bluuebunny/crossref_metadata_2025 huggingface dataset:
The West Africa Swell Project (WASP)
Authors: Forristall George Z. , Ewans Kevin , Olagnon Michel , Prevosto Marc
Published: November 2013

The responses of floating systems are sensitive to the detailed shape of the swell portion of the wave spectrum. Knowledge of swell is particularly important for sites off West Africa. The West Africa Swell Project (WASP JIP) was formed to analyze the available data on West African swell. Measurements were obtained from Shell, Ifremer, Chevron and Marathon. Hindcast data came from Oceanweather and the NOAA Wavewatch model. Sites ranging from Nigeria to Namibia were considered.

Modeling the dispersion of swell over long distances indicates that the resulting power spectrum will have a triangular or lognormal shape. Sampling variability makes it difficult to distinguish between those shapes or Jonswap or Gaussian forms, but lognormal spectra generally provided good fits. The models also indicate that the width of the spectrum in both frequency and direction should be inversely related to the peak frequency. Fits to the measurements established detailed relationships for each location.

Calculating the response of single degree of freedom oscillators to the measured and hindcast spectra produces response spectra which give the maximum response as a function of natural period and damping. Extreme values of system response can be calculated from the response spectra. The largest responses come from uni-modal spectra, and design spectra can be estimated by inflating them.
On the Extreme Rotor and Support Structure Response of an Offshore Wind Turbine in an Evolving Hurricane
Authors: Kim E. , Manuel L.
Published: November 2013

This study examines extreme response statistics for a monopile-supported 5-MW offshore wind turbine in 20 meters of water that is subjected to coupled wind and wave input fields during a hurricane. Over approximately 120 hours, these hurricane-induced input fields yield changing characteristics of the excitation and the response of a parked turbine. As the storm evolves, the directionality of the wind and waves changes; short-crested waves are simulated and associated wind velocity fields are generated. Aerodynamic loads on the rotor and hydrodynamic loads on the support structure are simulated in coupled response analyses. Because yaw control backup power is not assured during the hurricane, different assumptions on yaw misalignment are assumed in the turbine response simulations. Time series of various turbine response measures are evaluated. Response extremes are of particular interest; we discuss the relative importance of wind and waves on the overall turbine performance during the storm. We also assess the role of yaw control systems and the effect of loss of power to such systems during tropical storms by examining the turbine response for alternative situations of turbine misalignment. Ultimately, this study seeks to provide the framework for assessing turbine designs for tropical cyclone conditions.
Riser Base Jumper Slugging Analysis by CFD Simulations
Authors: Bakkouch Maya , Minguez Matthieu
Published: November 2013

Slugging is one of the operational hazards of subsea pipelines associated with the transportation of multiphase fluids. Such phenomenon can results in cyclic loading in the lines, leading to fatigue damage or high stress (possible strength concern) that need to be considered in the design process. However, there is a real lack in the literature of clear guidance addressing the way of investigation of such possible Flow Induced Vibration (FIV) issue.

One solution is to perform Fluid Structure Interaction (FSI) analysis. However, for this purpose, it appears fundamental to recover at the best the main flow features that develop in characteristic piping systems. Depending on the flow conditions, on the line path configuration, slug can be disturbed, dissociated and consequently results in multi-scale flow that could become an additional source of fatigue. Riser Base Jumper (RBJ) in M-shape configuration, due to its complex geometry can be prone to such multi scale-flow and should be consequently treated with particular attention.

The proposed paper aims to improve the understanding of the main flow features that accompany slug flow in a RBJ. It is proposed to use Computational Multiphase Fluid Dynamic (CMFD) to this end. The main objective of the analysis is to characterise at the best the different expected pressure variations and the related excitation frequencies.
Numerical Tool for Automatic Identification of Free Spans on Submarine Pipelines
Authors: Jacovazzo Bruno M. , Jacob Breno P.
Published: November 2013

It is well known that, after a submarine pipeline is laid over the seabed, free spans may appear due to the unevenness of the seafloor, associated to the relatively high bending stiffness of the pipe, and to the residual tension from the pipe laying process.

The identification of free spans along a given pipeline route is very important due to several factors. One of them is to allow the verification of design criteria related to fatigue induced by vortex induced vibrations (VIV), such as those presented on the DNV-RP-F105 code. Also, the number and length of free spans on a route may require extensive intervention works (e.g. rock dumping, digging, etc) to mitigate the spans and reduce unacceptable span lengths; or, alternatively, may require changes in the predetermined route of the pipeline.

