directory of Open Access Journals (Sweden)

    Marcel Kramer

    Full Text Available Acid sphingomyelinase (ASM or sphingomyelin phosphodiesterase, SMPD activity engages a critical role for regulation of immune response and development of organ failure in critically ill patients. Beside genetic variation in the human gene encoding ASM (SMPD1, alternative splicing of the mRNA is involved in regulation of enzymatic activity. Here we show that the patterns of alternatively spliced SMPD1 transcripts are significantly different in patients with systemic inflammatory response syndrome and severe sepsis/septic shock compared to control subjects allowing discrimination of respective disease entity. The different splicing patterns might contribute to the better understanding of the pathophysiology of human sepsis.

  16. A comprehensive evaluation of alignment algorithms in the context of RNA-seq.

    Directory of Open Access Journals (Sweden)

    Robert Lindner

    Full Text Available Transcriptome sequencing (RNA-Seq overcomes limitations of previously used RNA quantification methods and provides one experimental framework for both high-throughput characterization and quantification of transcripts at the nucleotide level. The first step and a major challenge in the analysis of such experiments is the mapping of sequencing reads to a transcriptomic origin including the identification of splicing events. In recent years, a large number of such mapping algorithms have been developed, all of which have in common that they require algorithms for aligning a vast number of reads to genomic or transcriptomic sequences. Although the FM-index based aligner Bowtie has become a de facto standard within mapping pipelines, a much larger number of possible alignment algorithms have been developed also including other variants of FM-index based aligners. Accordingly, developers and users of RNA-seq mapping pipelines have the choice among a large number of available alignment algorithms. To provide guidance in the choice of alignment algorithms for these purposes, we evaluated the performance of 14 widely used alignment programs from three different algorithmic classes: algorithms using either hashing of the reference transcriptome, hashing of reads, or a compressed FM-index representation of the genome. Here, special emphasis was placed on both precision and recall and the performance for different read lengths and numbers of mismatches and indels in a read. Our results clearly showed the significant reduction in memory footprint and runtime provided by FM-index based aligners at a precision and recall comparable to the best hash table based aligners. Furthermore, the recently developed Bowtie 2 alignment algorithm shows a remarkable tolerance to both sequencing errors and indels, thus, essentially making hash-based aligners obsolete.

  17. A comprehensive evaluation of alignment algorithms in the context of RNA-seq.

    Science.gov (United States)

    Lindner, Robert; Friedel, Caroline C

    2012-01-01

    Transcriptome sequencing (RNA-Seq) overcomes limitations of previously used RNA quantification methods and provides one experimental framework for both high-throughput characterization and quantification of transcripts at the nucleotide level. The first step and a major challenge in the analysis of such experiments is the mapping of sequencing reads to a transcriptomic origin including the identification of splicing events. In recent years, a large number of such mapping algorithms have been developed, all of which have in common that they require algorithms for aligning a vast number of reads to genomic or transcriptomic sequences. Although the FM-index based aligner Bowtie has become a de facto standard within mapping pipelines, a much larger number of possible alignment algorithms have been developed also including other variants of FM-index based aligners. Accordingly, developers and users of RNA-seq mapping pipelines have the choice among a large number of available alignment algorithms. To provide guidance in the choice of alignment algorithms for these purposes, we evaluated the performance of 14 widely used alignment programs from three different algorithmic classes: algorithms using either hashing of the reference transcriptome, hashing of reads, or a compressed FM-index representation of the genome. Here, special emphasis was placed on both precision and recall and the performance for different read lengths and numbers of mismatches and indels in a read. Our results clearly showed the significant reduction in memory footprint and runtime provided by FM-index based aligners at a precision and recall comparable to the best hash table based aligners. Furthermore, the recently developed Bowtie 2 alignment algorithm shows a remarkable tolerance to both sequencing errors and indels, thus, essentially making hash-based aligners obsolete. PMID:23300661

  18. Intragenic alternative splicing coordination is essential for Caenorhabditis elegans slo-1 gene function

    OpenAIRE

    Glauser, Dominique A; Johnson, Brandon E.; Aldrich, Richard W; Goodman, Miriam B.

    2012-01-01

    Alternative splicing is critical for diversifying eukaryotic proteomes, but the rules governing and coordinating splicing events among multiple alternate splice sites within individual genes are not well understood. We developed a quantitative PCR-based strategy to quantify the expression of the 12 transcripts encoded by the Caenorhabditis elegans slo-1 gene, containing three alternate splice sites. Using conditional probability-based models, we show that splicing events are coordinated acros...

  19. EVOLUTION OF SR PROTEIN AND HnRNP SPLICING REGULATORY FACTORS

    OpenAIRE

    Busch, A.; Hertel, KJ

    2011-01-01

    The splicing of pre-mRNAs is an essential step of gene expression in eukaryotes. Introns are removed from split genes through the activities of the spliceosome, a large ribonuclear machine that is conserved throughout the eukaryotic lineage. While unicellular eukaryotes are characterized by less complex splicing, pre-mRNA splicing of multicellular organisms is often associated with extensive alternative splicing that significantly enriches their proteome. The alternative selection of splice s...

  20. Editing efficiency of a Drosophila gene correlates with a distant splice site selection

    OpenAIRE

    AGRAWAL, RITESH; Stormo, Gary D.

    2005-01-01

    RNA editing and alternative splicing are two processes that increase protein diversity. The relationship between the two processes is not well understood. There are a few examples of correlations between editing and alternative splicing, but these are all nearby effects. A search for alternative splicing among 16 edited genes in Drosophila reveals two novel instances of alternative splicing. In one example where alternative splicing occurs downstream of editing, a strong correlation between e...

  1. Nascent-seq indicates widespread cotranscriptional pre-mRNA splicing in Drosophila

    OpenAIRE

    Khodor, Yevgenia L.; Rodriguez, Joseph; Abruzzi, Katharine C.; Tang, Chih-Hang Anthony; Marr, Michael T.; Rosbash, Michael

    2011-01-01

    Cotranscriptional splicing, in which mRNA is spliced as it is being transcribed, is thought to be necessary for proper gene regulation of many genes in eukaryotic cells. While studies have shown that splicing takes place cotranscriptionally in yeast, in higher eukaryotes, where genes contain multiple introns with widespread alternative splicing, the question of whether cotranscriptional splicing is a general phenomenon remains. Khodor et al. investigated what fractions of genes are cotranscri...

  2. Epstein-Barr Virus SM Protein Functions as an Alternative Splicing Factor ▿

    OpenAIRE

    Verma, Dinesh; Swaminathan, Sankar

    2008-01-01

    Alternative splicing of RNA increases the coding potential of the genome and allows for additional regulatory control over gene expression. The full extent of alternative splicing remains to be defined but is likely to significantly expand the size of the human transcriptome. There are several examples of mammalian viruses regulating viral splicing or inhibiting cellular splicing in order to facilitate viral replication. Here, we describe a viral protein that induces alternative splicing of a...

  3. The CMS Muon System Alignment

    CERN Document Server

    Martinez Ruiz-Del-Arbol, P

    2009-01-01

    The alignment of the muon system of CMS is performed using different techniques: photogrammetry measurements, optical alignment and alignment with tracks. For track-based alignment, several methods are employed, ranging from a hit and impact point (HIP) algorithm and a procedure exploiting chamber overlaps to a global fit method based on the Millepede approach. For start-up alignment as long as available integrated luminosity is still significantly limiting the size of the muon sample from collisions, cosmic muon and beam halo signatures play a very strong role. During the last commissioning runs in 2008 the first aligned geometries have been produced and validated with data. The CMS offline computing infrastructure has been used in order to perform improved reconstructions. We present the computational aspects related to the calculation of alignment constants at the CERN Analysis Facility (CAF), the production and population of databases and the validation and performance in the official reconstruction. Also...

  4. Correction of tau mis-splicing caused by FTDP-17 MAPT mutations by spliceosome-mediated RNA trans-splicing

    OpenAIRE

    Rodriguez-Martin, Teresa; Anthony, Karen; Garcia-Blanco, Mariano A.; Mansfield, S. Gary; Anderton, Brian H.; Gallo, Jean-Marc

    2009-01-01

    Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) is caused by mutations in the MAPT gene, encoding the tau protein that accumulates in intraneuronal lesions in a number of neurodegenerative diseases. Several FTDP-17 mutations affect alternative splicing and result in excess exon 10 (E10) inclusion in tau mRNA. RNA reprogramming using spliceosome-mediated RNA trans-splicing (SMaRT) could be a method of choice to correct aberrant E10 splicing resulting from FTDP-17 mu...

  5. Beam alignment system

    International Nuclear Information System (INIS)

    A patent is claimed for the invention of a beam alignment system. The aim of the invention is the obtention of an accurate monitoring of the beam position and direction. It is of great interest in the nuclear industry. The invention can be applied in an infrared laser beam for welding operations. An auxiliar radiation source is incorporated to the device. The system's configuration allows a simultaneous and separated utilisation of two beams. The description and the design of the proposed system are provided

  6. Alignment in hadronic interactions

    CERN Document Server

    Wibig, T

    2000-01-01

    The alignment of the products of very high energy interactions seen in mountain altitude experiments is one of the most puzzling phenomena in cosmic ray physics for quite a long time. The observations of the Pamir and Chacaltaya emulsion chamber groups and by the Tien-Shan extensive air shower experiment, together with a very clear event seen in the Concorde French-Japanese experiment in the stratosphere, makes the experimental basis very substantial. In the present paper a novel possible explanation is put forward.

  7. BinPacker: Packing-Based De Novo Transcriptome Assembly from RNA-seq Data.

    Science.gov (United States)

    Liu, Juntao; Li, Guojun; Chang, Zheng; Yu, Ting; Liu, Bingqiang; McMullen, Rick; Chen, Pengyin; Huang, Xiuzhen

    2016-02-01

    High-throughput RNA-seq technology has provided an unprecedented opportunity to reveal the very complex structures of transcriptomes. However, it is an important and highly challenging task to assemble vast amounts of short RNA-seq reads into transcriptomes with alternative splicing isoforms. In this study, we present a novel de novo assembler, BinPacker, by modeling the transcriptome assembly problem as tracking a set of trajectories of items with their sizes representing coverage of their corresponding isoforms by solving a series of bin-packing problems. This approach, which subtly integrates coverage information into the procedure, has two exclusive features: 1) only splicing junctions are involved in the assembling procedure; 2) massive pell-mell reads are assembled seemingly by moving a comb along junction edges on a splicing graph. Being tested on both real and simulated RNA-seq datasets, it outperforms almost all the existing de novo assemblers on all the tested datasets, and even outperforms those ab initio assemblers on the real dog dataset. In addition, it runs substantially faster and requires less memory space than most of the assemblers. BinPacker is published under GNU GENERAL PUBLIC LICENSE and the source is available from: http://sourceforge.net/projects/transcriptomeassembly/files/BinPacker_1.0.tar.gz/download. Quick installation version is available from: http://sourceforge.net/projects/transcriptomeassembly/files/BinPacker_binary.tar.gz/download. PMID:26894997

  8. Network of evolutionary processors with splicing rules and permitting context.

    Science.gov (United States)

    Choudhary, Ashish; Krithivasan, Kamala

    2007-02-01

    In this paper we consider networks of evolutionary processors with splicing rules and permitting context (NEPPS) as language generating and computational devices. Such a network consists of several processors placed on the nodes of a virtual graph and are able to perform splicing (which is a biologically motivated operation) on the words present in that node, according to the splicing rules present there. Before applying the splicing operation on words, we check for the presence of certain symbols (permitting context) in the strings on which the rule is applied. Each node is associated with an input and output filter. When the filters are based on random context conditions, one gets the computational power of Turing machines with networks of size two. We also show how these networks can be used to solve NP-complete problems in linear time. PMID:17045388

  9. Synaptic signaling and aberrant RNA splicing in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Ryan M Smith

    2011-01-01

    Full Text Available Interactions between presynaptic and postsynaptic cellular adhesion molecules drive synapse maturation during development. These trans-synaptic interactions are regulated by alternative splicing of cellular adhesion molecule RNAs, which ultimately determines neurotransmitter phenotype. The diverse assortment of RNAs produced by alternative splicing generates countless protein isoforms necessary for guiding specialized cell-to-cell connectivity. Failure to generate the appropriate synaptic adhesion proteins is associated with disrupted glutamatergic and gamma-aminobutyric acid signaling, resulting in loss of activity-dependent neuronal plasticity, and risk for developmental disorders, including autism. While the majority of genetic mutations currently linked to autism are rare variants that change the protein coding sequence of synaptic candidate genes, regulatory polymorphisms affecting constitutive and alternative splicing have emerged as risk factors in numerous other diseases, accounting for an estimated 40-60% of general disease risk. Here, we review the relationship between aberrant RNA splicing of synapse-related genes and autism spectrum disorders.

  10. A general purification platform for toxic proteins based on intein trans-splicing.

    Science.gov (United States)

    Shi, Changhua; Tarimala, Anirudh; Meng, Qing; Wood, David W

    2014-11-01

    Many important functional proteins often exhibit toxicity when overexpressed in heterologous hosts. Unfortunately, this toxicity can complicate the production of these proteins in recombinant systems, which can slow their characterization. Although a number of engineered expression strains and plasmids have been developed to optimize toxic protein expression, many targets remain recalcitrant in these systems due to extreme toxicity to the expression host. In this work, we have developed a novel protein purification platform based on intein trans-splicing, with special relevance for proteins that are extremely toxic to recombinant host cells. The toxic protein is split into two inactive fragments, which are separately expressed in fusion to the segments of a split intein. The N-terminal intein segment is first immobilized onto an affinity column and washed, followed by addition of the C-terminal segment and purification of the complex. The assembled intein controllably splices to deliver the mature target protein, simultaneously releasing the purified target from the affinity column. To optimize this method, we generated a hybrid split intein consisting of the N-terminus of the Npu DnaE intein and the C-terminus of the Ssp DnaE intein. This hybrid intein tolerates a wider range of amino acids at the +2 site of the C-terminal splicing junction than the Npu intein alone. In the production of the highly toxic homing endonuclease I-TevI, the yield from the hybrid intein is 50 % higher than the native Npu DnaE intein, while the I-TevI protein purified from both inteins showed native activity. PMID:25296714

  11. All about alignment

    CERN Multimedia

    2006-01-01

    The ALICE absorbers, iron wall and superstructure have been installed with great precision. The ALICE front absorber, positioned in the centre of the detector, has been installed and aligned. Weighing more than 400 tonnes, the ALICE absorbers and the surrounding support structures have been installed and aligned with a precision of 1-2 mm, hardly an easy task but a very important one. The ALICE absorbers are made of three parts: the front absorber, a 35-tonne cone-shaped structure, and two small-angle absorbers, long straight cylinder sections weighing 18 and 40 tonnes. The three pieces lined up have a total length of about 17 m. In addition to these, ALICE technicians have installed a 300-tonne iron filter wall made of blocks that fit together like large Lego pieces and a surrounding metal support structure to hold the tracking and trigger chambers. The absorbers house the vacuum chamber and are also the reference surface for the positioning of the tracking and trigger chambers. For this reason, the ab...

  12. Computing alignment plots efficiently

    CERN Document Server

    Krusche, Peter

    2009-01-01

    Dot plots are a standard method for local comparison of biological sequences. In a dot plot, a substring to substring distance is computed for all pairs of fixed-size windows in the input strings. Commonly, the Hamming distance is used since it can be computed in linear time. However, the Hamming distance is a rather crude measure of string similarity, and using an alignment-based edit distance can greatly improve the sensitivity of the dot plot method. In this paper, we show how to compute alignment plots of the latter type efficiently. Given two strings of length m and n and a window size w, this problem consists in computing the edit distance between all pairs of substrings of length w, one from each input string. The problem can be solved by repeated application of the standard dynamic programming algorithm in time O(mnw^2). This paper gives an improved data-parallel algorithm, running in time $O(mnw/\\gamma/p)$ using vector operations that work on $\\gamma$ values in parallel and $p$ processors. We show ex...

  13. Abnormalities in Alternative Splicing of Apoptotic Genes and Cardiovascular Diseases

    OpenAIRE

    Zodwa Dlamini; Tshidino, Shonisani C.; Rodney Hull

    2015-01-01

    Apoptosis is required for normal heart development in the embryo, but has also been shown to be an important factor in the occurrence of heart disease. Alternative splicing of apoptotic genes is currently emerging as a diagnostic and therapeutic target for heart disease. This review addresses the involvement of abnormalities in alternative splicing of apoptotic genes in cardiac disorders including cardiomyopathy, myocardial ischemia and heart failure. Many pro-apoptotic members of the Bcl-2 f...

  14. Alternative Splicing of Type II Procollagen: IIB or not IIB?

    OpenAIRE

    McAlinden, Audrey

    2014-01-01

    Over two decades ago, two isoforms of the type II procollagen gene (COL2A1) were discovered. These isoforms, named IIA and IIB, are generated in a developmentally-regulated manner by alternative splicing of exon 2. Chondroprogenitor cells synthesize predominantly IIA isoforms (containing exon 2) while differentiated chondrocytes produce mainly IIB transcripts (devoid of exon 2). Importantly, this IIA-to-IIB alternative splicing switch occurs only during chondrogenesis. More recently, two othe...

  15. Diagnosis of trypanosomatid infections : targeting the spliced leader RNA

    OpenAIRE

    Gonzalez-Andrade, P.; M. Camara; Ilboudo, H.; Buheton, B.; Jamonneau, Vincent; Deborggraeve, S

    2014-01-01

    Trypanosomatids transcribe their genes in Large polycistronic clusters that are further processed into mature mRNA molecules by trans-splicing. During this maturation process, a conserved spliced leader RNA (SL-RNA) sequence of 39 bp is physically linked to the 5' end of the pre-mRNA molecules. Trypanosomatid infections cause a series of devastating diseases in man (sleeping sickness, leishmaniasis, Chagas disease) and animals (nagana, surra, dourine). Here, we investigated the SL-RNA molecul...

  16. RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing

    OpenAIRE

    Guo, Wei; Schafer, Sebastian; Greaser, Marion L.; Radke, Michael H.; Liss, Martin; Govindarajan, Thirupugal; Maatz, Henrike; Schulz, Herbert; Li, Shijun; Parrish, Amanda M.; Dauksaite, Vita; Vakeel, Padmanabhan; Klaassen, Sabine; Gerull, Brenda; Thierfelder, Ludwig

    2012-01-01

    Alternative splicing plays a major role in the adaptation of cardiac function exemplified by the isoform switch of titin, which adjusts ventricular filling. We previously identified a rat strain deficient in titin splicing. Using genetic mapping, we found a loss-of-function mutation in RBM20 as the underlying cause for the pathological titin isoform expression. Mutations in human RBM20 have previously been shown to cause dilated cardiomyopathy. We showed that the phenotype of Rbm20 deficient ...

  17. Functional roles of alternative splicing factors in human disease

    OpenAIRE

    Cieply, Benjamin; Carstens, Russ P.

    2015-01-01

    Alternative splicing (AS) is an important mechanism used to generate greater transcriptomic and proteomic diversity from a finite genome. Nearly all human gene transcripts are alternatively spliced and can produce protein isoforms with divergent and even antagonistic properties that impact cell functions. Many AS events are tightly regulated in a cell-type or tissue-specific manner, and at different developmental stages. AS is regulated by RNA-binding proteins, including cell- or tissue-speci...

  18. Altered PLP1 splicing causes hypomyelination of early myelinating structures

    OpenAIRE

    Kevelam, Sietske H.; Taube, Jennifer R.; van Spaendonk, Rosalina M. L.; Bertini, Enrico; Sperle, Karen; Tarnopolsky, Mark; Tonduti, Davide; Valente, Enza Maria; Travaglini, Lorena; Sistermans, Erik A.; Bernard, Geneviève; Catsman-Berrevoets, Coriene E.; van Karnebeek, Clara D M; Østergaard, John R.; Friederich, Richard L

    2015-01-01

    Objective The objective of this study was to investigate the genetic etiology of the X-linked disorder “Hypomyelination of Early Myelinating Structures” (HEMS). Methods We included 16 patients from 10 families diagnosed with HEMS by brain MRI criteria. Exome sequencing was used to search for causal mutations. In silico analysis of effects of the mutations on splicing and RNA folding was performed. In vitro gene splicing was examined in RNA from patients’ fibroblasts and an immortalized immatu...

