bluuebunny/crossref_metadata_2025 huggingface dataset:
Seismic Isolation of the IRIS Nuclear Plant
Authors: Forni Massimo , Poggianti Alessandro , Bianchi Fosco , Forasassi Giuseppe , Lo Frano Rosa , Pugliese Giovanni , Perotti Federico , Corradi dell’Acqua Leone , Domaneschi Marco , Carelli Mario D. , Ahmed Mostafa A. , Maioli Andrea
Published: July 2010

The safety-by-design™ approach adopted for the design of the International Reactor Innovative and Secure (IRIS) resulted in the elimination by design of some of the main accident scenarios classically applicable to Pressurized Water Reactors (PWR) and to the reduction of either consequences or frequency of the remaining classical at-power accident initiators. As a result of such strategy the Core Damage Frequency (CDF) from at-power internal initiating events was reduced to the 10−8/ry order of magnitude, thus elevating CDF from external events (seismic above all) to an even more significant contributor than what currently experienced in the existing PWR fleet. The same safety-by-design™ approach was then exported from the design of the IRIS reactor and of its safety systems to the design of the IRIS Nuclear Steam Supply System (NSSS) building, with the goal of reducing the impact of seismically induced scenarios. The small footprint of the IRIS NSSS building, which includes all Engineered Safety Features (ESF), all the emergency heat sink and all the required support systems makes the idea of seismic isolation of the entire nuclear island a relatively easy and economically competitive solution. The seismically isolated IRIS NSSS building dramatically reduces the seismic excitation perceived by the reactor vessel, the containment structure and all the main IRIS ESF components, thus virtually eliminating the seismic-induced CDF. This solution is also contributing to the standardization of the IRIS plant, with a single design compatible with a variety of sites covering a wide spectrum of seismic conditions. The conceptual IRIS seismic isolation system is herein presented, along with a selection of the preliminary seismic analyses confirming the drastic reduction of the seismic excitation to the IRIS NSSS building. Along with the adoption of the seismic isolation system, a more refined approach to the computation of the fragility analysis of the components is also being developed, in order to reduce the undue conservatism historically affecting seismic analysis. The new fragility analysis methodology will be particularly focused on the analysis of the isolators themselves, which will now be the limiting components in the evaluation of the overall seismic induced CDF.
Adaptation of RCC-M Design and Construction Rules to the Evolution of Projects Needs, Regulatory Evolutions and International Exchanges
Authors: Grandemange Jean-Marie
Published: July 2010

The design and construction rules for mechanical components of LWR nuclear islands (RCC-M) constantly evolve to reflect the needs of the industry with the objective to fulfill the regulatory demands. Each year, an addendum is thus prepared by Afcen. The December 2008 addendum includes in particular new grades for products procurement, evolutions on destructive and non destructive examination provisions, consideration of new editions of standards, improvements of text for an easier application. For a better consistency with regulatory demands, technical code requirements have been updated (pressure test, overpressure protection, examination requirements or material properties), and in certain cases, provisions have been shifted in non-mandatory appendices established for various regulatory contexts for a better adaptation to applications abroad. In parallel, the conditions for consistency with the European Pressure Equipment Directive (PED) and the French Nuclear Pressure Equipment regulation (ESPN Order dated December 12, 2005) have been deepened and a comparison work was done in the context of the MDEP (Multinational Design Evaluation Procedure initiative of OECD) with equivalent ASME code provisions. The paper will present the content of the 2008 addendum of RCC-M, and the present status of these two studies on regulatory conformance and international comparisons, as well as some orientations for further evolutions.
Generating Confidence in Inspection Results
Authors: Booler R. V. , Daniels W. L. , Taggart J. P.
Published: July 2010

Crucial decisions, based upon NDE results, are made regarding the operation of safety critical components. Materials investigations identify degradation mechanisms, and defect assessments determine what defects are tolerable, but NDE is generally the only method of determining whether unacceptable defects actually exist in a component. Consequently, it is vital that we have confidence in the NDE results. This paper describes the measures that are taken to ensure confidence in the NDE being applied and the interactions that are needed with other structural integrity disciplines. In particular, we describe the role of Inspection Qualification as a formal process that has been adopted to address the uncertainties in NDE performance identified through round robin trials. Although the examples used are from the nuclear industry they pertain to any industry sector where NDE plays an important role in assessing structural integrity. Increasing interest in applying risk-informed inspection scopes, plant life extension and the world-wide nuclear new build programme are imposing new requirements on NDE of safety-critical components. We describe how the NDE community is responding to these challenges in providing quantitative inspection information (probability of detection) and maintaining a high level of confidence in the results. The paper aims to inform other structural integrity disciplines and plant operators of the impact their decisions may have on the NDE. For example, the pessimisms and safety margins applied to determine acceptance standards often impose extremely onerous requirements on the NDE resulting in long development times and high cost. In addition we discuss how the NDE can impact on the decisions regarding safe and reliable operation of plant.
CFD Estimation of the Flow-Induced Vibrations of a Fuel Rod Downstream a Mixing Grid
Authors: Benhamadouche S. , Moussou P. , Le Maitre C.
Published: July 2010

