bluuebunny/crossref_metadata_2025 huggingface dataset:
Extending the Life of F-Class Gas Turbine Rotors
Authors: Keller Scott , Day David
Published: August 2018

Unlike more mature E-Class heavy duty gas turbine rotors, F-Class gas turbine rotors have exhibited a variety of failure mechanisms over the past 20 years. From the liberation of nickel turbine posts to large (600 mm) cracks in marriage components, F-Class rotors have failed to achieve the reliability of older units. Now as the F-Class units are approaching the OEM-recommended end of life (EOL), operators are struggling to repair and/or replace as operations and maintenance (O&M) budgets are dwindling. As such, end users are routinely forced to turn to other service providers to provide targeted (limited) inspections aimed at extending the life of these capital parts. While suitable for more mature rotor systems, recent EOL investigations into multiple OEM F-Class rotors have revealed significant issues with limited inspections.

Utilizing comprehensive non-destructive testing (NDT), forging defects and surface cracks have been discovered throughout compressor and turbine rotors. However, inspection alone cannot determine if adequate life remains when an indication is found. In addition to the inspections, recommended analytical modeling and requisite material test data for CrMoV, NiCrMoV, and IN706 rotor materials will be overviewed. In some cases, the NDT indications have resulted in the retirement of individual components, as analytical predictions could not provide a suitable extension for those particular components. The concern is highlighted that a significant amount of these findings were in the cold end of the compressor, which would have been missed with more traditional, limited inspections. The goal of this paper is to provide the end user the information to reliably and safely extend the life of their rotor beyond the original OEM recommendation.
Influences of Micro Pin-Fin on Jet Array Impingement Heat Transfer: Effects of Jet to Target Distance, Micro Pin-Fin Shapes, Height, and Reynolds Number
Authors: Lu Xunfeng , Li Weihong , Li Xueying , Ren Jing , Jiang Hongde
Published: August 2018

In the current research of impingement on pin-fin wall, researchers mainly pay attention to macro pin-fin due to the limitation of manufacture. With the development of additive manufacturing, it is possible to manufacture the micro pin-fin. Hence, impingement on micro pin-fin wall becomes a new cooling technique that has attracted the researchers’ attention. With experimental methodology, the investigation utilizes different jet to target distance, micro pin-fin shapes, height and Reynolds number for impingement cooling augmentation to illustrate the effects on jet array impingement heat transfer. The area-averaged target surface heat transfer coefficient distributions are measured with lumped capacitance method. The impingement hole diameter (D) is 4 millimeter, with streamwise and spanwise jet-to-jet spacing 4D. Considered are effects of jet to target plate distance (Z/D:0.75,3), micro pin-fin shapes (rectangle, pentahedron), and pin-fin height (h/D:0.05,0.2,0.4). In total, ten different test surfaces are considered (smooth surface included). Tests are performed at impingement jet Reynolds numbers from 2000 to 10000 for configuration of Z/D = 0.75, from 5000–20000 for configuration of Z/D = 3.

The experimental results illustrate that there are significant heat transfer augmentation (30%–120% more than baseline flow condition) with micro pin-fin on impingement target surface, and discharge coefficient is almost the same.
The Comparison of Aerodynamic Performance Data Acquired From Thermal Measurements and a Torquemeter on a Compressor Impeller
Authors: Smith Natalie R. , Clarke Christopher , Allison Timothy C. , Cave Michael , Wilkes Jason C.
Published: August 2018

Full-thermal heat-soak of machinery is vital to acquiring accurate aerodynamic performance data, but this process often requires significant testing time to allow for all facility components to reach a steady state temperature. Even still, there is the potential for heat loss in a well-insulated facility, and this can lead to inaccurate results. The implementation of a torquemeter to calculate performance metrics, such as isentropic efficiency, has two potential advantages: 1) the method is not susceptible to effects due to thermal heat loss in the facility, and 2) a torquemeter directly measures actual torque, and thus work, input, which eliminates the need to fully heat-soak to measure the actual enthalpy rise of the gas. This paper presents a comparison of aerodynamic performance metrics calculated both from data acquired with thermal measurements as well as from a torquemeter.

These tests were conducted over five speedlines for a shrouded impeller in the Southwest Research Institute Single Stage Test Rig facility. Isentropic efficiency calculated from the torquemeter was approximately 1–2 efficiency points lower than the isentropic efficiency based on thermal measurements. This corresponds to approximately 0.5–1°C in heat loss in the discharge collector and piping. Furthermore, observations from three full-thermal heat-soak points indicate the significant difference in time required to reach steady state performance within measurement uncertainty tolerances between the torque-based and thermal-based methods. This comparison, while largely suspected, has not yet been studied in previous publications.
Experimental Validation of a Wide-Range Centrifugal Compressor Stage for Supercritical CO2 Power Cycles
Authors: Allison Timothy C. , Smith Natalie R. , Pelton Robert , Jung Sewoong , Wilkes Jason C.
Published: August 2018

Successful implementation of sCO2 power cycles requires high compressor efficiency at both the design-point and over a wide operating range in order to maximize cycle power output and maintain stable operation over a wide range of transient and part-load operating conditions. This requirement is particularly true for air-cooled cycles where compressor inlet density is a strong function of inlet temperature that is subject to daily and seasonal variations as well as transient events. In order to meet these requirements, a novel centrifugal compressor stage design was developed that incorporates multiple novel range extension features, including a passive recirculating casing treatment and semi-open impeller design. This design, presented and analyzed for CO2 operation in a previous paper, was fabricated via direct metal laser sintering and tested in an open-loop test rig in order to validate simulation results and the effectiveness of the casing treatment configuration. Predicted performance curves in air and CO2 conditions are compared, resulting in a reduced diffuser width requirement for the air test in order to match design velocities and demonstrate the casing treatment.

