bluuebunny/crossref_metadata_2025 huggingface dataset:
Design Approach for Large Foil Bearings Considering Rotordynamics
Authors: Honavara Prasad Srikanth , Kim Daejong
Published: August 2017

In recent years, gas foil bearings have gained increased attention due to potential applications in aerospace systems. Research and development efforts have been focused towards simplifying design and analysis methods or experimentally demonstrating stable bearing performance under various operating conditions. Many researchers have proposed design guidelines for parameters such as load capacity, stiffness, and damping etc., for extending the state of the art based on experimental data available in existing literature. The authors previously presented scaling laws for radial clearance and support structure stiffness of radial foil bearings. In that study, the criteria for selecting radial clearance and support structure stiffness for scale up or scale down of an existing bearing design was presented. In addition, the results from that paper showed that a hydrodynamic film could be sustained for large bearings (up to 300 mm diameter) demonstrating that the bearings would have adequate load capacity. However, the rotordynamic effects for the various bearing sizes were not considered in that study. This paper serves as an extension of the paper on scaling laws by the same authors. The subject of this paper is a four degree of freedom (4-DOF) rotordynamic analysis performed for turbomachinery systems that employ bearings designed using the scaling laws for radial clearance and support structure stiffness. Further, case studies to show feasibility of foil bearings for applications in Mega Watt range turbo blowers and turbo compressors is presented.
Study of Interlaminar Fracture Properties of Ceramic Matrix Composites at Room and Elevated Temperatures
Authors: Mansour Rabih , Singh Yogesh P. , Kannan Manigandan , Morscher Gregory N. , Abdi Frank , Ahmad Jalees , Godines Cody , DorMohammadi Saber , Choi Sung
Published: August 2017

Interlaminar fracture properties play an important role in predicting failure of structural components for CMC materials. In engine applications, components are subject to large thermal gradients which induce interlaminar stresses. One of the main challenges in evaluating interlaminar fracture toughness at room and elevated temperatures is the development of an experimental setup that provides ease for testing and allows for in-situ monitoring of the interlaminar crack growth. Therefore, a wedge-loaded DCB testing method is developed. The method utilize electrical resistance to monitor crack growth and was applied to a woven polymer infiltrated pyrolysis (PIP) SiC/SiNC composite. Post-testing inspection was carried out using optical microscopy of polished cross-sections, showing crack morphology. It was found that crack growth rate at room temperature is double the one at 815 °C for initial tests in this composite system. Estimates of Mode I energy release rate suggests flat R-curve behavior at room temperature in comparison to rising R-curve behavior at 815 °C.
Transonic Fan Performance Evaluated With Different Solution Limiters
Authors: Carpenter Forrest L. , Cizmas Paul G. A.
Published: August 2017

This paper presents an investigation of the effect of different solution limiters on the prediction of the performance of a transonic fan. The Dervieux, Venkatakrishnan, and Multidimensional Limiting Process (MLP) limiters were considered. In addition, a new limiter is presented that combines the amount of limiting proposed by Park and Kim with the Venkatakrishnan limiter function. The implementation of the new limiter was first tested on an inviscid convergent-divergent nozzle for flows with or without a discontinuity. The results of the nozzle tests were in excellent agreement with the analytic result. The NASA Rotor 67 geometry was then used to assess the limiter’s usefulness in computing turbomachinery flows. Both an inviscid and a turbulent configuration were considered. The inviscid results showed improved convergence for the new limiter over the Venkatakrishnan limiter. Good agreement with experimental data was seen for both the inviscid and turbulent test configurations.
A Probabilistic Simulation of Grain Size Effect on Small Crack Growth in a Nickel Based Superalloy
Authors: Hu Dianyin , Mao Jianxing , Wang Rongqiao , Song Jun , Wang Xiyuan
Published: August 2017

Considerable efforts have been conducted on the modeling of fatigue crack growth (FCG), aiming at an accurate prediction of fatigue life. However, due to the influence of microstructure, it is still challenging to describe FCG behavior, especially for small cracks.

The FCG exhibits obvious variation at small crack growth procedure. In this regard, a probabilistic model by integrating N-R model is proposed to simulate the FCG process at stage I. The concerned material is nickel based superalloy GH4169.

The proposed model involves both macroscopic and microscopic material parameters for the extension of dislocation with the impediment from grain boundary. Random grain size is represented by the fluctuation of FCG rate. Model validation is performed by comparing the simulation results and experimental data. It is revealed that the dependence tends to be less prominent on longer crack length, smaller grain size and higher applied stress.
Combustion Instabilities in a Lean Premixed Pre-Vaporized Combustor at High-Pressure High-Temperature
Authors: Han Xiao , Hui Xin , Zhang Chi , Lin Yuzhen , He Pei , Sung Chih-Jen
Published: August 2017

Experimental results correlating combustion instability and staging ratio in a RP-3 fueled lean premixed pre-vaporized (LPP) combustor is presented. All the experiments are operated at high-pressure and high-temperature conditions, and processed data has been collected and classified by the staging ratio. A low-frequency oscillation is found in the conditions that the main stage and pilot stage work together. There are two discrete frequencies laying in 50∼120 Hz and 420∼470 Hz, the former changes with staging ratio (SR) while the latter remains constant. Sensitivity analysis of flame model reveals that the low-frequency oscillation at 50∼120 Hz is highly suspected to be caused by an intrinsic mode of this combustor. RANS simulation of flame structure finds that delay time could be extended by decreasing SR, which is consistent with the theoretical analysis.
Twin-Fluid Atomized Spray Combustion of Straight Vegetable Oil at Elevated Pressures
Authors: Niguse Yonas G. , Agrawal Ajay K.
Published: August 2017