In this context, this work describes the development of a numerical tool for the determination of the final equilibrium configuration of a pipeline after its laying by any given method, providing the automatic identification of free spans on submarine pipelines. The tool is based on global Finite Element models, and simulates the evolution of the pipe laying process along a predetermined route, using the actual seabottom bathymetry data. The objective is to allow an easier implementation of the verification of VIV induced fatigue, and the assessment of a given route in terms of the number and length of its free spans; for this purpose the tool may be associated to a program oriented towards the synthesis and optimization of submarine pipelines. A case study is presented to illustrate the use of the tool.
Impact of Elastic Body on the Deep and Shallow Water
Authors: Korobkin Alexander A. , Khabakhpasheva Tatyana I.
Published: November 2013

Two-dimensional unsteady problem of elastic body impact on liquid free surface is considered. The water is either of infinite depth or shallow. We are concerned with the effect of the water depth on the bending stresses in the structure caused by the fluid-structure interaction. The Wagner model is used for infinite water depth. In the case of shallow water impact, the hydrodynamic problem is one-dimensional but nonlinear. Both problems for deep and shallow waters are solved numerically by the normal mode method. Two shapes of the body, cylindrical shell and elastic wedge, are considered. The impact conditions and the structural characteristic are identical. The bending stresses in the structure are investigated. It is shown that the bending stresses for impact on shallow water are greater than those for the infinite water depth. The developed methods and approaches can be combined with FFM to include complex structures.
A Reduced Modeling Methodology for Efficient Ocean Wave CFD Simulation of Fully Submerged Structures
Authors: Markus D. , Hojjat M. , Wüchner R. , Bletzinger K.-U. , Arnold M.
Published: November 2013

Complex offshore engineering problems are frequently solved using elaborate multiphase CFD models. As part of the procedures, realistic free surface information and wave characteristics are gained at the price of a high computation cost. This is particularly restrictive when multiple CFD simulations are required in the process of analyzing and optimizing a structure. In order to increase the simulation efficiency, a reduced ocean wave model is introduced for the analysis of fully submerged structures. The wave velocities and pressure computed with the model are analyzed and compared to reference solutions. Following, a correction model is introduced that reduces deviations observed in the pressure solution. Finally, the methodology is applied to the computation of wave loads as part of an elaborate design study. The results of the reduced wave modeling methodology match well with the solutions computed using a multiphase Volume of Fluid model, at a significantly lower computation cost.
The Economics of Multi-Axis Point Absorber Wave Energy Converters
Authors: Richardson Daniel S. , Aggidis George A.
Published: November 2013

This paper examines the economic advantages and disadvantages of multi-axis point absorber wave energy converters in comparison to conventional heave-only point absorbers. A multi-axis point absorber wave energy converter (MA-PAWEC) is classified as a point absorber device that has a power take off (PTO) system extracting energy from more than one mode of motion (e.g. heave and surge). The majority of existing point absorber devices operate in heave mode alone. Therefore the forces exerted along other axes must be resisted by the mooring system, any reciprocal component of which constitutes a wasted opportunity to extract energy. The economics of PAWECs are governed by the available resource, energy generated by the device, capital cost and operational cost. These factors are examined for MA-PAWECs and compared to a generic heave-PAWEC. For a performance comparison, a simple generic body PAWEC is examined under heave mode operation and multi-axis operation in a representative spectrum. The modelling is based on linear potential theory. The potential advantages of MA-PAWECS are identified as greater energy absorption, fewer installed devices for a given capacity, and greater array control. Disadvantages include higher capex, higher maintenance costs and sensitivity to PTO costs. The performance and costs are assigned an estimated economic scaling factor and are applied to a generic heave-PAWEC for an economic comparison of the two devices. This indicates that a multi-axis approach to point absorbers could offer a 21% lower cost of electricity than the incumbent heave-response devices.
Efficient Dynamic Analysis of Floating Bodies Nonlinear Behavior in Wave Energy Conversion
Authors: Spanos P. D. , Richichi A. , Arena F.
Published: November 2013

Floating oscillating-bodies are a kind of wave energy converter developed for harvesting the great amount of energy related to water waves; see Falcão [1] for a review.

In this paper a particular energy converter model is considered. A nonlinear analysis of its dynamic behavior is conducted both in the time and the frequency domains.

The model involves a tightly moored single-body floating wave energy converter. It captures motion in the horizontal and vertical directions. The nonlinear stiffness and damping forces are functions of the horizontal and vertical displacements and velocities and make the system a nonlinear one. In addition to the time-domain analysis of the nonlinear behavior of the system, the method of equivalent linearization is used to determine iteratively the effective linear stiffness and damping matrices and the response of the buoy in the frequency domain. The analysis pertains to the surge and the heave directions response of the wave energy converter under harmonic mono-frequency excitation (regular waves). The reliability of the linearization based approach is demonstrated by comparison with time domain integration data.

This approach offers the appealing feature of conducting efficiently a variety of parameter studies which can expedite preliminary evaluations, inter alia, of competing design scenarios for the energy converter. Suggestions for extending this approach to the case of fully nonlinear and random irregular waves are also included.
Large Diameter Pipeline PLEM Design for Remote, Arctic Application
Authors: Timmermans Jeroen , Luff Ian , Long Nicholas
Published: November 2013

While subsea production template and manifold designs have come to be dominated by standardized solutions tailored for specific hardware, the design of Pipeline End Manifolds (PLEM) remains largely project-specific. Nevertheless, some trends in PLEM design for large-diameter pipelines in moderate water depths have emerged in the past years in the North Sea and elsewhere; namely, large stand-alone structures on suction pile foundations with diverless spoolpiece tie-ins. This arrangement has proven successful on numerous projects; however, the move to remote arctic fields of significant production capacity and long design life introduces new design drivers that warrant a “fresh approach” to PLEM design.

