bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Adhesive Thickness on Interfacial Fracture of Bonded Steel Joints
Authors: Ji Gefu , Ouyang Zhenyu , Li Guoqiang , Pang Su-Seng , Ibekwe Samuel
Published: January 2011

The interfacial fracture of bonded structures is a critical issue for the extensive applications to a variety of modern industries. In the recent two decades, nonlinear fracture mechanics methods have been receiving intensive attentions for adhesively bonded joints. Extensive experimental efforts have been made to determine the toughness of adhesive joints. Several experimental studies have also been conducted to determine the interface cohesive law in bonded joints. However, very few studies investigated the effect of adhesive thickness on the interface cohesive laws. In the cohesive law, both fracture energy and the interfacial cohesive strength, as two critical parameters, have significant effect on the fracture behavior and joint’s structural capability. The present study presents the experimental investigation into how the adhesive’s thickness affect these two important parameters with the nonlinear fracture mechanics. At the mean time, the equivalent interface cohesive laws are experimentally determined for the bonded joints with various adhesive thicknesses. The experimental cohesive laws may provide valuable baseline data for simple analytical and numerical cohesive zone models. With the test results, the mechanism for the intrinsic fracture energy and plastic energy dissipation is discussed. Several other interesting conclusions are also obtained.
Coke Drum Design and Fabrication Issues
Authors: Shargay Cathleen , Singh Anil , Munsterman Tim , Antalffy Les
Published: January 2011

There are numerous design, materials and fabrication issues which significantly affect the cost, reliability and life of coke drums. Primarily in a pros and cons narrative, this paper discusses many of these critical decisions. It first outlines the potential damage mechanisms resulting from coke drum operation, which are primarily thermal fatigue and bulging and also embrittlement, sulfidation and erosion. Delayed Coking operation is described along with the ever present desire by owners to shorten cycle times to maximize unit throughput. Some examples of the decisions include the choices of alloys for base metals, cladding, and weld overlay, and the desire to maximize postweld heat treatment (PWHT) cycles while maintaining Minimum Design Metal Temperature (MDMT) toughness requirements to permit multiple future drum weld repairs. Design issues are reviewed such as uniform versus stepped thickness wall designs, and preferential placement of shell/cone plates to their optimum locations in relation to their individual thicknesses and yield strengths. Skirts also have options in attachment designs, thicknesses and the use of keyholes. The discussion of these and numerous other issues will hopefully assist the industry in the current development of a technical standard on coke drums being done by the American Petroleum Institute (API).
Background on the New ASME PCC-1-2010 Appendices D and O “Guidelines for Allowable Gasket Contact Surface Flatness and Defect Depth” and “Assembly Bolt Load Selection”
Authors: Brown Warren
Published: January 2011

ASME PCC-1 “Guidelines for Pressure Boundary Bolted Joint Assembly” has recently been published and includes several new or extensively revised appendices. Among those is a new Appendix D “Guidelines for Allowable Gasket Contact Surface Flatness and Defect Depth”, which outlines a more practical approach, based on the gasket type being used, to determining acceptable surface flatness and defect tolerances. The approach is based on basic gasket elastic compressibility properties and follows a methodology similar to vessel flaw evaluation to provide guidance for the acceptable depth and size of flange seating surface defects. It will enable independent assessment of the acceptability of defects on a flange facing by inspection personnel without the need for experienced-based judgment for each individual defect by others. An additional new appendix is Appendix O “Assembly Bolt Stress Determination”. In this appendix an alternative, more advanced method compared to the previous method employed in PCC-1 is outlined for the determination of the optimal assembly bolt stress for any bolted joint. The method is based on the maintenance of an acceptable level of gasket stress, with consideration of operating loads or effects acting on the joint. Sufficient data is contained within the appendix to enable the creation of site-specific target assembly bolt torque charts for all standard size flanges. In addition the method can be applied to non-standard joints for a site-wide approach to determining target assembly bolt stress levels on a systematic basis. This paper outlines the background into the development of both of these new appendices and includes further examples of the use of Appendix O.
Challenges in Verification of CWM Software to Compute Residual Stress and Distortion in Welds
Authors: Goldak John , Asadi Mahyar
Published: January 2011

Validation of a Computational Weld Mechanics (CWM) code for a particular welding application requires an estimate of the difference between experimentally measured parameters and parameters computed by a computational model. This requires estimates of the uncertainty in both the experimental data and the computational data and this requires careful design of both the experiment and the CWM model. The authors experience in performing validation tests for a Computational Weld Mechanics (CWM) code is summarized. An example of a validation test for a welding application that compares measured and computed transient temperatures, displacements and strains is described in detail that demonstrates that model can accurately predict this data. Challenges on both the experimental side and computational side are discussed but the greatest challenge is the limited availability of experimental data that has a measure of uncertainty.
Nanoclay Based Grid Stiffened Syntactic Foam Composites
Authors: Stampley Kamissia , Woldesenbet Eyassu , John Manu
Published: January 2011

