bluuebunny/crossref_metadata_2025 huggingface dataset:
Red blood cell transfusion‐transmitted acute hepatitis E in an immunocompetent subject in Europe: a case report
Authors: Riveiro‐Barciela Mar , Sauleda Silvia , Quer Josep , Salvador Fernando , Gregori Josep , Pirón María , Rodríguez‐Frías Francisco , Buti Maria
Published: October 2016

BACKGROUND

Acute hepatitis E in industrialized countries is usually related to intake or manipulation of undercooked or raw meat. Cases of transfusion‐transmitted hepatitis E have rarely been documented in immunosuppressed patients, mainly after receiving frozen plasma.

STUDY DESIGN AND METHODS

A 61‐year‐old man was admitted to hospital for jaundice. His personal history included disseminated bacillus Calmette‐Guerin infection treated with antituberculous drugs. He had received red blood cell (RBC) transfusion 2 months previously, during admission for mycotic aneurysm surgery. Since liver function tests worsened despite stopping antituberculous drugs, other causes of acute hepatitis were explored.

RESULTS

Acute hepatitis E was diagnosed by the presence of both immunoglobulin M and hepatitis E virus (HEV) RNA. Traceback procedure for the 8 RBC units was carried out, and one of the eight archive plasma samples tested positive for HEV RNA, with an estimated viral load of 75,000 IU/mL. Phylogenetic analysis revealed the same HEV strain Genotype 3 in one of the transfused RBC products and in the patient's serum sample.

CONCLUSION

Transfusion of RBCs with detectable HEV RNA is a risk factor for acute hepatitis E in immunocompetent patients in Europe.
GASIFICATION OF OIL PALM EMPTY FRUIT BUNCHES (OPEFB) BRIQUETTES FOR BIO-SYNGAS PRODUCTION
Authors: Nyakuma Bemgba Bevan , Ahmad Arshad , Johari Anwar , T. Abdullah Tuan A. , Oladokun Olagoke , Alkali Habib
Published: October 2016

Gasification of Oil Palm Empty Fruit Bunches (OPEFB) briquettes was investigated in an air blown 4.5 kW allothermal fluidized bed gasifier to examine the effects of bed temperature (600 – 800 °C) and equivalence ratio (λ = 0.25) on bio-syngas yield and composition. In addition, physicochemical and thermochemical characterization of the fuel properties of the OPEFB briquettes were also examined. The results demonstrate that pelletization improved the solid biomass fuel (SBF) properties of OPEFB including moisture content and higher heating value (HHV). The gasification of OPEFB briquettes produced bio-syngas comprising H2, CO, CO2, CH4 as well as solid biochar with a HHV higher than the original OPEFB briquettes. The highest yield of H2 was obtained at 600 °C while HHV of the bio-syngas was within the range 4 - 8 MJ/Nm3 for air gasification in fluidized bed gasifiers. In addition, agglomeration of bed materials did not occur during OPEFB briquettes gasification despite its high bed agglomeration potential (BAP). In conclusion, the gasification of OPEFB briquettes into bio-syngas and biochar is a practical route for bioenergy production in Malaysia
EMISSION FACTOR ESTABLISHMENT FOR PALM OIL MILL BOILER
Authors: Hanafi Nur H. , H. Hassim Mimi , M. Yusuf Mohd R.
Published: October 2016

A study to establish the total particulate emission factor (EFs) from boiler of a palm oil mill plant equipped with a multi-cyclones particulate arrestor was performed and reported in this research. The mill employs a 500 kg steam/ h capacity of water-tube typed boiler and processes 60 tonnes per hour of fresh fruit bunch (FFB). The samples of the dust were collected iso-kinetically using the USEPA method 17 sampling train through a sampling port located after a multidust cyclone unit. Results showed that the total dust generated from the boiler is 62.15 g/s and the calculated total dust emission factor based on the boiler capacity is 7.46 g/kg. Poor combustion process is among the main factor that leads to the high particulate emission. EFs data allows for early prediction of pollutants emission, which subsequently will assist in determining the degree of control and the air pollution control system needed, besides evaluating the effectiveness of the existing pollution control strategies. The establishment of EFs for palm oil mills will definitely bring benefits for a better management of health and safety risks in palm oil mills, now and in the future
OPTIMIZING FLAME SYNTHESIS OF CARBON NANOTUBES: EXPERIMENTAL AND MODELLING PERSPECTIVES
Authors: Zainal Muhammad Thalhah , Mohd Yasin Mohd Fairus , Abdul Wahid Mazlan
Published: October 2016

Synthesis of carbon nanotubes in flames has become highly attractive due to its rapid, inexpensive, and simple method of production. The study of flame synthesis of carbon nanotubes revolves around the control of flame and catalyst parameters to increase the synthesis efficiency and to produce high quality nanotubes. The control parameters include flame temperature, concentration of carbon source species, catalyst type, equivalence ratio, and fuel type. Carbon nanotubes which are produced with rapid growth rate and possess high degree of purity and alignment are often desired. The present study reviews various optimization techniques from the advanced studies of chemical vapour deposition which are applicable for the synthesis of nanotubes in flames. The water-assisted and catalyst free synthesis are seen as possible candidates to improve the growth rate, alignment, and purity of the synthesized nanotubes. The state-of-the-art of the flame synthesis modelling at particle and flame scales are reviewed. Based on the thorough review of the recent experimental findings related to the catalytic growth of nanotube, possible refinement of the existing particle scale model is discussed. The possibility of two-way coupling between the two scales in computational fluid dynamics may be a major contribution towards the optimization of the flame synthesis.
PRESSURE DISTRIBUTION ON THE BLADE SURFACE OF AN AUTOMOTIVE MIXED FLOW TURBOCHARGER TURBINE UNDER PULSATING FLOW CONDITIONS
Authors: Padzillah M.H. , Rajoo S. , Martinez-Botas R.F.
Published: October 2016

