14 CFR 23.677 - Trim systems.

Code of Federal Regulations, 2011 CFR

2011-01-01

... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Design and Construction Control... abrupt trim tab operation. There must be means near the trim control to indicate to the pilot the direction of trim control movement relative to airplane motion. In addition, there must be means to indicate...

14 CFR 23.677 - Trim systems.

Code of Federal Regulations, 2012 CFR

2012-01-01

... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Design and Construction Control... abrupt trim tab operation. There must be means near the trim control to indicate to the pilot the direction of trim control movement relative to airplane motion. In addition, there must be means to indicate...

14 CFR 23.677 - Trim systems.

Code of Federal Regulations, 2014 CFR

2014-01-01

... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Design and Construction Control... abrupt trim tab operation. There must be means near the trim control to indicate to the pilot the direction of trim control movement relative to airplane motion. In addition, there must be means to indicate...

14 CFR 23.677 - Trim systems.

Code of Federal Regulations, 2013 CFR

2013-01-01

... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Design and Construction Control... abrupt trim tab operation. There must be means near the trim control to indicate to the pilot the direction of trim control movement relative to airplane motion. In addition, there must be means to indicate...

14 CFR 23.677 - Trim systems.

Code of Federal Regulations, 2010 CFR

2010-01-01

... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Design and Construction Control... abrupt trim tab operation. There must be means near the trim control to indicate to the pilot the direction of trim control movement relative to airplane motion. In addition, there must be means to indicate...

14 CFR 25.677 - Trim systems.

Code of Federal Regulations, 2014 CFR

2014-01-01

... STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction Control Systems § 25.677 Trim systems. (a) Trim controls must be designed to prevent inadvertent or abrupt operation and to operate in the plane... designed to prevent creeping in flight. Trim tab controls must be irreversible unless the tab is...

14 CFR 25.677 - Trim systems.

Code of Federal Regulations, 2011 CFR

2011-01-01

... STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction Control Systems § 25.677 Trim systems. (a) Trim controls must be designed to prevent inadvertent or abrupt operation and to operate in the plane... designed to prevent creeping in flight. Trim tab controls must be irreversible unless the tab is...

14 CFR 25.677 - Trim systems.

Code of Federal Regulations, 2010 CFR

2010-01-01

... STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction Control Systems § 25.677 Trim systems. (a) Trim controls must be designed to prevent inadvertent or abrupt operation and to operate in the plane... designed to prevent creeping in flight. Trim tab controls must be irreversible unless the tab is...

14 CFR 25.677 - Trim systems.

Code of Federal Regulations, 2012 CFR

2012-01-01

... STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction Control Systems § 25.677 Trim systems. (a) Trim controls must be designed to prevent inadvertent or abrupt operation and to operate in the plane... designed to prevent creeping in flight. Trim tab controls must be irreversible unless the tab is...

Application of a Broadband Active Vibration Control System to a Helicopter Trim Panel

NASA Technical Reports Server (NTRS)

Cabell, Randolph H.; Schiller, Noah H.; Simon, Frank

2013-01-01

This paper discusses testing of a broadband active vibration control concept on an interior trim panel in a helicopter cabin mockup located at ONERA's Centre de Toulouse. The control system consisted of twelve diamond-shaped piezoelectric actuators distributed around a 1.2m x 1.2m trim panel. Accelerometers were mounted at the four vertices of each diamond. The aspect ratio of the diamond was based on the dielectric constants of the piezoelectric material in order to create an actuator-sensor pair that was collocated over a broad frequency range. This allowed robust control to be implemented using simple, low power analog electronics. Initial testing on a thick acrylic window demonstrated the capability of the controller, but actuator performance was less satisfactory when mounted on a composite sandwich trim panel. This may have been due to the orthotropic nature of the trim panel, or due to its much higher stiffness relative to the acrylic window. Insights gained from a finite element study of the actuator-sensor-structural system are discussed.

Download Trim.Fate

EPA Pesticide Factsheets

TRIM.FaTE is a spatially explicit, compartmental mass balance model that describes the movement and transformation of pollutants over time, through a user-defined, bounded system that includes both biotic and abiotic compartments.

Predictions of Control Inputs, Periodic Responses and Damping Levels of an Isolated Experimental Rotor in Trimmed Flight

NASA Technical Reports Server (NTRS)

Gaonkar, G. H.; Subramanian, S.

1996-01-01

Since the early 1990s the Aeroflightdynamics Directorate at the Ames Research Center has been conducting tests on isolated hingeless rotors in hover and forward flight. The primary objective is to generate a database on aeroelastic stability in trimmed flight for torsionally soft rotors at realistic tip speeds. The rotor test model has four soft inplane blades of NACA 0012 airfoil section with low torsional stiffness. The collective pitch and shaft tilt are set prior to each test run, and then the rotor is trimmed in the following sense: the longitudinal and lateral cyclic pitch controls are adjusted through a swashplate to minimize the 1/rev flapping moment at the 12 percent radial station. In hover, the database comprises lag regressive-mode damping with pitch variations. In forward flight the database comprises cyclic pitch controls, root flap moment and lag regressive-mode damping with advance ratio, shaft angle and pitch variations. This report presents the predictions and their correlation with the database. A modal analysis is used, in which nonrotating modes in flap bending, lag bending and torsion are computed from the measured blade mass and stiffness distributions. The airfoil aerodynamics is represented by the ONERA dynamic stall models of lift, drag and pitching moment, and the wake dynamics is represented by a state-space wake model. The trim analysis of finding, the cyclic controls and the corresponding, periodic responses is based on periodic shooting with damped Newton iteration; the Floquet transition matrix (FTM) comes out as a byproduct. The stabillty analysis of finding the frequencies and damping levels is based on the eigenvalue-eigenvector analysis of the FTM. All the structural and aerodynamic states are included from modeling to trim analysis. A major finding is that dynamic wake dramatically improves the correlation for the lateral cyclic pitch control. Overall, the correlation is fairly good.

Airplane automatic control force trimming device for asymmetric engine failures

NASA Technical Reports Server (NTRS)

Stewart, Eric C. (Inventor)

1987-01-01

The difference in dynamic pressure in the propeller slipstreams as measured by sensors is divided by the freestream dynamic pressure generating a quantity proportional to the differential thrust coefficient. This quantity is used to command an electric trim motor to change the position of trim tab thereby retrimming the airplane to the new asymmetric power condition. The change in position of the trim tab produced by the electric trim motor is summed with the pilot's input to produce the actual trim tab position.

14 CFR 25.407 - Trim tab effects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Trim tab effects. 25.407 Section 25.407... STANDARDS: TRANSPORT CATEGORY AIRPLANES Structure Control Surface and System Loads § 25.407 Trim tab effects. The effects of trim tabs on the control surface design conditions must be accounted for only where the...

14 CFR 25.407 - Trim tab effects.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Trim tab effects. 25.407 Section 25.407... STANDARDS: TRANSPORT CATEGORY AIRPLANES Structure Control Surface and System Loads § 25.407 Trim tab effects. The effects of trim tabs on the control surface design conditions must be accounted for only where the...

Total Risk Integrated Methodology (TRIM) - TRIM.Risk

EPA Pesticide Factsheets

TRIM.Riskis used to integrate the information on exposure received from TRIM.FaTE or TRIM.Expo with that on dose-response or hazard assessment and to provide quantitative descriptions of risk or hazard and some of the attendant uncertainties.

MATLAB Stability and Control Toolbox Trim and Static Stability Module

NASA Technical Reports Server (NTRS)

Kenny, Sean P.; Crespo, Luis

2012-01-01

MATLAB Stability and Control Toolbox (MASCOT) utilizes geometric, aerodynamic, and inertial inputs to calculate air vehicle stability in a variety of critical flight conditions. The code is based on fundamental, non-linear equations of motion and is able to translate results into a qualitative, graphical scale useful to the non-expert. MASCOT was created to provide the conceptual aircraft designer accurate predictions of air vehicle stability and control characteristics. The code takes as input mass property data in the form of an inertia tensor, aerodynamic loading data, and propulsion (i.e. thrust) loading data. Using fundamental nonlinear equations of motion, MASCOT then calculates vehicle trim and static stability data for the desired flight condition(s). Available flight conditions include six horizontal and six landing rotation conditions with varying options for engine out, crosswind, and sideslip, plus three take-off rotation conditions. Results are displayed through a unique graphical interface developed to provide the non-stability and control expert conceptual design engineer a qualitative scale indicating whether the vehicle has acceptable, marginal, or unacceptable static stability characteristics. If desired, the user can also examine the detailed, quantitative results.

14 CFR 23.407 - Trim tab effects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Trim tab effects. 23.407 Section 23.407... Loads § 23.407 Trim tab effects. The effects of trim tabs on the control surface design conditions must... deflections must correspond to the maximum degree of “out of trim” expected at the speed for the condition...

14 CFR 23.407 - Trim tab effects.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Trim tab effects. 23.407 Section 23.407... Loads § 23.407 Trim tab effects. The effects of trim tabs on the control surface design conditions must... deflections must correspond to the maximum degree of “out of trim” expected at the speed for the condition...

Total Risk Integrated Methodology (TRIM) - TRIM.Expo

EPA Pesticide Factsheets

The Exposure Event module of TRIM (TRIM.Expo), similar to most human exposure models, provides an analysis of the relationships between various chemical concentrations in the environment and exposure levels of humans.

Trim drag reduction concepts for horizontal takeoff single-stage-to-Orbit vehicles

NASA Technical Reports Server (NTRS)

Shaughnessy, John D.; Gregory, Irene M.

1991-01-01

The results of a study to investigate concepts for minimizing trim drag of horizontal takeoff single-stage-to-orbit (SSTO) vehicles are presented. A generic hypersonic airbreathing conical configuration was used as the subject aircraft. The investigation indicates that extreme forward migration of the aerodynamic center as the vehicle accelerates to orbital velocities causes severe aerodynamic instability and trim moments that must be counteracted. Adequate stability can be provided by active control of elevons and rudder, but use of elevons to produce trim moments results in excessive trim drag and fuel consumption. To alleviate this problem, two solution concepts are examined. Active control of the center of gravity (COG) location to track the aerodynamic center decreases trim moment requirements, reduces elevon deflections, and leads to significant fuel savings. Active control of the direction of the thrust vector produces required trim moments, reduces elevon deflections, and also results in significant fuel savings. It is concluded that the combination of active flight control to provide stabilization, (COG) position control to minimize trim moment requirements, and thrust vectoring to generate required trim moments has the potential to significantly reduce fuel consumption during ascent to orbit of horizontal takeoff SSTO vehicles.

14 CFR 25.255 - Out-of-trim characteristics.

Code of Federal Regulations, 2013 CFR

2013-01-01

...-trim characteristics. (a) From an initial condition with the airplane trimmed at cruise speeds up to.../MFC and VDF/MDF the direction of the primary longitudinal control force may not reverse. (c) Except as... flight test with regard to reversal of primary longitudinal control force, flight tests must be...

Download TRIM.Risk

EPA Pesticide Factsheets

TRIM.Risk is used to integrate the information on exposure received from TRIM.FaTE or TRIM.Expo with that on dose-response or hazard assessment and to provide quantitative descriptions of risk or hazard and some of the attendant uncertainties.

TRIM.FaTE Public Reference Library Documentation

EPA Pesticide Factsheets

TRIM.FaTE is a spatially explicit, compartmental mass balance model that describes the movement and transformation of pollutants over time, through a user-defined, bounded system that includes both biotic and abiotic compartments.

Trim and Structural Optimization of Subsonic Transport Wings Using Nonconventional Aeroelastic Tailoring

NASA Technical Reports Server (NTRS)

Stanford, Bret K.; Jutte, Christine V.

2014-01-01

Several minimum-mass aeroelastic optimization problems are solved to evaluate the effectiveness of a variety of novel tailoring schemes for subsonic transport wings. Aeroelastic strength and panel buckling constraints are imposed across a variety of trimmed maneuver loads. Tailoring with metallic thickness variations, functionally graded materials, composite laminates, tow steering, and distributed trailing edge control effectors are all found to provide reductions in structural wing mass with varying degrees of success. The question as to whether this wing mass reduction will offset the increased manufacturing cost is left unresolved for each case.

14 CFR 23.161 - Trim.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Trim. 23.161 Section 23.161 Aeronautics and...: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Flight Trim § 23.161 Trim. (a) General. Each airplane must meet the trim requirements of this section after being trimmed and without further pressure...

14 CFR 23.161 - Trim.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Trim. 23.161 Section 23.161 Aeronautics and...: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Flight Trim § 23.161 Trim. (a) General. Each airplane must meet the trim requirements of this section after being trimmed and without further pressure...

14 CFR 25.161 - Trim.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Trim. 25.161 Section 25.161 Aeronautics and...: TRANSPORT CATEGORY AIRPLANES Flight Trim § 25.161 Trim. (a) General. Each airplane must meet the trim requirements of this section after being trimmed, and without further pressure upon, or movement of, either the...

14 CFR 25.161 - Trim.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Trim. 25.161 Section 25.161 Aeronautics and...: TRANSPORT CATEGORY AIRPLANES Flight Trim § 25.161 Trim. (a) General. Each airplane must meet the trim requirements of this section after being trimmed, and without further pressure upon, or movement of, either the...

Body-induced vortical flows: a common mechanism for self-corrective trimming control in boxfishes.

PubMed

Bartol, Ian K; Gharib, Morteza; Webb, Paul W; Weihs, Daniel; Gordon, Malcolm S

2005-01-01

Boxfishes (Teleostei: Ostraciidae) are marine fishes having rigid carapaces that vary significantly among taxa in their shapes and structural ornamentation. We showed previously that the keels of the carapace of one species of tropical boxfish, the smooth trunkfish, produce leading edge vortices (LEVs) capable of generating self-correcting trimming forces during swimming. In this paper we show that other tropical boxfishes with different carapace shapes have similar capabilities. We conducted a quantitative study of flows around the carapaces of three morphologically distinct boxfishes (spotted boxfish, scrawled cowfish and buffalo trunkfish) using stereolithographic models and three separate but interrelated analytical approaches: digital particle image velocimetry (DPIV), pressure distribution measurements, and force balance measurements. The ventral keels of all three forms produced LEVs that grew in circulation along the bodies, resembling the LEVs produced around delta-winged aircraft. These spiral vortices formed above the keels and increased in circulation as pitch angle became more positive, and formed below the keels and increased in circulation as pitch angle became more negative. Vortices also formed along the eye ridges of all boxfishes. In the spotted boxfish, which is largely trapezoidal in cross section, consistent dorsal vortex growth posterior to the eye ridge was also present. When all three boxfishes were positioned at various yaw angles, regions of strongest concentrated vorticity formed in far-field locations of the carapace compared with near-field areas, and vortex circulation was greatest posterior to the center of mass. In general, regions of localized low pressure correlated well with regions of attached, concentrated vorticity, especially around the ventral keels. Although other features of the carapace also affect flow patterns and pressure distributions in different ways, the integrated effects of the flows were consistent for all forms

Thermal trim for luminaire

DOEpatents

Bazydola, Sarah; Ghiu, Camil-Daniel; Harrison, Robert; Jeswani, Anil

2013-11-19

A luminaire with a thermal pathway to reduce the junction temperature of the luminaire's light source, and methods for so doing, are disclosed. The luminaire includes a can, a light engine, and a trim, that define a substantially continuous thermal pathway from the light engine to a surrounding environment. The can defines a can cavity and includes a can end region. The light engine is within the can cavity and includes a light source and a heat sink, including a heat sink end region, coupled thereto. The trim is at least partially disposed within the can cavity and includes a first trim end region coupled to the heat sink end region and a second trim end region coupled to the can end region. Thermal interface material may be located between: the heat sink and the trim, the trim and the can, and/or the heat sink and the light source.

A novel TRIM family member, Trim69, regulates zebrafish development through p53-mediated apoptosis.

PubMed

Han, Ruiqin; Zhao, Qing; Zong, Shudong; Miao, Shiying; Song, Wei; Wang, Linfang

2016-05-01

Trim69 contains the hallmark domains of a tripartite motif (TRIM) protein, including a Ring-finger domain, B-box domain, and coiled-coil domain. Trim69 is structurally and evolutionarily conserved in zebrafish, mouse, rat, human, and chimpanzee. The role of this protein is unclear, however, so we investigated its function in zebrafish development. Trim69 is extensively expressed in zebrafish adults and developing embryos-particularly in the testis, brain, ovary, and heart-and its expression decreases in a time- and stage-dependent manner. Loss of trim69 in zebrafish induces apoptosis and activates apoptosis-related processes; indeed, the tp53 pathway was up-regulated in response to the knockdown. Expression of human trim69 rescued the apoptotic phenotype, while overexpression of trim69 does not increase cellular apoptosis. Taken together, our results suggest that trim69 participates in tp53-mediated apoptosis during zebrafish development. Mol. Reprod. Dev. 83: 442-454, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

MIMS for TRIM

EPA Pesticide Factsheets

MIMS supports complex computational studies that use multiple interrelated models / programs, such as the modules within TRIM. MIMS is used by TRIM to run various models in sequence, while sharing input and output files.

An Introduction To PC-TRIM.

Treesearch

John R. Mills

1989-01-01

The timber resource inventory model (TRIM) has been adapted to run on person al computers. The personal computer version of TRIM (PC-TRIM) is more widely used than its mainframe parent. Errors that existed in previous versions of TRIM have been corrected. Information is presented to help users with program input and output management in the DOS environment, to...

Automatic channel trimming for control systems: A concept

NASA Technical Reports Server (NTRS)

Vandervoort, R. J.; Sykes, H. A.

1977-01-01

Set of bias signals added to channel inputs automatically normalize differences between channels. Algorithm and second feedback loop compute trim biases. Concept could be applied to regulators and multichannel servosystems for remote manipulators in undersea mining.

TRIM24 protein promotes and TRIM32 protein inhibits cardiomyocyte hypertrophy via regulation of dysbindin protein levels

PubMed Central

Borlepawar, Ankush; Bernt, Alexander; Christen, Lynn; Sossalla, Samuel; Frank, Derk; Frey, Norbert

2017-01-01

We have previously shown that dysbindin is a potent inducer of cardiomyocyte hypertrophy via activation of Rho-dependent serum-response factor (SRF) signaling. We have now performed a yeast two-hybrid screen using dysbindin as bait against a cardiac cDNA library to identify the cardiac dysbindin interactome. Among several putative binding proteins, we identified tripartite motif-containing protein 24 (TRIM24) and confirmed this interaction by co-immunoprecipitation and co-immunostaining. Another tripartite motif (TRIM) family protein, TRIM32, has been reported earlier as an E3 ubiquitin ligase for dysbindin in skeletal muscle. Consistently, we found that TRIM32 also degraded dysbindin in neonatal rat ventricular cardiomyocytes as well. Surprisingly, however, TRIM24 did not promote dysbindin decay but rather protected dysbindin against degradation by TRIM32. Correspondingly, TRIM32 attenuated the activation of SRF signaling and hypertrophy due to dysbindin, whereas TRIM24 promoted these effects in neonatal rat ventricular cardiomyocytes. This study also implies that TRIM32 is a key regulator of cell viability and apoptosis in cardiomyocytes via simultaneous activation of p53 and caspase-3/-7 and inhibition of X-linked inhibitor of apoptosis. In conclusion, we provide here a novel mechanism of post-translational regulation of dysbindin and hypertrophy via TRIM24 and TRIM32 and show the importance of TRIM32 in cardiomyocyte apoptosis in vitro. PMID:28465353

Ship Trim Optimization: Assessment of Influence of Trim on Resistance of MOERI Container Ship

PubMed Central

Duan, Wenyang

2014-01-01

Environmental issues and rising fuel prices necessitate better energy efficiency in all sectors. Shipping industry is a stakeholder in environmental issues. Shipping industry is responsible for approximately 3% of global CO2 emissions, 14-15% of global NOX emissions, and 16% of global SOX emissions. Ship trim optimization has gained enormous momentum in recent years being an effective operational measure for better energy efficiency to reduce emissions. Ship trim optimization analysis has traditionally been done through tow-tank testing for a specific hullform. Computational techniques are increasingly popular in ship hydrodynamics applications. The purpose of this study is to present MOERI container ship (KCS) hull trim optimization by employing computational methods. KCS hull total resistances and trim and sinkage computed values, in even keel condition, are compared with experimental values and found in reasonable agreement. The agreement validates that mesh, boundary conditions, and solution techniques are correct. The same mesh, boundary conditions, and solution techniques are used to obtain resistance values in different trim conditions at Fn = 0.2274. Based on attained results, optimum trim is suggested. This research serves as foundation for employing computational techniques for ship trim optimization. PMID:24578649

TRIM5α and TRIM22 Are Differentially Regulated According to HIV-1 Infection Phase and Compartment

PubMed Central

Singh, Ravesh; Patel, Vinod; Mureithi, Marianne W.; Naranbhai, Vivek; Ramsuran, Duran; Tulsi, Sahil; Hiramen, Keshni; Werner, Lise; Mlisana, Koleka; Altfeld, Marcus; Luban, Jeremy; Kasprowicz, Victoria; Dheda, Keertan; Abdool Karim, Salim S.

2014-01-01

ABSTRACT The antiviral role of TRIM E3 ligases in vivo is not fully understood. To test the hypothesis that TRIM5α and TRIM22 have differential transcriptional regulation and distinct anti-HIV roles according to infection phase and compartment, we measured TRIM5α, TRIM22, and type I interferon (IFN-I)-inducible myxovirus resistance protein A (MxA) levels in peripheral blood mononuclear cells (PBMCs) during primary and chronic HIV-1 infection, with chronic infection samples being matched PBMCs and central nervous system (CNS)-derived cells. Associations with biomarkers of disease progression were explored. The impact of IFN-I, select proinflammatory cytokines, and HIV on TRIM E3 ligase-specific expression was investigated. PBMCs from individuals with primary and chronic HIV-1 infection had significantly higher levels of MxA and TRIM22 than did PBMCs from HIV-1-negative individuals (P < 0.05 for all comparisons). PBMCs from chronic infection had lower levels of TRIM5α than did PBMCs from primary infection or HIV-1-uninfected PBMCs (P = 0.0001 for both). In matched CNS-derived samples and PBMCs, higher levels of MxA (P = 0.001) and TRIM5α (P = 0.0001) in the CNS were noted. There was a negative correlation between TRIM22 levels in PBMCs and plasma viral load (r = −0.40; P = 0.04). In vitro, IFN-I and, rarely, proinflammatory cytokines induced TRIM5α and TRIM22 in a cell type-dependent manner, and the knockdown of either protein in CD4+ lymphocytes resulted in increased HIV-1 infection. These data suggest that there are infection-phase-specific and anatomically compartmentalized differences in TRIM5α and TRIM22 regulation involving primarily IFN-I and specific cell types and indicate subtle differences in the antiviral roles and transcriptional regulation of TRIM E3 ligases in vivo. IMPORTANCE Type I interferon-inducible TRIM E3 ligases are a family of intracellular proteins with potent antiviral activities mediated through diverse mechanisms. However, little

Thermal trim for a luminaire

DOEpatents

Bazydola, Sarah; Ghiu, Camil-Daniel; Harrison, Robert; Jeswani, Anil

2013-02-19

A luminaire with a thermal pathway to reduce the junction temperature of the luminaire's light source, and methods for so doing, are disclosed. The luminaire includes a can, a light engine, and a trim, that define a substantially continuous thermal pathway from the light engine to a surrounding environment. The can defines a can cavity and includes a can end region. The light engine is within the can cavity and includes a light source and a heat sink, including a heat sink end region, coupled thereto. The trim is at least partially disposed within the can cavity and includes a first trim end region coupled to the heat sink end region and a second trim end region coupled to the can end region. Thermal interface material may be located between: the heat sink and the trim, the trim and the can, and/or the heat sink and the light source.

Novel function of Trim44 promotes an antiviral response by stabilizing VISA.

PubMed

Yang, Bo; Wang, Jie; Wang, Yanming; Zhou, Haiyan; Wu, Xiaodong; Tian, Zhigang; Sun, Bing

2013-04-01

Virus-induced signaling adaptor (VISA) functions as a critical adaptor in the regulation of both the production of type I IFNs and the subsequent control of the innate antiviral response. In this study, we demonstrate that tripartite motif (Trim)44 interacts with VISA and promotes VISA-mediated antiviral responses. The overexpression of Trim44 enhances the cellular response to viral infection, whereas Trim44 knockdown yields the opposite effect. Trim44 stabilizes VISA by preventing VISA ubiquitination and degradation. These findings suggest that Trim44 functions as a positive regulator of the virus-triggered immune response by enhancing the stability of VISA.

7 CFR 51.607 - Well trimmed.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Well trimmed. 51.607 Section 51.607 Agriculture... Consumer Standards for Celery Stalks Definitions § 51.607 Well trimmed. Well trimmed means that the outside coarse and damaged branches have been removed and that the root or roots have been neatly trimmed to a...

7 CFR 51.607 - Well trimmed.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 2 2011-01-01 2011-01-01 false Well trimmed. 51.607 Section 51.607 Agriculture... Consumer Standards for Celery Stalks Definitions § 51.607 Well trimmed. Well trimmed means that the outside coarse and damaged branches have been removed and that the root or roots have been neatly trimmed to a...

TRIM41-Mediated Ubiquitination of Nucleoprotein Limits Influenza A Virus Infection.

PubMed

Patil, Girish; Zhao, Mengmeng; Song, Kun; Hao, Wenzhuo; Bouchereau, Daniel; Wang, Lingyan; Li, Shitao

2018-06-13

Influenza A virus (IAV) is a highly transmissible respiratory pathogen and a major cause of morbidity and mortality around the world. Nucleoprotein (NP) is an abundant IAV protein essential for multiple steps of viral life cycle. Our recent proteomic study of the IAV-host interaction network found that the tripartite motif containing 41 (TRIM41), a ubiquitin E3 ligase, interacted with NP. However, the role of TRIM41 in IAV infection is unknown. Here, we report that TRIM41 interacts with NP through its SPRY domain. Furthermore, TRIM41 is constitutively expressed in lung epithelial cells and overexpression of TRIM41 inhibits IAV infection. Conversely, RNA interference (RNAi) and knockout of TRIM41 increase host susceptibility to IAV infection. As a ubiquitin E3 ligase, TRIM41 ubiquitinates NP in vitro and in cells. The TRIM41 mutant lacking E3 ligase activity fails to inhibit IAV infection, suggesting that the E3 ligase activity is indispensable for TRIM41 antiviral function. Mechanistic analysis further revealed that the polyubiquitination leads to NP protein degradation and viral inhibition. Taken together, TRIM41 is a constitutively expressed intrinsic IAV restriction factor that targets NP for ubiquitination and protein degradation. IMPORTANCE Influenza control strategies rely on annual immunization and require frequent updates of the vaccine, which are not always a foolproof process. Furthermore, the current antivirals are also losing effectiveness as new viral strains are often refractory to conventional treatments. Thus, there is an urgent need to find new antiviral mechanisms and develop therapeutic drugs based on these mechanisms. Targeting the virus-host interface is an emerging new strategy because host factors controlling viral replication activity will be ideal candidates and cellular proteins are less likely to mutate under drug-mediated selective pressure. Here, we show that the ubiquitin E3 ligase TRIM41 is an intrinsic host restriction factor to IAV

Surface trimming of silicon photonics devices using controlled reactive ion etching chemistry

NASA Astrophysics Data System (ADS)

Chandran, S.; Das, B. K.

2015-06-01

Surface trimming of rib waveguides fabricated in 5-μm SOI substrate has been carried out successfully without any significant increase of propagation losses. A reactive ion etching chemistry has been optimized for trimming and an empirical model has been developed to obtain the resulting waveguide geometries. This technique has been used to demonstrate smaller footprint devices like multimode interference based power splitters and ring resonators after defining them photolithographically with relatively large cross-section rib waveguides. We have been also successful to fabricate 2D tapered spot-size converter useful for monolithic integration of waveguides with varying heights and widths. The taper length is again precisely controlled by photolithographic definition. Minimum insertion loss of such a spot-size converter integrated between waveguides with 3-μm height difference has been recorded to be ∼2 dB. It has been also shown that the overall fiber-to-chip coupling loss can be reduced by >3 dB by using such spot-size converters at the input/output side of the waveguides.

Elevated Rate of Fixation of Endogenous Retroviral Elements in Haplorhini TRIM5 and TRIM22 Genomic Sequences: Impact on Transcriptional Regulation

PubMed Central

Diehl, William E.; Johnson, Welkin E.; Hunter, Eric

2013-01-01

All genes in the TRIM6/TRIM34/TRIM5/TRIM22 locus are type I interferon inducible, with TRIM5 and TRIM22 possessing antiviral properties. Evolutionary studies involving the TRIM6/34/5/22 locus have predominantly focused on the coding sequence of the genes, finding that TRIM5 and TRIM22 have undergone high rates of both non-synonymous nucleotide replacements and in-frame insertions and deletions. We sought to understand if divergent evolutionary pressures on TRIM6/34/5/22 coding regions have selected for modifications in the non-coding regions of these genes and explore whether such non-coding changes may influence the biological function of these genes. The transcribed genomic regions, including the introns, of TRIM6, TRIM34, TRIM5, and TRIM22 from ten Haplorhini primates and one prosimian species were analyzed for transposable element content. In Haplorhini species, TRIM5 displayed an exaggerated interspecies variability, predominantly resulting from changes in the composition of transposable elements in the large first and fourth introns. Multiple lineage-specific endogenous retroviral long terminal repeats (LTRs) were identified in the first intron of TRIM5 and TRIM22. In the prosimian genome, we identified a duplication of TRIM5 with a concomitant loss of TRIM22. The transposable element content of the prosimian TRIM5 genes appears to largely represent the shared Haplorhini/prosimian ancestral state for this gene. Furthermore, we demonstrated that one such differentially fixed LTR provides for species-specific transcriptional regulation of TRIM22 in response to p53 activation. Our results identify a previously unrecognized source of species-specific variation in the antiviral TRIM genes, which can lead to alterations in their transcriptional regulation. These observations suggest that there has existed long-term pressure for exaptation of retroviral LTRs in the non-coding regions of these genes. This likely resulted from serial viral challenges and provided a

Compensation of the AKT signaling by ERK signaling in transgenic mice hearts overexpressing TRIM72

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ham, Young-Mi, E-mail: youngmi_ham@hms.harvard.edu; Department of Cell Biology, Harvard Medical School, Boston, MA 02115; Mahoney, Sarah Jane

The AKT and ERK signaling pathways are known to be involved in cell hypertrophy, proliferation, survival and differentiation. Although there is evidence for crosstalk between these two signaling pathways in cellulo, there is less evidence for cross talk in vivo. Here, we show that crosstalk between AKT and ERK signaling in the hearts of TRIM72-overexpressing transgenic mice (TRIM72-Tg) with alpha-MHC promoter regulates and maintains their heart size. TRIM72, a heart- and skeletal muscle-specific protein, downregulates AKT-mTOR signaling via IRS-1 degradation and reduces the size of rat cardiomyocytes and the size of postnatal TRIM72-Tg hearts. TRIM72 expression was upregulated by hypertrophicmore » inducers in cardiomyocytes, while IRS-1 was downregulated by IGF-1. TRIM72 specifically regulated IGF-1-dependent AKT-mTOR signaling, resulting in a reduction of the size of cardiomyocytes. Postnatal TRIM72-Tg hearts were smaller than control-treated hearts with inhibition of AKT-mTOR signaling. However, adult TRIM72-Tg hearts were larger than of control despite the suppression of AKT-mTOR signaling. Activation of ERK, PKC-α, and JNK were observed to be elevated in adult TRIM72-Tg, and these signals were mediated by ET-1 via the ET receptors A and B. Altogether, these results suggest that AKT signaling regulates cardiac hypertrophy in physiological conditions, and ERK signaling compensates for the absence of AKT signaling during TRIM72 overexpression, leading to pathological hypertrophy. -- Highlights: • TRIM72 inhibits AKT signaling through ubiquitination of IRS-1 in cardiac cells. • TRIM72 regulates the size of cardiac cells. • TRIM72 regulates size of postnatal TRIM72-overexpressing transgenic mice hearts. • Adult TRIM72-overexpressing transgenic mice hearts showed cardiac dysfunction. • Adult TRIM72 transgenic mice hearts showed higher expression of endothelin receptors.« less

Circuit-lead trimming template

NASA Technical Reports Server (NTRS)

Ofarrell, K.; Winn, E.

1979-01-01

Template for use in trimming leads on production wiring boards is low-cost means for eliminating rejections for short leads and improving lead-strength uniformity. Template is simply unclad piece of printed-circuit board material that is drilled using same drill control tape used in making original production board. Revisions in component layout of board can therefore be made simultaneously in template.

TRIM65 negatively regulates p53 through ubiquitination

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yang; Ma, Chengyuan; Zhou, Tong

2016-04-22

Tripartite-motif protein family member 65 (TRIM65) is an important protein involved in white matter lesion. However, the role of TRIM65 in human cancer remains less understood. Through the Cancer Genome Atlas (TCGA) gene alteration database, we found that TRIM65 is upregulated in a significant portion of non-small cell lung carcinoma (NSCLC) patients. Our cell growth assay revealed that TRIM65 overexpression promotes cell proliferation, while knockdown of TRIM65 displays opposite effect. Mechanistically, TRIM65 binds to p53, one of the most critical tumor suppressors, and serves as an E3 ligase toward p53. Consequently, TRIM65 inactivates p53 through facilitating p53 poly-ubiquitination and proteasome-mediatedmore » degradation. Notably, chemotherapeutic reagent cisplatin induction of p53 is markedly attenuated in response to ectopic expression of TRIM65. Cell growth inhibition by TRIM65 knockdown is more significant in p53 positive H460 than p53 negative H1299 cells, and knockdown of p53 in H460 cells also shows compromised cell growth inhibition by TRIM65 knockdown, indicating that p53 is required, at least in part, for TRIM65 function. Our findings demonstrate TRIM65 as a potential oncogenic protein, highly likely through p53 inactivation, and provide insight into development of novel approaches targeting TRIM65 for NSCLC treatment, and also overcoming chemotherapy resistance. - Highlights: • TRIM65 expression is elevated in NSCLC. • TRIM65 inactivates p53 through mediating p53 ubiquitination and degradation. • TRIM65 attenuates the response of NSCLC cells to cisplatin.« less

7 CFR 51.607 - Well trimmed.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 2 2012-01-01 2012-01-01 false Well trimmed. 51.607 Section 51.607 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Consumer Standards for Celery Stalks Definitions § 51.607 Well trimmed. Well trimmed means that the outside...

7 CFR 51.571 - Well trimmed.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 2 2014-01-01 2014-01-01 false Well trimmed. 51.571 Section 51.571 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing..., CERTIFICATION, AND STANDARDS) United States Standards for Celery Definitions § 51.571 Well trimmed. Well trimmed...

7 CFR 51.571 - Well trimmed.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 2 2013-01-01 2013-01-01 false Well trimmed. 51.571 Section 51.571 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing..., CERTIFICATION, AND STANDARDS) United States Standards for Celery Definitions § 51.571 Well trimmed. Well trimmed...

7 CFR 51.3063 - Well trimmed.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 2 2012-01-01 2012-01-01 false Well trimmed. 51.3063 Section 51.3063 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Florida Avocados Definitions § 51.3063 Well trimmed. Well trimmed means that the stem, when...

7 CFR 51.3063 - Well trimmed.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 2 2011-01-01 2011-01-01 false Well trimmed. 51.3063 Section 51.3063 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Florida Avocados Definitions § 51.3063 Well trimmed. Well trimmed means that the stem, when...

7 CFR 51.3063 - Well trimmed.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Well trimmed. 51.3063 Section 51.3063 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Florida Avocados Definitions § 51.3063 Well trimmed. Well trimmed means that the stem, when...

7 CFR 51.571 - Well trimmed.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 2 2012-01-01 2012-01-01 false Well trimmed. 51.571 Section 51.571 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Celery Definitions § 51.571 Well trimmed. Well trimmed means that not more than 2 relatively...

7 CFR 51.571 - Well trimmed.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Well trimmed. 51.571 Section 51.571 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Celery Definitions § 51.571 Well trimmed. Well trimmed means that not more than 2 relatively...

7 CFR 51.571 - Well trimmed.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 2 2011-01-01 2011-01-01 false Well trimmed. 51.571 Section 51.571 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Celery Definitions § 51.571 Well trimmed. Well trimmed means that not more than 2 relatively...

7 CFR 51.607 - Well trimmed.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 2 2014-01-01 2014-01-01 false Well trimmed. 51.607 Section 51.607 Agriculture..., CERTIFICATION, AND STANDARDS) United States Consumer Standards for Celery Stalks Definitions § 51.607 Well trimmed. Well trimmed means that the outside coarse and damaged branches have been removed and that the...

7 CFR 51.607 - Well trimmed.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 2 2013-01-01 2013-01-01 false Well trimmed. 51.607 Section 51.607 Agriculture..., CERTIFICATION, AND STANDARDS) United States Consumer Standards for Celery Stalks Definitions § 51.607 Well trimmed. Well trimmed means that the outside coarse and damaged branches have been removed and that the...

The ability of White Leghorn hens with trimmed comb and wattles to thermoregulate.

PubMed

Al-Ramamneh, D S; Makagon, M M; Hester, P Y

2016-08-01

It is estimated that each year over 19 million pullets in the United States have their combs partially trimmed at a young age to improve egg production and feed efficiency. A possible disadvantage of trimming is that the comb and wattles may be essential for thermoregulation during hot weather allowing for conductive cooling of the blood through vasodilation of superficial vessels in these integumentary tissues. The objective of this study was to investigate the effects of partial comb and wattle removal, performed at 21 d of age, on the ability of White Leghorns to thermoregulate before, during, and after an imposed heating episode that averaged 34.6°C for 50.5 h. An increase in mortality at 20 h and body temperature at 48 h post initiation of the heating episode demonstrated that hens with trimmed comb and wattles were not able to cope with heat stress as effectively as controls. The increase in wattle temperature in controls as compared to trimmed hens during the heating episode and following heat stress provides supportive evidence that blood pools to the peripheral surface for conductive heat loss. During high temperatures typical of summer, trimmed hens attempted to compensate for their lack of ability to transfer heat from their comb and wattles to the environment through increased proportion of panting and wing spreading. Under less extreme conditions with lowered ambient temperatures, the trimming of the comb and wattles did not impair the ability of hens to thermoregulate, as body temperatures and behavior were similar to controls with no mortality. Egg weight was the only production parameter adversely affected by the trimming of the comb and wattles as compared to controls. The implication is that hens need their combs and wattles to thermoregulate effectively during periods of high environmental temperature. Pullets should not be subjected to a comb and wattle trim if they are housed in laying facilities that are not appropriately cooled during the

7 CFR 51.3063 - Well trimmed.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 2 2014-01-01 2014-01-01 false Well trimmed. 51.3063 Section 51.3063 Agriculture..., CERTIFICATION, AND STANDARDS) United States Standards for Florida Avocados Definitions § 51.3063 Well trimmed. Well trimmed means that the stem, when present, is cut off fairly smoothly at a point not more than one...

7 CFR 51.3063 - Well trimmed.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 2 2013-01-01 2013-01-01 false Well trimmed. 51.3063 Section 51.3063 Agriculture..., CERTIFICATION, AND STANDARDS) United States Standards for Florida Avocados Definitions § 51.3063 Well trimmed. Well trimmed means that the stem, when present, is cut off fairly smoothly at a point not more than one...

The role of Trim25 in development, disease and RNA metabolism.

PubMed

Heikel, Gregory; Choudhury, Nila Roy; Michlewski, Gracjan

2016-08-15

Trim25 is a member of the tripartite motif family of E3 ubiquitin ligases. It plays major roles in innate immunity and defence against viral infection, control of cell proliferation and migration of cancer cells. Recent work identified Trim25 as being able to bind to RNA and to regulate Lin28a-mediated uridylation of pre-let-7. Here we review the current knowledge of the role of Trim25 in development, disease and RNA metabolism. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Development and wind tunnel evaluation of a shape memory alloy based trim tab actuator for a civil aircraft

NASA Astrophysics Data System (ADS)

Senthilkumar, P.; Jayasankar, S.; Satisha; Sateesh, V. L.; Kamaleshaiah, M. S.; Dayananda, G. N.

2013-09-01

This paper presents the development and wind tunnel evaluation of a shape memory alloy (SMA) based smart trim tab for a typical two seater civil aircraft. The SMA actuator was housed in the port side of the elevator for the purpose of actuating the trim tab. Wind tunnel tests were conducted on a full scale horizontal tail model with elevator and trim tab at free stream speeds of 25, 35 and 45 m s-1, and also for a number of deflections of the elevator (30° up, 0° neutral and 25° down) and trim tab (11° and 21° up and 15° and 31° down). To measure the hinge moment experienced by the trim tab under various test conditions, two miniaturized balances were designed and fabricated. A gain scheduled proportional integral (GSPI) controller was developed to control the SMA actuated smart trim tab. It was confirmed during the tests that the trim tab could be controlled at the desired position against the aerodynamic loads acting on it for the various test conditions.

The ubiquitin-specific protease USP15 promotes RIG-I-mediated antiviral signaling by deubiquitylating TRIM25.

PubMed

Pauli, Eva-Katharina; Chan, Ying Kai; Davis, Meredith E; Gableske, Sebastian; Wang, May K; Feister, Katharina F; Gack, Michaela U

2014-01-07

Ubiquitylation is an important mechanism for regulating innate immune responses to viral infections. Attachment of lysine 63 (Lys(63))-linked ubiquitin chains to the RNA sensor retinoic acid-inducible gene-I (RIG-I) by the ubiquitin E3 ligase tripartite motif protein 25 (TRIM25) leads to the activation of RIG-I and stimulates production of the antiviral cytokines interferon-α (IFN-α) and IFN-β. Conversely, Lys(48)-linked ubiquitylation of TRIM25 by the linear ubiquitin assembly complex (LUBAC) stimulates the proteasomal degradation of TRIM25, thereby inhibiting the RIG-I signaling pathway. Here, we report that ubiquitin-specific protease 15 (USP15) deubiquitylates TRIM25, preventing the LUBAC-dependent degradation of TRIM25. Through protein purification and mass spectrometry analysis, we identified USP15 as an interaction partner of TRIM25 in human cells. Knockdown of endogenous USP15 by specific small interfering RNA markedly enhanced the ubiquitylation of TRIM25. In contrast, expression of wild-type USP15, but not its catalytically inactive mutant, reduced the Lys(48)-linked ubiquitylation of TRIM25, leading to its stabilization. Furthermore, ectopic expression of USP15 enhanced the TRIM25- and RIG-I-dependent production of type I IFN and suppressed RNA virus replication. In contrast, depletion of USP15 resulted in decreased IFN production and markedly enhanced viral replication. Together, these data identify USP15 as a critical regulator of the TRIM25- and RIG-I-mediated antiviral immune response, thereby highlighting the intricate regulation of innate immune signaling.

The Ubiquitin-Specific Protease USP15 Promotes RIG-I–Mediated Antiviral Signaling by Deubiquitylating TRIM25

PubMed Central

Pauli, Eva-Katharina; Chan, Ying Kai; Davis, Meredith E.; Gableske, Sebastian; Wang, May K.; Feister, Katharina F.; Gack, Michaela U.

2014-01-01

Ubiquitylation is an important mechanism for regulating innate immune responses to viral infections. Attachment of lysine 63 (Lys63)–linked ubiquitin chains to the RNA sensor retinoic acid–inducible gene-I (RIG-I) by the ubiquitin E3 ligase tripartite motif protein 25 (TRIM25) leads to the activation of RIG-I and stimulates production of the antiviral cytokines interferon-α (IFN-α) and IFN-β. Conversely, Lys48-linked ubiquitylation of TRIM25 by the linear ubiquitin assembly complex (LUBAC) stimulates the proteasomal degradation of TRIM25, thereby inhibiting the RIG-I signaling pathway. Here, we report that ubiquitin-specific protease 15 (USP15) deubiquitylates TRIM25, preventing the LUBAC-dependent degradation of TRIM25. Through protein purification and mass spectrometry analysis, we identified USP15 as an interaction partner of TRIM25 in human cells. Knockdown of endogenous USP15 by specific small interfering RNA markedly enhanced the ubiquitylation of TRIM25. In contrast, expression of wild-type USP15, but not its catalytically inactive mutant, reduced the Lys48-linked ubiquitylation of TRIM25, leading to its stabilization. Furthermore, ectopic expression of USP15 enhanced the TRIM25- and RIG-I–dependent production of type I IFN and suppressed RNA virus replication. In contrast, depletion of USP15 resulted in decreased IFN production and markedly enhanced viral replication. Together, these data identify USP15 as a critical regulator of the TRIM25- and RIG-I–mediated antiviral immune response, thereby highlighting the intricate regulation of innate immune signaling. PMID:24399297

TRIM Family Proteins: Roles in Autophagy, Immunity, and Carcinogenesis.

PubMed

Hatakeyama, Shigetsugu

2017-04-01

Tripartite motif (TRIM) family proteins, most of which have E3 ubiquitin ligase activities, have various functions in cellular processes including intracellular signaling, development, apoptosis, protein quality control, innate immunity, autophagy, and carcinogenesis. The ubiquitin system is one of the systems for post-translational modifications, which play crucial roles not only as markers for degradation of target proteins by the proteasome but also as regulators of protein-protein interactions and of the activation of enzymes. Accumulating evidence has shown that TRIM family proteins have unique, important roles and that their dysregulation causes several diseases classified as cancer, immunological disease, or developmental disorders. In this review we focus on recent emerging topics on TRIM proteins in the regulation of autophagy, innate immunity, and carcinogenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Functional Laser Trimming Of Thin Film Resistors On Silicon ICs

NASA Astrophysics Data System (ADS)

Mueller, Michael J.; Mickanin, Wes

1986-07-01

Modern Laser Wafer Trimming (LWT) technology achieves exceptional analog circuit performance and precision while maintain-ing the advantages of high production throughput and yield. Microprocessor-driven instrumentation has both emphasized the role of data conversion circuits and demanded sophisticated signal conditioning functions. Advanced analog semiconductor circuits with bandwidths over 1 GHz, and high precision, trimmable, thin-film resistors meet many of todays emerging circuit requirements. Critical to meeting these requirements are optimum choices of laser characteristics, proper materials, trimming process control, accurate modeling of trimmed resistor performance, and appropriate circuit design. Once limited exclusively to hand-crafted, custom integrated circuits, designs are now available in semi-custom circuit configurations. These are similar to those provided for digital designs and supported by computer-aided design (CAD) tools. Integrated with fully automated measurement and trimming systems, these quality circuits can now be produced in quantity to meet the requirements of communications, instrumentation, and signal processing markets.

14 CFR 25.255 - Out-of-trim characteristics.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Out-of-trim characteristics. 25.255 Section...-trim characteristics. (a) From an initial condition with the airplane trimmed at cruise speeds up to... of out-of-trim in both the airplane nose-up and nose-down directions, which results from the greater...

7 CFR 51.585 - Fairly well trimmed.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 2 2012-01-01 2012-01-01 false Fairly well trimmed. 51.585 Section 51.585 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Celery Definitions § 51.585 Fairly well trimmed. Fairly well trimmed means that the main root...

7 CFR 51.585 - Fairly well trimmed.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Fairly well trimmed. 51.585 Section 51.585 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Celery Definitions § 51.585 Fairly well trimmed. Fairly well trimmed means that the main root...

7 CFR 51.585 - Fairly well trimmed.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 2 2011-01-01 2011-01-01 false Fairly well trimmed. 51.585 Section 51.585 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Standards for Celery Definitions § 51.585 Fairly well trimmed. Fairly well trimmed means that the main root...

TRIM-directed selective autophagy regulates immune activation.

PubMed

Kimura, Tomonori; Jain, Ashish; Choi, Seong Won; Mandell, Michael A; Johansen, Terje; Deretic, Vojo

2017-05-04

Selectivity of autophagy is achieved by target recognition; however, the number of autophagy receptors identified so far is limited. In this study we demonstrate that a subset of tripartite motif (TRIM) proteins mediate selective autophagy of key regulators of inflammatory signaling. MEFV/TRIM20, and TRIM21 act as autophagic receptors recognizing their cognate targets and delivering them for autophagic degradation. MEFV recognizes the inflammasome components NLRP3, CASP1 and NLRP1, whereas TRIM21 specifically recognizes the activated, dimeric from of IRF3 inducing type I interferon gene expression. MEFV and TRIM21 have a second activity, whereby they act not only as receptors but also recruit and organize key components of autophagic machinery consisting of ULK1, BECN1, ATG16L1, and mammalian homologs of Atg8, with a preference for GABARAP. MEFV capacity to organize the autophagy apparatus is affected by common mutations causing familial Mediterranean fever. These findings reveal a general mode of action of TRIMs as autophagic receptor-regulators performing a highly-selective type of autophagy (precision autophagy), with MEFV specializing in the suppression of inflammasome and CASP1 activation engendering IL1B/interleukin-1β production and implicated in the form of cell death termed pyroptosis, whereas TRIM21 dampens type I interferon responses.

14 CFR 23.255 - Out of trim characteristics.

Code of Federal Regulations, 2012 CFR

2012-01-01

... an initial condition with the airplane trimmed at cruise speeds up to VMO/MMO, the airplane must have... VDF/MDF , the direction of the primary longitudinal control force may not reverse. (c) Except as... exist during flight test with regard to reversal of primary longitudinal control force, flight tests...

7 CFR 51.585 - Fairly well trimmed.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 2 2014-01-01 2014-01-01 false Fairly well trimmed. 51.585 Section 51.585 Agriculture..., CERTIFICATION, AND STANDARDS) United States Standards for Celery Definitions § 51.585 Fairly well trimmed. Fairly well trimmed means that the main root has been cut off so that it does not extend more than 3...

7 CFR 51.585 - Fairly well trimmed.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 2 2013-01-01 2013-01-01 false Fairly well trimmed. 51.585 Section 51.585 Agriculture..., CERTIFICATION, AND STANDARDS) United States Standards for Celery Definitions § 51.585 Fairly well trimmed. Fairly well trimmed means that the main root has been cut off so that it does not extend more than 3...

TRIM25 has a dual function in the p53/Mdm2 circuit.

PubMed

Zhang, P; Elabd, S; Hammer, S; Solozobova, V; Yan, H; Bartel, F; Inoue, S; Henrich, T; Wittbrodt, J; Loosli, F; Davidson, G; Blattner, C

2015-11-12

P53 is an important tumor suppressor that, upon activation, induces growth arrest and cell death. Control of p53 is thus of prime importance for proliferating cells, but also for cancer therapy, where p53 activity contributes to the eradication of tumors. Mdm2 functionally inhibits p53 and targets the tumor suppressor protein for degradation. In a genetic screen, we identified TRIM25 as a novel regulator of p53 and Mdm2. TRIM25 increased p53 and Mdm2 abundance by inhibiting their ubiquitination and degradation in 26 S proteasomes. TRIM25 co-precipitated with p53 and Mdm2 and interfered with the association of p300 and Mdm2, a critical step for p53 polyubiquitination. Despite the increase in p53 levels, p53 activity was inhibited in the presence of TRIM25. Downregulation of TRIM25 resulted in an increased acetylation of p53 and p53-dependent cell death in HCT116 cells. Upon genotoxic insults, TRIM25 dampened the p53-dependent DNA damage response. The downregulation of TRIM25 furthermore resulted in massive apoptosis during early embryogenesis of medaka, which was rescued by the concomitant downregulation of p53, demonstrating the functional relevance of the regulation of p53 by TRIM25 in an organismal context.

TRIM proteins: another class of viral victims.

PubMed

Munir, Muhammad

2010-04-20

TRIM (tripartite motif) proteins are a family of RING (really interesting new gene) domain-containing proteins comprising more than 70 human members, with new members still being described. In addition to their involvement in cell proliferation, differentiation, development, morphogenesis, and apoptosis, roles in immune signaling and antiviral functions are emerging. In response to viral infection, TRIM25 ubiquitinates the N terminus of the viral RNA receptor retinoic acid-inducible gene-I (RIG-I), and this modification is essential for RIG-I to interact with its downstream partner mitochondrial antiviral signaling (MAVS). TRIM25 activity thus leads to activation of the RIG-I signaling pathway, which results in type I interferon production to limit viral replication. Recently, it has been demonstrated that influenza A viruses target TRIM25 and disable its antiviral function, thereby suppressing the host interferon response. This Journal Club article highlights the emerging roles of TRIM proteins in antiviral defense mechanisms and an immune evasion strategy in which influenza viruses target a member of the TRIM family.

14 CFR 25.677 - Trim systems.

Code of Federal Regulations, 2013 CFR

2013-01-01

... clearly visible means to indicate the position of the trim device with respect to the range of adjustment. The indicator must be clearly marked with the range within which it has been demonstrated that takeoff... appropriately balanced and shown to be free from flutter. (d) If an irreversible tab control system is used, the...

Cassini Orbit Trim Maneuvers at Saturn - Overview of Attitude Control Flight Operations

NASA Technical Reports Server (NTRS)

Burk, Thomas A.

2011-01-01

The Cassini spacecraft has been in orbit around Saturn since July 1, 2004. To remain on the planned trajectory which maximizes science data return, Cassini must perform orbit trim maneuvers using either its main engine or its reaction control system thrusters. Over 200 maneuvers have been executed on the spacecraft since arrival at Saturn. To improve performance and maintain spacecraft health, changes have been made in maneuver design command placement, in accelerometer scale factor, and in the pre-aim vector used to align the engine gimbal actuator prior to main engine burn ignition. These and other changes have improved maneuver performance execution errors significantly since 2004. A strategy has been developed to decide whether a main engine maneuver should be performed, or whether the maneuver can be executed using the reaction control system.

14 CFR 23.255 - Out of trim characteristics.

Code of Federal Regulations, 2013 CFR

2013-01-01

... apply: (a) From an initial condition with the airplane trimmed at cruise speeds up to VMO/MMO, the... speeds between VFC/MFC and VDF/MDF , the direction of the primary longitudinal control force may not... control force, flight tests must be accomplished from the normal acceleration at which a marginal...

The E3 ubiquitin ligase Trim7 mediates c-Jun/AP-1 activation by Ras signalling

PubMed Central

Chakraborty, Atanu; Diefenbacher, Markus E.; Mylona, Anastasia; Kassel, Olivier; Behrens, Axel

2015-01-01

The c-Jun/AP-1 transcription factor controls key cellular behaviours, including proliferation and apoptosis, in response to JNK and Ras/MAPK signalling. While the JNK pathway has been well characterised, the mechanism of activation by Ras was elusive. Here we identify the uncharacterised ubiquitin ligase Trim7 as a critical component of AP-1 activation via Ras. We found that MSK1 directly phosphorylates Trim7 in response to direct activation by the Ras–Raf–MEK–ERK pathway, and this modification stimulates Trim7 E3 ubiquitin ligase activity. Trim7 mediates Lys63-linked ubiquitination of the AP-1 coactivator RACO-1, leading to RACO-1 protein stabilisation. Consequently, Trim7 depletion reduces RACO-1 levels and AP-1-dependent gene expression. Moreover, transgenic overexpression of Trim7 increases lung tumour burden in a Ras-driven cancer model, and knockdown of Trim7 in established xenografts reduces tumour growth. Thus, phosphorylation-ubiquitination crosstalk between MSK1, Trim7 and RACO-1 completes the long sought-after mechanism linking growth factor signalling and AP-1 activation. PMID:25851810

Tumour suppressor TRIM33 targets nuclear β-catenin degradation

PubMed Central

Xue, Jianfei; Chen, Yaohui; Wu, Yamei; Wang, Zhongyong; Zhou, Aidong; Zhang, Sicong; Lin, Kangyu; Aldape, Kenneth; Majumder, Sadhan; Lu, Zhimin; Huang, Suyun

2014-01-01

Aberrant activation of β-catenin in the nucleus has been implicated in a variety of human cancers but the fate of nuclear β-catenin is unknown. Here we demonstrate that tripartite motif-containing protein 33 (TRIM33), acting as an E3 ubiquitin ligase, reduces the abundance of nuclear β-catenin protein. TRIM33-mediated β-catenin is destabilized and is GSK-3β or β-TrCP independent. TRIM33 interacts with and ubiquitylates nuclear β-catenin. Moreover, protein kinase Cδ, which directly phosphorylates β-catenin at Ser715, is required for the TRIM33–β-catenin interaction. The function of TRIM33 in suppressing tumour cell proliferation and brain tumour development depends on TRIM33-promoted β-catenin degradation. In human glioblastoma specimens, endogenous TRIM33 levels are inversely correlated with β-catenin. In summary, our findings identify TRIM33 as a tumour suppressor that can abolish tumour cell proliferation and tumorigenesis by degrading nuclear β-catenin. This work suggests a new therapeutic strategy against human cancers caused by aberrant activation of β-catenin. PMID:25639486

Compartment A1, trim tanks viewed aft to forward from watertight ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Compartment A-1, trim tanks viewed aft to forward from watertight bulkhead no. 6. Using remotely controlled valves, the tanks could be flooded with water or pumped clear to compensate for variations in the ship's displacement and maintain the water line at the desired point. The trim tanks could also be used to counteract the effect of variations in sea water density. (02) - USS Olympia, Penn's Landing, 211 South Columbus Boulevard, Philadelphia, Philadelphia County, PA

Periacetabular Osteotomy Provides Higher Survivorship Than Rim Trimming for Acetabular Retroversion.

