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Sample records for tension splice connector

  1. 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.

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

    International Nuclear Information System (INIS)

    Wang, Jy-An John; Lara-Curzio, Edgar; King Jr, Thomas J.; Graziano, Joe; Chan, John; Goodwin, Tip

    2009-01-01

    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

  3. Performance of Grouted Splice Sleeve Connector under Tensile Load

    Directory of Open Access Journals (Sweden)

    A. Alias

    2016-05-01

    Full Text Available The grouted splice sleeve connector system takes advantage of the bond-slip resistance of the grout and the mechanical gripping of reinforcement bars to provide resistance to tensile force. In this system, grout acts as a load-transferring medium and bonding material between the bars and sleeve. This study adopted the end-to-end rebars connection method to investigate the effect of development length and sleeve diameter on the bonding performance of the sleeve connector. The end-to-end method refers to the condition where reinforcement bars are inserted into the sleeve from both ends and meet at the centre before grout is filled. Eight specimens of grouted splice sleeve connector were tested under tensile load to determine their performance. The sleeve connector was designed using 5 mm thick circular hollow section (CHS steel pipe and consisted of one external and two internal sleeves. The tensile test results show that connectors with a smaller external and internal sleeve diameter appear to provide better bonding performance. Three types of failure were observed in this research, which are bar fracture (outside the sleeve, bar pullout, and internal sleeve pullout. With reference to these failure types, the development length of 200 mm is the optimum value due to its bar fracture type, which indicates that the tensile capacity of the connector is higher than the reinforcement bar. It is found that the performance of the grouted splice sleeve connector is influenced by the development length of the reinforcement bar and the diameter of the sleeve.

  4. The Lifetime Estimate for ACSR Single-Stage Splice Connector Operating at Higher Temperatures

    International Nuclear Information System (INIS)

    Wang, Jy-An John; Graziano, Joe; Chan, John

    2011-01-01

    This paper is the continuation of Part I effort to develop 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.1The Part II efforts are mainly focused on the thermal mechanical testing, thermal-cycling simulation and its impact on the effective lifetime of the SSC system. 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.

  5. Effect of tension lap splice on the behavior of high strength concrete (HSC beams

    Directory of Open Access Journals (Sweden)

    Ahmed El-Azab

    2014-12-01

    Full Text Available In the recent years, many research efforts have been carried out on the bond strength between normal strength concrete (NSC and reinforcing bars spliced in tension zones in beams. Many codes gave a minimum splice length for tension and compression reinforcement as a factor of the bar diameter depending on many parameters such as concrete strength, steel yield stress, shape of bar end, shape of bar surface and also bar location. Also, codes gave another restriction about the percentage of total reinforcement to be spliced at the same time. Comparatively limited attention has been directed toward the bond between high strength concrete (HSC and reinforcing bars spliced in tension zones in beams. HSC has high modulus of elasticity, high density and long-term durability. This research presents an experimental study on the bond between high strength concrete (HSC and reinforcing bars spliced in tension zones in beams. It reports the influence of several parameters on bond in splices. The parameters covered are casting position, splice length as a factor of bar diameter, bar diameter and reinforcement ratio. The research involved tests on sixteen simply-supported beams of 1800 mm span, 200 mm width and 400 mm thickness made of HSC. In each beam, the total tensile steel bars were spliced in the constant moment zone. Crack pattern, crack propagation, cracking load, failure load and mi span deflection were recorded and analyzed to study the mentioned parameters effect.

  6. IE Information No. 86-104: Unqualified butt splice connectors identified in qualified penetrations

    International Nuclear Information System (INIS)

    Jordan, E.L.

    1992-01-01

    During an NRC equipment qualification (EQ) inspection at Dresden Nuclear Power Station, May 19--23, 1986, a deficiency was discovered concerning a lack of similarity between tested and installed nylon insulated butt splices in EQ qualified GE electrical penetrations. commonwealth Edison sent four sample splices removed from Quad Cities Nuclear Power Station to Wyle Laboratory to further substantiate their qualification for use in a harsh environment. These splices were identical to those installed at Dresden. During the testing performed at Wyle Laboratory December 4--5, 1986, all four samples exhibited excessive leakage currents to ground when exposed to a steam environment. Commonwealth Edison consequently declared the splices unqualified and shut down its Quad Cities Unit 1 to rework the splices by wrapping them with previously qualified tape. Dresden Unit 2 has similarly reworked the splices by wrapping them with tape. Duane Arnold Energy Center also has commenced a shutdown in order to make repairs. The short circuits that occurred appeared to start by condensation entering the splice between the wire insulation and the nylon tubing. The arcing caused insulation degradation that then allowed arcs to pass through the insulation to the enclosure

  7. Post-tensioning and splicing of precast/prestressed bridge beams to extend spans

    Science.gov (United States)

    Collett, Brandon S.; Saliba, Joseph E.

    2002-06-01

    This paper explores the status and techniques of post-tensioning and splicing precast concrete I-beams in bridge applications. It will look at the current practices that have been used in the United States and comment on the advantages of these techniques. Representative projects are presented to demonstrate the application and success of specific methods used. To demonstrate the benefits of using post-tensioning and splicing to extend spans, multiple analysis of simple span post-tensioned I-beams were performed varying such characteristics as beam spacing, beam sections, beam depth and concrete strength. Tables were then developed to compare the maximum span length of a prestressed I-beam versus a one segment or a spliced three segment post-tensioned I-beam. The lateral stability of the beam during fabrication, transportation and erection is also examined and discussed. These tables are intended to aid designers and owners in preliminary project studies to determine if post-tensioning can be beneficial to their situation. AASHTO Standard Specifications(2) will be used as basic guidelines and specifications. In many cases, post-tensioning was found to extend the maximum span length of a typical 72-inch precast I-beam more than 40 feet over conventional prestress.

  8. Flexible connector

    Science.gov (United States)

    Savage, Mark E.; Simpson, Walter W.

    1999-01-01

    An electrical connector accommodates high current, is not labor intensive to assemble and disassemble, and allows a wide range of motion to accommodate mechanical variations and movement of connected components. The connector comprises several parts with joints therebetween, wherein each joint provides electrical connection between and allows relative motion of the joined parts. The combination of parts and joints maintains electrical connection between two electrical components even if the components are misaligned or move after connection.

  9. CareerConnector

    Data.gov (United States)

    US Agency for International Development — CareerConnector is USAID's premiere recruiting tool. It is powered by Monster and integrated with www.usajobs.gov. CareerConnector tracks the progression of a...

  10. Remote connector development study

    International Nuclear Information System (INIS)

    Parazin, R.J.

    1995-05-01

    Plutonium-uranium extraction (PUREX) connectors, the most common connectors used at the Hanford site, offer a certain level of flexibility in pipe routing, process system configuration, and remote equipment/instrument replacement. However, these desirable features have inherent shortcomings like leakage, high pressure drop through the right angle bends, and a limited range of available pipe diameters that can be connect by them. Costs for construction, maintenance, and operation of PUREX connectors seem to be very high. The PUREX connector designs include a 90 degree bend in each connector. This increases the pressure drop and erosion effects. Thus, each jumper requires at least two 90 degree bends. PUREX connectors have not been practically used beyond 100 (4 in.) inner diameter. This study represents the results of a survey on the use of remote pipe-connection systems in US and foreign plants. This study also describes the interdependence between connectors, remote handling equipment, and the necessary skills of the operators

  11. Seismic retrofit of spliced sleeve connections for precast bridge piers.

    Science.gov (United States)

    2017-03-01

    Grouted Splice Sleeve (GSS) connectors are being considered for connecting bridge columns, footings, and pier caps in Accelerated Bridge Construction (ABC). A repair technique for precast reinforced concrete bridge column-to-footing and column-to-pie...

  12. Modular Connector Keying Concept

    Science.gov (United States)

    Ishman, Scott; Dukes, Scott; Warnica, Gary; Conrad, Guy; Senigla, Steven

    2013-01-01

    For panel-mount-type connectors, keying is usually "built-in" to the connector body, necessitating different part numbers for each key arrangement. This is costly for jobs that require small quantities. This invention was driven to provide a cost savings and to reduce documentation of individual parts. The keys are removable and configurable in up to 16 combinations. Since the key parts are separate from the connector body, a common design can be used for the plug, receptacle, and key parts. The keying can then be set at the next higher assembly.

  13. Jumper connector analysis

    Science.gov (United States)

    Kanjilal, S. K.; Lindquist, M. R.; Ulbricht, L. E.

    1994-02-01

    Jumper connectors are used for remotely connecting pipe lines containing transfer fluids ranging from hazardous chemicals to other nonhazardous liquids. The jumper connector assembly comprises hooks, hookpins, a block, a nozzle, an operating screw, and a nut. The hooks are tightened against the nozzle flanges by the operating screw that is tightened with a remotely connected torque wrench. Stress analysis for the jumper connector assembly (used extensively on the US Department of Energy's Hanford Site, near Richland, Washington) is performed by using hand calculation and finite-element techniques to determine the stress levels resulting from operating and seismic loads on components of the assembly. The analysis addresses loading conditions such as prestress, seismic, operating, thermal, and leakage. The preload torque-generated forces at which each component reaches its stress limits are presented in a tabulated format. Allowable operating loads for the jumper assembly are provided to prevent leakage of the assembly during operating cycles.

  14. Flat-port connectors

    KAUST Repository

    Alrashed, Mohammed

    2017-05-26

    Disclosed are various embodiments for connectors used with electronic devices, such as input and/or output ports to connect peripheral equipment or accessories. More specifically, various flat-port are provided that can be used in place of standard connectors including, but not limited to, audio jacks and Universal Serial Bus (USB) ports. The flat-port connectors are an alternate connection design to replace the traditional receptacle port (female-port), making the device more sealed creation more dust and water resistant. It is unique in the way of using the outer surfaces of the device for the electrical connection between the ports. Flat-port design can allow the manufacture of extremely thin devices by eliminating the side ports slots that take a lot of space and contribute to the increase thickness of the device. The flat-port receptacle improves the overall appearance of the device and makes it more resistant to dust and water.

  15. Fiber optic connector

    Science.gov (United States)

    Rajic, Slobodan; Muhs, Jeffrey D.

    1996-01-01

    A fiber optic connector and method for connecting composite materials within which optical fibers are imbedded. The fiber optic connector includes a capillary tube for receiving optical fibers at opposing ends. The method involves inserting a first optical fiber into the capillary tube and imbedding the unit in the end of a softened composite material. The capillary tube is injected with a coupling medium which subsequently solidifies. The composite material is machined to a desired configuration. An external optical fiber is then inserted into the capillary tube after fluidizing the coupling medium, whereby the optical fibers are coupled.

  16. Safety grade pressurizer heater power supply connector assembly

    International Nuclear Information System (INIS)

    Burnett, J.M.; Daftari, R.M.; Reyns, R.M.

    1987-01-01

    This patent describes a pressurizer heater power supply connector assembly for attaching a power cable to an electric heater within a pressurizer of a pressurized water nuclear reactor system, the electric heater having pin contacts. The assembly comprises: a pin-socket type connector including a tubular body having a first open end carrying a pin-socket contact member and an insert intermediate a shell and the pin-socket contact member, the contact member having socket means for electrically receiving and contacting the pin contacts, and a second open end; a flexible sealed conduit including a flexible corrugated tube having one end connected to the second open end of the pin-socket type connector, and another end; and a shop splice assembly including a header adapter and a hose clamp interconnected between the header adapter and another end of the flexible corrugated tube

  17. Capacity of columns with splice imperfections

    International Nuclear Information System (INIS)

    Popov, E.P.; Stephen, R.M.

    1977-01-01

    To study the behavior of spliced columns subjected to tensile forces simulating situations which may develop in an earthquake, all of the spliced specimens were tested to failure in tension after first having been subjected to large compressive loads. The results of these tests indicate that the lack of perfect contact at compression splices of columns may not be important, provided that the gaps are shimmed and welding is used to maintain the sections in alignment

  18. Double-plug seismic connector

    International Nuclear Information System (INIS)

    Annoot, I.R.

    1984-01-01

    The double-plug seismic electric connector comprises an elongated insulating body. A male connector plug is at one end of the body and a female connector plug is at the opposite end of the body. Each plug has a pair of male and female contacts. A pair of spaced axial conductors is embedded within the insulating body for interconnecting the opposite male and female contacts. The inner end of a double-wire cable is embedded within the insulating body and each wire inner end is connected to one of the conductors

  19. Data Base On Cables And Connectors

    Science.gov (United States)

    Bowen, Arlen R.; Oliver, John D.

    1995-01-01

    Report describes Connector Adapter Cable Information Data Base (CONNAID) computer program, managing data base containing necessary information concerning electrical connectors, breakout boxes, adapter cables, backshells, and pertinent torque specifications for engineering project.

  20. Evaluation of fiber-optic connectors

    International Nuclear Information System (INIS)

    Reedy, R.P.

    1981-01-01

    Two fiber optic connectors for field use in high efficiency, long distance systems are described and evaluated in this report. The transmission testing arrangement and other considerations are included with the test results. Techniques for optimizing the transmission through these connectors are also described and the results are reported. Many desirable characteristics of connectors for field use are considered and compared to the ITT and Amphenol connectors tested here

  1. Influence of Connector Width on the Stress Distribution of Posterior Bridges under Loading

    Directory of Open Access Journals (Sweden)

    A. Azary

    2011-06-01

    Full Text Available Objective: In all ceramic fixed partial dentures the connector area is a common fracture location. The survival time of three-unit fixed partial dentures may be improved by altering the connector design in regions of maximum tension. The purpose of this study was to determine the effect of buccolingual increase of the connector width on the stress distribution in posterior fixed partial dentures made of IPS Empress 2. To simulate the anatomical condition, we used three-dimensional finite element analysis to generate.Materials and Methods: Three models of three-unit bridges replacing the first molar were prepared. The buccolingual connector width varied from 3.0 to 5.0 mm. Bridges were vertically loaded with 600 N at one point on the central fossa of the pontic, at 12 points along the cusp-fossa contact (50 N each, or at eight points along the cusp-marginal ridge contact (75 N each. Alternatively, a load of 225 N was applied at a 45º angle from the lingual side.Results: Stress concentrations were observed within or near the connectors. The von Mises stress decreased by increasing connector width, regardless of whether the loading was applied vertically or at an angle.Conclusion: Within the limitations of this study, we conclude that increasing the connector width decreases the failure probability when a vertical or angled load is applied.

  2. Proposed superscreened cables and connectors

    International Nuclear Information System (INIS)

    Fowler, E.P.

    1975-11-01

    The paper summarises the present availability of superscreened cables and proposes the specification of a family of cables to meet the foreseeable needs of the nuclear power industry. The cable numbering system is described, special tests outlined and important details given for the chosen cables. Appropriate connectors are also discussed and listed with an outline of their required screening performance. (author)

  3. Compact and Robust Refilling and Connectorization of Hollow Core Photonic Crystal Fiber Gas Reference Cells

    Science.gov (United States)

    Poberezhskiy, Ilya Y.; Meras, Patrick; Chang, Daniel H.; Spiers, Gary D.

    2007-01-01

    This slide presentation reviews a method for refilling and connectorization of hollow core photonic crystal fiber gas reference cells. Thees hollow-core photonic crystal fiber allow optical propagation in air or vacuum and are for use as gas reference cell is proposed and demonstrated. It relies on torch-sealing a quartz filling tube connected to a mechanical splice between regular and hollow-core fibers.

  4. Nuclear qualified in-containment electrical connectors and method of connecting electrical conductors

    Science.gov (United States)

    Powell, J. G.

    1991-01-01

    A nuclear qualified in-containment electrical connection comprises an insulated, sheathed instrument lead having electrical conductors extending from one end thereof to provide two exposed lead wires, a watertight cable having electrical conducting wires therein and extending from one end of the cable to provide two lead wires therefrom, two butt splice connectors each connecting the ends of respective ones of the lead wires from the instrument lead and cable, a length of heat shrinkable plastic tubing positioned over each butt splice connector and an adjacent portion of a respective lead wire from the cable and heat shrunk into position, a length of heat shrinkable plastic tubing on the end portion of the instrument lead adjacent the lead wires therefrom and heat shrunk thereon and a length of outer heat shrinkable plastic tubing extending over the end portion of the instrument lead and the heat shrinkable tubing thereon and over the butt splice connectors and a portion of the cable adjacent the cable lead lines, the outer heat shrinkable tubing being heat shrunk into sealing position on the instrument lead and cable.

  5. Jumper connector analysis: 2-inch by 2-inch connector

    International Nuclear Information System (INIS)

    Kanjilal, S.K.; Ulbricht, L.E.; Lindquist, M.R.

    1994-01-01

    Jumper connectors are used for remotely connecting pipe lines containing transfer fluids ranging from hazardous chemicals to other nonhazardous liquids. The jumper connector assembly comprises hooks, hookpins, a block, a nozzle, an operating screw, and a nut. The hooks are tightened against the nozzle flanges by the operating screw, and a nut. The hooks are tightened against the nozzle flanges by the operating screw that is tightened with a remotely connected torque wrench. Stress analysis for the jumper connector assembly (used extensively on the US Department of Energy's Hanford Site, near Richland, Washington) is performed by using hand calculation and finite-element techniques to determine the stress levels resulting from operating and seismic loads on components of the assembly. The analysis addresses loading conditions such as prestress, seismic, operating, thermal, and leakage. The preload torque-generated forces at which each component reaches its stress limits are presented in a tabulated format. Allowable operating loads for the jumper assembly are provided to prevent leakage of the assembly during operating cycles

  6. Lightning Arrestor Connectors Production Readiness

    Energy Technology Data Exchange (ETDEWEB)

    Marten, Steve; Linder, Kim; Emmons, Jim; Gomez, Antonio; Hasam, Dawud; Maurer, Michelle

    2008-10-20

    The Lightning Arrestor Connector (LAC), part “M”, presented opportunities to improve the processes used to fabricate LACs. The A## LACs were the first production LACs produced at the KCP, after the product was transferred from Pinnellas. The new LAC relied on the lessons learned from the A## LACs; however, additional improvements were needed to meet the required budget, yield, and schedule requirements. Improvement projects completed since 2001 include Hermetic Connector Sealing Improvement, Contact Assembly molding Improvement, development of a second vendor for LAC shells, general process improvement, tooling improvement, reduction of the LAC production cycle time, and documention of the LAC granule fabrication process. This report summarizes the accomplishments achieved in improving the LAC Production Readiness.

  7. Loop connectors in dentogenic diastema

    Directory of Open Access Journals (Sweden)

    Sanjna Nayar

    2015-01-01

    Full Text Available Patients with a missing tooth along with diastema have limited treatment options to restore the edentulous space. The use of a conventional fixed partial denture (FPD to replace the missing tooth may result in too wide anterior teeth leading to poor esthetics. Loss of anterior teeth with existing diastema may result in excess space available for pontic. This condition presents great esthetic challenge for prosthodontist. If implant supported prosthesis is not possible because of inadequate bone support, FPD along with loop connector may be a treatment option to maintain the diastema and provide optimal esthetic restoration. Here, we report a clinical case where FPD along with loop connector was used to achieve esthetic rehabilitation in maxillary anterior region in which midline diastema has been maintained.

  8. High current capacity electrical connector

    International Nuclear Information System (INIS)

    Bettis, E.S.; Watts, H.L.

    1976-01-01

    An electrical connector is provided for coupling high current capacity electrical conductors such as copper busses or the like. The connector is arranged in a ''sandwiched'' configuration in which a conductor plate contacts the busses along major surfaces clamped between two stainless steel backing plates. The conductor plate is provided with contact buttons in a spaced array such that the caps of the buttons extend above the conductor plate surface to contact the busses. When clamping bolts provided through openings in the sandwiched arrangement are tightened, Belleville springs provided under the rim of each button cap are compressed and resiliently force the caps into contact with the busses' contacting surfaces to maintain a predetermined electrical contact area provided by the button cap tops. The contact area does not change with changing thermal or mechanical stresses applied to the coupled conductors

  9. Smart patch integration development of compression connector structural health monitoring in overhead transmission lines

    Science.gov (United States)

    Wang, Hong; Wang, Jy-An J.; Ren, Fei; Chan, John

    2016-04-01

    Integration of smart patches into full-tension splice connectors in overhead power transmission lines was investigated. Lead zirconate titanate (PZT) -5A was used as a smart material and an aluminum beam was used as a host structure. Negative electrode termination was examined by using copper adhesive tape and direct bonding methods. Various commercial adhesives were studied for PZT integration onto the host structure. Aluminum beam specimens with integrated PZT smart patches were tested under thermal cycling at a temperature of 125°C, which is the higher-end temperature experienced by in-service aluminum conductor steel-reinforced cables. Electromechanical impedance (EMI) measurements were conducted at room temperature, and the root mean square deviation (RMSD) of the conductance signals was used to analyze the EMI data. It has been shown that the negative electrode method has an important effect on the performance of the integrated PZT. The PZT displayed more susceptibility to cracking when copper tape was used than when direct bonding was used. The reliability of PZT in direct bonding depended on the adhesives used in bonding layers. Although a hard alumina-based adhesive can lead to cracking of the PZT, a high-temperature epoxy with adequate flexibility, such as Duralco 4538D, can provide the desired performance under target thermal cycling conditions. The RMSD parameter can characterize conductance signatures effectively. It also was demonstrated that RMSD can be used to quantify the fatigue of the PZT integration system, although RMSD is used primarily as a damage index in monitoring structural health.

  10. Inline Electrical Connector Mate/Demate Pliers

    Science.gov (United States)

    Yutko, Brian; Dininny, Michael; Moscoso, Gerand; Dokos, Adam

    2010-01-01

    Military and aerospace industries use Mil-Spec type electrical connections on bulkhead panels that require inline access for mate and demate operations. These connectors are usually in tight proximity to other connectors, or recessed within panels. The pliers described here have been designed to work in such tight spaces, and consist of a mirrored set of parallel handles, two cross links, two return springs, and replaceable polyurethane-coated end effectors. The polyurethane eliminates metal-to-metal contact and provides a high-friction surface between the jaw and the connector. Operationally, the user would slide the pliers over the connector shell until the molded polyurethane lip makes contact with the connector shell edge. Then, by squeezing the handles, the end effector jaws grip the connector shell, allowing the connector to be easily disconnected by rotating the pliers. Mating the connector occurs by reversing the prescribed procedure, except the connector shell is placed into the jaws by hand. The molded lip within the jaw allows the user to apply additional force for difficult-to-mate connectors. Handle design has been carefully examined to maximize comfort, limit weight, incorporate tether locations, and improve ergonomics. They have been designed with an off-axis offset for wiring harness clearance, while placing the connector axis of rotation close to the user s axis of wrist rotation. This was done to eliminate fatigue during multiple connector panel servicing. To limit handle opening width, with user ergonomics in mind, the pliers were designed using a parallel jaw mechanism. A cross-link mechanism was used to complete this task, while ensuring smooth operation.

  11. Behavior of Tilted Angle Shear Connectors

    Science.gov (United States)

    Khorramian, Koosha; Maleki, Shervin; Shariati, Mahdi; Ramli Sulong, N. H.

    2015-01-01

    According to recent researches, angle shear connectors are appropriate to transfer longitudinal shear forces across the steel-concrete interface. Angle steel profile has been used in different positions as L-shaped or C-shaped shear connectors. The application of angle shear connectors in tilted positions is of interest in this study. This study investigates the behaviour of tilted-shaped angle shear connectors under monotonic loading using experimental push out tests. Eight push-out specimens are tested to investigate the effects of different angle parameters on the ultimate load capacity of connectors. Two different tilted angles of 112.5 and 135 degrees between the angle leg and steel beam are considered. In addition, angle sizes and lengths are varied. Two different failure modes were observed consisting of concrete crushing-splitting and connector fracture. By increasing the size of connector, the maximum load increased for most cases. In general, the 135 degrees tilted angle shear connectors have a higher strength and stiffness than the 112.5 degrees type. PMID:26642193

  12. Behavior of Tilted Angle Shear Connectors.

    Directory of Open Access Journals (Sweden)

    Koosha Khorramian

    Full Text Available According to recent researches, angle shear connectors are appropriate to transfer longitudinal shear forces across the steel-concrete interface. Angle steel profile has been used in different positions as L-shaped or C-shaped shear connectors. The application of angle shear connectors in tilted positions is of interest in this study. This study investigates the behaviour of tilted-shaped angle shear connectors under monotonic loading using experimental push out tests. Eight push-out specimens are tested to investigate the effects of different angle parameters on the ultimate load capacity of connectors. Two different tilted angles of 112.5 and 135 degrees between the angle leg and steel beam are considered. In addition, angle sizes and lengths are varied. Two different failure modes were observed consisting of concrete crushing-splitting and connector fracture. By increasing the size of connector, the maximum load increased for most cases. In general, the 135 degrees tilted angle shear connectors have a higher strength and stiffness than the 112.5 degrees type.

  13. Remote process connectors for the NWCF

    International Nuclear Information System (INIS)

    Jacobs, R.T.; Carter, J.A.; Hohback, A.C.

    1978-01-01

    The remote process connectors developed, used, and tested at the Remote Maintenance Development Facility are described. These connectors, including the 3-bolt kinematic-graphite flange and watertight-electrical connectors, are assembled on master jigs (holding-welding fixture) to form interchangeable pump and valve loop assemblies. These assemblies, with their guide-in platforms make possible a method of performing remote maintenance at the New Waste Calcining Facility that is a departure from methods which until now have been the standard of the industry

  14. Evaluation of remote piping connectors for fusion applications

    International Nuclear Information System (INIS)

    Welland, H.J.

    1985-08-01

    Four types of remotely actuated piping connectors were evaluated for their application to the fusion energy program. The evaluations are part of a study being performed by EG and G Idaho, Inc., for the fusion program at Kernforschungszentrum, Karlsruhe, GmbH. Results of the connector evaluation will be used to develop preliminary concepts for connector improvements and new connector configurations

  15. Waste Feed Delivery Purex Process Connector Design Pressure

    International Nuclear Information System (INIS)

    BRACKENBURY, P.J.

    2000-01-01

    The pressure retaining capability of the PUREX process connector is documented. A context is provided for the connector's current use within existing Projects. Previous testing and structural analyses campaigns are outlined. The deficient condition of the current inventory of connectors and assembly wrenches is highlighted. A brief history of the connector is provided. A bibliography of pertinent references is included

  16. On-line intermittent connector anomaly detection

    Data.gov (United States)

    National Aeronautics and Space Administration — This paper investigates a non-traditional use of differential current sensor and current sensor to detect intermittent disconnection problems in connectors. An...

  17. Inflatable Air Beam Standard Interface Connector

    Data.gov (United States)

    National Aeronautics and Space Administration — The project will develop a system of 3D-printed connectors that can be used as a kit of parts to connect inflatable air beams to form a variety of spacecraft...

  18. Tension Headache

    Science.gov (United States)

    ... tight band around your head. A tension headache (tension-type headache) is the most common type of headache, and ... Headache after a head injury, especially if the headache gets worse ... tension or stress. But research suggests muscle contraction isn't the ...

  19. Targeting Splicing in Prostate Cancer

    OpenAIRE

    Effrosyni Antonopoulou; Michael Ladomery

    2018-01-01

    Over 95% of human genes are alternatively spliced, expressing splice isoforms that often exhibit antagonistic functions. We describe genes whose alternative splicing has been linked to prostate cancer; namely VEGFA, KLF6, BCL2L2, ERG, and AR. We discuss opportunities to develop novel therapies that target specific splice isoforms, or that target the machinery of splicing. Therapeutic approaches include the development of small molecule inhibitors of splice factor kinases, splice isoform speci...

  20. Aesthetic rehabilitation with multiple loop connectors

    Directory of Open Access Journals (Sweden)

    Ashish Kalra

    2013-01-01

    Full Text Available Patients with a missing tooth along with diastema have limited treatment options to restore the edentulous space. The use of a conventional fixed partial denture (FPD to replace the missing tooth may result in too wide anterior teeth leading to poor esthetics. The diastema resulting from the missing central incisors can be managed with implant-supported prosthesis or FPD with loop connectors. An old lady reported with chief complaints of missing upper anterior teeth due to trauma. Her past dental history revealed that she was having generalized spacing between her upper anterior teeth. Considering her esthetic requirement of maintaining the diastema between 12, 11, 22, and 21, the treatment option of 06 units porcelain fused to metal FPD from canine to canine with intermittent loop connectors between 21, 22, 11, 12 was planned. Connectors basically link different parts of FPDs. The modified FPD with loop connectors enhanced the natural appearance of the restoration, maintained the diastemas and the proper emergence profile, and preserve the remaining tooth structure of abutment teeth. This clinical report discussed a method for fabrication of a modified FPD with loop connectors to restore the wide span created by missing central incisors.

  1. Mechanical rebar splicing

    Directory of Open Access Journals (Sweden)

    Milosavljević Branko

    2014-01-01

    Full Text Available Different mechanical rebar splicing systems are presented, and design situations where mechanical splicing has advantage over reinforcement splicing by overlapping and welding are defined in this paper. New international standards for testing and proof of systems for mechanical rebar splicing quality are considered. Mechanical splicing system for rebar and bolt connection, usable in steel and reinforced concrete structural elements connections, is presented in this paper. There are only few examples of mechanical rebar splicing in our country. The most significant one - the pylon and beam connection at Ada Bridge in Belgrade is presented in the paper. Intensive development of production and use of mechanical rebar splicing systems, research in this area, as well as the publication of international standards prescribing requirements for quality and procedures for proof of quality, represent very good base for development of the corresponding technical norms in Serbia. The legislation in this area would quicken proof of quality procedures, attest and approval issuing for individual products, leading to wider use of this system in all situations where it is in advantage over the classical reinforcement splicing.

  2. 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...

  3. 'Daisy petal' connectors for the ATLAS detector

    CERN Multimedia

    Laurent Guiraud

    1997-01-01

    These daisy-petal structures are conducting connectors embedded in kapton film. This was an innovative solution to the demands of the ATLAS detector. Straws are pushed through the petals and held in contact using plugs. The flexible kapton film allows as many petals to be built in any configuration, while acting as a printed circuit carrying the high voltage between circles.

  4. 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.

  5. Annual report 1999. Energy and connectors

    International Nuclear Information System (INIS)

    1999-01-01

    This report presents the industrial activities and the financial results of Framatome in 1999. Framatome's activities are divided into 2 sectors: energy and connectors, which represents respectively 54% and 46% of the turnover and 40% and 60% of the staff (26000 people). In 1999 the turnover reached 4.2 milliard euros. Framatome and Siemens have decided to merge their nuclear activities in a common company (66% for Framatome, 34% for Siemens). (A.C.)

  6. In vitro incorporation of the phage Phi29 connector complex

    International Nuclear Information System (INIS)

    Fu Chiyu; Prevelige, Peter E.

    2009-01-01

    The incorporation of the DNA packaging connector complex during lambdoid phage assembly in vivo is strictly controlled-one and only one of the twelve identical icosahedral vertices is differentiated by the inclusion of a portal or connector dodecamer. Proposed control mechanisms include obligate nucleation from a connector containing complex, addition of the connector as the final step during assembly, and a connector-mediated increase in the growth rate. The inability to recapitulate connector incorporation in vitro has made it difficult to obtain direct biochemical evidence in support of one model over another. Here we report the development an in vitro assembly system for the well characterized dsDNA phage Phi29 which results in the co-assembly of connector with capsid and scaffolding proteins to form procapsid-like particles (PLPs). Immuno-electron microscopy demonstrates the specific incorporation of connector vertex in PLPs. The connector protein increases both the yield and the rate of capsid assembly suggesting that the incorporation of the connector in Phi29 likely promotes nucleation of assembly.

  7. Tension headache.

    Science.gov (United States)

    Ziegler, D K

    1978-05-01

    Headache is an extremely common symptom, and many headaches undoubtedly have a relationship to stressful situations. The clear definition, however, of a "tension headache" complex and its differentiation from migraine in some patients is difficult. The problems are in the identification of a specific headache pattern induced by stress or "tension" and the relationship of the symptom to involuntary contraction of neck and scalp muscles. Treatment consists of analgesics and occasionally mild tranquilizers. Psychotherapy consists of reassurance and often other supportive measures, including modification of life styles. Various feedback techniques have been reported of value, but their superiority to suggestion and hypnosis is still problematic.

  8. Flexural Strengthening of RC Slabs Using a Hybrid FRP-UHPC System Including Shear Connector

    Directory of Open Access Journals (Sweden)

    Jiho Moon

    2017-01-01

    Full Text Available A polymeric hybrid composite system made of UHPC and CFRP was proposed as a retrofit system to enhance flexural strength and ductility of RC slabs. While the effectiveness of the proposed system was confirmed previously through testing three full-scale one-way slabs having two continuous spans, the slabs retrofitted with the hybrid system failed in shear. This sudden shear failure would stem from the excessive enhancement of the flexural strength over the shear strength. In this study, shear connectors were installed between the hybrid system and a RC slab. Using simple beam, only positive moment section was examined. Two full-scale RC slabs were cast and tested to failure: the first as a control and the second using this new strengthening technique. The proposed strengthening system increased the ultimate load carrying capacity of the slab by 70%, the stiffness by 60%, and toughness by 128%. The efficiency of shear connectors on ductile behavior of the retrofitted slab was also confirmed. After the UHPC top is separated from the slab, the shear connector transfer shear load and the slab system were in force equilibrium by compression in UHPC and tension in CFRP.

  9. ITP Hanford Type 40 pin electrical connector failure analysis

    International Nuclear Information System (INIS)

    Imrich, K.J.

    1993-01-01

    Corrosion products observed on the ITP Hanford Type 40 pin electrical connectors would be expected to adversely affect the power and control signals supplied to process equipment in the filter cell by the connectors. Corrosion products were consistent with those found on similar pins in DWPF. The recommendations based on the findings in this investigation are as follows: (1) Replace male and female rhodium plated pins with gold plated pins. (2) Replace the galvanized carbon steel spring on the male connector with a stainless steel spring. (3) Install protective caps over Hanford connectors when jumpers are removed

  10. The neurogenetics of alternative splicing.

    Science.gov (United States)

    Vuong, Celine K; Black, Douglas L; Zheng, Sika

    2016-05-01

    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 regulate splicing, both during development and in the adult brain.

  11. Low resistance, low-inductance power connectors

    Science.gov (United States)

    Coteus, Paul W.; Ferencz, Andrew; Hall, Shawn Anthony; Takken, Todd Edward

    2018-01-16

    An electrical connector includes an anode assembly for conducting an electrical supply current from a source to a destination, the anode assembly includes an anode formed into a first shape from sheet metal or other sheet-like conducting material. A cathode assembly conducts an electrical return current from the destination to the source, the cathode assembly includes a cathode formed into a second shape from sheet metal or other sheet-like conducting material. An insulator prevents electrical conduction between the anode and the cathode. The first and second shapes are such as to provide a conformity of one to the other, with the insulator therebetween having a predetermined relatively thin thickness. A predetermined low-resistance path for the supply current is provided by the anode, a predetermined low-resistance path for the return current is provided by the cathode, and the proximity of the anode to the cathode along these paths provides a predetermined low self-inductance of the connector, where the proximity is afforded by the conformity of the first and second shapes.

  12. Critical element development of standard pipe connector for remote handling

    International Nuclear Information System (INIS)

    Taguchi, Kou; Kakudate, Satoshi; Kanamori, Naokazu; Oka, Kiyoshi; Nakahira, Masataka; Obara, Kenjiro; Tada, Eisuke; Shibanuma, Kiyoshi; Seki, Masahiro

    1994-08-01

    In fusion experimental reactors such as ITER, the in-vessel components such as blanket and divertor are actively cooled and a large number of cooling pipes are located around the core of reactor, where personnel access is prohibited. Mechanical pipe connectors are highly required as standard components for easy and reliable connection/disconnection of cooling pipe by remote handling. For this purpose, a clamping chain type connector has been developed with special mechanisms such as plate springs and guide structures so as to enable concentric and axial movement of clamping chain for easy mounting and dismounting. The basic performance test of a prototypical connector for a 80-A pipe shows sufficient leak tightness and proof pressure capability as well as simple connection/disconnection operation. In addition to the clamp chain type connector, design efforts have been made to develop a quick coupling type connector and a preliminary model of air-actuated quick connector has been fabricated for further investigations. This paper gives the design concept of mechanical pipe connectors such as clamping chain type and quick coupler type, and the basic performance tests results of clamping chain type connector. (author)

  13. A Compositional Semantics for Stochastic Reo Connectors

    Directory of Open Access Journals (Sweden)

    Young-Joo Moon

    2010-07-01

    Full Text Available In this paper we present a compositional semantics for the channel-based coordination language Reo which enables the analysis of quality of service (QoS properties of service compositions. For this purpose, we annotate Reo channels with stochastic delay rates and explicitly model data-arrival rates at the boundary of a connector, to capture its interaction with the services that comprise its environment. We propose Stochastic Reo automata as an extension of Reo automata, in order to compositionally derive a QoS-aware semantics for Reo. We further present a translation of Stochastic Reo automata to Continuous-Time Markov Chains (CTMCs. This translation enables us to use third-party CTMC verification tools to do an end-to-end performance analysis of service compositions.

  14. A decking for erecting an insulating connector

    Energy Technology Data Exchange (ETDEWEB)

    Chuprikov, A Ye; Lagutin, V I; Sklyarov, A A; Sukhanov, G V

    1983-01-01

    The decking includes a parachute like dome, made of a material impenetrable to air, an air penetrable hood, attachment elements and a branch pipe for supplying the filler. To improve the sealing of the insulating connector upon contact with the walls and the roof of the drift being isolated and to reduce the labor intensity of operations, it is equipped with a housing made in the form of a cylinder from a material impenetrable to water, an advancible vertical upright and a spring loaded panel. The housing is installed between the parachute like dome and the air penetrable hood. The extendible vertical upright is installed on the side of the air penetrable hood and by means of a movable rack mechanism is kinematically linked with the spring loaded panel, installed with the capability of interacting with the air penetrable hood. The spring loaded plate is made in the form of perforated plates which have a telescopic disengagement in the horizontal plane.

  15. Alternative REST Splicing Underappreciated

    OpenAIRE

    Chen, Guo-Lin; Miller, Gregory

    2017-01-01

    As a major orchestrator of the cellular epigenome, the repressor element-1 silencing transcription factor (REST) can either repress or activate thousands of genes depending on cellular context, suggesting a highly context-dependent REST function tuned by environmental cues. While REST shows cell-type non-selective active transcription, an N-terminal REST4 isoform caused by alternative splicing - inclusion of an extra exon (N3c) which introduces a pre-mature stop codon - has been implicated in...

  16. Remote process connectors for the new waste calcining facility

    International Nuclear Information System (INIS)

    Jacobs, R.T.; Carter, J.A.; Hohback, A.C.

    1978-01-01

    The remote process connectors developed, used, and tested at the Remote Maintenance Development Facility are described. These connectors, including the three-bolt kinematic-graphite flange and watertight electrical connectors, are assembled on master jigs (holding-welding fixture) to form interchangeable pump and valve loop assemblies. These assemblies, with their guide-in platforms, make possible a method of performing remote maintenance at the New Waste Calcining Facility which is a departure from methods that until now have been the standard of the industry

  17. Alternative RNA splicing and cancer

    Science.gov (United States)

    Liu, Sali; Cheng, Chonghui

    2015-01-01

    Alternative splicing of pre-messenger RNA (mRNA) is a fundamental mechanism by which a gene can give rise to multiple distinct mRNA transcripts, yielding protein isoforms with different, even opposing, functions. With the recognition that alternative splicing occurs in nearly all human genes, its relationship with cancer-associated pathways has emerged as a rapidly growing field. In this review, we summarize recent findings that have implicated the critical role of alternative splicing in cancer and discuss current understandings of the mechanisms underlying dysregulated alternative splicing in cancer cells. PMID:23765697

  18. Mutual interdependence of splicing and transcription elongation.

    Science.gov (United States)

    Brzyżek, Grzegorz; Świeżewski, Szymon

    2015-01-01

    Transcription and splicing are intrinsically linked, as splicing needs a pre-mRNA substrate to commence. The more nuanced view is that the rate of transcription contributes to splicing regulation. On the other hand there is accumulating evidence that splicing has an active role in controlling transcription elongation by DNA-dependent RNA polymerase II (RNAP II). We briefly review those mechanisms and propose a unifying model where splicing controls transcription elongation to provide an optimal timing for successive rounds of splicing.

  19. Small form factor optical fiber connector evaluation for harsh environments

    Science.gov (United States)

    Ott, Melanie N.; Thomes, W. Joe, Jr.; Chuska, Richard F.; Switzer, Robert; Blair, Diana E.

    2011-09-01

    For the past decade NASA programs have utilized the Diamond AVIM connector for optical fiber assemblies on space flight instrumentation. These connectors have been used in communications, sensing and LIDAR systems where repeatability and high performance are required. Recently Diamond has released a smaller form factor optical fiber connector called the "Mini-AVIM" which although more compact still includes the tight tolerances and the ratcheting feature of the heritage AVIM. NASA Goddard Space Flight Center Photonics Group in the Parts, Packaging and Assembly Technologies Office has been performing evaluations of this connector to determine how it compares to the performance of the AVIM connector and to assess its feasibility for harsh environmental applications. Vibration and thermal testing were performed on the Mini-AVIM with both multi-mode and single-mode optical fiber using insitu optical transmission monitoring. Random vibration testing was performed using typical launch condition profiles for most NASA missions but extended to 35 Grms, which is much higher than most requirements. Thermal testing was performed incrementally up to a range of -55°C to +125°C. The test results include both unjacketed fiber and cabled assembly evaluations. The data presented here indicate that the Mini-AVIM provides a viable option for small form factor applications that require a high performance optical fiber connector.

  20. Structural health monitoring of compression connectors for overhead transmission lines

    Science.gov (United States)

    Wang, Hong; Wang, Jy-An John; Swindeman, Joseph P.; Ren, Fei; Chan, John

    2017-04-01

    Two-stage aluminum conductor steel-reinforced (ACSR) compression connectors are extensively used in US overhead transmission lines. The connectors are made by crimping a steel sleeve onto a steel core and an aluminum sleeve over electrical conducting aluminum strands. The connectors are designed to operate at temperatures up to 125°C, but their performance is increasingly degrading because of overloading of lines. Currently, electric utilities conduct routine line inspections using thermal and electrical measurements, but these methods do not provide information about the structural integrity of connectors. In this work, structural health monitoring (SHM) of compression connectors was studied using electromechanical impedance (EMI) analysis. Lead zirconate titanate (PZT)-5A was identified as a smart material for SHM. A flexible high-temperature bonding layer was used to address challenges in PZT integration due to a significant difference in the coefficients of thermal expansion of PZT and the aluminum substrate. The steel joint on the steel core was investigated because it is responsible for the ultimate tensile strength of the connector. Tensile testing was used to induce structural damage to the joint, or steel core pullout, and thermal cycling introduced additional structural perturbations. EMI measurements were conducted between the tests. The root mean square deviation (RMSD) of EMI was identified as a damage index. The use of steel joints has been shown to enable SHM under simulated conditions. The EMI signature is sensitive to variations in structural conditions. RMSD can be correlated to the structural health of a connector and has potential for use in the SHM and structural integrity evaluation.

  1. Homogeneous and single-side-operational connector mechanism for self-reconfigurable, self-assembly and self-healing systems

    Science.gov (United States)

    Shen, Wei-Min (Inventor); Kovac, Robert M. (Inventor)

    2012-01-01

    Designs of single-end-operative reconfigurable genderless connectors that include a base, a plurality of movable jaws that are formed on the base and can engage to the jaws of another connector, and an actuator that is mounted on the base and can engage and move the jaws of the reconfigurable connector to connect the reconfigurable connector with another connector.

  2. Catheter Occlusion in Home Infusion: The Influence of Needleless Connector Design on Central Catheter Occlusion.

    Science.gov (United States)

    Williams, Ann

    Thrombotic catheter occlusion is a common complication associated with central venous catheters (CVCs). A wide variety of needleless connectors that differ greatly in design and function are available for use with CVCs; however, there are a limited number of studies comparing the catheter occlusion rate associated with differently designed needleless connectors. This retrospective observational study compared occlusion rates associated with a split-septum neutral-displacement needleless connector versus those of a solid-surface neutral-reflux needleless connector in patients undergoing home infusion therapy. The neutral-reflux needleless connector was associated with a significant reduction in occlusion rate and thrombolytic use versus the neutral-displacement needleless connector.

  3. Handbook of knotting and splicing

    CERN Document Server

    Hasluck, Paul N

    2005-01-01

    Clearly written and amply illustrated with 208 figures, this classic guide ranges from simple and useful knots to complex varieties. Additional topics include rope splicing, working cordage, hammock making, more.

  4. Electrical connectors for blanket modules in ITER

    Energy Technology Data Exchange (ETDEWEB)

    Poddubnyi, I., E-mail: poddubnyyii@nikiet.ru [Open Joint-Stock Company “N.A. Dollezhal Research and Development Institute of Power Engineering”, 107140, Malaya Krasnoselskaya Street 2/8, Moscow (Russian Federation); Khomiakov, S.; Kolganov, V. [Open Joint-Stock Company “N.A. Dollezhal Research and Development Institute of Power Engineering”, 107140, Malaya Krasnoselskaya Street 2/8, Moscow (Russian Federation); Sadakov, S.; Calcagno, B.; Chappuis, Ph.; Roccella, R.; Raffray, R. [ITER Organization, Route de Vinon sur Verdon, 13115 St. Paul-Lez-Durance (France); Danilov, I.; Leshukov, A.; Strebkov, Y. [Open Joint-Stock Company “N.A. Dollezhal Research and Development Institute of Power Engineering”, 107140, Malaya Krasnoselskaya Street 2/8, Moscow (Russian Federation); Ulrickson, M. [Sandia National Laboratories MS-1129, PO Box 5800, Albuquerque, NM 87185 (United States)

    2014-10-15

    Highlights: • Analysis of static and cyclic strength for L-shaped and Z-shaped ES has been performed. • Analysis results do show that for L-shaped ES static and cyclic strength criteria are not satisfied. • Static and cyclic strength criteria are met well by ES with Z-shaped elastic elements. • ES with Z-shaped elastic elements has been adopted as a new baseline design for ITER. - Abstract: Blanket electrical connectors (E-straps, ES) are low-impedance electrical bridges crossing gaps between blanket modules (BMs) and vacuum vessel (VV). Similar ES are used between two parts on each BM: the first wall panel (FW) and shield block (SB). The main functions of E-straps are to: (a) conduct halo currents intercepting some rows of BM, (b) provide grounding paths for all BMs, and (c) operate as electrical shunts which protect water cooling pipes (branch pipes) from excessive halo and eddy currents. E-straps should be elastic enough to absorb 3-D imposed displacements of BM relative VV in a scale of ±2 mm and at the same time strong enough to not be damaged by EM loads. Each electrical strap is a package of flexible conductive sheets made of CuCrZr bronze. Halo current up to 137 kA and some components of eddy currents do pass through one E-strap for a few tens or hundreds milliseconds during the plasma vertical displacement events (VDE) and disruptions. These currents deposit Joule heat and cause rather high electromagnetic loads in a strong external magnetic field, reaching 9 T. A gradual failure of ES to conduct Halo and Eddy currents with low enough impedance gradually redistributes these currents into branch pipes and cause excessive EM loads. When branch pipes will be bent so much that will touch surrounding structures, the Joule heating in accidental electrical contact spots will cause local melting and may lead to a water leak. The paper presents and compares two design options of E-straps: with L-shaped and Z-shaped elastic elements. The latter option was

  5. Fibre optic connectors with high-return-loss performance

    Science.gov (United States)

    Knott, Michael P.; Johnson, R.; Cooke, K.; Longhurst, P. C.

    1990-09-01

    This paper describes the development of a single mode fibre optic connector with high return loss performance without the use of index matching. Partial reflection of incident light at a fibre optic connector interface is a recognised problem where the result can be increased noise and waveform distortion. This is particularly important for video transmission in subscriber networks which requires a high signal to noise ratio. A number of methods can be used to improve the return loss. The method described here uses a process which angles the connector endfaces. Measurements show typical return losses of -55dB can be achieved for an end angle of 6 degrees. Insertion loss results are also presented.

  6. Friction mediated by redox-active supramolecular connector molecules.

    Science.gov (United States)

    Bozna, B L; Blass, J; Albrecht, M; Hausen, F; Wenz, G; Bennewitz, R

    2015-10-06

    We report on a friction study at the nanometer scale using atomic force microscopy under electrochemical control. Friction arises from the interaction between two surfaces functionalized with cyclodextrin molecules. The interaction is mediated by connector molecules with (ferrocenylmethyl)ammonium end groups forming supramolecular complexes with the cyclodextrin molecules. With ferrocene connector molecules in solution, the friction increases by a factor of up to 12 compared to control experiments without connector molecules. The electrochemical oxidation of ferrocene to ferrocenium causes a decrease in friction owing to the lower stability of ferrocenium-cyclodextrin complex. Upon switching between oxidative and reduction potentials, a change in friction by a factor of 1.2-1.8 is observed. Isothermal titration calorimetry reveals fast dissociation and rebinding kinetics and thus an equilibrium regime for the friction experiments.

  7. MPO-type single-mode multi-fiber connector: Low-loss and high-return-loss intermateability of APC-MPO connectors

    Science.gov (United States)

    Satake, Toshiaki; Nagasawa, Shinji; Hughes, Mike; Lutz, Sharon

    2011-01-01

    The electrical communication laboratory of NTT started the research of MT (Mechanically Transferable) connector in early 1980s. The initial goal was to realize a multi-fiber connector which can repeat low loss, stable, reliable and low-cost connections of subscriber optical fiber cable networks for more than 20 years period in the field. We review the multi-fiber alignment design with two guide pins, and following several technical improvements toward the final MT connector used in the commercial telecommunication networks. And then, we review development histories to reach to the low-loss, high-return-loss and reliable APC-MPO (Angled Physical Contact Multi-fiber Push On) connectors introduced in NTT COs and in Verizon's FTTH (Fiber To The Home) networks. In the latter half, we propose the low-loss intermateability design for connectors made by different suppliers in order to enable mass introductions into large scale systems. In addition we also describe an accurate connector loss presumption method for different lots' ferrules based on the MT ferrule dimension data before assembling the connectors. We believe with a wide intermateability of APC-MPO connector will increase its use in the fields. The APC-MPO connector manufactured based on the proposed design had low insertion losses of less than 0.25 dB at the same level of simplex connectors and the higher level of return losses higher than 65 dB.

  8. Design and experimental analysis of a new shear connector for steel and concrete composite structures

    OpenAIRE

    Veríssimo, G. S.; Paes, J. L. R.; Valente, Isabel; Cruz, Paulo J. S.; Fakury, R. H.

    2006-01-01

    This work presents the design of a new shear connector and the corresponding results obtained on push-out tests. This new shear connector consists on a steel rib with indented cut shape that provides resistance to longitudinal shear and prevents transversal separation between the concrete slab and the steel profile (uplift). Adding to this, the connector openings cut makes easier the arrangement of transversal reinforcement bars. The installation of the connectors is simple and requires only ...

  9. Reactor vessel stud tensioner

    International Nuclear Information System (INIS)

    Malandra, L.J.; Beer, R.W.; Salton, R.B.; Spiegelman, S.R.; Cognevich, M.L.

    1982-01-01

    A quick-acting stud tensioner, for facilitating the loosening or tightening of a stud nut on a reactor vessel stud, has gripper jaws which when the tensioner is lowered into engagement with the upper end of the stud are moved inwards to grip the upper end and which when the tensioner is lifted move outward to release the upper end. (author)

  10. Influence of Cable Vibrations on Connectors Used in Automotive Applications

    Directory of Open Access Journals (Sweden)

    AMEL Bouzera

    2012-10-01

    Full Text Available In order to determine the influence of cable vibrations on the contact resistance of connectors, the cable resonant frequency and the resulting movement of both parts of the connector have been studied. The increase of contact voltage, followed by rapidfluctuations generated by wear particles, has been analysed. A test bench designed to monitor wire vibrations was used while the transferred amplitude was measured by a high sensitivity displacement sensor. The contact interface was made of copper alloy and tin coated. The connector was connected to a resistive power supplytransmitting different currents and voltage values. Two investigations were performed on the contact voltage measured with a fast sampling oscilloscope which enabled histograms and a Fast FourierTransform analysis to be obtained. The appearance of contact fluctuations observed during the fretting generated by cable vibrations, and depending upon the wear effect, is attributed toelectromechanical phenomena. Some slow fluctuations are well correlated to the vibration period while the rapid ones are linked to an electrical conduction perturbation in the granular interface caused by the connector movement.

  11. Endotracheal tube connector defect causing airway obstruction in an ...

    African Journals Online (AJOL)

    detected during routine visual inspection before their use, while some go unnoticed during such inspection and can lead to partial or complete airway obstruction in intubated patients. We report one case of partial airway obstruction resulting from manufacturing defect in the ET connector. A 3-month-old infant girl weighing 5 ...

  12. Electro-optics laboratory evaluation: Deutsch optical waveguide connectors

    Science.gov (United States)

    1980-01-01

    A description of a test program evaluating the performance of an optical waveguide connector system is presented. Both quality and effectiveness of connections made in an optical fiber, performance of the equipment used and applicability of equipment and components to field conditions are reviewed.

  13. Human Splicing Finder: an online bioinformatics tool to predict splicing signals

    OpenAIRE

    Desmet, Francois-Olivier; Hamroun, Dalil; Lalande, Marine; Collod-Beroud, Gwenaelle; Claustres, Mireille; Beroud, Christophe

    2009-01-01

    International audience; Thousands of mutations are identified yearly. Although many directly affect protein expression, an increasing proportion of mutations is now believed to influence mRNA splicing. They mostly affect existing splice sites, but synonymous, non-synonymous or nonsense mutations can also create or disrupt splice sites or auxiliary cis-splicing sequences. To facilitate the analysis of the different mutations, we designed Human Splicing Finder (HSF), a tool to predict the effec...

  14. Diverse alternative back-splicing and alternative splicing landscape of circular RNAs

    Science.gov (United States)

    Zhang, Xiao-Ou; Dong, Rui; Zhang, Yang; Zhang, Jia-Lin; Luo, Zheng; Zhang, Jun; Chen, Ling-Ling; Yang, Li

    2016-01-01

    Circular RNAs (circRNAs) derived from back-spliced exons have been widely identified as being co-expressed with their linear counterparts. A single gene locus can produce multiple circRNAs through alternative back-splice site selection and/or alternative splice site selection; however, a detailed map of alternative back-splicing/splicing in circRNAs is lacking. Here, with the upgraded CIRCexplorer2 pipeline, we systematically annotated different types of alternative back-splicing and alternative splicing events in circRNAs from various cell lines. Compared with their linear cognate RNAs, circRNAs exhibited distinct patterns of alternative back-splicing and alternative splicing. Alternative back-splice site selection was correlated with the competition of putative RNA pairs across introns that bracket alternative back-splice sites. In addition, all four basic types of alternative splicing that have been identified in the (linear) mRNA process were found within circRNAs, and many exons were predominantly spliced in circRNAs. Unexpectedly, thousands of previously unannotated exons were detected in circRNAs from the examined cell lines. Although these novel exons had similar splice site strength, they were much less conserved than known exons in sequences. Finally, both alternative back-splicing and circRNA-predominant alternative splicing were highly diverse among the examined cell lines. All of the identified alternative back-splicing and alternative splicing in circRNAs are available in the CIRCpedia database (http://www.picb.ac.cn/rnomics/circpedia). Collectively, the annotation of alternative back-splicing and alternative splicing in circRNAs provides a valuable resource for depicting the complexity of circRNA biogenesis and for studying the potential functions of circRNAs in different cells. PMID:27365365

  15. Development Of Remote Hanford Connector Gasket Replacement Tooling For DWPF

    International Nuclear Information System (INIS)

    Krementz, D.; Coughlin, Jeffrey

    2009-01-01

    The Defense Waste Processing Facility (DWPF) requested the Savannah River National Laboratory (SRNL) to develop tooling and equipment to remotely replace gaskets in mechanical Hanford connectors to reduce personnel radiation exposure as compared to the current hands-on method. It is also expected that radiation levels will continually increase with future waste streams. The equipment is operated in the Remote Equipment Decontamination Cell (REDC), which is equipped with compressed air, two master-slave manipulators (MSM's) and an electro-mechanical manipulator (EMM) arm for operation of the remote tools. The REDC does not provide access to electrical power, so the equipment must be manually or pneumatically operated. The MSM's have a load limit at full extension of ten pounds, which limited the weight of the installation tool. In order to remotely replace Hanford connector gaskets several operations must be performed remotely, these include: removal of the spent gasket and retaining ring (retaining ring is also called snap ring), loading the new snap ring and gasket into the installation tool and installation of the new gasket into the Hanford connector. SRNL developed and tested tools that successfully perform all of the necessary tasks. Removal of snap rings from horizontal and vertical connectors is performed by separate air actuated retaining ring removal tools and is manipulated in the cell by the MSM. In order install a new gasket, the snap ring loader is used to load a new snap ring into a groove in the gasket installation tool. A new gasket is placed on the installation tool and retained by custom springs. An MSM lifts the installation tool and presses the mounted gasket against the connector block. Once the installation tool is in position, the gasket and snap ring are installed onto the connector by pneumatic actuation. All of the tools are located on a custom work table with a pneumatic valve station that directs compressed air to the desired tool and

  16. 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.

