bluuebunny/crossref_metadata_2025 huggingface dataset:
Background on the New ASME PCC-1–2010 Appendix M “Washer Usage Guidance and Purchase Specification for Through-Hardened Washers”
Authors: Barron Joseph
Published: January 2011

A revised ASME PCC-1 has recently been published and includes several new appendices. Among these is a new Appendix M “Washer Usage Guidance and Purchase Specification for Through-Hardened Washers”, which outlines a purchase specification for the manufacture of through-hardened washers for use on pressure boundary bolted flanged connections. This paper outlines the background as to why the new appendix was considered necessary. It also details the logic behind the selected materials and the operational limits placed on those materials.
Hot Cracking Study of High Chromium Nickel-Base Weld Filler Metal 52MSS (ERNiCrFe-13) for Nuclear Applications
Authors: McCracken Steven L. , Alexandrov Boian T. , Lippold John C. , Sowards Jeffrey W. , Hope Adam T.
Published: January 2011

High chromium nickel-base weld filler metals 52 (ERNiCrFe-7) and 52M (ERNiCrFe-7A) have in recent years replaced filler metal 82 (ERNiCr-3) for new fabrication and for repair applications in commercial nuclear power plants. Filler metals 52 and 52M are selected because they have excellent resistance to primary water stress corrosion cracking (PWSCC). Unfortunately, filler metals 52 and 52M exhibit a higher susceptibility to ductility-dip cracking (DDC) compared to filler metal 82. Filler metal 52MSS (ERNiCrFe-13) is a new high chromium nickel-base alloy with Nb and Mo added to improve resistance to ductility-dip cracking. Increasing Nb has in previous research been shown to widen the solidification temperature range in nickel-base alloys. A wider solidification temperature range can potentially increase susceptibility to hot cracking. This study investigated the solidification behavior and hot cracking susceptibility of three heats of 52MSS and compared the results to a heat of filler metal 52M and a heat of filler metal 52i. The solidification behavior and hot cracking susceptibility were investigated by an optimized Transvarestraint test and by a next generation Cast Pin Tear Test (CPTT). The solidification temperature range and eutectic transformations were measured by a patented Single Sensor Differential Thermal Analysis (SS-DTA) technique. This study showed that filler metal 52MSS was slightly more susceptible to hot cracking than 52M and 52i. This study also demonstrated that the next generation CPTT and SS-DTA technique are effective methods for evaluating the solidification behavior and hot cracking susceptibility of high chromium nickel-base weld filler metals.
A Case Study on the Effect of Peaked Pipe Welds on Piping Life Expectancy
Authors: Brown Warren , Prager Martin , Wrobel Sarah
Published: January 2011

This paper details a case study on the effect of weld peak geometry on the expected creep life of a piping system operating in a refining environment. Inspection of the 1-1/4 Cr piping system revealed significant peaked geometry at the longitudinal weld locations. A Finite Element Analysis (FEA) assessment of the remaining life was made using the Omega method of creep life assessment. The sensitivity of the results to modeled pipe geometry and assumed material properties was assessed. The variability of life prediction that was obtained indicated a necessity to perform further more detailed assessment of the pipe geometry and material properties by the removal of samples at the weld locations. The improvement obtained in the assessment accuracy and final life predictions from the sample analysis is presented in the paper and practical implications on the operation of the piping system are detailed. Suggestions and cautions for the practical assessment of similar peaked pipe problems are also discussed.
A Statistical Intelligence (STI) Approach to Discovering Spurious Correlation in a Physical Model and Resolving the Problem With an Example of Designing a Pulse Jet Mixing System at Hanford
Authors: Amidan Brett G. , Piepel Greg F. , Heredia-Langner Alejandro , Meyer Perry A. , Wells Beric E. , Fort James A. , Bamberger Judith A. , Kuhn William L.
Published: January 2011

Pulse jet mixing tests were conducted to support the design of mixing systems for the Hanford Waste Treatment and Immobilization Plant. A physical approach (based on hydro-dynamic behavior) and two semi-empirical (SE) approaches were applied to the data to develop models for predicting two response variables (critical-suspension velocity and cloud height). Tests were conducted at three geometric scales using multiple noncohesive simulants and levels of possibly influential factors. The physical modeling approach based on hydrodynamic behavior was first attempted, but this approach can yield models with spurious correlation. To overcome this dilemma, two semi-empirical (SE) models were developed by generalizing the form of the physical model using dimensional and/or nondimensional (ND) variables. The results of applying statistical intelligence (STI) tools to resolve the spurious correlation problem via fitting the physical and SE models are presented and compared. Considering goodness-of-fit, prediction performance, spurious correlation, and the need to extrapolate, the SE models based on ND variables are recommended.
Design and Inspection Considerations for Cyclic Equipment
Authors: Jones J. Ryan
Published: January 2011