Turbulent-induced vibrations of fuel assemblies in PWR power plants is a potential cause of deformation and of fretting wear damage. Because of the complexity of a 17 × 17 rod assembly with a length exceeding four meters, the prediction of its vibrations is still a challenging task as regards computer simulation. The Large Eddy Simulation (LES) technique provides the instantaneous pressure and velocity fields inside the fluid as well as the shear stress and the pressure along the walls. EDF inhouse open source CFD tool Code_Saturne is used in the present work with a 8 million cells grid to compute the flow along four sub-channels all around one fuel rod by taking into account only one mixing grid. The computations are carried out on 1024 processors of a BlueGene/L supercomputer. Hence, the overall turbulent excitation upon one single rod is estimated numerically, taking into account the specific influence of the deflectors. As regards the structure, using the forces provided by the CFD computation, a linear model of the rod based on Euler beam theory and simplified boundary conditions is proposed. The first natural modes of the structure are hence obtained, and the modal forces are estimated using the standard techniques of modal projection and joint acceptance. Estimations of the vibration amplitude of rod induced by the local flow are finally obtained, using simplified expressions of the added mass and of the damping coefficient. The amplitudes are significant for the first mode essentially, and reach a value of the order of the μm, with a maximum around 6 μm.
An Overview of the Research by EC-JRC/IE on Enhancement of Maintenance Efficiency of Nuclear Power Plants
Authors: Contri Paolo , Kuzmina Irina
Published: July 2010

Economic deregulation of electricity markets in many countries has placed nuclear power plants (NPPs) in a new competitive environment where capital, operating and maintenance costs must be minimized. Optimization of the maintenance strategy, enhancement of the maintenance efficiency and monitoring the performance are becoming the key attributes to ensure the survival of nuclear utilities in the energy market. The need to collect relevant experience and suggest a consolidated system of performance indicators to measure the maintenance effectiveness was recognized by the Institute for Energy EC-JRC and research conducted aimed at suggesting such a system. The paper highlights the latest improvements to the system of maintenance performance indicators and discusses further steps and issues to be addressed in the course of the research on enhancing the effectiveness of maintenance at NPPs.
Fracture Property Testing of Carbon Steel in High Pressure Hydrogen
Authors: Duncan Andrew J. , Adams Thad M. , Lam Poh-Sang
Published: July 2010

An infrastructure of new and existing pipelines and systems will be required to carry and to deliver hydrogen as an alternative energy source to meet the energy demands of the future. Carbon and low alloy steels of moderate strength are currently used in hydrogen delivery systems as well as in the existing natural gas systems. It is critical to understand the material response of these standard pipeline materials when they are subjected to pressurized hydrogen environments. The methods and results from a testing program to quantify hydrogen effects on mechanical properties of carbon steel pipeline and pipeline weld materials are provided. Fracture toughness testing has been performed for one type of steel pipe material (A106 Grade B) in base metal, welded and heat affected zone conditions. C-shaped specimens were tested at room temperature in air and high pressure (102 ATM) hydrogen. A marked reduction in JQ was documented for both the base metal and HAZ metal tested in hydrogen. The results compliment a previous study on tensile properties of A106 Grade B material in high pressure hydrogen and are envisioned to be part of the basis for construction codes and structural integrity demonstrations of piping and pipelines for hydrogen service.
Flow-Induced Vibration and Fretting-Wear Performance of CANDU™ Steam Generator U-Tubes: Instrumentation
Authors: Mohany Atef , Janzen Victor
Published: July 2010

This paper describes a test program that was developed to measure the dynamic response of a bundle of steam generator U-tubes with Anti-Vibration Bar (AVB) supports, subjected to Freon two-phase cross-flow. The tube bundle has similar geometrical conditions to those expected for future CANDU™ steam generators. Future steam generators will be larger than previous CANDU steam generators, nearly twice the heat transfer area, with significant changes in process conditions in the U-bend region, such as increased steam quality and a broader range of flow velocities. This test program is one of the initiatives that AECL is undertaking to demonstrate that the tube support design for future CANDU steam generators meets the stringent requirements associated with a 60 year lifetime. The main objective of the tests is to address the issue of in- and out-of-plane fluidelastic instability and random turbulent excitation of a U-tube bundle with AVB supports. Details of the test rig, measurement techniques and preliminary instrumentation results are described in the paper.
Design Specifications to Ensure Flow-Induced Vibration and Fretting-Wear Performance in CANDU™ Steam Generators and Heat Exchangers
Authors: Janzen Victor , Han Yingke , Pettigrew Michel
Published: July 2010

Preventing flow-induced vibration and fretting-wear problems in steam generators and heat exchangers requires design specifications that bring together specific guidelines, analysis methods, requirements and appropriate performance criteria. This paper outlines the steps required to generate and support such design specifications for CANDU™ nuclear steam generators and heat exchangers, and relates them to typical steam-generator design features and computer modeling capabilities. It also describes current issues that are driving changes to flow-induced vibration and fretting-wear specifications that can be applied to the design process for component refurbishment, replacement or new designs. These issues include recent experimental or field evidence for new excitation mechanisms, e.g., the possibility of in-plane fluidelastic instability of U-tubes, the demand for longer reactor and component lifetimes, the need for better predictions of dynamic properties and vibration response, e.g., two-phase random-turbulence excitation, and requirements to consider system “excursions” or abnormal scenarios, e.g., a main steam line break in the case of steam generators. The paper describes steps being taken to resolve these issues.
Fluid Structure Interaction Analysis on a Transient Pitching Hydrofoil
Authors: Ducoin Antoine , Astolfi Jacques Andre´ , Deniset Franc¸ois , Sigrist Jean-Franc¸ois
Published: July 2010

