bluuebunny/crossref_metadata_2025 huggingface dataset:
Low sensitivity of the MPT64 identification test to detect lineage 5 of the Mycobacterium tuberculosis complex
Authors: Sanoussi C. N'Dira , de Jong Bouke C. , Odoun Mathieu , Arekpa Karamatou , Ali Ligali Moulikatou , Bodi Ousman , Harris Simon , Ofori-Anyinam Boatema , Yeboah-Manu Dorothy , Otchere Isaac Darko , Asante-Poku Adwoa , Anagonou Severin , Gagneux Sebastien , Coscolla Mireia , Rigouts Leen , Affolabi Dissou
Published: November 2018

Purpose. Differentiation of the Mycobacterium tuberculosis complex (MTBc) from non-tuberculous mycobacteria (NTM) is important for tuberculosis diagnosis and is a prerequisite for reliable phenotypic drug-resistance testing. We evaluated the performance of the rapid MPT64 antigen identification test for the detection of Mycobacterium africanum lineage 5 (MAF L5).

Methodology. Smear-positive tuberculosis patients’ sputa were included prospectively. Culture was performed on Löwenstein–Jensen medium and, when positive, the MPT64 test and the classical para-nitro benzoic acid susceptibility and heat-labile catalase (PNB/catalase) identification tests were performed. The MPT64 test was repeated 14 days after an initially negative first testing. Direct spoligotyping was performed for MTBc lineage determination.

Results. In total, 333 isolates were tested for all of the methods. Three hundred and twenty-two (96.7 %) were pure MTBc, by agreement between spoligotyping and PNB/catalase, and 11 were NTM or a mixture of MTBc/NTM. The MPT64 test conducted on day zero of culture-positivity correctly identified most of the pure MTBc isolates (93.2 %, 300/322), but it failed to detect 24 % of the L5 isolates (18/75) versus 2 % (4/202) of the L4 ones [OR=15.6 (5.3–45.8), P<0.0001], with improved sensitivity for L5 detection on repeat testing after 14 days. The L5-wide non-synonymous single-nucleotide polymorphism in the mpt64 gene may explain the poor performance of the MPT64 test for L5.

Conclusion. The MPT64 test has a lower sensitivity for detecting L5 isolates of the MTBc, and can be considered as a first-screening test that should be confirmed by another identification method when it produces negative results in countries with L5. Given the microbiological bias in both the isolation and identification of MAF lineages, diagnostics with high sensitivity for direct testing on clinical material are preferable.
Widespread Suppression of High-Order Visual Cortex During Blinks and External Predictable Visual Interruptions
Authors: Golan Tal , Grossman Shany , Deouell Leon Y , Malach Rafael
Published: November 2018

Spontaneous eye blinks generate frequent potent interruptions to the retinal input and yet go unnoticed. As such, they provide an attractive approach to the study of the neural correlates of visual awareness. Here, we tested the potential role of predictability in generating blink-related effects using fMRI. While participants attentively watched still images of faces and houses, we monitored naturally occurring spontaneous blinks and introduced three kinds of matched visual interruptions: cued voluntary blinks, self-initiated (and hence, predictable) external darkenings, and physically similar but unpredictable external darkenings. These events’ impact was inspected using fMRI across the visual hierarchy. In early visual cortex, both spontaneous and voluntary blinks, as well as predictable and unpredictable external darkenings, led to largely similar positive responses in peripheral representations. In mid- and high-level visual cortex, all predictable conditions (spontaneous blinks, voluntary blinks, and self-initiated external darkenings) were associated with signal decreases. In contrast, unpredictable darkenings were associated with signal increases. These findings suggest that general-purpose prediction-related mechanisms are involved in producing a small but widespread suppression of mid- and high-order visual regions during blinks. Such suppression may down-regulate responses to predictable transients in the human visual hierarchy.
New Insights into the Nature of Symbiotic Associations in Aphids: Initial Steps Involved in Aphid Gut Infection bySerratia symbioticaBacteria
Authors: Inès Pons , François Renoz , Christine Noël , Thierry Hance
Published: November 2018

Symbiotic microorganisms are widespread in nature and can play a major role in the ecology and evolution of animals. Theaphid-Serratia symbioticabacterium interaction provides a valuable model to study mechanisms behind these symbiotic associations. The recent discovery of cultivableS. symbioticastrains having the possibility of free-living lifestyle allowed us to simulate their environmental acquisition by aphids to examine the mechanisms involved in this infection pathway. Here, after oral ingestion, we analyzed the infection dynamic of cultivableS. symbioticastrains during the host’s lifetime using qPCR and fluorescence techniques and determined the immediate fitness consequences of these bacteria on their new host. We further examined the transmission behavior and phylogenetic position of cultivable strains. Usually,S. symbioticaare considered as maternally-transmitted bacteria living within aphid body cavity and bringing some benefits to their hosts despite their costs. Otherwise, our study revealed that cultivableS. symbioticaare predisposed to establish a symbiotic association with new aphid host, settling in its gut. We showed that cultivableS. symbioticacolonized the entire aphid digestive tract following infection, after which the bacterium multiplied exponentially during aphid development. Our results further revealed that gut colonization by the bacteria induce a fitness cost to their hosts. Nevertheless, it appeared that they also offer an immediate protection against parasitoids. Interestingly, cultivableS. symbioticaseem to be extracellularly transmitted, possibly through the honeydew. These findings provide new insights into the nature of symbiosis in aphids and the mechanisms underpinning these interactions.

