bluuebunny/crossref_metadata_2025 huggingface dataset:
An Improved Imperialist Competitive Algorithm to Solve the Selected Harmonic Elimination Pulse-Width Modulation in Multilevel Converters
Authors: Gong Zheng , Cui Qi , Zheng Xi , Dai Peng , Zhu Rongwu
Published: November 2018

The traditional intelligent algorithms for the selected harmonic elimination pulse-width modulation (SHEPWM) of multilevel converters provide low convergent rate and low accuracy of solutions when solving quarter-wave symmetry nonlinear equations. To obviate this problem and obtain a better modulating performance, an improved imperialist competition algorithm is proposed. The proposed algorithm enhances the global search ability by using moving imperialists. Also, a novel type of particles, named independent countries, are proposed to help the algorithm jump out of the local optimum. These independent countries change their positions using swarm intelligence. Compared with the existing particle swarm algorithm and genetic algorithm, the proposed algorithm has significant advantages by improving the accuracy of solutions and the rate of convergence. Finally, the correctness and effectiveness of the proposed algorithm are verified and evaluated by simulation and experimental results.
Structural and Electrochemical Properties of Dense Yttria-Doped Barium Zirconate Prepared by Solid-State Reactive Sintering
Authors: Yun Dae Sik , Kim Jaegyeom , Kim Seung-Joo , Lee Jong-Heun , Kim Jong-Nam , Yoon Hyung Chul , Yu Ji Haeng , Kwak Minseok , Yoon Hana , Cho Younghyun , Yoo Chung-Yul
Published: November 2018

For practical utilization of proton-conducting ceramic fuel cells and electrolyzers, it is essential to lower the sintering temperature and processing time of BaZrO3-based proton conductors. We investigated the effect of sintering temperature and time on the structural and electrochemical properties of dense BaZr0.8Y0.2O3−δ (BZY) prepared by a solid-state reactive sintering process, using NiO as a sintering aid. The sintered BZY prepared from the micronized precursor powder exhibited a density higher than 93%, and an average grain size in the range of 0.6 to 1.4 μm. The orthorhombic BaY2NiO5 phase was also observed in the sintered BZY from the combined conventional and synchrotron X-ray diffraction measurements. Electrochemical impedance spectroscopy showed that the total proton conductivities of BZY can be modulated by sintering temperature in a wet reducing atmosphere. The maximum total ion transport number achieved was 0.89 at 600 °C, and the maximum power density of the symmetric BZY electrolyte supported cell with Pt electrodes was 5.24 mW·cm−2 at 900 °C.
Estimation of Fuel Economy Improvement in Gasoline Vehicle Using Cylinder Deactivation
Authors: Lee Nankyu , Park Jinil , Lee Jonghwa , Park Kyoungseok , Choi Myoungsik , Kim Wongyu
Published: November 2018

Cylinder deactivation is a fuel economy improvement technology that has attracted particular attention recently. The currently produced cylinder deactivation engines utilize fixed-type cylinder deactivation in which only a fixed number of cylinders are deactivated. As fixed-type cylinder deactivation has some shortcomings, variable-type cylinder deactivation with no limit on the number of deactivated cylinders is under research. For variable-type cylinder deactivation, control is more complicated and production cost is higher than fixed-type cylinder deactivation. Therefore, it is necessary to select the cylinder deactivation control method considering both advantages and disadvantages of the two control methods. In this study, a fuel economy prediction simulation model was created using the measurement data of various vehicles with engine displacements of 1.0–5.0 L. The fuel economy improvement of fixed-type cylinder deactivation was compared with that of variable-type cylinder deactivation using the created simulation. As a result of examining the fuel economy improvement of the test vehicle in the FTP-75 driving cycle, the improvement was 2.2–10.0% for fixed-type cylinder deactivation and 2.2–12.8% for variable-type cylinder deactivation. Furthermore, the effect of the engine load on fuel economy improvement under cylinder deactivation and the effect of changes in engine control were examined via a simulation.
Multi-Step Short-Term Power Consumption Forecasting with a Hybrid Deep Learning Strategy
Authors: Yan Ke , Wang Xudong , Du Yang , Jin Ning , Huang Haichao , Zhou Hangxia
Published: November 2018

Electric power consumption short-term forecasting for individual households is an important and challenging topic in the fields of AI-enhanced energy saving, smart grid planning, sustainable energy usage and electricity market bidding system design. Due to the variability of each household’s personalized activity, difficulties exist for traditional methods, such as auto-regressive moving average models, machine learning methods and non-deep neural networks, to provide accurate prediction for single household electric power consumption. Recent works show that the long short term memory (LSTM) neural network outperforms most of those traditional methods for power consumption forecasting problems. Nevertheless, two research gaps remain as unsolved problems in the literature. First, the prediction accuracy is still not reaching the practical level for real-world industrial applications. Second, most existing works only work on the one-step forecasting problem; the forecasting time is too short for practical usage. In this study, a hybrid deep learning neural network framework that combines convolutional neural network (CNN) with LSTM is proposed to further improve the prediction accuracy. The original short-term forecasting strategy is extended to a multi-step forecasting strategy to introduce more response time for electricity market bidding. Five real-world household power consumption datasets are studied, the proposed hybrid deep learning neural network outperforms most of the existing approaches, including auto-regressive integrated moving average (ARIMA) model, persistent model, support vector regression (SVR) and LSTM alone. In addition, we show a k-step power consumption forecasting strategy to promote the proposed framework for real-world application usage.
A Wide Load Current and Voltage Range Switched Capacitor DC–DC Converter with Load Dependent Configurability for Dynamic Voltage Implementation in Miniature Sensors
Authors: Saif Hassan , Lee Yongmin , Lee Hyeonji , Kim Minsun , Khan Muhammad Bilawal , Chun Jung-Hoon , Lee Yoonmyung
Published: November 2018