The effect of the chamber pressure on combustion of a twin-fluid-atomized spray of straight vegetable oil (VO) in a swirl stabilized combustion system is experimentally studied. A system with high pressure capabilities was developed, and flame and emissions characteristics of VO are investigated at elevated pressures, up to about 5 bars, different heat release rates and atomizing air to liquid ratios (ALR) by mass. An image analysis technique was developed to infer flame and soot characteristics from visual images acquired by a digital camera. An increase in the ALR improved combustion characterized by blue flames, lower CO and NOx emissions, and minimal soot formation. For a given fuel flow rate, an increase in the chamber pressure resulted in smaller volume flames with lower CO levels but higher NOx emissions. Compared to diesel, as pressure increased, straight VO flames produced lower NOx and more voluminous flames characterized by distributed combustion with less soot formation. Overall, straight VO could be atomized and combusted at elevated pressures using the twin-fluid atomizer of the present study, and the resulting VO flames exhibited less sensitivity to chamber pressure variations.
Low-NOx Combustion of Fuel Spray-Air Mixtures From a Converging Splitter in a Co-Swirling Annular Air Flow
Authors: Oide Shunsaku , Iwakura Masanao , Takaoka Mai , Kasuga Shunsuke , Hayashi Shigeru
Published: August 2017

A unique burner consisting of a pressure swirl atomizer, a converging outer shroud, a coaxially assembled converging splitter, and coaxial swirlers at the inlets of the inner and outer circuits is being developed for low-NOx emissions (below 0.5 g/kg-fuel) at the higher inlet air temperatures and better flame stability at the lower inlet air temperatures. Liquid fuel is atomized only into the air flowing in the inner circuit and the resulting mixture jet is injected into the combustion chamber from the exit of the splitter, surrounded by the annular swirling air jet from the outer circuit. Emissions measurements, direct flame imaging, and Mie scattering imaging of the sprays were conducted for inner swirler vane angles of 40 and 50 degrees and a fixed outer swirler vane angle of 45 degrees at inlet air temperatures of 453 to 753 K (a 100-degree step) and atmospheric pressure. A lifted flame was stabilized with the flame front at a distance from the burner exit. Direct flame images were successfully used to correlate the NOx emissions with flame structure. Additionally, local gas sampling was done at 753 K. The measured distributions of equivalence ratio and of chemical species concentrations in the combustion chamber were used to explain the lower NOx emissions for the smaller vane angle.
On the Reliability of RANS Turbulence Models for Endwall Cooling Prediction
Authors: Li Xueying , Ren Jing , Jiang Hongde
Published: August 2017

The large scale coherent structures in the flow field of film cooling makes it difficult for the modeling of film cooling flow and heat transfer. The interaction between the complex secondary flows near the endwall and the film cooling jets makes it even worse.

A typical flat vane endwall with/without film cooling is investigated experimentally and numerically. The aerodynamic and heat transfer of the endwall is measured. Adiabatic film cooling effectiveness is measured using PSP technique and conjugate overall cooling effectiveness is measured by TSP technique for different conditions. The coolant to mainstream massflow ratio (MFR) is varied from 0.5% to 1.5% in the experiment. Several RANS turbulence models are tested in the prediction of endwall aerodynamics, heat transfer, film cooling and conjugate heat transfer. Detailed analyses of the computational results are performed. The algebraic anisotropic turbulence model proposed previously aiming at a more accurate modeling of the Reynolds stress and turbulent scalar flux is employed in the study.

The SST with transition model shows advantage in the prediction of endwall flow field and film cooling with high blowing ratios which is detached from the surface. The Realizable k-epsilon model is more suitable for predicting attached film cooling and conjugate heat transfer of the endwall. The algebraic anisotropic models show better agreement with the experimental data qualitatively and quantitatively for both adiabatic and conjugate situations.
First and Second Law Analysis of Radical Intercooling Concepts
Authors: Thulin Oskar , Petit Olivier , Xisto Carlos , Zhao Xin , Grönstedt Tomas
Published: August 2017

An exergy framework was developed taking into consideration a detailed analysis of the heat exchanger (intercooler) component irreversibilities. Moreover, it was further extended to include an adequate formulation for closed systems, e.g. a secondary cycle, moving with the aircraft. Afterwards the proposed framework was employed to study two radical intercooling concepts. The first proposed concept uses already available wetted surfaces, i.e. nacelle surfaces, to reject the core heat and contribute to an overall drag reduction. The second concept uses the rejected core heat to power a secondary organic Rankine cycle and produces useful power to the aircraft-engine system. Both radical concepts are integrated into a high bypass ratio turbofan engine, with technology levels assumed to be available by year 2025. A reference intercooled cycle incorporating a heat exchanger in the bypass duct is established for comparison. Results indicate that the radical intercooling concepts studied in this paper show similar performance levels to the reference cycle. This is mainly due to higher irreversibility rates created during the heat exchange process. A detailed assessment of the irreversibility contributors, including the considered heat exchangers and the secondary cycle major components is made. A striking strength of the present analysis is the assessment of the component irreversibility rate and its contribution to the overall aero-engine losses.
Comparing Human Driven and Automatic Blade Row Aerodynamic Designs
Authors: Puente Ricardo , Corral Roque , Parra Jorge
Published: August 2017

