bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of salinity and sugar concentration using microwave sensor
Authors: Rahman Md. Naimur , Hassan Sayed Amirul , Samsuzzaman Md. , Singh Mandeep Singh Jit , Islam Mohammad Tariqul
Published: November 2018

A microwave sensor is presented in this letter for the detection of salinity and sugar concentration. The microwave sensor is used for the transmission and reception of electromagnetic wave. The sensor has a circular shaped radiating patch with semi‐circular shaped slots. The antenna sensor is prototyped on a low‐cost FR4 substrate which is 1.60 mm thick. The sensor has a small size of 26 mm × 24 mm. The high‐frequency structural simulator (HFSS) is utilized to model the microwave sensor. The sensor detects the salinity and sugar concentration by means of the reflection coefficient. The dielectric constant changes with the increased percentages of the salt and sugar which reduces the reflection coefficient. The microwave sensing device shows considerable sensitivity to determine the salinity and sugar concentration.
Validation of Current Good Manufacturing Practice Compliant Human Pluripotent Stem Cell-Derived Hepatocytes for Cell-Based Therapy
Authors: Blackford Samuel J.I. , Ng Soon Seng , Segal Joe M. , King Aileen J.F. , Austin Amazon L. , Kent Deniz , Moore Jennifer , Sheldon Michael , Ilic Dusko , Dhawan Anil , Mitry Ragai R. , Rashid S. Tamir
Published: November 2018

Recent advancements in the production of hepatocytes from human pluripotent stem cells (hPSC-Heps) afford tremendous possibilities for treatment of patients with liver disease. Validated current good manufacturing practice (cGMP) lines are an essential prerequisite for such applications but have only recently been established. Whether such cGMP lines are capable of hepatic differentiation is not known. To address this knowledge gap, we examined the proficiency of three recently derived cGMP lines (two hiPSC and one hESC) to differentiate into hepatocytes and their suitability for therapy. hPSC-Heps generated using a chemically defined four-step hepatic differentiation protocol uniformly demonstrated highly reproducible phenotypes and functionality. Seeding into a 3D poly(ethylene glycol)-diacrylate fabricated inverted colloid crystal scaffold converted these immature progenitors into more advanced hepatic tissue structures. Hepatic constructs could also be successfully encapsulated into the immune-privileged material alginate and remained viable as well as functional upon transplantation into immune competent mice. This is the first report we are aware of demonstrating cGMP-compliant hPSCs can generate cells with advanced hepatic function potentially suitable for future therapeutic applications. Stem Cells Translational Medicine  2019;8:124&14
Preparation of Hollow Nitrogen Doped Carbon via Stresses Induced Orientation Contraction
Authors: Wang Min Jie , Mao Zhan Xin , Liu Lu , Peng Lishan , Yang Na , Deng Jianghai , Ding Wei , Li Jing , Wei Zidong
Published: November 2018

Hollow structured materials are widely applicable in various fields. Although many routes have been explored for getting such materials, a strategy mainly based on physical effect is still deficient. Herein, a “stresses induced orientation contraction” mechanism for preparation of hollow structures is reported. The composites constructed by zeolite imidazolate framework‐8 (ZIF8) cores and polymerized dopamine (PDA) shells, upon annealing, form intensive interfacial interactions, which drag the ZIF8 cores outward to restrain their shrinkage. The gradually accumulated stresses in the central position of ZIF8 dodecahedron nanoparticles, then destroy the ZIF8 crystalline cores to form the hollow structures. In this stress‐based route for creating hollow interiors with core–shell composites as the starting materials, three critical factors are necessary: 1) an intensive core–shell interfacial interaction; 2) the distinctly higher shrinkage degree of the cores than the shells; and 3) the relatively loose core structures. In oxygen reduction reaction (ORR) tested with three‐electrode solution system and Zn–O2 battery, the achieved hollow nitrogen doped carbon (NC) demonstrates ultrahigh catalytic activities. This work gives an absolutely novel strategy for preparation of hollow structures, which may afford the exploration of a wider range of materials system with hollow interiors.
Testing MapReduce programs: A systematic mapping study
Authors: Morán Jesús , de la Riva Claudio , Tuya Javier
Published: November 2018

Context

MapReduce is a processing model used in Big Data to facilitate the analysis of large data under a distributed architecture.

Objective

The aim of this study is to identify and categorize the state of the art of software testing in MapReduce applications, determining trends and gaps.