PubMed

Zurmühle, Corinne A; Anwander, Helen; Albers, Christoph E; Hanke, Markus S; Steppacher, Simon D; Siebenrock, Klaus A; Tannast, Moritz

2017-04-01

Acetabular retroversion can cause impaction-type femoroacetabular impingement leading to hip pain and osteoarthritis. It can be treated by anteverting periacetabular osteotomy (PAO) or acetabular rim trimming with refixation of the labrum. There is increasing evidence that acetabular retroversion is a rotational abnormality of the entire hemipelvis and not a focal overgrowth of the anterior acetabular wall, which favors an anteverting PAO. However, it is unknown if this larger procedure would be beneficial in terms of survivorship and Merle d'Aubigné scores in a midterm followup compared with rim trimming. We asked if anteverting PAO results in increased survivorship of the hip compared with rim trimming through a surgical hip dislocation in patients with symptomatic acetabular retroversion. We performed a retrospective, comparative study evaluating the midterm survivorship of two matched patient groups with symptomatic acetabular retroversion undergoing either anteverting PAO or acetabular rim trimming through a surgical hip dislocation. Acetabular retroversion was defined by a concomitantly present positive crossover, posterior wall, and ischial spine sign. A total of 279 hips underwent a surgical intervention for acetabular retroversion at our center between 1997 and 2012 (166 periacetabular osteotomies, 113 rim trimmings through surgical hip dislocation). A total of 99 patients (60%) were excluded from the PAO group and 56 patients (50%) from the rim trimming group because they had any of several prespecified conditions (eg, dysplasia or pediatric conditions 61 [37%] for the PAO group and two [2%] for the rim trimming group), matching (10 [6%]/10 [9%] hips), deficient records (10 [6%]/13 [12%] hips), or the patient declined or was lost to followup (18 [11%]/31 [27%] hips). This left 67 hips (57 patients) that underwent anteverting PAO and 57 hips (52 patients) that had acetabular rim trimming. The two groups did not differ in terms of age, sex, body mass

Computational aspects of helicopter trim analysis and damping levels from Floquet theory

NASA Technical Reports Server (NTRS)

Gaonkar, Gopal H.; Achar, N. S.

1992-01-01

Helicopter trim settings of periodic initial state and control inputs are investigated for convergence of Newton iteration in computing the settings sequentially and in parallel. The trim analysis uses a shooting method and a weak version of two temporal finite element methods with displacement formulation and with mixed formulation of displacements and momenta. These three methods broadly represent two main approaches of trim analysis: adaptation of initial-value and finite element boundary-value codes to periodic boundary conditions, particularly for unstable and marginally stable systems. In each method, both the sequential and in-parallel schemes are used and the resulting nonlinear algebraic equations are solved by damped Newton iteration with an optimally selected damping parameter. The impact of damped Newton iteration, including earlier-observed divergence problems in trim analysis, is demonstrated by the maximum condition number of the Jacobian matrices of the iterative scheme and by virtual elimination of divergence. The advantages of the in-parallel scheme over the conventional sequential scheme are also demonstrated.

Peak-Seeking Optimization of Trim for Reduced Fuel Consumption: Flight-Test Results

NASA Technical Reports Server (NTRS)

Brown, Nelson Andrew; Schaefer, Jacob Robert

2013-01-01

A peak-seeking control algorithm for real-time trim optimization for reduced fuel consumption has been developed by researchers at the National Aeronautics and Space Administration (NASA) Dryden Flight Research Center to address the goals of the NASA Environmentally Responsible Aviation project to reduce fuel burn and emissions. The peak-seeking control algorithm is based on a steepest-descent algorithm using a time-varying Kalman filter to estimate the gradient of a performance function of fuel flow versus control surface positions. In real-time operation, deflections of symmetric ailerons, trailing-edge flaps, and leading-edge flaps of an F/A-18 airplane (McDonnell Douglas, now The Boeing Company, Chicago, Illinois) are used for optimization of fuel flow. Results from six research flights are presented herein. The optimization algorithm found a trim configuration that required approximately 3 percent less fuel flow than the baseline trim at the same flight condition. The algorithm consistently rediscovered the solution from several initial conditions. These results show that the algorithm has good performance in a relevant environment.

Peak-Seeking Optimization of Trim for Reduced Fuel Consumption: Flight-test Results

NASA Technical Reports Server (NTRS)

Brown, Nelson Andrew; Schaefer, Jacob Robert

2013-01-01

A peak-seeking control algorithm for real-time trim optimization for reduced fuel consumption has been developed by researchers at the National Aeronautics and Space Administration (NASA) Dryden Flight Research Center to address the goals of the NASA Environmentally Responsible Aviation project to reduce fuel burn and emissions. The peak-seeking control algorithm is based on a steepest-descent algorithm using a time-varying Kalman filter to estimate the gradient of a performance function of fuel flow versus control surface positions. In real-time operation, deflections of symmetric ailerons, trailing-edge flaps, and leading-edge flaps of an F/A-18 airplane (McDonnell Douglas, now The Boeing Company, Chicago, Illinois) are used for optimization of fuel flow. Results from six research flights are presented herein. The optimization algorithm found a trim configuration that required approximately 3 percent less fuel flow than the baseline trim at the same flight condition. The algorithm consistently rediscovered the solution from several initial conditions. These results show that the algorithm has good performance in a relevant environment.

Resistive RAMs as analog trimming elements

NASA Astrophysics Data System (ADS)

Aziza, H.; Perez, A.; Portal, J. M.

2018-04-01

This work investigates the use of Resistive Random Access Memory (RRAM) as an analog trimming device. The analog storage feature of the RRAM cell is evaluated and the ability of the RRAM to hold several resistance states is exploited to propose analog trim elements. To modulate the memory cell resistance, a series of short programming pulses are applied across the RRAM cell allowing a fine calibration of the RRAM resistance. The RRAM non volatility feature makes the analog device powers up already calibrated for the system in which the analog trimmed structure is embedded. To validate the concept, a test structure consisting of a voltage reference is evaluated.

30 CFR 56.9314 - Trimming stockpile and muckpile faces.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Trimming stockpile and muckpile faces. 56.9314... Dumping Sites § 56.9314 Trimming stockpile and muckpile faces. Stockpile and muckpile faces shall be trimmed to prevent hazards to persons. ...

30 CFR 56.9314 - Trimming stockpile and muckpile faces.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Trimming stockpile and muckpile faces. 56.9314... Dumping Sites § 56.9314 Trimming stockpile and muckpile faces. Stockpile and muckpile faces shall be trimmed to prevent hazards to persons. ...

30 CFR 57.9314 - Trimming stockpile and muckpile faces.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Trimming stockpile and muckpile faces. 57.9314... Dumping Sites § 57.9314 Trimming stockpile and muckpile faces. Stockpile and muckpile faces shall be trimmed to prevent hazards to persons. ...

30 CFR 57.9314 - Trimming stockpile and muckpile faces.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Trimming stockpile and muckpile faces. 57.9314... Dumping Sites § 57.9314 Trimming stockpile and muckpile faces. Stockpile and muckpile faces shall be trimmed to prevent hazards to persons. ...

Activation of duck RIG-I by TRIM25 is independent of anchored ubiquitin.

PubMed

Miranzo-Navarro, Domingo; Magor, Katharine E

2014-01-01

Retinoic acid inducible gene I (RIG-I) is a viral RNA sensor crucial in defense against several viruses including measles, influenza A and hepatitis C. RIG-I activates type-I interferon signalling through the adaptor for mitochondrial antiviral signaling (MAVS). The E3 ubiquitin ligase, tripartite motif containing protein 25 (TRIM25), activates human RIG-I through generation of anchored K63-linked polyubiquitin chains attached to lysine 172, or alternatively, through the generation of unanchored K63-linked polyubiquitin chains that interact non-covalently with RIG-I CARD domains. Previously, we identified RIG-I of ducks, of interest because ducks are the host and natural reservoir of influenza viruses, and showed it initiates innate immune signaling leading to production of interferon-beta (IFN-β). We noted that K172 is not conserved in RIG-I of ducks and other avian species, or mouse. Because K172 is important for both mechanisms of activation of human RIG-I, we investigated whether duck RIG-I was activated by TRIM25, and if other residues were the sites for attachment of ubiquitin. Here we show duck RIG-I CARD domains are ubiquitinated for activation, and ubiquitination depends on interaction with TRIM25, as a splice variant that cannot interact with TRIM25 is not ubiquitinated, and cannot be activated. We expressed GST-fusion proteins of duck CARD domains and characterized TRIM25 modifications of CARD domains by mass spectrometry. We identified two sites that are ubiquitinated in duck CARD domains, K167 and K193, and detected K63 linked polyubiquitin chains. Site directed mutagenesis of each site alone, does not alter the ubiquitination profile of the duck CARD domains. However, mutation of both sites resulted in loss of all attached ubiquitin and polyubiquitin chains. Remarkably, the double mutant duck RIG-I CARD still interacts with TRIM25, and can still be activated. Our results demonstrate that anchored ubiquitin chains are not necessary for TRIM25

Activation of Duck RIG-I by TRIM25 Is Independent of Anchored Ubiquitin

PubMed Central

Miranzo-Navarro, Domingo; Magor, Katharine E.

2014-01-01

Retinoic acid inducible gene I (RIG-I) is a viral RNA sensor crucial in defense against several viruses including measles, influenza A and hepatitis C. RIG-I activates type-I interferon signalling through the adaptor for mitochondrial antiviral signaling (MAVS). The E3 ubiquitin ligase, tripartite motif containing protein 25 (TRIM25), activates human RIG-I through generation of anchored K63-linked polyubiquitin chains attached to lysine 172, or alternatively, through the generation of unanchored K63-linked polyubiquitin chains that interact non-covalently with RIG-I CARD domains. Previously, we identified RIG-I of ducks, of interest because ducks are the host and natural reservoir of influenza viruses, and showed it initiates innate immune signaling leading to production of interferon-beta (IFN-β). We noted that K172 is not conserved in RIG-I of ducks and other avian species, or mouse. Because K172 is important for both mechanisms of activation of human RIG-I, we investigated whether duck RIG-I was activated by TRIM25, and if other residues were the sites for attachment of ubiquitin. Here we show duck RIG-I CARD domains are ubiquitinated for activation, and ubiquitination depends on interaction with TRIM25, as a splice variant that cannot interact with TRIM25 is not ubiquitinated, and cannot be activated. We expressed GST-fusion proteins of duck CARD domains and characterized TRIM25 modifications of CARD domains by mass spectrometry. We identified two sites that are ubiquitinated in duck CARD domains, K167 and K193, and detected K63 linked polyubiquitin chains. Site directed mutagenesis of each site alone, does not alter the ubiquitination profile of the duck CARD domains. However, mutation of both sites resulted in loss of all attached ubiquitin and polyubiquitin chains. Remarkably, the double mutant duck RIG-I CARD still interacts with TRIM25, and can still be activated. Our results demonstrate that anchored ubiquitin chains are not necessary for TRIM25

A Viking satellite orbit trim strategy

NASA Technical Reports Server (NTRS)

Hintz, G. R.

1971-01-01

One strategy is submitted for meeting the varied and stringent requirements of the Viking Project on the control of the satellite orbit to obtain reconnaissance and to prepare for lander release. To satisfy these requirements, different orbit trim maneuver strategies were developed for two typical Viking missions. In addition, a summary of recent numerical results is included to show that this strategy satisfies the mission requirements which have been identified.

Atropos: specific, sensitive, and speedy trimming of sequencing reads.

PubMed

Didion, John P; Martin, Marcel; Collins, Francis S

2017-01-01

A key step in the transformation of raw sequencing reads into biological insights is the trimming of adapter sequences and low-quality bases. Read trimming has been shown to increase the quality and reliability while decreasing the computational requirements of downstream analyses. Many read trimming software tools are available; however, no tool simultaneously provides the accuracy, computational efficiency, and feature set required to handle the types and volumes of data generated in modern sequencing-based experiments. Here we introduce Atropos and show that it trims reads with high sensitivity and specificity while maintaining leading-edge speed. Compared to other state-of-the-art read trimming tools, Atropos achieves significant increases in trimming accuracy while remaining competitive in execution times. Furthermore, Atropos maintains high accuracy even when trimming data with elevated rates of sequencing errors. The accuracy, high performance, and broad feature set offered by Atropos makes it an appropriate choice for the pre-processing of Illumina, ABI SOLiD, and other current-generation short-read sequencing datasets. Atropos is open source and free software written in Python (3.3+) and available at https://github.com/jdidion/atropos.

Atropos: specific, sensitive, and speedy trimming of sequencing reads

PubMed Central

Collins, Francis S.

2017-01-01

A key step in the transformation of raw sequencing reads into biological insights is the trimming of adapter sequences and low-quality bases. Read trimming has been shown to increase the quality and reliability while decreasing the computational requirements of downstream analyses. Many read trimming software tools are available; however, no tool simultaneously provides the accuracy, computational efficiency, and feature set required to handle the types and volumes of data generated in modern sequencing-based experiments. Here we introduce Atropos and show that it trims reads with high sensitivity and specificity while maintaining leading-edge speed. Compared to other state-of-the-art read trimming tools, Atropos achieves significant increases in trimming accuracy while remaining competitive in execution times. Furthermore, Atropos maintains high accuracy even when trimming data with elevated rates of sequencing errors. The accuracy, high performance, and broad feature set offered by Atropos makes it an appropriate choice for the pre-processing of Illumina, ABI SOLiD, and other current-generation short-read sequencing datasets. Atropos is open source and free software written in Python (3.3+) and available at https://github.com/jdidion/atropos. PMID:28875074

Piloted simulation study of the effects of an automated trim system on flight characteristics of a light twin-engine airplane with one engine inoperative

NASA Technical Reports Server (NTRS)

Stewart, E. C.; Brown, P. W.; Yenni, K. R.

1986-01-01

A simulation study was conducted to investigate the piloting problems associated with failure of an engine on a generic light twin-engine airplane. A primary piloting problem for a light twin-engine airplane after an engine failure is maintaining precise control of the airplane in the presence of large steady control forces. To address this problem, a simulated automatic trim system which drives the trim tabs as an open-loop function of propeller slipstream measurements was developed. The simulated automatic trim system was found to greatly increase the controllability in asymmetric powered flight without having to resort to complex control laws or an irreversible control system. However, the trim-tab control rates needed to produce the dramatic increase in controllability may require special design consideration for automatic trim system failures. Limited measurements obtained in full-scale flight tests confirmed the fundamental validity of the proposed control law.

16 CFR 303.12 - Trimmings of household textile articles.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Trimmings of household textile articles. 303... household textile articles. (a) Trimmings incorporated in articles of wearing apparel and other household textile articles may, among other forms of trim, include: (1) Rick-rack, tape, belting, binding, braid...

16 CFR 303.12 - Trimmings of household textile articles.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Trimmings of household textile articles. 303... household textile articles. (a) Trimmings incorporated in articles of wearing apparel and other household textile articles may, among other forms of trim, include: (1) Rick-rack, tape, belting, binding, braid...

16 CFR 303.12 - Trimmings of household textile articles.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Trimmings of household textile articles. 303... household textile articles. (a) Trimmings incorporated in articles of wearing apparel and other household textile articles may, among other forms of trim, include: (1) Rick-rack, tape, belting, binding, braid...

16 CFR 303.12 - Trimmings of household textile articles.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 16 Commercial Practices 1 2013-01-01 2013-01-01 false Trimmings of household textile articles. 303... household textile articles. (a) Trimmings incorporated in articles of wearing apparel and other household textile articles may, among other forms of trim, include: (1) Rick-rack, tape, belting, binding, braid...

16 CFR 303.12 - Trimmings of household textile articles.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Trimmings of household textile articles. 303... CONGRESS RULES AND REGULATIONS UNDER THE TEXTILE FIBER PRODUCTS IDENTIFICATION ACT § 303.12 Trimmings of household textile articles. (a) Trimmings incorporated in articles of wearing apparel and other household...

Application of the concept of dynamic trim control to automatic landing of carrier aircraft. [utilizing digital feedforeward control

NASA Technical Reports Server (NTRS)

Smith, G. A.; Meyer, G.

1980-01-01

The results of a simulation study of an alternative design concept for an automatic landing control system are presented. The alternative design concept for an automatic landing control system is described. The design concept is the total aircraft flight control system (TAFCOS). TAFCOS is an open loop, feed forward system that commands the proper instantaneous thrust, angle of attack, and roll angle to achieve the forces required to follow the desired trajector. These dynamic trim conditions are determined by an inversion of the aircraft nonlinear force characteristics. The concept was applied to an A-7E aircraft approaching an aircraft carrier. The implementation details with an airborne digital computer are discussed. The automatic carrier landing situation is described. The simulation results are presented for a carrier approach with atmospheric disturbances, an approach with no disturbances, and for tailwind and headwind gusts.

Tinning/Trimming Robot System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fureigh, M.L.

In a new surface mount assembly area at AlliedSignal Inc., Kansas City Division (KCD), a tinning/trimming robot system tins and trims the gold-plated leads of surface mount technology (SMT) transistors. The KCD-designed system uses a Unimation PUMA 260 robot, a General Production Devices SP-2000 solder pot; water-soluble Blackstone No. 2508 flux; and a Virtual Industries high-temperature, ESD-conductive, miniature suction cup. After the manual cleaning operation, the processed SMT transistors go to the QUADSTAR Automated Component Placement System for a Radar Logic Assembly. The benefits are reductions in the cost of nonconformance, worker fatigue, and standard hours.

Antibody- and TRIM21-dependent intracellular restriction of Salmonella enterica.

PubMed

Rakebrandt, Nikolas; Lentes, Sabine; Neumann, Heinz; James, Leo C; Neumann-Staubitz, Petra

2014-11-01

TRIM21 ('tripartite motif-containing protein 21', Ro52) is a ubiquitously expressed cytosolic Fc receptor, which has a potent role in protective immunity against nonenveloped viruses. TRIM21 mediates intracellular neutralisation of antibody-coated viruses, a process called ADIN (antibody-dependent intracellular neutralisation). Our results reveal a similar mechanism to fight bacterial infections. TRIM21 is recruited to the intracellular pathogen Salmonella enterica in epithelial cells early in infection. TRIM21 does not bind directly to S. enterica, but to antibodies opsonising it. Most importantly, bacterial restriction is dependent on TRIM21 as well as on the opsonisation state of the bacteria. Finally, Salmonella and TRIM21 colocalise with the autophagosomal marker LC3, and intracellular defence is enhanced in starved cells suggesting an involvement of the autophagocytic pathway. Our data extend the protective role of TRIM21 from viruses to bacteria and thereby strengthening the general role of ADIN in cellular immunity. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Molecular Characterization, Tissue Distribution and Expression, and Potential Antiviral Effects of TRIM32 in the Common Carp (Cyprinus carpio).

PubMed

Wang, Yeda; Li, Zeming; Lu, Yuanan; Hu, Guangfu; Lin, Li; Zeng, Lingbing; Zhou, Yong; Liu, Xueqin

2016-10-09

Tripartite motif-containing protein 32 (TRIM32) belongs to the tripartite motif (TRIM) family, which consists of a large number of proteins containing a RING (Really Interesting New Gene) domain, one or two B-box domains, and coiled coil motif followed by different C-terminal domains. The TRIM family is known to be implicated in multiple cellular functions, including antiviral activity. However, it is presently unknown whether TRIM32 of common carp ( Cyprinus carpio ) has the antiviral effect. In this study, the sequence, expression, and antiviral function of TRIM32 homolog from common carp were analyzed. The full-length coding sequence region of trim32 was cloned from common carp. The results showed that the expression of TRIM32 (mRNA) was highest in the brain, remained stably expressed during embryonic development, and significantly increased following spring viraemia of carp virus (SVCV) infection. Transient overexpression of TRIM32 in affected Epithelioma papulosum cyprinid cells led to significant decrease of SVCV production as compared to the control group. These results suggested a potentially important role of common carp TRIM32 in enhancing host immune response during SVCV infection both in vivo and in vitro.

Molecular Characterization, Tissue Distribution and Expression, and Potential Antiviral Effects of TRIM32 in the Common Carp (Cyprinus carpio)

PubMed Central

Wang, Yeda; Li, Zeming; Lu, Yuanan; Hu, Guangfu; Lin, Li; Zeng, Lingbing; Zhou, Yong; Liu, Xueqin

2016-01-01

Tripartite motif-containing protein 32 (TRIM32) belongs to the tripartite motif (TRIM) family, which consists of a large number of proteins containing a RING (Really Interesting New Gene) domain, one or two B-box domains, and coiled coil motif followed by different C-terminal domains. The TRIM family is known to be implicated in multiple cellular functions, including antiviral activity. However, it is presently unknown whether TRIM32 of common carp (Cyprinus carpio) has the antiviral effect. In this study, the sequence, expression, and antiviral function of TRIM32 homolog from common carp were analyzed. The full-length coding sequence region of trim32 was cloned from common carp. The results showed that the expression of TRIM32 (mRNA) was highest in the brain, remained stably expressed during embryonic development, and significantly increased following spring viraemia of carp virus (SVCV) infection. Transient overexpression of TRIM32 in affected Epithelioma papulosum cyprinid cells led to significant decrease of SVCV production as compared to the control group. These results suggested a potentially important role of common carp TRIM32 in enhancing host immune response during SVCV infection both in vivo and in vitro. PMID:27735853

7 CFR 58.725 - Trimming and cleaning.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Trimming and cleaning. 58.725 Section 58.725 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Procedures § 58.725 Trimming and cleaning. The natural cheese shall be cleaned free of all non-edible...

7 CFR 58.725 - Trimming and cleaning.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 3 2011-01-01 2011-01-01 false Trimming and cleaning. 58.725 Section 58.725 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Procedures § 58.725 Trimming and cleaning. The natural cheese shall be cleaned free of all non-edible...

The Effectiveness of the Component Impact Test Method for the Side Impact Injury Assessment of the Door Trim

NASA Astrophysics Data System (ADS)

Youn, Younghan; Koo, Jeong-Seo

The complete evaluation of the side vehicle structure and the occupant protection is only possible by means of the full scale side impact crash test. But, auto part manufacturers such as door trim makers can not conduct the test especially when the vehicle is under the developing process. The main objective of this study is to obtain the design guidelines by a simple component level impact test. The relationship between the target absorption energy and impactor speed were examined using the energy absorbed by the door trim. Since each different vehicle type required different energy levels on the door trim. A simple impact test method was developed to estimate abdominal injury by measuring reaction force of the impactor. The reaction force will be converted to a certain level of the energy by the proposed formula. The target of absorption energy for door trim only and the impact speed of simple impactor are derived theoretically based on the conservation of energy. With calculated speed of dummy and the effective mass of abdomen, the energy allocated in the abdomen area of door trim was calculated. The impactor speed can be calculated based on the equivalent energy of door trim absorbed during the full crash test. With the proposed design procedure for the door trim by a simple impact test method was demonstrated to evaluate the abdominal injury. This paper describes a study that was conducted to determine sensitivity of several design factors for reducing abdominal injury values using the matrix of orthogonal array method. In conclusion, with theoretical considerations and empirical test data, the main objective, standardization of door trim design using the simple impact test method was established.

Trimmed noncoplanar planforms with minimum vortex drag

NASA Technical Reports Server (NTRS)

Lamar, J. E.

1977-01-01

Vortex-lattice subsonic method determines mean camber surface for trimmed noncoplanar planforms with minimum vortex drag. Multiple surfaces can be designed together to yield trimmed configuration with minimum induced drag at some specified lift coefficient. Program is applicable to isolated wings, wing-canard configuration, tandem wing, and wing-winglet configuration.

Static Aeroelastic and Longitudinal Trim Model of Flexible Wing Aircraft Using Finite-Element Vortex-Lattice Coupled Solution

NASA Technical Reports Server (NTRS)

Ting, Eric; Nguyen, Nhan; Trinh, Khanh

2014-01-01

This paper presents a static aeroelastic model and longitudinal trim model for the analysis of a flexible wing transport aircraft. The static aeroelastic model is built using a structural model based on finite-element modeling and coupled to an aerodynamic model that uses vortex-lattice solution. An automatic geometry generation tool is used to close the loop between the structural and aerodynamic models. The aeroelastic model is extended for the development of a three degree-of-freedom longitudinal trim model for an aircraft with flexible wings. The resulting flexible aircraft longitudinal trim model is used to simultaneously compute the static aeroelastic shape for the aircraft model and the longitudinal state inputs to maintain an aircraft trim state. The framework is applied to an aircraft model based on the NASA Generic Transport Model (GTM) with wing structures allowed to flexibly deformed referred to as the Elastically Shaped Aircraft Concept (ESAC). The ESAC wing mass and stiffness properties are based on a baseline "stiff" values representative of current generation transport aircraft.

Backbone resonance assignments of the PRYSPRY domain of TRIM25.

PubMed

Kong, Chen; Penumutchu, Srinivasa R; Hung, Kuo-Wei; Huang, Huiying; Lin, Tianwei; Yu, Chin

2015-10-01

TRIM25 is a member of the tripartite motif (TRIM) family and has been implicated in the regulation of innate immune signaling via the RIG-I (retinoic acid-inducible gene-I) pathway for antiviral defense. As the essential first step towards the structural and functional characterization of the TRIM25/RIG-I interaction, the backbone resonance of the PRYSPRY domain of TRIM25 is assigned here based on triple-resonance experiments using uniformly [(2)H, (13)C, (15)N]-labeled protein.

16 CFR 300.23 - Linings, paddings, stiffening, trimmings and facings.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Linings, paddings, stiffening, trimmings and... Linings, paddings, stiffening, trimmings and facings. (a) In labeling or marking garments or articles of apparel which are wool products, the fiber content of any linings, paddings, stiffening, trimmings or...

16 CFR 300.23 - Linings, paddings, stiffening, trimmings and facings.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Linings, paddings, stiffening, trimmings and... Linings, paddings, stiffening, trimmings and facings. (a) In labeling or marking garments or articles of apparel which are wool products, the fiber content of any linings, paddings, stiffening, trimmings or...

Intracellular antibody signalling is regulated by phosphorylation of the Fc receptor TRIM21

PubMed Central

Vaysburd, Marina; Yang, Ji-Chun; Mallery, Donna L; Zeng, Jingwei; Johnson, Christopher M; McLaughlin, Stephen H; Skehel, Mark; Maslen, Sarah; Cruickshank, James; Huguenin-Dezot, Nicolas; Chin, Jason W; Neuhaus, David

2018-01-01

Cell surface Fc receptors activate inflammation and are tightly controlled to prevent autoimmunity. Antibodies also simulate potent immune signalling from inside the cell via the cytosolic antibody receptor TRIM21, but how this is regulated is unknown. Here we show that TRIM21 signalling is constitutively repressed by its B-Box domain and activated by phosphorylation. The B-Box occupies an E2 binding site on the catalytic RING domain by mimicking E2-E3 interactions, inhibiting TRIM21 ubiquitination and preventing immune activation. TRIM21 is derepressed by IKKβ and TBK1 phosphorylation of an LxxIS motif in the RING domain, at the interface with the B-Box. Incorporation of phosphoserine or a phosphomimetic within this motif relieves B-Box inhibition, promoting E2 binding, RING catalysis, NF-κB activation and cytokine transcription upon infection with DNA or RNA viruses. These data explain how intracellular antibody signalling is regulated and reveal that the B-Box is a critical regulator of RING E3 ligase activity. PMID:29667579

TRIM24 links glucose metabolism with transformation of human mammary epithelial cells.

PubMed

Pathiraja, T N; Thakkar, K N; Jiang, S; Stratton, S; Liu, Z; Gagea, M; Shi, X; Shah, P K; Phan, L; Lee, M-H; Andersen, J; Stampfer, M; Barton, M C

2015-05-28

Tripartite motif 24 protein (TRIM24) is a plant homeodomain/bromodomain histone reader, recently associated with poor overall survival of breast-cancer patients. At a molecular level, TRIM24 is a negative regulator of p53 levels and a co-activator of estrogen receptor. However, the role of TRIM24 in breast tumorigenesis remains largely unknown. We used an isogenic human mammary epithelial cell (HMEC) culture model, derived from reduction mammoplasty tissue, and found that ectopic expression of TRIM24 in immortalized HMECs (TRIM24 iHMECs) greatly increased cellular proliferation and induced malignant transformation. Subcutaneous injection of TRIM24 iHMECs in nude mice led to growth of intermediate to high-grade tumors in 60-70% of mice. Molecular analysis of TRIM24 iHMECs revealed a glycolytic and tricarboxylic acid cycle gene signature, alongside increased glucose uptake and activated aerobic glycolysis. Collectively, these results identify a role for TRIM24 in breast tumorigenesis through reprogramming of glucose metabolism in HMECs, further supporting TRIM24 as a viable therapeutic target in breast cancer.

The ubiquitin ligase TRIM25 inhibits hepatocellular carcinoma progression by targeting metastasis associated 1 protein.

PubMed

Zang, Hong-Liang; Ren, Sheng-Nan; Cao, Hong; Tian, Xiao-Feng

2017-10-01

Metastasis associated 1 protein (MTA1) is one of the prime facilitators of metastatic progression in all solid tumors including hepatocellular carcinoma (HCC). However, the underlying regulatory mechanism of MTA1 expression in HCC is not clear. In this study, we evaluated MTA1 transcript and protein expression in HCC and normal hepatic cell lines. The results revealed that MTA1 protein expression had a significantly increase in HCC cell line, HuH6, compared with that in normal hepatic cell line, THLE-2. Determination of protein half-life using cycloheximide (CHX) treatment did not reveal any statistically significant difference in protein turn-over rates between THLE-2 (3.3 ± 0.25 h) and HuH6 (3.6 ± 0.15 h) cell lines. MTA1 protein level was stabilized in THLE-2 cells after treatment with MG-132 to levels similar to those observed in HuH6 cells. Mass spectrometric analysis of FLAG immunoprecipitates of FLAG-MTA1 transfected THLE-2 cells after MG-132 treated revealed candidate ubiquitin ligases that were interacting with MTA1. RNAi-mediated silencing of each prospective ubiquitin ligase in THLE-2 cells indicated that knockdown of TRIM25 resulted in stabilization of MTA1 protein, indicating TRIM25 as a putative E3 ligase for MTA1. Coimmunoprecipitation of FLAG-tagged MTA1, but not IgG, in MG-132 treated and untreated THLE-2 cells cotransfected with either FLAG-MTA1 or Myc-TRIM25 revealed robust polyubiquitinated MTA1, confirming that the TRIM25 is the ubiquitin ligase for MTA1 degradation. Overexpression of TRIM25 in HuH6 and RNAi mediated silencing of TRIM25 in THLE-2 cells inhibited and increased the cell migration and invasion, respectively. Analysis of The Cancer Genome Atlas data for assessment of TRIM25 transcript level and MTA1 protein expression in 25 HCC patients confirmed an inverse correlation between the expression of TRIM25 and MTA1. Cumulatively, our data reveal a novel mechanism of post-translational to regulate MTA1 expression in normal

Associations between polymorphisms in the antiviral TRIM genes and measles vaccine immunity.

PubMed

Ovsyannikova, Inna G; Haralambieva, Iana H; Vierkant, Robert A; O'Byrne, Megan M; Poland, Gregory A

2013-06-01

The role of polymorphisms within the antiviral tripartite motif (TRIM) genes in measles vaccine adaptive immune responses was examined. A limited association was found between TRIM5 (rs7122620) and TRIM25 (rs205499) gene polymorphisms and measles-specific antibody levels. However, many associations were found between TRIM gene SNPs and variations in cellular responses (IFN-γ Elispot and secreted cytokines IL-2, IL-6, IL-10, IFN-γ, and TNF-α). TRIM22 rs2291841 was significantly associated with an increased IFN-γ Elispot response (35 vs. 102 SFC per 2×10(5)PBMC, p=0.009, q=0.71) in Caucasians. A non-synonymous TRIM25 rs205498 (in LD with other SNPs, r(2)≥0.56), as well as the TRIM25 AAAGGAAAGGAGT haplotype, was associated with a decreased IFN-γ Elispot response (t-statistic -2.32, p=0.02) in African-Americans. We also identified polymorphisms in the TRIM5, TRIM22, and TRIM25 genes that were associated with significant differences in cytokine responses. Additional studies are necessary to replicate our findings and to examine the functional consequences of these associations. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

UrQt: an efficient software for the Unsupervised Quality trimming of NGS data.

PubMed

Modolo, Laurent; Lerat, Emmanuelle

2015-04-29

Quality control is a necessary step of any Next Generation Sequencing analysis. Although customary, this step still requires manual interventions to empirically choose tuning parameters according to various quality statistics. Moreover, current quality control procedures that provide a "good quality" data set, are not optimal and discard many informative nucleotides. To address these drawbacks, we present a new quality control method, implemented in UrQt software, for Unsupervised Quality trimming of Next Generation Sequencing reads. Our trimming procedure relies on a well-defined probabilistic framework to detect the best segmentation between two segments of unreliable nucleotides, framing a segment of informative nucleotides. Our software only requires one user-friendly parameter to define the minimal quality threshold (phred score) to consider a nucleotide to be informative, which is independent of both the experiment and the quality of the data. This procedure is implemented in C++ in an efficient and parallelized software with a low memory footprint. We tested the performances of UrQt compared to the best-known trimming programs, on seven RNA and DNA sequencing experiments and demonstrated its optimality in the resulting tradeoff between the number of trimmed nucleotides and the quality objective. By finding the best segmentation to delimit a segment of good quality nucleotides, UrQt greatly increases the number of reads and of nucleotides that can be retained for a given quality objective. UrQt source files, binary executables for different operating systems and documentation are freely available (under the GPLv3) at the following address: https://lbbe.univ-lyon1.fr/-UrQt-.html .

Optimum Edging and Trimming of Hardwood Lumber

Treesearch

Carmen Regalado; D. Earl Kline; Philip A. Araman

1992-01-01

Before the adoption of an automated system for optimizing edging and trimming in hardwood mills, the performance of present manual systems must be evaluated to provide a basis for comparison. a study was made in which lumber values recovered in actual hardwood operations were compared to the output of a computer-based procedure for edging and trimming optimization. The...

Measurement of axial injection displacement with trim coil current unbalance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Covo, Michel Kireeff, E-mail: mkireeffcovo@lbl.gov

The Dee probe used for measuring internal radial beam intensity shows large losses inside the radius of 20 cm of the 88 in. cyclotron. The current of the top and bottom innermost trim coil 1 is unbalanced to study effects of the axial injection displacement. A beam profile monitor images the ion beam bunches, turn by turn. The experimental bunch center of mass position is compared with calculations of the magnetic mirror effect displacement and shows good agreement.

TRIM56 Is an Essential Component of the TLR3 Antiviral Signaling Pathway*

PubMed Central

Shen, Yang; Li, Nan L.; Wang, Jie; Liu, Baoming; Lester, Sandra; Li, Kui

2012-01-01

Members of the tripartite motif (TRIM) proteins are being recognized as important regulators of host innate immunity. However, specific TRIMs that contribute to TLR3-mediated antiviral defense have not been identified. We show here that TRIM56 is a positive regulator of TLR3 signaling. Overexpression of TRIM56 substantially potentiated extracellular dsRNA-induced expression of interferon (IFN)-β and interferon-stimulated genes (ISGs), while knockdown of TRIM56 greatly impaired activation of IRF3, induction of IFN-β and ISGs, and establishment of an antiviral state by TLR3 ligand and severely compromised TLR3-mediated chemokine induction following infection by hepatitis C virus. The ability to promote TLR3 signaling was independent of the E3 ubiquitin ligase activity of TRIM56. Rather, it correlated with a physical interaction between TRIM56 and TRIF. Deletion of the C-terminal portion of TRIM56 abrogated the TRIM56-TRIF interaction as well as the augmentation of TLR3-mediated IFN response. Together, our data demonstrate TRIM56 is an essential component of the TLR3 antiviral signaling pathway and reveal a novel role for TRIM56 in innate antiviral immunity. PMID:22948160

Wrinkling reduction of membrane structure by trimming edges

NASA Astrophysics Data System (ADS)

Liu, Mingjun; Huang, Jin; Liu, Mingyue

2017-05-01

Thin membranes have negligible bending stiffness, compressive stresses inevitably lead to wrinkling. Therefore, it is important to keep the surface of membrane structures flat in order to guarantee high precision. Edge-trimming is an effective method to passively diminish wrinkles, however a key difficulty in this process is the determination of the optimal trimming level. In this paper, regular polygonal membrane structures subjected to equal radial forces were analyzed, and a new stress field distribution model for arc-edge square membrane structure was proposed to predict the optimal trimming level. This model is simple and applicable to any polygonal membrane structures. Comparison among the results of the finite element analysis, and the experimental and analytical results showed that the proposed model accurately described the stress field distribution and guaranteed that there are no wrinkles appear inside the effective inscribed circle region for the optimal trimming level.

Utilization of smoked salmon trim in extruded smoked salmon jerky.

PubMed

Kong, J; Dougherty, M P; Perkins, L B; Camire, M E

2012-06-01

During smoked salmon processing, the dark meat along the lateral line is removed before packaging; this by-product currently has little economic value. In this study, the dark meat trim was incorporated into an extruded jerky. Three formulations were processed: 100% smoked trim, 75% : 25% smoked trim : fresh salmon fillet, and 50% : 50% smoked trim : fresh salmon blends (w/w basis). The base formulation contained salmon (approximately 83.5%), tapioca starch (8%), pregelatinized potato starch (3%), sucrose (4%), salt (1.5%), sodium nitrate (0.02%), and ascorbyl palmitate (0.02% of the lipid content). Blends were extruded in a laboratory-scale twin-screw extruder and then hot-smoked for 5 h. There were no significant differences among formulations in moisture, water activity, and pH. Protein was highest in the 50 : 50 blend jerky. Ash content was highest in the jerky made with 100% trim. Total lipids and salt were higher in the 100% trim jerky than in the 50 : 50 blend. Hot smoking did not adversely affect docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) content in lipids from 100% smoked trim jerky. Servings of salmon jerky made with 75% and 100% smoked trim provided at least 500 mg of EPA and DHA. The 50 : 50 formulation had the highest Intl. Commission on Illumination (CIE) L*, a*, and b* color values. Seventy consumers rated all sensory attributes as between "like slightly" and "like moderately." With some formulation and processing refinements, lateral line trim from smoked salmon processors has potential to be incorporated into acceptable, healthful snack products. Dark meat along the lateral line is typically discarded by smoked salmon processors. This omega-3 fatty acid rich by-product can be used to make a smoked salmon jerky that provides a convenient source of these healthful lipids for consumers. © 2012 Institute of Food Technologists®

Microstructural investigations of the trimmed edge of DP980 steel sheets

NASA Astrophysics Data System (ADS)

Bhattacharya, S.; Green, D. E.; Sohmshetty, R.; Alpas, A. T.

2017-10-01

In order to reduce vehicle weight while maintaining crashworthiness, advanced high strength steels (AHSSs), such as DP980, are extensively used for manufacturing automotive body components. During trimming operations, the high tensile strength of DP980 sheets tends to cause damage of the trim edge of D2 die inserts, which result in deterioration of the edge quality. The objective of this work is to study the damage microstructures at the trimmed edge of DP980 steel sheets as a function of the number of trimming cycles. A mechanical press equipped with AISI D2 tool steel inserts was used to continuously trim 1.4 mm thick sheets of DP980 at a rate of 30 strokes/min. Cross-sectional SEM images of the trimmed edges revealed that the sheared edge quality of the DP980 sheets decreased, indicated by an increase in the burr width, with an increase in the number of trims from 40,000 to 70,000. Plastic strains were estimated using the displacements of the martensite plates within plastic flow fields of ferrite. Site-specific cross-sectional TEM samples, excised from the trimmed edge using the in-situ `lift-out' technique by focused ion-beam (FIB)-milling, revealed cracking at the ferrite/martensite interfaces after 70,000 cycles indicating an increase in the depth of deformation zone possibly due to trimming with a chipped and blunted die edge.

Dengue Non-coding RNA: TRIMmed for Transmission.

PubMed

Göertz, Giel P; Pijlman, Gorben P

2015-08-12

Dengue virus RNA is trimmed by the 5'→3' exoribonuclease XRN1 to produce an abundant, non-coding subgenomic flavivirus RNA (sfRNA) in infected cells. In a recent paper in Science, Manokaran et al. (2015) report that sfRNA binds TRIM25 to evade innate immune sensing of viral RNA by RIG-I. Copyright © 2015 Elsevier Inc. All rights reserved.

A novel prognostic factor TRIM44 promotes cell proliferation and migration, and inhibits apoptosis in testicular germ cell tumor.

PubMed

Yamada, Yuta; Takayama, Ken-Ichi; Fujimura, Tetsuya; Ashikari, Daisaku; Obinata, Daisuke; Takahashi, Satoru; Ikeda, Kazuhiro; Kakutani, Shigenori; Urano, Tomohiko; Fukuhara, Hiroshi; Homma, Yukio; Inoue, Satoshi

2017-01-01

Tripartite motif 44 (TRIM44) is one of the TRIM family proteins that are involved in ubiquitination and degradation of target proteins by modulating E3 ubiquitin ligases. TRIM44 overexpression has been observed in various cancers. However, its association with testicular germ cell tumor (TGCT) is unknown. We aimed to investigate the clinical significance of TRIM44 and its function in TGCT. High expression of TRIM44 was significantly associated with α feto-protein levels, clinical stage, nonseminomatous germ cell tumor (NSGCT), and cancer-specific survival (P = 0.0009, P = 0.0035, P = 0.0004, and P = 0.0140, respectively). Multivariate analysis showed that positive TRIM44 IR was an independent predictor of cancer-specific mortality (P = 0.046). Gain-of-function study revealed that overexpression of TRIM44 promoted cell proliferation and migration of NTERA2 and NEC8 cells. Knockdown of TRIM44 using siRNA promoted apoptosis and repressed cell proliferation and migration in these cells. Microarray analysis of NTERA2 cells revealed that tumor suppressor genes such as CADM1, CDK19, and PRKACB were upregulated in TRIM44-knockdown cells compared to control cells. In contrast, oncogenic genes including C3AR1, ST3GAL5, and NT5E were downregulated in those cells. These results suggest that high expression of TRIM44 is associated with poor prognosis and that TRIM44 plays significant role in cell proliferation, migration, and anti-apoptosis in TGCT. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

TRIM E3 ligases in HIV infection: can these intrinsic immunity factors be harnessed for novel vaccines or therapies?

PubMed

Ndung'u, Thumbi

2011-01-01

Tripartite motif-containing (TRIM) E3 ligases are a recently identified family of proteins with potent antiviral activity in mammalian cells. The prototype TRIM E3 ligase, TRIM5α was initially identified as a species-specific antiviral restriction factor but subsequent studies suggest some antiviral activity by several TRIM E3 ligases in human cells. However, the mechanisms of antiviral activity by these proteins and their transcriptional, translational and post-translational regulation are poorly understood. Furthermore, the contribution of TRIM E3 ligases to relative resistance or viral control in vivo is largely unknown. Emerging data from our laboratory and other groups suggests that these proteins may have antiviral activity in vivo and contribute to HIV pathogenesis. Considering the significant difficulties so far encountered in developing an effective HIV vaccine and with the use of antiretroviral therapies, it will be important to further investigate the potential of TRIM E3 ligases as novel prophylactics or therapies.

Subcellular Localizations of RIG-I, TRIM25, and MAVS Complexes

PubMed Central

Sánchez-Aparicio, M. T.; Ayllón, J.; Leo-Macias, A.; Wolff, T.

2016-01-01

ABSTRACT The retinoic acid-inducible gene 1 (RIG-I) signaling pathway is essential for the recognition of viruses and the initiation of host interferon (IFN)-mediated antiviral responses. Once activated, RIG-I interacts with polyubiquitin chains generated by TRIM25 and binds mitochondrial antiviral signaling protein (MAVS), leading to the production of type I IFN. We now show specific interactions among these key partners in the RLR pathway through the use of bimolecular fluorescence complementation (BiFC) and super-resolution microscopy. Dimers of RIG-I, TRIM25, and MAVS localize into different compartments. Upon activation, we show that TRIM25 is redistributed into cytoplasmic dots associated with stress granules, while RIG-I associates with TRIM25/stress granules and with mitochondrial MAVS. In addition, MAVS competes with TRIM25 for RIG-I binding, and this suggests that upon TRIM25-mediated activation of RIG-I, RIG-I moves away from TRIM25 to interact with MAVS at the mitochondria. For the first time, the distribution of these three proteins was analyzed at the same time in virus-infected cells. We also investigated how specific viral proteins modify some of the protein complexes in the pathway. The protease NS3/4A from hepatitis C virus redistributes the complexes RIG-I/MAVS and MAVS/MAVS but not RIG-I/TRIM25. In contrast, the influenza A virus NS1 protein interacts with RIG-I and TRIM25 in specific areas in the cell cytoplasm and inhibits the formation of TRIM25 homocomplexes but not the formation of RIG-I/TRIM25 heterocomplexes, preventing the formation of RIG-I/MAVS complexes. Thus, we have localized spatially in the cell different complexes formed between RIG-I, TRIM25, and MAVS, in the presence or absence of two viral IFN antagonistic proteins. IMPORTANCE The first line of defense against viral infections is the innate immune response. Viruses are recognized by pathogen recognition receptors, such as the RIG-I like receptor family, that activate a

Subcellular Localizations of RIG-I, TRIM25, and MAVS Complexes.

PubMed

Sánchez-Aparicio, M T; Ayllón, J; Leo-Macias, A; Wolff, T; García-Sastre, A

2017-01-15

The retinoic acid-inducible gene 1 (RIG-I) signaling pathway is essential for the recognition of viruses and the initiation of host interferon (IFN)-mediated antiviral responses. Once activated, RIG-I interacts with polyubiquitin chains generated by TRIM25 and binds mitochondrial antiviral signaling protein (MAVS), leading to the production of type I IFN. We now show specific interactions among these key partners in the RLR pathway through the use of bimolecular fluorescence complementation (BiFC) and super-resolution microscopy. Dimers of RIG-I, TRIM25, and MAVS localize into different compartments. Upon activation, we show that TRIM25 is redistributed into cytoplasmic dots associated with stress granules, while RIG-I associates with TRIM25/stress granules and with mitochondrial MAVS. In addition, MAVS competes with TRIM25 for RIG-I binding, and this suggests that upon TRIM25-mediated activation of RIG-I, RIG-I moves away from TRIM25 to interact with MAVS at the mitochondria. For the first time, the distribution of these three proteins was analyzed at the same time in virus-infected cells. We also investigated how specific viral proteins modify some of the protein complexes in the pathway. The protease NS3/4A from hepatitis C virus redistributes the complexes RIG-I/MAVS and MAVS/MAVS but not RIG-I/TRIM25. In contrast, the influenza A virus NS1 protein interacts with RIG-I and TRIM25 in specific areas in the cell cytoplasm and inhibits the formation of TRIM25 homocomplexes but not the formation of RIG-I/TRIM25 heterocomplexes, preventing the formation of RIG-I/MAVS complexes. Thus, we have localized spatially in the cell different complexes formed between RIG-I, TRIM25, and MAVS, in the presence or absence of two viral IFN antagonistic proteins. The first line of defense against viral infections is the innate immune response. Viruses are recognized by pathogen recognition receptors, such as the RIG-I like receptor family, that activate a signaling cascade that

General Model for Retroviral Capsid Pattern Recognition by TRIM5 Proteins.

PubMed

Wagner, Jonathan M; Christensen, Devin E; Bhattacharya, Akash; Dawidziak, Daria M; Roganowicz, Marcin D; Wan, Yueping; Pumroy, Ruth A; Demeler, Borries; Ivanov, Dmitri N; Ganser-Pornillos, Barbie K; Sundquist, Wesley I; Pornillos, Owen

2018-02-15

Restriction factors are intrinsic cellular defense proteins that have evolved to block microbial infections. Retroviruses such as HIV-1 are restricted by TRIM5 proteins, which recognize the viral capsid shell that surrounds, organizes, and protects the viral genome. TRIM5α uses a SPRY domain to bind capsids with low intrinsic affinity ( K D of >1 mM) and therefore requires higher-order assembly into a hexagonal lattice to generate sufficient avidity for productive capsid recognition. TRIMCyp, on the other hand, binds HIV-1 capsids through a cyclophilin A domain, which has a well-defined binding site and higher affinity ( K D of ∼10 μM) for isolated capsid subunits. Therefore, it has been argued that TRIMCyp proteins have dispensed with the need for higher-order assembly to function as antiviral factors. Here, we show that, consistent with its high degree of sequence similarity with TRIM5α, the TRIMCyp B-box 2 domain shares the same ability to self-associate and facilitate assembly of a TRIMCyp hexagonal lattice that can wrap about the HIV-1 capsid. We also show that under stringent experimental conditions, TRIMCyp-mediated restriction of HIV-1 is indeed dependent on higher-order assembly. Both forms of TRIM5 therefore use the same mechanism of avidity-driven capsid pattern recognition. IMPORTANCE Rhesus macaques and owl monkeys are highly resistant to HIV-1 infection due to the activity of TRIM5 restriction factors. The rhesus macaque TRIM5α protein blocks HIV-1 through a mechanism that requires self-assembly of a hexagonal TRIM5α lattice around the invading viral core. Lattice assembly amplifies very weak interactions between the TRIM5α SPRY domain and the HIV-1 capsid. Assembly also promotes dimerization of the TRIM5α RING E3 ligase domain, resulting in synthesis of polyubiquitin chains that mediate downstream steps of restriction. In contrast to rhesus TRIM5α, the owl monkey TRIM5 homolog, TRIMCyp, binds isolated HIV-1 CA subunits much more tightly

Pain in Chickens and Effects of Beak Trimming

USDA-ARS?s Scientific Manuscript database

Beak trimming may cause pain (acute, chronic or both) in trimmed chickens due to tissue damage and nerve injury. The complexity and plasticity of the nervous system and the animal’s inability to communicate verbally make pain difficult to measure directly. However, pain in animals can be recognized...

Nonhuman TRIM5 Variants Enhance Recognition of HIV-1-Infected Cells by CD8+ T Cells

PubMed Central

Jimenez-Moyano, Esther; Ruiz, Alba; Kløverpris, Henrik N.; Rodriguez-Plata, Maria T.; Peña, Ruth; Blondeau, Caroline; Selwood, David L.; Izquierdo-Useros, Nuria; Moris, Arnaud; Clotet, Bonaventura; Goulder, Philip; Towers, Greg J.

2016-01-01

-cyclophilin A (TCyp), are attractive candidates owing to their potency in sensing HIV-1 and blocking its activity. Here, we show that expression of RhT5 and TCyp in HIV-1-infected cells improves CD8+ T-cell-mediated inhibition through the direct activation of HIV-1-specific CD8+ T-cell responses. We found that the potency in CD8+ activation was stronger for RhT5 variants and capsid-specific CD8+ T cells in a mechanism that relies on TRIM5-dependent particle recruitment to cellular proteasomes. This novel mechanism couples innate viral sensing with cellular immunity in a single protein and could be exploited to develop innovative therapeutics for control of HIV-1 infection. PMID:27440884

Evaluation of the UnTRIM model for 3-D tidal circulation

USGS Publications Warehouse

Cheng, R.T.; Casulli, V.; ,

2001-01-01

A family of numerical models, known as the TRIM models, shares the same modeling philosophy for solving the shallow water equations. A characteristic analysis of the shallow water equations points out that the numerical instability is controlled by the gravity wave terms in the momentum equations and by the transport terms in the continuity equation. A semi-implicit finite-difference scheme has been formulated so that these terms and the vertical diffusion terms are treated implicitly and the remaining terms explicitly to control the numerical stability and the computations are carried out over a uniform finite-difference computational mesh without invoking horizontal or vertical coordinate transformations. An unstructured grid version of TRIM model is introduced, or UnTRIM (pronounces as "you trim"), which preserves these basic numerical properties and modeling philosophy, only the computations are carried out over an unstructured orthogonal grid. The unstructured grid offers the flexibilities in representing complex study areas so that fine grid resolution can be placed in regions of interest, and coarse grids are used to cover the remaining domain. Thus, the computational efforts are concentrated in areas of importance, and an overall computational saving can be achieved because the total number of grid-points is dramatically reduced. To use this modeling approach, an unstructured grid mesh must be generated to properly reflect the properties of the domain of the investigation. The new modeling flexibility in grid structure is accompanied by new challenges associated with issues of grid generation. To take full advantage of this new model flexibility, the model grid generation should be guided by insights into the physics of the problems; and the insights needed may require a higher degree of modeling skill.

46 CFR 116.422 - Ceilings, linings, trim, interior finish and decorations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Ceilings, linings, trim, interior finish and decorations... PASSENGERS CONSTRUCTION AND ARRANGEMENT Fire Protection § 116.422 Ceilings, linings, trim, interior finish... accommodation spaces may have a combustible veneer trim and decorations that do not meet the requirements of...

46 CFR 116.422 - Ceilings, linings, trim, interior finish and decorations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Ceilings, linings, trim, interior finish and decorations... PASSENGERS CONSTRUCTION AND ARRANGEMENT Fire Protection § 116.422 Ceilings, linings, trim, interior finish... accommodation spaces may have a combustible veneer trim and decorations that do not meet the requirements of...

All Paths Lead to TRIM25.

PubMed

Zhou, Hengbo; Costello, James C

2017-10-01

Identifying key factors that regulate the transition from primary to metastatic cancer is a fundamental challenge. Walsh et al. took a systems biology approach integrating computational, in vitro, and in vivo experiments to identify TRIM25 (tripartite motif containing 25) as a key factor that regulates metastatic gene signatures both at the transcriptional and post-transcriptional level in breast cancer. Targeting TRIM25 therapeutically is attractive because it governs a broad set of coordinated transcriptional modules that dictate metastatic progression. Copyright © 2017 Elsevier Inc. All rights reserved.

Methodology for determining elevon deflections to trim and maneuver the DAST vehicle with negative static margin

NASA Technical Reports Server (NTRS)

Perry, B., III

1982-01-01

The relationships between elevon deflection and static margin using elements from static and dynamic stability and control and from classical control theory are emphasized. Expressions are derived and presented for calculating elevon deflections required to trim the vehicle in lg straight-and-level flight and to perform specified longitudinal and lateral maneuvers. Applications of this methodology are made at several flight conditions for the ARW-2 wing. On the basis of these applications, it appears possible to trim and maneuver the vehicle with the existing elevons at -15% static margin.

Quantifying the variability in stiffness and damping of an automotive vehicle's trim-structure mounts

NASA Astrophysics Data System (ADS)

Abolfathi, Ali; O'Boy, Dan J.; Walsh, Stephen J.; Dowsett, Amy; Fisher, Stephen A.

2016-09-01

Small plastic clips are used in large numbers in automotive vehicles to connect interior trims to vehicle structures. The variability in their properties can contribute to the overall variability in noise and vibration response of the vehicle. The variability arises due to their material and manufacturing tolerances and more importantly due to the boundary condition. To measure their stiffness and damping, a simple experimental rig is used where a mass is supported by the clip which is modelled as a single degree of freedom system. The rig is designed in a way that it simulates the boundary condition as those of the real vehicle. The variability in clip and also due to the boundary condition at the structure side is first examined which is 7% for stiffness and 8% for damping. To simulate the connection of the trim side, a mount is built using a 3D printer. Rattling occurs in the response of the clips with loose connections, however by preloading the mount the effective stiffness increases and the rattling is eliminated. The variability due to the boundary condition at the trim side was as large as 40% for stiffness and 52% for damping.

Molecular characterization, tissue distribution and expression analysis of TRIM25 in Gallus gallus domesticus.

PubMed

Feng, Ze-Qing; Cheng, Yang; Yang, Hui-Ling; Zhu, Qing; Yu, Dandan; Liu, Yi-Ping

2015-04-25

TRIM25, a member of the tripartite motif-containing (TRIM) family of proteins, plays an important role in cell proliferation, protein modification, and the RIG-I-mediated antiviral signaling pathway. However, relatively few studies have investigated the molecular characterization, tissue distribution, and potential function of TRIM25 in chickens. In this study, we cloned the full-length cDNA of chicken TRIM25 that is composed of 2706 bp. Sequence analyses revealed that TRIM25 contains a 1902-bp open-reading frame that probably encodes a 633-amino acid protein. Multiple comparisons with deduced amino acid sequences revealed that the RING finger and B30.2 domains of chicken TRIM25 share a high sequence similarity with human and murine TRIM25, indicating that these domains are critical for the function of chicken TRIM25. qPCR assays revealed that TRIM25 is highly expressed in the spleen, thymus and lungs in chickens. Furthermore, we observed that TRIM25 expression was significantly upregulated both in vitro and in vivo following infection with Newcastle disease virus. TRIM25 expression was also significantly upregulated in chicken embryo fibroblasts upon stimulation with poly(I:C) or poly(dA:dT). Taken together, these findings suggest that TRIM25 plays an important role in antiviral signaling pathways in chickens. Copyright © 2015 Elsevier B.V. All rights reserved.

RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination.

PubMed

Choudhury, Nila Roy; Heikel, Gregory; Trubitsyna, Maryia; Kubik, Peter; Nowak, Jakub Stanislaw; Webb, Shaun; Granneman, Sander; Spanos, Christos; Rappsilber, Juri; Castello, Alfredo; Michlewski, Gracjan

2017-11-08

TRIM25 is a novel RNA-binding protein and a member of the Tripartite Motif (TRIM) family of E3 ubiquitin ligases, which plays a pivotal role in the innate immune response. However, there is scarce knowledge about its RNA-related roles in cell biology. Furthermore, its RNA-binding domain has not been characterized. Here, we reveal that the RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain, which we postulate to be a novel RNA-binding domain. Using CLIP-seq and SILAC-based co-immunoprecipitation assays, we uncover TRIM25's endogenous RNA targets and protein binding partners. We demonstrate that TRIM25 controls the levels of Zinc Finger Antiviral Protein (ZAP). Finally, we show that the RNA-binding activity of TRIM25 is important for its ubiquitin ligase activity towards itself (autoubiquitination) and its physiologically relevant target ZAP. Our results suggest that many other proteins with the PRY/SPRY domain could have yet uncharacterized RNA-binding potential. Together, our data reveal new insights into the molecular roles and characteristics of RNA-binding E3 ubiquitin ligases and demonstrate that RNA could be an essential factor in their enzymatic activity.

Precision-Trimming 2D Inverse-Opal Lattice on Elastomer to Ordered Nanostructures with Variable Size and Morphology.

PubMed

Zhan, Haoran; Chen, Yanqiu; Liu, Yu; Lau, Woonming; Bao, Chao; Li, Minggan; Lu, Yunlong; Mei, Jun; Hui, David

2017-05-23

A low-cost and scalable method is developed for producing large-area elastomer surfaces having ordered nanostructures with a variety of lattice features controllable to nanometer precision. The method adopts the known technique of molding a PDMS precursor film with a close-packed monolayer of monodisperse submicron polystyrene beads on water to form an inverse-opal dimple lattice with the dimple size controlled by the bead selection and the dimple depth by the molding condition. The subsequent novel precision engineering of the inverse-opal lattice comprises trimming the PDMS precursor by a combination of polymer curing temperature/time and polymer dissolution parameters. The resultant ordered surface nanostructures, fabricated with an increasing degree of trimming, include (a) submicron hemispherical dimples with nanothin interdimple rims and walls; (b) nanocones with variable degrees of tip-sharpness by trimming off the top part of the nanothin interdimple walls; and (c) soup-plate-like submicron shallow dimples with interdimple rims and walls by anisotropically trimming off the nanocones and forming close-packed shallow dimples. As exemplars of industrial relevance of these lattice features, tunable Young's modulus and wettability are demonstrated.

TRIM25 in the Regulation of the Antiviral Innate Immunity.

PubMed

Martín-Vicente, María; Medrano, Luz M; Resino, Salvador; García-Sastre, Adolfo; Martínez, Isidoro

2017-01-01

TRIM25 is an E3 ubiquitin ligase enzyme that is involved in various cellular processes, including regulation of the innate immune response against viruses. TRIM25-mediated ubiquitination of the cytosolic pattern recognition receptor RIG-I is an essential step for initiation of the intracellular antiviral response and has been thoroughly documented. In recent years, however, additional roles of TRIM25 in early innate immunity are emerging, including negative regulation of RIG-I, activation of the melanoma differentiation-associated protein 5-mitochondrial antiviral signaling protein-TRAF6 antiviral axis and modulation of p53 levels and activity. In addition, the ability of TRIM25 to bind RNA may uncover new mechanisms by which this molecule regulates intracellular signaling and/or RNA virus replication.

TRIM25 in the Regulation of the Antiviral Innate Immunity

PubMed Central

Martín-Vicente, María; Medrano, Luz M.; Resino, Salvador; García-Sastre, Adolfo; Martínez, Isidoro

2017-01-01

TRIM25 is an E3 ubiquitin ligase enzyme that is involved in various cellular processes, including regulation of the innate immune response against viruses. TRIM25-mediated ubiquitination of the cytosolic pattern recognition receptor RIG-I is an essential step for initiation of the intracellular antiviral response and has been thoroughly documented. In recent years, however, additional roles of TRIM25 in early innate immunity are emerging, including negative regulation of RIG-I, activation of the melanoma differentiation-associated protein 5–mitochondrial antiviral signaling protein–TRAF6 antiviral axis and modulation of p53 levels and activity. In addition, the ability of TRIM25 to bind RNA may uncover new mechanisms by which this molecule regulates intracellular signaling and/or RNA virus replication. PMID:29018447

Iterative Ellipsoidal Trimming.

DTIC Science & Technology

1980-02-11

to above. Iterative ellipsoidal trimming has been investigated before by other statisticians, most notably by Gnanadesikan and his coworkers...J., Gnanadesikan R., and Kettenring, J. R. (1975). "Robust estimation and outlier detection with correlation coefficients." Biometrika. 62, 531-45. [6...Duda, Richard, and Hart, Peter (1973). Pattern Classification and Scene Analysis. Wiley, New York. [7] Gnanadesikan , R. (1977). Methods for

AfterQC: automatic filtering, trimming, error removing and quality control for fastq data.

PubMed

Chen, Shifu; Huang, Tanxiao; Zhou, Yanqing; Han, Yue; Xu, Mingyan; Gu, Jia

2017-03-14

Some applications, especially those clinical applications requiring high accuracy of sequencing data, usually have to face the troubles caused by unavoidable sequencing errors. Several tools have been proposed to profile the sequencing quality, but few of them can quantify or correct the sequencing errors. This unmet requirement motivated us to develop AfterQC, a tool with functions to profile sequencing errors and correct most of them, plus highly automated quality control and data filtering features. Different from most tools, AfterQC analyses the overlapping of paired sequences for pair-end sequencing data. Based on overlapping analysis, AfterQC can detect and cut adapters, and furthermore it gives a novel function to correct wrong bases in the overlapping regions. Another new feature is to detect and visualise sequencing bubbles, which can be commonly found on the flowcell lanes and may raise sequencing errors. Besides normal per cycle quality and base content plotting, AfterQC also provides features like polyX (a long sub-sequence of a same base X) filtering, automatic trimming and K-MER based strand bias profiling. For each single or pair of FastQ files, AfterQC filters out bad reads, detects and eliminates sequencer's bubble effects, trims reads at front and tail, detects the sequencing errors and corrects part of them, and finally outputs clean data and generates HTML reports with interactive figures. AfterQC can run in batch mode with multiprocess support, it can run with a single FastQ file, a single pair of FastQ files (for pair-end sequencing), or a folder for all included FastQ files to be processed automatically. Based on overlapping analysis, AfterQC can estimate the sequencing error rate and profile the error transform distribution. The results of our error profiling tests show that the error distribution is highly platform dependent. Much more than just another new quality control (QC) tool, AfterQC is able to perform quality control, data

A brief history of TRIM5alpha.

PubMed

Newman, Ruchi M; Johnson, Welkin E

2007-01-01

In spite of the fact that the first isolates of HIV-1 became available more than 20 years ago, there is still no robust animal model for HIV-1 replication and pathogenesis. This is largely due to the existence of multiple genetic barriers to HIV-1 replication in most nonhuman primates, including a severe block targeting the early, post-entry phase of the viral replication cycle. It is now known that a protein called TRIM5alpha mediates this early restriction in nonhuman primate cells. Tissue culture experiments, together with genetic association studies involving multiple HIV/AIDS cohorts, indicate that the human orthologue of TRIM5alpha does not have a significant impact on HIV-1 replication. However, most human alleles encode a functional protein that can restrict at least one retrovirus unrelated to HIV-1 (N-tropic murine leukemia virus), although one deleterious mutation (H43Y) is present at high frequency in human populations. Phylogenetic analyses of the TRIM5 locus reveal that prehistoric retroviral epidemics, not unlike the current HIV/AIDS pandemic, played a significant role in the evolutionary history of humans and their primate relatives. The discovery of TRIM5alpha's antiretroviral activity sparked the imaginations of many laboratories, and considerable effort has now been channeled into characterizing the protein and determining its possible mechanism(s) of action. It is hoped that research on TRIM5alpha will contribute to the establishment of new and improved models for HIV replication and AIDS pathogenesis, point the way towards novel therapeutic targets to stem the tide of the human AIDS epidemic, provide an experimental window onto the early, post-entry stages of the retroviral replication cycle, and even inspire the search for other cellular factors that modulate retroviral infection.

Neuroanatomy-based matrix-guided trimming protocol for the rat brain.

PubMed

Defazio, Rossella; Criado, Ana; Zantedeschi, Valentina; Scanziani, Eugenio

2015-02-01

Brain trimming through defined neuroanatomical landmarks is recommended to obtain consistent sections in rat toxicity studies. In this article, we describe a matrix-guided trimming protocol that uses channels to reproduce coronal levels of anatomical landmarks. Both setup phase and validation study were performed on Han Wistar male rats (Crl:WI(Han)), 10-week-old, with bodyweight of 298 ± 29 (SD) g, using a matrix (ASI-Instruments(®), Houston, TX) fitted for brains of rats with 200 to 400 g bodyweight. In the setup phase, we identified eight channels, that is, 6, 8, 10, 12, 14, 16, 19, and 21, matching the recommended landmarks midway to the optic chiasm, frontal pole, optic chiasm, infundibulum, mamillary bodies, midbrain, middle cerebellum, and posterior cerebellum, respectively. In the validation study, we trimmed the immersion-fixed brains of 60 rats using the selected channels to determine how consistently the channels reproduced anatomical landmarks. Percentage of success (i.e., presence of expected targets for each level) ranged from 89 to 100%. Where 100% success was not achieved, it was noted that the shift in brain trimming was toward the caudal pole. In conclusion, we developed and validated a trimming protocol for the rat brain that allow comparable extensiveness, homology, and relevance of coronal sections as the landmark-guided trimming with the advantage of being quickly learned by technicians. © 2014 by The Author(s).

TRIM45 negatively regulates NF-{kappa}B-mediated transcription and suppresses cell proliferation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shibata, Mio; Sato, Tomonobu; Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638

2012-06-22

Highlights: Black-Right-Pointing-Pointer NF-{kappa}B plays an important role in cell survival and carcinogenesis. Black-Right-Pointing-Pointer TRIM45 negatively regulates TNF{alpha}-induced NF-{kappa}B-mediated transcription. Black-Right-Pointing-Pointer TRIM45 overexpression suppresses cell growth. Black-Right-Pointing-Pointer TRIM45 acts as a repressor for the NF-{kappa}B signal and regulates cell growth. -- Abstract: The NF-{kappa}B signaling pathway plays an important role in cell survival, immunity, inflammation, carcinogenesis, and organogenesis. Activation of NF-{kappa}B is regulated by several posttranslational modifications including phosphorylation, neddylation and ubiquitination. The NF-{kappa}B signaling pathway is activated by two distinct signaling mechanisms and is strictly modulated by the ubiquitin-proteasome system. It has been reported that overexpression of TRIM45, one ofmore » the TRIM family ubiquitin ligases, suppresses transcriptional activities of Elk-1 and AP-1, which are targets of the MAPK signaling pathway. In this study, we showed that TRIM45 also negatively regulates TNF{alpha}-induced NF-{kappa}B-mediated transcription by a luciferase reporter assay and that TRIM45 lacking a RING domain also has an activity to inhibit the NF-{kappa}B signal. Moreover, we found that TRIM45 overexpression suppresses cell growth. These findings suggest that TRIM45 acts as a repressor for the NF-{kappa}B signal and regulates cell growth.« less

Trauma risk management (TRiM) in the UK Armed Forces.

PubMed

Greenberg, N; Langston, V; Jones, N

2008-06-01

Trauma Risk Management (TRiM) is a novel system of post incident management which intend to allow commanders to provide appropriate support to their subordinates in the aftermath of traumatic events. Given the current very considerable operational tempo being experienced by the majority of the UK Armed Forces, it is perhaps not surprising that TRiM has been in use in both Iraq and Afghanistan. Although TRiM originated from within the Royal Marines, it is now widely used in both the Royal Navy and Army; there are also plans to introduce it into specific components of the Royal Air Force such as for the RAF Regiment. This paper aims to explore the basis behind the TRiM system and to explore the evidence for its growing popularity within hierarchical organisations such as the military.

30 CFR 56.9314 - Trimming stockpile and muckpile faces.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Trimming stockpile and muckpile faces. 56.9314 Section 56.9314 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Dumping Sites § 56.9314 Trimming stockpile and muckpile faces. Stockpile and muckpile faces shall be...

30 CFR 57.9314 - Trimming stockpile and muckpile faces.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Trimming stockpile and muckpile faces. 57.9314 Section 57.9314 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Dumping Sites § 57.9314 Trimming stockpile and muckpile faces. Stockpile and muckpile faces shall be...

30 CFR 57.9314 - Trimming stockpile and muckpile faces.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Trimming stockpile and muckpile faces. 57.9314 Section 57.9314 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Dumping Sites § 57.9314 Trimming stockpile and muckpile faces. Stockpile and muckpile faces shall be...

30 CFR 57.9314 - Trimming stockpile and muckpile faces.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Trimming stockpile and muckpile faces. 57.9314 Section 57.9314 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Dumping Sites § 57.9314 Trimming stockpile and muckpile faces. Stockpile and muckpile faces shall be...

30 CFR 56.9314 - Trimming stockpile and muckpile faces.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Trimming stockpile and muckpile faces. 56.9314 Section 56.9314 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Dumping Sites § 56.9314 Trimming stockpile and muckpile faces. Stockpile and muckpile faces shall be...

30 CFR 56.9314 - Trimming stockpile and muckpile faces.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Trimming stockpile and muckpile faces. 56.9314 Section 56.9314 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Dumping Sites § 56.9314 Trimming stockpile and muckpile faces. Stockpile and muckpile faces shall be...

TRIM.FaTE Evaluation Report

EPA Pesticide Factsheets

The TRIM.FaTE Evaluation Report is composed of three volumes. Volume I presents conceptual, mechanistic, and structural complexity evaluations of various aspects of the model. Volumes II and III present performance evaluation.

Development of a multiple-step process for the microbial decontamination of beef trim.

PubMed

Kang, D H; Koohmaraie, M; Dorsa, W J; Siragusa, G R

2001-01-01

A multiple-hurdle antimicrobial process for beef trim was developed. The microbial profiles of inoculated lean beef trim tissue (BTL) and fat-covered lean beef trim (BTF) were monitored during prolonged refrigerated storage following the application of successive multiple antimicrobial treatments applied to inoculated beef trim on a processing conveyor belt set at a belt speed of 1 cm/s. Beef trim (meat size approximately 15 by 15 cm) was preinoculated with bovine feces before all treatments that included the following: control, no treatment; water wash at 65 psi for five passes; water plus lactic acid (2% [vol/vol] room temperature lactic acid wash at 30 psi for three passes); combination treatment 1 (water plus 65 degrees C hot water at 30 psi for one pass plus hot air at 510 degrees C for four passes plus lactic acid), combination treatment 2 (water plus hot water at 82 degrees C for one pass plus hot air at 510 degrees C for five passes plus lactic acid), and combination treatment 3 (water plus hot water at 82 degrees C for three passes plus hot air at 510 degrees C for six passes plus lactic acid). The effects of treatments on bacterial populations were monitored by enumerating mesophilic aerobic bacteria (APC), presumptive lactic acid bacteria (PLAB), psychrotrophic bacteria (PCT), coliforms, and Escherichia coli biotype 1 on product stored for up to 7 days at 4 degrees C. In the case of BTL, the numbers of APC, PCT, and PLAB increased during storage at 5 degrees C, whereas the numbers of coliform and E. coli decreased on average by 1.8 log CFU/cm2, then remained constant following the initial reduction. Negligible effects on color quality were observed from multihurdle treatment combination 1. In the case of the BTF, the microbial reductions by treatments were much greater than the reduction on BTL. The pH of treated BTF increased more slowly than the pH of treated BTL, resulting in further reduction of the microflora on BTF. Except for control and water

Grid generation on trimmed Bezier and NURBS quilted surfaces

NASA Technical Reports Server (NTRS)

Woan, Chung-Jin; Clever, Willard C.; Tam, Clement K.

1995-01-01

This paper presents some recently added capabilities to RAGGS, Rockwell Automated Grid Generation System. Included are the trimmed surface handling and display capability and structures and unstructured grid generation on trimmed Bezier and NURBS (non-uniform rational B-spline surfaces) quilted surfaces. Samples are given to demonstrate the new capabilities.

Aeroelastic Analysis of a Trimmed Generic Hypersonic Vehicle

NASA Technical Reports Server (NTRS)

Nydick, I.; Friedmann, P. P.

1999-01-01

The aeroelastic equations of motion governing a hypersonic vehicle in free flight are derived. The equations of motion for a translating and rotating flexible body using Lagrange's equations in terms of quasi-coordinates are presented. These equations are simplified for the case of a vehicle with pitch and plunge rigid body degrees of freedom and small elastic displacements. The displacements are approximated by a truncated series of the unrestrained mode shapes, which are obtained using equivalent plate theory. Subsequently, the nonlinear equations of motion are linearized about the trim state, which is obtained using a rigid body trim model and steady hypersonic aerodynamics. The appropriate flutter derivatives are calculated from piston theory. Results describing mode shapes, trim behavior, and aeroelastic stability of a generic hypersonic vehicle are presented.

Germline mutations and somatic inactivation of TRIM28 in Wilms tumour

PubMed Central

Halliday, Benjamin J.; Markie, David M.; Grundy, Richard G.; Ludgate, Jackie L.; Black, Michael A.; Weeks, Robert J.; Catchpoole, Daniel R.; Reeve, Anthony E.

2018-01-01

Wilms tumour is a childhood tumour that arises as a consequence of somatic and rare germline mutations, the characterisation of which has refined our understanding of nephrogenesis and carcinogenesis. Here we report that germline loss of function mutations in TRIM28 predispose children to Wilms tumour. Loss of function of this transcriptional co-repressor, which has a role in nephrogenesis, has not previously been associated with cancer. Inactivation of TRIM28, either germline or somatic, occurred through inactivating mutations, loss of heterozygosity or epigenetic silencing. TRIM28-mutated tumours had a monomorphic epithelial histology that is uncommon for Wilms tumour. Critically, these tumours were negative for TRIM28 immunohistochemical staining whereas the epithelial component in normal tissue and other Wilms tumours stained positively. These data, together with a characteristic gene expression profile, suggest that inactivation of TRIM28 provides the molecular basis for defining a previously described subtype of Wilms tumour, that has early age of onset and excellent prognosis. PMID:29912901

Nasal Sculpting: Calculated and Predictable Tip Elevation With Cephalic Trim

PubMed Central

Redstone, Jeremiah S.; Nguyen, Jonathan; North, Durham Alan; Hazani, Ron; Drury, Brad; Yoder, Eric M.; Cooperman, Ross D.; Yoder, Virginia; Little, Jarrod A.; Florman, Larry D.; Wilhelmi, Bradon J.

2015-01-01

Background: Rhinoplasty techniques to affect nasal tip rotation are well described. Cephalic alar trim is a powerful method for achieving tip elevation. Previous studies and texts provide aesthetic guidelines for nasolabial angles. Often, surgeon experience determines the degree of lower lateral cartilage resection to achieve optimal results. This study analyzes the change in tip elevation with measured resections of the lower lateral cartilages. This can aid the surgeon in accurately predicting the effect of cephalic alar trim on tip elevation. Methods: Ten fresh cadaveric dissections were performed to determine the change in nasolabial angles after cephalic trim of the lower lateral cartilage. Closed rhinoplasty technique was performed using marginal and intercartilaginous incisions to expose the lower lateral cartilage. Caliper measurements of the lower lateral cartilage were recorded. Serial cephalic trim was performed in 25% increments. True lateral photographs were obtained before and after each serial excision. Nasolabial angle measurements were obtained using a digital goniometer for digital photo analysis. Results: Four female and 6 male cadavers were evaluated. The mean initial nasolabial angle was 106° ± 2°. The mean lower lateral cartilage width was 9.45 ± 1.38 mm. Serial 25% reductions in lower lateral cartilage height resulted in a mean total nasolabial angle change of 7.4°, 12.9°, and 19.6°, respectively. The mean incremental change in the nasolabial angle was 6.47° ± 1.25°. Conclusion: The nasolabial angle is an essential aesthetic feature. Cephalic trim is a key maneuver in affecting the nasolabial angle. A 25% lower lateral cartilage cephalic trim correlates with an average change in the nasolabial angle of 6.47°. Knowledge of the cephalic trim to nasolabial angle relationship aids in achieving desired tip elevation. PMID:26171091

The ubiquitin ligase TRIM25 targets ERG for degradation in prostate cancer.

PubMed

Wang, Shan; Kollipara, Rahul K; Humphries, Caroline G; Ma, Shi-Hong; Hutchinson, Ryan; Li, Rui; Siddiqui, Javed; Tomlins, Scott A; Raj, Ganesh V; Kittler, Ralf

2016-10-04

Ets related gene (ERG) is a transcription factor that is overexpressed in 40% of prostate tumors due to a gene fusion between ERG and TMPRSS2. Because ERG functions as a driver of prostate carcinogenesis, understanding the mechanisms that influence its turnover may provide new molecular handles to target the protein. Previously, we found that ERG undergoes ubiquitination and then is deubiquitinated by USP9X in prostate cancer cells to prevent its proteasomal degradation. Here, we identify Tripartite motif-containing protein 25 (TRIM25) as the E3 ubiquitin ligase that ubiquitinates the protein prior to its degradation. TRIM25 binds full-length ERG, and it also binds the N-terminally truncated variants of ERG that are expressed in tumors with TMPRSS2-ERG fusions. We demonstrate that TRIM25 polyubiquitinates ERG in vitro and that inactivation of TRIM25 resulted in reduced polyubiquitination and stabilization of ERG. TRIM25 mRNA and protein expression was increased in ERG rearrangement-positive prostate cancer specimens, and we provide evidence that ERG upregulates TRIM25 expression. Thus, overexpression of ERG in prostate cancer may cause an increase in TRIM25 activity, which is mitigated by the expression of the deubiquitinase USP9X, which is required to stabilize ERG.

The ubiquitin ligase TRIM25 targets ERG for degradation in prostate cancer

PubMed Central

Wang, Shan; Kollipara, Rahul K.; Humphries, Caroline G.; Ma, Shi-Hong; Hutchinson, Ryan; Li, Rui; Siddiqui, Javed; Tomlins, Scott A.; Raj, Ganesh V.; Kittler, Ralf

2016-01-01

Ets related gene (ERG) is a transcription factor that is overexpressed in 40% of prostate tumors due to a gene fusion between ERG and TMPRSS2. Because ERG functions as a driver of prostate carcinogenesis, understanding the mechanisms that influence its turnover may provide new molecular handles to target the protein. Previously, we found that ERG undergoes ubiquitination and then is deubiquitinated by USP9X in prostate cancer cells to prevent its proteasomal degradation. Here, we identify Tripartite motif-containing protein 25 (TRIM25) as the E3 ubiquitin ligase that ubiquitinates the protein prior to its degradation. TRIM25 binds full-length ERG, and it also binds the N-terminally truncated variants of ERG that are expressed in tumors with TMPRSS2-ERG fusions. We demonstrate that TRIM25 polyubiquitinates ERG in vitro and that inactivation of TRIM25 resulted in reduced polyubiquitination and stabilization of ERG. TRIM25 mRNA and protein expression was increased in ERG rearrangement-positive prostate cancer specimens, and we provide evidence that ERG upregulates TRIM25 expression. Thus, overexpression of ERG in prostate cancer may cause an increase in TRIM25 activity, which is mitigated by the expression of the deubiquitinase USP9X, which is required to stabilize ERG. PMID:27626314

The Host E3-Ubiquitin Ligase TRIM6 Ubiquitinates the Ebola Virus VP35 Protein and Promotes Virus Replication.

PubMed

Bharaj, Preeti; Atkins, Colm; Luthra, Priya; Giraldo, Maria Isabel; Dawes, Brian E; Miorin, Lisa; Johnson, Jeffrey R; Krogan, Nevan J; Basler, Christopher F; Freiberg, Alexander N; Rajsbaum, Ricardo

2017-09-15

Ebola virus (EBOV), a member of the Filoviridae family, is a highly pathogenic virus that causes severe hemorrhagic fever in humans and is responsible for epidemics throughout sub-Saharan, central, and West Africa. The EBOV genome encodes VP35, an important viral protein involved in virus replication by acting as an essential cofactor of the viral polymerase as well as a potent antagonist of the host antiviral type I interferon (IFN-I) system. By using mass spectrometry analysis and coimmunoprecipitation assays, we show here that VP35 is ubiquitinated on lysine 309 (K309), a residue located on its IFN antagonist domain. We also found that VP35 interacts with TRIM6, a member of the E3-ubiquitin ligase tripartite motif (TRIM) family. We recently reported that TRIM6 promotes the synthesis of unanchored K48-linked polyubiquitin chains, which are not covalently attached to any protein, to induce efficient antiviral IFN-I-mediated responses. Consistent with this notion, VP35 also associated noncovalently with polyubiquitin chains and inhibited TRIM6-mediated IFN-I induction. Intriguingly, we also found that TRIM6 enhances EBOV polymerase activity in a minigenome assay and TRIM6 knockout cells have reduced replication of infectious EBOV, suggesting that VP35 hijacks TRIM6 to promote EBOV replication through ubiquitination. Our work provides evidence that TRIM6 is an important host cellular factor that promotes EBOV replication, and future studies will focus on whether TRIM6 could be targeted for therapeutic intervention against EBOV infection. IMPORTANCE EBOV belongs to a family of highly pathogenic viruses that cause severe hemorrhagic fever in humans and other mammals with high mortality rates (40 to 90%). Because of its high pathogenicity and lack of licensed antivirals and vaccines, EBOV is listed as a tier 1 select-agent risk group 4 pathogen. An important mechanism for the severity of EBOV infection is its suppression of innate immune responses. The EBOV VP35

The Host E3-Ubiquitin Ligase TRIM6 Ubiquitinates the Ebola Virus VP35 Protein and Promotes Virus Replication

PubMed Central

Bharaj, Preeti; Atkins, Colm; Luthra, Priya; Giraldo, Maria Isabel; Dawes, Brian E.; Miorin, Lisa; Johnson, Jeffrey R.; Krogan, Nevan J.; Basler, Christopher F.; Freiberg, Alexander N.

2017-01-01

ABSTRACT Ebola virus (EBOV), a member of the Filoviridae family, is a highly pathogenic virus that causes severe hemorrhagic fever in humans and is responsible for epidemics throughout sub-Saharan, central, and West Africa. The EBOV genome encodes VP35, an important viral protein involved in virus replication by acting as an essential cofactor of the viral polymerase as well as a potent antagonist of the host antiviral type I interferon (IFN-I) system. By using mass spectrometry analysis and coimmunoprecipitation assays, we show here that VP35 is ubiquitinated on lysine 309 (K309), a residue located on its IFN antagonist domain. We also found that VP35 interacts with TRIM6, a member of the E3-ubiquitin ligase tripartite motif (TRIM) family. We recently reported that TRIM6 promotes the synthesis of unanchored K48-linked polyubiquitin chains, which are not covalently attached to any protein, to induce efficient antiviral IFN-I-mediated responses. Consistent with this notion, VP35 also associated noncovalently with polyubiquitin chains and inhibited TRIM6-mediated IFN-I induction. Intriguingly, we also found that TRIM6 enhances EBOV polymerase activity in a minigenome assay and TRIM6 knockout cells have reduced replication of infectious EBOV, suggesting that VP35 hijacks TRIM6 to promote EBOV replication through ubiquitination. Our work provides evidence that TRIM6 is an important host cellular factor that promotes EBOV replication, and future studies will focus on whether TRIM6 could be targeted for therapeutic intervention against EBOV infection. IMPORTANCE EBOV belongs to a family of highly pathogenic viruses that cause severe hemorrhagic fever in humans and other mammals with high mortality rates (40 to 90%). Because of its high pathogenicity and lack of licensed antivirals and vaccines, EBOV is listed as a tier 1 select-agent risk group 4 pathogen. An important mechanism for the severity of EBOV infection is its suppression of innate immune responses. The EBOV VP

The C-Terminal Tail of TRIM56 Dictates Antiviral Restriction of Influenza A and B Viruses by Impeding Viral RNA Synthesis

PubMed Central

Liu, Baoming; Li, Nan L.; Shen, Yang; Bao, Xiaoyong; Elbahesh, Husni; Webby, Richard J.

2016-01-01

-influenza virus activity of TRIM56 was independent of the E3 ligase activity. Rather, expression of a short segment within the very C-terminal tail of TRIM56 inhibited the replication of influenza viruses as effectively as that of full-length TRIM56 by specifically targeting viral RNA synthesis. These data reveal the remarkable multifaceted activity of TRIM56, which has developed multiple domains to inhibit multiple viral families. They also raise the possibility of developing a broad-spectrum, TRIM56-based antiviral approach for addition to influenza prophylaxis and/or control strategies. PMID:26889027

The effects of different bill-trimming methods on the well-being of Pekin ducks.

PubMed

Gustafson, L A; Cheng, H-W; Garner, J P; Pajor, E A; Mench, J A

2007-09-01

Pekin ducks are often bill-trimmed to prevent feather pecking and cannibalism, but this practice has been criticized because of the resulting potential for acute and chronic pain. The goal of this experiment was to compare 2 different bill-trimming methods, hot blade trimming with cautery (TRIM) and cautery only (tip-searing; SEAR), on the behavior, bill morphology, and weight gain of Pekin ducks. Ducklings (n = 192, 96 per sex) were trimmed at the hatchery and assigned to 12 floor pens (3.66 x0.91 m) by treatment. Behavior was evaluated by scan sampling, and plumage condition was scored using a 0 to 3 scoring system. Thirty-six ducks were randomly euthanized at 3 and 6 wk of age, and their bills were collected for examination. Following fixation and decalcification, the bills were embedded in paraffin wax and sectioned longitudinally. Alternate sections were stained with hematoxylin and eosin and Masson's trichrome for the connective tissues, and with Bielschowsky's silver impregnation, Bodian's staining, and Holmes' staining for the nerve fibers. Trimmed ducks engaged in fewer bill-related behaviors and rested more than untrimmed ducks (NOTRIM) during the first 2 wk posttrim. Ducks in the SEAR and NOTRIM groups showed similar patterns of weight gain, but those in the TRIM group had a lower rate of gain than ducks in the SEAR group during the first week posttrim and had a lower rate of gain than those in the NOTRIM group for 2 wk posttrim. Feather scores of ducks in the NOTRIM group were significantly worse than those in the TRIM or SEAR group by 18 d, and scores continued to deteriorate at a greater rate than those of trimmed ducks throughout the study. Both trimming methods caused connective tissue proliferation in the bill stumps, but the TRIM method caused thicker scar tissue than the SEAR method. No neuromas were found with either trimming method, but there were more nerve fibers in bill stumps of the SEAR ducks than the TRIM ducks. These results suggest that

Trimming Line Design using New Development Method and One Step FEM

NASA Astrophysics Data System (ADS)

Chung, Wan-Jin; Park, Choon-Dal; Yang, Dong-yol

2005-08-01

In most of automobile panel manufacturing, trimming is generally performed prior to flanging. To find feasible trimming line is crucial in obtaining accurate edge profile after flanging. Section-based method develops blank along section planes and find trimming line by generating loop of end points. This method suffers from inaccurate results for regions with out-of-section motion. On the other hand, simulation-based method can produce more accurate trimming line by iterative strategy. However, due to limitation of time and lack of information in initial die design, it is still not widely accepted in the industry. In this study, new fast method to find feasible trimming line is proposed. One step FEM is used to analyze the flanging process because we can define the desired final shape after flanging and most of strain paths are simple in flanging. When we use one step FEM, the main obstacle is the generation of initial guess. Robust initial guess generation method is developed to handle bad-shaped mesh, very different mesh size and undercut part. The new method develops 3D triangular mesh in propagational way from final mesh onto the drawing tool surface. Also in order to remedy mesh distortion during development, energy minimization technique is utilized. Trimming line is extracted from the outer boundary after one step FEM simulation. This method shows many benefits since trimming line can be obtained in the early design stage. The developed method is successfully applied to the complex industrial applications such as flanging of fender and door outer.

TRIM16 inhibits proliferation and migration through regulation of interferon beta 1 in melanoma cells

PubMed Central

Sutton, Selina K.; Koach, Jessica; Tan, Owen; Liu, Bing; Carter, Daniel R.; Wilmott, James S.; Yosufi, Benafsha; Haydu, Lauren E.; Mann, Graham J.; Thompson, John F.; Long, Georgina V.; Liu, Tao; McArthur, Grant; Zhang, Xu Dong; Scolyer, Richard A.; Cheung, Belamy B.; Marshall, Glenn M.

2014-01-01

High basal or induced expression of the tripartite motif protein, TRIM16, leads to reduce cell growth and migration of neuroblastoma and skin squamous cell carcinoma cells. However, the role of TRIM16 in melanoma is currently unknown. TRIM16 protein levels were markedly reduced in human melanoma cell lines, compared with normal human epidermal melanocytes due to both DNA methylation and reduced protein stability. TRIM16 knockdown strongly increased cell migration in normal human epidermal melanocytes, while TRIM16 overexpression reduced cell migration and proliferation of melanoma cells in an interferon beta 1 (IFNβ1)-dependent manner. Chromatin immunoprecipitation assays revealed TRIM16 directly bound the IFNβ1 gene promoter. Low level TRIM16 expression in 91 melanoma patient samples, strongly correlated with lymph node metastasis, and, predicted poor patient prognosis in a separate cohort of 170 melanoma patients with lymph node metastasis. The BRAF inhibitor, vemurafenib, increased TRIM16 protein levels in melanoma cells in vitro, and induced growth arrest in BRAF-mutant melanoma cells in a TRIM16-dependent manner. High levels of TRIM16 in melanoma tissues from patients treated with Vemurafenib correlated with clinical response. Our data, for the first time, demonstrates TRIM16 is a marker of cell migration and metastasis, and a novel treatment target in melanoma. PMID:25333256

Type I IFN augments IL-27-dependent TRIM25 expression to inhibit HBV replication.

PubMed

Tan, Guangyun; Xiao, Qingfei; Song, Hongxiao; Ma, Feng; Xu, Fengchao; Peng, Di; Li, Na; Wang, Xiaosong; Niu, Junqi; Gao, Pujun; Qin, F Xiao-Feng; Cheng, Genhong

2018-03-01

Hepatitis B virus (HBV) can cause chronic hepatitis B, which may lead to cirrhosis and liver cancer. Type I interferon (IFN) is an approved drug for the treatment of chronic hepatitis B. However, the fundamental mechanisms of antiviral action by type I IFN and the downstream signaling pathway are unclear. TRIM25 is an IFN-stimulated gene (ISG) that has an important role in RIG-I ubiquitination and activation. Whether TRIM25 is induced in liver cells by type I IFN to mediate anti-HBV function remains unclear. Here we report that interleukin-27 (IL-27) has a critical role in IFN-induced TRIM25 upregulation. TRIM25 induction requires both STAT1 and STAT3. In TRIM25 knockout HepG2 cells, type I IFN production was consistently attenuated and HBV replication was increased, whereas overexpression of TRIM25 in HepG2 cells resulted in elevated IFN production and reduced HBV replication. More interestingly, we found that TRIM25 expression was downregulated in HBV patients and the addition of serum samples from HBV patients could inhibit TRIM25 expression in HepG2 cells, suggesting that HBV might have involved a mechanism to inhibit antiviral ISG expression and induce IFN resistance. Collectively, our results demonstrate that type I IFN -induced TRIM25 is an important factor in inhibiting HBV replication, and the IFN-IL-27-TRIM25 axis may represent a new target for treating HBV infection.

Periodic trim solutions with hp-version finite elements in time

NASA Technical Reports Server (NTRS)

Peters, David A.; Hou, Lin-Jun

1990-01-01

Finite elements in time as an alternative strategy for rotorcraft trim problems are studied. The research treats linear flap and linearized flap-lag response both for quasi-trim and trim cases. The connection between Fourier series analysis and hp-finite elements for periodic a problem is also examined. It is proved that Fourier series is a special case of space-time finite elements in which one element is used with a strong displacement formulation. Comparisons are made with respect to accuracy among Fourier analysis, displacement methods, and mixed methods over a variety parameters. The hp trade-off is studied for the periodic trim problem to provide an optimum step size and order of polynomial for a given error criteria. It is found that finite elements in time can outperform Fourier analysis for periodic problems, and for some given error criteria. The mixed method provides better results than does the displacement method.

Knockdown of Tripartite-59 (TRIM59) Inhibits Cellular Proliferation and Migration in Human Cervical Cancer Cells.

PubMed

Aierken, Gulijiahan; Seyiti, Ayinuer; Alifu, Mayinuer; Kuerban, Gulina

2017-03-13

The tripartite motif (TRIM) family of proteins is a class of highly conservative proteins that have been implicated in multiple processes. TRIM59, one member of the TRIM family, has now received recognition as a key regulator in the development and progression of human diseases. However, its role in human tumorigenesis has remained largely unknown. In this study, the effects of TRIM59 expression on cell proliferation and migration were investigated in human cervical cancer cells. The expression of TRIM59 in clinical cervical cancer tissues and cervical cancer cells was initially determined by RT-PCR and Western blot. Specific shRNA against TRIM59 was then employed to knock down the expression of TRIM59 in cervical cancer lines HeLa and SiHa. The effects of TRIM59 knockdown on cell proliferation was assessed by MTT assay and colony formation assay. Transwell assay was conducted to reveal cell migration and invasion abilities before and after TRIM59 knockdown. Our results showed that the expression of TRIM59 was significantly elevated in cervical cancers. Knockdown of TRIM59 significantly inhibited cell proliferation and colony formation as well as cell migration and invasion abilities in cervical cancer HeLa and SiHa cells. Cell cycle progression analysis showed that TRIM59-depleted cells preferred to accumulate in the S phase. These data suggest that TRIM59 is a potential target that promotes the progression of cervical cancer.

Proper Edging and Trimming Will Help Improve Lumber Value

Treesearch

Philip A. Araman

1991-01-01

Decisions on where to edge and trim waning edged boards, or to trim other boards, can have a major effect on the performance of a sawmill. Optimum decisions are difficult for a number of reasons, including: complexity of grading rules; operator skills; operator fatigue or lack of interest at times; and, the inability of operators to include lumber prices in decisions....

RING domain is essential for the antiviral activity of TRIM25 from orange spotted grouper.

PubMed

Yang, Ying; Huang, Youhua; Yu, Yepin; Yang, Min; Zhou, Sheng; Qin, Qiwei; Huang, Xiaohong

2016-08-01

Tripartite motif-containing 25 (TRIM25) has been demonstrated to exert crucial roles in the regulation of innate immune signaling. However, the roles of fish TRIM25 in antiviral immune response still remained uncertain. Here, a novel fish TRIM25 gene from orange spotted grouper (EcTRIM25) was cloned and its roles in grouper virus infection were elucidated. EcTRIM25 encoded a 734-aa protein which shared 68% identity to large yellow croaker (Larimichthys crocea). Amino acid alignment showed that EcTRIM25 contained three conserved domains, including a RING-finger domain, a B box/coiled-coil domain and a SPRY domain. In healthy grouper, the transcript of EcTRIM25 was predominantly detected in skin, spleen and intestine. After stimulation with Singapore grouper iridovirus (SGIV) or poly I:C, the relative expression of EcTRIM25 in grouper spleen was significantly increased at the early stage of injection. Subcellular localization analysis showed that EcTRIM25 distributed throughout the cytoplasm in grouper cells. Notably, the deletion RING domain affected its accurate localization and displayed microtubule like structures or bright aggregates in GS cells. After incubation with SGIV or red spotted grouper nervous necrosis virus (RGNNV), overexpression of full length of EcTRIM25 in vitro significantly decreased the viral gene transcription of SGIV and RGNNV. Consistently, the deletion of RING domain obviously affected the inhibitory effect of EcTRIM25. Furthermore, overexpression of EcTRIM25 significantly increased the expression level of interferon related signaling molecules, including interferon regulatory factor (IRF) 3, interferon-induced 35-kDa protein (IFP35), MXI, IRF7 and myeloid differentiation factor 88 (MyD88), suggesting that the positive regulation of interferon immune response by EcTRIM25 might affected RGNNV replication directly. Meanwhile, the expression levels of pro-inflammation cytokines were differently regulated by the ectopic expression of EcTRIM25

Simulation of router action on a lathe to test the cutting tool performance in edge-trimming of graphite/epoxy composite

NASA Astrophysics Data System (ADS)

Ramulu, M.; Rogers, E.

1994-04-01

The predominant machining application with graphite/epoxy composite materials in aerospace industry is peripheral trimming. The computer numerically controlled (CNC) high speed routers required to do edge trimming work are generally scheduled for production work in industry and are not available for extensive cutter testing. Therefore, an experimental method of simulating the conditions of periphery trim using a lathe is developed in this paper. The validity of the test technique will be demonstrated by conducting carbide tool wear tests under dry cutting conditions. The experimental results will be analyzed to characterize the wear behavior of carbide cutting tools in machining the composite materials.

The Ubiquitin Ligase RNF125 Targets Innate Immune Adaptor Protein TRIM14 for Ubiquitination and Degradation.

PubMed

Jia, Xue; Zhou, Hongli; Wu, Chao; Wu, Qiankun; Ma, Shichao; Wei, Congwen; Cao, Ye; Song, Jingdong; Zhong, Hui; Zhou, Zhuo; Wang, Jianwei

2017-06-15

Tripartite motif-containing 14 (TRIM14) is a mitochondrial adaptor that facilitates innate immune signaling. Upon virus infection, the expression of TRIM14 is significantly induced, which stimulates the production of type-I IFNs and proinflammatory cytokines. As excessive immune responses lead to harmful consequences, TRIM14-mediated signaling needs to be tightly balanced. In this study, we identify really interesting new gene-type zinc finger protein 125 (RNF125) as a negative regulator of TRIM14 in the innate antiviral immune response. Overexpression of RNF125 inhibits TRIM14-mediated antiviral response, whereas knockdown of RNF125 has the opposite effect. RNF125 interacts with TRIM14 and acts as an E3 ubiquitin ligase that catalyzes TRIM14 ubiquitination. RNF125 promotes K48-linked polyubiquitination of TRIM14 and mediates its degradation via the ubiquitin-proteasome pathway. Consequently, wild-type mouse embryonic fibroblasts show significantly reduced TRIM14 protein levels in late time points of viral infection, whereas TRIM14 protein is retained in RNF125-deficient mouse embryonic fibroblasts. Collectively, our data suggest that RNF125 plays a new role in innate immune response by regulating TRIM14 ubiquitination and degradation. Copyright © 2017 by The American Association of Immunologists, Inc.

A large new subset of TRIM genes highly diversified by duplication and positive selection in teleost fish

PubMed Central

van der Aa, Lieke M; Levraud, Jean-Pierre; Yahmi, Malika; Lauret, Emilie; Briolat, Valérie; Herbomel, Philippe; Benmansour, Abdenour; Boudinot, Pierre

2009-01-01

Background In mammals, the members of the tripartite motif (TRIM) protein family are involved in various cellular processes including innate immunity against viral infection. Viruses exert strong selective pressures on the defense system. Accordingly, antiviral TRIMs have diversified highly through gene expansion, positive selection and alternative splicing. Characterizing immune TRIMs in other vertebrates may enlighten their complex evolution. Results We describe here a large new subfamily of TRIMs in teleosts, called finTRIMs, identified in rainbow trout as virus-induced transcripts. FinTRIMs are formed of nearly identical RING/B-box regions and C-termini of variable length; the long variants include a B30.2 domain. The zebrafish genome harbors a striking diversity of finTRIMs, with 84 genes distributed in clusters on different chromosomes. A phylogenetic analysis revealed different subsets suggesting lineage-specific diversification events. Accordingly, the number of fintrim genes varies greatly among fish species. Conserved syntenies were observed only for the oldest fintrims. The closest mammalian relatives are trim16 and trim25, but they are not true orthologs. The B30.2 domain of zebrafish finTRIMs evolved under strong positive selection. The positions under positive selection are remarkably congruent in finTRIMs and in mammalian antiviral TRIM5α, concentrated within a viral recognition motif in mammals. The B30.2 domains most closely related to finTRIM are found among NOD-like receptors (NLR), indicating that the evolution of TRIMs and NLRs was intertwined by exon shuffling. Conclusion The diversity, evolution, and features of finTRIMs suggest an important role in fish innate immunity; this would make them the first TRIMs involved in immunity identified outside mammals. PMID:19196451

TRIM25 Enhances the Antiviral Action of Zinc-Finger Antiviral Protein (ZAP)

PubMed Central

Lau, Zerlina; Cheung, Pamela; Schneider, William M.; Bozzacco, Leonia; Buehler, Eugen; Takaoka, Akinori; Rice, Charles M.; Felsenfeld, Dan P.; MacDonald, Margaret R.

2017-01-01

The host factor and interferon (IFN)-stimulated gene (ISG) product, zinc-finger antiviral protein (ZAP), inhibits a number of diverse viruses by usurping and intersecting with multiple cellular pathways. To elucidate its antiviral mechanism, we perform a loss-of-function genome-wide RNAi screen to identify cellular cofactors required for ZAP antiviral activity against the prototype alphavirus, Sindbis virus (SINV). In order to exclude off-target effects, we carry out stringent confirmatory assays to verify the top hits. Important ZAP-liaising partners identified include proteins involved in membrane ion permeability, type I IFN signaling, and post-translational protein modification. The factor contributing most to the antiviral function of ZAP is TRIM25, an E3 ubiquitin and ISG15 ligase. We demonstrate here that TRIM25 interacts with ZAP through the SPRY domain, and TRIM25 mutants lacking the RING or coiled coil domain fail to stimulate ZAP’s antiviral activity, suggesting that both TRIM25 ligase activity and its ability to form oligomers are critical for its cofactor function. TRIM25 increases the modification of both the short and long ZAP isoforms by K48- and K63-linked polyubiquitin, although ubiquitination of ZAP does not directly affect its antiviral activity. However, TRIM25 is critical for ZAP’s ability to inhibit translation of the incoming SINV genome. Taken together, these data uncover TRIM25 as a bona fide ZAP cofactor that leads to increased ZAP modification enhancing its translational inhibition activity. PMID:28060952

TRIM25 Enhances the Antiviral Action of Zinc-Finger Antiviral Protein (ZAP).

PubMed

Li, Melody M H; Lau, Zerlina; Cheung, Pamela; Aguilar, Eduardo G; Schneider, William M; Bozzacco, Leonia; Molina, Henrik; Buehler, Eugen; Takaoka, Akinori; Rice, Charles M; Felsenfeld, Dan P; MacDonald, Margaret R

2017-01-01

The host factor and interferon (IFN)-stimulated gene (ISG) product, zinc-finger antiviral protein (ZAP), inhibits a number of diverse viruses by usurping and intersecting with multiple cellular pathways. To elucidate its antiviral mechanism, we perform a loss-of-function genome-wide RNAi screen to identify cellular cofactors required for ZAP antiviral activity against the prototype alphavirus, Sindbis virus (SINV). In order to exclude off-target effects, we carry out stringent confirmatory assays to verify the top hits. Important ZAP-liaising partners identified include proteins involved in membrane ion permeability, type I IFN signaling, and post-translational protein modification. The factor contributing most to the antiviral function of ZAP is TRIM25, an E3 ubiquitin and ISG15 ligase. We demonstrate here that TRIM25 interacts with ZAP through the SPRY domain, and TRIM25 mutants lacking the RING or coiled coil domain fail to stimulate ZAP's antiviral activity, suggesting that both TRIM25 ligase activity and its ability to form oligomers are critical for its cofactor function. TRIM25 increases the modification of both the short and long ZAP isoforms by K48- and K63-linked polyubiquitin, although ubiquitination of ZAP does not directly affect its antiviral activity. However, TRIM25 is critical for ZAP's ability to inhibit translation of the incoming SINV genome. Taken together, these data uncover TRIM25 as a bona fide ZAP cofactor that leads to increased ZAP modification enhancing its translational inhibition activity.

Functional role of TRIM E3 ligase oligomerization and regulation of catalytic activity.

PubMed

Koliopoulos, Marios G; Esposito, Diego; Christodoulou, Evangelos; Taylor, Ian A; Rittinger, Katrin

2016-06-01

TRIM E3 ubiquitin ligases regulate a wide variety of cellular processes and are particularly important during innate immune signalling events. They are characterized by a conserved tripartite motif in their N-terminal portion which comprises a canonical RING domain, one or two B-box domains and a coiled-coil region that mediates ligase dimerization. Self-association via the coiled-coil has been suggested to be crucial for catalytic activity of TRIMs; however, the precise molecular mechanism underlying this observation remains elusive. Here, we provide a detailed characterization of the TRIM ligases TRIM25 and TRIM32 and show how their oligomeric state is linked to catalytic activity. The crystal structure of a complex between the TRIM25 RING domain and an ubiquitin-loaded E2 identifies the structural and mechanistic features that promote a closed E2~Ub conformation to activate the thioester for ubiquitin transfer allowing us to propose a model for the regulation of activity in the full-length protein. Our data reveal an unexpected diversity in the self-association mechanism of TRIMs that might be crucial for their biological function. © 2016 Francis Crick Institute. Published under the terms of the CC BY 4.0 license.

A novel role for Gtb1p in glucose trimming of N-linked glycans

PubMed Central

Quinn, Robert P; Mahoney, Sarah J; Wilkinson, Barrie M; Thornton, David J; Stirling, Colin J

2009-01-01

Glucosidase II (GluII) is a glycan-trimming enzyme active on nascent glycoproteins in the endoplasmic reticulum (ER). It trims the middle and innermost glucose residues (Glc2 and Glc1) from N-linked glycans. The monoglucosylated glycan produced by the first GluII trimming reaction is recognized by calnexin/calreticulin and serves as the signal for entry into this folding pathway. GluII is a heterodimer of α and β subunits corresponding to yeast Gls2p and Gtb1p, respectively. While Gls2p contains the glucosyl hydrolase active site, the Gtb1p subunit has previously been shown to be essential for the Glc1 trimming event. Here we demonstrate that Gtb1p also determines the rate of Glc2 trimming. In order to further dissect these activities we mutagenized a number of conserved residues across the protein. Our data demonstrate that both the MRH and G2B domains of Gtb1p contribute to the Glc2 trimming event but that the MRH domain is essential for Glc1 trimming. PMID:19542522

Lead intoxication in dogs: risk assessment of feeding dogs trimmings of lead-shot game.

PubMed

Høgåsen, Helga R; Ørnsrud, Robin; Knutsen, Helle K; Bernhoft, Aksel

2016-07-25

Expanding lead-based bullets, commonly used for hunting of big game, produce a scattering of lead particles in the carcass around the wound channel. Trimmings around this channel, which are sometimes fed to dogs, may contain lead particles. The aim of this study was to assess potential health effects of feeding dogs such trimmings. Lead ingestion most commonly causes gastrointestinal and neurological clinical signs, although renal, skeletal, haematological, cardiovascular and biochemical effects have also been reported. Experimental data indicate that a daily dose of around 1 mg lead as lead acetate/kg body weight for ten days may be considered as a Lowest Observed Effect Level in dogs. Acute toxicity documentation from the Centers for Disease Control and Prevention indicates 300 mg/kg body weight as the lowest dose of lead acetate causing death in dogs after oral ingestion. Our assessment suggests that dogs fed trimmings of lead-shot game may be affected by the amounts of lead present, and that even deadly exposure could occasionally occur. The intestinal absorption of lead from bullets was assumed to be 10-80 % of that of lead acetate, reflecting both the variability in particle size and uncertainty about the bioavailability of metallic lead in dogs. Despite data gaps, this study indicates that feeding dogs trimmings of lead-shot game may represent a risk of lead intoxication. More research is needed to assess the exact consequences, if lead-based bullets are still to be used. Meanwhile, we recommend that trimmings close to the wound channel should be made inaccessible to dogs, as well as to other domestic or wild animals.

Overlapping and Distinct Molecular Determinants Dictating the Antiviral Activities of TRIM56 against Flaviviruses and Coronavirus

PubMed Central

Liu, Baoming; Li, Nan L.; Wang, Jie; Shi, Pei-Yong; Wang, Tianyi; Miller, Mark A.

2014-01-01

ABSTRACT The tripartite motif-containing (TRIM) proteins have emerged as a new class of host antiviral restriction factors, with several demonstrating roles in regulating innate antiviral responses. Of >70 known TRIMs, TRIM56 inhibits replication of bovine viral diarrhea virus, a ruminant pestivirus of the family Flaviviridae, but has no appreciable effect on vesicular stomatitis virus (VSV), a rhabdovirus. Yet the antiviral spectrum of TRIM56 remains undefined. In particular, how TRIM56 impacts human-pathogenic viruses is unknown. Also unclear are the molecular determinants governing the antiviral activities of TRIM56. Herein, we show that TRIM56 poses a barrier to infections by yellow fever virus (YFV), dengue virus serotype 2 (DENV2), and human coronavirus virus (HCoV) OC43 but not encephalomyocarditis virus (EMCV). Moreover, by engineering cell lines conditionally expressing various TRIM56 mutants, we demonstrated that TRIM56's antiflavivirus effects required both the E3 ligase activity that lies in the N-terminal RING domain and the integrity of its C-terminal portion, while the restriction of HCoV-OC43 relied upon the TRIM56 E3 ligase activity alone. Furthermore, TRIM56 was revealed to impair YFV and DENV2 propagation by suppressing intracellular viral RNA accumulation but to compromise HCoV-OC43 infection at a later step in the viral life cycle, suggesting that distinct TRIM56 domains accommodate differing antiviral mechanisms. Altogether, TRIM56 is a versatile antiviral host factor that confers resistance to YFV, DENV2, and HCoV-OC43 through overlapping and distinct molecular determinants. IMPORTANCE We previously reported tripartite motif protein 56 (TRIM56) as a host restriction factor of bovine viral diarrhea virus, a ruminant pathogen. However, the impact of TRIM56 on human-pathogenic RNA viruses is unknown. Herein, we demonstrate that TRIM56 restricts two medically important flaviviruses, yellow fever virus (YFV) and dengue virus serotype 2 (DENV2

Overlapping and distinct molecular determinants dictating the antiviral activities of TRIM56 against flaviviruses and coronavirus.

PubMed

Liu, Baoming; Li, Nan L; Wang, Jie; Shi, Pei-Yong; Wang, Tianyi; Miller, Mark A; Li, Kui

2014-12-01

The tripartite motif-containing (TRIM) proteins have emerged as a new class of host antiviral restriction factors, with several demonstrating roles in regulating innate antiviral responses. Of >70 known TRIMs, TRIM56 inhibits replication of bovine viral diarrhea virus, a ruminant pestivirus of the family Flaviviridae, but has no appreciable effect on vesicular stomatitis virus (VSV), a rhabdovirus. Yet the antiviral spectrum of TRIM56 remains undefined. In particular, how TRIM56 impacts human-pathogenic viruses is unknown. Also unclear are the molecular determinants governing the antiviral activities of TRIM56. Herein, we show that TRIM56 poses a barrier to infections by yellow fever virus (YFV), dengue virus serotype 2 (DENV2), and human coronavirus virus (HCoV) OC43 but not encephalomyocarditis virus (EMCV). Moreover, by engineering cell lines conditionally expressing various TRIM56 mutants, we demonstrated that TRIM56's antiflavivirus effects required both the E3 ligase activity that lies in the N-terminal RING domain and the integrity of its C-terminal portion, while the restriction of HCoV-OC43 relied upon the TRIM56 E3 ligase activity alone. Furthermore, TRIM56 was revealed to impair YFV and DENV2 propagation by suppressing intracellular viral RNA accumulation but to compromise HCoV-OC43 infection at a later step in the viral life cycle, suggesting that distinct TRIM56 domains accommodate differing antiviral mechanisms. Altogether, TRIM56 is a versatile antiviral host factor that confers resistance to YFV, DENV2, and HCoV-OC43 through overlapping and distinct molecular determinants. We previously reported tripartite motif protein 56 (TRIM56) as a host restriction factor of bovine viral diarrhea virus, a ruminant pathogen. However, the impact of TRIM56 on human-pathogenic RNA viruses is unknown. Herein, we demonstrate that TRIM56 restricts two medically important flaviviruses, yellow fever virus (YFV) and dengue virus serotype 2 (DENV2), and a human

Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition.