Test results show that the casing treatment performance generally matched CFD predictions, demonstrating an operating range of 69% and efficiency above air predictions across the entire map. The casing treatment configuration demonstrated improvements over the solid wall configuration in stage performance and flow characteristics at low flows, resulting in an effective 14% increase in operating range with a 0.5-point efficiency penalty. The test results are also compared to a traditional fully shrouded impeller with the same flow coefficient and similar head coefficient, showing a 42% range improvement over traditional designs.
Feature Extraction From Time Resolved Reacting Flow Data Sets
Authors: Ek H. , Chterev I. , Rock N. , Emerson B. , Seitzman J. , Lieuwen T. , Jiang N. , Proscia W.
Published: August 2018

This paper presents measurements of the simultaneous fuel distribution, flame position and flow velocity in a high pressure, liquid fueled combustor. Its objective is to develop methods to process, display and compare large quantities of instantaneous data with computations. However, time-averaged flow fields rarely represent the instantaneous, dynamical flow fields in combustion systems. It is therefore important to develop methods that can algorithmically extract dynamical flow features and be directly compared between measurements and computations. While a number of data-driven approaches have been previously presented in the literature, the purpose of this paper is to propose several approaches that are based on understanding of key physical features of the flow — for this reacting swirl flow, these include the annular jet, the swirling flow which may be precessing, the recirculating flow between the annular jets, and the helical flow structures in the shear layers. This paper demonstrates nonlinear averaging of axial and azimuthal velocity profiles, which provide insights into the structure of the recirculation zone and degree of flow precession. It also presents probability fields for the location of vortex cores that enables a convenient method for comparison of their trajectory and phasing with computations. Taken together, these methods illustrate the structure and relative locations of the annular fluid jet, recirculating flow zone, spray location, flame location, and trajectory of the helical vortices.
Temperature Dependence of Crack Growth Under LCF for Different Alloys
Authors: Rabbolini S. , Foletti S. , Beretta S.
Published: August 2018

Fatigue crack growth in plastic regions is one of the main factors for life assessment of components subjected to plastic strains. Residual life can be evaluated considering a crack growing from component first load cycle, considering an appropriate crack growth model. The aim of this work is to discuss the effects of temperature on crack propagation during low cycle fatigue. In particular, a series of experiments at high temperature (up to T = 700°C) were performed on a Ni-based superalloy, to determine crack growth rates in the LCF regime. During tests interruptions, crack growth was measured using the plastic replica technique. Experimental results were examined in terms of crack growth rates and a model based on elastic-plastic J-Integral. Results showed that at high temperature there is a significant increase of crack growth rates respect to models usually valid at room temperature.
A High Speed Test Rig Capable of Running at 190,000rpm to Characterize Gas Foil Thrust Bearings
Authors: LaTray Nguyen T. , Kim Daejong
Published: August 2018

This paper details the design and performance of a high-speed (up to 190,000rpm) gas foil thrust bearing (GFTB) test rig to measure bearing load capacity. Several GFTB test rigs were reported in the literature for operating speed up to 90krpm. A few recently presented works show successful runs at 135krpm for testing gas thrust bearing with viscoelastic support and 130krpm tilting pad thrust bearing with compliant structure. However, a GFTB test rig for speed range over 100krpm has not been reported. At high speed operation, the gas film thickness of the GFTB is around a few microns which makes it difficult to achieve in testing. In many cases, the measured thrust load from experiments is well below the predicted data due to difficulty in testing and instrumentation. Difficulty in validating the actual load capacity of the bearings leads to increasing the thrust bearing size to ensure sufficient load capacity in actual applications, which results in higher power consumption. This work presents detail feature of a novel GFTB test rig and test results of 38mm GFTB. The developed test rig runs up to 190krpm and measures bearing load capacity, frictional torque and temperature across bearing ID and OD. The test rig is suitable for testing GFTB with OD from 30 mm to 40 mm. The test facility successfully tests a 38 mm GFTB to its predicted load capacity of 75N (110kPa).
Large Eddy Simulation of a Premixed Flame in Hot Vitiated Crossflow With Analytically Reduced Chemistry
Authors: Schulz Oliver , Noiray Nicolas
Published: August 2018