  17. A Dissipative Connector for CLT Buildings: Concept, Design and Testing

    Science.gov (United States)

    Scotta, Roberto; Marchi, Luca; Trutalli, Davide; Pozza, Luca

    2016-01-01

    This paper deals with the conception and characterization of an innovative connection for cross-laminated timber (CLT) panels. The connection is designed to provide an adequate level of dissipative capacity to CLT structures also when realized with large horizontal panels and therefore prone to fragile shear sliding failure. The connector, named X-bracket, has been theorized and designed by means of numerical parametric analyses. Furthermore, its cyclic behavior has been verified with experimental tests and compared to that of traditional connectors. Numerical simulations of cyclic tests of different CLT walls anchored to the foundation with X-brackets were also performed to assess their improved seismic performances. Finally, the analysis of the response of a 6 m × 3 m squat wall demonstrates that the developed connection provides good ductility and dissipation capacities also to shear walls realized with a single CLT panel. PMID:28773265

  18. A Dissipative Connector for CLT Buildings: Concept, Design and Testing.

    Science.gov (United States)

    Scotta, Roberto; Marchi, Luca; Trutalli, Davide; Pozza, Luca

    2016-02-26

    This paper deals with the conception and characterization of an innovative connection for cross-laminated timber (CLT) panels. The connection is designed to provide an adequate level of dissipative capacity to CLT structures also when realized with large horizontal panels and therefore prone to fragile shear sliding failure. The connector, named X-bracket, has been theorized and designed by means of numerical parametric analyses. Furthermore, its cyclic behavior has been verified with experimental tests and compared to that of traditional connectors. Numerical simulations of cyclic tests of different CLT walls anchored to the foundation with X-brackets were also performed to assess their improved seismic performances. Finally, the analysis of the response of a 6 m × 3 m squat wall demonstrates that the developed connection provides good ductility and dissipation capacities also to shear walls realized with a single CLT panel.

  19. Spliced RNA of woodchuck hepatitis virus.

    Science.gov (United States)

    Ogston, C W; Razman, D G

    1992-07-01

    Polymerase chain reaction was used to investigate RNA splicing in liver of woodchucks infected with woodchuck hepatitis virus (WHV). Two spliced species were detected, and the splice junctions were sequenced. The larger spliced RNA has an intron of 1300 nucleotides, and the smaller spliced sequence shows an additional downstream intron of 1104 nucleotides. We did not detect singly spliced sequences from which the smaller intron alone was removed. Control experiments showed that spliced sequences are present in both RNA and DNA in infected liver, showing that the viral reverse transcriptase can use spliced RNA as template. Spliced sequences were detected also in virion DNA prepared from serum. The upstream intron produces a reading frame that fuses the core to the polymerase polypeptide, while the downstream intron causes an inframe deletion in the polymerase open reading frame. Whereas the splicing patterns in WHV are superficially similar to those reported recently in hepatitis B virus, we detected no obvious homology in the coding capacity of spliced RNAs from these two viruses.

  20. Aberrant alternative splicing is another hallmark of cancer.

    Science.gov (United States)

    Ladomery, Michael

    2013-01-01

    The vast majority of human genes are alternatively spliced. Not surprisingly, aberrant alternative splicing is increasingly linked to cancer. Splice isoforms often encode proteins that have distinct and even antagonistic properties. The abnormal expression of splice factors and splice factor kinases in cancer changes the alternative splicing of critically important pre-mRNAs. Aberrant alternative splicing should be added to the growing list of cancer hallmarks.

  1. Aberrant Alternative Splicing Is Another Hallmark of Cancer

    OpenAIRE

    Ladomery, Michael

    2013-01-01

    The vast majority of human genes are alternatively spliced. Not surprisingly, aberrant alternative splicing is increasingly linked to cancer. Splice isoforms often encode proteins that have distinct and even antagonistic properties. The abnormal expression of splice factors and splice factor kinases in cancer changes the alternative splicing of critically important pre-mRNAs. Aberrant alternative splicing should be added to the growing list of cancer hallmarks.

  2. Tension type headache

    Directory of Open Access Journals (Sweden)

    Debashish Chowdhury

    2012-01-01

    Full Text Available Tension type headaches are common in clinical practice. Earlier known by various names, the diagnosis has had psychological connotations. Recent evidence has helped clarify the neurobiological basis and the disorder is increasingly considered more in the preview of neurologists. The classification, clinical features, differential diagnosis and treatment of tension type headache are discussed in this paper.

  3. Tensions in Distributed Leadership

    Science.gov (United States)

    Ho, Jeanne; Ng, David

    2017-01-01

    Purpose: This article proposes the utility of using activity theory as an analytical lens to examine the theoretical construct of distributed leadership, specifically to illuminate tensions encountered by leaders and how they resolved these tensions. Research Method: The study adopted the naturalistic inquiry approach of a case study of an…

  4. Design and fabrication of composite wing panels containing a production splice

    Science.gov (United States)

    Reed, D. L.

    1975-01-01

    Bolted specimens representative of both upper and lower wing surface splices of a transport aircraft were designed and manufactured for static and random load tension and compression fatigue testing including ground-air-ground load reversals. The specimens were fabricated with graphite-epoxy composite material. Multiple tests were conducted at various load levels and the results were used as input to a statistical wearout model. The statically designed specimens performed very well under highly magnified fatigue loadings. Two large panels, one tension and compression, were fabricated for testing by NASA-LRC.

  5. SplicePlot: a utility for visualizing splicing quantitative trait loci.

    Science.gov (United States)

    Wu, Eric; Nance, Tracy; Montgomery, Stephen B

    2014-04-01

    RNA sequencing has provided unprecedented resolution of alternative splicing and splicing quantitative trait loci (sQTL). However, there are few tools available for visualizing the genotype-dependent effects of splicing at a population level. SplicePlot is a simple command line utility that produces intuitive visualization of sQTLs and their effects. SplicePlot takes mapped RNA sequencing reads in BAM format and genotype data in VCF format as input and outputs publication-quality Sashimi plots, hive plots and structure plots, enabling better investigation and understanding of the role of genetics on alternative splicing and transcript structure. Source code and detailed documentation are available at http://montgomerylab.stanford.edu/spliceplot/index.html under Resources and at Github. SplicePlot is implemented in Python and is supported on Linux and Mac OS. A VirtualBox virtual machine running Ubuntu with SplicePlot already installed is also available.

  6. The connection between splicing and cancer

    OpenAIRE

    Srebrow, Anabella; Kornblihtt, Alberto Rodolfo

    2017-01-01

    Alternative splicing is a crucial mechanism for generating protein diversity. Different splice variants of a given protein can display different and even antagonistic biological functions. Therefore, appropriate control of their synthesis is required to assure the complex orchestration of cellular processes within multicellular organisms. Mutations in cisacting splicing elements or changes in the activity of regulatory proteins that compromise the accuracy of either constitutive or alternativ...

  7. Alternative Splicing in Neurogenesis and Brain Development.

    Science.gov (United States)

    Su, Chun-Hao; D, Dhananjaya; Tarn, Woan-Yuh

    2018-01-01

    Alternative splicing of precursor mRNA is an important mechanism that increases transcriptomic and proteomic diversity and also post-transcriptionally regulates mRNA levels. Alternative splicing occurs at high frequency in brain tissues and contributes to every step of nervous system development, including cell-fate decisions, neuronal migration, axon guidance, and synaptogenesis. Genetic manipulation and RNA sequencing have provided insights into the molecular mechanisms underlying the effects of alternative splicing in stem cell self-renewal and neuronal fate specification. Timely expression and perhaps post-translational modification of neuron-specific splicing regulators play important roles in neuronal development. Alternative splicing of many key transcription regulators or epigenetic factors reprograms the transcriptome and hence contributes to stem cell fate determination. During neuronal differentiation, alternative splicing also modulates signaling activity, centriolar dynamics, and metabolic pathways. Moreover, alternative splicing impacts cortical lamination and neuronal development and function. In this review, we focus on recent progress toward understanding the contributions of alternative splicing to neurogenesis and brain development, which has shed light on how splicing defects may cause brain disorders and diseases.

  8. Alternative Splicing in Neurogenesis and Brain Development

    Directory of Open Access Journals (Sweden)

    Chun-Hao Su

    2018-02-01

    Full Text Available Alternative splicing of precursor mRNA is an important mechanism that increases transcriptomic and proteomic diversity and also post-transcriptionally regulates mRNA levels. Alternative splicing occurs at high frequency in brain tissues and contributes to every step of nervous system development, including cell-fate decisions, neuronal migration, axon guidance, and synaptogenesis. Genetic manipulation and RNA sequencing have provided insights into the molecular mechanisms underlying the effects of alternative splicing in stem cell self-renewal and neuronal fate specification. Timely expression and perhaps post-translational modification of neuron-specific splicing regulators play important roles in neuronal development. Alternative splicing of many key transcription regulators or epigenetic factors reprograms the transcriptome and hence contributes to stem cell fate determination. During neuronal differentiation, alternative splicing also modulates signaling activity, centriolar dynamics, and metabolic pathways. Moreover, alternative splicing impacts cortical lamination and neuronal development and function. In this review, we focus on recent progress toward understanding the contributions of alternative splicing to neurogenesis and brain development, which has shed light on how splicing defects may cause brain disorders and diseases.

  9. Parachute Cord Tension Sensor

    Data.gov (United States)

    National Aeronautics and Space Administration — To design and fabricate a light weight (few oz), very small (~2 inch length) parachute cord tension sensor demonstrator device.A major challenge for the CPAS (The...

  10. Leadership. Using Creative Tension.

    Science.gov (United States)

    Cook, David L.

    1986-01-01

    Leadership involves maintaining a balance of the variables which comprise leadership. Love and fear, types of power, success and effectiveness, and driving and restraining forces are discussed as sources of the creative tension a leader uses to influence others. (MT)

  11. Optic nerve oxygen tension

    DEFF Research Database (Denmark)

    la Cour, M; Kiilgaard, Jens Folke; Eysteinsson, T

    2000-01-01

    To investigate the influence of acute changes in intraocular pressure on the oxygen tension in the vicinity of the optic nerve head under control conditions and after intravenous administration of 500 mg of the carbonic anhydrase inhibitor dorzolamide.......To investigate the influence of acute changes in intraocular pressure on the oxygen tension in the vicinity of the optic nerve head under control conditions and after intravenous administration of 500 mg of the carbonic anhydrase inhibitor dorzolamide....

  12. Spontaneous tension haemopneumothorax

    OpenAIRE

    Patterson, Benjamin Oliver; Itam, Sarah; Probst, Fey

    2008-01-01

    Abstract We present a patient with sudden onset progressive shortness of breath and no history of trauma, who rapidly became haemodynamically compromised with a pneumothorax and pleural effusion seen on chest radiograph. He was treated for spontaneous tension pneumothorax but this was soon revealed to be a tension haemopneumothorax. He underwent urgent thoracotomy after persistent bleeding to explore an apical vascular abnormality seen on CT scanning. To our knowledge this is the first such c...

  13. 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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. MWTF jumper connector integral seal block development and leak testing

    International Nuclear Information System (INIS)

    Ruff, E.S.; Jordan, S.R.

    1995-01-01

    In fiscal year 1993, tests of an o-ring/tetraseal retainer designed to replace a gasket-type seal used in PUREX-type process jumper connectors encouraged the design of an improved seal block. This new seal block combines several parts into one unitized component called an integral seal block. This report summarizes development and leak testing of the new integral seal block. The integral seal block uses a standard o-ring nested in a groove to accomplish leak tightness. This seal block eliminates the need to machine acme threads into the lower skirt casting and seal retainers, eliminates tolerance stack-up, reduces parts inventory, and eliminates an unnecessary leak path in the jumper connector assembly. This report also includes test data on various types of o-ring materials subjected to heat and pressure. Materials tested included Viton, Kalrez, and fluorosilicone, with some incidental data on teflon coated silicone o-rings. Test experience clearly demonstrates the need to test each seal material for temperature and pressure in its intended application. Some materials advertised as being open-quotes betterclose quotes at higher temperatures did not perform up to expectations. Inspection of the fluorosilicone and Kalrez seals after thermal testing indicates that they are much more susceptible to heat softening than Viton

  15. Gamma irradiation effects in optical fibres, splitters, and connectors

    Directory of Open Access Journals (Sweden)

    Srećković Milesa Ž.

    2017-01-01

    Full Text Available The paper presents a brief overview of contemporary ELION techniques with stress on their use for material modification and dosimetry. In the attempt to avoid some common misjudges of irradiation effects, special attention is paid to exact definition of irradiation geometry and careful adjustment of dose rates, which enable a proper elaboration of experimental results. In particular, effects of g-rays irradiation on properties of commercial optical fibres, splitters, connectors, and fibre joints are examined, which enables monitoring of irradiation effects in complex configurations made of materials with different radiation hardness (resistance. It has been established that g-rays irradiation of the investigated elements influences, in different ways, the transmission of laser beam signals of various wavelengths, under different modulation regimes. After irradiation, the signal attenuation is noticeably larger, both in optical connectors and optical splitter, than before it, and the effect increases in time. The effects are more pronounced at the 99 % than at the 1 % Y-splitter output at both measured wavelengths, and are more pronounced at 1310 nm than at 1550 nm. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III43009 and Grant no. III45012

  16. Fluid moderator control system fuel assembly seal connector

    International Nuclear Information System (INIS)

    Veronesi, L.; Tower, S.N.; Klassen, W.E.

    1987-01-01

    A nuclear reactor is described comprising fuel assemblies having one or more flow channels therethrough, a core support plate having one or more flow channels therethrough, and seal connectors for sealingly connecting the one or more flow channels in the core support plate with the one or more flow channels in the fuel assemblies. The seal connectors each comprises a first portion and second portion each comprising an elongated member having a flow channel therethrough and being in substantial axial alignment with each other and being separated by a space therebetween, means for sealingly connecting the first portion o one or the one or more flow channels in the fuel assemblies, means for sealingly connecting the second portion to the first portion and for allowing relative motion between the portions, means for limiting the relative motion of the first and second portion in directions toward and away from each other, means for reconnectingly connecting and resealingly sealing the second portion to one of the one or more flow channels in the core support plate. It comprises a slip fit connection whereby the remote end of the second portion fits within whereby the remote end of the second portion fits within an opening in the core support plate which is in flow communication with the one or more flow channels in the core support plate and further comprises a ball and cones seal in series with axially spaced ring seals

  17. Evolution of low-profile and lightweight electrical connectors for soldier-worn applications

    Science.gov (United States)

    Gans, Eric; Lee, Kang; Jannson, Tomasz; Walter, Kevin

    2011-06-01

    In addition to military radios, modern warfighters carry cell phones, GPS devices, computers, and night-vision aids, all of which require electrical cables and connectors for data and power transmission. Currently each electrical device operates via independent cables using conventional cable and connector technology. Conventional cables are stiff and difficult to integrate into a soldier-worn garment. Conventional connectors are tall and heavy, as they were designed to ensure secure connections to bulkhead-type panels, and being tall, represent significant snag-hazards in soldier-worn applications. Physical Optics Corporation has designed a new, lightweight and low-profile electrical connector that is more suitable for body-worn applications and operates much like a standard garment snap. When these connectors are mated, the combined height is <0.3 in. - a significant reduction from the 2.5 in. average height of conventional connectors. Electrical connections can be made with one hand (gloved or bare) and blindly (without looking). Furthermore, POC's connectors are integrated into systems that distribute data or power from a central location on the soldier's vest, reducing the length and weight of the cables necessary to interconnect various mission-critical electronic systems. The result is a lightweight power/data distribution system offering significant advantages over conventional electrical connectors in soldier-worn applications.

  18. Non-rigid connector: The wand to allay the stresses on abutment

    OpenAIRE

    Banerjee, Saurav; Khongshei, Arlingstone; Gupta, Tapas; Banerjee, Ardhendu

    2011-01-01

    The use of rigid connectors in 5-unit fixed dental prosthesis with a pier abutment can result in failure of weaker retainer in the long run as the pier abutment acts as a fulcrum. Non-rigid connector placed on the distal aspect of pier seems to reduce potentially excess stress concentration on the pier abutment.

  19. Comparison of Adaptation between the Major Connectors Fabricated from Intraoral Digital Impressions and Extraoral Digital Impressions.

    Science.gov (United States)

    Gan, Ning; Ruan, Yaye; Sun, Jian; Xiong, Yaoyang; Jiao, Ting

    2018-01-11

    The objective was to compare the adaptation between the major connectors of removable partial dentures derived from intraoral digital impressions and extraoral digital impressions. Twenty-four volunteers were enrolled. Each volunteer received an intraoral digital impression and one extraoral digital impression digitized from conventional gypsum impression. A software was used to create the major connectors on digital impression datasets. After all the virtual major connectors designed from Group intraoral digital impressions (Group I) and Group extraoral digital impressions (Group E) were directly fabricated by 3D printing technique, the adaptation of the final major connectors in volunteers' mouths were measured. The adaptation ranged from 159.87 to 577.99 μm in Group I while from 120.83 to 536.17 μm in Group E. The adaptation of major connectors in Group I were found better at the midline palatine suture while the adaptation of major connectors in Group E were found better at the two sides of the palatal vault. In both groups, the highest accuracy in adaptation was revealed at the anterior margin of the major connectors. It is feasible to manufacture the major connectors by digital impression and 3D printing technique. Both the adaptation of the two kinds of digital impressions were clinical acceptable.

  20. MEMS and EFF technology based micro connector for future miniature devices

    International Nuclear Information System (INIS)

    Bhuiyan, M M I; Alamgir, T; Bhuiyan, M; Kajihara, M

    2013-01-01

    The development of a miniature; size, light and high performance electronic devices; has been accelerated for further development. In commercial stamping method, connector pitch size (radius) is more than 300μm due to its size limitation. Therefore, the stamped contact hertz stress becomes lower and less suitable for fine pitch connector. To overcome this pitch size problem a narrow pitch Board-to-Board (BtoB) interface connectors are in demand for the current commercial design. Therefore, this paper describes a fork type micro connector design with high Hertz-Stress using MEMS and Electro Fine Forming (EFF) fabrication techniques. The connector is designed high aspect ratio and high-density packaging using UV thick resist and electroforming. In this study a newly fabricated micro connector's maximum aspect ratio is 50μm and pitch is 80μm is designed successfully which is most compact fork-type connector in the world. When these connectors are connected, a contact resistance of less than 50mΩ has been attained by using four-point probe technique

  1. Alternative Splicing Control of Abiotic Stress Responses.

    Science.gov (United States)

    Laloum, Tom; Martín, Guiomar; Duque, Paula

    2018-02-01

    Alternative splicing, which generates multiple transcripts from the same gene, is an important modulator of gene expression that can increase proteome diversity and regulate mRNA levels. In plants, this post-transcriptional mechanism is markedly induced in response to environmental stress, and recent studies have identified alternative splicing events that allow rapid adjustment of the abundance and function of key stress-response components. In agreement, plant mutants defective in splicing factors are severely impaired in their response to abiotic stress. Notably, mounting evidence indicates that alternative splicing regulates stress responses largely by targeting the abscisic acid (ABA) pathway. We review here current understanding of post-transcriptional control of plant stress tolerance via alternative splicing and discuss research challenges for the near future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Spliced

    DEFF Research Database (Denmark)

    Addison, Courtney Page

    2017-01-01

    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...

  3. Spontaneous tension haemopneumothorax.

    Science.gov (United States)

    Patterson, Benjamin Oliver; Itam, Sarah; Probst, Fey

    2008-10-31

    We present a patient with sudden onset progressive shortness of breath and no history of trauma, who rapidly became haemodynamically compromised with a pneumothorax and pleural effusion seen on chest radiograph. He was treated for spontaneous tension pneumothorax but this was soon revealed to be a tension haemopneumothorax. He underwent urgent thoracotomy after persistent bleeding to explore an apical vascular abnormality seen on CT scanning. To our knowledge this is the first such case reported.Aetiology and current approach to spontaneous haemothorax are discussed briefly.

  4. Spontaneous tension haemopneumothorax

    Directory of Open Access Journals (Sweden)

    Itam Sarah

    2008-10-01

    Full Text Available Abstract We present a patient with sudden onset progressive shortness of breath and no history of trauma, who rapidly became haemodynamically compromised with a pneumothorax and pleural effusion seen on chest radiograph. He was treated for spontaneous tension pneumothorax but this was soon revealed to be a tension haemopneumothorax. He underwent urgent thoracotomy after persistent bleeding to explore an apical vascular abnormality seen on CT scanning. To our knowledge this is the first such case reported. Aetiology and current approach to spontaneous haemothorax are discussed briefly.

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

    International Nuclear Information System (INIS)

    Wang Yuedi; McNally, Mark T.

    2003-01-01

    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

  6. Open Source GIS Connectors to NASA GES DISC Satellite Data

    Science.gov (United States)

    Kempler, Steve; Pham, Long; Yang, Wenli

    2014-01-01

    The NASA Goddard Earth Sciences Data and Information Services Center (GES DISC) houses a suite of high spatiotemporal resolution GIS data including satellite-derived and modeled precipitation, air quality, and land surface parameter data. The data are valuable to various GIS research and applications at regional, continental, and global scales. On the other hand, many GIS users, especially those from the ArcGIS community, have difficulties in obtaining, importing, and using our data due to factors such as the variety of data products, the complexity of satellite remote sensing data, and the data encoding formats. We introduce a simple open source ArcGIS data connector that significantly simplifies the access and use of GES DISC data in ArcGIS.

  7. Depolarization-mediated regulation of alternative splicing

    Directory of Open Access Journals (Sweden)

    Alok eSharma

    2011-12-01

    Full Text Available Alternative splicing in eukaryotes plays an important role in regulating gene expression by selectively including alternative exons. A wealth of information has been accumulated that explains how alternative exons are selected in a developmental stage- or tissue-specific fashion. However, our knowledge of how cells respond to environmental changes to alter alternative splicing is very limited. For example, although a number of alternative exons have been shown to be regulated by calcium level alterations, the underlying mechanisms are not well understood. As calcium signaling in neurons plays a crucial role in essential neuronal functions such as learning and memory formation, it is important to understand how this process is regulated at every level in gene expression. The significance of the dynamic control of alternative splicing in response to changes of calcium levels has been largely unappreciated. In this communication, we will summarize the recent advances in calcium signaling-mediated alternative splicing that have provided some insights into the important regulatory mechanisms. In addition to describing the cis-acting RNA elements on the pre-mRNA molecules that respond to changes of intracellular calcium levels, we will summarize how splicing regulators change and affect alternative splicing in this process. We will also discuss a novel mode of calcium-mediated splicing regulation at the level of chromatin structure and transcription.

  8. Creating Tension in Writing.

    Science.gov (United States)

    Folta, Bernarr

    This paper discusses the rationale and teaching methods for a six-week unit, for a high school freshman English Class, on perception, semantics, and writing, which places special focus on developing tension in student writing. The first four objectives of the course focus on perception and the next two focus on semantics. The seventh…

  9. Tension-filled Governance?

    DEFF Research Database (Denmark)

    Celik, Tim Holst

    on the statesituated tension-filled functional relationship between legitimation and accumulation, the study both historically and theoretically reworks this approach and reapplies it for the post-1970s/1990s governance period. It asks whether and to what extent governance has served as a distinctive post- 1970s/1990s...

  10. Rein tension during canter

    NARCIS (Netherlands)

    Egenvall, Agneta; Eisersiö, Marie; Rhodin, Marie; van Weeren, P.R.; Roepstorff, Lars

    2015-01-01

    Riders generally use reins as a means for communication with the horse. At present, the signalling pattern is poorly understood. The aim of this study was to illustrate and analyse the rein tension patterns in a number of rider/horse combinations across a variety of exercises in the canter gait. Our

  11. Optic nerve oxygen tension

    DEFF Research Database (Denmark)

    Kiilgaard, Jens Folke; Pedersen, D B; Eysteinsson, T

    2004-01-01

    The authors have previously reported that carbonic anhydrase inhibitors such as acetazolamide and dorzolamide raise optic nerve oxygen tension (ONPO(2)) in pigs. The purpose of the present study was to investigate whether timolol, which belongs to another group of glaucoma drugs called beta...

  12. RAGE splicing variants in mammals.

    Science.gov (United States)

    Sterenczak, Katharina Anna; Nolte, Ingo; Murua Escobar, Hugo

    2013-01-01

    The receptor for advanced glycation end products (RAGE) is a multiligand receptor of environmental stressors which plays key roles in pathophysiological processes, including immune/inflammatory disorders, Alzheimer's disease, diabetic arteriosclerosis, tumorigenesis, and metastasis. Besides the full-length RAGE protein in humans nearly 20 natural occurring RAGE splicing variants were described on mRNA and protein level. These naturally occurring isoforms are characterized by either N-terminally or C-terminally truncations and are discussed as possible regulators of the full-length RAGE receptor either by competitive ligand binding or by displacing the full-length protein in the membrane. Accordingly, expression deregulations of the naturally occurring isoforms were supposed to have significant effect on RAGE-mediated disorders. Thereby the soluble C-truncated RAGE isoforms present in plasma and tissues are the mostly focused isoforms in research and clinics. Deregulations of the circulating levels of soluble RAGE forms were reported in several RAGE-associated pathological disorders including for example atherosclerosis, diabetes, renal failure, Alzheimer's disease, and several cancer types. Regarding other mammalian species, the canine RAGE gene showed high similarities to the corresponding human structures indicating RAGE to be evolutionary highly conserved between both species. Similar to humans the canine RAGE showed a complex and extensive splicing activity leading to a manifold pattern of RAGE isoforms. Due to the similarities seen in several canine and human diseases-including cancer-comparative structural and functional analyses allow the development of RAGE and ligand-specific therapeutic approaches beneficial for human and veterinary medicine.

  13. Splicing pattern - ASTRA | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available List Contact us ASTRA Splicing pattern Data detail Data name Splicing pattern DOI 10.18908/lsdba.nbdc00371-0...04 Description of data contents The patterns of alternative splicing/transcriptional initiation Data file Fi...le name: astra_splicing_pattern.zip File URL: ftp://ftp.biosciencedbc.jp/archive/astra/LATEST/astra_splicing_patt...ogodb/view/astra_splicing_pattern#en Data acquisition method For the five organisms (H. sapiens, M. musculus...apping data into bit arrays, detection of splicing patterns and distribution to t

  14. Time domain calculation of connector loads of a very large floating structure

    Science.gov (United States)

    Gu, Jiayang; Wu, Jie; Qi, Enrong; Guan, Yifeng; Yuan, Yubo

    2015-06-01

    Loads generated after an air crash, ship collision, and other accidents may destroy very large floating structures (VLFSs) and create additional connector loads. In this study, the combined effects of ship collision and wave loads are considered to establish motion differential equations for a multi-body VLFS. A time domain calculation method is proposed to calculate the connector load of the VLFS in waves. The Longuet-Higgins model is employed to simulate the stochastic wave load. Fluid force and hydrodynamic coefficient are obtained with DNV Sesam software. The motion differential equation is calculated by applying the time domain method when the frequency domain hydrodynamic coefficient is converted into the memory function of the motion differential equation of the time domain. As a result of the combined action of wave and impact loads, high-frequency oscillation is observed in the time history curve of the connector load. At wave directions of 0° and 75°, the regularities of the time history curves of the connector loads in different directions are similar and the connector loads of C1 and C2 in the X direction are the largest. The oscillation load is observed in the connector in the Y direction at a wave direction of 75° and not at 0°. This paper presents a time domain calculation method of connector load to provide a certain reference function for the future development of Chinese VLFS

  15. Shear Capacity of C-Shaped and L-Shaped Angle Shear Connectors

    Science.gov (United States)

    Tahmasbi, Farzad; Maleki, Shervin; Shariati, Mahdi; Ramli Sulong, N. H.; Tahir, M. M.

    2016-01-01

    This paper investigates the behaviour of C-shaped and L-shaped angle shear connectors embedded in solid concrete slabs. An effective finite element model is proposed to simulate the push out tests of these shear connectors that encompass nonlinear material behaviour, large displacement and damage plasticity. The finite element models are validated against test results. Parametric studies using this nonlinear model are performed to investigate the variations in concrete strength and connector dimensions. The finite element analyses also confirm the test results that increasing the length of shear connector increases their shear strength proportionately. It is observed that the maximum stress in L-shaped angle connectors takes place in the weld attachment to the beam, whereas in the C-shaped angle connectors, it is in the attached leg. The location of maximum concrete compressive damage is rendered in each case. Finally, a new equation for prediction of the shear capacity of C-shaped angle connectors is proposed. PMID:27478894

  16. Study of light transmission through optical fiber-to-fiber connector assemblies

    International Nuclear Information System (INIS)

    Chung, M.; Gutowski, M.; Adams, M.; Solomon, J.

    1998-01-01

    Optical fiber-to-fiber connectors are now being used widely in particle tracking detectors. We describe the properties of the connectors, their production, and measurements of the light transmission through the gap of the connector assembly. We studied light transmission for various types of connectors illuminated by several different light sources. The light transmission was found to be dependent on the angular distribution of the light rays passing through a connector assembly. Two arrangements were studied, a point source and a diffuse source. A green LED with a diffuser is believed to best reproduce the angular distributions of light in the real detector applications. We also studied the transmission as a function of the index of refraction of the optical couplants. The light transmission depends on the index of refraction of an optical couplant placed in the gap, and improves as it approaches the index of refraction of the fiber core. Light transmissions of 80%∼88% were obtained without any optical couplant in the connector gap and transmissions of 89%∼99% with various optical couplants. A Monte Carlo study using measured light distributions from a fiber end produced a reasonable agreement with the transmission measurements made on a connector assembly

  17. Shear Capacity of C-Shaped and L-Shaped Angle Shear Connectors.

    Directory of Open Access Journals (Sweden)

    Farzad Tahmasbi

    Full Text Available This paper investigates the behaviour of C-shaped and L-shaped angle shear connectors embedded in solid concrete slabs. An effective finite element model is proposed to simulate the push out tests of these shear connectors that encompass nonlinear material behaviour, large displacement and damage plasticity. The finite element models are validated against test results. Parametric studies using this nonlinear model are performed to investigate the variations in concrete strength and connector dimensions. The finite element analyses also confirm the test results that increasing the length of shear connector increases their shear strength proportionately. It is observed that the maximum stress in L-shaped angle connectors takes place in the weld attachment to the beam, whereas in the C-shaped angle connectors, it is in the attached leg. The location of maximum concrete compressive damage is rendered in each case. Finally, a new equation for prediction of the shear capacity of C-shaped angle connectors is proposed.

  18. Study of light transmission through optical fiber-to-fiber connector assemblies

    International Nuclear Information System (INIS)

    Chung, M.; Gutowski, M.; Adams, M.; Solomon, J.

    1998-01-01

    Optical fiber-to-fiber connectors are now being used widely in particle tracking detectors. We describe the properties of the connectors, their production, and measurements of the light transmission through the gap of the connector assembly. We studied light transmission for various types of connectors illuminated by several different light sources. The light transmission was found to be dependent on the angular distribution of the light rays passing through a connector assembly. Two arrangements were studied, a point source and a diffuse source. A green LED with a diffuser is believed to best reproduce the angular distributions of light in the real detector applications. We also studied the transmission as a function of the index of refraction of the optical couplants. The light transmission depends on the index of refraction of an optical couplant placed in the gap, and improves as it approaches the index of refraction of the fiber core. Light transmissions of 80%∼88% were obtained without any optical couplant in the connector gap and transmissions of 89%∼99% with various optical couplants. A Monte Carlo study using measured light distributions from a fiber end produced a reasonable agreement with the transmission measurements made on a connector assembly. copyright 1998 American Institute of Physics

  19. Coulomb string tension, asymptotic string tension, and the gluon chain

    OpenAIRE

    Greensite, Jeff; Szczepaniak, Adam P.

    2014-01-01

    We compute, via numerical simulations, the non-perturbative Coulomb potential of pure SU(3) gauge theory in Coulomb gauge. We find that that the Coulomb potential scales nicely in accordance with asymptotic freedom, that the Coulomb potential is linear in the infrared, and that the Coulomb string tension is about four times larger than the asymptotic string tension. We explain how it is possible that the asymptotic string tension can be lower than the Coulomb string tension by a factor of four.

  20. Effect of confinement on bond strength of hot-dip galvanized lap splices in concrete structures

    International Nuclear Information System (INIS)

    Fakhran, Mazen

    2004-01-01

    Galvanizing the reinforcing steel is one of the methods used to protect bars against corrosion. Galvanizing is a hot dip process where the reinforcing bars are immersed in an aqueous pre flux solution of zinc ammonium chloride at a controlled temperature between 840 and 850 degrees F. In 2001, a research program was started at AUB to evaluate experimentally the effect of hot dip galvanizing on the bond capacity of tension lap splices anchored in full-scale beam specimens designed to fail in bond splitting mode. The test results indicated that the use of galvanized bars had a negligible effect on bond strength of reinforcement in normal strength. However, galvanizing caused an average of 20 percent decrease in bond strength of reinforcement in high strength concrete. The primary objective of research reported in this thesis, is the need to find a solution to eliminate the bond reduction of galvanized bars in high strength concrete. It is significant to evaluate the positive effect of the addition of transverse reinforcement in the splice region. The hypothesis to be tested is that such transverse reinforcement will insure uniform bond stress distribution over the entire splice region, thus mobilizing all bar lugs along the splice in the stress transfer mechanism between the bar and the surrounding concrete. Such mechanism might reduce the significant decrease in bond strength in high strength concrete due to galvanizing. To achieve this objective, eighteen full-scale beam specimens were tested in positive bending. Each beam was reinforced with bars spliced in a constant moment region at midspam. The splice length was chosen in such a way that the beams failed in bond splitting of the concrete cover in the splice region. The main variables were type of coating (black or galvanized bars), bar size (20, 25 and 32 mm), and amount of transverse reinforcement in the splice region (0, 2 or 4 stirrups). The test results indicated that confinement did not have a significant

  1. Analysis of the Shear Behavior of Stubby Y-Type Perfobond Rib Shear Connectors for a Composite Frame Structure.

    Science.gov (United States)

    Kim, Sang-Hyo; Kim, Kun-Soo; Lee, Do-Hoon; Park, Jun-Seung; Han, Oneil

    2017-11-22

    Shear connectors are used in steel beam-concrete slabs of composite frame and bridge structures to transfer shear force according to design loads. The existing Y-type perfobond rib shear connectors are designed for girder slabs of composite bridges. Therefore, the rib and transverse rebars of the conventional Y-type perfobond rib shear connectors are extremely large for the composite frames of building structures. Thus, this paper proposes stubby Y-type perfobond rib shear connectors, redefining the existing connectors, for composite frames of building structures; these were used to perform push-out tests. These shear connectors have relatively small ribs compared to the conventional Y-type perfobond rib shear connectors. To confirm the shear resistance of these stubby shear connectors, we performed an experiment by using transverse rebars D13 and D16. The results indicate that these shear connectors have suitable shear strength and ductility for application in composite frame structures. The shear strengths obtained using D13 and D16 were not significantly different. However, the ductility of the shear connectors with D16 was 45.1% higher than that of the shear connectors with D13.

  2. Human Splicing Finder: an online bioinformatics tool to predict splicing signals.

    Science.gov (United States)

    Desmet, François-Olivier; Hamroun, Dalil; Lalande, Marine; Collod-Béroud, Gwenaëlle; Claustres, Mireille; Béroud, Christophe

    2009-05-01

    Thousands of mutations are identified yearly. Although many directly affect protein expression, an increasing proportion of mutations is now believed to influence mRNA splicing. They mostly affect existing splice sites, but synonymous, non-synonymous or nonsense mutations can also create or disrupt splice sites or auxiliary cis-splicing sequences. To facilitate the analysis of the different mutations, we designed Human Splicing Finder (HSF), a tool to predict the effects of mutations on splicing signals or to identify splicing motifs in any human sequence. It contains all available matrices for auxiliary sequence prediction as well as new ones for binding sites of the 9G8 and Tra2-beta Serine-Arginine proteins and the hnRNP A1 ribonucleoprotein. We also developed new Position Weight Matrices to assess the strength of 5' and 3' splice sites and branch points. We evaluated HSF efficiency using a set of 83 intronic and 35 exonic mutations known to result in splicing defects. We showed that the mutation effect was correctly predicted in almost all cases. HSF could thus represent a valuable resource for research, diagnostic and therapeutic (e.g. therapeutic exon skipping) purposes as well as for global studies, such as the GEN2PHEN European Project or the Human Variome Project.

  3. Reliability aspects of a composite bolted scarf joint. [in wing skin splice

    Science.gov (United States)

    Reed, D. L.; Eisenmann, J. R.

    1975-01-01

    The design, fabrication, static test, and fatigue test of both tension and compression graphite-epoxy candidates for a wing splice representative of a next-generation transport aircraft was the objective of the reported research program. A single-scarf bolted joint was selected as the design concept. Test specimens were designed and fabricated to represent an upper-surface and a lower-surface panel containing the splice. The load spectrum was a flight-by-flight random-load history including ground-air-ground loads. The results of the fatigue testing indicate that, for this type of joint, the inherent fatigue resistance of the laminate is reflected in the joint behavior and, consequently, the rate of damage accumulation is very slow under realistic fatigue loadings.

  4. HOLLYWOOD: a comparative relational database of alternative splicing.

    Science.gov (United States)

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

    2006-01-01

    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 about the splicing of orthologous genes in different species, we have developed the Hollywood system. This database was built upon genomic annotation of splicing patterns of known genes derived from spliced alignment of complementary DNAs (cDNAs) and expressed sequence tags, and links features such as splice site sequence and strength, exonic splicing enhancers and silencers, conserved and non-conserved patterns of splicing, and cDNA library information for inferred alternative exons. Hollywood was implemented as a relational database and currently contains comprehensive information for human and mouse. It is accompanied by a web query tool that allows searches for sets of exons with specific splicing characteristics or splicing regulatory element composition, or gives a graphical or sequence-level summary of splicing patterns for a specific gene. A streamlined graphical representation of gene splicing patterns is provided, and these patterns can alternatively be layered onto existing information in the UCSC Genome Browser. The database is accessible at http://hollywood.mit.edu.

  5. 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.

  6. Variation in alternative splicing across human tissues

    OpenAIRE

    Yeo, Gene; Holste, Dirk; Kreiman, Gabriel; Burge, Christopher B

    2004-01-01

    Background: Alternative pre-mRNA splicing (AS) is widely used by higher eukaryotes to generate different protein isoforms in specific cell or tissue types. To compare AS events across human tissues, we analyzed the splicing patterns of genomically aligned expressed sequence tags (ESTs) derived from libraries of cDNAs from different tissues. Results: Controlling for differences in EST coverage among tissues, we found that the brain and testis had the highest levels of exon skipping. The most p...

  7. Thermopriming Triggers Splicing Memory in Arabidopsis

    KAUST Repository

    Ling, Yu

    2018-02-20

    Abiotic and biotic stresses limit crop productivity. Exposure to a non-lethal stress, referred to as priming, can allow plants to survive subsequent and otherwise lethal conditions; the priming effect persists even after a prolonged stress-free period. However, the molecular mechanisms underlying priming are not fully understood. Here, we investigated the molecular basis of heat shock memory and the role of priming in Arabidopsisthaliana. Comprehensive analysis of transcriptome-wide changes in gene expression and alternative splicing in primed and non-primed plants revealed that alternative splicing functions as a novel component of heat shock memory. We show that priming of plants with a non-lethal heat stress results in de-repression of splicing after a second exposure to heat stress. By contrast, non-primed plants showed significant repression of splicing. These observations link ‘splicing memory’ to the ability of plants to survive subsequent and otherwise lethal heat stress. This newly discovered priming-induced splicing memory may represent a general feature of heat stress responses in plants and other organisms as many of the key components of heat shock responses are conserved among eukaryotes. Furthermore, this finding could facilitate the development of novel approaches to improve plant survival under extreme heat stress.

  8. Combined effects of fretting and pollutant particles on the contact resistance of the electrical connectors

    Directory of Open Access Journals (Sweden)

    Zhigang Kong

    2017-06-01

    Full Text Available Usually, when electrical connectors operate in vibration environments, fretting will be produced at the contact interfaces. In addition, serious environmental pollution particles will affect contact resistance of the connectors. The fretting will worsen the reliability of connectors with the pollutant particles. The combined effects of fretting and quartz particles on the contact resistance of the gold plating connectors are studied with a fretting test system. The results show that the frequencies have obvious effect on the contact resistance. The higher the frequency, the higher the contact resistance is. The quartz particles cause serious wear of gold plating, which make the nickel and copper layer exposed quickly to increase the contact resistance. Especially in high humidity environments, water supply certain adhesion function and make quartz particles easy to insert or cover the contact surfaces, and even cause opening resistance.

  9. New approach for high reliability, low loss splicing between silica and ZBLAN fibers

    Science.gov (United States)

    Carbonnier, Robin; Zheng, Wenxin

    2018-02-01

    In the past decade, ZBLAN (ZrF4-BaF2-LaF3-NaF) fibers have drawn increasing interest for laser operations at wavelengths where Fused Silica-based (SiO2) fibers do not perform well. One limitation to the expansion of ZBLAN fiber lasers today is the difficulty to efficiently inject and extract light in/from the guiding medium using SiO2 fibers. Although free space and butt coupling have provided acceptable results, consistent and long lasting physical joints between SiO2 and ZBLAN fibers will allow smaller, cheaper, and more robust component manufacturing. While low loss splices have been reported using a traditional splicing approach, the very low mechanical strength of the joint makes it difficult to scale. Difficulties in achieving a strong bond are mainly due to the large difference of transition temperature between ZBLAN and SiO2 fibers ( 260°C vs 1175°C). This paper presents results obtained by using the high thermal expansion coefficient of the ZBLAN fiber to encapsulate a smaller SiO2 fiber. A CO2 laser glass processing system was used to control the expansion and contraction of the ZBLAN material during the splicing process for optimum reliability. This method produced splices between 125μm ZBLAN to 80μm SiO2 fibers with average transmission loss of 0.225dB (measured at 1550nm) and average ultimate tension strength of 121.4gf. The Resulting splices can be durably packaged without excessive care. Other combinations using 125μm SiO2 fibers tapered to 80μm are also discussed.

  10. A conceptual framework for designing micro electrical connectors for hearing aid instruments

    OpenAIRE

    Doagou Rad, Saeed; Islam, Aminul; Fuglsang-Philip, M.

    2016-01-01

    Electrical connectors play vital roles in modern electronic instruments. Hearing aid devices as advanced combinations of micro mechanics and electronics comprise various electrical connectors for different purposes. However, the current trend in the miniaturization along with the sharp technological advancements have urged them to incorporate increased number of electrical contacts. The current paper presents a conceptual framework for designing and manufacturing novel plug and socket systems...

  11. Genetics of alternative splicing evolution during sunflower domestication.

    Science.gov (United States)

    Smith, Chris C R; Tittes, Silas; Mendieta, J Paul; Collier-Zans, Erin; Rowe, Heather C; Rieseberg, Loren H; Kane, Nolan C

    2018-06-11

    Alternative splicing enables organisms to produce the diversity of proteins necessary for multicellular life by using relatively few protein-coding genes. Although differences in splicing have been identified among divergent taxa, the shorter-term evolution of splicing is understudied. The origins of novel splice forms, and the contributions of alternative splicing to major evolutionary transitions, are largely unknown. This study used transcriptomes of wild and domesticated sunflowers to examine splice differentiation and regulation during domestication. We identified substantial splicing divergence between wild and domesticated sunflowers, mainly in the form of intron retention. Transcripts with divergent splicing were enriched for seed-development functions, suggesting that artificial selection impacted splicing patterns. Mapping of quantitative trait loci (QTLs) associated with 144 differential splicing cases revealed primarily trans -acting variation affecting splicing patterns. A large proportion of identified QTLs contain known spliceosome proteins and are associated with splicing variation in multiple genes. Examining a broader set of wild and domesticated sunflower genotypes revealed that most differential splicing patterns in domesticated sunflowers likely arose from standing variation in wild Helianthus annuus and gained frequency during the domestication process. However, several domesticate-associated splicing patterns appear to be introgressed from other Helianthus species. These results suggest that sunflower domestication involved selection on pleiotropic regulatory alleles. More generally, our findings indicate that substantial differences in isoform abundances arose rapidly during a recent evolutionary transition and appear to contribute to adaptation and population divergence.

  12. Alternative RNA splicing and gastric cancer.

    Science.gov (United States)

    Li, Ying; Yuan, Yuan

    2017-07-01

    Alternative splicing (AS) linked to diseases, especially to tumors. Recently, more and more studies focused on the relationship between AS and gastric cancer (GC). This review surveyed the hot topic from four aspects: First, the common types of AS in cancer, including exon skipping, intron retention, mutually exclusive exon, alternative 5 ' or 3' splice site, alternative first or last exon and alternative 3' untranslated regions. Second, basic mechanisms of AS and its relationship with cancer. RNA splicing in eukaryotes follows the GT-AG rule by both cis-elements and trans-acting factors regulatory. Through RNA splicing, different proteins with different forms and functions can be produced and may be associated with carcinogenesis. Third, AS types of GC-related genes and their splicing variants. In this paper, we listed 10 common genes with AS and illustrated its possible molecular mechanisms owing to genetic variation (mutation and /or polymorphism). Fourth, the splicing variants of GC-associated genes and gastric carcinogenesis, invasion and metastasis. Many studies have found that the different splicing variants of the same gene are differentially expressed in GC and its precancerous diseases, suggesting AS has important implications in GC development. Taking together, this review highlighted the role of AS and splicing variants in the process of GC. We hope that this is not only beneficial to advances in the study field of GC, but also can provide valuable information to other similar tumor research.Although we already know some gene splicing and splicing variants play an important role in the development of GC, but many phenomena and mechanisms are still unknown. For example, how the tumor microenvironment and signal transduction pathway effect the forming and function of AS? Unfortunately, this review did not cover the contents because the current study is limited. It is no doubt that clarifying the phenomena and mechanisms of these unknown may help to reveal

  13. HIV-1 splicing is controlled by local RNA structure and binding of splicing regulatory proteins at the major 5' splice site

    NARCIS (Netherlands)

    Mueller, Nancy; Berkhout, Ben; Das, Atze T.

    2015-01-01

    The 5' leader region of the human immunodeficiency virus 1 (HIV-1) RNA genome contains the major 5' splice site (ss) that is used in the production of the many spliced viral RNAs. This splice-donor (SD) region can fold into a stable stem-loop structure and the thermodynamic stability of this RNA

  14. Development of a Skewed Pipe Shear Connector for Precast Concrete Structures.

    Science.gov (United States)

    Kim, Sang-Hyo; Choi, Jae-Gu; Park, Sejun; Lee, Hyunmin; Heo, And Won-Ho

    2017-05-13

    Joint connection methods, such as shear key and loop bar, improve the structural performance of precast concrete structures; consequently, there is usually decreased workability or constructional efficiency. This paper proposes a high-efficiency skewed pipe shear connector. To resist shear and pull-out forces, the proposed connectors are placed diagonally between precast concrete segments and a cast-in-place concrete joint part on a girder. Design variables (such as the pipe diameter, length, and insertion angle) have been examined to investigate the connection performance of the proposed connector. The results of our testing indicate that the skewed pipe shear connectors have 50% higher ductility and a 15% higher ratio of maximum load to yield strength as compared to the corresponding parameters of the loop bar. Finite element analysis was used for validation. The resulting validation indicates that, compared to the loop bar, the skewed pipe shear connector has a higher ultimate shear and pull-out resistance. These results indicate that the skewed pipe shear connector demonstrates more idealized behavior than the loop bar in precast concrete structures.

  15. Modular glovebox connector and associated good practices for control of radioactive and chemically toxic materials

    International Nuclear Information System (INIS)

    Hoover, M.D.; Mewhinney, C.J.; Newton, G.J.

    1999-01-01

    Design and associated good practices are described for a modular glovebox connector to improve control of radioactive and chemically toxic materials. The connector consists of an anodized aluminum circular port with a mating spacer, gaskets, and retaining rings for joining two parallel ends of commercially available or custom-manufactured glovebox enclosures. Use of the connector allows multiple gloveboxes to be quickly assembled or reconfigured in functional units. Connector dimensions can be scaled to meet operational requirements for access between gloveboxes. Options for construction materials are discussed, along with recommendations for installation of the connector in new or retrofitted systems. Associated good practices include application of surface coatings and caulking, use of disposable glovebags, and proper selection and protection of gasket and glove materials. Use of the connector at an inhalation toxicology research facility has reduced the time and expense required to reconfigure equipment for changing operational requirements, the dispersion of contamination during reconfigurations, and the need for decommissioning and disposal of contaminated enclosures

  16. NRC Information No. 89-23: Environmental qualification of Litton-Veam CIR series electrical connectors

    International Nuclear Information System (INIS)

    Rossi, C.E.

    1992-01-01

    Litton-Veam CIR series multi-pin electrical connectors are used in core exit thermocouple (CET) and reactor vessel level monitoring (RVLM) systems supplied to numerous plants by Combustion Engineering, Inc., and are used in other applications in at least three additional plants. A proprietary qualification test report has been used to document environmental qualification of the connectors for loss of coolant accident (LOCA) conditions in the CE-supplied systems. During LOCA testing, the connector face seal gasket was completely degraded and elastomeric inserts interacted with simulated containment spray solution which leaked into the connector. Insulation resistances near 1,000 ohms were measured. CE has performed analyses to show that resultant errors are acceptable in CE-supplied CET and RVLM system thermocouple circuits. However, the moisture ingress and resultant low insulation resistances are not acceptable for heater circuits in the RVLM. For that application, CE developed two remedies; one is a clamp, and the other is a new connector design. CE has advised that one of these remedies has been used for all of the RVLM heater circuits. Unmodified CIR connectors are believed to be still in use in other applications

  17. Behaviour of C-shaped angle shear connectors under monotonic and fully reversed cyclic loading: An experimental study

    International Nuclear Information System (INIS)

    Shariati, Mahdi; Ramli Sulong, N.H.; Suhatril, Meldi; Shariati, Ali; Arabnejad Khanouki, M.M.; Sinaei, Hamid

    2012-01-01

    Highlights: ► C-shaped angle connectors show 8.8–33.1% strength degradation under cyclic loading. ► Connector fracture type of failure was experienced in C-shaped angle shear connectors. ► In push-out samples, more cracking was observed in those slabs with longer angles. ► C-shaped angle connectors show good behaviour in terms of the ultimate shear capacity. ► C-shaped angle connectors did not fulfil the requirements for ductility criteria. -- Abstract: This paper presents an evaluation of the structural behaviour of C-shaped angle shear connectors in composite beams, suitable for transferring shear force in composite structures. The results of the experimental programme, including eight push-out tests, are presented and discussed. The results include resistance, strength degradation, ductility, and failure modes of C-shaped angle shear connectors, under monotonic and fully reversed cyclic loading. The results show that connector fracture type of failure was experienced in C-shaped angle connectors and after the failure, more cracking was observed in those slabs with longer angles. On top of that, by comparing the shear resistance of C-shaped angle shear connectors under monotonic and cyclic loading, these connectors showed 8.8–33.1% strength degradation, under fully reversed cyclic loading. Furthermore, it was concluded that the mentioned shear connector shows a proper behaviour, in terms of the ultimate shear capacity, but it does not satisfy the ductility criteria, imposed by the Eurocode 4, to perform a plastic distribution of the shear force between different connectors along the beam length.

  18. Vitamin D and alternative splicing of RNA.

    Science.gov (United States)

    Zhou, Rui; Chun, Rene F; Lisse, Thomas S; Garcia, Alejandro J; Xu, Jianzhong; Adams, John S; Hewison, Martin

    2015-04-01

    The active form of vitamin D (1α,25-dihydroxyvitamin D, 1,25(OH)2D) exerts its genomic effects via binding to a nuclear high-affinity vitamin D receptor (VDR). Recent deep sequencing analysis of VDR binding locations across the complete genome has significantly expanded our understanding of the actions of vitamin D and VDR on gene transcription. However, these studies have also promoted appreciation of the extra-transcriptional impact of vitamin D on gene expression. It is now clear that vitamin D interacts with the epigenome via effects on DNA methylation, histone acetylation, and microRNA generation to maintain normal biological functions. There is also increasing evidence that vitamin D can influence pre-mRNA constitutive splicing and alternative splicing, although the mechanism for this remains unclear. Pre-mRNA splicing has long been thought to be a post-transcription RNA processing event, but current data indicate that this occurs co-transcriptionally. Several steroid hormones have been recognized to coordinately control gene transcription and pre-mRNA splicing through the recruitment of nuclear receptor co-regulators that can both control gene transcription and splicing. The current review will discuss this concept with specific reference to vitamin D, and the potential role of heterogeneous nuclear ribonucleoprotein C (hnRNPC), a nuclear factor with an established function in RNA splicing. hnRNPC, has been shown to be involved in the VDR transcriptional complex as a vitamin D-response element-binding protein (VDRE-BP), and may act as a coupling factor linking VDR-directed gene transcription with RNA splicing. In this way hnRNPC may provide an additional mechanism for the fine-tuning of vitamin D-regulated target gene expression. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Tension-type headache

    DEFF Research Database (Denmark)

    Bendtsen, Lars; Jensen, Rigmor; Bendtsen, Lars

    2009-01-01

    The substantial societal and individual burdens associated with tension-type headache (TTH) constitute a previously overlooked major public health issue. TTH is prevalent, affecting up to 78% of the general population, and 3% suffer from chronic TTH. Pericranial myofascial nociception probably...... is important for the pathophysiology of episodic TTH, whereas sensitization of central nociceptive pathways seems responsible for the conversion of episodic to chronic TTH. Headache-related disability usually can be reduced by identification of trigger factors combined with nonpharmacologic and pharmacologic...... treatments, but effective treatment modalities are lacking. Benefits can be gained by development of specific and effective treatment strategies....

  20. 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.

  1. Homologous SV40 RNA trans-splicing: Special case or prime example of viral RNA trans-splicing?

    Directory of Open Access Journals (Sweden)

    Sushmita Poddar

    2014-06-01

    Full Text Available To date the Simian Virus 40 (SV40 is the only proven example of a virus that recruits the mechanism of RNA trans-splicing to diversify its sequences and gene products. Thereby, two identical viral transcripts are efficiently joined by homologous trans-splicing triggering the formation of a highly transforming 100 kDa super T antigen. Sequences of other viruses including HIV-1 and the human adenovirus type 5 were reported to be involved in heterologous trans-splicing towards cellular or viral sequences but the meaning of these events remains unclear. We computationally and experimentally investigated molecular features associated with viral RNA trans-splicing and identified a common pattern: Viral RNA trans-splicing occurs between strong cryptic or regular viral splice sites and strong regular or cryptic splice sites of the trans-splice partner sequences. The majority of these splice sites are supported by exonic splice enhancers. Splice sites that could compete with the trans-splicing sites for cis-splice reactions are weaker or inexistent. Finally, all but one of the trans-splice reactions seem to be facilitated by one or more complementary binding domains of 11 to 16 nucleotides in length which, however occur with a statistical probability close to one for the given length of the involved sequences. The chimeric RNAs generated via heterologous viral RNA trans-splicing either did not lead to fusion proteins or led to proteins of unknown function. Our data suggest that distinct viral RNAs are highly susceptible to trans-splicing and that heterologous viral trans-splicing, unlike homologous SV40 trans-splicing, represents a chance event.

  2. Modelling reveals kinetic advantages of co-transcriptional splicing.

    Directory of Open Access Journals (Sweden)

    Stuart Aitken

    2011-10-01

    Full Text Available Messenger RNA splicing is an essential and complex process for the removal of intron sequences. Whereas the composition of the splicing machinery is mostly known, the kinetics of splicing, the catalytic activity of splicing factors and the interdependency of transcription, splicing and mRNA 3' end formation are less well understood. We propose a stochastic model of splicing kinetics that explains data obtained from high-resolution kinetic analyses of transcription, splicing and 3' end formation during induction of an intron-containing reporter gene in budding yeast. Modelling reveals co-transcriptional splicing to be the most probable and most efficient splicing pathway for the reporter transcripts, due in part to a positive feedback mechanism for co-transcriptional second step splicing. Model comparison is used to assess the alternative representations of reactions. Modelling also indicates the functional coupling of transcription and splicing, because both the rate of initiation of transcription and the probability that step one of splicing occurs co-transcriptionally are reduced, when the second step of splicing is abolished in a mutant reporter.

  3. Modelling reveals kinetic advantages of co-transcriptional splicing.

    Science.gov (United States)

    Aitken, Stuart; Alexander, Ross D; Beggs, Jean D

    2011-10-01

    Messenger RNA splicing is an essential and complex process for the removal of intron sequences. Whereas the composition of the splicing machinery is mostly known, the kinetics of splicing, the catalytic activity of splicing factors and the interdependency of transcription, splicing and mRNA 3' end formation are less well understood. We propose a stochastic model of splicing kinetics that explains data obtained from high-resolution kinetic analyses of transcription, splicing and 3' end formation during induction of an intron-containing reporter gene in budding yeast. Modelling reveals co-transcriptional splicing to be the most probable and most efficient splicing pathway for the reporter transcripts, due in part to a positive feedback mechanism for co-transcriptional second step splicing. Model comparison is used to assess the alternative representations of reactions. Modelling also indicates the functional coupling of transcription and splicing, because both the rate of initiation of transcription and the probability that step one of splicing occurs co-transcriptionally are reduced, when the second step of splicing is abolished in a mutant reporter.

  4. The 20S proteasome splicing activity discovered by SpliceMet.

    Directory of Open Access Journals (Sweden)

    Juliane Liepe

    2010-06-01

    Full Text Available The identification of proteasome-generated spliced peptides (PSP revealed a new unpredicted activity of the major cellular protease. However, so far characterization of PSP was entirely dependent on the availability of patient-derived cytotoxic CD8+ T lymphocytes (CTL thus preventing a systematic investigation of proteasome-catalyzed peptide splicing (PCPS. For an unrestricted PSP identification we here developed SpliceMet, combining the computer-based algorithm ProteaJ with in vitro proteasomal degradation assays and mass spectrometry. By applying SpliceMet for the analysis of proteasomal processing products of four different substrate polypeptides, derived from human tumor as well as viral antigens, we identified fifteen new spliced peptides generated by PCPS either by cis or from two separate substrate molecules, i.e., by trans splicing. Our data suggest that 20S proteasomes represent a molecular machine that, due to its catalytic and structural properties, facilitates the generation of spliced peptides, thereby providing a pool of qualitatively new peptides from which functionally relevant products may be selected.