  19. A Unique, Consistent Identifier for Alternatively Spliced Transcript Variants

    OpenAIRE

    Riva, Alberto; Pesole, Graziano

    2009-01-01

    Background As research into alternative splicing reveals the fundamental importance of this phenomenon in the genome expression of higher organisms, there is an increasing need for a standardized, consistent and unique identifier for alternatively spliced isoforms. Such an identifier would be useful to eliminate ambiguities in references to gene isoforms, and would allow for the reliable comparison of isoforms from different sources (e.g., known genes vs. computational predictions). Commonly ...

  20. Interrogation of alternative splicing events in duplicated genes during evolution

    OpenAIRE

    Chen Ting-Wen; Wu Timothy H; Ng Wailap V; Lin Wen-Chang

    2011-01-01

    Abstract Background Gene duplication provides resources for developing novel genes and new functions while retaining the original functions. In addition, alternative splicing could increase the complexity of expression at the transcriptome and proteome level without increasing the number of gene copy in the genome. Duplication and alternative splicing are thought to work together to provide the diverse functions or expression patterns for eukaryotes. Previously, it was believed that duplicati...

  1. Conditional alignment random fields for multiple motion sequence alignment.

    Science.gov (United States)

    Kim, Minyoung

    2013-11-01

    We consider the multiple time-series alignment problem, typically focusing on the task of synchronizing multiple motion videos of the same kind of human activity. Finding an optimal global alignment of multiple sequences is infeasible, while there have been several approximate solutions, including iterative pairwise warping algorithms and variants of hidden Markov models. In this paper, we propose a novel probabilistic model that represents the conditional densities of the latent target sequences which are aligned with the given observed sequences through the hidden alignment variables. By imposing certain constraints on the target sequences at the learning stage, we have a sensible model for multiple alignments that can be learned very efficiently by the EM algorithm. Compared to existing methods, our approach yields more accurate alignment while being more robust to local optima and initial configurations. We demonstrate its efficacy on both synthetic and real-world motion videos including facial emotions and human activities. PMID:24051737

  2. Purifying Selection on Exonic Splice Enhancers in Intronless Genes.

    Science.gov (United States)

    Savisaar, Rosina; Hurst, Laurence D

    2016-06-01

    Exonic splice enhancers (ESEs) are short nucleotide motifs, enriched near exon ends, that enhance the recognition of the splice site and thus promote splicing. Are intronless genes under selection to avoid these motifs so as not to attract the splicing machinery to an mRNA that should not be spliced, thereby preventing the production of an aberrant transcript? Consistent with this possibility, we find that ESEs in putative recent retrocopies are at a higher density and evolving faster than those in other intronless genes, suggesting that they are being lost. Moreover, intronless genes are less dense in putative ESEs than intron-containing ones. However, this latter difference is likely due to the skewed base composition of intronless sequences, a skew that is in line with the general GC richness of few exon genes. Indeed, after controlling for such biases, we find that both intronless and intron-containing genes are denser in ESEs than expected by chance. Importantly, nucleotide-controlled analysis of evolutionary rates at synonymous sites in ESEs indicates that the ESEs in intronless genes are under purifying selection in both human and mouse. We conclude that on the loss of introns, some but not all, ESE motifs are lost, the remainder having functions beyond a role in splice promotion. These results have implications for the design of intronless transgenes and for understanding the causes of selection on synonymous sites. PMID:26802218

  3. The functional modulation of epigenetic regulators by alternative splicing

    Directory of Open Access Journals (Sweden)

    Martínez-Balbás Marian

    2007-07-01

    Full Text Available Abstract Background Epigenetic regulators (histone acetyltransferases, methyltransferases, chromatin-remodelling enzymes, etc play a fundamental role in the control of gene expression by modifying the local state of chromatin. However, due to their recent discovery, little is yet known about their own regulation. This paper addresses this point, focusing on alternative splicing regulation, a mechanism already known to play an important role in other protein families, e.g. transcription factors, membrane receptors, etc. Results To this end, we compiled the data available on the presence/absence of alternative splicing for a set of 160 different epigenetic regulators, taking advantage of the relatively large amount of unexplored data on alternative splicing available in public databases. We found that 49 % (70 % in human of these genes express more than one transcript. We then studied their alternative splicing patterns, focusing on those changes affecting the enzyme's domain composition. In general, we found that these sequence changes correspond to different mechanisms, either repressing the enzyme's function (e.g. by creating dominant-negative inhibitors of the functional isoform or creating isoforms with new functions. Conclusion We conclude that alternative splicing of epigenetic regulators can be an important tool for the function modulation of these enzymes. Considering that the latter control the transcriptional state of large sets of genes, we propose that epigenetic regulation of gene expression is itself strongly regulated by alternative splicing.

  4. SF3B1 Association with Chromatin Determines Splicing Outcomes

    Directory of Open Access Journals (Sweden)

    Nir Kfir

    2015-04-01

    Full Text Available Much remains unknown concerning the mechanism by which the splicing machinery pinpoints short exons within intronic sequences and how splicing factors are directed to their pre-mRNA targets. One probable explanation lies in differences in chromatin organization between exons and introns. Proteomic, co-immunoprecipitation, and sedimentation analyses described here indicate that SF3B1, an essential splicing component of the U2 snRNP complex, is strongly associated with nucleosomes. ChIP-seq and RNA-seq analyses reveal that SF3B1 specifically binds nucleosomes located at exonic positions. SF3B1 binding is enriched at nucleosomes positioned over short exons flanked by long introns that are also characterized by differential GC content between exons and introns. Disruption of SF3B1 binding to such nucleosomes affects splicing of these exons similarly to SF3B1 knockdown. Our findings suggest that the association of SF3B1 with nucleosomes is functionally important for splice-site recognition and that SF3B1 conveys splicing-relevant information embedded in chromatin structure.

  5. Abnormalities in Alternative Splicing of Apoptotic Genes and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Zodwa Dlamini

    2015-11-01

    Full Text Available Apoptosis is required for normal heart development in the embryo, but has also been shown to be an important factor in the occurrence of heart disease. Alternative splicing of apoptotic genes is currently emerging as a diagnostic and therapeutic target for heart disease. This review addresses the involvement of abnormalities in alternative splicing of apoptotic genes in cardiac disorders including cardiomyopathy, myocardial ischemia and heart failure. Many pro-apoptotic members of the Bcl-2 family have alternatively spliced isoforms that lack important active domains. These isoforms can play a negative regulatory role by binding to and inhibiting the pro-apoptotic forms. Alternative splicing is observed to be increased in various cardiovascular diseases with the level of alternate transcripts increasing elevated in diseased hearts compared to healthy subjects. In many cases these isoforms appear to be the underlying cause of the disease, while in others they may be induced in response to cardiovascular pathologies. Regardless of this, the detection of alternate splicing events in the heart can serve as useful diagnostic or prognostic tools, while those splicing events that seem to play a causative role in cardiovascular disease make attractive future drug targets.

  6. Tafazzin splice variants and mutations in Barth syndrome.

    Science.gov (United States)

    Kirwin, Susan M; Manolakos, Athena; Barnett, Sarah Swain; Gonzalez, Iris L

    2014-01-01

    Barth syndrome is caused by mutations in the TAZ (tafazzin) gene on human chromosome Xq28. The human tafazzin gene produces four major mRNA splice variants; two of which have been shown to be functional (TAZ lacking exon 5 and full-length) in complementation studies with yeast and Drosophila. This study characterizes the multiple alternative splice variants of TAZ mRNA and their proportions in blood samples from a cohort of individuals with Barth syndrome (BTHS). Because it has been reported that collection and processing methods can affect the expression of various genes, we tested and chose a stabilizing medium for collecting, shipping and processing of the blood samples of these individuals. In both healthy controls and in BTHS individuals, we found a greater variety of alternatively spliced forms than previously described, with a sizeable proportion of minor splice variants besides the four dominant isoforms. Individuals with certain exonic and intronic splice mutations produce additional mutant mRNAs that could be translated into two or more proteins with different amino acid substitutions in a single individual. A fraction of the minor splice variants is predicted to be non-productive. PMID:24342716

  7. Modulation of Splicing by Single-Stranded Silencing RNAs.

    Science.gov (United States)

    Liu, Jing; Hu, Jiaxin; Hicks, Jessica A; Prakash, Thazha P; Corey, David R

    2015-06-01

    Single-stranded silencing RNAs (ss-siRNAs) are chemically modified single-stranded oligonucleotides that can function through the cellular RNA interference (RNAi) machinery to modulate gene expression. Because their invention is recent, few studies have appeared describing their use and the potential of ss-siRNAs as a platform for controlling gene expression remains largely unknown. Using oligonucleotides to modulate splicing is an important area for therapeutic development and we tested the hypothesis that ss-siRNAs targeting splice sites might also be capable of directing increased production of therapeutically promising protein isoforms. Here we observe that ss-siRNAs alter splicing of dystrophin. Altered splicing requires a seed sequence complementarity to the target and expression of the RNAi factor argonaute 2. These results demonstrate that ss-siRNAs can be used to modulate splicing, providing another option for therapeutic development programs that aim to increase production of key protein isoforms. Splicing is a classical nuclear process and our data showing that it can be modulated through the action of RNA and RNAi factors offers further evidence that RNAi can take place in mammalian cell nuclei. PMID:25757055

  8. Width of gene expression profile drives alternative splicing.

    Directory of Open Access Journals (Sweden)

    Daniel Wegmann

    Full Text Available Alternative splicing generates an enormous amount of functional and proteomic diversity in metazoan organisms. This process is probably central to the macromolecular and cellular complexity of higher eukaryotes. While most studies have focused on the molecular mechanism triggering and controlling alternative splicing, as well as on its incidence in different species, its maintenance and evolution within populations has been little investigated. Here, we propose to address these questions by comparing the structural characteristics as well as the functional and transcriptional profiles of genes with monomorphic or polymorphic splicing, referred to as MS and PS genes, respectively. We find that MS and PS genes differ particularly in the number of tissues and cell types where they are expressed.We find a striking deficit of PS genes on the sex chromosomes, particularly on the Y chromosome where it is shown not to be due to the observed lower breadth of expression of genes on that chromosome. The development of a simple model of evolution of cis-regulated alternative splicing leads to predictions in agreement with these observations. It further predicts the conditions for the emergence and the maintenance of cis-regulated alternative splicing, which are both favored by the tissue specific expression of splicing variants. We finally propose that the width of the gene expression profile is an essential factor for the acquisition of new transcript isoforms that could later be maintained by a new form of balancing selection.

  9. Assembly of microsystems for optical and fluidic applications

    OpenAIRE

    Haasl, Sjoerd

    2005-01-01

    This thesis addresses assembly issues encountered in optical and fluidic microsystem applications. In optics, the first subject concerns the active alignment of components in optical fibersystems. A solution for reducing the cost of optical component assembly while retaining submicron accuracy is to integrate the alignment mechanism onto the optical substrate. A polymer V-shaped actuator is presented that can carry the weight of the large components - on a micromechanical scale - and that can...

  10. Two Influential Primate Classifications Logically Aligned

    Science.gov (United States)

    Franz, Nico M.; Pier, Naomi M.; Reeder, Deeann M.; Chen, Mingmin; Yu, Shizhuo; Kianmajd, Parisa; Bowers, Shawn; Ludäscher, Bertram

    2016-01-01

    Classifications and phylogenies of perceived natural entities change in the light of new evidence. Taxonomic changes, translated into Code-compliant names, frequently lead to name:meaning dissociations across succeeding treatments. Classification standards such as the Mammal Species of the World (MSW) may experience significant levels of taxonomic change from one edition to the next, with potential costs to long-term, large-scale information integration. This circumstance challenges the biodiversity and phylogenetic data communities to express taxonomic congruence and incongruence in ways that both humans and machines can process, that is, to logically represent taxonomic alignments across multiple classifications. We demonstrate that such alignments are feasible for two classifications of primates corresponding to the second and third MSW editions. Our approach has three main components: (i) use of taxonomic concept labels, that is name sec. author (where sec. means according to), to assemble each concept hierarchy separately via parent/child relationships; (ii) articulation of select concepts across the two hierarchies with user-provided Region Connection Calculus (RCC-5) relationships; and (iii) the use of an Answer Set Programming toolkit to infer and visualize logically consistent alignments of these input constraints. Our use case entails the Primates sec. Groves (1993; MSW2–317 taxonomic concepts; 233 at the species level) and Primates sec. Groves (2005; MSW3–483 taxonomic concepts; 376 at the species level). Using 402 RCC-5 input articulations, the reasoning process yields a single, consistent alignment and 153,111 Maximally Informative Relations that constitute a comprehensive meaning resolution map for every concept pair in the Primates sec. MSW2/MSW3. The complete alignment, and various partitions thereof, facilitate quantitative analyses of name:meaning dissociation, revealing that nearly one in three taxonomic names are not reliable across

  11. Two Influential Primate Classifications Logically Aligned.

    Science.gov (United States)

    Franz, Nico M; Pier, Naomi M; Reeder, Deeann M; Chen, Mingmin; Yu, Shizhuo; Kianmajd, Parisa; Bowers, Shawn; Ludäscher, Bertram

    2016-07-01

    Classifications and phylogenies of perceived natural entities change in the light of new evidence. Taxonomic changes, translated into Code-compliant names, frequently lead to name:meaning dissociations across succeeding treatments. Classification standards such as the Mammal Species of the World (MSW) may experience significant levels of taxonomic change from one edition to the next, with potential costs to long-term, large-scale information integration. This circumstance challenges the biodiversity and phylogenetic data communities to express taxonomic congruence and incongruence in ways that both humans and machines can process, that is, to logically represent taxonomic alignments across multiple classifications. We demonstrate that such alignments are feasible for two classifications of primates corresponding to the second and third MSW editions. Our approach has three main components: (i) use of taxonomic concept labels, that is name sec. author (where sec. means according to), to assemble each concept hierarchy separately via parent/child relationships; (ii) articulation of select concepts across the two hierarchies with user-provided Region Connection Calculus (RCC-5) relationships; and (iii) the use of an Answer Set Programming toolkit to infer and visualize logically consistent alignments of these input constraints. Our use case entails the Primates sec. Groves (1993; MSW2-317 taxonomic concepts; 233 at the species level) and Primates sec. Groves (2005; MSW3-483 taxonomic concepts; 376 at the species level). Using 402 RCC-5 input articulations, the reasoning process yields a single, consistent alignment and 153,111 Maximally Informative Relations that constitute a comprehensive meaning resolution map for every concept pair in the Primates sec. MSW2/MSW3. The complete alignment, and various partitions thereof, facilitate quantitative analyses of name:meaning dissociation, revealing that nearly one in three taxonomic names are not reliable across treatments

  12. Identification of cis-Acting Elements and Splicing Factors Involved in the Regulation of BIM Pre-mRNA Splicing

    OpenAIRE

    Juan, Wen Chun; Roca, Xavier; Ong, S. Tiong

    2014-01-01

    Aberrant changes in the expression of the pro-apoptotic protein, BCL-2-like 11 (BIM), can result in either impaired or excessive apoptosis, which can contribute to tumorigenesis and degenerative disorders, respectively. Altering BIM pre-mRNA splicing is an attractive approach to modulate apoptosis because BIM activity is partly determined by the alternative splicing of exons 3 or 4, whereby exon 3-containing transcripts are not apoptotic. Here we identified several cis-acting elements and spl...

  13. Dust alignment in astrophysical environments

    Science.gov (United States)

    Lazarian, Alex; Thiem Hoang, Chi

    Dust is known to be aligned in interstellar medium and the arising polarization is extensively used to trace magnetic fields. What process aligns dust grains was one of the most long-standing problems of astrophysics in spite of the persistent efforts to solve it. For years the Davis-Greenstein paramagnetic alignment was the primary candidate for explaining grain alignment. However, the situation is different now and the most promising mechanism is associated with radiative torques (RATs) acting on irregular grains. I shall present the analytical theory of RAT alignment, discuss the observational tests that support this theory. I shall also discuss in what situations we expect to see the dominance of paramagnetic alignment.

  14. Nova laser alignment control system

    International Nuclear Information System (INIS)

    Alignment of the Nova laser requires control of hundreds of optical components in the ten beam paths. Extensive application of computer technology makes daily alignment practical. The control system is designed in a manner which provides both centralized and local manual operator controls integrated with automatic closed loop alignment. Menudriven operator consoles using high resolution color graphics displays overlaid with transport touch panels allow laser personnel to interact efficiently with the computer system. Automatic alignment is accomplished by using image analysis techniques to determine beam references points from video images acquired along the laser chain. A major goal of the design is to contribute substantially to rapid experimental turnaround and consistent alignment results. This paper describes the computer-based control structure and the software methods developed for aligning this large laser system

  15. A 5' splice site enhances the recruitment of basal transcription initiation factors in vivo

    DEFF Research Database (Denmark)

    Damgaard, Christian Kroun; Kahns, Søren; Lykke-Andersen, Søren;

    2008-01-01

    promoter docking of transcription initiation factors TFIID, TFIIB, and TFIIH on a gene containing a functional 5′ splice site. In addition to their promoter association, the TFIID and TFIIH components, TBP and p89, are specifically recruited to the 5′ splice site region. Our data suggest a model in which a......Transcription and pre-mRNA splicing are interdependent events. Although mechanisms governing the effects of transcription on splicing are becoming increasingly clear, the means by which splicing affects transcription remain elusive. Using cell lines stably expressing HIV-1 or β-globin m......RNAs, harboring wild-type or various 5′ splice site mutations, we demonstrate a strong positive correlation between splicing efficiency and transcription activity. Interestingly, a 5′ splice site can stimulate transcription even in the absence of splicing. Chromatin immunoprecipitation experiments show enhanced...

  16. U4 small nuclear RNA dissociates from a yeast spliceosome and does not participate in the subsequent splicing reaction.

    OpenAIRE

    Yean, S L; Lin, R J

    1991-01-01

    U4 and U6 small nuclear RNAs reside in a single ribonucleoprotein particle, and both are required for pre-mRNA splicing. The U4/U6 and U5 small nuclear ribonucleoproteins join U1 and U2 on the pre-mRNA during spliceosome assembly. Binding of U4 is then destabilized prior to or concomitant with the 5' cleavage-ligation. In order to test the role of U4 RNA, we isolated a functional spliceosome by using extracts prepared from yeast cells carrying a temperature-sensitive allele of prp2 (rna2). Th...

  17. Probing Nucleic Acid Interactions and Pre-mRNA Splicing by Förster Resonance Energy Transfer (FRET Microscopy

    Directory of Open Access Journals (Sweden)

    David Staněk

    2012-11-01

    Full Text Available Förster resonance energy transfer (FRET microscopy is a powerful technique routinely used to monitor interactions between biomolecules. Here, we focus on the techniques that are used for investigating the structure and interactions of nucleic acids (NAs. We present a brief overview of the most commonly used FRET microscopy techniques, their advantages and drawbacks. We list experimental approaches recently used for either in vitro or in vivo studies. Next, we summarize how FRET contributed to the understanding of pre-mRNA splicing and spliceosome assembly.

  18. Structural Studies of RNA Helicases Involved in Eukaryotic Pre-mRNA Splicing, Ribosome Biogenesis, and Translation Initiation

    DEFF Research Database (Denmark)

    He, Yangzi

    Ribonucleic acids (RNAs) take centre stage in gene expression. In eukaryotes, most RNAs are transcribed as precursors, and these precursors are co- or post-transcriptionally processed and assemble with particular proteins to form ribonucleoproteins (RNPs). Mature RNPs participate in various gene...... expression events, are then subject to recycling, disassembly or degradation. RNA helicases are highly conserved enzymes that use ATP to bind or remodel RNA or RNPs. They function in nearly every aspect of eukaryotic RNA metabolism. The spliceosome catalyzes pre-mRNAs splicing, which removes introns and...