The management of pressure equipment operating in a cyclic service can be difficult as little guidance is provided in the codes of construction or in any of the post construction guidance documents. In terms of design, the ASME Section VIII, Division 2 Code does provide guidance for the design and fabrication of vessels that will be in a fatigue service. Of specific interest are those vessels that were designed to ASME Section VIII, Division 1 with varying levels of attention paid to the cyclic nature of the operation. This becomes a problem when operating facilities must determine the long term strategy for a piece of equipment where fatigue is the only (or dominant) method of degradation. With the variation in design methods, methods of addressing fatigue crack growth, material properties, and the desire to minimize inspection expenditures for this type of equipment; practical guidance for long term inspection considerations is presented in this paper. A case history for a Pressure Swing Adsorbtion (PSA) vessel that is subject to cyclic pressure only is discussed to illustrate design considerations, inspection strategies, and determination of remaining life. This provides a fairly simple and approachable example for determination of remaining life and inspection strategies, as well as highlighting regions of interest in these types of vessels. The same approach can then be applied to equipment where more complex (mechanical, thermal) cycling occurs.
Evaluating the Failure Pressure of Corroded Pipeline
Authors: Shuai Jian
Published: January 2011

This paper presented a review on ASME B31G, DNV RP-F101 and PCORRC methods in evaluating the remaining strength of corroded pipeline. These methods are validated by 67 sets of data about full-scale burst test of pipe with a defect. A numerical model for predicting the burst failure of corroded pipeline was constructed using the non-linear finite element method. Using this model, the full-size pipe burst experiments of pipelines in different material, size and defect was analyzed and computed. The proposed FEM model was validated. Based on the calculation result using the model, a new formula predicting failure pressure was presented, in which depth, length and width of a defect was involved. Comparison of the formula with the other assessment method and experiments showed the formula had a satisfactory precision.
Non-Cyclic Shakedown-Ratcheting Boundary Determination: Analytical Examples
Authors: Adibi-Asl R. , Reinhardt W.
Published: January 2011

The classical lower and upper bound shakedown theorems cannot predict the complete boundary between shakedown and ratcheting (ratchet boundary) since they address only shakedown to elastic action. This limits the usefulness of the classical shakedown theorems for pressure vessel design, since in practice stresses often locally exceed the elastic limit. A convenient method to obtain the entire ratchet boundary without the need for cyclic analysis was previously proposed by the authors. This method is applied in the present paper to determine the elastic and plastic ratchet boundary of several practically significant configurations analytically. The examples include some classical problems found in the literature (such as Bree problem) and new solutions for configurations with uniaxial and multiaxial stress states.
Development of Stress Reduction Method in the Pipe Welded Zone by Heating
Authors: Fukuda Yuka , Okido Shinobu
Published: January 2011

Some cases of Stress Corrosion Cracking (SCC) failures in the proximity of welded zone of core internals and pipes in Primary Loop Recirculation, which are made of austenitic stainless steel, were reported in existing boiling water reactors, from the late 1970s to 1980s. As a countermeasure against SCC, low-carbon stainless steel was developed in order to reduce susceptibility to SCC, and used as standard material at that time. However, SCC failures were still observed in the core internals and pipes made of low-carbon stainless steel in recent years. It is well understood that residual tensile stress due to welding largely affects occurrence and growth of SCC in low-carbon stainless steel. Based on these observations, stress reduction methods for the pipe welded zone have already been developed such as Induction Heating Stress Improvement (IHSI) and Heat Sink Welding (HSW). However, these stress reduction methods are applied to only large-bore, thick-wall pipes, because it is difficult to apply these established countermeasures to the small-bore, thin-wall pipes which diameter is 50A and below. Thus stress reduction method for small-bore pipe has not been established. In this study, residual tensile stress reduction method that is applicable to the welded zone of small-bore pipe has been developed. The stress reduction method uses rapid quenching of inner surface of the pipe by cooling water after heating outer surface of the pipe by a heating device. Just after starting to cool the inside of the pipe, the temperature of the inner surface is low and tensile stress is generated. On the other hand, since temperature of outer surface is high, large temperature difference between inside and outside surface of the pipe develop and the high through-wall thermal stress is generated. When the temperature difference between the inner and outer surfaces of the pipe is large, thermal stress exceeds the yield stress on the pipe inner surface, and plastic deformation occurs on the inner surface of the pipe. The residual stress of the inner surface becomes compressive after the heat treatment due to the residual layer of plastic strain. In this study, the effectiveness of this method is shown by comparing the residual stress on the inner surface of the pipe before and after the application of this method by mock-up tests.
A Fundamental Study of the Interaction of Residual Stress and Applied Loading on Fracture
Authors: Aird C. J. , Pavier M. J. , Smith D. J.
Published: January 2011

This paper presents the results of a fundamental finite-element based study of the crack-closure effects associated with combined residual and applied loading. First, an analytical expression for a representative two-dimensional residual stress field is derived. This residual stress field contains a central compressive region surrounded by an equilibrating tensile region. The analytical expression allows the size and shape of the field to be varied along with the magnitude of the residual stress. The residual stress field is then used as a prescribed initial stress field in a finite element model, in addition to a far field applied load. By introducing cracks of increasing length into these models, charts of stress-intensity-factor versus crack length are produced for different relative magnitudes of residual stress and applied load and for different sizes and shape of the residual stress field. These charts provide insight into the way in which crack-tip conditions evolve with crack growth under conditions of combined residual and applied loading and also enable conditions of crack closure and partial closure to be identified.
Gun Liner Emplacement Using Elastomeric Materials
Authors: Carter Robert H. , Gray David M.
Published: January 2011