In this paper, the structural behavior of a deformable hydrofoil in forced pitching motion is analyzed through an experimental approach. The experimental study is based on the measurement in a hydrodynamic tunnel of the foil displacement obtained with a video camera. Tip section displacement is compared to the hydrodynamic loading obtained on a rigid hydrofoil using wall pressure measurement. The structural response appears to be strongly linked to hydrodynamic phenomena such as laminar to turbulent transition and leading edge vortex shedding. The influence of pitching velocity is discussed. Finally, the paper presents displacement measurements in cavitating flows.
Post Weld Overlay Residual Stresses in Dissimilar Metal Welds Considering Various Butt Weld and Weld Repair Fabrication Sequences
Authors: Ku Francis H. , Lohse Christopher S. , Dijamco David G. , Fourcade Charles J. , Bax Richard L. , Cofie Nathaniel G.
Published: July 2010

Weld overlays have been used to repair or mitigate stress corrosion cracking (SCC) in both boiling water reactor (BWR) and pressurized water reactor (PWR) nozzle-to-pipe dissimilar metal welds (DMW). One of the contributing factors to SCC is the high tensile residual stresses produced during the fabrication of the original butt weld, especially when local weld repairs were present during the welding process. In analytical simulations to determine the post weld overlay residual stresses, complete simulation of the original butt weld, weld repair and the overlay is desired. However, to reduce the computational effort, it is commonly assumed that the weld repair stresses overwhelm the original butt weld residual stresses such that the original butt weld need not be simulated and only the weld repair is simulated before the application of the overlay. Questions have also been raised as to why the butt weld and/or the weld repair need to be simulated since it is assumed that both of these fabrication processes would be overcome by the weld overlay process. This paper investigates three fabrication sequences in order to determine their effect on the post weld overlay residual stresses: (1) the butt weld is simulated followed by a weld repair and then the weld overlay is applied; (2) the butt weld is simulated followed by the weld overlay with no consideration of a weld repair; (3) the butt weld is not simulated but a weld repair is assumed and the weld overlay is applied. Five different nozzle-to-pipe size configurations were used in the study to determine the effect of pipe size on the three fabrication sequences described above. The investigation indicates that the post weld overlay residual stresses for Cases 1 and 3 are similar and hence simulation of the weld repair alone (without the butt weld simulation) prior to simulating the weld overlay is a reasonable assumption. However, not simulating the weld repair (corresponding to Case 2) may provide different residual stress distribution.
Coupling a Detonation Shock Dynamics Code to an Eulerian Hydrocode
Authors: Littlefield David L. , Kim Young-Ho , Lambert David E.
Published: July 2010

In this technical effort we have incorporated the Detonation Shock Dynamics (DSD) methodology into the Eulerian hydrocode CTH by coupling it to a DSD code called WAVETRACKER. Based on some preliminary work, we developed a strategy for coupling these two codes. Both CTH and WAVETRACKER are stand-alone codes. In the coupled code, CTH calls WAVETRACKER as a subroutine. Interface routines are developed to pass geometry, mesh and boundary information from CTH to WAVETRACKER. Additional parameters required by WAVETRACKER are read directly from a user input file. Results in the form of a burn table are interpolated and passed back from WAVETRACKER to CTH.
Microstrucutural Characterization of RPV Steels Irradiated to High Fluences
Authors: Tomimatsu Minoru , Sakamoto Hiroyuki , Dohi Kenji , Watanabe Toshiyuki , Matsuzawa Hiroshi
Published: July 2010

Neutron radiation embrittlement of reactor pressure vessel (RPV) steels is one of critical issues for the structural integrity assessment of the RPVs. Especially, the embrittlement at high fluences is of great interest for the long term operation of light water reactors because information on the mechanical property changes as well as embrittlement mechanisms is limited at high fluences. In this study, microstructural analyses were conducted on the RPV steels irradiated to high fluences in order to confirm the applicability of the trend curve at high fluence region. Steels investigated are five base metals and a weld metal with their copper content ranging from 0.02 to 0.25 wt. %. These steels were irradiated in the material test reactors to fluence up to 1.3 × 1020 n/cm2, E > 1MeV, at temperature of about 290 °C. After irradiation, transmission electron microscope (TEM) observations were performed to characterize the nano-meter scale microstructural changes due to irradiation. Formation of dislocation loops was observed. Number density and diameter of dislocation loop was investigated. Effects of chemical composition of steel and fluence on dislocation loop formation are discussed.
Welding Residual Stress and Multiple Flaw Evaluation for Reactor Pressure Vessel Head Replacement Welds With Alloy 52
Authors: Zhang T. , Brust F. W. , Wilkowski G. , Rudland D. L. , Csontos A.
Published: July 2010