  19. The splicing activator DAZAP1 integrates splicing control into MEK/Erk-regulated cell proliferation and migration

    Science.gov (United States)

    Choudhury, Rajarshi; Roy, Sreerupa Ghose; Tsai, Yihsuan S.; Tripathy, Ashutosh; Graves, Lee M.; Wang, Zefeng

    2014-01-01

    Alternative splicing of pre-messenger RNA (mRNA) is a critical stage of gene regulation in response to environmental stimuli. Here we show that DAZAP1, an RNA-binding protein involved in mammalian development and spermatogenesis, promotes inclusion of weak exons through specific recognition of diverse cis-elements. The carboxy-terminal proline-rich domain of DAZAP1 interacts with and neutralizes general splicing inhibitors, and is sufficient to activate splicing when recruited to pre-mRNA. This domain is phosphorylated by the MEK/Erk (extracellular signal-regulated protein kinase) pathway and this modification is essential for the splicing regulatory activity and the nuclear/cytoplasmic translocation of DAZAP1. Using mRNA-seq, we identify endogenous splicing events regulated by DAZAP1, many of which are involved in maintaining cell growth. Knockdown or over-expression of DAZAP1 causes a cell proliferation defect. Taken together, these studies reveal a molecular mechanism that integrates splicing control into MEK/Erk-regulated cell proliferation.

  20. Catalyzing alignment processes

    DEFF Research Database (Denmark)

    Lauridsen, Erik Hagelskjær; Jørgensen, Ulrik

    2004-01-01

    time and in combination with other social processes establish more aligned and standardized environmental performance between countries. However, examples of the introduction of environmental management suggests that EMS’ only plays a minor role in developing the actual environmental objectives......This paper describes how environmental management systems (EMS) spur the circulation of processes that support the constitution of environmental issues as specific environ¬mental objects and objectives. EMS catalyzes alignmentprocesses that produce coherence among the different elements involved...... they are implemented in and how the changing context is reflected in the environmental objectives that are established and prioritised. Our argument is, that the ability of the standard to achieve an impact is dependant on the constitution of ’coherent’ environmental issues in the context, where the management system...

  1. On aligning trees

    CERN Document Server

    Calder, J

    1997-01-01

    The increasing availability of corpora annotated for linguistic structure prompts the question: if we have the same texts, annotated for phrase structure under two different schemes, to what extent do the annotations agree on structuring within the text? We suggest the term tree alignment to indicate the situation where two markup schemes choose to bracket off the same text elements. We propose a general method for determining agreement between two analyses. We then describe an efficient implementation, which is also modular in that the core of the implementation can be reused regardless of the format of markup used in the corpora. The output of the implementation on the Susanne and Penn treebank corpora is discussed.

  2. GraphAlignment: Bayesian pairwise alignment of biological networks

    Directory of Open Access Journals (Sweden)

    Kolář Michal

    2012-11-01

    Full Text Available Abstract Background With increased experimental availability and accuracy of bio-molecular networks, tools for their comparative and evolutionary analysis are needed. A key component for such studies is the alignment of networks. Results We introduce the Bioconductor package GraphAlignment for pairwise alignment of bio-molecular networks. The alignment incorporates information both from network vertices and network edges and is based on an explicit evolutionary model, allowing inference of all scoring parameters directly from empirical data. We compare the performance of our algorithm to an alternative algorithm, Græmlin 2.0. On simulated data, GraphAlignment outperforms Græmlin 2.0 in several benchmarks except for computational complexity. When there is little or no noise in the data, GraphAlignment is slower than Græmlin 2.0. It is faster than Græmlin 2.0 when processing noisy data containing spurious vertex associations. Its typical case complexity grows approximately as O(N2.6. On empirical bacterial protein-protein interaction networks (PIN and gene co-expression networks, GraphAlignment outperforms Græmlin 2.0 with respect to coverage and specificity, albeit by a small margin. On large eukaryotic PIN, Græmlin 2.0 outperforms GraphAlignment. Conclusions The GraphAlignment algorithm is robust to spurious vertex associations, correctly resolves paralogs, and shows very good performance in identification of homologous vertices defined by high vertex and/or interaction similarity. The simplicity and generality of GraphAlignment edge scoring makes the algorithm an appropriate choice for global alignment of networks.

  3. Wettability gradient-induced alignment of peptide nanotubes as templates for biosensing applications

    OpenAIRE

    Almohammed, Sawsan; Oladapo, Sarah O.; Ryan, Kate; Kholkin, Andrei L.; Rice, James H.; Rodriguez, Brian J.

    2016-01-01

    Self-assembled diphenylalanine (FF) peptide nanotubes (PNTs) have attracted significant attention due to their well-ordered supramolecular structure and wide range of functional capabilities that may enable potential nanobiotechnology applications. However, self-assembled PNTs are generally inhomogeneous at the macroscale, which has limited their potential use. Reproducibly controlling the assembly and alignment of PNTs is therefore critical to enable the widespread use of PNTs, e.g., in sens...

  4. MaxAlign: maximizing usable data in an alignment

    DEFF Research Database (Denmark)

    Oliveira, Rodrigo Gouveia; Sackett, Peter Wad; Pedersen, Anders Gorm

    2007-01-01

    of gaps in any given sequence does not seem to disturb the phylogenetic estimates of other sequences. The MaxAlign web-server is freely available online at http://www.cbs.dtu.dk/services/MaxAlign where supplementary information can also be found. The program is also freely available as a Perl stand...

  5. Pyro-Align: Sample-Align based Multiple Alignment system for Pyrosequencing Reads of Large Number

    CERN Document Server

    Saeed, Fahad

    2009-01-01

    Pyro-Align is a multiple alignment program specifically designed for pyrosequencing reads of huge number. Multiple sequence alignment is shown to be NP-hard and heuristics are designed for approximate solutions. Multiple sequence alignment of pyrosequenceing reads is complex mainly because of 2 factors. One being the huge number of reads, making the use of traditional heuristics,that scale very poorly for large number, unsuitable. The second reason is that the alignment cannot be performed arbitrarily, because the position of the reads with respect to the original genome is important and has to be taken into account.In this report we present a short description of the multiple alignment system for pyrosequencing reads.

  6. Capillary Self-Alignment of Microchips on Soft Substrates

    Directory of Open Access Journals (Sweden)

    Bo Chang

    2016-03-01

    Full Text Available Soft micro devices and stretchable electronics have attracted great interest for their potential applications in sensory skins and wearable bio-integrated devices. One of the most important steps in building printed circuits is the alignment of assembled micro objects. Previously, the capillary self-alignment of microchips driven by surface tension effects has been shown to be able to achieve high-throughput and high-precision in the integration of micro parts on rigid hydrophilic/superhydrophobic patterned surfaces. In this paper, the self-alignment of microchips on a patterned soft and stretchable substrate, which consists of hydrophilic pads surrounded by a superhydrophobic polydimethylsiloxane (PDMS background, is demonstrated for the first time. A simple process has been developed for making superhydrophobic soft surface by replicating nanostructures of black silicon onto a PDMS surface. Different kinds of PDMS have been investigated, and the parameters for fabricating superhydrophobic PDMS have been optimized. A self-alignment strategy has been proposed that can result in reliable self-alignment on a soft PDMS substrate. Our results show that capillary self-alignment has great potential for building soft printed circuits.

  7. mRNA 5′-leader trans-splicing in the chordates

    OpenAIRE

    Vandenberghe, Amanda E.; Meedel, Thomas H.; Hastings, Kenneth E.M.

    2001-01-01

    We report the discovery of mRNA 5′-leader trans-splicing (SL trans-splicing) in the chordates. In the ascidian protochordate Ciona intestinalis, the mRNAs of at least seven genes undergo trans-splicing of a 16-nucleotide 5′-leader apparently derived from a 46-nucleotide RNA that shares features with previously characterized splice donor SL RNAs. SL trans-splicing was known previously to occur in several protist and metazoan phyla, however, this is the first report of SL trans-splicing within ...

  8. Leveraging intrinsic chain anisotropy to align coil-coil block copolymers with magnetic fields

    Science.gov (United States)

    Rokhlenko, Yekaterina; Zhang, Kai; Gopinadhan, Manesh; Larson, Steve; Majewski, Pawel; Yager, Kevin; Gopalan, Padma; O'Hern, Corey; Osuji, Chinedum

    Magnetic field alignment of block copolymers (BCPs) has typically relied on the presence of liquid crystalline or crystalline assemblies to provide sufficient magnetic anisotropy to drive alignment. Recent experiments however show that alignment is also possible in simple coil-coil BCPs. In particular, alignment of lamellae was observed in poly(styrene-b-4-vinylpyridine) (PS-P4VP) on cooling across the order-disorder transition at field strengths as low as 1 T, with alignment improving markedly with increasing field strength and decreasing cooling rate. Here we discuss the intrinsic chain anisotropy which drives the observed alignment, and its display as a net microdomain anisotropy due to chain tethering at the block interface. We use in-situ X-ray scattering to study the phase behavior and temperature-, time-, and field- dependent dynamics of magnetic alignment in coil-coil BCPs, highlighting the important roles of chain anisotropy and grain size in alignment. For the right combination of field strength and grain size, we can leverage intrinsic chain anisotropy to magnetically direct self-assembly in other coil-coil systems, including cylinder-forming poly(styrene-b-dimethylsiloxane). Field alignment of PS-P4VP with PEO and other blends provides a route to form functional materials such as nanoporous films and ion conducting polymers.

  9. Lexical alignment in triadic communication

    Directory of Open Access Journals (Sweden)

    Anouschka eFoltz

    2015-02-01

    Full Text Available Lexical alignment refers to the adoption of one’s interlocutor’s lexical items. Accounts of the mechanisms underlying such lexical alignment differ (among other aspects in the role assigned to addressee-centered behavior. In this study, we used a triadic communicative situation to test which factors may modulate the extent to which participants’ lexical alignment reflects addressee-centered behavior. Pairs of naïve participants played a picture matching game and received information about the order in which pictures were to be matched from a voice over headphones. On critical trials, participants did or did not hear a name for the picture to be matched next over headphones. Importantly, when the voice over headphones provided a name, it did not match the name that the interlocutor had previously used to describe the object. Participants overwhelmingly used the word that the voice over headphones provided. This result points to non-addressee-centered behavior and is discussed in terms of disrupting alignment with the interlocutor as well as in terms of establishing alignment with the voice over headphones. In addition, the type of picture (line drawing vs. tangram shape independently modulated lexical alignment, such that participants showed more lexical alignment to their interlocutor for (more ambiguous tangram shapes compared to line drawings. Overall, the results point to a rather large role for non-addressee-centered behavior during lexical alignment.

  10. Comparing de novo assemblers for 454 transcriptome data

    Directory of Open Access Journals (Sweden)

    Blaxter Mark L

    2010-10-01

    Full Text Available Abstract Background Roche 454 pyrosequencing has become a method of choice for generating transcriptome data from non-model organisms. Once the tens to hundreds of thousands of short (250-450 base reads have been produced, it is important to correctly assemble these to estimate the sequence of all the transcripts. Most transcriptome assembly projects use only one program for assembling 454 pyrosequencing reads, but there is no evidence that the programs used to date are optimal. We have carried out a systematic comparison of five assemblers (CAP3, MIRA, Newbler, SeqMan and CLC to establish best practices for transcriptome assemblies, using a new dataset from the parasitic nematode Litomosoides sigmodontis. Results Although no single assembler performed best on all our criteria, Newbler 2.5 gave longer contigs, better alignments to some reference sequences, and was fast and easy to use. SeqMan assemblies performed best on the criterion of recapitulating known transcripts, and had more novel sequence than the other assemblers, but generated an excess of small, redundant contigs. The remaining assemblers all performed almost as well, with the exception of Newbler 2.3 (the version currently used by most assembly projects, which generated assemblies that had significantly lower total length. As different assemblers use different underlying algorithms to generate contigs, we also explored merging of assemblies and found that the merged datasets not only aligned better to reference sequences than individual assemblies, but were also more consistent in the number and size of contigs. Conclusions Transcriptome assemblies are smaller than genome assemblies and thus should be more computationally tractable, but are often harder because individual contigs can have highly variable read coverage. Comparing single assemblers, Newbler 2.5 performed best on our trial data set, but other assemblers were closely comparable. Combining differently optimal assemblies

  11. Oncogenes and RNA splicing of human tumor viruses.

    Science.gov (United States)

    Ajiro, Masahiko; Zheng, Zhi-Ming

    2014-09-01

    Approximately 10.8% of human cancers are associated with infection by an oncogenic virus. These viruses include human papillomavirus (HPV), Epstein-Barr virus (EBV), Merkel cell polyomavirus (MCV), human T-cell leukemia virus 1 (HTLV-1), Kaposi's sarcoma-associated herpesvirus (KSHV), hepatitis C virus (HCV) and hepatitis B virus (HBV). These oncogenic viruses, with the exception of HCV, require the host RNA splicing machinery in order to exercise their oncogenic activities, a strategy that allows the viruses to efficiently export and stabilize viral RNA and to produce spliced RNA isoforms from a bicistronic or polycistronic RNA transcript for efficient protein translation. Infection with a tumor virus affects the expression of host genes, including host RNA splicing factors, which play a key role in regulating viral RNA splicing of oncogene transcripts. A current prospective focus is to explore how alternative RNA splicing and the expression of viral oncogenes take place in a cell- or tissue-specific manner in virus-induced human carcinogenesis. PMID:26038756

  12. Two new splice variants in porcine PPARGC1A

    Directory of Open Access Journals (Sweden)

    Peelman Luc J

    2008-12-01

    Full Text Available Abstract Background Peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A is a coactivator with a vital and central role in fat and energy metabolism. It is considered to be a candidate gene for meat quality in pigs and is involved in the development of obesity and diabetes in humans. How its many functions are regulated, is however still largely unclear. Therefore a transcription profile of PPARGC1A in 32 tissues and 4 embryonic developmental stages in the pig was constructed by screening its cDNA for possible splice variants with exon-spanning primers. Findings This led to the discovery of 2 new splice variants in the pig, which were subsequently also detected in human tissues. In these variants, exon 8 was either completely or partly (the last 66 bp were conserved spliced out, potentially coding for a much shorter protein of respectively 337 and 359 amino acids (aa, of which the first 291 aa would be the same compared to the complete protein (796 aa. Conclusion Considering the functional domains of the PPARGC1A protein, it is very likely these splice variants considerably affect the function of the protein and alternative splicing could be one of the mechanisms by which the diverse functions of PPARGC1A are regulated.

  13. LHC dipole magnet splice resistance from SM18 data mining

    International Nuclear Information System (INIS)

    The splice incident which happened during commissioning of the LHC on the 19. of September 2008 caused damage to several magnets and adjacent equipment. This raised not only the question of how it happened, but also about the state of all other splices. The inter magnet splices were immediately studied and new measurements recorded, but the internal magnet splices were still a concern. At the Chamonix meeting in January 2009, the CERN management decided to create a working group to analyse quench data of the magnet acceptance tests in an attempt to find indications for bad splices in the main dipoles. This resulted in a data-mining project that took about one year to complete. This presentation describes how the data was stored, extracted and analysed reusing existing 'LabVIEW' based tools, during this campaign more than 23000 magnet performance measurements were scrutinized. We also present the encountered difficulties and the importance of combining measured data with operator notes in the logbook. (authors)

  14. BRR2a Affects Flowering Time via FLC Splicing.

    Science.gov (United States)

    Mahrez, Walid; Shin, Juhyun; Muñoz-Viana, Rafael; Figueiredo, Duarte D; Trejo-Arellano, Minerva S; Exner, Vivien; Siretskiy, Alexey; Gruissem, Wilhelm; Köhler, Claudia; Hennig, Lars

    2016-04-01

    Several pathways control time to flowering in Arabidopsis thaliana through transcriptional and posttranscriptional gene regulation. In recent years, mRNA processing has gained interest as a critical regulator of flowering time control in plants. However, the molecular mechanisms linking RNA splicing to flowering time are not well understood. In a screen for Arabidopsis early flowering mutants we identified an allele of BRR2a. BRR2 proteins are components of the spliceosome and highly conserved in eukaryotes. Arabidopsis BRR2a is ubiquitously expressed in all analyzed tissues and involved in the processing of flowering time gene transcripts, most notably FLC. A missense mutation of threonine 895 in BRR2a caused defects in FLC splicing and greatly reduced FLC transcript levels. Reduced FLC expression increased transcription of FT and SOC1 leading to early flowering in both short and long days. Genome-wide experiments established that only a small set of introns was not correctly spliced in the brr2a mutant. Compared to control introns, retained introns were often shorter and GC-poor, had low H3K4me1 and CG methylation levels, and were often derived from genes with a high-H3K27me3-low-H3K36me3 signature. We propose that BRR2a is specifically needed for efficient splicing of a subset of introns characterized by a combination of factors including intron size, sequence and chromatin, and that FLC is most sensitive to splicing defects. PMID:27100965

  15. Alignments in the nobelium isotopes

    Institute of Scientific and Technical Information of China (English)

    ZHENG Shi-Zie; XU Fu-Rong; YUAN Cen-Xi; QI Chong

    2009-01-01

    Total-Routhian-Surface calculations have been performed to investigate the deformation and align-ment properties of the No isotopes. It is found that normal deformed and superdeformed states in these nuclei can coexist at low excitation energies. In neutron-deficient No isotopes, the superdeformed shapes can even become the ground states. Moreover, we plotted the kinematic moments of inertia of the No isotopes, which follow very nicely available experimental data. It is noted that, as the rotational frequency increases, align-ments develop at hω=0.2-0.3 MeV. Our calculations show that the occupation of the vj orbital plays an important role in the alignments of the No isotopes.

  16. The CMS Silicon Tracker Alignment

    CERN Document Server

    Castello, R

    2008-01-01

    The alignment of the Strip and Pixel Tracker of the Compact Muon Solenoid experiment, with its large number of independent silicon sensors and its excellent spatial resolution, is a complex and challenging task. Besides high precision mounting, survey measurements and the Laser Alignment System, track-based alignment is needed to reach the envisaged precision.\\\\ Three different algorithms for track-based alignment were successfully tested on a sample of cosmic-ray data collected at the Tracker Integration Facility, where 15\\% of the Tracker was tested. These results, together with those coming from the CMS global run, will provide the basis for the full-scale alignment of the Tracker, which will be carried out with the first \\emph{p-p} collisions.

  17. High-throughput sequence alignment using Graphics Processing Units

    Directory of Open Access Journals (Sweden)

    Trapnell Cole

    2007-12-01

    Full Text Available Abstract Background The recent availability of new, less expensive high-throughput DNA sequencing technologies has yielded a dramatic increase in the volume of sequence data that must be analyzed. These data are being generated for several purposes, including genotyping, genome resequencing, metagenomics, and de novo genome assembly projects. Sequence alignment programs such as MUMmer have proven essential for analysis of these data, but researchers will need ever faster, high-throughput alignment tools running on inexpensive hardware to keep up with new sequence technologies. Results This paper describes MUMmerGPU, an open-source high-throughput parallel pairwise local sequence alignment program that runs on commodity Graphics Processing Units (GPUs in common workstations. MUMmerGPU uses the new Compute Unified Device Architecture (CUDA from nVidia to align multiple query sequences against a single reference sequence stored as a suffix tree. By processing the queries in parallel on the highly parallel graphics card, MUMmerGPU achieves more than a 10-fold speedup over a serial CPU version of the sequence alignment kernel, and outperforms the exact alignment component of MUMmer on a high end CPU by 3.5-fold in total application time when aligning reads from recent sequencing projects using Solexa/Illumina, 454, and Sanger sequencing technologies. Conclusion MUMmerGPU is a low cost, ultra-fast sequence alignment program designed to handle the increasing volume of data produced by new, high-throughput sequencing technologies. MUMmerGPU demonstrates that even memory-intensive applications can run significantly faster on the relatively low-cost GPU than on the CPU.