The developments currently being considered for the arctic will have to deal with:

- Remote location making mobilization of installation assets a significant cost driver such that separate installation of pipeline and PLEM is relatively unattractive

- Harsh conditions and short weather windows for installation favoring designs that reduce the number of separate installation steps and vessels

- Poorer access for maintenance and repair during the operating life favoring designs that are modular and that allow recovery of critical components using the smallest possible intervention vessels.

When combined with envisioned field production lives of 40 to 50 years, this means a very different set of design drivers will apply to the PLEM design. This paper presents an alternative PLEM design developed to overcome these challenges by:

- Integrating of the PLEM with the pipeline to work around current industry limitations for large diameter diverless tie-in connector systems and to minimize ROV rotated sealing surfaces subsea in normal operation,

- Introducing plug technology to remove the critical dependence on long-term trouble-free performance of large bore valves,

- Introducing driven pile foundations to reduce structure size, prevent long-term settlements and eliminate the need for separate pipeline support frames by maintaining the pipe centerline close to the mudline,

- Modularizing the system such that key components (all remaining valves) can be retrieved without complete shutdown of flow and such that installation / intervention can be performed using a wide range of vessels, and

- Incorporating lessons learned from the successful design of a North Sea vertical diverless pig launcher unit.

This paper presents an overview of the alternative PLEM design and discusses the status of the technologies required.
Auxiliary Kite Propulsion Contribution to Ship Thrust
Authors: Ran Heng , Janson Carl-Erik , Allenström Björn
Published: November 2013

Low speed transportation is more energy efficient than high speed transportation in general. At the same time of maintain speed, ships with lower design speeds provide possibilities for further reducing fuel consumption by using auxiliary wind propulsion devices. A kite is one type of auxiliary wind propulsion device that can be used for this purpose. The aim of this study is to investigate the influence of auxiliary kite propulsion on the performance of a Panamax tanker, specifically on engine power reduction, maneuverability in different wind/wave directions and on course-keeping ability of the ship. The study was carried out by means of computer-based simulations. Scenario combinations are established for various ship speeds, headings and weather conditions. For the purpose of simulation, a simplified auxiliary kite propulsion model was built. Throughout the simulations, forces, moments and motions of the tanker were recorded, and so were rudder angle, ship thrust and engine power. The result shows that auxiliary kite propulsion can play a significant role in reducing engine power in following up to beam sea conditions. The present study is a first step towards a fully dynamic kite model where a control mechanism will be introduced to find the most favorable flying trajectory.
TLP Survivability Against Progressive Failure of Tendon and Foundation Systems in Offshore Western Australian Harsh Environment
Authors: Mansour Alaa M. , Gordon Brian J. , Ling Qi , Shen Qiang
Published: November 2013

In this paper the design robustness of Tension Leg Platform (TLP) tendon and tendon foundation systems of a TLP that is located in offshore Western Australia is investigated.

A case study of a TLP that is self-stable (without tendons) has been considered. The study involves the numerical simulation of progressive failure of tendons in cyclonic events. The TLP response during the transition from a restrained TLP with all tendons to the free-floating condition has been numerically simulated. The numerical results from this simulation have been verified against physical model test measurements. The numerical simulation is repeated for a TLP with an optimized hull design that does not maintain stability when all tendons fail. Cost versus benefit in these two cases is quantified and compared.

The progressive failure of the TLP Gravity Base Foundation (GBF) system has also been investigated in this paper. One of the potential failure modes for this type of foundation is the loss of suction underneath the foundation. Increasing the amount of solid ballast in the GBF increases the net downward load on the soil and reduces the reliance on the soil suction. Numerical simulations of the progressive loss of suction are performed for two cases; 1) slightly over designed foundation to include extra ballast and 2) optimized foundation design that is highly rely on the soil suction. Again, cost versus benefit in these two cases is presented.

The paper provides clear insights supported by calculations and model tests for proposed design robustness that could be built in a TLP design at a relatively small additional cost to address uncertainties associated with designing TLP in offshore Western Australian harsh environment region.
A Study on an Active Hybrid Decomposed Mooring System for Model Testing in Ocean Basin for Offshore Platforms
Authors: Cao Yusong , Tahchiev Galin
Published: November 2013

The paper presents a theoretical study on an active hybrid decomposed mooring system for model testing of offshore platform in wave basin. The basic concept and the working principles are described. Important issues for achieving a correct simulation will be discussed. The feasibility of the approach is demonstrated based on numerical investigations. Plans for potential implementation in an ocean basin are also discussed.
Severe Slugging Control Methods Used in Offshore Multiphase Riser
Authors: Cheng Bing , Li Qingping , Yao Haiyuan
Published: November 2013

Severe slugging control in offshore riser is an important aspect of flow assurance, if not well controlled, normal production could be interrupted and jeopardized. In this paper, firstly mitigation methods for severe slugging used in different oilfields are investigated, and their pros&cons, on-site applications and application scope are summarized. Then three severe slugging control methods adopted by CNOOC are introduced, respectively GLCC separation, auto choking, as well as gas lift. GLCC combined with the original slug catcher has solved the slug problem of the QK17-2 Oilfield, saving a lot of space and money. A set of online monitoring and auto-choking system was successfully installed and applied in WC Oilfield, contributing a lot to the production stability and production rate. The delicately designed gas lift annulus and gas injection system are expected to mitigate severe slugging and boost production of a west Africa deepwater oilfield co-explored by CNOOC. The introduction of these on-site cases will be of some value to for future design and analysis of severe slugging control for oil and gas fields.
Simplified Approach for Fracture Integrity Assessment of Bimetallic Girth Weld Joint
Authors: Bonora N. , Carlucci A. , Ruggiero A. , Iannitti G.
Published: November 2013

Recent extensive use of Corrosion Resistance Alloy (CRA) as internal protection layer of standard carbon-steel pipes (clad and lined pipe) in the oil and gas industry requires an intensive use of bimetallic welds.