The increment of the contribution to CO2 release by transportation industry as other sectors are decarbonizing is evident. As number of world population continue to increase, the task of developing highly downsized high power-to-weight ratio engines are critical. Over more than a hundred years of invention, turbocharger remains a key technology that enable highly boosted efficient engine. Despite its actual operating environment which is pulsating flow, the turbocharger turbine that is available to date is still designed and assessed under the assumption of steady flow conditions. This is attributable to the lack of understanding on the insight of the flow field effect towards the torque generation of the turbine blade under pulsating flow conditions. This paper presents an effort towards investigating the influence of pulsating flow on the blade loading and its differences from steady state conditions through the use of Computational Fluid Dynamics (CFD). For this purpose, a lean-vaned mixed-flow turbine with rotational speed of 30000 rpm at 20 Hz flow frequency, which represent turbine operation for 3-cylinder 4-stroke engine operating at 800 rpm has been used. Results presented in terms of spanwise location of the blade indicated different behavior at each location. Close to the hub, there are strong flow separation that hinders torque generation is seen while at mid-span more torque is generated under unsteady flow as compared to its steady counterpart. Moreover, close to the shroud, the pressure difference between steady and pulsating flow is almost identical
REDUCING SOAK AIR TEMPERATURE INSIDE A CAR COMPARTMENT USING VENTILATION FANS
Authors: Mohamed Kamar Haslinda , Kamsah Nazri , Sabri Intan Sabariah , Musa Md Nor
Published: October 2016

This article presents an investigation on the effects of using ventilation fans on the air temperature inside a car passenger compartment when the car is parked under the sun. It was found from a measurement that the air temperature inside the passenger compartment could raise up to 48°C. Computational fluid dynamics method was used to develop model of the compartment and carry out flow simulations to predict the air temperature distribution at 1 pm for two conditions: without ventilation fans and with ventilation fans. The effects of fan location, number of fans used and fan airflow velocity were examined. Results of flow simulations show that a 17% temperature reduction was achieved when two ventilation fans with airflow velocity of 2.84 m/s were placed at the rear deck. When three fans were used, an additional 3.4% temperature reduction was attained. Placing two ventilation fans at the middle of the roof also reduced the air temperature by 17%. When four fans were used a further 4.8% temperature reduction was achieved. Increasing the airflow velocity at the four fans placed at the roof, from 2.84 m/s to 15.67 m/s, caused only a small reduction in the air temperature inside the passenger compartment
PROPERTIES OF COAL BOTTOM ASH FROM POWER PLANTS IN MALAYSIA AND ITS SUITABILITY AS GEOTECHNICAL ENGINEERING MATERIAL
Authors: Marto Aminaton , Tan Choy Soon
Published: October 2016

Coal is one of the world’s most important sources of energy, fuelling almost 40% of electricity worldwide. Some power plants in Malaysia use coal as a raw material in generating the electricity since the year 1988. During the burning process of coal for the electricity generation, coal waste is produced which includes coal ash in the fraction of about 75-85 % Fly Ash (FA) and 15-25 % Bottom Ash (BA). The FA has been widely used in the cement industry but the BA is still not largely utilised in Malaysia. This might be due to the fears on the environmental hazard that might be occurred as a result of possible leaching of metal from the BA to the ground water. Research on the possible usage of BA in Geotechnical Engineering work has been taken place in Universiti Teknologi Malaysia since 2008, in collaboration with the Tanjung Bin, Sultan Salahuddin Abdul Aziz Shah (or Kapar) and Sultan Azlan Shah (or Manjung) power plants in Johor, Selangor and Perak, respectively. This paper presents the physical, morphological, mineralogical, chemical and mechanical properties of BA and explores the possibility of using BA as alternative materials in Geotechnical Engineering works. Analysis of the results from the laboratory and physical model tests show a huge potential of utilising this BA.
THERMAL PROPERTIES OF MALAYSIAN COHESIVE SOILS
Authors: Amaludin Adriana , Marto Aminaton , M. Satar Muhd. Hatta , Amaludin Hassanel , Dullah Salinah
Published: October 2016

The thermal properties of soils surrounding energy piles are required for the efficient and optimal design of shallow geothermal energy pile systems. In this study, the thermal conductivity, thermal resistivity and volumetric specific heat of two types of Malaysian cohesive soil were obtained through a series of laboratory experiments using a thermal needle probe. This study was conducted to determine the effect of moisture content on the thermal conductivity, thermal resistivity and volumetric specific heat values of the cohesive soil at a given value of soil density. For soils with low to medium moisture content, a linear increase in the thermal conductivity and volumetric heat capacity was observed as the moisture content gradually increased, while the thermal resistivity values of the soil had decreased. Meanwhile, for soils with high moisture content, the thermal conductivity was observed to have decreased, and a marked increase was seen in the thermal resistivity. This is due to the disruption of the thermal flow continuity in the soil matrix with the presence of moisture in the soil which adversely affects the thermal conductivity
CHARACTERISTICS OF BOULDERS FORMED IN TROPICAL WEATHERED GRANITE: A REVIEW
Authors: Md Dan Mohd Firdaus , Mohamad Edy Tonnizam , Komoo Ibrahim
Published: October 2016

