bluuebunny/crossref_metadata_2025 huggingface dataset:
Pipeline Integrity Assessment: Methodology
Authors: Shaik Mohammed Riyazuddin
Published: July 2015

With ever increasing energy demands, approximately 90 million barrels of oil per day and 3314 billion cubic meters of gas per year are consumed around the world [1]. To meet such huge energy demands a complicated and vast network of offshore and onshore production and distribution pipelines is necessary. Pipelines connect areas that are relatively rich in resources with areas that are demand-hungry but poor in resources. They play a central role in providing to the energy needs of businesses and public, forming the veins and arteries of the Oil and Gas industry. These pipelines are susceptible to damage, both internal and external based on the type of product in the pipeline and the environment in the vicinity of the pipeline i.e. offshore or onshore. The damage to the pipeline needs to be identified and the significance of the damage clearly defined. The inline inspection (ILI) tools help to identify the damage and record the extent and type of damage. Inability to prioritize the damaged areas and carry out necessary intervention to at least curtail the damage may occasionally lead to calamitous consequences. One such example is of a 30-inch Liquid pipeline failure that occurred in Michigan on July 25, 2010. The National Transportation Safety Board (NTSB) reported that the corrosion fatigue cracks that grew and coalesced from corrosion defects resulted in the rupture and prolonged release from the 30-inch oil pipeline [2]. This failure resulted in a revenue loss of approximately $16 million and estimated costs of $767 million for regulatory and professional support in connection with the clean-up operations. Condition assessment of the pipelines as part of the pipeline integrity management system is the primary means through which such catastrophic pipeline system failures could be prevented. This paper presents the methodology that is adopted for “Integrity Assessment” of the pipelines.
Deepwater Pipeline Challenges
Authors: Sinha Nitesh , Kishore Raj
Published: July 2015

With the ever-increasing demand of energy in the country, the Indian exploration and production is now compelled to move into deepwater frontiers. The country’s energy reserve is getting exhausted with drying shallow water assets and the mainland is already overwhelmed with the pressure of sustaining the world’s second largest population. Therefore, “the upstream oil and gas fraternity of the country” has to now enter “less explored” Indian deepwater block which has already started with the launch of the NELP block by the government.

Although, the world has moved into deepwater long back, the Indian industry is still developing the ways and means to tackle the challenges involved in deep water. This paper presents the insights into design and installation of deepwater pipelines along with case study of Middle East to India Deepwater Pipeline (MEIDP) of M/s SAGE, which shall be laid at a maximum water depth of 3450 m.

This paper broadly elucidates the challenges in designing the deepwater pipelines such as requirement of thick-walled line pipes to sustain collapse due to external over-pressure and tensile stresses generated due to installation forces, pipeline route selection and optimization, geo-hazard assessment & mitigation, design against fault line crossings/ seismic design, free span, repair systems, seabed intervention etc. It also covers the additional manufacturing & testing requirements including tighter tolerances for line pipes suitable for deepwater installations. It also highlights the deepwater installation capabilities of Pipe lay Barges for the laying of pipeline in the deepwater to ultra-deep waters along with new evolving testing and commissioning philosophies.

This paper intends to bring awareness among the “oil and gas fraternity” regarding challenges involved in deep water pipelines with respect to design, installation etc.
Composite Material Pipes for Transportation of Effluent and Hydrocarbon
Authors: Mohan Vidit , Ramesh Ashwin P. , Toshniwal Anirudh , Mohan Prakhar
Published: July 2015

The objective of this paper is to evaluate current and potential use of composite pipe especially Glass Reinforced Epoxy (GRE) for transportation of effluent and hydrocarbon in onshore field. This paper brings out the followings:

1. Details of composite pipes along with its advantages like corrosion resistance, less weight, low maintenance requirement and better flow characteristics etc. compared to conventional steel.

2. Comparison of composite material pipes to conventional CS pipes.

3. Standards, specifications & recommended practices for use of GRE pipelines.

4. Current and planned use of GRE pipes in India.

5. Repair and maintenance of GRE pipelines.

6. Limitations of use of GRE pipes for hydrocarbon transportation.

7. Safety and environmental considerations for use of GRE pipelines.

8. Regulatory framework for use of GRE pipeline in India.
Establishment of Cold Wire Addition Technology® in Multiwire Submerged Arc Welding for Line Pipe Manufacturing to Improve the Weldment Quality
Authors: Mannarsamy Ramakrishnan , Shrivastava S. K. , Thakor Piyush , Chauhan Gautam , Joshi S. K. , Korada Ram
Published: July 2015