Advancements in low power circuits and batteries have enabled the design of miniature sensors with tiny batteries. In such systems, implementing dynamic voltage scaling (DVS) is crucial for maximizing system lifetime. In this paper, a new switched capacitor (SC) converter that is capable of handling a wide range of load currents and output voltages is presented for on-chip DVS implementation. The proposed converter consists of multi-ratio multi-leaf SC stages and reconfigurable interconnect, enabling fine voltage resolution. The stage interconnect scheme enables cascaded or parallel connection of stages. The multi-leaf structure allows load-dependent switch size selection, offering a better trade-off between losses over a wide load range. A limited-voltage-swing switch-driving scheme allows efficient down-conversion from high battery voltage input. A prototype was fabricated in a 180 nm process, providing an output voltage with effective resolution of 16 mV over a load current range of 300 nA to 300 μA (1000×) from a 4 V battery. Efficiency greater than 62% and a peak efficiency of 77% are achieved under a light load (500 nA) over a voltage range of 400 mV to 1.6 V. Efficiency greater than 64% and a peak efficiency of 72% are achieved under a heavy load (200 μA) over a voltage range of 700 mV to 1.6 V.
Analysis of Environment-Marker Associations in American Chestnut
Authors: Müller Markus , Nelson C. Dana , Gailing Oliver
Published: November 2018

American chestnut (Castanea dentata Borkh.) was a dominant tree species in its native range in eastern North America until the accidentally introduced fungus Cryphonectria parasitica (Murr.) Barr, that causes chestnut blight, led to a collapse of the species. Different approaches (e.g., genetic engineering or conventional breeding) are being used to fight against chestnut blight and to reintroduce the species with resistant planting stock. Because of large climatic differences within the distribution area of American chestnut, successful reintroduction of the species requires knowledge and consideration of local adaptation to the prevailing environmental conditions. Previous studies revealed clear patterns of genetic diversity along the northeast-southwest axis of the Appalachian Mountains, but less is known about the distribution of potentially adaptive genetic variation within the distribution area of this species. In this study, we investigated neutral and potentially adaptive genetic variation in nine American chestnut populations collected from sites with different environmental conditions. In total, 272 individuals were genotyped with 24 microsatellite (i.e., simple sequence repeat (SSR)) markers (seven genomic SSRs and 17 EST-SSRs). An FST-outlier analysis revealed five outlier loci. The same loci, as well as five additional ones, were significantly associated with environmental variables of the population sites in an environmental association analysis. Four of these loci are of particular interest, since they were significant in both methods, and they were associated with environmental variation, but not with geographic variation. Hence, these loci might be involved in (temperature-related) adaptive processes in American chestnut. This work aims to help understanding the genetic basis of adaptation in C. dentata, and therefore the selection of suitable provenances for further breeding efforts.
Harvesting of Microalgae by Flocculation
Authors: Branyikova Irena , Prochazkova Gita , Potocar Tomas , Jezkova Zuzana , Branyik Tomas
Published: November 2018

Due to increasing demands for microalgal biomass and products originating from microalgae, large-scale production systems are necessary. However, current microalgal production technologies are not cost-effective and are hindered by various bottlenecks, one of which is the harvesting of microalgal biomass. Cell separation is difficult because of the low sedimentation velocity of microalgae, their colloidal character with repelling negative surface charges, and low biomass concentrations in culture broths; therefore, large volumes need to be processed in order to concentrate the cells. Flocculation is considered to be one of the most suitable methods for harvesting microalgal biomass. This article provides an overview of flocculation methods suitable for microalgal harvesting, their mechanisms, advantages and drawbacks. Special attention is paid to the role of surface charge in the mechanism of flocculation. The novelty of the review lies in the interconnection between the context of technological applications and physico-chemical surface phenomena.
Increasing Editorial Diversity: Strategies for Structural Change
Authors: Smith Annabel L.
Published: November 2018

Editorial boards should be representative of the people doing science but they are often plagued with inequality. This article presents some starting points towards increasing editorial diversity, hoping to spark new initiatives to recruit people of under-represented groups to editorial boards. I argue there should be a greater focus on what journals and publishers should do instead of focusing on stories and celebrations of extraordinary individuals overcoming barriers. Transparent reporting, diversity targets, strategic invitations, mentoring programs, self-assigned workloads are all strategies which might lead to structural change. New, creative ways to recruit editors are needed so that women and all under-represented groups are given more opportunities to shape the direction of science.
Novel Modelling Approaches to Characterize and Quantify Carryover Effects on Sensory Acceptability
Authors: Torrico Damir Dennis , Jirangrat Wannita , Wang Jing , Chompreeda Penkwan , Sriwattana Sujinda , Prinyawiwatkul Witoon
Published: November 2018