  5. Landscape of the spliced leader trans-splicing mechanism in Schistosoma mansoni.

    Science.gov (United States)

    Boroni, Mariana; Sammeth, Michael; Gava, Sandra Grossi; Jorge, Natasha Andressa Nogueira; Macedo, Andréa Mara; Machado, Carlos Renato; Mourão, Marina Moraes; Franco, Glória Regina

    2018-03-01

    Spliced leader dependent trans-splicing (SLTS) has been described as an important RNA regulatory process that occurs in different organisms, including the trematode Schistosoma mansoni. We identified more than seven thousand putative SLTS sites in the parasite, comprising genes with a wide spectrum of functional classes, which underlines the SLTS as a ubiquitous mechanism in the parasite. Also, SLTS gene expression levels span several orders of magnitude, showing that SLTS frequency is not determined by the expression level of the target gene, but by the presence of particular gene features facilitating or hindering the trans-splicing mechanism. Our in-depth investigation of SLTS events demonstrates widespread alternative trans-splicing (ATS) acceptor sites occurring in different regions along the entire gene body, highlighting another important role of SLTS generating alternative RNA isoforms in the parasite, besides the polycistron resolution. Particularly for introns where SLTS directly competes for the same acceptor substrate with cis-splicing, we identified for the first time additional and important features that might determine the type of splicing. Our study substantially extends the current knowledge of RNA processing by SLTS in S. mansoni, and provide basis for future studies on the trans-splicing mechanism in other eukaryotes.

  6. 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.

  7. Alternative splicing in cancers: From aberrant regulation to new therapeutics.

    Science.gov (United States)

    Song, Xiaowei; Zeng, Zhenyu; Wei, Huanhuan; Wang, Zefeng

    2018-03-01

    Alternative splicing is one of the most common mechanisms for gene regulation in humans, and plays a vital role to increase the complexity of functional proteins. In this article, we seek to provide a general review on the relationships between alternative splicing and tumorigenesis. We briefly introduce the basic rules for regulation of alternative splicing, and discuss recent advances on dynamic regulation of alternative splicing in cancers by highlighting the roles of a variety of RNA splicing factors in tumorigenesis. We further discuss several important questions regarding the splicing of long noncoding RNAs and back-splicing of circular RNAs in cancers. Finally, we discuss the current technologies that can be used to manipulate alternative splicing and serve as potential cancer treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. General definition of gravitational tension

    International Nuclear Information System (INIS)

    Harmark, T.; Obers, N.A.

    2004-01-01

    In this note we give a general definition of the gravitational tension in a given asymptotically translationally-invariant spatial direction of a space-time. The tension is defined via the extrinsic curvature in analogy with the Hawking-Horowitz definition of energy. We show the consistency with the ADM tension formulas for asymptotically-flat space-times, in particular for Kaluza-Klein black hole solutions. Moreover, we apply the general tension formula to near-extremal branes, constituting a check for non-asymptotically flat space-times. (author)

  9. SPA: a probabilistic algorithm for spliced alignment.

    Directory of Open Access Journals (Sweden)

    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

  10. Hereditary cancer genes are highly susceptible to splicing mutations

    Science.gov (United States)

    Soemedi, Rachel; Maguire, Samantha; Murray, Michael F.; Monaghan, Sean F.

    2018-01-01

    Substitutions that disrupt pre-mRNA splicing are a common cause of genetic disease. On average, 13.4% of all hereditary disease alleles are classified as splicing mutations mapping to the canonical 5′ and 3′ splice sites. However, splicing mutations present in exons and deeper intronic positions are vastly underreported. A recent re-analysis of coding mutations in exon 10 of the Lynch Syndrome gene, MLH1, revealed an extremely high rate (77%) of mutations that lead to defective splicing. This finding is confirmed by extending the sampling to five other exons in the MLH1 gene. Further analysis suggests a more general phenomenon of defective splicing driving Lynch Syndrome. Of the 36 mutations tested, 11 disrupted splicing. Furthermore, analyzing past reports suggest that MLH1 mutations in canonical splice sites also occupy a much higher fraction (36%) of total mutations than expected. When performing a comprehensive analysis of splicing mutations in human disease genes, we found that three main causal genes of Lynch Syndrome, MLH1, MSH2, and PMS2, belonged to a class of 86 disease genes which are enriched for splicing mutations. Other cancer genes were also enriched in the 86 susceptible genes. The enrichment of splicing mutations in hereditary cancers strongly argues for additional priority in interpreting clinical sequencing data in relation to cancer and splicing. PMID:29505604

  11. Hereditary cancer genes are highly susceptible to splicing mutations.

    Directory of Open Access Journals (Sweden)

    Christy L Rhine

    2018-03-01

    Full Text Available Substitutions that disrupt pre-mRNA splicing are a common cause of genetic disease. On average, 13.4% of all hereditary disease alleles are classified as splicing mutations mapping to the canonical 5' and 3' splice sites. However, splicing mutations present in exons and deeper intronic positions are vastly underreported. A recent re-analysis of coding mutations in exon 10 of the Lynch Syndrome gene, MLH1, revealed an extremely high rate (77% of mutations that lead to defective splicing. This finding is confirmed by extending the sampling to five other exons in the MLH1 gene. Further analysis suggests a more general phenomenon of defective splicing driving Lynch Syndrome. Of the 36 mutations tested, 11 disrupted splicing. Furthermore, analyzing past reports suggest that MLH1 mutations in canonical splice sites also occupy a much higher fraction (36% of total mutations than expected. When performing a comprehensive analysis of splicing mutations in human disease genes, we found that three main causal genes of Lynch Syndrome, MLH1, MSH2, and PMS2, belonged to a class of 86 disease genes which are enriched for splicing mutations. Other cancer genes were also enriched in the 86 susceptible genes. The enrichment of splicing mutations in hereditary cancers strongly argues for additional priority in interpreting clinical sequencing data in relation to cancer and splicing.

  12. An elastic elements calculation in the construction of electrical connectors based on flexible printed cables

    Directory of Open Access Journals (Sweden)

    Yefimenko A. A.

    2016-05-01

    Full Text Available In this article we consider the method of constructive parameters calculation of the elastic elements, which are used in electrical connectors of flexible printed cables. Electrical connectors characterized by the fact that the contact pair is needed to provide pressure. It is also important to know the optimum ratio between stability of the contact connection and the necessary value of the transition resistance. These ratios are studied sufficiently for discrete electrical connectors, however for connectors of flexible printed cables this theme is not explored enough. The purpose of this work is to develop methods that will allow to carry out calculations for elastic elements, which provide communication, and to determine the size of case elements for electrical connectors. We consider two types of connectors. First are removable electrical connections where it is necessary to find a compromise between the resistance value and the separating (engaging force. Second are permanent connections, where counts only the value of the transition resistance. For the first type of connectors were considered a simple form of the liner, in the shape of a rubber block, as in this case, the pressure should be created only by the compression of the liner and fixing it. It is important to get accurate results of the pressure calculation for removable electrical connections, because in this case we consider especial shape of elastomeric liner, which allows to create the pressure not only by compression of the liner, but by deformation it as a spring. For this task, the engaging force was specified on the basis of already known facts. It was important to set the amount of deformation that defines the shape and size of the liner and the case. We solved the problem of transition from the units of measuring hardness, specified in the technical specifications of rubber, to the value of the Young's modulus used in the calculations of constructive parameters of

  13. Using Three-Dimensional Printing to Fabricate a Tubing Connector for Dilation and Evacuation.

    Science.gov (United States)

    Stitely, Michael L; Paterson, Helen

    2016-02-01

    This is a proof-of-concept study to show that simple instrumentation problems encountered in surgery can be solved by fabricating devices using a three-dimensional printer. The device used in the study is a simple tubing connector fashioned to connect two segments of suction tubing used in a surgical procedure where no commercially available product for this use is available through our usual suppliers in New Zealand. A cylindrical tubing connector was designed using three-dimensional printing design software. The tubing connector was fabricated using the Makerbot Replicator 2X three-dimensional printer. The connector was used in 15 second-trimester dilation and evacuation procedures. Data forms were completed by the primary operating surgeon. Descriptive statistics were used with the expectation that the device would function as intended in all cases. The three-dimensional printed tubing connector functioned as intended in all 15 instances. Commercially available three-dimensional printing technology can be used to overcome simple instrumentation problems encountered during gynecologic surgical procedures.

  14. MIL-L-87177 and CLT:X-10 Lubricants Improve Electrical Connector Fretting Corrosion Behavior

    International Nuclear Information System (INIS)

    AUKLAND, NEIL R.; HANLON, JAMES T.

    1999-01-01

    We have conducted a fretting research project using MIL-L-87177 and CLT: X-10 lubricants on Nano-miniature connectors. When they were fretted without lubricant, individual connectors first exceeded our 0.5 ohm failure criteria from 2,341 to 45,238 fretting cycles. With additional fretting, their contact resistance increased to more than 100,000 ohms. Unmodified MIL-L-87177 lubricant delayed the onset of first failure to between 430,000 and over 20,000,000 fretting cycles. MIL-L-87177 modified by addition of Teflon powder delayed first failure to beyond 5 million fretting cycles. Best results were obtained when Teflon was used and also when both the straight and modified lubricants were poured into and then out of the connector. CLT: X-10 lubricant delayed the onset of first failure to beyond 55 million cycles in one test where a failure was actually observed and to beyond 20 million cycles in another that was terminated without failure. CLT: X-10 recovered an unlubricated connector driven deeply into failure, with six failed pins recovering immediately and four more recovering during an additional 420 thousand fretting cycles. MIL-L-87177 was not able to recover a connector under similar conditions

  15. Effect of shear connectors on local buckling and composite action in steel concrete composite walls

    International Nuclear Information System (INIS)

    Zhang, Kai; Varma, Amit H.; Malushte, Sanjeev R.; Gallocher, Stewart

    2014-01-01

    Steel concrete composite (SC) walls are being used for the third generation nuclear power plants, and also being considered for small modular reactors. SC walls consist of thick concrete walls with exterior steel faceplates serving as reinforcement. These steel faceplates are anchored to the concrete infill using shear connectors, for example, headed steel studs. The steel faceplate thickness (t p ) and yield stress (F y ), and the shear connector spacing (s), stiffness (k s ), and strength (Q n ) determine: (a) the level of composite action between the steel plates and the concrete infill, (b) the development length of steel faceplates, and (c) the local buckling of the steel faceplates. Thus, the shear connectors have a significant influence on the behavior of composite SC walls, and should be designed accordingly. This paper presents the effects of shear connector design on the level of composite action and development length of steel faceplates in SC walls. The maximum steel plate slenderness, i.e., ratio of shear connector spacing-to-plate thickness (s/t p ) ratio to prevent local buckling before yielding is also developed based on the existing experimental database and additional numerical analysis

  16. Effect of shear connectors on local buckling and composite action in steel concrete composite walls

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Kai, E-mail: kai-zh@purdue.edu [School of Civil Engineering, Purdue University, West Lafayette, IN (United States); Varma, Amit H., E-mail: ahvarma@purdue.edu [School of Civil Engineering, Purdue University, West Lafayette, IN (United States); Malushte, Sanjeev R., E-mail: smalusht@bechtel.com [Bechtel Power Corporation, Frederick, MD (United States); Gallocher, Stewart, E-mail: stewart.gallocher@steelbricks.com [Modular Walling Systems Ltd., Glasgow (United Kingdom)

    2014-04-01

    Steel concrete composite (SC) walls are being used for the third generation nuclear power plants, and also being considered for small modular reactors. SC walls consist of thick concrete walls with exterior steel faceplates serving as reinforcement. These steel faceplates are anchored to the concrete infill using shear connectors, for example, headed steel studs. The steel faceplate thickness (t{sub p}) and yield stress (F{sub y}), and the shear connector spacing (s), stiffness (k{sub s}), and strength (Q{sub n}) determine: (a) the level of composite action between the steel plates and the concrete infill, (b) the development length of steel faceplates, and (c) the local buckling of the steel faceplates. Thus, the shear connectors have a significant influence on the behavior of composite SC walls, and should be designed accordingly. This paper presents the effects of shear connector design on the level of composite action and development length of steel faceplates in SC walls. The maximum steel plate slenderness, i.e., ratio of shear connector spacing-to-plate thickness (s/t{sub p}) ratio to prevent local buckling before yielding is also developed based on the existing experimental database and additional numerical analysis.

  17. An in vivo genetic screen for genes involved in spliced leader trans-splicing indicates a crucial role for continuous de novo spliced leader RNP assembly.

    Science.gov (United States)

    Philippe, Lucas; Pandarakalam, George C; Fasimoye, Rotimi; Harrison, Neale; Connolly, Bernadette; Pettitt, Jonathan; Müller, Berndt

    2017-08-21

    Spliced leader (SL) trans-splicing is a critical element of gene expression in a number of eukaryotic groups. This process is arguably best understood in nematodes, where biochemical and molecular studies in Caenorhabditis elegans and Ascaris suum have identified key steps and factors involved. Despite this, the precise details of SL trans-splicing have yet to be elucidated. In part, this is because the systematic identification of the molecules involved has not previously been possible due to the lack of a specific phenotype associated with defects in this process. We present here a novel GFP-based reporter assay that can monitor SL1 trans-splicing in living C. elegans. Using this assay, we have identified mutants in sna-1 that are defective in SL trans-splicing, and demonstrate that reducing function of SNA-1, SNA-2 and SUT-1, proteins that associate with SL1 RNA and related SmY RNAs, impairs SL trans-splicing. We further demonstrate that the Sm proteins and pICln, SMN and Gemin5, which are involved in small nuclear ribonucleoprotein assembly, have an important role in SL trans-splicing. Taken together these results provide the first in vivo evidence for proteins involved in SL trans-splicing, and indicate that continuous replacement of SL ribonucleoproteins consumed during trans-splicing reactions is essential for effective trans-splicing. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Tension type headaches: a review

    African Journals Online (AJOL)

    Location of the pain:There is often a typical location for tension- type headaches, as ... Cranial nerve abnormalities, including papilloedema. • Signs of ... peripheral and central mechanisms underlie tension-type ... Physiotherapy has been shown to be an effective management option for .... Acupuncture in primary headache.

  19. 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...

  20. The fitness cost of mis-splicing is the main determinant of alternative splicing patterns.

    Science.gov (United States)

    Saudemont, Baptiste; Popa, Alexandra; Parmley, Joanna L; Rocher, Vincent; Blugeon, Corinne; Necsulea, Anamaria; Meyer, Eric; Duret, Laurent

    2017-10-30

    Most eukaryotic genes are subject to alternative splicing (AS), which may contribute to the production of protein variants or to the regulation of gene expression via nonsense-mediated messenger RNA (mRNA) decay (NMD). However, a fraction of splice variants might correspond to spurious transcripts and the question of the relative proportion of splicing errors to functional splice variants remains highly debated. We propose a test to quantify the fraction of AS events corresponding to errors. This test is based on the fact that the fitness cost of splicing errors increases with the number of introns in a gene and with expression level. We analyzed the transcriptome of the intron-rich eukaryote Paramecium tetraurelia. We show that in both normal and in NMD-deficient cells, AS rates strongly decrease with increasing expression level and with increasing number of introns. This relationship is observed for AS events that are detectable by NMD as well as for those that are not, which invalidates the hypothesis of a link with the regulation of gene expression. Our results show that in genes with a median expression level, 92-98% of observed splice variants correspond to errors. We observed the same patterns in human transcriptomes and we further show that AS rates correlate with the fitness cost of splicing errors. These observations indicate that genes under weaker selective pressure accumulate more maladaptive substitutions and are more prone to splicing errors. Thus, to a large extent, patterns of gene expression variants simply reflect the balance between selection, mutation, and drift.

  1. Capillary Electrophoresis Analysis of Conventional Splicing Assays

    DEFF Research Database (Denmark)

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

    2014-01-01

    of these assays is often challenging. Here, we explore this issue by conducting splicing assays in 31 BRCA2 genetic variants. All variants were assessed by RT-PCR followed by capillary electrophoresis and direct sequencing. If assays did not produce clear-cut outputs (Class-2 or Class-5 according to analytical...

  2. Effect of Temperature and Vibration on Electrical Connectors with Different Number of Contact Cores

    Directory of Open Access Journals (Sweden)

    Song W. L.

    2016-01-01

    Full Text Available In this paper, we presented the results from three related analysis performed by adopting the failure models, which provided an explanation of performance influencing factors caused by different number of contact cores, for the purpose of measuring the temperature change and deformation value, which were the factors causing contact failure. The failures were localized in contact parts of the connectors. Performed investigations included thermal analysis, modal analysis, harmonic response analysis and contact failure analysis. From the results of these simulations, related temperature and vibration analysis nephograms were got respectively. And the correctness of results of thermal analysis was verified by Fourier law. The research results of this paper provide a reference for thermal analysis and vibration analysis of electrical connectors, which is important for ensuring the reliability and safety of electrical connectors.

  3. Push-out tests and evaluation of FRP perfobond rib shear connectors performance

    Science.gov (United States)

    Kolpasky, Ludvik; Ryjacek, Pavel

    2017-09-01

    The behavioural characteristics of FRP (fibre-reinforced polymer) perfobond rib shear connector was examined through push-out tests in order to verify the applicability for pedestrian bridge structure. The aim of this study is to determine interaction between high performance concrete slab and handmade FRP plate which represent web of the composite beam. Combination of these modern materials leads to structural system with both great load bearing capacity and also sufficient flexural stiffness of the composite element. Openings cut into the GFRP plate at a variable spacing allow GFRP reinforcement bars to be inserted to act as shear studs. Hand lay-up process can increase suitable properties of FRP for connection by perfobond rib shear connectors. In this study, three push-out tests on fiber-reinforced polymer were performed to investigate their shear behaviour. The results of the push-out tests on FRP perfobond rib shear connector indicates great promise for application in full scale structures.

  4. MUSCLE TENSION DYSPHONIA

    Directory of Open Access Journals (Sweden)

    Irena Hočevar Boltežar

    2004-07-01

    Full Text Available Background. Muscle tension dysphonia (MTD is the cause of hoarseness in almost one half of the patients with voice disorders. The otorhinolaryngologic examination discovers no evident organic lesions in the larynx at least in the beginning of the voice problems. The reason for the hoarse voice is a disordered and maladjusted activity of the muscles taking part in phonation and/or articulation. In some patients, the irregular function of the larynx results in mucosal lesions on vocal folds. The factors participating in the development of MTD, directly or indirectly influence the quality of laryngeal mucosa, the activity of the phonatory muscles and/or increase of the vocal load. In the diagnostics and treatment of the MTD a phoniatrician, a speech and language therapist and a psychologist closely cooperate with the patient who must take an active role. The treatment is a long-lasting one but resulted in a high percentage of clinical success.Conclusions. Most likely, MTD is not a special disease but only a reflection of any disorder in the complicated system of regulation and realization of phonation. The prognosis of treatment is good when all unfavourable factors participating in development of MTD are eliminated and a proper professional voice- and psychotherapy started.

  5. Impedance Discontinuity Reduction Between High-Speed Differential Connectors and PCB Interfaces

    Science.gov (United States)

    Navidi, Sal; Agdinaoay, Rodell; Walter, Keith

    2013-01-01

    High-speed serial communication (i.e., Gigabit Ethernet) requires differential transmission and controlled impedances. Impedance control is essential throughout cabling, connector, and circuit board construction. An impedance discontinuity arises at the interface of a high-speed quadrax and twinax connectors and the attached printed circuit board (PCB). This discontinuity usually is lower impedance since the relative dielectric constant of the board is higher (i.e., polyimide approx. = 4) than the connector (Teflon approx. = 2.25). The discontinuity can be observed in transmit or receive eye diagrams, and can reduce the effective link margin of serial data networks. High-speed serial data network transmission improvements can be made at the connector-to-board interfaces as well as improving differential via hole impedances. The impedance discontinuity was improved by 10 percent by drilling a 20-mil (approx. = 0.5-mm) hole in between the pin of a differential connector spaced 55 mils (approx. = 1.4 mm) apart as it is attached to the PCB. The effective dielectric constant of the board can be lowered by drilling holes into the board material between the differential lines in a quadrax or twinax connector attachment points. The differential impedance is inversely proportional to the square root of the relative dielectric constant. This increases the differential impedance and thus reduces the above described impedance discontinuity. The differential via hole impedance can also be increased in the same manner. This technique can be extended to multiple smaller drilled holes as well as tapered holes (i.e., big in the middle followed by smaller ones diagonally).

  6. Widespread alternative and aberrant splicing revealed by lariat sequencing

    Science.gov (United States)

    Stepankiw, Nicholas; Raghavan, Madhura; Fogarty, Elizabeth A.; Grimson, Andrew; Pleiss, Jeffrey A.

    2015-01-01

    Alternative splicing is an important and ancient feature of eukaryotic gene structure, the existence of which has likely facilitated eukaryotic proteome expansions. Here, we have used intron lariat sequencing to generate a comprehensive profile of splicing events in Schizosaccharomyces pombe, amongst the simplest organisms that possess mammalian-like splice site degeneracy. We reveal an unprecedented level of alternative splicing, including alternative splice site selection for over half of all annotated introns, hundreds of novel exon-skipping events, and thousands of novel introns. Moreover, the frequency of these events is far higher than previous estimates, with alternative splice sites on average activated at ∼3% the rate of canonical sites. Although a subset of alternative sites are conserved in related species, implying functional potential, the majority are not detectably conserved. Interestingly, the rate of aberrant splicing is inversely related to expression level, with lowly expressed genes more prone to erroneous splicing. Although we validate many events with RNAseq, the proportion of alternative splicing discovered with lariat sequencing is far greater, a difference we attribute to preferential decay of aberrantly spliced transcripts. Together, these data suggest the spliceosome possesses far lower fidelity than previously appreciated, highlighting the potential contributions of alternative splicing in generating novel gene structures. PMID:26261211

  7. Language study on Spliced Semigraph using Folding techniques

    Science.gov (United States)

    Thiagarajan, K.; Padmashree, J.

    2018-04-01

    In this paper, we proposed algorithm to identify cut vertices and cut edges for n-Cut Spliced Semigraph and splicing the n-Cut Spliced Semigraph using cut vertices else cut edges or combination of cut vertex and cut edge and applying sequence of folding to the spliced semigraph to obtain the semigraph quadruple η(S)=(2, 1, 1, 1). We observed that the splicing and folding using both cut vertices and cut edges is applicable only for n-Cut Spliced Semigraph where n > 2. Also, we transformed the spliced semigraph into tree structure and studied the language for the semigraph with n+2 vertices and n+1 semivertices using Depth First Edge Sequence algorithm and obtain the language structure with sequence of alphabet ‘a’ and ‘b’.

  8. Facilitating the Easy Use of Earth Observation Data in Earth System Models through CyberConnector

    Science.gov (United States)

    Di, L.; Sun, Z.; Zhang, C.

    2017-12-01

    Earth system models (ESM) are an important tool used to understand the Earth system and predict its future states. On other hand, Earth observations (EO) provides the current state of the system. EO data are very useful in ESM initialization, verification, validation, and inter-comparison. However, EO data often cannot directly be consumed by ESMs because of the syntactic and semantic mismatches between EO products and ESM requirements. In order to remove the mismatches, scientists normally spend long time to customize EO data for ESM consumption. CyberConnector, a NSF EarthCube building block, is intended to automate the data customization so that scientists can be relieved from the laborious EO data customization. CyberConnector uses web-service-based geospatial processing models (GPM) as the mechanism to automatically customize the EO data into the right products in the right form needed by ESMs. It can support many different ESMs through its standard interfaces. It consists of seven modules: GPM designer, GPM binder, GPM runner, GPM monitor, resource register, order manager, and result display. In CyberConnector, EO data instances and GPMs are independent and loosely coupled. A modeler only needs to create a GPM in the GMP designer for EO data customization. Once the modeler specifies a study area, the designed GPM will be activated and take the temporal and spatial extents as constraints to search the data sources and customize the available EO data into the ESM-acceptable form. The execution of GMP is completely automatic. Currently CyberConnector has been fully developed. In order to validate the feasibility, flexibility, and ESM independence of CyberConnector, three ESMs from different geoscience disciplines, including the Cloud-Resolving Model (CRM), the Finite Volume Coastal Ocean Model (FVCOM), and the Community Multiscale Air Quality Model (CMAQ), have been experimented with CyberConnector through closely collaborating with modelers. In the experiment

  9. USING PARAMETERIZATION OF OBJECTS IN AUTODESK INVENTOR IN DESIGNING STRUCTURAL CONNECTORS

    Directory of Open Access Journals (Sweden)

    Gabriel Borowski

    2015-05-01

    Full Text Available The article presents the parameterization of objects used for designing the type of elements as structural connectors and making modifications of their characteristics. The design process was carried out using Autodesk Inventor 2015. We show the latest software tools, which were used for parameterization and modeling selected types of structural connectors. We also show examples of the use of parameterization facilities in the process of constructing some details and making changes to geometry with holding of the shape the element. The presented method of Inventor usage has enabled fast and efficient creation of new objects based on sketches created.

  10. Multiple splicing defects in an intronic false exon.

    Science.gov (United States)

    Sun, H; Chasin, L A

    2000-09-01

    Splice site consensus sequences alone are insufficient to dictate the recognition of real constitutive splice sites within the typically large transcripts of higher eukaryotes, and large numbers of pseudoexons flanked by pseudosplice sites with good matches to the consensus sequences can be easily designated. In an attempt to identify elements that prevent pseudoexon splicing, we have systematically altered known splicing signals, as well as immediately adjacent flanking sequences, of an arbitrarily chosen pseudoexon from intron 1 of the human hprt gene. The substitution of a 5' splice site that perfectly matches the 5' consensus combined with mutation to match the CAG/G sequence of the 3' consensus failed to get this model pseudoexon included as the central exon in a dhfr minigene context. Provision of a real 3' splice site and a consensus 5' splice site and removal of an upstream inhibitory sequence were necessary and sufficient to confer splicing on the pseudoexon. This activated context also supported the splicing of a second pseudoexon sequence containing no apparent enhancer. Thus, both the 5' splice site sequence and the polypyrimidine tract of the pseudoexon are defective despite their good agreement with the consensus. On the other hand, the pseudoexon body did not exert a negative influence on splicing. The introduction into the pseudoexon of a sequence selected for binding to ASF/SF2 or its replacement with beta-globin exon 2 only partially reversed the effect of the upstream negative element and the defective polypyrimidine tract. These results support the idea that exon-bridging enhancers are not a prerequisite for constitutive exon definition and suggest that intrinsically defective splice sites and negative elements play important roles in distinguishing the real splicing signal from the vast number of false splicing signals.

  11. Distinguishability and identifiability of products with small bore connectors according to ISO DIS 80369 series: risk analysis and summative evaluation

    Directory of Open Access Journals (Sweden)

    Ibenthal Elisabeth

    2017-09-01

    Full Text Available The ISO 80369-series replace Luer-connectors in five application areas to fight misconnections. Although the standard avoids the mechanical problem of misconnections, the design of products and packages remains arbitrary. So, packages and products with same functions but different connectors could have similar designs and hence could be mixed-up.

  12. The Human Splicing Factor ASF/SF2 can Specifically Recognize Pre-mRNA 5' Splice Sites

    Science.gov (United States)

    Zuo, Ping; Manley, James L.

    1994-04-01

    ASF/SF2 is a human protein previously shown to function in in vitro pre-mRNA splicing as an essential factor necessary for all splices and also as an alternative splicing factor, capable of switching selection of 5' splice sites. To begin to study the protein's mechanism of action, we have investigated the RNA binding properties of purified recombinant ASF/SF2. Using UV crosslinking and gel shift assays, we demonstrate that the RNA binding region of ASF/SF2 can interact with RNA in a sequence-specific manner, recognizing the 5' splice site in each of two different pre-mRNAs. Point mutations in the 5' splice site consensus can reduce binding by as much as a factor of 100, with the largest effects observed in competition assays. These findings support a model in which ASF/SF2 aids in the recognition of pre-mRNA 5' splice sites.

  13. Tension pneumocephalus: Mount Fuji sign

    Directory of Open Access Journals (Sweden)

    Pulastya Sanyal

    2015-01-01

    Full Text Available A 13-year-old male was operated for a space occupying lesion in the brain. A noncontrast computed tomography scan done in the late postoperative period showed massive subdural air collection causing compression of bilateral frontal lobes with widening of interhemispheric fissure and the frontal lobes acquiring a peak like configuration - causing tension pneumocephalus-"Mount Fuji sign." Tension pneumocephalus occurs when air enters the extradural or intradural spaces in sufficient volume to exert a mass or pressure effect on the brain, leading to brain herniation. Tension pneumocephalus is a surgical emergency, which needs immediate intervention in the form of decompression of the cranial cavity by a burr hole or needle aspiration. The Mount Fuji sign differentiates tension pneumocephalus from pneumocephalus.

  14. Mitochondrial Respiration and Oxygen Tension.

    Science.gov (United States)

    Shaw, Daniel S; Meitha, Karlia; Considine, Michael J; Foyer, Christine H

    2017-01-01

    Measurements of respiration and oxygen tension in plant organs allow a precise understanding of mitochondrial capacity and function within the context of cellular oxygen metabolism. Here we describe methods that can be routinely used for the isolation of intact mitochondria, and the determination of respiratory electron transport, together with techniques for in vivo determination of oxygen tension and measurement of respiration by both CO 2 production and O 2 consumption that enables calculation of the respiratory quotient [CO 2 ]/[O 2 ].

  15. Chronic, percutaneous connector for electrical recording and stimulation with microelectrode arrays.

    Science.gov (United States)

    Shah, Kedar G; Lee, Kye Young; Tolosa, Vanessa; Tooker, Angela; Felix, Sarah; Benett, William; Pannu, Satinderpall

    2014-01-01

    The translation of advances in neural stimulation and recording research into clinical practice hinges on the ability to perform chronic experiments in awake and behaving animal models. Advances in microelectrode array technology, most notably flexible polymer arrays, have significantly improved reliability of the neural interface. However, electrical connector technology has lagged and is prone to failure from non-biocompatibility, large size, contamination, corrosion, and difficulty of use. We present a novel chronic, percutaneous electrical connector system that is suitable for neural stimulation and recording. This system features biocompatible materials, low connect and disconnect forces, passive alignment, and a protective cap during non-use. We have successfully designed, assembled, and tested in vitro both a 16-channel system and a high density 64-channel system. Custom, polyimide, 16-channel, microelectrode arrays were electrically assembled with the connector system and tested using cyclic voltammetry and electrochemical impedance spectroscopy. This connector system is versatile and can be used with a variety of microelectrode array technologies for chronic studies.

  16. Exploring the impact of the care sport connector in the Netherlands

    NARCIS (Netherlands)

    Leenaars, Karlijn E.F.; Smit, Eva; Wagemakers, Annemarie; Molleman, Gerard R.M.; Koelen, Maria A.

    2017-01-01

    Background: Regular physical activity (PA) is deemed to contribute to the primary and secondary prevention of several chronic diseases, like diabetes mellitus, cancer, cardiovascular diseases, and osteoporosis. In 2012, Care Sport Connectors (CSC), to whom a broker has been ascribed, were introduced

  17. Exploring the impact of the care sport connector in the Netherlands

    NARCIS (Netherlands)

    Leenaars, K.E.; Smit, E.; Wagemakers, A.; Molleman, G.R.M.; Koelen, Maria

    2017-01-01

    BACKGROUND: Regular physical activity (PA) is deemed to contribute to the primary and secondary prevention of several chronic diseases, like diabetes mellitus, cancer, cardiovascular diseases, and osteoporosis. In 2012, Care Sport Connectors (CSC), to whom a broker has been ascribed, were introduced

  18. Discourse Connector Usage in Argumentative Essays by American and Thai University Students

    Science.gov (United States)

    Jangarun, Kamolphan; Luksaneeyanawin, Sudaporn

    2016-01-01

    This study investigated the similarities and differences in the use of discourse connectors (DCs) in argumentative essays of American undergraduate students (AMs), Thai with high-English exposure (THHs) and Thai with low-English exposure (THLs). The data of these three groups were collected from 60 essays; 20 essays were from the corpus of…

  19. Innovative, wearable snap connector technology for improved device networking in electronic garments

    Science.gov (United States)

    Kostrzewski, Andrew A.; Lee, Kang S.; Gans, Eric; Winterhalter, Carole A.; Jannson, Tomasz P.

    2007-04-01

    This paper discusses Physical Optics Corporation's (POC) wearable snap connector technology that provides for the transfer of data and power throughout an electronic garment (e-garment). These connectors resemble a standard garment button and can be mated blindly with only one hand. Fully compatible with military clothing, their application allows for the networking of multiple electronic devices and an intuitive method for adding/removing existing components from the system. The attached flexible cabling also permits the rugged snap connectors to be fed throughout the standard webbing found in military garments permitting placement in any location within the uniform. Variations of the snap electronics/geometry allow for integration with USB 2.0 devices, RF antennas, and are capable of transferring high bandwidth data streams such as the 221 Mbps required for VGA video. With the trend towards providing military officers with numerous electronic devices (i.e., heads up displays (HMD), GPS receiver, PDA, etc), POC's snap connector technology will greatly improve cable management resulting in a less cumbersome uniform. In addition, with electronic garments gaining widespread adoption in the commercial marketplace, POC's technology is finding applications in such areas as sporting good manufacturers and video game technology.

  20. Magnetic Actuation Connector Between Extension Shaft and Armature for Bottom Mounted Control Rod Drive Mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Huh, Hyung; Cho, Yeong Garp; Kim, Jong In [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-10-15

    The electromagnet and armature inside the guide tube interact and produce magnetism, thus making the armature, connecting extension shaft and control rod move up and down to control the power of reactor. During the overhaul, the control absorber rod (CAR), extension shaft, and armature of BMCRDM are lifted together for closing a seal valve. But total length of CAR assembly is so long that it cannot be lifted due to exposure above the water level of pool which is strictly controlled. In addition to this, it is difficult to calibrate a position indicator and lifting force of electromagnet without armature assembly as a seal valve is closed. For this reason, it is necessary to install a disconnecting system between armature and extension shaft. Therefore, KAERI has developed magnetic actuation connector using plunger between armature and extension shaft for the bottom mounted control rod drive mechanism in research reactor. The results of a FEM and the experiments in this work lead to the following conclusions: The FEM result for the design of the magnetic actuation connector is compared with the measured lifting force of prototype production. As a result, it is shown that the lifting force of the prototype connector has a good agreement with the result of the FEM. A newly developed technique of prototype magnetic actuation connector which is designed by FEM analysis result is proposed.

  1. Irradiation test on connector part for nuclear instrumentation of nuclear powered ship 'Mutsu'

    International Nuclear Information System (INIS)

    Kudo, Takahiro; Mizushima, Toshihiko; Tsunoda, Tsunemi; Nakazawa, Toshio

    1991-01-01

    The nuclear instrumetnation facility of the nuclear powered ship 'Mutsu' is composed of neutron detectors, signal cables and the circuits for measurement, and ocntinuously monitors neutron flux. Since this facility treats very faint signals, for the signal cables, coaxial cables and triple coaxial cables are used. The coaxial cables for the nuclear instrumentation are equipped with connectors at both ends, and those are called prefabricated cable. The prefabricated cables are connected to neutron detectors, and installed in the detection holes of the primary shielding tank in the containment vessel. Therefore, at the time of reactor operation, they are exposed to high radiation, and the deterioration of the characteristics of the prefabricated cables is feared. For the purpose of confirming that the part of deteriorating the insulation of the prefabricated cables is connectors, and clarifying the cause of the deterioration of insulation in connector part, the irradiation test of this time was carried out. The environment in which the prefabricated cables are laid, the specifications of the cables and connectors, the materials, gamma ray irradiation and the test results are reported. (K.I.)

  2. ESCC standards, evaluation and qualification of optical fiber connectors for space application

    Science.gov (United States)

    Taugwalder, Frédéric

    2017-11-01

    Optical fiber connectors have been used for the past fifteen years in space application. Reviewing the heritage left from past and current mission, the status of ESCC standards for these components and assemblies will help future use of fiber in space applications. In the frame of the ESA ECI program, Diamond has evaluated and is currently qualifying according to ESCC standards the AVIM and Mini-AVIM connectors. The configuration retained to qualify the connector sets is using a polarization maintaining fiber at 1550nm with a loose tube in PEEK as cable structure. The evaluation has been used to step-stress specific characteristics of the optical fiber connectors with a particular aim at possible failure modes to establish a safety factor for the qualification. The evaluation results presented can be used on a case by case to evaluate special applications that would require to extend the specification. The qualification components can be extended further and a structure for assemblies is proposed in order to simplify fiber optics implementation in space projects.

  3. 24-ch microlens-integrated no-polish connector for optical interconnection with polymer waveguides

    Science.gov (United States)

    Shiraishi, Takashi; Yagisawa, Takatoshi; Ikeuchi, Tadashi; Daikuhara, Osamu; Tanaka, Kazuhiro

    2013-02-01

    We successfully developed a new 24-ch optical connector for polymer waveguides. The connector consists of a transparent thermoplastic resin that has two rectangular slits on one side for alignment of the waveguide films and integrated microlens arrays on the other side for coupling to the MT connector. Two 12-ch waveguide films were cut to a 3-mm width. The thickness of each waveguide film was controlled at 100 μm. The waveguide films were inserted into the slits until they touched the bottom face of the slit. Ultraviolet curing adhesive was used to achieve a short hardening process. The expanded beam in the transparent material is focused by the microlens arrays formed on the connector surface. This lens structure enables assembly without the need for a polishing process. We designed the lens for coupling between a step-index 40-μm rectangular waveguide and a graded-index 50-μm fiber. We achieved low-loss optical coupling by designing a method of providing asymmetric magnification between the horizontal and vertical directions in order to compensate for the asymmetric numerical aperture of the waveguide. The typical measured coupling losses from/to the waveguide to/from the fiber were 1.2 dB and 0.6 dB, respectively. The total coupling loss was as small as that of a physical contact connection.

  4. Magnetic Actuation Connector Between Extension Shaft and Armature for Bottom Mounted Control Rod Drive Mechanism

    International Nuclear Information System (INIS)

    Huh, Hyung; Cho, Yeong Garp; Kim, Jong In

    2013-01-01

    The electromagnet and armature inside the guide tube interact and produce magnetism, thus making the armature, connecting extension shaft and control rod move up and down to control the power of reactor. During the overhaul, the control absorber rod (CAR), extension shaft, and armature of BMCRDM are lifted together for closing a seal valve. But total length of CAR assembly is so long that it cannot be lifted due to exposure above the water level of pool which is strictly controlled. In addition to this, it is difficult to calibrate a position indicator and lifting force of electromagnet without armature assembly as a seal valve is closed. For this reason, it is necessary to install a disconnecting system between armature and extension shaft. Therefore, KAERI has developed magnetic actuation connector using plunger between armature and extension shaft for the bottom mounted control rod drive mechanism in research reactor. The results of a FEM and the experiments in this work lead to the following conclusions: The FEM result for the design of the magnetic actuation connector is compared with the measured lifting force of prototype production. As a result, it is shown that the lifting force of the prototype connector has a good agreement with the result of the FEM. A newly developed technique of prototype magnetic actuation connector which is designed by FEM analysis result is proposed

  5. Entropic contributions to the splicing process

    International Nuclear Information System (INIS)

    Osella, Matteo; Caselle, Michele

    2009-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    Xavier Gérard

    2015-01-01

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

  7. 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.

  8. 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

    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...

  9. 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

  10. Development of an electrical connector for liquid sodium environment. Final Report

    International Nuclear Information System (INIS)

    Kataoka, Hajime; Noguchi, Koichi; Takatsudo, Hiroshi; Miyakawa, Shun-ichi

    1998-07-01

    The INstrumented irradiation Test Assembly (INTA) has been used to conduct precision on-line instrumented irradiation tests in the experimental fast reactor JOYO. In INTA, direct instrumentation wiring between the irradiation test section in the core and the upper structure section in the rotating plug makes INTA structurally complex and expensive. Instead of direct wiring, if an electrical connector capable of withstanding a heated liquid sodium environment could be used between the irradiation test section and the upper structure section, the upper mechanism of INTA could be reused and testing costs would be drastically reduced. Moreover, the reactor load factor would be improved because of reduced handling time for INTA. In an attempt to gain this advantage, research and development of an electric connector in a sodium environment was carried out from 1988 to 1996 at PNC. As no previous R and D had been conducted in this area, this development activity was conducted in a boot strap manner. The first test was carried out for a small model fabrication, the second was for a water partial model, and the third was for a sodium partial model. Based on those tests, a prototype design specification of the connector was determined. In the sodium partial model test, the resilience of the electrical connector insulation to the sodium environment was investigated. However, severe cracking in the ceramic insulator caused by the high temperature sodium environment was discovered at the junction of ceramic insulator and metallic electrode. Although additional sodium partial tests were performed for various material combinations of ceramic insulators, metallic electrodes, brazing materials and metallization materials, the results of the tests were unsatisfactory. Therefore, it was decided that the development of the connector in sodium should cease at PNC in 1997. (J.P.N.)

  11. Semantic integration of gene expression analysis tools and data sources using software connectors

    Science.gov (United States)

    2013-01-01

    Background The study and analysis of gene expression measurements is the primary focus of functional genomics. Once expression data is available, biologists are faced with the task of extracting (new) knowledge associated to the underlying biological phenomenon. Most often, in order to perform this task, biologists execute a number of analysis activities on the available gene expression dataset rather than a single analysis activity. The integration of heteregeneous tools and data sources to create an integrated analysis environment represents a challenging and error-prone task. Semantic integration enables the assignment of unambiguous meanings to data shared among different applications in an integrated environment, allowing the exchange of data in a semantically consistent and meaningful way. This work aims at developing an ontology-based methodology for the semantic integration of gene expression analysis tools and data sources. The proposed methodology relies on software connectors to support not only the access to heterogeneous data sources but also the definition of transformation rules on exchanged data. Results We have studied the different challenges involved in the integration of computer systems and the role software connectors play in this task. We have also studied a number of gene expression technologies, analysis tools and related ontologies in order to devise basic integration scenarios and propose a reference ontology for the gene expression domain. Then, we have defined a number of activities and associated guidelines to prescribe how the development of connectors should be carried out. Finally, we have applied the proposed methodology in the construction of three different integration scenarios involving the use of different tools for the analysis of different types of gene expression data. Conclusions The proposed methodology facilitates the development of connectors capable of semantically integrating different gene expression analysis tools

  12. 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.

  13. Approaches to link RNA secondary structures with splicing regulation

    DEFF Research Database (Denmark)

    Plass, Mireya; Eyras, Eduardo

    2014-01-01

    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 facilitat...... describes the steps in the analysis of the secondary structure of the pre-mRNA and its possible relation to splicing. As a working example, we use the case of yeast and the problem of the recognition of the 3' splice site (3'ss).......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...

  14. 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

  15. The emerging role of alternative splicing in senescence and aging.

    Science.gov (United States)

    Deschênes, Mathieu; Chabot, Benoit

    2017-10-01

    Deregulation of precursor mRNA splicing is associated with many illnesses and has been linked to age-related chronic diseases. Here we review recent progress documenting how defects in the machinery that performs intron removal and controls splice site selection contribute to cellular senescence and organismal aging. We discuss the functional association linking p53, IGF-1, SIRT1, and ING-1 splice variants with senescence and aging, and review a selection of splicing defects occurring in accelerated aging (progeria), vascular aging, and Alzheimer's disease. Overall, it is becoming increasingly clear that changes in the activity of splicing factors and in the production of key splice variants can impact cellular senescence and the aging phenotype. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  16. Systematic Analysis of Splice-Site-Creating Mutations in Cancer

    Directory of Open Access Journals (Sweden)

    Reyka G. Jayasinghe

    2018-04-01

    Full Text Available Summary: For the past decade, cancer genomic studies have focused on mutations leading to splice-site disruption, overlooking those having splice-creating potential. Here, we applied a bioinformatic tool, MiSplice, for the large-scale discovery of splice-site-creating mutations (SCMs across 8,656 TCGA tumors. We report 1,964 originally mis-annotated mutations having clear evidence of creating alternative splice junctions. TP53 and GATA3 have 26 and 18 SCMs, respectively, and ATRX has 5 from lower-grade gliomas. Mutations in 11 genes, including PARP1, BRCA1, and BAP1, were experimentally validated for splice-site-creating function. Notably, we found that neoantigens induced by SCMs are likely several folds more immunogenic compared to missense mutations, exemplified by the recurrent GATA3 SCM. Further, high expression of PD-1 and PD-L1 was observed in tumors with SCMs, suggesting candidates for immune blockade therapy. Our work highlights the importance of integrating DNA and RNA data for understanding the functional and the clinical implications of mutations in human diseases. : Jayasinghe et al. identify nearly 2,000 splice-site-creating mutations (SCMs from over 8,000 tumor samples across 33 cancer types. They provide a more accurate interpretation of previously mis-annotated mutations, highlighting the importance of integrating data types to understand the functional and the clinical implications of splicing mutations in human disease. Keywords: splicing, RNA, mutations of clinical relevance

  17. Alternative Splicing as a Target for Cancer Treatment.

    Science.gov (United States)

    Martinez-Montiel, Nancy; Rosas-Murrieta, Nora Hilda; Anaya Ruiz, Maricruz; Monjaraz-Guzman, Eduardo; Martinez-Contreras, Rebeca

    2018-02-11

    Alternative splicing is a key mechanism determinant for gene expression in metazoan. During alternative splicing, non-coding sequences are removed to generate different mature messenger RNAs due to a combination of sequence elements and cellular factors that contribute to splicing regulation. A different combination of splicing sites, exonic or intronic sequences, mutually exclusive exons or retained introns could be selected during alternative splicing to generate different mature mRNAs that could in turn produce distinct protein products. Alternative splicing is the main source of protein diversity responsible for 90% of human gene expression, and it has recently become a hallmark for cancer with a full potential as a prognostic and therapeutic tool. Currently, more than 15,000 alternative splicing events have been associated to different aspects of cancer biology, including cell proliferation and invasion, apoptosis resistance and susceptibility to different chemotherapeutic drugs. Here, we present well established and newly discovered splicing events that occur in different cancer-related genes, their modification by several approaches and the current status of key tools developed to target alternative splicing with diagnostic and therapeutic purposes.

  18. 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......, 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....

  19. The biomechanical effect of transverse connectors use in a pre- and postlaminectomy model of the posterior cervical spine: an in vitro cadaveric study.

    Science.gov (United States)

    Majid, Kamran; Gudipally, Manasa; Hussain, Mir; Moldavsky, Mark; Khalil, Saif

    2011-12-15

    An in vitro biomechanical study investigating the effect of transverse connectors on posterior cervical stabilization system in a laminectomy model. To evaluate the optimal design, number, and location of the transverse connectors in stabilizing long segment posterior instrumentation in the cervical spine. In the cervical spine, lateral mass screw (LMS) fixation is used for providing stability after decompression. Transverse connectors have been used to augment segmental posterior instrumentation. However, in the cervical region the optimal design, number, and the location of transverse connectors is not known. Seven fresh human cervicothoracic cadaveric spines (C2-T1) were tested by applying ±1.5 Nm moments in flexion (F), extension (E), lateral bending (LB), and axial rotation (AR). After testing the intact condition, LMS/rods were placed and then were tested with two different transverse connectors (top-loading connector [TL] and the head-to-head [HH] connector) in multiple levels, pre- and postlaminectomy (PL). LMS significantly reduced segmental motion by 77.2% in F, 75.6% in E, 86.6% in LB, and 86.1% in AR prelaminectomy and by 75.4% in F, 76% in E, 80.6% in LB, and 76.4% in AR postlaminectomy compared to intact (P transverse connectors is significant in AR, when using two connectors at the proximal and distal ends, compared to one connector. In a clinical setting, this data may guide surgeons on transverse connector configurations to consider during posterior cervical instrumentation.

  20. Magnetic tension and gravitational collapse

    International Nuclear Information System (INIS)

    Tsagas, Christos G

    2006-01-01

    The gravitational collapse of a magnetized medium is investigated by studying qualitatively the convergence of a timelike family of non-geodesic worldlines in the presence of a magnetic field. Focusing on the field's tension, we illustrate how the winding of the magnetic forcelines due to the fluid's rotation assists the collapse, while shear-like distortions in the distribution of the field's gradients resist contraction. We also show that the relativistic coupling between magnetism and geometry, together with the tension properties of the field, lead to a magneto-curvature stress that opposes the collapse. This tension stress grows stronger with increasing curvature distortion, which means that it could potentially dominate over the gravitational pull of the matter. If this happens, a converging family of non-geodesic worldlines can be prevented from focusing without violating the standard energy conditions

  1. 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.

  2. Qualified measurement setup of polarization extinction ratio for Panda PMF with LC/UPC connector

    Science.gov (United States)

    Thongdaeng, Rutsuda; Worasucheep, Duang-rudee; Ngiwprom, Adisak

    2018-03-01

    Polarization Extinction Ratio (PER) is one of the key parameters for Polarization Maintaining Fiber (PMF) connector. Based on our previous studies, the bending radius of fiber greater than 1.5 cm will not affect the insertion loss of PMF [1]. Moreover, the measured PER of Panda PMF with LC/UPC connectors is more stable when that PMF is coiled around a hot rod with a minimum of 3-cm in diameter at 75°C temperature [2]. Hence, the hot rod with less constrained 6-cm in diameter at constant 75°C was selected for this PER measurement. Two PER setups were verified and compared for measuring LC/UPC PMF connectors. The Polarized Laser Source (PLS) at 1550 nm wavelength and PER meter from OZ Optics were used in both setups, in which the measured connector was connected to PLS at 0° angle while the other end was connected to PER meter. In order to qualify our setups, the percentage of Repeatability and Reproducibility (%R&R) were tested and calculated. In each setup, the PER measurement was repeated 3 trials by 3 appraisers using 10 LC/UPC PMF connectors (5 LC/UPC PMF patchcords with 3.5+/-0.5 meters in length) in random order. The 1st setup, PMF was coiled at a larger 20-cm diameter for 3 to 5 loops and left in room temperature during the test. The 2nd setup, PMF was coiled around a hot rod at constant 75°C with 6-cm diameter for 8 to 10 loops for at least 5 minutes before testing. There are 3 ranges of %R&R acceptation guide line: <10% is acceptable, between 10% - 30% is marginal, and <30% is unacceptable. According to our results, the %R&R of the 1st PER test setup was 16.2% as marginality, and the 2nd PER test setup was 8.9% as acceptance. Thus, providing the better repeatability and reproducibility, this 2nd PER test setup having PMF coiled around a hot rod at constant 75°C with 6-cm diameter was selected for our next study of the impact of hot temperature on PER in LC/UPC PMF connector.

  3. 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

  4. Mechanical splicing of superelastic Cu–Al–Mn alloy bars with headed ends

    Science.gov (United States)

    Kise, S.; Mohebbi, A.; Saiidi, M. S.; Omori, T.; Kainuma, R.; Shrestha, K. C.; Araki, Y.

    2018-06-01

    This paper examines the feasibility of mechanical splicing using a steel coupler to connect headed ends of superelastic Cu–Al–Mn alloy (Camalloy) bars and steel reinforcing bars to be used in concrete structures. Although threading of Camalloy is as easy as that of steel, mechanical splicing using threaded ends requires machining of Camalloy bars into dog-bone shape to avoid brittle fracture at the threaded ends. The machining process requires significant time and cost and wastes substantial amount of the material. This paper attempts to resolve this issue by applying mechanical splicing using steel couplers to connect headed ends of Camalloy and steel reinforcing bars. To study its feasibility, we prepare 3 specimens wherein both ends of each Camalloy bar (13 mm diameter and 300 mm length) are connected to steel reinforcing bars. The specimens are tested under monotonic, single-cycle, and full-cycle tension loading conditions. From these tests, we observed (1) excellent superelasticity with recoverable strain of around 6% and (2) large ductility with fracture strain of over 19%. It should be emphasized here that, in all the specimens, ductile fracture occurred at the locations apart from the headed ends. This is in sharp contrast with brittle fracture of headed superelastic Ni–Ti SMA bars, most of which took place around the headed ends. From the results of the microstructural analysis, we identified the following reasons for avoiding brittle fracture at the headed ends: (1) Precipitation hardening increases the strength around the boundary between the straight and headed (tapered) portions, where stress concentration takes place. (2) The strength of the straight portion does not increase significantly up to the ductile fracture if its grain orientation is close to 〈0 0 1〉.

  5. Functions for fission yeast splicing factors SpSlu7 and SpPrp18 in alternative splice-site choice and stress-specific regulated splicing.

    Directory of Open Access Journals (Sweden)

    Geetha Melangath

    Full Text Available Budding yeast spliceosomal factors ScSlu7 and ScPrp18 interact and mediate intron 3'ss choice during second step pre-mRNA splicing. The fission yeast genome with abundant multi-intronic transcripts, degenerate splice signals and SR proteins is an apt unicellular fungal model to deduce roles for core spliceosomal factors in alternative splice-site choice, intron retention and to study the cellular implications of regulated splicing. From our custom microarray data we deduce a stringent reproducible subset of S. pombe alternative events. We examined the role of factors SpSlu7 or SpPrp18 for these splice events and investigated the relationship to growth phase and stress. Wild-type log and stationary phase cells showed ats1+ exon 3 skipped and intron 3 retained transcripts. Interestingly the non-consensus 5'ss in ats1+ intron 3 caused SpSlu7 and SpPrp18 dependent intron retention. We validated the use of an alternative 5'ss in dtd1+ intron 1 and of an upstream alternative 3'ss in DUF3074 intron 1. The dtd1+ intron 1 non-canonical 5'ss yielded an alternative mRNA whose levels increased in stationary phase. Utilization of dtd1+ intron 1 sub-optimal 5' ss required functional SpPrp18 and SpSlu7 while compromise in SpSlu7 function alone hampered the selection of the DUF3074 intron 1 non canonical 3'ss. We analysed the relative abundance of these splice isoforms during mild thermal, oxidative and heavy metal stress and found stress-specific splice patterns for ats1+ and DUF3074 intron 1 some of which were SpSlu7 and SpPrp18 dependent. By studying ats1+ splice isoforms during compromised transcription elongation rates in wild-type, spslu7-2 and spprp18-5 mutant cells we found dynamic and intron context-specific effects in splice-site choice. Our work thus shows the combinatorial effects of splice site strength, core splicing factor functions and transcription elongation kinetics to dictate alternative splice patterns which in turn serve as an additional

  6. Stress analysis of single port (ISB) jumper connectors for 2-, 3-, and 4-in. sizes

    International Nuclear Information System (INIS)

    Islam, M.A.; Julyk, J.L.; Weiner, E.O.

    1995-01-01

    Jumper connectors are used in the Hanford site for remotely connecting jumper pipe lines in the radioactive zones. The jumper pipes are used for transporting radioactive fluids and hazardous chemicals. This report evaluates the adequacy and the integrity of the 2-, 3-, and 4-in. single-port integral seal block (ISB) jumper connector assemblies, as well as the three-way 2-in. configuration. The evaluation considers limiting forces from the piping to the nozzle. A stress evaluation of the jumper components (hook, hook pin, operating screw, nozzle and nozzle flange, and block) under operational (pressure, thermal, dead weight, and axial torquing of the jumper) and seismic loading is addressed in the report

  7. Structural insights into the backbone-circularized granulocyte colony-stimulating factor containing a short connector.

    Science.gov (United States)

    Miyafusa, Takamitsu; Shibuya, Risa; Honda, Shinya

    2018-06-02

    Backbone circularization is a powerful approach for enhancing the structural stability of polypeptides. Herein, we present the crystal structure of the circularized variant of the granulocyte colony-stimulating factor (G-CSF) in which the terminal helical region was circularized using a short, two-amino acid connector. The structure revealed that the N- and C-termini were indeed connected by a peptide bond. The local structure of the C-terminal region transited from an α helix to 3 10 helix with a bend close to the N-terminal region, indicating that the structural change offset the insufficient length of the connector. This is the first-ever report of a crystal structure of the backbone of a circularized protein. It will facilitate the development of backbone circularization methodology. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Stress analysis of single port (ISB) jumper connectors for 2-, 3-, and 4-in. sizes

    Energy Technology Data Exchange (ETDEWEB)

    Islam, M A; Julyk, J L; Weiner, E O [ICF Kaiser Hanford Co., Richland, WA (United States)

    1995-05-26

    Jumper connectors are used in the Hanford site for remotely connecting jumper pipe lines in the radioactive zones. The jumper pipes are used for transporting radioactive fluids and hazardous chemicals. This report evaluates the adequacy and the integrity of the 2-, 3-, and 4-in. single-port integral seal block (ISB) jumper connector assemblies, as well as the three-way 2-in. configuration. The evaluation considers limiting forces from the piping to the nozzle. A stress evaluation of the jumper components (hook, hook pin, operating screw, nozzle and nozzle flange, and block) under operational (pressure, thermal, dead weight, and axial torquing of the jumper) and seismic loading is addressed in the report.

  9. Splicing aberrations caused by constitutional RB1 gene mutations in ...

    Indian Academy of Sciences (India)

    in this family revealed skipping of exon 22 in three members of this family. In one proband, a ... This study reveals novel effects of RB1 mutations on splicing and suggests the utility of RNA analysis as an ... of life) and presence of multiple tumors (multifocal). The ..... spliced RNA have been linked to parent of origin as well as.