Small indications were found in one replacement reactor pressure vessel head (RPVH) mock-up being fabricated from Alloy 690 material and compatible weld metals, Alloy 52/152. The mockups were non-destructively examined and the lowest number of cracks found was five and the highest number was 22. There are numerous indications with some of them quite long (50 mm) in length. The source of these weld fabrication cracks is unknown. However, from experience with other difficult to weld materials, the source can range from slag inclusions in the weld metal to hot cracking during the weld deposition process. Hot cracking includes solidification cracking (weld), liquation cracking (HAZ), and ductility dip cracking (DDC). The indications were mostly circumferential in orientation (with respect to the nozzle axis) but some were axial. This paper includes two parts. The first part includes the welding residual stress analysis of RPVH using Alloy 52/152 metal and provides comparison with similar Alloy 82/182 welds. Alloy 82/182 was the material used in the original dissimilar metal welds in these heads. Primary Water Stress Corrosion Cracking (PWSCC) can occur in the primary coolant system when the welds are exposed to water, tensile stress, and temperature (usually higher than 250 C). PWSCC rates are higher in Alloy 82/182 material due to its lower chromium content compared with the replacement alloy. The results for both center hole (0-degree) and side hill (53-degree) nozzles will be discussed. The second part deals with assessment of multiple small cracks in the reactor pressure vessel head penetration nozzles. The finite element alternating method (FEAM) was used for calculating stress intensity factors for cases where multiple cracks exist. More than twenty cracks, which were inserted based on field measurements, are considered in the analyses for both center hole and side hill nozzles. It is observed that the overall stress trends are similar to those without adding cracks. However, cracks introduce more local stress fluctuations. The magnitude of the local fluctuation can be around 100MPa. Limit analysis was also conducted. A new finite element model with a voided-out weld region was used to simulate loss of structural capacity due to multiple flaws. The voided out volume effects on the structural integrity and future performance of RPVH were examined. Discussions based on weld residual stress, multiple flaw analysis and limit analysis conclude the paper.
The Effect of Boring After Autofrettage of Pressure Cylinders
Authors: Majzoobi G. H. , Mahmoudi A. H. , Zahirnia S.
Published: July 2010

In this work, the effect of boring on residual stress distribution in thick walled pressure cylinders after autofrettage is studied by numerical simulation using finite element method. Autofrettage is performed using mandrelling technique. The simulations are validated by experiment. In this regard, some cylinders are autofrettaged through mandrelling technique and residual stress is measured using central hole drilling method. The simulation of boring is performed by removing elements of cylindrical layers of small thickness after the loading and unloading processes (autofrettage) are completed. The diametral interferences of 0.4 mm and 0.6 mm between the mandrel and the cylinder are considered for the simulations. The results indicate that boring increases the through thickness residual Von-Mises and compressive hoop stresses from the inner surface up to a certain radius thereafter the trend changes and the stresses begin to reduce. Boring has reducing effect on radial stress distribution across the wall of the cylinder. Since residual stress measurement on the inner surface of the cylinder is difficult, the measurements are made only on the outer surface of the vessel. A good agreement between the trend of numerical predictions and experimental results are observed for boring. On the whole, boring can increase the residual stress at the inner surface and reduce it at the outer surface of pressure cylinder.
Technical Approach for the Reduction of Fugitive Emissions
Authors: Schaaf Manfred , Schoeckle Friedrich
Published: July 2010

The demands on industry to reduce fugitive emissions are increasing, steadily. For the European Union the Integrated Pollution Prevention and Control (IPPC) directive determines emission levels. Individual countries can adopt even tighter legislation like the TA-Luft (“Technical Instructions on Air Quality Control”) in Germany. E. g. the TA-Luft gives specific emission levels for valves according to the German VDI guideline 2440 - Emission reduction in oil refineries. In industrial applications in which the demands of the TA-Luft have to be met only certified sealing materials can be used in future. There are several requirements the sealants must fulfill, the most important in this respect is the tightness proof in a first-time test according to VDI 2440. In this objective, new packing materials were developed to be in compliance with the TA-Luft needs. The knowledge of the material characteristic is the basis for the improvement of the tightness capability and therefore for the reduction of fugitive emissions. But in almost the same manner the mounting procedure of the packing rings is important. It is necessary to perform the mounting procedure in two steps: a pre-deformation step (high stress level for seating) and a prestressing step (stress level must meet tightness requirements). Mounting by use of torque wrenches is time consuming, if this 2-step procedure is followed. Thus, mounting by use of hydraulic tensioner becomes effective. In the paper the most relevant packing material characteristics and the necessary tests to determine these characteristics are summarized. Then the mounting tools for hydraulic tensioning are introduced. Finally, some results of packing tests according to VDI 2440 are presented.
Effects of Cr Content and Environmental Factors on FAC Rate of Carbon Steels
Authors: Watanabe Yutaka , Sue Kiwamu , Abe Hiroshi
Published: July 2010

Combined effects of Cr content and environmental factors, pH and dissolved oxygen concentration, on removal rate of carbon steels due to flow accelerated corrosion have been examined by experiments. The effects of environmental factors on FAC rate have been attempted to interpret based on oxide solubility, which has been precisely evaluated by separate experiments and numerical estimations. pH dependency of the FAC rate has been found to be directly related to solubility of magnetite. Cr content holds a strong impact on the FAC rate regardless of pH values from 6.84 to 10.4. Addition of 1% Cr to a carbon steel reduces the FAC rate by one order of magnitude under the environmental conditions, where magnetite forms. Addition of oxygen up to 1200ppb changes the oxide from magnetite to hematite, resulting in significant improvement in corrosion resistance. Oxide film characteristics, e.g. compositional distributions and types of oxide compound, have been also examined and their correlation to the FAC rate has been discussed.
Presence of Enteric Viruses in Source Waters for Drinking Water Production in the Netherlands
Authors: Lodder W. J. , van den Berg H. H. J. L. , Rutjes S. A. , de Roda Husman A. M.
Published: July 2010