Boulder is well known as one of the obstruction material and problematic to the underground excavations and constructions. Although the presence of boulder in weathered rock mass was revealed and reported by many researchers, but the occurrence and physical characteristics of boulders in weathering profile are still not clearly understood.  This paper attempts to revise the issues and characteristics of boulder formed in weathered granite which include the formation, distribution, properties and location of boulders found in tropical weathering profile. As a weathering product, boulder is dominantly found in moderately to completely weathered zone of rock mass (Grade III to V). Boulder consists of corestone Grade I or II and surrounded by some concentric sheet of weathered rock Grade III to V or rindlets which formed due the reaction of spheroidal weathering. The rindlets with thickness ranges 0.2 mm to 2.0 m is the zone of decomposition and dissolution of biotite and feldspar that gradually transforming to saprolite. This information is useful to geotechnical engineers and researchers for engineering purposes and weathering zone classification especially in underground excavation and structure design.
INTEGRATION OF SPT (N-VALUE), MACKINTOSH PROBE (M-VALUE) AND RESISTIVITY VALUES FOR SOFT SOIL ASSESSMENT
Authors: Tarmizi Tarmizi , Saad Rosli , Mohd Muztaza Nordiana , Ismail Nur Azwin , Saidin Mohd Mokhtar , Mohamad Edy Tonnizam
Published: October 2016

2-D resistivity method has been used in association with Mackintosh probe and Standard Penetration Test (SPT) to investigate the ground properties at Universiti Sains Malaysia, Pulau Pinang. The purpose of this study was to determine the resistivity value of the subsurface material together with N-value and M-value of the particular location. The study also aimed to evaluate whether there is any correlation could be made by the parameters measured. Borehole record revealed that two types of soil exist up to 13 m; loose sand and stiff sandy silt. The loose sand recorded N-value of 8 and M-value of 170 having resistivity value of 790 Ohm.m. On the other hand, stiff sandy silt recorded N-value of 9-11, M-value of 135-170 and showing resistivity value of 415-785 Ohm.m. The results showed no clear relation between those geotechnical strength parameters with the resistivity imaging result. It is due to non-existence of distinctive differences in the electrical conductivity of the mentioned ground material when they are in the low strength bracket. However, the resistivity result suggested the presence of higher resistance material that is dry loose sand. The resistivity result was able to detect the water saturated zone near the ground surface, which showed low N-value and M-value
POTENTIAL OF HIGH QUALITY LIMESTONE AS ADSORBENT FOR IRON AND MANGANESE REMOVAL IN GROUNDWATER
Authors: Akbar Nor Azliza , Abdul Aziz Hamidi , Adlan Mohd Nordin
Published: October 2016

Adsorption using low cost of media plays more attention to this current research. Previous literature found that high quality of limestone was effective in removing heavy metals in water and wastewater. In this study, the potential use of limestone media was investigated. Groundwater sample and limestone properties were characterized to determine the physical and chemical composition. The batch experiments were conducted to determine the effect of varied dosage and contact time.   Analysis on isotherm and kinetic was carried out in this study. Batch study results showed that the maximum removal of both Fe and Mn was greater than 95 and 80% respectively which occurs at optimum dosage of 40g. Moreover, the optimum contact time of Fe and Mn was 90 and 120 minutes, respectively. At the optimum contact time, 96.8% of Fe and 87.4 % of Mn was removed using limestone adsorbent media. In isotherm study, the result revealed that Langmuir isotherm fitted the experimental data better than Freundlich isotherm for both Fe and Mn adsorption. In Langmuir isotherm, the maximum adsorption capacity for both Fe and Mn were 0.018mg/g and 0.011mg/g. Based on kinetic study, the removal of Fe and Mn followed the pseudo-second order kinetic model which R2 (>0.99) greater than in pseudo-first order. This indicates that the chemisorption is the mechanism of adsorption, which contributed to the Fe and Mn removal from the groundwater sample. Thus, from these results, limestone could be used as an alternative for the removal of Fe and Mn from groundwater
THE COMPARISON OF EMPIRICAL FORMULA TO PREDICT THE INCIPIENT MOTION OF WEAK COHESIVE SEDIMENT MIXTURE
Authors: Porhemmat Mojtaba , Wan Mohtar Wan Hanna Melini , En Chuah Run , Abd Jalil Juliana
Published: October 2016