The development of a process to emplace a refractory metal liner inside a gun tube is described. The process consists of filling the liner with an elastomeric material and then slipping this arrangement into the gun tube whose inner diameter is close to the outer diameter of the liner. The ends of the liner are plugged with plastic disks and pressure is applied to the elastomeric material by a load frame. This pressure can produce a residual internal stress within the steel gun tube that produces a frictional bond between the liner and gun tube. Initial efforts have resulted in bond strengths over 3 ksi (21 MPa). In addition, by tailoring the degree of lubrication between the elastomeric material and the liner, a graded autofrettage can be produced in the steel gun tube.
Dynamics of Cavitating Flow and Flexural Waves in Fluid-Filled Tubes Subject to Axial Impact
Authors: Inaba Kazuaki , Shepherd Joseph E.
Published: January 2011

We have experimentally studied the coupling of flexural waves in water-filled tubes with cavitating flow. To examine the cavitation events in the tube, we used a transparent polycarbonate (PC) tube. The flexural waves are generated by stress waves in the water propagating along the tube axis. A steel impactor is accelerated by gravity and strikes a polycarbonate buffer placed on top of the water surface within the tube. Strain gages measure hoop strain along the polycarbonate tube and a piezoelectric pressure gage measures the pressure at the bottom of the tube. The events were visualized by a high-speed video camera synchronized with the strain and pressure measurements. The impact of the projectile creates a stress wave propagating along the tube and coupled to the pressure wave in water. A sequence of traveling waves results and when the pressure in the waves drops below the vapor pressure, cavitation occurs in the tube. When cavitation bubbles are present, the tube vibrates at the natural frequency of the second mode of the circular ring. The duration of the cavitation can be estimated from a balance between the buffer kinetic energy and the work done in accelerating the fluid. Cavitation does not occur uniformly or simultaneously; cavitation events are observed near the bottom surface of the buffer, the middle of the tube, and at the bottom (closed) end. High-speed video of the cavitation events reveals that the cavities are clusters of bubbles that have a rosary or grape-bunch appearance.
Flow-Induced Vibrations: Shortcuts and Pitfalls in Estimating Structural Response to Turbulence
Authors: Jobert Nicolas , Nilsson Kenth , Chambrin Jean-Luc , Migot Benoiˆt , Muller Thierry
Published: January 2011

Very often, verification of components experiencing flow-induced vibrations is conducted using “design by rule” approach, where sound engineering practice judiciously replaces sophisticated analyses. This generally results in design precluding any detrimental phenomena, such as amplification by resonance and/or lock-in. However, even for well-designed structures, it is sometimes necessary to estimate structural response due to turbulent buffeting which — though generally being a secondary contributor — can not be avoided. The aim of this paper is to review typical engineering configurations where a best-estimate structural response is sought, and discuss the merits and shortcomings of standard approaches. Both conventional engineering rules and commercially available numerical packages are reviewed. Some practical examples are provided, illustrating the needs and benefit of developing specific solutions for FIV evaluation.
Technical Basis for Case N-766 Nickel Alloy Reactor Coolant Inlay and Onlay for Mitigation of PWR Full Penetration Circumferential Nickel Alloy Welds in Class 1 Items
Authors: Donavin Paul , Marlette S. , Bamford W. , Stuckey K. , Poling G.
Published: January 2011

Primary Water Stress Corrosion Cracking (PWSCC) has been observed in pressurized water reactor (PWR) coolant system pressure boundary components. Recently this cracking has been observed in Alloy 82/182 butt welds. Various repair and mitigation schemes have been proposed or employed to address this cracking. Case N-766 was developed as an alternative method for PWSCC mitigation. It is especially useful for applications in PWSCC susceptible regions where accessibility to the outer surfaces for performing other PWSCC mitigation techniques are difficult or impractical. The method in Case N-766 involves isolating the PWSCC susceptible material from its environment, in this case PWR reactor coolant fluid, thereby eliminating one of the three (3) simultaneous conditions that must exist for PWSCC to occur. Inlays provide for mitigation of flaws or repair of existing flaws and also permit maintaining the inside surface contour essentially in its original configuration, without flow path restriction. Onlays, which do not require an excavation into the pipe ID, permit maintaining the inside surface contour essentially in its original configuration, or permitting weld buildup on the inside surface. This paper presents the technical basis for the design, fabrication, and inspection requirements for inlays and onlays.
Physical vapor deposition and patterning of calcium fluoride films
Authors: Piñol L. , Rebello K. , Caruso K. , Francomacaro A. S. , Coles G. L.
Published: January 2011

Physical vapor deposition of calcium fluoride (CaF2) thin films was performed via electron beam evaporation, resistive/thermal evaporation, and nonreactive radio frequency sputtering. Patterning of the resultant “usable” thin films was then also attempted in several ways, including by shadow mask deposition, liftoff, and direct chemical etching. Resistive evaporation produced the most stable films, having polycrystalline morphology with a moderately strong preference to the 331 orientation. The cleanest patterning results were obtained via a polymer/metal liftoff. The results and implications of each of the various deposition and patterning techniques are discussed.
2500 Years of European Climate Variability and Human Susceptibility
Authors: Büntgen Ulf , Tegel Willy , Nicolussi Kurt , McCormick Michael , Frank David , Trouet Valerie , Kaplan Jed O. , Herzig Franz , Heussner Karl-Uwe , Wanner Heinz , Luterbacher Jürg , Esper Jan
Published: January 2011