PubMed

Koliopoulos, Marios G; Lethier, Mathilde; van der Veen, Annemarthe G; Haubrich, Kevin; Hennig, Janosch; Kowalinski, Eva; Stevens, Rebecca V; Martin, Stephen R; Reis E Sousa, Caetano; Cusack, Stephen; Rittinger, Katrin

2018-05-08

RIG-I is a viral RNA sensor that induces the production of type I interferon (IFN) in response to infection with a variety of viruses. Modification of RIG-I with K63-linked poly-ubiquitin chains, synthesised by TRIM25, is crucial for activation of the RIG-I/MAVS signalling pathway. TRIM25 activity is targeted by influenza A virus non-structural protein 1 (NS1) to suppress IFN production and prevent an efficient host immune response. Here we present structures of the human TRIM25 coiled-coil-PRYSPRY module and of complexes between the TRIM25 coiled-coil domain and NS1. These structures show that binding of NS1 interferes with the correct positioning of the PRYSPRY domain of TRIM25 required for substrate ubiquitination and provide a mechanistic explanation for how NS1 suppresses RIG-I ubiquitination and hence downstream signalling. In contrast, the formation of unanchored K63-linked poly-ubiquitin chains is unchanged by NS1 binding, indicating that RING dimerisation of TRIM25 is not affected by NS1.

Tripartite motif-containing 29 (TRIM29) is a novel marker for lymph node metastasis in gastric cancer.

PubMed

Kosaka, Yoshimasa; Inoue, Hiroshi; Ohmachi, Takahiro; Yokoe, Takeshi; Matsumoto, Toshifumi; Mimori, Koshi; Tanaka, Fumiaki; Watanabe, Masahiko; Mori, Masaki

2007-09-01

Tripartite motif-containing 29 (TRIM29) belongs to the TRIM protein family, which has unique structural characteristics, including multiple zinc finger motifs and a leucine zipper motif. TRIM29, also known as ataxia telangiectasia group D complementing gene, possesses radiosensitivity suppressor functions. Although TRIM29 has been reported to be underexpressed in prostate and breast cancer, its expression in gastrointestinal cancer has not been studied. By use of real-time reverse transcriptase-polymerase chain reaction, we analyzed TRIM29 mRNA expression status with respect to various clinicopathological parameters in 124 patients with gastric cancer. An immunohistochemical study was also conducted. The expression of TRIM29 was far higher in gastric cancer tumor tissue. Increased TRIM29 mRNA expression was markedly associated with such parameters as histological grade, large tumor size, extent of tumor invasion, and lymph node metastasis. In the TRIM29 high-expression group, it was an independent predictor for lymph node metastasis. Furthermore, patients with high TRIM29 mRNA expression showed a far poorer survival rate than those with low TRIM29 mRNA expression. TRIM29 expression may serve as a good marker of lymph node metastasis in gastric cancer.

Isolated resonator gyroscope with isolation trimming using a secondary element

NASA Technical Reports Server (NTRS)

Challoner, A. Dorian (Inventor); Shcheglov, Kirill V. (Inventor)

2006-01-01

The present invention discloses a resonator gyroscope including an isolated resonator. One or more flexures support the isolated resonator and a baseplate is affixed to the resonator by the flexures. Drive and sense elements are affixed to the baseplate and used to excite the resonator and sense movement of the gyroscope. In addition, at least one secondary element (e.g., another electrode) is affixed to the baseplate and used for trimming isolation of the resonator. The resonator operates such that it transfers substantially no net momentum to the baseplate when the resonator is excited. Typically, the isolated resonator comprises a proof mass and a counterbalancing plate.

On the Use pf Active Flow Control to Trim and Control a Tailles Aircraft Model

NASA Astrophysics Data System (ADS)

Jentzsch, Marvin

The Stability And Control CONfiguration (SACCON) model represents an emerging trend in airplane design where the classical tube, wing and empennage are replaced by a single tailless configuration. The challenge is to assure that these designs are stable and controllable. Nonlinear aerodynamic behavior is observed on the SACCON at higher incidence angles due to leading edge vortex structures. Active Flow Control (AFC) used in preliminary design represents a promising solution to the longitudinal stability problems and this was demonstrated experimentally on a semi span model. AFC can be used to trim the SACCON in pitch and it alters forces and moments comparable to common control surface deflections. A combination of AFC and control surface deflection may increase the overall efficiency and opens up a variety of maneuvering possibilities. This implies that AFC should be treated concomitantly with other design parameters and should be considered in the preliminary design process already and not as an add-on tool. Integral force and moment data was supplemented by observations using Pressure Sensitive Paint (PSP) and flow visualization. Two arrays of individually controlled sweeping jets, one located along the leading edge and the other along the flap hinge provided the AFC input needed to alter the flow. The array positioned over the flap-hinge of the model was most effective in stabilizing the wing by decreasing the pitching moment at lower and intermediate angles of incidence. This effect was achieved by reducing the spanwise flow on the swept back portion of the wing through jet-entrainment that also affected the leading edge vortex. Leading edge actuation showed some beneficial effects by inhibiting the formation of the leading edge vortex near the wing tip. A preliminary study using suction was carried out. The tests were carried out at Mach numbers smaller than 0.2 and Reynolds numbers based on the root chord of the model that approached 106.

Feasibility of Supersonic Aircraft Concepts for Low-Boom and Flight Trim Constraints

NASA Technical Reports Server (NTRS)

Li, Wu

2015-01-01

This paper documents a process for analyzing whether a particular supersonic aircraft configuration layout and a given cruise condition are feasible to achieve a trimmed low-boom design. This process was motivated by the need to know whether a particular configuration at a given cruise condition could be reshaped to satisfy both low-boom and flight trim constraints. Without such a process, much effort could be wasted on shaping a configuration layout at a cruise condition that could never satisfy both low-boom and flight trim constraints simultaneously. The process helps to exclude infeasible configuration layouts with minimum effort and allows a designer to develop trimmed low-boom concepts more effectively. A notional low-boom supersonic demonstrator concept is used to illustrate the analysis/design process.

Potential role of TRIM3 as a novel tumour suppressor in colorectal cancer (CRC) development.

PubMed

Piao, Mei-Yu; Cao, Hai-Long; He, Na-Na; Xu, Meng-Que; Dong, Wen-Xiao; Wang, Wei-Qiang; Wang, Bang-Mao; Zhou, Bing

2016-01-01

Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in the United States. Recent cancer genome-sequencing efforts and complementary functional studies have led to the identification of a collection of candidate 'driver' genes involved in CRC tumorigenesis. Tripartite motif (TRIM3) is recently identified as a tumour suppressor in glioblastoma but this tumour-suppressive function has not been investigated in CRC. In this study, we investigated the potential role of TRIM3 as a tumour suppressor in CRC development by manipulating the expression of TRIM3 in two authentic CRC cell lines, HCT116 and DLD1, followed by various functional assays, including cell proliferation, colony formation, scratch wound healing, soft agar, and invasion assays. Xenograft experiment was performed to examine in vivo tumour-suppressive properties of TRIM3. Small-interfering RNA (siRNA) mediated knockdown of TRIM3 conferred growth advantage in CRC cells. In contrast, overexpression of TRIM3 affected cell survival, cell migration, anchorage independent growth and invasive potential in CRC cells. In addition, TRIM3 was found to be down-regulated in human colon cancer tissues compared with matched normal colon tissues. Overexpression of TRIM3 significantly inhibited tumour growth in vivo using xenograft mouse models. Mechanistic investigation revealed that TRIM3 can regulate p53 protein level through its stabilisation. TRIM3 functions as a tumour suppressor in CRC progression. This tumour-suppressive function is exerted partially through regulation of p53 protein. Therefore, this protein may represent a novel therapeutic target for prevention or intervention of CRC.

Visualization of a proteasome-independent intermediate during restriction of HIV-1 by rhesus TRIM5α

PubMed Central

Campbell, Edward M.; Perez, Omar; Anderson, Jenny L.; Hope, Thomas J.

2008-01-01

TRIM5 proteins constitute a class of restriction factors that prevent host cell infection by retroviruses from different species. TRIM5α restricts retroviral infection early after viral entry, before the generation of viral reverse transcription products. However, the underlying restriction mechanism remains unclear. In this study, we show that during rhesus macaque TRIM5α (rhTRIM5α)–mediated restriction of HIV-1 infection, cytoplasmic HIV-1 viral complexes can associate with concentrations of TRIM5α protein termed cytoplasmic bodies. We observe a dynamic interaction between rhTRIM5α and cytoplasmic HIV-1 viral complexes, including the de novo formation of rhTRIM5α cytoplasmic body–like structures around viral complexes. We observe that proteasome inhibition allows HIV-1 to remain stably sequestered into large rhTRIM5α cytoplasmic bodies, preventing the clearance of HIV-1 viral complexes from the cytoplasm and revealing an intermediate in the restriction process. Furthermore, we can measure no loss of capsid protein from viral complexes arrested at this intermediate step in restriction, suggesting that any rhTRIM5α-mediated loss of capsid protein requires proteasome activity. PMID:18250195

Application of multiple antimicrobial interventions for microbial decontamination of commercial beef trim.

PubMed

Kang, D H; Koohmaraie, M; Siragusa, G R

2001-02-01

Commercially produced, irregularly sized (range, 100 to 400 cm2), uninoculated beef trim was treated by a previously optimized multihurdle antimicrobial process under spray system or hot air gun with set-up speed (1 cm/s): W (water wash at 65 psi for five passes) + HW (82 degrees C water at 30 psi for three passes) + HA (510 degrees C air for five passes) + L (2% [vol/vol] room temperature lactic acid wash at 30 psi for three passes). After treatment, the trim was finely ground, vacuum packaged, and stored at 4 degrees C for up to 20 days. At regular intervals (0, 5, 10, 15, and 20 days of storage at 4 degrees C), the ground beef was analyzed to measure mesophilic aerobic bacteria (APC), coliforms, psychrotrophic bacteria (PCT), and presumptive lactic acid bacteria (PLAB) and compared with the untreated control. The numbers of APC, coliforms, PCT, and PLAB were reduced to nearly nondetectable levels immediately after treatment, with significant differences compared with the control (P < 0.05), then started to increase after 5 to 10 days of storage at 4 degrees C. After 20 days, microbial populations of treated ground beef were significantly lower than those of nontreated ground beef for the numbers of APC, coliforms, PCT, and PLAB (P < 0.05), with differences of 1.2, 2.4, 1.6, and 1.6 log CFU/g, respectively. Based on microbial reduction and quality aspects, the multihurdle antimicrobial process was identified as an effective intervention to reduce coliforms on beef trim.

Some technical aspects of trimming lumber in the planing mill

Treesearch

Peter Koch

1952-01-01

This paper discusses four classes of lumber timming machines applicable to the planning mill. The classification is made according to function as follows: Irregularity or defect removal to increase the value of residual portion. Double end trimming to a length standard acceptable by the trade, trimming to specified length of the higher grades of stock after it has been...

Genetic evaluation of claw health traits accounting for potential preselection of cows to be trimmed.

PubMed

Croué, Iola; Fikse, Freddy; Johansson, Kjell; Carlén, Emma; Thomas, Gilles; Leclerc, Hélène; Ducrocq, Vincent

2017-10-01

Claw lesions are one of the most important health issues in dairy cattle. Although the frequency of claw lesions depends greatly on herd management, the frequency can be lowered through genetic selection. A genetic evaluation could be developed based on trimming records collected by claw trimmers; however, not all cows present in a herd are usually selected by the breeder to be trimmed. The objectives of this study were to investigate the importance of the preselection of cows for trimming, to account for this preselection, and to estimate genetic parameters of claw health traits. The final data set contained 25,511 trimming records of French Holstein cows. Analyzed claw lesion traits were digital dermatitis, heel horn erosion, interdigital hyperplasia, sole hemorrhage circumscribed, sole hemorrhage diffused, sole ulcer, and white line fissure. All traits were analyzed as binary traits in a multitrait linear animal model. Three scenarios were considered: including only trimmed cows in a 7-trait model (scenario 1); or trimmed cows and contemporary cows not trimmed but present at the time of a visit (considering that nontrimmed cows were healthy) in a 7-trait model (scenario 2); or trimmed cows and contemporary cows not trimmed but present at the time of a visit (considering lesion records for trimmed cows only), in an 8-trait model, including a 0/1 trimming status trait (scenario 3). For scenario 3, heritability estimates ranged from 0.02 to 0.09 on the observed scale. Genetic correlations clearly revealed 2 groups of traits (digital dermatitis, heel horn erosion, and interdigital hyperplasia on the one hand, and sole hemorrhage circumscribed, sole hemorrhage diffused, sole ulcer, and white line fissure on the other hand). Heritabilities on the underlying scale did not vary much depending on the scenario: the effect of the preselection of cows for trimming on the estimation of heritabilities appeared to be negligible. However, including untrimmed cows as healthy

Structure and catalytic activation of the TRIM23 RING E3 ubiquitin ligase: DAWIDZIAK et al.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dawidziak, Daria M.; Sanchez, Jacint G.; Wagner, Jonathan M.

Tripartite motif (TRIM) proteins comprise a large family of RING-type ubiquitin E3 ligases that regulate important biological processes. An emerging general model is that TRIMs form elongated antiparallel coiled-coil dimers that prevent interaction of the two attendant RING domains. The RING domains themselves bind E2 conjugating enzymes as dimers, implying that an active TRIM ligase requires higher-order oligomerization of the basal coiled-coil dimers. Here, we report crystal structures of the TRIM23 RING domain in isolation and in complex with an E2–ubiquitin conjugate. Our results indicate that TRIM23 enzymatic activity requires RING dimerization, consistent with the general model of TRIM activation.

Mechanism of TRIM25 Catalytic Activation in the Antiviral RIG-I Pathway.

PubMed

Sanchez, Jacint G; Chiang, Jessica J; Sparrer, Konstantin M J; Alam, Steven L; Chi, Michael; Roganowicz, Marcin D; Sankaran, Banumathi; Gack, Michaela U; Pornillos, Owen

2016-08-02

Antiviral response pathways induce interferon by higher-order assembly of signaling complexes called signalosomes. Assembly of the RIG-I signalosome is regulated by K63-linked polyubiquitin chains, which are synthesized by the E3 ubiquitin ligase, TRIM25. We have previously shown that the TRIM25 coiled-coil domain is a stable, antiparallel dimer that positions two catalytic RING domains on opposite ends of an elongated rod. We now show that the RING domain is a separate self-association motif that engages ubiquitin-conjugated E2 enzymes as a dimer. RING dimerization is required for catalysis, TRIM25-mediated RIG-I ubiquitination, interferon induction, and antiviral activity. We also provide evidence that RING dimerization and E3 ligase activity are promoted by binding of the TRIM25 SPRY domain to the RIG-I effector domain. These results indicate that TRIM25 actively participates in higher-order assembly of the RIG-I signalosome and helps to fine-tune the efficiency of the RIG-I-mediated antiviral response. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Mechanism of TRIM25 Catalytic Activation in the Antiviral RIG-I Pathway

PubMed Central

Sanchez, Jacint G.; Chiang, Jessica J.; Sparrer, Konstantin M.J.; Alam, Steven L.; Chi, Michael; Roganowicz, Marcin D.; Sankaran, Banumathi; Gack, Michaela U.; Pornillos, Owen

2016-01-01

SUMMARY Antiviral response pathways induce interferon by higher-order assembly of signaling complexes called signalosomes. Assembly of the RIG-I signalosome is regulated by K63-linked polyubiquitin chains, which are synthesized by the E3 ubiquitin ligase, TRIM25. We have previously shown that the TRIM25 coiled-coil domain is a stable, antiparallel dimer that positions two catalytic RING domains on opposite ends of an elongated rod. We now show that the RING domain is a separate self-association motif that engages ubiquitin-conjugated E2 enzymes as a dimer. RING dimerization is required for catalysis, TRIM25-mediated RIG-I ubiquitination, interferon induction, and antiviral activity. We also provide evidence that RING dimerization and E3 ligase activity are promoted by binding of the TRIM25 SPRY domain to the RIG-I effector domain. These results indicate that TRIM25 actively participates in higher-order assembly of the RIG-I signalosome and helps to fine-tune the efficiency of the RIG-I-mediated antiviral response. PMID:27425606

Mechanism of TRIM25 Catalytic Activation in the Antiviral RIG-I Pathway

DOE PAGES

Sanchez, Jacint G.; Chiang, Jessica J.; Sparrer, Konstantin M. J.; ...

2016-07-14

Antiviral response pathways induce interferon by higher-order assembly of signaling complexes called signalosomes. Assembly of the RIG-I signalosome is regulated by K63-linked polyubiquitin chains, which are synthesized by the E3 ubiquitin ligase, TRIM25. We have previously shown that the TRIM25 coiled-coil domain is a stable, antiparallel dimer that positions two catalytic RING domains on opposite ends of an elongated rod. We now show that the RING domain is a separate self-association motif that engages ubiquitin-conjugated E2 enzymes as a dimer. RING dimerization is required for catalysis, TRIM25-mediated RIG-I ubiquitination, interferon induction, and antiviral activity. We also provide evidence that RINGmore » dimerization and E3 ligase activity are promoted by binding of the TRIM25 SPRY domain to the RIG-I effector domain. These results indicate that TRIM25 actively participates in higher-order assembly of the RIG-I signalosome and helps to fine-tune the efficiency of the RIG-I-mediated antiviral response.« less

Computation of the Distribution of the Fiber-Matrix Interface Cracks in the Edge Trimming of CFRP

NASA Astrophysics Data System (ADS)

Wang, Fu-ji; Zhang, Bo-yu; Ma, Jian-wei; Bi, Guang-jian; Hu, Hai-bo

2018-04-01

Edge trimming is commonly used to bring the CFRP components to right dimension and shape in aerospace industries. However, various forms of undesirable machining damage occur frequently which will significantly decrease the material performance of CFRP. The damage is difficult to predict and control due to the complicated changing laws, causing unsatisfactory machining quality of CFRP components. Since the most of damage has the same essence: the fiber-matrix interface cracks, this study aims to calculate the distribution of them in edge trimming of CFRP, thereby to obtain the effects of the machining parameters, which could be helpful to guide the optimal selection of the machining parameters in engineering. Through the orthogonal cutting experiments, the quantitative relation between the fiber-matrix interface crack depth and the fiber cutting angle, cutting depth as well as cutting speed is established. According to the analysis on material removal process on any location of the workpiece in edge trimming, the instantaneous cutting parameters are calculated, and the formation process of the fiber-matrix interface crack is revealed. Finally, the computational method for the fiber-matrix interface cracks in edge trimming of CFRP is proposed. Upon the computational results, it is found that the fiber orientations of CFRP workpieces is the most significant factor on the fiber-matrix interface cracks, which can not only change the depth of them from micrometers to millimeters, but control the distribution image of them. Other machining parameters, only influence the fiber-matrix interface cracks depth but have little effect on the distribution image.

Nuclear TRIM25 Specifically Targets Influenza Virus Ribonucleoproteins to Block the Onset of RNA Chain Elongation.

PubMed

Meyerson, Nicholas R; Zhou, Ligang; Guo, Yusong R; Zhao, Chen; Tao, Yizhi J; Krug, Robert M; Sawyer, Sara L

2017-11-08

TRIM25 is an E3 ubiquitin ligase that activates RIG-I to promote the antiviral interferon response. The NS1 protein from all strains of influenza A virus binds TRIM25, although not all virus strains block the interferon response, suggesting alternative mechanisms for TRIM25 action. Here we present a nuclear role for TRIM25 in specifically restricting influenza A virus replication. TRIM25 inhibits viral RNA synthesis through a direct mechanism that is independent of its ubiquitin ligase activity and the interferon pathway. This activity can be inhibited by the viral NS1 protein. TRIM25 inhibition of viral RNA synthesis results from its binding to viral ribonucleoproteins (vRNPs), the structures containing individual viral RNA segments, the viral polymerase, and multiple viral nucleoproteins. TRIM25 binding does not inhibit initiation of capped-RNA-primed viral mRNA synthesis by the viral polymerase. Rather, the onset of RNA chain elongation is inhibited because TRIM25 prohibits the movement of RNA into the polymerase complex. Copyright © 2017 Elsevier Inc. All rights reserved.

TRIM21 ubiquitylates SQSTM1/p62 and suppresses protein sequestration to regulate redox homeostasis

PubMed Central

Pan, Ji-An; Sun, Yu; Jiang, Ya-Ping; Bott, Alex J.; Jaber, Nadia; Dou, Zhixun; Yang, Bin; Chen, Juei-Suei; Catanzaro, Joseph M.; Du, Chunying; Ding, Wen-Xing; Diaz-Meco, Maria T.; Moscat, Jorge; Ozato, Keiko; Lin, Richard Z.; Zong, Wei-Xing

2016-01-01

Summary TRIM21 is a RING finger domain-containing ubiquitin E3 ligase whose expression is elevated in autoimmune disease. While TRIM21 plays an important role in immune activation during pathogen infection, little is known about its inherent cellular function. Here we show that TRIM21 plays an essential role in redox regulation by directly interacting with SQSTM1/p62 and ubiquitylating p62 at lysine(K)7 via K63-linkage. As p62 oligomerizes and sequesters client proteins in inclusions, the TRIM21-mediated p62 ubiquitylation abrogates p62 oligomerization and sequestration of proteins including Keap1, a negative regulator of antioxidant response. TRIM21-deficient cells display an enhanced antioxidant response and reduced cell death in response to oxidative stress. Genetic ablation of TRIM21 in mice confers protection from oxidative damages caused by arsenic-induced liver insult and pressure overload heart injury. Therefore, TRIM21 plays an essential role in p62-regulated redox homeostasis and may be a viable target for treating pathological conditions resulting from oxidative damage. PMID:26942676

The common missense mutation D489N in TRIM32 causing limb girdle muscular dystrophy 2H leads to loss of the mutated protein in knock-in mice resulting in a Trim32-null phenotype.

PubMed

Kudryashova, Elena; Struyk, Arie; Mokhonova, Ekaterina; Cannon, Stephen C; Spencer, Melissa J

2011-10-15

Mutations in tripartite motif protein 32 (TRIM32) are responsible for several hereditary disorders that include limb girdle muscular dystrophy type 2H (LGMD2H), sarcotubular myopathy (STM) and Bardet Biedl syndrome. Most LGMD2H mutations in TRIM32 are clustered in the NHL β-propeller domain at the C-terminus and are predicted to interfere with homodimerization. To get insight into TRIM32's role in the pathogenesis of LGMD2H and to create an accurate model of disease, we have generated a knock-in mouse (T32KI) carrying the c.1465G > A (p.D489N) mutation in murine Trim32 corresponding to the human LGMD2H/STM pathogenic mutation c.1459G > A (p.D487N). Our data indicate that T32KI mice have both a myopathic and a neurogenic phenotype, very similar to the one described in the Trim32-null mice that we created previously. Analysis of Trim32 gene expression in T32KI mice revealed normal mRNA levels, but a severe reduction in mutant TRIM32 (D489N) at the protein level. Our results suggest that the D489N pathogenic mutation destabilizes the protein, leading to its degradation, and results in the same mild myopathic and neurogenic phenotype as that found in Trim32-null mice. Thus, one potential mechanism of LGMD2H might be destabilization of mutated TRIM32 protein leading to a null phenotype.

TRIM25 Is Required for the Antiviral Activity of Zinc Finger Antiviral Protein

PubMed Central

Zheng, Xiaojiao; Wang, Xinlu; Tu, Fan; Wang, Qin; Fan, Zusen

2017-01-01

ABSTRACT Zinc finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses by binding to viral mRNAs and repressing the translation and/or promoting the degradation of target mRNA. In addition, ZAP regulates the expression of certain cellular genes. Here, we report that tripartite motif-containing protein 25 (TRIM25), a ubiquitin E3 ligase, is required for the antiviral activity of ZAP. Downregulation of endogenous TRIM25 abolished ZAP's antiviral activity. The E3 ligase activity of TRIM25 is required for this regulation. TRIM25 mediated ZAP ubiquitination, but the ubiquitination of ZAP itself did not seem to be required for its antiviral activity. Downregulation of endogenous ubiquitin or overexpression of the deubiquitinase OTUB1 impaired ZAP's activity. We provide evidence indicating that TRIM25 modulates the target RNA binding activity of ZAP. These results uncover a mechanism by which the antiviral activity of ZAP is regulated. IMPORTANCE ZAP is a host antiviral factor that specifically inhibits the replication of certain viruses, including HIV-1, Sindbis virus, and Ebola virus. ZAP binds directly to target mRNA, and it represses the translation and promotes the degradation of target mRNA. While the mechanisms by which ZAP posttranscriptionally inhibits target RNA expression have been extensively studied, how its antiviral activity is regulated is not very clear. Here, we report that TRIM25, a ubiquitin E3 ligase, is required for the antiviral activity of ZAP. Downregulation of endogenous TRIM25 remarkably abolished ZAP's activity. TRIM25 is required for ZAP optimal binding to target mRNA. These results help us to better understand how the antiviral activity of ZAP is regulated. PMID:28202764

TRIM25 Is Required for the Antiviral Activity of Zinc Finger Antiviral Protein.

PubMed

Zheng, Xiaojiao; Wang, Xinlu; Tu, Fan; Wang, Qin; Fan, Zusen; Gao, Guangxia

2017-05-01

Zinc finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses by binding to viral mRNAs and repressing the translation and/or promoting the degradation of target mRNA. In addition, ZAP regulates the expression of certain cellular genes. Here, we report that tripartite motif-containing protein 25 (TRIM25), a ubiquitin E3 ligase, is required for the antiviral activity of ZAP. Downregulation of endogenous TRIM25 abolished ZAP's antiviral activity. The E3 ligase activity of TRIM25 is required for this regulation. TRIM25 mediated ZAP ubiquitination, but the ubiquitination of ZAP itself did not seem to be required for its antiviral activity. Downregulation of endogenous ubiquitin or overexpression of the deubiquitinase OTUB1 impaired ZAP's activity. We provide evidence indicating that TRIM25 modulates the target RNA binding activity of ZAP. These results uncover a mechanism by which the antiviral activity of ZAP is regulated. IMPORTANCE ZAP is a host antiviral factor that specifically inhibits the replication of certain viruses, including HIV-1, Sindbis virus, and Ebola virus. ZAP binds directly to target mRNA, and it represses the translation and promotes the degradation of target mRNA. While the mechanisms by which ZAP posttranscriptionally inhibits target RNA expression have been extensively studied, how its antiviral activity is regulated is not very clear. Here, we report that TRIM25, a ubiquitin E3 ligase, is required for the antiviral activity of ZAP. Downregulation of endogenous TRIM25 remarkably abolished ZAP's activity. TRIM25 is required for ZAP optimal binding to target mRNA. These results help us to better understand how the antiviral activity of ZAP is regulated. Copyright © 2017 American Society for Microbiology.

The Effect of Trim5 Polymorphisms on the Clinical Course of HIV-1 Infection

PubMed Central

van Manen, Daniëlle; Rits, Maarten A. N; Beugeling, Corrine; van Dort, Karel; Schuitemaker, Hanneke; Kootstra, Neeltje A

2008-01-01

The antiviral factor tripartite interaction motif 5α (Trim5α) restricts a broad range of retroviruses in a species-specific manner. Although human Trim5α is unable to block HIV-1 infection in human cells, a modest inhibition of HIV-1 replication has been reported. Recently two polymorphisms in the Trim5 gene (H43Y and R136Q) were shown to affect the antiviral activity of Trim5α in vitro. In this study, participants of the Amsterdam Cohort studies were screened for polymorphisms at amino acid residue 43 and 136 of the Trim5 gene, and the potential effects of these polymorphisms on the clinical course of HIV-1 infection were analyzed. In agreement with the reported decreased antiviral activity of Trim5α that contains a Y at amino acid residue 43 in vitro, an accelerated disease progression was observed for individuals who were homozygous for the 43Y genotype as compared to individuals who were heterozygous or homozygous for the 43H genotype. A protective effect of the 136Q genotype was observed but only after the emergence of CXCR4-using (X4) HIV-1 variants and when a viral load of 104.5 copies per ml plasma was used as an endpoint in survival analysis. Interestingly, naive CD4 T cells, which are selectively targeted by X4 HIV-1, revealed a significantly higher expression of Trim5α than memory CD4 T cells. In addition, we observed that the 136Q allele in combination with the −2GG genotype in the 5′UTR was associated with an accelerated disease progression. Thus, polymorphisms in the Trim5 gene may influence the clinical course of HIV-1 infection also underscoring the antiviral effect of Trim5α on HIV-1 in vivo. PMID:18248091

Parametric Investigation on the Use of Lateral and Logitudinal Rotor Trim Flapping for Tiltrotor Noise Reduction

NASA Technical Reports Server (NTRS)

Malpica, Carlos

2017-01-01

This paper presents an acoustics parametric study of the effect of varying lateral and longitudinal rotor trim flapping angles (tip-path-plane tilt) on noise radiated by an isolated 26-ft diameter proprotor, similar to that of the AW609 tiltrotor, in edgewise flight. Three tip-path-plane angle of attack operating conditions of -9, 0 and 6 deg, at 80 knots, were investigated. Results showed that: 1) minimum noise was attained for the tip-path-plane angle of attack value of -9 deg, and 2) changing the cyclic trim state (i.e., controls) altered the airloads and produced noticeable changes to the low-frequency (LF) and blade-vortex interaction (BVI) radiated-noise magnitude and directionality. In particular, by trimming the rotor to a positive (inboard) lateral flapping angle of 4 deg, further reductions up to 3 dB in the low-frequency noise sound pressure level were attained without significantly impacting the BVI noise for longitudinal tip-path-plane angles of -9 and 6 deg.

Polyubiquitylation of AMF requires cooperation between the gp78 and TRIM25 ubiquitin ligases.

PubMed

Wang, Ying; Ha, Seung-Wook; Zhang, Tianpeng; Kho, Dhong-Hyo; Raz, Avraham; Xie, Youming

2014-04-30

gp78 is a ubiquitin ligase that plays a vital role in endoplasmic reticulum (ER)-associated degradation (ERAD). Here we report that autocrine motility factor (AMF), also known as phosphoglucose isomerase (PGI), is a novel substrate of gp78. We show that polyubiquitylation of AMF requires cooperative interaction between gp78 and the ubiquitin ligase TRIM25 (tripartite motif-containing protein 25). While TRIM25 mediates the initial round of ubiquitylation, gp78 catalyzes polyubiquitylation of AMF. The E4-like activity of gp78 was illustrated by an in vitro polyubiquitylation assay using Ub-DHFR as a model substrate. We further demonstrate that TRIM25 ubiquitylates gp78 and that overexpression of TRIM25 accelerates the degradation of gp78. Our data suggest that TRIM25 not only cooperates with gp78 in polyubiquitylation of AMF but also gauges the steady-state level of gp78. This study uncovers a previously unknown functional link between gp78 and TRIM25 and provides mechanistic insight into gp78-mediated protein ubiquitylation.

Polyubiquitylation of AMF requires cooperation between the gp78 and TRIM25 ubiquitin ligases

PubMed Central

Kho, Dhong-Hyo; Raz, Avraham; Xie, Youming

2014-01-01

gp78 is a ubiquitin ligase that plays a vital role in endoplasmic reticulum (ER)-associated degradation (ERAD). Here we report that autocrine motility factor (AMF), also known as phosphoglucose isomerase (PGI), is a novel substrate of gp78. We show that polyubiquitylation of AMF requires cooperative interaction between gp78 and the ubiquitin ligase TRIM25 (tripartite motif-containing protein 25). While TRIM25 mediates the initial round of ubiquitylation, gp78 catalyzes polyubiquitylation of AMF. The E4-like activity of gp78 was illustrated by an in vitro polyubiquitylation assay using Ub-DHFR as a model substrate. We further demonstrate that TRIM25 ubiquitylates gp78 and that overexpression of TRIM25 accelerates the degradation of gp78. Our data suggest that TRIM25 not only cooperates with gp78 in polyubiquitylation of AMF but also gauges the steady-state level of gp78. This study uncovers a previously unknown functional link between gp78 and TRIM25 and provides mechanistic insight into gp78-mediated protein ubiquitylation. PMID:24810856

Characterization and biological function analysis of the TRIM47 gene from common carp (Cyprinus carpio).

PubMed

Wang, Yeda; Kuang, Ming; Lu, Yuanan; Lin, Li; Liu, Xueqin

2017-09-05

The TRIM family protein was known to play an important role in many cellular processes, including potential antiviral activity, which has attracted lots of attention. In this study, a TRIM47 homolog from common carp (Cyprinus carpio) was cloned and the full length coding DNA sequence (CDS) of this gene was analyzed, results showed that there was a 97% similarity between common carp and zebrafish (Danio rerio), but only 18% similarity with that of human (Homo sapiens) and mouse (Mus musculus). The tissue distribution analysis showed TRIM47 had the highest mRNA level in the brain, a few immune related organs such as liver and kidney also had a relatively high level of TRIM47 expression. SVCV infection decreased TRIM47 mRNA level significantly both in vitro and in vivo, but its expression was not affected by the virus at the protein level. The recombinant plasmid pcDNA4-TRIM47-His was constructed, the subcellular localization in FHM cells showed that TRIM47 uniformly distributed in the cytoplasm at the form of tiny spots, and partially localized in the mitochondria. Overexpression TRIM47 in FHM cells significantly decreased the mRNA level of SVCV-G gene, and it was accompanied with the increasing of IFN1, a member of type I IFN, at the case of SVCV stimulation. In summary, our results had first demonstrated that TRIM47 of the common carp played an important role in viral resistance processes as well as the regulation of IFN signaling pathway. Copyright © 2017. Published by Elsevier B.V.

TRIM67 Protein Negatively Regulates Ras Activity through Degradation of 80K-H and Induces Neuritogenesis*

PubMed Central

Yaguchi, Hiroaki; Okumura, Fumihiko; Takahashi, Hidehisa; Kano, Takahiro; Kameda, Hiroyuki; Uchigashima, Motokazu; Tanaka, Shinya; Watanabe, Masahiko; Sasaki, Hidenao; Hatakeyama, Shigetsugu

2012-01-01

Tripartite motif (TRIM)-containing proteins, which are defined by the presence of a common domain structure composed of a RING finger, one or two B-box motifs and a coiled-coil motif, are involved in many biological processes including innate immunity, viral infection, carcinogenesis, and development. Here we show that TRIM67, which has a TRIM motif, an FN3 domain and a SPRY domain, is highly expressed in the cerebellum and that TRIM67 interacts with PRG-1 and 80K-H, which is involved in the Ras-mediated signaling pathway. Ectopic expression of TRIM67 results in degradation of endogenous 80K-H and attenuation of cell proliferation and enhances neuritogenesis in the neuroblastoma cell line N1E-115. Furthermore, morphological and biological changes caused by knockdown of 80K-H are similar to those observed by overexpression of TRIM67. These findings suggest that TRIM67 regulates Ras signaling via degradation of 80K-H, leading to neural differentiation including neuritogenesis. PMID:22337885

TRIM67 protein negatively regulates Ras activity through degradation of 80K-H and induces neuritogenesis.

PubMed

Yaguchi, Hiroaki; Okumura, Fumihiko; Takahashi, Hidehisa; Kano, Takahiro; Kameda, Hiroyuki; Uchigashima, Motokazu; Tanaka, Shinya; Watanabe, Masahiko; Sasaki, Hidenao; Hatakeyama, Shigetsugu

2012-04-06

Tripartite motif (TRIM)-containing proteins, which are defined by the presence of a common domain structure composed of a RING finger, one or two B-box motifs and a coiled-coil motif, are involved in many biological processes including innate immunity, viral infection, carcinogenesis, and development. Here we show that TRIM67, which has a TRIM motif, an FN3 domain and a SPRY domain, is highly expressed in the cerebellum and that TRIM67 interacts with PRG-1 and 80K-H, which is involved in the Ras-mediated signaling pathway. Ectopic expression of TRIM67 results in degradation of endogenous 80K-H and attenuation of cell proliferation and enhances neuritogenesis in the neuroblastoma cell line N1E-115. Furthermore, morphological and biological changes caused by knockdown of 80K-H are similar to those observed by overexpression of TRIM67. These findings suggest that TRIM67 regulates Ras signaling via degradation of 80K-H, leading to neural differentiation including neuritogenesis.

Peak-Seeking Optimization of Trim for Reduced Fuel Consumption: Architecture and Performance Predictions

NASA Technical Reports Server (NTRS)

Schaefer, Jacob; Brown, Nelson

2013-01-01

A peak-seeking control approach for real-time trim configuration optimization for reduced fuel consumption has been developed by researchers at the National Aeronautics and Space Administration (NASA) Dryden Flight Research Center to address the goals of the NASA Environmentally Responsible Aviation project to reduce fuel burn and emissions. The peak-seeking control approach is based on a steepest-descent algorithm using a time-varying Kalman filter to estimate the gradient of a performance function of fuel flow versus control surface positions. In real-time operation, deflections of symmetric ailerons, trailing-edge flaps, and leading-edge flaps of an FA-18 airplane (McDonnell Douglas, now The Boeing Company, Chicago, Illinois) are controlled for optimization of fuel flow. This presentation presents the design and integration of this peak-seeking controller on a modified NASA FA-18 airplane with research flight control computers. A research flight was performed to collect data to build a realistic model of the performance function and characterize measurement noise. This model was then implemented into a nonlinear six-degree-of-freedom FA-18 simulation along with the peak-seeking control algorithm. With the goal of eventual flight tests, the algorithm was first evaluated in the improved simulation environment. Results from the simulation predict good convergence on minimum fuel flow with a 2.5-percent reduction in fuel flow relative to the baseline trim of the aircraft.

Endoscopic removal and trimming of distal self-expandable metallic biliary stents

PubMed Central

Ishii, Kentaro; Itoi, Takao; Sofuni, Atsushi; Itokawa, Fumihide; Tsuchiya, Takayoshi; Kurihara, Toshio; Tsuji, Shujiro; Ikeuchi, Nobuhito; Umeda, Junko; Moriyasu, Fuminori; Tsuchida, Akihiko

2011-01-01

AIM: To evaluate the efficacy and safety of endoscopic removal and trimming of self-expandable metallic stents (SEMS). METHODS: All SEMS had been placed for distal biliary strictures. Twenty-seven endoscopic procedures were performed in 19 patients in whom SEMS (one uncovered and 18 covered) removal had been attempted, and 8 patients in whom stent trimming using argon plasma coagulation (APC) had been attempted at Tokyo Medical University Hospital. The APC settings were: voltage 60-80 W and gas flow at 1.5 L/min. RESULTS: The mean stent indwelling period for all patients in whom stent removal had been attempted was 113.7 ± 77.6 d (range, 8-280 d). Of the 19 patients in whom removal of the SEMS had been attempted, the procedure was successful in 14 (73.7%) without procedure-related adverse events. The indwelling period in the stent removable group was shorter than that in the unremovable group (94.9 ± 71.5 d vs 166.2 ± 76.2 d, P = 0.08). Stent trimming was successful for all patients with one minor adverse event consisting of self-limited hemorrhage. Trimming time ranged from 11 to 16 min. CONCLUSION: Although further investigations on larger numbers of cases are necessary to accumulate evidence, the present data suggested that stent removal and stent trimming is feasible and effective for stent-related complications. PMID:21677835

S-nitrosylation of TRIM72 at cysteine 144 is critical for protection against oxidation-induced protein degradation and cell death.

PubMed

Kohr, Mark J; Evangelista, Alicia M; Ferlito, Marcella; Steenbergen, Charles; Murphy, Elizabeth

2014-04-01

Oxidative stress and membrane damage following myocardial ischemia/reperfusion injury are important contributors to cardiomyocyte death and the loss of myocardial function. Our previous study identified cysteine 144 (C144) of tripartite motif-containing protein 72 (TRIM72) as a potential site for S-nitrosylation (SNO). TRIM72 is a cardioprotective membrane repair protein that can be both activated and targeted for degradation by different oxidative modifications. Consistent with the potential regulation of TRIM72 by various oxidative modifications, we found that SNO levels increased at C144 of TRIM72 with ischemic preconditioning. Therefore, to investigate the role of C144 in the regulation of TRIM72 function, we mutated C144 of TRIM72 to a serine residue (TRIM72(C144S)), and expressed either TRIM72(WT) or TRIM72(C144S) in HEK-293 cells, which lack endogenous TRIM72, in order to examine the effect of this mutation on the functional stability of TRIM72 and on cell survival. We hypothesized that SNO of TRIM72 stabilizes the protein, thus allowing for membrane repair and enhanced cell survival. Upon treatment with hydrogen peroxide (H2O2), we found that TRIM72(WT) levels were decreased, but not TRIM72(C144S) and this correlated with increased H2O2-induced cell death in TRIM72(WT) cells. Additionally, we found that treatment with the cardioprotective S-nitrosylating agent S-nitrosoglutathione (GSNO), was able to preserve TRIM72(WT) protein levels and enhance TRIM72(WT)-mediated cell survival, but had no effect on TRIM72(C144S) levels. Consistent with our hypothesis, GSNO was also found to increase SNO levels and inhibit H2O2-induced irreversible oxidation for TRIM72(WT) without affecting TRIM72(C144S). In further support of our hypothesis, GSNO blocked the ischemia/reperfusion-induced decrease in TRIM72 levels and reduced infarct size in a Langendorff-perfused heart model. The results of these studies have important implications for cardioprotection and suggest that

TRIM21 Ubiquitylates SQSTM1/p62 and Suppresses Protein Sequestration to Regulate Redox Homeostasis.

PubMed

Pan, Ji-An; Sun, Yu; Jiang, Ya-Ping; Bott, Alex J; Jaber, Nadia; Dou, Zhixun; Yang, Bin; Chen, Juei-Suei; Catanzaro, Joseph M; Du, Chunying; Ding, Wen-Xing; Diaz-Meco, Maria T; Moscat, Jorge; Ozato, Keiko; Lin, Richard Z; Zong, Wei-Xing

2016-03-03

TRIM21 is a RING finger domain-containing ubiquitin E3 ligase whose expression is elevated in autoimmune disease. While TRIM21 plays an important role in immune activation during pathogen infection, little is known about its inherent cellular function. Here we show that TRIM21 plays an essential role in redox regulation by directly interacting with SQSTM1/p62 and ubiquitylating p62 at lysine 7 (K7) via K63-linkage. As p62 oligomerizes and sequesters client proteins in inclusions, the TRIM21-mediated p62 ubiquitylation abrogates p62 oligomerization and sequestration of proteins including Keap1, a negative regulator of antioxidant response. TRIM21-deficient cells display an enhanced antioxidant response and reduced cell death in response to oxidative stress. Genetic ablation of TRIM21 in mice confers protection from oxidative damages caused by arsenic-induced liver insult and pressure overload heart injury. Therefore, TRIM21 plays an essential role in p62-regulated redox homeostasis and may be a viable target for treating pathological conditions resulting from oxidative damage. Copyright © 2016 Elsevier Inc. All rights reserved.

Object Trimming: When Masking Dots Alter Rather than Replace Target Representations

ERIC Educational Resources Information Center

Kahan, Todd A.; Enns, James T.

2010-01-01

Five experiments demonstrate that when dots appear beside a briefly presented target object, and persist on view longer than the target, the flanked object is perceptually altered by the dots. Three methods are used to explore this "object trimming effect". Experiments 1-3 assess participants' conscious reports of trimmed digits, Experiment 4 uses…

TRIM29 Negatively Regulates the Type I IFN Production in Response to RNA Virus.

PubMed

Xing, Junji; Zhang, Ao; Minze, Laurie J; Li, Xian Chang; Zhang, Zhiqiang

2018-05-16

The innate immunity is critically important in protection against virus infections, and in the case of RNA viral infections, the signaling mechanisms that initiate robust protective innate immunity without triggering autoimmune inflammation remain incompletely defined. In this study, we found the E3 ligase TRIM29 was specifically expressed in poly I:C-stimulated human myeloid dendritic cells. The induced TRIM29 played a negative role in type I IFN production in response to poly I:C or dsRNA virus reovirus infection. Importantly, the challenge of wild-type mice with reovirus led to lethal infection. In contrast, deletion of TRIM29 protected the mice from this developing lethality. Additionally, TRIM29 -/- mice have lower titers of reovirus in the heart, intestine, spleen, liver, and brain because of elevated production of type I IFN. Mechanistically, TRIM29 was shown to interact with MAVS and subsequently induce its K11-linked ubiquitination and degradation. Taken together, TRIM29 regulates negatively the host innate immune response to RNA virus, which could be employed by RNA viruses for viral pathogenesis. Copyright © 2018 by The American Association of Immunologists, Inc.

Building Trades. Block VIII. Interior Trim.

ERIC Educational Resources Information Center

Texas A and M Univ., College Station. Vocational Instructional Services.

This curriculum for interior trim provides instructional materials for 18 informational and manipulative lessons. A list of 11 references precedes the course materials. The instructor's plan for each informational lesson begins by providing this information: subject, aim, required teaching aids, required materials, references, and prerequisite…

TRIM25 blockade by RNA interference inhibited migration and invasion of gastric cancer cells through TGF-β signaling.

PubMed

Zhu, Zhenya; Wang, Yong; Zhang, Chunhui; Yu, Shiyong; Zhu, Qi; Hou, Kun; Yan, Bo

2016-01-12

Tripartite Motif Containing 25 (TRIM25), a member of TRIM proteins, has been found abnormally expressed in cancers of female reproductive system. Here, TRIM25 was conspicuously expressed in human gastric cancer (GC) tissues in which its higher expression generally correlated with the poor prognosis of patients. Small interfering RNA (siRNA)-mediated knockdown of TRIM25 expression in MGC-803 and AGS cells had no effects on cell proliferation, whereas reduced cell migration and invasion. Gene set enrichment analysis on The Cancer Genome Atlas stomach adenocarcinoma (STAD) dataset revealed that several signaling pathways, including the migration, E-cadherin and transforming growth factor-β (TGF-β) pathways, were enriched in TRIM25 higher expression patients. Moreover, ectopic expression of TRIM25 in a GC cell line with lower expression of TRIM25 significantly promoted the migration and invasion. Further experiments with TGF-β inhibitor suggested that TRIM25 may exert its function through TGF-β pathway. In summary, our results indicate that TRIM25 acts as an oncogene in GC and thus presents a novel target for the detection and treatment of GC.

The Timber Resource Inventory Model (TRIM): a projection model for timber supply and policy analysis.

Treesearch

P.L. Tedder; R.N. La Mont; J.C. Kincaid

1987-01-01

TRIM (Timber Resource Inventory Model) is a yield table projection system developed for timber supply projections and policy analysis. TRIM simulates timber growth, inventories, management and area changes, and removals over the projection period. Programs in the TRIM system, card-by-card descriptions of required inputs, table formats, and sample results are presented...

Lentiviral gene therapy against human immunodeficiency virus type 1, using a novel human TRIM21-cyclophilin A restriction factor.

PubMed

Chan, Emma; Schaller, Torsten; Eddaoudi, Ayad; Zhan, Hong; Tan, Choon Ping; Jacobsen, Marianne; Thrasher, Adrian J; Towers, Greg J; Qasim, Waseem

2012-11-01

TRIM5α (tripartite motif-containing protein-5, isoform α)-cyclophilin A fusion proteins are anti-human immunodeficiency virus (HIV) restriction factors that have evolved in certain nonhuman primates over millions of years and protect against HIV and related viruses. Restriction by TRIM5αCypA is potent and highly resistant to viral escape by mutation and, in combination with a suitable gene delivery platform, offers the possibility of novel therapeutic approaches against HIV. Here we report that lentiviral vector delivery of human mimics of TRIM5α-cyclophilin A (TRIM5CypA) fusion proteins afforded robust and durable protection against HIV-1, but resulted in downregulation of host cell antiviral responses mediated by endogenous TRIM5α. We found that substitution of TRIM5α RING, B-box, and coiled-coil domains with similar domains from a related TRIM protein, TRIM21, produced a novel and equally potent inhibitor of HIV-1. Both TRIM5CypA and TRIM21CypA inhibited transduction by HIV-1-derived viral vectors and prevented propagation of replication-competent HIV-1 in human cell lines and in primary human T cells. Restriction factor-modified T cells exhibited preferential survival in the presence of wild-type HIV. Restriction was dependent on proteasomal degradation and was reversed in the presence of the cyclophilin inhibitor cyclosporin. Importantly, TRIM21CypA did not disturb endogenous TRIM5α-mediated restriction of gammaretroviral infection. Furthermore, endogenous TRIM21 antiviral activity was assessed by measuring inhibition of adenovirus-antibody complexes and was found to be preserved in all TRIMCypA-modified groups. We conclude that lentivirus-mediated expression of the novel chimeric restriction factor TRIM21CypA provides highly potent protection against HIV-1 without loss of normal innate immune TRIM activity.

Identification and characterization of a nuclear localization signal of TRIM28 that overlaps with the HP1 box

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moriyama, Tetsuji; Sangel, Percival; Yamaguchi, Hiroki

2015-07-03

Tripartite motif-containing 28 (TRIM28) is a transcription regulator, which forms a repressor complex containing heterochromatin protein 1 (HP1). Here, we report identification of a nuclear localization signal (NLS) within the 462-494 amino acid region of TRIM28 that overlaps with its HP1 binding site, HP1 box. GST-pulldown experiments revealed the interaction of the arginine-rich TRIM28 NLS with various importin α subtypes (α1, α2 and α4). In vitro transport assay demonstrated that nuclear localization of GFP-TRIM28 NLS is mediated by importin αs, in conjunction with importin β1 and Ran. Further, we demonstrated that HP1 and importin αs compete for binding to TRIM28. Together,more » our findings suggest that importin α has an essential role in the nuclear delivery and preferential HP1 interaction of TRIM28. - Highlights: • TRIM28 contains an NLS within the 462-494 amino acid region. • The nuclear import of TRIM28 is mediated by importin α/importin β1. • TRIM28 NLS overlaps with HP1 Box. • HP1 and importin α compete for binding to TRIM28.« less

Disturbed P53-MDM2 Feedback Loop Contributes to Thoracic Aortic Dissection Formation and May be a Result of TRIM25 Overexpression.

PubMed

Gong, Bin; Wang, Zhiwei; Zhang, Min; Hu, Zhipeng; Ren, Zongli; Tang, Zheng; Jiang, Wanli; Cheng, Lianghao; Huang, Jun; Ren, Wei; Wang, Qingtao

2017-04-01

The development of thoracic aortic dissection (TAD) is attributed to a broad range of degenerative, genetic, structural, oxidative, apoptotic, and acquired disease states. In this study, we examined the role of the disturbed p53-MDM2 (murine double minute 2) feedback loop in the formation of TAD, and one of a potential feedback loop regulator, TRIM25 (tripartite motif protein-25). Surgical specimens of the aorta from TAD patients (n = 10) and controls (n = 10) were tested for α-smooth muscle actin (α-SMA), p53, MDM2, and TRIM25 by western blot, immunohistochemical staining, and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), respectively. When compared with controls, western blot shows that the protein levels of p53, MDM2, and TRIM25 were increased significantly in the aortic media of TAD patients. qRT-PCR further verified that the mRNA expression of MDM2 and TRIM25 was also increased 6- and 4-folds, respectively, in the TAD media of the aortic wall. Immunohistochemistry results showed significantly decreased staining of α-SMA, smooth muscle cells, and more collagen deposition in the media of the aortic wall from patients with TAD. This study provided a new insight into the disturbed p53-MDM2 feedback loop in the pathogenesis of TAD, and this may be because of the TRIM25 overexpression. Copyright © 2016 Elsevier Inc. All rights reserved.

The polar warhead of a TRIM24 bromodomain inhibitor rearranges a water-mediated interaction network.

PubMed

Liu, Jiuyang; Li, Fudong; Bao, Hongyu; Jiang, Yiyang; Zhang, Shuya; Ma, Rongsheng; Gao, Jia; Wu, Jihui; Ruan, Ke

2017-04-01

Tripartite motif-containing protein 24 (TRIM24) is closely correlated with multiple cancers, and a recent study demonstrated that the bromodomain of TRIM24 is essential for the proliferation of lethal castration-resistant prostate cancer. Here, we identify three new inhibitors of the TRIM24 bromodomain using NMR fragment-based screening. The crystal structures of two new inhibitors in complex with the TRIM24 bromodomain reveal that the water-bridged interaction network is conserved in the same fashion as those for known benzoimidazolone inhibitors. Interestingly, the polar substitution on the warhead of one new inhibitor pulls the whole ligand approximately 2 Å into the inner side pocket of the TRIM24 bromodomain, and thus exhibits a binding mode significantly different from other known bromodomain ligands. This mode provides a useful handle for further hit-to-lead evolution toward novel inhibitors of the TRIM24 bromodomain. Structural data are available in the PDB under the accession numbers 5H1T, 5H1U, and 5H1V. © 2017 Federation of European Biochemical Societies.

TRIM29 Overexpression Promotes Proliferation and Survival of Bladder Cancer Cells through NF-κB Signaling.

PubMed

Tan, Shu-Tao; Liu, Sheng-Ye; Wu, Bin

2016-10-01

TRIM29 overexpression has been reported in several human malignancies and showed correlation with cancer cell malignancy. The aim of the current study is to examine its clinical significance and biological roles in human bladder cancer tissues and cell lines. A total of 102 cases of bladder cancer tissues were examined for TRIM29 expression by immunohistochemistry. siRNA and plasmid transfection were performed in 5637 and BIU-87 cell lines. Cell Counting Kit-8, flow cytometry, western blot, and real-time polymerase chain reaction were performed to examine its biological roles and mechanism in bladder cancer cells. We found that TRIM29 overexpression showed correlation with invading depth (p=0.0087). Knockdown of TRIM29 expression in bladder cancer cell line 5637 inhibited cell growth rate and cell cycle transition while its overexpression in BIU-87 cells accelerated cell proliferation and cell cycle progression. TRIM29 overexpression also inhibited cell apoptosis induced by cisplatin. In addition, we demonstrated that TRIM29 depletion decreased while its overexpression led to upregulated expression of cyclin D1, cyclin E, and Bcl-2. We also showed that TRIM29 knockdown inhibited protein kinase C (PKC) and nuclear factor κB (NF-κB) signaling while its overexpression stimulated the PKC and NF-κB pathways. BAY 11-7082 (NF-κB inhibitor) partly attenuated the effect of TRIM29 on expression of cyclin and Bcl-2. Treatment with PKC inhibitor staurosporine resulted in ameliorated TRIM29 induced activation of NF-κB. The current study demonstrated that TRIM29 upregulates cyclin and Bcl family proteins level to facilitate malignant cell growth and inhibit drug-induced apoptosis in bladder cancer, possibly through PKC-NF-κB signaling pathways.

TRIM25 blockade by RNA interference inhibited migration and invasion of gastric cancer cells through TGF-β signaling

PubMed Central

Zhu, Zhenya; Wang, Yong; Zhang, Chunhui; Yu, Shiyong; Zhu, Qi; Hou, Kun; Yan, Bo

2016-01-01

Tripartite Motif Containing 25 (TRIM25), a member of TRIM proteins, has been found abnormally expressed in cancers of female reproductive system. Here, TRIM25 was conspicuously expressed in human gastric cancer (GC) tissues in which its higher expression generally correlated with the poor prognosis of patients. Small interfering RNA (siRNA)-mediated knockdown of TRIM25 expression in MGC-803 and AGS cells had no effects on cell proliferation, whereas reduced cell migration and invasion. Gene set enrichment analysis on The Cancer Genome Atlas stomach adenocarcinoma (STAD) dataset revealed that several signaling pathways, including the migration, E-cadherin and transforming growth factor-β (TGF-β) pathways, were enriched in TRIM25 higher expression patients. Moreover, ectopic expression of TRIM25 in a GC cell line with lower expression of TRIM25 significantly promoted the migration and invasion. Further experiments with TGF-β inhibitor suggested that TRIM25 may exert its function through TGF-β pathway. In summary, our results indicate that TRIM25 acts as an oncogene in GC and thus presents a novel target for the detection and treatment of GC. PMID:26754079

46 CFR 72.05-15 - Ceilings, linings, trim, and decorations in accommodation spaces and safety areas.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 3 2011-10-01 2011-10-01 false Ceilings, linings, trim, and decorations in... Ceilings, linings, trim, and decorations in accommodation spaces and safety areas. (a) Ceilings and linings... volume of combustible face trim, moldings, and decorations, including veneers, in any compartment shall...

46 CFR 72.05-15 - Ceilings, linings, trim, and decorations in accommodation spaces and safety areas.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 3 2010-10-01 2010-10-01 false Ceilings, linings, trim, and decorations in... Ceilings, linings, trim, and decorations in accommodation spaces and safety areas. (a) Ceilings and linings... volume of combustible face trim, moldings, and decorations, including veneers, in any compartment shall...

Viral attachment induces rapid recruitment of an innate immune sensor (TRIM5α) to the plasma membrane.