  10. Androgen Receptor Splice Variants and Resistance to Taxane Chemotherapy

    Science.gov (United States)

    2017-10-01

    resistant prostate cancer ; docetaxel; cabazitaxel; chemotherapy; androgen receptor splice variants; microtubule; ligand-binding domain; microtubule... receptor splice variants (AR-Vs) are associated with resistance to taxane chemotherapy in castration- resistant prostate cancer (CRPC). However, this...androgen receptor inhibitors in prostate cancer . Nat Rev Cancer . 2015;15:701–11.

  11. Revealing the Determinants of Widespread Alternative Splicing Perturbation in Cancer

    Directory of Open Access Journals (Sweden)

    Yongsheng Li

    2017-10-01

    Full Text Available It is increasingly appreciated that alternative splicing plays a key role in generating functional specificity and diversity in cancer. However, the mechanisms by which cancer mutations perturb splicing remain unknown. Here, we developed a network-based strategy, DrAS-Net, to investigate more than 2.5 million variants across cancer types and link somatic mutations with cancer-specific splicing events. We identified more than 40,000 driver variant candidates and their 80,000 putative splicing targets deregulated in 33 cancer types and inferred their functional impact. Strikingly, tumors with splicing perturbations show reduced expression of immune system-related genes and increased expression of cell proliferation markers. Tumors harboring different mutations in the same gene often exhibit distinct splicing perturbations. Further stratification of 10,000 patients based on their mutation-splicing relationships identifies subtypes with distinct clinical features, including survival rates. Our work reveals how single-nucleotide changes can alter the repertoires of splicing isoforms, providing insights into oncogenic mechanisms for precision medicine.

  12. Antitumorigenic potential of STAT3 alternative splicing modulation.

    Science.gov (United States)

    Zammarchi, Francesca; de Stanchina, Elisa; Bournazou, Eirini; Supakorndej, Teerawit; Martires, Kathryn; Riedel, Elyn; Corben, Adriana D; Bromberg, Jacqueline F; Cartegni, Luca

    2011-10-25

    Signal transducer and activator of transcription 3 (STAT3) plays a central role in the activation of multiple oncogenic pathways. Splicing variant STAT3β uses an alternative acceptor site within exon 23 that leads to a truncated isoform lacking the C-terminal transactivation domain. Depending on the context, STAT3β can act as a dominant-negative regulator of transcription and promote apoptosis. We show that modified antisense oligonucleotides targeted to a splicing enhancer that regulates STAT3 exon 23 alternative splicing specifically promote a shift of expression from STAT3α to STAT3β. Induction of endogenous STAT3β leads to apoptosis and cell-cycle arrest in cell lines with persistent STAT3 tyrosine phosphorylation compared with total STAT3 knockdown obtained by forced splicing-dependent nonsense-mediated decay (FSD-NMD). Comparison of the molecular effects of splicing redirection to STAT3 knockdown reveals a unique STAT3β signature, with a down-regulation of specific targets (including lens epithelium-derived growth factor, p300/CBP-associated factor, CyclinC, peroxisomal biogenesis factor 1, and STAT1β) distinct from canonical STAT3 targets typically associated with total STAT3 knockdown. Furthermore, similar in vivo redirection of STAT3 alternative splicing leads to tumor regression in a xenograft cancer model, demonstrating how pharmacological manipulation of a single key splicing event can manifest powerful antitumorigenic properties and validating endogenous splicing reprogramming as an effective cancer therapeutic approach.

  13. 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 o...

  14. Connecting the dots: chromatin and alternative splicing in EMT.

    Science.gov (United States)

    Warns, Jessica A; Davie, James R; Dhasarathy, Archana

    2016-02-01

    Nature has devised sophisticated cellular machinery to process mRNA transcripts produced by RNA Polymerase II, removing intronic regions and connecting exons together, to produce mature RNAs. This process, known as splicing, is very closely linked to transcription. Alternative splicing, or the ability to produce different combinations of exons that are spliced together from the same genomic template, is a fundamental means of regulating protein complexity. Similar to transcription, both constitutive and alternative splicing can be regulated by chromatin and its associated factors in response to various signal transduction pathways activated by external stimuli. This regulation can vary between different cell types, and interference with these pathways can lead to changes in splicing, often resulting in aberrant cellular states and disease. The epithelial to mesenchymal transition (EMT), which leads to cancer metastasis, is influenced by alternative splicing events of chromatin remodelers and epigenetic factors such as DNA methylation and non-coding RNAs. In this review, we will discuss the role of epigenetic factors including chromatin, chromatin remodelers, DNA methyltransferases, and microRNAs in the context of alternative splicing, and discuss their potential involvement in alternative splicing during the EMT process.

  15. Conservation and sex-specific splicing of the doublesex gene

    Indian Academy of Sciences (India)

    Genetic control of sex determination in insects has been best characterized in Drosophila melanogaster, where the master gene Sxl codes for RNA that is sex specifically spliced to produce a functional protein only in females. SXL regulates the sex-specific splicing of transformer (tra) RNA which, in turn, regulates the ...

  16. 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

    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...

  17. AUTOGENIC THERAPY IN TENSION HEADACHE

    Science.gov (United States)

    Amruthraj, Brunda; Mishra, H.; Kumaraiah, V.

    1987-01-01

    SUMMARY Ten subjects diagnosed as Psychalgia were taken for study. A multiple baseline design was adapted and clients were subjected to 30 sessions of autogenic training. They were assessed using physiological (EMG and thermal change) and behavioural measures (Visual analogue scale and behavioural symptom checklist). Findings revealed autogenic therapy to be effective in reducing tension headache. PMID:21927245

  18. Tensions of Corporate Social Responsibility

    DEFF Research Database (Denmark)

    Strand, Robert

    , and formally rational tools like key performance indicators (KPIs) can be developed and employed in service of the selected substantively rational ends. I show how these KPIs can serve to highlight tensions between substantively rational ends. As such, I argue the CSR bureaucracy can create a space...

  19. AUTOGENIC THERAPY IN TENSION HEADACHE

    OpenAIRE

    Amruthraj, Brunda; Mishra, H.; Kumaraiah, V.

    1987-01-01

    SUMMARY Ten subjects diagnosed as Psychalgia were taken for study. A multiple baseline design was adapted and clients were subjected to 30 sessions of autogenic training. They were assessed using physiological (EMG and thermal change) and behavioural measures (Visual analogue scale and behavioural symptom checklist). Findings revealed autogenic therapy to be effective in reducing tension headache.

  20. Use of monolingual and comparable corpora in the classroom to translate adverbial connectors

    Directory of Open Access Journals (Sweden)

    Beatriz Sánchez Cárdenas

    2016-04-01

    This research explored the reasons why certain adverbial discourse connectors, apparently easy to translate, are a source of translation problems that cannot be easily resolved with a bilingual dictionary. Moreover, this study analyzed the use of parallel corpora in the translation classroom and how it can increase the quality of text production. For this purpose, we compared student translations before and after receiving training on the use of corpus analysis tools.

  1. Experimental study on AR fiberglass connectors for bridges made of composite materials

    Directory of Open Access Journals (Sweden)

    Tolosana, N.

    2006-06-01

    Full Text Available One highly relevant aspect in composite material bridgedesing is the study of the shear connectors to be used.Composite material bridges most commonly comprise acomposite deck resting on steel or reinforced concrete girders.This article analyzes the connectors most frequentlyused in such bridges.It also reviews the connectors used in the King StormwaterChannel Bridge, whose fibreglass deck is supported bygirders made of concrete-filled carbon fibre girders.The paper advances proposals for several types of connectorsand discusses the results of push-out test run ona number of prototypes with different geometries.The results are analyzed to identify the optimum model forthe “Autovia del Cantabrico” Overpass, with its 46-m span,carbon fibre girders and AR glass shear connectors.Un aspecto relevante dentro del proyecto de un puenterealizado en materiales compuestos es el estudio de losconectores. El caso mas frecuente de puente en materialescompuestos es aquel que presenta un tablero de materialescompuestos soportado por vigas metalicas o de hormigonarmado. En este trabajo se analizaran los tipos deconectores mas utilizados en este tipo de puentesSe analizaran tambien los conectores utilizados en elKing Stormwater Channel Bridge, donde ademas deltablero en fibra de vidrio, se fabricaron las vigas en fibrasde carbono rellenas de hormigon.En este articulo se propondran varios tipos de conectoresy se presentaran los resultados experimentales correspondientesal ensayo de “push-out” de varios prototipos condiferentes geometrias.Tras evaluar los resultados, se determinara el mas idoneopara su implantacion en el Paso Superior de la Autovia delCantabrico, de 46 metros de luz y que presenta las vigasen fibra de carbono y los conectores de vidrio AR.

  2. Annual report 1999. Energy and connectors; Rapport annuel 1999. Energie connectique

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-07-01

    This report presents the industrial activities and the financial results of Framatome in 1999. Framatome's activities are divided into 2 sectors: energy and connectors, which represents respectively 54% and 46% of the turnover and 40% and 60% of the staff (26000 people). In 1999 the turnover reached 4.2 milliard euros. Framatome and Siemens have decided to merge their nuclear activities in a common company (66% for Framatome, 34% for Siemens). (A.C.)

  3. Annual report 1999. Energy and connectors; Rapport annuel 1999. Energie connectique

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-07-01

    This report presents the industrial activities and the financial results of Framatome in 1999. Framatome's activities are divided into 2 sectors: energy and connectors, which represents respectively 54% and 46% of the turnover and 40% and 60% of the staff (26000 people). In 1999 the turnover reached 4.2 milliard euros. Framatome and Siemens have decided to merge their nuclear activities in a common company (66% for Framatome, 34% for Siemens). (A.C.)

  4. Alternative splicing of mutually exclusive exons--a review.

    Science.gov (United States)

    Pohl, Martin; Bortfeldt, Ralf H; Grützmann, Konrad; Schuster, Stefan

    2013-10-01

    Alternative splicing (AS) of pre-mRNAs in higher eukaryotes and several viruses is one major source of protein diversity. Usually, the following major subtypes of AS are distinguished: exon skipping, intron retention, and alternative 3' and 5' splice sites. Moreover, mutually exclusive exons (MXEs) represent a rare subtype. In the splicing of MXEs, two (or more) splicing events are not independent anymore, but are executed or disabled in a coordinated manner. In this review, several bioinformatics approaches for analyzing MXEs are presented and discussed. In particular, we revisit suitable definitions and nomenclatures, and bioinformatics tools for finding MXEs, adjacent and non-adjacent MXEs, clustered and grouped MXEs. Moreover, the molecular mechanisms for splicing MXEs proposed in the literature are reviewed and discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. 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...

  6. Behaviour of steel-concrete composite beams using bolts as shear connectors

    Science.gov (United States)

    Tran, Minh-Tung; Nguyen Van Do, Vuong; Nguyen, Tuan-Anh

    2018-04-01

    The paper presents an experimental program on the application of bolts as shear connectors for steel-composite beams. Four steel- concrete composite beams and a reference steel beam were made and tested. The aim of the testing program is to examine which forms of the steel bolts can be used effectively for steel-composite beams. The four types of the bolts include: Type 1 the bolt with the nut at the end; Type 2 the bolt bending at 900 hook; Type 3 the bolt without the nut at the end and Type 4 the bolt with the nut at the end but connected with the steel beam by hand welding in other to be connected with the steel beam by bolt connection as in the first three types. The test results showed that beside the traditional shear connectors like shear studs, angle type, channel type, bolts can be used effectively as the shear connectors in steel-composite beams and the application of bolts in Types 1 and 2 in the composite beams gave the better performance for the tested beam.

  7. Experimental analysis of reinforced concrete columns strengthened with self-compacting concrete and connectors

    Directory of Open Access Journals (Sweden)

    P. P. Nascimento

    Full Text Available There are many problems involving cases of destruction of buildings and other structures. The columns can deteriorate for several reasons such as the evolution and changing habits of the loads. The experimental phase of this work was based on a test involving nine reinforced concrete columns under combined bending and axial compression, at an initial eccentricity of 60 mm. Two columns were used as reference, one having the original dimensions of the column and the other, monolithic, had been cast along the thickness of the strengthened piece. The remaining columns received a 35 mm thick layer of self-compacting concrete on their compressed face. For the preparation of the interface between the two materials, this surface was scarified and furrowed and connectors were inserted onto the columns' shear reinforcement in various positions and amounts.As connectors, 5 mm diameter steel bars were used (the same as for stirrups, bent in the shape of a "C" with 25 mm coatings. >As a conclusion, not only the quantity, but mainly, the location of the connectors used in the link between substrate and reinforcement is crucial to increase strength and to change failure mode.

  8. Plasma treatment of fiber facets for increased (de)mating endurance in physical contact fiber connectors

    Science.gov (United States)

    Van Erps, Jürgen; Voss, Kevin; De Witte, Martijn; Radulescu, Radu; Beri, Stefano; Watté, Jan; Thienpont, Hugo

    2016-04-01

    It is known that cleaving an optical fiber introduces a number of irregularities and defects to the fiber's end-face, such as hackles and shockwaves. These defects can act as failure initiators when stress is applied to the end-face. Given the fiber's small diameter of 125 ffm, a large amount of mechanical stress can be expected to be applied on its end-face during the mating-demating cycle. In addition, a connector in a fiber-to-the-home (FTTH) network can be expected to be mated and demated more than 30 times during its lifetime for purposes such as testing, churning, or provisioning. For this reason, the performance of a connector that displays low optical loss when first installed can dramatically degrade after few mating-demating cycles and catastrophic connector failure due to end-face breakage is likely. We present plasma discharge shaping of cleaved fiber tips to strongly improve the endurance of the fibers to repeated mating-demating cycles. We quantify the dependency of the plasma-induced surface curvature of the fiber tip on the plasma duration and on the position of the fiber tip within the plasma cloud. Finally we present data showing the improved endurance of fibers that are exposed to plasma compared to conventional as-cleaved fibers.

  9. Salt Spray Test to Determine Galvanic Corrosion Levels of Electroless Nickel Connectors Mounted on an Aluminum Bracket

    Science.gov (United States)

    Rolin, T. D.; Hodge, R. E.; Torres, P. D.; Jones, D. D.; Laird, K. R.

    2014-01-01

    During preliminary vehicle design reviews, requests were made to change flight termination systems from an electroless nickel (EN) connector coating to a zinc-nickel (ZN) plating. The reason for these changes was due to a new NASA-STD-6012 corrosion requirement where connectors must meet the performance requirement of 168 hr of exposure to salt spray. The specification for class F connectors, MIL-DTL-38999, certifies the EN coating will meet a 48-hr salt spray test, whereas the ZN is certified to meet a 168-hr salt spray test. The ZN finish is a concern because Marshall Space Flight Center has no flight experience with ZN-finished connectors, and MSFC-STD-3012 indicates that zinc and zinc alloys should not be used. The purpose of this test was to run a 168-hr salt spray test to verify the electrical and mechanical integrity of the EN connectors and officially document the results. The salt spray test was conducted per ASTM B117 on several MIL-DTL-38999 flight-like connectors mounted to an aluminum 6061-T6 bracket that was alodined. The configuration, mounting techniques, electrical checks, and materials used were typical of flight and ground support equipment.

  10. Blocking of an intronic splicing silencer completely rescues IKBKAP exon 20 splicing in familial dysautonomia patient cells

    DEFF Research Database (Denmark)

    Bruun, Gitte H; Bang, Jeanne Mv; Christensen, Lise L

    2018-01-01

    designed splice switching oligonucleotides (SSO) that blocks the intronic hnRNP A1 binding site, and demonstrate that this completely rescues splicing of IKBKAP exon 20 in FD patient fibroblasts and increases the amounts of IKAP protein. We propose that this may be developed into a potential new specific...

  11. Urinary incontinence - tension-free vaginal tape

    Science.gov (United States)

    ... ency/article/007377.htm Urinary incontinence - tension-free vaginal tape To use the sharing features on this page, please enable JavaScript. Placement of tension-free vaginal tape is surgery to help control stress urinary ...

  12. Robust Tensioned Kevlar Suspension Design

    Science.gov (United States)

    Young, Joseph B.; Naylor, Bret J.; Holmes, Warren A.

    2012-01-01

    One common but challenging problem in cryogenic engineering is to produce a mount that has excellent thermal isolation but is also rigid. Such mounts can be achieved by suspending the load from a network of fibers or strings held in tension. Kevlar fibers are often used for this purpose owing to their high strength and low thermal conductivity. A suite of compact design elements has been developed to improve the reliability of suspension systems made of Kevlar.

  13. Surface Tension Confines Cryogenic Liquid

    Science.gov (United States)

    Castles, Stephen H.; Schein, Michael E.

    1989-01-01

    New type of Dewar provides passive, constant-temperature cryogenic cooling for scientific instruments under normal-to low-gravity conditions. Known as Surface-Tension-Contained Liquid Cryogen Cooler (STCLCC), keeps liquid cryogen in known location inside the Dewar by trapping liquid inside spongelike material. Unique sponge material fills most of volume of inner tank. Sponge is all-silica, open-cell material similar to that used for Space Shuttle thermal-protection tiles.

  14. Delayed Tension Pneumothorax During Surgery

    Directory of Open Access Journals (Sweden)

    Ying-Lun Chen

    2005-10-01

    Full Text Available Tension pneumothorax is a life-threatening emergency that rapidly results in cardiopulmonary arrest. It requires prompt diagnosis and treatment. We present 2 cases from our practice, 1 caused by blunt chest trauma and the other resulting from laparoscopic surgery. Both were successfully treated by insertion of a chest tube. The diagnosis and treatment of intraoperative pneumothorax is discussed together with a review of the literature.

  15. Low resistance splices for HTS devices and applications

    Science.gov (United States)

    Lalitha, S. L.

    2017-09-01

    This paper discusses the preparation methodology and performance evaluation of low resistance splices made of the second generation (2G) high-temperature superconductor (HTS). These splices are required in a broad spectrum of HTS devices including a large aperture, high-field solenoid built in the laboratory to demonstrate a superconducting magnetic energy storage (SMES) device. Several pancake coils are assembled in the form of a nested solenoid, and each coil requires a hundred meters or more of 2G (RE)BCO tape. However, commercial availability of this superconductor with a very uniform physical properties is currently limited to shorter piece lengths. This necessitates us having splices to inter-connect the tape pieces within a pancake coil, between adjacent pancake coils, and to attach HTS current leads to the magnet assembly. As a part of the optimization and qualification of splicing process, a systematic study was undertaken to analyze the electrical performance of splices in two different configurations suitable for this magnet assembly: lap joint and spiral joint. The electrical performance is quantified in terms of the resistance of splices estimated from the current-voltage characteristics. It has been demonstrated that a careful application of this splicing technique can generate lap joints with resistance less than 1 nΩ at 77 K.

  16. Aberrant and alternative splicing in skeletal system disease.

    Science.gov (United States)

    Fan, Xin; Tang, Liling

    2013-10-01

    The main function of skeletal system is to support the body and help movement. A variety of factors can lead to skeletal system disease, including age, exercise, and of course genetic makeup and expression. Pre-mRNA splicing plays a crucial role in gene expression, by creating multiple protein variants with different biological functions. The recent studies show that several skeletal system diseases are related to pre-mRNA splicing. This review focuses on the relationship between pre-mRNA splicing and skeletal system disease. On the one hand, splice site mutation that leads to aberrant splicing often causes genetic skeletal system disease, like COL1A1, SEDL and LRP5. On the other hand, alternative splicing without genomic mutation may generate some marker protein isoforms, for example, FN, VEGF and CD44. Therefore, understanding the relationship between pre-mRNA splicing and skeletal system disease will aid in uncovering the mechanism of disease and contribute to the future development of gene therapy. © 2013 Elsevier B.V. All rights reserved.

  17. Herboxidiene triggers splicing repression and abiotic stress responses in plants

    KAUST Repository

    Alshareef, Sahar

    2017-03-27

    Background Constitutive and alternative splicing of pre-mRNAs from multiexonic genes controls the diversity of the proteome; these precisely regulated processes also fine-tune responses to cues related to growth, development, and stresses. Small-molecule inhibitors that perturb splicing provide invaluable tools for use as chemical probes to uncover the molecular underpinnings of splicing regulation and as potential anticancer compounds. Results Here, we show that herboxidiene (GEX1A) inhibits both constitutive and alternative splicing. Moreover, GEX1A activates genome-wide transcriptional patterns involved in abiotic stress responses in plants. GEX1A treatment -activated ABA-inducible promoters, and led to stomatal closure. Interestingly, GEX1A and pladienolide B (PB) elicited similar cellular changes, including alterations in the patterns of transcription and splicing, suggesting that these compounds might target the same spliceosome complex in plant cells. Conclusions Our study establishes GEX1A as a potent splicing inhibitor in plants that can be used to probe the assembly, dynamics, and molecular functions of the spliceosome and to study the interplay between splicing stress and abiotic stresses, as well as having potential biotechnological applications.

  18. Diversification of the muscle proteome through alternative splicing.

    Science.gov (United States)

    Nakka, Kiran; Ghigna, Claudia; Gabellini, Davide; Dilworth, F Jeffrey

    2018-03-06

    Skeletal muscles express a highly specialized proteome that allows the metabolism of energy sources to mediate myofiber contraction. This muscle-specific proteome is partially derived through the muscle-specific transcription of a subset of genes. Surprisingly, RNA sequencing technologies have also revealed a significant role for muscle-specific alternative splicing in generating protein isoforms that give specialized function to the muscle proteome. In this review, we discuss the current knowledge with respect to the mechanisms that allow pre-mRNA transcripts to undergo muscle-specific alternative splicing while identifying some of the key trans-acting splicing factors essential to the process. The importance of specific splicing events to specialized muscle function is presented along with examples in which dysregulated splicing contributes to myopathies. Though there is now an appreciation that alternative splicing is a major contributor to proteome diversification, the emergence of improved "targeted" proteomic methodologies for detection of specific protein isoforms will soon allow us to better appreciate the extent to which alternative splicing modifies the activity of proteins (and their ability to interact with other proteins) in the skeletal muscle. In addition, we highlight a continued need to better explore the signaling pathways that contribute to the temporal control of trans-acting splicing factor activity to ensure specific protein isoforms are expressed in the proper cellular context. An understanding of the signal-dependent and signal-independent events driving muscle-specific alternative splicing has the potential to provide us with novel therapeutic strategies to treat different myopathies.

  19. 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

    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...... a promoter-proximal 5′ splice site via its U1 snRNA interaction can feed back to stimulate transcription initiation by enhancing preinitiation complex assembly....

  20. TJC: plan and prepare for the transition to new tubing connectors to minimize the risk of dangerous misconnections, clinician frustration.

    Science.gov (United States)

    2014-12-01

    To reduce the risk of dangerous tubing misconnections, the ISO is rolling out new tubing connector standards that will eventually make it nearly impossible for tubing associated with one delivery system to be connected to a delivery system that serves a different purpose. Experts welcome the change, noting that tubing misconnections that cause injury and even death have been happening for years. However, TJC has issued a Sentinel Event Alert, warning that health care organizations need to be vigilant in managing the risk posed by these misconnections during the phased-in transition to the new connectors. Experts explain that tubing misconnections occur because many different types of tubing utilize the same Leur connector, making it possible for a clinician to mistakenly connect a tube to the wrong delivery system. The most common type of tubing misconnection reported to the ISMP is when a clinician wants to administer something to a patient through a feeding tube, but accidently administers the substance through an IV tube instead. The first new connector, called the ENFit, is going to be for enteral feeding tubes. It will not connect to IV tubing, making that type of misconnection unlikely. The new connector should be available early next year. Since hospitals will continue to use older tubing until their supplies are exhausted, manufacturers will temporarily provide adapters capable of making new administration sets compatible with older tubing.

  1. SpliceSeq: a resource for analysis and visualization of RNA-Seq data on alternative splicing and its functional impacts.

    Science.gov (United States)

    Ryan, Michael C; Cleland, James; Kim, RyangGuk; Wong, Wing Chung; Weinstein, John N

    2012-09-15

    SpliceSeq is a resource for RNA-Seq data that provides a clear view of alternative splicing and identifies potential functional changes that result from splice variation. It displays intuitive visualizations and prioritized lists of results that highlight splicing events and their biological consequences. SpliceSeq unambiguously aligns reads to gene splice graphs, facilitating accurate analysis of large, complex transcript variants that cannot be adequately represented in other formats. SpliceSeq is freely available at http://bioinformatics.mdanderson.org/main/SpliceSeq:Overview. The application is a Java program that can be launched via a browser or installed locally. Local installation requires MySQL and Bowtie. mryan@insilico.us.com Supplementary data are available at Bioinformatics online.

  2. Conditional Toxin Splicing Using a Split Intein System.

    Science.gov (United States)

    Alford, Spencer C; O'Sullivan, Connor; Howard, Perry L

    2017-01-01

    Protein toxin splicing mediated by split inteins can be used as a strategy for conditional cell ablation. The approach requires artificial fragmentation of a potent protein toxin and tethering each toxin fragment to a split intein fragment. The toxin-intein fragments are, in turn, fused to dimerization domains, such that addition of a dimerizing agent reconstitutes the split intein. These chimeric toxin-intein fusions remain nontoxic until the dimerizer is added, resulting in activation of intein splicing and ligation of toxin fragments to form an active toxin. Considerations for the engineering and implementation of conditional toxin splicing (CTS) systems include: choice of toxin split site, split site (extein) chemistry, and temperature sensitivity. The following method outlines design criteria and implementation notes for CTS using a previously engineered system for splicing a toxin called sarcin, as well as for developing alternative CTS systems.

  3. Research on Splicing Method of Digital Relic Fragment Model

    Science.gov (United States)

    Yan, X.; Hu, Y.; Hou, M.

    2018-04-01

    In the course of archaeological excavation, a large number of pieces of cultural relics were unearthed, and the restoration of these fragments was done manually by traditional arts and crafts experts. In this process, cultural relics experts often try to splice the existing cultural relics, and then use adhesive to stick together the fragments of correct location, which will cause irreversible secondary damage to cultural relics. In order to minimize such damage, the surveyors combine 3D laser scanning with computer technology, and use the method of establishing digital cultural relics fragments model to make virtual splicing of cultural relics. The 3D software on the common market can basically achieve the model translation and rotation, using this two functions can be achieved manually splicing between models, mosaic records after the completion of the specific location of each piece of fragments, so as to effectively reduce the damage to the relics had tried splicing process.

  4. Herboxidiene triggers splicing repression and abiotic stress responses in plants

    KAUST Repository

    Alshareef, Sahar; Ling, Yu; Butt, Haroon; Mariappan, Kiruthiga G.; Benhamed, Moussa; Mahfouz, Magdy M.

    2017-01-01

    Constitutive and alternative splicing of pre-mRNAs from multiexonic genes controls the diversity of the proteome; these precisely regulated processes also fine-tune responses to cues related to growth, development, and stresses. Small

  5. Arranging ISO 13606 archetypes into a knowledge base using UML connectors.

    Science.gov (United States)

    Kopanitsa, Georgy

    2014-01-01

    To enable the efficient reuse of standard based medical data we propose to develop a higher-level information model that will complement the archetype model of ISO 13606. This model will make use of the relationships that are specified in UML to connect medical archetypes into a knowledge base within a repository. UML connectors were analysed for their ability to be applied in the implementation of a higher-level model that will establish relationships between archetypes. An information model was developed using XML Schema notation. The model allows linking different archetypes of one repository into a knowledge base. Presently it supports several relationships and will be advanced in future.

  6. Microorganisms present on peripheral intravenous needleless connectors in the clinical environment.

    Science.gov (United States)

    Slater, Karen; Cooke, Marie; Whitby, Michael; Fullerton, Fiona; Douglas, Joel; Hay, Jennine; Rickard, Claire

    2017-08-01

    The aim of this study was to quantify culturable microorganisms on needleless connectors (NCs) attached to peripheral intravenous catheters in hospitalized adult medical patients. Half (50%) of 40 NCs were contaminated with microorganisms commonly found on the skin or mouth. Staphylococcus capitis and Staphylococcus epidermidis were most commonly isolated. Emergency department insertion and higher patient dependency were statistically associated with positive NC microorganism growth. These results reaffirm the need for NC decontamination prior to access. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  7. Open Source GIS Connectors to the NASA GES DISC Satellite Data

    Science.gov (United States)

    Pham, L.; Kempler, S. J.; Yang, W.

    2014-12-01

    The NASA Goddard Earth Sciences Data and Information Services Center (GES DISC) houses a suite of satellite-derived GIS data including high spatiotemporal resolution precipitation, air quality, and modeled land surface parameter data. The data are extremely useful to various GIS research and applications at regional, continental, and global scales, as evidenced by the growing GIS user requests to the data. On the other hand, we also found that some GIS users, especially those from the ArcGIS community, having difficulties in obtaining, importing, and using our data, primarily due to the unfamiliarity of the users with our products and GIS software's lack of capabilities in dealing with the predominately raster form data in various sometimes very complicated formats. In this presentation, we introduce a set of open source ArcGIS data connectors that significantly simplify the access and use of our data in ArcGIS. With the connectors, users do not need to know the data access URLs, the access protocols or syntaxes, and data formats. Nor do they need to browse through a long list of variables that are often embedded into one single science data file and whose names may sometimes be confusing to those not familiar with the file (such as variable CH4_VMR_D for "CH4 Volume mixing ratio from the descending orbit" and variable EVPsfc for "Total Evapotranspiration"). The connectors will expose most GIS-related variables to the users with easy to understand names. User can simply define the spatiotemporal range of their study, select interested parameter(s), and have the needed data be downloaded, imported, and displayed in ArcGIS. The connectors are python text files and there is no installation process. They can be placed at any user directory and be started by simply clicking on it. In the presentation, we'll also demonstrate how to use the tools to load GES DISC time series air quality data with a few clicks and how such data depict the spatial and temporal patterns of

  8. The Plastic Tension Field Method

    DEFF Research Database (Denmark)

    Hansen, Thomas

    2005-01-01

    This paper describes a calculation method for steel plate girders with transverse web stiffeners subjected to shear. It may be used for predicting the failure load or, as a design method, to determine the optimal amount of internal web stiffeners. The new method is called the plastic tension field...... method. The method is based on the theory of plasticity and is analogous to the so-called diagonal compression field method developed for reinforced concrete beams with transverse stirrups, which is adopted in the common European concrete code (Eurocode 2). Many other theories have been developed...

  9. Axelrod's model with surface tension

    Science.gov (United States)

    Pace, Bruno; Prado, Carmen P. C.

    2014-06-01

    In this work we propose a subtle change in Axelrod's model for the dissemination of culture. The mechanism consists of excluding from the set of potentially interacting neighbors those that would never possibly exchange. Although the alteration proposed does not alter the state space topologically, it yields significant qualitative changes, specifically the emergence of surface tension, driving the system in some cases to metastable states. The transient behavior is considerably richer, and cultural regions become stable leading to the formation of different spatiotemporal patterns. A metastable "glassy" phase emerges between the globalized phase and the disordered, multicultural phase.

  10. The peculiarities of large intron splicing in animals.

    Directory of Open Access Journals (Sweden)

    Samuel Shepard

    Full Text Available In mammals a considerable 92% of genes contain introns, with hundreds and hundreds of these introns reaching the incredible size of over 50,000 nucleotides. These "large introns" must be spliced out of the pre-mRNA in a timely fashion, which involves bringing together distant 5' and 3' acceptor and donor splice sites. In invertebrates, especially Drosophila, it has been shown that larger introns can be spliced efficiently through a process known as recursive splicing-a consecutive splicing from the 5'-end at a series of combined donor-acceptor splice sites called RP-sites. Using a computational analysis of the genomic sequences, we show that vertebrates lack the proper enrichment of RP-sites in their large introns, and, therefore, require some other method to aid splicing. We analyzed over 15,000 non-redundant, large introns from six mammals, 1,600 from chicken and zebrafish, and 560 non-redundant large introns from five invertebrates. Our bioinformatic investigation demonstrates that, unlike the studied invertebrates, the studied vertebrate genomes contain consistently abundant amounts of direct and complementary strand interspersed repetitive elements (mainly SINEs and LINEs that may form stems with each other in large introns. This examination showed that predicted stems are indeed abundant and stable in the large introns of mammals. We hypothesize that such stems with long loops within large introns allow intron splice sites to find each other more quickly by folding the intronic RNA upon itself at smaller intervals and, thus, reducing the distance between donor and acceptor sites.

  11. Splicing regulatory factors, ageing and age-related disease.

    Science.gov (United States)

    Latorre, Eva; Harries, Lorna W

    2017-07-01

    Alternative splicing is a co-transcriptional process, which allows for the production of multiple transcripts from a single gene and is emerging as an important control point for gene expression. Alternatively expressed isoforms often have antagonistic function and differential temporal or spatial expression patterns, yielding enormous plasticity and adaptability to cells and increasing their ability to respond to environmental challenge. The regulation of alternative splicing is critical for numerous cellular functions in both pathological and physiological conditions, and deregulated alternative splicing is a key feature of common chronic diseases. Isoform choice is controlled by a battery of splicing regulatory proteins, which include the serine arginine rich (SRSF) proteins and the heterogeneous ribonucleoprotein (hnRNP) classes of genes. These important splicing regulators have been implicated in age-related disease, and in the ageing process itself. This review will outline the important contribution of splicing regulator proteins to ageing and age-related disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Reflections on protein splicing: structures, functions and mechanisms

    Science.gov (United States)

    Anraku, Yasuhiro; Satow, Yoshinori

    2009-01-01

    Twenty years ago, evidence that one gene produces two enzymes via protein splicing emerged from structural and expression studies of the VMA1 gene in Saccharomyces cerevisiae. VMA1 consists of a single open reading frame and contains two independent genetic information for Vma1p (a catalytic 70-kDa subunit of the vacuolar H+-ATPase) and VDE (a 50-kDa DNA endonuclease) as an in-frame spliced insert in the gene. Protein splicing is a posttranslational cellular process, in which an intervening polypeptide termed as the VMA1 intein is self-catalytically excised out from a nascent 120-kDa VMA1 precursor and two flanking polypeptides of the N- and C-exteins are ligated to produce the mature Vma1p. Subsequent studies have demonstrated that protein splicing is not unique to the VMA1 precursor and there are many operons in nature, which implement genetic information editing at protein level. To elucidate its structure-directed chemical mechanisms, a series of biochemical and crystal structural studies has been carried out with the use of various VMA1 recombinants. This article summarizes a VDE-mediated self-catalytic mechanism for protein splicing that is triggered and terminated solely via thiazolidine intermediates with tetrahedral configurations formed within the splicing sites where proton ingress and egress are driven by balanced protonation and deprotonation. PMID:19907126

  13. Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction

    Directory of Open Access Journals (Sweden)

    Marcin Szczot

    2017-12-01

    Full Text Available Summary: Piezo2 is a mechanically activated ion channel required for touch discrimination, vibration detection, and proprioception. Here, we discovered that Piezo2 is extensively spliced, producing different Piezo2 isoforms with distinct properties. Sensory neurons from both mice and humans express a large repertoire of Piezo2 variants, whereas non-neuronal tissues express predominantly a single isoform. Notably, even within sensory ganglia, we demonstrate the splicing of Piezo2 to be cell type specific. Biophysical characterization revealed substantial differences in ion permeability, sensitivity to calcium modulation, and inactivation kinetics among Piezo2 splice variants. Together, our results describe, at the molecular level, a potential mechanism by which transduction is tuned, permitting the detection of a variety of mechanosensory stimuli. : Szczot et al. find that the mechanoreceptor Piezo2 is extensively alternatively spliced, generating multiple distinct isoforms. Their findings indicate that these splice products have specific tissue and cell type expression patterns and exhibit differences in receptor properties. Keywords: Piezo, touch, sensation, ion-channel, splicing

  14. Systematic Analysis of Splice-Site-Creating Mutations in Cancer.

    Science.gov (United States)

    Jayasinghe, Reyka G; Cao, Song; Gao, Qingsong; Wendl, Michael C; Vo, Nam Sy; Reynolds, Sheila M; Zhao, Yanyan; Climente-González, Héctor; Chai, Shengjie; Wang, Fang; Varghese, Rajees; Huang, Mo; Liang, Wen-Wei; Wyczalkowski, Matthew A; Sengupta, Sohini; Li, Zhi; Payne, Samuel H; Fenyö, David; Miner, Jeffrey H; Walter, Matthew J; Vincent, Benjamin; Eyras, Eduardo; Chen, Ken; Shmulevich, Ilya; Chen, Feng; Ding, Li

    2018-04-03

    For the past decade, cancer genomic studies have focused on mutations leading to splice-site disruption, overlooking those having splice-creating potential. Here, we applied a bioinformatic tool, MiSplice, for the large-scale discovery of splice-site-creating mutations (SCMs) across 8,656 TCGA tumors. We report 1,964 originally mis-annotated mutations having clear evidence of creating alternative splice junctions. TP53 and GATA3 have 26 and 18 SCMs, respectively, and ATRX has 5 from lower-grade gliomas. Mutations in 11 genes, including PARP1, BRCA1, and BAP1, were experimentally validated for splice-site-creating function. Notably, we found that neoantigens induced by SCMs are likely several folds more immunogenic compared to missense mutations, exemplified by the recurrent GATA3 SCM. Further, high expression of PD-1 and PD-L1 was observed in tumors with SCMs, suggesting candidates for immune blockade therapy. Our work highlights the importance of integrating DNA and RNA data for understanding the functional and the clinical implications of mutations in human diseases. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  15. The Functional Impact of Alternative Splicing in Cancer.

    Science.gov (United States)

    Climente-González, Héctor; Porta-Pardo, Eduard; Godzik, Adam; Eyras, Eduardo

    2017-08-29

    Alternative splicing changes are frequently observed in cancer and are starting to be recognized as important signatures for tumor progression and therapy. However, their functional impact and relevance to tumorigenesis remain mostly unknown. We carried out a systematic analysis to characterize the potential functional consequences of alternative splicing changes in thousands of tumor samples. This analysis revealed that a subset of alternative splicing changes affect protein domain families that are frequently mutated in tumors and potentially disrupt protein-protein interactions in cancer-related pathways. Moreover, there was a negative correlation between the number of these alternative splicing changes in a sample and the number of somatic mutations in drivers. We propose that a subset of the alternative splicing changes observed in tumors may represent independent oncogenic processes that could be relevant to explain the functional transformations in cancer, and some of them could potentially be considered alternative splicing drivers (AS drivers). Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. 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.

  17. Update on normal tension glaucoma

    Directory of Open Access Journals (Sweden)

    Jyotiranjan Mallick

    2016-01-01

    Full Text Available Normal tension glaucoma (NTG is labelled when typical glaucomatous disc changes, visual field defects and open anterior chamber angles are associated with intraocular pressure (IOP constantly below 21 mmHg. Chronic low vascular perfusion, Raynaud's phenomenon, migraine, nocturnal systemic hypotension and over-treated systemic hypertension are the main causes of normal tension glaucoma. Goldmann applanation tonometry, gonioscopy, slit lamp biomicroscopy, optical coherence tomography and visual field analysis are the main tools of investigation for the diagnosis of NTG. Management follows the same principles of treatment for other chronic glaucomas: To reduce IOP by a substantial amount, sufficient to prevent disabling visual loss. Treatment is generally aimed to lower IOP by 30% from pre-existing levels to 12-14 mmHg. Betaxolol, brimonidine, prostaglandin analogues, trabeculectomy (in refractory cases, systemic calcium channel blockers (such as nifedipine and 24-hour monitoring of blood pressure are considered in the management of NTG. The present review summarises risk factors, causes, pathogenesis, diagnosis and management of NTG.

  18. Pipe connector

    International Nuclear Information System (INIS)

    Sullivan, T.E.; Pardini, J.A.

    1978-01-01

    A safety test facility for testing sodium-cooled nuclear reactor components includes a reactor vessel and a heat exchanger submerged in sodium in the tank. The reactor vessel and heat exchanger are connected by an expansion/deflection pipe coupling comprising a pair of coaxially and slidably engaged tubular elements having radially enlarged opposed end portions of which at least a part is of spherical contour adapted to engage conical sockets in the ends of pipes leading out of the reactor vessel and in to the heat exchanger. A spring surrounding the pipe coupling urges the end portions apart and into engagement with the spherical sockets. Since the pipe coupling is submerged in liquid a limited amount of leakage of sodium from the pipe can be tolerated

  19. The Spliced Leader Trans-Splicing Mechanism in Different Organisms: Molecular Details and Possible Biological Roles

    Directory of Open Access Journals (Sweden)

    Mainá eBitar

    2013-10-01

    Full Text Available The spliced leader (SL is a gene that generates a functional ncRNA that is composed of two regions: an intronic region of unknown function (SLi and an exonic region (SLe, which is transferred to the 5’ end of independent transcripts yielding mature mRNAs, in a process known as spliced leader trans-splicing (SLTS. The best described function for SLTS is to solve polycistronic transcripts into monocistronic units, specifically in Trypanosomatids. In other metazoans, it is speculated that the SLe addition could lead to increased mRNA stability, differential recruitment of the translational machinery, modification of the 5' region or a combination of these effects. Although important aspects of this mechanism have been revealed, several features remain to be elucidated. We have analyzed 157 SLe sequences from 148 species from 7 phyla and found a high degree of conservation among the sequences of species from the same phylum, although no considerable similarity seems to exist between sequences of species from different phyla. When analyzing case studies, we found evidence that a given SLe will always be related to a given set of transcripts in different species from the same phylum, and therefore, different SLe sequences from the same species would regulate different sets of transcripts. In addition, we have observed distinct transcript categories to be preferential targets for the SLe addition in different phyla. This work sheds light into crucial and controversial aspects of the SLTS mechanism. It represents a comprehensive study concerning various species and different characteristics of this important post-transcriptional regulatory mechanism.

  20. Research on Poppers Used as Electrical Connectors in High Speed Textile Transmission Lines

    Directory of Open Access Journals (Sweden)

    Leśnikowski Jacek

    2016-12-01

    Full Text Available This paper presents results of research on poppers used as electrical connectors connecting fragments of textile signal lines. These lines can be used in intelligent clothing for connecting electronic modules implemented in it. Intelligent (smart clothing can be used, among others, in the health monitoring of the elderly, newborn babies, or people working in hazardous conditions, for example, firefighters and soldiers. The aim of the present study was to examine the usefulness of poppers, widely used in clothing, as electrical connectors connecting parts of the textile signal lines designed for transmission of high-speed digital signals. The paper presents examples of measured parameters characterizing transmission properties of two fragments of the coplanar, textile transmission line connected to each other using conventional poppers. The presented measurement results contain the so-called s parameters, characteristic impedance of the poppers, and eye measurements characterizing distortions of digital signals passing through the tested line. In the article, the effect of temperature and humidity of air surrounding the tested poppers on their characteristic impedance was also presented. This property and its stability are important in signal lines designed for high-speed data transmission.

  1. Metallurgical failure investigation of a pipe connector fracture of an expansion vessel

    International Nuclear Information System (INIS)

    Neidel, Andreas

    2016-01-01

    A pipe connector of an expansion vessel of a safety heat exchanger was torn off in a test facility's natural gas compressor. From a material point of view, the cause of the damage is a fatigue fracture induced by pulsating bending stress. The fatigue fracture originated from both, the pipe's outer surface as well as from its inner surface, which is consistent with the given stress situation (pulsating bending stress). Material defects or welding-induced flaws were not observed. Corrosion, wear, or thermal overload which may have promoted the damage, were not observed either. The primary cause was a major design error. Cases of dynamic load were obviously not duly taken into account during designing, so that the free-swinging mass of the expansion vessel which was mounted to a pipe of a diameter of only half an inch and, furthermore, installed in an angle of 45 (additional static preload.), could cause the fatigue failure induced by pulsating bending stress in the zone of highest stresses at the transition of the expansion vessel and the the pipe connector due to dynamic operating loads which always occur in plants like these.

  2. Experiment on Behavior of a New Connector Used in Bamboo (Timber Frame Structure under Cyclic Loading

    Directory of Open Access Journals (Sweden)

    Junwen Zhou

    2018-01-01

    Full Text Available Connection is an important part of the bamboo and timber structure, and it directly influences the overall structural performance and safety. Based on a comprehensive analysis of the mechanical performance of several wood connections, a new connector for the bamboo (timber frame joint was proposed in this paper. Three full-scale T-type joint specimens were designed to study the mechanical performance under cyclic loading. The thickness of the hollow steel column was different among three specimens. The specimens were loaded under displacement control with a rate of 10 mm per minute until the specimens reach failure. It was observed that the failures of three specimens were caused by the buckling of flanges in the compression and that the steel of connections does not yield. The load-displacement hysteretic curve for three specimens is relatively plump, and the stiffness of connection degenerates with the increasing of cyclic load. The maximum rotation is 0.049 rad, and the energy dissipation coefficient is 1.77. The thickness of the hollow steel column of the connector has significant impact on the energy dissipation capacity and the strength of the connection. A simplified moment-rotation hysteresis model for the joint was proposed.

  3. The study and design of tension controller

    Science.gov (United States)

    Jun, G.; Lamei, X.

    2018-02-01

    Tension control is a wide used technology in areas such as textiles, paper and plastic films. In this article, the tension control system release and winding process is analyzed and the mathematical model of tension control system is established, and a high performance tension controller is designed. In hardware design, STM32F130 single chip microcomputer is used as the control core, which has the characteristics of fast running speed and rich peripheral features. In software design, μC/OS-II operating system is introduced to improve the efficiency of single chip microcomputer, and enhance the independence of each module, and make development and maintenance more convenient. The taper tension control is adopted in the winding part, which can effectively solve the problem of rolling shrinkage. The results show that the tension controller has the characteristics of simple structure, easy operation and stable performance.

  4. Soft-tissue tension total knee arthroplasty.

    Science.gov (United States)

    Asano, Hiroshi; Hoshino, Akiho; Wilton, Tim J

    2004-08-01

    It is far from clear how best to define the proper strength of soft-tissue tensioning in total knee arthroplasty (TKA). We attached a torque driver to the Monogram balancer/tensor device and measured soft-tissue tension in full extension and 90 degrees flexion during TKA. In our surgical procedure, when we felt proper soft-tissue tension was being applied, the mean distraction force was noted to be 126N in extension and 121N in flexion. There was no significant correlation between soft-tissue tension and the postoperative flexion angle finally achieved. To the best of our knowledge, this is the first study to assess the actual distraction forces in relation to soft-tissue tension in TKA. Further study may reveal the most appropriate forces to achieve proper soft-tissue tension in the wide variety of circumstances presenting at knee arthroplasty.

  5. Proposal for the award of a blanket purchase agreement, without competitive tendering, for the supply of Burndy connectors

    CERN Document Server

    2004-01-01

    This document concerns the award of a blanket purchase agreement, without competitive tendering, for the supply of Burndy connectors. The Finance Committee is invited to agree to the negotiation of a blanket purchase agreement, without competitive tendering, with SOURIAU (CH), for the supply of Burndy connectors over a period of three years, for a total amount not exceeding 600 000 euros (932 000 Swiss francs), subject to revision for inflation from 1st January 2006. The amount in Swiss francs has been calculated using the present rate of exchange.

  6. The Equilibrium Spreading Tension of Pulmonary Surfactant

    OpenAIRE

    Dagan, Maayan P.; Hall, Stephen B.

    2015-01-01

    Monomolecular films at an air/water interface coexist at the equilibrium spreading tension (γe) with the bulk phase from which they form. For individual phospholipids, γe is single-valued, and separates conditions at which hydrated vesicles adsorb from tensions at which overcompressed monolayers collapse. With pulmonary surfactant, isotherms show that monolayers compressed on the surface of bubbles coexist with the three-dimensional collapsed phase over a range of surface tensions. γe therefo...

  7. 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.

  8. Actin filaments as tension sensors.

    Science.gov (United States)

    Galkin, Vitold E; Orlova, Albina; Egelman, Edward H

    2012-02-07

    The field of mechanobiology has witnessed an explosive growth over the past several years as interest has greatly increased in understanding how mechanical forces are transduced by cells and how cells migrate, adhere and generate traction. Actin, a highly abundant and anomalously conserved protein, plays a large role in forming the dynamic cytoskeleton that is so essential for cell form, motility and mechanosensitivity. While the actin filament (F-actin) has been viewed as dynamic in terms of polymerization and depolymerization, new results suggest that F-actin itself may function as a highly dynamic tension sensor. This property may help explain the unusual conservation of actin's sequence, as well as shed further light on actin's essential role in structures from sarcomeres to stress fibers. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Statistical analysis of LHC main interconnection splices room temperature resistance (R-8) results

    CERN Document Server

    Heck, S

    2012-01-01

    During the 2008/2009 shutdown the so-called R-8/R-16 room temperature resistance test has been introduced for the quality control of the LHC main interconnection splices. It has been found that at present two groups of LHC main interconnection splices can be distinguished, so-called “old” splices produced during LHC installation, and so-called “new” splices produced during 2009. 2009 production splices are considered as the state-of-the art, which is reflected by a much smaller R-8 distribution as compared to that of splices produced during first LHC installation.

  10. Human Splice-Site Prediction with Deep Neural Networks.

    Science.gov (United States)

    Naito, Tatsuhiko

    2018-04-18

    Accurate splice-site prediction is essential to delineate gene structures from sequence data. Several computational techniques have been applied to create a system to predict canonical splice sites. For classification tasks, deep neural networks (DNNs) have achieved record-breaking results and often outperformed other supervised learning techniques. In this study, a new method of splice-site prediction using DNNs was proposed. The proposed system receives an input sequence data and returns an answer as to whether it is splice site. The length of input is 140 nucleotides, with the consensus sequence (i.e., "GT" and "AG" for the donor and acceptor sites, respectively) in the middle. Each input sequence model is applied to the pretrained DNN model that determines the probability that an input is a splice site. The model consists of convolutional layers and bidirectional long short-term memory network layers. The pretraining and validation were conducted using the data set tested in previously reported methods. The performance evaluation results showed that the proposed method can outperform the previous methods. In addition, the pattern learned by the DNNs was visualized as position frequency matrices (PFMs). Some of PFMs were very similar to the consensus sequence. The trained DNN model and the brief source code for the prediction system are uploaded. Further improvement will be achieved following the further development of DNNs.

  11. RNA splicing in a new rhabdovirus from Culex mosquitoes.

    Science.gov (United States)

    Kuwata, Ryusei; Isawa, Haruhiko; Hoshino, Keita; Tsuda, Yoshio; Yanase, Tohru; Sasaki, Toshinori; Kobayashi, Mutsuo; Sawabe, Kyoko

    2011-07-01

    Among members of the order Mononegavirales, RNA splicing events have been found only in the family Bornaviridae. Here, we report that a new rhabdovirus isolated from the mosquito Culex tritaeniorhynchus replicates in the nuclei of infected cells and requires RNA splicing for viral mRNA maturation. The virus, designated Culex tritaeniorhynchus rhabdovirus (CTRV), shares a similar genome organization with other rhabdoviruses, except for the presence of a putative intron in the coding region for the L protein. Molecular phylogenetic studies indicated that CTRV belongs to the family Rhabdoviridae, but it is yet to be assigned a genus. Electron microscopic analysis revealed that the CTRV virion is extremely elongated, unlike virions of rhabdoviruses, which are generally bullet shaped. Northern hybridization confirmed that a large transcript (approximately 6,500 nucleotides [nt]) from the CTRV L gene was present in the infected cells. Strand-specific reverse transcription-PCR (RT-PCR) analyses identified the intron-exon boundaries and the 76-nt intron sequence, which contains the typical motif for eukaryotic spliceosomal intron-splice donor/acceptor sites (GU-AG), a predicted branch point, and a polypyrimidine tract. In situ hybridization exhibited that viral RNAs are primarily localized in the nucleus of infected cells, indicating that CTRV replicates in the nucleus and is allowed to utilize the host's nuclear splicing machinery. This is the first report of RNA splicing among the members of the family Rhabdoviridae.

  12. A Challenging Pie to Splice: Drugging the Spliceosome.

    Science.gov (United States)

    León, Brian; Kashyap, Manoj K; Chan, Warren C; Krug, Kelsey A; Castro, Januario E; La Clair, James J; Burkart, Michael D

    2017-09-25

    Since its discovery in 1977, the study of alternative RNA splicing has revealed a plethora of mechanisms that had never before been documented in nature. Understanding these transitions and their outcome at the level of the cell and organism has become one of the great frontiers of modern chemical biology. Until 2007, this field remained in the hands of RNA biologists. However, the recent identification of natural product and synthetic modulators of RNA splicing has opened new access to this field, allowing for the first time a chemical-based interrogation of RNA splicing processes. Simultaneously, we have begun to understand the vital importance of splicing in disease, which offers a new platform for molecular discovery and therapy. As with many natural systems, gaining clear mechanistic detail at the molecular level is key towards understanding the operation of any biological machine. This minireview presents recent lessons learned in this emerging field of RNA splicing chemistry and chemical biology. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. 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.

  14. The determinants of alternative RNA splicing in human cells.

    Science.gov (United States)

    Ramanouskaya, Tatsiana V; Grinev, Vasily V

    2017-12-01

    Alternative splicing represents an important level of the regulation of gene function in eukaryotic organisms. It plays a critical role in virtually every biological process within an organism, including regulation of cell division and cell death, differentiation of tissues in the embryo and the adult organism, as well as in cellular response to diverse environmental factors. In turn, studies of the last decade have shown that alternative splicing itself is controlled by different mechanisms. Unfortunately, there is no clear understanding of how these diverse mechanisms, or determinants, regulate and constrain the set of alternative RNA species produced from any particular gene in every cell of the human body. Here, we provide a consolidated overview of alternative splicing determinants including RNA-protein interactions, epigenetic regulation via chromatin remodeling, coupling of transcription-to-alternative splicing, effect of secondary structures in pre-RNA, and function of the RNA quality control systems. We also extensively and critically discuss some mechanistic insights on coordinated inclusion/exclusion of exons during the formation of mature RNA molecules. We conclude that the final structure of RNA is pre-determined by a complex interplay between cis- and trans-acting factors. Altogether, currently available empirical data significantly expand our understanding of the functioning of the alternative splicing machinery of cells in normal and pathological conditions. On the other hand, there are still many blind spots that require further deep investigations.

  15. Normal-tension glaucoma (Low-tension glaucoma)

    Science.gov (United States)

    Anderson, Douglas R

    2011-01-01

    Glaucoma is now considered an abnormal physiology in the optic nerve head that interacts with the level of intraocular pressure (IOP), with the degree and rate of damage depending on the IOP and presumably the degree of abnormal physiology. Diagnosis of normal-tension glaucoma (NTG), defined as glaucoma without a clearly abnormal IOP, depends on recognizing symptoms and signs associated with optic nerve vulnerability, in addition to absence of other explanations for disc abnormality and visual field loss. Among the findings are a halo or crescent of absence of retinal pigment epithelium around the disc, bilateral pre-chiasmal visual field defects, splinter hemorrhages at the disc margin, vascular dysregulation (low blood pressure, cold hands and feet, migraine headache with aura, and the like), or a family history of glaucoma. Possibly relevant, is a history of hemodynamic crisis, arterial obstructive disease, or sleep apnea. Neurological evaluation with imaging is needed only for atypical cases or ones that progress unexpectedly. Management follows the same principle of other chronic glaucomas, to lower the IOP by a substantial amount, enough to prevent disabling visual loss. However, many NTG cases are non-progressive. Therefore, it may often be wisein mild cases to determine whether the case is progressive and the rate of progression before deciding on how aggressivene to be with therapy. Efforts at neuroprotection and improvement in blood flow have not yet been shown effective. PMID:21150042

  16. Normal-tension glaucoma (Low-tension glaucoma

    Directory of Open Access Journals (Sweden)

    Anderson Douglas

    2011-12-01

    Full Text Available Glaucoma is now considered an abnormal physiology in the optic nerve head that interacts with the level of intraocular pressure (IOP, with the degree and rate of damage depending on the IOP and presumably the degree of abnormal physiology. Diagnosis of normal-tension glaucoma (NTG, defined as glaucoma without a clearly abnormal IOP, depends on recognizing symptoms and signs associated with optic nerve vulnerability, in addition to absence of other explanations for disc abnormality and visual field loss. Among the findings are a halo or crescent of absence of retinal pigment epithelium around the disc, bilateral pre-chiasmal visual field defects, splinter hemorrhages at the disc margin, vascular dysregulation (low blood pressure, cold hands and feet, migraine headache with aura, and the like, or a family history of glaucoma. Possibly relevant, is a history of hemodynamic crisis, arterial obstructive disease, or sleep apnea. Neurological evaluation with imaging is needed only for atypical cases or ones that progress unexpectedly. Management follows the same principle of other chronic glaucomas, to lower the IOP by a substantial amount, enough to prevent disabling visual loss. However, many NTG cases are non-progressive. Therefore, it may often be wisein mild cases to determine whether the case is progressive and the rate of progression before deciding on how aggressivene to be with therapy. Efforts at neuroprotection and improvement in blood flow have not yet been shown effective.

  17. Traumatic tension pneumocephalus: Two case reports

    Directory of Open Access Journals (Sweden)

    Abubaker Al-Aieb

    2017-01-01

    Conclusions: These are two rare cases with posttraumatic tension pneumocephalus treated conservatively with a favorable outcome. Early diagnosis of tension pneumocephalus is a crucial step to facilitate early recovery; however, the associated injuries need attention as they could influence the hospital course.

  18. Embracing Tensions in Feminist Organizational Communication Pedagogies

    Science.gov (United States)

    Linabary, Jasmine R.; Long, Ziyu; Mouton, Ashton; Rao, Ranjani L.; Buzzanell, Patrice M.