Available incipient sediment motion models were mostly developed based on homogeneous non-cohesive sediment. In non-homogeneous sediment mixture, particularly with fraction of cohesive particles might have an effect on the values of incipient sediment motion using the available models. In this study the effects of weak cohesive material on the incipient motion of sand-silt mixture were investigated in laboratory and compared with different existing formulas. Fine sand with median grain size of d50=153 µm was used whilst the cohesive material is kaolinite-silt with d50=28 µm. The sand-silt mixtures were prepared with sand percentage (Sa)/Silt percentage (Si) distributions ranging from 100Sa/0Si to 0Sa/100Si. The condition for incipient sediment motion was defined in categories number 4 (i.e. frequent particle movement at nearly all locations) and number 6 (i.e. permanent particle movement at all locations) of 7 categories introduced by the Delft Hydraulic. Values of critical Shields parameter were monotonously increased as the percentage of silt increased but reached a relatively constant value as the silt percentage reached 50%. Comparing the data for the particular sediment range used in this study proved that the Brownlie, Van Rijn and Miedema relationships are capable to calculate the Shields parameter within the range of category 4 and 6
Model Ḥalālan Ṭayyibā Berdasarkan Tafsiran Istilah Sarjana Mufasir al-Quran
Authors: Wan Harun Mohammad Amir
Published: October 2016

This article discuss on the development of Ḥalālan Ṭayyibā Model (MHT) based on term interpretation which was described by the mufasir al-Quran scholars. Implementation of the research driven due the attention increasing of Ḥalālan Ṭayyibā branding in the halal market which lead to the emergence of various versions of Ḥalālan Ṭayyibā interpretations, thus creating chances of manipulations by certain parties. In order to reintegrate the existed various interpretations of Ḥalālan Ṭayyibā, this research explored the true interpretation of Ḥalālan Ṭayyibā described by mufasir al-Quran scholars. Data was collected using non-probability sampling based on Documentary Research design from 20 Quran tafsirs including tafsīr bi al-ma’thūr, tafsīr bi al-ra’y, and tafsīr bi al-ra’y / al-mu‘āṣir. Afterwards the data was analysed inductive thematically using Nvivo10 software to develop the finding themes and to identify the percentage of frequency analysis units. The findings discovered six principles of Ḥalālan Ṭayyibā; halal (100%), accepted by purely and prosperous soul (65%), hygiene (55%), nutritious (45%), safe (40%) and syubhah-free (25%). Thus, this research suggests the Ḥalālan Ṭayyibā Model to be benefited by authorities agencies for making a benchmark of Ḥalālan Ṭayyibā branding to be followed by every Ḥalālan Ṭayyibā product entrepreneurs.
Pemindahan Hak Milik Dalam Instrumen Al-Ijarah Thumma Al-Bay’ (AITAB) di Malaysia
Authors: Muhammad Zin Hakimah , Salamon Hussin , Abdullah Nurdianawati Irwani
Published: October 2016

The transfer of ownership at the end of a leasing contract is an important element in al-ijarah thumma al-bay’ (AITAB) structure.  In AITAB structure, the ownership is transferred from owner to the hirer by the execution of a sale contract upon the expiry of the lease contract.  The execution of sale contract must satisfy Shariah requirements.  Nonetheless, legal framework of Islamic financial system in Malaysia which is subjected to civil law; and the absence of a comprehensive regulatory framework to govern AITAB transaction has caused the practice of AITAB in Malaysia to be subjected to the Hire Purchase Act 1967.  Therefore, this study aims to identify the Shariah and legal issues that would arise in the implementation of ownership transfer in AITAB instrument as practised in Malaysia. This study also intends to determine the extent to which the Act is compatible to govern and enforce Syariah requirements in the execution of ownership transfer in AITAB transaction.  This study employs qualitative methodology through document  analysis.  In its analysis, this study applies three methods; inductive, deductive and comparative methods.  It analyses Syariah requirements in relations to ownership transfer and compares with the Hire Purchase Act 1967.  The study also analyses the practice of ownership transfer in AITAB transaction in Malaysia.  The finding of the study shows that the Hire Purchase Act 1967 possesses loopholes to govern and enforce Syariah requirements on ownership transfer in AITAB.  Thus, the execution of ownership transfer in AITAB though satisfy Shariah requirements, would encounter legal issues.
Ratib al-Attas Menurut Perspektif al-Quran dan Hadis
Authors: Mohsin Mohd Azman , Md Baharudin Md Hamzaimi Azrol , Abdullah Nasri , Md. Sawari Siti Salwa , Napiah Othman , Mohd. Noor Sulaiman Shakib , Jasmi Kamarul Azmi
Published: October 2016

This article aims to evaluate the source of 17 dhikr in Ratib al-Άttas based on Quran, Hadith and scholar views on the meaning and purpose of dhikr. Applications Ratib al-Attas ceremony was conducted over 90 years ago in the state of Johor. In addition, the application Ratib al-Άttas assessment and justification is given from the perspective of Islamic practices. The method used is by clarifying the position of remembrance 17 Ratib al-Άttas more reliable by practitioners; avoid confusion and misunderstanding of the doctrine of Ratib al-Attas. The results showed that all 17 dhikr Ratib al-Άttas and the practice carried out are consistent with the arguments of al-Quran and Hadith. Based on this finding several suggestions is made to encourage the expend development of dhikr al-Άttas Ratib practice among the Muslim community in Malaysia.
Optimization of Carbon Black Polymer Composite Microstructure for Rupture Resistance
Authors: San Bingbing , Waisman Haim
Published: October 2016

