bluuebunny/crossref_metadata_2025 huggingface dataset:
Failure Probability Analysis by Probabilistic Fracture Mechanics Based on FRI SCC Model
Authors: Maeda Noriyoshi , Shoji Tetsuo
Published: January 2011

Failure Probability of a weld by stress corrosion cracking (SCC) in austenitic stainless steel piping was analyzed by probabilistic fracture mechanics (PFM) approach based on electro-chemical crack growth model (FRI model). In this model, crack growth rate da/dt where a is crack depth is anticipated as the rate of chemical corrosion process defined by electro-chemical Coulomb’s law. The process is also related to the strain rate at the crack tip, taking small scale yielding condition into consideration. Derived transcendental equation is solved numerically by iterative method. Compared to the mechanical crack growth equation like Paris’ law for SCC, FRI model can introduce many electro-chemical parameters such as electric current associated with corrosion of newly born SCC crack surface, the frequency of protective film break and mechanical parameters such as stress intensity factor change with time dK/dt. Stratified Monte-Carlo method was introduced which define the cell of sampling space by the ranges of a/c (c is crack length at surface) and the width of K of sampling space, Kw which has to be defined referring to KSCC below which no SCC is caused. Log-normal distributions were anticipated for a/c distribution and K distribution. Parameter survey performed shows that failure probability which is defined as the ratio of crack number whose depth reached 80% of wall thickness to the total crack number depends on many parameters introduced, especially on yielding stress, electric current decay parameter m, strain hardening index n in Ramberg-Osgood equation and dK/dt. From the requirements of FRI model, two types of threshold value of initial crack depth, cracks having smaller depth than this value can not grow, are proposed. Calculated failure probability does not reach 1 when cracks having smaller initial depth than the threshold value are included in the distribution of analyzing cracks.
Development of Reduced Pressure Electron Beam Welding Process for Thick Section Pressure Vessel Welds
Authors: Ayres K. R. , Hurrell P. R. , Gill C. M. , Bridger K. , Burling L. D. , Punshon C. S. , Wei Liwu , Bagshaw N.
Published: January 2011

A reduced pressure electron beam (RPEB) process is being developed in the UK by ‘The Welding Institute’ (TWI) for the manufacture of thick section plate, forging and pipe welds. Potential gains include minimal distortion, fewer weld defects and rapid production times, compared to conventional arc welding processes. To date, RPEB welding equipment and parameters have been successfully developed and applied in a sealed chamber under partial vacuum (∼1mbar), to produce 1-pass seam welds in low alloy steel plates and forgings. Rolls-Royce commissioned TWI to produce RPEB welds in SA508 Grade 3 Class 1 steel forgings of between 100mm and 160mm thickness, as part of a feasibility study for nuclear pressure vessel applications. This paper presents results of micro-structural examinations, material property tests and residual stress analyses of RPEB welds in SA508 Grade 3 steel forgings, both in the as-welded condition and after post weld heat treatment (PWHT). This data was required in order to assess the structural integrity of the weldment. A narrow uniform fusion zone approximately 10mm wide and 3mm deep heat affected zone (HAZ) was produced. High hardness levels were measured in the weld HAZ, but the application of PWHT at 600°C had a beneficial tempering effect, reducing the maximum hardness to below 300Hv. A 3D finite element model was used and deep hole-drilling measurements were independently performed, to determine welding residual stress distributions. In both cases yield magnitude tri-axial tensile stresses were evaluated in the centre of the weld and adjacent HAZ, of up to +600MPa. This result is as expected since the centre region is the last to solidify and cool, with a high degree of restraint to weld shrinkage. However effective stress relaxation occurs during PWHT, mainly due to creep, reducing the maximum residual stress to about 100MPa (or 20% yield strength). This feasibility study has shown that RPEB welding is a viable method for fabricating large pressure vessels in low alloy steels. Sound joints can be produced in sections up to 160mm thick in a vacuum chamber. Further development work is being done by TWI in order to apply the technique out-of-chamber using a local vacuum seal.
Evaluation of Pipe Flange Gaskets Relaxation
Authors: Araujo Roberto H. G. , Lowenberg Jose´ L. C.
Published: January 2011

Relaxation is a characteristic observed in any gasket type, being affected by a series of factors, such as composition, manufacturing process, temperature, etc. Therefore the relaxation of the gasket cannot be treated in a generic way. This paper presents a test protocol, based upon an existing test standard, as well as actual relaxation results for spiral wound gasket and compressed non-asbestos, the most used gaskets in pipe flanges. The objective is to have data to allow a better evaluation of the gasket relaxation behavior in order to determine the additional bolt pre-load to compensate for it.
Development of Computational Framework and Architecture for Extremely Low Probability of Rupture (XLPR) Code
Authors: Rudland D. , Mattie P. , Kurth R. , Klasky H. , Bishop B. , Harris D.
Published: January 2011