Sensory biases caused by the residual sensations of previously served samples are known as carryover effects (COE). Contrast and convergence effects are the two possible outcomes of carryover. COE can lead to misinterpretations of acceptability, due to the presence of intrinsic psychological/physiological biases. COE on sensory acceptability (hedonic liking) were characterized and quantified using mixed and nonlinear models. N = 540 subjects evaluated grape juice samples of different acceptability qualities (A = good, B = medium, C = poor) for the liking of color (C), taste (T), and overall (OL). Three models were used to quantify COE: (1) COE as an interaction effect; (2) COE as a residual effect; (3) COE proportional to the treatment effect. For (1), COE was stronger for C than T and OL, although COE was minimal. For (2), C showed higher estimates (−0.15 to +0.10) of COE than did T and OL (−0.09 to +0.07). COE mainly took the form of convergence. For (3), the absolute proportionality parameter estimate (λ) was higher for C than for T and OL (−0.155 vs. −0.004 to −0.039), which represented −15.46% of its direct treatment effect. Model (3) showed a significant COE for C. COE cannot be ignored as they may lead to the misinterpretation of sensory acceptability results.
Epidemiology of Hepatitis B Virus Infection in Bangladesh: Prevalence among General Population, Risk Groups and Genotype Distribution
Authors: Uz-Zaman Md. Hassan , Rahman Ayesha , Yasmin Mahmuda
Published: November 2018

Despite a considerable body of published research on hepatitis B in Bangladesh, researchers continue to lament the lack of reliable information about hepatitis B virus (HBV) infection epidemiology. The present review aims to provide a comprehensive survey of the literature with particular focus on a number of epidemiological questions, as well as a commentary on the trends of hepatitis B research as it has taken place in Bangladesh. The key themes to emerge from this review are: first, beyond noting a declining trend, it is difficult to provide conclusive estimates about HBV prevalence in the general population of Bangladesh. The majority of the studies, even the ones conducted on apparently healthy populations, fail to be adequately representative for the reasons explored in the article. Secondly, HBV infection in Bangladesh is sharply stratified across sociodemographic lines, which speaks to the role of awareness and risk exposure in HBV prevalence. Third, more research on occult infection rates is required to estimate the extent of risk posed by the current blood donation screening program, which relies exclusively on hepatitis B surface antigen as a biomarker. The same considerations apply for the comparative importance of vertical versus horizontal transmission and prevalence among particular risk groups like healthcare workers with high occupational exposure. Finally, while recent studies do allow us, albeit with some ambiguity, to draw conclusions about distribution of HBV genotypes in Bangladesh, there needs to be an added emphasis on molecular epidemiology. It is hoped that the present review, the first of its kind in Bangladesh, will serve as an up-to-date summary of the course HBV epidemiology research in Bangladesh has taken thus far, as well as crucial gaps to address going forward.
Harnessing Rhizobia to Improve Heavy-Metal Phytoremediation by Legumes
Authors: Fagorzi Camilla , Checcucci Alice , DiCenzo George C. , Debiec-Andrzejewska Klaudia , Dziewit Lukasz , Pini Francesco , Mengoni Alessio
Published: November 2018

Rhizobia are bacteria that can form symbiotic associations with plants of the Fabaceae family, during which they reduce atmospheric di-nitrogen to ammonia. The symbiosis between rhizobia and leguminous plants is a fundamental contributor to nitrogen cycling in natural and agricultural ecosystems. Rhizobial microsymbionts are a major reason why legumes can colonize marginal lands and nitrogen-deficient soils. Several leguminous species have been found in metal-contaminated areas, and they often harbor metal-tolerant rhizobia. In recent years, there have been numerous efforts and discoveries related to the genetic determinants of metal resistance by rhizobia, and on the effectiveness of such rhizobia to increase the metal tolerance of host plants. Here, we review the main findings on the metal resistance of rhizobia: the physiological role, evolution, and genetic determinants, and the potential to use native and genetically-manipulated rhizobia as inoculants for legumes in phytoremediation practices.
Hydrodynamic and Debris-Damming Failure of Bridge Decks and Piers in Steady Flow
Authors: Oudenbroek Kevin , Naderi Nader , Bricker Jeremy D. , Yang Yuguang , Van der Veen Cor , Uijttewaal Wim , Moriguchi Shuji , Jonkman Sebastiaan N.
Published: November 2018

In countries with steep rivers, such as Japan and the United States, bridges fail on an annual basis. Bridges on spread footings are especially susceptible to failure by hydrodynamic loading, often exacerbated by debris damming. Here, such failures are investigated via small scale model laboratory experiments and full scale numerical simulations. In the laboratory, lift and drag forces and overturning moment on bridge decks, piers, and deck-pier systems, are measured and compared with threshold of failure criteria used in design guidelines. Effects of debris on lift, drag, and moment, as well as three-dimensional effects, are quantified. Via numerical simulations, flow patterns and free surface behaviour responsible for these forces are investigated, and described in a framework as a function of the water depth, flow speed, deck clearance, and girder height. Results show that current guidelines are non-conservative in some cases. Importantly, failure of both decks and piers can be prevented by strengthening pier-deck connections, or by streamlining decks.
Geochemical Features of Fallow Land in Ancient Plots in the Chora of Chersonesos
Authors: Lisetskii Fedor , Zelenskaya Eugenia , Rodionova Maria
Published: November 2018