Optimization of material microstructure is strongly tied with the performance of composite materials at the macroscale and can be used to control desired macroscopic properties. In this paper, we study the optimal location of carbon black (CB) particle inclusions in a natural rubber (NR) matrix with the objective to maximize the rupture resistance of such polymer composites. Hyperelasticity is used to model the rubber matrix and stiff inclusions, and the phase field method is used to model the fracture accounting for large deformation kinematics. A genetic algorithm is employed to solve the inverse problem in which three parameters are proposed as optimization objective, including maximum peak force, maximum deformation at failure-point, and maximum fracture energy at failure-point. Two kinds of optimization variables, continuous and discrete variables, are adopted to describe the location of particles, and several numerical examples are carried out to provide insight into the optimal locations for different objectives.
Modeling and Analysis for Thermal Management in Gallium Nitride HEMTs Using Microfluidic Cooling
Authors: Agarwal Gunjan , Kazior Thomas , Kenny Thomas , Weinstein Dana
Published: October 2016

In this paper, thermal management in GaN (gallium nitride) based microelectronic devices is addressed using microfluidic cooling. Numerical modeling is done using finite element analysis (FEA), and the results for temperature distribution are presented for a system comprising multiple cooling channels underneath GaN high-electron mobility transistors (HEMTs). The thermal stack modeled is compatible for heterogeneous integration with conventional silicon-based CMOS devices. Parametric studies for cooling performance are done over a range of geometric and flow factors to determine the optimal cooling configuration within the specified constraints. A power dissipation of 2–4 W/mm is modeled along each HEMT finger in the proposed configuration. The cooling arrangements modeled here hold promising potential for implementation in high-performance radio-frequency (RF) systems for power amplifiers, transmission lines, and other applications in defense and military.
Transmission electron imaging in the Delft multibeam scanning electron microscope 1
Authors: Ren Yan , Kruit Pieter
Published: October 2016

Our group is developing a multibeam scanning electron microscope (SEM) with 196 beams in order to increase the throughput of SEM. Three imaging systems using, respectively, transmission electron detection, secondary electron detection, and backscatter electron detection are designed in order to make it as versatile as a single beam SEM. This paper focuses on the realization of the transmission electron imaging system, which is motivated by biologists' interest in the particular contrast this can give. A thin sample is placed on fluorescent material which converts the transmitted electrons to photons. Then, the 196 photon beams are focused with a large magnification onto a camera via a high quality optical microscope integrated inside the vacuum chamber. Intensities of the transmission beams are retrieved from the camera images and constructed to form each beam's image using an off line image processing program. Experimental results prove the working principle of transmission electron imaging and show that details of 10–20 nm in images of biological specimen are visible. Problems encountered in the results are discussed and plans for future improvements are suggested.
Long-term data storage in diamond
Authors: Dhomkar Siddharth , Henshaw Jacob , Jayakumar Harishankar , Meriles Carlos A.
Published: October 2016

Optical control of trapped charge in diamond makes it possible to store and retrieve arbitrary data sets in three dimensions.
Gravity field of the Orientale basin from the Gravity Recovery and Interior Laboratory Mission
Authors: Zuber Maria T. , Smith David E. , Neumann Gregory A. , Goossens Sander , Andrews-Hanna Jeffrey C. , Head James W. , Kiefer Walter S. , Asmar Sami W. , Konopliv Alexander S. , Lemoine Frank G. , Matsuyama Isamu , Melosh H. Jay , McGovern Patrick J. , Nimmo Francis , Phillips Roger J. , Solomon Sean C. , Taylor G. Jeffrey , Watkins Michael M. , Wieczorek Mark A. , Williams James G. , Jansen Johanna C. , Johnson Brandon C. , Keane James T. , Mazarico Erwan , Miljković Katarina , Park Ryan S. , Soderblom Jason M. , Yuan Dah-Ning
Published: October 2016

On the origin of Orientale basin

Orientale basin is a major impact crater on the Moon, which is hard to see from Earth because it is right on the western edge of the lunar nearside. Relatively undisturbed by later events, Orientale serves as a prototype for understanding large impact craters throughout the solar system. Zuber
et al.
used the Gravity Recovery and Interior Laboratory (GRAIL) mission to map the gravitational field around the crater in great detail by flying the twin spacecraft as little as 2 km above the surface. Johnson
et al.
performed a sophisticated computer simulation of the impact and its subsequent evolution, designed to match the data from GRAIL. Together, these studies reveal how major impacts affect the lunar surface and will aid our understanding of other impacts on rocky planets and moons.

Science
, this issue pp.
438
and
441
Dealing with details in Marrakesh
Authors: Espinosa Patricia
Published: October 2016

Over the next few weeks, two major events will take place—the 2015 Paris Agreement on climate change will enter into force on 4 November, and 3 days later, nearly 200 countries will convene in Marrakesh, Morocco, at the 22nd United Nations (UN) Conference of the Parties (COP22) to decide on how to rapidly implement the agreement. Indeed, the agreement's governing body will hold its first meeting during COP22. This swift action to commit and come up with climate action plans is a welcome departure for the international community, and it sends a clear message that success in tackling climate challenges requires more than just a historic political agreement.
Interferon Regulatory Factor 1 and Type I Interferon Cooperate To Control Acute Gammaherpesvirus Infection
Authors: Mboko Wadzanai P. , Rekow Michaela M. , Ledwith Mitchell P. , Lange Philip T. , Schmitz Kaitlin E. , Anderson Sean , Tarakanova Vera L.
Published: October 2016

Gammaherpesviruses are ubiquitous pathogens that establish lifelong infection in >95% of adults worldwide and are associated with a variety of malignancies. Coevolution of gammaherpesviruses with their hosts has resulted in an intricate relationship between the virus and the host immune system, and perturbation of the virus-host balance results in pathology. Interferon regulatory factor 1 (IRF-1) is a tumor suppressor that is also involved in the regulation of innate and adaptive immune responses. Here, we show that type I interferon (IFN) and IRF-1 cooperate to control acute gammaherpesvirus infection. Specifically, we demonstrate that a combination of IRF-1 and type I IFN signaling ensures host survival during acute gammaherpesvirus infection and supports IFN gamma-mediated suppression of viral replication. Thus, our studies reveal an intriguing cross talk between IRF-1 and type I and II IFNs in the induction of the antiviral state during acute gammaherpesvirus infection.