The Nuclear Regulatory Commission (NRC) Standard Review Plan (SRP) 3.6.3 describes Leak-Before-Break (LBB) assessment procedures that can be used to demonstrate compliance with the 10CFR50 Appendix A, GDC-4 requirement that primary system pressure piping exhibit an extremely low probability of rupture. SRP 3.6.3 does not allow for assessment of piping systems with active degradation mechanisms, such as Primary Water Stress Corrosion Cracking (PWSCC) which is currently occurring in systems that have been granted LBB exemptions. Along with the existing qualitative steps to assuring safety in LBB lines with PWSCC, the NRC staff, working cooperatively with the nuclear industry through a memorandum of understanding, is developing a new, modular based, comprehensive piping system assessment methodology to directly demonstrate compliance with the regulations. This tool, called xLPR (eXtremely Low Probability of Rupture), would properly model the effects and uncertainties of both active degradation mechanisms and the associated mitigation activities. The tool will be comprehensive with respect to known challenges, vetted with respect to scientific adequacy of models and inputs, flexible enough to permit analysis of a variety of in-service situations and adaptable such as to accommodate evolving and improving knowledge. A multi-year project has begun that will first focus on the development of a viable method and approach to address the effects of PWSCC as well as define the requirements necessary for a modular-based assessment tool. A prototype xLPR model and pilot study case is first being conducted leveraging existing fracture mechanics models and software coupled to both a commercial and open source code framework to determine the framework and architecture requirements appropriate for building a modular-based code with this complexity. The pilot study phase is focusing on PWSCC in pressurizer surge nozzles. Later development phases will broaden the scope of xLPR to all primary piping systems in pressurized and boiling water reactors (PWR and BWR), using an incremental approach that incorporates the design requirements and lessons learned from previous iterations. This paper specifically examines the prototype xLPR model and includes the methods and approach used to couple existing models and software as modules within a probabilistic software framework. Since the pilot study is currently still ongoing, this paper provides a discussion of the current status and plans to move forward after the pilot study is complete.
Spiral Wound Versus Flexible Graphite Faced Serrated Metal Pipe Flange Gaskets in Thermal Cycling and Pressure Comparative Testing
Authors: Veiga Jose´ C. , Cipolatti Carlos F. , Reeves David
Published: January 2011

Spiral Wound gaskets have been successfully used in ASME B16.5 pipe flanges. However, in the last few years, to increase the reliability and safety, there has been a trend to replace them by graphite faced serrated metal gaskets. These are assumed to be better in terms of relaxation and installation. This paper shows a comparison between these two gasket styles. Relaxation and leak tests were performed using standard studs and flanges to simulate actual field conditions.
German Engineering Methods for Critical Crack Size Assessment in Ductile Regime Based on Envelop Flow Stress
Authors: Blasset Se´bastien , Tiete Ralf , Keim Elisabeth
Published: January 2011

The purpose of this paper is to present engineering methods used in Germany for integrity assessment of structural components with a flaw in the ductile regime. The methods are validated by more than 1500 experiments and cover through wall crack as well as part-through wall cracks (in either axial or circumferential orientation) located in base material, heat affected zone, homogeneous or dissimilar metal welds. By fulfilling the toughness requirement, the structural integrity of a cracked component in the ductile regime can be assessed conservatively (safely) by considering simplified methods for which only strength and impact energies values are needed. The physical and mathematical background of the methods for circumferential cracks (flow stress concept FSC; plastic limit load PLL) and for axial cracks (Battelle approach BMI; Ruiz approach RUIZ), as well as the historical connection with the German basis safety concept will be reviewed. Similarity with other international methods (like R6, Section XI of ASME Code, SRP 3.6.3) will be emphasized. The range of validity resulting from experimental investigations (experimental database built from own research or from literature) is summarized and the validation procedure of the methods (FSC, PLL, BMI, RUIZ) is explained. The resulting correction factors on flow stress (envelop flow stress) to account for elastic-plastic fracture conditions and to result in conservative (safe) predictions of crack instability depending on the method (FSC, PLL, BMI, RUIZ), crack orientation (circumferential and axial) and type of material (ferritic and austenitic) is given. The ratio of the computed experimental to the theoretical stress gained by these several engineering methods (German flow stress based simplified methods and other international methods) will be presented on the basis of the experimental database (with a various combination of geometry, materials and loading combination) which covers also elbows and vessels. Recommendations on the good use of the methods for ductile integrity assessment are given including also dissimilar metal welds consideration.
Partial Safety Factors Assessment of Pipes With a Circumferential Surface Flaw
Authors: Machida Hideo , Chitose Hiromasa , Arakawa Manabu
Published: January 2011

This paper describes the evaluation of partial safety factors (PSF’s) for parameters related to flaw evaluation of pipes which have a circumferential surface flaw, and proposes the important matter which should be pay attention in the setup of the safety factors used in flaw evaluation. PSF’s were evaluated considering randomness of flaw size, a fracture resistance curve (J-R curve) and applied loads using load and resistance factor design method (LRFD). The limit state function is expressed by fracture resistance (resistance-related parameter) and applied J integral (load-related parameter). The measure parameters in the reliability assessment are the flaw size and the J-R curve, and PSF’s of them are larger than those of applied loads. Since the material properties used in the flaw evaluation are generally set to the engineering lower limit of their variation (e.g., 95% lower confidence limit), variation of the flaw size is considered to have important role on flaw evaluation. Therefore, when setting up the safely factors used in Rules on Fitness-for-Service (FFS), it is necessary to take into consideration not only the influence of variation of loads or material strength but the influence of variation of flaw size.
Seismic Behavior of Buried PE Pipelines Subject to Fault Offsets
Authors: O’Rourke Michael J. , Abdoun Tarek H. , Ha Da
Published: January 2011