The ancient city of Chersonesos created an agricultural zone in the 4th and 3rd centuries BC (under the conditions of climate aridization); this zone was initially used for viticulture and the export of wine, and grain farming later developed at the distant chora (in North-Western (NW) Crimea). The purpose of our work was to verify whether the ampeloecological conditions, especially the geochemical features of the soil and rock, limited viticulture in NW Crimea. Fallow lands in 13 plots in the near and distant chora of Chersonesos were studied using ampelopedology; specifically, we compared agrochemical properties and the concentrations of macro- and trace elements in the renaturation soil horizon and in the parent rock. The main differences between the soils of the two regions were determined by the accumulation of cinnamonic soils of Chersonesos Si, K, Fe, Al, P2O5; in the distant chora, there are specific elements, including V, Pb, Rb, Cr. The climate and the biogeochemical diversity of soils and rock could be significant factors causing the differences in wine quality in the two regions of western Crimea; these factors are still reflected in modern viticultural practices when using the concept of “terroir”. These findings are consistent with the different roles of ancient viticulture in SW (South-Western) and NW (North-Western) Crimea (i.e., export and local consumption, respectively), which have been highlighted by historians.
The Second World War, Imperial, and Colonial Nostalgia: The North Africa Campaign and Battlefields of Memory
Authors: Kingsepp Eva
Published: November 2018

The article addresses the function of (post)colonial nostalgia in a context of multidirectional memory (Rothberg 2009) in contemporary Europe. How can different cultural memories of the Second Word War be put into respectful dialogue with each other? The text is based on a contrapuntal reading (Said 1994) of British and Egyptian popular narratives, mainly British documentary films about the North Africa Campaign, but also feature films and novels, and data from qualitative interviews collected during ethnographic fieldwork in Alexandria and Cairo, Egypt, during visits 2013–2015. The study highlights the considerable differences between the British and Egyptian narratives, but also the significant similarities regarding the use and function of nostalgia. In addition, the Egyptian narrative expresses a profound cosmopolitan nostalgia and a longing for what is regarded as Egypt’s lost, modern Golden Age, identified as the decades before the nation’s fundamental change from western-oriented monarchy to Nasser’s Arab nationalist military state. The common elements between the two national narratives indicate a possibly fruitful way to open up for a shared popular memory culture about the war years, including postcolonial aspects.
Performance of Excess Heat Factor Severity as a Global Heatwave Health Impact Index
Authors: Nairn John , Ostendorf Bertram , Bi Peng
Published: November 2018

The establishment of an effective policy response to rising heatwave impacts is most effective when the history of heatwaves, their current impacts and future risks, are mapped by a common metric. In response meteorological agencies aim to develop seamless climate, forecast, and warning heat impact services, spanning all temporal and spatial scales. The ability to diagnose heatwave severity using the Excess Heat Factor (EHF) has allowed the Australian Bureau of Meteorology (the Bureau) to publicly release 7-day heatwave severity maps since 2014. National meteorological agencies in the UK and the United States are evaluating global 7-day and multi-week EHF heatwave severity probability forecasts, whilst the Bureau contributes to a Copernicus project to supply the health sector with global EHF severity heatwave projection scenarios. In an evaluation of impact skill within global forecast systems, EHF intensity and severity is reviewed as a predictor of human health impact, and extended using climate observations and human health data for sites around the globe. Heatwave intensity, determined by short and long-term temperature anomalies at each locality, is normalized to permit spatial analysis and inter-site comparison. Dimensionless heatwave event moments of peak severity and accumulated severity are shown to correlate with noteworthy events around the globe, offering new insights into current and future heatwave variability and vulnerability. The EHF severity metric permits the comparison of international heatwave events and their impacts, and is readily implemented within international heatwave early warning systems.
Moral or Dirty Leadership: A Qualitative Study on How Juniors Are Managed in Dutch Consultancies
Authors: Bouwmeester Onno , Kok Tessa Elisabeth
Published: November 2018

Professional service firms in Western Europe have a reputation for putting huge pressures on their junior employees, resulting in very long work hours, and as a consequence health risks. This study explores moral leadership as a possible response to the stigma of such dirty leadership. We conducted semi-structured interviews with 12 consultant managers and with each one of their juniors, and found that managers put several pressures on their juniors; these pressures bring high levels of stress, lowered wellbeing and burnout. Society considers such a pressuring leadership style morally dirty. To counteract the experience of being seen as morally dirty, we found that consultant managers were normalizing such criticisms as commonly assumed in dirty work literature. However, they also employed several moral leadership tactics to counteract the negative consequences criticized in society. However, in addition to the well-known individual-level tactics, consultant managers and their juniors also reported moral leadership support at the organizational level, like institutionalized performance talks after every project, trainings, specific criteria for hiring juniors, and policies to recognize and compliment high performance. Still, we cannot conclude these moral leadership approaches are moral by definition. They can be used in an instrumental way as well, to further push performance.
The Elephant in the Room: Informality in Tanzania’s Rural Waterscape
Authors: Katomero Jesper , Georgiadou Yola
Published: November 2018