Importance

For the first time, our study provides experimental data that highlight a new kind of symbiotic associations in aphids. By successfully isolating microbial symbiont from aphids and by cultivating itin vitroin our laboratory, we established artificial association by simulating new bacterial acquisitions involved in aphid gut infection. Our results showed the early stages involved in this route of infection. Until now,Serratia symbioticais considered as a maternally-transmitted aphid endosymbiont. Nevertheless, here, we showed that our cultivable strains having an intermediate status between a strict free-living bacterium and a facultative endosymbiont, occupy and replicate in aphid gut and seem to be transmitted over generations through an environmental transmission mechanism. Moreover, they are both parasites and mutualists given the context, as many of the endosymbionts in aphids. Our findings give new perception of associations involved in aphids’ symbiosis.
Structuring Time in Human Lateral Entorhinal Cortex
Authors: Bellmund Jacob L.S. , Deuker Lorena , Doeller Christian F.
Published: November 2018

Remembering event sequences is central to episodic memory and thought to be supported by the hippocampal-entorhinal region. We previously demonstrated that the hippocampus maps spatial and temporal distances between events encountered along a fixed route through a virtual city (Deuker et al., 2016), but the content of entorhinal mnemonic representations remains unclear. Here, we demonstrate that, after learning, multi-voxel representations in the anterior-lateral entorhinal cortex (alEC) specifically reflect the temporal event structure. Holistic representations of the temporal structure related to memory recall and the temporal event structure could be reconstructed from entorhinal multi-voxel patterns. Our findings demonstrate representations of temporal structure in the alEC in line with temporal information carried by population signals in the lateral entorhinal cortex of navigating rodents and activations of its human homologue during temporal memory retrieval. Our results provide novel evidence for the role of the human alEC in representing time for episodic memory.
The Archaellum ofMethanospirillum hungateiis Electrically Conductive
Authors: Walker David J.F. , Martz Eric , Holmes Dawn E. , Zhou Zimu , Nonnenmann Stephen S. , Lovley Derek R.
Published: November 2018

Here we report that the archaellum ofMethanospirillum hungateiis electrically conductive. Our analysis of the previously published archaellum structure suggests that a core of tightly packed phenylalanines is one likely route for electron conductance. This is the first demonstration that electrically conductive protein filaments (e-PFs) have evolved in Archaea and is the first e-PF for which a structure is known, facilitating mechanistic evaluation of long-range electron transport in e-PFs.
Neural auditory contrast enhancement in humans
Authors: Mehta Anahita H. , Feng Lei , Oxenham Andrew J.
Published: November 2018

The perception of sensory events can be suppressed or enhanced by the surrounding spatial and temporal context in ways that help in detecting novel objects and establishing perceptual constancy. In the auditory system, the phenomenon known as auditory enhancement reflects a general principle of contrast enhancement, where a target sound embedded within a background sound becomes perceptually more salient if the background is presented first by itself. This effect is highly robust, producing an effective enhancement of the target of between 5 and 25 dB (more than two orders of magnitude in intensity), depending on the task. Despite their ubiquity in vision, neural correlates of auditory contrast enhancement have yet to be identified in humans. Here we used the auditory steady-state response to probe the neural response to a target sound under conditions of enhancement. The probe was simultaneously modulated in amplitude with two modulation frequencies, to distinguish cortical from subcortical contributions to this phenomenon. We found robust auditory cortical, but not subcortical, enhancement that correlates with behavior and is consistent with an early theoretical model that postulates neural adaptation of inhibition. Our findings provide empirical support for a previously unverified theory of auditory enhancement and point to new approaches for improving sensory prostheses for hearing loss, such as hearing aids and cochlear implants.

Significance Statement

A target sound embedded within a background sound becomes perceptually more salient if the background is presented first by itself. This phenomenon, where the target “pops out”, is known as auditory enhancement. It reflects a general principle of contrast enhancement, and helps in the detection of new acoustic events in the environment and in establishing the perceptual constancy of speech and other biologically relevant sounds under varying acoustic conditions. We use EEG in humans to reveal a cortical correlate of this perceptual phenomenon that provides empirical support for a longstanding but previously unverified theoretical account.
Differential attenuation of β2 integrin-dependent and -independent neutrophil migration by Ly6G ligation
Authors: Cunin Pierre , Lee Pui Y. , Kim Edy , Schmider Angela B. , Cloutier Nathalie , Pare Alexandre , Gunzer Matthias , Soberman Roy J. , Lacroix Steve , Boilard Eric , Lefort Craig T. , Nigrovic Peter A.
Published: November 2018