Method

Systematic mapping study to discuss and classify according to international standards 54 relevant studies in relation to reasons for testing, types of testing, quality characteristics, test activities, tools, roles, processes, test levels, and research validations.

Results

The principal reasons for testing MapReduce applications are performance issues, potential failures, issues related to the data, or to satisfy the agreements with efficient resources. The efforts are focused on performance and, to a lesser degree, on functionality. Performance testing is carried out through simulation and evaluation, whereas functional testing considers some program characteristics (such as specification and structure). Despite the type of testing, the majority of efforts are focused at the unit and integration test levels of the specific MapReduce functions without considering other parts of the technology stack.

Conclusions

Researchers have both opportunities and challenges in performance and functional testing, and there is room to improve their research though the use of mature and standard validation methods.
Gravitating scalar stars in the large D limit
Authors: Rozali Moshe , Way Benson
Published: November 2018

Abstract

We develop the large D limit of general relativity for spherically symmetric scalar fields in both asymptotically flat and asymptotically anti-de Sitter spaces. The leading order equations in the 1/D expansion can be solved analytically, providing a large D description of oscillating soliton stars. When the amplitude reaches a critical threshold, certain divergences occur which we interpret as signal of horizon formation. We estimate the size of the resulting black hole and obtain a scaling exponent. We speculate on some connections to Choptuik critical collapse.
Efficient transposition of Tn 4556 by alterations in inverted repeats using a delivery vector carrying a counter-selectable marker for Streptomyces
Authors: Sota Masahiro , Sakoda Akiko , Ikeda Haruo
Published: November 2018

A 6625-base pair transposon, Tn 4556, was initially isolated from a Streptomyces strain and a sequence analysis was performed; however, its annotation data remain incomplete. At least three positions were identified as frameshift and base-exchange errors by resequencing. The revised sequence revealed that Tn 4556 contains four open reading frames that encode transposase, methyltransferase, isoprenyl diphosphate transferase, and resolvase, respectively. Thirty-eight-base pair inverted repeat (IR) sequences at both ends contained a 1-bp mismatch flanked by a target duplication site, and transposition efficiency was improved by the replacement of imperfectly matched IR-L to perfectly matched IR-L. The detection of Tn 4556 transposition was markedly facilitated using a delivery vector carrying a strictly counter-selectable marker for Streptomyces strains.
Adventist Millennials: Measuring Emerging Adults’ Connection to Church
Authors: Jacobs Douglas , Tilstra Douglas , Benjamin Finbar , Pittman Sharon , James Hollis , Thayer Jerome , Klingbeil Thandi , Arellano Jordan , Tyler Chelsy
Published: November 2018

Numerous research studies have demonstrated an exodus of emerging adults from Christian denominations. The Adventist Connection Study examined how emerging adult graduates of Seventh-day Adventist universities in the United States connect with or disconnect from Adventist churches in the context of identity, community, orthodoxy, and orthopraxy. Through a two-phased mixed methodology approach, researchers conducted semi-structured interviews with self-selected focus groups of recent college graduates, developed an inductively generated survey instrument, and then electronically distributed the survey via email to recent Adventist college graduates. The results suggested several themes for further discussion. Particularly notable is the influence personal religiosity has on the sample's acceptance of Adventist teachings and faith practice, as well as the negative impact participants’ media usage and transitory lifestyles have on their connection to local churches. Overall, the majority of the sample identified as connected to the Adventist Church, and many who appear to have disconnected from the Adventist Church remain engaged in a variety of nontraditional ways.
Impact of neuroimmune activation induced by alcohol or drug abuse on adolescent brain development
Authors: Guerri Consuelo , Pascual María
Published: November 2018

Evidence obtained in recent decades has demonstrated that the brain still matures in adolescence. Changes in neural connectivity occur in different regions, including cortical and subcortical structures, which undergo modifications in white and gray matter densities. These alterations concomitantly occur in some neurotransmitter systems and hormone secretion, which markedly influence the refinement of certain brain areas and neural circuits. The immaturity of the adolescent brain makes it more vulnerable to the effects of alcohol and drug abuse, whose use can trigger long‐term behavioral dysfunction. This article reviews the action of alcohol and drug abuse (cannabis, cocaine, opioids, amphetamines, anabolic androgenic steroids) in the adolescent brain, and their impact on both cognition and behavioral dysfunction, including predisposition to drug abuse in later life. It also discusses recent evidence that indicates the role of the neuroimmune system response and neuroinflammation as mechanisms that participate in many actions of ethanol and drug abuse in adolescence, including the neurotoxicity and alterations in neurocircuitry that contribute to the dysfunctional behaviors associated with addiction. The new data suggest the therapeutic potential of anti‐inflammatory targets to prevent the long‐term consequences of drug abuse in adolescence.
Improving the quality of life of care home residents with dementia: Cost‐effectiveness of an optimized intervention for residents with clinically significant agitation in dementia
Authors: Romeo Renee , Zala Darshan , Knapp Martin , Orrell Martin , Fossey Jane , Ballard Clive
Published: November 2018