In this research work, a novel nanoparticle based syntactic foam was employed to form a grid structure with conventional syntactic foams filled in the bay area. Initially, a big slab of the syntactic foam was fabricated and later on cut into squares. These squares were properly arranged in a mold to have an orthogrid arrangement with empty channels between them. These channels were in turn filled with nanoparticle incorporated syntactic foams and cured. Care was taken to properly orient the squares to attain the desired orthogrid geometry. K46 and S22 type of microballoons with volume fractions of 30% and 60% respectively were used in this study. The volume fraction of nanoclay used in the syntactic foams poured within the channels was 1%. Low velocity impact and flexural tests were conducted on these novel nanoparticle based grid syntactic foams. From the low velocity impact results, it is clear that the nanoclay based grid stiffened syntactic foam with S22 type microballoons in the bay area and K46 type microballoons in the grid channels performed well in terms of the load bearing capacity, elastic energy absorption and damage suppression characteristics. On the other hand, under flexural testing, it was clear that the strain at break values for the S2260K4660-1 configuration was close to that of the K4660S2230–1 configuration.
An Ultrasonic Phased Array Evaluation of Intergranular Stress Corrosion Crack (IGSCC) Detection in Austenitic Stainless Steel Piping Welds
Authors: Diaz Aaron A. , Anderson Michael T. , Cinson Anthony D. , Crawford Susan L. , Cumblidge Stephen E.
Published: January 2011

Research is being conducted for the U.S. Nuclear Regulatory Commission at the Pacific Northwest National Laboratory to assess the effectiveness and reliability of advanced nondestructive examination (NDE) methods for the inspection of light water reactor (LWR) components and challenging material/component configurations. This study assessed the effectiveness of far-side inspections on wrought stainless steel piping with austenitic welds, as found in thin-walled, boiling water reactor (BWR) component configurations, for the detection and characterization of intergranular stress corrosion cracks (IGSCC).
Clamp Load Loss in a Bolted Joint Model With Plastic Bolt Elongation and Eccentric Service Load
Authors: Yang Xianjie , Nassar Sayed , Wu Zhijun , Meng Aidong
Published: January 2011

The nonlinear plastic deformation behavior of a clamped bolted joint model under a separating service load is investigated using analytical, finite element, and experimental techniques. An elastic-plastic model is used for the bolt material while the joint material remains in the linear elastic range. Both the analytical and FEA models investigate the variation in the tension of a preloaded bolt, and the corresponding change in the joint clamp load, due to a separating service load that is placed away from the bolt center. Experimental verification is provided for both the analytical and finite element results on the bolt tension variation, clamp load variation and the clamp load loss caused by the incremental plastic bolt elongation under cyclic separating force.
Experimental and CFD Evaluation of a Bubble Column Reactor
Authors: McGuffie Sean M. , Porter Mike A. , Martens Dennis H.
Published: January 2011

During the scale-up design of a slurry bubble column reactor from a pilot demonstration facility to a production reactor, the design team used computational fluid dynamics (CFD) as a tool to quantify design variables, such as gas holdup and liquid velocities/structural pressures within the reactor. At the time of the analysis, all available physics models for modeling the multi-phase flow had significant limitations that would require “tuning” of the CFD input parameters to ensure confidence in the results. The authors initially conducted a literature search to find data that could be used to calibrate the model. While a wide variety of literature is available, none provided the exact data required for model calibration. For this reason, the authors constructed a test column and performed experiments to derive data for tuning the CFD models. Statistical analysis of the experimental data provided distributions on the input parameters of interest. CFD studies were then used to tune the CFD input parameters to match the experimental data. A correlation was developed, tested and verified. This correlation was then used to provide confidence in the results of the design analysis performed on the scaled up reactor.
Diaphragm Closure Analysis Using Nonlinear FEA and CFD
Authors: McGuffie Sean , Porter Mike , Martens Dennis
Published: January 2011

In the previous work PVP2006-93731 “Reinvestigation of Heat Exchanger Flange Leak” (Porter [1]), a series of finite element (FE) models were constructed of a heat exchanger flange. Current FE capabilities were used to further elucidate the reasons for the flange’s leakage in-service, reported in a 1994 paper (Porter [2]). The flange leakage was primarily caused by differential thermal expansion causing yield in the flange bolts and gasket scuffing. Correcting the leakage required the implementation of a weld ring gasket. A similar service exchanger was later designed to eliminate the critical differential thermal expansions. This exchanger employed a diaphragm closure method to eliminate the possibility of gasket leakage. This design included an internal pass partition arrangement such that the end closure flanges were exposed to a single process fluid temperature. In the authors’ experience, typically the exchanger vendor provides proprietary calculations verifying the serviceability of the closure design. This prompted the question, “What analysis methodology would be required for an engineer to qualify or verify the design of a welded diaphragm closure configuration?” The authors have used a thorough methodology for the analysis of a diaphragm closure. This was used for verification of the design suitability for design temperature gradients and related thermal expansion. To conduct the analysis, the authors performed a series of computational fluid dynamics (CFD) and non-linear FE analyses on a representative diaphragm closure geometry (under specific service conditions) to determine the closure’s capability to withstand the design load cases. This paper serves to demonstrate how such analyses can be used to qualify a diaphragm closure’s suitability for a specific service. It should be noted that this paper does not represent a complete analysis of a diaphragm closure. Code (ASME [3]) specifies all procedures that shall be employed. The procedures under investigation were applied to the 2 cases analyzed. Complete engineering of the closure may require the analysis of additional cases.
Design Methodology for the Support Beams of Internal Beds in Vertical Vessels
Authors: Garg Devki Nandan
Published: January 2011