In this paper a fast automatic design environment is developed, making use of a well established and validated turbomachinery design software system for geometry generation and flow analysis. The design is updated via a gradient based algorithm, where gradients are obtained via the adjoint method. The computational advantages of Graphics Processing Units are used to accelerate the mesh generation and flow analysis stages. The capabilities of the system are illustrated by automatically generating two Low Pressure Turbine vanes, and comparing them to the ones arrived at by a human designer, respecting the same explicit design criteria. The quality of the automatically designed airfoils is assessed against the human generated ones, and insight on the influence of implicit criteria is extracted. It is concluded that acceptable quality geometries can be designed automatically in a short time. For instance, the automatic procedure takes of the order of two days for an equivalent human driven case, where the designer took of the order of two weeks.
A Numerical Study of Secondary Flows in a 1.5 Stage Axial Turbine Guiding the Design of a Non-Axisymmetric Hub
Authors: Obaida Hayder M. B. , Kadhim Hakim T. K. , Rona Aldo , Leschke Katrin , Gostelow J. Paul
Published: August 2017

The performance of axial flow turbines is affected by losses from secondary flows that result in entropy generation. Reducing these secondary flow losses improves the turbine performance. This paper investigates the effect of applying a non-axisymmetric contour to the hub of a representative one-and-half stage axial turbine on the turbine performance. An analytical end-wall hub surface definition with a guide groove is used to direct the pressure side branch of the horseshoe vortex away from the blade suction side, so to retard its interaction with the suction side secondary flow and thus decrease the losses. This groove design is a development of the concept outlined in Obaida et al. (2016). A baseline three-dimensional steady RANS k-ω SST model, with axisymmetric walls, is validated against reference experimental measurements from a one-and-half stage turbine at the Institute of Jet Propulsion and Turbomachinery at RWTH Aachen, Germany. The CFD predictions of the non-axisymmetric hub with the guide groove show a decrease in the total pressure loss coefficient. The design work-flow is generated using the Alstom Process and Optimisation Workbench (APOW), which sensibly reduced the designer workload. The implementation of the guide groove has excellent portability to the turbomachinery industry and this makes this method promising for delivering the UK energy agenda through more efficient power turbines.
Further Development and Initial Validation of Innovative DES-Based Approaches for the Prediction of Jet Noise Installation Effects
Authors: Mockett Charles , Fuchs Marian , Kramer Felix , Michel Ulf , Thiele Frank , Steger Mathias
Published: August 2017

Further development and validation of an innovative DES-based methodology for the prediction of jet noise from installed configurations is presented. A Grey-Area improved Delayed Detached-Eddy Simulation (DDES) model has been implemented in an industrial solver and validated for a static single-stream jet. The measured far-field sound directivity was predicted to within 2 dB and frequencies up to around St = 2 to 3 were resolved on a grid of 15.4M cells. To address the key problem of defining a suitable location of the data surface for Ffowcs Williams & Hawkings (FWH) far-field integration, a sensor function based on a statistical evaluation of the vorticity magnitude is proposed. This is applied to a complex installed jet/wing configuration, for which predicted far-field noise levels are shown. A strong increase in noise due to the presence of the wing of up to 18 dB in the forward arc is reported. This interaction noise becomes stronger and shifts to higher frequencies when the wing is moved closer to the jet.
Gas Turbine Combined Cycle Optimized for Post-Combustion Carbon Capture
Authors: Gülen S. Can , Hall Chris
Published: August 2017

This paper describes a gas turbine combined cycle (GTCC) power plant system, which addresses the three key design challenges of post-combustion CO2 capture from the stack gas of a GTCC power plant using aqueous amine-based scrubbing method by offering the following: (i) low heat recovery steam generator (HRSG) stack gas temperature, (ii) increased HRSG stack gas CO2 content and (iii) decreased HRSG stack gas O2 content. This is achieved by combining two bottoming cycle modifications in an inventive manner, i.e., (i) high supplementary (duct) firing in the HRSG and (ii) recirculation of the HRSG stack gas. It is shown that, compared to an existing natural gas-fired GTCC power plant with post-combustion capture, it is possible to reduce the CO2 capture penalty — power diverted away from generation — by almost 65 percent and the overall capital cost ($/kW) by about 35 percent.
Nanofluidic/nanoelectronic study on solvent-processed nanoscale organic transistors
Authors: Li Da , Ryu Byunghoon , Cui Qingyu , Chen Mikai , Jay Guo Lingjie , Ma Biwu , Liang Xiaogan
Published: August 2017

Organic thin-film transistors (OTFTs) and other organic electronic devices have attracted more and more attention for next-generation wearable and flexible devices. Because of low conductivity of organic materials, working OTFTs need a channel structure with a very large aspect ratio (or ratio between channel width and length) to enable a sizable drive current. Therefore, to produce densely arranged OTFTs with microscale footprint areas, the OTFT channel length needs to be scaled down to sub-100 nm regimes. To enable cost-effective manufacturing of such nanoscale OTFT arrays, solvent-processing methods, such as spin-coating and roll-to-roll coating, are highly desirable, but such processes inevitably result in air voids in nanoscale OTFT channels, leading to poor and inconsistent gate modulation characteristics. In this work, the authors reveal the nanofluidic mechanisms responsible for the formation of air voids through characterizing the cross-sectional morphologies of as-fabricated nanoscale OTFT channels using electron microscopy and simulating the nanofluidic flows of organic materials into nanoscale transistor channel gaps using a computational fluidic dynamics tool. This work suggests that a post-fabrication thermal pressing process is needed for eliminating air voids and significantly improving gate modulation characteristics. Using this process, the authors demonstrate poly(3-hexylthiophene) OTFT arrays with channel length of 66 nm, which exhibits highly consistent on/off ratios up to ∼106. This work advances the technical and scientific knowledge for processing solution-based organic electronic materials into nanoscale devices. The presented thermal pressing process can be generically implemented for processing a broad range of solution-based organic materials.
Fabrication of hard x-ray zone plates with high aspect ratio using metal-assisted chemical etching
Authors: Li Kenan , Wojcik Michael J. , Divan Ralu , Ocola Leonidas E. , Shi Bing , Rosenmann Daniel , Jacobsen Chris
Published: August 2017