  18. Testing the tidal alignment model of galaxy intrinsic alignment

    International Nuclear Information System (INIS)

    Weak gravitational lensing has become a powerful probe of large-scale structure and cosmological parameters. Precision weak lensing measurements require an understanding of the intrinsic alignment of galaxy ellipticities, which can in turn inform models of galaxy formation. It is hypothesized that elliptical galaxies align with the background tidal field and that this alignment mechanism dominates the correlation between ellipticities on cosmological scales (in the absence of lensing). We use recent large-scale structure measurements from the Sloan Digital Sky Survey to test this picture with several statistics: (1) the correlation between ellipticity and galaxy overdensity, wg+; (2) the intrinsic alignment auto-correlation functions; (3) the correlation functions of curl-free, E, and divergence-free, B, modes, the latter of which is zero in the linear tidal alignment theory; (4) the alignment correlation function, wg(rp,θ), a recently developed statistic that generalizes the galaxy correlation function to account for the angle between the galaxy separation vector and the principle axis of ellipticity. We show that recent measurements are largely consistent with the tidal alignment model and discuss dependence on galaxy luminosity. In addition, we show that at linear order the tidal alignment model predicts that the angular dependence of wg(rp,θ) is simply wg+(rp)cos (2θ) and that this dependence is consistent with recent measurements. We also study how stochastic nonlinear contributions to galaxy ellipticity impact these statistics. We find that a significant fraction of the observed LRG ellipticity can be explained by alignment with the tidal field on scales ∼> 10 \\hMpc. These considerations are relevant to galaxy formation and evolution

  19. Cloning, expression and alternative splicing of the novel isoform of hTCP11 gene

    DEFF Research Database (Denmark)

    Ma, Yong-xin; Zhang, Si-zhong; Wu, Qia-qing;

    2003-01-01

    To identify a novel isoform of hTCP11 gene and investigate its expression and alternative splicing.......To identify a novel isoform of hTCP11 gene and investigate its expression and alternative splicing....

  20. Functional Characterization of NIPBL Physiological Splice Variants and Eight Splicing Mutations in Patients with Cornelia de Lange Syndrome

    Directory of Open Access Journals (Sweden)

    María E. Teresa-Rodrigo

    2014-06-01

    Full Text Available Cornelia de Lange syndrome (CdLS is a congenital developmental disorder characterized by distinctive craniofacial features, growth retardation, cognitive impairment, limb defects, hirsutism, and multisystem involvement. Mutations in five genes encoding structural components (SMC1A, SMC3, RAD21 or functionally associated factors (NIPBL, HDAC8 of the cohesin complex have been found in patients with CdLS. In about 60% of the patients, mutations in NIPBL could be identified. Interestingly, 17% of them are predicted to change normal splicing, however, detailed molecular investigations are often missing. Here, we report the first systematic study of the physiological splicing of the NIPBL gene, that would reveal the identification of four new splicing isoforms ΔE10, ΔE12, ΔE33,34, and B’. Furthermore, we have investigated nine mutations affecting splice-sites in the NIPBL gene identified in twelve CdLS patients. All mutations have been examined on the DNA and RNA level, as well as by in silico analyses. Although patients with mutations affecting NIPBL splicing show a broad clinical variability, the more severe phenotypes seem to be associated with aberrant transcripts resulting in a shift of the reading frame.

  1. The hnRNP 2H9 gene, which is involved in the splicing reaction, is a multiply spliced gene

    DEFF Research Database (Denmark)

    Honoré, B

    2000-01-01

    The hnRNP 2H9 gene products are involved in the splicing process and participate in early heat shock-induced splicing arrest. By combining low/high stringency hybridisation, database search, Northern and Western blotting it is shown that the gene is alternatively spliced into at least six...... transcripts: hnRNPs 2H9, 2H9A, 2H9B, 2H9C, 2H9D and 2H9E predicting proteins containing 346, 331, 297, 215, 145 and 139 amino acids, respectively. The hnRNP 2H9A cDNA sequence was used to obtain a genomic BAC clone and the structure of the hnRNP 2H9 gene was revealed by sequencing two subclones together...... indicates that the alternatively spliced transcripts give rise to different sets and levels of proteins expressed among various human cells and tissues. Due to their great structural variations the different proteins may thus possess different functions in the splicing reaction. Udgivelsesdato: 2000-Jun-21...

  2. RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing

    Science.gov (United States)

    Guo, Wei; Schafer, Sebastian; Greaser, Marion L.; Radke, Michael H.; Liss, Martin; Govindarajan, Thirupugal; Maatz, Henrike; Schulz, Herbert; Li, Shijun; Parrish, Amanda M.; Dauksaite, Vita; Vakeel, Padmanabhan; Klaassen, Sabine; Gerull, Brenda; Thierfelder, Ludwig; Regitz-Zagrosek, Vera; Hacker, Timothy A.; Saupe, Kurt W.; Dec, G. William; Ellinor, Patrick T.; MacRae, Calum A.; Spallek, Bastian; Fischer, Robert; Perrot, Andreas; Özcelik, Cemil; Saar, Kathrin; Hubner, Norbert; Gotthardt, Michael

    2013-01-01

    Alternative splicing plays a major role in the adaptation of cardiac function exemplified by the isoform switch of titin, which adjusts ventricular filling. We previously identified a rat strain deficient in titin splicing. Using genetic mapping, we found a loss-of-function mutation in RBM20 as the underlying cause for the pathological titin isoform expression. Mutations in human RBM20 have previously been shown to cause dilated cardiomyopathy. We showed that the phenotype of Rbm20 deficient rats resembles the human pathology. Deep sequencing of the human and rat cardiac transcriptome revealed an RBM20 dependent regulation of alternative splicing. Additionally to titin we identified a set of 30 genes with conserved regulation between human and rat. This network is enriched for genes previously linked to cardiomyopathy, ion-homeostasis, and sarcomere biology. Our studies emphasize the importance of posttranscriptional regulation in cardiac function and provide mechanistic insights into the pathogenesis of human heart failure. PMID:22466703

  3. Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.

    Science.gov (United States)

    Yang, Xinping; Coulombe-Huntington, Jasmin; Kang, Shuli; Sheynkman, Gloria M; Hao, Tong; Richardson, Aaron; Sun, Song; Yang, Fan; Shen, Yun A; Murray, Ryan R; Spirohn, Kerstin; Begg, Bridget E; Duran-Frigola, Miquel; MacWilliams, Andrew; Pevzner, Samuel J; Zhong, Quan; Trigg, Shelly A; Tam, Stanley; Ghamsari, Lila; Sahni, Nidhi; Yi, Song; Rodriguez, Maria D; Balcha, Dawit; Tan, Guihong; Costanzo, Michael; Andrews, Brenda; Boone, Charles; Zhou, Xianghong J; Salehi-Ashtiani, Kourosh; Charloteaux, Benoit; Chen, Alyce A; Calderwood, Michael A; Aloy, Patrick; Roth, Frederick P; Hill, David E; Iakoucheva, Lilia M; Xia, Yu; Vidal, Marc

    2016-02-11

    While alternative splicing is known to diversify the functional characteristics of some genes, the extent to which protein isoforms globally contribute to functional complexity on a proteomic scale remains unknown. To address this systematically, we cloned full-length open reading frames of alternatively spliced transcripts for a large number of human genes and used protein-protein interaction profiling to functionally compare hundreds of protein isoform pairs. The majority of isoform pairs share less than 50% of their interactions. In the global context of interactome network maps, alternative isoforms tend to behave like distinct proteins rather than minor variants of each other. Interaction partners specific to alternative isoforms tend to be expressed in a highly tissue-specific manner and belong to distinct functional modules. Our strategy, applicable to other functional characteristics, reveals a widespread expansion of protein interaction capabilities through alternative splicing and suggests that many alternative "isoforms" are functionally divergent (i.e., "functional alloforms"). PMID:26871637

  4. Alternative splice variants of the human PD-1 gene

    DEFF Research Database (Denmark)

    Nielsen, Christian; Ohm-Laursen, Line; Barington, Torben;

    2005-01-01

    PD-1 is an immunoregulatory receptor expressed on the surface of activated T cells, B cells, and monocytes. We describe four alternatively spliced PD-1 mRNA transcripts (PD-1Deltaex2, PD-1Deltaex3, PD-1Deltaex2,3, and PD-1Deltaex2,3,4) in addition to the full length isoform. PD-1Deltaex2 and PD-1......Deltaex3 are generated by alternative splicing where exon 2 (extracellular IgV-like domain) and exon 3 (transmembrane domain) respectively are spliced out. PD-1Deltaex3 is therefore likely to encode a soluble form of PD-1. PD-1Deltaex2,3 lacks exon 2 and 3. These three variants have unaffected open...

  5. Widespread evolutionary conservation of alternatively spliced exons in caenorhabditis

    DEFF Research Database (Denmark)

    Irimia, Manuel; Rukov, Jakob L; Penny, David;

    2007-01-01

    Alternative splicing (AS) contributes to increased transcriptome and proteome diversity in various eukaryotic lineages. Previous studies showed low levels of conservation of alternatively spliced (cassette) exons within mammals and within dipterans. We report a strikingly different pattern in...... patterns of splicing. The functionality of the vast majority of cassette exons is underscored by various other features. We suggest that differences in conservation between lineages reflect differences in levels of functionality and further suggest that these differences are due to differences in intron...... length and the strength of consensus boundaries across lineages. Finally, we demonstrate an inverse relationship between AS and gene duplication, suggesting that the latter may be primarily responsible for the emergence of new functional transcripts in nematodes. Udgivelsesdato: 2008-Feb...

  6. Fuel assembly

    International Nuclear Information System (INIS)

    Purpose: To improve the thermal and mechanical safety of fuel rods and structural components by making the local power coefficient of jointed fuel rods greater than that of other fuel rods in a fuel assembly. Constitution: In a fuel assembly comprising a plurality of fuel rods bundled by a spacer and held at the upper and the lower positions with tie plates for insertion into a channel, the degree of enrichment of uranium 235 for uranium dioxide fuel pellets charged in jointed fuel rods is adjusted such that the local power coefficient of the jointed fuel rods is made greater than that of the other fuel rods. In the case if the upper tie plate is moved upwardly by the extension of the jointed fuel rods, other fuel rods axially free from the upper tie plate receives no tension, whereby the safety of the fuel assembly can be improved. (Moriyama, K.)

  7. Alternative splicing of the AGAMOUS orthologous gene in double flower of Magnolia stellata (Magnoliaceae).

    Science.gov (United States)

    Zhang, Bo; Liu, Zhi-Xiong; Ma, Jiang; Song, Yi; Chen, Fa-Ju

    2015-12-01

    Magnolia stellata is a woody ornamental shrub with more petaloid tepals than related plants from family Magnoliaceae. Recent studies revealed that expression changes in an AGAMOUS (AG) orthologous gene could resulted in double flowers with increased numbers of petals. We isolated three transcripts encoding different isoforms of a single AG orthologous gene, MastAG, mastag_2 and mastag_3, from M. stellata. Sequence alignments and Southern blot analyses suggested that MastAG was a single-copy gene in M. stellata genomes, and that mastag_2 and mastag_3 were abnormally spliced isoforms of MastAG. An 144bp exon skipping in MastAG results in the truncated mastag_2 protein lacking the completely I domain and 18 aa of the K1 subdomain, whereas an 165bp exon skipping of MastAG produces a truncated mastag_3 protein lacking 6 aa of the K3 subdomain and the completely C terminal region. Expression analyses showed that three alternative splicing (AS) isoforms expressed only in developing stamens and carpels. Functional analyses revealed that MastAG could mimic the endogenous AG to specify carpel identity, but failed to regulate stamen development in an Arabidopsis ag-1 mutant. Moreover, the key domain or subdomain deletions represented by mastag_2 and mastag_3 resulted in loss of C-function. However, ectopic expression of mastag_2 in Arabidopsis produced flowers with sepals converted into carpeloid organs, but without petals and stamens, whereas ectopic expression of mastag_3 in Arabidopsis could mimic the flower phenotype of the ag mutant and produced double flowers with homeotic transformation of stamens into petals and carpels into another ag flower. Our results also suggest that mastag_3 holds some potential for biotechnical engineering to create multi-petal phenotypes in commercial ornamental cultivars. PMID:26706078

  8. Aligning for Innovation - Alignment Strategy to Drive Innovation

    Science.gov (United States)

    Johnson, Hurel; Teltschik, David; Bussey, Horace, Jr.; Moy, James

    2010-01-01

    With the sudden need for innovation that will help the country achieve its long-term space exploration objectives, the question of whether NASA is aligned effectively to drive the innovation that it so desperately needs to take space exploration to the next level should be entertained. Authors such as Robert Kaplan and David North have noted that companies that use a formal system for implementing strategy consistently outperform their peers. They have outlined a six-stage management systems model for implementing strategy, which includes the aligning of the organization towards its objectives. This involves the alignment of the organization from the top down. This presentation will explore the impacts of existing U.S. industrial policy on technological innovation; assess the current NASA organizational alignment and its impacts on driving technological innovation; and finally suggest an alternative approach that may drive the innovation needed to take the world to the next level of space exploration, with NASA truly leading the way.

  9. Oncogenic Alternative Splicing Switches: Role in Cancer Progression and Prospects for Therapy

    OpenAIRE

    Serena Bonomi; Stefania Gallo; Morena Catillo; Daniela Pignataro; Giuseppe Biamonti; Claudia Ghigna

    2013-01-01

    Alterations in the abundance or activities of alternative splicing regulators generate alternatively spliced variants that contribute to multiple aspects of tumor establishment, progression and resistance to therapeutic treatments. Notably, many cancer-associated genes are regulated through alternative splicing suggesting a significant role of this post-transcriptional regulatory mechanism in the production of oncogenes and tumor suppressors. Thus, the study of alternative splicing in cancer ...

  10. DEDB: a database of Drosophila melanogaster exons in splicing graph form

    OpenAIRE

    Tan Tin; Lee Bernett TK; Ranganathan Shoba

    2004-01-01

    Abstract Background A wealth of quality genomic and mRNA/EST sequences in recent years has provided the data required for large-scale genome-wide analysis of alternative splicing. We have capitalized on this by constructing a database that contains alternative splicing information organized as splicing graphs, where all transcripts arising from a single gene are collected, organized and classified. The splicing graph then serves as the basis for the classification of the various types of alte...

  11. A reliable method for quantification of splice variants using RT-qPCR

    OpenAIRE

    Camacho Londoño, Julia; Philipp, Stephan E.

    2016-01-01

    Background The majority of protein isoforms arise from alternative splicing of the encoding primary RNA transcripts. To understand the significance of single splicing events, reliable techniques are needed to determine their incidence. However, existing methods are labour-intensive, error-prone or of limited use. Results Here, we present an improved method to determine the relative incidence of transcripts that arise from alternative splicing at a single site. Splice variants were quantified ...

  12. Normal and abnormal mechanisms of gene splicing and relevance to inherited skin diseases

    OpenAIRE

    Wessagowit, Vesarat; Nalla, Vijay K.; Rogan, Peter K; McGrath, John A

    2005-01-01

    The process of excising introns from pre-mRNA complexes is directed by specific genomic DNA sequences at intron—exon borders known as splice sites. These regions contain well-conserved motifs which allow the splicing process to proceed in a regulated and structured manner. However, as well as conventional splicing, several genes have the inherent capacity to undergo alternative splicing, thus allowing synthesis of multiple gene transcripts, perhaps with different functional properties. Within...

  13. SASD: the Synthetic Alternative Splicing Database for identifying novel isoform from proteomics

    OpenAIRE

    Zhang, Fan; Drabier, Renee

    2013-01-01

    Background Alternative splicing is an important and widespread mechanism for generating protein diversity and regulating protein expression. High-throughput identification and analysis of alternative splicing in the protein level has more advantages than in the mRNA level. The combination of alternative splicing database and tandem mass spectrometry provides a powerful technique for identification, analysis and characterization of potential novel alternative splicing protein isoforms from pro...

  14. Genome-wide survey of allele-specific splicing in humans

    OpenAIRE

    Nembaware, Victoria; Lupindo, Bukiwe; Schouest, Katherine; Spillane, Charles; Scheffler, Konrad; Seoighe, Cathal

    2008-01-01

    Background Accurate mRNA splicing depends on multiple regulatory signals encoded in the transcribed RNA sequence. Many examples of mutations within human splice regulatory regions that alter splicing qualitatively or quantitatively have been reported and allelic differences in mRNA splicing are likely to be a common and important source of phenotypic diversity at the molecular level, in addition to their contribution to genetic disease susceptibility. However, because the effect of a mutation...

  15. Genome-wide survey of allele-specific splicing in humans

    OpenAIRE

    Scheffler Konrad; Spillane Charles; Schouest Katherine; Lupindo Bukiwe; Nembaware Victoria; Seoighe Cathal

    2008-01-01

    Abstract Background Accurate mRNA splicing depends on multiple regulatory signals encoded in the transcribed RNA sequence. Many examples of mutations within human splice regulatory regions that alter splicing qualitatively or quantitatively have been reported and allelic differences in mRNA splicing are likely to be a common and important source of phenotypic diversity at the molecular level, in addition to their contribution to genetic disease susceptibility. However, because the effect of a...

  16. Quantification of stochastic noise of splicing and polyadenylation in Entamoeba histolytica

    OpenAIRE

    Hon, Chung-Chau; Weber, Christian; Sismeiro, Odile; Proux, Caroline; Koutero, Mikael; Deloger, Marc; Das, Sarbashis; Agrahari, Mridula; Dillies, Marie-Agnes; JAGLA, BERND; Coppee, Jean-Yves; Bhattacharya, Alok; Guillen, Nancy

    2012-01-01

    Alternative splicing and polyadenylation were observed pervasively in eukaryotic messenger RNAs. These alternative isoforms could either be consequences of physiological regulation or stochastic noise of RNA processing. To quantify the extent of stochastic noise in splicing and polyadenylation, we analyzed the alternative usage of splicing and polyadenylation sites in Entamoeba histolytica using RNA-Seq. First, we identified a large number of rarely spliced alternative junctions and then show...

  17. The Alternative Splicing Gallery (ASG): bridging the gap between genome and transcriptome

    OpenAIRE

    Leipzig, Jeremy; Pevzner, Pavel; Heber, Steffen

    2004-01-01

    Alternative splicing essentially increases the diversity of the transcriptome and has important implications for physiology, development and the genesis of diseases. Conventionally, alternative splicing is investigated in a case-by-case fashion, but this becomes cumbersome and error prone if genes show a huge abundance of different splice variants. We use a different approach and integrate all transcripts derived from a gene into a single splicing graph. Each transcript corresponds to a path ...

  18. Context-dependent splicing regulation: Exon definition, co-occurring motif pairs and tissue specificity

    OpenAIRE

    Ke, Shengdong; CHASIN, LAWRENCE A.

    2011-01-01

    Splicing is a crucial process in gene expression in higher organisms because: (1) most vertebrate genes contain introns; and (2) alternative splicing is primarily responsible for increasing proteomic complexity and functional diversity. Intron definition, the coordination across an intron, is a mandatory step in the splicing process. However, exon definition, the coordination across an exon, is also thought to be required for the splicing of most vertebrate exons. Recent investigations of exo...

  19. Pre-mRNA splicing during transcription in the mammalian system

    OpenAIRE

    Pandya-Jones, Amy

    2011-01-01

    Splicing of RNA polymerase II (polII) transcripts is a crucial step in gene expression and a key generator of mRNA diversity. Splicing and transcription have been generally been studied in isolation, although in vivo pre-mRNA splicing occurs in concert with transcription. The two processes appear to be functionally connected because a number of variables that regulate transcription have been identified as also influencing splicing. However, the mechanisms that couple the two processes are lar...

  20. Rectifier of aberrant mRNA splicing recovers tRNA modification in familial dysautonomia

    OpenAIRE

    Yoshida, Mayumi; Kataoka, Naoyuki; Miyauchi, Kenjyo; Ohe, Kenji; Iida, Kei; Yoshida, Suguru; Nojima, Takayuki; Okuno, Yukiko; Onogi, Hiroshi; Usui, Tomomi; Takeuchi, Akihide; Hosoya, Takamitsu; Suzuki, Tsutomu; Hagiwara, Masatoshi

    2015-01-01

    Familial dysautonomia (FD) is caused by missplicing of the IκB kinase complex-associated protein (IKAP) gene, which results in the skipping of exon 20, especially in neurons. FD would be treatable if exon 20 inclusion were increased correctly to reestablish correct splicing. Here, we have established a dual-color splicing reporter that recapitulates FD-type splicing. By using this reporter, we have identified a small chemical compound, named rectifier of aberrant splicing (RECTAS), that recti...