In the Petro-Chemical and other industries, vertical pressure vessels frequently have internal beds which are supported by the vessel walls. Hydrocracking and hydrotreating reactors, packed, tray and distillation columns and filters to name a few, are the common examples of such vessels. Each such bed is generally supported by a set of support beams, sectional bed supports (gratings) and a segmented circumferential ring; the ring supporting the peripheral edges of the gratings. The design details of these beds vary considerably. This paper covers a simple and user friendly procedure for the design of bed support beams, regardless of the complexities of the design details and can be applied in all the design situations. From practical stand point even number of beams are used for each bed which are symmetrically placed with respect to the vessel cross sectional centerline. It is also desirable that such beams be equally spaced to enable standard width grating (grid) sections. The spacing of beams, especially in complex hydrocracker reactor beds with high design pressures (3,000 psi) and design temperatures (900°F) is dictated by the size and weight of the largest beams and bed (grid) sections, which are installed through the top reactor man way openings.
Parametric Study on Determining Optimal Eddy Current Testing Method for Inspection of Steam Generator Tubes in SMART Plant
Authors: Kim Dae-Kwang , Han Sung-Jin , Kim Hak-Joon , Song Sung-Jin , Choung Yun-hang
Published: January 2011

The SMART (System-integrated Modular Advanced ReacTor) is small sized integral type pressurized water reactor designed by KAERI (Korea Atomic Energy Research Institute), Korea. But, shape of steam generator (SG) in SMART plant differs from those in operated nuclear power plants (NPPs). Especially, SG tubes in SAMRT plant is helical type with around 600 mm of innermost diameter and thickness of 2.5 mm which is thicker than general NPPs one. For providing integrity of SG tube in SMART plant, new types of ECT method are needed because eddy current testing (ECT) is one of widely adopted method for inspection of SG tubes in NPPs. Therefore, in this study, we investigate optimal conditions or parameters for detecting and evaluating of flaws in the SG tubes in SMART plant by simulation of ECT signals with various testing condition or parameter such as frequency, coil gap and etc. From the simulated ECT signals optimal eddy current test condition or parameters are proposed.
Using Industry Standards for Designing Composite Repair Systems for Corroded Process Piping
Authors: Alexander Chris , Worth Franz
Published: January 2011

A significant amount of work has transpired over the past several years in generating consensus-based standards that include ASME PCC-2 and ISO 24817 for developing composite repair systems. The intent in developing these standards has been to provide industry with guidelines for designing composite repair systems to ensure that damaged piping and pipelines are safely and properly reinforced. With the numerous composite repair systems currently available to operators, the importance of evaluating the capabilities of each system cannot be overstated. The fundamental design variables available to manufacturers are stiffness, strength, and thickness of the composite. A properly-designed repair system ensures that strains in the reinforced steel and reinforcing composite material do not reach unacceptable levels. This paper provides a basic overview of the design philosophy embedded into the current design codes, as well as presenting results associated with several specific studies that were conducted to evaluate composite repair performance.
A Spatial Resolution of Residual Stress Measurements Using the Deep Hole Drilling Technique
Authors: Skouras Alexandros , Pavier Martyn J. , Shterenlikht Anton
Published: January 2011

This paper describes a study of the ability of the DHD technique to measure the spatial distribution of residual stresses. A two dimensional finite element model of a metal plate has been generated together with a representative state of residual stress. A simulation of the DHD technique is then carried out to provide a series of measurements of the residual stress which can be compared with the known residual stress. This simulation allows the effect of the varying trepan diameters on the accuracy of the DHD technique to be explored. The results of the simulation show that the DHD technique can be used to measure residual stress with a high accuracy, but the increase in the trepan diameter introduce some errors. Suggestions and techniques for reducing these errors are presented.
Development of Composite Pipes for Riser Application in Deep Water
Authors: Sobrinho Ledjane L. , Calado Veroˆnica M. A. , Bastian Fernando L.
Published: January 2011