Variability of central European temperature and precipitation shows correlations with some major historical changes.
Hospital Epidemiology and Infection Control in Acute-Care Settings
Authors: Sydnor Emily R. M. , Perl Trish M.
Published: January 2011

Health care-associated infections (HAIs) have become more common as medical care has grown more complex and patients have become more complicated. HAIs are associated with significant morbidity, mortality, and cost. Growing rates of HAIs alongside evidence suggesting that active surveillance and infection control practices can prevent HAIs led to the development of hospital epidemiology and infection control programs. The role for infection control programs has grown and continues to grow as rates of antimicrobial resistance rise and HAIs lead to increasing risks to patients and expanding health care costs. In this review, we summarize the history of the development of hospital epidemiology and infection control, common HAIs and the pathogens causing them, and the structure and role of a hospital epidemiology and infection control program.
Zoonotic Potential and Molecular Epidemiology ofGiardiaSpecies and Giardiasis
Authors: Feng Yaoyu , Xiao Lihua
Published: January 2011

Molecular diagnostic tools have been used recently in assessing the taxonomy, zoonotic potential, and transmission ofGiardiaspecies and giardiasis in humans and animals. The results of these studies have firmly established giardiasis as a zoonotic disease, although host adaptation at the genotype and subtype levels has reduced the likelihood of zoonotic transmission. These studies have also identified variations in the distribution ofGiardia duodenalisgenotypes among geographic areas and between domestic and wild ruminants and differences in clinical manifestations and outbreak potentials of assemblages A and B. Nevertheless, our efforts in characterizing the molecular epidemiology of giardiasis and the roles of various animals in the transmission of human giardiasis are compromised by the lack of case-control and longitudinal cohort studies and the sampling and testing of humans and animals living in the same community, the frequent occurrence of infections with mixed genotypes and subtypes, and the apparent heterozygosity at some genetic loci for someG. duodenalisgenotypes. With the increased usage of multilocus genotyping tools, the development of next-generation subtyping tools, the integration of molecular analysis in epidemiological studies, and an improved understanding of the population genetics ofG. duodenalisin humans and animals, we should soon have a better appreciation of the molecular epidemiology of giardiasis, the disease burden of zoonotic transmission, the taxonomy status and virulences of variousG. duodenalisgenotypes, and the ecology of environmental contamination.
Real-Time Quantitative PCR Assay for Monitoring of Nervous Necrosis Virus Infection in Grouper Aquaculture
Authors: Kuo Hsiao-Che , Wang Ting-Yu , Chen Peng-Peng , Chen Young-Mao , Chuang Hui-Ching , Chen Tzong-Yueh
Published: January 2011

Viral nervous necrosis caused by nervous necrosis virus (NNV) exacts a high mortality and results in huge economic losses in grouper aquaculture in Taiwan. The present study developed a real-time quantitative PCR (qPCR) method for NNV monitoring. The assay showed a strong linear correlation (
r
2
= 0.99) between threshold cycle (

C
T

) and RNA quantities, which allowed identification of infected groupers by the

C
T

value and could be exploited to warn of NNV infection prior to an outbreak in grouper fish farms. Real-time qPCR also confirmed the copious content of NNV in grouper fin, similar to that in primary tissues; the result was verified by using
in situ
reverse transcription-PCR (RT-PCR). This indicated that grouper fin was a suitable sample for NNV detection, in a manner that could be relatively benign to the fish. The rapid spread of NNV infection to the entire population of affected farms was evident. The developed real-time qPCR method is rapid, highly sensitive, and applicable to routine high-throughput detection of large numbers of samples and has potential as a suitable tool for diagnostic, epidemiological, and genetic studies of grouper aquaculture.
Investigation of lameness in dogs
Authors: Scott Harry , Witte Philip
Published: January 2011

Lameness associated with musculoskeletal disorders of the forelimb accounts for approximately 25 per cent of the authors' canine referral caseload. Lameness due to an underlying neurological disorder is less common and is often associated with weakness and, in some dogs, neurological deficits. Most cases of chronic forelimb lameness of musculoskeletal origin seen at the authors' clinic involve the elbow or, less frequently, the shoulder. The practitioner should, however, be mindful of the fact that lameness can be associated with any aspect of forelimb function. When dealing with chronic forelimb lameness, a diagnosis can be elusive and, with limited investigative techniques, frustrating. A structured approach to the investigation of lameness is therefore vital if the practitioner is to treat or refer animals appropriately. This article describes a step‐by‐step approach to investigating lameness in the forelimb in dogs. A second article, to be published in the February issue of In Practice, will describe the approach for investigating hindlimb lameness.
Blitz therapy for the eradication of Streptococcus agalactiae infections in dairy cattle
Authors: Edmondson Peter
Published: January 2011