  1. Muon System alignment with tracks

    CERN Document Server

    Calderón, Alicia; Virto, A L; Martínez, P; Martínez-Rivero, C; Matorras, Francisco; Rodrigo, Teresa; Sobron, M; Vila, Ivan

    2006-01-01

    We describe here some of the techniques foreseen to align the Muon System with muon tracks. Two methods are proposed, one based on the Tracker which measures the position of a Muon chamber with respect to the Tracker, and another one which aligns internally the Muon System. A mathematical model is described for the general case. It is simplified for several particular cases of the Muon System alignment and applied to realistic examples on full simulation. Some estimates of the expected precision and limitation of the method are presented.

  2. Interplay between DMD point mutations and splicing signals in Dystrophinopathy phenotypes.

    Directory of Open Access Journals (Sweden)

    Jonàs Juan-Mateu

    Full Text Available DMD nonsense and frameshift mutations lead to severe Duchenne muscular dystrophy while in-frame mutations lead to milder Becker muscular dystrophy. Exceptions are found in 10% of cases and the production of alternatively spliced transcripts is considered a key modifier of disease severity. Several exonic mutations have been shown to induce exon-skipping, while splice site mutations result in exon-skipping or activation of cryptic splice sites. However, factors determining the splicing pathway are still unclear. Point mutations provide valuable information regarding the regulation of pre-mRNA splicing and elements defining exon identity in the DMD gene. Here we provide a comprehensive analysis of 98 point mutations related to clinical phenotype and their effect on muscle mRNA and dystrophin expression. Aberrant splicing was found in 27 mutations due to alteration of splice sites or splicing regulatory elements. Bioinformatics analysis was performed to test the ability of the available algorithms to predict consequences on mRNA and to investigate the major factors that determine the splicing pathway in mutations affecting splicing signals. Our findings suggest that the splicing pathway is highly dependent on the interplay between splice site strength and density of regulatory elements.

  3. DEDB: a database of Drosophila melanogaster exons in splicing graph form

    Directory of Open Access Journals (Sweden)

    Tan Tin

    2004-12-01

    Full Text Available Abstract Background A wealth of quality genomic and mRNA/EST sequences in recent years has provided the data required for large-scale genome-wide analysis of alternative splicing. We have capitalized on this by constructing a database that contains alternative splicing information organized as splicing graphs, where all transcripts arising from a single gene are collected, organized and classified. The splicing graph then serves as the basis for the classification of the various types of alternative splicing events. Description DEDB http://proline.bic.nus.edu.sg/dedb/index.html is a database of Drosophila melanogaster exons obtained from FlyBase arranged in a splicing graph form that permits the creation of simple rules allowing for the classification of alternative splicing events. Pfam domains were also mapped onto the protein sequences allowing users to access the impact of alternative splicing events on domain organization. Conclusions DEDB's catalogue of splicing graphs facilitates genome-wide classification of alternative splicing events for genome analysis. The splicing graph viewer brings together genome, transcript, protein and domain information to facilitate biologists in understanding the implications of alternative splicing.

  4. Tracking and Alignment in the CMS detector

    CERN Document Server

    Ronga, Frederic Jean

    2007-01-01

    This Report summarises the alignment strategy of the CMS detector. Track reconstruction in the silicon tracker and muon chambers is briefly described. We then present the different sources of alignment information, in particular alignment algorithms using reconstructed tracks.

  5. Pupil Alignment Considerations for Large, Deployable Space Telescopes

    Science.gov (United States)

    Bos, Brent J.; Ohl, Raymond G.; Kubalak, Daivd A.

    2011-01-01

    For many optical systems the properties and alignment of the internal apertures and pupils are not critical or controlled with high precision during optical system design, fabrication or assembly. In wide angle imaging systems, for instance, the entrance pupil position and orientation is typically unconstrained and varies over the system s field of view in order to optimize image quality. Aperture tolerances usually do not receive the same amount of scrutiny as optical surface aberrations or throughput characteristics because performance degradation is typically graceful with misalignment, generally only causing a slight reduction in system sensitivity due to vignetting. But for a large deployable space-based observatory like the James Webb Space Telescope (JWST), we have found that pupil alignment is a key parameter. For in addition to vignetting, JWST pupil errors cause uncertainty in the wavefront sensing process that is used to construct the observatory on-orbit. Furthermore they also open stray light paths that degrade the science return from some of the telescope s instrument channels. In response to these consequences, we have developed several pupil measurement techniques for the cryogenic vacuum test where JWST science instrument pupil alignment is verified. These approaches use pupil alignment references within the JWST science instruments; pupil imaging lenses in three science instrument channels; and unique pupil characterization features in the optical test equipment. This will allow us to verify and crosscheck the lateral pupil alignment of the JWST science instruments to approximately 1-2% of their pupil diameters.

  6. Harmonic Analysis of Linac Alignment

    CERN Document Server

    McCrady, Rodney C

    2005-01-01

    We have analyzed the requirements on alignment of the focusing elements (quadrupole doublets) in the Los Alamos Neutron Science Center (LANSCE) side coupled linac. The analysis is performed in terms of harmonics of the quardrupole spacing. This allows us to determine the effect of intentional deviations from a straight line, such as following the curvature of the Earth, and of unintentional deviations introduced by measurement and alignment errors. Results are compared to measured positions of the doublets.

  7. Expressive alignment language and implementation

    OpenAIRE

    Euzenat, Jérôme; Scharffe, François; Zimmermann, Antoine

    2007-01-01

    euzenat2007e This deliverable provides the description of an alignment language which is both expressive and independent from ontology languages. It defines the language through its abstract syntax and semantics depending on ontology language semantics. It then describes two concrete syntax: an exchange syntax in RDF/XML and a surface syntax for human consumption. Finally, it presents the current implementation of this expressive language within the Alignment API taking advantage of the OM...

  8. A specific pattern of splicing for the horse $\\alpha$S1-Casein mRNA and partial genomic characterization of the relevant locus

    OpenAIRE

    Milenkovic, Dragan; Martin, Patrice; Guérin, Gérard; Leroux, Christine

    2002-01-01

    Mares' milk has a composition very different from that of cows' milk. It is much more similar to human milk, in particular in its casein fraction. This study reports on the sequence of a 994 bp amplified fragment corresponding to a horse $\\alpha$S1-Casein ($\\alpha$ S1-Cn) cDNA and its comparison with its caprine, pig, rabbit and human counterparts. The alignment of these sequences revealed a specific pattern of splicing for this horse primary transcript. As in humans, exons 3$'$, 6$'$ and 13$...

  9. The reciprocal regulation between splicing and 3'-end processing.

    Science.gov (United States)

    Kaida, Daisuke

    2016-07-01

    Most eukaryotic precursor mRNAs are subjected to RNA processing events, including 5'-end capping, splicing and 3'-end processing. These processing events were historically studied independently; however, since the early 1990s tremendous efforts by many research groups have revealed that these processing factors interact with each other to control each other's functions. U1 snRNP and its components negatively regulate polyadenylation of precursor mRNAs. Importantly, this function is necessary for protecting the integrity of the transcriptome and for regulating gene length and the direction of transcription. In addition, physical and functional interactions occur between splicing factors and 3'-end processing factors across the last exon. These interactions activate or inhibit splicing and 3'-end processing depending on the context. Therefore, splicing and 3'-end processing are reciprocally regulated in many ways through the complex protein-protein interaction network. Although interesting questions remain, future studies will illuminate the molecular mechanisms underlying the reciprocal regulation. WIREs RNA 2016, 7:499-511. doi: 10.1002/wrna.1348 For further resources related to this article, please visit the WIREs website. PMID:27019070

  10. SmD1 is required for spliced leader biogenesis

    Czech Academy of Sciences Publication Activity Database

    Zeiner, G. M.; Foldynová, Silvie; Sturm, N. R.; Lukeš, Julius; Campbell, D. A.

    2004-01-01

    Roč. 3, č. 1 (2004), s. 241-244. ISSN 1535-9778 Grant ostatní: NIH(US) AI34536; NIH(US) AI054496 Institutional research plan: CEZ:AV0Z6022909 Keywords : Kinetoplastida * Trypanosoma * spliced leader RNA Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.954, year: 2004

  11. Leveraging transcript quantification for fast computation of alternative splicing profiles.

    Science.gov (United States)

    Alamancos, Gael P; Pagès, Amadís; Trincado, Juan L; Bellora, Nicolás; Eyras, Eduardo

    2015-09-01

    Alternative splicing plays an essential role in many cellular processes and bears major relevance in the understanding of multiple diseases, including cancer. High-throughput RNA sequencing allows genome-wide analyses of splicing across multiple conditions. However, the increasing number of available data sets represents a major challenge in terms of computation time and storage requirements. We describe SUPPA, a computational tool to calculate relative inclusion values of alternative splicing events, exploiting fast transcript quantification. SUPPA accuracy is comparable and sometimes superior to standard methods using simulated as well as real RNA-sequencing data compared with experimentally validated events. We assess the variability in terms of the choice of annotation and provide evidence that using complete transcripts rather than more transcripts per gene provides better estimates. Moreover, SUPPA coupled with de novo transcript reconstruction methods does not achieve accuracies as high as using quantification of known transcripts, but remains comparable to existing methods. Finally, we show that SUPPA is more than 1000 times faster than standard methods. Coupled with fast transcript quantification, SUPPA provides inclusion values at a much higher speed than existing methods without compromising accuracy, thereby facilitating the systematic splicing analysis of large data sets with limited computational resources. The software is implemented in Python 2.7 and is available under the MIT license at https://bitbucket.org/regulatorygenomicsupf/suppa. PMID:26179515

  12. Electromechanical behaviour of REBCO tape lap splices under transverse compressive loading

    CERN Document Server

    Grether, A; Ballarino, A.; Bottura, L.

    2016-01-01

    We have studied the influence of transverse compressive stress on the resistance and critical current (Ic) of soldered REBCO tape lap splices. Internal contact resistances dominate the overall REBCO lap splice resistances. Application of transverse compressive stress up to 250 MPa during the resistance measurements does not alter the resistance and Ic of the soldered REBCO splices that were studied. The resistance of unsoldered REBCO tape lap splices depends strongly on the contact pressure. At a transverse compressive stress of 100 MPa to which Roebel cables are typically exposed in high field magnets, the crossover splice contact resistance is comparable to the internal tape resistances.

  13. Sip1, a Novel RS Domain-Containing Protein Essential for Pre-mRNA Splicing

    OpenAIRE

    Zhang, Wan-jiang; Jane Y Wu

    1998-01-01

    Previous studies have shown that protein-protein interactions among splicing factors may play an important role in pre-mRNA splicing. We report here identification and functional characterization of a new splicing factor, Sip1 (SC35-interacting protein 1). Sip1 was initially identified by virtue of its interaction with SC35, a splicing factor of the SR family. Sip1 interacts with not only several SR proteins but also with U1-70K and U2AF65, proteins associated with 5′ and 3′ splice sites, res...

  14. Protein Trans-Splicing as a Means for Viral Vector-Mediated In Vivo Gene Therapy

    OpenAIRE

    Li, Juan; Sun, Wenchang; Wang, Bing; Xiao, Xiao; Liu, Xiang-Qin

    2008-01-01

    Inteins catalyze protein splicing in a fashion similar to how self-splicing introns catalyze RNA splicing. Split-inteins catalyze precise ligation of two separate polypeptides through trans-splicing in a highly specific manner. Here we report a method of using protein trans-splicing to circumvent the packaging size limit of gene therapy vectors. To demonstrate this method, we chose a large dystrophin gene and an adeno-associated viral (AAV) vector, which has a small packaging size. A highly f...

  15. Electromechanical behaviour of REBCO tape lap splices under transverse compressive loading

    Science.gov (United States)

    Grether, A.; Scheuerlein, C.; Ballarino, A.; Bottura, L.

    2016-07-01

    We have studied the influence of transverse compressive stress on the resistance and critical current (I c ) of soldered REBCO tape lap splices. Internal contact resistances dominate the overall REBCO lap splice resistances. Application of transverse compressive stress up to 250 MPa during the resistance measurements does not alter the resistance and I c of the soldered REBCO splices that were studied. The resistance of unsoldered REBCO tape lap splices depends strongly on the contact pressure. At a transverse compressive stress of 100 MPa, to which Roebel cables are typically exposed in high field magnets, the crossover splice contact resistance is comparable to the internal tape resistances.

  16. Fuel assembly

    International Nuclear Information System (INIS)

    A fuel assembly is composed of a fuel bundle surrounded by a channel box. The fuel bundle comprises a large number of fuel rods and a water rod secured to upper and lower tie plate by way of a plurality of fuel spacers. Grooves (libretti) are formed in the direction along the flowing direction of coolants to at least one of the surface of the fuel rods, the inner surface of the channel box, the surface of the water rod and spacer constituting components. In this case, the lateral width of the libretto in the flowing direction is determined as the minimum thickness of the bottom layer of a layered flow determined by a coolant flow rate. With such a constitution, abrasion resistance relative to coolants is reduced to reduce the pressure loss of fuel assemblies. (I.N.)

  17. Influence of intron length on interaction characters between post-spliced intron and its CDS in ribosomal protein genes

    Science.gov (United States)

    Zhao, Xiaoqing; Li, Hong; Bao, Tonglaga; Ying, Zhiqiang

    2012-09-01

    Many experiment evidences showed that sequence structures of introns and intron loss/gain can influence gene expression, but current mechanisms did not refer to the functions of post-spliced introns directly. We propose that postspliced introns play their functions in gene expression by interacting with their mRNA sequences and the interaction is characterized by the matched segments between introns and their CDS. In this study, we investigated the interaction characters with length series by improved Smith-Waterman local alignment software for the ribosomal protein genes in C. elegans and D. melanogaster. Our results showed that RF values of five intron groups are significantly high in the central non-conserved region and very low in 5'-end and 3'-end splicing region. It is interesting that the number of the optimal matched regions gradually increases with intron length. Distributions of the optimal matched regions are different for five intron groups. Our study revealed that there are more interaction regions between longer introns and their CDS than shorter, and it provides a positive pattern for regulating the gene expression.

  18. The splicing fate of plant SPO11 genes

    Directory of Open Access Journals (Sweden)

    Thorben eSprink

    2014-05-01

    Full Text Available Towards the global understanding of plant meiosis, it seems to be essential to decipher why all as yet sequenced plants need or at least encode for two different meiotic SPO11 genes. This is in contrast to mammals and fungi, where only one SPO11 is present. Both SPO11 in plants are essential for the initiation of double strand breaks (DSBs during the meiotic prophase. In nearly all eukaryotic organisms DSB induction by SPO11 leads to meiotic DSB repair, thereby ensuring the formation of a necessary number of crossovers (CO as physical connections between the allelic chromosomes. We aim to investigate the specific functions and evolution of both SPO11 genes in land plants. Therefore, we identified and cloned the respective orthologous genes from Brassica rapa, Carica papaya, Oryza sativa and Physcomitrella patens. In parallel we determined the full length cDNA sequences of SPO11-1 and -2 from all of these plants by RT-PCR. During these experiments we observed that the analyzed plants exhibit a pattern of aberrant splicing products of both SPO11 mRNAs. Such an aberrant splicing has previously been described for Arabidopsis and therefore seems to be conserved throughout evolution. Most of the splicing forms of SPO11-1 and -2 seem to be non functional as they either showed intron retention or shortened exons accompanied by a frameshift leading to premature termination codons (PTCs in most cases. Nevertheless, we could detect one putative functional alternatively spliced mRNA for SPO11-1 and -2 each, indicating that splicing of SPO11 does not depend only on the gene sequence but also on the plant species and that it might play a regulatory role.

  19. NMR studies of two spliced leader RNAs using isotope labeling

    Energy Technology Data Exchange (ETDEWEB)

    Lapham, J.; Crothers, D.M. [Yale Univ., New Haven, CT (United States)

    1994-12-01

    Spliced leader RNAs are a class of RNA molecules (<200 nts) involved in the trans splicing of messenger RNA found in trypanosomes, nematodes, and other lower eukaryotes. The spliced leader RNA from the trypanosome Leptomonas Collosoma exists in two alternate structural forms with similar thermal stabilities. The 54 nucleotides on the 5{prime} end of the SL molecule is structurally independent from the 3{prime} half of the RNA, and displays the two structural forms. Furthermore, the favored of the two structures was shown to contain anomalous nuclease sensitivity and thermal stability features, which suggests that there may be tertiary interactions between the splice site and other nucleotides in the 5{prime} end. Multidimensional NMR studies are underway to elucidate the structural elements present in the SL RNAs that give rise to their physical properties. Two spliced leader sequences have been studied. The first, the 54 nucleotides on the 5{prime} end of the L. Collosoma sequence, was selected because of earlier studies in our laboratory. The second sequence is the 5{prime} end of the trypanosome Crithidia Fasciculata, which was chosen because of its greater sequence homology to other SL sequences. Given the complexity of the NMR spectra for RNA molecules of this size, we have incorporated {sup 15}N/{sup 13}C-labeled nucleotides into the RNA. One of the techniques we have developed to simplify the spectra of these RNA molecules is isotope labeling of specific regions of the RNA. This has been especially helpful in assigning the secondary structure of molecules that may be able to adopt multiple conformations. Using this technique one can examine a part of the molecule without spectral interference from the unlabeled portion. We hope this approach will promote an avenue for studying the structure of larger RNAs in their native surroundings.

  20. A general definition and nomenclature for alternative splicing events.

    Directory of Open Access Journals (Sweden)

    Michael Sammeth

    Full Text Available Understanding the molecular mechanisms responsible for the regulation of the transcriptome present in eukaryotic cells is one of the most challenging tasks in the postgenomic era. In this regard, alternative splicing (AS is a key phenomenon contributing to the production of different mature transcripts from the same primary RNA sequence. As a plethora of different transcript forms is available in databases, a first step to uncover the biology that drives AS is to identify the different types of reflected splicing variation. In this work, we present a general definition of the AS event along with a notation system that involves the relative positions of the splice sites. This nomenclature univocally and dynamically assigns a specific "AS code" to every possible pattern of splicing variation. On the basis of this definition and the corresponding codes, we have developed a computational tool (AStalavista that automatically characterizes the complete landscape of AS events in a given transcript annotation of a genome, thus providing a platform to investigate the transcriptome diversity across genes, chromosomes, and species. Our analysis reveals that a substantial part--in human more than a quarter-of the observed splicing variations are ignored in common classification pipelines. We have used AStalavista to investigate and to compare the AS landscape of different reference annotation sets in human and in other metazoan species and found that proportions of AS events change substantially depending on the annotation protocol, species-specific attributes, and coding constraints acting on the transcripts. The AStalavista system therefore provides a general framework to conduct specific studies investigating the occurrence, impact, and regulation of AS.

  1. A unique, consistent identifier for alternatively spliced transcript variants.

    Directory of Open Access Journals (Sweden)

    Alberto Riva

    Full Text Available BACKGROUND: As research into alternative splicing reveals the fundamental importance of this phenomenon in the genome expression of higher organisms, there is an increasing need for a standardized, consistent and unique identifier for alternatively spliced isoforms. Such an identifier would be useful to eliminate ambiguities in references to gene isoforms, and would allow for the reliable comparison of isoforms from different sources (e.g., known genes vs. computational predictions. Commonly used identifiers for gene transcripts prove to be unsuitable for this purpose. METHODOLOGY: We propose an algorithm to compute an isoform signature based on the arrangement of exons and introns in a primary transcript. The isoform signature uniquely identifies a transcript structure, and can therefore be used as a key in databases of alternatively spliced isoforms, or to compare alternative splicing predictions produced by different methods. In this paper we present the algorithm to generate isoform signatures, we provide some examples of its application, and we describe a web-based resource to generate isoform signatures and use them in database searches. CONCLUSIONS: Isoform signatures are simple, so that they can be easily generated and included in publications and databases, but flexible enough to unambiguously represent all possible isoform structures, including information about coding sequence position and variable transcription start and end sites. We believe that the adoption of isoform signatures can help establish a consistent, unambiguous nomenclature for alternative splicing isoforms. The system described in this paper is freely available at http://genome.ufl.edu/genesig/, and supplementary materials can be found at http://genome.ufl.edu/genesig-files/.