This work deals with the development of composite pipes for riser application in deep water. Initially, an epoxy resin system was toughened by rubber CTBN addition (10 wt%) as a way of improving the flexibility of future risers. Mechanical and thermal analyses were carried out for characterizing the polymeric systems. As expected, due to the fact that the modulus of the CTBN is much lower than that of the epoxy phase, the tensile modulus decreased with the addition of CTBN, from 3.45 to 2.75 GPa, and the elongation at fracture increased from 2.96 to 5.24%. On the other hand, the glass transition temperature (Tg) of the CTBN-epoxy system changed from 141°C to 136°C. Later, composite tubes were prepared and mechanically characterized. The influence of matrix toughening and the number of composite layers on the mechanical behavior of the tubes were studied using hydrostatic and split-disk tests. In both tests, the results indicate that the matrix plays an important role in composite fracture processes. In the split-disk tests, the tensile strength and the elongation at fracture increased with the addition of CTBN, from 731 to 831 MPa and from 2.34 to 3.09%, respectively. In the case of the hydrostatic tests, the pipes colapse and bursting pressures increased about 14% and 19%, respectively, with the rubber addition to the polymeric matrix. At last, it was verified that the strength of the tubes increases linearly with the number of layers. These results confirm the feasibility of the developed tubes for application as risers in deep water.
Numerical 3-D Fatigue Crack Growth Analyses of Real-Life Components
Authors: Bremberg Daniel , Dhondt Guido
Published: January 2011

This paper presents a numerical concept for fatigue crack propagation computations, within the theory of the finite element method and the theory of linear elastic fracture mechanics, capable of automatic analysis of curved 3-D crack fronts and non-planar crack surfaces. The general modelling of fatigue crack growth and the present algorithm based on a remeshing technique are described. A comparison to existing analytical solutions for an embedded elliptical crack shows satisfying agreement and a fatigue crack growth analysis of a real-life component illustrates the framework applicability.
Overview of RPV Sub-Project of PERFORM 60
Authors: Lidbury David , Keim Elisabeth , Marini Bernard , Malerba Lorenzo , Zeghadi Asmahana
Published: January 2011

PERFORM 60 (prediction of the effects of radiation for reactor pressure vessel and in-core materials using multi-scale modelling - 60 years foreseen plant lifetime) is a 48-month project of the 7th Framework of the European Atomic Energy Community (EURATOM) being carried out under the auspices of the Directorate General Research, Technology and Development (DG.RTD) of the European Commission. Launched in March 2009, and building on the achievements of PERFECT, a EURATOM 6th Framework project, PERFORM 60 has as its main objective the development of multi-scale modelling tools integrated onto a common software platform, aimed at predicting for PWRs (i) the effects of irradiation on RPV materials (low alloy bainitic steels), and (ii) the combined effects of irradiation and corrosion on internals (austenitic stainless steels). Accordingly, PERFORM 60 is based on two main technical sub-projects (i) RPV and (ii) Internals. An Integration sub-project serves to facilitate software development. A Users’ Group supports the main technical sub-projects and allows representatives of constructors, utilities, regulators and research organizations from Europe and further afield to receive the information and training needed to make their own appraisal as to the validity of the developed tools. A significant effort is also being made to train young researchers in the field of physical modelling of materials degradation due to neutron irradiation. The paper describes the general background to PERFORM 60 and provides an overview of the RPV sub-project (SP-1) in terms of its organisation, objectives and technical work programme.
The Model of Fatigue Crack Growth in High Pressure Cylinder Wall
Authors: Brumek Jan , Strnadel Bohumir , Dlouhy´ Ivo
Published: January 2011

This paper presents numerical study to predict crack growth rate under fatigue loading in a high pressure cylinder wall made of high strength steel. Experimental fatigue crack growth data on three point bending test samples were applied to simulate and predict crack growth process using detailed three dimensional parametric finite element models. The fatigue crack propagation was based on linear elastic fracture mechanics and stress intensity factor determination. Finite element model provides results of crack growth analysis optimized for the stress levels of operating pressure level. Results are plotted on S-N curves and the disparity was explained in terms of crack growth rates near threshold stress intensity factor range. Results were compared with an experimental fatigue test.
Using Computational Fluid Dynamics and Finite Element Analysis to Determine Bolt Stresses Due to Thermal Cyclic Loading
Authors: Martinez Phil , McGuffie Sean M. , Porter Michael A.
Published: January 2011

This paper details the procedures necessary to accurately determine the stress in the bolts on a coke gasifier inlet flange using current state-of-the-art practices. Using accepted ASME Code practices (ASME [1]), the stress results are then used to justify the elimination of the spacers that were specified in the original design. Computational fluid dynamics (CFD) is employed to determine heat transfer coefficient distributions in the areas of interest. Finite element (FE) analysis is used to compute the transient assembly temperatures and related bolt stresses. By evaluating the bolt stresses as specified in ASME Div. 1 [1], these analyses were used to determine that the spacers could safely be eliminated during operation.
Some Useful Tests for the Finite Element Meshes of Polycrystals With Explicit Account of the Grains and Grain Boundaries
Authors: Simonovski Igor , Cizelj Leon
Published: January 2011