Informality is pervasive in Tanzania’s rural waterscape, but not acknowledged by development partners (donors and beneficiaries), despite persistent warnings by development scholars. Informality is thus the proverbial elephant in the room. In this paper, we examine a case of superior rural water access in two geographical locales—Hai and Siha districts—in Tanzania, where actors not only acknowledge, but actively harness informality to provide access to water to rural populations. We employ concepts from organization and institutional theory to show that when informal programs and related informal sanctions/rewards complement their formal counterparts, chances for achieving the Sustainable Development Goals (SDG) target 6.1 ‘By 2030, achieve universal and equitable access to safe and affordable drinking water for all’ are significantly increased.
Landslide Susceptibility Mapping Using Logistic Regression Analysis along the Jinsha River and Its Tributaries Close to Derong and Deqin County, Southwestern China
Authors: Sun Xiaohui , Chen Jianping , Bao Yiding , Han Xudong , Zhan Jiewei , Peng Wei
Published: November 2018

The objective of this study was to identify the areas that are most susceptible to landslide occurrence, and to find the key factors associated with landslides along Jinsha River and its tributaries close to Derong and Deqin County. Thirteen influencing factors, including (a) lithology, (b) slope angle, (c) slope aspect, (d) TWI, (e) curvature, (f) SPI, (g) STI, (h) topographic relief, (i) rainfall, (j) vegetation, (k) NDVI, (l) distance-to-river, (m) and distance-to-fault, were selected as the landslide conditioning factors in landslide susceptibility mapping. These factors were mainly obtained from the field survey, digital elevation model (DEM), and Landsat 4–5 imagery using ArcGIS software. A total of 40 landslides were identified in the study area from field survey and aerial photos’ interpretation. First, the frequency ratio (FR) method was used to clarify the relationship between the landslide occurrence and the influencing factors. Then, the principal component analysis (PCA) was used to eliminate multiple collinearities between the 13 influencing factors and to reduce the dimension of the influencing factors. Subsequently, the factors that were reselected using the PCA were introduced into the logistic regression analysis to produce the landslide susceptibility map. Finally, the receiver operating characteristic (ROC) curve was used to evaluate the accuracy of the logistic regression analysis model. The landslide susceptibility map was divided into the following five classes: very low, low, moderate, high, and very high. The results showed that the ratios of the areas of the five susceptibility classes were 23.14%, 22.49%, 18.00%, 19.08%, and 17.28%, respectively. And the prediction accuracy of the model was 83.4%. The results were also compared with the FR method (79.9%) and the AHP method (76.9%), which meant that the susceptibility model was reasonable. Finally, the key factors of the landslide occurrence were determined based on the above results. Consequently, this study could serve as an effective guide for further land use planning and for the implementation of development.
Automatic Parametrization of Urban Areas Using ALS Data: The Case Study of Santiago de Compostela
Authors: Soilán Mario , Riveiro Belén , Liñares Patricia , Pérez-Rivas Andrea
Published: November 2018

Nowadays, gathering accurate and meaningful information about the urban environment with the maximum efficiency in terms of cost and time has become more relevant for city administrations, as this information is essential if the sustainability or the resilience of the urban structure has to be improved. This work presents a methodology for the automatic parametrization and characterization of different urban typologies, for the specific case study of Santiago de Compostela (Spain), using data from Aerial Laser Scanners (ALS). This methodology consists of a number of sequential processes of point cloud data, using exclusively their geometric coordinates. Three of the main elements of the urban structure are assessed in this work: intersections, building blocks, and streets. Different geometric and contextual metrics are automatically extracted for each of the elements, defining the urban typology of the studied area. The accuracy of the measurements is validated against a manual reference, obtaining average errors of less than 3%, proving that the input data is valid for this assessment.
A Nationwide Survey on Danon Disease in Japan
Authors: Sugie Kazuma , Komaki Hirofumi , Eura Nobuyuki , Shiota Tomo , Onoue Kenji , Tsukaguchi Hiroyasu , Minami Narihiro , Ogawa Megumu , Kiriyama Takao , Kataoka Hiroshi , Saito Yoshihiko , Nonaka Ikuya , Nishino Ichizo
Published: November 2018

Danon disease, an X-linked dominant cardioskeletal myopathy, is caused by primary deficiency of lysosome-associated membrane protein-2 (LAMP-2). To clarify the clinicopathological features and management, we performed the first nationwide, questionnaire-based survey on Danon disease in Japan. A total of 39 patients (17 males, 22 females) from 20 families were identified in the analysis. All patients had cardiomyopathy. Of the 21 patients who died, 20 (95%) died of cardiac failure or sudden cardiac arrest. Most patients had hypertrophic cardiomyopathy. Wolf–Parkinson–White syndrome was present at a comparatively high incidence (54% in males, 22% in females). Only one female patient received a heart transplant, which is the most effective therapy. Histopathologically, all male patients showed autophagic vacuoles with sarcolemmal features in muscle. Half of the probands showed de novo mutations. Male patients showed completely absent LAMP-2 expression in muscle. In contrast, female patients showed decreased LAMP-2 expression, which is suggested to reflect LAMP-2 haploinsufficiency due to a heterozygous null mutation. In conclusion, Danon disease is an extremely rare muscular disorder in Japan. Cardiomyopathy is the most significant prognostic factor and the main cause of death. Our findings suggest that the present survey can extend our understanding of the clinical features of this rare disease.
Impact of Melatonin in Solid Organ Transplantation—Is It Time for Clinical Trials? A Comprehensive Review
Authors: Stiegler Philipp , Bausys Augustinas , Leber Bettina , Strupas Kestutis , Schemmer Peter
Published: November 2018