The quality of drinking water in the Netherlands has to comply with the Dutch Drinking Water Directive: less than one infection in 10,000 persons per year may occur due to consumption of unboiled drinking water. Since virus concentrations in drinking waters may be below the detection limit but entail a public health risk, the infection risk from drinking water consumption requires the assessment of the virus concentrations in source waters and of the removal efficiency of treatment processes. In this study, samples of source waters were taken during 4 years of regular sampling (1999 to 2002), and enteroviruses, reoviruses, somatic phages, and F-specific phages were detected in 75% (range, 0.0033 to 5.2 PFU/liter), 83% (0.0030 to 5.9 PFU/liter), 100% (1.1 to 114,156 PFU/liter), and 97% (0.12 to 14,403 PFU/liter), respectively, of 75 tested source water samples originating from 10 locations for drinking water production. By endpoint dilution reverse transcription-PCR (RT-PCR), 45% of the tested source water samples were positive for norovirus RNA (0.22 to 177 PCR-detectable units [PDU]/liter), and 48% were positive for rotavirus RNA (0.65 to 2,249 PDU/liter). Multiple viruses were regularly detected in the source water samples. A significant correlation between the concentrations of the two phages and those of the enteroviruses could be demonstrated. The virus concentrations varied greatly between 10 tested locations, and a seasonal effect was observed. Peak concentrations of pathogenic viruses occur in source waters used for drinking water production. If seasonal and short-term fluctuations coincide with less efficient or failing treatment, an unacceptable public health risk from exposure to this drinking water may occur.
Enhanced Production and Secretion of Heterologous Proteins by the Filamentous Fungus
Aspergillus oryzae
via Disruption of Vacuolar Protein Sorting Receptor Gene
Aovps10
Authors: Yoon Jaewoo , Aishan Tuerxun , Maruyama Jun-ichi , Kitamoto Katsuhiko
Published: July 2010

Filamentous fungi have received attention as hosts for heterologous protein production because of their high secretion capability and eukaryotic posttranslational modifications. However, despite these positive attributes, a bottleneck in posttranscriptional processing limits protein yields. The vacuolar protein sorting gene
VPS10
encodes a sorting receptor for the recognition and delivery of several yeast vacuolar proteins. Although it can also target recombinant and aberrant proteins for vacuolar degradation, there is limited knowledge of the effect of its disruption on heterologous protein production. In this study, cDNA encoding AoVps10 from the filamentous fungus
Aspergillus oryzae
was cloned and sequenced. Microscopic observation of the transformant expressing AoVps10 fused with enhanced green fluorescent protein showed that the fusion protein localized at the Golgi and prevacuolar compartments. Moreover, disruption of the
Aovps10
gene resulted in missorting and secretion of vacuolar carboxypeptidase AoCpyA into the medium, indicating that AoVps10 is required for sorting of vacuolar proteins to vacuoles. To investigate the extracellular production levels of heterologous proteins, Δ
Aovps10
mutants expressing either bovine chymosin (CHY) or human lysozyme (HLY) were constructed. Interestingly, the Δ
Aovps10
mutation increased the maximum extracellular production levels of CHY and HLY by 3- and 2.2-fold, respectively. Western blot analysis of extracellular heterologous proteins also demonstrated an improvement in productivity. These results suggest that AoVps10 plays a role in the regulation of heterologous protein secretion in
A. oryzae
and may be involved in the vacuolar protein degradation through the Golgi apparatus.
Molecular Characterization of GrlA, a Specific Positive Regulator of
ler
Expression in Enteropathogenic
Escherichia coli
Authors: Jiménez Rafael , Cruz-Migoni Sara B. , Huerta-Saquero Alejandro , Bustamante Víctor H. , Puente José L.
Published: July 2010

Enteropathogenic
Escherichia coli
(EPEC) infections are characterized by the formation of attaching and effacing (A/E) lesions on the surfaces of infected epithelial cells. The genes required for the formation of A/E lesions are located within the locus of enterocyte effacement (LEE). Ler is the key regulatory factor controlling the expression of LEE genes. Expression of the
ler
gene is positively regulated by GrlA, which is encoded by the LEE. Here, we analyze the mechanism by which GrlA positively regulates
ler
expression and show that in the absence of H-NS, GrlA is no longer essential for
ler
activation, further confirming that GrlA acts in part as an H-NS antagonist on the
ler
promoter. Single-amino-acid mutants were constructed to test the functional significance of the putative helix-turn-helix (HTH) DNA binding motif found in the N-terminal half of GrlA, as well as at the C-terminal domain of the protein. Several mutations within the HTH motif, but not all, completely abolished GrlA activity, as well as specific binding to its target sequence downstream from position −54 in the
ler
regulatory region. Some of these mutants, albeit inactive, were still able to interact with the negative regulator GrlR, indicating that loss of activity was not a consequence of protein misfolding. Additional residues in the vicinity of the HTH domain, as well as at the end of the protein, were also shown to be important for GrlA activity as a transcriptional regulator, but not for its interaction with GrlR. In summary, GrlA consists of at least two functional domains, one involved in transcriptional activation and DNA binding and the other in heterodimerization with GrlR.
Dual Two-Component Regulatory Systems Are Involved in Aromatic Compound Degradation in a Polychlorinated-Biphenyl Degrader,
Rhodococcus jostii
RHA1
Authors: Takeda Hisashi , Shimodaira Jun , Yukawa Kiyoshi , Hara Naho , Kasai Daisuke , Miyauchi Keisuke , Masai Eiji , Fukuda Masao
Published: July 2010