A growing number of computational material science and computational mechanics research is currently devoted to the explicit modeling of microstructures at various length and time scales. The finite element models of grains and grain boundaries in polycrystals include discretization of the grain interior. In addition, grain boundaries are explicitly discretized as cohesive zones with appropriate damage properties to facilitate the simulation of intergranular cracking. Such finite element models may easily involve hundreds of grains and millions of finite elements. They may also be combined with advanced lattice orientation dependent constitutive models, such as for example anisotropic elasticity and crystal plasticity. The complexity of the model, including the random lattice orientations, may therefore represent a serious difficulty in detecting possible issues in the finite element model and the interpretation of the results. A number of self-consistency model-checks are therefore needed to verify the model. Two tests are proposed and demonstrated in the paper. The first is aiming at the assessment of the finite element mesh quality within the grains in terms of the results. The second is primarily aiming at the verification of the consistent modeling of the cohesive layer at the grain boundaries. In addition, some useful information about the finite element mesh quality in terms of results is also given.
A Novel Comparison of Design-by-Analysis Methods
Authors: Stonehouse Mark , Seipp Trevor G. , Kanamaru Shinichiro , Morrison Shawn
Published: January 2011

There exist some atypical loads on pressure vessels during transportation. This is particularly true when the pressure vessel weighs over 500 tonnes. In this example vessel, the transportation was via rail on a “Schnabel Car”, in which the vessel is suspended horizontally between the top nozzle and the skirt, and a significant axial compressive load is applied. During the evaluation of the stresses in the top head, a particularly novel situation was encountered which brought about some interesting issues with regards to the three Design-By-Analysis methods: Elastic, Limit Load, and Elastic-Plastic. This paper discusses the comparison between all three of these Design-By-Analysis methods, and provides recommendations for which is most appropriate for this type of evaluation. Additional recommendations and warnings are provided for the use of the Elastic and Limit Load methods as well.
Inspection of Bottom Mounted Instrumentation (BMI) J-Weld
Authors: Burat Olivier , Piriou Marc , Kernin Yann , Debroise Mikael , Moreau Christophe , Glass Samuel W. , Casula Olivier
Published: January 2011

Reactor Pressure Vessel (RPV) Bottom Mounted Instrumentation (BMI) primary nozzle ultrasonic (UT) inspections have been performed by AREVA for more than 15 years. EPRI demonstrations were performed in 2004 and an RSEM qualification was obtained in 2005, This UT inspection detects and characterizes cracks in the base metal of the penetration and its interface with the weld. A complementary Visual Examination of the weld or an Eddy Current examination may also be performed but these tests are understood to be marginal with a possibility to miss indications or to mistake inclusions or weld voids for in-service cracks and therefore could force an unnecessary repair. Difficulties associated with examination of this area include: • Unpredictable ultrasonic behaviour in the weld material; • Wavy and complex OD weld surface profile; • Restricted accessibility around the weld surface. AREVA’s Non Destructive Examination Technical Center (NETEC), has developed and/or evaluated several techniques to improve surface and volumetric inspection of this weld including: • A TOFD ultrasonic (UT) probe to detect and characterize cracks within the weld metal from the ID surface of the nozzle. • A flexible UT Phased Array probe to accommodate the wavy and complex weld surface, in partnership with CEA, • Reduced surface ET probes and flexible ET multi-coils (in partnership with CEA), for improved surface inspection, • Infrared Photo-Thermal Camera examination of the weld surface. This paper discusses the designs and performances of these specific probes and NDT techniques as applied to the BMI nozzles, J-welds, and other similar components.
Dielectric layers suitable for high voltage integrated trench capacitors
Authors: vom Dorp J. , Erlbacher T. , Bauer A. J. , Ryssel H. , Frey L.
Published: January 2011

In this work, two different dielectric stacks consisting of silicon dioxide (SiO2) and silicon nitride (Si3N4) are analyzed regarding their suitability as dielectrics in a high voltage trench capacitor. The processing of the dielectric layers and the resulting edge-coverage in the trench holes are described. Voltage and temperature dependence of the trench capacitance are analyzed and compared with planar capacitors for reference. The leakage currents are measured and the current transport mechanisms are analyzed. The outstanding properties of the devices are a high capacitance per area (1.25 nF/mm2 for SiO2 and 1.5 nF/mm2 for Si3N4), a low temperature coefficient (SiO2: 18 ppm/K; Si3N4: 85 ppm/K from 25–100 °C), and a low leakage current (<1×10−6 A) for voltages up to 400 V for Si3N4.
Challenges of Antibacterial Discovery
Authors: Silver Lynn L.
Published: January 2011

The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort.
Farm cat with TB
Authors: Cannon Martha
Published: January 2011

One of your dairy farming clients has a pet cat, Suzie, which has been losing weight for some months and recently developed large firm submandibular lymph nodes and a soft cough. A lymph node biopsy revealed granulomatous inflammation and a PCR test was positive for Mycobacterium bovis. There are 14 other farm cats, which don't come into the house. The dairy farm had a number of reactors at the last tuberculosis (TB) test and is currently under movement restrictions. Suzie is the much‐loved pet of the farmer's young daughter. What is the best course of action?
Tackling the welfare issues of dog breeding
Authors: Crispin Sheila
Published: January 2011