Abstract

Antibody ligation of the murine neutrophil surface protein Ly6G disrupts neutrophil migration in some contexts but not others. We tested whether this variability reflected divergent dependence of neutrophil migration on β2 integrins, adhesion molecules that interact with Ly6G at the neutrophil surface. In integrin-dependent murine arthritis, Ly6G ligation attenuated joint inflammation, even though mice lacking Ly6G altogether developed arthritis normally. By contrast, Ly6G ligation had no impact on integrin- independent neutrophil migration into inflamed lung. In peritoneum, the role of β2 integrins varied with stimulus, proving dispensable for neutrophil entry inE. coliperitonitis but contributory in IL-1-mediated sterile peritonitis. Correspondingly, Ly6G ligation attenuated only IL-1 peritonitis, disrupting the molecular association between integrins and Ly6G and inducing cell-intrinsic blockade restricted to integrin-dependent migration. Consistent with this observation, Ly6G ligation impaired integrin-mediated postadhesion strengthening for neutrophils arresting on activated cremaster endotheliumin vivo. Together, these findings identify selective inhibition of integrin- mediated neutrophil emigration through Ly6G ligation, highlighting the marked site and stimulus specificity of β2 integrin dependence in neutrophil migration.

KEY POINTS

The contribution of β2 integrins to neutrophil migration into inflamed tissues varies with site and stimulus.

Ligation of Ly6G, a GPI-linked neutrophil surface protein, selectively attenuates β2 integrin-dependent neutrophil migration in vivo.

Blockade correlates with disrupted interaction between Ly6G and β2 integrins and impaired integrin-mediated postadhesion strengthening.
Comparison of Approaches to the identification of Symptom Burden in Hemodialysis Patients Utilizing Electronic Health Records
Authors: Chan Lili , Beers Kelly , Chauhan Kinsuk , Debnath Neha , Saha Aparna , Pattharanitima Pattharawin , Cho Judy , Kotanko Peter , Federman Alex , Coca Steven , Vleck Tielman Van , Nadkarni Girish N.
Published: November 2018

Background

Identification of symptoms is challenging with surveys, which are time-intensive and low-throughput. Natural language processing (NLP) could be utilized to identify symptoms from narrative documentation in the electronic health record (EHR).

Methods

We utilized NLP to parse notes for maintenance hemodialysis (HD) patients from two EHR databases (BioMe and MIMIC-III) to identify fatigue, nausea/vomiting, anxiety, depression, cramping, itching, and pain. We compared NLP performance with International Classification of Diseases (ICD) codes and validated the performance of both NLP and codes against manual chart review in a representative subset.

Results

We identified 1034 and 929 HD patients from BioMe and MIMIC-III respectively. The most frequently identified symptoms by NLP from both cohorts were fatigue, pain, and nausea and/or vomiting. NLP was significantly more sensitive than ICD codes for nearly all symptoms. In the BioMe dataset, sensitivity for NLP ranged from 0.85-0.99 vs. 0.09-0.59 for ICD codes. In the MIMIC-III dataset, NLP sensitivity was 0.8-0.98 vs. 0.02-0.53 for ICD. ICD codes were significantly more specific for nausea and/or vomiting (NLP 0.57 vs. ICD 0.97, P=0.03) in BioMe and for depression (NLP 0.67 vs. ICD 0.99, P=0.002) in MIMIC-III. A majority of patients in both cohorts had ?4 symptoms. The more encounters available for a patient the more likely NLP was to identify a symptom.

Conclusions

NLP out performed ICD codes for identification of symptoms on several tests parameters including sensitivity for a majority of symptoms. NLP may be useful for the high-throughput identification of patient centered outcomes from EHR.

Significance Statement

Patients on maintenance hemodialysis experience a high frequency of symptoms. However, symptoms have been measured utilizing time-intensive surveys. This paper compares natural language processing (NLP) to administrative codes for the identification of seven key symptoms from two cohorts with electronic health records and validation through manual chart review. NLP identified high rates of symptoms; the most common were fatigue, pain, and nausea and/or vomiting. A majority of patients had ≥4 symptoms. NLP was significantly more sensitive at identifying symptoms compared to administrative codes for nearly all symptoms but specificity was not significantly different compared to codes. This paper demonstrates utility of a high throughput method of identifying symptoms from EHR which may advance the field of patient centered research in nephrology.
Instantaneous isotropic volumetric imaging of fast biological processes
Authors: Wagner Nils , Norlin Nils , Gierten Jakob , de Medeiros Gustavo , Balázs Bálint , Wittbrodt Joachim , Hufnagel Lars , Prevedel Robert
Published: November 2018

Capturing highly dynamic biological processes at sub-cellular resolution is a recurring challenge in biology. Here we show that combining selective volume illumination with simultaneous acquisition of orthogonal light-fields yields 3D images with high, isotropic spatial resolution and free of reconstruction artefacts, thereby overcoming current limitations of light-field microscopy implementations. We demonstrate Medaka heart and blood flow imaging with single-cell resolution and free of motion artefacts at volume rates up to 200Hz.
Discrete Mechanical Growth Model for Plant Tissue
Authors: Weise Louis D. , ten Tusscher Kirsten H. W. J.
Published: November 2018