This numerical study deals with a premixed ethylene-air jet at 300 K injected into a hot vitiated crossflow at 1500 K and atmospheric pressure. The reactive jet in crossflow (RJICF) was simulated with compressible 3-D large eddy simulations (LES) with an analytically reduced chemistry (ARC) mechanism and the dynamic thickened flame (DTF) model. ARC enables simulations of mixed combustion modes, such as autoignition and flame propagation, that are both present in this RJICF. 0-D and 1-D simulations provide a comparison with excellent agreement between ARC and detailed chemistry in terms of autoignition time and laminar flame speed. The effect of the DTF model on autoignition was investigated for varying species compositions and mesh sizes. Comparisons between LES and experiments are in good agreement for average velocity distributions and jet trajectories; LES remarkably capture experimentally observed flame dynamics. An analysis of the simulated RJICF shows that the leeward propagating flame has a stable flame root close to the jet exit. The lifted windward flame, on the contrary, is anchored in an intermittent fashion due to autoignition flame stabilization. The windward flame base convects downstream and is “brought back” by autoignition alternately. These autoignition events occur close to a thin layer that is associated with radical build-up and that stretches down to the jet exit.
Direct Experimental Measurements of Heat Transfer Coefficient Augmentation due to Approach Flow Effects
Authors: Anderson Joshua B. , Bogard David G. , Dyson Thomas E. , Webster Zachary
Published: August 2018

The injection of film cooling can have a strong impact on the heat transfer coefficient (HTC) between the overflowing freestream gas and the cooled surface. This study investigated the influence of approach flow characteristics, including the boundary layer thickness and character (laminar and turbulent), as well as the approach flow Reynolds number, on the HTC. The influence of these parameters was previously unreported in the open film cooling literature. The figure of merit for this study was the HTC augmentation, that is the ratio of heat transfer coefficients for a cooled vs. uncooled surface. For this work, a direct measurement of the heat transfer coefficient was made, using a heated foil surface which provided a known wall heat flux. Generally for this type of measurement, a flux foil is placed downstream of the coolant hole. However, for this experimental program a heat flux foil was also placed upstream of the film cooling holes, in order to generate an upstream thermal boundary layer which would be more representative of actual engine conditions. Such a configuration has rarely been seen in published studies. An open-literature shaped-hole design was used, known as the 7-7-7 hole, in order to compare with existing results in the literature. A variety of blowing conditions were tested from M = 0.5–3.0. Two elevated density ratios of DR = 1.20 and DR = 1.80 were used. High-resolution IR thermography was used for these measurements, providing a highly-accurate and spatially-resolved measurement of HTC augmentation. The results indicated that turbulent boundary layer thickness had a modest effect on HTC augmentation, whereas a very high level of augmentation was observed for a laminar approach boundary layer. The presence of upstream heating greatly increased the HTC augmentation in the near-hole region, although these effects died out by 10–15 diameters from the holes.
Approach for Zero Defect Manufacturing: Geometric Calibration of Five-Axis Machine Tools for Blisk Manufacturing Process
Authors: Lee Tae Hun , Behrens Jan , Gierlings Sascha , Brecher Christian
Published: August 2018

Five-axis machining is a key technology of blisk manufacturing process. Blisks generally require high accuracy due to their high performance and safety-critical conditions. However, recent research show that the design of the blisks and turbine blades are getting more complex and require even higher accuracy. This leads also to the application of wide and rare area of movement axes of the machine. Thus, the machine accuracy has to be assured within the overall machine volume. The geometric accuracy demonstrates the base accuracy of the machine. This paper presents a geometric calibration method optimized for the axes movement area of blisk machining process.

The accurate calibration of the five-axis machine tool is challenging and hardly possible due to limited error measurement of standard measurement devices. Some measurement methods enable complete calibration of the machine but with complex, time-consuming process and expensive measurement devices. Also, due to the rare axes travel, there is no standard calibration method for the blisk machining process.

The calibration method in this paper is developed based on so called ‘R-test’ method. The machine and the errors are modelled mathematically for the measurement. An adapter is applied for the measurement of maximum axis positions. Automation units are developed for the full machine integration and automation of calibration procedure. With the developed method, the machine is calibrated from 130 μm to 10 μm in maximum measurement time of 90 minutes. The calibration quality is validated at an independent measurement position with continuous movement of the five axes.
Radial Variation in Distortion Transfer and Generation Through a Highly Loaded Fan Stage
Authors: Soderquist Daniel R. , Gorrell Steven E. , List Michael G.
Published: August 2018

An important consideration for fan and compressor design is quantifying distortion transfer and generation blade row by blade row. Detailed information about the magnitude of distortion and the shape of the distortion profile and how it changes through blade rows increases the understanding of flow physics and helps predict aerodynamic performance. Using full annulus URANS simulations, this paper analyzes what happens to distortion as it passes through the rotor and stator blade rows at 10%, 30%, 50%, 70%, and 90% span. Fourier distortion descriptors are used in this study to quantitatively describe distortion transfer and generation. With these descriptors, evidence of pressure-induced swirl is shown at the fan inlet. It is also shown that although there is very little distortion at the 10% span of the inlet, after passing through the rotor blade row the 10% span has the greatest amount of total pressure and total temperature distortion. This radial migration of distortion is attributed to the high hade angle of the hub. The total pressure and total temperature profiles have significant circumferential phase shifts after passing through the rotor and slight phase shifts after passing through the stator. In general, the calculated phase shifts are greatest at the 10% and 90% spans, the nearest locations to the hub and the tip clearance gap, respectively.
Evolution of MHPS Large Frame Gas Turbines: J to Air-Cooled JAC
Authors: Suzuki Kentaro , Matsumura Yoshikazu , Takata Kazumasa , Hada Satoshi , Yuri Masanori , Masada Junichiro
Published: August 2018