The paper presents the results of a series of centrifuge tests on the behavior of buried PE pipe subject to the fault offset hazard. The tests simulated both Strike-Slip (SS) and Normal offsets. Besides fault type, the three main parameters that were varied include the pipe burial depth, the intersection angle between the pipe axis and the fault (SS faults) and the direction of faulting (SS with right lateral or left lateral offset). Instrumentation allowed acquisition of pipe strain data which was decomposed into axial strain and flexural (bending) strain components. The paper will describe the rates at which strain decreases with distance from the fault, and the strong influence of burial depth and intersection angle on the magnitude of axial and flexural strain. New instrumentation allowed acquisition of the normal pressure between the buried PE pipe and the surrounding soil. As one might expect the normal pressure varied in the circumferential direction, as well as with distance from the fault. These pressures were used to estimate force-deformation characteristics of the equivalent ‘soil-springs’. Unlike the 2-D behavior assumed for soil-spring models currently used in practice, the centrifuge results show that the behavior is actually 3-D in nature. Fortunately, as will be shown in the paper, 2-D soil-spring models yield conservative results in terms of pipe strains.
Measurement of Fracture Toughness of Materials With Non-Uniform Microstructure Based on Spiral Notch Torsion Test
Authors: Zhang Wei , Feng Zhili , Wang Jy-An
Published: January 2011

Materials such as welds consist of highly non-uniform distribution of microstructure. It is typically difficult to measure fracture toughness of those materials using the conventional testing approaches such as ASTM compact tension test, since the non-uniform microstructure can induce irregular crack propagation front. In this study, the spiral notch torsion test (SNTT) is enhanced to measure the fracture toughness of welds. The test specimen resembles a round tensile bar with a spiral-shaped notch on the circumference. To introduce nonuniform microstructure, the heat treatment with a Gleeble system is used to rapidly heat and quench the specimen. The heating and cooling rates applied are typical of those experienced in welding. The hardness distribution in the axial direction of as-heat-treated specimen has a bell shape centered in the middle of the specimen. This distribution resembles that in a transverse section of a weldment. During loading, the specimen is twisted about its axis. It is possible to achieve a Mode I crack front that is long enough to meet the plain strain state and other fracture mechanics requirements for testing the local toughness of weld region. Fracture toughness calculation based on finite element analysis is performed to convert the recorded load-displacement into the fracture toughness KIc.
Manufacturing Technologies of Breeding Blanket Components Using Reduced Activation Ferritic/Martensitic Steel
Authors: Hirose Takanori , Tanigawa Hiroyasu , Enoeda Mikio
Published: January 2011

Put abstract text here. This paper summarizes manufacturing technologies of the water-cooled-solid-breeder (WCSB) blanket module for a fusion reactor using reduced activation ferritic/martensitic steel (RAFM). Although RAFM is very similar to commercial 9 Cr heat resistant steel, RAFM in the blanket is to be used as thin wall structure. Moreover, it is necessary to employ some new manufacturing technologies for the components such as hot-isostatic-pressing (HIP) and fiber-laser-welding (FLW). Some full-scale mock-ups of the blanket have been developed using conventional and newly developed method. The mock-ups have been developed in industrial scale, and the mock-ups demonstrated integrity in the service condition of the blanket without non-nuclear environment. The mock-ups demonstrated their soundness under the service condition of the blanket.
Development of a Probabilistic Pipe Rupture Assessment Code
Authors: Csontos Aladar , Harrington Craig
Published: January 2011

Appendix A, General Design Criteria (GDC) 4, of 10 CFR Part 50 states, in part, that the dynamic effects associated with postulated reactor coolant system pipe ruptures may be excluded from the design basis when analyses reviewed and approved by NRC demonstrate that the probability of fluid system piping rupture is extremely low under conditions consistent with the design basis. Licensees have typically demonstrated compliance with this probabilistic criterion through deterministic analyses that do not accurately simulate typical piping degradation. Given recent advances in probabilistic methodologies, the NRC staff and industry believe that performing a probabilistic analysis of primary system piping that fully addresses and quantifies uncertainties and directly demonstrates compliance with GDC 4 is more appropriate. NRC and industry expect that a robust probabilistic software tool, developed cooperatively, will facilitate meeting this goal; will improve licensing, regulatory decision making, and design; and will be mutually beneficial. Based on the terminology of GDC 4, this project is titled Extremely Low Probability of Rupture (xLPR). Development of the xLPR methodology and the corresponding software tool will involve many challenging technical decisions, modeling judgments, and sensitivity analyses. The purpose of the xLPR project is to develop a probabilistic assessment tool that can be used to demonstrate direct compliance with the requirements of 10 CFR 50 Appendix A GDC 4. The xLPR software tool will model active degradation mechanisms, such as primary water stress corrosion cracking, and the associated mitigation activities. The tool will be comprehensive with respect to known challenges, vetted with respect to scientific adequacy of models and inputs, flexible enough to permit analysis of a variety of in-service situations, and adaptable to accommodate evolving and improving knowledge. Successful execution of the xLPR project will involve a complex and diverse array of technical specialties and will require a well-organized and structured team of experts. This paper summarizes the objectives, organizational structure, and program plan of the collaborative NRC / Industry xLPR Project to develop a robust, flexible, probabilistic piping rupture assessment code. While the listed authors are individually responsible within their respective organizations for this project, the project organization includes a management team representing the xLPR Project task group structure. Individual members of this team will be listed in the paper along with their individual roles and contributions within the project. Companion papers from three of the four technical Task Groups of the xLPR Program (Computational, Modeling, and Inputs) provide substantial additional information detailing the technical approach and direction of this project.
Failure Mechanism of Laser Welds in Lap-Shear Specimens of a High Strength Low Alloy Steel
Authors: Asim Kamran , Lee Jaewon , Pan Jwo
Published: January 2011