  2. Transcriptome analysis reveals differential splicing events in IPF lung tissue.

    Directory of Open Access Journals (Sweden)

    Tracy Nance

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a complex disease in which a multitude of proteins and networks are disrupted. Interrogation of the transcriptome through RNA sequencing (RNA-Seq enables the determination of genes whose differential expression is most significant in IPF, as well as the detection of alternative splicing events which are not easily observed with traditional microarray experiments. We sequenced messenger RNA from 8 IPF lung samples and 7 healthy controls on an Illumina HiSeq 2000, and found evidence for substantial differential gene expression and differential splicing. 873 genes were differentially expressed in IPF (FDR<5%, and 440 unique genes had significant differential splicing events in at least one exonic region (FDR<5%. We used qPCR to validate the differential exon usage in the second and third most significant exonic regions, in the genes COL6A3 (RNA-Seq adjusted pval = 7.18e-10 and POSTN (RNA-Seq adjusted pval = 2.06e-09, which encode the extracellular matrix proteins collagen alpha-3(VI and periostin. The increased gene-level expression of periostin has been associated with IPF and its clinical progression, but its differential splicing has not been studied in the context of this disease. Our results suggest that alternative splicing of these and other genes may be involved in the pathogenesis of IPF. We have developed an interactive web application which allows users to explore the results of our RNA-Seq experiment, as well as those of two previously published microarray experiments, and we hope that this will serve as a resource for future investigations of gene regulation in IPF.

  3. Characterization of a novel splicing variant in the RAPTOR gene

    International Nuclear Information System (INIS)

    The mammalian target of rapamycin (mTOR) plays an essential role in the regulation of cell growth, proliferation and apoptosis. Raptor, the regulatory associated protein of mTOR, is an important member in this signaling pathway. In the present report, we identified and characterized a novel splicing variant of this gene, RAPTORv2, in which exons 14-17, 474 bp in total, are omitted from the mRNA. This deletion does not change the open reading frame, but causes a nearly complete absence of HEAT repeats, which were shown to be involved in the binding of mTOR substrates. Real time PCR performed on 48 different human tissues demonstrated the ubiquitous presence of this splice variant. Quantification of mRNA levels in lymphoblastoid cell lines (LCL) from 56 unrelated HapMap individuals revealed that the expression of this splicing form is quite variable. One synonymous SNP, rs2289759 in exon 14, was predicted by ESEfinder to cause a significant gain/loss of SRp55 and/or SF2/ASF binding sites, and thus potentially influence splicing. This prediction was confirmed by linear regression analysis between the ratio of RAPTORv2 to total RAPTOR mRNA levels and the SNP genotype in the above 56 individuals (r = 0.281 and P = 0.036). Moreover, the functional evaluation indicated that this splicing isoform is expected to retain the ability to bind mTOR, but is unlikely to bind mTOR substrates, hence affecting signal transduction and further cell proliferation

  4. The optimization of steelcord belt splices; Optimierung von Stahlseilgurtverbindungen

    Energy Technology Data Exchange (ETDEWEB)

    Hager, M. [Hannover Univ. (Germany); Keller, M. [ContiTech Transportbandsysteme GmbH, Northeim (Germany)

    2002-03-01

    Belt-conveyors have proven themselves for the continuous bulk conveying under technical and economic points of view for a long time. For long belt conveyors and big mass flows, steelcord conveyor belts technologically represent the state of the art. In a steelcord belt splice, the tensile force between the spliced belt ends is transmitted almost completely by locally differing shear forces in the rubber of the elastomer composite construction. Under the dynamically swelling load, to which the belt is exposed in operation, the splices represent the weakest part of a conveyor belt. In experimental examinations of this paper it was found, that the characteristic behavior of the material of the elastomer and the constructive design influences distortion behavior under force of steelcord belt test samples. As most important parameter of the compound design, the filler proves itself as the strongest influence on the dynamic shear modulus, which characterizes the non linear dynamic stiffness of the elastomer. The filling degree and the filler composition influence the degree of non linearity of the dynamic shear modulus and its complex components. On the basis of the results of the experimental examinations, an approximation model of the non linear dynamic shear modulus was employed, with which it is possible, to characterize the non linear, amplitude dependent material behavior of the examined elastomer. In the scope of this paper, a program system was developed on basis of the finite element method, that allows the arithmetical simulation of the force flow in steelcord belt splices and in highly stressed areas of the splices. (orig.)

  5. General Assembly

    CERN Multimedia

    Staff Association

    2016-01-01

    5th April, 2016 – Ordinary General Assembly of the Staff Association! In the first semester of each year, the Staff Association (SA) invites its members to attend and participate in the Ordinary General Assembly (OGA). This year the OGA will be held on Tuesday, April 5th 2016 from 11:00 to 12:00 in BE Auditorium, Meyrin (6-2-024). During the Ordinary General Assembly, the activity and financial reports of the SA are presented and submitted for approval to the members. This is the occasion to get a global view on the activities of the SA, its financial management, and an opportunity to express one’s opinion, including taking part in the votes. Other points are listed on the agenda, as proposed by the Staff Council. Who can vote? Only “ordinary” members (MPE) of the SA can vote. Associated members (MPA) of the SA and/or affiliated pensioners have a right to vote on those topics that are of direct interest to them. Who can give his/her opinion? The Ordinary General Asse...

  6. Splicing of phenylalanine hydroxylase (PAH) exon 11 is vulnerable - Molecular pathology of mutations in PAH exon 11

    DEFF Research Database (Denmark)

    Heintz, Caroline; Dobrowolski, Steven F.; Andersen, Henriette Skovgaard;

    2012-01-01

    molecular pathology is important. Mutations that disturb the splicing of exons (e.g. interplay between splice site strength and regulatory sequences like exon splicing enhancers (ESEs)/exon splicing silencers (ESSs)) may cause different severity of PKU. In this study, we identified PAH exon 11 as a...

  7. Perispeckles are major assembly sites for the exon junction core complex.

    Science.gov (United States)

    Daguenet, Elisabeth; Baguet, Aurélie; Degot, Sébastien; Schmidt, Ute; Alpy, Fabien; Wendling, Corinne; Spiegelhalter, Coralie; Kessler, Pascal; Rio, Marie-Christine; Le Hir, Hervé; Bertrand, Edouard; Tomasetto, Catherine

    2012-05-01

    The exon junction complex (EJC) is loaded onto mRNAs as a consequence of splicing and regulates multiple posttranscriptional events. MLN51, Magoh, Y14, and eIF4A3 form a highly stable EJC core, but where this tetrameric complex is assembled in the cell remains unclear. Here we show that EJC factors are enriched in domains that we term perispeckles and are visible as doughnuts around nuclear speckles. Fluorescence resonance energy transfer analyses and EJC assembly mutants show that perispeckles do not store free subunits, but instead are enriched for assembled cores. At the ultrastructural level, perispeckles are distinct from interchromatin granule clusters that may function as storage sites for splicing factors and intermingle with perichromatin fibrils, where nascent RNAs and active RNA Pol II are present. These results support a model in which perispeckles are major assembly sites for the tetrameric EJC core. This subnuclear territory thus represents an intermediate region important for mRNA maturation, between transcription sites and splicing factor reservoirs and assembly sites. PMID:22419818

  8. A study of lapped splices in reinforced concrete columns under severe cyclic loads

    Science.gov (United States)

    Lukose, K.; Gergely, P.; White, R. N.

    1981-07-01

    In an investigation of the behavior of overlapped reinforcing rods under high level, inelastic, reversing cyclic loads, 14 tests were conducted on column specimens with No. 6 spliced bars at the corners of surrounding No. 3 stirrups, subjected to combined bending and shear. The relationship between the splice length and the stirrup spacing was studied in detail. The most significant result is that a reasonable level of ductility in splices under combined bending and shear was achieved by providing uniformly spaced stirrups along the splice, and closely spaced stirrups just outside the high moment splice end. An equation for splice design was developed for specimens of the type tested. Experimental results are discussed in terms of load versus displacement, energy absorption, stiffness reduction, main bar strain variation, compression splice behavior and bond-shear interaction.

  9. Increased dosage of Dyrk1A alters alternative splicing factor (ASF)-regulated alternative splicing of tau in Down syndrome.

    Science.gov (United States)

    Shi, Jianhua; Zhang, Tianyi; Zhou, Chunlei; Chohan, Muhammad Omar; Gu, Xiaosong; Wegiel, Jerzy; Zhou, Jianhua; Hwang, Yu-Wen; Iqbal, Khalid; Grundke-Iqbal, Inge; Gong, Cheng-Xin; Liu, Fei

    2008-10-17

    Two groups of tau, 3R- and 4R-tau, are generated by alternative splicing of tau exon 10. Normal adult human brain expresses equal levels of them. Disruption of the physiological balance is a common feature of several tauopathies. Very early in their life, individuals with Down syndrome (DS) develop Alzheimer-type tau pathology, the molecular basis for which is not fully understood. Here, we demonstrate that Dyrk1A, a kinase encoded by a gene in the DS critical region, phosphorylates alternative splicing factor (ASF) at Ser-227, Ser-234, and Ser-238, driving it into nuclear speckles and preventing it from facilitating tau exon 10 inclusion. The increased dosage of Dyrk1A in DS brain due to trisomy of chromosome 21 correlates to an increase in 3R-tau level, which on abnormal hyperphosphorylation and aggregation of tau results in neurofibrillary degeneration. Imbalance of 3R- and 4R-tau in DS brain by Dyrk1A-induced dysregulation of alternative splicing factor-mediated alternative splicing of tau exon 10 represents a novel mechanism of neurofibrillary degeneration and may help explain early onset tauopathy in individuals with DS. PMID:18658135

  10. Versatile alignment layer method for new types of liquid crystal photonic devices

    International Nuclear Information System (INIS)

    Liquid crystal photonic devices are becoming increasingly popular. These devices often present a challenge when it comes to creating a robust alignment layer in pre-assembled cells. In this paper, we describe a method of infusing a dye into a microcavity to produce an effective photo-definable alignment layer. However, previous research on such alignment layers has shown that they have limited stability, particularly against subsequent light exposure. As such, we further describe a method of utilizing a pre-polymer, infused into the microcavity along with the liquid crystal, to provide photostability. We demonstrate that the polymer layer, formed under ultraviolet irradiation of liquid crystal cells, has been effectively localized to a thin region near the substrate surface and provides a significant improvement in the photostability of the liquid crystal alignment. This versatile alignment layer method, capable of being utilized in devices from the described microcavities to displays, offers significant promise for new photonics applications

  11. Versatile alignment layer method for new types of liquid crystal photonic devices

    Energy Technology Data Exchange (ETDEWEB)

    Finnemeyer, V.; Bryant, D.; Lu, L.; Bos, P. [Liquid Crystal Institute, Kent State University, Kent, Ohio 44242 (United States); Reich, R.; Clark, H.; Berry, S.; Bozler, C. [MIT Lincoln Laboratory, 244 Wood St., Lexington, Massachusetts 02420 (United States); Yaroshchuk, O. [Institute of Physics, NAS of Ukraine, 44 Prospect Nauky, Kyiv 03680 (Ukraine)

    2015-07-21

    Liquid crystal photonic devices are becoming increasingly popular. These devices often present a challenge when it comes to creating a robust alignment layer in pre-assembled cells. In this paper, we describe a method of infusing a dye into a microcavity to produce an effective photo-definable alignment layer. However, previous research on such alignment layers has shown that they have limited stability, particularly against subsequent light exposure. As such, we further describe a method of utilizing a pre-polymer, infused into the microcavity along with the liquid crystal, to provide photostability. We demonstrate that the polymer layer, formed under ultraviolet irradiation of liquid crystal cells, has been effectively localized to a thin region near the substrate surface and provides a significant improvement in the photostability of the liquid crystal alignment. This versatile alignment layer method, capable of being utilized in devices from the described microcavities to displays, offers significant promise for new photonics applications.

  12. Geodetic alignment of laser power installations

    International Nuclear Information System (INIS)

    Main problems occuring in applied geodesy under initial alignment of laser power installation optical channel are considered. Attention is paid to alignment of lens beamguide telescopic pairs and alignment quality control. Methods and means of geodetic measurements under alignment are indicated. Conclusions are made about the degree of working through certain aspects of the problem

  13. Adaptive Processing for Sequence Alignment

    KAUST Repository

    Zidan, Mohammed Affan

    2012-01-26

    Disclosed are various embodiments for adaptive processing for sequence alignment. In one embodiment, among others, a method includes obtaining a query sequence and a plurality of database sequences. A first portion of the plurality of database sequences is distributed to a central processing unit (CPU) and a second portion of the plurality of database sequences is distributed to a graphical processing unit (GPU) based upon a predetermined splitting ratio associated with the plurality of database sequences, where the database sequences of the first portion are shorter than the database sequences of the second portion. A first alignment score for the query sequence is determined with the CPU based upon the first portion of the plurality of database sequences and a second alignment score for the query sequence is determined with the GPU based upon the second portion of the plurality of database sequences.

  14. Strategic Alignment and New Product Development

    DEFF Research Database (Denmark)

    Acur, Nuran; Kandemir, Destan; Boer, Harry

    2012-01-01

    Strategic alignment is widely accepted as a prerequisite for a firm’s success, but insight into the role of alignment in, and its impact on, the new product evelopment (NPD) process and its performance is less well developed. Most publications on this topic either focus on one form of alignment or...... of NPD performance indicators. Strategic planning and innovativeness appear to affect technological, market, and NPD-marketing alignment positively. Environmental munificence is negatively associated with NPD-marketing alignment, but has no effect on the two other forms of alignment. Technological...... change has a positive effect on technological alignment, a negative effect on NPD-marketing alignment, but no effect on market alignment. These findings suggest that internal capabilities are more likely to be associated with the development of strategic alignment than environmental factors are...

  15. AtRTD2: A Reference Transcript Dataset for accurate quantification of alternative splicing and expression changes in Arabidopsis thaliana RNA-seq data

    KAUST Repository

    Zhang, Runxuan

    2016-05-06

    Background Alternative splicing is the major post-transcriptional mechanism by which gene expression is regulated and affects a wide range of processes and responses in most eukaryotic organisms. RNA-sequencing (RNA-seq) can generate genome-wide quantification of individual transcript isoforms to identify changes in expression and alternative splicing. RNA-seq is an essential modern tool but its ability to accurately quantify transcript isoforms depends on the diversity, completeness and quality of the transcript information. Results We have developed a new Reference Transcript Dataset for Arabidopsis (AtRTD2) for RNA-seq analysis containing over 82k non-redundant transcripts, whereby 74,194 transcripts originate from 27,667 protein-coding genes. A total of 13,524 protein-coding genes have at least one alternatively spliced transcript in AtRTD2 such that about 60% of the 22,453 protein-coding, intron-containing genes in Arabidopsis undergo alternative splicing. More than 600 putative U12 introns were identified in more than 2,000 transcripts. AtRTD2 was generated from transcript assemblies of ca. 8.5 billion pairs of reads from 285 RNA-seq data sets obtained from 129 RNA-seq libraries and merged along with the previous version, AtRTD, and Araport11 transcript assemblies. AtRTD2 increases the diversity of transcripts and through application of stringent filters represents the most extensive and accurate transcript collection for Arabidopsis to date. We have demonstrated a generally good correlation of alternative splicing ratios from RNA-seq data analysed by Salmon and experimental data from high resolution RT-PCR. However, we have observed inaccurate quantification of transcript isoforms for genes with multiple transcripts which have variation in the lengths of their UTRs. This variation is not effectively corrected in RNA-seq analysis programmes and will therefore impact RNA-seq analyses generally. To address this, we have tested different genome

  16. Topology independent protein structural alignment

    Directory of Open Access Journals (Sweden)

    DasGupta Bhaskar

    2007-10-01

    Full Text Available Abstract Background Identifying structurally similar proteins with different chain topologies can aid studies in homology modeling, protein folding, protein design, and protein evolution. These include circular permuted protein structures, and the more general cases of non-cyclic permutations between similar structures, which are related by non-topological rearrangement beyond circular permutation. We present a method based on an approximation algorithm that finds sequence-order independent structural alignments that are close to optimal. We formulate the structural alignment problem as a special case of the maximum-weight independent set problem, and solve this computationally intensive problem approximately by iteratively solving relaxations of a corresponding integer programming problem. The resulting structural alignment is sequence order independent. Our method is also insensitive to insertions, deletions, and gaps. Results Using a novel similarity score and a statistical model for significance p-value, we are able to discover previously unknown circular permuted proteins between nucleoplasmin-core protein and auxin binding protein, between aspartate rasemase and 3-dehydrogenate dehydralase, as well as between migration inhibition factor and arginine repressor which involves an additional strand-swapping. We also report the finding of non-cyclic permuted protein structures existing in nature between AML1/core binding factor and ribofalvin synthase. Our method can be used for large scale alignment of protein structures regardless of the topology. Conclusion The approximation algorithm introduced in this work can find good solutions for the problem of protein structure alignment. Furthermore, this algorithm can detect topological differences between two spatially similar protein structures. The alignment between MIF and the arginine repressor demonstrates our algorithm's ability to detect structural similarities even when spatial

  17. Heater assembly

    International Nuclear Information System (INIS)

    An electrical resistance heater, installed in the H1 borehole, is used to thermally perturb the rock mass through a controlled heating and cooling cycle. Heater power levels are controlled by a Variac power transformer and are measured by wattmeters. Temperatures are measured by thermocouples on the borehole wall and on the heater assembly. Power and temperature values are recorded by the DAS described in Chapter 12. The heater assembly consists of a 3.55-m (11.6-ft) long by 20.3-cm (8-in.) O.D., Type 304 stainless steel pipe, containing a tubular hairpin heating element. The element has a heated length of 3 m (9.84 ft). The power rating of the element is 10 kW; however, we plan to operate the unit at a maximum power of only 3 kW. The heater is positioned with its midpoint directly below the axis of the P2 borehole, as shown in the borehole configuration diagram. This heater midpoint position corresponds to a distance of approximately 8.5 m (27.9 ft) from the H1 borehole collar. A schematic of the heater assembly in the borehole is shown. The distance from the borehole collar to the closest point on the assembly (the front end) is 6.5 m (21.3 ft). A high-temperature inflatable packer, used to seal the borehole for moisture collection, is positioned 50 cm (19.7 in.) ahead of the heater front end. The heater is supported and centralized within the borehole by two skids, fabricated from 25-mm (1-in.) O.D. stainless steel pipe. Thermocouples are installed at a number of locations in the H1 borehole. Four thermocouples that are attached to the heater skin monitor temperatures on the outer surface of the can, while three thermocouples that are held in place by rock sections monitor borehole wall temperatures beneath the heater. Temperatures are also monitored at the heater terminal and on the packer hardware

  18. Assembling consumption

    DEFF Research Database (Denmark)

    Assembling Consumption marks a definitive step in the institutionalisation of qualitative business research. By gathering leading scholars and educators who study markets, marketing and consumption through the lenses of philosophy, sociology and anthropology, this book clarifies and applies the i...... societies. This is an essential reading for both seasoned scholars and advanced students of markets, economies and social forms of consumption....... the investigative tools offered by assemblage theory, actor-network theory and non-representational theory. Clear theoretical explanation and methodological innovation, alongside empirical applications of these emerging frameworks will offer readers new and refreshing perspectives on consumer culture and market...

  19. Hardware Accelerated Sequence Alignment with Traceback

    OpenAIRE

    Scott Lloyd; Snell, Quinn O

    2009-01-01

    Biological sequence alignment is an essential tool used in molecular biology and biomedical applications. The growing volume of genetic data and the complexity of sequence alignment present a challenge in obtaining alignment results in a timely manner. Known methods to accelerate alignment on reconfigurable hardware only address sequence comparison, limit the sequence length, or exhibit memory and I/O bottlenecks. A space-efficient, global sequence alignment algorithm and architecture is pres...