Mitsubishi Hitachi Power Systems, Ltd. (MHPS) has continued to contribute to the preservation of the global environment and the stable supply of energy through the constant development of gas turbines. The contribution is based on the abundant operating results, research, and verification of state-of-the-art technology. Since 2014 MHPS has been using progressive knowledge obtained from the Japanese National Project’s “1700°C Class Ultrahigh-Temperature Gas Turbine Component Technology Development.” The highly-efficient M501J gas turbine was successfully developed and has achieved the world’s first turbine inlet temperature of 1600°C because of this effort. Verification operation of the M501J at T-point, the verification plant, which MHPS owns in Takasago, started in 2011. Thereafter, M501J gas turbines have been delivered all over the world, and have accumulated more than 500,000 Actual Operating Hours (AOH). To further improve the efficiency and power output of the gas turbine combined cycle (GTCC), a new enhanced air-cooled system for the combustor was installed replacing the steam-cooled system employed in the J-series. The compressor was also redesigned with an advanced design approach that ensures the mechanical soundness of the parts and the performance upgrade in inlet flow as well as start-up characteristics.
Effects of Effusion Cooling Pattern Near the Dilution Hole for a Double-Walled Combustor Liner: Part 2 — Flowfield Measurements
Authors: Shrager Adam C. , Thole Karen A. , Mongillo Dominic
Published: August 2018

The complex flowfield inside a gas turbine combustor creates a difficult challenge in cooling the combustor walls. Many modern combustors are designed with a double-wall that contain both impingement cooling on the backside of the wall and effusion cooling on the external side of the wall. Complicating matters is the fact that these double-walls also contain large dilution holes whereby the cooling film from the effusion holes is interrupted by the high-momentum dilution jets. Given the importance of cooling the entire panel, including the metal surrounding the dilution holes, the focus of this paper is understanding the flow in the region near the dilution holes. Near-wall flowfield measurements are presented for three different effusion cooling hole patterns near the dilution hole. The effusion cooling hole patterns were varied in the region near the dilution hole and include: no effusion holes; effusion holes pointed radially outward from the dilution hole; and effusion holes pointed radially inward toward the dilution hole. Particle image velocimetry (PIV) was used to capture the time-averaged flowfield at approaching freestream turbulence intensities of 0.5% and 13%.

Results showed evidence of downward motion at the leading edge of the dilution hole for all three effusion hole patterns. In comparing the three geometries, the outward effusion holes showed significantly higher velocities toward the leading edge of the dilution jet relative to the other two geometries. Although the flowfield generated by the dilution jet dominated the flow downstream, each cooling hole pattern interacted with the flowfield uniquely. Approaching freestream turbulence did not have a significant effect on the flowfield.
Energy Deficiency During Cold Weather Mountain Training in NSW SEAL Qualification Students
Authors: Beals Kim , Perlsweig Katherine A. , Haubenstriker John E. , Lovalekar Mita , Beck Chris P. , Yount Darcie L. , Darnell Matthew E. , Allison Katelyn , Nindl Bradley C.
Published: August 2018

Special operation forces participating in mountain warfare/cold weather (MWCW) training have higher energy demands, but adequate fueling is difficult to achieve. The purpose of the study was to determine energy expenditure relative to energy intake and examine fueling patterns during 3 days of MWCW training in Naval Special Warfare Sea, Air, Land (SEAL) Qualification Training (SQT) students. Ten SQT students (age: 23.3 ± 1.8 years, height: 182.3 ± 6.4 cm, and weight: 83.6 ± 4.5 kg) were fitted for heart rate and accelerometer monitors during MWCW training. Total daily energy expenditure was determined using a combination of direct observation and heart rate-VO2 regression. Total daily energy intake was collected using the Automated Self-Administered 24 (ASA24) assessment tool. Total daily energy expenditure for river crossing, alpine skills, and mountain patrol were 3,913 ± 293, 4,207 ± 400, and 5,457 ± 828 kcals, respectively. Reported total daily energy intakes were 2,854 ± 657 (river crossing) and 2,289 ± 680 kcals (mountain patrol), producing 1,044 ± 784 and 3,112 ± 1,420 kcal deficits, respectively. SQT students consumed 258 ± 95 g (3.1 ± 1.3 g·kg−1·day−1) of carbohydrates, 130 ± 55 g (1.6 ± 0.7 g·kg−1·day−1) of protein, and 113 ± 39 g (1.4 ± 0.5 g·kg−1·day−1) of fat. MWCW training evolutions elicited high total daily energy expenditure and inadequate energy intake, especially before and during active training sessions, which may lead to decreased work output, early onset fatigue, and increased risk of injury. Increasing total daily energy intake by providing fuel/fluids, primarily carbohydrates, during the planned breaks and “downtime” of each training evolution and focusing on provision of the balance of calories/macronutrients needed for a more complete and expedited recovery over dinner and evening snacks will help bridge the energy gap.
Accurate Prediction Equation to Assess Body Fat in Male and Female Adolescent Football Players
Authors: Lozano-Berges Gabriel , Matute-Llorente Ángel , Gómez-Bruton Alejandro , González-Agüero Alejandro , Vicente-Rodríguez Germán , Casajús José A.
Published: August 2018