IMPORTANCE
Gammaherpesviruses establish chronic infection in a majority of adults, and this long-term infection is associated with virus-driven development of a range of malignancies. In contrast, a brief period of active gammaherpesvirus replication during acute infection of a naive host is subclinical in most individuals. Here, we discovered that a combination of type I interferon (IFN) signaling and interferon regulatory factor 1 (IRF-1) expression is required to ensure survival of a gammaherpesvirus-infected host past the first 8 days of infection. Specifically, both type I IFN receptor and IRF-1 expression potentiated antiviral effects of type II IFN to restrict gammaherpesvirus replication
in vivo
, in the lungs, and
in vitro
, in primary macrophage cultures.
Dysregulated Glycoprotein B-Mediated Cell-Cell Fusion Disrupts Varicella-Zoster Virus and Host Gene Transcription during Infection
Authors: Oliver Stefan L. , Yang Edward , Arvin Ann M.
Published: October 2016

The highly conserved herpesvirus glycoprotein complex gB/gH-gL mediates membrane fusion during virion entry and cell-cell fusion. Varicella-zoster virus (VZV) characteristically forms multinucleated cells, or syncytia, during the infection of human tissues, but little is known about this process. The cytoplasmic domain of VZV gB (gB
cyt
) has been implicated in cell-cell fusion regulation because a gB[Y881F] substitution causes hyperfusion. gB
cyt
regulation is necessary for VZV pathogenesis, as the hyperfusogenic mutant gB[Y881F] is severely attenuated in human skin xenografts. In this study, gB
cyt
-regulated fusion was investigated by comparing melanoma cells infected with wild-type-like VZV or hyperfusogenic mutants. The gB[Y881F] mutant exhibited dramatically accelerated syncytium formation in melanoma cells caused by fusion of infected cells with many uninfected cells, increased cytoskeleton reorganization, and rapid displacement of nuclei to dense central structures compared to pOka using live-cell confocal microscopy. VZV and human transcriptomes were concurrently investigated using whole transcriptome sequencing (RNA-seq) to identify viral and cellular responses induced when gB
cyt
regulation was disrupted by the gB[Y881F] substitution. The expression of four vital VZV genes, ORF61 and the genes for glycoproteins gC, gE, and gI, was significantly reduced at 36 h postinfection for the hyperfusogenic mutants. Importantly, hierarchical clustering demonstrated an association of differential gene expression with dysregulated gB
cyt
-mediated fusion. A subset of Ras GTPase genes linked to membrane remodeling were upregulated in cells infected with the hyperfusogenic mutants. These data implicate gB
cyt
in the regulation of gB fusion function that, if unmodulated, triggers cellular processes leading to hyperfusion that attenuates VZV infection.

IMPORTANCE
The highly infectious, human-restricted pathogen varicella-zoster virus (VZV) causes chickenpox and shingles. Postherpetic neuralgia (PHN) is a common complication of shingles that manifests as prolonged excruciating pain, which has proven difficult to treat. The formation of fused multinucleated cells in ganglia might be associated with this condition. An effective vaccine against VZV is available but not recommended for immunocompromised individuals, highlighting the need for new therapies. This study investigated the viral and cellular responses to hyperfusion, a condition where the usual constraints of cell membranes are overcome and cells form multinucleated cells. This process hinders VZV and is regulated by a viral glycoprotein, gB. A combination of live-cell imaging and next-generation genomics revealed an alteration in viral and cellular responses during hyperfusion that was caused by the loss of gB regulation. These studies reveal mechanisms central to VZV pathogenesis, potentially leading to improved therapies.
The Glycoprotein B Cytoplasmic Domain Lysine Cluster Is Critical for Varicella-Zoster Virus Cell-Cell Fusion Regulation and Infection
Authors: Yang Edward , Arvin Ann M. , Oliver Stefan L.
Published: October 2016

The conserved glycoproteins gB and gH-gL are essential for herpesvirus entry and cell-cell fusion induced syncytium formation, a characteristic of varicella-zoster virus (VZV) pathology in skin and sensory ganglia. VZV syncytium formation, which has been implicated in the painful condition of postherpetic neuralgia, is regulated by the cytoplasmic domains of gB (gBcyt) via an immunoreceptor tyrosine-based inhibition motif (ITIM) and gH (gHcyt). A lysine cluster (K894, K897, K898, and K900) in the VZV gBcyt was identified by sequence alignment to be conserved among alphaherpesviruses, suggesting a functional role. Alanine and arginine substitutions were used to determine if the positive charge and susceptibility to posttranslational modifications of these lysines contributed to gB/gH-gL cell-cell fusion. Critically, the positive charge of the lysine residues was necessary for fusion regulation, as alanine substitutions induced a 440% increase in fusion compared to that of the wild-type gBcyt while arginine substitutions had wild-type-like fusion levels in an
in vitro
gB/gH-gL cell fusion assay. Consistent with these results, the alanine substitutions in the viral genome caused exaggerated syncytium formation, reduced VZV titers (−1.5 log
10
), and smaller plaques than with the parental Oka (pOka) strain. In contrast, arginine substitutions resulted in syncytia with only 2-fold more nuclei, a −0.5-log
10
reduction in titers, and pOka-like plaques. VZV mutants with both an ITIM mutation and either alanine or arginine substitutions had reduced titers and small plaques but differed in syncytium morphology. Thus, effective VZV propagation is dependent on cell-cell fusion regulation by the conserved gBcyt lysine cluster, in addition to the gBcyt ITIM and the gHcyt.