  20. Measurements of magnetic field alignment

    International Nuclear Information System (INIS)

    The procedure for installing Superconducting Super Collider (SSC) dipoles in their respective cryostats involves aligning the average direction of their field with the vertical to an accuracy of 0.5 mrad. The equipment developed for carrying on these measurements is described and the measurements performed on the first few prototypes SSC magnets are presented. The field angle as a function of position in these 16.6 m long magnets is a characteristic of the individual magnet with possible feedback information to its manufacturing procedure. A comparison of this vertical alignment characteristic with a magnetic field intensity (by NMR) characteristic for one of the prototypes is also presented. 5 refs., 7 figs

  1. XUV ionization of aligned molecules

    Energy Technology Data Exchange (ETDEWEB)

    Kelkensberg, F.; Siu, W.; Gademann, G. [FOM Institute AMOLF, Science Park 104, NL-1098 XG Amsterdam (Netherlands); Rouzee, A.; Vrakking, M. J. J. [FOM Institute AMOLF, Science Park 104, NL-1098 XG Amsterdam (Netherlands); Max-Born-Institut, Max-Born Strasse 2A, D-12489 Berlin (Germany); Johnsson, P. [FOM Institute AMOLF, Science Park 104, NL-1098 XG Amsterdam (Netherlands); Department of Physics, Lund University, Post Office Box 118, SE-221 00 Lund (Sweden); Lucchini, M. [Department of Physics, Politecnico di Milano, Istituto di Fotonica e Nanotecnologie CNR-IFN, Piazza Leonardo da Vinci 32, 20133 Milano (Italy); Lucchese, R. R. [Department of Chemistry, Texas A and M University, College Station, Texas 77843-3255 (United States)

    2011-11-15

    New extreme-ultraviolet (XUV) light sources such as high-order-harmonic generation (HHG) and free-electron lasers (FELs), combined with laser-induced alignment techniques, enable novel methods for making molecular movies based on measuring molecular frame photoelectron angular distributions. Experiments are presented where CO{sub 2} molecules were impulsively aligned using a near-infrared laser and ionized using femtosecond XUV pulses obtained by HHG. Measured electron angular distributions reveal contributions from four orbitals and the onset of the influence of the molecular structure.

  2. Position list word aligned hybrid

    DEFF Research Database (Denmark)

    Deliege, Francois; Pedersen, Torben Bach

    2010-01-01

    Compressed bitmap indexes are increasingly used for efficiently querying very large and complex databases. The Word Aligned Hybrid (WAH) bitmap compression scheme is commonly recognized as the most efficient compression scheme in terms of CPU efficiency. However, WAH compressed bitmaps use a lot...... of storage space. This paper presents the Position List Word Aligned Hybrid (PLWAH) compression scheme that improves significantly over WAH compression by better utilizing the available bits and new CPU instructions. For typical bit distributions, PLWAH compressed bitmaps are often half the size of WAH...

  3. Assembly of Aditya upgrade tokamak

    International Nuclear Information System (INIS)

    The existing Aditya tokamak, a medium sized tokamak with limiter configuration is being upgraded to a tokamak with divertor configuration. At present the existing ADITYA tokamak has been dismantled up to bottom plinth on which the whole assembly of toroidal field (TF) coils and vacuum vessel rested. The major components of ADITYA machine includes 20 TF coils and its structural components, 9 Ohmic coils and its clamps, 4 BV coils and its clamps as well as their busbar connections, vacuum vessel and its supports and buckling cylinder, which are all being dismantled. The re-assembly of the ADITYA Upgrade tokamak started with installation and positioning of new buckling cylinder and central solenoid (TR1) coil. After that the inner sections of TF coils are placed following which in-situ winding, installation, positioning and support mounting of two pairs of new inner divertor coils have been carried out. After securing the TF coils with top I-beams the new torus shaped vacuum vessel with circular cross-section in 2 halves have been installed. The assembly of TF structural components such as top and bottom guiding wedges, driving wedges, top and bottom compression ring, inner and outer fish plates and top inverted triangle has been carried out in an appropriate sequence. The assembly of outer sections of TF coils along with the proper placements of top auxiliary TR and vertical field coils with proper alignment and positioning with the optical metrology instrument mainly completes the reassembly. Detailed re-assembly steps and challenges faced during re-assembly will be discussed in this paper. (author)

  4. Passive micro-assembly of modular, hot embossed, polymer microfluidic devices using exact constraint design

    International Nuclear Information System (INIS)

    Low-cost microfluidic platforms have the potential to change accepted practices in many fields, including biology and medicine, in the near future. Micro-assembly of molded polymer microfluidic devices is one approach to cost-effective mass production of modular, microfluidic instruments. Polymer, passive alignment structures were used to precisely assemble molded polymer components to prevent infinitesimal motions and minimize the misalignment between assembled components and devices. The motion and constraint of the assemblies were analyzed using screw theory to identify combinations of passive alignment structures that would provide exact constraint of all degrees of freedom of the two mating parts without over-constraint. One option identified by kinematic analysis was a set of three v-groove and hemisphere-tipped pin joints, which are well known from precision engineering and suitable for microfabrication. To validate the passive alignment scheme, brass mold inserts containing alignment structures were micro-milled and used to hot emboss components in polycarbonate (PC). Dimensional and location variations of prototype alignment structures were measured to quantify the difference between the as-designed and actual dimensions and the locations of the alignment structures. The dimensional variation was 0.2–3% less than the designed dimensions and the location variation was 0.7% less. The alignment accuracy of an assembly was characterized by measuring the mismatch and vertical variation between molded alignment standards embossed on each pair of mating plates. With molded, polymer alignment structures the mean mismatch and mean vertical variation were as low as 13 ± 3 µm in the lateral plane along the x- and y-axes and −6 ± 15 µm with respect to the nominal value of 107 µm. This micro-assembly technology is applicable to the integration of all microsystems including the interconnection of microfluidic devices, the assembly of hybrid microsystems

  5. Picture languages generated by splicing and assembling til·les

    OpenAIRE

    Sagaya Mary, Anthonath Roslin

    2016-01-01

    Idiomes imatge generats per Empalme i Muntatge Rajoles. L'extensió de l'estudi de les llengües oficials sobre el cas string 2 idiomes dimensionals o idiomes imatge ha estat d'interès per molt temps per les seves vastes aplicacions. En la tesi i l'objecte de dues dimensions més comú estudiat és una imatge que és una matriu rectangular de símbols presos a partir d'un alfabet finit. L 'objectiu d'aquesta tesi se centra en l'estudi de la generació de les classes d'idiomes d'imatge per les oper...

  6. Chemical correction of pre-mRNA splicing defects associated with sequestration of muscleblind-like 1 protein by expanded r(CAG)-containing transcripts.

    Science.gov (United States)

    Kumar, Amit; Parkesh, Raman; Sznajder, Lukasz J; Childs-Disney, Jessica L; Sobczak, Krzysztof; Disney, Matthew D

    2012-03-16

    Recently, it was reported that expanded r(CAG) triplet repeats (r(CAG)(exp)) associated with untreatable neurological diseases cause pre-mRNA mis-splicing likely due to sequestration of muscleblind-like 1 (MBNL1) splicing factor. Bioactive small molecules that bind the 5'CAG/3'GAC motif found in r(CAG)(exp) hairpin structure were identified by using RNA binding studies and virtual screening/chemical similarity searching. Specifically, a benzylguanidine-containing small molecule was found to improve pre-mRNA alternative splicing of MBNL1-sensitive exons in cells expressing the toxic r(CAG)(exp). The compound was identified by first studying the binding of RNA 1 × 1 nucleotide internal loops to small molecules known to have affinity for nucleic acids. Those studies identified 4',6-diamidino-2-phenylindole (DAPI) as a specific binder to RNAs with the 5'CAG/3'GAC motif. DAPI was then used as a query molecule in a shape- and chemistry alignment-based virtual screen to identify compounds with improved properties, which identified 4-guanidinophenyl 4-guanidinobenzoate, a small molecule that improves pre-mRNA splicing defects associated with the r(CAG)(exp)-MBNL1 complex. This compound may facilitate the development of therapeutics to treat diseases caused by r(CAG)(exp) and could serve as a useful chemical tool to dissect the mechanisms of r(CAG)(exp) toxicity. The approach used in these studies, defining the small RNA motifs that bind small molecules with known affinity for nucleic acids and then using virtual screening to optimize them for bioactivity, may be generally applicable for designing small molecules that target other RNAs in the human genomic sequence. PMID:22252896

  7. General Assembly

    CERN Multimedia

    Staff Association

    2016-01-01

    Mardi 5 avril à 11 h 00 BE Auditorium Meyrin (6-2-024) Conformément aux statuts de l’Association du personnel, une Assemblée générale ordinaire est organisée une fois par année (article IV.2.1). Projet d’ordre du jour : Adoption de l’ordre du jour. Approbation du procès-verbal de l’Assemblée générale ordinaire du 5 mai 2015. Présentation et approbation du rapport d’activités 2015. Présentation et approbation du rapport financier 2015. Présentation et approbation du rapport des vérificateurs aux comptes pour 2015. Programme de travail 2016. Présentation et approbation du projet de budget 2016 Approbation du taux de cotisation pour 2017. Modifications aux Statuts de l'Association du personnel proposée. Élections des membres de la Commissio...

  8. General Assembly

    CERN Multimedia

    Staff Association

    2015-01-01

    Mardi 5 mai à 11 h 00 Salle 13-2-005 Conformément aux statuts de l’Association du personnel, une Assemblée générale ordinaire est organisée une fois par année (article IV.2.1). Projet d’ordre du jour : 1- Adoption de l’ordre du jour. 2- Approbation du procès-verbal de l’Assemblée générale ordinaire du 22 mai 2014. 3- Présentation et approbation du rapport d’activités 2014. 4- Présentation et approbation du rapport financier 2014. 5- Présentation et approbation du rapport des vérificateurs aux comptes pour 2014. 6- Programme 2015. 7- Présentation et approbation du projet de budget 2015 et taux de cotisation pour 2015. 8- Pas de modifications aux Statuts de l'Association du personnel proposée. 9- Élections des membres de la Commission é...

  9. General assembly

    CERN Multimedia

    Staff Association

    2015-01-01

    Mardi 5 mai à 11 h 00 Salle 13-2-005 Conformément aux statuts de l’Association du personnel, une Assemblée générale ordinaire est organisée une fois par année (article IV.2.1). Projet d’ordre du jour : Adoption de l’ordre du jour. Approbation du procès-verbal de l’Assemblée générale ordinaire du 22 mai 2014. Présentation et approbation du rapport d’activités 2014. Présentation et approbation du rapport financier 2014. Présentation et approbation du rapport des vérificateurs aux comptes pour 2014. Programme 2015. Présentation et approbation du projet de budget 2015 et taux de cotisation pour 2015. Pas de modifications aux Statuts de l'Association du personnel proposée. Élections des membres de la Commission électorale. &am...

  10. Fuel assembly

    International Nuclear Information System (INIS)

    The cross section of a fuel assembly is divided to a first region containing corner portions at which channel fasteners are situated and a second region not containing corner portions. The average enrichment degree of plutonium in the first region is decreased than that of the second region, and the number of fuel rods containing burnable poisons is increased at the first region than that of the second region. In the first region of the fuel assembly, the effect of moderating neutrons is enhanced since the cross section of a moderator flow channel at the outer side of the channel box is large. Therefore, local power peaking is increased in the first region while it is decreased in the second region that opposes to a narrow gap. The average enrichment degree of plutonium in the first region is decreased and that in the second region is increased by so much, to flatten the power distribution. Then, the reduction of the reactivity worth of gadolinia, as burnable poisons, can be suppressed. (N.H.)

  11. Hatch assembly

    International Nuclear Information System (INIS)

    This patent describes a nuclear reactor installation including means defining a fuel handling area and means defining a containment area separated from the fuel handling area and including a refuelling cavity; the improvement comprising: (a) a fuel transfer tube connecting the refuelling cavity with the fuel handling area; the fuel transfer tube having a first end in the fuel handling area and a second end in the refueling cavity; (b) valve means for opening and closing the first end; and (c) a hatch assembly mounted on the second end; the hatch assembly including (1) a hatch ring affixed to the fuel transfer tube at the second end the hatch ring has an integral annular seat surrounded by the hatch ring and defines a hatch opening in the second end of the fuel transfer tube; (2) a hatch cover adapts to be positioned on the annular seat for covering the hatch opening; (3) latching units are supported on the hatch ring about the hatch opening, each latching unit

  12. Fuel assembly

    International Nuclear Information System (INIS)

    The present invention concerns a fuel assembly of a BWR type reactor, and prevents aging change of flow rate of coolants leaked from a gap between a lower tie plate and a channel box. That is, in the fuel assembly, a great number of fuel rods and a plurality of water rods are bundled by a plurality of spacers, the upper and the lower ends thereof are supported by upper and lower tie plates, and they are contained in a channel box. Plate-like protrusions are disposed rotatably to the lower tie plate at a position corresponding to the lower end of the channel box. In addition, through holes are disposed on the side wall of the lower tie plate. With such a constitution, the protrusions rotate at a connection portion by hydraulic pressure of leaking coolants, and urge the channel box by the other end to control leakage of coolants. Further, since the through holes are disposed on the side wall of the lower tie plate, pressure difference is caused between the upper and the lower surfaces of the plate of the protrusion, to rotate the protrusions at the connection portion, and the other end of the protrusions presses the channel box to obtain the same effect. (I.S.)

  13. Characterization of aberrant splicing of von Willebrand factor in von Willebrand disease: an underrecognized mechanism.

    Science.gov (United States)

    Hawke, Lindsey; Bowman, Mackenzie L; Poon, Man-Chiu; Scully, Mary-Frances; Rivard, Georges-Etienne; James, Paula D

    2016-07-28

    Approximately 10% of von Willebrand factor (VWF) gene mutations are thought to alter messenger RNA (mRNA) splicing through disruption of consensus splice sites. This mechanism is likely underrecognized and affected by mutations outside consensus splice sites. During VWF synthesis, splicing abnormalities lead to qualitative defects or quantitative deficiencies in VWF. This study investigated the pathologic mechanism acting in 3 von Willebrand disease (VWD) families with putative splicing mutations using patient-derived blood outgrowth endothelial cells (BOECs) and a heterologous human embryonic kidney (HEK 293(T)) cell model. The exonic mutation c.3538G>A causes 3 in-frame splicing variants (23del, 26del, and 23/26del) which cannot bind platelets, blood coagulation factor VIII, or collagen, causing VWD through dominant-negative intracellular retention of coexpressed wild-type (WT) VWF, and increased trafficking to lysosomes. Individuals heterozygous for the c.5842+1G>C mutation produce exon 33 skipping, exons 33-34 skipping, and WT VWF transcripts. Pathogenic intracellular retention of VWF lacking exons 33-34 causes their VWD. The branch site mutation c.6599-20A>T causes type 1 VWD through mRNA degradation of exon 38 skipping transcripts. Splicing ratios of aberrant transcripts and coexpressed WT were altered in the BOECs with exposure to shear stress. This study provides evidence of mutations outside consensus splice sites disrupting splicing and introduces the concept that VWF splicing is affected by shear stress on endothelial cells. PMID:27317792

  14. Footprints of a trypanosomatid RNA world: pre-small subunit rRNA processing by spliced leader addition trans-splicing

    Directory of Open Access Journals (Sweden)

    Mario Gustavo Mayer

    2012-06-01

    Full Text Available The addition of a capped mini-exon [spliced leader (SL] through trans-splicing is essential for the maturation of RNA polymerase (pol II-transcribed polycistronic pre-mRNAs in all members of the Trypanosomatidae family. This process is an inter-molecular splicing reaction that follows the same basic rules of cis-splicing reactions. In this study, we demonstrated that mini-exons were added to precursor ribosomal RNA (pre-rRNA are transcribed by RNA pol I, including the 5' external transcribed spacer (ETS region. Additionally, we detected the SL-5'ETS molecule using three distinct methods and located the acceptor site between two known 5'ETS rRNA processing sites (A' and A1 in four different trypanosomatids. Moreover, we detected a polyadenylated 5'ETS upstream of the trans-splicing acceptor site, which also occurs in pre-mRNA trans-splicing. After treatment with an indirect trans-splicing inhibitor (sinefungin, we observed SL-5'ETS decay. However, treatment with 5-fluorouracil (a precursor of RNA synthesis that inhibits the degradation of pre-rRNA led to the accumulation of SL-5'ETS, suggesting that the molecule may play a role in rRNA degradation. The detection of trans-splicing in these molecules may indicate broad RNA-joining properties, regardless of the polymerase used for transcription.

  15. Incorporating evolutionary information and functional domains for identifying RNA splicing factors in humans.

    Directory of Open Access Journals (Sweden)

    Justin Bo-Kai Hsu

    Full Text Available Regulation of pre-mRNA splicing is achieved through the interaction of RNA sequence elements and a variety of RNA-splicing related proteins (splicing factors. The splicing machinery in humans is not yet fully elucidated, partly because splicing factors in humans have not been exhaustively identified. Furthermore, experimental methods for splicing factor identification are time-consuming and lab-intensive. Although many computational methods have been proposed for the identification of RNA-binding proteins, there exists no development that focuses on the identification of RNA-splicing related proteins so far. Therefore, we are motivated to design a method that focuses on the identification of human splicing factors using experimentally verified splicing factors. The investigation of amino acid composition reveals that there are remarkable differences between splicing factors and non-splicing proteins. A support vector machine (SVM is utilized to construct a predictive model, and the five-fold cross-validation evaluation indicates that the SVM model trained with amino acid composition could provide a promising accuracy (80.22%. Another basic feature, amino acid dipeptide composition, is also examined to yield a similar predictive performance to amino acid composition. In addition, this work presents that the incorporation of evolutionary information and domain information could improve the predictive performance. The constructed models have been demonstrated to effectively classify (73.65% accuracy an independent data set of human splicing factors. The result of independent testing indicates that in silico identification could be a feasible means of conducting preliminary analyses of splicing factors and significantly reducing the number of potential targets that require further in vivo or in vitro confirmation.

  16. Alignment induced aberration fields of next generation telescopes

    Science.gov (United States)

    Schmid, Tobias; Thompson, Kevin; Rolland, Jannick

    2008-08-01

    There is a long list of new ground-based optical telescopes being considered around the world. While many are conventional Cassegrain and Ritchey-Chretien designs, some are from a family of three mirror anastigmatic (TMA) telescopes that are configured with an offset field (but still obscured) that trace back to designs developed in the 1970s for military applications. The nodal theory of aberrations, developed in the late 1970s, provides valuable insights into the response of TMA telescopes to alignment errors. Here it is shown for the first time that the alignment limiting aberration in any TMA telescope is a 3rd order astigmatism term with a new field dependence, termed field-asymmetric, field-linear 3rd order astigmatism. It is also shown that a TMA telescope under assembly that is only measured to have excellent/perfect performance onaxis is not aligned in any significant way. This is because the new astigmatic term is always zero on-axis, even though it is large over the field of view. Knowledge of this intrinsic misalignment aberration field for any TMA telescope aids greatly in ensuring it can be aligned successfully. The James Webb Space Telescope (JWST), is used an example of a relevant TMA system.

  17. Aligned natural inflation with modulations

    Science.gov (United States)

    Choi, Kiwoon; Kim, Hyungjin

    2016-08-01

    The weak gravity conjecture applied for the aligned natural inflation indicates that generically there can be a modulation of the inflaton potential, with a period determined by sub-Planckian axion scale. We study the oscillations in the primordial power spectrum induced by such modulation, and discuss the resulting observational constraints on the model.

  18. Aligned natural inflation with modulations

    CERN Document Server

    Choi, Kiwoon

    2015-01-01

    The weak gravity conjecture applied for the aligned natural inflation indicates that generically there can be a modulation of the inflaton potential, with a period determined by sub-Planckian axion scale. We study the oscillations in the primordial power spectrum induced by such modulation, and discuss the resulting observational constraints on the model.