For achieving high productivity multiple wire submerged arc welding such as tandem wire, three wires and five wires submerged arc welding was introduced in recent past years. Due to adding of additional wires in a pipe mill faced process difficulties such as controlling the current supply to each wire and further challenges for consumable design in order to give effective slag characteristics and bead shape control at these higher welding speeds and heat inputs. To gain maximum productivity, welding speed must be as fast as possible (in excess of 2 m/min) consistent with reliable high speed wire feeding and the characteristics of the SAW flux considering these factors in determining the balance of heat input, penetration, bead shape, dilution, weld metal chemistry and mechanical properties such as toughness. Steels containing high strength low alloying elements like Manganese, Molybdenum, Titanium and boron have favorable physical properties such as higher subzero toughness, resistance to improve the mechanical properties because of which there is substantial saving in the material. High strength low alloy steels materials are utilized in offshore and onshore at critical services. However, such benefits can be exploited provided these steels can be welded with appropriate development of welding process such as cold wire addition® in multi wires with process controller using WINCC programmer, Z5 version to give better weldments, which will not compromise the integrity, and operating condition. To obtain higher productivity and quality, it is necessary to develop a welding procedure for butt joint of line pipe steels. This paper describes the recent work carried out by Welspun, in this regard to establish the welding procedure using GMAW and submerged arc welding process and evaluation of mechanical properties. Macro and micro structural analysis were also made to characterize the weld metal properties.
Investigation of strain sensors based on thin graphite wires
Authors: Saito Takanari , Shimoda Hiroshi , Shirakashi Jun-ichi
Published: July 2015

In this study, the electrical properties of thin graphite wires were investigated for strain sensors. The thin graphite wires were simply and easily fabricated from pyrolytic graphite sheet, which can be formed by firing a polymer film (such as a polyimide film) at high temperatures. The resistance of the thin graphite wires increased under increasing tensile bending strains and decreased under increasing compressive bending strains. Notably, the sensitivity of the sensors increased when the thickness of the thin graphite wires was reduced. This property was investigated via modeling of the strain-induced changes in the overlap area and conduction pathways of the graphite flakes. Multiple-cycle tests were carried out to evaluate the long-term stability of the thin graphite wires; specifically, the electrical response was monitored under repeated cycling, for approximately 1000 cycles. The thin graphite wires were assembled on ultrathin gloves to fabricate data gloves that could detect finger motions. The results of this study indicate that the thin graphite wires that were simply and easily fabricated from pyrolytic graphite sheet have great potential for a wide range of applications, including human motion detectors.
Investigation of mobility enhancement of junctionless nanowire transistor at low temperatures
Authors: Wang Hao , Han Weihua , Ma Liuhong , Li Xiaoming , Yang Fuhua
Published: July 2015

N-type single-channel junctionless nanowire transistor (JNT) is fabricated on silicon-on-insulator substrate by the two-photon femtosecond laser lithography. The electrical properties of the device are investigated at room and low temperatures. At room temperature, the JNT demonstrates good performance, such as positive threshold voltage, subthreshold swing of 156 mV/dec, and on/off current ratio larger than 105. At low temperatures below 100 K, current oscillations are clearly observed in the initial stage of the conduction, resulting from the quantum confinement effects. In addition, the single channel device exhibits large low field electron mobility of ∼900 cm2 V−1 s−1 at the temperature of 100 K, which has been resulted from the bulk electron transport and incomplete ionization of impurities.
Impact of different meander sizes on the RF transmit performance and coupling of microstrip line elements at 7 T
Authors: Rietsch Stefan H. G. , Quick Harald H. , Orzada Stephan
Published: July 2015

Purpose:

In this work, the transmit performance and interelement coupling characteristics of radio frequency (RF) antenna microstrip line elements are examined in simulations and measurements.

Methods:

The initial point of the simulations is a microstrip line element loaded with a phantom. Meander structures are then introduced at the end of the element. The size of the meanders is increased in fixed steps and the magnetic field is optimized. In continuative simulations, the coupling between identical elements is evaluated for different element spacing and loading conditions. Verification of the simulation results is accomplished in measurements of the coupling between two identical elements for four different meander sizes. Image acquisition on a 7 T magnetic resonance imaging (MRI) system provides qualitative and quantitative comparisons to confirm the simulation results.

Results:

Simulations point out an optimum range of meander sizes concerning coupling in all chosen geometric setups. Coupling measurement results are in good agreement with the simulations. Qualitative and quantitative comparisons of the acquired MRI images substantiate the coupling results.

Conclusions:

The coupling between coil elements in RF antenna arrays consisting of the investigated element types can be optimized under consideration of the central magnetic field strength or efficiency depending on the desired application.
Automated cortical bone segmentation for multirow‐detector CT imaging with validation and application to human studies
Authors: Li Cheng , Jin Dakai , Chen Cheng , Letuchy Elena M. , Janz Kathleen F. , Burns Trudy L. , Torner James C , Levy Steven M. , Saha Punam K
Published: July 2015

Purpose:

Cortical bone supports and protects human skeletal functions and plays an important role in determining bone strength and fracture risk. Cortical bone segmentation at a peripheral site using multirow‐detector CT (MD‐CT) imaging is useful for in vivo assessment of bone strength and fracture risk. Major challenges for the task emerge from limited spatial resolution, low signal‐to‐noise ratio, presence of cortical pores, and structural complexity over the transition between trabecular and cortical bones. An automated algorithm for cortical bone segmentation at the distal tibia from in vivo MD‐CT imaging is presented and its performance and application are examined.

Methods:

The algorithm is completed in two major steps—(1) bone filling, alignment, and region‐of‐interest computation and (2) segmentation of cortical bone. After the first step, the following sequence of tasks is performed to accomplish cortical bone segmentation—(1) detection of marrow space and possible pores, (2) computation of cortical bone thickness, detection of recession points, and confirmation and filling of true pores, and (3) detection of endosteal boundary and delineation of cortical bone. Effective generalizations of several digital topologic and geometric techniques are introduced and a fully automated algorithm is presented for cortical bone segmentation.