Sheila Crispin is chair of the new Advisory Council on the Welfare Issues of Dog Breeding. Here, she describes the background to the Council, outlines its priorities and offers some thoughts on the issues that need to be addressed
Immune and nonimmune components orchestrate the pathogenesis of inflammatory bowel disease
Authors: Danese Silvio
Published: January 2011

Inflammatory bowel disease (IBD) pathogenesis is driven by the interactions between the innate and the adaptive immune system. Both systems are actually expressed not only by immune cells, but also by essentially all types of nonimmune cells. Nonimmune cells have classically been considered as simple targets of the aberrant inflammatory process occurring in IBD. However, the discovery that many of the functions traditionally attributed to immune cells are also performed by nonimmune cells has caused a shift to a multidirectional hypothesis in which nonimmune cells and even acellular elements are considered active players of IBD pathogenesis. The aim of this review is to summarize the current role played by each cell type in IBD pathogenesis.
Acute antioxidant supplementation and skeletal muscle vascular conductance in aged rats: role of exercise and fiber type
Authors: Hirai Daniel M. , Copp Steven W. , Schwagerl Peter J. , Haub Mark D. , Poole David C. , Musch Timothy I.
Published: January 2011

Age-related increases in oxidative stress contribute to impaired skeletal muscle vascular control. However, recent evidence indicates that antioxidant treatment with tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) attenuates flow-mediated vasodilation in isolated arterioles from the highly oxidative soleus muscle of aged rats. Whether antioxidant treatment with tempol evokes similar responses in vivo at rest and during exercise in senescent individuals and whether this effect varies based on muscle fiber type composition are unknown. We tested the hypothesis that redox modulation via acute systemic tempol administration decreases vascular conductance (VC) primarily in oxidative hindlimb locomotor muscles at rest and during submaximal whole body exercise (treadmill running at 20 m/min, 5% grade) in aged rats. Eighteen old (25–26 mo) male Fischer 344 x Brown Norway rats were assigned to either rest ( n = 8) or exercise ( n = 10) groups. Regional VC was determined via radiolabeled microspheres before and after intra-arterial administration of tempol (302 μmol/kg). Tempol decreased mean arterial pressure significantly by 9% at rest and 16% during exercise. At rest, similar VC in 26 out of 28 individual hindlimb muscles or muscle parts following tempol administration compared with control resulted in unchanged total hindlimb muscle VC (control: 0.18 ± 0.02; tempol: 0.17 ± 0.05 ml·min−1·100 g−1·mmHg−1; P > 0.05). During exercise, all individual hindlimb muscles or muscle parts irrespective of fiber type composition exhibited either an increase or no change in VC with tempol (i.e., ↑11 and ↔17 muscles or muscle parts), such that total hindlimb VC increased by 25% (control: 0.93 ± 0.04; tempol: 1.15 ± 0.09 ml·min−1·100 g−1·mmHg−1; P ≤ 0.05). These results demonstrate that acute systemic administration of the antioxidant tempol significantly impacts the control of regional vascular tone in vivo presumably via redox modulation and improves skeletal muscle vasodilation independently of fiber type composition during submaximal whole body exercise in aged rats.
Measuring myosin cross-bridge attachment time in activated muscle fibers using stochastic vs. sinusoidal length perturbation analysis
Authors: Tanner Bertrand C. W. , Wang Yuan , Maughan David W. , Palmer Bradley M.
Published: January 2011

The average time myosin cross bridges remain bound to actin ( ton) can be measured by sinusoidal length perturbations (sinusoidal analysis) of striated muscle fibers using recently developed analytic methods. This approach allows measurements of ton in preparations possessing a physiologically relevant myofilament lattice. In this study, we developed an approach to measure ton in 5–10% of the time required for sinusoidal analysis by using stochastic length perturbations (white noise analysis). To compare these methods, we measured the influence of MgATP concentration ([MgATP]) on ton in demembranated myocardial strips from mice, sampling muscle behavior from 0.125 to 200 Hz with a 20-s burst of white noise vs. a 300-s series of sinusoids. Both methods detected a similar >300% increase in ton as [MgATP] decreased from 5 to 0.25 mM, differing by only 3–14% at any [MgATP]. Additional experiments with Drosophila indirect flight muscle fibers demonstrated that faster cross-bridge cycling kinetics permit further reducing of the perturbation time required to measure ton. This reduced sampling time allowed strain-dependent measurements of ton in flight muscle fibers by combining 10-s bursts of white noise during periods of linear shortening and lengthening. Analyses revealed longer ton values during shortening and shorter ton values during lengthening. This asymmetry may provide a mechanism that contributes to oscillatory energy transfer between the flight muscles and thoracic cuticle to power flight. This study demonstrates that white noise analysis can detect underlying molecular processes associated with dynamic muscle contraction comparable to sinusoidal analysis, but in a fraction of the time.
A Phase I Clinical-Pharmacodynamic Study of the Farnesyltransferase Inhibitor Tipifarnib in Combination with the Proteasome Inhibitor Bortezomib in Advanced Acute Leukemias
Authors: Lancet Jeffrey E. , Duong Vu H. , Winton Elliott F. , Stuart Robert K. , Burton Michelle , Zhang Shumin , Cubitt Christopher , Blaskovich Michelle A. , Wright John J. , Sebti Said , Sullivan Daniel M.
Published: January 2011

Purpose: To determine the safety, target inhibition, and signals of clinical activity of tipifarnib in combination with bortezomib in patients with advanced acute leukemias.