Since some degree of defects in welds is inevitable, and in codes and standards (such as BS7910) the case of bi-metallic joint is usually not considered, some R&D’s activities are ongoing to define specific design guidance for an Engineering Critical Assessment (ECA) aimed at determining flaw acceptance criteria for fabrication of bimetallic joints.

Based on the limited guidance in the literature, proposed procedures for ECA on CRA welds seem not cover the root/hot pass weld region, for which the requirement of “zero defect” became mandatory. As direct consequence, it penalizes the weld fabrication rate, particularly if “J-lay” or “S-Lay” methods are adopted. Furthermore, they are investigating on cases where weld material is overmatching the base metal or for a limited partial overmatching, despite for CRA welds, such conditions, seem quite difficult to be fully met, if current consumable materials present in the marked are selected.

Aim of present paper is to describe how any standard ECA procedure (ordinarily used to assess carbon-steel welds) may be alternatively adopted to assess CRA welds for clad & lined pipe material, if specific conditions are respected. For this purpose a few number of elastic-plastic Finite Element Analysis (FEA) is required to identify and/or extends the validity limits which have to be met in order to be conservative in the use of selected standard procedure. Outer, inner and under clad flaws, located along the weld fusion line, were investigated. Such approach, certainly leads to a quite conservatism, but gives the advantage to provide a safe flaws acceptance criterion in root/hot pass weld, and it may be also applied for any level of weld partial overmatching condition.

Despite proposed simplified approach is suitable until moderate plastic straining, it may be appropriated for any ECA on CRA pipe when “J-lay” or “S-lay” installation method is adopted, and/or for many riser’s configuration, and/or for several flowline routing also if exposed to post-buckling condition. It is demonstrated that the proposed simplified approach, when applied under moderate plastic strain conditions, provides accurate J-integral solutions compared to the complex method as proposed by current R&D.
Newer Frontiers in the Design of Steel Catenary Risers for Floating Production Systems
Authors: Mekha Basim , Bhat Shankar
Published: November 2013

It is not uncommon nowadays to have a new floating production facility installed with steel catenary risers (SCRs) as the main method for receiving and exporting fluids. The use of steel catenary in deeper and shallower waters alike where it was challenging and even unthinkable some years back is now feasible. Advancements in the SCR technology cover not only design and software, but also manufacturing, installation methods and capabilities.

Since the first author’s OMAE 2001 paper “New Frontiers in the Design of Steel Catenary Risers for Floating Production Systems” [1] was published, a number of significant advances have been made in the design, manufacture and installation of steel catenary risers. In design aspects for example, the soil structure interaction and modeling of soil stiffness and trench formation has been the topic of many publications and research. The manufacturing capabilities of the pipe mills to produce and machine SCR pipe joints with upset ends has been advanced and implemented in recent projects. Advancement in the capability of Automated Ultrasonic Testing (AUT) systems to detect very small flaws in thick carbon steel and clad pipe welds is expanding the manufacturing envelop of SCRs while meeting design requirements. In addition, there is improvement in the capabilities of installation vessels; and more comprehensive material and fatigue test data have been accumulated providing data better basis to design and perform fracture mechanics analysis of SCRs. Lazy wave SCR configurations are being used to significantly expand the application of SCR technology to high motion vessels and more severe environments.

This paper contains a review of the current state of the art with a description of some of the important advancements that have extended the range of applicability of SCR technology. The SCR technology advancements presented and discussed in this paper include a better understanding of the soil behavior and trench formation with some analytical results, the use of upset ends and their manufacturing options, improvement in the AUT systems and flaw detection capabilities, CRA clad SCRs and Lazy Wave SCRs.
Coupled Transient CFD and Diffraction Modeling for Installation of Subsea Equipment/Structures in Splash Zone
Authors: Jia David , Agrawal Madhusuden
Published: November 2013