    2017-01-01

    Feminist pedagogies hold potential to create more inclusive and transformative classrooms. Adopting a tension-centered approach, we draw on our individual and collective reflections on the design and instruction of a multi-section undergraduate organizational communication course to build an autoethnographic account of the tensions associated with…

  19. Tending the tensions in co-creation

    DEFF Research Database (Denmark)

    Phillips, Professor MSO Louise; Nordentoft, Helle Merete; Pedersen, Lektor Christina Hee

    -for-granted positive value. In the panel we de-romanticise “co-creation” and explore how it is enacted in particular organisational contexts, concentrating on context-specific tensions arising in the meeting between different knowledge forms and interests. These include tensions BETWEEN dialogic views of knowledge co-creation...

  20. Post-tensioning system surveillance program

    International Nuclear Information System (INIS)

    Drew, G.E.

    1979-01-01

    Nuclear power plant containment structure post-tensioning system tendon surveillance program is described in detail. Data collected over three yearly post-tensioning system Surveillance Programs is presented and evaluated to correlate anticipated stress losses with actual losses. In addition corrosion protected system performance is analyzed

  1. Tension and robustness in multitasking cellular networks.

    Directory of Open Access Journals (Sweden)

    Jeffrey V Wong

    Full Text Available Cellular networks multitask by exhibiting distinct, context-dependent dynamics. However, network states (parameters that generate a particular dynamic are often sub-optimal for others, defining a source of "tension" between them. Though multitasking is pervasive, it is not clear where tension arises, what consequences it has, and how it is resolved. We developed a generic computational framework to examine the source and consequences of tension between pairs of dynamics exhibited by the well-studied RB-E2F switch regulating cell cycle entry. We found that tension arose from task-dependent shifts in parameters associated with network modules. Although parameter sets common to distinct dynamics did exist, tension reduced both their accessibility and resilience to perturbation, indicating a trade-off between "one-size-fits-all" solutions and robustness. With high tension, robustness can be preserved by dynamic shifting of modules, enabling the network to toggle between tasks, and by increasing network complexity, in this case by gene duplication. We propose that tension is a general constraint on the architecture and operation of multitasking biological networks. To this end, our work provides a framework to quantify the extent of tension between any network dynamics and how it affects network robustness. Such analysis would suggest new ways to interfere with network elements to elucidate the design principles of cellular networks.

  2. Tension Pneumothorax following an Accidental Kerosene Poisoning ...

    African Journals Online (AJOL)

    Tension pneumothorax is a rare complication following an accidental kerosene poisoning. In such situation, a bed-side needle thoracocentesis is performed because of its potential of becoming fatal; hence its clinical importance. A case of 15 month old boy with tension pneumothorax following accidental kerosene ...

  3. Development of radiation-hard electric connector with ball bearing for in-vessel remote maintenance equipment of ITER

    International Nuclear Information System (INIS)

    Ito, Akira; Obara, Kenjiro; Tada, Eisuke; Morita, Yousuke; Yagi, Toshiaki; Iida, Kazuhisa; Sato, Masaru.

    1997-12-01

    Development of radiation-hard electric connector with ball bearing for in-vessel remote maintenance equipment of ITER (International Thermonuclear Experimental Reactor) has been conducted. Since the in-vessel remote maintenance equipment is operated under the condition of 10 6 R/h gamma ray dose rate, the electric connector has to be radiation hard for an accumulation dose of 10 10 R. In addition, the simple attachment/removal mechanism is essential for remote operation. For this, the alumina (Al203) ceramics and a ball bearing were adopted to electric insulator and plug (male) of connector, respectively. The handling tests on attachment/removal of the connector were conducted by using master slave manipulator and general purpose robot with handling tool, and as a result, the validity of the attachment/removal mechanism was verified. In the gamma ray irradiation tests, which are under way, no degradation in break down voltage (1000V 1min.) up to 10 10 R was confirmed. However insulation resistance and contact resistance between contact pin and contact socket were deteriorated in proportion to the accumulation dose. Increase of contact resistance is considered due to an erosion of contact pin. (author)

  4. The influence of charge injection from intermediate connectors on the performance of tandem organic light-emitting devices

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Dong-Ying [Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu 215123 (China); Department of Electrical and Computer Engineering and Waterloo Institute for Nanotechnology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1 (Canada); Siboni, Hossein Zamani; Wang, Qi; Aziz, Hany, E-mail: lsliao@suda.edu.cn, E-mail: h2aziz@uwaterloo.ca [Department of Electrical and Computer Engineering and Waterloo Institute for Nanotechnology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1 (Canada); Liao, Liang-Sheng, E-mail: lsliao@suda.edu.cn, E-mail: h2aziz@uwaterloo.ca [Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu 215123 (China)

    2014-12-14

    Charge generation in a typical intermediate connector, composed of “n-type doped layer/transition metal oxide (TMO)/hole transporting layer (HTL),” of a tandem organic light-emitting device (OLED) has recently been found to arise from charge transfer at the TMO/HTL interfaces. In this paper, we investigate the effect of hole injection barriers from intermediate connectors on the performance of tandem OLEDs. The hole injection barriers are caused by the offset of the highest occupied molecular orbital (HOMO) energy levels between HTLs contained in the intermediate connector and the top electroluminescence (EL) unit. We also find that although charge generation can occur at the interfaces between the TMO and a wide variety of HTLs of different HOMO values, an increase in the hole injection barrier however limits the electroluminescence efficiency of the top EL units. In the case of large hole injection barriers, significant charge accumulation in the HTLs makes the intermediate connector lose its functionality gradually over operating time, and limits device stability.

  5. Initial tension loss in cerclage cables.

    Science.gov (United States)

    Ménard, Jérémie; Émard, Maxime; Canet, Fanny; Brailovski, Vladimir; Petit, Yvan; Laflamme, George Y

    2013-10-01

    Cerclage cables, frequently used in the management of fractures and osteotomies, are associated with a high failure rate and significant loosening during surgery. This study compared the capacity to maintain tension of different types of orthopaedic cable systems. Multifilament Cobalt-Chrome (CoCr) cables with four different crimp/clamp devices (DePuy, Stryker, Zimmer and Smith&Nephew) and one non-metallic Nylon (Ny) cable from Kinamed were instrumented with a load cell to measure tension during insertion. Significant tension loss was observed with crimping for all cables (Ptensioner led to an additional unexpected tension loss (CoCr-DePuy: 18%, CoCr-Stryker: 29%, CoCr-Smith&Nephew: 33%, Ny: 46%, and CoCr-Zimmer: 52%). The simple CoCr (DePuy) cable system outperformed the more sophisticated locking devices due to its significantly better ability to prevent tension loss. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Running CMS remote analysis builder jobs on advanced resource connector middleware

    International Nuclear Information System (INIS)

    Edelmann, E; Happonen, K; Koivumäki, J; Lindén, T; Välimaa, J

    2011-01-01

    CMS user analysis jobs are distributed over the grid with the CMS Remote Analysis Builder application (CRAB). According to the CMS computing model the applications should run transparently on the different grid flavours in use. In CRAB this is handled with different plugins that are able to submit to different grids. Recently a CRAB plugin for submitting to the Advanced Resource Connector (ARC) middleware has been developed. The CRAB ARC plugin enables simple and fast job submission with full job status information available. CRAB can be used with a server which manages and monitors the grid jobs on behalf of the user. In the presentation we will report on the CRAB ARC plugin and on the status of integrating it with the CRAB server and compare this with using the gLite ARC interoperability method for job submission.

  7. Low background materials and fabrication techniques for cables and connectors in the Majorana Demonstrator

    Science.gov (United States)

    Busch, M.; Abgrall, N.; Alvis, S. I.; Arnquist, I. J.; Avignone, F. T.; Barabash, A. S.; Barton, C. J.; Bertrand, F. E.; Bode, T.; Bradley, A. W.; Brudanin, V.; Buuck, M.; Caldwell, T. S.; Chan, Y.-D.; Christofferson, C. D.; Chu, P.-H.; Cuesta, C.; Detwiler, J. A.; Dunagan, C.; Efremenko, Yu.; Ejiri, H.; Elliott, S. R.; Gilliss, T.; Giovanetti, G. K.; Green, M. P.; Gruszko, J.; Guinn, I. S.; Guiseppe, V. E.; Haufe, C. R.; Hehn, L.; Henning, R.; Hoppe, E. W.; Howe, M. A.; Keeter, K. J.; Kidd, M. F.; Konovalov, S. I.; Kouzes, R. T.; Lopez, A. M.; Martin, R. D.; Massarczyk, R.; Meijer, S. J.; Mertens, S.; Myslik, J.; O'Shaughnessy, C.; Othman, G.; Poon, A. W. P.; Radford, D. C.; Rager, J.; Reine, A. L.; Rielage, K.; Robertson, R. G. H.; Rouf, N. W.; Shanks, B.; Shirchenko, M.; Suriano, A. M.; Tedeschi, D.; Trimble, J. E.; Varner, R. L.; Vasilyev, S.; Vetter, K.; Vorren, K.; White, B. R.; Wilkerson, J. F.; Wiseman, C.; Xu, W.; Yakushev, E.; Yu, C.-H.; Yumatov, V.; Zhitnikov, I.; Zhu, B. X.

    2018-01-01

    The Majorana Collaboration is searching for the neutrinoless double-beta decay of the nucleus 76Ge. The Majorana Demonstrator is an array of germanium detectors deployed with the aim of implementing background reduction techniques suitable for a tonne scale 76Ge-based search (the LEGEND collaboration). In the Demonstrator, germanium detectors operate in an ultra-pure vacuum cryostat at 80 K. One special challenge of an ultra-pure environment is to develop reliable cables, connectors, and electronics that do not significantly contribute to the radioactive background of the experiment. This paper highlights the experimental requirements and how these requirements were met for the Majorana Demonstrator, including plans to upgrade the wiring for higher reliability in the summer of 2018. Also described are requirements for LEGEND R&D efforts underway to meet these additional requirements

  8. Pre-mRNA mis-splicing of sarcomeric genes in heart failure.

    Science.gov (United States)

    Zhu, Chaoqun; Chen, Zhilong; Guo, Wei

    2017-08-01

    Pre-mRNA splicing is an important biological process that allows production of multiple proteins from a single gene in the genome, and mainly contributes to protein diversity in eukaryotic organisms. Alternative splicing is commonly governed by RNA binding proteins to meet the ever-changing demands of the cell. However, the mis-splicing may lead to human diseases. In the heart of human, mis-regulation of alternative splicing has been associated with heart failure. In this short review, we focus on alternative splicing of sarcomeric genes and review mis-splicing related heart failure with relatively well studied Sarcomeric genes and splicing mechanisms with identified regulatory factors. The perspective of alternative splicing based therapeutic strategies in heart failure has also been discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Alternative splicing: the pledge, the turn, and the prestige : The key role of alternative splicing in human biological systems.

    Science.gov (United States)

    Gallego-Paez, L M; Bordone, M C; Leote, A C; Saraiva-Agostinho, N; Ascensão-Ferreira, M; Barbosa-Morais, N L

    2017-09-01

    Alternative pre-mRNA splicing is a tightly controlled process conducted by the spliceosome, with the assistance of several regulators, resulting in the expression of different transcript isoforms from the same gene and increasing both transcriptome and proteome complexity. The differences between alternative isoforms may be subtle but enough to change the function or localization of the translated proteins. A fine control of the isoform balance is, therefore, needed throughout developmental stages and adult tissues or physiological conditions and it does not come as a surprise that several diseases are caused by its deregulation. In this review, we aim to bring the splicing machinery on stage and raise the curtain on its mechanisms and regulation throughout several systems and tissues of the human body, from neurodevelopment to the interactions with the human microbiome. We discuss, on one hand, the essential role of alternative splicing in assuring tissue function, diversity, and swiftness of response in these systems or tissues, and on the other hand, what goes wrong when its regulatory mechanisms fail. We also focus on the possibilities that splicing modulation therapies open for the future of personalized medicine, along with the leading techniques in this field. The final act of the spliceosome, however, is yet to be fully revealed, as more knowledge is needed regarding the complex regulatory network that coordinates alternative splicing and how its dysfunction leads to disease.

  10. 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 Caenorhabditis nematodes-more than 92% of cassette exons from Caenorhabditis elegans are conserved in Caenorhabditis briggsae and/or Caenorhabditis remanei. High levels of conservation extend to minor-form exons (present in a minority of transcripts) and are particularly pronounced for exons showing complex...... 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...

  11. Body Temperature Cycles Control Rhythmic Alternative Splicing in Mammals.

    Science.gov (United States)

    Preußner, Marco; Goldammer, Gesine; Neumann, Alexander; Haltenhof, Tom; Rautenstrauch, Pia; Müller-McNicoll, Michaela; Heyd, Florian

    2017-08-03

    The core body temperature of all mammals oscillates with the time of the day. However, direct molecular consequences of small, physiological changes in body temperature remain largely elusive. Here we show that body temperature cycles drive rhythmic SR protein phosphorylation to control an alternative splicing (AS) program. A temperature change of 1°C is sufficient to induce a concerted splicing switch in a large group of functionally related genes, rendering this splicing-based thermometer much more sensitive than previously described temperature-sensing mechanisms. AS of two exons in the 5' UTR of the TATA-box binding protein (Tbp) highlights the general impact of this mechanism, as it results in rhythmic TBP protein levels with implications for global gene expression in vivo. Together our data establish body temperature-driven AS as a core clock-independent oscillator in mammalian peripheral clocks. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. 3D Architecture of the Trypanosoma brucei Flagella Connector, a Mobile Transmembrane Junction.

    Directory of Open Access Journals (Sweden)

    Johanna L Höög

    2016-01-01

    Full Text Available Cellular junctions are crucial for the formation of multicellular organisms, where they anchor cells to each other and/or supportive tissue and enable cell-to-cell communication. Some unicellular organisms, such as the parasitic protist Trypanosoma brucei, also have complex cellular junctions. The flagella connector (FC is a three-layered transmembrane junction that moves with the growing tip of a new flagellum and attaches it to the side of the old flagellum. The FC moves via an unknown molecular mechanism, independent of new flagellum growth. Here we describe the detailed 3D architecture of the FC suggesting explanations for how it functions and its mechanism of motility.We have used a combination of electron tomography and cryo-electron tomography to reveal the 3D architecture of the FC. Cryo-electron tomography revealed layers of repetitive filamentous electron densities between the two flagella in the interstitial zone. Though the FC does not change in length and width during the growth of the new flagellum, the interstitial zone thickness decreases as the FC matures. This investigation also shows interactions between the FC layers and the axonemes of the new and old flagellum, sufficiently strong to displace the axoneme in the old flagellum. We describe a novel filament, the flagella connector fibre, found between the FC and the axoneme in the old flagellum.The FC is similar to other cellular junctions in that filamentous proteins bridge the extracellular space and are anchored to underlying cytoskeletal structures; however, it is built between different portions of the same cell and is unique because of its intrinsic motility. The detailed description of its structure will be an important tool to use in attributing structure / function relationships as its molecular components are discovered in the future. The FC is involved in the inheritance of cell shape, which is important for the life cycle of this human parasite.

  13. Design and fabrication of advanced fiber alignment structures for field-installable fiber connectors

    Science.gov (United States)

    Van Erps, Jürgen; Vervaeke, Michael; Sánchez Martínez, Alberto; Beri, Stefano; Debaes, Christof; Watté, Jan; Thienpont, Hugo

    2012-06-01

    Fiber-To-The-Home (FTTH) networks have been adopted as a potential replacement of traditional electrical connections for the 'last mile' transmission of information at bandwidths over 1Gb/s. However, the success and adoption of optical access networks critically depend on the quality and reliability of connections between optical fibers. In particular a further reduction of insertion loss of field-installable connectors must be achieved without a significant increase in component cost. This requires precise alignment of fibers that can differ in terms of ellipticity, eccentricity or diameter and seems hardly achievable using today's widespread ferrule-based alignment systems. Novel low-cost structures for bare fiber alignment with outstanding positioning accuracies are strongly desired as they would allow reducing loss beyond the level achievable with ferrule-bore systems. However, the realization of such alignment system is challenging as it should provide sufficient force to position the fiber with sub-micron accuracy required in positioning the fiber. In this contribution we propose, design and prototype a bare-fiber alignment system which makes use of deflectable/compressible micro-cantilevers. Such cantilevers behave as springs and provide self-centering functionality to the structure. Simulations of the mechanical properties of the cantilevers are carried out in order to get an analytical approximation and a mathematical model of the spring constant and stress in the structure. Elastic constants of the order of 104 to 105N/m are found out to be compatible with a proof stress of 70 MPa. Finally a first self-centering structure is prototyped in PMMA using our Deep Proton Writing technology. The spring constants of the fabricated cantilevers are in the range of 4 to 6 × 104N/m and the stress is in the range 10 to 20 MPa. These self-centering structures have the potential to become the basic building blocks for a new generation of field-installable connectors.

  14. Genome-wide survey of allele-specific splicing in humans

    Directory of Open Access Journals (Sweden)

    Scheffler Konrad

    2008-06-01

    Full Text Available 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 mutation on the efficiency of mRNA splicing is often difficult to predict, many mutations that cause disease through an effect on splicing are likely to remain undiscovered. Results We have combined a genome-wide scan for sequence polymorphisms likely to affect mRNA splicing with analysis of publicly available Expressed Sequence Tag (EST and exon array data. The genome-wide scan uses published tools and identified 30,977 SNPs located within donor and acceptor splice sites, branch points and exonic splicing enhancer elements. For 1,185 candidate splicing polymorphisms the difference in splicing between alternative alleles was corroborated by publicly available exon array data from 166 lymphoblastoid cell lines. We developed a novel probabilistic method to infer allele-specific splicing from EST data. The method uses SNPs and alternative mRNA isoforms mapped to EST sequences and models both regulated alternative splicing as well as allele-specific splicing. We have also estimated heritability of splicing and report that a greater proportion of genes show evidence of splicing heritability than show heritability of overall gene expression level. Our results provide an extensive resource that can be used to assess the possible effect on splicing of human polymorphisms in putative splice-regulatory sites. Conclusion We report a set of genes showing evidence of allele-specific splicing from an integrated analysis of genomic polymorphisms, EST data and exon array

  15. Analysis for Behavior of Reinforcement Lap Splices in Deep Beams

    Directory of Open Access Journals (Sweden)

    Ammar Yaser Ali

    2018-03-01

    Full Text Available The present study includes an experimental and theoretical investigation of reinforced concrete deep beams containing tensile reinforcement lap splices at constant moment zone under static load. The study included two stages: in the first one, an experimental work included testing of eight simply supported RC deep beams having a total length (L = 2000 mm, overall depth (h= 600 mm and width (b = 150 mm. The tested specimens were divided into three groups to study the effect of main variables: lap length, location of splice, internal confinement (stirrups and external confinement (strengthening by CFRP laminates. The experimental results showed that the use of CFRP as external strengthening in deep beam with lap spliced gives best behavior such as increase in stiffness, decrease in deflection, delaying the cracks appearance and reducing the crack width. The reduction in deflection about (14-21 % than the unstrengthened beam and about (5-14 % than the beam with continuous bars near ultimate load. Also, it was observed that the beams with unstrengthened tensile reinforcement lap splices had three types of cracks: flexural, flexural-shear and splitting cracks while the beams with strengthened tensile reinforcement lap splices or continuous bars don’t observe splitting cracks. In the second stage, a numerical analysis of three dimensional finite element analysis was utilized to explore the behavior of the RC deep beams with tensile reinforcement lap splices, in addition to parametric study of many variables. The comparison between the experimental and theoretical results showed reasonable agreement. The average difference of the deflection at service load was less than 5%.

  16. Dynamical modeling of surface tension

    International Nuclear Information System (INIS)

    Brackbill, J.U.; Kothe, D.B.

    1996-01-01

    In a recent review it is said that free-surface flows ''represent some of the difficult remaining challenges in computational fluid dynamics''. There has been progress with the development of new approaches to treating interfaces, such as the level-set method and the improvement of older methods such as the VOF method. A common theme of many of the new developments has been the regularization of discontinuities at the interface. One example of this approach is the continuum surface force (CSF) formulation for surface tension, which replaces the surface stress given by Laplace's equation by an equivalent volume force. Here, we describe how CSF might be made more useful. Specifically, we consider a derivation of the CSF equations from a minimization of surface energy as outlined by Jacqmin. This reformulation suggests that if one eliminates the computation of curvature in terms of a unit normal vector, parasitic currents may be eliminated For this reformulation to work, it is necessary that transition region thickness be controlled. Various means for this, in addition to the one discussed by Jacqmin are discussed

  17. Bilateral tension pneumothorax after acupuncture.

    Science.gov (United States)

    Mohammad, Nurashikin

    2018-04-19

    Acupuncture is an ancient complementary medicine which is currently used worldwide. Many serious adverse events have been reported which include a spectrum of mild-to-fatal complications. However, the level of awareness with regard to complications is still low both to physicians and patients. We report a 63-year-old who presented with acute shortness of breath 2 hours after having had acupuncture. On examination, there was absent breath sound heard on the left lung and slightly reduced breath sound on the right lung. She had type 1 respiratory failure. Urgent chest radiograph confirmed bilateral pneumothorax which was more severe on the left with tension pneumothorax and mediastinal shift. Chest tubes were inserted bilaterally after failed needle aspiration attempts. Subsequently, the pneumothoraces resolved, and she was discharged well. The bilateral pneumothoraces caused by acupuncture were curable but could have been potentially fatal if diagnosis was delayed. This case report adds to the limited current literature on the complications of acupuncture leading to bilateral pneumothoraces. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Multibreath alveolar oxygen tension imaging.

    Science.gov (United States)

    Clapp, Justin; Hamedani, Hooman; Kadlecek, Stephen; Xin, Yi; Shaghaghi, Hoora; Siddiqui, Sarmad; Rossman, Milton D; Rizi, Rahim R

    2016-10-01

    This study tested the ability of a multibreath hyperpolarized HP (3) He MRI protocol to increase the accuracy of regional alveolar oxygen tension (PA O2 ) measurements by lessening the influence of gas-flow artifacts. Conventional single-breath PA O2 measurement has been susceptible to error induced by intervoxel gas flow, particularly when used to study subjects with moderate-to-severe chronic obstructive pulmonary disease (COPD). Both single-breath and multibreath PA O2 imaging schemes were implemented in seven human subjects (one healthy, three asymptomatic smokers, and three COPD). The number and location of voxels with nonphysiologic PA O2 values generated by intervoxel gas flow were compared between the two protocols. The multibreath scheme resulted in a significantly lower total percentage of nonphysiologic PA O2 values (6.0%) than the single-breath scheme (13.7%) (P = 0.006). PA O2 maps showed several patterns of gas-flow artifacts that were present in the single-breath protocol but mitigated by the multibreath approach. Multibreath imaging also allowed for the analysis of slow-filling areas that presented no signal after a single breath. A multibreath approach enhances the accuracy and completeness of noninvasive PA O2 measurement by significantly lessening the proportion of nonphysiologic values generated by intervoxel gas flow. Magn Reson Med 76:1092-1101, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  19. A novel splicing mutation in the V2 vasopressin receptor

    DEFF Research Database (Denmark)

    Kamperis, Konstantinos; Siggaard, C; Herlin, Troels

    2000-01-01

    as clinical investigations comprising a fluid deprivation test and a 1-deamino-8-D-arginine-vasopressin (dDAVP) infusion test in the study subject and his mother. We found a highly unusual, novel, de novo 1447A-->C point mutation (gDNA), involving the invariable splice acceptor of the second intron...... of the gene in both the affected male (hemizygous) and his mother (heterozygous). This mutation is likely to cause aberrant splicing of the terminal intron of the gene, leading to a non-functional AVP receptor. The clinical studies were consistent with such a hypothesis, as the affected subject had a severe...

  20. 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.

  1. 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.

  2. Analysis and recognition of 5 ' UTR intron splice sites in human pre-mRNA

    DEFF Research Database (Denmark)

    Eden, E.; Brunak, Søren

    2004-01-01

    Prediction of splice sites in non-coding regions of genes is one of the most challenging aspects of gene structure recognition. We perform a rigorous analysis of such splice sites embedded in human 5' untranslated regions (UTRs), and investigate correlations between this class of splice sites and...

  3. ISVASE: identification of sequence variant associated with splicing event using RNA-seq data.

    Science.gov (United States)

    Aljohi, Hasan Awad; Liu, Wanfei; Lin, Qiang; Yu, Jun; Hu, Songnian

    2017-06-28

    Exon recognition and splicing precisely and efficiently by spliceosome is the key to generate mature mRNAs. About one third or a half of disease-related mutations affect RNA splicing. Software PVAAS has been developed to identify variants associated with aberrant splicing by directly using RNA-seq data. However, it bases on the assumption that annotated splicing site is normal splicing, which is not true in fact. We develop the ISVASE, a tool for specifically identifying sequence variants associated with splicing events (SVASE) by using RNA-seq data. Comparing with PVAAS, our tool has several advantages, such as multi-pass stringent rule-dependent filters and statistical filters, only using split-reads, independent sequence variant identification in each part of splicing (junction), sequence variant detection for both of known and novel splicing event, additional exon-exon junction shift event detection if known splicing events provided, splicing signal evaluation, known DNA mutation and/or RNA editing data supported, higher precision and consistency, and short running time. Using a realistic RNA-seq dataset, we performed a case study to illustrate the functionality and effectiveness of our method. Moreover, the output of SVASEs can be used for downstream analysis such as splicing regulatory element study and sequence variant functional analysis. ISVASE is useful for researchers interested in sequence variants (DNA mutation and/or RNA editing) associated with splicing events. The package is freely available at https://sourceforge.net/projects/isvase/ .

  4. [Genetic diagnostics of pathogenic splicing abnormalities in the clinical laboratory--pitfalls and screening approaches].

    Science.gov (United States)

    Niimi, Hideki; Ogawa, Tomomi; Note, Rhougou; Hayashi, Shirou; Ueno, Tomohiro; Harada, Kenu; Uji, Yoshinori; Kitajima, Isao

    2010-12-01

    In recent years, genetic diagnostics of pathogenic splicing abnormalities are increasingly recognized as critically important in the clinical genetic diagnostics. It is reported that approximately 10% of pathogenic mutations causing human inherited diseases are splicing mutations. Nonetheless, it is still difficult to identify splicing abnormalities in routine genetic diagnostic settings. Here, we studied two different kinds of cases with splicing abnormalities. The first case is a protein S deficiency. Nucleotide analyses revealed that the proband had a previously reported G to C substitution in the invariant AG dinucleotide at the splicing acceptor site of intronl/exon2, which produces multiple splicing abnormalities resulting in protein S deficiency. The second case is an antithrombin (AT) deficiency. This proband had a previously reported G to A substitution, at nucleotide position 9788 in intron 4, 14 bp in front of exon 5, which created a de novo exon 5 splice site and resulted in AT deficiency. From a practical standpoint, we discussed the pitfalls, attentions, and screening approaches in genetic diagnostics of pathogenic splicing abnormalities. Due to the difficulty with full-length sequence analysis of introns, and the lack of RNA samples, splicing mutations may escape identification. Although current genetic testing remains to be improved, to screen for splicing abnormalities more efficiently, it is significant to use an appropriate combination of various approaches such as DNA and/or RNA samples, splicing mutation databases, bioinformatic tools to detect splice sites and cis-regulatory elements, and in vitro and/or in vivo experimentally methods as needed.

  5. Systematic profiling of alternative splicing signature reveals prognostic predictor for ovarian cancer.

    Science.gov (United States)

    Zhu, Junyong; Chen, Zuhua; Yong, Lei

    2018-02-01

    The majority of genes are alternatively spliced and growing evidence suggests that alternative splicing is modified in cancer and is associated with cancer progression. Systematic analysis of alternative splicing signature in ovarian cancer is lacking and greatly needed. We profiled genome-wide alternative splicing events in 408 ovarian serous cystadenocarcinoma (OV) patients in TCGA. Seven types of alternative splicing events were curated and prognostic analyses were performed with predictive models and splicing network built for OV patients. Among 48,049 mRNA splicing events in 10,582 genes, we detected 2,611 alternative splicing events in 2,036 genes which were significant associated with overall survival of OV patients. Exon skip events were the most powerful prognostic factors among the seven types. The area under the curve of the receiver-operator characteristic curve for prognostic predictor, which was built with top significant alternative splicing events, was 0.937 at 2,000 days of overall survival, indicating powerful efficiency in distinguishing patient outcome. Interestingly, splicing correlation network suggested obvious trends in the role of splicing factors in OV. In summary, we built powerful prognostic predictors for OV patients and uncovered interesting splicing networks which could be underlying mechanisms. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Gastrothorax or tension pneumothorax: A diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Singh Sarvesh

    2011-01-01

    Full Text Available Gastrothorax, a rare complication following thoracoabdominal aortic aneurysm repair, is reported. The clinical features of a gastrothorax and tension pneumothorax are similar and thus, a gastrothorax can masquerade as a tension pneumothorax. The diagnosis is made by a high level of clinical suspicion, chest X-ray shows a distended stomach with air fluid levels and a computerised tomography is useful in assessing the diaphragm and establishing the positions of the various intra-abdominal organs. Also, the risk of an intercostal drainage tube placement and the role of nasogastric tube in avoiding the development of a tension gastrothorax is highlighted.

  7. Large exon size does not limit splicing in vivo.

    Science.gov (United States)

    Chen, I T; Chasin, L A

    1994-03-01

    Exon sizes in vertebrate genes are, with a few exceptions, limited to less than 300 bases. It has been proposed that this limitation may derive from the exon definition model of splice site recognition. In this model, a downstream donor site enhances splicing at the upstream acceptor site of the same exon. This enhancement may require contact between factors bound to each end of the exon; an exon size limitation would promote such contact. To test the idea that proximity was required for exon definition, we inserted random DNA fragments from Escherichia coli into a central exon in a three-exon dihydrofolate reductase minigene and tested whether the expanded exons were efficiently spliced. DNA from a plasmid library of expanded minigenes was used to transfect a CHO cell deletion mutant lacking the dhfr locus. PCR analysis of DNA isolated from the pooled stable cotransfectant populations displayed a range of DNA insert sizes from 50 to 1,500 nucleotides. A parallel analysis of the RNA from this population by reverse transcription followed by PCR showed a similar size distribution. Central exons as large as 1,400 bases could be spliced into mRNA. We also tested individual plasmid clones containing exon inserts of defined sizes. The largest exon included in mRNA was 1,200 bases in length, well above the 300-base limit implied by the survey of naturally occurring exons. We conclude that a limitation in exon size is not part of the exon definition mechanism.

  8. Insights into alternative splicing of sarcomeric genes in the heart

    NARCIS (Netherlands)

    Weeland, Cornelis J.; van den Hoogenhof, Maarten M.; Beqqali, Abdelaziz; Creemers, Esther E.

    2015-01-01

    Driven by rapidly evolving technologies in next-generation sequencing, alternative splicing has emerged as a crucial layer in gene expression, greatly expanding protein diversity and governing complex biological processes in the cardiomyocyte. At the core of cardiac contraction, the physical

  9. Minor class splicing shapes the zebrafish transcriptome during development

    DEFF Research Database (Denmark)

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

    2014-01-01

    known as Taybi-Linder syndrome or microcephalic osteodysplastic primordial dwarfism 1, and a hereditary intestinal polyposis condition, Peutz-Jeghers syndrome. Although a key mechanism for regulating gene expression, the impact of impaired U12-type splicing on the transcriptome is unknown. Here, we...

  10. The Database Management Module of the Splice System.

    Science.gov (United States)

    1983-06-01

    standardization is the only wise chocs . E. FUNCTIONS OF THE EATABASE MkNAGEMENT MODULE As a result of onqoing research in thmc impl1msntaticn of SPLICE, thns...u an e-v Offset by one or mc--l orders of ma#-inuIs inorcvesnnt --L tue execution time cf user transacdrioas. Purthermore, ’is s-toraqe requlrement

  11. A novel CDX2 isoform regulates alternative splicing.

    Directory of Open Access Journals (Sweden)

    Matthew E Witek

    Full Text Available Gene expression is a dynamic and coordinated process coupling transcription with pre-mRNA processing. This regulation enables tissue-specific transcription factors to induce expression of specific transcripts that are subsequently amplified by alternative splicing allowing for increased proteome complexity and functional diversity. The intestine-specific transcription factor CDX2 regulates development and maintenance of the intestinal epithelium by inducing expression of genes characteristic of the mature enterocyte phenotype. Here, sequence analysis of CDX2 mRNA from colonic mucosa-derived tissues revealed an alternatively spliced transcript (CDX2/AS that encodes a protein with a truncated homeodomain and a novel carboxy-terminal domain enriched in serine and arginine residues (RS domain. CDX2 and CDX2/AS exhibited distinct nuclear expression patterns with minimal areas of co-localization. CDX2/AS did not activate the CDX2-dependent promoter of guanylyl cyclase C nor inhibit transcriptional activity of CDX2. Unlike CDX2, CDX2/AS co-localized with the putative splicing factors ASF/SF2 and SC35. CDX2/AS altered splicing patterns of CD44v5 and Tra2-β1 minigenes in Lovo colon cancer cells independent of CDX2 expression. These data demonstrate unique dual functions of the CDX2 gene enabling it to regulate gene expression through both transcription (CDX2 and pre-mRNA processing (CDX2/AS.

  12. Stiff, Strong Splice For A Composite Sandwich Structure

    Science.gov (United States)

    Schmaling, D.

    1991-01-01

    New type of splice for composite sandwich structure reduces peak shear stress in structure. Layers of alternating fiber orientation interposed between thin ears in adhesive joint. Developed for structural joint in spar of helicopter rotor blade, increases precision of control over thickness of adhesive at joint. Joint easy to make, requires no additional pieces, and adds little weight.

  13. Alanine repeats influence protein localization in splicing speckles and paraspeckles.

    Science.gov (United States)

    Chang, Shuo-Hsiu; Chang, Wei-Lun; Lu, Chia-Chen; Tarn, Woan-Yuh

    2014-12-16

    Mammalian splicing regulatory protein RNA-binding motif protein 4 (RBM4) has an alanine repeat-containing C-terminal domain (CAD) that confers both nuclear- and splicing speckle-targeting activities. Alanine-repeat expansion has pathological potential. Here we show that the alanine-repeat tracts influence the subnuclear targeting properties of the RBM4 CAD in cultured human cells. Notably, truncation of the alanine tracts redistributed a portion of RBM4 to paraspeckles. The alanine-deficient CAD was sufficient for paraspeckle targeting. On the other hand, alanine-repeat expansion reduced the mobility of RBM4 and impaired its splicing activity. We further took advantage of the putative coactivator activator (CoAA)-RBM4 conjoined splicing factor, CoAZ, to investigate the function of the CAD in subnuclear targeting. Transiently expressed CoAZ formed discrete nuclear foci that emerged and subsequently separated-fully or partially-from paraspeckles. Alanine-repeat expansion appeared to prevent CoAZ separation from paraspeckles, resulting in their complete colocalization. CoAZ foci were dynamic but, unlike paraspeckles, were resistant to RNase treatment. Our results indicate that the alanine-rich CAD, in conjunction with its conjoined RNA-binding domain(s), differentially influences the subnuclear localization and biogenesis of RBM4 and CoAZ. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. fruitless alternative splicing and sex behaviour in insects

    Indian Academy of Sciences (India)

    In Drosophila melanogaster, male courtship requires proteins encoded by the fruitless (fru) gene that are produced in different sex-specific isoforms via alternative splicing. Drosophila mutant flies with loss-of-function alleles of the fru gene exhibit blocked male courtship behaviour. However, various individual steps in the ...

  15. Managing Tensions And Forging Creative Synergies Between ...

    African Journals Online (AJOL)

    Managing Tensions And Forging Creative Synergies Between Indigenous And Modern Settlement Planning Concepts And Practices: Lessons For The Design And Planning For Sustainable Settlements And Built-Forms In Southern Africa.

  16. Tension perturbations of black brane spacetimes

    International Nuclear Information System (INIS)

    Traschen, Jennie; Fox, Daniel

    2004-01-01

    We consider black brane spacetimes that have at least one spatial translation Killing field that is tangent to the brane. A new parameter, the tension of a spacetime, is defined. The tension parameter is associated with spatial translations in much the same way that the ADM mass is associated with the time translation Killing field. In this work, we explore the implications of the spatial translation symmetry for small perturbations around a background black brane. For static-charged black branes we derive a law which relates the tension perturbation to the surface gravity times the change in the horizon area, plus terms that involve variations in the charges and currents. We find that as a black brane evaporates the tension decreases. We also give a simple derivation of a first law for black brane spacetimes. These constructions hold when the background stress-energy is governed by a Hamiltonian, and the results include arbitrary perturbative stress-energy sources

  17. Notch effects in uniaxial tension specimens

    International Nuclear Information System (INIS)

    Delph, T.J.

    1979-03-01

    Results of a literature survey on the effect of notches on the time-dependent failure of uniaxial tension specimens at elevated temperatures are presented. Particular attention is paid to the failure of notched specimens containing weldments

  18. Tension waves in tethered satellite cables

    Science.gov (United States)

    Lallman, F. J.

    1984-01-01

    A one-degree-of-freedom simulation of the Tethered Satellite System (TSS) was programmed using a distributed system model of the tether based on the one-dimensional wave equation. This model represents the time varying tension profile along the tether as the sum of two traveling waves of tension moving in opposite directions. A control loop was devised which combines a deployment rate command with the measured tension at the deployer to produce a smooth, stable rate of deployment of the subsatellite. Simulation results show a buildup of periodic bursts of high frequency oscillation in tension. This report covers the mathematical modelling and simulation results and explains the reason for the observed oscillations. The design of a possible vibration damping device is discussed.

  19. Tension Hydrothorax Related to Disseminated Endometriosis

    Directory of Open Access Journals (Sweden)

    AnnaKate Deal, MD

    2016-01-01

    Full Text Available We present the case of a 34-year-old woman presenting to the emergency department (ED with dyspnea, cough, and fever. She was found to have a tension hydrothorax and was treated with ultrasound-guided thoracentesis in the ED. Subsequent inpatient evaluation showed the patient had disseminated endometriosis. Tension hydrothorax has not been previously described in the literature as a complication of this disease.

  20. Effects of secondary structure on pre-mRNA splicing: hairpins sequestering the 5' but not the 3' splice site inhibit intron processing in Nicotiana plumbaginifolia.

    Science.gov (United States)

    Liu, H X; Goodall, G J; Kole, R; Filipowicz, W

    1995-01-16

    We have performed a systematic study of the effect of artificial hairpins on pre-mRNA splicing in protoplasts of a dicot plant, Nicotiana plumbaginifolia. Hairpins with a potential to form 18 or 24 bp stems strongly inhibit splicing when they sequester the 5' splice site or are placed in the middle of short introns. However, similar 24 bp hairpins sequestering the 3' splice site do not prevent this site from being used as an acceptor. Utilization of the stem-located 3' site requires that the base of the stem is separated from the upstream 5' splice site by a minimum of approximately 45 nucleotides and that another 'helper' 3' splice site is present downstream of the stem. The results indicate that the spliceosome or factors associated with it may have a potential to unfold secondary structure present in the downstream portion of the intron, prior to or at the step of the 3' splice site selection. The finding that the helper 3' site is required for utilization of the stem-located acceptor confirms and extends previous observations, obtained with HeLa cell in vitro splicing systems, indicating that the 3' splice site may be recognized at least twice during spliceosome assembly.

  1. Chinmo prevents transformer alternative splicing to maintain male sex identity.

    Directory of Open Access Journals (Sweden)

    Lydia Grmai

    2018-02-01

    Full Text Available Reproduction in sexually dimorphic animals relies on successful gamete production, executed by the germline and aided by somatic support cells. Somatic sex identity in Drosophila is instructed by sex-specific isoforms of the DMRT1 ortholog Doublesex (Dsx. Female-specific expression of Sex-lethal (Sxl causes alternative splicing of transformer (tra to the female isoform traF. In turn, TraF alternatively splices dsx to the female isoform dsxF. Loss of the transcriptional repressor Chinmo in male somatic stem cells (CySCs of the testis causes them to "feminize", resembling female somatic stem cells in the ovary. This somatic sex transformation causes a collapse of germline differentiation and male infertility. We demonstrate this feminization occurs by transcriptional and post-transcriptional regulation of traF. We find that chinmo-deficient CySCs upregulate tra mRNA as well as transcripts encoding tra-splice factors Virilizer (Vir and Female lethal (2d (Fl(2d. traF splicing in chinmo-deficient CySCs leads to the production of DsxF at the expense of the male isoform DsxM, and both TraF and DsxF are required for CySC sex transformation. Surprisingly, CySC feminization upon loss of chinmo does not require Sxl but does require Vir and Fl(2d. Consistent with this, we show that both Vir and Fl(2d are required for tra alternative splicing in the female somatic gonad. Our work reveals the need for transcriptional regulation of tra in adult male stem cells and highlights a previously unobserved Sxl-independent mechanism of traF production in vivo. In sum, transcriptional control of the sex determination hierarchy by Chinmo is critical for sex maintenance in sexually dimorphic tissues and is vital in the preservation of fertility.

  2. A Comprehensive Analysis of Alternative Splicing in Paleopolyploid Maize

    Directory of Open Access Journals (Sweden)

    Wenbin Mei

    2017-05-01

    Full Text Available Identifying and characterizing alternative splicing (AS enables our understanding of the biological role of transcript isoform diversity. This study describes the use of publicly available RNA-Seq data to identify and characterize the global diversity of AS isoforms in maize using the inbred lines B73 and Mo17, and a related species, sorghum. Identification and characterization of AS within maize tissues revealed that genes expressed in seed exhibit the largest differential AS relative to other tissues examined. Additionally, differences in AS between the two genotypes B73 and Mo17 are greatest within genes expressed in seed. We demonstrate that changes in the level of alternatively spliced transcripts (intron retention and exon skipping do not solely reflect differences in total transcript abundance, and we present evidence that intron retention may act to fine-tune gene expression across seed development stages. Furthermore, we have identified temperature sensitive AS in maize and demonstrate that drought-induced changes in AS involve distinct sets of genes in reproductive and vegetative tissues. Examining our identified AS isoforms within B73 × Mo17 recombinant inbred lines (RILs identified splicing QTL (sQTL. The 43.3% of cis-sQTL regulated junctions are actually identified as alternatively spliced junctions in our analysis, while 10 Mb windows on each side of 48.2% of trans-sQTLs overlap with splicing related genes. Using sorghum as an out-group enabled direct examination of loss or conservation of AS between homeologous genes representing the two subgenomes of maize. We identify several instances where AS isoforms that are conserved between one maize homeolog and its sorghum ortholog are absent from the second maize homeolog, suggesting that these AS isoforms may have been lost after the maize whole genome duplication event. This comprehensive analysis provides new insights into the complexity of AS in maize.

  3. Chinmo prevents transformer alternative splicing to maintain male sex identity.

    Science.gov (United States)

    Grmai, Lydia; Hudry, Bruno; Miguel-Aliaga, Irene; Bach, Erika A

    2018-02-01

    Reproduction in sexually dimorphic animals relies on successful gamete production, executed by the germline and aided by somatic support cells. Somatic sex identity in Drosophila is instructed by sex-specific isoforms of the DMRT1 ortholog Doublesex (Dsx). Female-specific expression of Sex-lethal (Sxl) causes alternative splicing of transformer (tra) to the female isoform traF. In turn, TraF alternatively splices dsx to the female isoform dsxF. Loss of the transcriptional repressor Chinmo in male somatic stem cells (CySCs) of the testis causes them to "feminize", resembling female somatic stem cells in the ovary. This somatic sex transformation causes a collapse of germline differentiation and male infertility. We demonstrate this feminization occurs by transcriptional and post-transcriptional regulation of traF. We find that chinmo-deficient CySCs upregulate tra mRNA as well as transcripts encoding tra-splice factors Virilizer (Vir) and Female lethal (2)d (Fl(2)d). traF splicing in chinmo-deficient CySCs leads to the production of DsxF at the expense of the male isoform DsxM, and both TraF and DsxF are required for CySC sex transformation. Surprisingly, CySC feminization upon loss of chinmo does not require Sxl but does require Vir and Fl(2)d. Consistent with this, we show that both Vir and Fl(2)d are required for tra alternative splicing in the female somatic gonad. Our work reveals the need for transcriptional regulation of tra in adult male stem cells and highlights a previously unobserved Sxl-independent mechanism of traF production in vivo. In sum, transcriptional control of the sex determination hierarchy by Chinmo is critical for sex maintenance in sexually dimorphic tissues and is vital in the preservation of fertility.

  4. 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.

  5. Characterization of a novel splicing variant in the RAPTOR gene

    International Nuclear Information System (INIS)

    Sun Chang; Southard, Catherine; Di Rienzo, Anna

    2009-01-01

    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, RAPTOR v 2, 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 RAPTOR v 2 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

  6. Density and surface tension of ionic liquids.

    Science.gov (United States)

    Kolbeck, C; Lehmann, J; Lovelock, K R J; Cremer, T; Paape, N; Wasserscheid, P; Fröba, A P; Maier, F; Steinrück, H-P

    2010-12-30

    We measured the density and surface tension of 9 bis[(trifluoromethyl)sulfonyl]imide ([Tf(2)N](-))-based and 12 1-methyl-3-octylimidazolium ([C(8)C(1)Im](+))-based ionic liquids (ILs) with the vibrating tube and the pendant drop method, respectively. This comprehensive set of ILs was chosen to probe the influence of the cations and anions on density and surface tension. When the alkyl chain length in the [C(n)C(1)Im][Tf(2)N] series (n = 1, 2, 4, 6, 8, 10, 12) is increased, a decrease in density is observed. The surface tension initially also decreases but reaches a plateau for alkyl chain lengths greater than n = 8. Functionalizing the alkyl chains with ethylene glycol groups results in a higher density as well as a higher surface tension. For the dependence of density and surface tension on the chemical nature of the anion, relations are only found for subgroups of the studied ILs. Density and surface tension values are discussed with respect to intermolecular interactions and surface composition as determined by angle-resolved X-ray photoelectron spectroscopy (ARXPS). The absence of nonvolatile surface-active contaminants was proven by ARXPS.

  7. Oxygen tension level and human viral infections

    Energy Technology Data Exchange (ETDEWEB)

    Morinet, Frédéric, E-mail: frederic.morinet@sls.aphp.fr [Centre des Innovations Thérapeutiques en Oncologie et Hématologie (CITOH), CHU Saint-Louis, Paris (France); Université Denis Diderot, Sorbonne Paris Cité Paris, Paris (France); Casetti, Luana [Institut Cochin INSERM U1016, Paris (France); François, Jean-Hugues; Capron, Claude [Institut Cochin INSERM U1016, Paris (France); Laboratoire d' Hématologie, Hôpital Ambroise Paré, Boulogne (France); Université de Versailles Saint-Quentin en Yvelynes, Versailles (France); Pillet, Sylvie [Laboratoire de Bactériologie-Virologie-Hygiène, CHU de Saint-Etienne, Saint-Etienne (France); Université de Lyon et Université de Saint-Etienne, Jean Monnet, GIMAP EA3064, F-42023 Saint-Etienne, Lyon (France)

    2013-09-15

    The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition. - Highlights: • Oxygen tension level regulates viral replication in vitro and possibly in vivo. • Hypoxia-inducible factor 1 (HIF-1α) is the principal factor involved in Oxygen tension level. • HIF-1α upregulates gene expression for example of HIV, JC and Kaposi sarcoma viruses. • In addition to classical chemotherapy inhibition of HIF-1α may constitute a new track to treat human viral infections.

  8. Flexural behavior of concrete beam with mechanical splices of reinforcement subjected to cyclic loading

    International Nuclear Information System (INIS)

    Nab, H. S.; Kim, W. B.

    2008-01-01

    In nuclear power plant structures, the mechanical rebar splices are designated and constructed on the basis of ACI and ASME code. Regardless of good performance on mechanical rebar splices, these splicing methods that did not be registered on ASME code have not restricted to apply to construction site. In this study, the main candidate splice is cold roll formed parallel threaded splice. This was registered newly in ASME Section III division 2 CC 4333 'Mechanical Splices' in 2004. To compare the traditional rebar splice with mechanical rebar splices, concrete beams were made to evaluate the ductility of spliced reinforcing bars. Based on Experimental results, it was identified that the mechanical rebar splices by parallel threaded coupler had better accumulated dissipation energy capacity to resist seismic behavior than the traditional lapping splices. It showed that concrete specimens with D36 reinforcing bar coupler are 1.8 times better performance and that concrete specimens with D22 reinforcing bar coupler are 2.8 times better performance. (authors)

  9. Toward a general psychological model of tension and suspense.

    Science.gov (United States)

    Lehne, Moritz; Koelsch, Stefan

    2015-01-01

    Tension and suspense are powerful emotional experiences that occur in a wide variety of contexts (e.g., in music, film, literature, and everyday life). The omnipresence of tension and suspense suggests that they build on very basic cognitive and affective mechanisms. However, the psychological underpinnings of tension experiences remain largely unexplained, and tension and suspense are rarely discussed from a general, domain-independent perspective. In this paper, we argue that tension experiences in different contexts (e.g., musical tension or suspense in a movie) build on the same underlying psychological processes. We discuss key components of tension experiences and propose a domain-independent model of tension and suspense. According to this model, tension experiences originate from states of conflict, instability, dissonance, or uncertainty that trigger predictive processes directed at future events of emotional significance. We also discuss possible neural mechanisms underlying tension and suspense. The model provides a theoretical framework that can inform future empirical research on tension phenomena.

  10. Mammalian tissues defective in nonsense-mediated mRNA decay display highly aberrant splicing patterns

    DEFF Research Database (Denmark)

    Weischenfeldt, Joachim Lütken; Waage, Johannes Eichler; Tian, Geng

    2012-01-01

    ABSTRACT: BACKGROUND: Nonsense-mediated mRNA decay (NMD) affects the outcome of alternative splicing by degrading mRNA isoforms with premature termination codons. Splicing regulators constitute important NMD targets; however, the extent to which loss of NMD causes extensive deregulation...... of alternative splicing has not previously been assayed in a global, unbiased manner. Here, we combine mouse genetics and RNA-seq to provide the first in vivo analysis of the global impact of NMD on splicing patterns in two primary mouse tissues ablated for the NMD factor UPF2. RESULTS: We developed...... importance, the latter events are associated with high intronic conservation. CONCLUSIONS: Our data demonstrate that NMD regulates alternative splicing outcomes through an intricate web of splicing regulators and that its loss leads to the deregulation of a panoply of splicing events, providing novel...

  11. Muscle-Specific Mis-Splicing and Heart Disease Exemplified by RBM20.

    Science.gov (United States)

    Rexiati, Maimaiti; Sun, Mingming; Guo, Wei

    2018-01-05

    Alternative splicing is an essential post-transcriptional process to generate multiple functional RNAs or proteins from a single transcript. Progress in RNA biology has led to a better understanding of muscle-specific RNA splicing in heart disease. The recent discovery of the muscle-specific splicing factor RNA-binding motif 20 (RBM20) not only provided great insights into the general alternative splicing mechanism but also demonstrated molecular mechanism of how this splicing factor is associated with dilated cardiomyopathy. Here, we review our current knowledge of muscle-specific splicing factors and heart disease, with an emphasis on RBM20 and its targets, RBM20-dependent alternative splicing mechanism, RBM20 disease origin in induced Pluripotent Stem Cells (iPSCs), and RBM20 mutations in dilated cardiomyopathy. In the end, we will discuss the multifunctional role of RBM20 and manipulation of RBM20 as a potential therapeutic target for heart disease.

  12. PathwaySplice: An R package for unbiased pathway analysis of alternative splicing in RNA-Seq data.

    Science.gov (United States)

    Yan, Aimin; Ban, Yuguang; Gao, Zhen; Chen, Xi; Wang, Lily

    2018-04-24

    Pathway analysis of alternative splicing would be biased without accounting for the different number of exons or junctions associated with each gene, because genes with higher number of exons or junctions are more likely to be included in the "significant" gene list in alternative splicing. We present PathwaySplice, an R package that (1) Performs pathway analysis that explicitly adjusts for the number of exons or junctions associated with each gene; (2) Visualizes selection bias due to different number of exons or junctions for each gene and formally tests for presence of bias using logistic regression; (3) Supports gene sets based on the Gene Ontology terms, as well as more broadly defined gene sets (e.g. MSigDB) or user defined gene sets; (4) Identifies the significant genes driving pathway significance and (5) Organizes significant pathways with an enrichment map, where pathways with large number of overlapping genes are grouped together in a network graph. https://bioconductor.org/packages/release/bioc/html/PathwaySplice.html. lily.wangg@gmail.com, xi.steven.chen@gmail.com.

  13. 机械设计中联接件的自动选用%Autoselection of the Connector in Mechanical Design

    Institute of Scientific and Technical Information of China (English)

    徐静; 翁慧燕; 董雁

    2001-01-01

    介绍机械静联接在机械设计中的选用方法。建立了联接件的国标数据库及其查询、维护程序;编制了对所选联接件的计算校核程序;并开发了自动绘制联接件的软件,从而实现了机械CAD中联接件自动选用、校核、绘图的集成。%This paper deals with the selection of connector in mechanical design. Database of connector and its corresponding function for indexing, safekeeping and proof calculating are built up. Software for the drawing of connector on the environment of AutoCAD is also developed. So automatics selection, proof calculating and drawing of connector are achieved in mechanical computer aided design.

  14. The SiBI connector: a new medical device to facilitate preoxygenation and reduce waste anesthetic gases during inhaled induction with sevoflurane.

    Science.gov (United States)

    Colas, M J; Tétrault, J P; Dumais, L; Truong, P; Claprood, Y; Martin, R

    2000-12-01

    The SiBI connector is a new medical device used for vital capacity inhaled induction with sevoflurane. It allows efficient preoxygenation of patients and reduces waste anesthetic gases in the operation room during induction.

  15. Development of 30-pin connectors for electronic modules of C and I systems for NPP's confirming to customized MIL STD-1344 requirements

    International Nuclear Information System (INIS)

    Marathe, P.P.; Madala, Kalyan C.; Ramakrishna, P.

    2014-01-01

    The electrical connectors form an important constituent of C and I system where customized circuits and hardware is required to be configured meeting the Nuclear Power Plant regulatory requirements. C and I hardware has to handle multiple hundreds of I/O's and the system architectures are made in modular construction having C and I system hardware packaged in plug-in electronic modules in the required form factors. In addition if the system has to satisfy customized JSS 55555 requirements meeting stringent shock, vibration and environmental specifications, the connectors used for the electronic modules shall meet the customized MIL STD-1344 requirements and meet reliability target for the system. 30-pin type special connectors for electronic modules and 2x30 (60) pin field cabling connectors were developed meeting the required qualification specifications. (author)

  16. DEVELOPMENT OF REMOTE HANFORD CONNECTOR GASKET REPLACEMENT TOOLING FOR THE SAVANNAH RIVER SITE'S DEFENSE WASTE PROCESSING FACILITY

    International Nuclear Information System (INIS)

    Krementz, D

    2007-01-01

    The Savannah River Site's (SRS) Defense Waste Processing Facility (DWPF) requested development of tooling for remote replacement of gaskets in mechanical Hanford connectors. The facility has compressed air supply, two master-slave manipulators (MSM's) and a lightweight robotic arm for operation of the remote tools. The Savannah River National Laboratory (SRNL) developed and tested multiple tools to perform the gasket replacement tasks. Separate pneumatic snap-ring removal tools that use the connector skirt as a reaction surface were developed for removal of the snap ring and spent gasket on both vertical and horizontal Hanford connectors. A pneumatic tool that clamps and centers on the jumper pipe ID was developed to simultaneously install the new gasket and snap ring. A pneumatic snap-ring-loading tool was developed that compresses the snap ring and places it in a groove in the installation tool. All of the tools are located on a custom work table with a pneumatic valve station that directs compressed air to the desired tool and vents the tools as needed. The entire system has been successfully tested using MSM's to manipulate the various tools. Deployment of the entire system is expected during FY08. The Hanford connector gasket replacement tooling has been successfully tested using MSM's to manipulate the various tools. Nitric acid is used in many of the decontamination processes performed in the REDC, where the tooling will be deployed. Although most of the tool components were fabricated/purchased with nitric acid and radioactive service in mind, some of the prototype parts must be replaced with parts that are more compatible with nitric acid/radioactive service. Several modifications to the various tools are needed to facilitate maintenance and replacement of failed components. Development of installation tools for replacement of 1-inch, 2-inch and multi-hole gaskets is being considered. Deployment of the existing system in the DWPF REDC is expected during FY

  17. 1 GSPS digitizer based on the FPGA Mezzanine Card (FMC) standard with low-count pin connector.

    CERN Document Server

    Vasilyev, Mikhail

    2015-01-01

    Under the scope of a CERN summer student project, the schematic for ADC based on FMC mezzanine card with 1 GSPS sampling rate and 8 bit resolution was developed. The mezzanine is fully compatible with the standard: FPGA Mezzanine Card (FMC) [1]. A low-pin count connector was used to connect the mezzanine with the “carrier”. The carrier was an Open Hardware project: Simple PCIe FMC carrier (SPEC).