PubMed

Ohmine, Seiga; Singh, Raman Deep; Marks, David L; Meyer, Melissa A; Pagano, Richard E; Ikeda, Yasuhiro

2013-01-01

TRIM5α (tripartite motif 5α) acts as a pattern recognition receptor specific for the retrovirus capsid lattice and blocks infection by HIV-1 immediately after entry. However, the precise mechanisms underlying this rapid recognition of viral components remain elusive. Here, we analyzed the influence of viral exposure on TRIM5α. Total internal reflection fluorescence microscopy and lipid flotation assays revealed rapid recruitment of a TRIM5α subpopulation to the plasma membrane (PM) upon exposure to vesicular stomatitis virus-G-pseudotyped HIV-1 viral-like particles (VLPs), but not to envelope (Env)-less HIV-1 VLPs. TRIM5α signals were frequently colocalized with those of HIV-1 capsid at the PM. Exposure to HIV-1 Env-pseudotyped HIV-1 vectors also triggered translocation of endogenous TRIM5α to lipid microdomains within human T cells. Similarly, clustering of lipid microdomains by a glycosphingolipid stereoisomer resulted in rapid TRIM5α recruitment to the PM. Of note, recruitment of endogenous rhesus TRIM5α to the PM prior to HIV-1 infection significantly increased the potency of viral restriction. Our data therefore suggest the importance of TRIM5α recruitment to the PM for TRIM5α-mediated innate immune sensing and restriction of retroviral infection. Copyright © 2013 S. Karger AG, Basel.

Peak-Seeking Optimization of Trim for Reduced Fuel Consumption: Architecture and Performance Predictions

NASA Technical Reports Server (NTRS)

Schaefer, Jacob; Brown, Nelson A.

2013-01-01

A peak-seeking control approach for real-time trim configuration optimization for reduced fuel consumption has been developed by researchers at the National Aeronautics and Space Administration (NASA) Dryden Flight Research Center to address the goals of the NASA Environmentally Responsible Aviation project to reduce fuel burn and emissions. The peak-seeking control approach is based on a steepest-descent algorithm using a time-varying Kalman filter to estimate the gradient of a performance function of fuel flow versus control surface positions. In real-time operation, deflections of symmetric ailerons, trailing-edge flaps, and leading-edge flaps of an F/A-18 airplane (McDonnell Douglas, now The Boeing Company, Chicago, Illinois) are controlled for optimization of fuel flow. This paper presents the design and integration of this peak-seeking controller on a modified NASA F/A-18 airplane with research flight control computers. A research flight was performed to collect data to build a realistic model of the performance function and characterize measurement noise. This model was then implemented into a nonlinear six-degree-of-freedom F/A-18 simulation along with the peak-seeking control algorithm. With the goal of eventual flight tests, the algorithm was first evaluated in the improved simulation environment. Results from the simulation predict good convergence on minimum fuel flow with a 2.5-percent reduction in fuel flow relative to the baseline trim of the aircraft.

An Integrated Systems Biology Approach Identifies TRIM25 as a Key Determinant of Breast Cancer Metastasis.

PubMed

Walsh, Logan A; Alvarez, Mariano J; Sabio, Erich Y; Reyngold, Marsha; Makarov, Vladimir; Mukherjee, Suranjit; Lee, Ken-Wing; Desrichard, Alexis; Turcan, Şevin; Dalin, Martin G; Rajasekhar, Vinagolu K; Chen, Shuibing; Vahdat, Linda T; Califano, Andrea; Chan, Timothy A

2017-08-15

At the root of most fatal malignancies are aberrantly activated transcriptional networks that drive metastatic dissemination. Although individual metastasis-associated genes have been described, the complex regulatory networks presiding over the initiation and maintenance of metastatic tumors are still poorly understood. There is untapped value in identifying therapeutic targets that broadly govern coordinated transcriptional modules dictating metastatic progression. Here, we reverse engineered and interrogated a breast cancer-specific transcriptional interaction network (interactome) to define transcriptional control structures causally responsible for regulating genetic programs underlying breast cancer metastasis in individual patients. Our analyses confirmed established pro-metastatic transcription factors, and they uncovered TRIM25 as a key regulator of metastasis-related transcriptional programs. Further, in vivo analyses established TRIM25 as a potent regulator of metastatic disease and poor survival outcome. Our findings suggest that identifying and targeting keystone proteins, like TRIM25, can effectively collapse transcriptional hierarchies necessary for metastasis formation, thus representing an innovative cancer intervention strategy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A technique using a nonlinear helicopter model for determining trims and derivatives

NASA Technical Reports Server (NTRS)

Ostroff, A. J.; Downing, D. R.; Rood, W. J.

1976-01-01

A technique is described for determining the trims and quasi-static derivatives of a flight vehicle for use in a linear perturbation model; both the coupled and uncoupled forms of the linear perturbation model are included. Since this technique requires a nonlinear vehicle model, detailed equations with constants and nonlinear functions for the CH-47B tandem rotor helicopter are presented. Tables of trims and derivatives are included for airspeeds between -40 and 160 knots and rates of descent between + or - 10.16 m/sec (+ or - 200 ft/min). As a verification, the calculated and referenced values of comparable trims, derivatives, and linear model poles are shown to have acceptable agreement.

Effects of trimming weight-for-height data on growth-chart percentiles1–3

PubMed Central

Flegal, Katherine M; Carroll, Margaret D; Ogden, Cynthia L

2016-01-01

Background Before estimating smoothed percentiles of weight-for-height and BMI-for-age to construct the WHO growth charts, WHO excluded observations that were considered to represent unhealthy weights for height. Objective The objective was to estimate the effects of similar data trimming on empirical percentiles from the CDC growth-chart data set relative to the smoothed WHO percentiles for ages 24–59 mo. Design We used the nationally representative US weight and height data from 1971 to 1994, which was the source data for the 2000 CDC growth charts. Trimming cutoffs were calculated on the basis of weight-for-height for 9722 children aged 24–71 mo. Empirical percentiles for 7315 children aged 24–59 mo were compared with the corresponding smoothed WHO percentiles. Results Before trimming, the mean empirical percentiles for weight-for-height in the CDC data set were higher than the corresponding smoothed WHO percentiles. After trimming, the mean empirical 95th and 97th percentiles of weight-for-height were lower than the WHO percentiles, and the proportion of children in the CDC data set above the WHO 95th percentile decreased from 7% to 5%. The findings were similar for BMI-for-age. However, for weight-for-age, which had not been trimmed by the WHO, the empirical percentiles before trimming agreed closely with the upper percentiles from the WHO charts. Conclusion WHO data-trimming procedures may account for some of the differences between the WHO growth charts and the 2000 CDC growth charts. PMID:22990032

TRIM24 promotes glioma progression and enhances chemoresistance through activation of the PI3K/Akt signaling pathway.

PubMed

Zhang, L-H; Yin, A-A; Cheng, J-X; Huang, H-Y; Li, X-M; Zhang, Y-Q; Han, N; Zhang, X

2015-01-29

The tripartite motif protein TRIM24 (tripartite motif-containing 24) has been found to play distinct roles in tumor development and progression, according to different tumor contexts. However, it remains elusive whether TRIM24 plays a role in malignant gliomas that are the most common and deadly primary brain tumors in adults. We report here that TRIM24 expression is positively correlated with glioma malignancy and is negatively associated with prognosis of patients with newly diagnosed glioblastoma, which is the most malignant form of gliomas but displays highly heterogeneous clinical outcome. The multivariate Cox regression analysis demonstrates the independent predictive value of TRIM24 expression level for overall and progression-free survival. Knockdown of TRIM24 suppresses cell proliferation, cell cycle progression, clone formation and in vivo tumor development, whereas overexpression of TRIM24 promotes cell growth. Chromatin immunoprecipitation, real-time reverse transcription-PCR and mutation analyses demonstrate that TRIM24 binds to the PIK3CA promoter via its PHD-Bromo domain to activate the transcription of PIK3CA gene, thus enhancing phosphatidylinositide 3-kinase (PI3K)/Akt signaling. The pan-PI3K inhibitor LY294002 and small interfering RNA targeting PIK3CA both abrogate the growth-promoting effect of TRIM24. Moreover, TRIM24 regulates the expression of DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) through PI3K/Akt/nuclear factor-κB signaling transduction and enhances resistance to temozolomide, the standard chemotherapeutic agent for glioblastoma. Finally, glioblastoma patients with low TRIM24 expression benefit from chemotherapy, whereas those with high TRIM24 expression do not have such benefit. Our results suggest that TRIM24 might serve as a potential prognostic marker and therapeutic target for the management of malignant gliomas.

A Novel Terminal-Repeat Retrotransposon in Miniature (TRIM) Is Massively Expressed in Echinococcus multilocularis Stem Cells

PubMed Central

Koziol, Uriel; Radio, Santiago; Smircich, Pablo; Zarowiecki, Magdalena; Fernández, Cecilia; Brehm, Klaus

2015-01-01

Taeniid cestodes (including the human parasites Echinococcus spp. and Taenia solium) have very few mobile genetic elements (MGEs) in their genome, despite lacking a canonical PIWI pathway. The MGEs of these parasites are virtually unexplored, and nothing is known about their expression and silencing. In this work, we report the discovery of a novel family of small nonautonomous long terminal repeat retrotransposons (also known as terminal-repeat retrotransposons in miniature, TRIMs) which we have named ta-TRIM (taeniid TRIM). ta-TRIMs are only the second family of TRIM elements discovered in animals, and are likely the result of convergent reductive evolution in different taxonomic groups. These elements originated at the base of the taeniid tree and have expanded during taeniid diversification, including after the divergence of closely related species such as Echinococcus multilocularis and Echinococcus granulosus. They are massively expressed in larval stages, from a small proportion of full-length copies and from isolated terminal repeats that show transcriptional read-through into downstream regions, generating novel noncoding RNAs and transcriptional fusions to coding genes. In E. multilocularis, ta-TRIMs are specifically expressed in the germinative cells (the somatic stem cells) during asexual reproduction of metacestode larvae. This would provide a developmental mechanism for insertion of ta-TRIMs into cells that will eventually generate the adult germ line. Future studies of active and inactive ta-TRIM elements could give the first clues on MGE silencing mechanisms in cestodes. PMID:26133390

The effect of routine hoof trimming on locomotion score, ruminating time, activity, and milk yield of dairy cows.

PubMed

Van Hertem, T; Parmet, Y; Steensels, M; Maltz, E; Antler, A; Schlageter-Tello, A A; Lokhorst, C; Romanini, C E B; Viazzi, S; Bahr, C; Berckmans, D; Halachmi, I

2014-01-01

The objective of this study was to quantify the effect of hoof trimming on cow behavior (ruminating time, activity, and locomotion score) and performance (milk yield) over time. Data were gathered from a commercial dairy farm in Israel where routine hoof trimming is done by a trained hoof trimmer twice per year on the entire herd. In total, 288 cows spread over 6 groups with varying production levels were used for the analysis. Cow behavior was measured continuously with a commercial neck activity logger and a ruminating time logger (HR-Tag, SCR Engineers Ltd., Netanya, Israel). Milk yield was recorded during each milking session with a commercial milk flow sensor (Free Flow, SCR Engineers Ltd.). A trained observer assigned on the spot 5-point locomotion scores during 19 nighttime milking occasions between 22 October 2012 and 4 February 2013. Behavioral and performance data were gathered from 1wk before hoof trimming until 1wk after hoof trimming. A generalized linear mixed model was used to statistically test all main and interactive effects of hoof trimming, parity, lactation stage, and hoof lesion presence on ruminating time, neck activity, milk yield, and locomotion score. The results on locomotion scores show that the proportional distribution of cows in the different locomotion score classes changes significantly after trimming. The proportion of cows with a locomotion score ≥3 increases from 14% before to 34% directly after the hoof trimming. Two months after the trimming, the number of cows with a locomotion score ≥3 reduced to 20%, which was still higher than the baseline values 2wk before the trimming. The neck activity level was significantly reduced 1d after trimming (380±6 bits/d) compared with before trimming (389±6 bits/d). Each one-unit increase in locomotion score reduced cow activity level by 4.488 bits/d. The effect of hoof trimming on ruminating time was affected by an interaction effect with parity. The effect of hoof trimming on

TRIM44 Is a Poor Prognostic Factor for Breast Cancer Patients as a Modulator of NF-κB Signaling.

PubMed

Kawabata, Hidetaka; Azuma, Kotaro; Ikeda, Kazuhiro; Sugitani, Ikuko; Kinowaki, Keiichi; Fujii, Takeshi; Osaki, Akihiko; Saeki, Toshiaki; Horie-Inoue, Kuniko; Inoue, Satoshi

2017-09-08

Many of the tripartite motif (TRIM) proteins function as E3 ubiquitin ligases and are assumed to be involved in various events, including oncogenesis. In regard to tripartite motif-containing 44 (TRIM44), which is an atypical TRIM family protein lacking the RING finger domain, its pathophysiological significance in breast cancer remains unknown. We performed an immunohistochemical study of TRIM44 protein in clinical breast cancer tissues from 129 patients. The pathophysiological role of TRIM44 in breast cancer was assessed by modulating TRIM44 expression in MCF-7 and MDA-MB-231 breast cancer cells. TRIM44 strong immunoreactivity was significantly associated with nuclear grade ( p = 0.033), distant disease-free survival ( p = 0.031) and overall survival ( p = 0.027). Multivariate analysis revealed that the TRIM44 status was an independent prognostic factor for distant disease-free survival ( p = 0.005) and overall survival ( p = 0.002) of patients. siRNA-mediated TRIM44 knockdown significantly decreased the proliferation of MCF-7 and MDA-MB-231 cells and inhibited the migration of MDA-MB-231 cells. Microarray analysis and qRT-PCR showed that TRIM44 knockdown upregulated CDK19 and downregulated MMP1 in MDA-MB-231 cells. Notably, TRIM44 knockdown impaired nuclear factor-kappa B (NF-κB)-mediated transcriptional activity stimulated by tumor necrosis factor α (TNFα). Moreover, TRIM44 knockdown substantially attenuated the TNFα-dependent phosphorylation of the p65 subunit of NF-κB and IκBα in both MCF-7 and MDA-MB-231 cells. TRIM44 would play a role in the progression of breast cancer by promoting cell proliferation and migration, as well as by enhancing NF-κB signaling.

Prognostic significance of TRIM24/TIF-1α gene expression in breast cancer.

PubMed

Chambon, Monique; Orsetti, Béatrice; Berthe, Marie-Laurence; Bascoul-Mollevi, Caroline; Rodriguez, Carmen; Duong, Vanessa; Gleizes, Michel; Thénot, Sandrine; Bibeau, Frédéric; Theillet, Charles; Cavaillès, Vincent

2011-04-01

In this study, we have analyzed the expression of TRIM24/TIF-1α, a negative regulator of various transcription factors (including nuclear receptors and p53) at the genomic, mRNA, and protein levels in human breast tumors. In breast cancer biopsy specimens, TRIM24/TIF-1α mRNA levels (assessed by Real-Time Quantitative PCR or microarray expression profiling) were increased as compared to normal breast tissues. At the genomic level, array comparative genomic hybridization analysis showed that the TRIM24/TIF-1α locus (7q34) exhibited both gains and losses that correlated with mRNA levels. By re-analyzing a series of 238 tumors, high levels of TRIM24/TIF-1α mRNA significantly correlated with various markers of poor prognosis (such as the molecular subtype) and were associated with worse overall survival. By using a rabbit polyclonal antibody for immunochemistry, the TRIM24/TIF-1α protein was detected in nuclei of normal luminal epithelial breast cells, but not in myoepithelial cells. Tissue microarray analysis confirmed that its expression was increased in epithelial cells from normal to breast infiltrating duct carcinoma and correlated with worse overall survival. Altogether, this work is the first study that shows that overexpression of the TRIM24/TIF-1α gene in breast cancer is associated with poor prognosis and worse survival, and it suggests that this transcription coregulator may play a role in mammary carcinogenesis and represent a novel prognostic marker. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by RIG-I

PubMed Central

Gack, Michaela Ulrike; Albrecht, Randy Allen; Urano, Tomohiko; Inn, Kyung-Soo; Huang, I-Chueh; Carnero, Elena; Farzan, Michael; Inoue, Satoshi; Jung, Jae Ung; García-Sastre, Adolfo

2009-01-01

SUMMARY TRIM25 mediates Lys 63-linked ubiquitination of the N-terminal CARDs of the viral RNA sensor RIG-I, leading to type I interferon (IFN) production. Here, we report that the influenza A virus non-structural protein 1 (NS1) specifically inhibits TRIM25-mediated RIG-I CARD ubiquitination, thereby suppressing RIG-I signal transduction. A novel domain in NS1 comprising E96/E97 residues mediates its interaction with the coiled-coil domain of TRIM25, thus blocking TRIM25 multimerization and RIG-I CARD ubiquitination. Furthermore, a recombinant influenza A virus expressing an E96A/E97A NS1 mutant is defective in blocking TRIM25-mediated anti-viral IFN response and loses virulence in mice. Our findings reveal a novel mechanism of influenza virus to inhibit host IFN response and also emphasize the vital role of TRIM25 in modulating viral infections. PMID:19454348

Seasat-A attitude control system

NASA Technical Reports Server (NTRS)

Weiss, R.; Rodden, J. J.; Hendricks, R. J.

1977-01-01

The Seasat-A attitude control system controls the attitude of the satellite system during injection into final circular orbit after Atlas boost, during orbit adjust and trim phases, and throughout the 3-year mission. Ascent and injection guidance and attitude control are provided by the Agena spacecraft with a gyrocompassed mass expulsion system. On-orbit attitude control functions are performed by a system that has its functional roots in the gravity-gradient momentum bias technology. The paper discusses hardware, control laws, and simulation results.

A Novel Terminal-Repeat Retrotransposon in Miniature (TRIM) Is Massively Expressed in Echinococcus multilocularis Stem Cells.

PubMed

Koziol, Uriel; Radio, Santiago; Smircich, Pablo; Zarowiecki, Magdalena; Fernández, Cecilia; Brehm, Klaus

2015-07-01

Taeniid cestodes (including the human parasites Echinococcus spp. and Taenia solium) have very few mobile genetic elements (MGEs) in their genome, despite lacking a canonical PIWI pathway. The MGEs of these parasites are virtually unexplored, and nothing is known about their expression and silencing. In this work, we report the discovery of a novel family of small nonautonomous long terminal repeat retrotransposons (also known as terminal-repeat retrotransposons in miniature, TRIMs) which we have named ta-TRIM (taeniid TRIM). ta-TRIMs are only the second family of TRIM elements discovered in animals, and are likely the result of convergent reductive evolution in different taxonomic groups. These elements originated at the base of the taeniid tree and have expanded during taeniid diversification, including after the divergence of closely related species such as Echinococcus multilocularis and Echinococcus granulosus. They are massively expressed in larval stages, from a small proportion of full-length copies and from isolated terminal repeats that show transcriptional read-through into downstream regions, generating novel noncoding RNAs and transcriptional fusions to coding genes. In E. multilocularis, ta-TRIMs are specifically expressed in the germinative cells (the somatic stem cells) during asexual reproduction of metacestode larvae. This would provide a developmental mechanism for insertion of ta-TRIMs into cells that will eventually generate the adult germ line. Future studies of active and inactive ta-TRIM elements could give the first clues on MGE silencing mechanisms in cestodes. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Identification of TRIM27 as a novel degradation target of herpes simplex virus 1 ICP0.

PubMed

Conwell, Sara E; White, Anne E; Harper, J Wade; Knipe, David M

2015-01-01

The herpes simplex virus 1 (HSV-1) immediate early protein ICP0 performs many functions during infection, including transactivation of viral gene expression, suppression of innate immune responses, and modification and eviction of histones from viral chromatin. Although these functions of ICP0 have been characterized, the detailed mechanisms underlying ICP0's complex role during infection warrant further investigation. We thus undertook an unbiased proteomic approach to identifying viral and cellular proteins that interact with ICP0 in the infected cell. Cellular candidates resulting from our analysis included the ubiquitin-specific protease USP7, the transcriptional repressor TRIM27, DNA repair proteins NBN and MRE11A, regulators of apoptosis, including BIRC6, and the proteasome. We also identified two HSV-1 early proteins involved in nucleotide metabolism, UL39 and UL50, as novel candidate interactors of ICP0. Because TRIM27 was the most statistically significant cellular candidate, we investigated the relationship between TRIM27 and ICP0. We observed rapid, ICP0-dependent loss of TRIM27 during HSV-1 infection. TRIM27 protein levels were restored by disrupting the RING domain of ICP0 or by inhibiting the proteasome, arguing that TRIM27 is a novel degradation target of ICP0. A mutant ICP0 lacking E3 ligase activity interacted with endogenous TRIM27 during infection as demonstrated by reciprocal coimmunoprecipitation and supported by immunofluorescence data. Surprisingly, ICP0-null mutant virus yields decreased upon TRIM27 depletion, arguing that TRIM27 has a positive effect on infection despite being targeted for degradation. These results illustrate a complex interaction between TRIM27 and viral infection with potential positive or negative effects of TRIM27 on HSV under different infection conditions. During productive infection, a virus must simultaneously redirect multiple cellular pathways to replicate itself while evading detection by the host's defenses. To

Effect of Hardwood Sawmill Edging and Trimming Practices on Furniture Part Production

Treesearch

D. Earl Kline; Carmen Regalado; Eugene M. Wengert; Fred M. Lamb; Philip A. Araman

1993-01-01

In a recent edging and trimming study at three hardwood sawmills, it was observed that the lumber volume produced was approximately 10 percent less than would be necessary to make the most valuable lumber. Furthermore, the excess portion of wood that was removed from the edging and trimming process contained a large percentage of clear wood. In light of rising costs...

Experimental trim drag values for conventional and supercritical wings. M.S. Thesis

NASA Technical Reports Server (NTRS)

Jacobs, P. F.

1981-01-01

Supercritical wings were studied to determine whether they incur higher trim drag values at cruise conditions than wide body technology wings. Relative trim drag increments were measured in an experimental wind tunnel investigation. The tests utilized high aspect ratio supercritical wing and a wide body wing in conjunction with five different horizontal tail configurations, mounted on a representative wide body fuselage. The three low tail configurations and two T tail configurations were chosen to measure the effects on horizontal tail size, location, and camber on the trim drag increments for the two wings. The increase in performance (lift to drag ratio) for supercritical wing over the wide body wing was 11 percent for both the optimum low tail and T tail configurations.

Moving characteristics of single file passengers considering the effect of ship trim and heeling

NASA Astrophysics Data System (ADS)

Sun, Jinlu; Lu, Shouxiang; Lo, Siuming; Ma, Jian; Xie, Qimiao

2018-01-01

Ship listing and motion affects the movement pattern of passengers on board, thus pedestrian traffic and evacuation dynamics would be significantly different from those on level ground. To quantify the influence of ship listing and motion on passenger evacuation, we designed a ship corridor simulator, with which we performed single-file pedestrian movement experiments considering the effect of trim and heeling. Results indicated that density is not the only factor that affects pedestrian speed under ship trim or heeling conditions, for that both individual walking speed and group walking speed would be greatly attenuated due to the influence of the trim angles. However, heeling angles show less impact on speed when compared with trim angles. In addition, the speed correlation coefficient between the adjacent experimental subjects would be higher with larger angles and lower speed. Moreover, both female and male experimental subjects need similar distance headway for walking in different trim or heeling conditions. Furthermore, experimental subjects with lower individual walking speed need longer time headway to keep enough distance headway. This work will provide fundamental guidance to the development of evacuation models and the design of evacuation facilities on board.

76 FR 72978 - Premier Trim, LLC, Spectrum Trim, LLC and Grant Products International, Inc. D/B/A Spectrum Grant...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-28

..., Spectrum Trim, LLC and Grant Products International, Inc. D/B/A Spectrum Grant De Mexico Including Workers Whose Unemployment Insurance (UI) Wages Are Paid Through Grant Products International, Inc... Brownsville, TX; Amended Certification Regarding Eligibility To Apply for Worker Adjustment Assistance In...

77 FR 67399 - Trim Systems Operating Corp., a Subsidiary of Commercial Vehicle Group, Inc., Including On-Site...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-09

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-81,393] Trim Systems Operating..., applicable to workers and former workers of Trim Systems Operating Corp., a subsidiary of Commercial Vehicle.... The amended notice applicable to TA-W-81,393 is hereby issued as follows: All workers of Trim Systems...

Linear ubiquitin assembly complex negatively regulates RIG-I and TRIM25 mediated type-I interferon induction

PubMed Central

Inn, Kyung-Soo; Gack, Michaela U.; Tokunaga, Fuminori; Shi, Mude; Wong, Lai-Yee; Iwai, Kazuhiro; Jung, Jae U.

2011-01-01

Summary Upon detection of viral RNA, retinoic acid inducible gene I (RIG-I) undergoes TRIM25-mediated Lys-63 linked ubiquitination, leading to type-I interferon (IFN) production. In this study, we demonstrate that the linear ubiquitin assembly complex (LUBAC), comprised of two RING-IBR-RING (RBR)-containing E3 ligases HOIL-1L and HOIP, independently targets TRIM25 and RIG-I to effectively suppress virus-induced IFN production. RBR E3 ligase domains of HOIL-1L and HOIP bind and induce proteosomal degradation of TRIM25, whereas the NZF domain of HOIL-1L competes with TRIM25 for RIG-I binding. Consequently, both actions by the HOIL-1L/HOIP LUBAC potently inhibit RIG-I ubiquitination and anti-viral activity, but in a mechanistically separate manner. Conversely, the genetic deletion or depletion of HOIL-1L and HOIP robustly enhances virus-induced type-I IFN production. Taken together, the HOIL-1L/HOIP LUBAC specifically suppresses RIG-I ubiquitination and activation by inducing TRIM25 degradation and inhibiting TRIM25 interaction with RIG-I, resulting in the comprehensive suppression of the IFN-mediated anti-viral signaling pathway. PMID:21292167

Linear ubiquitin assembly complex negatively regulates RIG-I- and TRIM25-mediated type I interferon induction.

PubMed

Inn, Kyung-Soo; Gack, Michaela U; Tokunaga, Fuminori; Shi, Mude; Wong, Lai-Yee; Iwai, Kazuhiro; Jung, Jae U

2011-02-04

Upon detection of viral RNA, retinoic acid-inducible gene I (RIG-I) undergoes TRIM25-mediated K63-linked ubiquitination, leading to type I interferon (IFN) production. In this study, we demonstrate that the linear ubiquitin assembly complex (LUBAC), comprised of two RING-IBR-RING (RBR)-containing E3 ligases, HOIL-1L and HOIP, independently targets TRIM25 and RIG-I to effectively suppress virus-induced IFN production. RBR E3 ligase domains of HOIL-1L and HOIP bind and induce proteasomal degradation of TRIM25, whereas the NZF domain of HOIL-1L competes with TRIM25 for RIG-I binding. Consequently, both actions by the HOIL-1L/HOIP LUBAC potently inhibit RIG-I ubiquitination and antiviral activity, but in a mechanistically separate manner. Conversely, the genetic deletion or depletion of HOIL-1L and HOIP robustly enhances virus-induced type I IFN production. Taken together, the HOIL-1L/HOIP LUBAC specifically suppresses RIG-I ubiquitination and activation by inducing TRIM25 degradation and inhibiting TRIM25 interaction with RIG-I, resulting in the comprehensive suppression of the IFN-mediated antiviral signaling pathway. Copyright © 2011 Elsevier Inc. All rights reserved.

Molecular characterization of tripartite motif protein 25 (TRIM25) involved in ERα-mediated transcription in the Korean rose bitterling Rhodeus uyekii.

PubMed

Kong, Hee Jeong; Lee, Ye Ji; Shin, Jihye; Cho, Hyun Kook; Kim, Woo-Jin; Kim, Hyung Soo; Cheong, Jaehun; Sohn, Young Chang; Lee, Sang-Jun; Kim, Bong-Seok

2012-09-01

Tripartite motif-containing 25 (TRIM25), also known as estrogen-responsive finger protein (EFP), plays an essential role in cell proliferation and innate immunity. In the present study, we isolated and characterized the TRIM25 cDNA of the Korean rose bitterling Rhodeus uyekii, designated RuTRIM25. It encodes an open reading frame of 669 amino acids containing an N-terminal RBCC motif composed of a RING domain, two B boxes, and a coiled-coil domain and a C-terminal B30.2 (PRY/SPRY) domain. RuTRIM25 shows strong homology (79.7%) to zebrafish TRIM25 and shared 32.4-28.8% homology with TRIM25 from other species, including mammals. RuTRIM25 mRNA was expressed ubiquitously. It was highly expressed in the ovary, spleen, and liver and moderately in the stomach and intestine of normal Korean rose bitterling. The intracellular localization of RuTRIM25 in HEK293T cells was diffusely localized in the cytoplasm and its RING domain deletion mutant (RuTRIM25ΔR) was detected diffusely with some aggregates in the cytoplasm. RuTRIM25, but not RuTRIM25ΔR, is ubiquitinated in vivo. Ectopic expression of RuTRIM25 synergistically activated the estrogen receptor (ER)-mediated luciferase reporter activity in a dose-dependent manner in HEK293T cells. Together, these results suggest that the RuTRIM25 regulates the ER-mediated transcription in fish similarly to its mammalian counterpart. Copyright © 2012 Elsevier Inc. All rights reserved.

77 FR 60103 - Approval of Subzone Status; TST NA TRIM, LLC; Hidalgo, TX

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-02

... DEPARTMENT OF COMMERCE Foreign-Trade Zones Board [S-90-2012] Approval of Subzone Status; TST NA TRIM, LLC; Hidalgo, TX On August 3, 2012, the Executive Secretary of the Foreign-Trade Zones (FTZ..., requesting subzone status subject to the existing activation limit of FTZ 12, on behalf of TST NA TRIM, LLC...

Conceptual Design of Low-Boom Aircraft with Flight Trim Requirement

NASA Technical Reports Server (NTRS)

Ordaz, Irian; Geiselhart, Karl A.; Fenbert, James W.

2014-01-01

A new low-boom target generation approach is presented which allows the introduction of a trim requirement during the early conceptual design of supersonic aircraft. The formulation provides an approximation of the center of pressure for a presumed aircraft configuration with a reversed equivalent area matching a low-boom equivalent area target. The center of pressure is approximated from a surrogate lift distribution that is based on the lift component of the classical equivalent area. The assumptions of the formulation are verified to be sufficiently accurate for a supersonic aircraft of high fineness ratio through three case studies. The first two quantify and verify the accuracy and the sensitivity of the surrogate center of pressure corresponding to shape deformation of lifting components. The third verification case shows the capability of the approach to achieve a trim state while maintaining the low-boom characteristics of a previously untrimmed configuration. Finally, the new low-boom target generation approach is demonstrated through the early conceptual design of a demonstrator concept that is low-boom feasible, trimmed, and stable in cruise.

Endogenous TRIM5α Function Is Regulated by SUMOylation and Nuclear Sequestration for Efficient Innate Sensing in Dendritic Cells

PubMed Central

Portilho, Débora M.; Fernandez, Juliette; Ringeard, Mathieu; Machado, Anthony K.; Boulay, Aude; Mayer, Martha; Müller-Trutwin, Michaela; Beignon, Anne-Sophie; Kirchhoff, Frank; Nisole, Sébastien; Arhel, Nathalie J.

2015-01-01

Summary During retroviral infection, viral capsids are subject to restriction by the cellular factor TRIM5α. Here, we show that dendritic cells (DCs) derived from human and non-human primate species lack efficient TRIM5α-mediated retroviral restriction. In DCs, endogenous TRIM5α accumulates in nuclear bodies (NB) that partly co-localize with Cajal bodies in a SUMOylation-dependent manner. Nuclear sequestration of TRIM5α allowed potent induction of type I interferon (IFN) responses during infection, mediated by sensing of reverse transcribed DNA by cGAS. Overexpression of TRIM5α or treatment with the SUMOylation inhibitor ginkgolic acid (GA) resulted in enforced cytoplasmic TRIM5α expression and restored efficient viral restriction but abrogated type I IFN production following infection. Our results suggest that there is an evolutionary trade-off specific to DCs in which restriction is minimized to maximize sensing. TRIM5α regulation via SUMOylation-dependent nuclear sequestration adds to our understanding of how restriction factors are regulated. PMID:26748714

Molecular characterization of a CpTRIM35-like protein and its splice variants from whitespotted bamboo shark (Chiloscyllium plagiosum)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Xinshang, E-mail: sanmaosound@163.com; Zhao, Heng, E-mail: hengzhao2000@gmail.com; Chen, Yeyu, E-mail: cyyleaf@126.com

2014-10-24

Highlights: • A TRIM gene and three splice variants were firstly cloned from elasmobranch fish. • The genes were constitutively expressed with high levels in spleen and kidney. • The gene products were distributed in cytoplasm alone or cytoplasm and nucleus. • As E3 ubiquitin ligases, the proteins differed in immune responses to challenges. - Abstract: The tripartite motif (TRIM) proteins play important roles in a broad range of biological processes, including apoptosis, cell proliferation and innate immunity response. In this study, a TRIM gene and its three splice variants were cloned from an elasmobranch fish—whitespotted bamboo shark (Chiloscyllium plagiosummore » Bennett). Phylogenetic analysis indicated that the gene was closely related to TRIM35 homologs, thus termed CpTRIM35-like. Deduced CpTRIM35 has a RBCC-PRY/SPRY structure typical of TRIM proteins, and its splice variants (CpTRIM35-1–3) have different truncations at the C-terminus. The gene products were constitutively expressed in adult sharks with the highest levels in spleen and kidney. The different subcellular locations, upregulation upon LPS and poly I:C stimulation, and significant E3 ubiquitin ligase activities suggested their different roles in immune responses as an E3 ubiquitin ligase. This is the first TRIM protein ever characterized in elasmobranch fish.« less

TRIM28, a new molecular marker predicting metastasis and survival in early-stage non-small cell lung cancer.

PubMed

Liu, Lei; Zhao, Enhong; Li, Chunhui; Huang, Liang; Xiao, Lijun; Cheng, Luyang; Huang, Xu; Song, Youxin; Xu, Dawei

2013-02-01

TRIM28 is a universal corepressor for Kruppel-associated box zinc finger proteins. In this study, we demonstrated the expression of TRIM28 gene was significantly higher in cancerous tissues than in noncancerous tissues (P < 0.001). TRIM28 knockdown resulted in a decrease in cell proliferation in liquid media as well as in soft agar. The proliferation rate was impaired and the cell cycle progression was inhibited after knockdown of TRIM28 in non-small cell lung cancer cell lines PAa and SK-MES-1. We used real-time polymerase chain reaction to detect circulating cancer cells in 138 non-small cell lung cancer patients. The overall positive detection rate was 30.4% (42 of 138) in peripheral blood of NSCLC patients and was 29.9% (29 of 97) in early-stage patients. In a 70-month follow-up study, 20 of 29 patients (69.0%) in TRIM28 positive group had recurrence and/or metastasis, significantly higher (P = 0.004) than in the TRIM28 negative group (25 of 68, 36.8%). In addition, non-small cell lung cancer patients whose circulating cancer cells expressed TRIM28 suffered shorter tumor-specific survival compared with those with absent TRIM28 expression (P < 0.001). Results of our study showed that TRIM28 provides a survival advantage to lung cancer cells and may be a new marker to predict metastasis and prognosis in early-stage non-small cell lung cancer patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effects of Beak Trimming on Pecking Force

USDA-ARS?s Scientific Manuscript database

Beak trimming in the production laying hen has come under great scrutiny by welfare and consumer advocacy groups as a potential source of acute and chronic pain as well as having the potential to inhibit the freedom to express normal behaviors such as feeding behaviors. Although several studies have...

Tani trims his hair in Node 2

NASA Image and Video Library

2008-02-10

S122-E-007645 (10 Feb. 2008) --- Astronaut Daniel Tani, Expedition 16 flight engineer, trims his hair in the Harmony node of the International Space Station while Space Shuttle Atlantis is docked with the station. Tani used hair clippers fashioned with a vacuum device to garner freshly cut hair.

Tani trims his hair in Node 2

NASA Image and Video Library

2008-02-10

S122-E-007643 (10 Feb. 2008) --- Astronaut Daniel Tani, Expedition 16 flight engineer, trims his hair in the Harmony node of the International Space Station while Space Shuttle Atlantis is docked with the station. Tani used hair clippers fashioned with a vacuum device to garner freshly cut hair.

Precision autophagy directed by receptor regulators - emerging examples within the TRIM family.

PubMed

Kimura, Tomonori; Mandell, Michael; Deretic, Vojo

2016-03-01

Selective autophagy entails cooperation between target recognition and assembly of the autophagic apparatus. Target recognition is conducted by receptors that often recognize tags, such as ubiquitin and galectins, although examples of selective autophagy independent of these tags are emerging. It is less known how receptors cooperate with the upstream autophagic regulators, beyond the well-characterized association of receptors with Atg8 or its homologs, such as LC3B (encoded by MAP1LC3B), on autophagic membranes. The molecular details of the emerging role in autophagy of the family of proteins called TRIMs shed light on the coordination between cargo recognition and the assembly and activation of the principal autophagy regulators. In their autophagy roles, TRIMs act both as receptors and as platforms ('receptor regulators') for the assembly of the core autophagy regulators, such as ULK1 and Beclin 1 in their activated state. As autophagic receptors, TRIMs can directly recognize endogenous or exogenous targets, obviating a need for intermediary autophagic tags, such as ubiquitin and galectins. The receptor and regulatory features embodied within the same entity allow TRIMs to govern cargo degradation in a highly exact process termed 'precision autophagy'. © 2016. Published by The Company of Biologists Ltd.

21. First floor, west wall, detail of molding trim ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

21. First floor, west wall, detail of molding trim - Veterans Administration Center, Officers Duplex Quarters, 5302 East Kellogg (Legal Address); 5500 East Kellogg (Common Address), Wichita, Sedgwick County, KS

A study of tyre cavity resonance and noise reduction using inner trim

NASA Astrophysics Data System (ADS)

Mohamed, Zamri; Wang, Xu

2015-01-01

A study of tyre inner trim as a method for reducing tyre cavity resonance noise is presented. The tyre is modelled as a rectangular toroid where only the outside shell is flexible. A modal series solution of the sound pressure frequency response inside the tyre cavity is derived from the wave equation using modal superposition. In the solution with the rigid and flexible wall boundary condition, the effect of placing a trim layer onto the inner surface of the tyre tread plate wall is reflected by adding a damping loss term in the sound pressure frequency response function. The numerical simulation result was then compared with the result obtained from a roving impact test performed on a tyre. The results show that selective trim material may be effective for reducing the structure-borne noise magnitude resulting from the tyre cavity resonance.

Ivanishin trims his hair in the Node 3

NASA Image and Video Library

2011-12-18

ISS030-E-012662 (18 Dec. 2011) --- Russian cosmonaut Anatoly Ivanishin, Expedition 30 flight engineer, trims his hair in the Tranquility node of the International Space Station. Ivanishin used hair clippers fashioned with a vacuum device to garner freshly cut hair.

Concerted In Vitro Trimming of Viral HLA-B27-Restricted Ligands by Human ERAP1 and ERAP2 Aminopeptidases

PubMed Central

Lorente, Elena; Barriga, Alejandro; Johnstone, Carolina; Mir, Carmen; Jiménez, Mercedes; López, Daniel

2013-01-01

In the classical human leukocyte antigen (HLA) class I antigen processing and presentation pathway, the antigenic peptides are generated from viral proteins by multiple proteolytic cleavages of the proteasome (and in some cases other cytosolic proteases) and transported to the endoplasmic reticulum (ER) lumen where they are exposed to aminopeptidase activity. In human cells, two different ER-resident enzymes, ERAP1 and ERAP2, can trim the N-terminally extended residues of peptide precursors. In this study, the possible cooperative effect of generating five naturally processed HLA-B27 ligands by both proteases was analyzed. We identified differences in the products obtained with increased detection of natural HLA-B27 ligands by comparing double versus single enzyme digestions by mass spectrometry analysis. These in vitro data suggest that each enzyme can use the degradation products of the other as a substrate for new N-terminal trimming, indicating concerted aminoproteolytic activity of ERAP 1 and ERAP2. PMID:24223975

Concerted in vitro trimming of viral HLA-B27-restricted ligands by human ERAP1 and ERAP2 aminopeptidases.

PubMed

Lorente, Elena; Barriga, Alejandro; Johnstone, Carolina; Mir, Carmen; Jiménez, Mercedes; López, Daniel

2013-01-01

In the classical human leukocyte antigen (HLA) class I antigen processing and presentation pathway, the antigenic peptides are generated from viral proteins by multiple proteolytic cleavages of the proteasome (and in some cases other cytosolic proteases) and transported to the endoplasmic reticulum (ER) lumen where they are exposed to aminopeptidase activity. In human cells, two different ER-resident enzymes, ERAP1 and ERAP2, can trim the N-terminally extended residues of peptide precursors. In this study, the possible cooperative effect of generating five naturally processed HLA-B27 ligands by both proteases was analyzed. We identified differences in the products obtained with increased detection of natural HLA-B27 ligands by comparing double versus single enzyme digestions by mass spectrometry analysis. These in vitro data suggest that each enzyme can use the degradation products of the other as a substrate for new N-terminal trimming, indicating concerted aminoproteolytic activity of ERAP 1 and ERAP2.

Expression levels of the innate response gene RIG-I and its regulators RNF125 and TRIM25 in HIV-1-infected adult and pediatric individuals.

PubMed

Britto, Alan M A; Amoedo, Nívea D; Pezzuto, Paula; Afonso, Adriana O; Martínez, Ana M B; Silveira, Jussara; Sion, Fernando S; Machado, Elizabeth S; Soares, Marcelo A; Giannini, Ana L M

2013-07-31

TLRs (Toll-like receptors) and RLRs (RIG-I-like receptors) mediate innate immune responses by detecting microorganism invasion. RIG-I activation results in the production of interferon (IFN) type 1 and IFN responsive genes (ISGs). As the ubiquitin ligases RNF125 and TRIM25 are involved in regulating RIG-I function, our aim was to assess whether the levels of these three genes vary between healthy and HIV-infected individuals and whether these levels are related to disease progression. Gene expression analyses for RIG-I, RNF125, and TRIM25 were performed for HIV-infected adults and the children's peripheral blood mononuclear cells (PBMCs). Reverse transcription-quantitative PCRs (RT-qPCRs) were performed in order to quantify the expression levels of RIG-I, RNF125 and TRIM25 from PBMCs purified from control or HIV-infected individuals. Controls express higher levels of the three genes when compared to HIV-infected patients. These expressions are clearly distinct between healthy and progressors, and are reproduced in adults and children. In controls, RNF125 is the highest expressed gene, whereas in progressors, RIG-I is either the highest expressed gene or is expressed similarly to RNF125 and TRIM25. A pattern of expression of RIG-I, RNF125, and TRIM25 genes in HIV patients is evident. The high expression of RNF125 in healthy individuals reflects the importance of keeping RIG-I function off, inhibiting unnecessary IFN production. Consistent with this assumption, RNF125 levels are lower in HIV patients and importantly, the RNF125/RIG-I ratio is lower in patients who progress to AIDS. Our results might help to predict disease progression and unveil the role of poorly characterized host genes during HIV infection.

Trauma Risk Management (TRiM): Promoting Help Seeking for Mental Health Problems Among Combat-Exposed U.K. Military Personnel.

PubMed

Jones, Norman; Burdett, Howard; Green, Kevin; Greenberg, Neil

2017-01-01

Trauma Risk Management (TRiM) is a peer-led, occupational mental health support process that aims to identify and assist U.K. military personnel with persistent mental ill health related to potentially traumatic events (PTEs). This study compared help seeking, mental disorder symptoms, and alcohol use between TRiM recipients and personnel experiencing similar combat events who did not receive TRiM; an unexposed group provided context. Records of TRiM activity during a U.K. military deployment in Afghanistan were linked to contemporaneous survey data assessing mental health and combat experiences. The resulting deployment data set was amalgamated with mental health, alcohol use, and help-seeking data collected within 12 weeks of homecoming and again one to two years later. Mental health and help-seeking outcomes were compared between a nonexposed, non-TRiM sample (n = 161), an exposed, non-TRiM sample (n = 149), and an exposed, TRiM-recipient sample (n = 328) using logistic regression analyses. At follow-up, TRiM recipients were significantly more likely to seek help from mental health services than exposed, non-TRiM personnel. At baseline, TRiM recipients had significantly greater adjusted odds of reporting possible posttraumatic stress disorder (PTSD) symptoms than exposed non-TRiM personnel; the difference was not significant at follow-up. TRiM recipients were significantly more likely to report persistent mental disorder and alcohol misuse caseness over the follow-up period. TRiM recipients were significantly more likely to seek help from mental health services than a similar PTE-exposed group that did not receive TRiM; however, TRiM recipients experienced more persistent mental ill-health symptoms and hazardous alcohol use over the period of follow-up despite seeking help.

Trim9 Deletion Alters the Morphogenesis of Developing and Adult-Born Hippocampal Neurons and Impairs Spatial Learning and Memory

PubMed Central

Winkle, Cortney C.; Olsen, Reid H. J.; Kim, Hyojin; Moy, Sheryl S.

2016-01-01

During hippocampal development, newly born neurons migrate to appropriate destinations, extend axons, and ramify dendritic arbors to establish functional circuitry. These developmental stages are recapitulated in the dentate gyrus of the adult hippocampus, where neurons are continuously generated and subsequently incorporate into existing, local circuitry. Here we demonstrate that the E3 ubiquitin ligase TRIM9 regulates these developmental stages in embryonic and adult-born mouse hippocampal neurons in vitro and in vivo. Embryonic hippocampal and adult-born dentate granule neurons lacking Trim9 exhibit several morphological defects, including excessive dendritic arborization. Although gross anatomy of the hippocampus was not detectably altered by Trim9 deletion, a significant number of Trim9−/− adult-born dentate neurons localized inappropriately. These morphological and localization defects of hippocampal neurons in Trim9−/− mice were associated with extreme deficits in spatial learning and memory, suggesting that TRIM9-directed neuronal morphogenesis may be involved in hippocampal-dependent behaviors. SIGNIFICANCE STATEMENT Appropriate generation and incorporation of adult-born neurons in the dentate gyrus are critical for spatial learning and memory and other hippocampal functions. Here we identify the brain-enriched E3 ubiquitin ligase TRIM9 as a novel regulator of embryonic and adult hippocampal neuron shape acquisition and hippocampal-dependent behaviors. Genetic deletion of Trim9 elevated dendritic arborization of hippocampal neurons in vitro and in vivo. Adult-born dentate granule cells lacking Trim9 similarly exhibited excessive dendritic arborization and mislocalization of cell bodies in vivo. These cellular defects were associated with severe deficits in spatial learning and memory. PMID:27147649

Kuipers trims his hair in the Node 3

NASA Image and Video Library

2011-12-30

ISS030-E-033523 (30 Dec. 2011) --- European Space Agency astronaut Andre Kuipers, Expedition 30 flight engineer, trims his hair in the Tranquility node of the International Space Station. Kuipers used hair clippers fashioned with a vacuum device to garner freshly cut hair.

Kuipers trims his hair in the Node 3

NASA Image and Video Library

2011-12-30

ISS030-E-033548 (30 Dec. 2011) --- European Space Agency astronaut Andre Kuipers, Expedition 30 flight engineer, trims his hair in the Tranquility node of the International Space Station. Kuipers used hair clippers fashioned with a vacuum device to garner freshly cut hair.

Effect of hot water treatment of beef trimmings on processing characteristics and eating quality of ground beef.

PubMed

Pietrasik, Z; Gaudette, N J; Klassen, M

2016-03-01

The effect of hot water treatment of beef trimmings on the processing characteristics, shelf-life and consumer acceptability of ground beef was evaluated. Hot water treatment (85°C for 40s) substantially enhanced the microbial quality of trimmings during refrigerated storage and this was independent of the fat level of the trimmings. Treatment had no effect on the oxidative stability of trimmings stored up to 7days, ground beef displayed in a retail cabinet for up to 3days, and had minimal effect on textural properties. Instrumental results demonstrate that ground beef from hot water treated trimmings was slightly lighter and tended to have less red color compared to non-treated beef. These color differences did not impact the consumer acceptance of raw patties, and in addition, hot water treatment did not significantly affect the consumer acceptability of cooked patty attributes. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Total Risk Integrated Methodology (TRIM) - Peer Review and Publications

EPA Pesticide Factsheets

Peer review: Consistent with Agency peer review policy, and the 1994 Agency Task Force on Environmental Regulatory Modeling, internal and external peer review has been an integral part of the TRIM development plan.

Trim25 Is an RNA-Specific Activator of Lin28a/TuT4-Mediated Uridylation.

PubMed

Choudhury, Nila Roy; Nowak, Jakub S; Zuo, Juan; Rappsilber, Juri; Spoel, Steven H; Michlewski, Gracjan

2014-11-20

RNA binding proteins have thousands of cellular RNA targets and often exhibit opposite or passive molecular functions. Lin28a is a conserved RNA binding protein involved in pluripotency and tumorigenesis that was previously shown to trigger TuT4-mediated pre-let-7 uridylation, inhibiting its processing and targeting it for degradation. Surprisingly, despite binding to other pre-microRNAs (pre-miRNAs), only pre-let-7 is efficiently uridylated by TuT4. Thus, we hypothesized the existence of substrate-specific cofactors that stimulate Lin28a-mediated pre-let-7 uridylation or restrict its functionality on non-let-7 pre-miRNAs. Through RNA pull-downs coupled with quantitative mass spectrometry, we identified the E3 ligase Trim25 as an RNA-specific cofactor for Lin28a/TuT4-mediated uridylation. We show that Trim25 binds to the conserved terminal loop (CTL) of pre-let-7 and activates TuT4, allowing for more efficient Lin28a-mediated uridylation. These findings reveal that protein-modifying enzymes, only recently shown to bind RNA, can guide the function of canonical ribonucleoprotein (RNP) complexes in cis, thereby providing an additional level of specificity.

The Specificity of Trimming of MHC Class I-Presented Peptides in the Endoplasmic Reticulum1

PubMed Central

Hearn, Arron; York, Ian A.; Rock, Kenneth L.

2010-01-01

Aminopeptidases in the endoplasmic reticulum (ER) can cleave antigenic peptides and in so doing either create or destroy MHC class I-presented epitopes. However the specificity of this trimming process overall and of the major ER aminopeptidase ERAP1 in particular is not well understood. This issue is important because peptide trimming influences the magnitude and specificity of CD8 T cell responses. By systematically varying the N-terminal flanking sequences of peptides in a cell free biochemical system and in intact cells, we elucidated the specificity of ERAP1 and of ER trimming overall. ERAP1 can cleave after many amino acids on the N-terminus of epitope precursors but does so at markedly different rates. The specificity seen with purified ERAP1 is similar to that observed for trimming and presentation of epitopes in the ER of intact cells. We define N-terminal sequences that are favorable or unfavorable for antigen presentation in ways that are independent from the epitopes core sequence. When databases of known presented peptides were analyzed, the residues that were preferred for the trimming of model peptide precursors were found to be overrepresented in N-terminal flanking sequences of epitopes generally. These data define key determinants in the specificity of antigen processing. PMID:19828632

Automatic Edging and Trimming of Hardwood Lumber

Treesearch

D. Earl Kline; Eugene M. Wengert; Philip A. Araman

1990-01-01

Studies have shown that there is a potential to increase hardwood lumber value by more than 20 percent through optimum edging and trimming. Even a small portion of this percentage can boost the profitability of hardwood lumber manufacturers substantially. The objective of this research project is to develop an automated system which would assist in correct edging and...

TRIM5α requires Ube2W to anchor Lys63-linked ubiquitin chains and restrict reverse transcription

PubMed Central

Fletcher, Adam J; Christensen, Devin E; Nelson, Chad; Tan, Choon Ping; Schaller, Torsten; Lehner, Paul J; Sundquist, Wesley I; Towers, Greg J

2015-01-01

TRIM5α is an antiviral, cytoplasmic, E3 ubiquitin (Ub) ligase that assembles on incoming retroviral capsids and induces their premature dissociation. It inhibits reverse transcription of the viral genome and can also synthesize unanchored polyubiquitin (polyUb) chains to stimulate innate immune responses. Here, we show that TRIM5α employs the E2 Ub-conjugating enzyme Ube2W to anchor the Lys63-linked polyUb chains in a process of TRIM5α auto-ubiquitination. Chain anchoring is initiated, in cells and in vitro, through Ube2W-catalyzed monoubiquitination of TRIM5α. This modification serves as a substrate for the elongation of anchored Lys63-linked polyUb chains, catalyzed by the heterodimeric E2 enzyme Ube2N/Ube2V2. Ube2W targets multiple TRIM5α internal lysines with Ub especially lysines 45 and 50, rather than modifying the N-terminal amino group, which is instead αN-acetylated in cells. E2 depletion or Ub mutation inhibits TRIM5α ubiquitination in cells and restores restricted viral reverse transcription, but not infection. Our data indicate that the stepwise formation of anchored Lys63-linked polyUb is a critical early step in the TRIM5α restriction mechanism and identify the E2 Ub-conjugating cofactors involved. PMID:26101372

A Comparison of the Long Term Effects of Infrared Beak Treatment and Hot Blade Beak Trimming in Laying Hens

USDA-ARS?s Scientific Manuscript database

The poultry industry is under intense pressure from the public and animal welfare advocates to eliminate the practice of beak trimming due to the potential for acute and chronic pain in the trimmed birds. However, elimination of beak trimming may have severe implications for animal welfare, as peck...

Regulation of MDA5-MAVS Antiviral Signaling Axis by TRIM25 through TRAF6-Mediated NF-κB Activation.

PubMed

Lee, Na-Rae; Kim, Hye-In; Choi, Myung-Soo; Yi, Chae-Min; Inn, Kyung-Soo

2015-09-01

Tripartite motif protein 25 (TRIM25), mediates K63-linked polyubiquitination of Retinoic acid inducible gene I (RIG-I) that is crucial for downstream antiviral interferon signaling. Here, we demonstrate that TRIM25 is required for melanoma differentiation-associated gene 5 (MDA5) and MAVS mediated activation of NF-κB and interferon production. TRIM25 is required for the full activation of NF-κB at the downstream of MAVS, while it is not involved in IRF3 nuclear translocation. Mechanical studies showed that TRIM25 is involved in TRAF6-mediated NF-κB activation. These collectively indicate that TRIM25 plays an additional role in RIG-I/MDA5 signaling other than RIG-I ubiquitination via activation of NF-κB.

Regulation of MDA5-MAVS Antiviral Signaling Axis by TRIM25 through TRAF6-Mediated NF-κB Activation

PubMed Central

Lee, Na-Rae; Kim, Hye-In; Choi, Myung-Soo; Yi, Chae-Min; Inn, Kyung-Soo

2015-01-01

Tripartite motif protein 25 (TRIM25), mediates K63-linked polyubiquitination of Retinoic acid inducible gene I (RIG-I) that is crucial for downstream antiviral interferon signaling. Here, we demonstrate that TRIM25 is required for melanoma differentiation-associated gene 5 (MDA5) and MAVS mediated activation of NF-κB and interferon production. TRIM25 is required for the full activation of NF-κB at the downstream of MAVS, while it is not involved in IRF3 nuclear translocation. Mechanical studies showed that TRIM25 is involved in TRAF6-mediated NF-κB activation. These collectively indicate that TRIM25 plays an additional role in RIG-I/MDA5 signaling other than RIG-I ubiquitination via activation of NF-κB. PMID:26299329

Trim9 Deletion Alters the Morphogenesis of Developing and Adult-Born Hippocampal Neurons and Impairs Spatial Learning and Memory.

PubMed

Winkle, Cortney C; Olsen, Reid H J; Kim, Hyojin; Moy, Sheryl S; Song, Juan; Gupton, Stephanie L

2016-05-04

During hippocampal development, newly born neurons migrate to appropriate destinations, extend axons, and ramify dendritic arbors to establish functional circuitry. These developmental stages are recapitulated in the dentate gyrus of the adult hippocampus, where neurons are continuously generated and subsequently incorporate into existing, local circuitry. Here we demonstrate that the E3 ubiquitin ligase TRIM9 regulates these developmental stages in embryonic and adult-born mouse hippocampal neurons in vitro and in vivo Embryonic hippocampal and adult-born dentate granule neurons lacking Trim9 exhibit several morphological defects, including excessive dendritic arborization. Although gross anatomy of the hippocampus was not detectably altered by Trim9 deletion, a significant number of Trim9(-/-) adult-born dentate neurons localized inappropriately. These morphological and localization defects of hippocampal neurons in Trim9(-/-) mice were associated with extreme deficits in spatial learning and memory, suggesting that TRIM9-directed neuronal morphogenesis may be involved in hippocampal-dependent behaviors. Appropriate generation and incorporation of adult-born neurons in the dentate gyrus are critical for spatial learning and memory and other hippocampal functions. Here we identify the brain-enriched E3 ubiquitin ligase TRIM9 as a novel regulator of embryonic and adult hippocampal neuron shape acquisition and hippocampal-dependent behaviors. Genetic deletion of Trim9 elevated dendritic arborization of hippocampal neurons in vitro and in vivo Adult-born dentate granule cells lacking Trim9 similarly exhibited excessive dendritic arborization and mislocalization of cell bodies in vivo These cellular defects were associated with severe deficits in spatial learning and memory. Copyright © 2016 the authors 0270-6474/16/364940-19$15.00/0.

