bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient Drilling of Ultra-HPHT Wells in the Gulf of Thailand
Authors: Araujo Joy , Kaotun Keittipong , Dumrongthai Panupun , Adrian A
Published: June 2014

Development of gas fields in the Gulf of Thailand requires drilling and production from reservoirs that are at static temperatures above 200 °C. Safe and economic production from these ultra-high-pressure/high-temperature (HP/HT)fields is crucial to deliver on gas contracts that support the region's economic activity. The operational limit of equipment used to drill these wells, such as measurement-while-drilling (MWD) and logging-while-drilling (LWD) tools, is 175 °C. If the electronic components, elastomers, and sensors in these tools are exposed to high temperatures, the reliability of the tool is significantly decreased, and therefore it requires extensive time-consuming maintenance.

The lack of technology enabling MWD/LWD tools to operate reliably in a high-temperature environment increases well construction risks. Important questions such as " can we reach the target successfully" or " are the anti-collision requirements fulfilled" cannot be answered reliably. High-temperature equipment is therefore key: it allows maintaining the directional trajectory as well as obtaining real-time downhole measurements to confirm successful well placement.

New technologies have been developed and qualified during the last decade that enable electronics, sensors, and elastomers to operate in these HP/HT environments with the same level of reliability as that in what is nowadays considered " normal environmental conditions." Anew MWD tool has been designed utilizing these novel technologies. The tool can operate reliably at 200 °C and 207 MPa, providing real-time direction and inclination surveys, azimuthal gamma ray, annular and internal pressure while drilling, and shock and vibration measurements.

An operator in the Gulf of Thailand used this new MWD technology to drill wells in these ultra-HP/HT reservoirs without the need to stop operation due to temperature limitations. Savings of one-half day per well have been achieved. Reliability and maintainability were proven by executing four runs above 180 °C, where the maximum operating temperature recorded by the tool was 193 °C and total operating hours without the need for maintenance between runs was more than 250 hours. With 50 to 75 wells per year to be drilled above 175 °C, this operator now has access to a new workflow that can save 25 to 37 days of drilling per year. These time savings translate into considerable savings in rig spread rate and the ability to bring production online earlier.
Flexible Fiber-reinforced Pipe for 10,000-foot Water Depths: Performance Assessments and Future Challenges
Authors: Jha V. , Dodds N. , Finch D. , Latto J. , Karabelas G. , Anderson T.A. , Baehmann P. , Vermilyea M.E.
Published: June 2014

The primary aim of the present composite development program is to enhance access to deepwater fields in the Gulf of Mexico, Brazil, and West Africa. To accomplish that goal, composite materials are being incorporated in unbonded flexible pipelines to lower mass and enhance the overall system performance to expand the operational design envelope. In addition, the use of composite materials will allow a significant improvement in pipe operating pressure (>70 MPa), pipe operating temperature (>125C) and due to increased CO2 and H2S resistance, will improve sour service performance and lifespan.

Composite materials are well known for their low density and high specific strength, stiffness and fatigue performance. These properties are desirable and will certainly enhance pipe performance, but the overall performance of the pipe during all stages of manufacture and deployment must be considered, as well as a conservative approach to introducing these new materials. Some of the key factors that need to be assessed are material failure modes under varied pipe loadings, dynamic interactions and exposure to severe oil field environments. There are several individual standards, specifications and joint industry projects (JIPs) focused on composite pipes that address some of these issues, but there is also a general lack of consensus with regard to testing standards and understanding of the long-term performance. As flexible pipe suppliers, the industry must aim to provide performance assessments and address all key challenges to allow the flexible pipe industry to build confidence in the new and enabling composite pipe technologies.

In a previous paper, we presented design concepts and a toolbox approach to construct different composite pipe solutions to meet all the aforementioned performance parameters. The present paper selectively highlights important failure modes and design considerations, demonstrates an understanding of behavior in the matrix and fiber phases, and addresses concerns related to the chemical performance of composite materials. The present paper also highlights and addresses some of the concerns of composite pipes and focuses on areas for future development and testing. These results will help support the selection and standardization of analysis tools and testing methods across the industry. Bespoke testing capabilities to address the relevant failure mechanisms and installation strategies for composite pipes will also be discussed.
Steel Catenary Riser Design for Cylindrical FPSO Application in Ultra-Deep GoM
Authors: Vidic-Perunovic J. , Guo X. S. , Wang L. , Hopen F. , Head W. J.
Published: June 2014

The exploitation of Gulf of Mexico (GoM) Lower Tertiary reservoirs is confronted with many physical, technical and economic challenges, including ultra-deep water depth, remote locations, complex fluids and high reservoir pressure, harsh met-ocean conditions, and increased capital expenditure, etc. To address these challenges different floater and riser concepts have been studied by the industry. This paper documents a study on an FPSO concept with the Sevan-type cylindrical hull (CFPSO) in combination with Steel Catenary Risers (SCRs). In comparison to the ship-shaped FPSO combined with Free Standing Hybrid Riser (FSHR) solution, the CFPSO has inherently more favorable motion characteristics and is therefore more SCR friendly. In addition, the hull was designed with a central moonpool for hanging off SCRs and therefore coupling from roll/pitch motions was minimized. The CFPSO and SCR design is based on a hypothetical field in ultra-deepwater GoM Lower Tertiary play with HPHT reservoirs and central GoM met-ocean conditions. Based on preliminary motion data of the CFPSO, feasibility of SCR has been numerically evaluated in terms of strength and fatigue performances. Results based on first order wave response analysis show that strength and fatigue criteria were both satisfied in critical riser locations, indicating feasibility of the concept in this stage of the study.