IMPORTANCE
Varicella-zoster virus (VZV) is a ubiquitous pathogen that causes chickenpox and shingles. Individuals afflicted with shingles risk developing the painful condition of postherpetic neuralgia (PHN), which has been difficult to treat because the underlying cause is not well understood. Additional therapies are needed, as the current vaccine is not recommended for immunocompromised individuals and its efficacy decreases with the age of the recipient. VZV is known to induce the formation of multinuclear cells in neuronal tissue, which has been proposed to be a factor contributing to PHN. This study examines the role of a lysine cluster in the cytoplasmic domain of the VZV fusion protein, gB, in the formation of VZV induced multinuclear cells and in virus replication kinetics and spread. The findings further elucidate how VZV self-regulates multinuclear cell formation and may provide insight into the development of new PHN therapies.
Simultaneous Deletion of the
9GL
and
UK
Genes from the African Swine Fever Virus Georgia 2007 Isolate Offers Increased Safety and Protection against Homologous Challenge
Authors: O'Donnell Vivian , Risatti Guillermo R. , Holinka Lauren G. , Krug Peter W. , Carlson Jolene , Velazquez-Salinas Lauro , Azzinaro Paul A. , Gladue Douglas P. , Borca Manuel V.
Published: October 2016

African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal viral disease of domestic pigs that has significant economic consequences for the swine industry. The control of African swine fever (ASF) has been hampered by the unavailability of vaccines. Successful experimental vaccines have been derived from naturally occurring, cell culture-adapted, or genetically modified live attenuated ASFV. Recombinant viruses harboring engineered deletions of specific virulence-associated genes induce solid protection against challenge with parental viruses. Deletion of the
9GL
(
B119L
) gene in the highly virulent ASFV isolates Malawi Lil-20/1 (Mal) and Pretoriuskop/96/4 (Δ9GL viruses) resulted in complete protection when challenged with parental isolates. When similar deletions were created within the ASFV Georgia 2007 (ASFV-G) genome, attenuation was achieved but the protective and lethal doses were too similar. To enhance attenuation of ASFV-G, we deleted another gene,
UK
(
DP96R
), which was previously shown to be involved in attenuation of the ASFV E70 isolate. Here, we report the construction of a double-gene-deletion recombinant virus, ASFV-G-Δ9GL/ΔUK. When administered intramuscularly (i.m.) to swine, there was no induction of disease, even at high doses (10
6
HAD
50
). Importantly, animals infected with 10
4
50% hemadsorbing doses (HAD
50
) of ASFV-G-Δ9GL/ΔUK were protected as early as 14 days postinoculation when challenged with ASFV-G. The presence of protection correlates with the appearance of serum anti-ASFV antibodies, but not with virus-specific circulating ASFV-specific gamma interferon (IFN-γ)-producing cells. ASFV-G-Δ9GL/ΔUK is the first rationally designed experimental ASFV vaccine that protects against the highly virulent ASFV Georgia 2007 isolate as early as 2 weeks postvaccination.

IMPORTANCE
Currently, there is no commercially available vaccine against African swine fever. Outbreaks of the disease are devastating to the swine industry and are caused by circulating strains of African swine fever virus. Here, we report a putative vaccine derived from a currently circulating strain but containing two deletions in two separate areas of the virus, allowing increased safety. Using this genetically modified virus, we were able to vaccinate swine and protect them from developing ASF. We were able to achieve protection from disease as early as 2 weeks after vaccination, even when the pigs were exposed to a higher than normal concentration of ASFV.
CD8
+
T Cells and Macrophages Regulate Pathogenesis in a Mouse Model of Middle East Respiratory Syndrome
Authors: Coleman Christopher M. , Sisk Jeanne M. , Halasz Gabor , Zhong Jixin , Beck Sarah E. , Matthews Krystal L. , Venkataraman Thiagarajan , Rajagopalan Sanjay , Kyratsous Christos A. , Frieman Matthew B.
Published: October 2016

Middle East respiratory syndrome coronavirus (MERS-CoV) is an important emerging pathogen that was first described in 2012. While the cell surface receptor for MERS-CoV has been identified as dipeptidyl peptidase 4 (DPP4), the mouse DPP4 homologue does not allow virus entry into cells. Therefore, development of mouse models of MERS-CoV has been hampered by the fact that MERS-CoV does not replicate in commonly available mouse strains. We have previously described a mouse model in which mDPP4 was replaced with hDPP4 such that hDPP4 is expressed under the endogenous mDPP4 promoter. In this study, we used this mouse model to analyze the host response to MERS-CoV infection using immunological assays and transcriptome analysis. Depletion of CD4
+
T cells, CD8
+
T cells, or macrophages has no effect on MERS-CoV replication in the lungs of infected mice. However, we found that depletion of CD8
+
T cells protects and depletion of macrophages exacerbates MERS-CoV-induced pathology and clinical symptoms of disease. Overall, we demonstrate an important role for the inflammatory response in regulating MERS-CoV pathogenesis
in vivo
.