Results:

An accuracy of 95.1% in terms of volume of agreement with manual outlining of cortical bone was observed in human MD‐CT scans, while an accuracy of 88.5% was achieved when compared with manual outlining on postregistered high resolution micro‐CT imaging. An intraclass correlation coefficient of 0.98 was obtained in cadaveric repeat scans. A pilot study was conducted to describe gender differences in cortical bone properties. This study involved 51 female and 46 male participants (age: 19–20 yr) from the Iowa Bone Development Study. Results from this pilot study suggest that, on average after adjustment for height and weight differences, males have thicker cortex (mean difference 0.33 mm and effect size 0.92 at the anterior region) with lower bone mineral density (mean difference −28.73 mg/cm3 and effect size 1.35 at the posterior region) as compared to females.

Conclusions:

The algorithm presented is suitable for fully automated segmentation of cortical bone in MD‐CT imaging of the distal tibia with high accuracy and reproducibility. Analysis of data from a pilot study demonstrated that the cortical bone indices allow quantification of gender differences in cortical bone from MD‐CT imaging. Application to larger population groups, including those with compromised bone, is needed.
The acoustic nonlinearity parameter in Fluorinert up to 381 K and 13.8 MPa
Authors: Sturtevant Blake T. , Pantea Cristian , Sinha Dipen N.
Published: July 2015

This work reports on the determination of the acoustic nonlinearity parameter, B/A, from measured sound speed data, in Fluorinert FC-43 at temperatures up to 381 K and pressures up to 13.8 MPa using the thermodynamic method. Sound speed was measured using Swept Frequency Acoustic Interferometry at 11 pressures between ambient and 13.8 MPa along 6 isotherms between ambient and 381 K. Second-order least-squares polynomial fits of measured sound speeds were used to determine temperature and pressure dependence. A room temperature B/A = 11.7 was determined and this parameter was found to increase by a factor of 2.5 over the temperature/pressure range investigated.
Cancer's copper connections
Authors: Garber Ken
Published: July 2015

Tumors may be especially dependent on the metal copper.
Pluto caps one man's odyssey
Authors: Hand Eric
Published: July 2015

NASA veteran Tom Krimigis has been on missions to all of the sun's planets, and beyond.
Climate change impacts on bumblebees converge across continents
Authors: Kerr Jeremy T. , Pindar Alana , Galpern Paul , Packer Laurence , Potts Simon G. , Roberts Stuart M. , Rasmont Pierre , Schweiger Oliver , Colla Sheila R. , Richardson Leif L. , Wagner David L. , Gall Lawrence F. , Sikes Derek S. , Pantoja Alberto
Published: July 2015

Bucking the trend

Responses to climate change have been observed across many species. There is a general trend for species to shift their ranges poleward or up in elevation. Not all species, however, can make such shifts, and these species might experience more rapid declines. Kerr
et al.
looked at data on bumblebees across North America and Europe over the past 110 years. Bumblebees have not shifted northward and are experiencing shrinking distributions in the southern ends of their range. Such failures to shift may be because of their origins in a cooler climate, and suggest an elevated susceptibility to rapid climate change.

Science
, this issue p.
177
Response to Comment on “Asymmetric syntheses of sceptrin and massadine and evidence for biosynthetic enantiodivergence”
Authors: Ma Zhiqiang , Wang Xiaolei , Wang Xiao , Rodriguez Rodrigo A. , Moore Curtis E. , Gao Shuanhu , Tan Xianghui , Ma Yuyong , Rheingold Arnold L. , Baran Phil S. , Chen Chuo
Published: July 2015

Sherman
et al
. commented on the precedence of enantiodivergence, listing a number of congeneric natural products with opposite chirality. However, these “congeners” are not derived from enantiodivergent biosyntheses. Instead, they are antipodes arising from separate enantiomeric biosyntheses. A distinct feature of the biosynthesis of the cyclic pyrrole-imidazole dimers is the production of antipodal congeners without the corresponding enantiomers.
Autoassociative dynamics in the generation of sequences of hippocampal place cells
Authors: Pfeiffer Brad E. , Foster David J.
Published: July 2015

Memory storage in neural networks

Neuronal networks can store and retrieve discrete memories, but often fail to retrieve stored sequences. This is because error decreases over time for a static attractor, but builds up drastically over time if patterns are not trained to retrieve themselves but to retrieve the next item in a sequence. Pfeiffer and Foster studied brain activity in awake but immobile rats. Recording simultaneously from a large number of place cells in the hippocampal formation, they found that internally generated sequences alternated between periods of hovering in place while being strengthened, and periods of abrupt transition to a new place.

Science
, this issue p.
180
A 3D-printed, functionally graded soft robot powered by combustion
Authors: Bartlett Nicholas W. , Tolley Michael T. , Overvelde Johannes T. B. , Weaver James C. , Mosadegh Bobak , Bertoldi Katia , Whitesides George M. , Wood Robert J.
Published: July 2015

Making jack jump efficiently

In the future, soft-bodied robots may be able to squeeze into tight spaces or work in environments where they could be crushed. However, it is hard to ensure efficient power transmission in a soft-bodied device. One promising solution is to use explosions to drive the robot, using efficient weight-to-power energy sources. Using three-dimensional printing to fuse together multiple materials, Bartlett
et al.
built a combustion-powered robot. The robot has a rigid core that transitions to a soft exterior. They produced an efficient jumping robot in which the gradations in the hardness of the body materials also improved robustness.