Solid organ transplantation is the “gold standard” for patients with end-stage organ disease. However, the supply of donor organs is critical, with an increased organ shortage over the last few years resulting in a significant mortality of patients on waiting lists. New strategies to overcome the shortage of organs are urgently needed. Some experimental studies focus on melatonin to improve the donor pool and to protect the graft; however, current research has not reached the clinical level. Therefore, this review provides a comprehensive overview of the data available, indicating that clinical evaluation is warranted.
A Mutation in the Mesorhizobium loti oatB Gene Alters the Physicochemical Properties of the Bacterial Cell Wall and Reduces Survival inside Acanthamoeba castellanii
Authors: Karaś Magdalena Anna , Turska-Szewczuk Anna , Marczak Małgorzata , Jaszek Magdalena , Janczarek Monika , Dworaczek Katarzyna , Stefaniuk Dawid , Wydrych Jerzy
Published: November 2018

In our previous report, we had shown that the free-living amoeba Acanthamoeba castellanii influenced the abundance, competiveness, and virulence of Mesorhizobium loti NZP2213, the microsymbiont of agriculturally important plants of the genus Lotus. The molecular basis of this phenomenon; however, had not been explored. In the present study, we demonstrated that oatB, the O-acetyltransferase encoding gene located in the lipopolysaccharide (LPS) synthesis cluster of M. loti, was responsible for maintaining the protective capacity of the bacterial cell envelope, necessary for the bacteria to fight environmental stress and survive inside amoeba cells. Using co-culture assays combined with fluorescence and electron microscopy, we showed that an oatB mutant, unlike the parental strain, was efficiently destroyed after rapid internalization by amoebae. Sensitivity and permeability studies of the oatB mutant, together with topography and nanomechanical investigations with the use of atomic force microscopy (AFM), indicated that the incomplete substitution of lipid A-core moieties with O-polysaccharide (O-PS) residues rendered the mutant more sensitive to hydrophobic compounds. Likewise, the truncated LPS moieties, rather than the lack of O-acetyl groups, made the oatB mutant susceptible to the bactericidal mechanisms (nitrosative stress and the action of lytic enzymes) of A. castellanii.
Synthesis and Transformation of (-)-Isopulegol-Based Chiral β-Aminolactones and β-Aminoamides
Authors: Le Tam Minh , Bérdi Péter , Zupkó István , Fülöp Ferenc , Szakonyi Zsolt
Published: November 2018

A library of isopulegol-based β-amino acid derivatives has been developed from commercially-available (-)-isopulegol. Michael addition of primary and secondary amines towards α,β-unsaturated γ-lactones was accomplished resulting in β-aminolactones in highly-stereoselective reactions. Ring-opening of β-aminolactones with different amines furnished excellent yields of β-aminoamides. Moreover, the applicability of aminolactones in peptide synthesis was examined by opening the lactone ring with α- and β-aminoesters, providing dipeptides as promising chiral substrates for the synthesis of foldamers. The antiproliferative activities of β-aminolactones and β-aminoamides were explored, and the structure-activity relationships were studied from the aspects of the stereochemistry of the monoterpene ring and the substituent effects on the β-aminoamide ring system. The N-unsubstituted (-)-isopulegol-based β-aminoamides exhibited considerable antiproliferative activity against a panel of human adherent cancer cell lines (HeLa, MCF7 and MDA-MB-231).
Atomistic Analysis of ToxN and ToxI Complex Unbinding Mechanism
Authors: Hu Guodong , Yu Xiu , Bian Yunqiang , Cao Zanxia , Xu Shicai , Zhao Liling , Ji Baohua , Wang Wei , Wang Jihua
Published: November 2018

ToxIN is a triangular structure formed by three protein toxins (ToxNs) and three specific noncoding RNA antitoxins (ToxIs). To respond to stimuli, ToxI is preferentially degraded, releasing the ToxN. Thus, the dynamic character is essential in the normal function interactions between ToxN and ToxI. Here, equilibrated molecular dynamics (MD) simulations were performed to study the stability of ToxN and ToxI. The results indicate that ToxI adjusts the conformation of 3′ and 5′ termini to bind to ToxN. Steered molecular dynamics (SMD) simulations combined with the recently developed thermodynamic integration in 3nD (TI3nD) method were carried out to investigate ToxN unbinding from the ToxIN complex. The potentials of mean force (PMFs) and atomistic pictures suggest the unbinding mechanism as follows: (1) dissociation of the 5′ terminus from ToxN, (2) missing the interactions involved in the 3′ terminus of ToxI without three nucleotides (G31, A32, and A33), (3) starting to unfold for ToxI, (4) leaving the binding package of ToxN for three nucleotides of ToxI, (5) unfolding of ToxI. This work provides information on the structure-function relationship at the atomistic level, which is helpful for designing new potent antibacterial drugs in the future.
Structural Studies of the 3′,3′-cGAMP Riboswitch Induced by Cognate and Noncognate Ligands Using Molecular Dynamics Simulation
Authors: Li Chaoqun , Zhao Xiaojia , Zhu Xiaomin , Xie Pengtao , Chen Guangju
Published: November 2018