IMPORTANCE
The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic respiratory virus that emerged from zoonotic sources in 2012. Human infections are still occurring throughout Saudi Arabia at a 38% case fatality rate, with the potential for worldwide spread via air travel. In this work, we identify the host response to the virus and identify inflammatory pathways and cell populations that are critical for protection from severe lung disease. By understanding the immune response to MERS-CoV we can develop targeted therapies to inhibit pathogenesis in the future.
Remission of pre-diabetes to normal glucose tolerance in obese adults with high protein versus high carbohydrate diet: randomized control trial
Authors: Stentz Frankie B , Brewer Amy , Wan Jim , Garber Channing , Daniels Blake , Sands Chris , Kitabchi Abbas E
Published: October 2016

Objective

Remission of pre-diabetes to normal is an important health concern which has had little success in the past. This study objective was to determine the effect on remission of pre-diabetes with a high protein (HP) versus high carbohydrate (HC) diet and effects on metabolic parameters, lean and fat body mass in prediabetic, obese subjects after 6 months of dietary intervention.

Research design and methods

We recruited and randomized 24 pre-diabetes women and men to either a HP (30% protein, 30% fat, 40% carbohydrate; n=12) or HC (15% protein, 30% fat, 55% carbohydrate; n=12) diet feeding study for 6 months in this randomized controlled trial. All meals were provided to subjects for 6 months with daily food menus for HP or HC compliance with weekly food pick-up and weight measurements. At baseline and after 6 months on the respective diets oral glucose tolerance and meal tolerance tests were performed with glucose and insulin measurements and dual energy X-ray absorptiometry scans.

Results

After 6 months on the HP diet, 100% of the subjects had remission of their pre-diabetes to normal glucose tolerance, whereas only 33.3% of subjects on the HC diet had remission of their pre-diabetes. The HP diet group exhibited significant improvement in (1) insulin sensitivity (p=0.001), (2) cardiovascular risk factors (p=0.04), (3) inflammatory cytokines (p=0.001), (4) oxidative stress (p=0.001), (5) increased percent lean body mass (p=0.001) compared with the HC diet at 6 months.

Conclusions

This is the first dietary intervention feeding study, to the best of our knowledge, to report 100% remission of pre-diabetes with a HP diet and significant improvement in metabolic parameters and anti-inflammatory effects compared with a HC diet at 6 months.

Trial registration number

NCT0164284.
Injury incidence in a Premier League youth soccer academy using the consensus statement: a prospective cohort study
Authors: Renshaw Andrew , Goodwin Peter C
Published: October 2016

Background

There is an established risk of injury to young athletes exposed to high training loads. Identifying and monitoring injury risk is essential to aid prevention. The aim of this study was to use the consensus statement to determine the incidence and pattern of injury in 1 English Premier League soccer academy during 1 season.

Methods

A prospective cohort study included 181 elite academy soccer players during the 2012–2013 season. Players were divided into 5 age groups between 9 and 18 years. The number, type and incidence of injuries were recorded during matches and training. Incidence was calculated per 1000 hours of exposure.

Results

127 injuries occurred during 29 346 hours of soccer exposure. 72% of injuries were non-contact related. Under (U)18 players sustained the highest number of match injuries. U12–14 players sustained the highest number of training injuries and injuries overall. U16 players sustained the highest number of severe injuries, and U18 players sustained the highest number of moderate injuries. U18 players sustained the highest number of injuries/1000 hours of training and overall. U15 players sustained the highest number of injuries/1000 hours of matches, the highest number of recurrent injuries and the highest incidence of recurrence. The most common injuries were muscle injuries in U15 and U18 players. The most common injury location was the anterior thigh, with the majority of these occurring in training.

Conclusions

Using the consensus statement, this study used a repeatable method to identify the injury profile of elite academy-level soccer players.
Injection‐site lesion prevalence and potential risk factors in UK beef cattle
Authors: Cresswell E. , Remnant J. , Butterworth A. , Wapenaar W.
Published: October 2016

Injectable veterinary medicinal products (VMPs) are widely used in cattle in the UK, and in particular vaccines are often used on large numbers of animals in the herd. The formation of injection‐site lesions (ISLs) is a risk when using injectable products and has potential consequences for meat quality, animal welfare and beef industry income. This study used carcase observation in four abattoirs in England to determine ISL prevalence in beef cattle. Additionally, a questionnaire survey was used to investigate vaccination technique among UK beef farmers. The ISL prevalence was 4.1 per cent (95 per cent CI 3.4 per cent to 4.9 per cent). A potential difference between sites being used for vaccination and the distribution of ISLs on carcases suggested that factors other than vaccination were contributing to ISL incidence. Questionnaire responses highlighted deficits in good vaccination practices such as using the recommended site of injection and needle hygiene. The role of the veterinarian in knowledge transfer is crucial in providing practical injection advice when prescribing vaccines and other VMPs. This study identified factors to address when aiming to reduce ISL formation in UK beef animals.