Science
, this issue p.
161
Crystal structure of a mycobacterial Insig homolog provides insight into how these sensors monitor sterol levels
Authors: Ren Ruobing , Zhou Xinhui , He Yuan , Ke Meng , Wu Jianping , Liu Xiaohui , Yan Chuangye , Wu Yixuan , Gong Xin , Lei Xiaoguang , Yan S. Frank , Radhakrishnan Arun , Yan Nieng
Published: July 2015

Structure of a sterol sensor

The aberrant accumulation of sterols contributes to heart attack and stroke. Two proteins embedded in the membrane of the endoplasmic reticulum, Insig-1 and Insig-2, are key players in the cellular pathway that regulates cellular sterol levels. Ren
et al.
report the structure of a mycobacterial homolog of Insig. The structure, together with biochemical experiments, suggests how Insig interacts with other components of the sterol regulatory pathway.

Science
, this issue p.
187
Mid-infrared plasmonic biosensing with graphene
Authors: Rodrigo Daniel , Limaj Odeta , Janner Davide , Etezadi Dordaneh , García de Abajo F. Javier , Pruneri Valerio , Altug Hatice
Published: July 2015

Graphene-based biosensors

The mid-infrared (mid-IR) range is particularly well suited for biosensing because it encompasses the molecular vibrations that identify the biochemical building blocks of life, such as proteins, lipids, and DNA. However, the resulting optical signal is extremely weak and often requires complex techniques to enhance the biological detection. Rodrigo
et al.
present a graphene-based biosensor that they dynamically tuned over a broad spectral range through electrical gating. The authors selectively probed protein molecules at different mid-IR frequencies using a single device.

Science
, this issue p.
165
Intellectuals and the rise of the modern economy
Authors: Mokyr Joel
Published: July 2015

Well-educated elites enabled scientific and technological creativity during the Industrial Revolution
COPI gets a fancy new coat
Authors: Noble Alex J. , Stagg Scott M.
Published: July 2015

An interconnected scaffolding of proteins bends the membrane to form vesicles

[Also see Report by

Dodonova
et al.

]
DNA Topoisomerases
Authors: Bush Natassja G. , Evans-Roberts Katherine , Maxwell Anthony
Published: July 2015

DNA topoisomerases are enzymes that control the topology of DNA in all cells. There are two types, I and II, classified according to whether they make transient single- or double-stranded breaks in DNA. Their reactions generally involve the passage of a single- or double-strand segment of DNA through this transient break, stabilized by DNA-protein covalent bonds. All topoisomerases can relax DNA, but DNA gyrase, present in all bacteria, can also introduce supercoils into DNA. Because of their essentiality in all cells and the fact that their reactions proceed via DNA breaks, topoisomerases have become important drug targets; the bacterial enzymes are key targets for antibacterial agents. This article discusses the structure and mechanism of topoisomerases and their roles in the bacterial cell. Targeting of the bacterial topoisomerases by inhibitors, including antibiotics in clinical use, is also discussed.
Case-Control Study of Risk Factors for Sporadic Giardiasis and Parasite Assemblages in North West England
Authors: Minetti Corrado , Lamden Kenneth , Durband Caroline , Cheesbrough John , Platt Katherine , Charlett Andre , O'Brien Sarah J. , Fox Andrew , Wastling Jonathan M.
Published: July 2015

Giardia duodenalisis a major cause of infectious gastroenteritis worldwide, and it is diversified into eight genetic assemblages (A to H), which are distinguishable only by molecular typing. There is some evidence that the assemblages infecting humans (assemblages A and B) may have different transmission routes, but systematically acquired data, combining epidemiological and molecular findings, are required. We undertook a case-control study withGiardiagenotyping in North West England, to determine general and parasite assemblage-specific risk factors. For people without a history of foreign travel, swimming in swimming pools and changing diapers were the most important risk factors for the disease. People infected with assemblage B reported a greater number of symptoms and higher frequencies of vomiting, abdominal pain, swollen stomach, and loss of appetite, compared with people infected with assemblage A. More importantly, keeping a dog was associated only with assemblage A infections, suggesting the presence of a potential zoonotic reservoir for this assemblage. This is the first case-control study to combine epidemiological data withGiardiagenotyping, and it shows the importance of integrating these two levels of information for better understanding of the epidemiology of this pathogen.
Infectious Middle East Respiratory Syndrome Coronavirus Excretion and Serotype Variability Based on Live Virus Isolates from Patients in Saudi Arabia
Authors: Muth Doreen , Corman Victor M. , Meyer Benjamin , Assiri Abdullah , Al-Masri Malak , Farah Mohamed , Steinhagen Katja , Lattwein Erik , Al-Tawfiq Jaffar A. , Albarrak Ali , Müller Marcel A. , Drosten Christian , Memish Ziad A.
Published: July 2015