The paper represents one sub-scope of the RPSEA study "Low Cost Flexible Production System for Remote Ultra-Deepwater Gulf of Mexico Field Development.", Project No. 10121–4404–03.
Impact of Water Cut on Asphaltene Deposition Tendency
Authors: Wang J. , Fan T. , Buckley J.S. , Creek J.L.
Published: June 2014

A systematic lab study was conducted to investigate the impact of water on asphaltene deposition tendency, with emphasis on percent water cut and ion composition. Two crude oils from Gulf of Mexico with different properties were applied as probe oils to study asphaltene deposition using a capillary deposition flowloop. Distilled (DI) water and a synthetic brine with 6.5% NaCl salinity were used to create water-in-oil emulsions to study the impact of water on asphaltene deposition. For one oil sample, it was observed that adding as few as 2 vol% DI water to the oil/n-heptane mixture could cause as much as 56% reduction on deposition rate. When DI water was replaced by the synthetic brine, the reduction in deposition rate decreased. However, when the synthetic brine also contained ferric ion (Fe3+) or aluminium ion (Al3+), the deposition rate was restored back to the same or an even higher level as the base case without water. ICP analysis revealed that deposits collected from tests with ferric ion or aluminium ion also contains significant amount of those two ions, plus remarkable increases on other divalent ions including Ni and V. In the second oil, adding 10–20% synthetic brine also reduced deposition rate 10–25%. With only 10 ppm ferric ion in the brine, the deposition rate for the second oil was largely restored back to the original level without water.
API 17N – Recommended Practise for Subsea Production System Reliability, Technical Risk & Integrity Management
Authors: Strutt John , Wells Don
Published: June 2014

API RP 17N provides a structured approach which organizations can adopt to manage risk and uncertainties related to reliability and integrity performance throughout the life of a project. This may range from the management of general project risk through to the identification and removal of potential failure modes in particular equipment. The basic approach is simple and consistent, and when applied correctly has the potential to greatly reduce the financial risk of designing, manufacturing, installing and operating subsea equipment and/or systems. This paper presents the principals and approaches used in API 17N, what it is in general, and why it was written. It will describe the status of its update, including the reasons for the revision and the addition of Integrity Management. It will not cover the detail of the RP, but instead it will describe the underlying paradigm and key processes and how it is being written to facilitate and enable wider application to other technical disciplines. Finally the paper will outline its relationship to other API documents, standards and industry initiatives and what we have learnt from the recent events.
Status of Equation of State Project at the NETL
Authors: Gamwo I.K. , Burgess W.A. , Morreale B. D. , Soong Y. , Bamgbade B. A. , McHugh M. A. , Baled H. O. , Enick R. M. , Wu Y. , Tapriyal D.
Published: June 2014

We describe a collaborative effort to accelerate the development of Equation of State (EoS) models to predict density and viscosity of crude oils at temperatures up to 533 K and pressures up to 276 MPa. These conditions are consistent with reservoirs encountered in ultra-deep formations such as in the Gulf of Mexico. The collaboration is organized by the U.S. Department of Energy-National Energy Technology Laboratory and two universities (University of Pittsburgh and Virginia Commonwealth University). This is being done by conducting well-defined validation experiments and by developing cubic and SAFT-based mathematical expressions for density and viscosity. The net result of this effort will be a suite of validated equations of state for crude oil at high temperature and high pressure conditions, and the widespread usage of these equations in reservoir simulators. Such reservoir models are critical not only to assess the magnitude of oil spills associated with failures in the wells or of production equipment but also to develop the appropriate response strategies should such accidents occur.
Flow Assurance Issues Related to Flexible Riser and Pipeline System Configuration
Authors: Yu Leyuan , Mohammad Saif , Button Scott , Li Mingxiu
Published: June 2014

Flexible riser and pipeline systems have been proposed as a promising solution for offshore oil and gas production systems in various harsh and challenging marine environments. They have many advantages compared with traditional rigid riser and pipeline systems, including: relatively low axial bending stiffness; ability to spool on a reel for easy transport and faster installation; and suitability for various floating systems.

Flexible riser and pipeline systems typically have buoyancy modules to produce a lazy wave or similar configuration in the riser to decouple the floating vessel motions from the touchdown point. However, the buoyancy modules may move or even drag the riser in the horizontal direction, which may cause the riser shape to change or the riser bottom to move on the seabed. The riser shape/configuration may change, even slightly, with the movement of buoyancy modules or flexible riser, resulting in potentially significant changes in flow assurance design issues related to slugging and system blowdown.

Case studies were carried out using transient multiphase simulation software, as reported in this paper, to investigate the slugging issues impacted by slight variations in the riser configuration in flexible pipeline/riser systems, including slight uphill and downhill riser base configurations. These small changes in the riser shape/configuration can also cause significant differences in the resulting residual pressures in the subsea pipeline and riser after blowing down the system.