We present a discrete mechanical model to study plant development. The method is built up of mass points, springs and hinges mimicking the plant cell wall’s microstructure. To model plastic growth the resting lengths of springs are adjusted; when springs exceed a threshold length, new mass points, springs and hinges, are added. We formulate a stiffness tensor for the springs and hinges as a function of the fourth rank tensor of elasticity and the geometry of the mesh. This allows us to approximate the material law as a generalized orthotropic Hooke’s law, and control material properties during growth. The material properties of the model are illustrated in numerical simulations for finite strain and plastic growth. To solve the equations of motion of mass points we assume elastostatics and use Verlet integration. The method is demonstrated in simulations when anisotropic growth causes emergent residual strain fields in cell walls and a bending of bulk tissue. The method can be used in multilevel models to study plant development, for example by coupling it to models for cytoskeletal, hormonal and gene regulatory processes.
One Model to Rule Them All: An Integrative Approach to Matrix-Based Analyses in Neuroimaging Connectomics
Authors: Chen Gang , Bürkner Paul-Christian , Taylor Paul A. , Li Zhihao , Yin Lijun , Glen Daniel R. , Kinniso Joshua , Cox Robert W. , Pessoa Luiz
Published: November 2018

Network modeling in neuroimaging holds promise in probing the interrelationships among brain regions and potential clinical applications. Two types of matrix-based analysis (MBA) are usually seen in neuroimaging connectomics: one is the functional attribute matrix (FAM) of, for example, correlations, that measures the similarity of BOLD response patterns among a list of predefined regions of interest (ROIs). Another type of MBA involves the structural attribute matrix (SAM), e.g., describing the properties of white matter between any pair of gray-matter regions such as fractional anisotropy, mean diffusivity, axial and radial diffusivity. There are different methods that have been developed or adopted to summarize such matrices across subjects, including general linear models (GLMs) and various versions of graph theoretic analysis. We argue that these types of modeling strategies tend to be “inefficient” in statistical inferences and have many pitfalls, such as having strong dependence on arbitrary thresholding under conventional statistical frameworks.

Here we offer an alternative approach that integrates the analyses of all the regions, region pairs (RPs) and subjects into one framework, called Bayesian multilevel (BML) modeling. In this approach, the intricate relationships across regions as well as across RPs are quantitatively characterized. This integrative approach avoids the multiple testing issue that typically plagues the conventional statistical analysis in neuroimaging, and it provides a principled way to quantify both the effect and its uncertainty at each region as well as for each RP. As a result, a unique feature of BML is that the effect at each region and the corresponding uncertainty can be estimated, revealing the relative strength or importance of each region; in addition, the effect at each RP is obtained along with its uncertainty as statistical evidence. Most importantly, the BML approach can be scrutinized for consistency through validation and comparisons with alternative assumptions or models. We demonstrate the BML methodology with a real dataset with 16 ROIs from 41 subjects, and compare it to the conventional GLM approach in terms of model efficiency, performance and inferences. Furthermore, we emphasize the notion of full results reporting through “highlighting,” instead of through the common practice of “hiding.” The associated program will be available as part of the AFNI suite for general use.
Taxonomy, ecology and distribution of Juniperus oxycedrus L. group in the Mediterranean Region using morphometric, phytochemical and bioclimatic approaches
Authors: Cano Ortiz Ana , Musarella Carmelo M. , Piñar Fuentes José C. , Pinto Gomes Carlos J. , Spampinato Giovanni , Cano Eusebio
Published: November 2018

The ecology, taxonomy and distribution of the Juniperus oxycedrus L. group of taxa are studied. From an ecological aspect, this work proposes a new ombroedaphoxeric index to explain the presence of populations of Juniperus in ombrotypes that are not the optimum for these taxa. The controversy among various authors on the taxonomy of the oxycedrus group with regard to J. oxycedrus subsp. badia and J. oxycedrus subsp. lagunae is clarified. The phytochemical differences in essential oils are addressed, and their similarities analysed; greater similarities are observed between oxycedrus and badia (H. Gay) Debeaux, and between navicularis Grand. and macrocarpa (Sm.) Ball. The phytochemical, molecular and distribution differences allow J. macrocarpa and J. navicularis to be maintained as species.
Single-Cell Modeling of CD8+ T Cell Exhaustion Predicts Response to Cancer Immunotherapy
Authors: Jin Guangxu , Xue Gang , Wang Rui-Sheng , Wu Ling-Yun , Miller Lance , Lu Yong , Zhang Wei
Published: November 2018