Streptococcus agalactiae responds very well to intramammary antibiotic treatment. This allows a system of ‘blitz therapy’ to be used to eliminate these infections. Blitz therapy involves antibiotic intramammary treatment into all four quarters during lactation to eradicate S agalactiae infections. Its use became popular in herds with high cell counts that were caused by S agalactiae. Cell counts have fallen significantly since the early 1980s, and the prevalence of S agalactiae and the need to employ blitz therapy has reduced. This article discusses the epidemiology, diagnosis and therapeutic options where S agalactiae is the sole or predominant cause of a high cell count. It describes how to decide whether blitz therapy is appropriate, outlines the key principles of treatment and highlights how to avoid any subsequent problems.
Stem cells as a resource for regenerative neurology
Authors: Connick P , Patani R , Chandran S
Published: January 2011

Public and media interest in the potential applications of stem cells in regenerative neurology has led to growing hope and expectation. This interest is heightened by the current paucity of treatments available for neurodegenerative diseases and their generally poor prognosis. Patient discussions about stem cells are therefore a common occurrence in clinical practice, requiring neurologists to offer clear and accurate information. In the context of a complex and rapidly evolving field, this can be extremely challenging. Here we address issues around stem cell populations relevant to regenerative neurology, including the opportunities they offer for research and their potential application as direct therapies, concluding with a pragmatic assessment of the likely clinical benefits of stem cell research.
Hypoxic-ischaemic brain injury
Authors: Howard Robin S , Holmes Paul A , Koutroumanidis Michalis A
Published: January 2011

Hypoxic–ischaemic brain injury is common and usually due to cardiac arrest or profound hypotension. The clinical pattern and outcome depend on the severity of the initial insult, the effectiveness of immediate resuscitation and transfer, and the post-resuscitation management on the intensive care unit. Clinical assessment is difficult and so often these days compromised by sedation, neuromuscular blockade, ventilation, hypothermia and inotropic management. Investigations can add valuable information, in particular brain MRI shows characteristic patterns depending on the severity of the injury and the timing of imaging. EEG patterns may also suggest the possibility of a good outcome. There is no entirely reliable algorithm of clinical signs or investigations which allow a definitive prognosis but the combination of careful repeated observations and appropriate ancillary investigations allows the neurologist to give an informed and accurate opinion of the likely outcome, and to advise on management. Overall, the prognosis is extremely poor and only a quarter of patients survive to hospital discharge, and often even then with severe neurological or cognitive deficits.
Mesenchymal cell proliferation and programmed cell death: key players in fibrogenesis and new targets for therapeutic intervention
Authors: Luna Jeroni , Masamunt Maria Carme , Lawrance Ian Craig , Sans Miquel
Published: January 2011

An exquisite equilibrium between cell proliferation and programmed cell death is required to maintain physiological homeostasis. In inflammatory bowel disease, and especially in Crohn's disease, enhanced proliferation along with defective apoptosis of immune cells are considered key elements of pathogenesis. Despite the relatively limited attention that has been given to research efforts devoted to intestinal fibrosis to date, there is evidence suggesting that enhanced proliferation along with defective programmed cell death of mesenchymal cells can significantly contribute to the development of excessive fibrogenesis in many different tissues. Moreover, some therapies have demonstrated potential antifibrogenic efficacy through the regulation of mesenchymal cell proliferation and programmed cell death. Further understanding of the pathways involved in the regulation of mesenchymal cell proliferation and apoptosis is, however, required.
Treatment of diabetic rats with a peroxynitrite decomposition catalyst prevents induction of renal COX-2
Authors: Chen Yu-Jung , Santos Margarita , Quilley John
Published: January 2011

Cyclooxygenase (COX)-2 expression is increased in the kidney of rats made diabetic with streptozotocin and associated with enhanced release of prostaglandins stimulated by arachidonic acid (AA). Treatment of diabetic rats with nitro-l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthase or with tempol to reduce superoxide prevented these changes, suggesting the possibility that peroxynitrite (ONOO) may be the stimulus for the induction of renal COX-2 in diabetes. Consequently, we tested the effects of an ONOO decomposition catalyst, 5,10,15,20-tetrakis( N-methyl-4′-pyridyl)porphyrinato iron(III) (FeTMPyP), which was administered for 3–4 wk after the induction of diabetes. FeTMPyP treatment normalized the twofold increase in the expression of nitrotyrosine, a marker for ONOO formation, in the diabetic rat and prevented the increase in renal COX-2 expression without modifying the two- to threefold increases in renal release of prostaglandins PGE2 and 6-ketoPGF1α in response to AA. FeTMPyP treatment of diabetic rats reduced the elevated creatinine clearance and urinary excretion of TNF-α and transforming growth factor (TGF)-β, suggesting a renoprotective effect. Double immunostaining of renal sections and immunoprecipitation of COX-2 and nitrotyrosine suggested nitration of COX-2 in diabetic rats. In cultured human umbilical vein endothelial cells (HUVECs) exposed to elevated glucose (450 mg/dl) or ONOO derived from 3-morpholinosydnonimine (SIN-1), expression of COX-2 was increased and was prevented when endothelial cells were treated with FeTMPyP. These results indicate that elevated glucose increases the formation of ONOO, which contributes to the induction of renal COX-2 in the diabetic rat.
Characterization of fibroblasts recruited from bone marrow-derived precursor in neonatal bronchopulmonary dysplasia mice
Authors: Deng Chun , Wang Jin , Zou Youfu , Zhao Qianqian , Feng Jie , Fu Zhou , Guo Chunbao
Published: January 2011