Introduction

To examine whether an optimized intervention is a more cost‐effective option than treatment as usual (TAU) for improving agitation and quality of life in nursing home residents with clinically significant agitation and dementia.

Methods

A cost‐effectiveness analysis within a cluster‐randomized factorial study in 69 care homes with 549 residents was conducted. Each cluster was randomized to receive either the Well‐being and Health for people with Dementia (WHELD) intervention or TAU for nine months. Health and social care costs, agitation, and quality of life outcomes were evaluated.

Results

Improvements in agitation and quality of life were evident in residents allocated to the WHELD intervention group. The additional cost of the WHELD intervention was offset by the higher health and social care costs incurred by TAU group residents (mean difference, £2103; 95% confidence interval, −13 to 4219).

Discussion

The WHELD intervention has clinical and economic benefits when used in residents with clinically significant agitation.
From Rebellion to Opposition: UNITA’s Social Engagement in Post-War Angola
Authors: Pearce Justin
Published: November 2018

The endurance and indeed the growing electoral support manifested by the Angolan opposition party UNITA since its defeat as an armed movement in 2002 defies generally gloomy prognoses both for opposition parties in dominant party systems and for defeated rebel movements that recast themselves as political parties. This article examines social service and training projects implemented by UNITA in the Angolan Central Highlands. I argue that the case of UNITA illustrates the need to take into account the importance of resources that accrue outside of the space of formal politics, including historical narratives and social relationships, which UNITA has mobilized and built upon in order to expand its vote share and consolidate its place within electoral politics.
Where and when? How phenological patterns of armyworm moths (Lepidoptera: Noctuidae) change along a latitudinal gradient in Brazil
Authors: Piovesan M. , Carneiro E. , Specht A. , Casagrande M.M.
Published: November 2018

The phenological patterns exhibited by different organisms are known as adaptive responses to the cyclical environmental conditions. However, only a limited number of researches explore which factors are responsible for these phenological patterns in pest species. In the current study, abundance patterns were studied in the phenology of three Spodoptera Guenée, 1852 species, along the 29° latitudinal gradient in South America. The goal was to test whether widely distributed and abundant crop pest species would exhibit different phenological responses to seasonal meteorological variables and host plant availability. To test this, 13 light traps were set up in Brazil to collect adult Spodoptera samples at the time of the new moon, every month, from June 2015 to May 2016. The time of occurrence and intensity of the phenology were determined for each species, employing circular statistics. Both metrics revealed significant variations among the different species, as well as the factors associated with them. Latitude was found to affect the period of occurrence in Spodoptera cosmioides (Walker, 1858) and Spodoptera albula (Walker, 1857), whereas in Spodoptera frugiperda (J. E. Smith, 1797) its effect was evident only in the intensity of its phenology. Further, both meteorological variables and host plant availability in the sampling sites produced predictive models to account for the phenological patterns expressed. These findings suggest that different species of Spodoptera exhibit different adaptive strategies in their life cycles in response to environmental conditions, thus necessitating specific management practices regarding their seasonal population fluctuation.
Wartime Wilsonianism and the Crisis of Empire, 1941–43
Authors: YELLEN JEREMY A.
Published: November 2018

One striking feature of the Pacific War was the extent to which Wilsonian ideals informed the war aims of both sides. By 1943, the Atlantic Charter and Japan's Pacific Charter (Greater East Asia Joint Declaration) outlined remarkably similar visions for the postwar order. This comparative study of the histories surrounding both charters highlights parallels between the foreign policies of Great Britain and Imperial Japan. Both empires engaged with Wilsonianism in similar ways, to similar ends. Driven by geopolitical desperation, both reluctantly enshrined Wilsonian values into their war aims to survive a gruelling war with empire intact. But the endorsement of national self-determination, in particular, gave elites in dependent states a means to protest the realities of both British and Japanese rule and to demand that both empires practise what they preach. This comparative analysis of Britain and Japan thus sheds light on the part Wilsonian ideology played in the global crisis of empire during the Second World War.
Hepatic fatty acid synthesis and partitioning: the effect of metabolic and nutritional state
Authors: Hodson Leanne
Published: November 2018