Accurate prediction of response to immune checkpoint blockade (ICB) and simultaneous development of new efficacious ICB strategy are unmet needs for cancer immunotherapy1-5. Despite the advance of existing clinical or computational biomarkers6-10, it is very limited in explicating phenotypic variability of tumor-infiltrating CD8+ T lymphocytes (TILs) at the single-cell level, including tumor-specificity11,12 and distinct exhaustion profiles13-16, that are crucial for the responsiveness to ICB. Here we show that a quantitative criterion, D value, for evaluating tumor-specific TIL exhaustion, identified by our new high-dimensional single-cell-based computational method, called HD-scMed, accurately predicts response to the ICB, i.e., αPD-1, αCTLA-4, and αPD-1+αCTLA-4, with the performance of AUC=100% in human tumors. D-value is the Euclidean distance from a subset of exhausted CD8+ TILs, identified as Pareto Front (PF)18-21 by HD-scMed within the high-dimensional expression space of a variety of exhaustion markers, to the baseline TILs excluded by the PF. We phenotypically distinguished two types of TIL “exhaustion” by the D value, namely “D Extremely-high” in non-responders, associating with high tumor-specificity imprinted with enhanced exhaustion and inactivated effector and cytotoxic signatures; and “D low” specific to responders, alternatively enriched with T cell activation and cytolytic effector T cell signatures. We also observed a large portion of “D negative” bystander T cells irrelevant to response. Notably, D-low TILs in clinical responders display very low LAG3 expression. To reverse the functionality of the LAG3-high TILs after receiving αPD-1+αCTLA-4, we combined αLAG3 with αPD-1+αCTLA-4 in treating a murine tumor model. Remarkably, αLAG3+αPD-1+αCTLA-4 displays extraordinary antitumor efficacy to eradicate advanced tumors, which is associated with burst GZMBhi TIL populations; whereas αPD-1+αCTLA-4 or αPD-1+αCTLA-4 plus other ICBs as control only induce moderate tumor growth inhibition. Our study has important implications for cancer immunotherapy as providing both accurate predictions of ICB response and alternative strategy to reverse ICB resistance.
GANai: Standardizing CT Images using Generative Adversarial Network with Alternative Improvement
Authors: Liang Gongbo , Fouladvand Sajjad , Zhang Jie , Brooks Michael A. , Jacobs Nathan , Chen Jin
Published: November 2018

Computed tomography (CT) is a widely-used diag-reproducibility regarding radiomic features, such as intensity, nostic image modality routinely used for assessing anatomical tissue characteristics. However, non-standardized imaging pro-tocols are commonplace, which poses a fundamental challenge in large-scale cross-center CT image analysis. One approach to address the problem is to standardize CT images using generative adversarial network models (GAN). GAN learns the data distribution of training images and generate synthesized images under the same distribution. However, existing GAN models are not directly applicable to this task mainly due to the lack of constraints on the mode of data to generate. Furthermore, they treat every image equally, but in real applications, some images are more difficult to standardize than the others. All these may lead to the lack-of-detail problem in CT image synthesis. We present a new GAN model called GANai to mitigate the differences in radiomic features across CT images captured using non-standard imaging protocols. Given source images, GANai composes new images by specifying a high-level goal that the image features of the synthesized images should be similar to those of the standard images. GANai introduces an alternative improvement training strategy to alternatively and steadily improve model performance. The new training strategy enables a series of technical improvements, including phase-specific loss functions, phase-specific training data, and the adoption of ensemble learning, leading to better model performance. The experimental results show that GANai is significantly better than the existing state-of-the-art image synthesis algorithms on CT image standardization. Also, it significantly improves the efficiency and stability of GAN model training.
Resilience to oxidative and nitrosative stress is mediated by the stressosome, RsbP and SigB inBacillus subtilis.
Authors: Tran Vina , Geraci Kara , Midili Giovanni , Satterwhite William , Wright Rachel , Bonilla Carla Yaneth
Published: November 2018

A bacterium’s ability to thrive in the presence of multiple environmental stressors simultaneously determines its resilience. We showed that activation of the SigB-controlled general stress response by mild environmental or nutritional stress provided significant cross-protection to subsequent lethal oxidative, disulfide and nitrosative stress exposure. SigB activation is mediated via the stressosome and RsbP, the main conduits of environmental and nutritional stress, respectively. Cells exposed to mild environmental stress while lacking the major stressosome components RsbT or RsbRA were highly sensitive to subsequent oxidative stress, whereasrsbRB, rsbRC, rsbRDandytvAnull mutants showed a spectrum of sensitivity, confirming their redundant roles and suggesting they could modulate the signal generated by environmental stress or oxidative stress. Furthermore, from mutant analysis we infer that RsbRA phosphorylation by RsbT was important for this cross-resistance to oxidative stress. By contrast, cells encountering stationary phase stress required RsbP but not RsbT to survive subsequent oxidative stress caused by hydrogen peroxide and diamide. Interestingly, optimum cross-protection against nitrosative stress caused by SNP required SigB but not the known regulators, RsbT and RsbP, suggesting an additional and as yet uncharacterized route of SigB activation independent of the known environmental and energy-stress pathways. Together, these results provide a mechanism for howBacillus subtilispromotes enhanced resistance against lethal oxidative stress during likely physiologically relevant conditions such as mild environmental or nutrient stress.
Crystal structure of human endothelin ETb receptor in complex with peptide inverse agonist IRL2500
Authors: Nagiri Chisae , Shihoya Wataru , Inoue Asuka , Ngako Kadji Francois Marie , Aoki Junken , Nureki Osamu
Published: November 2018