The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 1,082 people, including 439 fatalities. So far, no empirical virus isolation study has been done to elucidate infectious virus secretion or serotype variability. Here, we used 51 respiratory samples from 32 patients with confirmed MERS-CoV infection for virus isolation in Vero B4 and Caco-2 cells. We found Caco-2 cells to significantly enhance isolation success over routinely used Vero cells. Isolation success correlated with viral RNA concentration and time after diagnosis as well as with the amount of IgA antibodies secreted in respiratory samples used for isolation. Results from plaque reduction neutralization assays using a representative range of serum samples and virus isolates suggested that all circulating human MERS-CoV strains represent one single serotype. The choice of prototype strain is not likely to influence the success of candidate MERS-CoV vaccines. However, vaccine formulations should be evaluated for their potential to induce IgA.
Downregulation of Poly(ADP-Ribose) Polymerase 1 by a Viral Processivity Factor Facilitates Lytic Replication of Gammaherpesvirus
Authors: Cheong Woo-Chang , Park Joo-Hee , Kang Hye-Ri , Song Moon Jung
Published: July 2015

In Kaposi's sarcoma-associated herpesvirus (KSHV), poly(ADP-ribose) polymerase 1 (PARP-1) acts as an inhibitor of lytic replication. Here, we demonstrate that KSHV downregulated PARP-1 upon reactivation. The viral processivity factor of KSHV (PF-8) interacted with PARP-1 and was sufficient to degrade PARP-1 in a proteasome-dependent manner; this effect was conserved in murine gammaherpesvirus 68. PF-8 knockdown in KSHV-infected cells resulted in reduced lytic replication upon reactivation with increased levels of PARP-1, compared to those in control cells. PF-8 overexpression reduced the levels of the poly(ADP-ribosyl)ated (PARylated) replication and transcription activator (RTA) and further enhanced RTA-mediated transactivation. These results suggest a novel viral mechanism for overcoming the inhibitory effect of a host factor, PARP-1, thereby promoting the lytic replication of gammaherpesvirus.

IMPORTANCE
Gammaherpesviruses are important human pathogens, as they are associated with various kinds of tumors and establish latency mainly in host B lymphocytes. Replication and transcription activator (RTA) of Kaposi's sarcoma-associated herpesvirus (KSHV) is a central molecular switch for lytic replication, and its expression is tightly regulated by many host and viral factors. In this study, we investigated a viral strategy to overcome the inhibitory effect of poly(ADP-ribose) polymerase 1 (PARP-1) on RTA's activity. PARP-1, an abundant multifunctional nuclear protein, was downregulated during KSHV reactivation. The viral processivity factor of KSHV (PF-8) directly interacted with PARP-1 and was sufficient and necessary to degrade PARP-1 protein in a proteasome-dependent manner. PF-8 reduced the levels of PARylated RTA and further promoted RTA-mediated transactivation. As this was also conserved in another gammaherpesvirus, murine gammaherpesvirus 68, our results suggest a conserved viral modulation of a host inhibitory factor to facilitate its lytic replication.
Generation of a Recombinant Akabane Virus Expressing Enhanced Green Fluorescent Protein
Authors: Takenaka-Uema Akiko , Murata Yousuke , Gen Fumihiro , Ishihara-Saeki Yukari , Watanabe Ken-ichi , Uchida Kazuyuki , Kato Kentaro , Murakami Shin , Haga Takeshi , Akashi Hiroomi , Horimoto Taisuke
Published: July 2015

We generated a recombinant Akabane virus (AKAV) expressing enhanced green fluorescence protein (eGFP-AKAV) by using reverse genetics. We artificially constructed an ambisense AKAV S genome encoding N/NSs on the negative-sense strand, and eGFP on the positive-sense strand with an intergenic region (IGR) derived from the Rift Valley fever virus (RVFV) S genome. The recombinant virus exhibited eGFP fluorescence and had a cytopathic effect in cell cultures, even after several passages. These results indicate that the gene encoding eGFP in the ambisense RNA could be stably maintained. Transcription of N/NSs and eGFP mRNAs of eGFP-AKAV was terminated within the IGR. The mechanism responsible for this appears to be different from that in RVFV, where the termination sites for N and NSs are determined by a defined signal sequence. We inoculated suckling mice intraperitoneally with eGFP-AKAV, which resulted in neurological signs and lethality equivalent to those seen for the parent AKAV. Fluorescence from eGFP in frozen brain slices from the eGFP-AKAV-infected mice was localized to the cerebellum, pons, and medulla oblongata. Our approach to producing a fluorescent virus, using an ambisense genome, helped obtain eGFP-AKAV, a fluorescent bunyavirus whose viral genes are intact and which can be easily visualized.

IMPORTANCE
AKAV is the etiological agent of arthrogryposis-hydranencephaly syndrome in ruminants, which causes considerable economic loss to the livestock industry. We successfully generated a recombinant enhanced green fluorescent protein-tagged AKAV containing an artificial ambisense S genome. This virus could become a useful tool for analyzing AKAV pathogenesis in host animals. In addition, our approach of using an ambisense genome to generate an orthobunyavirus stably expressing a foreign gene could contribute to establishing alternative vaccine strategies, such as bivalent vaccine virus constructs, for veterinary use against infectious diseases.
Selective Involvement of the Checkpoint Regulator VISTA in Suppression of B-Cell, but Not T-Cell, Responsiveness by Monocytic Myeloid-Derived Suppressor Cells from Mice Infected with an Immunodeficiency-Causing Retrovirus
Authors: Green Kathy A. , Wang Li , Noelle Randolph J. , Green William R.
Published: July 2015