Burbank trims Shkaplero's hair in the Node 3

NASA Image and Video Library

2011-12-18

ISS030-E-012660 (18 Dec. 2011) --- NASA astronaut Dan Burbank, Expedition 30 commander, trims the hair of Russian cosmonaut Anton Shkaplerov, flight engineer, in the Tranquility node of the International Space Station. Burbank used hair clippers fashioned with a vacuum device to garner freshly cut hair.

Burbank trims Shkaplerov's hair in the Node 3

NASA Image and Video Library

2012-03-18

ISS030-E-161707 (18 March 2012) --- NASA astronaut Dan Burbank, Expedition 30 commander, trims the hair of Russian cosmonaut Anton Shkaplerov, flight engineer, in the Tranquility node of the International Space Station. Burbank used hair clippers fashioned with a vacuum device to garner freshly cut hair.

Shkaplerov trims Burbank's hair in the Node 3

NASA Image and Video Library

2011-12-18

ISS030-E-012655 (18 Dec. 2011) --- Russian cosmonaut Anton Shkaplerov, Expedition 30 flight engineer, trims the hair of NASA astronaut Dan Burbank, commander, in the Tranquility node of the International Space Station. Shkaplerov used hair clippers fashioned with a vacuum device to garner freshly cut hair.

Experimental trim drag values and flow-field measurements for a wide-body transport model with conventional and supercritical wings

NASA Technical Reports Server (NTRS)

Jacobs, P. F.

1982-01-01

The purpose of this study was to determine if advanced supercritical wings incur higher trim drag values at cruise conditions than current wide body technology wings. Relative trim drag increments were measured in an experimental wind tunnel investigation conducted in the Langley 8 Foot Transonic Pressure Tunnel. The tests utilized a high aspect ratio supercritical wing and a wide body aircraft wing, in conjunction with five different horizontal tail configurations, mounted on a representative wide body fuselage. The three low tail and two T-tail configurations were designed to measure the effects of horizontal tail size, location, and camber on the trim drag increments for the two wings. Longitudinal force and moment data were taken at a Mach number of 0.82 and design cruise lift coefficients for the wide body and supercritical wings of 0.45 and 0.55, respectively. The data indicate that the supercritical wing does not have significantly higher trim drag than the wide body wing. A reduction in tail size, combined with relaxed static stability, produced trim drag reductions for both wings. The cambered tails had higher trim drag increments than the symmetrical tails for both wings, and the T-tail configurations had lower trim drag increments than the low tail configurations.

TRIM25 Identification in the Chinese Goose: Gene Structure, Tissue Expression Profiles, and Antiviral Immune Responses In Vivo and In Vitro.

PubMed

Wei, Yunan; Zhou, Hao; Wang, Anqi; Sun, Lipei; Wang, Mingshu; Jia, Renyong; Zhu, Dekang; Liu, Mafeng; Yang, Qiao; Wu, Ying; Sun, Kunfeng; Chen, Xiaoyue; Cheng, Anchun; Chen, Shun

2016-01-01

The retinoic acid-inducible gene I (RIG-I) and the RIG-I-like receptor (RLR) protein play a critical role in the interferon (IFN) response during RNA virus infection. The tripartite motif containing 25 proteins (TRIM25) was reported to modify caspase activation and RIG-I recruitment domains (CARDs) via ubiquitin. These modifications allow TRIM25 to interact with mitochondrial antiviral signaling molecules (MAVs) and form CARD-CARD tetramers. Goose TRIM25 was cloned from gosling lungs, which possess a 1662 bp open reading flame (ORF). This ORF encodes a predicted 554 amino acid protein consisting of a B-box domain, a coiled-coil domain, and a PRY/SPRY domain. The protein sequence has 89.25% sequence identity with Anas platyrhynchos TRIM25, 78.57% with Gallus gallus TRIM25, and 46.92% with Homo sapiens TRIM25. TRIM25 is expressed in all gosling and adult goose tissues examined. QRT-PCR revealed that goose TRIM25 transcription could be induced by goose IFN- α , goose IFN- γ , and goose IFN- λ , as well as a35 s polyinosinic-polycytidylic acid (poly(I:C)), oligodeoxynucleotides 2006 (ODN 2006), and resiquimod (R848) in vitro; however, it is inhibited in H9N2 infected goslings for unknown reasons. These data suggest that goose TRIM25 might play a positive role in the regulation of the antiviral immune response.

TRIM25 Identification in the Chinese Goose: Gene Structure, Tissue Expression Profiles, and Antiviral Immune Responses In Vivo and In Vitro

PubMed Central

Zhou, Hao; Wang, Anqi; Sun, Lipei; Wang, Mingshu; Jia, Renyong; Zhu, Dekang; Liu, Mafeng; Yang, Qiao; Wu, Ying; Sun, Kunfeng; Chen, Xiaoyue

2016-01-01

The retinoic acid-inducible gene I (RIG-I) and the RIG-I-like receptor (RLR) protein play a critical role in the interferon (IFN) response during RNA virus infection. The tripartite motif containing 25 proteins (TRIM25) was reported to modify caspase activation and RIG-I recruitment domains (CARDs) via ubiquitin. These modifications allow TRIM25 to interact with mitochondrial antiviral signaling molecules (MAVs) and form CARD-CARD tetramers. Goose TRIM25 was cloned from gosling lungs, which possess a 1662 bp open reading flame (ORF). This ORF encodes a predicted 554 amino acid protein consisting of a B-box domain, a coiled-coil domain, and a PRY/SPRY domain. The protein sequence has 89.25% sequence identity with Anas platyrhynchos TRIM25, 78.57% with Gallus gallus TRIM25, and 46.92% with Homo sapiens TRIM25. TRIM25 is expressed in all gosling and adult goose tissues examined. QRT-PCR revealed that goose TRIM25 transcription could be induced by goose IFN-α, goose IFN-γ, and goose IFN-λ, as well as a35 s polyinosinic-polycytidylic acid (poly(I:C)), oligodeoxynucleotides 2006 (ODN 2006), and resiquimod (R848) in vitro; however, it is inhibited in H9N2 infected goslings for unknown reasons. These data suggest that goose TRIM25 might play a positive role in the regulation of the antiviral immune response. PMID:27995135

EDEM2 initiates mammalian glycoprotein ERAD by catalyzing the first mannose trimming step

PubMed Central

Ninagawa, Satoshi; Okada, Tetsuya; Sumitomo, Yoshiki; Kamiya, Yukiko; Kato, Koichi; Horimoto, Satoshi; Ishikawa, Tokiro; Takeda, Shunichi; Sakuma, Tetsushi; Yamamoto, Takashi

2014-01-01

Glycoproteins misfolded in the endoplasmic reticulum (ER) are subjected to ER-associated glycoprotein degradation (gpERAD) in which Htm1-mediated mannose trimming from the oligosaccharide Man8GlcNAc2 to Man7GlcNAc2 is the rate-limiting step in yeast. In contrast, the roles of the three Htm1 homologues (EDEM1/2/3) in mammalian gpERAD have remained elusive, with a key controversy being whether EDEMs function as mannosidases or as lectins. We therefore conducted transcription activator-like effector nuclease–mediated gene knockout analysis in human cell line and found that all endogenous EDEMs possess mannosidase activity. Mannose trimming from Man8GlcNAc2 to Man7GlcNAc2 is performed mainly by EDEM3 and to a lesser extent by EDEM1. Most surprisingly, the upstream mannose trimming from Man9GlcNAc2 to Man8GlcNAc2 is conducted mainly by EDEM2, which was previously considered to lack enzymatic activity. Based on the presence of two rate-limiting steps in mammalian gpERAD, we propose that mammalian cells double check gpERAD substrates before destruction by evolving EDEM2, a novel-type Htm1 homologue that catalyzes the first mannose trimming step from Man9GlcNAc2. PMID:25092655

Gas formation in ground beef chubs due to Hafnia alvei is reduced by multiple applications of antimicrobial interventions to artificially inoculated beef trim stock.

PubMed

Kang, Dong-Hyun; Arthur, Terrance M; Siragusa, Gregory R

2002-10-01

Gas-forming microorganisms were isolated from gas-swollen ground beef chubs obtained from a commercial source and were phenotypically identified as Hafnia alvei. In in situ experiments, the isolated H. alvei strains produced gas in inoculated irradiation-sterilized ground beef chubs. A five-strain cocktail of H. alvei isolates was inoculated on beef trim. The inoculated beef trim samples were treated with either a water wash (W) at 65 psi for five passes (a pass refers to the application of successive multiple antimicrobial treatments to inoculated beef trim on a moving processing conveyor belt at a speed of 1 cm/s under heat ducts or oscillating spray nozzles), W plus a 2% (vol/vol) lactic acid wash (L) at room temperature at 30 psi for three passes (W/L), or a combination treatment (COMB) consisting of W plus 82 degrees C water for three passes plus 510 degrees C hot air for six passes plus L, or were not treated (control). After treatment, the beef trim was ground and vacuum packaged. The numbers of H. alvei were reduced with water alone and with the aforementioned antimicrobial intervention treatments. For the untreated and inoculated control samples, the numbers of H. alvei increased from 7.03 to 8.40 log CFU/g after 7 days of incubation at 4 degrees C. However, the numbers of H. alvei treated by successive antimicrobial interventions (COMB) were initially reduced to 5.25 log CFU/g and increased to just 6.9 log CFU/g after 7 days of incubation at 4 degrees C. Gas was produced in untreated control samples after 3 days at 15 degrees C (15 of 15 inoculated chubs). However, in meat treated with W, W/L, and COMB, gas was produced after 4 to 5, 7 to 8, and 9 to 10 days of storage at 15 degrees C, respectively. These results demonstrate the effectiveness of multiple antimicrobial interventions in reducing H. alvei numbers on beef trim and subsequently delaying gas formation in the resulting ground beef chubs.

[Tripartite motif-containing protein 34 (TRIM34) colocalized with micronuclei chromosome and hampers its movement to equatorial plate during the metaphase stage of mitosis].

PubMed

Sun, Dakang; An, Xinye; Ji, Bing; Cheng, Yanli; Gao, Honglian; Tian, Mingming

2016-06-01

Objective To examine whether tripartite motif-containing protein 34 (TRIM34) is colocalized with micronuclei and investigate the influence on the movement of micronuclei chromosome in mitosis. Methods The eukaryotic expression vector TRIM34-pEGFP-N3 was constructed, identified and then transfected into HEK293T cells. With 4', 6-diamidino-2-phenylindole 2HCI (DAPI) staining, the colocalization between TRIM34 and micronuclei was observed under a fluorescence microscope. Moreover, MitoTracker(R)Deep Red was used to identify the colocalization between the complex of TRIM34-micronulei and mitochondria under a confocal microscope. Finally, the effect of TRIM34 on the movement of micronuclei chromosome in mitosis was examined. Results DNA sequencing confirmed that the vector TRIM34-pEGFP-N3 was constructed successfully. A fluorescence microscope revealed that TRIM34 could be colocalized with micronuclei in HEK293T cells transfected with TRIM34-pEGFP-N3. In the same manner, a confocal microscope distinctly showed that TRIM34 was colocalized with micronuclei similarly in appearance. However, there was no distinguished colocalization relationship between the complex of TRIM34-micronulei and mitochondria. Interestingly, the micronuclei chromosome conjugated with TRIM34 was hardly transferred to equatorial plate during the metaphase stage of mitosis. Conclusion TRIM34 is colocalized with micronuclei chromosome and hampers its movement to equatorial plate in mitosis.

Ubiquitylation by Trim32 causes coupled loss of desmin, Z-bands, and thin filaments in muscle atrophy

PubMed Central

Cohen, Shenhav; Zhai, Bo; Gygi, Steven P.

2012-01-01

During muscle atrophy, myofibrillar proteins are degraded in an ordered process in which MuRF1 catalyzes ubiquitylation of thick filament components (Cohen et al. 2009. J. Cell Biol. http://dx.doi.org/10.1083/jcb.200901052). Here, we show that another ubiquitin ligase, Trim32, ubiquitylates thin filament (actin, tropomyosin, troponins) and Z-band (α-actinin) components and promotes their degradation. Down-regulation of Trim32 during fasting reduced fiber atrophy and the rapid loss of thin filaments. Desmin filaments were proposed to maintain the integrity of thin filaments. Accordingly, we find that the rapid destruction of thin filament proteins upon fasting was accompanied by increased phosphorylation of desmin filaments, which promoted desmin ubiquitylation by Trim32 and degradation. Reducing Trim32 levels prevented the loss of both desmin and thin filament proteins. Furthermore, overexpression of an inhibitor of desmin polymerization induced disassembly of desmin filaments and destruction of thin filament components. Thus, during fasting, desmin phosphorylation increases and enhances Trim32-mediated degradation of the desmin cytoskeleton, which appears to facilitate the breakdown of Z-bands and thin filaments. PMID:22908310

14 CFR 25.255 - Out-of-trim characteristics.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Out-of-trim characteristics. 25.255 Section 25.255 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT... the positive and negative values specified in paragraph (c) of this section— (1) The stick force vs. g...

14 CFR 25.255 - Out-of-trim characteristics.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Out-of-trim characteristics. 25.255 Section 25.255 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT... the positive and negative values specified in paragraph (c) of this section— (1) The stick force vs. g...

Crystal structure of the TRIM25 B30.2 (PRYSPRY) domain: a key component of antiviral signalling.

PubMed

D'Cruz, Akshay A; Kershaw, Nadia J; Chiang, Jessica J; Wang, May K; Nicola, Nicos A; Babon, Jeffrey J; Gack, Michaela U; Nicholson, Sandra E

2013-12-01

TRIM (tripartite motif) proteins primarily function as ubiquitin E3 ligases that regulate the innate immune response to infection. TRIM25 [also known as Efp (oestrogen-responsive finger protein)] has been implicated in the regulation of oestrogen receptor α signalling and in the regulation of innate immune signalling via RIG-I (retinoic acid-inducible gene-I). RIG-I senses cytosolic viral RNA and is subsequently ubiquitinated by TRIM25 at its N-terminal CARDs (caspase recruitment domains), leading to type I interferon production. The interaction with RIG-I is dependent on the TRIM25 B30.2 domain, a protein-interaction domain composed of the PRY and SPRY tandem sequence motifs. In the present study we describe the 1.8 Å crystal structure of the TRIM25 B30.2 domain, which exhibits a typical B30.2/SPRY domain fold comprising two N-terminal α-helices, thirteen β-strands arranged into two β-sheets and loop regions of varying lengths. A comparison with other B30.2/SPRY structures and an analysis of the loop regions identified a putative binding pocket, which is likely to be involved in binding target proteins. This was supported by mutagenesis and functional analyses, which identified two key residues (Asp(488) and Trp(621)) in the TRIM25 B30.2 domain as being critical for binding to the RIG-I CARDs.

Crystal structure of the TRIM25 B30.2 (PRYSPRY) domain: a key component of antiviral signalling

PubMed Central

D'Cruz, Akshay A.; Kershaw, Nadia J.; Chiang, Jessica J.; Wang, May K.; Nicola, Nicos A.; Babon, Jeffrey J.; Gack, Michaela U.; Nicholson, Sandra E.

2014-01-01

TRIM (tripartite motif) proteins primarily function as ubiquitin E3 ligases that regulate the innate immune response to infection. TRIM25 [also known as Efp (oestrogen-responsive finger protein)] has been implicated in the regulation of oestrogen receptor α signalling and in the regulation of innate immune signalling via RIG-I (retinoic acid-inducible gene-I). RIG-I senses cytosolic viral RNA and is subsequently ubiquitinated by TRIM25 at its N-terminal CARDs (caspase recruitment domains), leading to type I interferon production. The interaction with RIG-I is dependent on the TRIM25 B30.2 domain, a protein-interaction domain composed of the PRY and SPRY tandem sequence motifs. In the present study we describe the 1.8 Å crystal structure of the TRIM25 B30.2 domain, which exhibits a typical B30.2/SPRY domain fold comprising two N-terminal α-helices, thirteen β-strands arranged into two β-sheets and loop regions of varying lengths. A comparison with other B30.2/SPRY structures and an analysis of the loop regions identified a putative binding pocket, which is likely to be involved in binding target proteins. This was supported by mutagenesis and functional analyses, which identified two key residues (Asp488 and Trp621) in the TRIM25 B30.2 domain as being critical for binding to the RIG-I CARDs. PMID:24015671

TRIM79α, an interferon-stimulated gene product, restricts tick-borne encephalitis virus replication by degrading the viral RNA polymerase

PubMed Central

Taylor, R. Travis; Lubick, Kirk J.; Robertson, Shelly J.; Broughton, James P.; Bloom, Marshall E.; Bresnahan, Wade A.; Best, Sonja M.

2011-01-01

In response to virus infection, type I interferons (IFNs) induce several genes, most of whose functions are largely unknown. Here we show that the tripartite motif (TRIM) protein, TRIM79α, is an IFN-stimulated gene (ISG) product that specifically targets tick-borne encephalitis virus (TBEV), a Flavivirus that causes encephalitides in humans. TRIM79α restricts TBEV replication by mediating lysosome-dependent degradation of the flavivirus NS5 protein, an RNA-dependent RNA polymerase essential for virus replication. NS5 degradation was specific to tick-borne flaviviruses as TRIM79α did not recognize NS5 from West Nile virus (WNV) or inhibit WNV replication. In the absence of TRIM79α, IFN-β was less effective in inhibiting tick-borne flavivirus infection of mouse macrophages, highlighting the importance of a single virus-specific ISG in establishing an antiviral state. The specificity of TRIM79α for TBEV reveals a remarkable ability of the innate IFN response to discriminate between closely related flaviviruses. PMID:21925107

Astronaut Owen Garriott trims hair of Astronaut Alan Bean

NASA Technical Reports Server (NTRS)

1973-01-01

Scientist-Astronaut Owen K. Garriott, Skylab 3 science pilot, trims the hair of Astronaut Alan L. Bean, commander, in this on-board photograph from the Skylab Orbital Workshop (OWS). Bean holds a vacuum hose to gather in loose hair.

33 CFR 401.30 - Ballast water and trim.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Ballast water and trim. 401.30... OF TRANSPORTATION SEAWAY REGULATIONS AND RULES Regulations Seaway Navigation § 401.30 Ballast water... exclusive economic zone must agree to comply with the “Code of Best Practices for Ballast Water Management...

33 CFR 401.30 - Ballast water and trim.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Ballast water and trim. 401.30... OF TRANSPORTATION SEAWAY REGULATIONS AND RULES Regulations Seaway Navigation § 401.30 Ballast water... exclusive economic zone must agree to comply with the “Code of Best Practices for Ballast Water Management...

33 CFR 401.30 - Ballast water and trim.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Ballast water and trim. 401.30... OF TRANSPORTATION SEAWAY REGULATIONS AND RULES Regulations Seaway Navigation § 401.30 Ballast water... exclusive economic zone must agree to comply with the “Code of Best Practices for Ballast Water Management...

TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity.

PubMed

Gack, Michaela U; Shin, Young C; Joo, Chul-Hyun; Urano, Tomohiko; Liang, Chengyu; Sun, Lijun; Takeuchi, Osamu; Akira, Shizuo; Chen, Zhijian; Inoue, Satoshi; Jung, Jae U

2007-04-19

Retinoic-acid-inducible gene-I (RIG-I; also called DDX58) is a cytosolic viral RNA receptor that interacts with MAVS (also called VISA, IPS-1 or Cardif) to induce type I interferon-mediated host protective innate immunity against viral infection. Furthermore, members of the tripartite motif (TRIM) protein family, which contain a cluster of a RING-finger domain, a B box/coiled-coil domain and a SPRY domain, are involved in various cellular processes, including cell proliferation and antiviral activity. Here we report that the amino-terminal caspase recruitment domains (CARDs) of RIG-I undergo robust ubiquitination induced by TRIM25 in mammalian cells. The carboxy-terminal SPRY domain of TRIM25 interacts with the N-terminal CARDs of RIG-I; this interaction effectively delivers the Lys 63-linked ubiquitin moiety to the N-terminal CARDs of RIG-I, resulting in a marked increase in RIG-I downstream signalling activity. The Lys 172 residue of RIG-I is critical for efficient TRIM25-mediated ubiquitination and for MAVS binding, as well as the ability of RIG-I to induce antiviral signal transduction. Furthermore, gene targeting demonstrates that TRIM25 is essential not only for RIG-I ubiquitination but also for RIG-I-mediated interferon- production and antiviral activity in response to RNA virus infection. Thus, we demonstrate that TRIM25 E3 ubiquitin ligase induces the Lys 63-linked ubiquitination of RIG-I, which is crucial for the cytosolic RIG-I signalling pathway to elicit host antiviral innate immunity.

Real-time value optimization of edging and trimming operations for rough, green hardwood lumber

Treesearch

Daniel L. Schmoldt; Hang Song; Philip A. Araman

2001-01-01

For edging/trimming operations in hardwood sawmills, an operator examines both sides—or just the waney-edged side—of each board, and makes a quick assessment of grade potential. The operator then decides where to edge and/or trim the board to achieve the intended grade and, presumably, maximum value. However, human operators can only achieve lumber values that are 62-...

14 CFR 23.255 - Out of trim characteristics.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Out of trim characteristics. 23.255 Section 23.255 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT... force versus g curve must have a positive slope at any speed up to and including VFC/MFC; and (2) At...

Effects of two trimming methods of dairy cattle on concrete or rubber-covered slatted floors.

PubMed

Ouweltjes, W; Holzhauer, M; van der Tol, P P J; van der Werf, J

2009-03-01

This study monitored claw health, claw conformation, locomotion, activity, and step traits of cows from a single dairy herd that were trimmed according to the standard Dutch method or with an alternative "concave" trimming method. Half of the cows were kept in a stall section with concrete slatted floors in the alleys. The other cows were kept in a pen within the same housing with an identical concrete slatted floor in the alleys, but with a rubber top layer. All experimental cows were kept in the same environment for at least 3 mo before and after trimming. It was hypothesized that trimming for more-concave soles (i.e., with 3 to 5 mm of sole dug out under the claw bone) was preferred to the standard Dutch trimming with flat sole surfaces for cows kept in stalls with soft alley floors. None of the claw health or locomotion traits differed for the trimming methods. No interactions were found between flooring and trimming method. Floor effects were significant for several traits. Cows on the rubber-topped floors had significantly fewer sole hemorrhages (prevalence of 22 vs. 48% in mo 3) and larger claws (claw length 76.1 +/- 5.0 vs. 72.5 +/- 4.9 mm; heel height 49.3 +/- 6.3 vs. 46.0 +/- 6.4 mm; claw diagonal 129 +/- 6.4 vs. 125 +/- 6.9 mm), spent more time standing in the alleys (55.4 +/- 2.8 vs. 49.6 +/- 2.8%), and had higher activity (61.0 +/- 3.7 vs. 53.0 +/- 3.7 steps/h). This suggests greater claw comfort on rubber flooring compared with concrete flooring. Kinetic patterns during claw-floor contact while walking were similar for all treatments. During the double-support (stance) phase, claw-floor contact area increased to a maximum in the first 30% of double-support phase time, remained more or less stable until 80% of double-support phase time, and sharply decreased as the animal pushed off as shown by the change in center of pressure. A gradual change of center of pressure in the medial direction during double-support phase time was shown. The research

Paramyxovirus V Proteins Interact with the RIG-I/TRIM25 Regulatory Complex and Inhibit RIG-I Signaling.

PubMed

Sánchez-Aparicio, Maria T; Feinman, Leighland J; García-Sastre, Adolfo; Shaw, Megan L

2018-03-15

Paramyxovirus V proteins are known antagonists of the RIG-I-like receptor (RLR)-mediated interferon induction pathway, interacting with and inhibiting the RLR MDA5. We report interactions between the Nipah virus V protein and both RIG-I regulatory protein TRIM25 and RIG-I. We also observed interactions between these host proteins and the V proteins of measles virus, Sendai virus, and parainfluenza virus. These interactions are mediated by the conserved C-terminal domain of the V protein, which binds to the tandem caspase activation and recruitment domains (CARDs) of RIG-I (the region of TRIM25 ubiquitination) and to the SPRY domain of TRIM25, which mediates TRIM25 interaction with the RIG-I CARDs. Furthermore, we show that V interaction with TRIM25 and RIG-I prevents TRIM25-mediated ubiquitination of RIG-I and disrupts downstream RIG-I signaling to the mitochondrial antiviral signaling protein. This is a novel mechanism for innate immune inhibition by paramyxovirus V proteins, distinct from other known V protein functions such as MDA5 and STAT1 antagonism. IMPORTANCE The host RIG-I signaling pathway is a key early obstacle to paramyxovirus infection, as it results in rapid induction of an antiviral response. This study shows that paramyxovirus V proteins interact with and inhibit the activation of RIG-I, thereby interrupting the antiviral signaling pathway and facilitating virus replication. Copyright © 2018 American Society for Microbiology.

Dairy cows change locomotion score and sensitivity to pain with trimming and infectious or non-infectious lesions.

PubMed

Passos, L T; Cruz, E A da; Fischer, V; Porciuncula, G C da; Werncke, D; Dalto, A G C; Stumpf, M T; Vizzotto, E F; da Silveira, I D B

2017-04-01

Lameness can negatively affect production, but there is still controversy about the perception of pain in dairy cows. This study aimed to verify the effects of hoof affections in dairy cows on locomotion score, physiological attributes, pressure nociceptive threshold, and thermographic variables, as well as assess improvement on these variables after corrective trimming and treatment. Thirty-four lame lactating cows were gait-scored, and all cows with locomotion score ≥4 were retained for this study 1 day before trimming. Lame cows were diagnosed, pressure nociceptive threshold at sound, and affected hooves were measured, thermographic images were recorded, and physiological attributes were evaluated. Hooves with lesions were trimmed and treated and cows were re-evaluated 1 week after such procedures. The experimental design was a completely randomized design. Each cow was considered an experimental unit and traits were analyzed using paired t test, linear correlation, and linear regression. Digital and interdigital dermatitis were classified as infectious diseases while laminitis sequels, sole ulcers, and white line were classified as non-infectious diseases. After 1 week, the locomotion score was reduced on average in 1.5 points. Trimming increased the pressure nociceptive threshold for cows with non-infectious affections while tended to increase the pressure nociceptive threshold for cows with infectious affections. Physiological attributes and thermographic values did not change with trimming. Trimming and treatment have benefic effects on animal welfare as gait is improved and sensitivity to pain is reduced.

Effect of irradiation of frozen meat/fat trimmings on microbiological and physicochemical quality attributes of dry fermented sausages.

PubMed

Chouliara, I; Samelis, J; Kakouri, A; Badeka, A; Savvaidis, I N; Riganakos, K; Kontominas, M G

2006-10-01

Changes in microbiological and physicochemical quality attributes resulting from the use of irradiation in the production of Greek dry fermented sausage were investigated as a function of fermentation/ripening time. Results showed that irradiating meat/fat trimmings at 2 or 4kGy prior to sausage production eliminated natural contamination with Listeria spp., and reduced pseudomonads, enterococci and pathogenic staphylococci, and enterobacteria, to less than 2 and 1logcfug(-1), respectively. Pseudomonads were very sensitive (>3.4 log reduction) to either radiation dose. Yeasts were the most resistant followed by inherent lactic acid bacteria; their reductions on the trimmings were radiation dose-dependent. Residual effects of irradiation were noted against enterococci, but not against gram-negatives which died off fast during fermentation even in non-irradiated samples. Growth of the starter bacteria, Lactobacillus pentosus and Staphylococcus carnosus, inoculated in the sausage batters post-irradiation was unaffected by the 2 or 4kGy pre-treatment of the trimmings. Irradiation had little or no effect at the end of ripening period (28 days) on pH, moisture content and color (parameters L(∗), a(∗), and b(∗)). Changes in TBA values were small but statistically significant with irradiated samples having higher TBA values than control samples.

Trim25 Is an RNA-Specific Activator of Lin28a/TuT4-Mediated Uridylation

PubMed Central

Choudhury, Nila Roy; Nowak, Jakub S.; Zuo, Juan; Rappsilber, Juri; Spoel, Steven H.; Michlewski, Gracjan

2014-01-01

Summary RNA binding proteins have thousands of cellular RNA targets and often exhibit opposite or passive molecular functions. Lin28a is a conserved RNA binding protein involved in pluripotency and tumorigenesis that was previously shown to trigger TuT4-mediated pre-let-7 uridylation, inhibiting its processing and targeting it for degradation. Surprisingly, despite binding to other pre-microRNAs (pre-miRNAs), only pre-let-7 is efficiently uridylated by TuT4. Thus, we hypothesized the existence of substrate-specific cofactors that stimulate Lin28a-mediated pre-let-7 uridylation or restrict its functionality on non-let-7 pre-miRNAs. Through RNA pull-downs coupled with quantitative mass spectrometry, we identified the E3 ligase Trim25 as an RNA-specific cofactor for Lin28a/TuT4-mediated uridylation. We show that Trim25 binds to the conserved terminal loop (CTL) of pre-let-7 and activates TuT4, allowing for more efficient Lin28a-mediated uridylation. These findings reveal that protein-modifying enzymes, only recently shown to bind RNA, can guide the function of canonical ribonucleoprotein (RNP) complexes in cis, thereby providing an additional level of specificity. PMID:25457611

Identification of a second binding site on the TRIM25 B30.2 domain.

PubMed

D'Cruz, Akshay A; Kershaw, Nadia J; Hayman, Thomas J; Linossi, Edmond M; Chiang, Jessica J; Wang, May K; Dagley, Laura F; Kolesnik, Tatiana B; Zhang, Jian-Guo; Masters, Seth L; Griffin, Michael D W; Gack, Michaela U; Murphy, James M; Nicola, Nicos A; Babon, Jeffrey J; Nicholson, Sandra E

2018-01-23

The r etinoic acid- i nducible g ene- I (RIG-I) receptor recognizes short 5'-di- and triphosphate base-paired viral RNA and is a critical mediator of the innate immune response against viruses such as influenza A, Ebola, HIV and hepatitis C. This response is reported to require an orchestrated interaction with the tri partite m otif 25 (TRIM25) B30.2 protein-interaction domain. Here, we present a novel second RIG-I-binding interface on the TRIM25 B30.2 domain that interacts with CARD1 and CARD2 ( c aspase a ctivation and r ecruitment d omains) of RIG-I and is revealed by the removal of an N-terminal α-helix that mimics dimerization of the full-length protein. Further characterization of the TRIM25 coiled-coil and B30.2 regions indicated that the B30.2 domains move freely on a flexible tether, facilitating RIG-I CARD recruitment. The identification of a dual binding mode for the TRIM25 B30.2 domain is a first for the SPRY/B30.2 domain family and may be a feature of other SPRY/B30.2 family members. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Intracellular disposal of incompletely folded human alpha1-antitrypsin involves release from calnexin and post-translational trimming of asparagine-linked oligosaccharides.

PubMed

Liu, Y; Choudhury, P; Cabral, C M; Sifers, R N

1997-03-21

Protection of lung elastin fibers from proteolytic destruction is compromised by inefficient secretion of incompletely folded allelic variants of human alpha1-antitrypsin from hepatocytes. Pulse-chase radiolabeling with [35S]methionine and sucrose gradient sedimentation and coimmunoprecipitation techniques were employed to investigate quality control of human alpha1-antitrypsin secretion from stably transfected mouse hepatoma cells. The secretion-incompetent variant null(Hong Kong) (Sifers, R. N., Brashears-Macatee, S., Kidd, V. J., Muensch, H., and Woo, S. L. C. (1988) J. Biol. Chem. 263, 7330-7335) cannot fold into a functional conformation and was quantitatively associated with the molecular chaperone calnexin following biosynthesis. Assembly with calnexin required cotranslational trimming of glucose from asparagine-linked oligosaccharides. Intracellular disposal of pulse-radiolabeled molecules coincided with their release from calnexin. Released monomers and intracellular disposal were nonexistent in cells chased with cycloheximide, an inhibitor of protein synthesis. Post-translational trimming of asparagine-linked oligosaccharides and intracellular disposal were abrogated by 1-deoxymannojirimycin, an inhibitor of alpha-mannosidase activity, without affecting the monomer population. The data are consistent with a recently proposed quality control model (Hammond, C., Braakman, I., and Helenius, A. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 913-917) in which intracellular disposal requires dissociation from calnexin and post-translational trimming of mannose from asparagine-linked oligosaccharides.

14 CFR 23.145 - Longitudinal control.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Longitudinal control. 23.145 Section 23.145... Maneuverability § 23.145 Longitudinal control. (a) With the airplane as nearly as possible in trim at 1.3 VS1, it... application of single-handed control forces exceeding those specified in § 23.143(c). The trimming controls...

14 CFR 23.145 - Longitudinal control.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Longitudinal control. 23.145 Section 23.145... Maneuverability § 23.145 Longitudinal control. (a) With the airplane as nearly as possible in trim at 1.3 VS1, it... application of single-handed control forces exceeding those specified in § 23.143(c). The trimming controls...

14 CFR 23.145 - Longitudinal control.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Longitudinal control. 23.145 Section 23.145... Maneuverability § 23.145 Longitudinal control. (a) With the airplane as nearly as possible in trim at 1.3 VS1, it... application of single-handed control forces exceeding those specified in § 23.143(c). The trimming controls...

14 CFR 25.145 - Longitudinal control.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Longitudinal control. 25.145 Section 25.145... control. (a) It must be possible, at any point between the trim speed prescribed in § 25.103(b)(6) and..., no change in trim control, or exertion of more than 50 pounds control force (representative of the...

14 CFR 25.145 - Longitudinal control.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Longitudinal control. 25.145 Section 25.145... control. (a) It must be possible, at any point between the trim speed prescribed in § 25.103(b)(6) and..., no change in trim control, or exertion of more than 50 pounds control force (representative of the...

14 CFR 23.145 - Longitudinal control.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Longitudinal control. 23.145 Section 23.145... Maneuverability § 23.145 Longitudinal control. (a) With the airplane as nearly as possible in trim at 1.3 VS1, it... application of single-handed control forces exceeding those specified in § 23.143(c). The trimming controls...

Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma

PubMed Central

Naruto, Takuya; Kohmoto, Tomohiro; Watabnabe, Miki; Tsuboi, Mitsuhiro; Takizawa, Hiromitsu; Kondo, Kazuya; Tangoku, Akira; Imoto, Issei

2017-01-01

In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG. TRIM58 was robustly silenced by hypermethylation even in early-stage primary LADC, and the restoration of TRIM58 expression in LADC cell lines inhibited cell growth in vitro and in vivo in anchorage-dependent and -independent manners. Our findings suggest that aberrant inactivation of TRIM58 consequent to CGI hypermethylation might stimulate the early carcinogenesis of LADC regardless of smoking status; furthermore, TRIM58 methylation might be a possible early diagnostic and epigenetic therapeutic target in LADC. PMID:27926516

Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma.

PubMed

Kajiura, Koichiro; Masuda, Kiyoshi; Naruto, Takuya; Kohmoto, Tomohiro; Watabnabe, Miki; Tsuboi, Mitsuhiro; Takizawa, Hiromitsu; Kondo, Kazuya; Tangoku, Akira; Imoto, Issei

2017-01-10

In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG. TRIM58 was robustly silenced by hypermethylation even in early-stage primary LADC, and the restoration of TRIM58 expression in LADC cell lines inhibited cell growth in vitro and in vivo in anchorage-dependent and -independent manners. Our findings suggest that aberrant inactivation of TRIM58 consequent to CGI hypermethylation might stimulate the early carcinogenesis of LADC regardless of smoking status; furthermore, TRIM58 methylation might be a possible early diagnostic and epigenetic therapeutic target in LADC.

14 CFR 23.145 - Longitudinal control.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Maneuverability § 23.145 Longitudinal control. (a) With the airplane as nearly as possible in trim at 1.3 VS1, it must be possible, at speeds below the trim speed, to pitch the nose downward so that the rate of increase in airspeed allows prompt acceleration to the trim speed with— (1) Maximum continuous power on...

Microbial degradation and humification of the lawn care pesticide 2,4-dichlorophenoxyacetic acid during the composting of yard trimmings.

PubMed Central

Michel, F C; Reddy, C A; Forney, L J

1995-01-01

The fate of the widely used lawn care herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) during the composting of yard trimmings consisting of primarily leaves and grass is an important unexplored question. In this study, we determined the extent of 2,4-D mineralization, incorporation into humic matter, volatilization, and sorption during the composting of yard trimmings. Yard trimmings (2:1 [wt/wt] leaves-grass) were amended with 14C-ring-labeled 2,4-D (17 mg/kg of dry weight) and composted in a temperature-controlled laboratory scale compost system. During composting, thermophilic microbes were numerically dominant, reaching a maximum of 2 x 10(11)/g. At the end of composting, 46% of the organic matter (OM) present in the yard trimmings was lost and the compost was stable, with an oxygen uptake rate of 0.09 mg of O2 per g of OM per h, and was well humified (humification index, 0.39). Mineralization of the OM temporally paralleled mineralization of 2,4-D. In the final compost, 47% of the added 2,4-D carbon was mineralized, about 23% was complexed with high-molecular-weight humic acids, and about 20% was not extractable (humin fraction). Less than 1% of the added 14C was present in water expressed from the finished compost, suggesting a low potential for leaching of 2,4-D. Very little volatilization of 2,4-D occurred during composting. It is of interest that our results indicate active mineralization of 2,4-D at composting temperatures of 60 degrees C because microbial 2,4-D degradation at thermophilic temperatures has not been previously documented. PMID:7618868

Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I.

PubMed

Gack, Michaela Ulrike; Albrecht, Randy Allen; Urano, Tomohiko; Inn, Kyung-Soo; Huang, I-Chueh; Carnero, Elena; Farzan, Michael; Inoue, Satoshi; Jung, Jae Ung; García-Sastre, Adolfo

2009-05-08

The ubiquitin ligase TRIM25 mediates Lysine 63-linked ubiquitination of the N-terminal CARD domains of the viral RNA sensor RIG-I to facilitate type I interferon (IFN) production and antiviral immunity. Here, we report that the influenza A virus nonstructural protein 1 (NS1) specifically inhibits TRIM25-mediated RIG-I CARD ubiquitination, thereby suppressing RIG-I signal transduction. A novel domain in NS1 comprising E96/E97 residues mediates its interaction with the coiled-coil domain of TRIM25, thus blocking TRIM25 multimerization and RIG-I CARD domain ubiquitination. Furthermore, a recombinant influenza A virus expressing an E96A/E97A NS1 mutant is defective in blocking TRIM25-mediated antiviral IFN response and loses virulence in mice. Our findings reveal a mechanism by which influenza virus inhibits host IFN response and also emphasize the vital role of TRIM25 in modulating antiviral defenses.

SeqTrim: a high-throughput pipeline for pre-processing any type of sequence read

PubMed Central

2010-01-01

Background High-throughput automated sequencing has enabled an exponential growth rate of sequencing data. This requires increasing sequence quality and reliability in order to avoid database contamination with artefactual sequences. The arrival of pyrosequencing enhances this problem and necessitates customisable pre-processing algorithms. Results SeqTrim has been implemented both as a Web and as a standalone command line application. Already-published and newly-designed algorithms have been included to identify sequence inserts, to remove low quality, vector, adaptor, low complexity and contaminant sequences, and to detect chimeric reads. The availability of several input and output formats allows its inclusion in sequence processing workflows. Due to its specific algorithms, SeqTrim outperforms other pre-processors implemented as Web services or standalone applications. It performs equally well with sequences from EST libraries, SSH libraries, genomic DNA libraries and pyrosequencing reads and does not lead to over-trimming. Conclusions SeqTrim is an efficient pipeline designed for pre-processing of any type of sequence read, including next-generation sequencing. It is easily configurable and provides a friendly interface that allows users to know what happened with sequences at every pre-processing stage, and to verify pre-processing of an individual sequence if desired. The recommended pipeline reveals more information about each sequence than previously described pre-processors and can discard more sequencing or experimental artefacts. PMID:20089148

Influenza A virus TRIMs the type I interferon response.

PubMed

Ludwig, Stephan; Wolff, Thorsten

2009-05-08

The virulence of many pathogenic viruses depends on suppression of the innate type I interferon defense. For influenza viruses, a unique strategy has now been unraveled, as the viral nonstructural protein 1 was shown to inhibit activation of the pathogen recognition receptor RIG-I by binding the ubiquitin ligase TRIM25.

Aircraft interior noise models - Sidewall trim, stiffened structures, and cabin acoustics with floor partition

NASA Technical Reports Server (NTRS)

Pope, L. D.; Wilby, E. G.; Willis, C. M.; Mayes, W. H.

1983-01-01

As part of the continuing development of an aircraft interior noise prediction model, in which a discrete modal representation and power flow analysis are used, theoretical results are considered for inclusion of sidewall trim, stiffened structures, and cabin acoustics with floor partition. For validation purposes, predictions of the noise reductions for three test articles (a bare ring-stringer stiffened cylinder, an unstiffened cylinder with floor and insulation, and a ring-stringer stiffened cylinder with floor and sidewall trim) are compared with measurements.

Computing Trimmed, Mean-Camber Surfaces At Minimum Drag

NASA Technical Reports Server (NTRS)

Lamar, John E.; Hodges, William T.

1995-01-01

VLMD computer program determines subsonic mean-camber surfaces of trimmed noncoplanar planforms with minimum vortex drag at specified lift coefficient. Up to two planforms designed together. Method used that of subsonic vortex lattice method of chord loading specification, ranging from rectangular to triangular, left specified by user. Program versatile and applied to isolated wings, wing/canard configurations, tandem wing, and wing/-winglet configuration. Written in FORTRAN.

Advanced control concepts. [for shuttle ascent vehicles

NASA Technical Reports Server (NTRS)

Sharp, J. B.; Coppey, J. M.

1973-01-01

The problems of excess control devices and insufficient trim control capability on shuttle ascent vehicles were investigated. The trim problem is solved at all time points of interest using Lagrangian multipliers and a Simplex based iterative algorithm developed as a result of the study. This algorithm has the capability to solve any bounded linear problem with physically realizable constraints, and to minimize any piecewise differentiable cost function. Both solution methods also automatically distribute the command torques to the control devices. It is shown that trim requirements are unrealizable if only the orbiter engines and the aerodynamic surfaces are used.

Polyubiquitin conjugation to NEMO by triparite motif protein 23 (TRIM23) is critical in antiviral defense

PubMed Central

Arimoto, Kei-ichiro; Funami, Kenji; Saeki, Yasushi; Tanaka, Keiji; Okawa, Katsuya; Takeuchi, Osamu; Akira, Shizuo; Murakami, Yoshiki; Shimotohno, Kunitada

2010-01-01

The rapid induction of type I IFN is a central event of the innate defense against viral infections and is tightly regulated by a number of cellular molecules. Viral components induce strong type I IFN responses through the activation of toll-like receptors (TLRs) and intracellular cytoplasmic receptors such as an RNA helicase RIG-I and/or MDA5. According to recent studies, the NF-κB essential modulator (NEMO, also called IKKγ) is crucial for this virus-induced antiviral response. However, the precise roles of signal activation by NEMO adaptor have not been elucidated. Here, we show that virus-induced IRF3 and NF-κB activation depends on the K(lys)-27-linked polyubiquitination to NEMO by the novel ubiquitin E3 ligase triparite motif protein 23 (TRIM23). Virus-induced IRF3 and NF-κB activation, as well as K27-linked NEMO polyubiquitination, were abrogated in TRIM23 knockdown cells, whereas TRIM23 knockdown had no effect on TNFα-mediated NF-κB activation. Furthermore, in NEMO-deficient mouse embryo fibroblast cells, IFN-stimulated response element-driven reporter activity was restored by ectopic expression of WT NEMO, as expected, but only partial recovery by NEMO K165/309/325/326/344R multipoints mutant on which TRIM23-mediated ubiquitin conjugation was substantially reduced. Thus, we conclude that TRIM23-mediated ubiquitin conjugation to NEMO is essential for TLR3- and RIG-I/MDA5-mediated antiviral innate and inflammatory responses. PMID:20724660

The HUSH complex cooperates with TRIM28 to repress young retrotransposons and new genes.

PubMed

Robbez-Masson, Luisa; Tie, Christopher H C; Conde, Lucia; Tunbak, Hale; Husovsky, Connor; Tchasovnikarova, Iva A; Timms, Richard T; Herrero, Javier; Lehner, Paul J; Rowe, Helen M

2018-05-04

Retrotransposons encompass half of the human genome and contribute to the formation of heterochromatin, which provides nuclear structure and regulates gene expression. Here, we asked if the human silencing hub (HUSH) complex is necessary to silence retrotransposons and whether it collaborates with TRIM28 and the chromatin remodeler ATRX at specific genomic loci. We show that the HUSH complex contributes to de novo repression and DNA methylation of a SVA retrotransposon reporter. By using naïve vs. primed mouse pluripotent stem cells, we reveal a critical role for the HUSH complex in naïve cells, implicating it in programming epigenetic marks in development. While the HUSH component FAM208A binds to endogenous retroviruses (ERVs) and long interspersed element-1s (LINE-1s or L1s), it is mainly required to repress evolutionarily young L1s (mouse-specific lineages less than 5 million years old). TRIM28, in contrast, is necessary to repress both ERVs and young L1s. Genes co-repressed by TRIM28 and FAM208A are evolutionarily young, or exhibit tissue-specific expression, are enriched in young L1s and display evidence for regulation through LTR promoters. Finally, we demonstrate that the HUSH complex is also required to repress L1 elements in human cells. Overall, these data indicate that the HUSH complex and TRIM28 co-repress young retrotransposons and new genes rewired by retrotransposon non-coding DNA. Published by Cold Spring Harbor Laboratory Press.

Solid-state anaerobic co-digestion of spent mushroom substrate with yard trimmings and wheat straw for biogas production.

PubMed

Lin, Yunqin; Ge, Xumeng; Li, Yebo

2014-10-01

Spent mushroom substrate (SMS) is a biomass waste generated from mushroom production. About 5 kg of SMS is generated for every kg of mushroom produced. In this study, solid state anaerobic digestion (SS-AD) of SMS, wheat straw, yard trimmings, and their mixtures was investigated at different feedstock to effluent ratios. SMS was found to be highly degradable, which resulted in inhibition of SS-AD due to volatile fatty acid (VFA) accumulation and a decrease in pH. This issue was addressed by co-digestion of SMS with either yard trimmings or wheat straw. SS-AD of SMS/yard trimmings achieved a cumulative methane yield of 194 L/kg VS, which was 16 and 2 times higher than that from SMS and yard trimmings, respectively. SS-AD of SMS/wheat straw obtained a cumulative methane yield of 269 L/kg VS, which was 23 times as high as that from SMS and comparable to that from wheat straw. Copyright © 2014 Elsevier Ltd. All rights reserved.

TRIM25 is associated with cisplatin resistance in non-small-cell lung carcinoma A549 cell line via downregulation of 14-3-3σ.

PubMed

Qin, Xia; Qiu, Feng; Zou, Zhen

2017-11-04

Lung cancer, in particular, non-small cell lung cancer (NSCLC), is the leading cause of cancer-related mortality. Cis-Diamminedichloroplatinum (cisplatin, CDDP) as first-line chemotherapy for NSCLC, but resistance occurs frequently. We previously reported that Tripartite motif protein 25 (TRIM25) was highly expressed in cisplatin-resistant human lung adenocarcinoma A549 cells (A549/CDDP) in comparison with its parental A549 cells. Herein, we take a further step to demonstrate the association of TRIM25 and cisplatin resistance and also the underlying mechanisms. Knockdown of TRIM25 by RNA interference in A549/CDDP cells decreased half maximal inhibitory concentration (IC 50 ) values and promoted apoptosis in response to cisplatin, whereas overexpression of TRIM25 had opposite effects. More importantly, we found that concomitant knockdown of 14-3-3σ and TRIM25 absolutely reversed the decreased MDM2, increased p53, increased cleaved-Capsese3 and decreased IC 50 value induced by knockdown of TRIM25 individually, suggesting that TRIM25 mediated cisplatin resistance primarily through downregulation of 14-3-3σ. Our results indicate that TRIM25 is associated with cisplatin resistance and 14-3-3σ-MDM2-p53 signaling pathway is involved in this process, suggesting targeting TRIM25 may be a potential strategy for the reversal of cisplatin resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

Trimming algorithm of frequency modulation for CIAE-230 MeV proton superconducting synchrocyclotron model cavity

NASA Astrophysics Data System (ADS)

Li, Pengzhan; Zhang, Tianjue; Ji, Bin; Hou, Shigang; Guo, Juanjuan; Yin, Meng; Xing, Jiansheng; Lv, Yinlong; Guan, Fengping; Lin, Jun

2017-01-01

A new project, the 230 MeV proton superconducting synchrocyclotron for cancer therapy, was proposed at CIAE in 2013. A model cavity is designed to verify the frequency modulation trimming algorithm featuring a half-wave structure and eight sets of rotating blades for 1 kHz frequency modulation. Based on the electromagnetic (EM) field distribution analysis of the model cavity, the variable capacitor works as a function of time and the frequency can be written in Maclaurin series. Curve fitting is applied for theoretical frequency and original simulation frequency. The second-order fitting excels at the approximation given its minimum variance. Constant equivalent inductance is considered as an important condition in the calculation. The equivalent parameters of theoretical frequency can be achieved through this conversion. Then the trimming formula for rotor blade outer radius is found by discretization in time domain. Simulation verification has been performed and the results show that the calculation radius with minus 0.012 m yields an acceptable result. The trimming amendment in the time range of 0.328-0.4 ms helps to reduce the frequency error to 0.69% in Simulation C with an increment of 0.075 mm/0.001 ms, which is half of the error in Simulation A (constant radius in 0.328-0.4 ms). The verification confirms the feasibility of the trimming algorithm for synchrocyclotron frequency modulation.

Quantitative biomechanical analysis of wrist motion in bone-trimming jobs in the meat packing industry.

PubMed

Marklin, R W; Monroe, J F

1998-02-01

This study was motivated by the serious impact that cumulative trauma disorders (CTDs) of the upper extremities have on the meat packing industry. To date, no quantitative data have been gathered on the kinematics of hand and wrist motion required in bone-trimming jobs in the red-meat packing industry and how these motions are related to the risk of CTDs. The wrist motion of bone-trimming workers from a medium-sized plant was measured, and the kinematic data were compared to manufacturing industry's preliminary wrist motion benchmarks from industrial workers who performed hand-intensive, repetitive work in jobs that were of low and high risk of hand/wrist CTDs. Results of this comparison show that numerous wrist motion variables in both the left and right hands of bone-trimming workers are in the high-risk category. This quantitative analysis provides biomechanical support for the high incidence of CTDs in the meat packing industry. The research reported in this paper established a preliminary database of wrist and hand kinematics required in bone-trimming jobs in the red-meat packing industry. This kinematic database could augment the industry's efforts to reduce the severity and cost of CTDs. Ergonomics practitioners in the industry could use the kinematic methods employed in this research to assess the CTD risk of jobs that require repetitious, hand-intensive work.

Correlation of the Trim Limits of Stability Obtained for a PB2Y-3 Flying Boat and a 1/8-Size Powered Dynamic Model

NASA Technical Reports Server (NTRS)

Garrison, Charlie C.; Hacskaylo, Andrew

1947-01-01

Tests of a PB2Y-3 flying boat were made at the U.S> Naval Air Station, Patuxent River, Md., to determine its hydrodynamic trim limits of stability. Corresponding tests were also made of a 1/8-size powered dynamic model of the same flying boat in Langley tank no. 1. During the tank tests, the full-size testing procedure was reproduced as closely as possible in order to obtain data for a direct correlation of the results. As a nominal gross load of 66,000 pounds, the lower trim limits of the full-size and model were in good agreement above a speed of 80 feet per second. As the speed decreased below 80 feet per second, the difference between the model trim limits and full-scale trim limits gradually became larger. The upper trim limit of the model with flaps deflected 0 deg was higher than that of the full-size, but the difference was small over the speed range compared. At flap deflections greater than 0 deg, it was not possible to trim either the model of the airplane to the upper limit with the center of gravity at 28 percent of the mean aerodynamic chord. The decrease in the lower trim limits with increase in flap deflection showed good agreement for the airplane and model. The lower trim limits obtained at different gross loads for the full-size airplane were reduced to approximately a single curve by plotting trim against the square root of C(sub delta (sub o)) divided by C(sub V).

A novel compound which sensitizes BRAF wild-type melanoma cells to vemurafenib in a TRIM16-dependent manner.

PubMed

Sutton, Selina K; Carter, Daniel R; Kim, Patrick; Tan, Owen; Arndt, Greg M; Zhang, Xu Dong; Baell, Jonathan; Noll, Benjamin D; Wang, Shudong; Kumar, Naresh; McArthur, Grant A; Cheung, Belamy B; Marshall, Glenn M

2016-08-09

There is an urgent need for better therapeutic options for advanced melanoma patients, particularly those without the BRAFV600E/K mutation. In melanoma cells, loss of TRIM16 expression is a marker of cell migration and metastasis, while the BRAF inhibitor, vemurafenib, induces melanoma cell growth arrest in a TRIM16-dependent manner. Here we identify a novel small molecule compound which sensitized BRAF wild-type melanoma cells to vemurafenib. High throughput, cell-based, chemical library screening identified a compound (C012) which significantly reduced melanoma cell viability, with limited toxicity for normal human fibroblasts. When combined with the BRAFV600E/K inhibitor, vemurafenib, C012 synergistically increased vemurafenib potency in 5 BRAFWT and 4 out of 5 BRAFV600E human melanoma cell lines (Combination Index: CI < 1), and, dramatically reduced colony forming ability. In addition, this drug combination was significantly anti-tumorigenic in vivo in a melanoma xenograft mouse model. The combination of vemurafenib and C012 markedly increased expression of TRIM16 protein, and knockdown of TRIM16 significantly reduced the growth inhibitory effects of the vemurafenib and C012 combination. These findings suggest that the combination of C012 and vemurafenib may have therapeutic potential for the treatment of melanoma, and, that reactivation of TRIM16 may be an effective strategy for patients with this disease.

A novel compound which sensitizes BRAF wild-type melanoma cells to vemurafenib in a TRIM16-dependent manner

PubMed Central

Sutton, Selina K.; Carter, Daniel R.; Kim, Patrick; Tan, Owen; Arndt, Greg M.; Zhang, Xu Dong; Baell, Jonathan; Noll, Benjamin D.; Wang, Shudong; Kumar, Naresh; McArthur, Grant A.; Cheung, Belamy B.; Marshall, Glenn M.

2016-01-01

There is an urgent need for better therapeutic options for advanced melanoma patients, particularly those without the BRAFV600E/K mutation. In melanoma cells, loss of TRIM16 expression is a marker of cell migration and metastasis, while the BRAF inhibitor, vemurafenib, induces melanoma cell growth arrest in a TRIM16-dependent manner. Here we identify a novel small molecule compound which sensitized BRAF wild-type melanoma cells to vemurafenib. High throughput, cell-based, chemical library screening identified a compound (C012) which significantly reduced melanoma cell viability, with limited toxicity for normal human fibroblasts. When combined with the BRAFV600E/K inhibitor, vemurafenib, C012 synergistically increased vemurafenib potency in 5 BRAFWT and 4 out of 5 BRAFV600E human melanoma cell lines (Combination Index: CI < 1), and, dramatically reduced colony forming ability. In addition, this drug combination was significantly anti-tumorigenic in vivo in a melanoma xenograft mouse model. The combination of vemurafenib and C012 markedly increased expression of TRIM16 protein, and knockdown of TRIM16 significantly reduced the growth inhibitory effects of the vemurafenib and C012 combination. These findings suggest that the combination of C012 and vemurafenib may have therapeutic potential for the treatment of melanoma, and, that reactivation of TRIM16 may be an effective strategy for patients with this disease. PMID:27447557

TRIM25 enhances cell growth and cell survival by modulating p53 signals via interaction with G3BP2 in prostate cancer.

PubMed

Takayama, Ken-Ichi; Suzuki, Takashi; Tanaka, Tomoaki; Fujimura, Tetsuya; Takahashi, Satoru; Urano, Tomohiko; Ikeda, Kazuhiro; Inoue, Satoshi

2018-04-01

Prostate cancer growth is promoted by the gene regulatory action of androgen receptor (AR) and its downstream signals. The aberrant dysfunction of tumor suppressor p53 has an important role in the prognosis of cancer. We previously found that androgen treatments translocate p53 to the cytoplasm. The mechanism of this translocation depends on sumoylation of p53 by complex of SUMO E3 ligase RanBP2 with androgen-induced GTPase-activating protein-binding protein 2 (G3BP2). Here, we identified tripartite motif-containing protein 25 (TRIM25)/estrogen-responsive finger protein (Efp) as a novel interacting partner of G3BP2 protein complex. Then, we demonstrated that TRIM25 knockdown resulted in p53 downstream activation for cell cycle inhibition and apoptosis induction in LNCaP and 22Rv1 cells. In contrast, overexpression of TRIM25 promoted prostate cancer cell proliferation and inhibited apoptosis by docetaxel treatment in LNCaP cells. We observed that p53 activity was reduced by mechanism of G3BP2-mediated nuclear export in TRIM25-overexpressing prostate cancer cells. We also found TRIM25 is important for G3BP2/RanBP2-mediated p53 modification. Clinically, we newly demonstrated that TRIM25 is a prognostic factor for prostate cancer patients. Expression of TRIM25 is significantly associated with cytoplasmic p53 expression and G3BP2. Moreover, TRIM25 knockdown results in reduced tumor growth and increased p53 activity in the mouse xenograft model of prostate cancer. Thus, our findings show that overexpression of TRIM25 promoted prostate cancer cell proliferation and cell survival by modulating p53 nuclear export mechanism with G3BP2 interaction.