The aims of this study were (a) to determine which of the most used anthropometric equations was the most accurate to estimate percentage of body fat (%BF), (b) to develop a new specific anthropometric equation, and (c) to validate this football-specific equation. A total of 126 (13.3 ± 0.6 years) football players (86 males and 40 females) participated in the present study. Participants were divided into two groups: 98 players were included in the assessment of existing equations and in the development of the new prediction equation, and 28 players were used to validate it. %BF was measured with dual-energy X-ray absorptiometry (DXA) and also estimated with six different %BF anthropometric equations: Johnston, Slaughter, Carter, Faulkner, Deurenberg, and Santi-Maria. Paired t tests were used to analyze differences between methods. A football-specific equation was developed by a stepwise linear regression. The existing anthropometric equations showed significant bias for %BF when compared with DXA (p < .001; constant error ranged from −4.57% to 9.24%; standard error of estimate ranged from 2.46 to 4.20). On the other hand, the developed football-specific equation was %BF = 11.115 + 0.775 (triceps skinfold) + 0.193 (iliac crest skinfold) − 1.606 (sex). The developed equation demonstrated neither %BF differences (p = .121; constant error = 0.57%; standard error of estimate = 0.36) when compared with DXA, presenting a high cross-validation prediction power (R2 = .85). Published anthropometric equations were not accurate to estimate %BF in adolescent football players. Due to the fact that the developed football-specific equation showed neither differences nor heteroscedasticity when compared with DXA, this equation is recommended to assess %BF in adolescent football players.
In dogs, CRISPR fixes a muscular dystrophy
Authors: Cohen Jon
Published: August 2018

Treatment repairs gene in beagles by further mutating it, but human trials are far off.
Global carbon intensity of crude oil production
Authors: Masnadi Mohammad S. , El-Houjeiri Hassan M. , Schunack Dominik , Li Yunpo , Englander Jacob G. , Badahdah Alhassan , Monfort Jean-Christophe , Anderson James E. , Wallington Timothy J. , Bergerson Joule A. , Gordon Deborah , Koomey Jonathan , Przesmitzki Steven , Azevedo Inês L. , Bi Xiaotao T. , Duffy James E. , Heath Garvin A. , Keoleian Gregory A. , McGlade Christophe , Meehan D. Nathan , Yeh Sonia , You Fengqi , Wang Michael , Brandt Adam R.
Published: August 2018

New data enable targeted policy to lessen GHG emissions
Comment on “Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water”
Authors: Best Robert B. , Zheng Wenwei , Borgia Alessandro , Buholzer Karin , Borgia Madeleine B. , Hofmann Hagen , Soranno Andrea , Nettels Daniel , Gast Klaus , Grishaev Alexander , Schuler Benjamin
Published: August 2018

Riback
et al
. (Reports, 13 October 2017, p. 238) used small-angle x-ray scattering (SAXS) experiments to infer a degree of compaction for unfolded proteins in water versus chemical denaturant that is highly consistent with the results from Förster resonance energy transfer (FRET) experiments. There is thus no “contradiction” between the two methods, nor evidence to support their claim that commonly used FRET fluorophores cause protein compaction.
Directional control of a processive molecular hopper
Authors: Qing Yujia , Ionescu Sandra A. , Pulcu Gökçe Su , Bayley Hagan
Published: August 2018

Tiny cargos ferried along a track

Control of molecules at the nanometer scale requires motors that convert potential energy into movement. Qing
et al.
designed a small molecule that could hop along a track of cysteine residues within a membrane-embedded protein pore. The direction of processive movement along the track was reversible, driven by an applied potential across the membrane. Cargos were attached to a carrier motor, and their position and chemical identity read out from changes in the current through the pore. These features enabled repeat observations of a single molecule as it moved back and forth on the track.

Science
, this issue p.
908
CRISPR-Cas guides the future of genetic engineering
Authors: Knott Gavin J. , Doudna Jennifer A.
Published: August 2018

The diversity, modularity, and efficacy of CRISPR-Cas systems are driving a biotechnological revolution. RNA-guided Cas enzymes have been adopted as tools to manipulate the genomes of cultured cells, animals, and plants, accelerating the pace of fundamental research and enabling clinical and agricultural breakthroughs. We describe the basic mechanisms that set the CRISPR-Cas toolkit apart from other programmable gene-editing technologies, highlighting the diverse and naturally evolved systems now functionalized as biotechnologies. We discuss the rapidly evolving landscape of CRISPR-Cas applications, from gene editing to transcriptional regulation, imaging, and diagnostics. Continuing functional dissection and an expanding landscape of applications position CRISPR-Cas tools at the cutting edge of nucleic acid manipulation that is rewriting biology.
Three-dimensional genome structures of single diploid human cells
Authors: Tan Longzhi , Xing Dong , Chang Chi-Han , Li Heng , Xie X. Sunney
Published: August 2018

The structure of the genome

Beyond the sequence of the genome, its three-dimensional structure is important in regulating gene expression. To understand cell-to-cell variation, the structure needs to be understood at a single-cell level. Chromatin conformation capture methods have allowed characterization of genome structure in haploid cells. Now, Tan
et al.
report a method called Dip-C that allows them to reconstruct the genome structures of single diploid human cells. Their examination of different cell types highlights the tissue dependence of three-dimensional genome structures.