Inhibition of T-cell responses in tumor microenvironments by myeloid-derived suppressor cells (MDSCs) is widely accepted. We demonstrated augmentation of monocytic MDSCs whose suppression of not only T-cell, but also B-cell, responsiveness paralleled the immunodeficiency during LP-BM5 retrovirus infection. MDSCs inhibited T cells by inducible nitric oxide synthase (iNOS)/nitric oxide (NO), but uniquely, inhibition of B cells was ∼50% dependent each on iNOS/NO and the MDSC-expressed negative-checkpoint regulator VISTA. Blockade with a combination of iNOS/NO and VISTA caused additive or synergistic abrogation of MDSC-mediated suppression of B-cell responsiveness.
Systemic Foot-and-Mouth Disease Vaccination in Cattle Promotes Specific Antibody-Secreting Cells at the Respiratory Tract and Triggers Local Anamnestic Responses upon Aerosol Infection
Authors: Pega J. , Di Giacomo S. , Bucafusco D. , Schammas J. M. , Malacari D. , Barrionuevo F. , Capozzo A. V. , Rodríguez L. L. , Borca M. V. , Pérez-Filgueira M.
Published: July 2015

Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting biungulate species. Commercial vaccines, formulated with inactivated FMD virus (FMDV), are regularly used worldwide to control the disease. Here, we studied the generation of antibody responses in local lymphoid tissues along the respiratory system in vaccinated and further aerosol-infected cattle. Animals immunized with a high-payload monovalent FMD vaccine developed high titers of neutralizing antibodies at 7 days postvaccination (dpv), reaching a plateau at 29 dpv. FMDV-specific antibody-secreting cells (ASC), predominantly IgM, were evident at 7 dpv in the prescapular lymph node (LN) draining the vaccination site and in distal LN draining the respiratory mucosa, although in lower numbers. At 29 dpv, a significant switch to IgG1 was clear in prescapular LN, while FMDV-specific ASC were detected in all lymphoid tissues draining the respiratory tract, mostly as IgM-secreting cells. None of the animals (
n
= 10) exhibited FMD symptoms after oronasal challenge at 30 dpv. Three days postinfection, a large increase in ASC numbers and rapid isotype switches to IgG1 were observed, particularly in LN-draining virus replication sites already described. These results indicate for the first time that systemic FMD vaccination in cattle effectively promotes the presence of anti-FMDV ASC in lymphoid tissues associated with the respiratory system. Oronasal infection triggered an immune reaction compatible with a local anamnestic response upon contact with the replicating FMDV, suggesting that FMD vaccination induces the circulation of virus-specific B lymphocytes, including memory B cells that differentiate into ASC soon after contact with the infective virus.

IMPORTANCE
Over recent decades, world animal health organizations as well as national sanitary authorities have supported the use of vaccination as an essential component of the official FMD control programs in both endemic and disease-free settings. Very few works studied the local immunity induced by FMD vaccines at the respiratory mucosa, and local responses induced in vaccinated animals after aerosol infection have not been described yet. In this work, we demonstrate for the first time that systemic FMD vaccination (i) induced the early presence of active antigen-specific ASC along the respiratory tract and (ii) prompted a rapid local antibody response in the respiratory mucosa, triggered upon oronasal challenge and congruent with a memory B-cell response. This information may help to understand novel aspects of protective responses induced by current FMD vaccines as well as to provide alternative parameters to establish protection efficiency for new vaccine developments.
A Dynein Light Chain 1 Binding Motif in Rabies Virus Polymerase L Protein Plays a Role in Microtubule Reorganization and Viral Primary Transcription
Authors: Bauer Anja , Nolden Tobias , Nemitz Sabine , Perlson Eran , Finke Stefan
Published: July 2015

Rabies virus (RABV) polymerase L together with phosphoprotein P forms the PL polymerase complex that is essential for replication and transcription. However, its exact mechanism of action, interactions with cellular factors, and intracellular distribution are yet to be understood. Here by imaging a fluorescently tagged polymerase (mCherry-RABV-L), we show that L accumulates at acetylated and reorganized microtubules (MT).
In silico
analysis revealed a dynein light chain 1 (DLC1) binding motif in L that could mediate MT binding through dynein motors. As DLC1 binding by polymerase cofactor P is known, we compared the impact of the DLC1-binding motifs in P and L. Viruses with mutations in the respective motifs revealed that both motifs are required for efficient primary transcription, indicating that DLC1 acts as a transcription enhancer by binding to both P and L. Notably, also the levels of cellular DLC1 protein were regulated by both motifs, suggesting regulation of the DLC1 gene expression by both P and L. Finally, disruption of the motif in L resulted in a cell-type-specific loss of MT localization, demonstrating that DLC1 is involved in L-mediated cytoskeleton reorganization. Overall, we conclude that DLC1 acts as a transcription factor that stimulates primary RABV transcription by binding to both P and L. We further conclude that L influences MT organization and posttranslational modification, suggesting a model in which MT manipulation by L contributes to efficient intracellular transport of virus components and thus may serve as an important step in virus replication.