In this study, the failure mechanism of laser welds in lap-shear specimens of a high strength low alloy (HSLA) steel under quasi-static loading conditions is examined based on the experimental results. Optical micrographs of the welds in specimens before tests were examined to understand the microstructure near the weld. A micrographic analysis of the failed welds in lap-shear specimens indicates a ductile necking/shear failure mechanism near the heat affected zone. Micro-hardness tests were conducted to provide an assessment of the mechanical properties of the joint area which has varying microstructure due to the welding process. A finite element analysis was also carried out to identify the effects of the weld geometry and different mechanical properties of the weld and heat affected zones on the failure mechanism. The computational results of the finite element analysis indicate that the material inhomogeneity and geometry of the weld bead play an important role in the ductile necking/shear failure mechanism. The computational results match well with the experimental observations of the necking/shear failure and its location. A finite element analysis with consideration of void nucleation and growth based on the Gurson yield function was also carried out. The results of the finite element analysis based on the Gurson yield function are in good agreement with the experimental observations of the initiation of ductile fracture and its location.
EMS: developing a structured approach
Authors: Mahoney Paul , Martin Nicola
Published: January 2011

Extramural studies (EMS) are compulsory for all veterinary students in the UK. The benefits of a strong EMS programme are considerable, and have been clearly set out by the RCVS in its EMS recommendations, policy and guidance notes. Although universities take primary responsibility for delivering ‘Day 1 competencies’ for students, EMS placements provide the ‘real world’ environment in which undergraduates can develop their practical skills further and continue to build the professional skills essential for a successful career. Here, Paul Mahoney and Nicola Martin outline how the Royal Veterinary College and the People's Dispensary for Sick Animals are working together to ensure that students get the most from their EMS placements.
Comments on the dilemma in the November/December issue: ‘Tethered dog dies’
Authors: De Beukelaer Edward
Published: January 2011

The dilemma in the November/December issue concerned a vet who transported a dog between clinics in the boot of an estate car (In Practice, November/December 2010, volume 32, pages 514–515). The animal was secured with a lead, but on arrival it was found dead, trapped with the lead around its neck. The noises the dog had been making seemed to be agitation, and when they stopped the vet assumed the dog had gone to sleep. Pippa Swan commented that it could be assumed that the cause of death was strangulation and that the dog had suffered. It might have been a tragic misjudgement, but that could not absolve the vet's responsibility for the animal. A possible way forward would be to consider whether a vet who had behaved in this way should be judged more harshly than a member of the public. While vets should know the consequences of tying up a dog without proper supervision, they were also human and could make mistakes. Were the incident to be reported, the consequences for the vet might not stop at going to court; the RCVS Disciplinary Committee might decide that the vet was guilty of serious professional misconduct. If there was no evidence that the behaviour had any implications for future conduct, a decision for no further action, or a warning or reprimand might be sufficient.
Diagnosis and treatment of urolithiasis in horses
Authors: Edwards Barrie , Archer Debra
Published: January 2011

Obstructive disease of the urinary tract of horses is an uncommon but potentially serious disorder. Urolithiasis, the most prevalent form of this disorder, can occur at any location in the urinary tract but is most typically seen in the bladder of male adult horses. The presenting signs of urolithiasis are highly variable and depend on the anatomical location of the obstruction. This article discusses the diagnosis and treatment of various forms of urolithiasis in the horse.
Urinalysis in practice – an update
Authors: Ristic Jelena , Skeldon Niki
Published: January 2011

Urinalysis is performed on a daily basis in most practices. It is a simple technique, requires minimal equipment and provides information not only about the urinary tract, but also other body systems. This article highlights how to get the most out of routine urinalysis in the typical practice laboratory. Additional information can be gained by submitting samples to an external laboratory for, for example, culture and sensitivity testing, and urine protein:creatinine ratio analysis. However, in general, basic urinalysis comprising dipstick testing, sediment examination and specific gravity is best performed in‐house while samples are still fresh.
Veterinary care of raptors
Authors: Kubiak Marie , Forbes Neil
Published: January 2011

Raptors are commonly presented to veterinary surgeons in practice and typically comprise injured wild birds, individuals kept for falconry, zoo and conservation exhibits, and captive breeding birds. This article describes the common problems seen in captive and wild birds and outlines the basic approach to dealing with sick birds of prey. It provides practitioners with a basic understanding of the most frequently seen pathologies and highlights how to recognise when treatment is appropriate and when referral to specialist centres might be required. An article to be published in the February issue of In Practice will review musculoskeletal diseases in these birds.
Creutzfeldt–Jacob disease mimics, or how to sort out the subacute encephalopathy patient
Authors: Murray Katherine
Published: January 2011