  18. Mould insert fabrication of a single-mode fibre connector alignment structure optimized by justified partial metallization

    International Nuclear Information System (INIS)

    Wissmann, Markus; Barié, Nicole; Guttmann, Markus; Schneider, Marc; Kolew, Alexander; Besser, Heino; Pfleging, Wilhelm; Hofmann, Andreas; Van Erps, Jürgen; Beri, Stefano; Watté, Jan

    2015-01-01

    For mass production of multiscale-optical components, microstructured moulding tools are needed. Metal tools are used for hot embossing or injection moulding of microcomponents made of a thermoplastic polymer. Microstructures with extremely tight specifications, e.g. low side wall roughness and high aspect ratios are generally made by lithographic procedures such as x-ray lithography or deep proton writing. However, these processes are unsuitable for low-cost mass production. An alternative manufacturing method of moulding tools has been developed at the Karlsruhe Institute of Technology (KIT). This article describes a mould insert fabrication and a new replication process for self-centring fibre alignment structures for low loss field installable single-mode fibre connectors, developed and fabricated by the Vrije Universiteit Brussel (VUB) in collaboration with TE Connectivity. These components are to be used in fibre-to-the-home networks and support the deployment and maintenance of fibre optic links. The special feature of this particular fibre connector is a self-centring fibre alignment, achieved by means of a through hole with deflectable cantilevers acting as micro-springs. The particular challenge is the electroforming of through holes with a centre hole diameter smaller than 125 µm. The fibre connector structure is prototyped by deep proton writing in polymethylmethacrylate and used as a sacrificial part. Using joining, physical vapour deposition and electroforming technology, a negative copy of the prototyped connector is transferred into nickel to be used as a moulding tool. The benefits of this replication technique are a rapid and economical fabrication of moulding tools with high-precision microstructures and a long tool life. With these moulding tools low-cost mass production is possible. We present the manufacturing chain we have established. Each individual manufacturing step of the mould insert fabrication will be shown in this report. The

  19. Phosphoproteomics reveals that glycogen synthase kinase-3 phosphorylates multiple splicing factors and is associated with alternative splicing

    Science.gov (United States)

    Shinde, Mansi Y.; Sidoli, Simone; Kulej, Katarzyna; Mallory, Michael J.; Radens, Caleb M.; Reicherter, Amanda L.; Myers, Rebecca L.; Barash, Yoseph; Lynch, Kristen W.; Garcia, Benjamin A.; Klein, Peter S.

    2017-01-01

    Glycogen synthase kinase-3 (GSK-3) is a constitutively active, ubiquitously expressed protein kinase that regulates multiple signaling pathways. In vitro kinase assays and genetic and pharmacological manipulations of GSK-3 have identified more than 100 putative GSK-3 substrates in diverse cell types. Many more have been predicted on the basis of a recurrent GSK-3 consensus motif ((pS/pT)XXX(S/T)), but this prediction has not been tested by analyzing the GSK-3 phosphoproteome. Using stable isotope labeling of amino acids in culture (SILAC) and MS techniques to analyze the repertoire of GSK-3–dependent phosphorylation in mouse embryonic stem cells (ESCs), we found that ∼2.4% of (pS/pT)XXX(S/T) sites are phosphorylated in a GSK-3–dependent manner. A comparison of WT and Gsk3a;Gsk3b knock-out (Gsk3 DKO) ESCs revealed prominent GSK-3–dependent phosphorylation of multiple splicing factors and regulators of RNA biosynthesis as well as proteins that regulate transcription, translation, and cell division. Gsk3 DKO reduced phosphorylation of the splicing factors RBM8A, SRSF9, and PSF as well as the nucleolar proteins NPM1 and PHF6, and recombinant GSK-3β phosphorylated these proteins in vitro. RNA-Seq of WT and Gsk3 DKO ESCs identified ∼190 genes that are alternatively spliced in a GSK-3–dependent manner, supporting a broad role for GSK-3 in regulating alternative splicing. The MS data also identified posttranscriptional regulation of protein abundance by GSK-3, with ∼47 proteins (1.4%) whose levels increased and ∼78 (2.4%) whose levels decreased in the absence of GSK-3. This study provides the first unbiased analysis of the GSK-3 phosphoproteome and strong evidence that GSK-3 broadly regulates alternative splicing. PMID:28916722

  20. A prospective clinical trial to assess peripheral venous catheter-related phlebitis using needleless connectors in a surgery department.

    Science.gov (United States)

    Ronen, Ohad; Shlomo, Fanny; Ben-Adiva, Gila; Edri, Zehava; Shema-Didi, Lilach

    2017-10-01

    The use of intravascular catheters is often complicated by phlebitis, which is associated with increased morbidity and extended duration of hospitalization. We conducted a study to investigate the impact of needleless intravenous access devices on the rate of phlebitis in peripheral venous catheters (PVCs). We prospectively recruited patients in 2 phases. The first group was treated with a regular cap, and the second group was treated with a needleless connector. The incidence of catheter-related phlebitis (CRP) was recorded as the primary end point. A total of 620 PVCs using regular caps were inserted into 340 patients and CRP rates were recorded. In the second phase of the study, 169 PVCs using needleless connectors were inserted into 135 patients. In the group treated with the regular cap, the CRP rate was 60% compared with 7% in the group treated with the needleless cap (P phlebitis had a statistically significant longer mean hospitalization period (P <.001), as were patients in the regular cap group (P <.01). The use of needleless connectors was found to be associated with a significant reduction of CRP in peripheral veins in a surgery department setting. The decreased morbidity resulted in a lower number of catheter replacements and duration of hospitalization. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  1. Failure Analysis of a Nickel-Plated Electronic Connector Due to Salt-Induced Corrosion (ENGE 2014).

    Science.gov (United States)

    Lee, Na-Ri; Choi, Hyoung-Seuk; Choi, Duck-Kyun

    2015-10-01

    When electronic connectors in mobile devices are miniaturized, the thickness of plating decreases. However, this thin plating is expected to decrease the life of the connector due to problems with corrosion. In this study, salt spray aging tests were performed on miniaturized nickel-plated stainless steel electronic connectors to observe failure mechanisms in realistic environments. The tests were performed three times using a 5% NaCl solution in an atmosphere of 45 °C; each test included several cycles where one cycle was one 24-h period consisting of 8 h of salt spray and 16 h without salt spray. The nickel-plating layers were periodically observed by electron probe X-ray micro-analyzer, wavelength dispersive spectroscopy, and field-emission scanning electron microscopy to analyze and identify the corrosion mechanism. We found that the primary failure mode of the nickel plating is blistering and delamination. The corrosion mechanism is typically a chain reaction of several corrosion mechanisms: pitting corrosion --> stress corrosion cracking --> hydrogen-induced cracking --> blistering and delamination. Finally, we discuss countermeasures to prevent corrosion of the nickel layer based on the corrosion mechanisms identified in this study.

  2. A novel approach to pipeline tensioner modeling

    Energy Technology Data Exchange (ETDEWEB)

    O' Grady, Robert; Ilie, Daniel; Lane, Michael [MCS Software Division, Galway (Ireland)

    2009-07-01

    As subsea pipeline developments continue to move into deep and ultra-deep water locations, there is an increasing need for the accurate prediction of expected pipeline fatigue life. A significant factor that must be considered as part of this process is the fatigue damage sustained by the pipeline during installation. The magnitude of this installation-related damage is governed by a number of different agents, one of which is the dynamic behavior of the tensioner systems during pipe-laying operations. There are a variety of traditional finite element methods for representing dynamic tensioner behavior. These existing methods, while basic in nature, have been proven to provide adequate forecasts in terms of the dynamic variation in typical installation parameters such as top tension and sagbend/overbend strain. However due to the simplicity of these current approaches, some of them tend to over-estimate the frequency of tensioner pay out/in under dynamic loading. This excessive level of pay out/in motion results in the prediction of additional stress cycles at certain roller beds, which in turn leads to the prediction of unrealistic fatigue damage to the pipeline. This unwarranted fatigue damage then equates to an over-conservative value for the accumulated damage experienced by a pipeline weld during installation, and so leads to a reduction in the estimated fatigue life for the pipeline. This paper describes a novel approach to tensioner modeling which allows for greater control over the velocity of dynamic tensioner pay out/in and so provides a more accurate estimation of fatigue damage experienced by the pipeline during installation. The paper reports on a case study, as outlined in the proceeding section, in which a comparison is made between results from this new tensioner model and from a more conventional approach. The comparison considers typical installation parameters as well as an in-depth look at the predicted fatigue damage for the two methods

  3. Emergency percutaneous needle decompression for tension pneumoperitoneum

    Directory of Open Access Journals (Sweden)

    Körner Markus

    2011-05-01

    Full Text Available Abstract Background Tension pneumoperitoneum as a complication of iatrogenic bowel perforation during endoscopy is a dramatic condition in which intraperitoneal air under pressure causes hemodynamic and ventilatory compromise. Like tension pneumothorax, urgent intervention is required. Immediate surgical decompression though is not always possible due to the limitations of the preclinical management and sometimes to capacity constraints of medical staff and equipment in the clinic. Methods This is a retrospective analysis of cases of pneumoperitoneum and tension pneumoperitoneum due to iatrogenic bowel perforation. All patients admitted to our surgical department between January 2005 and October 2010 were included. Tension pneumoperitoneum was diagnosed in those patients presenting signs of hemodynamic and ventilatory compromise in addition to abdominal distension. Results Between January 2005 and October 2010 eleven patients with iatrogenic bowel perforation were admitted to our surgical department. The mean time between perforation and admission was 36 ± 14 hrs (range 30 min - 130 hrs, between ER admission and begin of the operation 3 hrs and 15 min ± 47 min (range 60 min - 9 hrs. Three out of eleven patients had clinical signs of tension pneumoperitoneum. In those patients emergency percutaneous needle decompression was performed with a 16G venous catheter. This improved significantly the patients' condition (stabilization of vital signs, reducing jugular vein congestion, bridging the time to the start of the operation. Conclusions Hemodynamical and respiratory compromise in addition to abdominal distension shortly after endoscopy are strongly suggestive of tension pneumoperitoneum due to iatrogenic bowel perforation. This is a rare but life threatening condition and it can be managed in a preclinical and clinical setting with emergency percutaneous needle decompression like tension pneumothorax. Emergency percutaneous decompression is no

  4. Carrier behavior in special multilayer device composed of different transition metal oxide-based intermediate connectors

    International Nuclear Information System (INIS)

    Deng, Yan-Hong; Chen, Xiang-Yu; Ou, Qing-Dong; Wang, Qian-Kun; Jiang, Xiao-Cheng; Zhang, Dan-Dan; Li, Yan-Qing

    2014-01-01

    The impact of illumination on the connection part of the tandem organic light-emitting diodes was studied by using a special organic multilayer sample consisted of two organic active layers coupled with different transition metal oxide (TMO)-based intermediate connectors (ICs). Through measuring the current density-voltage characteristic, interfacial electronic structures, and capacitance-voltage characteristic, we observe an unsymmetrical phenomenon in current density-voltage and capacitance-voltage curves of Mg:Alq 3 /MoO 3 and MoO 3 composed devices, which was induced by the charge spouting zone near the ICs region and the recombination state in the MoO 3 layer. Moreover, Mg:Alq 3 /MoO 3 composed device displays a photovoltaic effect and the V oc shifts to forward bias under illumination. Our results demonstrate that the TMO-based IC structure coupled with photovoltaic effect can be a good approach for the study of photodetector, light sensor, and so on.

  5. Use of monolingual and comparable corpora in the classroom to translate adverbial connectors

    Directory of Open Access Journals (Sweden)

    Beatriz Sánchez Cárdenas

    2016-06-01

    Full Text Available Research in terminology has traditionally focused on nouns. Considerably less attention has been paid to other grammatical categories such as adverbs. However, these words can also be problematic for the novice translator, who tends to use the translation correspondences in bilingual dictionaries without realizing that formal equivalence is not necessarily the same as textual equivalence. However, semantic values, acquired in context, go far beyond dictionary meaning and are related to phenomena such as semantic prosody and preferences of lexical selection that can vary, depending on text type and specialized domain. This research explored the reasons why certain adverbial discourse connectors, apparently easy to translate, are a source of translation problems that cannot be easily resolved with a bilingual dictionary. Moreover, this study analyzed the use of parallel corpora in the translation classroom and how it can increase the quality of text production. For this purpose, we compared student translations before and after receiving training on the use of corpus analysis tools

  6. Optimization of traceable coaxial RF reflection standards with 7-mm-N-connector using genetic algorithms

    Directory of Open Access Journals (Sweden)

    T. Schrader

    2003-01-01

    Full Text Available A new coaxial device with 7-mm-N-connector was developed providing calculable complex reflection coefficients for traceable calibration of vector network analyzers (VNA. It was specifically designed to fill the gap between 0 Hz (DC, direct current and 250MHz, though the device was tested up to 10GHz. The frequency dependent reflection coefficient of this device can be described by a model, which is characterized by traceable measurements. It is therefore regarded as a “traceable model". The new idea of using such models for traceability has been verified, found to be valid and was used for these investigations. The DC resistance value was extracted from RF measurements up to 10 GHz by means of Genetic Algorithms (GA. The GA was used to obtain the elements of the model describing the reflection coefficient Γ of a network of SMD resistors. The DC values determined with the GA from RF measurements match the traceable value at DC within 3·10-3, which is in good agreement with measurements using reference air lines at GHz frequencies.

  7. Expression of TGF-β in Fractures Fixed by Nitinol Swan-like Memory Compressive Connectors

    Science.gov (United States)

    Li, M.; Zhang, C. C.; Xu, S. G.; Fu, Q. G.

    2011-07-01

    In this article, the effect of internal fixation of a Nitinol swan-like memory compressive connector (SMC) on the temporal expression of transforming growth factor-β (TGF-β) at fracture sites is evaluated. Specimens were collected from 35 New Zealand rabbits modeled for bilateral humeral fracture fixed with either SMC or stainless dynamic compression plate (DCP). Five rabbits each were killed at day 1, 3, 7, 14, 21, 28, and 56. The local positive staining potency, positive area ratio, and positive index of TGF-β were measured using an immunohistochemistry approach (EnVision) in combination with a computerized image analysis system. TGF-β staining was seen in mesenchymal cells, osteoblasts, chondrocytes, and in the extracellular matrix of fractures fixed in both the SMC and the DCP samples without a significant difference in staining at both the early stages (days 1 and 3) and day 56. A higher TGF-β content was observed in the fractures fixed with SMC when compared to that of DCP from day 7 to 28. As a conclusion, TGF-β is highly expressed in fractures fixed with SMC during chondrogenesis stage and entochondrostosis stage. Finally, the mechanism of how SMC promoting synthesis and secretion of TGF-β in the process of fracture healing has been discussed.

  8. Experimental investigation on the electrical contact behavior of rolling contact connector

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Junxing; Yang, Fei, E-mail: yfei2007@mail.xjtu.edu.cn; Luo, Kaiyu; Zhu, Mingliang; Wu, Yi; Rong, Mingzhe [State Key Laboratory of Electrical Insulation and Power Equipment, Xi’an Jiaotong University, Xi’an 710049 (China)

    2015-12-15

    Rolling contact connector (RCC) is a new technology utilized in high performance electric power transfer systems with one or more rotating interfaces, such as radars, satellites, wind generators, and medical computed tomography machines. Rolling contact components are used in the RCC instead of traditional sliding contacts to transfer electrical power and/or signal. Since the requirement of the power transmission is increasing in these years, the rolling electrical contact characteristics become more and more important for the long-life design of RCC. In this paper, a typical form of RCC is presented. A series of experimental work are carried out to investigate the rolling electrical contact characteristics during its lifetime. The influence of a variety of factors on the electrical contact degradation behavior of RCC is analyzed under both vacuum and air environment. Based on the surface morphology and elemental composition changes in the contact zone, which are assessed by field emission scanning electron microscope and confocal laser scanning microscope, the mechanism of rolling electrical contact degradation is discussed.

  9. Surface tension in soap films: revisiting a classic demonstration

    International Nuclear Information System (INIS)

    Behroozi, F

    2010-01-01

    We revisit a classic demonstration for surface tension in soap films and introduce a more striking variation of it. The demonstration shows how the film, pulling uniformly and normally on a loose string, transforms it into a circular arc under tension. The relationship between the surface tension and the string tension is analysed and presented in a useful graphical form. (letters and comments)

  10. Surface tension in soap films: revisiting a classic demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Behroozi, F [Department of Physics, University of Northern Iowa, Cedar Falls, IA 50614 (United States)], E-mail: behroozi@uni.edu

    2010-01-15

    We revisit a classic demonstration for surface tension in soap films and introduce a more striking variation of it. The demonstration shows how the film, pulling uniformly and normally on a loose string, transforms it into a circular arc under tension. The relationship between the surface tension and the string tension is analysed and presented in a useful graphical form. (letters and comments)

  11. Mentoring Preservice Teachers: Identifying Tensions and Possible Resolutions

    Science.gov (United States)

    Hudson, Peter; Hudson, Sue

    2018-01-01

    Tensions can occur in the mentor-mentee relationship during school-based professional experiences that require problem solving. What are the tensions for mentor teachers in preservice teacher education and how might these tensions be resolved? This qualitative study collected data from 31 high school mentor teachers about tensions experienced with…

  12. Exploratory experimental investigations on post-tensioned structural glass beams

    DEFF Research Database (Denmark)

    Louter, C.; Nielsen, Jens Henrik; Belis, J.

    2013-01-01

    This paper discusses two projects on post-tensioned glass beams, performed at EPFL and DTU, respectively. In these projects small scale glass beams (length of 1.5m and 1m) are post-tensioned by means of steel threaded rods tensioned at the beam ends. The purpose of post-tensioning glass beams...

  13. Interplay between estrogen receptor and AKT in estradiol-induced alternative splicing.

    Science.gov (United States)

    Bhat-Nakshatri, Poornima; Song, Eun-Kyung; Collins, Nikail R; Uversky, Vladimir N; Dunker, A Keith; O'Malley, Bert W; Geistlinger, Tim R; Carroll, Jason S; Brown, Myles; Nakshatri, Harikrishna

    2013-06-11

    Alternative splicing is critical for generating complex proteomes in response to extracellular signals. Nuclear receptors including estrogen receptor alpha (ERα) and their ligands promote alternative splicing. The endogenous targets of ERα:estradiol (E2)-mediated alternative splicing and the influence of extracellular kinases that phosphorylate ERα on E2-induced splicing are unknown. MCF-7 and its anti-estrogen derivatives were used for the majority of the assays. CD44 mini gene was used to measure the effect of E2 and AKT on alternative splicing. ExonHit array analysis was performed to identify E2 and AKT-regulated endogenous alternatively spliced apoptosis-related genes. Quantitative reverse transcription polymerase chain reaction was performed to verify alternative splicing. ERα binding to alternatively spliced genes was verified by chromatin immunoprecipitation assay. Bromodeoxyuridine incorporation-ELISA and Annexin V labeling assays were done to measure cell proliferation and apoptosis, respectively. We identified the targets of E2-induced alternative splicing and deconstructed some of the mechanisms surrounding E2-induced splicing by combining splice array with ERα cistrome and gene expression array. E2-induced alternatively spliced genes fall into at least two subgroups: coupled to E2-regulated transcription and ERα binding to the gene without an effect on rate of transcription. Further, AKT, which phosphorylates both ERα and splicing factors, influenced ERα:E2 dependent splicing in a gene-specific manner. Genes that are alternatively spliced include FAS/CD95, FGFR2, and AXIN-1. E2 increased the expression of FGFR2 C1 isoform but reduced C3 isoform at mRNA level. E2-induced alternative splicing of FAS and FGFR2 in MCF-7 cells correlated with resistance to FAS activation-induced apoptosis and response to keratinocyte growth factor (KGF), respectively. Resistance of MCF-7 breast cancer cells to the anti-estrogen tamoxifen was associated with ER

  14. U2AF1 mutations alter splice site recognition in hematological malignancies.

    Science.gov (United States)

    Ilagan, Janine O; Ramakrishnan, Aravind; Hayes, Brian; Murphy, Michele E; Zebari, Ahmad S; Bradley, Philip; Bradley, Robert K

    2015-01-01

    Whole-exome sequencing studies have identified common mutations affecting genes encoding components of the RNA splicing machinery in hematological malignancies. Here, we sought to determine how mutations affecting the 3' splice site recognition factor U2AF1 alter its normal role in RNA splicing. We find that U2AF1 mutations influence the similarity of splicing programs in leukemias, but do not give rise to widespread splicing failure. U2AF1 mutations cause differential splicing of hundreds of genes, affecting biological pathways such as DNA methylation (DNMT3B), X chromosome inactivation (H2AFY), the DNA damage response (ATR, FANCA), and apoptosis (CASP8). We show that U2AF1 mutations alter the preferred 3' splice site motif in patients, in cell culture, and in vitro. Mutations affecting the first and second zinc fingers give rise to different alterations in splice site preference and largely distinct downstream splicing programs. These allele-specific effects are consistent with a computationally predicted model of U2AF1 in complex with RNA. Our findings suggest that U2AF1 mutations contribute to pathogenesis by causing quantitative changes in splicing that affect diverse cellular pathways, and give insight into the normal function of U2AF1's zinc finger domains. © 2015 Ilagan et al.; Published by Cold Spring Harbor Laboratory Press.

  15. Histone and RNA-binding protein interaction creates crosstalk network for regulation of alternative splicing.

    Science.gov (United States)

    Kim, Yong-Eun; Park, Chungoo; Kim, Kyoon Eon; Kim, Kee K

    2018-04-30

    Alternative splicing is an essential process in eukaryotes, as it increases the complexity of gene expression by generating multiple proteins from a single pre-mRNA. However, information on the regulatory mechanisms for alternative splicing is lacking, because splicing occurs over a short period via the transient interactions of proteins within functional complexes of the spliceosome. Here, we investigated in detail the molecular mechanisms connecting alternative splicing with epigenetic mechanisms. We identified interactions between histone proteins and splicing factors such as Rbfox2, Rbfox3, and splicing factor proline and glutamine rich protein (SFPQ) by in vivo crosslinking and immunoprecipitation. Furthermore, we confirmed that splicing factors were bound to specific modified residues of histone proteins. Additionally, changes in histone methylation due to histone methyltransferase inhibitor treatment notably affected alternative splicing in selected genes. Therefore, we suggested that there may be crosstalk mechanisms connecting histone modifications and RNA-binding proteins that increase the local concentration of RNA-binding proteins in alternative exon loci of nucleosomes by binding specific modified histone proteins, leading to alternative splicing. This crosstalk mechanism may play a major role in epigenetic processes such as histone modification and the regulation of alternative splicing. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Features generated for computational splice-site prediction correspond to functional elements

    Directory of Open Access Journals (Sweden)

    Wilbur W John

    2007-10-01

    Full Text Available Abstract Background Accurate selection of splice sites during the splicing of precursors to messenger RNA requires both relatively well-characterized signals at the splice sites and auxiliary signals in the adjacent exons and introns. We previously described a feature generation algorithm (FGA that is capable of achieving high classification accuracy on human 3' splice sites. In this paper, we extend the splice-site prediction to 5' splice sites and explore the generated features for biologically meaningful splicing signals. Results We present examples from the observed features that correspond to known signals, both core signals (including the branch site and pyrimidine tract and auxiliary signals (including GGG triplets and exon splicing enhancers. We present evidence that features identified by FGA include splicing signals not found by other methods. Conclusion Our generated features capture known biological signals in the expected sequence interval flanking splice sites. The method can be easily applied to other species and to similar classification problems, such as tissue-specific regulatory elements, polyadenylation sites, promoters, etc.

  17. RRM domain of Arabidopsis splicing factor SF1 is important for pre-mRNA splicing of a specific set of genes

    KAUST Repository

    Lee, Keh Chien; Jang, Yun Hee; Kim, SoonKap; Park, Hyo-Young; Thu, May Phyo; Lee, Jeong Hwan; Kim, Jeong-Kook

    2017-01-01

    , but not the abscisic acid sensitivity response during seed germination. The alternative splicing of FLOWERING LOCUS M (FLM) pre-mRNA is involved in flowering time control. We found that the RRM domain of AtSF1 protein alters the production of alternatively spliced FLM

  18. 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.

  19. RRM domain of Arabidopsis splicing factor SF1 is important for pre-mRNA splicing of a specific set of genes

    KAUST Repository

    Lee, Keh Chien

    2017-04-11

    The RNA recognition motif of Arabidopsis splicing factor SF1 affects the alternative splicing of FLOWERING LOCUS M pre-mRNA and a heat shock transcription factor HsfA2 pre-mRNA. Splicing factor 1 (SF1) plays a crucial role in 3\\' splice site recognition by binding directly to the intron branch point. Although plant SF1 proteins possess an RNA recognition motif (RRM) domain that is absent in its fungal and metazoan counterparts, the role of the RRM domain in SF1 function has not been characterized. Here, we show that the RRM domain differentially affects the full function of the Arabidopsis thaliana AtSF1 protein under different experimental conditions. For example, the deletion of RRM domain influences AtSF1-mediated control of flowering time, but not the abscisic acid sensitivity response during seed germination. The alternative splicing of FLOWERING LOCUS M (FLM) pre-mRNA is involved in flowering time control. We found that the RRM domain of AtSF1 protein alters the production of alternatively spliced FLM-β transcripts. We also found that the RRM domain affects the alternative splicing of a heat shock transcription factor HsfA2 pre-mRNA, thereby mediating the heat stress response. Taken together, our results suggest the importance of RRM domain for AtSF1-mediated alternative splicing of a subset of genes involved in the regulation of flowering and adaptation to heat stress.

  20. On relation between the quark-gluon bag surface tension and the colour tube string tension

    International Nuclear Information System (INIS)

    Bugaev, K.A.; Zinovjev, G.M.

    2010-01-01

    We revisit the bag phenomenology of deconfining phase transition aiming to replenish it by introducing systematically the bag surface tension. Comparing the free energies of such bags and the strings confining the static quark-antiquark pair, we express the string tension in terms of the bag surface tension and the bulk pressure in order to estimate the bag characteristics using the lattice QCD (LQCD) data. Our analysis of the bag entropy density demonstrates that the surface tension coefficient is amazingly negative at the cross-over (continuous transition). The approach developed allows us to naturally account for an origin of a pronounced maximum (observed in the LQCD studies) in the behaviour of heavy quark-antiquark pair entropy. The vicinity of the (tri-)critical endpoint is also analyzed to clarify the meaning of vanishing surface tension coefficient.

  1. Optical fabrication of large area photonic microstructures by spliced lens

    Science.gov (United States)

    Jin, Wentao; Song, Meng; Zhang, Xuehua; Yin, Li; Li, Hong; Li, Lin

    2018-05-01

    We experimentally demonstrate a convenient approach to fabricate large area photorefractive photonic microstructures by a spliced lens device. Large area two-dimensional photonic microstructures are optically induced inside an iron-doped lithium niobate crystal. The experimental setups of our method are relatively compact and stable without complex alignment devices. It can be operated in almost any optical laboratories. We analyze the induced triangular lattice microstructures by plane wave guiding, far-field diffraction pattern imaging and Brillouin-zone spectroscopy. By designing the spliced lens appropriately, the method can be easily extended to fabricate other complex large area photonic microstructures, such as quasicrystal microstructures. Induced photonic microstructures can be fixed or erased and re-recorded in the photorefractive crystal.

  2. Fatigue in tension perpendicular to the grain

    DEFF Research Database (Denmark)

    Clorius, Christian Odin; Pedersen, Martin Bo Uhre; Hoffmeyer, Preben

    1999-01-01

    Traditinally fatigue resistance is quantified as number of cycles to failure at a given stress level. A previous study by the authors showed that fatigue in compression parallel to the grain is governed partly by duration of load and partly by an effect of loading, i.e. a combination of a creep...... mechanism and a mechanism connected to damage introduce in the loading sequences. The purpose of the present study is to disentangle the effect of duration of load from the effect of load oscillation in fatigue in tension perpendicular to the grain. Fatigue experiments are made on small specimens...... and on dowel type joints with slotted in steel plates. In series of ten, the small specimens are taken to fatigue failure in uniform tension at square wave shaped load cycles at 0.01 Hz and 0.1 Hz. In order to test the predictive validity of the result from the small tension specimens, fatigue experiments...

  3. Fatigue In Tension Perpendicular to the Grain

    DEFF Research Database (Denmark)

    Clorius, Christian Odin; Pedersen, Martin Uhre; Hoffmeyer, Preben

    2004-01-01

    Traditionally fatigue resistance is quantified as number of cycles to failure at a given stress level. A previous study by the authors showed that fatigue in compression parallel to the grain is governed partly by duration of load and partly by an effect of loading, i.e. a combination of a creep...... mechanism and a mechanism connected to damage introduced in the loading sequences. The purpose of the present study is to disentangle the effect of duration of load from the effect of load oscillation in fatigue in tension perpendicular to the grain. Fatigue experiments are made on small specimens...... and on dowel type joints with slotted in steel plates. In series of ten, the small specimens are taken to fatigue failure in uniform tension at square wave shaped load cycles at 0.01 Hz and 0.1 Hz. In arder to test the predictive validity of the result from the small tension specimens, fatigue experiments...

  4. Tensions between Teams and Their Leaders

    Directory of Open Access Journals (Sweden)

    J. David Johnson

    2016-10-01

    Full Text Available The intersection of teamwork and leadership results in tensions, dilemmas, and paradoxes for both individuals and for institutions such as simultaneously empowering individuals at the same time it frustrates them when our naive, cultural understanding of leadership centralizes power and values leaders who can impose their will and vision on others. Perhaps the fundamental paradox of teamwork and leadership is that the more leadership is focused on an individual the less likely a team’s potential will be realized. Six specific domains where tensions arise are: at team boundaries; culture; who is in charge, rationality/cognition; diversity; and collaborations. Three approaches - clarifying different levels of analysis, temporal factors, and overarching concepts - to resolving tensions are discussed. New conceptions of leadership and the importance of the larger cultural frame within which they are embedded are needed for the management of technology and innovation.

  5. Cellular control of connective tissue matrix tension.

    Science.gov (United States)

    Langevin, Helene M; Nedergaard, Maiken; Howe, Alan K

    2013-08-01

    The biomechanical behavior of connective tissue in response to stretching is generally attributed to the molecular composition and organization of its extracellular matrix. It also is becoming apparent that fibroblasts play an active role in regulating connective tissue tension. In response to static stretching of the tissue, fibroblasts expand within minutes by actively remodeling their cytoskeleton. This dynamic change in fibroblast shape contributes to the drop in tissue tension that occurs during viscoelastic relaxation. We propose that this response of fibroblasts plays a role in regulating extracellular fluid flow into the tissue, and protects against swelling when the matrix is stretched. This article reviews the evidence supporting possible mechanisms underlying this response including autocrine purinergic signaling. We also discuss fibroblast regulation of connective tissue tension with respect to lymphatic flow, immune function, and cancer. Copyright © 2013 Wiley Periodicals, Inc.

  6. Surface tension of normal and heavy water

    International Nuclear Information System (INIS)

    Straub, J.; Rosner, N.; Grigull, V.

    1980-01-01

    A Skeleton Table and simple interpolation equation for the surface tension of light water was developed by the Working Group III of the International Association for the Properties of Steam and is recommended as an International Standard. The Skeleton Table is based on all known measurements of the surface tension and individual data were weighted corresponding to the accuracy of the measurements. The form of the interpolation equation is based on a physical concept. It represents an extension of van der Waals-equation, where the exponent conforms to the 'Scaling Laws'. In addition for application purposes simple relations for the Laplace-coefficient and for the density difference between the liquid and gaseous phases of light water are given. The same form of interpolation equation for the surface tension can be used for heavy water, for which the coefficients are given. However, this equation is based only on a single set of data. (orig.) [de

  7. Tension Stiffened and Tendon Actuated Manipulator

    Science.gov (United States)

    Doggett, William R. (Inventor); Dorsey, John T. (Inventor); Ganoe, George G. (Inventor); King, Bruce D. (Inventor); Jones, Thomas C. (Inventor); Mercer, Charles D. (Inventor); Corbin, Cole K. (Inventor)

    2015-01-01

    A tension stiffened and tendon actuated manipulator is provided performing robotic-like movements when acquiring a payload. The manipulator design can be adapted for use in-space, lunar or other planetary installations as it is readily configurable for acquiring and precisely manipulating a payload in both a zero-g environment and in an environment with a gravity field. The manipulator includes a plurality of link arms, a hinge connecting adjacent link arms together to allow the adjacent link arms to rotate relative to each other and a cable actuation and tensioning system provided between adjacent link arms. The cable actuation and tensioning system includes a spreader arm and a plurality of driven and non-driven elements attached to the link arms and the spreader arm. At least one cable is routed around the driven and non-driven elements for actuating the hinge.

  8. Intergenic mRNA molecules resulting from trans-splicing.

    Science.gov (United States)

    Finta, Csaba; Zaphiropoulos, Peter G

    2002-02-22

    Accumulated recent evidence is indicating that alternative splicing represents a generalized process that increases the complexity of human gene expression. Here we show that mRNA production may not necessarily be limited to single genes, as human liver also has the potential to produce a variety of hybrid cytochrome P450 3A mRNA molecules. The four known cytochrome P450 3A genes in humans, CYP3A4, CYP3A5, CYP3A7, and CYP3A43, share a high degree of similarity, consist of 13 exons with conserved exon-intron boundaries, and form a cluster on chromosome 7. The chimeric CYP3A mRNA molecules described herein are characterized by CYP3A43 exon 1 joined at canonical splice sites to distinct sets of CYP3A4 or CYP3A5 exons. Because the CYP3A43 gene is in a head-to-head orientation with the CYP3A4 and CYP3A5 genes, bypassing transcriptional termination can not account for the formation of hybrid CYP3A mRNAs. Thus, the mechanism generating these molecules has to be an RNA processing event that joins exons of independent pre-mRNA molecules, i.e. trans-splicing. Using quantitative real-time polymerase chain reaction, the ratio of one CYP3A43/3A4 intergenic combination was estimated to be approximately 0.15% that of the CYP3A43 mRNAs. Moreover, trans-splicing has been found not to interfere with polyadenylation. Heterologous expression of the chimeric species composed of CYP3A43 exon 1 joined to exons 2-13 of CYP3A4 revealed catalytic activity toward testosterone.

  9. An Engineered Split Intein for Photoactivated Protein Trans-Splicing.

    Directory of Open Access Journals (Sweden)

    Stanley Wong

    Full Text Available Protein splicing is mediated by inteins that auto-catalytically join two separated protein fragments with a peptide bond. Here we engineered a genetically encoded synthetic photoactivatable intein (named LOVInC, by using the light-sensitive LOV2 domain from Avena sativa as a switch to modulate the splicing activity of the split DnaE intein from Nostoc punctiforme. Periodic blue light illumination of LOVInC induced protein splicing activity in mammalian cells. To demonstrate the broad applicability of LOVInC, synthetic protein systems were engineered for the light-induced reassembly of several target proteins such as fluorescent protein markers, a dominant positive mutant of RhoA, caspase-7, and the genetically encoded Ca2+ indicator GCaMP2. Spatial precision of LOVInC was demonstrated by targeting activity to specific mammalian cells. Thus, LOVInC can serve as a general platform for engineering light-based control for modulating the activity of many different proteins.

  10. 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.

  11. Changes in RNA Splicing in Developing Soybean (Glycine max Embryos

    Directory of Open Access Journals (Sweden)

    Delasa Aghamirzaie

    2013-11-01

    Full Text Available Developing soybean seeds accumulate oils, proteins, and carbohydrates that are used as oxidizable substrates providing metabolic precursors and energy during seed germination. The accumulation of these storage compounds in developing seeds is highly regulated at multiple levels, including at transcriptional and post-transcriptional regulation. RNA sequencing was used to provide comprehensive information about transcriptional and post-transcriptional events that take place in developing soybean embryos. Bioinformatics analyses lead to the identification of different classes of alternatively spliced isoforms and corresponding changes in their levels on a global scale during soybean embryo development. Alternative splicing was associated with transcripts involved in various metabolic and developmental processes, including central carbon and nitrogen metabolism, induction of maturation and dormancy, and splicing itself. Detailed examination of selected RNA isoforms revealed alterations in individual domains that could result in changes in subcellular localization of the resulting proteins, protein-protein and enzyme-substrate interactions, and regulation of protein activities. Different isoforms may play an important role in regulating developmental and metabolic processes occurring at different stages in developing oilseed embryos.

  12. Evaluation of using ferrofluid as an interface material for a field-reversible thermal connector

    Science.gov (United States)

    Yousif, Ahmed S.

    The electrical functionality of an avionics chassis is limited due to heat dissipation limits. The limits arise due to the fact that components in an avionic computer boxes are packed very compactly, with the components mounted onto plug-in cards, and the harsh environment experienced by the chassis limits how heat can be dissipated from the cards. Convective and radiative heat transfer to the ambient are generally not possible. Therefore it is necessary to have heat transferred from the components conducted to the edge of the plug-in cards. The heat then needs to conduct from the card edge to a cold block that not only holds the card in place, but also removes the generated heat by some heat transfer fluid that is circulated through the cold block. The interface between the plug-in card and the cold block typically has a high thermal resistance since it is necessary for the card to have the capability to be re-workable, meaning that the card can be removed and then returned to the chassis. Reducing the thermal resistance of the interface is the objective of the current study and the topic of this thesis. The current design uses a pressure interface between the card and cold block. The contact pressure is increased through the addition of a wedgelock, which is a field-reversible mechanical connector. To use a wedgelock, the cold block has channels milled on the surface with widths that are larger than the thickness of the plug-in card and the un-expanded wedgelock. The card edge is placed in the channel and placed against one of the channel walls. A wedgelock is then placed between the card and the other channel wall. The wedgelock is then expanded by using either a screw or a lever. As the wedgelock expands it fills in the remaining channel gap and bears against the other face of the plug-in card. The majority of heat generated by the components on the plug-in card is forced to conduct from the card into the wall of the cold block, effectively a single sided, dry

  13. Genome-wide analysis of SRSF10-regulated alternative splicing by deep sequencing of chicken transcriptome

    Directory of Open Access Journals (Sweden)

    Xuexia Zhou

    2014-12-01

    Full Text Available Splicing factor SRSF10 is known to function as a sequence-specific splicing activator that is capable of regulating alternative splicing both in vitro and in vivo. We recently used an RNA-seq approach coupled with bioinformatics analysis to identify the extensive splicing network regulated by SRSF10 in chicken cells. We found that SRSF10 promoted both exon inclusion and exclusion. Functionally, many of the SRSF10-verified alternative exons are linked to pathways of response to external stimulus. Here we describe in detail the experimental design, bioinformatics analysis and GO/pathway enrichment analysis of SRSF10-regulated genes to correspond with our data in the Gene Expression Omnibus with accession number GSE53354. Our data thus provide a resource for studying regulation of alternative splicing in vivo that underlines biological functions of splicing regulatory proteins in cells.

  14. Automated Inspection of Defects in Optical Fiber Connector End Face Using Novel Morphology Approaches.

    Science.gov (United States)

    Mei, Shuang; Wang, Yudan; Wen, Guojun; Hu, Yang

    2018-05-03

    Increasing deployment of optical fiber networks and the need for reliable high bandwidth make the task of inspecting optical fiber connector end faces a crucial process that must not be neglected. Traditional end face inspections are usually performed by manual visual methods, which are low in efficiency and poor in precision for long-term industrial applications. More seriously, the inspection results cannot be quantified for subsequent analysis. Aiming at the characteristics of typical defects in the inspection process for optical fiber end faces, we propose a novel method, “difference of min-max ranking filtering” (DO2MR), for detection of region-based defects, e.g., dirt, oil, contamination, pits, and chips, and a special model, a “linear enhancement inspector” (LEI), for the detection of scratches. The DO2MR is a morphology method that intends to determine whether a pixel belongs to a defective region by comparing the difference of gray values of pixels in the neighborhood around the pixel. The LEI is also a morphology method that is designed to search for scratches at different orientations with a special linear detector. These two approaches can be easily integrated into optical inspection equipment for automatic quality verification. As far as we know, this is the first time that complete defect detection methods for optical fiber end faces are available in the literature. Experimental results demonstrate that the proposed DO2MR and LEI models yield good comprehensive performance with high precision and accepted recall rates, and the image-level detection accuracies reach 96.0 and 89.3%, respectively.

  15. The ontology-based answers (OBA) service: a connector for embedded usage of ontologies in applications.

    Science.gov (United States)

    Dönitz, Jürgen; Wingender, Edgar

    2012-01-01

    The semantic web depends on the use of ontologies to let electronic systems interpret contextual information. Optimally, the handling and access of ontologies should be completely transparent to the user. As a means to this end, we have developed a service that attempts to bridge the gap between experts in a certain knowledge domain, ontologists, and application developers. The ontology-based answers (OBA) service introduced here can be embedded into custom applications to grant access to the classes of ontologies and their relations as most important structural features as well as to information encoded in the relations between ontology classes. Thus computational biologists can benefit from ontologies without detailed knowledge about the respective ontology. The content of ontologies is mapped to a graph of connected objects which is compatible to the object-oriented programming style in Java. Semantic functions implement knowledge about the complex semantics of an ontology beyond the class hierarchy and "partOf" relations. By using these OBA functions an application can, for example, provide a semantic search function, or (in the examples outlined) map an anatomical structure to the organs it belongs to. The semantic functions relieve the application developer from the necessity of acquiring in-depth knowledge about the semantics and curation guidelines of the used ontologies by implementing the required knowledge. The architecture of the OBA service encapsulates the logic to process ontologies in order to achieve a separation from the application logic. A public server with the current plugins is available and can be used with the provided connector in a custom application in scenarios analogous to the presented use cases. The server and the client are freely available if a project requires the use of custom plugins or non-public ontologies. The OBA service and further documentation is available at http://www.bioinf.med.uni-goettingen.de/projects/oba.

  16. Automated Inspection of Defects in Optical Fiber Connector End Face Using Novel Morphology Approaches

    Directory of Open Access Journals (Sweden)

    Shuang Mei

    2018-05-01

    Full Text Available Increasing deployment of optical fiber networks and the need for reliable high bandwidth make the task of inspecting optical fiber connector end faces a crucial process that must not be neglected. Traditional end face inspections are usually performed by manual visual methods, which are low in efficiency and poor in precision for long-term industrial applications. More seriously, the inspection results cannot be quantified for subsequent analysis. Aiming at the characteristics of typical defects in the inspection process for optical fiber end faces, we propose a novel method, “difference of min-max ranking filtering” (DO2MR, for detection of region-based defects, e.g., dirt, oil, contamination, pits, and chips, and a special model, a “linear enhancement inspector” (LEI, for the detection of scratches. The DO2MR is a morphology method that intends to determine whether a pixel belongs to a defective region by comparing the difference of gray values of pixels in the neighborhood around the pixel. The LEI is also a morphology method that is designed to search for scratches at different orientations with a special linear detector. These two approaches can be easily integrated into optical inspection equipment for automatic quality verification. As far as we know, this is the first time that complete defect detection methods for optical fiber end faces are available in the literature. Experimental results demonstrate that the proposed DO2MR and LEI models yield good comprehensive performance with high precision and accepted recall rates, and the image-level detection accuracies reach 96.0 and 89.3%, respectively.

  17. Characterization of TTN Novex Splicing Variants across Species and the Role of RBM20 in Novex-Specific Exon Splicing

    Directory of Open Access Journals (Sweden)

    Zhilong Chen

    2018-02-01

    Full Text Available Titin (TTN is a major disease-causing gene in cardiac muscle. Titin (TTN contains 363 exons in human encoding various sizes of TTN protein due to alternative splicing regulated mainly by RNA binding motif 20 (RBM20. Three isoforms of TTN protein are produced by mutually exclusive exons 45 (Novex 1, 46 (Novex 2, and 48 (Novex 3. Alternatively splicing in Novex isoforms across species and whether Novex isoforms are associated with heart disease remains completely unknown. Cross-species exon comparison with the mVISTA online tool revealed that exon 45 is more highly conserved across all species than exons 46 and 48. Importantly, a conserved region between exons 47 and 48 across species was revealed for the first time. Reverse transcript polymerase chain reaction (RT-PCR and DNA sequencing confirmed a new exon named as 48′ in Novex 3. In addition, with primer pairs for Novex 1, a new truncated form preserving introns 44 and 45 was discovered. We discovered that Novex 2 is not expressed in the pig, mouse, and rat with Novex 2 primer pairs. Unexpectedly, three truncated forms were identified. One TTN variant with intron 46 retention is mainly expressed in the human and frog heart, another variant with co-expression of exons 45 and 46 exists predominantly in chicken and frog heart, and a third with retention of introns 45 and 46 is mainly expressed in pig, mouse, rat, and chicken. Using Rbm20 knockout rat heart, we revealed that RBM20 is not a splicing regulator of Novex variants. Furthermore, the expression levels of Novex variants in human hearts with cardiomyopathies suggested that Novexes 2 and 3 could be associated with dilated cardiomyopathy (DCM and/or arrhythmogenic right ventricular cardiomyopathy (ARVC. Taken together, our study reveals that splicing diversity of Novex exons across species and Novex variants might play a role in cardiomyopathy.

  18. Identification of genome-wide non-canonical spliced regions and analysis of biological functions for spliced sequences using Read-Split-Fly.

    Science.gov (United States)

    Bai, Yongsheng; Kinne, Jeff; Ding, Lizhong; Rath, Ethan C; Cox, Aaron; Naidu, Siva Dharman

    2017-10-03

    It is generally thought that most canonical or non-canonical splicing events involving U2- and U12 spliceosomes occur within nuclear pre-mRNAs. However, the question of whether at least some U12-type splicing occurs in the cytoplasm is still unclear. In recent years next-generation sequencing technologies have revolutionized the field. The "Read-Split-Walk" (RSW) and "Read-Split-Run" (RSR) methods were developed to identify genome-wide non-canonical spliced regions including special events occurring in cytoplasm. As the significant amount of genome/transcriptome data such as, Encyclopedia of DNA Elements (ENCODE) project, have been generated, we have advanced a newer more memory-efficient version of the algorithm, "Read-Split-Fly" (RSF), which can detect non-canonical spliced regions with higher sensitivity and improved speed. The RSF algorithm also outputs the spliced sequences for further downstream biological function analysis. We used open access ENCODE project RNA-Seq data to search spliced intron sequences against the U12-type spliced intron sequence database to examine whether some events could occur as potential signatures of U12-type splicing. The check was performed by searching spliced sequences against 5'ss and 3'ss sequences from the well-known orthologous U12-type spliceosomal intron database U12DB. Preliminary results of searching 70 ENCODE samples indicated that the presence of 5'ss with U12-type signature is more frequent than U2-type and prevalent in non-canonical junctions reported by RSF. The selected spliced sequences have also been further studied using miRBase to elucidate their functionality. Preliminary results from 70 samples of ENCODE datasets show that several miRNAs are prevalent in studied ENCODE samples. Two of these are associated with many diseases as suggested in the literature. Specifically, hsa-miR-1273 and hsa-miR-548 are associated with many diseases and cancers. Our RSF pipeline is able to detect many possible junctions

  19. Investigation of tissue-specific human orthologous alternative splice events in pig

    DEFF Research Database (Denmark)

    Hillig, Ann-Britt Nygaard; Jørgensen, Claus Bøttcher; Salicio, Susanna Cirera

    2010-01-01

    Alternative splicing of pre-mRNA can contribute to differences between tissues or cells either by regulating gene expression or creating proteins with various functions encoded by one gene. The number of investigated alternative splice events in pig has so far been limited. In this study we have ...... in preservation of open reading frame are indicative of a functional significance of the splice variants of the gene....

  20. Quantifying alternative splicing from paired-end RNA-sequencing data

    OpenAIRE

    Rossell, David; Stephan-Otto Attolini, Camille; Kroiss, Manuel; Stöcker, Almond

    2014-01-01

    RNA-sequencing has revolutionized biomedical research and, in particular, our ability to study gene alternative splicing. The problem has important implications for human health, as alternative splicing may be involved in malfunctions at the cellular level and multiple diseases. However, the high-dimensional nature of the data and the existence of experimental biases pose serious data analysis challenges. We find that the standard data summaries used to study alternative splicing are severely...

  1. Focal adhesions, stress fibers and mechanical tension

    Energy Technology Data Exchange (ETDEWEB)

    Burridge, Keith, E-mail: Keith_Burridge@med.unc.edu [Department of Cell Biology and Physiology, and Lineberger Comprehensive Cancer Center, 12-016 Lineberger, CB#7295, University of North Carolina, Chapel Hill, NC (United States); Guilluy, Christophe, E-mail: christophe.guilluy@univ-nantes.fr [Inserm UMR-S1087, CNRS UMR-C6291, L' institut du Thorax, and Université de Nantes, Nantes (France)

    2016-04-10

    Stress fibers and focal adhesions are complex protein arrays that produce, transmit and sense mechanical tension. Evidence accumulated over many years led to the conclusion that mechanical tension generated within stress fibers contributes to the assembly of both stress fibers themselves and their associated focal adhesions. However, several lines of evidence have recently been presented against this model. Here we discuss the evidence for and against the role of mechanical tension in driving the assembly of these structures. We also consider how their assembly is influenced by the rigidity of the substratum to which cells are adhering. Finally, we discuss the recently identified connections between stress fibers and the nucleus, and the roles that these may play, both in cell migration and regulating nuclear function. - Highlights: • The different types of stress fiber and focal adhesion are described. • We discuss the controversy about tension and assembly of these structures. • We describe the different models used to investigate assembly of these structures. • The influence of substratum rigidity is discussed. • Stress fiber connections to the nucleus are reviewed.

  2. Inclusion and Participation: Working with the Tensions

    Directory of Open Access Journals (Sweden)

    Gideon Calder

    2011-12-01

    Full Text Available Democracy is crucially about inclusion: a theory of democracy must account for who is to be included in the democratic process, how, and on what terms. Inclusion, if conceived democratically, is fraught with tensions. This article identifies three such tensions, arising respectively in: (i the inauguration of the democratic public; (ii enabling equal participation; and (iii the relationship between instrumental and non-instrumental accounts of democracy’s value. In each case, I argue, rather than seeking somehow to dissolve or avoid such tensions, theories of democracy should allow us to live with their implications reflexively: to work with them. Such tensions are counter-democratic to the extent that they derail what Nancy Fraser calls “participatory parity,” under which citizens count as “full partners in social interaction.” But the extent to which they do this is not itself dependent on points of paradox in the very idea of inclusion. Such parity relies on complex factors, social and economic, which democratic institutions and procedures will not by themselves address. To achieve full democratic inclusion we must already have addressed such factors; no account of democracy itself, however finely-tuned, will do this.

  3. Tension and relaxation in the individual.

    Science.gov (United States)

    Newbury, C R

    1979-06-01

    Increasing materialism in society is resulting in more wide spread nervous tension in all age groups. While some degree of nervous tension is necessary in everyday living, its adverse effects require that we must learn to bring it under control. Total tension is shown to have two components: a controllable element arising from factors in the environment and the inbuilt uncontrollable residue which is basic in the individual temperament. The effects of excessive or uncontrolled stress can be classified as 1) emotional reactions such as neurotic behaviour (anxiety hypochondria, hysteria, phobia, depression obsessions and compulsions) or psychotic behaviour and 2) psychosomatic reactions (nervous asthma, headache, insomnia, heart attack). Nervous energy can be wastefully expended by such factors as loss of temper, wrong attitudes to work, job frustration and marital strains. Relaxation is the only positive way to control undesirable nervous tension and its techniques require to be learned. A number of techniques (progressive relaxation, differential relaxation, hypnosis, the use of biofeedback, Yoga and Transcendental Meditation) are described and their application to dental practice is discussed.

  4. WORRY, ANXIETY AND TENSION — IMPORTANCE ...

    African Journals Online (AJOL)

    Enrique

    cognitive. Tension: Increased and unpleasant motor and psychological activity or a state of mental or ... MRC Research Unit on Anxiety and Stress. Disorders ... and brain imaging. Worry ... serve an adaptive function to the daily challenges of our environment. ... connection to physical symptoms ... Experience-conditioning.

  5. Surface Tension Measurements with a Smartphone

    Science.gov (United States)

    Goy, Nicolas-Alexandre; Denis, Zakari; Lavaud, Maxime; Grolleau, Adrian; Dufour, Nicolas; Deblais, Antoine; Delabre, Ulysse

    2017-01-01

    Smartphones are increasingly used in higher education and at university in mechanics, acoustics, and even thermodynamics as they offer a unique way to do simple science experiments. In this article, we show how smartphones can be used in fluid mechanics to measure surface tension of various liquids, which could help students understand the concept…

  6. Rebellion and Agrarian Tensions in Sierra Leone

    NARCIS (Netherlands)

    Peters, K.; Richards, P.

    2011-01-01

    This paper assesses the extent to which customary governance in Sierra Leone can be held responsible for an increasingly unstable two-class agrarian society. A case is made for regarding the civil war (1991–2002) as being an eruption of long-term, entrenched agrarian tensions exacerbated by chiefly

  7. Normal tension glaucoma and Alzheimer disease

    DEFF Research Database (Denmark)

    Bach-Holm, Daniella; Kessing, Svend Vedel; Mogensen, Ulla Brasch

    2012-01-01

    Purpose: To investigate whether normal tension glaucoma (NTG) is associated with increased risk of developing dementia/Alzheimer disease (AD). Methods: A total of 69 patients with NTG were identified in the case note files in the Glaucoma Clinic, University Hospital of Copenhagen (Rigshospitalet...

  8. Coexisting tensions between the 'traditionmodernity' and the ...

    African Journals Online (AJOL)

    Coexisting tensions between the 'traditionmodernity' and the 'sustainability- integration' approaches to urban development policy and planning practices in Botswana. ... exists at several levels and manifest in urban planning's preoccupation with the physicality of spatial forms, often justified in the embracing of globalization.

  9. Tension and Approximation in Poetic Translation

    Science.gov (United States)

    Al-Shabab, Omar A. S.; Baka, Farida H.

    2015-01-01

    Simple observation reveals that each language and each culture enjoys specific linguistic features and rhetorical traditions. In poetry translation difference and the resultant linguistic tension create a gap between Source Language and Target language, a gap that needs to be bridged by creating an approximation processed through the translator's…

  10. Transcutaneous oxygen tension in imminent foot gangrene

    DEFF Research Database (Denmark)

    Tønnesen, K H

    1978-01-01

    Transcutaneous oxygen tension at 44 degree C and maximal isotope clearance (90m Tc-pretechnetate + histramine) just proximal to the 1st toe and systolic toe blood pressure (strain gauge) were studied on a tilt table in patients with various degrees of obstructive arteriosclerotic disease. In legs...

  11. Internationalization and Global Tension: Lessons From History

    Science.gov (United States)

    Altbach, Philip G.; de Wit, Hans

    2015-01-01

    Increasing political and military tension in several parts of the world will inevitably affect international higher education. Nationalist, religious, and ideological conflicts challenge the original ideas of international cooperation and exchange in higher education as promoters of peace and mutual understanding and of global engagement. Since…

  12. Educational Leadership: Key Challenges and Ethical Tensions

    Science.gov (United States)

    Duignan, Patrick

    2007-01-01

    "Educational Leadership" is a major research book on contemporary leadership challenges for educational leaders. In this groundbreaking new work, educational leaders in schools, including teachers, are provided with ways of analysing and resolving common but complex leadership challenges. Ethical tensions inherent in these challenges are…

  13. Tension Builds over AFT Reform Agenda

    Science.gov (United States)

    Sawchuk, Stephen

    2012-01-01

    Can a teachers' union successfully be both a hardball-playing defender of its rights and a collaborative force for the common good? It is both a question of philosophy and, increasingly, one of policy direction for the American Federation of Teachers (AFT), whose biennial convention in Detroit showed delegates grappling with the tension between…

  14. Exact analytical density profiles and surface tension

    Indian Academy of Sciences (India)

    journal of. May 2005 physics pp. 785–801. Classical charged fluids at equilibrium near ... is provided by the excess surface tension for an air–water interface, which is determined ... the potential drop created by the electric layer which appears as soon as the fluid has ...... radii, by symmetry, the charge density profile is flat,.

  15. Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types

    Directory of Open Access Journals (Sweden)

    Michael Seiler

    2018-04-01

    Full Text Available Summary: Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA, and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like, or hotspot mutation profile (oncogene-like. Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in cancer and may represent an underappreciated hallmark of tumorigenesis. : Seiler et al. report that 119 splicing factor genes carry putative driver mutations over 33 tumor types in TCGA. The most common mutations appear to be mutually exclusive and are associated with lineage-independent altered splicing. Samples with these mutations show deregulation of cell-autonomous pathways and immune infiltration. Keywords: splicing, SF3B1, U2AF1, SRSF2, RBM10, FUBP1, cancer, mutation

  16. Mechanism of protein splicing of the Pyrococcus abyssi lon protease intein

    International Nuclear Information System (INIS)

    O'Brien, Kevin M.; Schufreider, Ann K.; McGill, Melissa A.; O'Brien, Kathryn M.; Reitter, Julie N.; Mills, Kenneth V.

    2010-01-01

    Research highlights: → The Pyrococcus abyssi lon protease intein promotes efficient protein splicing. → Inteins with mutations that interfere with individual steps of splicing do not promote unproductive side reactions. → The intein splices with Lys in place of the highly conserved penultimate His. → The intein is flanked by a Gly-rich region at its C terminus that may increase the efficiency of the third step of splicing, Asn cyclization coupled to peptide bond cleavage. -- Abstract: Protein splicing is a post-translational process by which an intervening polypeptide, the intein, excises itself from the flanking polypeptides, the exteins, coupled to ligation of the exteins. The lon protease of Pyrococcus abyssi (Pab) is interrupted by an intein. When over-expressed as a fusion protein in Escherichia coli, the Pab lon protease intein can promote efficient protein splicing. Mutations that block individual steps of splicing generally do not lead to unproductive side reactions, suggesting that the intein tightly coordinates the splicing process. The intein can splice, although it has Lys in place of the highly conserved penultimate His, and mutants of the intein in the C-terminal region lead to the accumulation of stable branched-ester intermediate.