Fresnel zone plates are widely used as nanofocusing optics for x-ray microscopy, where the spatial resolution is set by the width of the finest rings while the efficiency is set by their thickness. This leads to the requirement for high aspect ratio nanofabrication. Metal-assisted chemical etching and atomic layer deposition has already been used to produce high aspect ratio zone plate structures on unthinned silicon wafers. The authors demonstrate here a substantial improvement on the achieved aspect ratio up to a value of 500:1, by producing 16 nm wide platinum zones with thicknesses up to 8 μm. At the same time, the silicon substrate was thinned to 15 μm as required for a practically useful optic. First tests have shown 4.8% diffraction efficiency using 20 keV x rays. This x-ray focusing efficiency is higher than most Fresnel zone plates for this photon energy and near what has been achieved with multilayer-coated Kirkpatrick–Baez mirrors, and multilayer Laue lenses. Hard x-ray zone plates offer the advantages of easy alignment, energy tunability, and one can make many zone plates in a batch on a single silicon chip.
Fabrication and comparative study of DC and low frequency noise characterization of GaN/AlGaN based MOS-HEMT and HEMT
Authors: Hasan Md Rezaul , Motayed Abhishek , Fahad Md Shamiul , Rao Mulpuri V.
Published: August 2017

This work presents the effect of Al mole fraction and gate oxide on the direct current and low frequency noise characterization of GaN/AlGaN high electron mobility transistor (HEMT). Metal–oxide–semiconductor (MOS)-HEMT with SiO2 in the gate stack improved the Id(on)/Id(off) ratio up to more than 8 orders, compared to fabricated HEMT without oxide. It was shown that the gate leakage and isolation leakage suppression efficiency improved dramatically with the gate oxide. Subthreshold swing of MOS-HEMTs with different Al mole fractions (from 20% to 35%) varies slightly from 72 mV/decade to 79 mV/decade. Low frequency noise study revealed the difference in transport mechanism between HEMT and MOS-HEMTs. By using carrier number fluctuation model on the measured data, it was found that the noise is predominantly coming from the surface states. While generation-recombination is very prominent in HEMT, it is very insignificant in both MOS-HEMTs at much higher frequencies. This study reveals that very high number of surface states, assisting the tunneling in Schottky/AlGaN barrier is responsible for unusually high leakage and higher noise level in HEMT without oxide. Leakage level is improved from mA/mm range for HEMT to pA/mm range for MOS-HEMTs. Leakage suppression improvement and minimization of noise level can be mainly attributed by to high quality SiO2. Hooge's constant was on the order of 5–6 × 10−3, which is 5 × 10−2 for HEMT without oxide.
Seismic evidence for complex sedimentary control of Greenland Ice Sheet flow
Authors: Kulessa Bernd , Hubbard Alun L. , Booth Adam D. , Bougamont Marion , Dow Christine F. , Doyle Samuel H. , Christoffersen Poul , Lindbäck Katrin , Pettersson Rickard , Fitzpatrick Andrew A. W. , Jones Glenn A.
Published: August 2017

Seismic data show that subglacial sediment slip causes a complex flow response of the Greenland Ice Sheet to climate warming.
Carryover effects of larval exposure to different environmental bacteria drive adult trait variation in a mosquito vector
Authors: Dickson Laura B. , Jiolle Davy , Minard Guillaume , Moltini-Conclois Isabelle , Volant Stevenn , Ghozlane Amine , Bouchier Christiane , Ayala Diego , Paupy Christophe , Moro Claire Valiente , Lambrechts Louis
Published: August 2017

The adult phenotype of mosquitoes depends on the types of bacteria encountered environmentally during development.
2.7-million-year-old ice opens window on past
Authors: Voosen Paul
Published: August 2017

Record-setting Antarctic core holds atmospheric carbon dioxide from start of the ice ages.
Australia to ax support for long-term ecology sites
Authors: Pickrell John
Published: August 2017

Threat leaves scientists scrambling to find alternative funding.
Astrophysics missions vie for NASA money
Authors: Clery Daniel
Published: August 2017

Three finalists for $250 million Explorer slot would probe exoplanets, galaxies, big bang.
On the trail of yellow fever
Authors: Kean Sam
Published: August 2017

Monkeys and mosquitoes hold clues to when and where the virus could resurge in Brazil.
Two-dimensional sp
2
carbon–conjugated covalent organic frameworks
Authors: Jin Enquan , Asada Mizue , Xu Qing , Dalapati Sasanka , Addicoat Matthew A. , Brady Michael A. , Xu Hong , Nakamura Toshikazu , Heine Thomas , Chen Qiuhong , Jiang Donglin
Published: August 2017

Conjugated covalent networks

Although graphene and related materials are two-dimensional (2D) fully conjugated networks, similar covalent organic frameworks (COFs) could offer tailored electronic and magnetic properties. Jin
et al.
synthesized a fully π-conjugated COF through condensation reactions of tetrakis(4-formylphenyl)pyrene and 1,4-phenylenediacetonitrile. The reactions were reversible, which provides the self-healing needed to form a crystalline material of stacked, π-bonded 2D sheets. Chemical oxidation of this semiconductor with iodine greatly enhanced its conductivity, and the radicals formed on the pyrene centers imparted a high spin density and paramagnetism.