The results from this paper suggest that the riser shape/configuration in flexible pipe systems has a significant impact on flow assurance concerns, especially the impact of slugging and blowdown residual pressures related to hydrate prevention and mitigation. Consequently, the sensitivity of riser shape/configuration in flexible riser and pipeline systems should be considered in early design phases to understand the impact on key flow assurance strategies.
Fatigue Assessment of Arrayed Pull-Tubes in a Truss Spar via Coupled Computational Fluid-Structure Interaction
Authors: Tognarelli M. A. , Gupta H. , Holmes S. , Calver W.
Published: June 2014

The truss spar is a proven floating production platform for a range of deepwater offshore oil and gas developments. From wells and manifolds on the seabed, catenary risers and umbilicals are routed from the keel of the platform to its topsides through steel pull tubes. Depending on the field architecture there may be a large number of pull tubes arranged within the truss in a complex, tightly-spaced array, where the spacing varies with elevation. Individual tubes may be fitted with strakes or other devices intended to suppress flow-induced vibrations. Fatigue of these tubes is an important consideration that influences their own design as well as riser and hull design. While relatively simple, semi-empirical programs do exist to analyze the fatigue due to vortex-induced vibrations (VIV) of isolated tubes in steady flows, none are generally available to analyze the complex fluid-structure interaction associated with this scenario. Existing models do not include the degradation of strake performance as a vibration suppressor in an arrayed, rather than isolated, configuration; buffeting of tubes in the turbulent wakes of the truss members and neighboring tubes; and, coupled fluid-tube interaction. Coupled computational fluid-structure inter-action (FSI) techniques - finite element (FE) solutions of a structural model coupled iteratively with computational fluid dynamics (CFD) solutions of a fluid model until convergence - are becoming progressively more feasible for addressing this type of problem as computing speeds and capacities continue to increase. This paper will demonstrate how one such computational coupled FSI has been used to deliver useful fatigue results in support of the design of a 35-tube array in a truss spar. It will also describe some key insights into the force-response mechanisms that would not have been discoverable via other analytical methods. Finally, it will make some qualitative comparisons to phenomena observed in physical model tests.
Improving Overhead and Reducing Time Consumption on P&A Operations with E-line, Explosion-free, Mechanical Cutter Tool
Authors: Krüger Christian , Faraoun Abderrahmane , Eikeland Tommy
Published: June 2014

With regards to most interventions there is a major interest in saving time on high cost items like daily rig charges, as well as improving the safety of the operations. Traditionally, pipe cutting operations are conducted using a rig to keep the tubing in tension in order to cut the pipes with explosives or other means. This paper will describe several plug and abandonment (P&A) intervention operations conducted on subsea wells in the North Sea without the use of explosives.

The overall objectives of the operation were to P&A and sidetrack two wells. After setting two 5 1/2? bridge plugs on the first well, the 5 1/2? tubing 23# 13% Cr was cut with a novel, e-line, mechanical cutter tool under compression (estimated at 1.5 to 2 tons), in one attempt, in two hours and 41 minutes. This enabled the rig to go directly to the pulling of the tubing instead of being involved in the release of the packer, saving time and overhead.

On the second well, two 5 1/2? bridge plugs had also been set prior to cutting a 5 1/2? tubing 23# 13% Cr S110, under compression, using standard cutting pads. The cut was successful on the first attempt. The actual cutting time lasted four hours and 40 minutes. In both cases, pre P&A work was conducted via Riserless Light Well intervention(RLWI) with the cutter run from the rig, but the cutter itself could also have been run on a RLWI operation with a more economical vessel than a drilling rig.

This paper will describe the planning process and operations, incl. the non-explosive design of the mechanical cutter that uses a rotating head to remove pipe incrementally, without creating shavings. Furthermore, the paper will discuss the lessons learned from these operations as well as future potential of this tool used as a rigless method.
Road to Offshore Gas Production Test - from Mallik to Nankai Trough
Authors: Saeki Tatsuo
Published: June 2014

The world's first offshore gas production test from methane hydrate deposits was conducted in March 2013, at the test site located on the margin of Daini Atsumi Knoll, off the coasts of Atsumi and Shima peninsulas, in the easten Nankai Trough, of Japan. Approximately 120, 000 cubic meters of methane gas was produced in 6 days using the depressurization technique.

The test was a significant advance in Japan's national program to construct the technical base for future commertial methane hydrate resource development. A series of researches for more than 10 years, including two times of onshore production tests in Mallik field and explorations in eastern Nankai Trough, were required to reach the test.

This report reviews Japan's research history for methane hydrates.
The Design Ice Island for Impact Against an Offshore Structure
Authors: Dunwoody A.B.
Published: June 2014

A method is presented by which an ice island may be selected for preliminary design of an offshore structure. The method involves:Estimation of the risk of an ice island impact.Determination of the distribution of kinetic energy amongst impacting ice islands.Selection of a design kinetic energy based on the maximum risk of failure which would be acceptable.Selection of a design ice island. The design ice island is chosen to be the ice island which is most likely to hit the offshore structure with the design kinetic energy.

The ice island statistics are reviewed and analysed using the above selection method to define a design ice island.