IMPORTANCE
Regulation of rabies virus polymerase complex by viral and cellular factors thus far has not been fully understood. Although cellular dynein light chain 1 (DLC1) has been reported to increase primary transcription by binding to polymerase cofactor phosphoprotein P, the detailed mechanism is unknown, and it is also not known whether the large enzymatic polymerase subunit L is involved. By fluorescence microscopy analysis of fluorescence-tagged rabies virus L,
in silico
identification of a potential DLC1 binding site in L, and characterization of recombinant rabies virus mutants, we show that a DLC1 binding motif in L is involved in cytoskeleton localization and reorganization, primary transcription regulation by DLC1, and regulation of cellular DLC1 gene expression. By providing evidence for a direct contribution of a DLC1 binding motif in L, our data significantly increase the understanding of rabies virus polymerase regulation and host manipulation by the virus as well.
Structural Basis of Human Parechovirus Neutralization by Human Monoclonal Antibodies
Authors: Shakeel Shabih , Westerhuis Brenda M. , Ora Ari , Koen Gerrit , Bakker Arjen Q. , Claassen Yvonne , Wagner Koen , Beaumont Tim , Wolthers Katja C. , Butcher Sarah J.
Published: July 2015

Since it was first recognized in 2004 that human parechoviruses (HPeV) are a significant cause of central nervous system and neonatal sepsis, their clinical importance, primarily in children, has started to emerge. Intravenous immunoglobulin treatment is the only treatment available in such life-threatening cases and has given moderate success. Direct inhibition of parechovirus infection using monoclonal antibodies is a potential treatment. We have developed two neutralizing monoclonal antibodies against HPeV1 and HPeV2, namely, AM18 and AM28, which also cross-neutralize other viruses. Here, we present the mapping of their epitopes using peptide scanning, surface plasmon resonance, fluorescence-based thermal shift assays, electron cryomicroscopy, and image reconstruction. We determined by peptide scanning and surface plasmon resonance that AM18 recognizes a linear epitope motif including the arginine-glycine-aspartic acid on the C terminus of capsid protein VP1. This epitope is normally used by the virus to attach to host cell surface integrins during entry and is found in 3 other viruses that AM18 neutralizes. Therefore, AM18 is likely to cause virus neutralization by aggregation and by blocking integrin binding to the capsid. Further, we show by electron cryomicroscopy, three-dimensional reconstruction, and pseudoatomic model fitting that ordered RNA interacts with HPeV1 VP1 and VP3. AM28 recognizes quaternary epitopes on the capsid composed of VP0 and VP3 loops from neighboring pentamers, thereby increasing the RNA accessibility temperature for the virus-AM28 complex compared to the virus alone. Thus, inhibition of RNA uncoating probably contributes to neutralization by AM28.

IMPORTANCE
Human parechoviruses can cause mild infections to severe diseases in young children, such as neonatal sepsis, encephalitis, and cardiomyopathy. Intravenous immunoglobulin treatment is the only treatment available in such life-threatening cases. In order to develop more targeted treatment, we have searched for human monoclonal antibodies that would neutralize human parechoviruses 1 and 2, associated with mild infections such as gastroenteritis and severe infections of the central nervous system, and thus allow safe treatment. In the current study, we show how two such promising antibodies interact with the virus, modeling the atomic interactions between the virus and the antibody to propose how neutralization occurs. Both antibodies can cause aggregation; in addition, one antibody interferes with the virus recognizing its target cell, while the other, recognizing only the whole virus, inhibits the genome uncoating and replication in the cell.
Isolated pancreatic cysticercal cyst presenting as a diagnostic challenge: diagnosis and treatment review
Authors: Sharma Raman , Neogi Sushanto
Published: July 2015

Human cysticercosis most commonly affects the subcutaneous tissues, skeletal muscles, lungs, brain, eyes, liver and, rarely, the heart, thyroid and pancreas. Owing to vague clinical presentation and unfamiliarity of clinicians with this entity, it is difficult to diagnosis when seen as an isolated cyst. We present a case of a 16-year-old boy who presented with an upper abdominal lump and jaundice. Ultrasonography (USG) and MRI of the abdomen were carried out, which revealed a cystic mass (8.5×7×7 cm) in the pancreas. No evidence of solid component or papillary projections was noted within the lesion. Tumour markers carcinoembryonic antigen (CEA) and cancer antigen (CA 19-9) were normal. Fine needle aspiration cytology was performed, which revealed the presence of cysticercus larvae, along with a foreign body giant cell reaction. The patient was treated with therapeutic aspiration and antihelminthic therapy. Since then, he has been symptom free and under regular follow-up for the last 1 year. A diagnosis of cysticercal cyst at atypical sites is very rare and depends mainly on histopathological examination, which, along with USG and MRI, can give an accurate analysis. These cysts can be very well treated non-surgically with antihelminthics and aspiration.
Depression among patients with tuberculosis: determinants, course and impact on pathways to care and treatment outcomes in a primary care setting in southern Ethiopia—a study protocol
Authors: Ambaw Fentie , Mayston Rosie , Hanlon Charlotte , Alem Atalay
Published: July 2015

Introduction

Depression is commonly comorbid with chronic physical illnesses and is associated with a range of adverse clinical outcomes. Currently, the literature on the role of depression in determining the course and outcome of tuberculosis (TB) is very limited.

Aim

Our aim is to examine the relationship between depression and TB among people newly diagnosed and accessing care for TB in a rural Ethiopian setting. Our objectives are to investigate: the prevalence and determinants of probable depression, the role of depression in influencing pathways to treatment of TB, the incidence of depression during treatment, the impact of anti-TB treatment on the prognosis of depression and the impact of depression on the outcomes of TB treatment.