Sporadic Creutzfeldt–Jacob disease (CJD) is a rare untreatable neurodegenerative disease which every neurologist will occasionally encounter during their career. However, it is likely to appear on their differential diagnosis list significantly more frequently. Numerous conditions can present with subacute encephalopathy whichmightbe sporadic CJD and this article explores these diagnoses. It includes the commonest sporadic CJD mimics which are neurodegenerative, and highlights the relatively rare treatable mimics which must not be missed. It discusses relevant investigations, including serum antibodies,CSF, electroencephalography and MR brain imaging, and strategies when preliminary investigations fail to support sporadic CJD but no alternative diagnosis is readily apparent.
Therapeutic targets in liver fibrosis
Authors: Fallowfield Jonathan A.
Published: January 2011

Detailed analysis of the cellular and molecular mechanisms that mediate liver fibrosis has provided a framework for therapeutic approaches to prevent, slow down, or even reverse fibrosis and cirrhosis. A pivotal event in the development of liver fibrosis is the activation of quiescent hepatic stellate cells (HSCs) to scar-forming myofibroblast-like cells. Consequently, HSCs and the factors that regulate HSC activation, proliferation, and function represent important antifibrotic targets. Drugs currently licensed in the US and Europe for other indications target HSC-related components of the fibrotic cascade. Their deployment in the near future looks likely. Ultimately, treatment strategies for liver fibrosis may vary on an individual basis according to etiology, risk of fibrosis progression, and the prevailing pathogenic milieu, meaning that a multiagent approach could be required. The field continues to develop rapidly and starts to identify exciting potential targets in proof-of-concept preclinical studies. Despite this, no antifibrotics are currently licensed for use in humans. With epidemiological predictions for the future prevalence of viral, obesity-related, and alcohol-related cirrhosis painting an increasingly gloomy picture, and a shortfall in donors for liver transplantation, the clinical urgency for new therapies is high. There is growing interest from stakeholders keen to exploit the market potential for antifibrotics. However, the design of future trials for agents in the developmental pipeline will depend on strategies that enable equal patient stratification, techniques to reliably monitor changes in fibrosis over time, and the definition of clinically meaningful end points.
Atrial tachycardia/fibrillation in the connexin 43 G60S mutant (Oculodentodigital dysplasia) mouse
Authors: Tuomi Jari M. , Tyml Karel , Jones Douglas L.
Published: January 2011

Atrial fibrillation (AF), the most common cardiac arrhythmia seen in general practice, can be promoted by conduction slowing. Cardiac impulse conduction depends on gap junction channels, which are composed of connexins (Cxs). While atrial Cx40 and Cx43 are equally expressed, AF studies have primarily focused on Cx40 reductions. The G60S Cx43 mutant (Cx43G60S/+) mouse model of Oculodentodigital dysplasia has a 60% reduction in Cx43 in the atria. Cx43G60S/+ mice were compared with Cx40-deficient (Cx40−/−) mice to determine the role of Cxs in atrial tachycardia/fibrillation (AT/F). Intracardiac electrophysiological studies were done in 6-mo-old male C57BL/6 Cx43G60S/+ mutant, littermate (Cx43+/+), Cx40−/−, and C57BL/6 wild-type (WT) mice. AT/F induction used an extra stimulus during sinus rhythm, programmed electrical stimulation, or burst pacing (1-ms pulses, 50-Hz, 400-ms train) in the absence and presence of carbachol (CCh). Atrial effective refractory periods did not differ between strains. Cx43G60S/+ mice were more susceptible to induction of sustained AT/F (duration >2 min, 9 of 12; maximum >35 min) compared with Cx43+/+ mice (3 of 11; χ2 = 5.24; P = 0.02). CCh enhanced sustained AT/F susceptibility in WT (from 1 of 12 without, to 7 of 10 with CCh; χ2 = 8.98; P < 0.01) but not in Cx40−/− mice (1 of 13 without vs. 2 of 9 with CCh; χ2 = 0.95; P = NS). The pattern of epicardial recordings during AT/F in Cx43G60S/+ mice was left preceding right, with left atrial fractionated activation patterns consistent with clinical observations of AF. In conclusions, while Cx43G60S/+ mice had severe AT/F, Cx40−/− mice were resistant to CCh-induced AT/F.
Mechanisms of gas exchange response to lung volume reduction surgery in severe emphysema
Authors: Cremona George , Barbara Joan A. , Melgosa Teresa , Appendini Lorenzo , Roca Josep , Casadio Caterina , Donner Claudio F. , Rodriguez-Roisin Roberto , Wagner Peter D.
Published: January 2011