Endothelin receptors (ET A and ET B) are G-protein coupled receptors activated by endothelin-1 and are involved in blood pressure regulation. IRL2500 is a peptide-mimetic of the C-terminal tripeptide of endothelin-1, and has been characterized as a potent ET B-selective antagonist, which has preventive effects against brain edema. Here, we report the crystal structure of the human ET B receptor in complex with IRL2500 at 2.7 A-resolution. The structure revealed the different binding modes between IRL2500 and ET-1, and provides structural insights into its ET B-selectivity. Notably, the biphenyl group of IRL2500 penetrates into the transmembrane core proximal to D2.50, stabilizing the inactive conformation. Using the newly-established constitutively active mutant, we clearly demonstrate that IRL2500 functions as an inverse agonist for the ET B receptor. The current findings will expand the chemical space of ETR antagonists and facilitate the design of inverse agonists for other class A GPCRs.
Solid riveting process optimization for the reduction of key point distortions caused by locating
Authors: Ni Jun , Ding Wuxue
Published: November 2018

Purpose

Determinative locating and riveting distortions are highly coupled at assembly locale. Recent methods only take every tested or assumed locating errors at the mating surface into the process planning for the assemblies in a simple form. However, the growth of part number makes it nearly infeasible to take every locating error at every mating surface into the dimensional precision calculation. This paper aims to provide a solid riveting process planning for the reduction of practical locating-related distortions.

Design/methodology/approach

Large-scale metrology firstly measures the determinative coordinates for the locating-deviated key points. Iterative finite element (FE) analyses then calculate the riveting-related key point distortions from every rivet upsetting directions (UDs) and assembly sequence. These key points on the actual assembly contour and relative FE nodes yield two virtual planes. Virtual plane manipulation adds the riveting distortions into the locating-deviated coordinates. Finally, optimal algorithm integrates the iterative FE analyses with virtual plane manipulation.

Findings

Case studies validate that the virtual plane manipulation coincides with the test well, and the proposed method has good compensation of practical locating distortion.

Research limitations/implications

The optimized rivet UDs may be set in a chaotic distribution, which may complicate the abundant riveting operations and the assembly appearance. Therefore, the use of automatic riveting systems can overcome the operational complexity, and the industrial design of rivet UD distribution will improve the assembly appearance.

Practical implications

The optimized UDs and assembly sequence are for assembly workers or automatic riveting systems.

Originality/value

The proposed method is the first to reduce the determinative locating distortion by a novel and efficient solid riveting process planning in detail, and the solid riveting process designed is conservative and accurate for practice.
Wall distance effect on heat transfer at high flow velocity
Authors: Kurowski Marcin , Szwaba Ryszard , Telega Janusz , Flaszynski Pawel , Tejero Fernando , Doerffer Piotr
Published: November 2018

Purpose

This paper aims to present the results of experimental and numerical research on heat transfer distribution under the impinging jets at various distances from the wall and high jet velocity. This work is a part of the INNOLOT Program financed by National Centre for Research and Development.

Design/methodology/approach

The air jets flow out from the common pipe and impinge on a surface which is cooled by them, and in this way, all together create a model of external cooling system of low-pressure gas turbine casing. Measurements were carried out for the arrangement of 26 in-line jets with orifice diameter of 0.9 mm. Heat transfer distribution was investigated for various Reynolds and Mach numbers. The cooled wall, made of transparent PMMA, was covered with a heater foil on which a layer of self-adhesive liquid crystal foil was placed. The jet-to-wall distance was set to h = from 4.5 to 6 d.

Findings

The influence of various Reynolds and Mach numbers on cooled flat plate and jet-to-wall distance in terms of heat transfer effectiveness is presented. Experimental results used for the computational fluid dynamics (CFD) model development, validation and comparison with numerical results are presented.

Practical implications

Impinging air jets is a commonly used technique to cool advanced turbines elements, as it produces large convection enhancing the local heat transfer, which is a critical issue in the development of aircraft engines.

Originality/value

The achieved results present experimental investigations carried out to study the heat transfer distribution between the orthogonally impinging jets from long round pipe and flat plate. Reynolds number based on the jet orifice exit conditions was varied between 2,500 and 4,000; meanwhile, for such Re, the flow velocity in jets was particularly very high, changing from M = 0.56 to M = 0.77. Such flow conditions combination, i.e. the low Reynolds number and very high flow velocity cannot be found in the existing literature.
Fast identification of transonic buffet envelope using computational fluid dynamics
Authors: Drofelnik Jernej , Da Ronch Andrea , Franciolini Matteo , Crivellini Andrea
Published: November 2018

Purpose

This paper aims to present a numerical method based on computational fluid dynamics that allows investigating the buffet envelope of reference equivalent wings at the equivalent cost of several two-dimensional, unsteady, turbulent flow analyses. The method bridges the gap between semi-empirical relations, generally dominant in the early phases of aircraft design, and three-dimensional turbulent flow analyses, characterised by high costs in analysis setups and prohibitive computing times.

Design/methodology/approach

Accuracy in the predictions and efficiency in the solution are two key aspects. Accuracy is maintained by solving a specialised form of the Reynolds-averaged Navier–Stokes equations valid for infinite-swept wing flows. Efficiency of the solution is reached by a novel implementation of the flow solver, as well as by combining solutions of different fidelity spatially.