Methods and analysis

We will use a prospective cohort design. 703 newly diagnosed cases of TB (469 without depression and 234 with depression) will be consecutively recruited from primary care health centres. Data collection will take place at baseline, 2 and 6 months after treatment initiation. The primary exposure variable is probable depression measured using the Patient Health Questionnaire-9. Outcome variables include: pathways to treatment, classical outcomes for anti-TB treatment quality of life and disability. Descriptive statistics, logistic regression and multilevel mixed-effect analysis will be used to test the study hypotheses.

Ethics and dissemination

Ethical approval has been obtained from the Institutional Review Board (IRB) of the College of Health Sciences, Addis Ababa University. Findings will be disseminated through scientific publications, conference presentations, community meetings and policy briefs.

Anticipated impact

Findings will contribute to a sparse evidence base on comorbidity of depression and TB. We hope the dissemination of findings will raise awareness of comorbidity among clinicians and service providers, and contribute to ongoing debates regarding the delivery of mental healthcare in primary care in Ethiopia.
New tumour antigen PLAC1/CP1, a potentially useful prognostic marker and immunotherapy target for gastric adenocarcinoma
Authors: Liu Fangfang , Shen Danhua , Kang Xiaoping , Zhang Chunfang , Song Qiujing
Published: July 2015

Aim

To evaluate protein expression and clinical significance of PLAC1/CP1 antigen in primary gastric adenocarcinoma.

Methods

Protein expression of PLAC1/CP1 was analysed by tissue chip and immunohistochemistry in surgical specimens obtained from 119 patients with gastric cancer. The data were analysed using SPSS V.16.0 software applying the χ2test and Kaplan-Meier method.

Results

The positive expression frequency of PLAC1/CP1 protein was 61.3% (73/119 patients). The overall survival of patients with PLAC1/CP1 protein-positive expression was significantly lower than that of patients with PLAC1/CP1 protein-negative expression (p<0.05). There was no significant relationship between PLAC1/CP1 expression and patient gender, age, tumour position, tumour size, differentiation, gross type, lymph node or TNM stage.

Conclusions

PLAC1/CP1 protein is expressed in over half of cases of primary gastric cancer, and PLAC1/CP1 protein expression is inversely correlated with patient survival. The data indicate that PLAC1/CP1 provides a marker for identifying gastric cancers with poor prognosis, and suggest that PLAC1/CP1 may provide a useful target for immunotherapy.
Tackling a mitey problem
Authors: Bartley Kathryn
Published: July 2015

The poultry ectoparasite Dermanyssus gallinae, known to poultry farmers as ‘red mite’, has a negative impact on animal health and is a vector of viruses and bacteria. It also sometimes attacks poultry farm workers, and human infestations have been reported originating from pigeons' nests in urban areas. A European project is currently investigating synergistic and holistic approaches to improving the health, welfare and productivity of laying hens through more effective prevention and control of the red mite. Kathryn Bartley reports from a two‐day conference held in Italy in May, which provided an update on progress with the project
Ionic effects of NaCl counter osmotic inhibition of germination and seedling growth ofScorzonera hispanicaand subsequent plantlet growth is not affected by salt
Authors: Dias Luís Silva , Dias Alexandra Soveral , Pereira Isabel Pires
Published: July 2015

Scorzonera (Scorzonera hispanica L.) is experiencing range reduction in Portugal while its distribution in the Iberian Peninsula largely coincides with areas affected by salinization. Thus, two experiments were conducted to evaluate the response of scorzonera to salinity. In the first experiment, seed germination and seedling growth were investigated under osmotic potentials down to –1.21 MPa using NaCl or iso-osmotic polyethylene glycol (PEG) solutions. Results of PEG treatments show that osmotic potential alone reduces germination and seedling growth while on NaCl reductions were much lower. Ionic effects of NaCl are stimulatory and clearly counteract osmotic effects. Most seeds completed germination after being transferred from PEG to distilled water. Conversely, on NaCl, recovery results essentially from more time allowed for seeds to complete germination. In the second experiment, young plantlets were treated with NaCl solutions up to 250 mmol·L−1. In general, plantlets were insensitive to NaCl except for a concentration-dependent increase of relative chlorophyll content, suggesting that scorzonera tolerance to NaCl might depend upon nitrogen availability. Altogether, results support the conclusion that scorzonera may be a naturally salt tolerant species able to accumulate and sequester NaCl, with its tolerance increasing as plants grow older.
Semi-automated identification of construction safety requirements using ontological and document modeling techniques
Authors: Wang Han-Hsiang
Published: July 2015

Construction safety is important in the domains of architecture, engineering, and construction. However, studies have rarely discussed safety issues from the perspectives of employers or employees’ ignorance of safety requirements. A novel approach with modeling and reasoning functionalities is applied for semi-automated identification of safety requirements from construction safety standards. The proposed approach is based on ontological modeling and document modeling techniques. These techniques model safety concepts and requirements in semantically-rich, human-readable and computer-interpretable format. These features further enable reasoning about the concepts and requirements needed to identify applicable safety requirements. Test cases are used to validate the approach and illustrate its advantages. Validation results are discussed, and conclusions and directions for future research are given. The proposed approach can benefit construction safety by improving participants’ awareness of safety requirements.