Science
, this issue p.
924
Systemic control of legume susceptibility to rhizobial infection by a mobile microRNA
Authors: Tsikou Daniela , Yan Zhe , Holt Dennis B. , Abel Nikolaj B. , Reid Dugald E. , Madsen Lene H. , Bhasin Hemal , Sexauer Moritz , Stougaard Jens , Markmann Katharina
Published: August 2018

Keeping the doors open for symbiosis

Nitrogen fixation by legumes results from a symbiotic partnership between plant and microbes. These together elaborate nodules on the plant roots that house the bacteria. Tsikou
et al.
identified a microRNA made in the aboveground shoots of
Lotus japonicus
that translocates to the plant's roots. In the roots, the microRNA posttranscriptionally regulates a key suppressor of symbiosis, thus keeping the uninfected root susceptible to productive infection by symbiotic bacteria.

Science
, this issue p.
233
18 electrons and counting
Authors: Armentrout P. B.
Published: August 2018

The bonding rule for transition metal complexes now extends to alkaline earth octacarbonyls
Screening the Pathogen Box for Molecules Active against Plasmodium Sexual Stages Using a New Nanoluciferase-Based Transgenic Line of P. berghei Identifies Transmission-Blocking Compounds
Authors: Calit Juliana , Dobrescu Irina , Gaitán Xiomara A. , Borges Miriam H. , Ramos Marisé S. , Eastman Richard T. , Bargieri Daniel Y.
Published: August 2018

Malaria remains an important parasitic disease with a large morbidity and mortality burden.
Plasmodium
transmission-blocking (TB) compounds are essential for achieving malaria elimination efforts.
Ultrasensitive Detection of Clostridioides difficile Toxins A and B by Use of Automated Single-Molecule Counting Technology
Authors: Sandlund Johanna , Bartolome Amelita , Almazan Anna , Tam Stanley , Biscocho Sheryl , Abusali Salina , Bishop Jeffrey J. , Nolan Niamh , Estis Joel , Todd John , Young Stephen , Senchyna Fiona , Banaei Niaz
Published: August 2018

Current tests for the detection of
Clostridioides
(formerly
Clostridium
)
difficile
free toxins in feces lack sensitivity, while nucleic acid amplification tests lack clinical specificity. We have evaluated the Singulex Clarity C.
Developing Course-Based Research Experiences in Discipline-Based Education Research: Lessons Learned and Recommendations
Authors: Cooper Katelyn M. , Brownell Sara E.
Published: August 2018

In this perspective, we highlight the opportunity for the biology education research community to develop course-based research experiences (CREs) or course-based undergraduate research experiences (CUREs) in discipline-based education research. Building on our prior experience developing and teaching four biology education research CREs, we present opportunities, potential pitfalls, and recommendations for discipline-based education researchers interested in integrating their research and teaching in the context of a CRE.
An N-Glycosylated Form of SERINC5 Is Specifically Incorporated into HIV-1 Virions
Authors: Sharma Shilpi , Lewinski Mary K. , Guatelli John
Published: August 2018

SERINC5 is a member of a family of multipass transmembrane proteins that inhibit the infectivity of retroviruses, including HIV-1. These proteins are incorporated into virions and inhibit infection of target cells unless counteracted by viral antagonists such as HIV-1 Nef. The only other biological function with which these proteins have been associated is the formation of serine-containing membrane lipids. Here we show that SERINC5 is a glycosylated protein and that N-glycosylation is important for its steady-state expression. In the absence of N-glycosylation, SERINC5 is prone to proteasomal degradation. Nonetheless, N-glycosylationper seis required neither for the ability of SERINC5 to inhibit HIV-1 infectivity nor for its sensitivity to antagonism by Nef.
Factors influencing macular atrophy growth rates in neovascular age-related macular degeneration treated with ranibizumab or aflibercept according to an observe-and-plan regimen
Authors: Mantel Irmela , Zola Marta , De Massougnes Sophie , Dirani Ali , Bergin Ciara
Published: August 2018

Background/aims

To investigate the factors associated with macular atrophy (MA) growth rates in neovascular age-related macular degeneration treated with either ranibizumab or aflibercept.

Methods

We obtained data from two identical prospective studies using ranibizumab or aflibercept under observe-and-plan variable dosing regimens. We analysed eyes that presented MA within 2 years. After applying square root transformations to MA sizes, we calculated MA growth rate from baseline to the year 2 endpoint and used univariate and multivariate analyses to detect ocular and treatment factors associated with the MA growth rate.