Qualification of a High Accuracy Dual-Axis Antenna Deployment and Trimming Mechanism

NASA Technical Reports Server (NTRS)

Gossant, Alain; Morichon, Francois

2010-01-01

The Antenna Deployment and Trimming Mechanism Mark 2 (ADTM Mk2) has been developed to answer today's need for a generic antenna deployment and high accuracy pointing mechanism, allowing RF sensing applications and easier dual deployments configurations. This paper presents the design and evolution from its predecessor, the experience of the design team from kick off to qualification and batch manufacture, as well as some lessons learned from ramping up "mass-production" capabilities while implementing customer driven changes. Astrium has manufactured and flown ADTM units for the past 20 years, from an initial deployment-only mechanism developed for the Orion program to today's Eurostar E3000 ADTM family. The Antenna ADTM Mk2 is an evolution of the original ADTM Mk1. Although it uses Mk1 building blocks to minimize risks associated with the development of a new product, it incorporates major evolutions and is the new baseline for Astrium latest generation of Eurostar E3000 telecom satellites.

Trimming and procrastination as inversion techniques

NASA Astrophysics Data System (ADS)

Backus, George E.

1996-12-01

By examining the processes of truncating and approximating the model space (trimming it), and by committing to neither the objectivist nor the subjectivist interpretation of probability (procrastinating), we construct a formal scheme for solving linear and non-linear geophysical inverse problems. The necessary prior information about the correct model xE can be either a collection of inequalities or a probability measure describing where xE was likely to be in the model space X before the data vector y0 was measured. The results of the inversion are (1) a vector z0 that estimates some numerical properties zE of xE; (2) an estimate of the error δz = z0 - zE. As y0 is finite dimensional, so is z0, and hence in principle inversion cannot describe all of xE. The error δz is studied under successively more specialized assumptions about the inverse problem, culminating in a complete analysis of the linear inverse problem with a prior quadratic bound on xE. Our formalism appears to encompass and provide error estimates for many of the inversion schemes current in geomagnetism, and would be equally applicable in geodesy and seismology if adequate prior information were available there. As an idealized example we study the magnetic field at the core-mantle boundary, using satellite measurements of field elements at sites assumed to be almost uniformly distributed on a single spherical surface. Magnetospheric currents are neglected and the crustal field is idealized as a random process with rotationally invariant statistics. We find that an appropriate data compression diagonalizes the variance matrix of the crustal signal and permits an analytic trimming of the idealized problem.

A next generation processing system for edging and trimming

Treesearch

A. Lynn Abbott; Daniel L. Schmoldt; Philip A. Araman

2000-01-01

This paper describes a prototype scanning system that is being developed for the processing of rough hardwood lumber. The overall goal of the system is to automate the selection of cutting positions for the edges and ends of rough, green lumber. Such edge and trim cuts are typically performed at sawmills in an effort to increase board value prior to sale, and this...

The E3 ligase for metastasis associated 1 protein, TRIM25, is targeted by microRNA-873 in hepatocellular carcinoma.

PubMed

Li, Yu-Hui; Zhong, Ming; Zang, Hong-Liang; Tian, Xiao-Feng

2018-07-01

Tumor metastasis accounts for 90% of all cancer-related deaths. Epithelial to mesenchymal transition (EMT) considered to be centrally important in acquired resistance to chemotherapy and in progression of tumors to secondary organs. One of the important mediators of metastatic progression in hepatocellular carcinoma (HCC) is the metastasis associated protein 1 (MTA-1). We have earlier shown that in the context of HCC and normal liver cell lines, MTA-1 protein is actively stabilized in HCC cell lines and actively degraded in normal liver cells. We have also shown that TRIM25 is the E3 ligase that interacts with and degrades MTA-1 protein. The identity of the factor regulating expression of TRIM25 in normal liver cells and HCC is unknown. In the current work we elucidate that microRNA (miR)- 873 targets TRIM25 in HCC cells. Both metagenomic analysis and quantification of miR-873 and TRIM25 in 25 HCC patients revealed an inverse correlation between the two in HCC patients with high miR-873 and low TRIM25 expression, respectively. The expression pattern was mimicked in the normal liver cells THLE-2 and the HCC cell line, HuH6. In vitro luciferase reporter assays confirmed TRIM25 as the target of miR-873. Transient transfection of HuH6 cells with an anti-miR-873 antagomir significantly decreased both transwell motility in these cells. Furthermore, in in vivo xenograft assays treatment with anti-miR-873 antagomir significantly decreased hepatic nodules formation. Cumulatively, our data indicate that suppression of TRIM25 expression by high levels of miR-873 dictates MTA1 protein upregulation in HCC. Copyright © 2018 Elsevier Inc. All rights reserved.

Roles of RIG-I N-terminal tandem CARD and splice variant in TRIM25-mediated antiviral signal transduction

PubMed Central

Gack, Michaela U.; Kirchhofer, Axel; Shin, Young C.; Inn, Kyung-Soo; Liang, Chengyu; Cui, Sheng; Myong, Sua; Ha, Taekjip; Hopfner, Karl-Peter; Jung, Jae U.

2008-01-01

The caspase recruitment domain (CARD) of intracellular adaptors and sensors plays a critical role in the assembly of signaling complexes involved in innate host defense against pathogens and in the regulation of inflammatory responses. The cytosolic receptor retinoic acid-inducible gene-I (RIG-I) recognizes viral RNA in a 5′-triphosphate-dependent manner and initiates an antiviral signaling cascade. Upon viral infection, the N-terminal CARDs of RIG-I undergo the K63-linked ubiquitination induced by tripartite motif protein 25 (TRIM25), critical for the interaction of RIG-I with its downstream signaling partner MAVS/VISA/IPS-1/Cardif. Here, we demonstrate the distinct roles of RIG-I first and second CARD in TRIM25-mediated RIG-I ubiquitination: TRIM25 binds the RIG-I first CARD and subsequently ubiquitinates its second CARD. The T55I mutation in RIG-I first CARD abolishes TRIM25 interaction, whereas the K172R mutation in the second CARD eliminates polyubiquitin attachment. The necessity of the intact tandem CARD for RIG-I function is further evidenced by a RIG-I splice variant (SV) whose expression is robustly up-regulated upon viral infection. The RIG-I SV carries a short deletion (amino acids 36–80) within the first CARD and thereby loses TRIM25 binding, CARD ubiquitination, and downstream signaling ability. Furthermore, because of its robust inhibition of virus-induced RIG-I multimerization and RIG-I-MAVS signaling complex formation, this SV effectively suppresses the RIG-I-mediated IFN-β production. This study not only elucidates the vital role of the intact tandem CARD for TRIM25-mediated RIG-I activation but also identifies the RIG-I SV as an off-switch regulator of its own signaling pathway. PMID:18948594

Roles of RIG-I N-terminal tandem CARD and splice variant in TRIM25-mediated antiviral signal transduction.

PubMed

Gack, Michaela U; Kirchhofer, Axel; Shin, Young C; Inn, Kyung-Soo; Liang, Chengyu; Cui, Sheng; Myong, Sua; Ha, Taekjip; Hopfner, Karl-Peter; Jung, Jae U

2008-10-28

The caspase recruitment domain (CARD) of intracellular adaptors and sensors plays a critical role in the assembly of signaling complexes involved in innate host defense against pathogens and in the regulation of inflammatory responses. The cytosolic receptor retinoic acid-inducible gene-I (RIG-I) recognizes viral RNA in a 5'-triphosphate-dependent manner and initiates an antiviral signaling cascade. Upon viral infection, the N-terminal CARDs of RIG-I undergo the K(63)-linked ubiquitination induced by tripartite motif protein 25 (TRIM25), critical for the interaction of RIG-I with its downstream signaling partner MAVS/VISA/IPS-1/Cardif. Here, we demonstrate the distinct roles of RIG-I first and second CARD in TRIM25-mediated RIG-I ubiquitination: TRIM25 binds the RIG-I first CARD and subsequently ubiquitinates its second CARD. The T(55)I mutation in RIG-I first CARD abolishes TRIM25 interaction, whereas the K(172)R mutation in the second CARD eliminates polyubiquitin attachment. The necessity of the intact tandem CARD for RIG-I function is further evidenced by a RIG-I splice variant (SV) whose expression is robustly up-regulated upon viral infection. The RIG-I SV carries a short deletion (amino acids 36-80) within the first CARD and thereby loses TRIM25 binding, CARD ubiquitination, and downstream signaling ability. Furthermore, because of its robust inhibition of virus-induced RIG-I multimerization and RIG-I-MAVS signaling complex formation, this SV effectively suppresses the RIG-I-mediated IFN-beta production. This study not only elucidates the vital role of the intact tandem CARD for TRIM25-mediated RIG-I activation but also identifies the RIG-I SV as an off-switch regulator of its own signaling pathway.

Nitroxoline shows antimyeloma activity by targeting the TRIM25/p53 axle.

PubMed

Mao, Hongwu; Du, Yanyun; Zhang, Zubin; Cao, Biyin; Zhao, Jun; Zhou, Haibin; Mao, Xinliang

2017-04-01

The aim of this study was to identify the most potent quinoline-based anti-infectives for the treatment of multiple myeloma (MM) and to understand the molecular mechanisms. A small-scale screen against a panel of marketed quinoline-based drugs was performed in MM cell lines. Cell apoptosis was examined by flow cytometry. Anti-MM activity was also evaluated in nude mice. Western blotting was performed to investigate mechanisms. Nitroxoline (NXQ) was the most effective in suppressing MM cell proliferation. NXQ induced more than 40% MM cell apoptosis within 24 h and potentiated anti-MM activities of current major drugs including doxorubicin and lenalidomide. This finding was shown by activation of caspase-3, a major executive apoptotic enzyme, and by inactivation of PARP, a major enzyme in DNA damage repair. NXQ also suppressed prosurvival proteins Bcl-xL and Mcl-1. Moreover, NXQ suppressed the growth of myeloma xenografts in nude mice models. In the mechanistic study, NXQ was found to downregulate TRIM25, a highly expressed ubiquitin ligase in MM. Notably, NXQ upregulated tumor suppressor p53, but not PTEN. Furthermore, overexpression of TRIM25 decreased p53 protein. This study indicated that the long-term use of anti-infective NXQ has potential for MM treatment by targeting the TRIM25/p53 axle.

Comparison of nerve trimming with the Er:YAG laser and steel knife

NASA Astrophysics Data System (ADS)

Josephson, G. D.; Bass, Lawrence S.; Kasabian, A. K.

1995-05-01

Best outcome in nerve repair requires precise alignment and minimization of scar at the repair interface. Surgeons attempt to create the sharpest cut surface at the nerve edge prior to approximation. Pulsed laser modalities are being investigated in several medical applications which require precise atraumatic cutting. We compared nerve trimming with the Er:YAG laser (1375 J/cm2) to conventional steel knife trimming prior to neurorrhaphy. Sprague- Dawley rats were anesthetized with ketamine and xylazine. Under operating microscope magnification the sciatic nerve was dissected and transected using one of the test techniques. In the laser group, the pulses were directed axially across the nerve using a stage which fixed laser fiber/nerve distance and orientation. Specimens were sent for scanning electron microscopy (SEM) at time zero. Epineurial repairs were performed with 10 - 0 nylon simple interrupted sutures. At intervals to 90 days, specimens were harvested and sectioned longitudinally and axially for histologic examination. Time zero SEM revealed clean cuts in both groups but individual axons were clearly visible in all laser specimens. Small pits were also visible on the cut surface of laser treated nerves. No significant differences in nerve morphology were seen during healing. Further studies to quantify axon counts, and functional outcome will be needed to assess this technique of nerve trimming. Delivery system improvements will also be required, to make the technique clinically practical.

TRIM timber projections: an evaluation based on forest inventory measurements.

Treesearch

John R. Mills

1989-01-01

Two consecutive timberland inventories collected from permanent plots in the natural pine type in North Carolina were used to evaluate the timber resource inventory model (TRIM). This study compares model predictions with field measurements and examines the effect of inventory data aggregation on the accuracy of projections. Projections were repeated for two geographic...

Research note: the performance of spring- and summer-reared broilers as affected by precision beak trimming at seven days of age.

PubMed

Christmas, R B

1993-12-01

In each of two duplicate trials approximately 2,500 day-old Peterson x Arbor Acres straight-run broiler chicks were equally divided between two treatments of three pens each. Treatment 1 was maintained as controls (C), and Treatment 2 birds were precision beak-trimmed (PBT) at 7 days of age. Feed and water were supplied for ad libitum consumption to both groups. Trials 1 and 2 were initiated in March and June, respectively. Performance of spring-reared broilers were comparable regardless of beak trimming procedure, except that PBT broilers experienced slightly higher mortality after PBT. Final body weights of the summer-reared broilers were 15% lower than those reared in the spring. Additionally, PBT resulted in significantly reduced final body weights and feed intake. There were no significant differences in mortality or feed conversion due to PBT.

GPER promotes tamoxifen-resistance in ER+ breast cancer cells by reduced Bim proteins through MAPK/Erk-TRIM2 signaling axis.

PubMed

Yin, Heng; Zhu, Qing; Liu, Manran; Tu, Gang; Li, Qing; Yuan, Jie; Wen, Siyang; Yang, Guanglun

2017-10-01

Tamoxifen resistance is a major clinical challenge in breast cancer treatment. Our previous studies find that GPER and its down-stream signaling play a pivotal role in the development of tamoxifen (TAM) resistance. cDNA array analysis indicated a set of genes associated with cell apoptosis are aberrant in GPER activated and TAM-resistant MCF-7R cells compared with TAM-sensitive MCF-7 cells. Among these genes, Bim (also named BCL2-L11), a member of the BH3-only pro-apoptotic protein family is significantly decreased, and TRIM RING finger protein TRIM2 (a ubiquitin ligase) is highly expressed in MCF-7R. To understand the mechanism of TAM-resistance in GPER activated ER+ breast cancer, the function of TRIM2 and Bim inducing cell apoptosis was studied. By using immunohistochemical and western blot analysis, there is an adverse correlation between TRIM2 and Bim in TAM-resistant breast tumor tissues and MCF-7R cells. Knockdown Bim in TAM-sensitive MCF-7 cells or overexpression of Bim in TAM-resistant MCF-7 cells significantly changed its sensibility to TAM through altering the levels of cleaved PARP and caspase-3. Activation of GPER and its downstream signaling MAPK/ERK, not PI3K/AKT, led to enhanced TRIM2 protein levels and affected the binding between TRIM2 and Bim which resulted in a reduced Bim in TAM-resistant breast cancer cells. Thus, the present study provides a novel insight to TAM-resistance in ER-positive breast cancer cells.

Helicopter Non-Unique Trim Strategies for Blade-Vortex Interaction (BVI) Noise Reduction

NASA Technical Reports Server (NTRS)

Malpica, Carlos; Greenwood, Eric; Sim, Ben W.

2016-01-01

An acoustics parametric analysis of the effect of fuselage drag and pitching moment on the Blade-Vortex Interaction (BVI) noise radiated by a medium lift helicopter (S-70UH-60) in a descending flight condition was conducted. The comprehensive analysis CAMRAD II was used for the calculation of vehicle trim, wake geometry and integrated air loads on the blade. The acoustics prediction code PSU-WOPWOP was used for calculating acoustic pressure signatures for a hemispherical grid centered at the hub. This paper revisits the concept of the X-force controller for BVI noise reduction, and investigates its effectiveness on an S-70 helicopter. The analysis showed that further BVI noise reductions were achievable by controlling the fuselage pitching moment. Reductions in excess of 6 dB of the peak BVI noise radiated towards the ground were demonstrated by compounding the effect of airframe drag and pitching moment simultaneously.

82. Neg. No. F66A, Apr 13, 1930, INTERIORASSEMBLY BUILDING, TRIM ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

82. Neg. No. F-66A, Apr 13, 1930, INTERIOR-ASSEMBLY BUILDING, TRIM LINE AND GLASS DEPARTMENTS - Ford Motor Company Long Beach Assembly Plant, Assembly Building, 700 Henry Ford Avenue, Long Beach, Los Angeles County, CA

Testing of the Trim Tab Parametric Model in NASA Langley's Unitary Plan Wind Tunnel

NASA Technical Reports Server (NTRS)

Murphy, Kelly J.; Watkins, Anthony N.; Korzun, Ashley M.; Edquist, Karl T.

2013-01-01

In support of NASA's Entry, Descent, and Landing technology development efforts, testing of Langley's Trim Tab Parametric Models was conducted in Test Section 2 of NASA Langley's Unitary Plan Wind Tunnel. The objectives of these tests were to generate quantitative aerodynamic data and qualitative surface pressure data for experimental and computational validation and aerodynamic database development. Six component force-and-moment data were measured on 38 unique, blunt body trim tab configurations at Mach numbers of 2.5, 3.5, and 4.5, angles of attack from -4deg to +20deg, and angles of sideslip from 0deg to +8deg. Configuration parameters investigated in this study were forebody shape, tab area, tab cant angle, and tab aspect ratio. Pressure Sensitive Paint was used to provide qualitative surface pressure mapping for a subset of these flow and configuration variables. Over the range of parameters tested, the effects of varying tab area and tab cant angle were found to be much more significant than varying tab aspect ratio relative to key aerodynamic performance requirements. Qualitative surface pressure data supported the integrated aerodynamic data and provided information to aid in future analyses of localized phenomena for trim tab configurations.

77 FR 47816 - Foreign-Trade Zone 12-McAllen, TX Application for Subzone TST NA TRIM, LLC Hidalgo, TX

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-10

... DEPARTMENT OF COMMERCE Foreign-Trade Zones Board [S-90-2012] Foreign-Trade Zone 12--McAllen, TX Application for Subzone TST NA TRIM, LLC Hidalgo, TX An application has been submitted to the Foreign-Trade...-purpose subzone status for the facility of TST NA TRIM, LLC, located in Hidalgo, Texas. The application...

Laser Trimming of CuAlMo Thin-Film Resistors: Effect of Laser Processing Parameters

NASA Astrophysics Data System (ADS)

Birkett, Martin; Penlington, Roger

2012-08-01

This paper reports the effect of varying laser trimming process parameters on the electrical performance of a novel CuAlMo thin-film resistor material. The films were prepared on Al2O3 substrates by direct-current (DC) magnetron sputtering, before being laser trimmed to target resistance value. The effect of varying key laser parameters of power, Q-rate, and bite size on the resistor stability and tolerance accuracy were systematically investigated. By reducing laser power and bite size and balancing this with Q-rate setting, significant improvements in resistor stability and resistor tolerance accuracies of less than ±0.5% were achieved.

The Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Inhibits Type I Interferon Production by Interfering with TRIM25-Mediated RIG-I Ubiquitination.

PubMed

Hu, Yong; Li, Wei; Gao, Ting; Cui, Yan; Jin, Yanwen; Li, Ping; Ma, Qingjun; Liu, Xuan; Cao, Cheng

2017-04-15

Severe acute respiratory syndrome (SARS) is a respiratory disease, caused by a coronavirus (SARS-CoV), that is characterized by atypical pneumonia. The nucleocapsid protein (N protein) of SARS-CoV plays an important role in inhibition of type I interferon (IFN) production via an unknown mechanism. In this study, the SARS-CoV N protein was found to bind to the SPRY domain of the tripartite motif protein 25 (TRIM25) E3 ubiquitin ligase, thereby interfering with the association between TRIM25 and retinoic acid-inducible gene I (RIG-I) and inhibiting TRIM25-mediated RIG-I ubiquitination and activation. Type I IFN production induced by poly I·C or Sendai virus (SeV) was suppressed by the SARS-CoV N protein. SARS-CoV replication was increased by overexpression of the full-length N protein but not N amino acids 1 to 361, which could not interact with TRIM25. These findings provide an insightful interpretation of the SARS-CoV-mediated host innate immune suppression caused by the N protein. IMPORTANCE The SARS-CoV N protein is essential for the viral life cycle and plays a key role in the virus-host interaction. We demonstrated that the interaction between the C terminus of the N protein and the SPRY domain of TRIM25 inhibited TRIM25-mediated RIG-I ubiquitination, which resulted in the inhibition of IFN production. We also found that the Middle East respiratory syndrome CoV (MERS-CoV) N protein interacted with TRIM25 and inhibited RIG-I signaling. The outcomes of these findings indicate the function of the coronavirus N protein in modulating the host's initial innate immune response. Copyright © 2017 American Society for Microbiology.

The Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Inhibits Type I Interferon Production by Interfering with TRIM25-Mediated RIG-I Ubiquitination

PubMed Central

Hu, Yong; Li, Wei; Gao, Ting; Cui, Yan; Jin, Yanwen; Li, Ping; Ma, Qingjun

2017-01-01

ABSTRACT Severe acute respiratory syndrome (SARS) is a respiratory disease, caused by a coronavirus (SARS-CoV), that is characterized by atypical pneumonia. The nucleocapsid protein (N protein) of SARS-CoV plays an important role in inhibition of type I interferon (IFN) production via an unknown mechanism. In this study, the SARS-CoV N protein was found to bind to the SPRY domain of the tripartite motif protein 25 (TRIM25) E3 ubiquitin ligase, thereby interfering with the association between TRIM25 and retinoic acid-inducible gene I (RIG-I) and inhibiting TRIM25-mediated RIG-I ubiquitination and activation. Type I IFN production induced by poly I·C or Sendai virus (SeV) was suppressed by the SARS-CoV N protein. SARS-CoV replication was increased by overexpression of the full-length N protein but not N amino acids 1 to 361, which could not interact with TRIM25. These findings provide an insightful interpretation of the SARS-CoV-mediated host innate immune suppression caused by the N protein. IMPORTANCE The SARS-CoV N protein is essential for the viral life cycle and plays a key role in the virus-host interaction. We demonstrated that the interaction between the C terminus of the N protein and the SPRY domain of TRIM25 inhibited TRIM25-mediated RIG-I ubiquitination, which resulted in the inhibition of IFN production. We also found that the Middle East respiratory syndrome CoV (MERS-CoV) N protein interacted with TRIM25 and inhibited RIG-I signaling. The outcomes of these findings indicate the function of the coronavirus N protein in modulating the host's initial innate immune response. PMID:28148787

Synergistic Modification Induced Specific Recognition between Histone and TRIM24 via Fluctuation Correlation Network Analysis

NASA Astrophysics Data System (ADS)

Zhang, Jinmai; Luo, Huajie; Liu, Hao; Ye, Wei; Luo, Ray; Chen, Hai-Feng

2016-04-01

Histone modification plays a key role in gene regulation and gene expression. TRIM24 as a histone reader can recognize histone modification. However the specific recognition mechanism between TRIM24 and histone modification is unsolved. Here, systems biology method of dynamics correlation network based on molecular dynamics simulation was used to answer the question. Our network analysis shows that the dynamics correlation network of H3K23ac is distinctly different from that of wild type and other modifications. A hypothesis of “synergistic modification induced recognition” is then proposed to link histone modification and TRIM24 binding. These observations were further confirmed from community analysis of networks with mutation and network perturbation. Finally, a possible recognition pathway is also identified based on the shortest path search for H3K23ac. Significant difference of recognition pathway was found among different systems due to methylation and acetylation modifications. The analysis presented here and other studies show that the dynamic network-based analysis might be a useful general strategy to study the biology of protein post-translational modification and associated recognition.

Determination of resistance and trimming moment of planing water craft

NASA Technical Reports Server (NTRS)

Schroder, P

1931-01-01

This report presents a new theory which makes it possible to interpret the resistance and the trimming moment for any loading of a planing aircraft when these values are given for one load. This application of the new theory forms the basis of the present paper. Derivations of various conversion formulas are given as well as numerous examples.

Microelectromechanical accelerometer with resonance-cancelling control circuit including an idle state

DOEpatents

Chu, Dahlon D.; Thelen, Jr., Donald C.; Campbell, David V.

2001-01-01

A digital feedback control circuit is disclosed for use in an accelerometer (e.g. a microelectromechanical accelerometer). The digital feedback control circuit, which periodically re-centers a proof mass in response to a sensed acceleration, is based on a sigma-delta (.SIGMA..DELTA.) configuration that includes a notch filter (e.g. a digital switched-capacitor filter) for rejecting signals due to mechanical resonances of the proof mass and further includes a comparator (e.g. a three-level comparator). The comparator generates one of three possible feedback states, with two of the feedback states acting to re-center the proof mass when that is needed, and with a third feedback state being an "idle" state which does not act to move the proof mass when no re-centering is needed. Additionally, the digital feedback control system includes an auto-zero trim capability for calibration of the accelerometer for accurate sensing of acceleration. The digital feedback control circuit can be fabricated using complementary metal-oxide semiconductor (CMOS) technology, bi-CMOS technology or bipolar technology and used in single- and dual-proof-mass accelerometers.

Astronaut Charles Conrad trims hair of Astronaut Paul Weitz

NASA Technical Reports Server (NTRS)

1973-01-01

Astronaut Charles Conrad Jr., Skylab 2 commander, trims the hair of Astronaut Paul J. Weitz, Skylab 2 pilot, during the 28-day Skylab 2 mission in Earth orbit. They are in the crew quarters wardroom of the Orbital Workshop of the Skylab 1 and 2 space station. Weitz is holding a vacuum hose in his right hand. This picture was taken by Scientist-Astronaut Joseph P. Kerwin, Skylab 2 science pilot.

Sample Size Determination for One- and Two-Sample Trimmed Mean Tests

ERIC Educational Resources Information Center

Luh, Wei-Ming; Olejnik, Stephen; Guo, Jiin-Huarng

2008-01-01

Formulas to determine the necessary sample sizes for parametric tests of group comparisons are available from several sources and appropriate when population distributions are normal. However, in the context of nonnormal population distributions, researchers recommend Yuen's trimmed mean test, but formulas to determine sample sizes have not been…

The Human Papillomavirus E6 Oncoprotein Targets USP15 and TRIM25 To Suppress RIG-I-Mediated Innate Immune Signaling.

PubMed

Chiang, Cindy; Pauli, Eva-Katharina; Biryukov, Jennifer; Feister, Katharina F; Meng, Melissa; White, Elizabeth A; Münger, Karl; Howley, Peter M; Meyers, Craig; Gack, Michaela U

2018-03-15

Retinoic acid-inducible gene I (RIG-I) is a key pattern recognition receptor that senses viral RNA and interacts with the mitochondrial adaptor MAVS, triggering a signaling cascade that results in the production of type I interferons (IFNs). This signaling axis is initiated by K63-linked ubiquitination of RIG-I mediated by the E3 ubiquitin ligase TRIM25, which promotes the interaction of RIG-I with MAVS. USP15 was recently identified as an upstream regulator of TRIM25, stabilizing the enzyme through removal of degradative K48-linked polyubiquitin, ultimately promoting RIG-I-dependent cytokine responses. Here, we show that the E6 oncoprotein of human papillomavirus type 16 (HPV16) as well as of other HPV types form a complex with TRIM25 and USP15 in human cells. In the presence of E6, the K48-linked ubiquitination of TRIM25 was markedly increased, and in line with this, TRIM25 degradation was enhanced. Our results further showed that E6 inhibited the TRIM25-mediated K63-linked ubiquitination of RIG-I and its CARD-dependent interaction with MAVS. HPV16 E6, but not E7, suppressed the RIG-I-mediated induction of IFN-β, chemokines, and IFN-stimulated genes (ISGs). Finally, CRISPR-Cas9 gene targeting in human keratinocytes showed that the TRIM25-RIG-I-MAVS triad is important for eliciting an antiviral immune response to HPV16 infection. Our study thus identifies a novel immune escape mechanism that is conserved among different HPV strains and further indicates that the RIG-I signaling pathway plays an important role in the innate immune response to HPV infection. IMPORTANCE Persistent infection and tumorigenesis by HPVs are known to require viral manipulation of a variety of cellular processes, including those involved in innate immune responses. Here, we show that the HPV E6 oncoprotein antagonizes the activation of the cytoplasmic innate immune sensor RIG-I by targeting its upstream regulatory enzymes TRIM25 and USP15. We further show that the RIG-I signaling cascade

Flight investigation of the effect of control centering springs on the apparent spiral stability of a personal-owner airplane

NASA Technical Reports Server (NTRS)

Campbell, John P; Hunter, Paul A; Hewes, Donald E; Whitten, James B

1952-01-01

Report presents the results of a flight investigation conducted on a typical high-wing personal-owner airplane to determine the effect of control centering springs on apparent spiral stability. Apparent spiral stability is the term used to describe the spiraling tendencies of an airplane in uncontrolled flight as affected both by the true spiral stability of the perfectly trimmed airplane and by out-of-trim control settings. Centering springs were used in both the aileron and rudder control systems to provide both a positive centering action and a means of trimming the airplane. The springs were preloaded so that when they were moved through neutral they produced a nonlinear force gradient sufficient to overcome the friction in the control surface at the proper setting for trim. The ailerons and rudder control surfaces did not have trim tabs that could be adjusted in flight.

Comparison of water wash, trimming, and combined hot water and lactic acid treatments for reducing bacteria of fecal origin on beef carcasses.

PubMed

Castillo, A; Lucia, L M; Goodson, K J; Savell, J W; Acuff, G R

1998-07-01

Cleaning treatments, such as high-pressure water wash at 35 degrees C or trim, alone and combined with sanitizing treatments, such as hot water (95 degrees C at the source), warm (55 degrees C) 2% lactic acid spray, and combinations of these two sanitizing methods, were compared for their effectiveness in reducing inoculated numbers (5.0 to 6.0 log CFU/cm2) of Salmonella typhimurium, Escherichia coli O157:H7, aerobic plate counts, Enterobacteriaceae, total coliforms, thermotolerant coliforms, and generic E. coli on hot beef carcass surface areas in a model carcass spray cabinet. Log reductions in numbers of all tested organisms by water wash or trim alone were significantly smaller than the log reductions obtained by the different combined treatments. Regardless of the cleaning treatment (water wash or trim) or surface area, the range for mean log reductions by hot water was from 4.0 to > 4.8 log CFU/cm2, by lactic acid spray was from 4.6 to > 4.9 log CFU/cm2, by hot water followed by lactic acid spray was from 4.5 to > 4.9 log CFU/cm2, and by lactic acid spray followed by hot water was from 4.4 to > 4.6 log CFU/cm2, for S. typhimurium and E. coli O157:H7. Identical reductions were obtained for thermotolerant coliforms and generic E. coli. No differences in bacterial reductions were observed for different carcass surface regions. Water wash and trim treatments caused spreading of the contamination to other areas of the carcass surface while providing an overall reduction in fecal or pathogenic contamination on carcass surface areas. This relocated contamination after either water wash or trim was most effectively reduced by following with hot water and then lactic acid spray. This combined treatment yielded 0% positive samples for S. typhimurium, E. coli O157:H7, thermotolerant coliforms, and generic E. coli on areas outside the inoculated areas, whereas percent positive samples after applying other combined treatments ranged from 22 to 44% for S. typhimurium, 0 to

A feasibility study regarding the addition of a fifth control to a rotorcraft in-flight simulator

NASA Technical Reports Server (NTRS)

Turner, Simon; Andrisani, Dominick, II

1992-01-01

The addition of a large movable horizontal tail surface to the control system of a rotorcraft in-flight simulator being developed from a Sikorsky UH-60A Black Hawk Helicopter is evaluated. The capabilities of the control surface as a trim control and as an active control are explored. The helicopter dynamics are modeled using the Generic Helicopter simulation program developed by Sikorsky Aircraft. The effect of the horizontal tail on the helicopter trim envelope is examined by plotting trim maps of the aircraft attitude and controls as a function of the flight speed and horizontal tail incidence. The control power of the tail surface relative to that of the other controls is examined by comparing control derivatives extracted from the simulation program over the flight speed envelope. The horizontal tail's contribution as an active control is evaluated using an explicit model following control synthesis involving a linear model of the helicopter in steady, level flight at a flight speed of eighty knots. The horizontal tail is found to provide additional control flexibility in the longitudinal axis. As a trim control, it provides effective control of the trim pitch attitude at mid to high forward speeds. As an active control, the horizontal tail provides useful pitching moment generating capabilities at mid to high forward speeds.

MASCOT - MATLAB Stability and Control Toolbox

NASA Technical Reports Server (NTRS)

Kenny, Sean; Crespo, Luis

2011-01-01

MASCOT software was created to provide the conceptual aircraft designer accurate predictions of air vehicle stability and control characteristics. The code takes as input mass property data in the form of an inertia tensor, aerodynamic loading data, and propulsion (i.e. thrust) loading data. Using fundamental non-linear equations of motion, MASCOT then calculates vehicle trim and static stability data for any desired flight condition. Common predefined flight conditions are included. The predefined flight conditions include six horizontal and six landing rotation conditions with varying options for engine out, crosswind and sideslip, plus three takeoff rotation conditions. Results are displayed through a unique graphical interface developed to provide stability and control information to the conceptual design engineers using a qualitative scale indicating whether the vehicle has acceptable, marginal, or unacceptable static stability characteristics. This software allows the user to prescribe the vehicle s CG location, mass, and inertia tensor so that any loading configuration between empty weight and maximum take-off weight can be analyzed. The required geometric and aerodynamic data as well as mass and inertia properties may be entered directly, passed through data files, or come from external programs such as Vehicle Sketch Pad (VSP). The current version of MASCOT has been tested with VSP used to compute the required data, which is then passed directly into the program. In VSP, the vehicle geometry is created and manipulated. The aerodynamic coefficients, stability and control derivatives, are calculated using VorLax, which is now available directly within VSP. MASCOT has been written exclusively using the technical computing language MATLAB . This innovation is able to bridge the gap between low-fidelity conceptual design and higher-fidelity stability and control analysis. This new tool enables the conceptual design engineer to include detailed static stability

Entropy-guided switching trimmed mean deviation-boosted anisotropic diffusion filter

NASA Astrophysics Data System (ADS)

Nnolim, Uche A.

2016-07-01

An effective anisotropic diffusion (AD) mean filter variant is proposed for filtering of salt-and-pepper impulse noise. The implemented filter is robust to impulse noise ranging from low to high density levels. The algorithm involves a switching scheme in addition to utilizing the unsymmetric trimmed mean/median deviation to filter image noise while greatly preserving image edges, regardless of impulse noise density (ND). It operates with threshold parameters selected manually or adaptively estimated from the image statistics. It is further combined with the partial differential equations (PDE)-based AD for edge preservation at high NDs to enhance the properties of the trimmed mean filter. Based on experimental results, the proposed filter easily and consistently outperforms the median filter and its other variants ranging from simple to complex filter structures, especially the known PDE-based variants. In addition, the switching scheme and threshold calculation enables the filter to avoid smoothing an uncorrupted image, and filtering is activated only when impulse noise is present. Ultimately, the particular properties of the filter make its combination with the AD algorithm a unique and powerful edge-preservation smoothing filter at high-impulse NDs.

A Note About HARP's State Trimming Method

NASA Technical Reports Server (NTRS)

Butler, Ricky W.; Hayhurst, Kelly J.; Johnson, Sally C.

1998-01-01

This short note provides some additional insight into how the HARP program works. In some cases, it is possible for HARP to tdm away too many states and obtain an optimistic result. The HARP Version 7.0 manual warns the user that 'Unlike the ALL model, the SAME model can automatically drop failure modes for certain system models. The user is cautioned to insure that no important failure modes are dropped; otherwise, a non-conservative result can be given.' This note provides an example of where this occurs and a pointer to further documentation that gives a means of bounding the error associated with trimming these states.

View of Expedition 21 Crew Members trimming hair in the Destiny Laboratory

NASA Image and Video Library

2009-10-11

ISS021-E-005070 (11 Oct. 2009) --- Russian cosmonaut Roman Romanenko, Expedition 21 flight engineer, trims Russian cosmonaut Maxim Suraev's hair in the Destiny laboratory of the International Space Station. Romanenko used hair clippers fashioned with a vacuum device to garner freshly cut hair.

Effect of partial comb and wattle trim on pullet behavior and thermoregulation

USDA-ARS?s Scientific Manuscript database

The wattles and comb of chickens are important for thermoregulation allowing for heat exchange during high temperatures. These integumentary tissues are sometimes trimmed to prevent tears if caught on cage equipment and to also improve feed efficiency; however, the procedure itself could be painful ...

A parameter-free variational coupling approach for trimmed isogeometric thin shells

NASA Astrophysics Data System (ADS)

Guo, Yujie; Ruess, Martin; Schillinger, Dominik

2017-04-01

The non-symmetric variant of Nitsche's method was recently applied successfully for variationally enforcing boundary and interface conditions in non-boundary-fitted discretizations. In contrast to its symmetric variant, it does not require stabilization terms and therefore does not depend on the appropriate estimation of stabilization parameters. In this paper, we further consolidate the non-symmetric Nitsche approach by establishing its application in isogeometric thin shell analysis, where variational coupling techniques are of particular interest for enforcing interface conditions along trimming curves. To this end, we extend its variational formulation within Kirchhoff-Love shell theory, combine it with the finite cell method, and apply the resulting framework to a range of representative shell problems based on trimmed NURBS surfaces. We demonstrate that the non-symmetric variant applied in this context is stable and can lead to the same accuracy in terms of displacements and stresses as its symmetric counterpart. Based on our numerical evidence, the non-symmetric Nitsche method is a viable parameter-free alternative to the symmetric variant in elastostatic shell analysis.

Effect of camber on the trimmed lift capability of a close-coupled canard-wing configuration. [test in the Langley high speed 7- by 10-foot tunnel

NASA Technical Reports Server (NTRS)

Gloss, B. B.

1978-01-01

A close-coupled canard-wing configuration was tested in the Langely high-speed 7 by 10 foot tunnel at a Mach number of 0.30 to determine the effect of changing wing camber on the trimmed lift capability. Trimmed lift coefficients of near 2.0 were attained; however, the data indicated that the highest buffet-free trimmed lift coefficient attainable was approximately 1.30. The buffet used in this investigation were qualitative in nature and gave no indication of buffet intensity. Thus, the trimmed lift coefficient of near 2.0 might be attainable if the buffet intensity was not too high. The data showed that there was approximately a 10 percent variation in drag coefficient, for different model configurations, at a given trimmed lift coefficient. Large increases in wing lift had only small effects on canard lift.

Air Pressure Controlled Mass Measurement System

NASA Astrophysics Data System (ADS)

Zhong, Ruilin; Wang, Jian; Cai, Changqing; Yao, Hong; Ding, Jin'an; Zhang, Yue; Wang, Xiaolei

Mass measurement is influenced by air pressure, temperature, humidity and other facts. In order to reduce the influence, mass laboratory of National Institute of Metrology, China has developed an air pressure controlled mass measurement system. In this system, an automatic mass comparator is installed in an airtight chamber. The Chamber is equipped with a pressure controller and associate valves, thus the air pressure can be changed and stabilized to the pre-set value, the preferred pressure range is from 200 hPa to 1100 hPa. In order to keep the environment inside the chamber stable, the display and control part of the mass comparator are moved outside the chamber, and connected to the mass comparator by feed-throughs. Also a lifting device is designed for this system which can easily lift up the upper part of the chamber, thus weights can be easily put inside the mass comparator. The whole system is put on a marble platform, and the temperature and humidity of the laboratory is very stable. The temperature, humidity, and carbon dioxide content inside the chamber are measured in real time and can be used to get air density. Mass measurement cycle from 1100 hPa to 200 hPa and back to 1100 hPa shows the effective of the system.

Optimization of an Aeroservoelastic Wing with Distributed Multiple Control Surfaces

NASA Technical Reports Server (NTRS)

Stanford, Bret K.

2015-01-01

This paper considers the aeroelastic optimization of a subsonic transport wingbox under a variety of static and dynamic aeroelastic constraints. Three types of design variables are utilized: structural variables (skin thickness, stiffener details), the quasi-steady deflection scheduling of a series of control surfaces distributed along the trailing edge for maneuver load alleviation and trim attainment, and the design details of an LQR controller, which commands oscillatory hinge moments into those same control surfaces. Optimization problems are solved where a closed loop flutter constraint is forced to satisfy the required flight margin, and mass reduction benefits are realized by relaxing the open loop flutter requirements.

Quasi-Linear Parameter Varying Representation of General Aircraft Dynamics Over Non-Trim Region

NASA Technical Reports Server (NTRS)

Shin, Jong-Yeob

2007-01-01

For applying linear parameter varying (LPV) control synthesis and analysis to a nonlinear system, it is required that a nonlinear system be represented in the form of an LPV model. In this paper, a new representation method is developed to construct an LPV model from a nonlinear mathematical model without the restriction that an operating point must be in the neighborhood of equilibrium points. An LPV model constructed by the new method preserves local stabilities of the original nonlinear system at "frozen" scheduling parameters and also represents the original nonlinear dynamics of a system over a non-trim region. An LPV model of the motion of FASER (Free-flying Aircraft for Subscale Experimental Research) is constructed by the new method.

Anatomical characterization of hoof growth pattern in six Iranian sheep breeds and its possible implication for trimming recommendations.

PubMed

Azarpajouh, S; Marchewka, J; Segura Correa, J C; Calderón Díaz, J A

2018-03-11

The objective of this study was to compare hoof anatomy, hoof growth pattern, and hoof weight-bearing surface of six different Iranian sheep breeds to identify possible differences in the hoof anatomical features that could help to minimize adverse effects of hoof trimming methods. Front and hind hooves of 2-year-old, previously untrimmed, pastured dairy ewes of six Iranian breeds (Afshari, Moghani, Kurdi, Makoui, Chaleshtori, and Lori-Bakhtiari; n = 180 ewes; 30 ewes per breed) were collected after slaughter. Medial and lateral claws were incised sagittally and anatomical measurements such as toe length, heel height, toe height, sole thickness, sole length, and toe angle were recorded in each claw. Data were analyzed using mixed model equations including breed, claw (lateral or medial), hoof (front or hind) and their interactions as fixed effects, and ewe as random effect. Breed differences were observed for all hoof measurements (P < 0.05). Chaleshtori sheep had higher measurements for most of the traits studied while Afshari and Makoui sheep had lower measurements. All measurements, except for toe length and toe height to solar surface to heel height ratio, were significantly greater in the front hooves than in the hind hooves (P < 0.05). Soles were longer in the medial claws compared to the lateral claws of the front hooves (P < 0.05). Results suggest the observed breed differences could interfere with establishing a standard, uniform hoof trimming method for sheep. For instance, it might be possible that while Afshari and Makoui sheep could require more conservative trimming, Chaleshtori sheep could require to be trimmed more. In consequence, hoof trimming methods might need to be adjusted to specific breed characteristics to avoid possible tissue damage.

Effects of Beak Trimming, Stocking Density and Sex on Carcass Yield, Carcass Components, Plasma Glucose and Triglyceride Levels in Large White Turkeys.

PubMed

Sengul, Turgay; Inci, Hakan; Sengul, Ahmet Y; Sogut, Bunyamin; Kiraz, Selahattin

2015-01-01

This study was conducted to determine the effects of beak trimming, stocking density (D) and sex (S) on live weight (LW), carcass yield and its component, and plasma glucose (PG) and triglyceride levels in Large White turkeys. To accomplish this aims, totally 288 d old large white turkey chicks (144 in each sex) were used. Beaks of 77 male and female poults were trimmed when 8 d old with an electrical beak trimmer. The birds were fed by commercial turkey rasion. Experiment was designed as 2 × 2 × 2 factorial arrangement with 3 replications in each group. Beak trimming and stocking density did not affect live weight, carcass composition and its components. The higher LW and carcass weight observed in trimmed groups. As expected, male birds are heavier than female, and carcass percentage (CP) would be adverse. However, in this study, CP of male was higher in trimmed, in 0.25 m(2)/bird. (D) × sex (S) interaction had an effect on both CP and thigh weights (p<0.05). Significantly D × S was observed in LW, CP and PG. The weight of carcass and its some components were higher in male. S × D interaction had an effect on plasma glucose level (p<0.05). Triglyceride level was affected (p<0.05) by sex. Significant relationships were found between percentage of thighs (r=0.447, p<0.01) and percentage of breast (r=0.400, p<0.01). According to this study, it can be said that trimming is useful with density of 0.25 m(2)/bird in turkey fattening.

Effects of Beak Trimming, Stocking Density and Sex on Carcass Yield, Carcass Components, Plasma Glucose and Triglyceride Levels in Large White Turkeys

PubMed Central

Kiraz, Selahattin

2015-01-01

This study was conducted to determine the effects of beak trimming, stocking density (D) and sex (S) on live weight (LW), carcass yield and its component, and plasma glucose (PG) and triglyceride levels in Large White turkeys. To accomplish this aims, totally 288 d old large white turkey chicks (144 in each sex) were used. Beaks of 77 male and female poults were trimmed when 8 d old with an electrical beak trimmer. The birds were fed by commercial turkey rasion. Experiment was designed as 2 × 2 × 2 factorial arrangement with 3 replications in each group. Beak trimming and stocking density did not affect live weight, carcass composition and its components. The higher LW and carcass weight observed in trimmed groups. As expected, male birds are heavier than female, and carcass percentage (CP) would be adverse. However, in this study, CP of male was higher in trimmed, in 0.25 m2/bird. (D) × sex (S) interaction had an effect on both CP and thigh weights (p<0.05). Significantly D × S was observed in LW, CP and PG. The weight of carcass and its some components were higher in male. S × D interaction had an effect on plasma glucose level (p<0.05). Triglyceride level was affected (p<0.05) by sex. Significant relationships were found between percentage of thighs (r=0.447, p<0.01) and percentage of breast (r=0.400, p<0.01). According to this study, it can be said that trimming is useful with density of 0.25 m2/bird in turkey fattening. PMID:26877630

Mountain Plains Learning Experience Guide: Electrical Wiring. Course: Electrical Wiring Trim-Out.

ERIC Educational Resources Information Center

Arneson, R.; And Others

One of two individualized courses included in an electrical wiring curriculum, this course covers electrical materials installation for the trim-out stage. The course is comprised of five units: (1) Outlets, (2) Fixtures, (3) Switches, (4) Appliances, and (5) Miscellaneous. Each unit begins with a Unit Learning Experience Guide that gives…

Trimming the fat: identification of risk factors associated with obesity in a pediatric emergency department.

PubMed

Thundiyil, Josef G; Christiano-Smith, Danielle; Greenberger, Sarah; Cramm, Kelly; Latimer-Pierson, Janese; Modica, Renee F

2010-10-01

The purpose of this study was to assess which knowledge deficits and dietary habits in an urban pediatric emergency department (ED) population are risk factors for obesity. This cross-sectional study in an urban pediatric ED used a modified version of the Diet and Health Knowledge Survey, an in-person interview questionnaire, to collect data on demographics, dietary knowledge, and practices. All patients aged 2 to 17 years were enrolled in the study over a 4-month period. Subjects were excluded if they were in extremis, pregnant, incarcerated, institutionalized, considered an emancipated minor, or consumed only a modified consistency diet. One hundred seventy-nine subjects were enrolled in this study. Based on body mass index, the prevalence of obesity in our study population was 24%. Parents with obese children answered a mean of 62.9% (95% confidence interval, 60.4%-65.5%) of knowledge questions correctly, whereas all others scored 60.3% (95% confidence interval, 58.3%-62.3%) correctly. Based on the univariate analysis, 10 predictors met inclusion criteria into logistic regression analysis: screen time (P = 0.03), race (P = 0.08), sex (P = 0.04), parental education (P = 0.08), parental estimation that child is overweight (P < 0.0001), parental estimation that child is underweight (P = 0.003), trimming fat from meat (P = 0.06), soft-drink consumption (P = 0.03), exercise (P = 0.07), and chip consumption (P = 0.04). In a multivariate analysis, only male sex, regularly trimming fat from meat, and parental assessment of obesity were independently associated with obesity. Knowledge deficiencies regarding healthy nutrition among parents in an urban pediatric ED population were not significantly associated with having obese children; however, specific habits were. Emergency physicians may provide a valuable role in identification and brief behavioral intervention in high-risk populations during the current epidemic of childhood obesity.

Control surfaces of aquatic vertebrates: active and passive design and function.

PubMed

Fish, Frank E; Lauder, George V

2017-12-01

Aquatic vertebrates display a variety of control surfaces that are used for propulsion, stabilization, trim and maneuvering. Control surfaces include paired and median fins in fishes, and flippers and flukes in secondarily aquatic tetrapods. These structures initially evolved from embryonic fin folds in fishes and have been modified into complex control surfaces in derived aquatic tetrapods. Control surfaces function both actively and passively to produce torque about the center of mass by the generation of either lift or drag, or both, and thus produce vector forces to effect rectilinear locomotion, trim control and maneuvers. In addition to fins and flippers, there are other structures that act as control surfaces and enhance functionality. The entire body can act as a control surface and generate lift for stability in destabilizing flow regimes. Furthermore, control surfaces can undergo active shape change to enhance their performance, and a number of features act as secondary control structures: leading edge tubercles, wing-like canards, multiple fins in series, finlets, keels and trailing edge structures. These modifications to control surface design can alter flow to increase lift, reduce drag and enhance thrust in the case of propulsive fin-based systems in fishes and marine mammals, and are particularly interesting subjects for future research and application to engineered systems. Here, we review how modifications to control surfaces can alter flow and increase hydrodynamic performance. © 2017. Published by The Company of Biologists Ltd.

Effects of mass on aircraft sidearm controller characteristics

NASA Technical Reports Server (NTRS)

Wagner, Charles A.

1994-01-01

When designing a flight simulator, providing a set of low mass variable-characteristic pilot controls can be very difficult. Thus, a strong incentive exists to identify the highest possible mass that will not degrade the validity of a simulation. The NASA Dryden Flight Research Center has conducted a brief flight program to determine the maximum acceptable mass (system inertia) of an aircraft sidearm controller as a function of force gradient. This information is useful for control system design in aircraft as well as development of suitable flight simulator controls. A modified Learjet with a variable-characteristic sidearm controller was used to obtain data. A boundary was defined between mass considered acceptable and mass considered unacceptable to the pilot. This boundary is defined as a function of force gradient over a range of natural frequencies. This investigation is limited to a study of mass-frequency characteristics only. Results of this investigation are presented in this paper.

Astronaut Owen Garriott trims hair of Astronaut Alan Bean

NASA Image and Video Library

1973-08-19

SL3-108-1292 (19 Aug. 1973) --- Scientist-astronaut Owen K. Garriott, Skylab 3 science pilot, trims the hair of astronaut Alan L. Bean, commander, in this onboard photograph from the Skylab Orbital Workshop (OWS) in Earth orbit. Astronaut Jack R. Lousma, pilot, took this picture with a 35mm Nikon camera. Bean holds a vacuum hose to gather in loose hair. The crew of the second manned Skylab flight went on to successfully complete 59 days aboard the Skylab space station cluster in Earth orbit. Photo credit: NASA

Ro52/TRIM21‐deficient expression and function in different subsets of peripheral blood mononuclear cells is associated with a proinflammatory cytokine response in patients with idiopathic inflammatory myopathies

PubMed Central

Gómez‐Martín, D.; Galindo‐Feria, A. S.; Barrera‐Vargas, A.; Merayo‐Chalico, J.; Juárez‐Vega, G.; Torres‐Ruiz, J.

2017-01-01

Summary The presence of anti‐Ro52/tripartite motif 21 (Trim21) autoantibodies has been associated with a distinctive clinical profile and has gained value as a prognostic marker in idiopathic inflammatory myopathies (IIM). The aim of the present work was to analyse Ro52/Trim21 expression in different subsets of peripheral blood mononuclear cells (PBMCs) of patients with IIM, as well as the ubiquitination profile and its association with proinflammatory cytokine production. We included 18 patients with recent‐onset IIM and 18 age‐ and gender‐matched healthy donors. PBMCs were isolated and different subsets (CD4+, CD8+, CD14+) were purified by magnetic selection. The expression of Ro52/Trim21 in different PBMC subsets of patients with IIM and healthy donors was analysed by Western blot. We assessed the presence of myositis‐specific and associated autoantibodies by enzyme‐linked immunosorbent assay (ELISA). Cytokine levels were measured by cytometric bead array. Patients with IIM showed decreased protein expression of Ro52/Trim21 in comparison to healthy controls in PBMC (0·97 ± 0·60 versus 1·84 ± 0·92, P = 0·016), CD4+ lymphocytes (0·79 ± 0·54 versus 2·41 ± 0·78, P = 0·017), and monocytes (0·87 ± 0·35 versus 1·89 ± 0·20, P < 0·001). There were no significant differences among IIM groups. Also, a lower K48‐mediated ubiquitination profile was found, predominantly in CD4+ lymphocytes. Furthermore, after mitogenic stimulation, there was a higher synthesis of proinflammatory cytokines by T cells [interleukin (IL)‐17A and tumour necrosis factor (TNF)‐α] and monocytes [IL‐6 and interferon (IFN)‐α] from IIM patients compared with healthy controls. Our data suggest that patients with IIM, mainly DM, are characterized by a deficient expression of Ro52/TRIM21 in different PBMC subsets (CD4+ lymphocytes and monocytes), along with lower K48‐mediated ubiquitination, which is associated with a

Sensitivity of TRIM projections to management, harvest, yield, and stocking adjustment assumptions.

Treesearch

Susan J. Alexander

1991-01-01

The Timber Resource Inventory Model (TRIM) was used to make several projections of forest industry timber supply for the Douglas-fir region. The sensitivity of these projections to assumptions about management and yields is discussed. A base run is compared to runs in which yields were altered, stocking adjustment was eliminated, harvest assumptions were changed, and...

46 CFR 72.05-15 - Ceilings, linings, trim, and decorations in accommodation spaces and safety areas.

Code of Federal Regulations, 2012 CFR

2012-10-01

... used in corridors or stairway enclosures. (d) Combustible veneers, trim, decorations, etc., shall not... subchapter Q (Specifications) of this chapter. This includes corridors, stairway enclosures, and hidden...

Ubiquitylation-dependent regulation of NEIL1 by Mule and TRIM26 is required for the cellular DNA damage response.

PubMed

Edmonds, Matthew J; Carter, Rachel J; Nickson, Catherine M; Williams, Sarah C; Parsons, Jason L

2017-01-25

Endonuclease VIII-like protein 1 (NEIL1) is a DNA glycosylase involved in initiating the base excision repair pathway, the major cellular mechanism for repairing DNA base damage. Here, we have purified the major E3 ubiquitin ligases from human cells responsible for regulation of NEIL1 by ubiquitylation. Interestingly, we have identified two enzymes that catalyse NEIL1 polyubiquitylation, Mcl-1 ubiquitin ligase E3 (Mule) and tripartite motif 26 (TRIM26). We demonstrate that these enzymes are capable of polyubiquitylating NEIL1 in vitro, and that both catalyse ubiquitylation of NEIL1 within the same C-terminal lysine residues. An siRNA-mediated knockdown of Mule or TRIM26 leads to stabilisation of NEIL1, demonstrating that these enzymes are important in regulating cellular NEIL1 steady state protein levels. Similarly, a mutant NEIL1 protein lacking residues for ubiquitylation is more stable than the wild type protein in vivo We also demonstrate that cellular NEIL1 protein is induced in response to ionising radiation (IR), although this occurs specifically in a Mule-dependent manner. Finally we show that stabilisation of NEIL1, particularly following TRIM26 siRNA, contributes to cellular resistance to IR. This highlights the importance of Mule and TRIM26 in maintaining steady state levels of NEIL1, but also those required for the cellular DNA damage response. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Hetero-oligomerization among the TIF family of RBCC/TRIM domain-containing nuclear cofactors: a potential mechanism for regulating the switch between coactivation and corepression.

PubMed

Peng, Hongzhuang; Feldman, Irina; Rauscher, Frank J

2002-07-12

The RING-B box-coiled-coil (RBCC) motif (also re-named recently as the tripartite motif (TRIM)) is a widely distributed motif that is hypothesized to be a protein-protein interface. The RBCC/TRIM domain of the corepressor KAP-1 is both necessary and sufficient to interact directly with the transcription repressor KRAB domain. Each subdomain of the KAP-1-RBCC contributes directly to the oligomerization and/or ligand recognition. Little is known about the function or the natural binding ligands for the RBCC/TRIM domain of the other TIF family members. In order to investigate whether hetero-oligomerization might be a biological regulatory mechanism, we have evaluated the hetero-oligomerization potential of the TIF family members including KAP-1, TIF1alpha, TIF1gamma, and the RBCC/TRIM family members including PML1, and MID1. We have reconstituted and characterized the oligomerization for these proteins using baculovirus and mammalian expression systems by biochemical approaches. Our data indicate that the RBCC/TRIM domains of KAP-1, TIF1alpha and TIF1gamma exist in a homo-oligomeric state. However, there is little cross-talk between KAP-1 and other TIF family members, suggesting that a high degree of specificity for oligomerization interface and ligand recognition is intrinsically built into the RBCC/TRIM domain of KAP-1. Finally, we demonstrate that TIF1alpha interacts with TIF1gamma and the coiled-coil region of TIF1gamma is necessary for this interaction. The hetero-oligomerization between TIF1alpha and TIF1gamma implies a potential regulatory mechanism for transcriptional regulation. (c) 2002 Elsevier Science Ltd.