Lung volume reduction surgery (LVRS) improves lung function, respiratory symptoms, and exercise tolerance in selected patients with chronic obstructive pulmonary disease, who have heterogeneous emphysema. However, the reported effects of LVRS on gas exchange are variable, even when lung function is improved. To clarify how LVRS affects gas exchange in chronic obstructive pulmonary disease, 23 patients were studied before LVRS, 14 of whom were again studied afterwards. We performed measurements of lung mechanics, pulmonary hemodynamics, and ventilation-perfusion (V̇a/Q̇) inequality using the multiple inert-gas elimination technique. LVRS improved arterial Po2 (PaO2) by a mean of 6 Torr ( P = 0.04), with no significant effect on arterial Pco2 (PaCO2), but with great variability in both. Lung mechanical properties improved considerably more than did gas exchange. Post-LVRS PaO2 depended mostly on its pre-LVRS value, whereas improvement in PaO2 was explained mostly by improved V̇a/Q̇ inequality, with lesser contributions from both increased ventilation and higher mixed venous Po2. However, no index of lung mechanical properties correlated with PaO2. Conversely, post-LVRS PaCO2 bore no relationship to its pre-LVRS value, whereas changes in PaCO2 were tightly related ( r2 = 0.96) to variables, reflecting decrease in static lung hyperinflation (intrinsic positive end-expiratory pressure and residual volume/total lung capacity) and increase in airflow potential (tidal volume and maximal inspiratory pressure), but not to V̇a/Q̇ distribution changes. Individual gas exchange responses to LVRS vary greatly, but can be explained by changes in combinations of determining variables that are different for oxygen and carbon dioxide.
Altered estrogen receptor expression in skeletal muscle and adipose tissue of female rats fed a high-fat diet
Authors: Gorres Brittany K. , Bomhoff Gregory L. , Gupte Anisha A. , Geiger Paige C.
Published: January 2011

Estrogen receptors (ERs) are expressed in adipose tissue and skeletal muscle, with potential implications for glucose metabolism and insulin signaling. Previous studies examining the role of ERs in glucose metabolism have primarily used knockout mouse models of ERα and ERβ, and it is unknown whether ER expression is altered in response to an obesity-inducing high-fat diet (HFD). The purpose of the current study was to determine whether modulation of glucose metabolism in response to a HFD in intact and ovariectomized (OVX) female rats is associated with alterations in ER expression. Our results demonstrate that a 6-wk HFD (60% calories from fat) in female rats induces whole body glucose intolerance with tissue-specific effects isolated to the adipose tissue, and no observed differences in insulin-stimulated glucose uptake, GLUT4, or ERα protein expression levels in skeletal muscle. In chow-fed rats, OVX resulted in decreased ERα with a trend toward decreased GLUT4 expression in adipose tissue. Sham-treated and OVX rats fed a HFD demonstrated a decrease in ERα and GLUT4 in adipose tissue. The HFD also increased activation of stress kinases (c-jun NH2-terminal kinase and inhibitor of κB kinase β) in the sham-treated rats and decreased expression of the protective heat shock protein 72 (HSP72) in both sham-treated and OVX rats. Our findings suggest that decreased glucose metabolism and increased inflammation in adipose tissue with a HFD in female rats could stem from a significant decrease in ERα expression.
NAD(P)H oxidase-derived reactive oxygen species contribute to age-related impairments of endothelium-dependent dilation in rat soleus feed arteries
Authors: Trott Daniel W. , Seawright John W. , Luttrell Meredith J. , Woodman Christopher R.
Published: January 2011

We tested the hypothesis that age-related endothelial dysfunction in rat soleus muscle feed arteries (SFA) is mediated in part by NAD(P)H oxidase-derived reactive oxygen species (ROS). SFA from young (4 mo) and old (24 mo) Fischer 344 rats were isolated and cannulated for examination of vasodilator responses to flow and acetylcholine (ACh) in the absence or presence of a superoxide anion (O2−) scavenger (Tempol; 100 μM) or an NAD(P)H oxidase inhibitor (apocynin; 100 μM). In the absence of inhibitors, flow- and ACh-induced dilations were attenuated in SFA from old rats compared with young rats. Tempol and apocynin improved flow- and ACh-induced dilation in SFA from old rats. In SFA from young rats, Tempol and apocynin had no effect on flow-induced dilation, and apocynin attenuated ACh-induced dilation. To determine the role of hydrogen peroxide (H2O2), dilator responses were assessed in the absence and presence of catalase (100 U/ml) or PEG-catalase (200 U/ml). Neither H2O2 scavenger altered flow-induced dilation, whereas both H2O2 scavengers blunted ACh-induced dilation in SFA from young rats. In old SFA, catalase improved flow-induced dilation whereas PEG-catalase improved ACh-induced dilation. Compared with young SFA, in response to exogenous H2O2 and NADPH, old rats exhibited blunted dilation and constriction, respectively. Immunoblot analysis revealed that the NAD(P)H oxidase subunit gp91phox protein content was greater in old SFA compared with young. These results suggest that NAD(P)H oxidase-derived reactive oxygen species contribute to impaired endothelium-dependent dilation in old SFA.
Flow-mediated vasodilation is impaired in adult rat offspring exposed to prenatal hypoxia
Authors: Morton J. S. , Rueda-Clausen C. F. , Davidge S. T.
Published: January 2011