Science
, this issue p.
673
Ductal sex determination
Authors: Swain Amanda
Published: August 2017

Females actively eliminate male reproductive ducts during mammalian embryogenesis
Circulating peptide prevents preeclampsia
Authors: Wirka Robert C. , Quertermous Thomas
Published: August 2017

Mouse ELA has a critical role in placental development and function, with implications for human pregnancy
Functional neuroimaging of high-risk 6-month-old infants predicts a diagnosis of autism at 24 months of age
Authors: Emerson Robert W. , Adams Chloe , Nishino Tomoyuki , Hazlett Heather Cody , Wolff Jason J. , Zwaigenbaum Lonnie , Constantino John N. , Shen Mark D. , Swanson Meghan R. , Elison Jed T. , Kandala Sridhar , Estes Annette M. , Botteron Kelly N. , Collins Louis , Dager Stephen R. , Evans Alan C. , Gerig Guido , Gu Hongbin , McKinstry Robert C. , Paterson Sarah , Schultz Robert T. , Styner Martin ,   IBIS Network, Schlaggar Bradley L. , Pruett John R. , Piven Joseph
Published: August 2017

Functional brain imaging of 6-month-old infants with a high familial risk for autism predicts a diagnosis of autism at 24 months of age.
Drugging the catalytically inactive state of RET kinase in RET-rearranged tumors
Authors: Plenker Dennis , Riedel Maximilian , Brägelmann Johannes , Dammert Marcel A. , Chauhan Rakhee , Knowles Phillip P. , Lorenz Carina , Keul Marina , Bührmann Mike , Pagel Oliver , Tischler Verena , Scheel Andreas H. , Schütte Daniel , Song Yanrui , Stark Justina , Mrugalla Florian , Alber Yannic , Richters André , Engel Julian , Leenders Frauke , Heuckmann Johannes M. , Wolf Jürgen , Diebold Joachim , Pall Georg , Peifer Martin , Aerts Maarten , Gevaert Kris , Zahedi René P. , Buettner Reinhard , Shokat Kevan M. , McDonald Neil Q. , Kast Stefan M. , Gautschi Oliver , Thomas Roman K. , Sos Martin L.
Published: August 2017

An examination of the activity profiles of RET inhibitors suggests potential treatment for
RET
-rearranged cancers.
A trust approach for sharing research reagents
Authors: Edwards Aled , Morgan Max , Al Chawaf Arij , Andrusiak Kerry , Charney Rachel , Cynader Zarya , ElDessouki Ahmed , Lee Yunjeong , Moeser Andrew , Stern Simon , Zuercher William J.
Published: August 2017

The core feature of trusts—holding property for the benefit of others—is well suited to constructing a research community that treats reagents as public goods.
Vaccine priming is restricted to draining lymph nodes and controlled by adjuvant-mediated antigen uptake
Authors: Liang Frank , Lindgren Gustaf , Sandgren Kerrie J. , Thompson Elizabeth A. , Francica Joseph R. , Seubert Anja , De Gregorio Ennio , Barnett Susan , O’Hagan Derek T. , Sullivan Nancy J. , Koup Richard A. , Seder Robert A. , Loré Karin
Published: August 2017

Vaccine responses are initiated in vaccine-draining lymph nodes and depend on the efficiency by which adjuvants influence antigen uptake.
The effects of treatment failure generalize across different routes of drug administration
Authors: Zunhammer Matthias , Ploner Markus , Engelbrecht Charlotte , Bock Johanna , Kessner Simon S. , Bingel Ulrike
Published: August 2017

A change in route of drug administration is not sufficient to counter carry-over effects of treatment failure to subsequent treatment attempts.
Combined immune checkpoint blockade as a therapeutic strategy for
BRCA1
-mutated breast cancer
Authors: Nolan Emma , Savas Peter , Policheni Antonia N. , Darcy Phillip K. , Vaillant François , Mintoff Christopher P. , Dushyanthen Sathana , Mansour Mariam , Pang Jia-Min B. , Fox Stephen B. ,   Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab), Perou Charles M. , Visvader Jane E. , Gray Daniel H. D. , Loi Sherene , Lindeman Geoffrey J.
Published: August 2017

BRCA1
-mutated tumors may be particularly vulnerable to dual checkpoint inhibition.
Say good night to your pain
Authors: Lehtinen Maria K.
Published: August 2017

Sleep deprivation induces pain hypersensitivity that can be reversed by increasing alertness.
Anti-VEGF AAV2 injections: The fewer the better
Authors: Byrne Leah C.
Published: August 2017

A single intravitreal injection of AAV2 provides sustained delivery of anti-VEGF protein for the treatment of neovascular AMD.
It’s reticulated: Diabetes, atherosclerosis, and reticulated platelets
Authors: Dupnik Kathryn
Published: August 2017

New research describes regulatory pathways for reticulated thrombocytosis in a mouse model of diabetes.
Zinc Salts Block Hepatitis E Virus Replication by Inhibiting the Activity of Viral RNA-Dependent RNA Polymerase
Authors: Kaushik Nidhi , Subramani Chandru , Anang Saumya , Muthumohan Rajagopalan , Shalimar  , Nayak Baibaswata , Ranjith-Kumar C. T. , Surjit Milan
Published: August 2017