In development of deep water oil and gas fields, successfully and economically installing subsea equipment and structure is critically important. This paper presents a state-of-the-art methodology for predicting the motions and loads of subsea equipment/structure during such operations basing on time domain simulations of the combined installation vessel and subsea equipment/structure. The time domain diffraction simulation of the moving lifting vessel is coupled with multiphase CFD simulation of subsea equipment/structure in splash zone. Transient CFD model with rigid body motion for the equipment/structure calculates added masses, forces and moments on the equipment/structure for diffraction analysis, while diffraction analysis calculates linear and angular velocities for CFD simulation. This paper has many potential applications, such as, installation of pile, manifold, subsea tree, PLET/PLEM, or other subsea equipment/structure. This coupled approach has been successfully implemented on a cylindrical structure. The results show that total load level, and dynamics of the subsea equipment/structure due to waves in splash zone are predicted. Current practice of installation analysis in accordance with the recommendations from DNV-RP-H103 [1] cannot determine in detail the wave loads either during the passage through splash zone, or added mass and damping when the equipment/structure is submerged. In order to determine wave loads in detail, model tests are needed. In the absence of tests, simplified equations or empirical formulations have to be used to calculate/estimate these hydrodynamics coefficients as recommended in DNV-RP-H103. Steady-state CFD simulations on a stationary equipment/structure are usually used to predict drag and added masses on submerged structures. However the steady-state assumption in CFD ignores the resonating motion of equipment/structure in calculating hydrodynamics coefficients, which can severely affect the accuracy of these predictions. The above methods often give overly conservative results for allowable sea state which results in uneconomical vessel time or inaccurate results for installation. The methodology of this paper gives more accurate results, and provides potentially economical vessel time during installation. The intent of this paper is to demonstrate the solution and methodology.
On Design and Building of a U-OWC Wave Energy Converter in the Mediterranean Sea: A Case Study
Authors: Arena Felice , Romolo Alessandra , Malara Giovanni , Ascanelli Alfredo
Published: November 2013

Since the nineties, the OWC (Oscillating Water Column) plants were developed at full scale to produce electrical power from ocean waves [1]. A prototype was built into a caisson breakwater of the Sakata Port, in Japan; other plants were built in India, in Scotland at Islay, in Portugal at the Azores. A new plant was built in Mutriku (Spain) recently. A new kind of OWC caisson, named U-OWC or REWEC3, was proposed by Boccotti [2]. With respect to a traditional OWC, a U-OWC plant includes an additional vertical duct, which enables to tune the eigenperiod of the plant to the peak period of the wave pressures acting on the converter-breakwater. In this way, resonance conditions can be reached without phase control devices and the wave pressures into the air pocket are increased in amplitude, amplifying the performance of the plant. In 2012, a full scale U-OWC (REWEC3) breakwater has been designed in Italy, for the harbour of Civitavecchia (the port of Rome – Port Authority of Civitavecchia). Such a breakwater embodies 19 caissons, each including 8 cells, 34m long. The paper disseminates the key issues pertaining the design stage. Further, it describes the main phases of the construction stage. The building of the caisson started in October 2012. The first caisson has been completed at the end of 2012. It is the first device for wave energy in the Mediterranean Sea and one of the biggest in the world.
Global-Local Analysis of a Full-Scale Composite Riser During Vortex-Induced Vibration
Authors: Chen Yu , Tan Long Bin , Jaiman Rajeev K. , Sun Xiushan , Tay Tong Earn , Tan Vincent Beng Chye
Published: November 2013

This paper presents a global-local analysis procedure to demonstrate the feasibility of a composite riser and its advantages over the traditional steel counterpart. This procedure starts from the local design of the sandwich tubular structure of riser section. The equivalent material properties of the sandwich tube are obtained using classic composite theory and they are used to parameterize the full-scale riser model in global analysis. The global analysis mainly focuses on the vortex-induced vibration (VIV). The methodology is first verified by comparison with experimental data and results produced by SHEAR 7. Four representative cases are then studied and the results show that the critical loads experienced by the composite riser are much lower than that of the steel one due to its lightweight. The lightweight composite riser requires lower top tension and fewer buoyancy cans, which is economically beneficial. The failure envelopes of both composite and steel riser sections are obtained by performing damage modelling techniques. The results show that composite riser yields larger safety margin. Overall, this paper demonstrates that composite riser is technically feasible and its high performance/weight ratio would make it a promising design for deepwater environment, where self-weight is a big challenge that is hindering the development of traditional steel riser.
Numerical modeling of carrier gas flow in atomic layer deposition vacuum reactor: A comparative study of lattice Boltzmann models
Authors: Pan Dongqing , Li Tao , Chien Jen Tien , Yuan Chris
Published: November 2013

This paper characterizes the carrier gas flow in the atomic layer deposition (ALD) vacuum reactor by introducing Lattice Boltzmann Method (LBM) to the ALD simulation through a comparative study of two LBM models. Numerical models of gas flow are constructed and implemented in two-dimensional geometry based on lattice Bhatnagar–Gross–Krook (LBGK)-D2Q9 model and two-relaxation-time (TRT) model. Both incompressible and compressible scenarios are simulated and the two models are compared in the aspects of flow features, stability, and efficiency. Our simulation outcome reveals that, for our specific ALD vacuum reactor, TRT model generates better steady laminar flow features all over the domain with better stability and reliability than LBGK-D2Q9 model especially when considering the compressible effects of the gas flow. The LBM-TRT is verified indirectly by comparing the numerical result with conventional continuum-based computational fluid dynamics solvers, and it shows very good agreement with these conventional methods. The velocity field of carrier gas flow through ALD vacuum reactor was characterized by LBM-TRT model finally. The flow in ALD is in a laminar steady state with velocity concentrated at the corners and around the wafer. The effects of flow fields on precursor distributions, surface absorptions, and surface reactions are discussed in detail. Steady and evenly distributed velocity field contribute to higher precursor concentration near the wafer and relatively lower particle velocities help to achieve better surface adsorption and deposition. The ALD reactor geometry needs to be considered carefully if a steady and laminar flow field around the wafer and better surface deposition are desired.
Diacylglycerol Kinase ζ Limits the Generation of Natural Regulatory T Cells
Authors: Schmidt Amanda M. , Zou Tao , Joshi Rohan P. , Leichner Theresa M. , Pimentel Matthew A. , Sommers Connie L. , Kambayashi Taku
Published: November 2013