Findings

Discovering the buffet envelope of a set of reference equivalent wings is accompanied with an estimate of the uncertainties in the numerical predictions. Just over 2,000 processor hours are needed if it is admissible to deal with an uncertainty of ±1.0° in the angle of attack at which buffet onset/offset occurs. Halving the uncertainty requires significantly more computing resources, close to a factor 200 compared with the larger uncertainty case.

Practical implications

To permit the use of the proposed method as a practical design tool in the conceptual/preliminary aircraft design phases, the method offers the designer with the ability to gauge the sensitivity of buffet on primary design variables, such as wing sweep angle and chord to thickness ratio.

Originality/value

The infinite-swept wing, unsteady Reynolds-averaged Navier–Stokes equations have been successfully applied, for the first time, to identify buffeting conditions. This demonstrates the adequateness of the proposed method in the conceptual/preliminary aircraft design phases.
Unsteady aerodynamic characteristics of a morphing wing
Authors: Xiang Jinwu , Liu Kai , Li Daochun , Cheng Chunxiao , Sha Enlai
Published: November 2018

Purpose

The purpose of this paper is to investigate the unsteady aerodynamic characteristics in the deflection process of a morphing wing with flexible trailing edge, which is based on time-accurate solutions. The dynamic effect of deflection process on the aerodynamics of morphing wing was studied.

Design/methodology/approach

The computational fluid dynamic method and dynamic mesh combined with user-defined functions were used to simulate the continuous morphing of the flexible trailing edge. The steady aerodynamic characteristics of the morphing deflection and the conventional deflection were studied first. Then, the unsteady aerodynamic characteristics of the morphing wing were investigated as the trailing edge deflects at different rates.

Findings

The numerical results show that the transient lift coefficient in the deflection process is higher than that of the static case one in large angle of attack. The larger the deflection frequency is, the higher the transient lift coefficient will become. However, the situations are contrary in a small angle of attack. The periodic morphing of the trailing edge with small amplitude and high frequency can increase the lift coefficient after the stall angle.

Practical implications

The investigation can afford accurate aerodynamic information for the design of aircraft with the morphing wing technology, which has significant advantages in aerodynamic efficiency and control performance.

Originality/value

The dynamic effects of the deflection process of the morphing trailing edge on aerodynamics were studied. Furthermore, time-accurate solutions can fully explore the unsteady aerodynamics and pressure distribution of the morphing wing.
Suntej Engineering: a struggle to stay afloat in the face of competition
Authors: George Sajeev Abraham , Tejwani Latika , Saini Anubha Kachhawa , Pathak Nikhil , Kanvinde Nimish
Published: November 2018

Learning outcomes

The case is intended to enable the student to understand: The dynamics of SME, particularly in the adhesive industry entrepreneurial dilemma faced by the owner of an SME, faced with an existential crisis; the application of analytical frameworks such as Porter’s five forces, PESTEL and SWOT in strategy formulation; importance of long-term supplier relationships and focus on quality in retaining relationship clients.

Case overview/synopsis

The case is set up in the context of a SME in the adhesive industry in India where the Managing Director of the company Suntej Engineering Private Ltd was engulfed with questions on the future of the firm. The firm was faced with multiple challenges mostly from the external environment. The case could help students to appreciate the process of strategic decision-making by the owner of a small firm, in response to a crisis situation, and how his vast experience and entrepreneurial mind-set helps him to tide over the crisis.

Supplementary materials

Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

Strategy
Technology roadmapping in security and defence foresight
Authors: Vicente Oliva Silvia , Martinez-Sanchez Angel
Published: November 2018

Purpose

This paper aims to provide an analysis of Spanish Defence National Foresight Exercise.

Design/methodology/approach

The analysis is based on a content analysis of public domain Spanish Defence National Foresight Exercise, and a study directed to analyse the impact on defence technological and industrial base.

Findings

Foresight studies on the defence and security environment uses hybrid methodologies, but rarely involve all the stakeholders, and specially the citizens. The authors place a particular emphasis on the impact of these defence and security foresight studies, and following policies to increase the competitiveness and advanced technologies in the future. The analysis of the Spanish contractors allows an evaluation of the roadmaps as a policy instrument for the industrial defence industry. The main challenges for the next exercises in the European countries are to increase the interest in the firms’ intelligence systems, and the participation and representation of citizens as a way to guarantee their rights. Therefore, a technology roadmap must be complemented with other more participative foresight methods.

Originality/value

Foresight studies on the defence and security environment have been the subject of very few systematic analyses of impact. This paper makes a contribution to such analysis.
Affective practices and the prison visit: learning at Port Arthur and the Cascades Female Factory
Authors: McKernan Amy
Published: November 2018

Purpose

The purpose of this paper is to consider the ways Port Arthur Historic Site and the Cascades Female Factory educate visitors using the often contentious and confronting histories of convictism in Australia.

Design/methodology/approach

The research was conducted between 2012 and 2015, and included analysis of exhibitions and education programs at the two sites, as well as interviews with core staff, and archival research. Analysis employed a methodological framework drawing on Margaret Wetherell’s (2012) notion of “affective practice”, as well as understandings of historical thinking in education developed by theorists and educators.