We sought to determine whether the extrapulmonary origin of fibroblasts derived from bone marrow (BM) progenitor cells is essential to lung fibrosis in bronchopulmonary dysplasia (BPD). Neonate mice were durably engrafted with BM isolated from transgenic reporter mice that expressed green fluorescent protein (GFP). Such chimera mice were subjected to 60% O2exposure for 14 days. A large number of fibroblast-specific protein-1 (FSP1) and GFP-positive fibroblasts were identified in active fibrotic lesions. More surprisingly, however, FSP1+fibroblasts also arose in considerable numbers from BM-derived alveolar type II cells (AT2) through epithelial-mesenchymal transition (EMT) during lung fibrogenesis. Cultured lung fibroblasts could express the CXC chemokine receptor (CXCR4) and responded chemotactically to their cognate ligand, chemokine (C-X-C motif) ligand 12 (CXCL12), which were elevated in the serum of BPD mice. These data suggest that lung fibroblasts in BPD fibrosis could variably arise from BM progenitor cells. This finding, which suggests the pathophysiological process of fibrosis, could contribute to a therapy for BPD that is characterized by extensive interstitial fibrosis.
Smad-Interacting Protein-1 and MicroRNA 200 Family Define a Nitric Oxide–Dependent Molecular Circuitry Involved in Embryonic Stem Cell Mesendoderm Differentiation
Authors: Rosati Jessica , Spallotta Francesco , Nanni Simona , Grasselli Annalisa , Antonini Annalisa , Vincenti Sara , Presutti Carlo , Colussi Claudia , D'Angelo Carmen , Biroccio Anna , Farsetti Antonella , Capogrossi Maurizio C. , Illi Barbara , Gaetano Carlo
Published: January 2011

Objective—

Smad-interacting protein-1 (Sip1/ZEB2) is a transcriptional repressor of the telomerase reverse transcriptase catalytic subunit (Tert) and has recently been identified as a key regulator of embryonic cell fate with a phenotypic effect similar, in our opinion, to that reported for nitric oxide (NO). Remarkably, SIP1/ZEB2 is a known target of the microRNA 200 (miR-200) family. In this light, we postulated that Sip1/ZEB2 and the miR-200 family could play a role during the NO-dependent differentiation of mES.

Methods and Results—

The results of the present study show that Sip1/ZEB2 expression is downregulated during the NO-dependent expression of mesendoderm and early cardiovascular precursor markers, including Flk1 and CXCR4 in mES. Coincidently, members of the miR-200 family, namely miR-429, -200a, -200b, and -200c, were transcriptionally induced in parallel to mouse Tert. This regulation occurred at the level of chromatin. Remarkably, miR-429/miR-200a overexpression or Sip1/ZEB2 knockdown by short hairpin RNA interference elicited a gene expression pattern similar to that of NO regardless of the presence of leukemia inhibitory factor.

Conclusion—

These results are the first demonstrating that the miR-200 family and Sip1/ZEB2 transcription factor are regulated by NO, indicating an unprecedented molecular circuitry important for telomerase regulation and early differentiation of mES.
Disruption of the Apelin-APJ System Worsens Hypoxia-Induced Pulmonary Hypertension
Authors: Chandra Suparna M. , Razavi Hedi , Kim Jongmin , Agrawal Rani , Kundu Ramendra K. , de Jesus Perez Vinicio , Zamanian Roham T. , Quertermous Thomas , Chun Hyung J.
Published: January 2011

Objective—

The G-protein–coupled receptor APJ and its ligand apelin are highly expressed in the pulmonary vasculature, but their function in this vascular bed is unclear. We hypothesized that disruption of apelin signaling would lead to worsening of the vascular remodeling associated with pulmonary hypertension (PH).

Methods and Results—

We found that apelin-null mice developed more severe PH compared with wild-type mice when exposed to chronic hypoxia. Micro-computed tomography of the pulmonary arteries demonstrated significant pruning of the microvasculature in the apelin-null mice. Apelin-null mice had a significant reduction of serum nitrate levels. This was secondary to downregulation of endothelial nitric oxide synthase (eNOS), which was associated with reduced expression of Kruppel-like factor 2 (KLF2), a known regulator of eNOS expression. In vitro knockdown studies targeting apelin in human pulmonary artery endothelial cells demonstrated decreased eNOS and KLF2 expression, as well as impaired phosphorylation of AMP-activated kinase and eNOS. Moreover, serum apelin levels of patients with PH were significantly lower than those of controls.

Conclusion—

These data demonstrate that disruption of apelin signaling can exacerbate PH mediated by decreased activation of AMP-activated kinase and eNOS, and they identify this pathway as a potentially important therapeutic target for treatment of this refractory human disease.
Epigenetic Regulation of Vascular Smooth Muscle Cell Proliferation and Neointima Formation by Histone Deacetylase Inhibition
Authors: Findeisen Hannes M. , Gizard Florence , Zhao Yue , Qing Hua , Heywood Elizabeth B. , Jones Karrie L. , Cohn Dianne , Bruemmer Dennis
Published: January 2011

Objective—

Proliferation of smooth muscle cells (SMC) in response to vascular injury is central to neointimal vascular remodeling. There is accumulating evidence that histone acetylation constitutes a major epigenetic modification for the transcriptional control of proliferative gene expression; however, the physiological role of histone acetylation for proliferative vascular disease remains elusive.