When we consume dietary fat, a series of complex metabolic processes ensures that fatty acids are absorbed, transported around the body and used/stored appropriately. The liver is a central metabolic organ within the human body and has a major role in regulating fat and carbohydrate metabolism. Studying hepatic metabolism in human subjects is challenging; the use of stable isotope tracers and measurement of particles or molecules secreted by the liver such as VLDL-TAG and 3-hydroxybutyrate offers the best insight into postprandial hepatic fatty acid metabolism in human subjects. Diet derived fatty acids are taken up by the liver and mix with fatty acids coming from the lipolysis of adipose tissue, and those already present in the liver (cytosolic TAG) and fatty acids synthesised de novo within the liver from non-lipid precursors (known as de novo lipogenesis). Fatty acids are removed from the liver by secretion as VLDL-TAG and oxidation. Perturbations in these processes have the potential to impact on metabolic health. Whether fatty acids are partitioned towards oxidation or esterification pathways appears to be dependent on a number of metabolic factors; not least ambient insulin concentrations. Moreover, along with the phenotype and lifestyle factors (e.g. habitual diet) of an individual, it is becoming apparent that the composition of the diet (macronutrient and fatty acid composition) may play pivotal roles in determining if intra-hepatic fat accumulates, although what remains to be elucidated is the influence these nutrients have on intra-hepatic fatty acid synthesis and partitioning.
Hearing loss and psychiatric disorders: a review
Authors: Blazer Dan G. , Tucci Debara L.
Published: November 2018

Hearing loss is one of the most common yet unrecognized impairments experienced by adults, especially as they age. Mental health investigators and practitioners require better understanding of hearing loss, its association with psychiatric disorders, and the treatment of these disorders in the presence of hearing loss as well as the treatment of hearing loss itself. In this review, the authors briefly explore the global burden of hearing loss. Next we provide an overview of the extant literature on hearing loss associated with cognitive impairment, depression, anxiety disorders, psychoses, and quality of life with attention focused on the strength of the association, possible mechanisms explaining the association, data on treatment options specific to these disorders, and future research opportunities for these disorders. Current approaches to the treatment of hearing loss are presented, including hearing aids, rehabilitation including psychotherapies, surgical procedures (specifically cochlear implants), and induction loops connected to telecoils. Finally, cutting edge research into the pathophysiology and potential biological treatments of hearing loss is described.
The role of English in developing countries
Authors: Haidar Sham
Published: November 2018

Research exploring the role of English in Pakistani education system usually focuses on the use of English as the medium of instruction. However, in this paper I argue that English language should also be discussed in the context of its indispensibility in social mobility and survival in Pakistan. In fact, English plays a number of crucial roles in some developing countries, of which Pakistan is one (Mansoor, 2003; Rahman, 2002). In Pakistan, English is one of the official languages and a prerequisite for professional jobs (Rahman, 2005). Because of its use in the domains of power, English can be seen as a source of self-improvement and as a means of career success (Mansoor, 2003; Rahman, 2002). Thus, the knowledge of English is a key indicator of social class and people consider it superior to other languages (Shamim, 2008). However, the use of English in education is one of the main sources of failure for many ordinary people (Bruthiaux, 2002). English is used as a control mechanism to play a gate-keeping role in access to higher education and key social positions (Coleman, 2010; Rahman, 2002). The imposition of English in education and its perceived prestige create additional problems for low socioeconomic status (SES) students who often have limited access to English.
Reassessing the Evidence of Chinese “Character Amnesia”
Authors: Almog Guy
Published: November 2018

Increasing numbers of Chinese and Japanese speakers have been reporting that their ability to handwrite Chinese characters has been steadily diminishing, a phenomenon which is most likely a result of the growing reliance upon digital technologies. This so-called “character amnesia” has recently attracted a great deal of concern from a large number of observers, especially within the People's Republic of China. Unsurprisingly, many of the concerned participants involved in the discourse on this issue tend to rely on various empirical means in order to illustrate why they consider “character amnesia” such a worrying phenomenon. This article argues, however, that the bulk of this empirical support is unreliable and/or invalid. The article also suggests possible amendments which could hopefully lead to a better understanding of this important subject.
Aktiv Beziehung leben
Authors: Finklenburg Udo
Published: November 2018