Hepatitis E virus (HEV) causes an acute, self-limiting hepatitis in healthy individuals and leads to chronic disease in immunocompromised individuals. HEV infection in pregnant women results in a more severe outcome, with the mortality rate going up to 30%. Though the virus usually causes sporadic infection, epidemics have been reported in developing and resource-starved countries. No specific antiviral exists against HEV. A combination of interferon and ribavirin therapy has been used to control the disease with some success. Zinc is an essential micronutrient that plays crucial roles in multiple cellular processes. Zinc salts are known to be effective in reducing infections caused by few viruses. Here, we investigated the effect of zinc salts on HEV replication. In a human hepatoma cell (Huh7) culture model, zinc salts inhibited the replication of genotype 1 (g-1) and g-3 HEV replicons and g-1 HEV infectious genomic RNA in a dose-dependent manner. Analysis of a replication-defective mutant of g-1 HEV genomic RNA under similar conditions ruled out the possibility of zinc salts acting on replication-independent processes. An ORF4-Huh7 cell line-based infection model of g-1 HEV further confirmed the above observations. Zinc salts did not show any effect on the entry of g-1 HEV into the host cell. Furthermore, our data reveal that zinc salts directly inhibit the activity of viral RNA-dependent RNA polymerase (RdRp), leading to inhibition of viral replication. Taken together, these studies unravel the ability of zinc salts in inhibiting HEV replication, suggesting their possible therapeutic value in controlling HEV infection.

IMPORTANCEHepatitis E virus (HEV) is a public health concern in resource-starved countries due to frequent outbreaks. It is also emerging as a health concern in developed countries owing to its ability to cause acute and chronic infection in organ transplant and immunocompromised individuals. Although antivirals such as ribavirin have been used to treat HEV cases, there are known side effects and limitations of such therapy. Our discovery of the ability of zinc salts to block HEV replication by virtue of their ability to inhibit the activity of viral RdRp is important because these findings pave the way to test the efficacy of zinc supplementation therapy in HEV-infected patients. Since zinc supplementation therapy is known to be safe in healthy individuals and since high-dose zinc is used in the treatment of Wilson's disease, it may be possible to control HEV-associated health problems following a similar treatment regimen.
Extracellular Matrix Proteins Mediate HIV-1 gp120 Interactions with α4β7
Authors: Plotnik David , Guo Wenjin , Cleveland Brad , von Haller Priska , Eng Jimmy K. , Guttman Miklos , Lee Kelly K. , Arthos James , Hu Shiu-Lok
Published: August 2017

Gut-homing α4β7highCD4+T lymphocytes have been shown to be preferentially targeted by human immunodeficiency virus type 1 (HIV-1) and are implicated in HIV-1 pathogenesis. Previous studies demonstrated that HIV-1 envelope protein gp120 binds and signals through α4β7and that this likely contributes to the infection of α4β7highT cells and promotes cell-to-cell virus transmission. Structures within the second variable loop (V2) of gp120, including the tripeptide motif LDV/I, are thought to mediate gp120-α4β7binding. However, lack of α4β7binding has been reported in gp120 proteins containing LDV/I, and the precise determinants of gp120-α4β7binding are not fully defined. In this work, we report the novel finding that fibronectins mediate indirect gp120-α4β7interactions. We show that Chinese hamster ovary (CHO) cells used to express recombinant gp120 produced fibronectins and other extracellular matrix proteins that copurified with gp120. CHO cell fibronectins were able to mediate the binding of a diverse panel of gp120 proteins to α4β7in anin vitrocell binding assay. The V2 loop was not required for fibronectin-mediated binding of gp120 to α4β7, nor did V2-specific antibodies block this interaction. Removal of fibronectin through anion-exchange chromatography abrogated V2-independent gp120-α4β7binding. Additionally, we showed a recombinant human fibronectin fragment mediated gp120-α4β7interactions similarly to CHO cell fibronectin. These findings provide an explanation for the apparently contradictory observations regarding the gp120-α4β7interaction and offer new insights into the potential role of fibronectin and other extracellular matrix proteins in HIV-1 biology.

IMPORTANCEImmune tissues within the gut are severely damaged by HIV-1, and this plays an important role in the development of AIDS. Integrin α4β7plays a major role in the trafficking of lymphocytes, including CD4+T cells, into gut lymphoid tissues. Previous reports indicate that some HIV-1 gp120 envelope proteins bind to and signal through α4β7, which may help explain the preferential infection of gut CD4+T cells. In this study, we demonstrate that extracellular matrix proteins can mediate interactions between gp120 and α4β7. This suggests that the extracellular matrix may be an important mediator of HIV-1 interaction with α4β7-expressing cells. These findings provide new insight into the nature of HIV-1–α4β7interactions and how these interactions may represent targets for therapeutic intervention.
BA71ΔCD2: a New Recombinant Live Attenuated African Swine Fever Virus with Cross-Protective Capabilities
Authors: Monteagudo Paula L. , Lacasta Anna , López Elisabeth , Bosch Laia , Collado Javier , Pina-Pedrero Sonia , Correa-Fiz Florencia , Accensi Francesc , Navas María Jesús , Vidal Enric , Bustos María J. , Rodríguez Javier M. , Gallei Andreas , Nikolin Veljko , Salas María L. , Rodríguez Fernando
Published: August 2017

African swine fever is a highly contagious viral disease of mandatory declaration to the World Organization for Animal Health (OIE). The lack of available vaccines makes its control difficult; thus, African swine fever virus (ASFV) represents a major threat to the swine industry. Inactivated vaccines do not confer solid protection against ASFV. Conversely, live attenuated viruses (LAV), either naturally isolated or obtained by genetic manipulation, have demonstrated reliable protection against homologous ASFV strains, although little or no protection has been demonstrated against heterologous viruses. Safety concerns are a major issue for the use of ASFV attenuated vaccine candidates and have hampered their implementation in the field so far. While trying to develop safer and efficient ASFV vaccines, we found that the deletion of the viral CD2v (EP402R) gene highly attenuated the virulent BA71 strain
in vivo
. Inoculation of pigs with the deletion mutant virus BA71ΔCD2 conferred protection not only against lethal challenge with the parental BA71 but also against the heterologous E75 (both genotype I strains). The protection induced was dose dependent, and the cross-protection observed
in vivo
correlated with the ability of BA71ΔCD2 to induce specific CD8
+
T cells capable of recognizing both BA71 and E75 viruses
in vitro
. Interestingly, 100% of the pigs immunized with BA71ΔCD2 also survived lethal challenge with Georgia 2007/1, the genotype II strain of ASFV currently circulating in continental Europe. These results open new avenues to design ASFV cross-protective vaccines, essential to fight ASFV in areas where the virus is endemic and where multiple viruses are circulating.