INTRODUCTION

Offshore structures have been bull t over the past several years for oil exploration in the Canadian and American Beaufort Seas. It is anticipated that larger, longer-term offshore structures will soon be built for oil production. Amongst the hazards which will have to be considered during the design of an oil production structure which have not been considered for exploration islands are ice islands. Ice islands are the largest individual ice features which could threaten an offshore structure in the Beaufort Sea. Originating from the ice shelves along the northern coast of Ellesmere Island, ice islands occasionally break-off and become incorporated in the permanent polar pack. Their Subsequent motions are controlled by winds, ocean currents, pack ice pressures and coriolis acceleration. The trend in the resulting motion is the familiar Beaufort Gyre. Approximately once every ten years, an ice island under the influence of the Gyre will pass through the Beaufort Sea. Eventually each island entering the Gyre will escape or disintegrate.

To date, all ice islands which have been observed to pass through the Canadian Beaufort Sea have passed far north of the exploration acreage. However, an ice island passing through the Beaufort Sea in the future could drift further south through the exploration acreage. If an ice island entered the exploration acreage during the open water season, its great mass coupled with the potentially high drift speeds possible in open water or loose pack would endow the ice island with tremendous kinetic energy. Any offshore structure which was struck would have to dissipate that kinetic energy safely or be destroyed.

In anticipation of designing a production structure, two questions must be answered with regard to ice island impacts during the summer. Is the risk of an ice island hitting an offshore structure great enough that the offshore structure should be designed to withstand such a hit? If the answer to the first question is yes, then what are the dimensions and other characteristics of the ice island against which the offshore structure should be designed. The simplest answer to those questions is to design the offshore structure to withstand an impact by the largest ice island imaginable. Although certainly conservative, that answer may be impractical or at least very expensive.
Random Analysis of a Riser for a Floating Production System (FPS) in a Northern North Sea Environment
Authors: Westin L.H.
Published: June 2014

The effects of the instantaneous position of the free wave surface and the non-linear wave loading on the riser response in the top part of the riser are determined by numerical time domain simulations. For the small diameter riser analysed in the paper it is shown that both these effects can have a significant influence on short term extreme peak predictions in severe environmental conditions.

INTRODUCTION

One option for the development of an offshore oil field in 305 m (1000 ft) water depth is a Floating Production System (FPS). Such a system comprising a purpose built floating production unit and a multibore production riser linking the subsea manifold to the floater is schematically shown in Fig. 1.

It is recognised that an accurate prediction of the dynamic behaviour of the riser is a key item in the development of such a system. An extensive analysis of this multibore riser has consequently been performed.

The riser is composed of 12 × 3.5" conduits arranged in a square array. The twelve conduits are split into four bundles of three conduits each. The square array is maintained by spacers that prevent inter-bundle collisions.

Selected extracts of observations made during the analysis are presented in this paper. The attention is focussed on the effects of the free wave surface and the non-linear wave loading in extreme peak predictions of riser response in the top part of the riser in severe environmental conditions in the northern North Sea

SIMULATION PROCEDURE

In order to achieve the objective of making accurate predictions of dynamic riser response it is recognised that computer codes for riser analysis must be able to simulate the random behaviour of the sea and the associated riser response. The results from this random analysis must be treated in a probabilistic manner (5, 6).

The analysis reported in this paper is made in the time-domain. A unidirectional random sea is realised with a Pierson-Moskowitz spectrum and linear wave theory (4). Correlated time series of wave particle kinematics and riser top motion are realised by discretising this input spectrum into a finite number of randomly phased components. It has been proved that the wave surface elevation, the riser top motion and the wave kinematics below mean sea level (MSL) are accurately simulated as random Gaussian processes in this manner. However, the linear wave theory breaks down above MSL. An empirical technique known as 'stretching' is used to map the wave kinematics as calculated below MSL up to the instantaneous position of the free wave surface on the riser, Fig. 1.

For the horizontal hydrodynamic forcing function the relative velocity form of the Morison equation is invoked.

In its disconnected and 'hung-off' mode the riser is vertically fixed to the floater. Due to the random floater heave motion (h) the tension in the riser will also be a random variable.

Two effects will contribute to the tension fluctuations provided that longitudinal vibrations are not in the frequency of predominant heave motion.
Towards the Worldwide Calibration of API RP2A-LRFD
Authors: Turner R.C. , Ellinas C.P. , Thomas G.A.N.
Published: June 2014

API RP2A-LRFD[l] is soon to be adopted by API for the design of fried offshore steel platforms, and will be available for use worldwide. The paper describes the work under taken to adapt LRFD for use in the North Sea. Sets of partial safety factors have been calibrated to suit specific environmental conditions, and design and operating practices using a reliability-baaed optimisation procedure.

INTRODUCTION

API RP2A[2] (henceforth denoted RP2A-WSD for Working Stress Design) forms the basis of steel jacket design throughout the world. It is widely used and has proved a popular design standard since fiit issued in October 1969. API have continually revised and updated it as a matter ofpolicy to include both new information and research, and to reflect current trends. RP2A-WSD is now on its 19th Edition.

Throughout most branches of structural engineering theinternational trend in design standards is to move from the working stress, or permissible stress, design format, typified by RP2A-WSD, towards a multiple factor format with partial safety factors applied to both loads or loading effects, and toresistances. By careful adjustment or calibration of the partial factors to reflect the uncertainty and variability in the different types of loads and resistances a much more consistent level ofcomponent reliability can be achieved. The partial factor format also offers more opportunity for influencing and improving design.