Increasing the activation of extracellular signal–regulated kinase promotes the generation of natural regulatory T cells.
Science Signaling
Podcast: 26 November 2013
Authors: Koretzky Gary , Kambayashi Taku , VanHook Annalisa M.
Published: November 2013

Differential catalytic activities of the α and ζ isoforms of diacylglycerol kinase contribute to differences in the effects of these enzymes on natural regulatory T cell development.
Shocking Response
Authors: Foley John F.
Published: November 2013

Macrophages responding to an RNA-binding protein released in response to shock trigger systemic inflammation.
Restricting Bone Metastasis
Authors: Ferrarelli Leslie K.
Published: November 2013

Signaling by the growth factor TGF-β2 prevents the growth of squamous carcinoma that metastasizes to the bone.
The Burkholderia pseudomallei Enoyl-Acyl Carrier Protein Reductase FabI1 Is Essential for
In Vivo
Growth and Is the Target of a Novel Chemotherapeutic with Efficacy
Authors: Cummings Jason E. , Kingry Luke C. , Rholl Drew A. , Schweizer Herbert P. , Tonge Peter J. , Slayden Richard A.
Published: November 2013

The bacterial fatty acid biosynthesis pathway is a validated target for the development of novel chemotherapeutics. However, since
Burkholderia pseudomallei
carries genes that encode both FabI and FabV enoyl-acyl carrier protein (ACP) reductase homologues, the enoyl-ACP reductase that is essential for
in vivo
growth needs to be defined so that the correct drug target can be chosen for development. Accordingly, Δ
fabI1
, Δ
fabI2
, and Δ
fabV
knockout strains were constructed and tested in a mouse model of infection. Mice infected with a Δ
fabI1
strain did not show signs of morbidity, mortality, or dissemination after 30 days of infection compared to the wild-type and Δ
fabI2
and Δ
fabV
mutant strains that had times to mortality of 60 to 84 h. Although signs of morbidity and mortality of Δ
fabI2
and Δ
fabV
strains were not significantly different from those of the wild-type strain, a slight delay was observed. A FabI1-specific inhibitor was used to confirm that inhibition of FabI1 results in reduced bacterial burden and efficacy in an acute
B. pseudomallei
murine model of infection. This work establishes that FabI1 is required for growth of
Burkholderia pseudomallei
in vivo
and is a potential molecular target for drug development.
Antifungal Application of Nonantifungal Drugs
Authors: Stylianou Marios , Kulesskiy Evgeny , Lopes José Pedro , Granlund Margareta , Wennerberg Krister , Urban Constantin F.
Published: November 2013

Candida
species are the cause of 60% of all mycoses in immunosuppressed individuals, leading to ∼150,000 deaths annually due to systemic infections, whereas the current antifungal therapies either have toxic side effects or are insufficiently efficient. We performed a screening of two compound libraries, the Enzo and the Institute for Molecular Medicine Finland (FIMM) oncology collection library, for anti-
Candida
activity based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. From a total of 844 drugs, 26 agents showed activity against
Candida albicans
. Of those, 12 were standard antifungal drugs (SADs) and 7 were off-target drugs previously reported to be active against
Candida
spp. The remaining 7 off-target drugs, amonafide, tosedostat, megestrol acetate, melengestrol acetate, stanozolol, trifluperidol, and haloperidol, were identified with this screen. The anti-
Candida
activities of the new agents were investigated by three individual assays using optical density, ATP levels, and microscopy. The antifungal activities of these drugs were comparable to those of the SADs found in the screen. The aminopeptidase inhibitor tosedostat, which is currently in a clinical trial phase for anticancer therapy, displayed a broad antifungal activity against different
Candida
spp., including
Candida glabrata
. Thus, this screen reveals agents that were previously unknown to be anti-
Candida
agents, which allows for the design of novel therapies against invasive candidiasis.
Identification of 50 Class D β-Lactamases and 65 Acinetobacter-Derived Cephalosporinases in Acinetobacter spp
Authors: Périchon Bruno , Goussard Sylvie , Walewski Violaine , Krizova Lenka , Cerqueira Gustavo , Murphy Cheryl , Feldgarden Michael , Wortman Jennifer , Clermont Dominique , Nemec Alexandr , Courvalin Patrice
Published: November 2013