Methods and Results—

In the present study, we investigated the role of histone deacetylase (HDAC) inhibition in SMC proliferation and neointimal remodeling. We demonstrate that mitogens induce transcription of HDAC 1, 2, and 3 in SMC. Short interfering RNA–mediated knockdown of either HDAC 1, 2, or 3 and pharmacological inhibition of HDAC prevented mitogen-induced SMC proliferation. The mechanisms underlying this reduction of SMC proliferation by HDAC inhibition involve a growth arrest in the G
1
phase of the cell cycle that is due to an inhibition of retinoblastoma protein phosphorylation. HDAC inhibition resulted in a transcriptional and posttranscriptional regulation of the cyclin-dependent kinase inhibitors p21
Cip1
and p27
Kip
. Furthermore, HDAC inhibition repressed mitogen-induced cyclin D1 mRNA expression and cyclin D1 promoter activity. As a result of this differential cell cycle-regulatory gene expression by HDAC inhibition, the retinoblastoma protein retains a transcriptional repression of its downstream target genes required for S phase entry. Finally, we provide evidence that these observations are applicable in vivo by demonstrating that HDAC inhibition decreased neointima formation and expression of cyclin D1 in a murine model of vascular injury.

Conclusion—

These findings identify HDAC as a critical component of a transcriptional cascade regulating SMC proliferation and suggest that HDAC might play a pivotal role in the development of proliferative vascular diseases, including atherosclerosis and in-stent restenosis.
Metrics for Measuring Quality of Care in Comprehensive Stroke Centers: Detailed Follow-Up to Brain Attack Coalition Comprehensive Stroke Center Recommendations
Authors: Leifer Dana , Bravata Dawn M. , Connors J.J. (Buddy) , Hinchey Judith A. , Jauch Edward C. , Johnston S. Claiborne , Latchaw Richard , Likosky William , Ogilvy Christopher , Qureshi Adnan I. , Summers Debbie , Sung Gene Y. , Williams Linda S. , Zorowitz Richard
Published: January 2011

Background—

Stroke is a major cause of disability and death. The Brain Attack Coalition has proposed establishment of primary and comprehensive stroke centers to provide appropriate care to stroke patients who require basic and more advanced interventions, respectively. Primary stroke centers have been designated by The Joint Commission since 2003, as well as by various states. The designation of comprehensive stroke centers (CSCs) is now being considered. To assist in this process, we propose a set of metrics and related data that CSCs should track to monitor the quality of care that they provide and to facilitate quality improvement.

Methods and Results—

We analyzed available guideline statements, reviews, and other literature to identify the major features that distinguish CSCs from primary stroke centers, drafted a set of metrics and related data elements to measure the key components of these aspects of stroke care, and then revised these through an iterative process to reach a consensus. We propose a set of metrics and related data elements that cover the major aspects of specialized care for patients with ischemic cerebrovascular disease and nontraumatic subarachnoid and intracerebral hemorrhages at CSCs.

Conclusions—

The metrics that we propose are intended to provide a framework for standardized data collection at CSCs to facilitate local quality improvement efforts and to allow for analysis of pooled data from different CSCs that may lead to development of national performance standards for CSCs in the future.
Biomarkers of Asymptomatic Carotid Stenosis in Patients Undergoing Coronary Artery Bypass Grafting
Authors: Kim Suk Jae , Song Pamela , Park Jae Hyun , Lee Young Tak , Kim Wook Sung , Park Yun Gyoung , Bang Oh Young , Chung Chin-Sang , Lee Kwang Ho , Kim Gyeong-Moon
Published: January 2011

Background and Purpose—

Carotid artery stenosis is an important etiologic factor of stroke related to coronary artery bypass surgery. We evaluated clinical and laboratory factors to identify biomarkers for pre-existing carotid artery stenosis in patients undergoing coronary artery bypass surgery.

Methods—

Between June 2006 and September 2008, 811 patients aged ≥50 years underwent preoperative carotid artery duplex scanning as part of a preoperative assessment for nonemergency cardiac procedures. Of these, 54 patients with previous stroke or transient ischemic attack were excluded. The association between various biomarkers and carotid artery stenosis was analyzed by multiple logistic regression analysis. The receiver operating characteristic curves were generated and analyzed to compare diagnostic performance and optimum diagnostic cutoff levels of biomarkers.

Results—

A total of 757 patients was included in the study. The prevalence of asymptomatic carotid stenosis of ≥50% and ≥70% was 26.4% and 8.6%, respectively. In multivariate analysis, plasma levels of apolipoprotein B (apoB):apoA-I, lipoprotein(a), and homocysteine were independently associated with carotid stenosis of ≥50%: the OR (95% CI) for apoB/apoA-I, lipoprotein(a), and homocysteine in the highest versus lowest quartile was 2.07 (1.18 to 3.66), 2.17 (1.16 to 4.05), and 2.13 (1.20 to 3.79), respectively. Receiver operating characteristic curve analysis indicated area under the curve values of 0.708 (apoB:apoA-I), 0.678 (lipoprotein[a]), and 0.689 (homocysteine). The sensitivity, specificity, positive and negative predictive values (%) for diagnosis of carotid stenosis ≥50% were 80.0, 50.4, 38.0, and 86.9 for apoB:apoA-I; 47.0, 78.9, 46.1, and 79.5 for lipoprotein(a); and 69.3, 62.1, 41.2, and 84.1 for homocysteine, respectively.