In 1979 API set up the PRAC-22 Committee to develop a partial factor format for RP2A; their work is reported inreference [3]. Following considerable development a draft Recommended practice 2A-LRFD was finally published in December 1989 and has been available for comment. The two year review period has now ended and RP2A-LRFD is soon expected to be issued as an API Recommended Practice.

In common with RP2A-WSD, LRFD has been written anddeveloped for use specifically in the Gulf of Mexico, the waters off Alaska, and the Pacit3cand Atlantic seaboards of the USA. When RP2A has been specified for design use in other areas of the world it has been subject to regional modifications and supplemented by additional guidance. When LRFD is internationalised it is hoped and intended that regional modification will be incorporated into Annexes for specific areas. In addition to area specific guidance, modified partial factors may be included which account for regional differencein environmental conditions, and in design and operating practices.

This ability to tailor the safety factors to suit specific conditions is a major advantage over the working stress approach and should have significant benefits for platform design and the internationalisation of RP2A-LRFD.

The calibration of the partial factors is undertaken using a reliability-based procedure. The general principles of the code calibration procedure are widely accepted. Firstly a set of one or more target reliabilities are assessed from a range of representative components which have been designed to an swept.ed code (usually the previous WSD version).
Lysophosphatidic Acid Receptor 5 Inhibits B Cell Antigen Receptor Signaling and Antibody Response
Authors: Hu Jiancheng , Oda Shannon K. , Shotts Kristin , Donovan Erin E. , Strauch Pamela , Pujanauski Lindsey M. , Victorino Francisco , Al-Shami Amin , Fujiwara Yuko , Tigyi Gabor , Oravecz Tamas , Pelanda Roberta , Torres Raul M.
Published: June 2014

Lysophospholipids have emerged as biologically important chemoattractants capable of directing lymphocyte development, trafficking, and localization. Lysophosphatidic acid (LPA) is a major lysophospholipid found systemically, and its levels are elevated in certain pathological settings, such as cancer and infections. In this study, we demonstrate that BCR signal transduction by mature murine B cells is inhibited upon LPA engagement of the LPA5 (GPR92) receptor via a Gα12/13-Arhgef1 pathway. The inhibition of BCR signaling by LPA5 manifests by impaired intracellular calcium store release and most likely by interfering with inositol 1,4,5-triphosphate receptor activity. We further show that LPA5 also limits Ag-specific induction of CD69 and CD86 expression and that LPA5-deficient B cells display enhanced Ab responses. Thus, these data show that LPA5 negatively regulates BCR signaling, B cell activation, and immune response. Our findings extend the influence of lysophospholipids on immune function and suggest that alterations in LPA levels likely influence adaptive humoral immunity.
Cutting Edge: Parathyroid Hormone Facilitates Macrophage Efferocytosis in Bone Marrow via Proresolving Mediators Resolvin D1 and Resolvin D2
Authors: McCauley Laurie K. , Dalli Jesmond , Koh Amy J. , Chiang Nan , Serhan Charles N.
Published: June 2014

Bone marrow macrophages stimulate skeletal wound repair and osteoblastic bone formation by poorly defined mechanisms. Specialized proresolving mediators of inflammation drive macrophage efferocytosis (phagocytosis of apoptotic cells) and resolution, but little is known regarding this process in the bone marrow. In this study, metabololipidomic profiling via liquid chromatography mass spectrometry revealed higher levels of specialized proresolving mediators in the bone marrow relative to the spleen. The endocrine and bone anabolic agent parathyroid hormone increased specialized proresolving mediator levels, including resolvins (Rvs), in bone marrow. Human and murine primary macrophages efferocytosed apoptotic osteoblasts in vitro, and RvD1 and RvD2 (10 pM–10 nM) enhanced this process. These findings support a unique profile of specialized lipid mediators in bone marrow that contribute to a feedback system for resolution of inflammation and maintenance of skeletal homeostasis.
IL-1β Promotes the Differentiation of Polyfunctional Human CCR6+CXCR3+ Th1/17 Cells That Are Specific for Pathogenic and Commensal Microbes
Authors: Duhen Thomas , Campbell Daniel J.
Published: June 2014

In humans, Th1/17 cells, identified by coexpression of the chemokine receptors CCR6 and CXCR3, are proposed to be highly pathogenic in several autoimmune disorders due in part to their expression of the proinflammatory cytokines IL-17, IFN-γ, and GM-CSF. However, their developmental requirements, relationship with “classic” Th17 and Th1 cells and physiological role in normal immune responses are not well understood. In this study, we examined CCR6+CXCR3+ Th1/17 cells from healthy individuals and found that ex vivo these cells produced the effector cytokines IL-17, IL-22, and IFN-γ in all possible combinations and were highly responsive to both IL-12 and IL-23. Moreover, although the Ag specificity of CCR6+CXCR3+ Th1/17 cells showed substantial overlap with that of Th1 and Th17 cells, this population was enriched in cells recognizing certain extracellular bacteria and expressing the intestinal homing receptor integrin β7. Finally, we identified IL-1β as a key cytokine that renders Th17 cells sensitive to IL-12, and both cytokines together potently induced the differentiation of cells that produce IL-17, IFN-γ, and GM-CSF. Therefore, interfering with IL-1β and IL-12 signaling in Th17 cells during inflammation may be a promising therapeutic approach to reduce their differentiation into “pathogenic” CCR6+CXCR3+ Th1/17 cells in patients with autoimmune diseases.
Gcsf-Chr19 Promotes Neutrophil Migration to Damaged Tissue through Blood Vessels in Zebrafish
Authors: Galdames Jorge A. , Zuñiga-Traslaviña Constanza , Reyes Ariel E. , Feijóo Carmen G.
Published: June 2014