Riboswtich RNAs can control gene expression through the structural change induced by the corresponding small-molecule ligands. Molecular dynamics simulations and free energy calculations on the aptamer domain of the 3′,3′-cGAMP riboswitch in the ligand-free, cognate-bound and noncognate-bound states were performed to investigate the structural features of the 3′,3′-cGAMP riboswitch induced by the 3′,3′-cGAMP ligand and the specificity of ligand recognition. The results revealed that the aptamer of the 3′,3′-cGAMP riboswitch in the ligand-free state has a smaller binding pocket and a relatively compact structure versus that in the 3′,3′-cGAMP-bound state. The binding of the 3′,3′-cGAMP molecule to the 3′,3′-cGAMP riboswitch induces the rotation of P1 helix through the allosteric communication from the binding sites pocket containing the J1/2, J1/3 and J2/3 junction to the P1 helix. Simultaneously, these simulations also revealed that the preferential binding of the 3′,3′-cGAMP riboswitch to its cognate ligand, 3′,3′-cGAMP, over its noncognate ligand, c-di-GMP and c-di-AMP. The J1/2 junction in the 3′,3′-cGAMP riboswitch contributing to the specificity of ligand recognition have also been found.
The Two-Faced Cytokine IL-6 in Host Defense and Diseases
Authors: Narazaki Masashi , Kishimoto Tadamitsu
Published: November 2018

Interleukein-6 (IL-6), is produced locally from infectious or injured lesions and is delivered to the whole body via the blood stream, promptly activating the host defense system to perform diverse functions. However, excessive or sustained production of IL-6 is involved in various diseases. In diseases, the IL-6 inhibitory strategy begins with the development of the anti-IL-6 receptor antibody, tocilizumab (TCZ). This antibody has shown remarkable effects on Castleman disease, rheumatoid arthritis and juvenile idiopathic arthritis. In 2017, TCZ was proven to work effectively against giant cell arteritis, Takayasu arteritis and cytokine releasing syndrome, initiating a new era for the treatment of these diseases. In this study, the defensive functions of IL-6 and various pathological conditions are compared. Further, the diseases of which TCZ has been approved for treatment are summarized, the updated results of increasing off-label use of TCZ for various diseases are reviewed and the conditions for which IL-6 inhibition might have a beneficial role are discussed. Given the involvement of IL-6 in many pathologies, the diseases that can be improved by IL-6 inhibition will expand. However, the important role of IL-6 in host defense should always be kept in mind in clinical practice.
Preliminary Design Considerations for Variable Geometry Radial Turbines with Multi-Points Specifications
Authors: Lauriau Pierre-Thomas , Binder Nicolas , Cros Sandrine , Roumeas Mathieu , Carbonneau Xavier
Published: November 2018

Radial turbines’ preliminary designs are usually carried out through some dimensionless approaches, such as the loading-to-flow-diagram and/or the blade speed ratio. In case of variable nozzle radial turbines, multi-points specifications must be considered, related to the improvement of the operating range. As preliminary design correlations and standards usually taken into consideration arise from studies dedicated to fixed geometry radial turbines, they need to be updated with regard to nozzle off-design opening configurations. This paper provides some theoretical basics in order to help designers considering variable geometry problems. Some complementary elements about the dimensionless methods are given by taking into account the nozzle opening effect. Then, useful considerations are brought regarding the preliminary design of variable geometry radial turbines with multi-points specifications.
Dielectric-Filled Reentrant Cavity Resonator as a Low-Intensity Proton Beam Diagnostic
Authors: Srinivasan Sudharsan , Duperrex Pierre-André
Published: November 2018

Measurement of the proton beam current (0.1–40 nA) at the medical treatment facility PROSCAN at the Paul Scherrer Institut (PSI) is performed with ionization chambers. To mitigate the scattering issues and to preserve the quality of the beam delivered to the patients, a non-interceptive monitor based on the principle of a reentrant cavity resonator has been built. The resonator with a fundamental resonance frequency of 145.7 MHz was matched to the second harmonic of the pulse repetition rate (72.85 MHz) of the beam extracted from the cyclotron. This was realized with the help of ANSYS HFSS (High Frequency Structural Simulator) for network analysis. Both, the pickup position and dielectric thickness were optimized. The prototype was characterized with a stand-alone test bench. There is good agreement between the simulated and measured parameters. The observed deviation in the resonance frequency is attributed to the frequency dependent dielectric loss tangent. Hence, the dielectric had to be resized to tune the resonator to the design resonance frequency. The measured sensitivity performances were in agreement with the expectations. We conclude that the dielectric reentrant cavity resonator is a promising candidate for measuring low proton beam currents in a non-destructive manner.
Post-Translational Modifications and Diastolic Calcium Leak Associated to the Novel RyR2-D3638A Mutation Lead to CPVT in Patient-Specific hiPSC-Derived Cardiomyocytes
Authors: Acimovic Ivana , Refaat Marwan , Moreau Adrien , Salykin Anton , Reiken Steve , Sleiman Yvonne , Souidi Monia , Přibyl Jan , Kajava Andrey , Richard Sylvain , Lu Jonathan , Chevalier Philippe , Skládal Petr , Dvořak Petr , Rotrekl Vladimir , Marks Andrew , Scheinman Melvin , Lacampagne Alain , Meli Albano
Published: November 2018