There is now a demonstrated association between low birth weight and increased mortality later in life. Changes in fetal development may program the cardiovascular system and lead to an increased risk of cardiovascular diseases later in life. In addition, aging is a risk factor for vascular endothelial-dependent dysfunction. However, the impact of being born intrauterine growth restricted (IUGR) on the normal aging mechanisms of vascular dysfunction is not clear. We hypothesized that IUGR would cause changes in vascular function that would affect the mechanisms of flow-induced vasodilation later in life in an age- or sex-dependent manner. To create an IUGR model, pregnant Sprague-Dawley rats were placed in a hypoxic (11.5% O2) or control (room air, 21% O2) environment from days 15 to 21 of pregnancy. Both male and female offspring were investigated at 4 or 12 mo of age. Vascular function was assessed in small mesenteric arteries using flow-induced vasodilation, a physiological stimuli of vasodilation, in a pressure myograph. Flow-induced vasodilation was unaffected at a young age, but was significantly reduced in aging IUGR compared with aging controls ( P < 0.05). Underlying vasodilator mechanisms were altered such that nitric oxide-mediated vasodilation was abolished in both young adult and aging IUGR males and females and in aging control females ( P > 0.05). Endothelium-derived hyperpolarizing factor-mediated vasodilation was maintained in all groups ( P < 0.01). A change in the mechanisms of vasodilation occurring at an earlier age in IUGR offspring may predispose them to develop cardiovascular diseases as an aging adult.
Incidence and Outcome of BRCA Mutations in Unselected Patients with Triple Receptor-Negative Breast Cancer
Authors: Gonzalez-Angulo Ana M. , Timms Kirsten M. , Liu Shuying , Chen Huiqin , Litton Jennifer K. , Potter Jennifer , Lanchbury Jerry S. , Stemke-Hale Katherine , Hennessy Bryan T. , Arun Banu K. , Hortobagyi Gabriel N. , Do Kim-Anh , Mills Gordon B. , Meric-Bernstam Funda
Published: January 2011

Purpose: To investigate the incidence of germline and somatic BRCA1/2 mutations in unselected patients with triple-negative breast cancer (TNBC) and determine the prognostic significance of carrying a mutation.

Methods: DNA was obtained from 77 TNBC and normal tissues. BRCA1/2 exons/flanking regions were sequenced from tumor and patients classified as mutant or wild type (WT). Sequencing was repeated from normal tissue to identify germline and somatic mutations. Patient characteristics were compared with chi-square. Survival was estimated by Kaplan–Meier method and compared with log-rank. Cox proportional hazards models were fit to determine the independent association of mutation status with outcome.

Results: Median age was 51 years (27–83 years). Fifteen patients (19.5%) had BRCA mutations: 12 (15.6%) in BRCA1 (one somatic), and 3 (3.9%) in BRCA2. Patients with BRCA mutations tended to be younger than WT, (P = 0.005). Grade, histology, and stage were not associated with mutation status. At a median follow-up of 43 months (7–214 months), there were 33 (42.9%) recurrences and 35 (45.5%) deaths. Five-year recurrence-free survival estimates were 51.7% for WT versus 86.2% for patients with mutations, (P = 0.031); and 5-year overall survival estimates were 52.8% for WT versus 73.3% for patients with mutations (P = 0.225). After adjustment, patients with BRCA mutations had a significantly better RFS (HR: 0.19, 95% CI: 0.045–0.79, P = 0.016) compared with WT.

Conclusions: In this unselected cohort of TNBC, we found a 19.5% incidence of BRCA mutations. Genetic testing should be discussed with patients with TNBC. Patients with TNBC with BRCA mutations had a significantly lower risk of relapse. Clin Cancer Res; 17(5); 1082–9. ©2011 AACR.
The CXCL16 A181V Mutation Selectively Inhibits Monocyte Adhesion to CXCR6 but Is Not Associated With Human Coronary Heart Disease
Authors: Petit Sarah J. , Wise Emma L. , Chambers John C. , Sehmi Jobanpreet , Chayen Naomi E. , Kooner Jaspal S. , Pease James E.
Published: January 2011

Objective—

The chemokine CXCL16 serves as a scavenger receptor for oxidized low-density lipoprotein and as an adhesion molecule and chemoattractant for cells expressing the receptor CXCR6. A commonly occurring
CXCL16
allele has been described containing 2 nonsynonymous single-nucleotide polymorphisms in complete linkage disequilibrium, although the effects on CXCL16 function are unknown. Here, we examined the effect of the single-nucleotide polymorphisms on CXCL16 function and assessed the association of the mutant allele with coronary heart disease (CHD).

Methods and Results—

Both wild-type and mutant T123V181-CXCL16 were readily expressed in vitro and were similarly functional in assays of oxidized low-density lipoprotein scavenging and chemotaxis. However, unlike wild-type CXCL16, T123V181-CXCL16 was unable to promote adhesion of CXCR6
+
cells. Findings were confirmed ex vivo, with monocytes from donors homozygous for the
T123V181
allele unable to facilitate adhesion of CXCR6 transfectants. In the London Life Sciences Prospective Population cohort (n=2797), we found that the
T123V181
allele was not associated with protection or susceptibility to CHD (adjusted odds ratio, 1.01; 95% CI, 0.95 to 1.10;
P
=0.74).

Conclusion—

CXCL16-mediated cell adhesion plays at best a modest role in CHD, and the scavenging and chemotactic properties of the chemokine are more likely to be more important in disease pathogenesis.
High Shear Stress and Flow Velocity in Partially Occluded Aneurysms Prone to Recanalization
Authors: Luo Bin , Yang Xinjian , Wang Shengzhang , Li Haiyun , Chen Jialiang , Yu Hongyu , Zhang Ying , Zhang Yisen , Mu Shiqing , Liu Zhicheng , Ding Guanghong
Published: January 2011

Background and Purpose—

Hemodynamic factors are thought to play an important role in the initiation, growth, and rupture of cerebral aneurysms. However, the hemodynamic features in the residual neck of the partially embolized aneurysms and their influences on recanalization are rarely reported. In this study, we characterized the hemodynamics of partially occluded aneurysms, which were proven to undergo recanalization during follow-up using computational fluid dynamic analysis.