G-CSF is an essential cytokine that regulates proliferation and differentiation of granulocytes from hematopoietic stem and progenitor cells. In mammals G-CSF has been identified as a key factor that promotes the release of neutrophils from the bone marrow into the blood circulation. In silico analysis indicates that zebrafish has two gcsf genes, gcsf-chr12 in chromosome 12 and gcsf-chr19 in chromosome 19. Gcsf-Chr12 participates in emergency myelopoiesis, but, in contrast to its mammalian orthologue, is not involved in neutrophil migration toward damaged tissue. In turn, the function of Gcsf-Chr19 has not been examined yet. In this study, we analyzed the role of Gcsf-Chr19 in regulating neutrophil migration toward the wound. Our results indicated that during the first h after caudal fin transection, neutrophils migrate from the hematopoietic tissue toward the injury, using the extracellular matrix as a substrate. Later, between 3 and 4 h postdamage, the recruitment mainly occurs through the bloodstream, and only a few neutrophils still use the extracellular matrix to migrate. During this process, the transcriptional levels of gcsf-chr19 are considerably increased, reaching a peak 1 h postdamage. The knockdown of Gcsf-chr19 indicated that the percentage of neutrophils that reach the wound decreased after the first h postinjury, suggesting that the knockdown specifically affects neutrophils that travel to the wound through blood vessels. Together, our data provide novel information about the regulation of neutrophil migration in zebrafish, positioning Gcsf-Chr19 as a key signal during the course of an inflammatory process triggered by severe damage.
Characterization of Conventional and Atypical Receptors for the Chemokine CCL2 on Mouse Leukocytes
Authors: Ford Laura B. , Cerovic Vuk , Milling Simon W. F. , Graham Gerard J. , Hansell Chris A. H. , Nibbs Robert J. B.
Published: June 2014

Chemokine-directed leukocyte migration is crucial for effective immune and inflammatory responses. Conventional chemokine receptors (cCKRs) directly control cell movement; atypical chemokine receptors (ACKRs) regulate coexpressed cCKRs; and both cCKRs and ACKRs internalize chemokines to limit their abundance in vivo, a process referred to as scavenging. A leukocyte’s migratory and chemokine-scavenging potential is determined by which cCKRs and ACKRs it expresses, and by the ligand specificity, signaling properties, and chemokine internalization capacity of these receptors. Most chemokines can bind at least one cCKR and one ACKR. CCL2 can bind to CCR2 (a cCKR) and two ACKRs (ACKR1 and ACKR2). In this study, by using fluorescent CCL2 uptake to label cells bearing functional CCL2 receptors, we have defined the expression profile, scavenging activity, and ligand specificity of CCL2 receptors on mouse leukocytes. We show that qualitative and quantitative differences in the expression of CCR2 and ACKR2 endow individual leukocyte subsets with distinctive CCL2 receptor profiles and CCL2-scavenging capacities. We reveal that some cells, including plasmacytoid dendritic cells, can express both CCR2 and ACKR2; that Ly6Chigh monocytes have particularly strong CCL2-scavenging potential in vitro and in vivo; and that CCR2 is a much more effective CCL2 scavenger than ACKR2. We confirm the unique, overlapping, ligand specificities of CCR2 and ACKR2 and, unexpectedly, find that cell context influences the interaction of CCL7 and CCL12 with CCR2. Fluorescent chemokine uptake assays were instrumental in providing these novel insights into CCL2 receptor biology, and the sensitivity, specificity, and versatility of these assays are discussed.
IL-27 Limits Central Nervous System Viral Clearance by Promoting IL-10 and Enhances Demyelination
Authors: de Aquino Maria Teresa P. , Kapil Parul , Hinton David R. , Phares Timothy W. , Puntambekar Shweta S. , Savarin Carine , Bergmann Cornelia C. , Stohlman Stephen A.
Published: June 2014