Findings

The two sites take differing approaches to educating visitors about the “uncomfortable” histories related to their heritage. Ultimately, this paper argues that the Cascades presents a greater ease with communicating the confronting aspects of the site’s history, while Port Arthur’s interpretive strategies are often focussed on countering widespread assumptions about the “darkness” and cruelty characteristic of the penal system in Australia. Overall, the analysis finds considerable potential in the “use” of confronting and contested history in teaching aimed at developing historical thought and empathy.

Originality/value

The research addresses an issue that is of central concern in heritage education at present – interpretations of confronting and contentious histories – and employs an innovative set of conceptual strategies and tools to gather insights of use to practitioners in heritage and education.
They teach, but do they apply?
Authors: Petrusch Anete , Roehe Vaccaro Guilherme Luís , Luchese Juliane
Published: November 2018

Purpose

Although discussed for more than 20 years, information about Lean adoption in higher education institutions (HEIs) is scarce, especially in developing countries. This research aims to investigate the degree of Lean thinking adoption on administrative services of Brazilian private HEIs. The results are compared to studies from USA and UK, highlighting the maturity on enablers, principles, tools and performance measures related to Lean.

Design/methodology/approach

A quantitative survey research was carried out. The instrument is adapted for HEIs from the proposal of Malmbrandt and Åhlström (2013) for Lean services. Cronbach’s alpha and factor analysis were used to validate the adapted instrument. Additional data analysis was based on non-parametric tests.

Findings

No evidence of broad implementation of Lean thinking in administrative processes of Brazilian private HEIs was found, with the adoption being incipient. The results are convergent to those presented by other studies in the USA and the UK. There is a gap between the existing knowledge about Lean in the academic sphere of the HEIs and its application on their academic processes.

Research limitations/implications

The effective sample size was of 47, despite contacts being sent to 2,090 institutions. This sample allows exploratory research, although further research is required. Results are adherent to those found in research from other countries.

Originality/value

The research presents descriptive and exploratory results regarding the adoption of Lean in Brazilian HEIs. No previous similar research was found in the literature.
Social media brand perceptions of millennials
Authors: Helal Guida , Ozuem Wilson , Lancaster Geoff
Published: November 2018

Purpose

A phenomenon that has revolutionized society is the technological millennial approach to communication. Social media has matured into a prime channel for regular interactions and development of brand–customer relationships that enrich a social identity. The purpose of this paper is to investigate how this affects business communications.

Design/methodology/approach

The study utilized a social constructivist perspective, adopting an inductive and embedded case study strategy.

Findings

Drawing on the social identity theory, this paper examines how evolving social media platforms have impacted on brand perceptions in the fashion apparel and accessories industries. Fashion brands’ online presence provide a platform for customers to supplement social identity based on associations with brands, and ultimately this can shape brand perceptions among customers through promised functional and symbolic benefits.

Research limitations/implications

The paper investigates a specialized marketing activity in the UK. A broader internationally based study would add strength to these findings.

Practical implications

The paper focuses on theoretical and managerial implications and proffers significant roles that social media and identity may play in keeping up with the design and development of marketing communications programs.

Social implications

Multinational corporations have embraced internet technologies and social media in adopting platforms that their brands can use to contribute content to followers.

Originality/value

In total, 30 potential participants, drawn from diverse backgrounds, were contacted via social networking sites, e-mails and telephone. In total, 22 agreed to participate and their mean age was 26. An open-ended questionnaire allowed for elaboration, providing appropriate responses for a second interviewing phase. Four industry professionals were recruited through the researchers’ personal networks to participate in in-depth interviews that sought to investigate the significance of social media as a marketing tool from an industry perspective.
Integrating the importance levels of friends into trust-based ant-colony recommender systems
Authors: Tengkiattrakul Phannakan , Maneeroj Saranya , Takasu Atsuhiro
Published: November 2018

Purpose

This paper aims to propose a trust-based ant-colony recommender system. It achieves high accuracy and coverage by integrating the importance level of friends. This paper has two main contributions, namely, selecting higher-quality raters and improving the prediction step. From these two contributions, the proposed trust-based ant-colony recommender system could provide more accurate and wider-coverage prediction than existing systems.

Design/methodology/approach

To obtain higher-quality raters, the data set was preprocessed, and then, trust values were calculated. The depth of search was increased to obtain higher coverage levels. This work also focuses on the importance level of friends in the system. Because the levels of influence on the active user of all friends are not equal, the importance level of friends is integrated into the system by transposing rater’s rating to the active user’s perspective and then assigning a weight to each rater.

Findings

The experimental evaluation clearly demonstrates that the proposed method achieves better results in terms of both accuracy and coverage than existing trust-based recommender systems. It was found that integrating the importance level of friends into the system, which transposes ratings and assigns weight to each user, can increase accuracy and coverage.

Originality/value

Existing trust-based ant-colony recommender systems do not consider the importance level of friends in the prediction step. Most of them only focus on finding raters and then using the rater’s real ratings in the prediction step. A new method is proposed that integrates the importance level of friends into the system by transposing a rater’s rating to match the active user’s perspective and assigning a weight for each rater. The experimental evaluation demonstrates that the proposed method achieves better accuracy and coverage than existing systems.