Whole-genome sequencing of a collection of 103
Acinetobacter
strains belonging to 22 validly named species and another 16 putative species allowed detection of genes for 50 new class D β-lactamases and 65 new
Acinetobacter
-derived cephalosporinases (ADC). All oxacillinases (OXA) contained the three typical motifs of class D β-lactamases, STFK, (F/Y)GN, and K(S/T)G. The phylogenetic tree drawn from the OXA sequences led to an increase in the number of OXA groups from 7 to 18. The topologies of the OXA and RpoB phylogenetic trees were similar, supporting the ancient acquisition of
bla
OXA
genes by
Acinetobacter
species. The class D β-lactamase genes appeared to be intrinsic to several species, such as
Acinetobacter baumannii
,
Acinetobacter pittii
,
Acinetobacter calcoaceticus
, and
Acinetobacter lwoffii
. Neither
bla
OXA-40/143
- nor
bla
OXA-58
-like genes were detected, and their origin remains therefore unknown. The phylogenetic tree analysis based on the alignment of the sequences deduced from
bla
ADC
revealed five main clusters, one containing ADC belonging to species closely related to
A. baumannii
and the others composed of cephalosporinases from the remaining species. No indication of
bla
OXA
or
bla
ADC
transfer was observed between distantly related species, except for
bla
OXA-279
, possibly transferred from
Acinetobacter
genomic species 6 to
Acinetobacter parvus
. Analysis of β-lactam susceptibility of seven strains harboring new oxacillinases and cloning of the corresponding genes in
Escherichia coli
and in a susceptible
A. baumannii
strain indicated very weak hydrolysis of carbapenems. Overall, this study reveals a large pool of β-lactamases in different
Acinetobacter
spp., potentially transferable to pathogenic strains of the genus.
Factors Associated with Treatment Failure in Vertebral Osteomyelitis Requiring Spinal Instrumentation
Authors: Arnold Ryan , Rock Clare , Croft Lindsay , Gilliam Bruce L. , Morgan Daniel J.
Published: November 2013

Patients with vertebral osteomyelitis may require instrumentation for spinal stabilization. Determining the optimal duration and type of antimicrobial therapy for these patients is challenging. The aim of this study was to examine risk factors for treatment failure, in particular antimicrobial duration, in a cohort of patients requiring spinal instrumentation for vertebral osteomyelitis. We conducted a retrospective cohort study of all patients with vertebral osteomyelitis who had spinal instrumentation between January 2002 and January 2012 at the University of Maryland Medical Center. The primary outcome measure was treatment failure >4 weeks postoperatively. We identified 131 patients with vertebral osteomyelitis requiring spinal instrumentation, 94 of whom had >4 weeks of follow-up and were included in the primary analysis. Treatment failure occurred in 22 of the 94 patients (23%) at a median of 4 months after surgery. Among patients who failed therapy, 20 of 22 failed within 1 year of surgery. Cervical and thoracic infection sites and the presence of negative cultures were associated with fewer treatment failures. Addition of rifampin and the use of chronic suppressive antimicrobials did not affect treatment failure rate. Twenty-three percent of patients with spinal instrumentation for vertebral osteomyelitis experienced treatment failure. Treatment failure almost always occurred within the first year of spinal instrumentation.
Predictive Value of Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Swab PCR Assay for MRSA Pneumonia
Authors: Dangerfield Benjamin , Chung Andrew , Webb Brandon , Seville Maria Teresa
Published: November 2013

Pneumonia due to methicillin-resistant
Staphylococcus aureus
(MRSA) is associated with poor outcomes and frequently merits empirical antibiotic consideration despite its relatively low incidence. Nasal colonization with MRSA is associated with clinical MRSA infection and can be reliably detected using the nasal swab PCR assay. In this study, we evaluated the performance of the nasal swab MRSA PCR in predicting MRSA pneumonia. A retrospective cohort study was performed in a tertiary care center from January 2009 to July 2011. All patients with confirmed pneumonia who had both a nasal swab MRSA PCR test and a bacterial culture within predefined time intervals were included in the study. These data were used to calculate sensitivity, specificity, positive predictive value, and negative predictive value for clinically confirmed MRSA pneumonia. Four hundred thirty-five patients met inclusion criteria. The majority of cases were classified as either health care-associated (HCAP) (54.7%) or community-acquired (CAP) (34%) pneumonia. MRSA nasal PCR was positive in 62 (14.3%) cases. MRSA pneumonia was confirmed by culture in 25 (5.7%) cases. The MRSA PCR assay demonstrated 88.0% sensitivity and 90.1% specificity, with a positive predictive value of 35.4% and a negative predictive value of 99.2%. In patients with pneumonia, the MRSA PCR nasal swab has a poor positive predictive value but an excellent negative predictive value for MRSA pneumonia in populations with low MRSA pneumonia incidence. In cases of culture-negative pneumonia where initial empirical antibiotics include an MRSA-active agent, a negative MRSA PCR swab can be reasonably used to guide antibiotic de-escalation.
In VitroandIn VivoAntibacterial Evaluation of Cadazolid, a New Antibiotic for Treatment of Clostridium difficile Infections
Authors: Locher Hans H. , Seiler Peter , Chen Xinhua , Schroeder Susanne , Pfaff Philippe , Enderlin Michel , Klenk Axel , Fournier Elvire , Hubschwerlen Christian , Ritz Daniel , Kelly Ciaran P. , Keck Wolfgang
Published: November 2013