IMPORTANCE
African swine fever virus (ASFV) remains enzootic in most countries of Sub-Saharan Africa, today representing a major threat for the development of their swine industry. The uncontrolled presence of ASFV has favored its periodic exportation to other countries, the last event being in Georgia in 2007. Since then, ASFV has spread toward neighboring countries, reaching the European Union's east border in 2014. The lack of available vaccines against ASFV makes its control difficult; so far, only live attenuated viruses have demonstrated solid protection against homologous experimental challenges, but they have failed at inducing solid cross-protective immunity against heterologous viruses. Here we describe a new LAV candidate with unique cross-protective abilities: BA71ΔCD2. Inoculation of BA71ΔCD2 protected pigs not only against experimental challenge with BA71, the virulent parental strain, but also against heterologous viruses, including Georgia 2007/1, the genotype II strain of ASFV currently circulating in Eastern Europe.
HIV-1 Exploits a Dynamic Multi-aminoacyl-tRNA Synthetase Complex To Enhance Viral Replication
Authors: Duchon Alice A. , St. Gelais Corine , Titkemeier Nathan , Hatterschide Joshua , Wu Li , Musier-Forsyth Karin
Published: August 2017

A hallmark of retroviruses such as human immunodeficiency virus type 1 (HIV-1) is reverse transcription of genomic RNA to DNA, a process that is primed by cellular tRNAs. HIV-1 recruits human tRNA
Lys3
to serve as the reverse transcription primer via an interaction between lysyl-tRNA synthetase (LysRS) and the HIV-1 Gag polyprotein. LysRS is normally sequestered in a multi-aminoacyl-tRNA synthetase complex (MSC). Previous studies demonstrated that components of the MSC can be mobilized in response to certain cellular stimuli, but how LysRS is redirected from the MSC to viral particles for packaging is unknown. Here, we show that upon HIV-1 infection, a free pool of non-MSC-associated LysRS is observed and partially relocalized to the nucleus. Heat inactivation of HIV-1 blocks nuclear localization of LysRS, but treatment with a reverse transcriptase inhibitor does not, suggesting that the trigger for relocalization occurs prior to reverse transcription. A reduction in HIV-1 infection is observed upon treatment with an inhibitor to mitogen-activated protein kinase that prevents phosphorylation of LysRS on Ser207, release of LysRS from the MSC, and nuclear localization. A phosphomimetic mutant of LysRS (S207D) that lacked the capability to aminoacylate tRNA
Lys3
localized to the nucleus, rescued HIV-1 infectivity, and was packaged into virions. In contrast, a phosphoablative mutant (S207A) remained cytosolic and maintained full aminoacylation activity but failed to rescue infectivity and was not packaged. These findings suggest that HIV-1 takes advantage of the dynamic nature of the MSC to redirect and coopt cellular translation factors to enhance viral replication.

IMPORTANCE
Human tRNA
Lys3
, the primer for reverse transcription, and LysRS are essential host factors packaged into HIV-1 virions. Previous studies found that tRNA
Lys3
packaging depends on interactions between LysRS and HIV-1 Gag; however, many details regarding the mechanism of tRNA
Lys3
and LysRS packaging remain unknown. LysRS is normally sequestered in a high-molecular-weight multi-aminoacyl-tRNA synthetase complex (MSC), restricting the pool of free LysRS-tRNA
Lys
. Mounting evidence suggests that LysRS is released under a variety of stimuli to perform alternative functions within the cell. Here, we show that HIV-1 infection results in a free pool of LysRS that is relocalized to the nucleus of target cells. Blocking this pathway in HIV-1-producing cells resulted in less infectious progeny virions. Understanding the mechanism by which LysRS is recruited into the viral assembly pathway can be exploited for the development of specific and effective therapeutics targeting this nontranslational function.
Chlamydomonas reinhardtii LFO1 Is an IsdG Family Heme Oxygenase
Authors: Lojek Lisa J. , Farrand Allison J. , Wisecaver Jennifer H. , Blaby-Haas Crysten E. , Michel Brian W. , Merchant Sabeeha S. , Rokas Antonis , Skaar Eric P.
Published: August 2017

This work establishes a protein in the freshwater alga
Chlamydomonas reinhardtii
as an IsdG family heme oxygenase. This protein, LFO1, exhibits predicted secondary structure and catalytic residues conserved in IsdG family members, in addition to a chloroplast localization sequence. Additionally, the catabolite that results from the degradation of heme by LFO1 is distinct from that of other heme degradation products. Using LFO1 as a seed, we performed phylogenetic analysis, revealing that the IsdG family is conserved in all domains of life. Additionally,
C. reinhardtii
contains two previously identified HO-1 family heme oxygenases, making
C. reinhardtii
the first organism shown to contain two families of heme oxygenases. These data indicate that
C. reinhardtii
may have unique mechanisms for regulating iron homeostasis within the chloroplast.
Correlation between baseline retinal microstructures in spectral-domain optic coherence tomography and need for early intervention in central serous chorioretinopathy
Authors: Lai Wei-Yu , Tseng Cheui-Lien , Wu Tsung-Tien , Lin Huey-Shyan , Sheu Shwu-Jiuan
Published: August 2017

Purpose

To investigate the association between baseline retinal microstructures observed with spectral-domain optical coherence tomography (OCT) and the need for early intervention in central serous chorioretinopathy (CSC).