Experimental Design: In a “3 + 3” design, patients received escalating doses of tipifarnib (days 1–14) and bortezomib (days 1, 4, 8, 11) every 3 weeks until maximum tolerated dose was reached. Peripheral blood mononuclear cells (PBMC) were collected at days 1, 8, and 22 for measurement of chymotrypsin-like and farnesyltransferase activity. Purified bone marrow leukemic blasts were collected at baseline and at day 8 for measurement of NF-κB activity.

Results: The combination was well-tolerated, and maximum tolerated dose was not reached. Dose-limiting toxicities included diarrhea, fatigue, and sensorimotor neuropathy. Chymotrypsin-like and farnesyltransferase activity within PBMCs were decreased in a majority of patients at day 8. NF-κB activity within leukemic blasts was decreased in a majority of patients at day 8. Complete response with incomplete count recovery was observed in 2 patients, and additional 5 patients had stable disease.

Conclusions: Tipifarnib and bortezomib combination in patients with advanced leukemias was well-tolerated, demonstrated relevant target inhibition, and was associated with signals of clinical activity in patients with advanced and refractory acute leukemias. Future studies of this combination may be warranted in more selected groups of patients in whom these molecular targets are of particular importance. Clin Cancer Res; 17(5); 1140–6. ©2011 AACR.
Murine Hematopoietic Cell Tissue Factor Pathway Inhibitor Limits Thrombus Growth
Authors: Maroney Susan A. , Cooley Brian C. , Ferrel Josephine P. , Bonesho Catherine E. , Mast Alan E.
Published: January 2011

Objective—

Tissue factor (TF)–factor VIIa initiates blood coagulation and is found on microparticles that accumulate within intravascular thrombi. Tissue factor pathway inhibitor (TFPI), a factor Xa (fXa)–dependent inhibitor of TF–factor VIIa, is produced by megakaryocytes and is present in platelets. We sought to determine the role of platelet TFPI in regulation of thrombus growth.

Methods and Results—

Western blot analyses demonstrated that murine platelets produce TFPIα, the most evolutionarily conserved alternatively spliced isoform of TFPI. A mouse model of hematopoietic cell TFPI deficiency was developed by transplanting irradiated TFPI
+/−
mice with TFPI
−/−
fetal liver cells. Platelets from transplanted mice totally lack TFPI inhibitory activity. An electrolytic vascular injury model was used to assess thrombus growth in the femoral vein and carotid artery. Mice lacking hematopoietic TFPI developed larger femoral vein and carotid artery thrombi than TFPI
+/−
mice transplanted with TFPI
+/+
hematopoietic cells, as evidenced by increased platelet accumulation.

Conclusion—

Hematopoietic TFPI limits thrombus growth following vascular injury. Because platelets are the primary hematopoietic cell accumulating within a growing thrombus, these findings suggest that TFPI present within platelets functions to limit intravascular thrombus growth, likely through inhibition of the procoagulant activity of blood borne TF.
Sustained Hemodynamic Stress Disrupts Normal Circadian Rhythms in Calcineurin-Dependent Signaling and Protein Phosphorylation in the Heart
Authors: Sachan Nita , Dey Asim , Rotter David , Grinsfelder D. Bennett , Battiprolu Pavan K. , Sikder Devanjan , Copeland Victoria , Oh Misook , Bush Erik , Shelton John M. , Bibb James A. , Hill Joseph A. , Rothermel Beverly A.
Published: January 2011

Rationale:

Despite overwhelming evidence of the importance of circadian rhythms in cardiovascular health and disease, little is known regarding the circadian regulation of intracellular signaling pathways controlling cardiac function and remodeling.

Objective:

To assess circadian changes in processes dependent on the protein phosphatase calcineurin, relative to changes in phosphorylation of cardiac proteins, in normal, hypertrophic, and failing hearts.

Methods and Results:

We found evidence of large circadian oscillations in calcineurin-dependent activities in the left ventricle of healthy C57BL/6 mice. Calcineurin-dependent transcript levels and nuclear occupancy of the NFAT (nuclear factor of activated T cells) regularly fluctuated as much as 20-fold over the course of a day, peaking in the morning when mice enter a period of rest. Phosphorylation of the protein phosphatase 1 inhibitor 1 (I-1), a direct calcineurin substrate, and phospholamban, an indirect target, oscillated directly out of phase with calcineurin-dependent signaling. Using a surgical model of cardiac pressure overload, we found that although calcineurin-dependent activities were markedly elevated, the circadian pattern of activation was maintained, whereas, oscillations in phospholamban and I-1 phosphorylation were lost. Changes in the expression of fetal gene markers of heart failure did not mirror the rhythm in calcineurin/NFAT activation, suggesting that these may not be direct transcriptional target genes. Cardiac function in mice subjected to pressure overload was significantly lower in the morning than in the evening when assessed by echocardiography.