A Gram-positive polychlorinated-biphenyl (PCB) degrader,
Rhodococcus jostii
RHA1, degrades PCBs by cometabolism with biphenyl. A two-component BphS1T1 system encoded by
bphS1
and
bphT1
(formerly
bphS
and
bphT
) is responsible for the transcription induction of the five gene clusters,
bphAaAbAcAdC1B1
,
etbAa1Ab1CbphD1
,
etbAa2Ab2AcD2
,
etbAdbphB2
, and
etbD1
, which constitute multiple enzyme systems for biphenyl/PCB degradation. The
bphS2
and
bphT2
genes, which encode BphS2 and BphT2, virtually identical to BphS1 (92%) and BphT1 (97%), respectively, were characterized. BphS2T2 induced the activation of the
bphAa
promoter in a host,
Rhodococcus erythropolis
IAM1399, in the presence of a variety of aromatics, including benzene, toluene, ethylbenzene, xylenes, isopropylbenzene, and chlorinated benzenes, as effectively as BphS1T1. The substrate spectrum of BphS2T2 was the same as that of BphS1T1, except for biphenyl, which is a substrate only for BphS1T1. BphS2T2 activated transcription from the five promoters of biphenyl/PCB degradation enzyme gene clusters as effectively as BphS1T1. The targeted disruptions of the
bphS1
,
bphS2
,
bphT1
, and
bphT2
genes indicated that all these genes are involved in the growth of RHA1 on aromatic compounds. The hybrid system with
bphS1
and
bphT2
and that with
bphS2
and
bphT1
were constructed, and both systems conducted induced activation of the
bphAa
promoter, indicating cross-communication. These results indicated that RHA1 employs not only multiple enzyme systems, but also dual regulatory systems for biphenyl/PCB degradation. Comparison of the sequences, including
bphS2T2
, with the
bphS1T1
-containing sequences and the corresponding sequences in other rhodococcal degraders suggests that
bphS2T2
might have originated from
bphS1T1
.
Functional Identification of theProteusmirabilisCore Lipopolysaccharide Biosynthesis Genes
Authors: Aquilini Eleonora , Azevedo Joana , Jimenez Natalia , Bouamama Lamiaa , Tomás Juan M. , Regué Miguel
Published: July 2010

In this study, we report the identification of genes required for the biosynthesis of the core lipopolysaccharides (LPSs) of two strains ofProteusmirabilis. SinceP.mirabilisandKlebsiellapneumoniaeshare a core LPS carbohydrate backbone extending up to the second outer-core residue, the functions of the commonP.mirabilisgenes was elucidated by genetic complementation studies using well-defined mutants ofK.pneumoniae. The functions of strain-specific outer-core genes were identified by using as surrogate acceptors LPSs from two well-definedK.pneumoniaecore LPS mutants. This approach allowed the identification of two new heptosyltransferases (WamA and WamC), a galactosyltransferase (WamB), and anN-acetylglucosaminyltransferase (WamD). In both strains, most of these genes were found in the so-calledwaagene cluster, although one common core biosynthetic gene (wabO) was found outside this cluster.
HIGH PERFORMANCE SCALABLE MIXED-RADIX-2n SERIAL-SERIAL MULTIPLIERS FOR GF(2m)
Authors: ALMILADI ABDURAZZAG SULAIMAN
Published: July 2010

In this paper, two new high performance bidirectional mixed radix-2n serial-serial multipliers for the finite field GF (2m) are presented. The input operands are serially entered one digit at a time for the first operand and two digits at a time for the second operand. The output result is computed serially one digit at a time. The reduction polynomial is also fed serially to the structure in the same manner so that changing the reduction polynomial will not require rewriting or rewiring the structure. The structures utilize a serial transfer which reduces the bus width needed to transfer data back and forth between memory and multiplication unit. The structures possess features of regularity, modularity and scalability which are a design requirement for an efficient utilization of FPGA resources. The new twin pipe design has improved the area-time performance by ~37% when compared with the best existing radix-2n serial-serial multipliers for the finite field GF (2m) . Furthermore, it is the first twin pipe bidirectional radix-2n serial-serial multiplier for the finite field GF (2m) reported in the literature. The twin pipe multiplier can be used to perform two successive K-digit multiplications in 2K + 6 cycles without truncating the results. As a consequence, a new data can be fed into the multiplier every K + 3 cycles. A radix-4 version of the proposed architecture has been designed, simulated and synthesized using Xilinx ISE 10.1 targeting a Xilinx Virtex-5 FPGA.
ELECTROMAGNETIC INTERFERENCE SUPPRESSION TECHNIQUES FOR COMPACT LED LAMP DRIVERS
Authors: CHIU HUANG-JEN , LO YU-KANG , YAO CHUN-JEN , WU KUAN-HUNG , WANG TAI-HUNG , CHUANG CHING-CHUN
Published: July 2010