  17. Analysis of Few-Mode Multi-Core Fiber Splice Behavior Using an Optical Vector Network Analyzer

    DEFF Research Database (Denmark)

    Rommel, Simon; Mendinueta, Jose Manuel Delgado; Klaus, Werner

    2017-01-01

    The behavior of splices in a 3-mode 36-core fiber is analyzed using optical vector network analysis. Time-domain response analysis confirms splices may cause significant mode-mixing, while frequency-domain analysis shows splices may affect system level mode-dependent loss both positively and negativ......The behavior of splices in a 3-mode 36-core fiber is analyzed using optical vector network analysis. Time-domain response analysis confirms splices may cause significant mode-mixing, while frequency-domain analysis shows splices may affect system level mode-dependent loss both positively...

  18. Transitions of tethered chain molecules under tension.

    Science.gov (United States)

    Luettmer-Strathmann, Jutta; Binder, Kurt

    2014-09-21

    An applied tension force changes the equilibrium conformations of a polymer chain tethered to a planar substrate and thus affects the adsorption transition as well as the coil-globule and crystallization transitions. Conversely, solvent quality and surface attraction are reflected in equilibrium force-extension curves that can be measured in experiments. To investigate these effects theoretically, we study tethered chains under tension with Wang-Landau simulations of a bond-fluctuation lattice model. Applying our model to pulling experiments on biological molecules we obtain a good description of experimental data in the intermediate force range, where universal features dominate and finite size effects are small. For tethered chains in poor solvent, we observe the predicted two-phase coexistence at transitions from the globule to stretched conformations and also discover direct transitions from crystalline to stretched conformations. A phase portrait for finite chains constructed by evaluating the density of states for a broad range of solvent conditions and tensions shows how increasing tension leads to a disappearance of the globular phase. For chains in good solvents tethered to hard and attractive surfaces we find the predicted scaling with the chain length in the low-force regime and show that our results are well described by an analytical, independent-bond approximation for the bond-fluctuation model for the highest tensions. Finally, for a hard or slightly attractive surface the stretching of a tethered chain is a conformational change that does not correspond to a phase transition. However, when the surface attraction is sufficient to adsorb a chain it will undergo a desorption transition at a critical value of the applied force. Our results for force-induced desorption show the transition to be discontinuous with partially desorbed conformations in the coexistence region.

  19. An evaluation of the spring finger solder joints on SA1358-10 and SA2052-4 connector assemblies (MC3617,W87)

    International Nuclear Information System (INIS)

    Kilgo, Alice C.; Vianco, Paul Thomas; Hlava, Paul Frank; Zender, Gary L.

    2006-01-01

    The SA1358-10 and SA2052-4 circular JT Type plug connectors are used on a number of nuclear weapons and Joint Test Assembly (JTA) systems. Prototype units were evaluated for the following specific defects associated with the 95Sn-5Sb (Sn-Sb, wt.%) solder joint used to attach the beryllium-copper (BeCu) spring fingers to the aluminum (Al) connector shell: (1) extended cracking within the fillet; (2) remelting of the solder joint during the follow-on, soldering step that attached the EMR adapter ring to the connector shell (and/or soldering the EMR shell to the adapter ring) that used the lower melting temperature 63Sn-37Pb (Sn-Pb) alloy; and (3) spalling of the Cd (Cr) layer overplating layer from the fillet surface. Several pedigrees of connectors were evaluated, which represented older fielded units as well as those assemblies that were recently constructed at Kansas City Plant. The solder joints were evaluated that were in place on connectors made with the current soldering process as well as an alternative induction soldering process for attaching the EMR adapter ring to the shell. Very similar observations were made, which crossed the different pedigrees of parts and processes. The extent of cracking in the top side fillets varied between the different connector samples and likely the EMR adapter ring to the shell. Very similar observations were made, which crossed the different pedigrees of parts and processes. The extent of cracking in the top side fillets varied between the different connector samples and likely reflected the different extents to which the connector was mated to its counterpart assembly. In all cases, the spring finger solder joints on the SA1358-10 connectors were remelted as a result of the subsequent EMR adapter ring attachment process. Spalling of the Cd (Cr) overplating layer was also observed for these connectors, which was a consequence of the remelting activity. On the other hand, the SA2052-4 connector did not exhibit evidence of

  20. Influence of the width and cross-sectional shape of major connectors of maxillary dentures on the accuracy of speech production.

    Science.gov (United States)

    Wada, Junichiro; Hideshima, Masayuki; Inukai, Shusuke; Matsuura, Hiroshi; Wakabayashi, Noriyuki

    2014-01-01

    To investigate the effects of the width and cross-sectional shape of the major connectors of maxillary dentures located in the middle area of the palate on the accuracy of phonetic output of consonants using an originally developed speech recognition system. Nine adults (4 males and 5 females, aged 24-26 years) with sound dentition were recruited. The following six sounds were considered: [∫i], [t∫i], [ɾi], [ni], [çi], and [ki]. The experimental connectors were fabricated to simulate bars (narrow, 8-mm width) and plates (wide, 20-mm width). Two types of cross-sectional shapes in the sagittal plane were specified: flat and plump edge. The appearance ratio of phonetic segment labels was calculated with the speech recognition system to indicate the accuracy of phonetic output. Statistical analysis was conducted using one-way ANOVA and Tukey's test. The mean appearance ratio of correct labels (MARC) significantly decreased for [ni] with the plump edge (narrow connector) and for [ki] with both the flat and plump edge (wide connectors). For [çi], the MARCs tended to be lower with flat plates. There were no significant differences for the other consonants. The width and cross-sectional shape of the connectors had limited effects on the articulation of consonants at the palate. © 2015 S. Karger AG, Basel.

  1. An in vitro comparison of standard cleaning to a continuous passive disinfection cap for the decontamination of needle-free connectors.

    Science.gov (United States)

    Casey, Anna L; Karpanen, Tarja J; Nightingale, Peter; Elliott, Tom S J

    2018-01-01

    The optimal decontamination method for needle-free connectors is still unresolved. The objective of this study was to determine if a continuous passive disinfection cap is as effective as standard cleaning for the microbial decontamination of injection ports of two types of needle-free connectors. The injection ports of needle-free connectors were inoculated with Staphylococcus aureus and allowed to dry. Disinfection caps containing 70% ( v / v ) isopropyl alcohol (IPA) were attached to the connectors for one, three or 7 days and were compared with needle-free connectors cleaned with 2% ( w / v ) chlorhexidine gluconate (CHG) in 70% ( v/v ) IPA. The number of S. aureus remaining on the injection ports was evaluated. Median log 10 reductions and 95% confidence interval (CI) were calculated and data analyzed using the Mann-Whitney test. The application of the disinfection cap resulted in a significantly higher reduction in S. aureus than the 2% ( w / v ) CHG in 70% ( v / v ) IPA wipe, achieving a > 5 Log 10 reduction in CFU at each time point. The disinfection caps resulted in a significantly higher reduction in S.aureus on the injection ports when compared to the use of a 2% ( w/v ) CHG in 70% ( v/v ) IPA wipe. This offers an explanation for the lower rates of central-line associated bloodstream infection (CLABSI) associated with the use of disinfection caps reported in clinical studies.

  2. Necessary Tension in Marine Risers Tension des colonnes montantes en mer

    Directory of Open Access Journals (Sweden)

    Lubinski A.

    2006-11-01

    Full Text Available The tension governing transverse static and dynamic deflections in a riser is not the actual tension but the so-called « effective tension » The concept of effective tension and effective compression is thoroughly explained, and means for calculating effective forces are given. Numerical examples are worked out for risers whose length is between 152 m (520 ft and 920 m (3020 ft. The reciprocal of maximum bending moment of the vicinity of the hall joint is plotted versus the effective tension of the ball joint. Bending moments used were obtained through use of static and dynamic computer programs applied ta a variety of conditions of wave loading, use or non-use of buoyant moterial sleeves, etc. The most important parameters affecting riser performance are the effective La tension régissant les déflections transversales statiques et dynamiques d'une colonne montante n'est pas la tension réelle mais ce qu'on appelle « la tension effective ». Le concept de tension ou de compression effective est expliqué en détail et la façon de calculer les forces effectives est indiquée dans cet article. Des exemples numériques sont développés pour des colonnes montantes de longueur comprise entre 152 m (520 ft et 920 m (3 020 ft. On a tracé la courbe de l'inverse du moment fléchissant en fonction de la tension effective à l'articulation. Les moments fléchissants utilisés ont été calculés par ordinateur en utilisant des programmes dynamiques et statiques pour des conditions variées d'action des vagues, la colonne montante étant ou non munie de manchettes de flottabilité, etc. Les deux paramètres les plus importants qui affectent le bon comportement d'une colonne montante sont la tension effective et la charge latérale.

  3. Bilateral tension pneumothorax following equipment improvisation.

    Science.gov (United States)

    Zambricki, Christine; Schmidt, Carol; Vos, Karen

    2014-02-01

    This case report describes an unexpected event that took place as a result of using improvised equipment. The patient, a 16-year-old female undergoing complex oral surgery, suffered bilateral pneumothorax following the improper use of an airway support device. During the immediate postoperative period with the patient still intubated, oxygen tubing was attached to a right angle elbow connector with the port closed and 10 L/minute oxygen flow was administered to the patient in a manner that did not allow the patient to exhale. Within seconds, pneumothorax was apparent as the patient's vital signs deteriorated, visible swelling was noted in the shoulders and neck, and there was an absence of breath sounds on auscultation. This case study has application beyond the immediate discussion of bilateral pneumothorax, serving as a caution about the unintended consequences of equipment improvisation. In addition to highlighting the hazards of providing patient care with a non-standard device, this study also provides a powerful example of the human factors that can contribute to medical errors in the healthcare setting.

  4. Exploring the impact of the care sport connector in the Netherlands.

    Science.gov (United States)

    Leenaars, Karlijn E F; Smit, Eva; Wagemakers, Annemarie; Molleman, Gerard R M; Koelen, Maria A

    2017-10-16

    Regular physical activity (PA) is deemed to contribute to the primary and secondary prevention of several chronic diseases, like diabetes mellitus, cancer, cardiovascular diseases, and osteoporosis. In 2012, Care Sport Connectors (CSC), to whom a broker has been ascribed, were introduced in the Netherlands to stimulate PA and guide primary care patients towards local sport facilities. The aim of this study was to explore which structural embedding is the most promising for CSCs' work. In three rounds of interviews, 13 CSCs were followed for 2 years in their work. In these interviews, a network survey was used to identify organisations in the CSCs' network, whether they collaborated with these organisations, and the role of the organisations in the connection. Data from the network survey were analysed using the RE-AIM framework and disaggregated into how CSCs were structurally embedded (Type A: only PA sector; Type B: different sectors; Type C: partnership). A related samples Wilcoxon signed rank test was performed to study how the CSCs' network developed between 2014 and 2016. All CSCs established a connection between the primary care and the PA sector in which the average number of organisations with which CSCs collaborated increased significantly between 2014 (8.3) and 2016 (19.8) (p = 0.002). However, differences were identified in the way CSCs were structurally embedded and in the way they established the connection. Type A CSCs established the connection mostly around their own activities, supported PA organisations with their activities, and collaborated with primary care and welfare professionals around their own activities. Type B and Type C CSCs established the connection by organising, supporting, and implementing different kinds of activities targeting different kinds of audiences, and collaborated mostly with primary care professionals around the referral of professionals' patients. The results of this study suggest that adopting an integral approach

  5. Exploring the impact of the care sport connector in the Netherlands

    Directory of Open Access Journals (Sweden)

    Karlijn E. F. Leenaars

    2017-10-01

    Full Text Available Abstract Background Regular physical activity (PA is deemed to contribute to the primary and secondary prevention of several chronic diseases, like diabetes mellitus, cancer, cardiovascular diseases, and osteoporosis. In 2012, Care Sport Connectors (CSC, to whom a broker has been ascribed, were introduced in the Netherlands to stimulate PA and guide primary care patients towards local sport facilities. The aim of this study was to explore which structural embedding is the most promising for CSCs’ work. Methods In three rounds of interviews, 13 CSCs were followed for 2 years in their work. In these interviews, a network survey was used to identify organisations in the CSCs’ network, whether they collaborated with these organisations, and the role of the organisations in the connection. Data from the network survey were analysed using the RE-AIM framework and disaggregated into how CSCs were structurally embedded (Type A: only PA sector; Type B: different sectors; Type C: partnership. A related samples Wilcoxon signed rank test was performed to study how the CSCs’ network developed between 2014 and 2016. Results All CSCs established a connection between the primary care and the PA sector in which the average number of organisations with which CSCs collaborated increased significantly between 2014 (8.3 and 2016 (19.8 (p = 0.002. However, differences were identified in the way CSCs were structurally embedded and in the way they established the connection. Type A CSCs established the connection mostly around their own activities, supported PA organisations with their activities, and collaborated with primary care and welfare professionals around their own activities. Type B and Type C CSCs established the connection by organising, supporting, and implementing different kinds of activities targeting different kinds of audiences, and collaborated mostly with primary care professionals around the referral of professionals’ patients

  6. Characterization of a splicing mutation in group A xeroderma pigmentosum

    International Nuclear Information System (INIS)

    Satokata, Ichiro; Tanaka, Kiyoji; Miura, Naoyuki; Miyamoto, Iwai; Okada, Yoshio; Satoh, Yoshiaki; Kondo, Seiji

    1990-01-01

    The molecular basis of group A xeroderma pigmentosum (WP) was investigated by comparison of the nucleotide sequences of multiple clones of the XP group A complementing gene (XPAC) from a patient with group A XP with that of a normal gene. The clones showed a G → C substitution at the 3' splice acceptor site of intron 3, which altered the obligatory AG acceptor dinucleotide to AC. Nucleotide sequencing of cDNAs amplified by the polymerase chain reaction revealed that this single base substitution abolishes the canonical 3' splice site, thus creating two abnormally spliced mRNA forms. The larger form is identical with normal mRNA except for a dinucleotide deletion at the 5' end of exon 4. This deletion results in a frameshift with premature translation termination in exon 4. The smaller form has a deletion of the entire exon 3 and the dinucleotide at the 5' end of exon 4. The result of a transfection study provided additional evidence that this single base substitution is the disease-causing mutation. This single base substitution creates a new cleavage site for the restriction nuclease AlwNI. Analysis of AlwNI restriction fragment length polymorphism showed a high frequency of this mutation in Japanese patients with group A XP: 16 of 21 unrelated Japanese patients were homozygous and 4 were heterozygous for this mutation. However, 11 Caucasians and 2 Blacks with group A XP did not have this mutant allele. The polymorphic AlwNI restriction fragments are concluded to be useful for diagnosis of group A XP in Japanese subjects, including prenatal cases and carriers

  7. Periostin shows increased evolutionary plasticity in its alternatively spliced region

    Directory of Open Access Journals (Sweden)

    Hoersch Sebastian

    2010-01-01

    Full Text Available Abstract Background Periostin (POSTN is a secreted extracellular matrix protein of poorly defined function that has been related to bone and heart development as well as to cancer. In human and mouse, it is known to undergo alternative splicing in its C-terminal region, which is devoid of known protein domains. Differential expression of periostin, sometimes of specific splicing isoforms, is observed in a broad range of human cancers, including breast, pancreatic, and colon cancer. Here, we combine genomic and transcriptomic sequence data from vertebrate organisms to study the evolution of periostin and particularly of its C-terminal region. Results We found that the C-terminal part of periostin is markedly more variable among vertebrates than the rest of periostin in terms of exon count, length, and splicing pattern, which we interpret as a consequence of neofunctionalization after the split between periostin and its paralog transforming growth factor, beta-induced (TGFBI. We also defined periostin's sequential 13-amino acid repeat units - well conserved in teleost fish, but more obscure in higher vertebrates - whose secondary structure is predicted to be consecutive beta strands. We suggest that these beta strands may mediate binding interactions with other proteins through an extended beta-zipper in a manner similar to the way repeat units in bacterial cell wall proteins have been reported to bind human fibronectin. Conclusions Our results, obtained with the help of the increasingly large collection of complete vertebrate genomes, document the evolutionary plasticity of periostin's C-terminal region, and for the first time suggest a basis for its functional role.

  8. Recurrent Hyperparathyroidism Due to a Novel CDC73 Splice Mutation.

    Science.gov (United States)

    Hattangady, Namita Ganesh; Wilson, Tremika Le-Shan; Miller, Barbra Sue; Lerario, Antonio Marcondes; Giordano, Thomas James; Choksi, Palak; Else, Tobias

    2017-08-01

    The recognition of hereditary causes of primary hyperparathyroidism (pHPT) is important because clinical care and surveillance differ significantly between sporadic and hereditary pHPT. In addition, the increasing number of genetic tests poses a challenge to classify mutations as benign or pathogenic. Functional work-up of variants remains a mainstay to provide evidence for pathogenicity. We describe a 52-year-old male patient with recurrent pHPT since age 35 years. Despite several neck surgeries with complete parathyroidectomy, he experienced persistent pHPT, necessitating repeated surgery for a forearm autotransplant, which finally resulted in unmeasurable parathyroid hormone (PTH) levels. Genetic testing revealed a new CDC73 variant (c.238-8G>A [IVS2-8G>A]), initially classified as a variant of uncertain significance. Parathyroid tissue from the initial surgeries showed loss of heterozygosity. Using an RT-PCR approach, we show that the mutation leads to the use of a cryptic splice site in peripheral mononuclear cells. In addition, a minigene approach confirms the use of the cryptic splice site in a heterologous cell system. The novel c.238-8G>A CDC73 variant activates a cryptic splice site, and the functional data provided justify the classification as a likely pathogenic variant. Our results underscore the importance of functional work-up for variant classification in the absence of other available data, such as presence in disease-specific databases, other syndromic clinical findings, or family history. In addition, the presented case exemplifies the importance to consider a hereditary condition in young patients with pHPT, particularly those with multi-gland involvement. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

  9. 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...... and flPD-1 upon activation suggests an important interplay between the putative soluble PD-1 and flPD-1 possibly involved in maintenance of peripheral self-tolerance and prevention of autoimmunity....

  10. Assessment and reduction of diaphragmatic tension during hiatal hernia repair.

    Science.gov (United States)

    Bradley, Daniel Davila; Louie, Brian E; Farivar, Alexander S; Wilshire, Candice L; Baik, Peter U; Aye, Ralph W

    2015-04-01

    During hiatal hernia repair there are two vectors of tension: axial and radial. An optimal repair minimizes the tension along these vectors. Radial tension is not easily recognized. There are no simple maneuvers like measuring length that facilitate assessment of radial tension. The aims of this project were to: (1) establish a simple intraoperative method to evaluate baseline tension of the diaphragmatic hiatal muscle closure; and, (2) assess if tension is reduced by relaxing maneuvers and if so, to what degree. Diaphragmatic characteristics and tension were assessed during hiatal hernia repair with a tension gage. We compared tension measured after hiatal dissection and after relaxing maneuvers were performed. Sixty-four patients (29 M:35F) underwent laparoscopic hiatal hernia repair. Baseline hiatal width was 2.84 cm and tension 13.6 dag. There was a positive correlation between hiatal width and tension (r = 0.55) but the strength of association was low (r (2) = 0.31). Four different hiatal shapes (slit, teardrop, "D", and oval) were identified and appear to influence tension and the need for relaxing incision. Tension was reduced by 35.8 % after a left pleurotomy (12 patients); by 46.2 % after a right crural relaxing incision (15 patients); and by 56.1 % if both maneuvers were performed (6 patients). Tension on the diaphragmatic hiatus can be measured with a novel device. There was a limited correlation with width of the hiatal opening. Relaxing maneuvers such as a left pleurotomy or a right crural relaxing incision reduced tension. Longer term follow-up will determine whether outcomes are improved by quantifying and reducing radial tension.

  11. Thermal Analysis of Bending Under Tension Test

    DEFF Research Database (Denmark)

    Ceron, Ermanno; Martins, Paulo A.F.; Bay, Niels

    2014-01-01

    during testing is similar to the one in the production tool. A universal sheet tribo-tester has been developed, which can run multiple tests automatically from coil. This allows emulating the temperature increase as in production. The present work performs finite element analysis of the evolution......The tribological conditions in deep drawing can be simulated in the Bending Under Tension test to evaluate the performance of new lubricants, tool materials, etc. Deep drawing production with automatic handling runs normally at high rate. This implies considerable heating of the tools, which...... sometimes can cause lubricant film breakdown and galling. In order to replicate the production conditions in bending under tension testing it is thus important to control the tool/workpiece interface temperature. This can be done by pre-heating the tool, but it is essential that the interface temperature...

  12. Quantum surface tension in ideal gases

    International Nuclear Information System (INIS)

    Sisman, A.

    2005-01-01

    Due to wave character of atoms, an ideal gas confined in a finite domain exhibits Casimir like size effects. These effects become appreciable in a domain with at least one dimension in the order of micron. On this scale, thermodynamic state functions of an ideal gas become shape and size dependent and some new effects appear. In the literature, only some domains of regular shapes have been considered. In this study, the results are generalized to a domain of an arbitrary shape by using Weyl s conjecture for density of states. It is seen that free energy expression of an ideal Maxwellian gas consists of a classical volume dependent term and also a quantum originated surface dependent term, which causes a quantum surface tension. In a rectangular box filled by an ideal gas and separated by a movable wall into two parts, it is shown that a lateral force appears on the movable wall due to quantum surface tension

  13. Separation anxiety: Stress, tension and cytokinesis

    International Nuclear Information System (INIS)

    Mohan, Krithika; Iglesias, Pablo A.; Robinson, Douglas N.

    2012-01-01

    Cytokinesis, the physical separation of a mother cell into two daughter cells, progresses through a series of well-defined changes in morphology. These changes involve distinct biochemical and mechanical processes. Here, we review the mechanical features of cells during cytokinesis, discussing both the material properties as well as sources of stresses, both active and passive, which lead to the observed changes in morphology. We also describe a mechanosensory feedback control system that regulates protein localization and shape progression during cytokinesis. -- Highlights: ► Cytokinesis progresses through three distinct mechanical phases. ► Cortical tension initially resists deformation of mother cell. ► Late in cytokinesis, cortical tension provides stress, enabling furrow ingression. ► A mechanosensory feedback control system regulates cytokinesis.

  14. Tension Tests On Bored Piles In Sand

    DEFF Research Database (Denmark)

    Krabbenhøft, Sven; Clausen, Johan; Damkilde, Lars

    2006-01-01

    The lengths of the bored piles varied from 2 m to 6 m and all were of a diameter of 140 mm. The piles were tested to failure in tension and the load-displacement relations were recorded. The investigation has shown pronounced differences between the load bearing capacities obtained by different...... design methods. The methods proposed by Fleming et al. and Reese & O’Neill seem to produce the best match with the test results....

  15. Surface tension confined liquid cryogen cooler

    Science.gov (United States)

    Castles, Stephen H. (Inventor); Schein, Michael E. (Inventor)

    1989-01-01

    A cryogenic cooler is provided for use in craft such as launch, orbital, and space vehicles subject to substantial vibration, changes in orientation, and weightlessness. The cooler contains a small pore, large free volume, low density material to restrain a cryogen through surface tension effects during launch and zero-g operations and maintains instrumentation within the temperature range of 10 to 140 K. The cooler operation is completely passive, with no inherent vibration or power requirements.

  16. Surface tension of H2O and D2O

    International Nuclear Information System (INIS)

    Vargaftik, N.B.; Voljak, L.D.; Volkov, B.N.

    1975-01-01

    There is a great number of works on surface tension of clean water (H 2 O) at temperatures up to 100 deg C and very few above the boiling point. Works on surface tension of heavy water (D 2 O) are insufficient. A review of works on surface tension of both kinds of water is given

  17. FOX-2 Dependent Splicing of Ataxin-2 Transcript Is Affected by Ataxin-1 Overexpression

    Science.gov (United States)

    Welzel, Franziska; Kaehler, Christian; Isau, Melanie; Hallen, Linda; Lehrach, Hans; Krobitsch, Sylvia

    2012-01-01

    Alternative splicing is a fundamental posttranscriptional mechanism for controlling gene expression, and splicing defects have been linked to various human disorders. The splicing factor FOX-2 is part of a main protein interaction hub in a network related to human inherited ataxias, however, its impact remains to be elucidated. Here, we focused on the reported interaction between FOX-2 and ataxin-1, the disease-causing protein in spinocerebellar ataxia type 1. In this line, we further evaluated this interaction by yeast-2-hybrid analyses and co-immunoprecipitation experiments in mammalian cells. Interestingly, we discovered that FOX-2 localization and splicing activity is affected in the presence of nuclear ataxin-1 inclusions. Moreover, we observed that FOX-2 directly interacts with ataxin-2, a protein modulating spinocerebellar ataxia type 1 pathogenesis. Finally, we provide evidence that splicing of pre-mRNA of ataxin-2 depends on FOX-2 activity, since reduction of FOX-2 levels led to increased skipping of exon 18 in ataxin-2 transcripts. Most striking, we observed that ataxin-1 overexpression has an effect on this splicing event as well. Thus, our results demonstrate that FOX-2 is involved in splicing of ataxin-2 transcripts and that this splicing event is altered by overexpression of ataxin-1. PMID:22666429

  18. Alternative splicing, a new target to block cellular gene expression by poliovirus 2A protease

    International Nuclear Information System (INIS)

    Alvarez, Enrique; Castello, Alfredo; Carrasco, Luis; Izquierdo, Jose M.

    2011-01-01

    Highlights: → Novel role for poliovirus 2A protease as splicing modulator. → Poliovirus 2A protease inhibits the alternative splicing of pre-mRNAs. → Poliovirus 2A protease blocks the second catalytic step of splicing. -- Abstract: Viruses have developed multiple strategies to interfere with the gene expression of host cells at different stages to ensure their own survival. Here we report a new role for poliovirus 2A pro modulating the alternative splicing of pre-mRNAs. Expression of 2A pro potently inhibits splicing of reporter genes in HeLa cells. Low amounts of 2A pro abrogate Fas exon 6 skipping, whereas higher levels of protease fully abolish Fas and FGFR2 splicing. In vitro splicing of MINX mRNA using nuclear extracts is also strongly inhibited by 2A pro , leading to accumulation of the first exon and the lariat product containing the unspliced second exon. These findings reveal that the mechanism of action of 2A pro on splicing is to selectively block the second catalytic step.

  19. Alternative splicing, a new target to block cellular gene expression by poliovirus 2A protease

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez, Enrique, E-mail: ealvarez@cbm.uam.es [Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Nicolas Cabrera, 1 Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain); Castello, Alfredo; Carrasco, Luis; Izquierdo, Jose M. [Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Nicolas Cabrera, 1 Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain)

    2011-10-14

    Highlights: {yields} Novel role for poliovirus 2A protease as splicing modulator. {yields} Poliovirus 2A protease inhibits the alternative splicing of pre-mRNAs. {yields} Poliovirus 2A protease blocks the second catalytic step of splicing. -- Abstract: Viruses have developed multiple strategies to interfere with the gene expression of host cells at different stages to ensure their own survival. Here we report a new role for poliovirus 2A{sup pro} modulating the alternative splicing of pre-mRNAs. Expression of 2A{sup pro} potently inhibits splicing of reporter genes in HeLa cells. Low amounts of 2A{sup pro} abrogate Fas exon 6 skipping, whereas higher levels of protease fully abolish Fas and FGFR2 splicing. In vitro splicing of MINX mRNA using nuclear extracts is also strongly inhibited by 2A{sup pro}, leading to accumulation of the first exon and the lariat product containing the unspliced second exon. These findings reveal that the mechanism of action of 2A{sup pro} on splicing is to selectively block the second catalytic step.

  20. Decreased alternative splicing of estrogen receptor-α mRNA in the Alzheimer's disease brain

    NARCIS (Netherlands)

    Ishunina, Tatjana A.; Swaab, Dick F.

    2012-01-01

    In this study we identified 62 estrogen receptor alpha (ERα) mRNA splice variants in different human brain areas of Alzheimer's disease (AD) and control cases and classified them into 12 groups. Forty-eight of these splice forms were identified for the first time. The distribution of alternatively

  1. Features of 5'-splice-site efficiency derived from disease-causing mutations and comparative genomics

    DEFF Research Database (Denmark)

    Roca, Xavier; Olson, Andrew J; Rao, Atmakuri R

    2008-01-01

    Many human diseases, including Fanconi anemia, hemophilia B, neurofibromatosis, and phenylketonuria, can be caused by 5'-splice-site (5'ss) mutations that are not predicted to disrupt splicing, according to position weight matrices. By using comparative genomics, we identify pairwise dependencies...

  2. Reprogramming the Dynamin 2 mRNA by Spliceosome-mediated RNA Trans-splicing

    Directory of Open Access Journals (Sweden)

    Delphine Trochet

    2016-01-01

    Full Text Available Dynamin 2 (DNM2 is a large GTPase, ubiquitously expressed, involved in membrane trafficking and regulation of actin and microtubule cytoskeletons. DNM2 mutations cause autosomal dominant centronuclear myopathy which is a rare congenital myopathy characterized by skeletal muscle weakness and histopathological features including nuclear centralization in absence of regeneration. No curative treatment is currently available for the DNM2-related autosomal dominant centronuclear myopathy. In order to develop therapeutic strategy, we evaluated here the potential of Spliceosome-Mediated RNA Trans-splicing technology to reprogram the Dnm2-mRNA in vitro and in vivo in mice. We show that classical 3′-trans-splicing strategy cannot be considered as accurate therapeutic strategy regarding toxicity of the pre-trans-splicing molecules leading to low rate of trans-splicing in vivo. Thus, we tested alternative strategies devoted to prevent this toxicity and enhance frequency of trans-splicing events. We succeeded to overcome the toxicity through a 5′-trans-splicing strategy which also allows detection of trans-splicing events at mRNA and protein levels in vitro and in vivo. These results suggest that the Spliceosome-Mediated RNA Trans-splicing strategy may be used to reprogram mutated Dnm2-mRNA but highlight the potential toxicity linked to the molecular tools which have to be carefully investigated during preclinical development.

  3. Global analysis of aberrant pre-mRNA splicing in glioblastoma using exon expression arrays

    Directory of Open Access Journals (Sweden)

    Nixon Tamara J

    2008-05-01

    Full Text Available Abstract Background Tumor-predominant splice isoforms were identified during comparative in silico sequence analysis of EST clones, suggesting that global aberrant alternative pre-mRNA splicing may be an epigenetic phenomenon in cancer. We used an exon expression array to perform an objective, genome-wide survey of glioma-specific splicing in 24 GBM and 12 nontumor brain samples. Validation studies were performed using RT-PCR on glioma cell lines, patient tumor and nontumor brain samples. Results In total, we confirmed 14 genes with glioma-specific splicing; seven were novel events identified by the exon expression array (A2BP1, BCAS1, CACNA1G, CLTA, KCNC2, SNCB, and TPD52L2. Our data indicate that large changes (> 5-fold in alternative splicing are infrequent in gliomagenesis ( Conclusion While we observed some tumor-specific alternative splicing, the number of genes showing exclusive tumor-specific isoforms was on the order of tens, rather than the hundreds suggested previously by in silico mining. Given the important role of alternative splicing in neural differentiation, there may be selective pressure to maintain a majority of splicing events in order to retain glial-like characteristics of the tumor cells.

  4. Functional characterisation of an intron retaining K+ transporter of barley reveals intron-mediated alternate splicing

    KAUST Repository

    Shahzad, K.; Rauf, M.; Ahmed, M.; Malik, Z. A.; Habib, I.; Ahmed, Z.; Mahmood, K.; Ali, R.; Masmoudi, K.; Lemtiri-Chlieh, Fouad; Gehring, Christoph A; Berkowitz, G. A.; Saeed, N. A.

    2015-01-01

    Intron retention in transcripts and the presence of 5 and 3 splice sites within these introns mediate alternate splicing, which is widely observed in animals and plants. Here, functional characterisation of the K+ transporter, HvHKT2;1, with stably

  5. Identification of a novel function of CX-4945 as a splicing regulator.

    Directory of Open Access Journals (Sweden)

    Hyeongki Kim

    Full Text Available Alternative splicing is a nearly ubiquitous versatile process that controls gene expression and creates numerous protein isoforms with different functions from a single gene. The significance of alternative splicing has been confirmed by the increasing number of human diseases that are caused by misregulation of splicing events. Very few compounds, however, have been reported to act as inhibitors of alternative splicing, and their potential clinical use needs to be evaluated. Here, we report that CX-4945, a previously well-characterized inhibitor of casein kinase 2 (CK2 and a molecule currently in clinical trials (Phase II for cancer treatment, regulates splicing in mammalian cells in a CK2-independent manner. Transcriptome-wide analysis using exon array also showed a widespread alteration in alternative splicing of numerous genes. We found that CX-4945 potently inhibits the Cdc2-like kinases (Clks in vitro and in turn, leads to suppression of the phosphorylation of serine/arginine-rich (SR proteins in mammalian cells. Surprisingly, the overall efficacy of CX-4945 on Clks (IC50 = 3-90 nM was stronger than that of TG-003, the strongest inhibitor reported to date. Of the Clks, Clk2 was most strongly inhibited by CX-4945 in an ATP-competitive manner. Our research revealed an unexpected activity of the drug candidate CX-4945 as a potent splicing modulator and also suggested a potential application for therapy of diseases caused by abnormal splicing.

  6. Alternative splicing in colon, bladder, and prostate cancer identified by exon-array analysis

    DEFF Research Database (Denmark)

    Thorsen, Kasper; Sørensen, Karina D.; Brems-Eskildsen, Anne Sofie

    2008-01-01

    , PIK4CB, TPM1, and VCL). The validated tumor-specific splicing alterations were highly consistent, enabling clear separation of normal and cancer samples and in some cases even of different tumor stages. A subset of the tumor-specific splicing alterations (ACTN1, CALD1, and VCL) was found in all three...

  7. The RNA splicing factor ASF/SF2 inhibits human topoisomerase I mediated DNA relaxation

    DEFF Research Database (Denmark)

    Andersen, Félicie Faucon; Tange, Thomas Ø.; Sinnathamby, Thayaline

    2002-01-01

    Human topoisomerase I interacts with and phosphorylates the SR-family of RNA splicing factors, including ASF/SF2, and has been suggested to play an important role in the regulation of RNA splicing. Here we present evidence to support the theory that the regulation can go the other way around...

  8. Identification of Alternative Splice Variants Using Unique Tryptic Peptide Sequences for Database Searches.

    Science.gov (United States)

    Tran, Trung T; Bollineni, Ravi C; Strozynski, Margarita; Koehler, Christian J; Thiede, Bernd

    2017-07-07

    Alternative splicing is a mechanism in eukaryotes by which different forms of mRNAs are generated from the same gene. Identification of alternative splice variants requires the identification of peptides specific for alternative splice forms. For this purpose, we generated a human database that contains only unique tryptic peptides specific for alternative splice forms from Swiss-Prot entries. Using this database allows an easy access to splice variant-specific peptide sequences that match to MS data. Furthermore, we combined this database without alternative splice variant-1-specific peptides with human Swiss-Prot. This combined database can be used as a general database for searching of LC-MS data. LC-MS data derived from in-solution digests of two different cell lines (LNCaP, HeLa) and phosphoproteomics studies were analyzed using these two databases. Several nonalternative splice variant-1-specific peptides were found in both cell lines, and some of them seemed to be cell-line-specific. Control and apoptotic phosphoproteomes from Jurkat T cells revealed several nonalternative splice variant-1-specific peptides, and some of them showed clear quantitative differences between the two states.

  9. Widespread Inhibition of Posttranscriptional Splicing Shapes the Cellular Transcriptome following Heat Shock

    Directory of Open Access Journals (Sweden)

    Reut Shalgi

    2014-06-01

    Full Text Available During heat shock and other proteotoxic stresses, cells regulate multiple steps in gene expression in order to globally repress protein synthesis and selectively upregulate stress response proteins. Splicing of several mRNAs is known to be inhibited during heat stress, often meditated by SRp38, but the extent and specificity of this effect have remained unclear. Here, we examined splicing regulation genome-wide during heat shock in mouse fibroblasts. We observed widespread retention of introns in transcripts from ∼1,700 genes, which were enriched for tRNA synthetase, nuclear pore, and spliceosome functions. Transcripts with retained introns were largely nuclear and untranslated. However, a group of 580+ genes biased for oxidation reduction and protein folding functions continued to be efficiently spliced. Interestingly, these unaffected transcripts are mostly cotranscriptionally spliced under both normal and stress conditions, whereas splicing-inhibited transcripts are mostly spliced posttranscriptionally. Altogether, our data demonstrate widespread repression of splicing in the mammalian heat stress response, disproportionately affecting posttranscriptionally spliced genes.

  10. Intrasplicing coordinates alternative first exons with alternative splicing in the protein 4.1R gene

    Energy Technology Data Exchange (ETDEWEB)

    Conboy, John G.; Parra, Marilyn K.; Tan, Jeff S.; Mohandas, Narla; Conboy, John G.

    2008-11-07

    In the protein 4.1R gene, alternative first exons splice differentially to alternative 3' splice sites far downstream in exon 2'/2 (E2'/2). We describe a novel intrasplicing mechanism by which exon 1A (E1A) splices exclusively to the distal E2'/2 acceptor via two nested splicing reactions regulated by novel properties of exon 1B (E1B). E1B behaves as an exon in the first step, using its consensus 5' donor to splice to the proximal E2'/2 acceptor. A long region of downstream intron is excised, juxtaposing E1B with E2'/2 to generate a new composite acceptor containing the E1B branchpoint/pyrimidine tract and E2 distal 3' AG-dinucleotide. Next, the upstream E1A splices over E1B to this distal acceptor, excising the remaining intron plus E1B and E2' to form mature E1A/E2 product. We mapped branch points for both intrasplicing reactions and demonstrated that mutation of the E1B 5' splice site or branchpoint abrogates intrasplicing. In the 4.1R gene, intrasplicing ultimately determines N-terminal protein structure and function. More generally, intrasplicing represents a new mechanism whereby alternative promoters can be coordinated with downstream alternative splicing.

  11. Bilateral tension pneumothorax related to acupuncture.

    Science.gov (United States)

    Tagami, Rumi; Moriya, Takashi; Kinoshita, Kosaku; Tanjoh, Katsuhisa

    2013-06-01

    We report on a patient with a rare case of bilateral tension pneumothorax that occurred after acupuncture. A 69-year-old large-bodied man, who otherwise had no risk factors for spontaneous pneumothorax, presented with chest pressure, cold sweats and shortness of breath. Immediately after bilateral pneumothorax had been identified on a chest radiograph in the emergency room, his blood pressure and percutaneous oxygen saturation suddenly decreased to 78 mm Hg and 86%, respectively. We confirmed deterioration in his cardiopulmonary status and diagnosed bilateral tension pneumothorax. We punctured his chest bilaterally and inserted chest tubes for drainage. His vital signs promptly recovered. After the bilateral puncture and drainage, we learnt that he had been treated with acupuncture on his upper back. We finally diagnosed a bilateral tension pneumothorax based on the symptoms that appeared 8 h after the acupuncture. Because the patient had no risk factors for spontaneous pneumothorax, no alternative diagnosis was proposed. We recommend that patients receiving acupuncture around the chest wall must be adequately informed of the possibility of complications and expected symptoms, as a definitive diagnosis can be difficult without complete information.

  12. Tension-induced binding of semiflexible biopolymers

    International Nuclear Information System (INIS)

    Benetatos, Panayotis; Heydt, Alice von der; Zippelius, Annette

    2014-01-01

    We investigate theoretically the effect of polymer tension on the collective behavior of reversibly binding cross-links. For this purpose, we employ a model of two weakly bending wormlike chains aligned in parallel by a tensile force, with a sequence of inter-chain binding sites regularly spaced along the contours. Reversible cross-links attach and detach at the sites with an affinity controlled by a chemical potential. In a mean-field approach, we calculate the free energy of the system and find the emergence of a free-energy barrier which controls the reversible (un)binding. The tension affects the conformational entropy of the chains which competes with the binding energy of the cross-links. This competition gives rise to a sudden increase in the fraction of bound sites as the tension increases. We show that this transition is related to the cross-over between weak and strong localization of a directed polymer in a pinning potential. The cross-over to the strongly bound state can be interpreted as a mechanism for force-stiffening which exceeds the capabilities of single-chain elasticity and thus available only to reversibly cross-linked polymers. (paper)

  13. Generalized surface tension bounds in vacuum decay

    Science.gov (United States)

    Masoumi, Ali; Paban, Sonia; Weinberg, Erick J.

    2018-02-01

    Coleman and De Luccia (CDL) showed that gravitational effects can prevent the decay by bubble nucleation of a Minkowski or AdS false vacuum. In their thin-wall approximation this happens whenever the surface tension in the bubble wall exceeds an upper bound proportional to the difference of the square roots of the true and false vacuum energy densities. Recently it was shown that there is another type of thin-wall regime that differs from that of CDL in that the radius of curvature grows substantially as one moves through the wall. Not only does the CDL derivation of the bound fail in this case, but also its very formulation becomes ambiguous because the surface tension is not well defined. We propose a definition of the surface tension and show that it obeys a bound similar in form to that of the CDL case. We then show that both thin-wall bounds are special cases of a more general bound that is satisfied for all bounce solutions with Minkowski or AdS false vacua. We discuss the limit where the parameters of the theory attain critical values and the bound is saturated. The bounce solution then disappears and a static planar domain wall solution appears in its stead. The scalar field potential then is of the form expected in supergravity, but this is only guaranteed along the trajectory in field space traced out by the bounce.

  14. Tension-induced binding of semiflexible biopolymers

    Science.gov (United States)

    Benetatos, Panayotis; von der Heydt, Alice; Zippelius, Annette

    2015-03-01

    We investigate theoretically the effect of polymer tension on the collective behaviour of reversible cross-links. We use a model of two parallel-aligned, weakly-bending wormlike chains with a regularly spaced sequence of binding sites subjected to a tensile force. Reversible cross-links attach and detach at the binding sites with an affinity controlled by a chemical potential. In a mean-field approach, we calculate the free energy of the system and we show the emergence of a free energy barrier which controls the reversible (un)binding. The tension affects the conformational entropy of the chains which competes with the binding energy of the cross-links. This competition gives rise to a sudden increase in the fraction of bound sites as the polymer tension increases. The force-induced first-order transition in the number of cross-links implies a sudden force-induced stiffening of the effective stretching modulus of the polymers. This mechanism may be relevant to the formation and stress-induced strengthening of stress fibers in the cytoskeleton. We acknowledge support by the Deutsche Forschungsgemeinschaft (DFG) via grant SFB-937/A1.

  15. Detection of low tension cosmic superstrings

    Science.gov (United States)

    Chernoff, David F.; Tye, S.-H. Henry

    2018-05-01

    Cosmic superstrings of string theory differ from conventional cosmic strings of field theory. We review how the physical and cosmological properties of the macroscopic string loops influence experimental searches for these relics from the epoch of inflation. The universe's average density of cosmic superstrings can easily exceed that of conventional cosmic strings having the same tension by two or more orders of magnitude. The cosmological behavior of the remnant superstring loops is qualitatively distinct because the string tension is exponentially smaller than the string scale in flux compactifications in string theory. Low tension superstring loops live longer, experience less recoil (rocket effect from the emission of gravitational radiation) and tend to cluster like dark matter in galaxies. Clustering enhances the string loop density with respect to the cosmological average in collapsed structures in the universe. The enhancement at the Sun's position is ~ 105. We develop a model encapsulating the leading order string theory effects, the current understanding of the string network loop production and the influence of cosmological structure formation suitable for forecasting the detection of superstring loops via optical microlensing, gravitational wave bursts and fast radio bursts. We evaluate the detection rate of bursts from cusps and kinks by LIGO- and LISA-like experiments. Clustering dominates rates for G μ 10‑14.2 (LIGO cusp), G μ>10‑15 (LISA cusp) and G μ>10‑ 14.1 (LISA kink).

  16. Metallurgical failure investigation of a pipe connector fracture of an expansion vessel; Werkstofftechnische Schadensuntersuchung des Abrisses einer Rohrverschraubung eines Ausgleichsbehaelters

    Energy Technology Data Exchange (ETDEWEB)

    Neidel, Andreas [Siemens AG, Power and Gas, Gas Turbines and Generators, Gasturbinenwerk Berlin (Germany). Werkstoffprueflabor

    2016-08-15

    A pipe connector of an expansion vessel of a safety heat exchanger was torn off in a test facility's natural gas compressor. From a material point of view, the cause of the damage is a fatigue fracture induced by pulsating bending stress. The fatigue fracture originated from both, the pipe's outer surface as well as from its inner surface, which is consistent with the given stress situation (pulsating bending stress). Material defects or welding-induced flaws were not observed. Corrosion, wear, or thermal overload which may have promoted the damage, were not observed either. The primary cause was a major design error. Cases of dynamic load were obviously not duly taken into account during designing, so that the free-swinging mass of the expansion vessel which was mounted to a pipe of a diameter of only half an inch and, furthermore, installed in an angle of 45 (additional static preload.), could cause the fatigue failure induced by pulsating bending stress in the zone of highest stresses at the transition of the expansion vessel and the the pipe connector due to dynamic operating loads which always occur in plants like these.

  17. Lithium hydride doped intermediate connector for high-efficiency and long-term stable tandem organic light-emitting diodes.

    Science.gov (United States)

    Ding, Lei; Tang, Xun; Xu, Mei-Feng; Shi, Xiao-Bo; Wang, Zhao-Kui; Liao, Liang-Sheng

    2014-10-22

    Lithium hydride (LiH) is employed as a novel n-dopant in the intermediate connector for tandem organic light-emitting diodes (OLEDs) because of its easy coevaporation with other electron transporting materials. The tandem OLEDs with two and three electroluminescent (EL) units connected by a combination of LiH doped 8-hydroxyquinoline aluminum (Alq3) and 1,4,5,8,9,11-hexaazatriphenylene-hexacarbonitrile (HAT-CN) demonstrate approximately 2-fold and 3-fold enhancement in current efficiency, respectively. In addition, no extra voltage drop across the intermediate connector is observed. Particularly, the lifetime (T75%) in the tandem OLED with two and three EL units is substantially improved by 3.8 times and 7.4 times, respectively. The doping effect of LiH into Alq3, the charge injection, and transport characteristics of LiH-doped Alq3 are further investigated by ultraviolet photoelectron spectroscopy (UPS) and X-ray photoemission spectroscopy (XPS).

  18. Verification of predicted alternatively spliced Wnt genes reveals two new splice variants (CTNNB1 and LRP5 and altered Axin-1 expression during tumour progression

    Directory of Open Access Journals (Sweden)

    Reich Jens G

    2006-06-01

    Full Text Available Abstract Background Splicing processes might play a major role in carcinogenesis and tumour progression. The Wnt pathway is of crucial relevance for cancer progression. Therefore we focussed on the Wnt/β-catenin signalling pathway in order to validate the expression of sequences predicted as alternatively spliced by bioinformatic methods. Splice variants of its key molecules were selected, which may be critical components for the understanding of colorectal tumour progression and may have the potential to act as biological markers. For some of the Wnt pathway genes the existence of splice variants was either proposed (e.g. β-Catenin and CTNNB1 or described only in non-colon tissues (e.g. GSK3β or hitherto not published (e.g. LRP5. Results Both splice variants – normal and alternative form – of all selected Wnt pathway components were found to be expressed in cell lines as well as in samples derived from tumour, normal and healthy tissues. All splice positions corresponded totally with the bioinformatical prediction as shown by sequencing. Two hitherto not described alternative splice forms (CTNNB1 and LRP5 were detected. Although the underlying EST data used for the bioinformatic analysis suggested a tumour-specific expression neither a qualitative nor a significant quantitative difference between the expression in tumour and healthy tissues was detected. Axin-1 expression was reduced in later stages and in samples from carcinomas forming distant metastases. Conclusion We were first to describe that splice forms of crucial genes of the Wnt-pathway are expressed in human colorectal tissue. Newly described splicefoms were found for β-Catenin, LRP5, GSK3β, Axin-1 and CtBP1. However, the predicted cancer specificity suggested by the origin of the underlying ESTs was neither qualitatively nor significant quantitatively confirmed. That let us to conclude that EST sequence data can give adequate hints for the existence of alternative splicing

  19. Nd:YAG-laser-based time-domain reflectometry measurements of the intrinsic reflection signature from PMMA fiber splices

    Science.gov (United States)

    Lawson, Christopher M.; Michael, Robert R., Jr.; Dressel, Earl M.; Harmony, David W.

    1991-12-01

    Optical time domain reflectometry (OTDR) measurements have been performed on polished polymethylmethacrylate (PMMA) plastic fiber splices. After the dominant splice reflection sources due to surface roughness, inexact index matching, and fiber core misalignment were eliminated, an intrinsic OTDR signature 3 - 8 dB above the Rayleigh backscatter floor remained with all tested fibers. This minimum splice reflectivity exhibits characteristics that are consistent with sub-surface polymer damage and can be used for detection of PMMA fiber splices.

  20. Identification of interleukin-26 in the dromedary camel (Camelus dromedarius): Evidence of alternative splicing and isolation of novel splice variants.

    Science.gov (United States)

    Premraj, Avinash; Nautiyal, Binita; Aleyas, Abi G; Rasool, Thaha Jamal

    2015-10-01

    Interleukin-26 (IL-26) is a member of the IL-10 family of cytokines. Though conserved across vertebrates, the IL-26 gene is functionally inactivated in a few mammals like rat, mouse and horse. We report here the identification, isolation and cloning of the cDNA of IL-26 from the dromedary camel. The camel cDNA contains a 516 bp open reading frame encoding a 171 amino acid precursor protein, including a 21 amino acid signal peptide. Sequence analysis revealed high similarity with other mammalian IL-26 homologs and the conservation of IL-10 cytokine family domain structure including key amino acid residues. We also report the identification and cloning of four novel transcript variants produced by alternative splicing at the Exon 3-Exon 4 regions of the gene. Three of the alternative splice variants had premature termination codons and are predicted to code for truncated proteins. The transcript variant 4 (Tv4) having an insertion of an extra 120 bp nucleotides in the ORF was predicted to encode a full length protein product with 40 extra amino acid residues. The mRNA transcripts of all the variants were identified in lymph node, where as fewer variants were observed in other tissues like blood, liver and kidney. The expression of Tv2 and Tv3 were found to be up regulated in mitogen induced camel peripheral blood mononuclear cells. IL-26-Tv2 expression was also induced in camel fibroblast cells infected with Camel pox virus in-vitro. The identification of the transcript variants of IL-26 from the dromedary camel is the first report of alternative splicing for IL-26 in a species in which the gene has not been inactivated. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. A directed approach for the identification of transcripts harbouring the spliced leader sequence and the effect of trans-splicing knockdown in Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Marina de Moraes Mourao

    2013-09-01

    Full Text Available Schistosomiasis is a major neglected tropical disease caused by trematodes from the genus Schistosoma. Because schistosomes exhibit a complex life cycle and numerous mechanisms for regulating gene expression, it is believed that spliced leader (SL trans-splicing could play an important role in the biology of these parasites. The purpose of this study was to investigate the function of trans-splicing in Schistosoma mansoni through analysis of genes that may be regulated by this mechanism and via silencing SL-containing transcripts through RNA interference. Here, we report our analysis of SL transcript-enriched cDNA libraries from different S. mansoni life stages. Our results show that the trans-splicing mechanism is apparently not associated with specific genes, subcellular localisations or life stages. In cross-species comparisons, even though the sets of genes that are subject to SL trans-splicing regulation appear to differ between organisms, several commonly shared orthologues were observed. Knockdown of trans-spliced transcripts in sporocysts resulted in a systemic reduction of the expression levels of all tested trans-spliced transcripts; however, the only phenotypic effect observed was diminished larval size. Further studies involving the findings from this work will provide new insights into the role of trans-splicing in the biology of S. mansoni and other organisms. All Expressed Sequence Tags generated in this study were submitted to dbEST as five different libraries. The accessions for each library and for the individual sequences are as follows: (i adult worms of mixed sexes (LIBEST_027999: JZ139310 - JZ139779, (ii female adult worms (LIBEST_028000: JZ139780 - JZ140379, (iii male adult worms (LIBEST_028001: JZ140380 - JZ141002, (iv eggs (LIBEST_028002: JZ141003 - JZ141497 and (v schistosomula (LIBEST_028003: JZ141498 - JZ141974.

  2. cis-Acting and trans-acting modulation of equine infectious anemia virus alternative RNA splicing

    International Nuclear Information System (INIS)

    Liao, Huey-Jane; Baker, Carl C.; Princler, Gerald L.; Derse, David

    2004-01-01

    Equine infectious anemia virus (EIAV), a lentivirus distantly related to HIV-1, encodes regulatory proteins, EIAV Tat (ETat) and Rev (ERev), from a four-exon mRNA. Exon 3 of the tat/rev mRNA contains a 30-nucleotide purine-rich element (PRE) which binds both ERev and SF2/ASF, a member of the SR family of RNA splicing factors. To better understand the role of this element in the regulation of EIAV pre-mRNA splicing, we quantified the effects of mutation or deletion of the PRE on exon 3 splicing in vitro and on alternative splicing in vivo. We also determined the branch point elements upstream of exons 3 and 4. In vitro splicing of exon 3 to exon 4 was not affected by mutation of the PRE, and addition of purified SR proteins enhanced splicing independently of the PRE. In vitro splicing of exon 2 to exon 3 was dependent on the PRE; under conditions of excess SR proteins, either the PRE or the 5' splice site of exon 3 was sufficient to activate splicing. We applied isoform-specific primers in real-time RT-PCR reactions to quantitatively analyze alternative splicing in cells transfected with rev-minus EIAV provirus constructs. In the context of provirus with wild-type exon 3, greater than 80% of the viral mRNAs were multiply spliced, and of these, less than 1% excluded exon 3. Deletion of the PRE resulted in a decrease in the relative amount of multiply spliced mRNA to about 40% of the total and approximately 39% of the viral mRNA excluded exon 3. Ectopic expression of ERev caused a decrease in the relative amount of multiply spliced mRNA to approximately 50% of the total and increased mRNAs that excluded exon 3 to about 4%. Over-expression of SF2/ASF in cells transfected with wild-type provirus constructs inhibited splicing but did not significantly alter exon 3 skipping

  3. Genetic variations and alternative splicing. The Glioma associated oncogene 1, GLI1.

    Directory of Open Access Journals (Sweden)

    Peter eZaphiropoulos

    2012-07-01

    Full Text Available Alternative splicing is a post-transcriptional regulatory process that is attaining stronger recognition as a modulator of gene expression. Alternative splicing occurs when the primary RNA transcript is differentially processed into more than one mature RNAs. This is the result of a variable definition/inclusion of the exons, the sequences that are excised from the primary RNA to form the mature RNAs. Consequently, RNA expression can generate a collection of differentially spliced RNAs, which may distinctly influence subsequent biological events, such as protein synthesis or other biomolecular interactions. Still the mechanisms that control exon definition and exon inclusion are not fully clarified. This mini-review highlights advances in this field as well as the impact of single nucleotide polymorphisms in affecting splicing decisions. The Glioma associated oncogene 1, GLI1, is taken as an example in addressing the role of nucleotide substitutions for splicing regulation.

  4. The Role of Alternative Splicing in the Control of Immune Homeostasis and Cellular Differentiation.

    Science.gov (United States)

    Yabas, Mehmet; Elliott, Hannah; Hoyne, Gerard F

    2015-12-22

    Alternative splicing of pre-mRNA helps to enhance the genetic diversity within mammalian cells by increasing the number of protein isoforms that can be generated from one gene product. This provides a great deal of flexibility to the host cell to alter protein function, but when dysregulation in splicing occurs this can have important impact on health and disease. Alternative splicing is widely used in the mammalian immune system to control the development and function of antigen specific lymphocytes. In this review we will examine the splicing of pre-mRNAs yielding key proteins in the immune system that regulate apoptosis, lymphocyte differentiation, activation and homeostasis, and discuss how defects in splicing can contribute to diseases. We will describe how disruption to trans-acting factors, such as heterogeneous nuclear ribonucleoproteins (hnRNPs), can impact on cell survival and differentiation in the immune system.

  5. SOAPsplice: genome-wide ab initio detection of splice junctions from RNA-Seq data

    Directory of Open Access Journals (Sweden)

    Songbo eHuang

    2011-07-01

    Full Text Available RNA-Seq, a method using next generation sequencing technologies to sequence the transcriptome, facilitates genome-wide analysis of splice junction sites. In this paper, we introduce SOAPsplice, a robust tool to detect splice junctions using RNA-Seq data without using any information of known splice junctions. SOAPsplice uses a novel two-step approach consisting of first identifying as many reasonable splice junction candidates as possible, and then, filtering the false positives with two effective filtering strategies. In both simulated and real datasets, SOAPsplice is able to detect many reliable splice junctions with low false positive rate. The improvement gained by SOAPsplice, when compared to other existing tools, becomes more obvious when the depth of sequencing is low. SOAPsplice is freely available at http://soap.genomics.org.cn/soapsplice.html.