Methods

Cases of acute CSC from July 2011 to December 2014 were retrospectively reviewed. OCT images were further classified using six parameters: foveal serous retinal detachment; pigment epithelial detachment; fibrinous exudates in the subretinal space; retinal pigment epithelium bumps; thickened outer retinal layer and hyper-reflective dots in the intraretinal and/or subretinal layer. Correlation among these parameters and the need for intervention was analysed. Receiver operating characteristic (ROC) curves were performed to identify the optimal number of parameters for prediction.

Results

A total of 47 eyes from 47 patients were included. Among these, 25 eyes required treatment. The presence of subretinal hyper-reflective dots was the only OCT factor having significant association with the need for intervention. An ROC curve analysis revealed that the optimal cut-off value (Youden index) was achieved when combining subretinal hyper-reflective dots with aged ≥50 years and female sex for analysis (area under the curve, 0.735; Youden index: 0.425).

Conclusion

The presence of subretinal/intraretinal hyper-reflective dots observed with OCT, female and aged ≥50 years might help predict the need for early intervention in acute CSC.
Device-assisted enteroscopy in the UK: description of a large tertiary case series under conscious sedation
Authors: Pattni Vijay , Tate David J , Terlevich Ana , Marden Peter , Hughes Steve
Published: August 2017

Objective

Device-assisted enteroscopy (DAE) has developed rapidly, particularly with the advent of double-balloon enteroscopy (DBE). This study reports a case series from a UK tertiary centre for DAE across two modalities—DBE and spiral enteroscopy (SE)—under conscious sedation.

Design

Retrospective observational study of 257 enteroscopy procedures from 2008 to 2014. Data were collected on demographics, indications, diagnosis, sedation requirements, duration, complications, tolerance, therapy performed and completion rate. Procedures were performed under conscious sedation using a combination of midazolam, pethidine and fentanyl in a solely outpatient setting.

Results

Obscure gastrointestinal bleeding (OGIB) was the commonest indication for DAE (n=164, 63.8%). Overall, yield of DAE was 47.2% and varied significantly across the indications (p=0.003). There was a greater likelihood of positive findings if the indication was polyposis syndrome (75%), abnormal capsule endoscopy (67%) or OGIB (53%) and in older patients (mean age normal exam 60.3 vs abnormal exam 67.9 years, p<0.001). Higher mean doses of midazolam were used for DBE from above (5.4 mg, SD 2.24) and SE (5.6 mg, SD 2.9) to DBE from below (4.4 mg, SD 1.8). No serious complications were recorded. Tolerance of DAE was good with the majority (240/257, 93.4%) of procedures tolerated with comfort scores 0 or 1. Therapy was performed in 121/257 (47.1%) of procedures. The strongest predictor indications for therapy to be performed at DAE were abnormal capsule endoscopy (88.9%) and occult gastrointestinal (GI) bleeding (54.9%). Completion rates were higher in DBEb (91.8%) compared to DBEa (76.5%) and SE (81.6%).

Conclusion

DAE under conscious sedation is safe and well tolerated. DAE has a high yield if performed for recognised indications and may be safely used to provide therapy where a diagnosis has been made using other modalities.
Serum ghrelin is associated with risk of colorectal adenocarcinomas in the ATBC study
Authors: Murphy Gwen , Cross Amanda J , Dawsey Sanford M , Stanczyk Frank Z , Kamangar Farin , Weinstein Stephanie J , Taylor Philip R , Männistö Satu , Albanes Demetrius , Abnet Christian C , Freedman Neal D
Published: August 2017

Background

Colorectal cancers are the third most common cancers in women and men in the USA. While dietary and lifestyle factors such as Western diet, physical inactivity and obesity have been linked to an increased risk of this malignancy, the mechanisms for these associations are unclear. GI hormones, including ghrelin, are involved in energy balance by mediating appetite and metabolism; however, the association between ghrelin and colorectal cancer has not been studied.

Methods

We conducted a case–control study nested within the all-male Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish smokers (aged 50–69 years) to examine serum ghrelin concentration and colorectal cancer risk. Data from 284 colon and 239 rectal cancers and 523 controls (matched on age, date of blood draw and serum availability) were analysed. ORs and 95% CIs were calculated using multivariable (conditional) logistic regression.

Results

Overall, low-serum ghrelin was significantly associated with increased risk of colorectal cancer (Q1 vs Q4: OR:1.57, 95% CI 1.05 to 2.34). For individuals developing tumours within 10 years of blood draw, those in the lowest quartile of serum ghrelin concentrations were statistically significantly more likely to develop colorectal cancers than those with higher serum ghrelin concentrations (OR: 10.86, 95% CI 5.01 to 23.55). However, for individuals with tumours developing more than 20 years after blood draw, low-serum ghrelin concentrations were associated with a decreased risk of colorectal cancer relative to those with the highest serum ghrelin concentrations (OR: 0.26, 95% CI 0.11 to 0.64).

Conclusion

Low-serum ghrelin was associated with an increased colorectal cancer risk within 10 years of blood draw with a decreased risk for developing colorectal cancer more than 20 years after blood draw. These results suggest that ghrelin concentrations may vary across the carcinogenic process.