Clostridium difficileis a leading cause of health care-associated diarrhea with significant morbidity and mortality, and new options for the treatment ofC. difficile-associated diarrhea (CDAD) are needed. Cadazolid is a new oxazolidinone-type antibiotic that is currently in clinical development for treatment of CDAD. Here, we report thein vitroandin vivoantibacterial evaluation of cadazolid againstC. difficile. Cadazolid showed potentin vitroactivity againstC. difficilewith a MIC range of 0.125 to 0.5 μg/ml, including strains resistant to linezolid and fluoroquinolones. In time-kill kinetics experiments, cadazolid showed a bactericidal effect againstC. difficileisolates, with >99.9% killing in 24 h, and was more bactericidal than vancomycin. In contrast to metronidazole and vancomycin, cadazolid strongly inhibitedde novotoxin A and B formation in stationary-phase cultures of toxigenicC. difficile. Cadazolid also inhibitedC. difficilespore formation substantially at growth-inhibitory concentrations. In the hamster and mouse models for CDAD, cadazolid was active, conferring full protection from diarrhea and death with a potency similar to that of vancomycin. These findings support further investigations of cadazolid for the treatment of CDAD.
Evaluation of Vancomycin in Combination with Piperacillin-Tazobactam or Oxacillin against Clinical Methicillin-Resistant Staphylococcus aureus Isolates and Vancomycin-Intermediate S. aureus Isolates
In Vitro
Authors: Dilworth Thomas J. , Sliwinski Jora , Ryan Keenan , Dodd Monique , Mercier Renée-Claude
Published: November 2013

Vancomycin with piperacillin-tazobactam is used as empirical therapy for critically ill patients. Studies of this combination against methicillin-resistant
Staphylococcus aureus
(MRSA) and vancomycin-intermediate
S. aureus
(VISA) are limited, but β-lactams in combination with vancomycin have shown synergistic activity against MRSA and VISA. The goal of this study was to evaluate whether piperacillin-tazobactam and vancomycin were synergistic against MRSA and VISA
in vitro
. Bloodstream MRSA (
n
= 20) and VISA (
n
= 4) strains were selected.
In vitro
antimicrobial activities of piperacillin-tazobactam and oxacillin were evaluated by disk diffusion, and MICs were determined by Etest using Muller-Hinton agar with and without vancomycin at one-half the MIC. Time-kill studies evaluated 14 MRSA and all 4 VISA isolates using piperacillin-tazobactam at 300/35 mg/liter or oxacillin at 40 mg/liter alone and with vancomycin at one-half the MIC. Mean zones of inhibition for piperacillin-tazobactam and oxacillin increased with vancomycin against MRSA and VISA (
P
< 0.001 for all), and the MIC
90
decreased with vancomycin against MRSA and VISA to values meeting susceptibility criteria for
S. aureus
(
P
< 0.001 for both antibiotics against MRSA). In MRSA time-kill studies, the mean 24-h reductions in inoculum for piperacillin-tazobactam, piperacillin-tazobactam with vancomycin, and oxacillin with vancomycin were 3.53, 3.69, and 2.62 log
10
CFU/ml, respectively. The mean 24-h reductions in VISA inoculum for piperacillin-tazobactam, piperacillin-tazobactam with vancomycin, and oxacillin with vancomycin were 2.85, 2.93, and 3.45 log
10
CFU/ml, respectively. Vancomycin with piperacillin-tazobactam or oxacillin demonstrated synergistic activity against MRSA and VISA. The clinical implications of these combinations against MRSA and VISA should be investigated.
Multicenter Study of Anidulafungin and Micafungin MIC Distributions and Epidemiological Cutoff Values for Eight Candida Species and the CLSI M27-A3 Broth Microdilution Method
Authors: Pfaller M. A. , Espinel-Ingroff A. , Bustamante B. , Canton E. , Diekema D. J. , Fothergill A. , Fuller J. , Gonzalez G. M. , Guarro J. , Lass-Flörl C. , Lockhart S. R. , Martin-Mazuelos E. , Meis J. F. , Ostrosky-Zeichner L. , Pelaez T. , St-Germain G. , Turnidge J.
Published: November 2013

Since epidemiological cutoff values (ECVs) using CLSI MICs from multiple laboratories are not available for
Candida
spp. and the echinocandins, we established ECVs for anidulafungin and micafungin on the basis of wild-type (WT) MIC distributions (for organisms in a species-drug combination with no detectable acquired resistance mechanisms) for 8,210
Candida albicans
, 3,102
C. glabrata
, 3,976
C. parapsilosis
, 2,042
C. tropicalis
, 617
C. krusei
, 258
C. lusitaniae
, 234
C. guilliermondii
, and 131
C. dubliniensis
isolates. CLSI broth microdilution MIC data gathered from 15 different laboratories in Canada, Europe, Mexico, Peru, and the United States were aggregated to statistically define ECVs. ECVs encompassing 97.5% of the statistically modeled population for anidulafungin and micafungin were, respectively, 0.12 and 0.03 μg/ml for
C. albicans
, 0.12 and 0.03 μg/ml for
C. glabrata
, 8 and 4 μg/ml for
C. parapsilosis
, 0.12 and 0.06 μg/ml for
C. tropicalis
, 0.25 and 0.25 μg/ml for
C. krusei
, 1 and 0.5 μg/ml for
C. lusitaniae
, 8 and 2 μg/ml for
C. guilliermondii
, and 0.12 and 0.12 μg/ml for
C. dubliniensis
. Previously reported single and multicenter ECVs defined in the present study were quite similar or within 1 2-fold dilution of each other. For a collection of 230 WT isolates (no
fks
mutations) and 51 isolates with
fks
mutations, the species-specific ECVs for anidulafungin and micafungin correctly classified 47 (92.2%) and 51 (100%) of the
fks
mutants, respectively, as non-WT strains. These ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin and micafungin due to
fks
mutations.