In this paper, some electromagnetic interference (EMI) suppression techniques are studied and discussed for compact LED lamp drivers in residential lighting applications. A laboratory prototype with EMI suppression design is built and tested. Experimental results verify the feasibility of the studied schemes.
BLUE OCEAN OR FAST-SECOND INNOVATION? A FOUR-BREAKTHROUGH MODEL TO EXPLAIN SUCCESSFUL MARKET DOMINATION
Authors: BUISSON BERNARD , SILBERZAHN PHILIPPE
Published: July 2010

Innovation is widely recognized as a major driver of long-term corporate growth. Successful innovators who manage to dominate new markets enjoy Schumpeterian rents for their inventions. How then can a firm dominate a new market? Two streams of literature have proposed opposite answers to this question.

The First Mover approach indicates that by setting up a strong differentiation strategy, companies are supposed to create a new area where profits abound. This approach is supported especially by Kim and Mauborgne (2004) who coined the term Blue Ocean to describe it.

The Fast Second approach, defended by Markides and Geroski (2005), contends, on the contrary, that companies should not try to become pioneers, but should target the newly created market in second position, and colonize it.

But neither Blue Ocean nor Fast Second are able to convincingly explain successful market domination. Our study of 24 innovation cases suggests that innovation which leads to market domination is instead achieved by using four kinds of breakthroughs, separately of simultaneously.
IMPROVING CUSTOMERS TARGETING WITH SHORT INTERVENTION TESTING
Authors: GOFMAN ALEX , MOSKOWITZ HOWARD R.
Published: July 2010

The proposed consumer-driven innovation approach allows for the creation of individual communications with heterogeneous customers. It utilizes Rule Developing Experimentation (a modified conjoint analysis-based approach) to create a database of messages specific to the product and to segment consumers based on the patterns of individual utilities assigned to the different test elements. The paper introduces a new approach to identify a small subset of classification messages that allows for an actionable and parsimonious classification of any new population into pattern-based segments to achieve better targeting.

The approach is demonstrated by a case study of identifying segment membership for better messages targeting prospective customers of a KIA car dealership.
Microscopic Imaging and Spectroscopy with Scattered Light
Authors: Boustany Nada N. , Boppart Stephen A. , Backman Vadim
Published: July 2010

Optical contrast based on elastic scattering interactions between light and matter can be used to probe cellular structure, cellular dynamics, and image tissue architecture. The quantitative nature and high sensitivity of light scattering signals to subtle alterations in tissue morphology, as well as the ability to visualize unstained tissue in vivo, has recently generated significant interest in optical-scatter-based biosensing and imaging. Here we review the fundamental methodologies used to acquire and interpret optical scatter data. We report on recent findings in this field and present current advances in optical scatter techniques and computational methods. Cellular and tissue data enabled by current advances in optical scatter spectroscopy and imaging stand to impact a variety of biomedical applications including clinical tissue diagnosis, in vivo imaging, drug discovery, and basic cell biology.
Osteocyte Mechanobiology and Pericellular Mechanics
Authors: Jacobs Christopher R. , Temiyasathit Sara , Castillo Alesha B.
Published: July 2010

An impressive range of tissues and cells are regulated by mechanical loading, and this regulation is central to disease processes such as osteoporosis, atherosclerosis, and osteoarthritis. However, other than a small number of specialized excitable cells involved in hearing and touch, cellular mechanosensing mechanisms are generally quite poorly understood. A lack of mechanistic understanding of these processes is one of the primary foci of the nascent field of mechanobiology, which, as a consequence, enjoys enormous potential to make critical new insights into both physiological function and etiology of disease. In this review we outline the process in bone by tracing mechanical effects from the organ level to the cellular and molecular levels and by integrating the biological response from molecule to organ. A case is made that a fundamental roadblock to advances in mechanobiology is the dearth of information in the area of pericellular mechanics.
Mesenchymal Stem Cells as Therapeutics
Authors: Parekkadan Biju , Milwid Jack M.
Published: July 2010

Mesenchymal stem cells (MSCs) are multipotent cells that are being clinically explored as a new therapeutic for treating a variety of immune-mediated diseases. First heralded as a regenerative therapy for skeletal tissue repair, MSCs have recently been shown to modulate endogenous tissue and immune cells. Preclinical studies of the mechanism of action suggest that the therapeutic effects afforded by MSC transplantation are short-lived and related to dynamic, paracrine interactions between MSCs and host cells. Therefore, representations of MSCs as drug-loaded particles may allow for pharmacokinetic models to predict the therapeutic activity of MSC transplants as a function of drug delivery mode. By integrating principles of MSC biology, therapy, and engineering, the field is armed to usher in the next generation of stem cell therapeutics.
Systems Biology through Mouse Imaging Centers: Experience and New Directions
Authors: Henkelman R. Mark
Published: July 2010