Results

Included were 109 eyes from 101 patients (mean age 80.6 years). The mean square-root-transformed MA growth rate was 0.54±0.34 mm/year. The univariate analyses revealed that MA growth rates were significantly associated with lower baseline visual acuities (p=0.001) and thicker subretinal tissue complexes (p=0.006) and near-significantly associated with the presence of pigment epithelium detachment (p=0.057) and choroidal neovascularisation subtypes (p=0.069). Our multivariate analysis confirmed the significance of lower baseline visual acuities (p=0.008) and pigment epithelium detachments higher than 200 µm (p=0.035). Furthermore, MA growth rates in neovascular eyes significantly correlated with MA growth rates in non-neovascular fellow eyes (n=61; p=0.003).

Conclusion

MA growth rates were associated with ocular factors in the study eyes and the fellow eyes but not with the drug or the number of injections within this variable dosing regimen.
Discharge of patients with an acute upper gastrointestinal bleed from the emergency department using an extended Glasgow-Blatchford Score
Authors: Banister Thomas , Spiking Josesph , Ayaru Lakshmana
Published: August 2018

Objective

To use an extended Glasgow-Blatchford Score (GBS) cut-off of ≤1 to aid discharge of patients presenting with acute upper gastrointestinal bleeding (AUGIB) from emergency departments.

Background

The GBS accurately predicts the need for intervention and death in AUGIB, and a cut-off of 0 is recommended to identify patients for discharge without endoscopy. However, this cut-off is limited by identifying a low percentage of low-risk patients. Extension of the cut-off to ≤1 or ≤2 has been proposed to increase this proportion, but there is controversy as to the optimal cut-off and little data on performance in routine clinical practice.

Methods

Dual-centre study in which patients with AUGIB and GBS ≤1 were discharged from the emergency department without endoscopy unless there was another reason for admission. Retrospective analysis of associated adverse outcome defined as a 30-day combined endpoint of blood transfusion, intervention or death.

Results

569 patients presented with AUGIB from 2015 to 2018. 146 (25.7%) had a GBS ≤1 (70, GBS=0; 76, GBS=1). Of these, 103 (70.5%) were managed as outpatients, and none had an adverse outcome. GBS ≤1 had a negative predictive value=100% and the GBS had an area under receiver operator characteristic​​ (AUROC)=0.89 (95% CI 0.86 to 0.91) in predicting adverse outcomes. In 2008–2009, prior to risk scoring (n=432), 6.5% of patients presenting with AUGIB were discharged safely from the emergency department in comparison with 18.1% (p<0.001) in this cohort. A GBS cut-off ≤2 was associated with an adverse outcome in 8% of cases.

Conclusion

GBS of ≤1 is the optimal cut-off for the discharge of patients with an AUGIB from the emergency department.
Early prediction of lenvatinib treatment efficacy by using18F-FDG PET/CT in patients with unresectable or advanced thyroid carcinoma that is refractory to radioiodine treatment: a protocol for a non-randomized single-arm multicenter observational study
Authors: Takeuchi Satoshi , Shiga Tohru , Hirata Kenji , Taguchi Jun , Magota Keiichi , Ariga Shin , Gouda Tomohiro , Ohhara Yoshihito , Homma Rio , Shimizu Yasushi , Kinoshita Ichiro , Tsuji Yasushi , Homma Akihiro , Iijima Hiroaki , Tamaki Nagara , Dosaka-Akita Hirotoshi
Published: August 2018

Introduction

Lenvatinib, an oral molecular targeted drug, is used to treat patients with unresectable or advanced thyroid carcinoma that is refractory to radioiodine treatment. Effective methods for evaluating molecular targeted drugs are a critical unmet need owing to their expensive costs and unique adverse events. The aim of this study is to determine whether18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT at 1 week after commencing lenvatinib can predict treatment outcomes.

Design and methods

This study is planned as a non-randomised single-arm multicentre study; patients with pathologically confirmed differentiated thyroid carcinoma (DTC) with lesions that are refractory to radioiodine treatment are eligible. The main exclusion criteria are medullary or anaplastic carcinoma, prior treatment with chemotherapy, poor general condition and thromboembolism-requiring treatment. Patients to be included in the study will be treated with lenvatinib and undergo FDG-PET/CT examination twice: before and 1 week after the initiation of treatment. Contrast-enhanced CT, the gold standard for evaluation, will be performed at least 4 weeks after the initiation of treatment. The primary objective is to evaluate the ability of the lesion maximum standard uptake value for FDG PET/CT performed 1 week after the initiation of treatment to predict outcomes compared with the response evaluation obtained via contrast-enhanced CT performed at least 4 weeks after the initiation of treatment.

Ethics and dissemination

This study is conducted in accordance with the Declaration of Helsinki and has received ethical approval from the institutional review board of the Hokkaido University Hospital (approval number: 015-402). The results of this study will be disseminated through a presentation at a conference and the publication of the data in a peer-reviewed journal. The study will be implemented and reported in line with the SPIRIT statement.

Trial registration number

UMIN000022592.
Impact of patient characteristics on the Canadian Patient Experiences Survey–Inpatient Care: survey analysis from an academic tertiary care centre
Authors: Rubens Fraser D , Rothwell Diana M , Al Zayadi Amal , Sundaresan Sudhir , Ramsay Tim , Forster Alan
Published: August 2018

Objective

To determine the role of patient demographics, care domains and self-perceived health status in the analysis and interpretation of results from the Canadian Patient Experience Survey–Inpatient Care.