  6. On splice site prediction using weight array models: a comparison of smoothing techniques

    International Nuclear Information System (INIS)

    Taher, Leila; Meinicke, Peter; Morgenstern, Burkhard

    2007-01-01

    In most eukaryotic genes, protein-coding exons are separated by non-coding introns which are removed from the primary transcript by a process called 'splicing'. The positions where introns are cut and exons are spliced together are called 'splice sites'. Thus, computational prediction of splice sites is crucial for gene finding in eukaryotes. Weight array models are a powerful probabilistic approach to splice site detection. Parameters for these models are usually derived from m-tuple frequencies in trusted training data and subsequently smoothed to avoid zero probabilities. In this study we compare three different ways of parameter estimation for m-tuple frequencies, namely (a) non-smoothed probability estimation, (b) standard pseudo counts and (c) a Gaussian smoothing procedure that we recently developed

  7. Coding potential of the products of alternative splicing in human.

    KAUST Repository

    Leoni, Guido

    2011-01-20

    BACKGROUND: Analysis of the human genome has revealed that as much as an order of magnitude more of the genomic sequence is transcribed than accounted for by the predicted and characterized genes. A number of these transcripts are alternatively spliced forms of known protein coding genes; however, it is becoming clear that many of them do not necessarily correspond to a functional protein. RESULTS: In this study we analyze alternative splicing isoforms of human gene products that are unambiguously identified by mass spectrometry and compare their properties with those of isoforms of the same genes for which no peptide was found in publicly available mass spectrometry datasets. We analyze them in detail for the presence of uninterrupted functional domains, active sites as well as the plausibility of their predicted structure. We report how well each of these strategies and their combination can correctly identify translated isoforms and derive a lower limit for their specificity, that is, their ability to correctly identify non-translated products. CONCLUSIONS: The most effective strategy for correctly identifying translated products relies on the conservation of active sites, but it can only be applied to a small fraction of isoforms, while a reasonably high coverage, sensitivity and specificity can be achieved by analyzing the presence of non-truncated functional domains. Combining the latter with an assessment of the plausibility of the modeled structure of the isoform increases both coverage and specificity with a moderate cost in terms of sensitivity.

  8. Coding potential of the products of alternative splicing in human.

    KAUST Repository

    Leoni, Guido; Le Pera, Loredana; Ferrè , Fabrizio; Raimondo, Domenico; Tramontano, Anna

    2011-01-01

    BACKGROUND: Analysis of the human genome has revealed that as much as an order of magnitude more of the genomic sequence is transcribed than accounted for by the predicted and characterized genes. A number of these transcripts are alternatively spliced forms of known protein coding genes; however, it is becoming clear that many of them do not necessarily correspond to a functional protein. RESULTS: In this study we analyze alternative splicing isoforms of human gene products that are unambiguously identified by mass spectrometry and compare their properties with those of isoforms of the same genes for which no peptide was found in publicly available mass spectrometry datasets. We analyze them in detail for the presence of uninterrupted functional domains, active sites as well as the plausibility of their predicted structure. We report how well each of these strategies and their combination can correctly identify translated isoforms and derive a lower limit for their specificity, that is, their ability to correctly identify non-translated products. CONCLUSIONS: The most effective strategy for correctly identifying translated products relies on the conservation of active sites, but it can only be applied to a small fraction of isoforms, while a reasonably high coverage, sensitivity and specificity can be achieved by analyzing the presence of non-truncated functional domains. Combining the latter with an assessment of the plausibility of the modeled structure of the isoform increases both coverage and specificity with a moderate cost in terms of sensitivity.

  9. Splicing Analysis of Exonic OCRL Mutations Causing Lowe Syndrome or Dent-2 Disease

    Directory of Open Access Journals (Sweden)

    Lorena Suarez-Artiles

    2018-01-01

    Full Text Available Mutations in the OCRL gene are associated with both Lowe syndrome and Dent-2 disease. Patients with Lowe syndrome present congenital cataracts, mental disabilities and a renal proximal tubulopathy, whereas patients with Dent-2 disease exhibit similar proximal tubule dysfunction but only mild, or no additional clinical defects. It is not yet understood why some OCRL mutations cause the phenotype of Lowe syndrome, while others develop the milder phenotype of Dent-2 disease. Our goal was to gain new insights into the consequences of OCRL exonic mutations on pre-mRNA splicing. Using predictive bioinformatics tools, we selected thirteen missense mutations and one synonymous mutation based on their potential effects on splicing regulatory elements or splice sites. These mutations were analyzed in a minigene splicing assay. Results of the RNA analysis showed that three presumed missense mutations caused alterations in pre-mRNA splicing. Mutation c.741G>T; p.(Trp247Cys generated splicing silencer sequences and disrupted splicing enhancer motifs that resulted in skipping of exon 9, while mutations c.2581G>A; p.(Ala861Thr and c.2581G>C; p.(Ala861Pro abolished a 5′ splice site leading to skipping of exon 23. Mutation c.741G>T represents the first OCRL exonic variant outside the conserved splice site dinucleotides that results in alteration of pre-mRNA splicing. Our results highlight the importance of evaluating the effects of OCRL exonic mutations at the mRNA level.

  10. Speaker and Observer Perceptions of Physical Tension during Stuttering.

    Science.gov (United States)

    Tichenor, Seth; Leslie, Paula; Shaiman, Susan; Yaruss, J Scott

    2017-01-01

    Speech-language pathologists routinely assess physical tension during evaluation of those who stutter. If speakers experience tension that is not visible to clinicians, then judgments of severity may be inaccurate. This study addressed this potential discrepancy by comparing judgments of tension by people who stutter and expert clinicians to determine if clinicians could accurately identify the speakers' experience of physical tension. Ten adults who stutter were audio-video recorded in two speaking samples. Two board-certified specialists in fluency evaluated the samples using the Stuttering Severity Instrument-4 and a checklist adapted for this study. Speakers rated their tension using the same forms, and then discussed their experiences in a qualitative interview so that themes related to physical tension could be identified. The degree of tension reported by speakers was higher than that observed by specialists. Tension in parts of the body that were less visible to the observer (chest, abdomen, throat) was reported more by speakers than by specialists. The thematic analysis revealed that speakers' experience of tension changes over time and that these changes may be related to speakers' acceptance of stuttering. The lack of agreement between speaker and specialist perceptions of tension suggests that using self-reports is a necessary component for supporting the accurate diagnosis of tension in stuttering. © 2018 S. Karger AG, Basel.

  11. Structural design significance of tension-tension fatigue data on composites

    Science.gov (United States)

    Grimes, G. C.

    1977-01-01

    Constant cycle tension-tension fatigue and related static tension data have been generated on six single composite material/orientation combinations and twenty-one hybrid composite material/orientation combinations. Anomalies are related to the temperature rise and stopped interval creep, whereas endurance limit stresses (runouts) are associated with static proportional limit values, when they occur, and internal damage. The significance of these room temperature-dry data on the design allowables and weight of aerodynamic structueres is discussed. Such structures are helicopter rotor blades and wing and horizontal stabilizer lower surfaces. Typical criteria for turning these data into preliminary allowables are shown, as are examples of such allowables developed from the data. These values are then compared to those that might be used if the structures were made of metal.

  12. Alternative splicing and nonsense-mediated decay of circadian clock genes under environmental stress conditions in Arabidopsis.

    Science.gov (United States)

    Kwon, Young-Ju; Park, Mi-Jeong; Kim, Sang-Gyu; Baldwin, Ian T; Park, Chung-Mo

    2014-05-19

    The circadian clock enables living organisms to anticipate recurring daily and seasonal fluctuations in their growth habitats and synchronize their biology to the environmental cycle. The plant circadian clock consists of multiple transcription-translation feedback loops that are entrained by environmental signals, such as light and temperature. In recent years, alternative splicing emerges as an important molecular mechanism that modulates the clock function in plants. Several clock genes are known to undergo alternative splicing in response to changes in environmental conditions, suggesting that the clock function is intimately associated with environmental responses via the alternative splicing of the clock genes. However, the alternative splicing events of the clock genes have not been studied at the molecular level. We systematically examined whether major clock genes undergo alternative splicing under various environmental conditions in Arabidopsis. We also investigated the fates of the RNA splice variants of the clock genes. It was found that the clock genes, including EARLY FLOWERING 3 (ELF3) and ZEITLUPE (ZTL) that have not been studied in terms of alternative splicing, undergo extensive alternative splicing through diverse modes of splicing events, such as intron retention, exon skipping, and selection of alternative 5' splice site. Their alternative splicing patterns were differentially influenced by changes in photoperiod, temperature extremes, and salt stress. Notably, the RNA splice variants of TIMING OF CAB EXPRESSION 1 (TOC1) and ELF3 were degraded through the nonsense-mediated decay (NMD) pathway, whereas those of other clock genes were insensitive to NMD. Taken together, our observations demonstrate that the major clock genes examined undergo extensive alternative splicing under various environmental conditions, suggesting that alternative splicing is a molecular scheme that underlies the linkage between the clock and environmental stress

  13. Alternative splicing and nonsense-mediated decay of circadian clock genes under environmental stress conditions in Arabidopsis

    Science.gov (United States)

    2014-01-01

    Background The circadian clock enables living organisms to anticipate recurring daily and seasonal fluctuations in their growth habitats and synchronize their biology to the environmental cycle. The plant circadian clock consists of multiple transcription-translation feedback loops that are entrained by environmental signals, such as light and temperature. In recent years, alternative splicing emerges as an important molecular mechanism that modulates the clock function in plants. Several clock genes are known to undergo alternative splicing in response to changes in environmental conditions, suggesting that the clock function is intimately associated with environmental responses via the alternative splicing of the clock genes. However, the alternative splicing events of the clock genes have not been studied at the molecular level. Results We systematically examined whether major clock genes undergo alternative splicing under various environmental conditions in Arabidopsis. We also investigated the fates of the RNA splice variants of the clock genes. It was found that the clock genes, including EARLY FLOWERING 3 (ELF3) and ZEITLUPE (ZTL) that have not been studied in terms of alternative splicing, undergo extensive alternative splicing through diverse modes of splicing events, such as intron retention, exon skipping, and selection of alternative 5′ splice site. Their alternative splicing patterns were differentially influenced by changes in photoperiod, temperature extremes, and salt stress. Notably, the RNA splice variants of TIMING OF CAB EXPRESSION 1 (TOC1) and ELF3 were degraded through the nonsense-mediated decay (NMD) pathway, whereas those of other clock genes were insensitive to NMD. Conclusion Taken together, our observations demonstrate that the major clock genes examined undergo extensive alternative splicing under various environmental conditions, suggesting that alternative splicing is a molecular scheme that underlies the linkage between the clock

  14. Cuerpo y subjetividad: materiales y tensiones

    OpenAIRE

    Cachorro, Gabriel

    2007-01-01

    En este artículo se efectúa un abordaje del tema cuerpo y subjetividad a través de un ejercicio exploratorio de sus materiales y tensiones. Las preguntas posibles de formular son: ¿Qué discusiones tenemos por debajo de la subjetividad corporal?, ¿cuáles son las raíces históricas de este tema?, ¿qué problemáticas lo atraviesan? La enunciación de estos interrogantes nos ayuda a establecer la posición de investigador y a explicitar los argumentos teóricos. Se desprende de esta propuest...

  15. Temporomandibular disorders and tension-type headache.

    Science.gov (United States)

    Mongini, Franco

    2007-12-01

    Pathologies currently defined as temporomandibular disorders may be different in nature. Temporomandibular joint (TMJ) disorders and craniofacial and cervical myogenous pain (MP) are distinct pathologies but may be superimposed and share some etiologic factors. Tension-type headache (TTH) may often be associated with craniofacial and cervical pain, and the same pharmacologic and nonpharmacologic treatment may be efficacious for both. Psychiatric comorbidity (depression and/or anxiety disorder) is less frequent in sheer TMJ disorders, compared with MP and TTH. A screening for the presence of an underlying psychiatric disorder should be part of the clinical evaluation in patients suffering from headache and facial pain.

  16. Small-Bolt Torque-Tension Tester

    Science.gov (United States)

    Posey, Alan J.

    2009-01-01

    The device described here measures the torque-tension relationship for fasteners as small as #0. The small-bolt tester consists of a plate of high-strength steel into which three miniature load cells are recessed. The depth of the recess is sized so that the three load cells can be shimmed, the optimum height depending upon the test hardware. The three miniature load cells are arranged in an equilateral triangular configuration with the test bolt aligned with the centroid of the three. This is a kinematic arrangement.

  17. Superficial tension: experimental model with simple materials

    Directory of Open Access Journals (Sweden)

    Tintori Ferreira, María Alejandra

    2012-09-01

    Full Text Available In this work appears a didactic offer based on an experimental activity using materials of very low cost, orientated to achieving that the student understand and interpret the phenomenon of superficial tension together with the importance of the modeling in sciences. It has as principal aim of education bring the student over to the mechanics of the static fluids and the intermolecular forces, combining scientific contents with questions near to the student what provides an additional motivation to the reflection of the scientific investigation.

  18. Effective tension and fluctuations in active membranes

    OpenAIRE

    Loubet, Bastien; Seifert, Udo; Lomholt, Michael Andersen

    2011-01-01

    We calculate the fluctuation spectrum of the shape of a lipid vesicle or cell exposed to a nonthermal source of noise. In particular we take into account constraints on the membrane area and the volume of fluid that it encapsulates when obtaining expressions for the dependency of the membrane tension on the noise. We then investigate three possible origins of the non-thermal noise taken from the literature: A direct force, which models an external medium pushing on the membrane. A curvature f...

  19. Evaluation of the role of Care Sport Connectors in connecting primary care, sport, and physical activity, and residents' participation in the Netherlands

    NARCIS (Netherlands)

    Smit, E.; Leenaars, K.E.F.; Wagemakers, M.A.E.; Molleman, G.R.M.; Koelen, M.A.; Velden, Van Der J.

    2015-01-01

    Background: The number of people with one or more chronic diseases is increasing, but this trend could be reduced by promoting physical activity. Therefore, in 2012, the Dutch Ministry of Health, Welfare, and Sport introduced Care Sport Connectors (CSCs), to whom a broker role has been ascribed.

  20. Dr Marta Bajko in front of the Gold pated "half-moon" connector of an LHC dipole Diode in SM18.

    CERN Multimedia

    Maximilien Brice

    2012-01-01

    Photo 1 : Cold Diode for the LHC superconducting dipoles protection. Prepared for cryogenic powering test OFF line in SM18. - Photo 2 : A gold plated bus bar of an LHC dipole diode ready for cryogenic powering test in Sm18. - Photo 3 : The gold pated “ half-moon” connector of an LHC dipole diode. Ready for a cryogenic powering test in SM18.

  1. Novel Fiber Optic Sensor Probe with a Pair of Highly Reflected Connectors and a Vessel of Water Absorption Material for Water Leak Detection

    Directory of Open Access Journals (Sweden)

    Tae-Sik Cho

    2012-08-01

    Full Text Available The use of a fiber optic quasi-distributed sensing technique for detecting the location and severity of water leakage is suggested. A novel fiber optic sensor probe is devised with a vessel of water absorption material called as water combination soil (WCS located between two highly reflected connectors: one is a reference connector and the other is a sensing connector. In this study, the sensing output is calculated from the reflected light signals of the two connectors. The first reflected light signal is a reference and the second is a sensing signal which is attenuated by the optical fiber bending loss due to the WCS expansion absorbing water. Also, the bending loss of each sensor probe is determined by referring to the total number of sensor probes and the total power budget of an entire system. We have investigated several probe characteristics to show the design feasibility of the novel fiber sensor probe. The effects of vessel sizes of the probes on the water detection sensitivity are studied. The largest vessel probe provides the highest sensitivity of 0.267 dB/mL, while the smallest shows relatively low sensitivity of 0.067 dB/mL, and unstable response. The sensor probe with a high output value provides a high sensitivity with various detection levels while the number of total installable sensor probes decreases.

  2. Novel fiber optic sensor probe with a pair of highly reflected connectors and a vessel of water absorption material for water leak detection.

    Science.gov (United States)

    Cho, Tae-Sik; Choi, Ki-Sun; Seo, Dae-Cheol; Kwon, Il-Bum; Lee, Jung-Ryul

    2012-01-01

    The use of a fiber optic quasi-distributed sensing technique for detecting the location and severity of water leakage is suggested. A novel fiber optic sensor probe is devised with a vessel of water absorption material called as water combination soil (WCS) located between two highly reflected connectors: one is a reference connector and the other is a sensing connector. In this study, the sensing output is calculated from the reflected light signals of the two connectors. The first reflected light signal is a reference and the second is a sensing signal which is attenuated by the optical fiber bending loss due to the WCS expansion absorbing water. Also, the bending loss of each sensor probe is determined by referring to the total number of sensor probes and the total power budget of an entire system. We have investigated several probe characteristics to show the design feasibility of the novel fiber sensor probe. The effects of vessel sizes of the probes on the water detection sensitivity are studied. The largest vessel probe provides the highest sensitivity of 0.267 dB/mL, while the smallest shows relatively low sensitivity of 0.067 dB/mL, and unstable response. The sensor probe with a high output value provides a high sensitivity with various detection levels while the number of total installable sensor probes decreases.

  3. Supplementary Material for: Herboxidiene triggers splicing repression and abiotic stress responses in plants

    KAUST Repository

    Alshareef, Sahar; Ling, Yu; Butt, Haroon; Mariappan, Kiruthiga; Benhamed, Moussa; Mahfouz, Magdy

    2017-01-01

    Abstract Background Constitutive and alternative splicing of pre-mRNAs from multiexonic genes controls the diversity of the proteome; these precisely regulated processes also fine-tune responses to cues related to growth, development, and stresses. Small-molecule inhibitors that perturb splicing provide invaluable tools for use as chemical probes to uncover the molecular underpinnings of splicing regulation and as potential anticancer compounds. Results Here, we show that herboxidiene (GEX1A) inhibits both constitutive and alternative splicing. Moreover, GEX1A activates genome-wide transcriptional patterns involved in abiotic stress responses in plants. GEX1A treatment -activated ABA-inducible promoters, and led to stomatal closure. Interestingly, GEX1A and pladienolide B (PB) elicited similar cellular changes, including alterations in the patterns of transcription and splicing, suggesting that these compounds might target the same spliceosome complex in plant cells. Conclusions Our study establishes GEX1A as a potent splicing inhibitor in plants that can be used to probe the assembly, dynamics, and molecular functions of the spliceosome and to study the interplay between splicing stress and abiotic stresses, as well as having potential biotechnological applications.

  4. TBX3 regulates splicing in vivo: a novel molecular mechanism for Ulnar-mammary syndrome.

    Directory of Open Access Journals (Sweden)

    Pavan Kumar P

    2014-03-01

    Full Text Available TBX3 is a member of the T-box family of transcription factors with critical roles in development, oncogenesis, cell fate, and tissue homeostasis. TBX3 mutations in humans cause complex congenital malformations and Ulnar-mammary syndrome. Previous investigations into TBX3 function focused on its activity as a transcriptional repressor. We used an unbiased proteomic approach to identify TBX3 interacting proteins in vivo and discovered that TBX3 interacts with multiple mRNA splicing factors and RNA metabolic proteins. We discovered that TBX3 regulates alternative splicing in vivo and can promote or inhibit splicing depending on context and transcript. TBX3 associates with alternatively spliced mRNAs and binds RNA directly. TBX3 binds RNAs containing TBX binding motifs, and these motifs are required for regulation of splicing. Our study reveals that TBX3 mutations seen in humans with UMS disrupt its splicing regulatory function. The pleiotropic effects of TBX3 mutations in humans and mice likely result from disrupting at least two molecular functions of this protein: transcriptional regulation and pre-mRNA splicing.

  5. TBX3 regulates splicing in vivo: a novel molecular mechanism for Ulnar-mammary syndrome.

    Science.gov (United States)

    Kumar P, Pavan; Franklin, Sarah; Emechebe, Uchenna; Hu, Hao; Moore, Barry; Lehman, Chris; Yandell, Mark; Moon, Anne M

    2014-03-01

    TBX3 is a member of the T-box family of transcription factors with critical roles in development, oncogenesis, cell fate, and tissue homeostasis. TBX3 mutations in humans cause complex congenital malformations and Ulnar-mammary syndrome. Previous investigations into TBX3 function focused on its activity as a transcriptional repressor. We used an unbiased proteomic approach to identify TBX3 interacting proteins in vivo and discovered that TBX3 interacts with multiple mRNA splicing factors and RNA metabolic proteins. We discovered that TBX3 regulates alternative splicing in vivo and can promote or inhibit splicing depending on context and transcript. TBX3 associates with alternatively spliced mRNAs and binds RNA directly. TBX3 binds RNAs containing TBX binding motifs, and these motifs are required for regulation of splicing. Our study reveals that TBX3 mutations seen in humans with UMS disrupt its splicing regulatory function. The pleiotropic effects of TBX3 mutations in humans and mice likely result from disrupting at least two molecular functions of this protein: transcriptional regulation and pre-mRNA splicing.

  6. A Systems-Level Analysis Reveals Circadian Regulation of Splicing in Colorectal Cancer.

    Science.gov (United States)

    El-Athman, Rukeia; Fuhr, Luise; Relógio, Angela

    2018-06-20

    Accumulating evidence points to a significant role of the circadian clock in the regulation of splicing in various organisms, including mammals. Both dysregulated circadian rhythms and aberrant pre-mRNA splicing are frequently implicated in human disease, in particular in cancer. To investigate the role of the circadian clock in the regulation of splicing in a cancer progression context at the systems-level, we conducted a genome-wide analysis and compared the rhythmic transcriptional profiles of colon carcinoma cell lines SW480 and SW620, derived from primary and metastatic sites of the same patient, respectively. We identified spliceosome components and splicing factors with cell-specific circadian expression patterns including SRSF1, HNRNPLL, ESRP1, and RBM 8A, as well as altered alternative splicing events and circadian alternative splicing patterns of output genes (e.g., VEGFA, NCAM1, FGFR2, CD44) in our cellular model. Our data reveals a remarkable interplay between the circadian clock and pre-mRNA splicing with putative consequences in tumor progression and metastasis. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Misregulation of Alternative Splicing in a Mouse Model of Rett Syndrome.

    Directory of Open Access Journals (Sweden)

    Ronghui Li

    2016-06-01

    Full Text Available Mutations in the human MECP2 gene cause Rett syndrome (RTT, a severe neurodevelopmental disorder that predominantly affects girls. Despite decades of work, the molecular function of MeCP2 is not fully understood. Here we report a systematic identification of MeCP2-interacting proteins in the mouse brain. In addition to transcription regulators, we found that MeCP2 physically interacts with several modulators of RNA splicing, including LEDGF and DHX9. These interactions are disrupted by RTT causing mutations, suggesting that they may play a role in RTT pathogenesis. Consistent with the idea, deep RNA sequencing revealed misregulation of hundreds of splicing events in the cortex of Mecp2 knockout mice. To reveal the functional consequence of altered RNA splicing due to the loss of MeCP2, we focused on the regulation of the splicing of the flip/flop exon of Gria2 and other AMPAR genes. We found a significant splicing shift in the flip/flop exon toward the flop inclusion, leading to a faster decay in the AMPAR gated current and altered synaptic transmission. In summary, our study identified direct physical interaction between MeCP2 and splicing factors, a novel MeCP2 target gene, and established functional connection between a specific RNA splicing change and synaptic phenotypes in RTT mice. These results not only help our understanding of the molecular function of MeCP2, but also reveal potential drug targets for future therapies.

  8. Genome wide identification of aberrant alternative splicing events in myotonic dystrophy type 2.

    Science.gov (United States)

    Perfetti, Alessandra; Greco, Simona; Fasanaro, Pasquale; Bugiardini, Enrico; Cardani, Rosanna; Garcia-Manteiga, Jose M; Manteiga, Jose M Garcia; Riba, Michela; Cittaro, Davide; Stupka, Elia; Meola, Giovanni; Martelli, Fabio

    2014-01-01

    Myotonic dystrophy type 2 (DM2) is a genetic, autosomal dominant disease due to expansion of tetraplet (CCTG) repetitions in the first intron of the ZNF9/CNBP gene. DM2 is a multisystemic disorder affecting the skeletal muscle, the heart, the eye and the endocrine system. According to the proposed pathological mechanism, the expanded tetraplets have an RNA toxic effect, disrupting the splicing of many mRNAs. Thus, the identification of aberrantly spliced transcripts is instrumental for our understanding of the molecular mechanisms underpinning the disease. The aim of this study was the identification of new aberrant alternative splicing events in DM2 patients. By genome wide analysis of 10 DM2 patients and 10 controls (CTR), we identified 273 alternative spliced exons in 218 genes. While many aberrant splicing events were already identified in the past, most were new. A subset of these events was validated by qPCR assays in 19 DM2 and 15 CTR subjects. To gain insight into the molecular pathways involving the identified aberrantly spliced genes, we performed a bioinformatics analysis with Ingenuity system. This analysis indicated a deregulation of development, cell survival, metabolism, calcium signaling and contractility. In conclusion, our genome wide analysis provided a database of aberrant splicing events in the skeletal muscle of DM2 patients. The affected genes are involved in numerous pathways and networks important for muscle physio-pathology, suggesting that the identified variants may contribute to DM2 pathogenesis.

  9. Judging the similarity of soundscapes does not require categorization: evidence from spliced stimuli.

    Science.gov (United States)

    Aucouturier, Jean-Julien; Defreville, Boris

    2009-04-01

    This study uses an audio signal transformation, splicing, to create an experimental situation where human listeners judge the similarity of audio signals, which they cannot easily categorize. Splicing works by segmenting audio signals into 50-ms frames, then shuffling and concatenating these frames back in random order. Splicing a signal masks the identification of the categories that it normally elicits: For instance, human participants cannot easily identify the sound of cars in a spliced recording of a city street. This study compares human performance on both normal and spliced recordings of soundscapes and music. Splicing is found to degrade human similarity performance significantly less for soundscapes than for music: When two spliced soundscapes are judged similar to one another, the original recordings also tend to sound similar. This establishes that humans are capable of reconstructing consistent similarity relations between soundscapes without relying much on the identification of the natural categories associated with such signals, such as their constituent sound sources. This finding contradicts previous literature and points to new ways to conceptualize the different ways in which humans perceive soundscapes and music.

  10. Postnatal Expression of V2 Vasopressin Receptor Splice Variants in the Rat Cerebellum

    Science.gov (United States)

    Vargas, Karina J.; Sarmiento, José M.; Ehrenfeld, Pamela; Añazco, Carolina C.; Villanueva, Carolina I.; Carmona, Pamela L.; Brenet, Marianne; Navarro, Javier; Müller-Esterl, Werner; Figueroa, Carlos D.; González, Carlos B.

    2010-01-01

    The V2 vasopressin receptor gene contains an alternative splice site in exon-3, which leads to the generation of two splice variants (V2a and V2b) first identified in the kidney. The open reading frame of the alternatively spliced V2b transcripten codes a truncated receptor, showing the same amino acid sequence as the canonical V2a receptor up to the 6th transmembrane segment, but displaying a distinct sequence to the corresponding 7th transmembrane segment and C-terminal domain relative to the V2a receptor. Here, we demonstrate the postnatal expression of V2a and V2b variants in the rat cerebellum. Most importantly, we showed by in situ hybridization and immunocytochemistry that both V2 splice variants were preferentially expressed in Purkinje cells, from early to late postnatal development. In addition, both variants were transiently expressed in the neuroblastic external granule cells and Bergmann fibers. These results indicate that the cellular distributions of both splice variants are developmentally regulated, and suggest that the transient expression of the V2 receptor is involved in the mechanisms of cerebellar cytodifferentiation by AVP. Finally, transfected CHO-K1 .expressing similar amounts of both V2 splice variants, as that found in the cerebellum, showed a significant reduction in the surface expression of V2a receptors, suggesting that the differential expression of the V2 splice variants regulate the vasopressin signaling in the cerebellum. PMID:19281786

  11. The role of polypyrimidine tract-binding proteins and other hnRNP proteins in plant splicing regulation

    Directory of Open Access Journals (Sweden)

    Andreas eWachter

    2012-05-01

    Full Text Available Alternative precursor mRNA splicing is a widespread phenomenon in multicellular eukaryotes and represents a major means for functional expansion of the transcriptome. While several recent studies have revealed an important link between splicing regulation and fundamental biological processes in plants, many important aspects, such as the underlying splicing regulatory mechanisms, are so far not well understood. Splicing decisions are in general based on a splicing code that is determined by the dynamic interplay of splicing-controlling factors and cis-regulatory elements. Several members of the group of heterogeneous nuclear ribonucleoprotein (hnRNP proteins are well-known regulators of splicing in animals and the comparatively few reports on some of their plant homologues revealed similar functions. This also applies to polypyrimidine tract-binding proteins (PTBs, a thoroughly investigated class of hnRNP proteins with splicing regulatory functions in both animals and plants. Further examples from plants are auto- and cross-regulatory splicing circuits of glycine-rich RNA-binding proteins (GRPs and splicing enhancement by oligouridylatebinding proteins. Besides their role in defining splice site choice, hnRNP proteins are also involved in multiple other steps of nucleic acid metabolism, highlighting the functional versatility of this group of proteins in higher eukaryotes.

  12. A method of predicting changes in human gene splicing induced by genetic variants in context of cis-acting elements

    Directory of Open Access Journals (Sweden)

    Hicks Chindo

    2010-01-01

    Full Text Available Abstract Background Polymorphic variants and mutations disrupting canonical splicing isoforms are among the leading causes of human hereditary disorders. While there is a substantial evidence of aberrant splicing causing Mendelian diseases, the implication of such events in multi-genic disorders is yet to be well understood. We have developed a new tool (SpliceScan II for predicting the effects of genetic variants on splicing and cis-regulatory elements. The novel Bayesian non-canonical 5'GC splice site (SS sensor used in our tool allows inference on non-canonical exons. Results Our tool performed favorably when compared with the existing methods in the context of genes linked to the Autism Spectrum Disorder (ASD. SpliceScan II was able to predict more aberrant splicing isoforms triggered by the mutations, as documented in DBASS5 and DBASS3 aberrant splicing databases, than other existing methods. Detrimental effects behind some of the polymorphic variations previously associated with Alzheimer's and breast cancer could be explained by changes in predicted splicing patterns. Conclusions We have developed SpliceScan II, an effective and sensitive tool for predicting the detrimental effects of genomic variants on splicing leading to Mendelian and complex hereditary disorders. The method could potentially be used to screen resequenced patient DNA to identify de novo mutations and polymorphic variants that could contribute to a genetic disorder.

  13. Fine-scale variation and genetic determinants of alternative splicing across individuals.

    Directory of Open Access Journals (Sweden)

    Jasmin Coulombe-Huntington

    2009-12-01

    Full Text Available Recently, thanks to the increasing throughput of new technologies, we have begun to explore the full extent of alternative pre-mRNA splicing (AS in the human transcriptome. This is unveiling a vast layer of complexity in isoform-level expression differences between individuals. We used previously published splicing sensitive microarray data from lymphoblastoid cell lines to conduct an in-depth analysis on splicing efficiency of known and predicted exons. By combining publicly available AS annotation with a novel algorithm designed to search for AS, we show that many real AS events can be detected within the usually unexploited, speculative majority of the array and at significance levels much below standard multiple-testing thresholds, demonstrating that the extent of cis-regulated differential splicing between individuals is potentially far greater than previously reported. Specifically, many genes show subtle but significant genetically controlled differences in splice-site usage. PCR validation shows that 42 out of 58 (72% candidate gene regions undergo detectable AS, amounting to the largest scale validation of isoform eQTLs to date. Targeted sequencing revealed a likely causative SNP in most validated cases. In all 17 incidences where a SNP affected a splice-site region, in silico splice-site strength modeling correctly predicted the direction of the micro-array and PCR results. In 13 other cases, we identified likely causative SNPs disrupting predicted splicing enhancers. Using Fst and REHH analysis, we uncovered significant evidence that 2 putative causative SNPs have undergone recent positive selection. We verified the effect of five SNPs using in vivo minigene assays. This study shows that splicing differences between individuals, including quantitative differences in isoform ratios, are frequent in human populations and that causative SNPs can be identified using in silico predictions. Several cases affected disease-relevant genes and

  14. TGFβ1-mediated expression and alternative splicing of Fibronectin Extra Domain A in human podocyte culture.

    Science.gov (United States)

    Madne, Tarunkumar Hemraj; Dockrell, Mark Edward Carl

    2018-02-28

    Alternative splicing is a fundamental phenomenon to build protein diversity in health and diseases. Extra Domain A+ Fibronectin (EDA+Fn) is an alternatively spliced form of fibronectin protein present in the extra cellular matrix (ECM) in renal fibrosis. Podocytes are spectacular cell type and play a key role in filtration and synthesise ECM proteins in renal physiology and pathology. TGFβ1 is a strong stimulator of ECM proteins in renal injury. In this study, we have investigated alternative splicing of EDA+ Fn in human podocytes in response to TGFβ1. We have performed western blotting and immunofluorescence to characterise the expression of the EDA+Fn protein, real-time PCR for RNA expression and RT-PCR to look for alternative splicing of EDA+Fn in conditionally immortalised human podocytes culture.We used TGFβ1 as a stimulator and SB431542 and SRPIN340 for inhibitory studies. In this work, for the first time we have demonstrated in human podocytes culture EDA+Fn is expressed in the basal condition and TGFβ1 2.5ng/ml induced the Fn mRNA and EDA+Fn protein expression demonstrated by real-time PCR, western blotting and immunofluorescence. TGFβ1 2.5ng/ml induced the alternative splicing of EDA+Fn shown by conventional RT-PCR. Studies with ALK5 inhibitor SB431542 and SRPIN340 show that TGFβ1 induced alternative splicing of EDA+Fn was by the ALK5 receptor and the SR proteins.  In human podocytes culture, alternative splicing of EDA+Fn occurs at basal conditions and TGFβ1 further induced the alternative splicing of EDA+Fn via ALK5 receptor activation and SR proteins. This is the first evidence of basal and TGFβ1 mediated alternative splicing of EDA+Fn in human podocytes culture.

  15. Diffusion MR imaging with PSIF and SPLICE. Experiences in phantom studies and the central nervous system

    International Nuclear Information System (INIS)

    Uchikoshi, Masato; Ueda, Takashi; Kaji, Yasushi

    2001-01-01

    Studies have shown that diffusion MR imaging is a reliable method for the diagnosis of central nervous system diseases, especially acute cerebral infarction. Although echo planar imaging (EPI) is a promising tool for that purpose, it is vulnerable to susceptibility artifacts that are responsible for image distortion or signal loss. Our purpose in this study was to evaluate the usefulness of diffusion MR imaging with PSIF (reversed fast imaging SSFP) and split acquisition of fast-spin-echo signals for diffusion imaging (SPLICE) in the central nervous system (CNS). First, PSIF and SPLICE were applied to the phantoms. Each phantom, including acetone, acetic acid, and water, was analyzed for apparent diffusion coefficient (ADC) based on SPLICE and for diffusion-related coefficient (DRC) based on PSIF. The ADCs based on SPLICE were 4.36±0.89 x 10 -3 mm 2 /sec, 1.25±0.04 x 10 -3 mm 2 /sec, and 2.35±0.04 x 10 -3 mm 2 /sec, and the DRCs based on PSIF were 0.353±0.25, 0.178±0.07, and 0.273±0.018 for acetone, acetic acid, and water, respectively. These calculated ADCs based on SPLICE were well correlated with known diffusion coefficients, showing a correlation coefficient of 0.995. Second, PSIF and SPLICE were applied to the CNS. The advantage of PSIF and SPLICE was that susceptibility artifacts were reduced in the images of spinal cord and brain stem. PSIF was especially useful for diffusion MR imaging in the spinal cord. The disadvantage of SPLICE was the decreased SN ratio. We conclude that PSIF or SPLICE may be helpful when EPI diffusion MR imaging is insufficient. (author)

  16. 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].

  17. Splice-Switching Therapy for Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Katharina E. Meijboom

    2017-06-01

    Full Text Available Spinal muscular atrophy (SMA is a genetic disorder with severity ranging from premature death in infants to restricted motor function in adult life. Despite the genetic cause of this disease being known for over twenty years, only recently has a therapy been approved to treat the most severe form of this disease. Here we discuss the genetic basis of SMA and the subsequent studies that led to the utilization of splice switching oligonucleotides to enhance production of SMN protein, which is absent in patients, through a mechanism of exon inclusion into the mature mRNA. Whilst approval of oligonucleotide-based therapies for SMA should be celebrated, we also discuss some of the limitations of this approach and alternate genetic strategies that are currently underway in clinical trials.

  18. Novel Alternative Splice Variants of Mouse Cdk5rap2.

    Directory of Open Access Journals (Sweden)

    Nadine Kraemer

    Full Text Available Autosomal recessive primary microcephaly (MCPH is a rare neurodevelopmental disorder characterized by a pronounced reduction of brain volume and intellectual disability. A current model for the microcephaly phenotype invokes a stem cell proliferation and differentiation defect, which has moved the disease into the spotlight of stem cell biology and neurodevelopmental science. Homozygous mutations of the Cyclin-dependent kinase-5 regulatory subunit-associated protein 2 gene CDK5RAP2 are one genetic cause of MCPH. To further characterize the pathomechanism underlying MCPH, we generated a conditional Cdk5rap2 LoxP/hCMV Cre mutant mouse. Further analysis, initiated on account of a lack of a microcephaly phenotype in these mutant mice, revealed the presence of previously unknown splice variants of the Cdk5rap2 gene that are at least in part accountable for the lack of microcephaly in the mice.

  19. Self-centering fiber alignment structures for high-precision field installable single-mode fiber connectors

    Science.gov (United States)

    Van Erps, Jürgen; Ebraert, Evert; Gao, Fei; Vervaeke, Michael; Berghmans, Francis; Beri, Stefano; Watté, Jan; Thienpont, Hugo

    2014-05-01

    There is a steady increase in the demand for internet bandwidth, primarily driven by cloud services and high-definition video streaming. Europe's Digital Agenda states the ambitious objective that by 2020 all Europeans should have access to internet at speeds of 30Mb/s or above, with 50% or more of households subscribing to connections of 100Mb/s. Today however, internet access in Europe is mainly based on the first generation of broadband, meaning internet accessed over legacy telephone copper and TV cable networks. In recent years, Fiber-To-The-Home (FTTH) networks have been adopted as a replacement of traditional electrical connections for the `last mile' transmission of information at bandwidths over 1Gb/s. However, FTTH penetration is still very low (economies. The main reason for this is the high deployment cost of FTTH networks. Indeed, the success and adoption of optical access networks critically depend on the quality and reliability of connections between optical fibers. In particular a further reduction of insertion loss of field- installable connectors must be achieved without a significant increase in component cost. This requires precise alignment of fibers that can differ in terms of ellipticity, eccentricity or diameter and seems hardly achievable using today's widespread ferrule-based alignment systems. In this paper, we present a field-installable connector based on deflectable/compressible spring structures, providing a self-centering functionality for the fiber. This way, it can accommodate for possible fiber cladding diameter variations (the tolerance on the cladding diameter of G.652 fiber is typically +/-0.7μm). The mechanical properties of the cantilever are derived through an analytical approximation and a mathematical model of the spring constant, and finite element-based simulations are carried out to find the maximum first principal stress as well as the stress distribution distribution in the fiber alignment structure. Elastic

  20. A polarized view on DNA under tension

    Science.gov (United States)

    van Mameren, Joost; Vermeulen, Karen; Wuite, Gijs J. L.; Peterman, Erwin J. G.

    2018-03-01

    In the past decades, sensitive fluorescence microscopy techniques have contributed significantly to our understanding of the dynamics of DNA. The specific labeling of DNA using intercalating dyes has allowed for quantitative measurement of the thermal fluctuations the polymers undergo. On the other hand, recent advances in single-molecule manipulation techniques have unraveled the mechanical and elastic properties of this intricate polymer. Here, we have combined these two approaches to study the conformational dynamics of DNA under a wide range of tensions. Using polarized fluorescence microscopy in conjunction with optical-tweezers-based manipulation of YOYO-intercalated DNA, we controllably align the YOYO dyes using DNA tension, enabling us to disentangle the rapid dynamics of the dyes from that of the DNA itself. With unprecedented control of the DNA alignment, we resolve an inconsistency in reports about the tilted orientation of intercalated dyes. We find that intercalated dyes are on average oriented perpendicular to the long axis of the DNA, yet undergo fast dynamics on the time scale of absorption and fluorescence emission. In the overstretching transition of double-stranded DNA, we do not observe changes in orientation or orientational dynamics of the dyes. Only beyond the overstretching transition, a considerable depolarization is observed, presumably caused by an average tilting of the DNA base pairs. Our combined approach thus contributes to the elucidation of unique features of the molecular dynamics of DNA.

  1. Shape accuracy optimization for cable-rib tension deployable antenna structure with tensioned cables

    Science.gov (United States)

    Liu, Ruiwei; Guo, Hongwei; Liu, Rongqiang; Wang, Hongxiang; Tang, Dewei; Song, Xiaoke

    2017-11-01

    Shape accuracy is of substantial importance in deployable structures as the demand for large-scale deployable structures in various fields, especially in aerospace engineering, increases. The main purpose of this paper is to present a shape accuracy optimization method to find the optimal pretensions for the desired shape of cable-rib tension deployable antenna structure with tensioned cables. First, an analysis model of the deployable structure is established by using finite element method. In this model, geometrical nonlinearity is considered for the cable element and beam element. Flexible deformations of the deployable structure under the action of cable network and tensioned cables are subsequently analyzed separately. Moreover, the influence of pretension of tensioned cables on natural frequencies is studied. Based on the results, a genetic algorithm is used to find a set of reasonable pretension and thus minimize structural deformation under the first natural frequency constraint. Finally, numerical simulations are presented to analyze the deployable structure under two kinds of constraints. Results show that the shape accuracy and natural frequencies of deployable structure can be effectively improved by pretension optimization.

  2. 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.

  3. Both sides of the same coin: Rac1 splicing regulating by EGF signaling.

    Science.gov (United States)

    Fu, Xiang-Dong

    2017-04-01

    EGF, a well-studied mitogen for cancer cells, is revealed to induce an E3 ubiquitin ligase adaptor SPSB1, which recruits the Elongin B/C-Collin complex to trigger ubiquitylation of the negative splicing regulator hnRNP A1. This event is synergized with EGF-activated SR proteins to alter alternative splicing of a key small GTPase Rac1 to enhance cell migration, highlighting converging EGF signals on both negative and positive splicing regulators to jointly promote a key cancer pathway.

  4. Splicing factor 1 modulates dietary restriction and TORC1 pathway longevity in C. elegans

    DEFF Research Database (Denmark)

    Heintz, Caroline; Doktor, Thomas K; Lanjuin, Anne

    2017-01-01

    via splicing factor 1 (SFA-1; the C. elegans homologue of SF1, also known as branchpoint binding protein, BBP). We show that SFA-1 is specifically required for lifespan extension by dietary restriction and by modulation of the TORC1 pathway components AMPK, RAGA-1 and RSKS-1/S6 kinase. We also...... homeostasis is a biomarker and predictor of life expectancy in Caenorhabditis elegans. Using transcriptomics and in-depth splicing analysis in young and old animals fed ad libitum or subjected to dietary restriction, we find defects in global pre-mRNA splicing with age that are reduced by dietary restriction...

  5. A novel approach to fabricate silk nanofibers containing hydroxyapatite nanoparticles using a three-way stopcock connector

    Science.gov (United States)

    Sheikh, Faheem A.; Ju, Hyung Woo; Moon, Bo Mi; Park, Hyun Jung; Kim, Jung Ho; Lee, Ok Joo; Park, Chan Hum

    2013-07-01

    Electrospinning technique is commonly used to produce micro- and/or nanofibers, which utilizes electrical forces to produce polymeric fibers with diameters ranging from several micrometers down to few nanometers. Desirably, electrospun materials provide highly porous structure and appropriate pore size for initial cell attachment and proliferation and thereby enable the exchange of nutrients. Composite nanofibers consisting of silk and hydroxyapatite nanoparticles (HAp) (NPs) had been considered as an excellent choice due to their efficient biocompatibility and bone-mimicking properties. To prepare these nanofiber composites, it requires the use of acidic solutions which have serious consequences on the nature of both silk and HAp NPs. It is ideal to create these nanofibers using aqueous solutions in which the physicochemical nature of both materials can be retained. However, to create those nanofibers is often difficult to obtain because of the fact that aqueous solutions of silk and HAp NPs can precipitate before they can be ejected into fibers during the electrospinning process. In this work, we had successfully used a three-way stopcock connector to mix the two different solutions, and very shortly, this solution is ejected out to form nanofibers due to electric fields. Different blend ratios consisting HAp NPs had been electrospun into nanofibers. The physicochemical aspects of fabricated nanofiber had been characterized by different state of techniques like that of FE-SEM, EDS, TEM, TEM-EDS, TGA, FT-IR, and XRD. These characterization techniques revealed that HAp NPs can be easily introduced in silk nanofibers using a stopcock connector, and this method favorably preserves the intact nature of silk fibroin and HAp NPs. Moreover, nanofibers obtained by this strategy were tested for cell toxicity and cell attachment studies using NIH 3 T3 fibroblasts which indicated non-toxic behavior and good attachment of cells upon incubation in the presence of nanofibers.

  6. Remote erosion and corrosion monitoring of subsea pipelines using acoustic telemetry and wet-mate connector technology

    Energy Technology Data Exchange (ETDEWEB)

    Painter, Howard; Barlow, Stewart [Teledyne ODI, Thousand Oaks, CA (United States); Clarke, Daniel [Teledyne Cormon, Thousand Oaks, CA (United States); Green, Dale [Teledyne Benthos, North Falmouth, MA (United States)

    2009-07-01

    This paper will present a novel approach for monitoring erosion and corrosion using proven sub sea technologies: intrusive erosion and corrosion monitoring, acoustic telemetry and wet-mateable connector technology. Intrusive metal loss based monitoring systems on sub sea pipelines are increasingly being used because of their ability to directly measure erosion and corrosion. These systems are integrated with the sub sea production control system or located close to the platform and hard-wired. However, locations remote from a sub sea control system or platform requires a dedicated communication system and long lengths of cable that can be cost prohibitive to procure and install. The system presented consists of an intrusive erosion or corrosion monitor with pressure and temperature transmitters, a retrievable electronics module with an acoustic modem, a data storage module, and a replaceable power module. Time-stamped erosion and corrosion data can be transmitted via an acoustic link to a surface platform, a vessel of opportunity or to a relaying modem. Acoustic signals can be transmitted up to 6 km from the monitoring location. The power module along with data module and acoustic modem are mounted on the erosion and corrosion module using wet-mateable connectors, allowing retrieval by remotely operated vehicles. The collected data can be used to assess the cumulative erosion and corrosion as well as use the real-time metal loss rate data to correlate with operational parameters. Benefits include optimization of corrosion inhibitor dosage rates, mitigation of damage caused by solids production, and increased flow assurance. (author)

  7. Control of HIV-1 env RNA splicing and transport: investigating the role of hnRNP A1 in exon splicing silencer (ESS3a) function

    International Nuclear Information System (INIS)

    Asai, Kengo; Platt, Craig; Cochrane, Alan

    2003-01-01

    The control of HIV-1 viral RNA splicing and transport plays an important role in the successful replication of the virus. Previous studies have identified both an exon splicing enhancer (ESE) and a bipartite exon splicing silencer (ESS3a and ESS3b) within the terminal exon of HIV-1 that are involved in modulating both splicing and Rev-mediated export of viral RNA. To define the mechanism of ESS3a function, experiments were carried out to better define the cis and trans components required for ESS3a activity. Mutations throughout the 30-nt element resulted in partial loss of ESS function. Combining mutations was found to have an additive effect, suggesting the presence of multiple binding sites. Analysis of interacting factors identified hnRNP A1 as one component of the complex that modulates ESS3a activity. However, subsequent binding analyses determined that hnRNP A1 interacts with only one portion of ESS3a, suggesting the involvement of another host factor. Parallel analysis of the effect of the mutations on Rev-mediated export determined that there is not a direct correlation between the effect of the mutations on splicing and RNA transport. Consistent with this hypothesis, replacement of ESS3a with consensus hnRNP A1 binding sites was found to be insufficient to block Rev-mediated RNA export

  8. The tension of framed membranes from computer simulations

    DEFF Research Database (Denmark)

    Hamkens, Daniel; Jeppesen, Claus; Ipsen, John H.

    2018-01-01

    the membranes display power-law characteristics for the equation of state, while higher tension levels includes both an extended linear (elastic) as well as a highly non-linear stretching regime. For semi-flexible membranes a transition from extended to buckled conformations takes place at negative frame......Abstract.: We have analyzed the behavior of a randomly triangulated, self-avoiding surface model of a flexible, fluid membrane subject to a circular boundary by Wang-Landau Monte Carlo computer simulation techniques. The dependence of the canonical free energy and frame tension on the frame area...... is obtained for flexible membranes. It is shown that for low bending rigidities the framed membrane is only stable above a threshold tension, suggesting a discontinuous transition from the collapsed (branched polymer) state to a finite tension extended state. In a tension range above this threshold tension...

  9. Surface tension of liquid Al-Cu binary alloys.

    OpenAIRE

    Schmitz, Julianna; Brillo, Jürgen; Egry, Ivan; Schmid-Fetzer, Rainer

    2009-01-01

    Surface tension data of liquid Al–Cu binary alloys have been measured contactlessly using the technique of electromagnetic levitation. A digital CMOS-camera (400 fps) recorded image sequences of the oscillating liquid sample and surface tensions were determined from analysis of the frequency spectra. Measurements were performed for samples covering the entire range of composition and precise data were obtained in a broad temperature range. It was found that the surface tensions can ...

  10. Bending Under Tension Test with Direct Friction Measurement

    DEFF Research Database (Denmark)

    Andreasen, Jan Lasson; Olsson, David Dam; Chodnikiewicz, K.

    2006-01-01

    A special Bending-Under-Tension (BUT) transducer has been developed in which friction around the tool radius can be directly measured when drawing a plane sheet strip around a cylindrical tool-pin under constant back tension. The front tension, back tension and torque on the tool-pin are all...... measured directly, thus enabling accurate measurement of friction and direct determination of lubricant film breakdown for varying normal pressure, sliding speed, tool radius and tool preheat temperature. The transducer is applied in an experimental investigation focusing on limits of lubrication...

  11. The law of corresponding states and surface tension of metals

    International Nuclear Information System (INIS)

    Digilov, R.

    2001-01-01

    Full Text: Surface tension of liquid metals is one of fundamental and most important quantities in theory and practice of material processing and its temperature dependence leads to the well-known Marangoni convection. Although currently methods are sufficiently precise to measure the surface tension, there are uncertainties in experimental data and its temperature dependence mainly due to impurity, which even a trace of it strongly affects the results of measurements. The theoretical treatment from the first principles is unwieldy and not always permits one to calculate the surface tension with certainty. Another active research field deals with empirical correlation between the surface tension and bulk thermodynamic properties, which we interpret as a simple consequence of the law of corresponding states. In order to relate the surface tension and to bulk properties of liquid metals the reduced formula is derived by scaling with the melting point T m (0) at p = 0 and atomic volume Ω 0 2/3 at T = 0 K as macroscopic parameters for scaling ε and a characterizing the interatomic potential in metals. The reduced surface tension and the reduced surface entropy obtained in high temperature limit are discussed and compared with the experiment. The reduced temperature coefficient of the surface tension found is a universal constant for the metals of the same structure. It is shown that pressure dependence of the surface tension, so called baric coefficient of the surface tension, can be described by pressure dependence of scaling parameters T m (p) and Ω 0 (p). (author)

  12. Strain Capacity of Reinforced Concrete Members Subjected to Uniaxial Tension

    DEFF Research Database (Denmark)

    Hagsten, Lars German; Rasmussen, Annette Beedholm; Fisker, Jakob

    2017-01-01

    The aim of this paper is to set up a method to determine the strain capacity of tension bars of reinforced concrete (RC) subjected to pure tension. Due to the interaction between reinforcement and concrete and due to the presence of cracks, the stresses in both reinforcement and concrete...... are varying along the length of the tension bar. The strain capacity of the tension bar is seen as the average strain in the reinforcement at the load level corresponding to the ultimate stress capacity of the reinforcement at the cracks. The result of the approach is in overall good agreement when comparing...

  13. An automatic tension measurement system of MWPC wires

    International Nuclear Information System (INIS)

    D'Antone, I.; Lolli, M.; Torromeo, G.

    1992-01-01

    An electronic system is presented for automatic mechanical tension measurement to test wire chambers. The developed system works in the tension range from 50 g to 300 g; this large working range is obtained by using a microcontroller that performs a digital control on the bridge of an oscillator containing the wire of which the tension has to be measured. The microcontroller automatically brings the system towards the oscillation condition and subsequently, measuring the frequency, it evaluates, displays and sends to a host computer the value of the mechanical tension of the wires. The system is precise and allows fast measurements. A description of the hardware and software design is given. (orig.)

  14. Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance

    Directory of Open Access Journals (Sweden)

    Claire Jackson

    2013-01-01

    Full Text Available Overexpression of human epidermal growth factor receptor (HER-2 occurs in 20–30% of breast cancers and confers survival and proliferative advantages on the tumour cells making HER-2 an ideal therapeutic target for drugs like Herceptin. Continued delineation of tumour biology has identified splice variants of HER-2, with contrasting roles in tumour cell biology. For example, the splice variant 16HER-2 (results from exon 16 skipping increases transformation of cancer cells and is associated with treatment resistance; conversely, Herstatin (results from intron 8 retention and p100 (results from intron 15 retention inhibit tumour cell proliferation. This review focuses on the potential clinical implications of the expression and coexistence of HER-2 splice variants in cancer cells in relation to breast cancer progression and drug resistance. “Individualised” strategies currently guide breast cancer management; in accordance, HER-2 splice variants may prove valuable as future prognostic and predictive factors, as well as potential therapeutic targets.

  15. Sex determination in insects: a binary decision based on alternative splicing.

    Science.gov (United States)

    Salz, Helen K

    2011-08-01

    The gene regulatory networks that control sex determination vary between species. Despite these differences, comparative studies in insects have found that alternative splicing is reiteratively used in evolution to control expression of the key sex-determining genes. Sex determination is best understood in Drosophila where activation of the RNA binding protein-encoding gene Sex-lethal is the central female-determining event. Sex-lethal serves as a genetic switch because once activated it controls its own expression by a positive feedback splicing mechanism. Sex fate choice in is also maintained by self-sustaining positive feedback splicing mechanisms in other dipteran and hymenopteran insects, although different RNA binding protein-encoding genes function as the binary switch. Studies exploring the mechanisms of sex-specific splicing have revealed the extent to which sex determination is integrated with other developmental regulatory networks. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Splicing analysis of 14 BRCA1 missense variants classifies nine variants as pathogenic

    DEFF Research Database (Denmark)

    Ahlborn, Lise B; Dandanell, Mette; Steffensen, Ane Y

    2015-01-01

    by functional analysis at the protein level. Results from a validated mini-gene splicing assay indicated that nine BRCA1 variants resulted in splicing aberrations leading to truncated transcripts and thus can be considered pathogenic (c.4987A>T/p.Met1663Leu, c.4988T>A/p.Met1663Lys, c.5072C>T/p.Thr1691Ile, c......Pathogenic germline mutations in the BRCA1 gene predispose carriers to early onset breast and ovarian cancer. Clinical genetic screening of BRCA1 often reveals variants with uncertain clinical significance, complicating patient and family management. Therefore, functional examinations are urgently...... needed to classify whether these uncertain variants are pathogenic or benign. In this study, we investigated 14 BRCA1 variants by in silico splicing analysis and mini-gene splicing assay. All 14 alterations were missense variants located within the BRCT domain of BRCA1 and had previously been examined...

  17. Analysis and prediction of gene splice sites in four Aspergillus genomes

    DEFF Research Database (Denmark)

    Wang, Kai; Ussery, David; Brunak, Søren

    2009-01-01

    Several Aspergillus fungal genomic sequences have been published, with many more in progress. Obviously, it is essential to have high-quality, consistently annotated sets of proteins from each of the genomes, in order to make meaningful comparisons. We have developed a dedicated, publicly available......, splice site prediction program called NetAspGene, for the genus Aspergillus. Gene sequences from Aspergillus fumigatus, the most common mould pathogen, were used to build and test our model. Compared to many animals and plants, Aspergillus contains smaller introns; thus we have applied a larger window...... better splice site prediction than other available tools. NetAspGene will be very helpful for the study in Aspergillus splice sites and especially in alternative splicing. A webpage for NetAspGene is publicly available at http://www.cbs.dtu.dk/services/NetAspGene....

  18. DORT and TORT workshop -- Outline for presentation for splicing with TORSED and TORSET

    International Nuclear Information System (INIS)

    Barnett, A.

    1998-04-01

    This paper addresses the problem of solving a problem which is larger than can be accommodated by the computer system at your disposal. This can result from two constrains: (1) The available memory of the machine is too small to contain the problem. (2) Individual files may be too large to store on-line. It also addresses the problem of what to do when you want to alter only a subset of a solution space of a larger problem and don't want to rerun the entire problem. These problems can be solved by splicing with TORSED AND TORSET. If the basic shape of your problem is cylindrical and azimuthally uniform, with only a small region of three-dimensionality, then the best splicing method is the TORSED -- DORT to TORT splice. However, if there is no part of the problem which is azimuthally constant, then one might want to consider a TORT to TORT splice. Both methods are discussed here

  19. Splice performance evaluation of enamel-coated rebar for structural safety.

    Science.gov (United States)

    2014-07-01

    This report summarizes the findings and results from an experimental study of vitreous enamel coating effects on the bond : strength between deformed rebar and normal strength concrete. A total of 24 beam splice specimens were tested under four-point...

  20. The group II intron maturase: a reverse transcriptase and splicing factor go hand in hand.

    Science.gov (United States)

    Zhao, Chen; Pyle, Anna Marie

    2017-12-01

    The splicing of group II introns in vivo requires the assistance of a multifunctional intron encoded protein (IEP, or maturase). Each IEP is also a reverse-transcriptase enzyme that enables group II introns to behave as mobile genetic elements. During splicing or retro-transposition, each group II intron forms a tight, specific complex with its own encoded IEP, resulting in a highly reactive holoenzyme. This review focuses on the structural basis for IEP function, as revealed by recent crystal structures of an IEP reverse transcriptase domain and cryo-EM structures of an IEP-intron complex. These structures explain how the same IEP scaffold is utilized for intron recognition, splicing and reverse transcription, while providing a physical basis for understanding the evolutionary transformation of the IEP into the eukaryotic splicing factor Prp8. Copyright © 2017 Elsevier Ltd. All rights reserved.