  19. Aligned natural inflation with modulations

    Directory of Open Access Journals (Sweden)

    Kiwoon Choi

    2016-08-01

    Full Text Available The weak gravity conjecture applied for the aligned natural inflation indicates that generically there can be a modulation of the inflaton potential, with a period determined by sub-Planckian axion scale. We study the oscillations in the primordial power spectrum induced by such modulation, and discuss the resulting observational constraints on the model.

  20. Aligned natural inflation with modulations

    OpenAIRE

    Kiwoon Choi; Hyungjin Kim

    2016-01-01

    The weak gravity conjecture applied for the aligned natural inflation indicates that generically there can be a modulation of the inflaton potential, with a period determined by sub-Planckian axion scale. We study the oscillations in the primordial power spectrum induced by such modulation, and discuss the resulting observational constraints on the model.

  1. Alternative Splicing of G9a Regulates Neuronal Differentiation

    OpenAIRE

    Ana Fiszbein; Luciana E. Giono; Ana Quaglino; Bruno G. Berardino; Lorena Sigaut; Catalina von Bilderling; Ignacio E. Schor; Juliana H. Enriqué Steinberg; Mario Rossi; Lía I. Pietrasanta; Julio J. Caramelo; Anabella Srebrow; Alberto R. Kornblihtt

    2016-01-01

    Chromatin modifications are critical for the establishment and maintenance of differentiation programs. G9a, the enzyme responsible for histone H3 lysine 9 dimethylation in mammalian euchromatin, exists as two isoforms with differential inclusion of exon 10 (E10) through alternative splicing. We find that the G9a methyltransferase is required for differentiation of the mouse neuronal cell line N2a and that E10 inclusion increases during neuronal differentiation of cultured cells, as well as i...

  2. A General Definition and Nomenclature for Alternative Splicing Events

    OpenAIRE

    Guigó Serra, Roderic; Sammeth, Michael; Foissac, Sylvain

    2008-01-01

    Understanding the molecular mechanisms responsible for the regulation of the transcriptome present in eukaryotic cells is one of the most challenging tasks in the postgenomic era. In this regard, alternative splicing (AS) is a key phenomenon contributing to the production of different mature transcripts from the same primary RNA sequence. As a plethora of different transcript forms is available in databases, a first step to uncover the biology that drives AS is to identify the dif...

  3. Oncogenes and RNA splicing of human tumor viruses

    OpenAIRE

    Ajiro, Masahiko; Zheng, Zhi-Ming

    2014-01-01

    Approximately 10.8% of human cancers are associated with infection by an oncogenic virus. These viruses include human papillomavirus (HPV), Epstein–Barr virus (EBV), Merkel cell polyomavirus (MCV), human T-cell leukemia virus 1 (HTLV-1), Kaposi's sarcoma-associated herpesvirus (KSHV), hepatitis C virus (HCV) and hepatitis B virus (HBV). These oncogenic viruses, with the exception of HCV, require the host RNA splicing machinery in order to exercise their oncogenic activities, a strategy that a...

  4. BRR2a Affects Flowering Time via FLC Splicing

    OpenAIRE

    Mahrez, Walid; Shin, Juhyun; Muñoz-Viana, Rafael; Figueiredo, Duarte D.; Trejo-Arellano, Minerva S.; Exner, Vivien; Siretskiy, Alexey; Gruissem, Wilhelm; Köhler, Claudia; Hennig, Lars

    2016-01-01

    Several pathways control time to flowering in Arabidopsis thaliana through transcriptional and posttranscriptional gene regulation. In recent years, mRNA processing has gained interest as a critical regulator of flowering time control in plants. However, the molecular mechanisms linking RNA splicing to flowering time are not well understood. In a screen for Arabidopsis early flowering mutants we identified an allele of BRR2a. BRR2 proteins are components of the spliceosome and highly conserve...

  5. Security controls in the Stockpoint Logistics Integrated Communications Environment (SPLICE)

    Science.gov (United States)

    Arseneault, D. S.

    1985-03-01

    This thesis examines security controls specified and implemented in the Stock Point Logistics Integrated Communications Environment (SPLICE) project. Controls provided by the Defense Data Network and the Tandem operating system are reviewed. Alternatives from current literature in areas of authentication, encryption, and dial-port protection are reviewed for the purpose of suggesting enhancements. Issues discussed apply to most interactive/decentralized systems in operation today and include administrative as well as technical recommendations.

  6. Estimation of alternative splicing variability in human populations

    OpenAIRE

    Gonz??lez-Porta, Mar; Calvo, Miquel; Sammeth, Michael; Guig?? Serra, Roderic

    2012-01-01

    DNA arrays have been widely used to perform transcriptome-wide analysis of gene expression, and many methods have been developed to measure gene expression variability and to compare gene expression between conditions. Because RNA-seq is also becoming increasingly popular for transcriptome characterization, the possibility exists for further quantification of individual alternative transcript isoforms, and therefore for estimating the relative ratios of alternative splice forms within a given...

  7. Grain Alignment and CMB Polarization Studies

    CERN Document Server

    Lazarian, A

    2008-01-01

    Polarized microwave emission from dust is an important foreground that may contaminate polarized CMB studies unless carefully accounted for. Modeling of polarization from dust requires a quantitative understanding of grain alignment. I review the current status of grain alignment theory outlining recent advances in quantitative description of the alignment. In particular, I show that the grain-alignment theory is a predictive one, and its results nicely match observations. Those indicate that the most important process of alignment is related to radiative torques acting on irregular grains. The recently developed analytical model of radiative torque alignment has proven to be a very efficient tool for predicting the degree of grain alignment. We expect the alignment theory to further mature before CMBPol flight, which would ensure a better accounting for the dust-related polarization. At the same time, CMBPol should provide the additional testing of grain alignment, clarifying the reliability of polarimetry f...

  8. Nanoscale Assembly Using DNA and Electromagnetic Fields

    OpenAIRE

    Eskelinen, Antti-Pekka

    2013-01-01

    In this work we demonstrate the control of nanoparticles and nanostructures with the help of the DNA origami method and dielectrophoresis. DNA nanotechnology is a subfield of nanotechnology where DNA is used as a construction material. The DNA origami method is a recent development in the field which enables the assembly of nanoparticles with nanometer scale accuracy through self-assembly. Here we take advantage of the method for efficient deposition and alignment of single-walled carbon nanotub...

  9. Co-localisation studies of Arabidopsis SR splicing factors reveal different types of speckles in plant cell nuclei

    International Nuclear Information System (INIS)

    SR proteins are multidomain splicing factors which are important for spliceosome assembly and for regulation of alternative splicing. In mammalian nuclei these proteins localise to speckles from where they are recruited to transcription sites. By using fluorescent protein fusion technology and different experimental approaches it has been shown that Arabidopsis SR proteins, in addition to diffuse nucleoplasmic staining, localise into an irregular nucleoplasmic network resembling speckles in mammalian cells. As Arabidopsis SR proteins fall into seven conserved sub-families we investigated co-localisation of members of the different sub-families in transiently transformed tobacco protoplast. Here we demonstrate the new finding that members of different SR protein sub-families localise into distinct populations of nuclear speckles with no, partial or complete co-localisation. This is particularly interesting as we also show that these proteins do interact in a yeast two-hybrid assay as well as in pull-down and in co-immunopreciptiation assays. Our data raise the interesting possibility that SR proteins are partitioned into distinct populations of nuclear speckles to allow a more specific recruitment to the transcription/pre-mRNA processing sites of particular genes depending on cell type and developmental stage

  10. Using intron splicing trick for preferential gene expression in transduced cells: an approach for suicide gene therapy.

    Science.gov (United States)

    Pourzadegan, F; Shariati, L; Taghizadeh, R; Khanahmad, H; Mohammadi, Z; Tabatabaiefar, M A

    2016-01-01

    Suicide gene therapy is one of the most innovative approaches in which a potential toxic gene is delivered to the targeted cancer cell by different target delivery methods. We constructed a transfer vector to express green fluorescent protein (GFP) in transduced cells but not in packaging cells. We placed gfp under the control of the cytomegalovirus (CMV) promoter, which is positioned between the two long-terminal repeats in reverse direction. The intron-2 sequence of the human beta globin gene with two poly-A signals and several stop codons on the antisense strand was placed on the leading strand between the CMV promoter and gfp. For lentiviral production, the HEK293T and line were co-transfected with the PMD2G, psPAX2 and pLentiGFP-Ins2 plasmids. The HEK293T and line were transduced with this virus. PCR was performed for evaluation of intron splicing in transduced cells. The GFP expression was seen in 65% of the cells transduced. The PCR amplification of the genomic DNA of transduced cells confirmed the splicing of intron 2. The strategy is significant to accomplish our goal for preserving the packaging cells from the toxic gene expression during viral assembly and the resultant reduction in viral titration. Also it serves to address several other issues in the gene therapy. PMID:26679755

  11. Involvement of Alternative Splicing in Barley Seed Germination.

    Directory of Open Access Journals (Sweden)

    Qisen Zhang

    Full Text Available Seed germination activates many new biological processes including DNA, membrane and mitochondrial repairs and requires active protein synthesis and sufficient energy supply. Alternative splicing (AS regulates many cellular processes including cell differentiation and environmental adaptations. However, limited information is available on the regulation of seed germination at post-transcriptional levels. We have conducted RNA-sequencing experiments to dissect AS events in barley seed germination. We identified between 552 and 669 common AS transcripts in germinating barley embryos from four barley varieties (Hordeum vulgare L. Bass, Baudin, Harrington and Stirling. Alternative 3' splicing (34%-45%, intron retention (32%-34% and alternative 5' splicing (16%-21% were three major AS events in germinating embryos. The AS transcripts were predominantly mapped onto ribosome, RNA transport machineries, spliceosome, plant hormone signal transduction, glycolysis, sugar and carbon metabolism pathways. Transcripts of these genes were also very abundant in the early stage of seed germination. Correlation analysis of gene expression showed that AS hormone responsive transcripts could also be co-expressed with genes responsible for protein biosynthesis and sugar metabolisms. Our RNA-sequencing data revealed that AS could play important roles in barley seed germination.

  12. APPRIS: annotation of principal and alternative splice isoforms.

    Science.gov (United States)

    Rodriguez, Jose Manuel; Maietta, Paolo; Ezkurdia, Iakes; Pietrelli, Alessandro; Wesselink, Jan-Jaap; Lopez, Gonzalo; Valencia, Alfonso; Tress, Michael L

    2013-01-01

    Here, we present APPRIS (http://appris.bioinfo.cnio.es), a database that houses annotations of human splice isoforms. APPRIS has been designed to provide value to manual annotations of the human genome by adding reliable protein structural and functional data and information from cross-species conservation. The visual representation of the annotations provided by APPRIS for each gene allows annotators and researchers alike to easily identify functional changes brought about by splicing events. In addition to collecting, integrating and analyzing reliable predictions of the effect of splicing events, APPRIS also selects a single reference sequence for each gene, here termed the principal isoform, based on the annotations of structure, function and conservation for each transcript. APPRIS identifies a principal isoform for 85% of the protein-coding genes in the GENCODE 7 release for ENSEMBL. Analysis of the APPRIS data shows that at least 70% of the alternative (non-principal) variants would lose important functional or structural information relative to the principal isoform. PMID:23161672

  13. Alternative Splicing of G9a Regulates Neuronal Differentiation.

    Science.gov (United States)

    Fiszbein, Ana; Giono, Luciana E; Quaglino, Ana; Berardino, Bruno G; Sigaut, Lorena; von Bilderling, Catalina; Schor, Ignacio E; Steinberg, Juliana H Enriqué; Rossi, Mario; Pietrasanta, Lía I; Caramelo, Julio J; Srebrow, Anabella; Kornblihtt, Alberto R

    2016-03-29

    Chromatin modifications are critical for the establishment and maintenance of differentiation programs. G9a, the enzyme responsible for histone H3 lysine 9 dimethylation in mammalian euchromatin, exists as two isoforms with differential inclusion of exon 10 (E10) through alternative splicing. We find that the G9a methyltransferase is required for differentiation of the mouse neuronal cell line N2a and that E10 inclusion increases during neuronal differentiation of cultured cells, as well as in the developing mouse brain. Although E10 inclusion greatly stimulates overall H3K9me2 levels, it does not affect G9a catalytic activity. Instead, E10 increases G9a nuclear localization. We show that the G9a E10(+) isoform is necessary for neuron differentiation and regulates the alternative splicing pattern of its own pre-mRNA, enhancing E10 inclusion. Overall, our findings indicate that by regulating its own alternative splicing, G9a promotes neuron differentiation and creates a positive feedback loop that reinforces cellular commitment to differentiation. PMID:26997278

  14. Alternative Splicing of G9a Regulates Neuronal Differentiation

    Directory of Open Access Journals (Sweden)

    Ana Fiszbein

    2016-03-01

    Full Text Available Chromatin modifications are critical for the establishment and maintenance of differentiation programs. G9a, the enzyme responsible for histone H3 lysine 9 dimethylation in mammalian euchromatin, exists as two isoforms with differential inclusion of exon 10 (E10 through alternative splicing. We find that the G9a methyltransferase is required for differentiation of the mouse neuronal cell line N2a and that E10 inclusion increases during neuronal differentiation of cultured cells, as well as in the developing mouse brain. Although E10 inclusion greatly stimulates overall H3K9me2 levels, it does not affect G9a catalytic activity. Instead, E10 increases G9a nuclear localization. We show that the G9a E10+ isoform is necessary for neuron differentiation and regulates the alternative splicing pattern of its own pre-mRNA, enhancing E10 inclusion. Overall, our findings indicate that by regulating its own alternative splicing, G9a promotes neuron differentiation and creates a positive feedback loop that reinforces cellular commitment to differentiation.

  15. A Network of Splice Isoforms for the Mouse.

    Science.gov (United States)

    Li, Hong-Dong; Menon, Rajasree; Eksi, Ridvan; Guerler, Aysam; Zhang, Yang; Omenn, Gilbert S; Guan, Yuanfang

    2016-01-01

    The laboratory mouse is the primary mammalian species used for studying alternative splicing events. Recent studies have generated computational models to predict functions for splice isoforms in the mouse. However, the functional relationship network, describing the probability of splice isoforms participating in the same biological process or pathway, has not yet been studied in the mouse. Here we describe a rich genome-wide resource of mouse networks at the isoform level, which was generated using a unique framework that was originally developed to infer isoform functions. This network was built through integrating heterogeneous genomic and protein data, including RNA-seq, exon array, protein docking and pseudo-amino acid composition. Through simulation and cross-validation studies, we demonstrated the accuracy of the algorithm in predicting isoform-level functional relationships. We showed that this network enables the users to reveal functional differences of the isoforms of the same gene, as illustrated by literature evidence with Anxa6 (annexin a6) as an example. We expect this work will become a useful resource for the mouse genetics community to understand gene functions. The network is publicly available at: http://guanlab.ccmb.med.umich.edu/isoformnetwork. PMID:27079421

  16. Diverse splicing patterns of exonized Alu elements in human tissues.

    Directory of Open Access Journals (Sweden)

    Lan Lin

    Full Text Available Exonization of Alu elements is a major mechanism for birth of new exons in primate genomes. Prior analyses of expressed sequence tags show that almost all Alu-derived exons are alternatively spliced, and the vast majority of these exons have low transcript inclusion levels. In this work, we provide genomic and experimental evidence for diverse splicing patterns of exonized Alu elements in human tissues. Using Exon array data of 330 Alu-derived exons in 11 human tissues and detailed RT-PCR analyses of 38 exons, we show that some Alu-derived exons are constitutively spliced in a broad range of human tissues, and some display strong tissue-specific switch in their transcript inclusion levels. Most of such exons are derived from ancient Alu elements in the genome. In SEPN1, mutations of which are linked to a form of congenital muscular dystrophy, the muscle-specific inclusion of an Alu-derived exon may be important for regulating SEPN1 activity in muscle. Realtime qPCR analysis of this SEPN1 exon in macaque and chimpanzee tissues indicates human-specific increase in its transcript inclusion level and muscle specificity after the divergence of humans and chimpanzees. Our results imply that some Alu exonization events may have acquired adaptive benefits during the evolution of primate transcriptomes.

  17. Detection of Splice Sites Using Support Vector Machine

    Science.gov (United States)

    Varadwaj, Pritish; Purohit, Neetesh; Arora, Bhumika

    Automatic identification and annotation of exon and intron region of gene, from DNA sequences has been an important research area in field of computational biology. Several approaches viz. Hidden Markov Model (HMM), Artificial Intelligence (AI) based machine learning and Digital Signal Processing (DSP) techniques have extensively and independently been used by various researchers to cater this challenging task. In this work, we propose a Support Vector Machine based kernel learning approach for detection of splice sites (the exon-intron boundary) in a gene. Electron-Ion Interaction Potential (EIIP) values of nucleotides have been used for mapping character sequences to corresponding numeric sequences. Radial Basis Function (RBF) SVM kernel is trained using EIIP numeric sequences. Furthermore this was tested on test gene dataset for detection of splice site by window (of 12 residues) shifting. Optimum values of window size, various important parameters of SVM kernel have been optimized for a better accuracy. Receiver Operating Characteristic (ROC) curves have been utilized for displaying the sensitivity rate of the classifier and results showed 94.82% accuracy for splice site detection on test dataset.

  18. Fuel assembly

    International Nuclear Information System (INIS)

    A fuel assembly of a BWR type reactor comprises a rectangular parallelopiped channel box and fuel bundles contained in the channel box. The fuel bundle comprises an upper tie plate, a lower tie plate, a plurality of spacers a plurality of fuel rods and a water rod. In each fuel rod, the amount of fission products is reduced at upper and lower end regions of an effective fuel portion than that in other regions of the effective fuel region. In a portion of the fuel rods, fuel pellets containing burnable poisons are disposed at the upper and lower end regions. In addition, the upper and lower portions are constituted with natural uranium. Each of the upper and lower end regions is not greater than 15% of the effective fuel length. Since this can enhance reactivity control effect without worsening fuel economy, the control amount for excess reactivity upon long-term cycle operation can be increased. (I.N.)

  19. Apparatus and method for assembling fuel elements

    International Nuclear Information System (INIS)

    A nuclear fuel element assembling method and apparatus is preferably operable under programmed control unit to receive fuel rods from storage, arrange them into axially aligned stacks of closely monitored length, and transfer the stacks of fuel rods to a loading device for insertion into longitudinal passages in the fuel elements. In order to handle large numbers of one or more classifications of fuel rods or other cylindrical parts, the assembling apparatus includes at least two feed troughs each formed by a pair of screw members with a movable table having a plurality of stacking troughs for alignment with the feed troughs and with a conveyor for delivering the stacks to the loading device, the fuel rods being moved along the stacking troughs upon a fluid cushion. 23 claims, 6 figures

  20. Photo polymerization-induced vertical phase separation and homeotropic alignment in liquid crystal and polymer mixtures

    International Nuclear Information System (INIS)

    We presented a novel method for the homeotropic alignment of LC by using the irradiation of UV light on the LC/NOA65 mixture cell, in which the photo-initiated-polymerization-induced phase separation lowers the surface energy. When the amount of polymer content is sufficiently small, the gravel and network patterns were formed at the substrates via the vertical phase separation. We found that surface roughness plays an important role in the formation of the homeotropic alignment of LC. We also observed the alignment transition of the cells by varying the mixing ratio of LC/NOA65 or the UV radiation time. Furthermore, the present proposed method has great potential for application in display devices. For decades, studies on the alignment of liquid crystal (LC) molecules have been of significant interest due to their immediate applications for display devices and the intriguing physiochemical properties they exhibit at the surface of mixtures. Usually, homeotropic (or vertical) alignment, in which the long axes of the LC molecules are oriented in a direction perpendicular to the surface, is achieved by using surfactants such as lecithin, silanes or polyimide. Recently homeotropic alignment of liquid crystal molecules was achieved by irradiating photosensitive polymers, by doping nanoparticles into LC, by utilizing nano/micro patterns, or by incorporating self-assembled monolayers (SAMs). However, a clear understanding about the alignment mechanism is still elusive. In this paper, we report a novel method for homeotropic alignment of LC by utilizing the phase separation of LC/polymer mixtures