Methods—

From May 2007 to June 2009, we identified 11 partial aneurysms during follow-up, including 5 recanalized cases and 6 stable cases with 3-dimensional digital subtraction angiography. We retrospectively characterized the hemodynamic features around the residual aneurismal pouch using the available postprocedural digital subtraction angiography image data. The occluded part of the aneurysm was regarded as completely separated from the circulation.

Results—

The overall blood flow patterns before embolization were almost the same in the recanalized and stable groups. After occlusion, the flow pattern changes, wall shear stress (WSS), and velocity at the remnant neck demonstrated different changes between the 2 groups. Specifically, in the recanalized group, high WSS regions were found near the neck in all 5 cases, with 4 of them being even higher than those before occlusion. Interestingly, in all cases, the high WSS area of the remnant neck coincided with the location where the aneurysm recanalization occurred. In the stable group, 5 out of 6 cases demonstrated lower WSS and velocity at the remnant neck after occlusion.

Conclusions—

High WSS and blood flow velocity were consistently observed near the remnant neck of partially embolized aneurysms prone to future recanalization, suggesting that hemodynamic factors may have an important role in aneurismal recurrence after endovascular treatment. The difference in flow pattern could be caused by the incomplete occlusion of the aneurysms.
Hypertensive Disorders in Pregnancy and Preterm Delivery and Subsequent Stroke in Asian Women
Authors: Wang I-Kuan , Chang Shih-Ni , Liao Chien-Chang , Liang Chih-Chia , Chang Chiz-Tzung , Lin Hsin-Hung , Liu Jiung-Hsiun , Liu Yao-Lung , Chuang Feng-Rong , Hsu Chung-Y. , Huang Chiu-Ching , Sung Fung-Chang
Published: January 2011

Background and Purpose—

Few studies exist concerning the risk of stroke associated with hypertensive disorders in pregnancy (HDP) in Asian women. This study investigates whether preterm delivery further complicates this risk in women with HDP in Taiwan.

Methods—

Based on universal insurance claims data, 1092 pregnant women with newly diagnosed HDP from 2000 to 2004 and aged 15 to 40 years were identified as the HDP cohort. Then, 4715 randomly selected persons without HDP frequency matched with the index year were designated as the non-HDP controls. Both cohorts were followed-up until the end of 2008 to measure the incidence of stroke.

Results—

The HDP cohort had a higher incidence of stroke than the non-HDP cohort (30.1 vs 12.8 per 10 000 person-years), with an overall adjusted hazard ratio of 2.04 (95% CI, 1.18- 3.51) for stroke. Preterm delivery increased the risk of stroke to 3.22-fold (95% CI, 1.48–6.99;
P
for trend=0.002). The age-specific V-shape risk association showed that the highest risk of stroke was noted among subjects 15 to 18 years old in the HDP group (hazard ratio, 13.4; 95% CI, 1.54–116.7) and followed by women aged 35 years and older (hazard ratio, 5.56; 95% CI, 1.47–21.0).

Conclusions—

Pregnant women with HDP have an increased risk of subsequent stroke. Preterm delivery and older ages increase the risk of subsequent stroke. Adolescents with HDP also have an elevated risk of stroke. Early identification of women with HDP is needed for prevention.
Precious African American Memories, Post-Racial Dreams & the American Nation
Authors: Martin Waldo E.
Published: January 2011

This interdisciplinary essay explores a fundamental paradox at the heart of American race relations since the 1960s: “the changing same.” The more things change; the more they remain the same. Combining historical and social-scientific evidence with autobiographical reflections, this discussion critically probes the paradoxical decline and persistence of two dimensions of our enduring racial quagmire: racial inequality and white supremacy. The essay argues that these powerful and interrelated elements of America's continuing racial dilemma demand a massive democratic movement to alleviate both at once. This wide-ranging struggle to realize the promise of American democracy requires more than just a revitalized African American Freedom Struggle that is both intraracial and interracial. Progress toward resolving the seemingly intractable problem of racial inequality in the United States demands far more than intensified efforts to alleviate economic inequality; it requires alleviating white supremacy as well.
A Syntacto-Cognitive Study of the Diachrony, Synchrony, Etymology and Gloss of the New Persian Formant am/an
Authors: Borbor Dariush
Published: January 2011

This paper presents a novel analysis of the Persian formant am-/an- in a broad context in order to clarify its diachrony, synchrony, etymology, and gloss. The formant is classified into two types: those derived from Old Iranian ham-/han- “together,” and those belonging to the cognitive process. These formants always convey four metaphoric cognitive percepts: collection/collocation, multiplicity, pluralism and infiltration. These percepts are manifested in three forms: receptacle; cluster, multiplicity, doubling; and, to a lesser degree, permeation. The study also explores the presence of some cross-language regularities in neighboring languages with the same cognitive concept of am-/an-, which conforms to the categories and classifications proposed by this paper.