IL-27 is a pleiotropic member of the IL-6 and IL-12 cytokine family composed of the IL-27p28 and the EBV-induced gene 3. IL-27 and its receptor mRNA are both upregulated in the CNS during acute encephalomyelitis induced by the JHM strain of mouse hepatitis virus (JHMV) and sustained during viral persistence. Contributions of IL-27 to viral pathogenesis were evaluated by infection of IL-27Rα-chain–deficient (IL-27Rα−/−) mice. The absence of IL-27 signaling accelerated virus control within the CNS associated with increased IFN-γ secreting virus-specific CD4+ and CD8+ T cells. Abrogation of IL-27 signaling did not affect virus-specific CD8+ T cell–mediated IL-10 production or cytolytic activity or Foxp3+ regulatory T cell populations. However, IL-10 production by virus-specific CD4+ T cells was reduced significantly. Despite increased T cell–mediated antiviral function in IL-27Rα−/− mice, the virus persisted in the CNS at similar levels as in wild-type mice. Nevertheless, IL-27Rα−/− mice exhibited decreased clinical disease during persistence, coincident with less severe demyelination, the hallmark tissue damage associated with JHMV infection. Overall, these data demonstrate that in contrast to viral infections at other sites, IL-27 does not play a proinflammatory role during JHMV-induced encephalomyelitis. Rather, it limits CNS inflammation and impairs control of CNS virus replication via induction of IL-10 in virus-specific CD4+ T cells. Furthermore, in contrast to its protective role in limiting CNS autoimmunity and preventing immunopathology, these data define a detrimental role of IL-27 in promoting demyelination by delaying viral control.
Tofacitinib Suppresses Antibody Responses to Protein Therapeutics in Murine Hosts
Authors: Onda Masanori , Ghoreschi Kamran , Steward-Tharp Scott , Thomas Craig , O’Shea John J. , Pastan Ira H. , FitzGerald David J.
Published: June 2014

Immunogenicity remains the “Achilles' heel” of protein-based therapeutics. Anti-drug Abs produced in response to protein therapeutics can severely limit both the safety and efficacy of this expanding class of agent. In this article, we report that monotherapy of mice with tofacitinib (the JAK inhibitor) quells Ab responses to an immunotoxin derived from the bacterial protein Pseudomonas exotoxin A, as well as to the model Ag keyhole limpet hemocyanin. Thousand-fold reductions in IgG1 titers to both Ags were observed 21 d post immunization. In fact, suppression was evident for all IgG isotypes and IgM. A reduction in IgG3 production was also noted with a thymus-independent type II Ag. Mechanistic investigations revealed that tofacitinib treatment led to reduced numbers of CD127+ pro–B cells. Furthermore, we observed fewer germinal center B cells and the impaired formation of germinal centers of mice treated with tofacitinib. Because normal Ig levels were still present during tofacitinib treatment, this agent specifically reduced anti-drug Abs, thus preserving the potential efficacy of biological therapeutics, including those used as cancer therapeutics.
Critical clinical appraisal of the role of computed tomography-guided minimally invasive aspiration cytology in evaluation of retroperitoneal masses
Authors: Das Chhanda , Sengupta Moumita , Mukhopadhyay Madhumita , Saha Ashis Kumar
Published: June 2014

Context: Fine-needle aspiration (FNA) is increasing in popularity as a means of diagnosing mass lesions in retroperitoneal area. With use of radiologic guidance for needle placement, this technique is an effective way to obtain diagnostic material. Aims: The aims of the study were (1) to establish the validity and reliability of fine needle aspiration cytology in preoperative diagnosis of retroperitoneal tumor, and (2) to compare the significance of cytological diagnosis with histopathological report. Settings and Design: A prospective, cross-sectional hospital-based study. Materials and Methods: A prospective, cross-sectional study was designed on 45 cases of clinically and radiologically diagnosed retroperitoneal tumor in a tertiary care hospital. Computerized tomography (CT)-guided percutaneous FNA was performed and cytology smears were stained with May-Grünwald-Giemsa stain and conventional Papanicolaou (Pap) stain. Smears were broadly categorized into unsatisfactory, benign, suspicious of malignancy and malignant lesion. The cytological diagnosis was compared with subsequent histopathology report. Statistical Analysis: Positive and negative predictive values, diagnostic accuracy, chi-square test and others. Results: The total number of cases studied was 45, which include both epithelial tumors and mesenchymal tumors. Age group varied from 15 to 70 years. The overall sensitivity in our study to diagnose benign and malignant tumors by FNA cytology is 86% and the specificity is 96% with positive and negative predictive value of 86% and 96%, respectively. Diagnostic accuracy was 93.55% with high statistical significance (P < 0.001). Conclusions: FNA cytology is a simple, fast, reliable and less expensive method for diagnosis of various retroperitoneal neoplasms.
Embryonal rhabdomyosarcoma of the broad ligament
Authors: Chandarana Mihir N. , Raghu Shankar , Bhagat Monica , Qureshi Sajid
Published: June 2014

Broad ligament tumors are uncommon. Sarcomas rarely arise from the broad ligament, leiomyosarcomas being the most common. Rhabdomyosarcomas of the broad ligament are very rare. To the best of our knowledge, no case of an embryonal rhabdomyosarcoma of the broad ligament has been reported in literature.
Regulation of Tumor Growth and Metastasis: The Role of Tumor Microenvironment
Authors: Goubran Hadi A. , Kotb Rami R. , Stakiw Julie , Emara Mohamed E. , Burnouf Thierry
Published: June 2014

The presence of abnormal cells with malignant potential or neoplastic characteristics is a relatively common phenomenon. The interaction of these abnormal cells with their microenvironment is essential for tumor development, protection from the body's immune or defence mechanisms, later progression and the development of life-threatening or metastatic disease. The tumor microenvironment is a collective term that includes the tumor's surrounding and supportive stroma, the different effectors of the immune system, blood platelets, hormones and other humoral factors. A better understanding of the interplay between the tumor cells and its microenvironment can provide efficient tools for cancer management, as well as better prevention, screening and risk assessment protocols.
Preliminary Investigation of the Contribution of CYP2A6, CYP2B6, and UGT1A9 Polymorphisms on Artesunate-Mefloquine Treatment Response in Burmese Patients with Plasmodium falciparum Malaria
Authors: Phompradit Papichaya , Muhamad Poonuch , Cheoymang Anurak , Na-Bangchang Kesara
Published: June 2014