Controlling Mass Transport in Microfluidic Devices

PubMed Central

Kuo, Jason S.; Chiu, Daniel T.

2017-01-01

Microfluidic platforms offer exquisite capabilities in controlling mass transport for biological studies. In this review, we focus on recent developments in manipulating chemical concentrations at the microscale. Some techniques prevent or accelerate mixing, whereas others shape the concentration gradients of chemical and biological molecules. We also highlight several in vitro biological studies in the areas of organ engineering, cancer, and blood coagulation that have benefited from accurate control of mass transfer. PMID:21456968

Precision technique for trimming dies using a magnification device.

PubMed

Beck, D B

1980-05-01

This article described a technique for trimming a die under magnification. However, the microscope is also useful for checking (1) margins of wax patterns for completeness, (2) the internal surfaces of castings for imperfections, bubbles, or retained investment particles which could prevent proper seating of the castings on the dies, (3) for cracks or contamination in dental porcelain as well as porcelain flash on margins; and (4) precision attachment operation after casting or soldering procedures. Attention to detail in these laboratory procedures greatly improves the final fit of dental castings and saves subsequent chairside adjustments and remakes.

Helicopter Non-Unique Trim Strategies for Blade-Vortex Interaction (BVI) Noise Reduction

DTIC Science & Technology

2016-01-22

levels of harmonic rotor noise are one of the key technical barriers preventing the widespread public acceptance of helicopters for commercial...transportation. Blade-Vortex Interaction (BVI) is one such mechanism of rotor noise. BVI noise is a problem for civilian helicopter terminal area...non-rotating frame) on the vehicle trim which in turn affects noise generation. For example, conventional single main rotor helicopters commonly

Controlling Gas-Flow Mass Ratios

NASA Technical Reports Server (NTRS)

Morris, Brian G.

1990-01-01

Proposed system automatically controls proportions of gases flowing in supply lines. Conceived for control of oxidizer-to-fuel ratio in new gaseous-propellant rocket engines. Gas-flow control system measures temperatures and pressures at various points. From data, calculates control voltages for electronic pressure regulators for oxygen and hydrogen. System includes commercially available components. Applicable to control of mass ratios in such gaseous industrial processes as chemical-vapor depostion of semiconductor materials and in automotive engines operating on compressed natural gas.

High-Speed Edge Trimming of CFRP and Online Monitoring of Performance of Router Tools Using Acoustic Emission

PubMed Central

Prakash, Rangasamy; Krishnaraj, Vijayan; Zitoune, Redouane; Sheikh-Ahmad, Jamal

2016-01-01

Carbon fiber reinforced polymers (CFRPs) have found wide-ranging applications in numerous industrial fields such as aerospace, automotive, and shipping industries due to their excellent mechanical properties that lead to enhanced functional performance. In this paper, an experimental study on edge trimming of CFRP was done with various cutting conditions and different geometry of tools such as helical-, fluted-, and burr-type tools. The investigation involves the measurement of cutting forces for the different machining conditions and its effect on the surface quality of the trimmed edges. The modern cutting tools (router tools or burr tools) selected for machining CFRPs, have complex geometries in cutting edges and surfaces, and therefore a traditional method of direct tool wear evaluation is not applicable. An acoustic emission (AE) sensing was employed for on-line monitoring of the performance of router tools to determine the relationship between AE signal and length of machining for different kinds of geometry of tools. The investigation showed that the router tool with a flat cutting edge has better performance by generating lower cutting force and better surface finish with no delamination on trimmed edges. The mathematical modeling for the prediction of cutting forces was also done using Artificial Neural Network and Regression Analysis. PMID:28773919

An Experimental Investigation to Determine the Effect of Speed-Brake Position on the Longitudinal Stability and Trim of a Swept-Wing Fighter Airplane

NASA Technical Reports Server (NTRS)

Taylor, Robert T.

1959-01-01

A 0.10-scale model of a swept-wing fighter airplane was tested in the Langley high-speed 7- by 10-foot tunnel at Mach numbers from 0.60 to 0.92 to determine the effects of adding underfuselage speed brakes. The results of brief spoiler-aileron lateral control tests also are included. The tests show acceptable trim and drag increments when the speed brakes are installed at the 32-71-inch fuselage station.

New gene evolution in the bonus-TIF1-γ/TRIM33 family impacted the architecture of the vertebrate dorsal-ventral patterning network.

PubMed

Wisotzkey, Robert G; Quijano, Janine C; Stinchfield, Michael J; Newfeld, Stuart J

2014-09-01

Uncovering how a new gene acquires its function and understanding how the function of a new gene influences existing genetic networks are important topics in evolutionary biology. Here, we demonstrate nonconservation for the embryonic functions of Drosophila Bonus and its newest vertebrate relative TIF1-γ/TRIM33. We showed previously that TIF1-γ/TRIM33 functions as an ubiquitin ligase for the Smad4 signal transducer and antagonizes the Bone Morphogenetic Protein (BMP) signaling network underlying vertebrate dorsal-ventral axis formation. Here, we show that Bonus functions as an agonist of the Decapentaplegic (Dpp) signaling network underlying dorsal-ventral axis formation in flies. The absence of conservation for the roles of Bonus and TIF1-γ/TRIM33 reveals a shift in the dorsal-ventral patterning networks of flies and mice, systems that were previously considered wholly conserved. The shift occurred when the new gene TIF1-γ/TRIM33 replaced the function of the ubiquitin ligase Nedd4L in the lineage leading to vertebrates. Evidence of this replacement is our demonstration that Nedd4 performs the function of TIF1-γ/TRIM33 in flies during dorsal-ventral axis formation. The replacement allowed vertebrate Nedd4L to acquire novel functions as a ubiquitin ligase of vertebrate-specific Smad proteins. Overall our data reveal that the architecture of the Dpp/BMP dorsal-ventral patterning network continued to evolve in the vertebrate lineage, after separation from flies, via the incorporation of new genes. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Velocity feedback control with a flywheel proof mass actuator

NASA Astrophysics Data System (ADS)

Kras, Aleksander; Gardonio, Paolo

2017-08-01

This paper presents four new proof mass actuators to be used in velocity feedback control systems for the control of vibrations of machines and flexible structures. A classical proof mass actuator is formed by a coil-magnet linear motor, with either the magnet or the armature-coil proof mass suspended on soft springs. This arrangement produces a net force effect at frequencies above the fundamental resonance frequency of the springs-proof mass system. Thus, it can be used to implement point velocity feedback loops, although the dynamic response and static deflection of the springs-proof mass system poses some stability and control performance limitations. The four proof mass actuators presented in this study include a flywheel element, which is used to augment the inertia effect of the suspended proof mass. The paper shows that the flywheel element modifies both the dynamic response and static deflection of the springs-proof mass system in such a way as the stability and control performance of velocity feedback loops using these actuators are significantly improved.

L-statistics for Repeated Measurements Data With Application to Trimmed Means, Quantiles and Tolerance Intervals.

PubMed

Assaad, Houssein I; Choudhary, Pankaj K

2013-01-01

The L -statistics form an important class of estimators in nonparametric statistics. Its members include trimmed means and sample quantiles and functions thereof. This article is devoted to theory and applications of L -statistics for repeated measurements data, wherein the measurements on the same subject are dependent and the measurements from different subjects are independent. This article has three main goals: (a) Show that the L -statistics are asymptotically normal for repeated measurements data. (b) Present three statistical applications of this result, namely, location estimation using trimmed means, quantile estimation and construction of tolerance intervals. (c) Obtain a Bahadur representation for sample quantiles. These results are generalizations of similar results for independently and identically distributed data. The practical usefulness of these results is illustrated by analyzing a real data set involving measurement of systolic blood pressure. The properties of the proposed point and interval estimators are examined via simulation.

View of an Expedition 21 Crew Member trimming his hair in the Destiny Laboratory

NASA Image and Video Library

2009-10-11

ISS021-E-005067 (11 Oct. 2009) --- Russian cosmonaut Maxim Suraev, Expedition 21 flight engineer, trims his hair in the Destiny laboratory of the International Space Station, using hair clippers fashioned with a vacuum device to garner freshly cut hair. Canadian Space Agency astronaut Robert Thirsk, flight engineer, is at right.

Trimming Surface Sugars Protects Histoplasma from Immune Attack.

PubMed

Brown, Gordon D

2016-04-26

Dectin-1 is an essential innate immune receptor that recognizes β-glucans in fungal cell walls. Its importance is underscored by the mechanisms that fungal pathogens have evolved to avoid detection by this receptor. One such pathogen is Histoplasma capsulatum, and in a recent article in mBio, Rappleye's group presented data showing that yeasts of this organism secrete a β-glucanase, Eng1, which acts to prune β-glucans that are exposed on the fungal cell surface [A. L. Garfoot et al., mBio 7(2):e01388-15, 2016, http://dx.doi.org/10.1128/mBio.01388-15]. The trimming of these sugars reduces immune recognition through Dectin-1 and subsequent inflammatory responses, enhancing the pathogenesis of H. capsulatum. Copyright © 2016 Brown.

A novel aminoacid determinant of HIV-1 restriction in the TRIM5α variable 1 region isolated in a random mutagenic screen.

PubMed

Pham, Quang Toan; Veillette, Maxime; Brandariz-Nuñez, Alberto; Pawlica, Paulina; Thibert-Lefebvre, Caroline; Chandonnet, Nadia; Diaz-Griffero, Felipe; Berthoux, Lionel

2013-05-01

Human-derived antiretroviral transgenes are of great biomedical interest and are actively pursued. HIV-1 is efficiently inhibited at post-entry, pre-integration replication stages by point mutations in the variable region 1 (v1) of the human restriction factor TRIM5α. Here we use a mutated megaprimer approach to create a mutant library of TRIM5αHu v1 and to isolate a mutation at Gly330 (G330E) that inhibits transduction of an HIV-1 vector as efficiently as the previously described mutants at positions Arg332 and Arg335. As was the case for these other mutations, modification of the local v1 charge toward increased acidity was key to inhibiting HIV-1. G330E TRIM5αHu also disrupted replication-competent HIV-1 propagation in a human T cell line. Interestingly, G330E did not enhance restriction of HIV-1 when combined with mutations at Arg332 or Arg335. Accordingly, the triple mutant G330E-R332G-R335G bound purified recombinant HIV-1 capsid tubes less efficiently than the double mutant R332G-R335G did. In a structural model of the TRIM5αHu PRYSPRY domain, the addition of G330E to the double mutant R332G-R335G caused extensive changes to the capsid-binding surface, which may explain why the triple mutant was no more restrictive than the double mutant. The HIV-1 inhibitory potential of Gly330 mutants was not predicted by examination of natural TRIM5α orthologs that are known to strongly inhibit HIV-1. This work underlines the potential of random mutagenesis to isolate novel variants of human proteins with antiviral properties. Copyright © 2013 Elsevier B.V. All rights reserved.

A theoretical study of the application of jet flap circulation control for reduction of rotor vibratory forces, addendum

NASA Technical Reports Server (NTRS)

Renka, A. R.

1975-01-01

The theoretical potential of a jet flap control system for reducing the vertical and horizontal non-cancelling helicopter rotor blade root shears was investigated. It was determined that the dominant contributor to the rotor power requirements is the requirement to maintain moment trim as well as force trim. It was also found that the requirement to maintain moment trim does not entail a power penalty.

An Improved Method to Control the Critical Parameters of a Multivariable Control System

NASA Astrophysics Data System (ADS)

Subha Hency Jims, P.; Dharmalingam, S.; Wessley, G. Jims John

2017-10-01

The role of control systems is to cope with the process deficiencies and the undesirable effect of the external disturbances. Most of the multivariable processes are highly iterative and complex in nature. Aircraft systems, Modern Power Plants, Refineries, Robotic systems are few such complex systems that involve numerous critical parameters that need to be monitored and controlled. Control of these important parameters is not only tedious and cumbersome but also is crucial from environmental, safety and quality perspective. In this paper, one such multivariable system, namely, a utility boiler has been considered. A modern power plant is a complex arrangement of pipework and machineries with numerous interacting control loops and support systems. In this paper, the calculation of controller parameters based on classical tuning concepts has been presented. The controller parameters thus obtained and employed has controlled the critical parameters of a boiler during fuel switching disturbances. The proposed method can be applied to control the critical parameters like elevator, aileron, rudder, elevator trim rudder and aileron trim, flap control systems of aircraft systems.

High Doses of GM-CSF Inhibit Antibody Responses in Rectal Secretions and Diminish Modified Vaccinia Ankara/Simian Immunodeficiency Virus Vaccine Protection in TRIM5α-Restrictive Macaques.

PubMed

Kannanganat, Sunil; Wyatt, Linda S; Gangadhara, Sailaja; Chamcha, Venkatesarlu; Chea, Lynette S; Kozlowski, Pamela A; LaBranche, Celia C; Chennareddi, Lakshmi; Lawson, Benton; Reddy, Pradeep B J; Styles, Tiffany M; Vanderford, Thomas H; Montefiori, David C; Moss, Bernard; Robinson, Harriet L; Amara, Rama Rao

2016-11-01

We tested, in rhesus macaques, the effects of a 500-fold range of an admixed recombinant modified vaccinia Ankara (MVA) expressing rhesus GM-CSF (MVA/GM-CSF) on the immunogenicity and protection elicited by an MVA/SIV macaque 239 vaccine. High doses of MVA/GM-CSF did not affect the levels of systemic envelope (Env)-specific Ab, but it did decrease the expression of the gut-homing receptor α4β7 on plasmacytoid dendritic cells (p < 0.01) and the magnitudes of Env-specific IgA (p = 0.01) and IgG (p < 0.05) in rectal secretions. The protective effect of the vaccine was evaluated using 12 weekly rectal challenges in rhesus macaques subgrouped by tripartite motif-containing protein 5α (TRIM5α) genotypes that are restrictive or permissive for infection by the challenge virus SIVsmE660. Eight of nine TRIM5α-restrictive animals receiving no or the lowest dose (1 × 10 5 PFU) of MVA/GM-CSF resisted all 12 challenges. In the comparable TRIM5α-permissive group, only 1 of 12 animals resisted all 12 challenges. In the TRIM5α-restrictive animals, but not in the TRIM5α-permissive animals, the number of challenges to infection directly correlated with the magnitudes of Env-specific rectal IgG (r = +0.6) and IgA (r = +0.6), the avidity of Env-specific serum IgG (r = +0.5), and Ab dependent cell-mediated virus inhibition (r = +0.6). Titers of neutralizing Ab did not correlate with protection. We conclude that 1) protection elicited by MVA/SIVmac239 is strongly dependent on the presence of TRIM5α restriction, 2) nonneutralizing Ab responses contribute to protection against SIVsmE660 in TRIM5α-restrictive animals, and 3) high doses of codelivered MVA/GM-CSF inhibit mucosal Ab responses and the protection elicited by MVA expressing noninfectious SIV macaque 239 virus-like particles. Copyright © 2016 by The American Association of Immunologists, Inc.

System precisely controls oscillation of vibrating mass

NASA Technical Reports Server (NTRS)

Hancock, D. J.

1967-01-01

System precisely controls the sinusoidal amplitude of a vibrating mechanical mass. Using two sets of coils, the system regulates the drive signal amplitude at the precise level to maintain the mechanical mass when it reaches the desired vibration amplitude.

CSN-associated USP48 confers stability to nuclear NF-κB/RelA by trimming K48-linked Ub-chains.

PubMed

Schweitzer, Katrin; Naumann, Michael

2015-02-01

Diligent balance of nuclear factor kappa B (NF-κB) activity is essential owing to NF-κB's decisive role in cellular processes including inflammation, immunity and cell survival. Ubiquitin/proteasome-system (UPS)-dependent degradation of activated NF-κB/RelA involves the cullin-RING-ubiquitin-ligase (CRL) ECS(SOCS1). The COP9 signalosome (CSN) controls ubiquitin (Ub) ligation by CRLs through the removal of the CRL-activating Ub-like modifier NEDD8 from their cullin subunits and through deubiquitinase (DUB) activity of associated DUBs. However, knowledge about DUBs involved in the regulation of NF-κB activity within the nucleus is scarce. In this study we observed that USP48, a DUB of hitherto ill-defined function identified through a siRNA screen, associates with the CSN and RelA in the nucleus. We show that USP48 trims rather than completely disassembles long K48-linked free and substrate-anchored Ub-chains, a catalytic property only shared with ataxin-3 (Atx3) and otubain-1 (OTU1), and that USP48 Ub-chain-trimming activity is regulated by casein-kinase-2 (CK2)-mediated phosphorylation in response to cytokine-stimulation. Functionally, we demonstrate for the first time the CSN and USP48 to cooperatively stabilize the nuclear pool of RelA, thereby facilitating timely induction and shutoff of NF-κB target genes. In summary, this study demonstrates that USP48, a nuclear DUB regulated by CK2, controls the UPS-dependent turnover of activated NF-κB/RelA in the nucleus together with the CSN. Thereby USP48 contributes to a timely control of immune responses. Copyright © 2014 Elsevier B.V. All rights reserved.

Attitude dynamics and control of a spacecraft using shifting mass distribution

NASA Astrophysics Data System (ADS)

Ahn, Young Tae

Spacecraft need specific attitude control methods that depend on the mission type or special tasks. The dynamics and the attitude control of a spacecraft with a shifting mass distribution within the system are examined. The behavior and use of conventional attitude control actuators are widely developed and performing at the present time. However, the advantage of a shifting mass distribution concept can complement spacecraft attitude control, save mass, and extend a satellite's life. This can be adopted in practice by moving mass from one tank to another, similar to what an airplane does to balance weight. Using this shifting mass distribution concept, in conjunction with other attitude control devices, can augment the three-axis attitude control process. Shifting mass involves changing the center-of-mass of the system, and/or changing the moments of inertia of the system, which then ultimately can change the attitude behavior of the system. This dissertation consists of two parts. First, the equations of motion for the shifting mass concept (also known as morphing) are developed. They are tested for their effects on attitude control by showing how shifting the mass changes the spacecraft's attitude behavior. Second, a method for optimal mass redistribution is shown using a combinatorial optimization theory under constraints. It closes with a simple example demonstrating an optimal reconfiguration. The procedure of optimal reconfiguration from one mass distribution to another to accomplish attitude control has been demonstrated for several simple examples. Mass shifting could work as an attitude controller for fine-tuning attitude behavior in small satellites. Various constraints can be applied for different situations, such as no mass shift between two tanks connected by a failed pipe or total amount of shifted mass per pipe being set for the time optimum solution. Euler angle changes influenced by the mass reconfiguration are accomplished while stability

Evaluation of beef trim sampling methods for detection of Shiga toxin-producing Escherichia coli (STEC)

USDA-ARS?s Scientific Manuscript database

Presence of Shiga toxin-producing Escherichia coli (STEC) is a major concern in ground beef. Several methods for sampling beef trim prior to grinding are currently used in the beef industry. The purpose of this study was to determine the efficacy of the sampling methods for detecting STEC in beef ...

Mass Shootings, Mental Illness, and Gun Control.

PubMed

Philpott-Jones, Sean

2018-03-01

In the wake of the Stoneman Douglas School shooting, Republican and Democratic leaders-like the American electorate they represent-remain sharply divided in their responses to gun violence. They are united in their condemnation of these mass shootings, but they disagree about whether stricter or looser gun control laws are the answer. Those on the right side of the political aisle suggest that the issue is one of mental illness rather than gun control. Conversely, those who are more liberal or progressive in their political learnings are quick to condemn attempts to reframe the issue of mass shootings as a mental health problem. Both sides are wrong. Mass shootings are indeed partially a mental health problem, albeit one poorly addressed by our current laws and policies. But the solution to mass shootings also needs to consider strategies that may reduce gun violence in general. © 2018 The Hastings Center.

Integrated flight/propulsion control design for a STOVL aircraft using H-infinity control design techniques

NASA Technical Reports Server (NTRS)

Garg, Sanjay; Ouzts, Peter J.

1991-01-01

Results are presented from an application of H-infinity control design methodology to a centralized integrated flight propulsion control (IFPC) system design for a supersonic Short Takeoff and Vertical Landing (STOVL) fighter aircraft in transition flight. The emphasis is on formulating the H-infinity control design problem such that the resulting controller provides robustness to modeling uncertainties and model parameter variations with flight condition. Experience gained from a preliminary H-infinity based IFPC design study performed earlier is used as the basis to formulate the robust H-infinity control design problem and improve upon the previous design. Detailed evaluation results are presented for a reduced order controller obtained from the improved H-infinity control design showing that the control design meets the specified nominal performance objectives as well as provides stability robustness for variations in plant system dynamics with changes in aircraft trim speed within the transition flight envelope. A controller scheduling technique which accounts for changes in plant control effectiveness with variation in trim conditions is developed and off design model performance results are presented.

Tripartite Motif 24 (Trim24/Tif1α) Tumor Suppressor Protein Is a Novel Negative Regulator of Interferon (IFN)/Signal Transducers and Activators of Transcription (STAT) Signaling Pathway Acting through Retinoic Acid Receptor α (Rarα) Inhibition*

PubMed Central

Tisserand, Johan; Khetchoumian, Konstantin; Thibault, Christelle; Dembélé, Doulaye; Chambon, Pierre; Losson, Régine

2011-01-01

Recent genetic studies in mice have established that the nuclear receptor coregulator Trim24/Tif1α suppresses hepatocarcinogenesis by inhibiting retinoic acid receptor α (Rara)-dependent transcription and cell proliferation. However, Rara targets regulated by Trim24 remain unknown. We report that the loss of Trim24 resulted in interferon (IFN)/STAT pathway overactivation soon after birth (week 5). Despite a transient attenuation of this pathway by the induction of several IFN/STAT pathway repressors later in the disease, this phenomenon became more pronounced in tumors. Remarkably, Rara haplodeficiency, which suppresses tumorigenesis in Trim24−/− mice, prevented IFN/STAT overactivation. Moreover, together with Rara, Trim24 bound to the retinoic acid-responsive element of the Stat1 promoter and repressed its retinoic acid-induced transcription. Altogether, these results identify Trim24 as a novel negative regulator of the IFN/STAT pathway and suggest that this repression through Rara inhibition may prevent liver cancer. PMID:21768647

Disruption of the ASTN2/TRIM32 locus at 9q33.1 is a risk factor in males for autism spectrum disorders, ADHD and other neurodevelopmental phenotypes

PubMed Central

Lionel, Anath C.; Tammimies, Kristiina; Vaags, Andrea K.; Rosenfeld, Jill A.; Ahn, Joo Wook; Merico, Daniele; Noor, Abdul; Runke, Cassandra K.; Pillalamarri, Vamsee K.; Carter, Melissa T.; Gazzellone, Matthew J.; Thiruvahindrapuram, Bhooma; Fagerberg, Christina; Laulund, Lone W.; Pellecchia, Giovanna; Lamoureux, Sylvia; Deshpande, Charu; Clayton-Smith, Jill; White, Ann C.; Leather, Susan; Trounce, John; Melanie Bedford, H.; Hatchwell, Eli; Eis, Peggy S.; Yuen, Ryan K.C.; Walker, Susan; Uddin, Mohammed; Geraghty, Michael T.; Nikkel, Sarah M.; Tomiak, Eva M.; Fernandez, Bridget A.; Soreni, Noam; Crosbie, Jennifer; Arnold, Paul D.; Schachar, Russell J.; Roberts, Wendy; Paterson, Andrew D.; So, Joyce; Szatmari, Peter; Chrysler, Christina; Woodbury-Smith, Marc; Brian Lowry, R.; Zwaigenbaum, Lonnie; Mandyam, Divya; Wei, John; MacDonald, Jeffrey R.; Howe, Jennifer L.; Nalpathamkalam, Thomas; Wang, Zhuozhi; Tolson, Daniel; Cobb, David S.; Wilks, Timothy M.; Sorensen, Mark J.; Bader, Patricia I.; An, Yu; Wu, Bai-Lin; Musumeci, Sebastiano Antonino; Romano, Corrado; Postorivo, Diana; Nardone, Anna M.; Monica, Matteo Della; Scarano, Gioacchino; Zoccante, Leonardo; Novara, Francesca; Zuffardi, Orsetta; Ciccone, Roberto; Antona, Vincenzo; Carella, Massimo; Zelante, Leopoldo; Cavalli, Pietro; Poggiani, Carlo; Cavallari, Ugo; Argiropoulos, Bob; Chernos, Judy; Brasch-Andersen, Charlotte; Speevak, Marsha; Fichera, Marco; Ogilvie, Caroline Mackie; Shen, Yiping; Hodge, Jennelle C.; Talkowski, Michael E.; Stavropoulos, Dimitri J.; Marshall, Christian R.; Scherer, Stephen W.

2014-01-01

Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders (NDDs). The vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronal migration during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89 985 individuals across 10 sites, including 64 114 NDD subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions of ASTN1 were much rarer. Deletions near the 3′ terminus of ASTN2, which would disrupt all transcript isoforms (a subset of these deletions also included TRIM32), were significantly enriched in the NDD subjects (P = 0.002) compared with 44 085 population-based controls. Frequent phenotypes observed in individuals with such deletions include autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), speech delay, anxiety and obsessive compulsive disorder (OCD). The 3′-terminal ASTN2 deletions were significantly enriched compared with controls in males with NDDs, but not in females. Upon quantifying ASTN2 human brain RNA, we observed shorter isoforms expressed from an alternative transcription start site of recent evolutionary origin near the 3′ end. Spatiotemporal expression profiling in the human brain revealed consistently high ASTN1 expression while ASTN2 expression peaked in the early embryonic neocortex and postnatal cerebellar cortex. Our findings shed new light on the role of the astrotactins in psychopathology and their interplay in human neurodevelopment. PMID:24381304

Disruption of the ASTN2/TRIM32 locus at 9q33.1 is a risk factor in males for autism spectrum disorders, ADHD and other neurodevelopmental phenotypes.

PubMed

Lionel, Anath C; Tammimies, Kristiina; Vaags, Andrea K; Rosenfeld, Jill A; Ahn, Joo Wook; Merico, Daniele; Noor, Abdul; Runke, Cassandra K; Pillalamarri, Vamsee K; Carter, Melissa T; Gazzellone, Matthew J; Thiruvahindrapuram, Bhooma; Fagerberg, Christina; Laulund, Lone W; Pellecchia, Giovanna; Lamoureux, Sylvia; Deshpande, Charu; Clayton-Smith, Jill; White, Ann C; Leather, Susan; Trounce, John; Melanie Bedford, H; Hatchwell, Eli; Eis, Peggy S; Yuen, Ryan K C; Walker, Susan; Uddin, Mohammed; Geraghty, Michael T; Nikkel, Sarah M; Tomiak, Eva M; Fernandez, Bridget A; Soreni, Noam; Crosbie, Jennifer; Arnold, Paul D; Schachar, Russell J; Roberts, Wendy; Paterson, Andrew D; So, Joyce; Szatmari, Peter; Chrysler, Christina; Woodbury-Smith, Marc; Brian Lowry, R; Zwaigenbaum, Lonnie; Mandyam, Divya; Wei, John; Macdonald, Jeffrey R; Howe, Jennifer L; Nalpathamkalam, Thomas; Wang, Zhuozhi; Tolson, Daniel; Cobb, David S; Wilks, Timothy M; Sorensen, Mark J; Bader, Patricia I; An, Yu; Wu, Bai-Lin; Musumeci, Sebastiano Antonino; Romano, Corrado; Postorivo, Diana; Nardone, Anna M; Monica, Matteo Della; Scarano, Gioacchino; Zoccante, Leonardo; Novara, Francesca; Zuffardi, Orsetta; Ciccone, Roberto; Antona, Vincenzo; Carella, Massimo; Zelante, Leopoldo; Cavalli, Pietro; Poggiani, Carlo; Cavallari, Ugo; Argiropoulos, Bob; Chernos, Judy; Brasch-Andersen, Charlotte; Speevak, Marsha; Fichera, Marco; Ogilvie, Caroline Mackie; Shen, Yiping; Hodge, Jennelle C; Talkowski, Michael E; Stavropoulos, Dimitri J; Marshall, Christian R; Scherer, Stephen W

2014-05-15

Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders (NDDs). The vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronal migration during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89 985 individuals across 10 sites, including 64 114 NDD subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions of ASTN1 were much rarer. Deletions near the 3' terminus of ASTN2, which would disrupt all transcript isoforms (a subset of these deletions also included TRIM32), were significantly enriched in the NDD subjects (P = 0.002) compared with 44 085 population-based controls. Frequent phenotypes observed in individuals with such deletions include autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), speech delay, anxiety and obsessive compulsive disorder (OCD). The 3'-terminal ASTN2 deletions were significantly enriched compared with controls in males with NDDs, but not in females. Upon quantifying ASTN2 human brain RNA, we observed shorter isoforms expressed from an alternative transcription start site of recent evolutionary origin near the 3' end. Spatiotemporal expression profiling in the human brain revealed consistently high ASTN1 expression while ASTN2 expression peaked in the early embryonic neocortex and postnatal cerebellar cortex. Our findings shed new light on the role of the astrotactins in psychopathology and their interplay in human neurodevelopment.

Human-animal interactions and safety during dairy cattle handling--Comparing moving cows to milking and hoof trimming.

PubMed

Lindahl, C; Pinzke, S; Herlin, A; Keeling, L J

2016-03-01

Cattle handling is a dangerous activity on dairy farms, and cows are a major cause of injuries to livestock handlers. Even if dairy cows are generally tranquil and docile, when situations occur that they perceive or remember as aversive, they may become agitated and hazardous to handle. This study aimed to compare human-animal interactions, cow behavior, and handler safety when moving cows to daily milking and moving cows to more rarely occurring and possibly aversive hoof trimming. These processes were observed on 12 Swedish commercial dairy farms. The study included behavioral observations of handler and cows and cow heart rate recordings, as well as recording frequencies of situations and incidents related to an increased injury risk to the handler. At milking, cows were quite easily moved using few interactions. As expected, the cows showed no behavioral signs of stress, fear, or resistance and their heart rate only rose slightly from the baseline (i.e., the average heart rate during an undisturbed period before handling). Moving cows to hoof trimming involved more forceful and gentle interactions compared with moving cows to milking. Furthermore, the cows showed much higher frequencies of behaviors indicative of aversion and fear (e.g., freezing, balking, and resistance), as well as a higher increase in heart rate. The risk of injury to which handlers were exposed also increased when moving cows to hoof trimming rather than to routine milking. Some interactions (such as forceful tactile interactions with an object and pulling a neck strap or halter) appeared to be related to potentially dangerous incidents where the handler was being kicked, head-butted, or run over by a cow. In conclusion, moving cows to hoof trimming resulted in higher frequencies of behaviors indicating fear, more forceful interactions, and increased injury risks to the handler than moving cows to milking. Improving potentially stressful handling procedures (e.g., by better animal handling

Microprocessor controlled proof-mass actuator

NASA Technical Reports Server (NTRS)

Horner, Garnett C.

1987-01-01

The objective of the microprocessor controlled proof-mass actuator is to develop the capability to mount a small programmable device on laboratory models. This capability will allow research in the active control of flexible structures. The approach in developing the actuator will be to mount all components as a single unit. All sensors, electronic and control devices will be mounted with the actuator. The goal for the force output capability of the actuator will be one pound force. The programmable force actuator developed has approximately a one pound force capability over the usable frequency range, which is above 2 Hz.

High doses of granulocyte-macrophage colony stimulating factor inhibit antibody responses in rectal secretions and diminish MVA/SIV vaccine protection in TRIM5α restrictive macaques

PubMed Central

Kannanganat, Sunil; Wyatt, Linda S; Gangadhara, Sailaja; Chamcha, Venkateswarlu; Chea, Lynette S.; Kozlowski, Pamela A; LaBranche, Celia C; Chennareddi, Lakshmi; Lawson, Benton; Reddy, Pradeep B. J.; Styles, Tiffany M.; Vanderford, Thomas H; Montefiori, David C; Moss, Bernard; Robinson, Harriet L; Amara, Rama Rao

2016-01-01

Here, we test in rhesus macaques the effects of a 500-fold range of an admixed recombinant modified vaccinia Ankara (MVA) expressing rhesus GM-CSF (MVA/GM-CSF) on the immunogenicity and protection elicited by an MVA/simian immunodeficiency macaque 239 (SIVmac239) vaccine. High doses of the MVA/GM-CSF did not affect the levels of systemic Env-specific Ab but did decrease the expression of the gut homing receptor α4β7 on plasmacytoid dendritic cells (p<0.01) and the magnitudes of Env-specific IgA (p=0.01) and IgG (p<0.05) in rectal secretions. The protective effect of the vaccine was evaluated using 12 weekly rectal challenges in rhesus subgrouped by tripartite motif-containing protein 5α (TRIM5α) genotypes that are restrictive or permissive for infection by the challenge virus, SIVsmE660. Eight of 9 TRIM5α-restrictive animals receiving no, or the lowest dose [1×105 plaque forming units (pfu)] of MVA/GM-CSF resisted all 12 challenges. In the comparable TRIM5α-permissive group only 1 of 12 animals resisted all 12 challenges. In the TRIM5α restrictive, but not permissive animals, the number of challenges to infection directly correlated with the magnitudes of Env-specific rectal IgG (r=0.6) and IgA (r=0.6), the avidity of Env-specific serum IgG (r=0.5), and antibody dependent cell-mediated virus inhibition (r=0.6). Titers of neutralizing Ab did not correlate with protection. We conclude that (i) protection elicited by MVA/SIVmac239 is strongly dependent on the presence of the TRIM5α restriction, (ii) in TRIM5α restrictive animals, non-neutralizing Ab responses contribute to protection against SIVsmE660, and (iii) high doses of co-expressed MVA/GM-CSF inhibit mucosal Ab responses and MVA/SIV239-elicited protection. PMID:27683750

Heteroscedastic Tests Statistics for One-Way Analysis of Variance: The Trimmed Means and Hall's Transformation Conjunction

ERIC Educational Resources Information Center

Luh, Wei-Ming; Guo, Jiin-Huarng

2005-01-01

To deal with nonnormal and heterogeneous data for the one-way fixed effect analysis of variance model, the authors adopted a trimmed means method in conjunction with Hall's invertible transformation into a heteroscedastic test statistic (Alexander-Govern test or Welch test). The results of simulation experiments showed that the proposed technique…

Transcriptional regulators TRIM28, SETDB1, and TP53 are aberrantly expressed in porcine embryos produced by in vitro fertilization in comparison to in vivo- and somatic-cell nuclear transfer-derived embryos

PubMed Central

Hamm, Jennifer; Tessanne, Kim; Murphy, Clifton N; Prather, Randall S

2014-01-01

In vitro embryo production is important for research in animal reproduction, embryo transfer, transgenics, and cloning. Yet, in vitro-fertilized (IVF) embryos are generally developmentally delayed and are inferior to in vivo-derived (IVV) embryos; this discrepancy is likely a result of aberrant gene expression. Transcription of three genes implicated to be important in normal preimplantation embryo development, TRIM28, SETDB1, and TP53, was determined by quanitative PCR in IVF, somatic-cell nuclear transfer (SCNT), parthenogenetic, and IVV porcine oocytes and embryos. There was no difference in TRIM28 or SETDB1 abundance between oocytes matured in vitro versus in vivo (P > 0.05), whereas TP53 levels were higher in in vitro-matured oocytes. TRIM28 increased from metaphase-II oocytes to the 4-cell and blastocyst stages in IVF embryos, whereas IVV embryos showed a reduction in TRIM28 abundance from maturation throughout development. The relative abundance of TP53 increased by the blastocyst stage in all treatment groups, but was higher in IVF embryos compared to IVV and SCNT embryos. In contrast, SETDB1 transcript levels decreased from the 2-cell to blastocyst stage in all treatments. For each gene analyzed, SCNT embryos of both hard-to-clone and easy-to-clone cell lines were more comparable to IVV than IVF embryos. Knockdown of TRIM28 also had no effect on blastocyst development or expression of SETDB1 or TP53. Thus, TRIM28, SETDB1, and TP53 are dynamically expressed in porcine oocytes and embryos. Furthermore, TRIM28 and TP53 abundances in IVV and SCNT embryos are similar, but different from quantities in IVF embryos. Mol. Reprod. Dev. 81: 552–556, 2014. © 2014 The Authors. Published by Wiley Periodicals, Inc. PMID:24659575

Model reduction by trimming for a class of semi-Markov reliability models and the corresponding error bound

NASA Technical Reports Server (NTRS)

White, Allan L.; Palumbo, Daniel L.

1991-01-01

Semi-Markov processes have proved to be an effective and convenient tool to construct models of systems that achieve reliability by redundancy and reconfiguration. These models are able to depict complex system architectures and to capture the dynamics of fault arrival and system recovery. A disadvantage of this approach is that the models can be extremely large, which poses both a model and a computational problem. Techniques are needed to reduce the model size. Because these systems are used in critical applications where failure can be expensive, there must be an analytically derived bound for the error produced by the model reduction technique. A model reduction technique called trimming is presented that can be applied to a popular class of systems. Automatic model generation programs were written to help the reliability analyst produce models of complex systems. This method, trimming, is easy to implement and the error bound easy to compute. Hence, the method lends itself to inclusion in an automatic model generator.

Talking with John Trim (Part I): A Career in Phonetics, Applied Linguistics and the Public Service

ERIC Educational Resources Information Center

Little, David; King, Lid

2013-01-01

As this issue was in preparation, the journal learned with great regret of the passing of John Trim. John was a long-serving member of the "Language Teaching" Board and his insight and advice proved invaluable for this and previous editors. An expert in the field of phonetics, linguistics, language didactics and policy, John worked…

Measuring the Transgression-Related Interpersonal Motivations Inventory in Marital Relationships: Forgiveness in the Chinese Context (C-TRIM)

ERIC Educational Resources Information Center

Wong, Lai Cheung; Chu, Amanda M. Y.; Chan, Cecilia L. W.

2014-01-01

Objective: Because forgiveness is an important aspect of studies in marital relationships, there is a need for a culturally relevant measure of forgiveness for Chinese couples. This study aims to validate the Transgression-related Interpersonal Motivations Inventory in marital relationships within a Chinese context (C-TRIM). Method: Data were…

Impaired Lysosomal Trimming of N-Linked Oligosaccharides Leads to Hyperglycosylation of Native Lysosomal Proteins in Mice with α-Mannosidosis ▿

PubMed Central

Damme, Markus; Morelle, Willy; Schmidt, Bernhard; Andersson, Claes; Fogh, Jens; Michalski, Jean-Claude; Lübke, Torben

2010-01-01

α-Mannosidosis is caused by the genetic defect of the lysosomal α-d-mannosidase (LAMAN), which is involved in the breakdown of free α-linked mannose-containing oligosaccharides originating from glycoproteins with N-linked glycans, and thus manifests itself in an extensive storage of mannose-containing oligosaccharides. Here we demonstrate in a model of mice with α-mannosidosis that native lysosomal proteins exhibit elongated N-linked oligosaccharides as shown by two-dimensional difference gel electrophoresis, deglycosylation assays, and mass spectrometry. The analysis of cathepsin B-derived oligosaccharides revealed a hypermannosylation of glycoproteins in mice with α-mannosidosis as indicated by the predominance of extended Man3GlcNAc2 oligosaccharides. Treatment with recombinant human α-mannosidase partially corrected the hyperglycosylation of lysosomal proteins in vivo and in vitro. These data clearly demonstrate that LAMAN is involved not only in the lysosomal catabolism of free oligosaccharides but also in the trimming of asparagine-linked oligosaccharides on native lysosomal proteins. PMID:19884343

Quadrotor Control in the Presence of Unknown Mass Properties

NASA Astrophysics Data System (ADS)

Duivenvoorden, Rikky Ricardo Petrus Rufino

Quadrotor UAVs are popular due to their mechanical simplicity, as well as their capability to hover and vertically take-off and land. As applications diversify, quadrotors are increasingly required to operate under unknown mass properties, for example as a multirole sensor platform or for package delivery operations. The work presented here consists of the derivation of a generalized quadrotor dynamic model without the typical simplifying assumptions on the first and second moments of mass. The maximum payload capacity of a quadrotor in hover, and the observability of the unknown mass properties are discussed. A brief introduction of L1 adaptive control is provided, and three different L 1 adaptive controllers were designed for the Parrot AR.Drone quadrotor. Their tracking and disturbance rejection performance was compared to the baseline nonlinear controller in experiments. Finally, the results of the combination of L1 adaptive control with iterative learning control are presented, showing high performance trajectory tracking under uncertainty.

Maximising municipal solid waste--legume trimming residue mixture degradation in composting by control parameters optimization.

PubMed

Cabeza, I O; López, R; Ruiz-Montoya, M; Díaz, M J

2013-10-15

Composting is one of the most successful biological processes for the treatment of the residues enriched in putrescible materials. The optimization of parameters which have an influence on the stability of the products is necessary in order to maximize recycling and recovery of waste components. The influence of the composting process parameters (aeration, moisture, C/N ratio, and time) on the stability parameters (organic matter, N-losses, chemical oxygen demand, nitrate, biodegradability coefficient) of the compost was studied. The composting experiment was carried out using Municipal Solid Waste (MSW) and Legume Trimming Residues (LTR) in 200 L isolated acrylic barrels following a Box-Behnken central composite experimental design. Second-order polynomial models were found for each of the studied compost stability parameter, which accurately described the relationship between the parameters. The differences among the experimental values and those estimated by using the equations never exceeded 10% of the former. Results of the modelling showed that excluding the time, the C/N ratio is the strongest variable influencing almost all the stability parameters studied in this case, with the exception of N-losses which is strongly dependent on moisture. Moreover, an optimized ratio MSW/LTR of 1/1 (w/w), moisture content in the range of 40-55% and moderate to low aeration rate (0.05-0.175 Lair kg(-)(1) min(-1)) is recommended to maximise degradation and to obtain a stable product during co-composting of MSW and LTR. Copyright © 2013 Elsevier Ltd. All rights reserved.

Active mass damper system for high-rise buildings using neural oscillator and position controller considering stroke limitation of the auxiliary mass

NASA Astrophysics Data System (ADS)

Hongu, J.; Iba, D.; Nakamura, M.; Moriwaki, I.

2016-04-01

This paper proposes a problem-solving method for the stroke limitation problem, which is related to auxiliary masses of active mass damper systems for high-rise buildings. The proposed method is used in a new simple control system for the active mass dampers mimicking the motion of bipedal mammals, which has a neural oscillator synchronizing with the acceleration response of structures and a position controller. In the system, the travel distance and direction of the auxiliary mass of the active mass damper is determined by reference to the output of the neural oscillator, and then, the auxiliary mass is transferred to the decided location by using a PID controller. The one of the purpose of the previouslyproposed system is stroke restriction problem avoidance of the auxiliary mass during large earthquakes by the determination of the desired value within the stroke limitation of the auxiliary mass. However, only applying the limited desired value could not rigorously restrict the auxiliary mass within the limitation, because the excessive inertia force except for the control force produced by the position controller affected on the motion of the auxiliary mass. In order to eliminate the effect on the auxiliary mass by the structural absolute acceleration, a cancellation method is introduced by adding a term to the control force of the position controller. We first develop the previously-proposed system for the active mass damper and the additional term for cancellation, and verity through numerical experiments that the new system is able to operate the auxiliary mass within the restriction during large earthquakes. Based on the comparison of the proposed system with the LQ system, a conclusion was drawn regarding which the proposed neuronal system with the additional term appears to be able to limit the stroke of the auxiliary mass of the AMD.

Data trimming, nuclear emissions, and climate change.

PubMed

Shrader-Frechette, Kristin Sharon

2009-03-01

Ethics requires good science. Many scientists, government leaders, and industry representatives support tripling of global-nuclear-energy capacity on the grounds that nuclear fission is "carbon free" and "releases no greenhouse gases." However, such claims are scientifically questionable (and thus likely to lead to ethically questionable energy choices) for at least 3 reasons. (i) They rely on trimming the data on nuclear greenhouse-gas emissions (GHGE), perhaps in part because flawed Kyoto Protocol conventions require no full nuclear-fuel-cycle assessment of carbon content. (ii) They underestimate nuclear-fuel-cycle releases by erroneously assuming that mostly high-grade uranium ore, with much lower emissions, is used. (iii) They inconsistently compare nuclear-related GHGE only to those from fossil fuels, rather than to those from the best GHG-avoiding energy technologies. Once scientists take account of (i)-(iii), it is possible to show that although the nuclear fuel cycle releases (per kWh) much fewer GHG than coal and oil, nevertheless it releases far more GHG than wind and solar-photovoltaic. Although there may be other, ethical, reasons to support nuclear tripling, reducing or avoiding GHG does not appear to be one of them.

Trimming the UCERF2 hazard logic tree

USGS Publications Warehouse

Porter, Keith A.; Field, Edward H.; Milner, Kevin

2012-01-01

The Uniform California Earthquake Rupture Forecast 2 (UCERF2) is a fully time‐dependent earthquake rupture forecast developed with sponsorship of the California Earthquake Authority (Working Group on California Earthquake Probabilities [WGCEP], 2007; Field et al., 2009). UCERF2 contains 480 logic‐tree branches reflecting choices among nine modeling uncertainties in the earthquake rate model shown in Figure 1. For seismic hazard analysis, it is also necessary to choose a ground‐motion‐prediction equation (GMPE) and set its parameters. Choosing among four next‐generation attenuation (NGA) relationships results in a total of 1920 hazard calculations per site. The present work is motivated by a desire to reduce the computational effort involved in a hazard analysis without understating uncertainty. We set out to assess which branching points of the UCERF2 logic tree contribute most to overall uncertainty, and which might be safely ignored (set to only one branch) without significantly biasing results or affecting some useful measure of uncertainty. The trimmed logic tree will have all of the original choices from the branching points that contribute significantly to uncertainty, but only one arbitrarily selected choice from the branching points that do not.

Seismic design of passive tuned mass damper parameters using active control algorithm

NASA Astrophysics Data System (ADS)

Chang, Chia-Ming; Shia, Syuan; Lai, Yong-An

2018-07-01

Tuned mass dampers are a widely-accepted control method to effectively reduce the vibrations of tall buildings. A tuned mass damper employs a damped harmonic oscillator with specific dynamic characteristics, thus the response of structures can be regulated by the additive dynamics. The additive dynamics are, however, similar to the feedback control system in active control. Therefore, the objective of this study is to develop a new tuned mass damper design procedure based on the active control algorithm, i.e., the H2/LQG control. This design facilitates the similarity of feedback control in the active control algorithm to determine the spring and damper in a tuned mass damper. Given a mass ratio between the damper and structure, the stiffness and damping coefficient of the tuned mass damper are derived by minimizing the response objective function of the primary structure, where the structural properties are known. Varying a single weighting in this objective function yields the optimal TMD design when the minimum peak in the displacement transfer function of the structure with the TMD is met. This study examines various objective functions as well as derives the associated equations to compute the stiffness and damping coefficient. The relationship between the primary structure and optimal tuned mass damper is parametrically studied. Performance is evaluated by exploring the h2-and h∞-norms of displacements and accelerations of the primary structure. In time-domain analysis, the damping effectiveness of the tune mass damper controlled structures is investigated under impulse excitation. Structures with the optimal tuned mass dampers are also assessed under seismic excitation. As a result, the proposed design procedure produces an effective tuned mass damper to be employed in a structure against earthquakes.

Herpesvirus deconjugases inhibit the IFN response by promoting TRIM25 autoubiquitination and functional inactivation of the RIG-I signalosome.

PubMed

Gupta, Soham; Ylä-Anttila, Päivi; Callegari, Simone; Tsai, Ming-Han; Delecluse, Henri-Jacques; Masucci, Maria G

2018-01-01

The N-terminal domains of the herpesvirus large tegument proteins encode a conserved cysteine protease with ubiquitin- and NEDD8-specific deconjugase activity. The proteins are expressed during the productive virus cycle and are incorporated into infectious virus particles, being delivered to the target cells upon primary infection. Members of this viral enzyme family were shown to regulate different aspects of the virus life cycle and the innate anti-viral response. However, only few substrates have been identified and the mechanisms of these effects remain largely unknown. In order to gain insights on the substrates and signaling pathways targeted by the viral enzymes, we have used co-immunoprecipitation and mass spectrometry to identify cellular proteins that interact with the Epstein-Barr virus encoded homologue BPLF1. Several members of the 14-3-3-family of scaffold proteins were found amongst the top hits of the BPLF1 interactome, suggesting that, through this interaction, BPLF1 may regulate a variety of cellular signaling pathways. Analysis of the shared protein-interaction network revealed that BPLF1 promotes the assembly of a tri-molecular complex including, in addition to 14-3-3, the ubiquitin ligase TRIM25 that participates in the innate immune response via ubiquitination of cytosolic pattern recognition receptor, RIG-I. The involvement of BPLF1 in the regulation of this signaling pathway was confirmed by inhibition of the type-I IFN responses in cells transfected with a catalytically active BPLF1 N-terminal domain or expressing the endogenous protein upon reactivation of the productive virus cycle. We found that the active viral enzyme promotes the dimerization and autoubiquitination of TRIM25. Upon triggering of the IFN response, RIG-I is recruited to the complex but ubiquitination is severely impaired, which functionally inactivates the RIG-I signalosome. The capacity to bind to and functionally inactivate the RIG-I signalosome is shared by the

Herpesvirus deconjugases inhibit the IFN response by promoting TRIM25 autoubiquitination and functional inactivation of the RIG-I signalosome

PubMed Central

Gupta, Soham; Callegari, Simone; Delecluse, Henri-Jacques

2018-01-01

The N-terminal domains of the herpesvirus large tegument proteins encode a conserved cysteine protease with ubiquitin- and NEDD8-specific deconjugase activity. The proteins are expressed during the productive virus cycle and are incorporated into infectious virus particles, being delivered to the target cells upon primary infection. Members of this viral enzyme family were shown to regulate different aspects of the virus life cycle and the innate anti-viral response. However, only few substrates have been identified and the mechanisms of these effects remain largely unknown. In order to gain insights on the substrates and signaling pathways targeted by the viral enzymes, we have used co-immunoprecipitation and mass spectrometry to identify cellular proteins that interact with the Epstein-Barr virus encoded homologue BPLF1. Several members of the 14-3-3-family of scaffold proteins were found amongst the top hits of the BPLF1 interactome, suggesting that, through this interaction, BPLF1 may regulate a variety of cellular signaling pathways. Analysis of the shared protein-interaction network revealed that BPLF1 promotes the assembly of a tri-molecular complex including, in addition to 14-3-3, the ubiquitin ligase TRIM25 that participates in the innate immune response via ubiquitination of cytosolic pattern recognition receptor, RIG-I. The involvement of BPLF1 in the regulation of this signaling pathway was confirmed by inhibition of the type-I IFN responses in cells transfected with a catalytically active BPLF1 N-terminal domain or expressing the endogenous protein upon reactivation of the productive virus cycle. We found that the active viral enzyme promotes the dimerization and autoubiquitination of TRIM25. Upon triggering of the IFN response, RIG-I is recruited to the complex but ubiquitination is severely impaired, which functionally inactivates the RIG-I signalosome. The capacity to bind to and functionally inactivate the RIG-I signalosome is shared by the

The Matrix Protein of Nipah Virus Targets the E3-Ubiquitin Ligase TRIM6 to Inhibit the IKKε Kinase-Mediated Type-I IFN Antiviral Response.

PubMed

Bharaj, Preeti; Wang, Yao E; Dawes, Brian E; Yun, Tatyana E; Park, Arnold; Yen, Benjamin; Basler, Christopher F; Freiberg, Alexander N; Lee, Benhur; Rajsbaum, Ricardo

2016-09-01

For efficient replication, viruses have developed mechanisms to evade innate immune responses, including the antiviral type-I interferon (IFN-I) system. Nipah virus (NiV), a highly pathogenic member of the Paramyxoviridae family (genus Henipavirus), is known to encode for four P gene-derived viral proteins (P/C/W/V) with IFN-I antagonist functions. Here we report that NiV matrix protein (NiV-M), which is important for virus assembly and budding, can also inhibit IFN-I responses. IFN-I production requires activation of multiple signaling components including the IκB kinase epsilon (IKKε). We previously showed that the E3-ubiquitin ligase TRIM6 catalyzes the synthesis of unanchored K48-linked polyubiquitin chains, which are not covalently attached to any protein, and activate IKKε for induction of IFN-I mediated antiviral responses. Using co-immunoprecipitation assays and confocal microscopy we show here that the NiV-M protein interacts with TRIM6 and promotes TRIM6 degradation. Consequently, NiV-M expression results in reduced levels of unanchored K48-linked polyubiquitin chains associated with IKKε leading to impaired IKKε oligomerization, IKKε autophosphorylation and reduced IFN-mediated responses. This IFN antagonist function of NiV-M requires a conserved lysine residue (K258) in the bipartite nuclear localization signal that is found in divergent henipaviruses. Consistent with this, the matrix proteins of Ghana, Hendra and Cedar viruses were also able to inhibit IFNβ induction. Live NiV infection, but not a recombinant NiV lacking the M protein, reduced the levels of endogenous TRIM6 protein expression. To our knowledge, matrix proteins of paramyxoviruses have never been reported to be involved in innate immune antagonism. We report here a novel mechanism of viral innate immune evasion by targeting TRIM6, IKKε and unanchored polyubiquitin chains. These findings expand the universe of viral IFN antagonism strategies and provide a new potential target for

The Matrix Protein of Nipah Virus Targets the E3-Ubiquitin Ligase TRIM6 to Inhibit the IKKε Kinase-Mediated Type-I IFN Antiviral Response

PubMed Central

Dawes, Brian E.; Yun, Tatyana E.; Park, Arnold; Yen, Benjamin; Basler, Christopher F.; Freiberg, Alexander N.; Lee, Benhur; Rajsbaum, Ricardo

2016-01-01

For efficient replication, viruses have developed mechanisms to evade innate immune responses, including the antiviral type-I interferon (IFN-I) system. Nipah virus (NiV), a highly pathogenic member of the Paramyxoviridae family (genus Henipavirus), is known to encode for four P gene-derived viral proteins (P/C/W/V) with IFN-I antagonist functions. Here we report that NiV matrix protein (NiV-M), which is important for virus assembly and budding, can also inhibit IFN-I responses. IFN-I production requires activation of multiple signaling components including the IκB kinase epsilon (IKKε). We previously showed that the E3-ubiquitin ligase TRIM6 catalyzes the synthesis of unanchored K48-linked polyubiquitin chains, which are not covalently attached to any protein, and activate IKKε for induction of IFN-I mediated antiviral responses. Using co-immunoprecipitation assays and confocal microscopy we show here that the NiV-M protein interacts with TRIM6 and promotes TRIM6 degradation. Consequently, NiV-M expression results in reduced levels of unanchored K48-linked polyubiquitin chains associated with IKKε leading to impaired IKKε oligomerization, IKKε autophosphorylation and reduced IFN-mediated responses. This IFN antagonist function of NiV-M requires a conserved lysine residue (K258) in the bipartite nuclear localization signal that is found in divergent henipaviruses. Consistent with this, the matrix proteins of Ghana, Hendra and Cedar viruses were also able to inhibit IFNβ induction. Live NiV infection, but not a recombinant NiV lacking the M protein, reduced the levels of endogenous TRIM6 protein expression. To our knowledge, matrix proteins of paramyxoviruses have never been reported to be involved in innate immune antagonism. We report here a novel mechanism of viral innate immune evasion by targeting TRIM6, IKKε and unanchored polyubiquitin chains. These findings expand the universe of viral IFN antagonism strategies and provide a new potential target for

Characterization of escherichia coli O157:H7 strains from contaminated raw beef trim during “high event periods”

USDA-ARS?s Scientific Manuscript database

The development and implementation of effective antimicrobial interventions by the beef processing industry in the United States have dramatically reduced the incidence of beef trim contamination by Escherichia coli O157:H7. However, individual processing plants still experience sporadic peaks in co...

Distribution and detection of Shiga toxin-producing Escherichia coli (STEC) during an industrial grinding process of beef trim

USDA-ARS?s Scientific Manuscript database

During the grinding and packaging processes, it is important to understand how Shiga toxin-producing Escherichia coli (STEC) would be distributed and how well it could be detected in beef trim. This study is important because it shows what would happen if contaminated meat is allowed into a commerc...

77 FR 73415 - Authorization of Export Production Activity, Foreign-Trade Subzone 12A, TST NA Trim, LLC (Fabric...

Federal Register 2010, 2011, 2012, 2013, 2014