Conclusions:

Normal, opposing circadian oscillations in calcineurin-dependent activities and phosphorylation of proteins that regulate contractility are disrupted in heart failure.
Advances in Brain Recovery and Rehabilitation 2010
Authors: Zorowitz Richard , Brainin Michael
Published: January 2011

Discoveries in the past year have impacted the understanding of brain recovery and there is more of a need than ever for a foothold in recovery and rehabilitation This review reports on translational efforts, new (and old) potential drugs, various approaches to neurorehabilitation, and brain imaging that demonstrate reorganization in the human brain during stroke rehabilitation.
“Obligations to Negroes who would be kin if they were not Negro”
Authors: Sollors Werner
Published: January 2011

The 1965/1966 Dcedalus issues on “The Negro American” reveal how America's racial future was imagined nearly a half-century ago, and at least one of the prophecies - voiced by sociologist Everett C. Hughes - found its fulfillment in an unexpected way at President Obama's inauguration in 2009. Short stories by Amina Gautier (“Been Meaning to Say” and “Pan is Dead”), Heidi Durrow's novel The Girl WhoFellfrom the Sky, plays by Thomas Bradshaw (Strom Thurmond Is Not a Racist and Cleansed), and poems by Terrance Hayes (“For Brothers and the Dragon” and “The Avocado”) suggest trends in recent works by African American authors who began their publishing careers in the twenty-first century.
Through the Looking Glass: Kingly Virtues in Safavid and Mughal Historiography
Authors: Quinn Sholeh A.
Published: January 2011

During the reigns of the Safavid Shah ‘Abbās I and the Mughal Emperor Akbar, two chroniclers, one from each dynasty, included in their texts lists of “kingly virtues.” This paper explores the possible historiographical precedents for this section in the chronicles, and places particular emphasis on the “mirrors for princes” literature. The paper concludes with a suggestion that reading the narrative portions of the chronicles in light of the mirrors for princes literature helps us understand why chroniclers may have included certain information in those sections.
Will the “Real” Candidates for President and Vice President Please Stand Up? 2008 Pre- and Post-Debate Viewer Perceptions of Candidate Image
Authors: Warner Benjamin R. , Carlin Diana B. , Winfrey Kelly , Schnoebelen James , Trosanovski Marko
Published: January 2011

This study of the 2008 first presidential and vice presidential debate builds on past research on viewers’ perceptions of candidate images. Going back to the Kennedy-Nixon debates in 1960, image research has been conducted in most presidential election cycles. Findings consistently show that viewers enter the debates with perceptions of candidates’ character and leadership qualities and that the debates tend to reinforce rather than change images unless the viewers are undecided or not well informed about a candidate. The results of the 2008 study confirmed trends from past research but also provided some surprises in that most changes in image perception were for senator Joe Biden, the longest-serving public official in the race. The study concludes that media often assume knowledge about candidates that might not exist and that in the 2008 match-ups, the debates did not provide the “game changer” that the McCain-Palin ticket needed to overcome a growing movement toward the Obama-Biden ticket that began shortly before the first debate.
Capitalist Systems, Deindustrialization, and the Politics of Public Education
Authors: Jensen Carsten
Published: January 2011

Recent years have seen a number of studies on the determinants of educational spending. Almost all of the existing work emphasizes the importance of left-wing governments as a motor of expansion because such expansion allegedly ensures both redistribution and the facilitation of a supply-side economy. The existing literature thereby corroborates the power resource theory. Against this common wisdom the article presents an argument building on the varieties of capitalism approach. It is argued that education is a poor instrument for redistribution because access is universal and high-income groups have a tendency to use education even more than low-income groups. Instead, we argue that deindustrialization is the main driver of educational spending because deindustrialization constitutes one of the most salient threats to workers in modern societies. As deindustrialization rises workers risk ending up with redundant skills, especially in countries where the average skills specificity is high, that is, coordinated market economies. The expectations find empirical support in a time-series cross-section regression analysis of 18 Western countries in the years 1980-2000.
Reducing Exposure to Trust-Related Risks to Avoid Self-Blame
Authors: Effron Daniel A. , Miller Dale T.
Published: January 2011

Three studies demonstrated that anticipated self-blame elicits more conservative decisions about risks that require trust than about otherwise economically identical risks that do not. Participants were more reluctant to invest money in a company when it risked failure due to fraud versus low consumer demand (Study 1), and to risk points in an economic game when its outcome ostensibly depended on another participant versus chance (Studies 2 and 3). These effects were mediated by anticipated self-blame (Studies 1 and 2). Additionally, participants who actually experienced a loss felt more self-blame when the loss violated their trust and became even more conservative in subsequent risk decisions relative to participants whose loss did not violate their trust (Study 3). No support emerged for alternative explanations based on either the perceived probability of incurring a loss or an aversion to losses that profit others. The motivational power of trust violations is discussed.