CYP2A6, CYP2B6, and UGT1A9 genetic polymorphisms and treatment response after a three-day course of artesunate-mefloquine was investigated in 71 Burmese patients with uncomplicated Plasmodium falciparum malaria. Results provide evidence for the possible link between CYP2A6 and CYP2B6 polymorphisms and plasma concentrations of artesunate/dihydroartemisinin and treatment response. In one patient who had the CYP2A6*1A/*4C genotype (decreased enzyme activity), plasma concentration of artesunate at one hour appeared to be higher, and the concentration of dihydroartemisinin was lower than for those carrying other genotypes (415 versus 320 ng/mL). The proportion of patients with adequate clinical and parasitologic response who had the CYP2B6*9/*9 genotype (mutant genotype) was significantly lower compared with those with late parasitologic failure (14.0% versus 19.0%). Confirmation through a larger study in various malaria-endemic areas is required before a definite conclusion on the role of genetic polymorphisms of these drug-metabolizing enzymes on treatment response after artesunate-based combination therapy can be made.
Fatal Melioidosis in Goats in Bangkok, Thailand
Authors: Tonpitak Walaiporn , Sornklien Chulabha , Chawanit Mongkol , Pavasutthipaisit Suvarin , Wuthiekanun Vanaporn , Hantrakun Viriya , Amornchai Premjit , Thaipadungpanit Janjira , Day Nicholas P. J. , Yingst Samuel , Peacock Sharon J. , Limmathurotsakul Direk
Published: June 2014

Bangkok, Thailand, is a city considered to be at low risk for melioidosis. We describe 10 goats that died of melioidosis in Bangkok. Half of them were born and reared in the city. Multilocus sequence typing ruled out an outbreak. This finding challenges the assumption that melioidosis is rarely acquired in central Thailand.
Ensino do empreendedorismo sob a ótica de alunos e professores do curso de administração de uma instituição de ensino superior (IES) privada em Minas Gerais
Authors: Rodrigues Solange Carvalho Moreira , Melo Marlene Catarina Oliveira Lopes , Lopes Ana Lucia Magri
Published: June 2014

Este artigo objetiva verificar a prática didático-pedagógica na área do empreendedorismo e sua interferência na propensão às atividades empreendedoras na percepção de alunos e professores do curso de Administração de uma Instituição de Ensino Superior (IES) privada localizada no Vale do Aço-MG. Este estudo de caso qualitativo descritivo teve como sujeitos de pesquisa quinze alunos do oitavo período do curso de Administração e quatro professores do referido curso, definidos por acessibilidade. Os dados foram coletados por meio de entrevistas semiestruturadas e análise documental. Posteriormente, foram ordenados, tabulados e classificados em unidades temáticas buscando-se os significados e a essência nos relatos. Evidenciou-se que a prática didático-pedagógica adotada na IES pesquisada propicia aos estudantes condições ao processo de empreender indicando a possibilidade de ensino formal do empreendedorismo. Como um fenômeno “multifacetado e multidisciplinar” demonstra não ser excludente uma via ou outra de aprendizado, exigindo no ambiente escolar, atividades práticas como nos moldes da Empresa-Ação ou de empresas simuladas. Do ponto de vista institucional destacam-se algumas contribuições para o campo como a adoção de mecanismos de apoio ao ensino, a realização de parcerias entre os atores institucionais privados e públicos, empresas de transferência de tecnologia ofertando condições estruturais, além das incubadoras.
Recent trends in aerosol optical properties derived from AERONET measurements
Authors: Li J. , Carlson B. E. , Dubovik O. , Lacis A. A.
Published: June 2014

Abstract. The Aerosol Robotic Network (AERONET) has been providing high-quality retrievals of aerosol optical properties from the surface at worldwide locations for more than a decade. Many sites have continuous and consistent records for more than 10 years, which enables the investigation of long-term trends of aerosol properties at these locations. In this study, we present trend analysis of AERONET data at 63 selected locations. In addition to commonly studied parameters such as Aerosol Optical Depth (AOD) and Ångström Exponent (AE), we also focus on Absorption Aerosol Optical Depth (ABS), Scattering Optical Depth (SCT), Single Scattering Albedo (SSA) and the Absorption Ångström Exponent (AAE). Two statistical methods are used to detect and estimate the trend: Mann–Kendall test associated with Sen's slope and linear least square fitting. Their results agree well in terms of the significance of the trend for the majority of the cases. The results indicate that Europe and North America experienced a uniform decrease in AOD and SCT, while significant (> 90%) increases of these two parameters are found for Kanpur, India. Most of European and North American sites also show negative trends for ABS, as well as three East Asian stations. The reduction in ABS results in positive SSA trends for these locations. The increase of SCT also leads to a positive SSA trend for Kanpur. Negative SSA trends are mostly found over South America, Australia and a few West European stations, which are mainly attributed to the increase of absorption. Fewer stations are found with significant trends for AE and AAE. In general, the trends do not exhibit obvious seasonality for the majority of the parameters and stations.