Background: Sarcoplasmic reticulum Ca2+ leak and post-translational modifications under stress have been implicated in catecholaminergic polymorphic ventricular tachycardia (CPVT), a highly lethal inherited arrhythmogenic disorder. Human induced pluripotent stem cells (hiPSCs) offer a unique opportunity for disease modeling. Objective: The aims were to obtain functional hiPSC-derived cardiomyocytes from a CPVT patient harboring a novel ryanodine receptor (RyR2) mutation and model the syndrome, drug responses and investigate the molecular mechanisms associated to the CPVT syndrome. Methods: Patient-specific cardiomyocytes were generated from a young athletic female diagnosed with CPVT. The contractile, intracellular Ca2+ handling and electrophysiological properties as well as the RyR2 macromolecular remodeling were studied. Results: Exercise stress electrocardiography revealed polymorphic ventricular tachycardia when treated with metoprolol and marked improvement with flecainide alone. We found abnormal stress-induced contractile and electrophysiological properties associated with sarcoplasmic reticulum Ca2+ leak in CPVT hiPSC-derived cardiomyocytes. We found inadequate response to metoprolol and a potent response of flecainide. Stabilizing RyR2 with a Rycal compound prevents those abnormalities specifically in CPVT hiPSC-derived cardiomyocytes. The RyR2-D3638A mutation is located in the conformational change inducing-central core domain and leads to RyR2 macromolecular remodeling including depletion of PP2A and Calstabin2. Conclusion: We identified a novel RyR2-D3638A mutation causing 3D conformational defects and aberrant biophysical properties associated to RyR2 macromolecular complex post-translational remodeling. The molecular remodeling is for the first time revealed using patient-specific hiPSC-derived cardiomyocytes which may explain the CPVT proband’s resistance. Our study promotes hiPSC-derived cardiomyocytes as a suitable model for disease modeling, testing new therapeutic compounds, personalized medicine and deciphering underlying molecular mechanisms.
Systematic Review and Meta-Analysis on the Impact of Thrombolytic Therapy in Liver Transplantation Following Donation after Circulatory Death
Authors: Jayant Kumar , Reccia Isabella , Virdis Francesco , Shapiro A.
Published: November 2018

Aim: The livers from DCD (donation after cardiac death) donations are often envisaged as a possible option to bridge the gap between the availability and increasing demand of organs for liver transplantation. However, DCD livers possess a heightened risk for complications and represent a formidable management challenge. The aim of this study was to evaluate the effects of thrombolytic flush in DCD liver transplantation. Methods: An extensive search of the literature database was made on MEDLINE, EMBASE, Cochrane, Crossref, Scopus databases, and clinical trial registry on 20 September 2018 to assess the role of thrombolytic tissue plasminogen activator (tPA) flush in DCD liver transplantation. Results: A total of four studies with 249 patients in the tPA group and 178 patients in the non-tPA group were included. The pooled data revealed a significant decrease in ischemic-type biliary lesions (ITBLs) (P = 0.04), re-transplantation rate (P = 0.0001), and no increased requirement of blood transfusion (P = 0.16) with a better one year graft survival (P = 0.02). Conclusions: To recapitulate, tPA in DCD liver transplantation decreased the incidence of ITBLs, re-transplantation and markedly improved 1-year graft survival, without any increased risk for blood transfusion, hence it has potential to expand the boundaries of DCD liver transplantation.
Characterization of Microbiota in Bronchiectasis Patients with Different Disease Severities
Authors: Lee Sang Hoon , Lee YeonJoo , Park Jong Sun , Cho Young-Jae , Yoon Ho Il , Lee Choon-Taek , Lee Jae Ho
Published: November 2018

The applications of the 16S rRNA gene pyrosequencing has expanded our knowledge of the respiratory tract microbiome originally obtained using conventional, culture-based methods. In this study, we employed DNA-based molecular techniques for examining the sputum microbiome in bronchiectasis patients, in relation to disease severity. Of the sixty-three study subjects, forty-two had mild and twenty-one had moderate or severe bronchiectasis, which was classified by calculating the FACED score, based on the FEV1 (forced expiratory volume in 1 s, %) (F, 0–2 points), age (A, 0–2 points), chronic colonization by Pseudomonas aeruginosa (C, 0–1 point), radiographic extension (E, 0–1 point), and dyspnoea (D, 0–1 point). Bronchiectasis was defined as mild, at 0–2 points, moderate at 3–4 points, and severe at 5–7 points. The mean age was 68.0 ± 9.3 years; thirty-three patients were women. Haemophilus (p = 0.005) and Rothia (p = 0.043) were significantly more abundant in the mild bronchiectasis group, whereas Pseudomonas (p = 0.031) was significantly more abundant in the moderate or severe group. However, in terms of the alpha and beta diversity, the sputum microbiota of the two groups did not significantly differ, i.e., the same dominant genera were found in all samples. Further large-scale studies are needed to investigate the sputum microbiome in bronchiectasis.