The completed sequencing of genomes has forced upon us the challenge of understanding how the detailed information in the genome gives rise to the specific characteristics—phenotype—of the individual. This is crucial for understanding not only normal development but also, from a medical perspective, the genetic basis of disease. Much of the mammalian genome-to-phenotype relationship will be worked out in the mouse, for which powerful genetic-manipulation tools are available. Mouse imaging combined with powerful statistical methods has a unique and growing role to play in phenotyping genetically modified mice. This review outlines the challenges for image-based phenotyping, summarizes the current state of three-dimensional imaging technologies for the mouse, and highlights new opportunities in systems biology that are opened by imaging mice.
Substrate specificity of Rhbg: ammonium and methyl ammonium transport
Authors: Nakhoul Nazih L. , Abdulnour-Nakhoul Solange M. , Boulpaep Emile L. , Rabon Edd , Schmidt Eric , Hamm L. Lee
Published: July 2010

Rhbg is a nonerythroid membrane glycoprotein belonging to the Rh antigen family. In the kidney, Rhbg is expressed at the basolateral membrane of intercalated cells of the distal nephron and is involved in NH4+ transport. We investigated the substrate specificity of Rhbg by comparing transport of NH3/NH4+ with that of methyl amine (hydrochloride) (MA/MA+), often used to replace NH3/NH4+, in oocytes expressing Rhbg. Methyl amine (HCl) in solution exists as neutral methyl amine (MA) in equilibrium with the protonated methyl ammonium (MA+). To assess transport, we used ion-selective microelectrodes and voltage-clamp experiments to measure NH3/NH4+- and MA/MA+-induced intracellular pH (pHi) changes and whole cell currents. Our data showed that in Rhbg oocytes, NH3/NH4+ caused an inward current and decrease in pHi consistent with electrogenic NH4+ transport. These changes were significantly larger than in H2O-injected oocytes. The NH3/NH4+-induced current was not inhibited in the presence of barium or in the absence of Na+. In Rhbg oocytes, MA/MA+ caused an inward current but an increase (rather than a decrease) in pHi. MA/MA+ did not cause any changes in H2O-injected oocytes. The MA/MA+-induced current and pHi increase were saturated at higher concentrations of MA/MA+. Amiloride inhibited MA/MA+-induced current and the increase in pHi in oocytes expressing Rhbg but had no effect on control oocytes. These results indicate that MA/MA+ is transported by Rhbg but differently than NH3/NH4+. The protonated MA+ is likely a direct substrate whose transport resembles that of NH4+. Transport of electroneutral MA is also enhanced by expression of Rhbg.
Monovalent ions control proliferation of Ehrlich Lettre ascites cells
Authors: Klausen Thomas Kjær , Preisler Sarah , Pedersen Stine Falsig , Hoffmann Else Kay
Published: July 2010

Channels and transporters of monovalent ions are increasingly suggested as putative anticarcinogenic targets. However, the mechanisms involved in modulation of proliferation by monovalent ions are poorly understood. Here, we investigated the role of K+, Na+, and Cl− ions for the proliferation of Ehrlich Lettre ascites (ELA) cells. We measured the intracellular concentration of each ion in G0, G1, and S phases of the cell cycle following synchronization by serum starvation and release. We show that intracellular concentrations and content of Na+ and Cl− were reduced in the G0–G1 phase transition, followed by an increased content of both ions in S phase concomitant with water uptake. The effect of substituting extracellular monovalent ions was investigated by bromodeoxyuridine incorporation and showed marked reduction after Na+ and Cl− substitution. In spectrofluorometric measurements with the pH-sensitive dye BCECF, substitution of Na+ was observed to upregulate the activity of the Na+/H+ exchanger NHE1 as well as of Na+-independent acid extrusion mechanisms, facilitating intracellular pH (pHi) recovery after acid loading and increasing pHi. Results using the potential sensitive dye DiBaC4( 3 ) showed a reduced Cl− conductance in S compared with G1 followed by transmembrane potential ( Em) hyperpolarization in S. Cl− substitution by impermeable anions strongly inhibited proliferation and increased free, intracellular Ca2+ ([Ca2+]i), whereas a more permeable anion had little effect. Western blots showed reduced chloride intracellular channel CLIC1 and chloride channel ClC-2 expression in the plasma membrane in S compared with G1. Our results suggest that Na+ regulates ELA cell proliferation by regulating intracellular pH while Cl− may regulate proliferation by fine-tuning of Em in S phase and altered Ca2+ signaling.
Continuous and less invasive central hemodynamic monitoring by blood pressure waveform analysis
Authors: Mukkamala Ramakrishna , Xu Da
Published: July 2010

Blood pressure waveform analysis may permit continuous (i.e., automated) and less invasive (i.e., safer and simpler) central hemodynamic monitoring in the intensive care unit and other clinical settings without requiring any instrumentation beyond what is already in use or available. This practical approach has been a topic of intense investigation for decades and may garner even more interest henceforth due to the evolving demographics as well as recent trends in clinical hemodynamic monitoring. Here, we review techniques that have appeared in the literature for mathematically estimating clinically significant central hemodynamic variables, such as cardiac output, from different blood pressure waveforms. We begin by providing the rationale for pursuing such techniques. We then summarize earlier techniques and thereafter overview recent techniques by our collaborators and us in greater depth while pinpointing both their strengths and weaknesses. We conclude with suggestions for future research directions in the field and a description of some potential clinical applications of the techniques.