Design

Cross-sectional survey.

Setting

Single large Canadian two campus tertiary care academic centre.

Participants

Random sampling of hospital patients postdischarge.

Intervention and main outcome measures

Logistic regression models were developed to analyse topbox scoring on four questions of global care (rate experience, recommend hospital, rate hospital, overall helped). Means of each composite domain were correlated to the four overall scores at the patient level to determine Spearman’s rank correlation coefficients which were plotted against the overall (hospital) domain score for the key driver analysis.

Results

Topbox scoring was decreased with worse degrees of perceived physical and mental health in all four global questions (p<0.05). Female gender and higher levels of education were associated with worse scoring on rate experience, recommend hospital and rate hospital (p<0.001). Whereas there was a significant difference between hospital departments in unadjusted measures, these differences were no longer evident after adjustment with patient covariates. Key driver analysis identified person-centred care, care transition and the domain related to emergency admission as areas of highest potential for improvement.

Conclusions

Global measures of overall care are influenced by patient-perceived physical and mental health. Caution should be exercised in using patient-satisfaction surveys to compare performance between different healthcare provision entities, as apparent differences could be explained by variation in patient mix rather than variation in performance.
Non-HFE mutations in haemochromatosis in China: combination of heterozygous mutations involving HJV signal peptide variants
Authors: Lv Tingxia , Zhang Wei , Xu Anjian , Li Yanmeng , Zhou Donghu , Zhang Bei , Li Xiaojin , Zhao Xinyan , Wang Yu , Wang Xiaoming , Duan Weijia , Wang Qianyi , Xu Hexiang , Zheng JiShun , Zhao Rongrong , Zhu Longdong , Dong Yuwei , Lu Lungen , Chen Yongpeng , Long Jiang , Zheng Sujun , Wang Wei , You Hong , Jia Jidong , Ou Xiaojuan , Huang Jian
Published: August 2018

Introduction

Hereditary haemochromatosis (HH) caused by a homozygous p.C282Y mutation in haemochromatosis (HFE) gene has been well documented. However, less is known about the causative non-HFE mutation. We aimed to assess mutation patterns of haemochromatosis-related genes in Chinese patients with primary iron overload.

Methods

Patients were preanalysed for mutations in the classic HH-related genes: HFE, HJV, HAMP, TFR2 and SLC40A1. Whole exome sequencing was conducted for cases with variants in HJV signal peptide region. Representative variants were analysed for biological function.

Results

None of the cases analysed harboured the HFE p.C282Y; however, 21 of 22 primary iron-overload cases harboured at least one non-synonymous variant in the non-HFE genes. Specifically, p.E3D or p.Q6H variants in the HJV signal peptide region were identified in nine cases (40.9%). In two of three probands with the HJV p.E3D, exome sequencing identified accompanying variants in BMP/SMAD pathway genes, including TMPRSS6 p.T331M and BMP4 p.R269Q, and interestingly, SUGP2 p.R639Q was identified in all the three cases. Pedigree analysis showed a similar pattern of combination of heterozygous mutations in cases with HJV p.E3D or p.Q6H, with SUGP2 p.R639Q or HJV p.C321X being common mutation. In vitro siRNA interference of SUGP2 showed a novel role of downregulating the BMP/SMAD pathway. Site-directed mutagenesis of HJV p.Q6H/p.C321X in cell lines resulted in loss of membrane localisation of mutant HJV, and downregulation of p-SMAD1/5 and HAMP.

Conclusion

Compound heterozygous mutations of HJV or combined heterozygous mutations of BMP/SMAD pathway genes, marked by HJV variants in the signal peptide region, may represent a novel aetiological factor for HH.
Estimating the effect of a potential policy to restrict tobacco retail availability in New Zealand
Authors: Robertson Lindsay , Marsh Louise
Published: August 2018

Introduction

Reducing tobacco retailer density is suggested to be a key component of tobacco endgames. Where tobacco retail reduction policies exist, ‘grandfathering’ is typically used, where existing retailers are exempt from restrictions aimed at reducing outlet density. We examined the possible impact on tobacco outlet density in New Zealand of a policy preventing new retail outlets from selling tobacco, but allowing existing retail outlets to continue selling tobacco until they ceased trading or relocated.

Methods

We obtained data on numbers of tobacco outlets and the number of outlet closures recorded annually from 2006 to 2016. We calculated the mean and the lowest and highest 3-year rolling average closure rates for each type of tobacco outlet. We projected decreases in the number of tobacco outlets that would hypothetically be permitted to sell tobacco from 2020 onwards and estimated when the combined number of tobacco outlets would decline by 50% and 95%.

Results

Based on mean annual closure rates, the total number of tobacco outlets would decrease by 50% by 2032 and a 95% reduction could be achieved by 2072. By 2025, the number of tobacco outlets would decrease by 27%; by 2050, this reduction would reach 84%.

Conclusion

A tobacco retail reduction policy that prevented new retail outlets from selling tobacco and grandfathered existing retailers would be unlikely to achieve New Zealand’s target of a 95% reduction in tobacco outlet density within several decades of being enacted. Nonetheless, this policy could achieve a 50% reduction in tobacco retail availability in the first decade of implementation.