Conclusion—

Our findings indicated that plasma levels of apoB/apoA-I, lipoprotein(a), and homocysteine can predict asymptomatic carotid stenosis in patients undergoing coronary artery bypass surgery.
Prevalence of Early Dementia After First-Ever Stroke
Authors: Béjot Yannick , Aboa-Eboulé Corine , Durier Jérôme , Rouaud Olivier , Jacquin Agnès , Ponavoy Eddy , Richard Dominique , Moreau Thibault , Giroud Maurice
Published: January 2011

Backgound and Purpose—

No data about temporal change in the prevalence of poststroke dementia are available. We aimed to evaluate trends in the prevalence of early poststroke dementia.

Methods—

From 1985 to 2008, overall first-ever strokes occurring within the population of the city of Dijon, France (150 000 inhabitants) were recorded. The presence of dementia was diagnosed during the first month after stroke, according to Diagnostic and Statistical Manual of Mental Disorders, Third and Fourth Editions criteria. Time trends were analyzed according to 4 periods: 1985 to 1990, 1991 to 1996, 1997 to 2002, and 2003 to 2008. Logistic regression was used for nonmultivariate analyses.

Results—

Over the 24 years, 3948 first-ever strokes were recorded. Among patients with stroke, 3201 (81%) were testable of whom 653 (20.4%) had poststroke dementia (337 women and 316 men). The prevalence of nontestable (mostly due to death) patients declined from 28.0% to 10.2% (
P
<0.0001). Multivariate analysis revealed significant temporal changes in the prevalence of poststroke dementia; prevalence in the second and fourth periods was, respectively, almost half and twice that in the first period. The prevalence of poststroke dementia associated with lacunar stroke was 7 times higher than that in intracerebral hemorrhage but declined over time as did prestroke antihypertensive medication. Age, several vascular risk factors, hemiplegia, and prestroke antiplatelet agents were associated with an increased prevalence of poststroke dementia.

Conclusions—

This study covering a period of 24 years highlights temporal changes in the prevalence of early dementia after first-ever stroke. These changes may be explained by concomitant determinants of survival and incidence such as stroke care management or prestroke medication.
Transcranial Direct Current Stimulation Improves Naming Reaction Time in Fluent Aphasia
Authors: Fridriksson Julius , Richardson Jessica D. , Baker Julie M. , Rorden Chris
Published: January 2011

Background and Purpose—

Previous evidence suggests that anodal transcranial direct current stimulation (A-tDCS) applied to the left hemisphere can improve aphasic participants' ability to name common objects. The current study further examined this issue in a more tightly controlled experiment in participants with fluent aphasia.

Methods—

We examined the effect of A-tDCS on reaction time during overt picture naming in 8 chronic stroke participants. Anode electrode placement targeted perilesional brain regions that showed the greatest activation on a pretreatment functional MRI scan administered during overt picture naming with the reference cathode electrode placed on the contralateral forehead. A-tDCS (1 mA; 20-minute) was compared with sham tDCS (S-tDCS) in a crossover design. Participants received 10 sessions of computerized anomia treatment; 5 sessions included A-tDCS and 5 included S-tDCS.

Results—

Coupling A-tDCS with behavioral language treatment reduced reaction time during naming of trained items immediately posttreatment (
Z
=1.96,
P
=0.025) and at subsequent testing 3 weeks later (
Z
=2.52,
P
=0.006).

Conclusions—

A-tDCS administered during language treatment decreased processing time during picture naming by fluent aphasic participants. Additional studies combining A-tDCS, an inexpensive method with no reported serious side effects, with behavioral language therapy are recommended.
Justice & Racial Conciliation: Two Visions
Authors: Shelby Tommie
Published: January 2011

As we attempt to measure racial progress in America today and chart a path toward further progress, we should look to the vision of Martin Luther King, Jr. Barack Obama has also offered an influential vision of race in America that is similar to and inspired by King's. This essay compares King's and Obama's respective visions for race relations in U.S. society. Both men profess a commitment to racial equality and integration as fundamental ideals; and both provide an astute analysis of the racial realities of his day. However, Shelby's comparison of their visions reveals moral deficiencies in Obama's political philosophy, particularly with regard to the proposed way forward and the worthy principles that would have to be compromised on by following his path. Liberal pragmatism in matters of race may yield some social benefits, but not without moral costs.
Poetry in a New Race Era
Authors: Jocson Korina
Published: January 2011

A growing literary arts movement is shaping discourses about youth and youth culture. With the historic election of President Obama serving as a departure point, this essay calls attention to poetry and the new race era to offer insights into the power of writing. For many youth who write in their own contexts or compete in the Brave New Voices Poetry Slam Festival, for example, such themes as voice, identity, citizenship, and leadership in the twenty-first century reveal how language is used to expose social realities often steeped in the margins. What do these themes suggest about the possibilities of poetry in a new race era? Indeed, what do they convey about inhabiting a new race era? Examples that tackle these themes are included in the essay.