Zusammenfassung. In diesem Artikel geht es um die Beziehungsgestaltung im ambulanten, aufsuchenden Um- feld, in welchem die Bedeutung der Beziehung und die darin liegende Verantwortung noch deutlicher wird.
Costa Receives 2018 Harry Elderfield Student Paper Award
Authors:   AGU
Published: November 2018

Kassandra Costa will receive the 2018 Harry Elderfield Student Paper Award at AGU's Fall Meeting 2018, to be held 10–14 December in Washington, D. C. The award recognizes “an exemplary manuscript from a Ph.D. graduate student and exceptional promise for continued contributions in the fields of paleoceanography and/or paleoclimatology.”
Wet Spots as Hotspots: Moisture Responses of Nitric and Nitrous Oxide Emissions From Poorly Drained Agricultural Soils
Authors: Hall S. J. , Reyes L. , Huang W. , Homyak P. M.
Published: November 2018

A classic framework for soil nitrogen (N) cycling, the hole in the pipe (HIP) model, posits a trade‐off in emissions of nitric oxide (NO) and nitrous oxide (N2O) as a function of soil moisture. This has been incorporated into ecosystem models but not tested experimentally and remains an important uncertainty for understanding potential hotspots of reactive N emissions: poorly drained agricultural soils that experience episodically high moisture following intensive fertilization. We incubated soils at moisture ranging from 44% to 100% water‐filled pore space (WFPS). Counter to HIP, we did not observe a consistent trade‐off in NO and N2O emissions at intermediate moisture levels following fertilization, and prefertilization emissions were low. Emissions of N as N2O exceeded NO by 2–200‐fold at all moisture levels and peaked at 73–82% WFPS. Emissions of NO declined with moisture but remained significant even under saturated conditions. Increases in nitrite and reduced iron at high moisture indicated possible NO production from chemodenitrification. Potential nitrification rates were 100–1,000‐fold greater than potential denitrification. Emission factors for fertilizer N ranged from 0.05% to 0.58% (mean = 0.2%) for NO and from 0.4% to 16.9% (mean = 5.3%) for N2O. Our results caution the use of WFPS to predict NO:N2O emission ratios as often employed in ecosystem models. Subsurface N cycling may suppress emissions of NO relative to N2O, and N2O emissions can persist under saturated conditions. Elevated N2O emissions from in‐fieldwet spotscomprising a small landscape extent could potentially address disparities between top‐down and bottom‐up N2O budgets.
High-entropy high-hardness metal carbides discovered by entropy descriptors
Authors: Sarker Pranab , Harrington Tyler , Toher Cormac , Oses Corey , Samiee Mojtaba , Maria Jon-Paul , Brenner Donald W. , Vecchio Kenneth S. , Curtarolo Stefano
Published: November 2018

High-entropy materials have attracted considerable interest due to the combination of useful properties and promising applications. Predicting their formation remains the major hindrance to the discovery of new systems. Here we propose a descriptor—entropy forming ability—for addressing synthesizability from first principles. The formalism, based on the energy distribution spectrum of randomized calculations, captures the accessibility of equally-sampled states near the ground state and quantifies configurational disorder capable of stabilizing high-entropy homogeneous phases. The methodology is applied to disordered refractory 5-metal carbides—promising candidates for high-hardness applications. The descriptor correctly predicts the ease with which compositions can be experimentally synthesized as rock-salt high-entropy homogeneous phases, validating the ansatz, and in some cases, going beyond intuition. Several of these materials exhibit hardness up to 50% higher than rule of mixtures estimations. The entropy descriptor method has the potential to accelerate the search for high-entropy systems by rationally combining first principles with experimental synthesis and characterization.
Cryo-EM structures of KdpFABC suggest a K+ transport mechanism via two inter-subunit half-channels
Authors: Stock C. , Hielkema L. , Tascón I. , Wunnicke D. , Oostergetel G. T. , Azkargorta M. , Paulino C. , Hänelt I.
Published: November 2018

P-type ATPases ubiquitously pump cations across biological membranes to maintain vital ion gradients. Among those, the chimeric K+ uptake system KdpFABC is unique. While ATP hydrolysis is accomplished by the P-type ATPase subunit KdpB, K+ has been assumed to be transported by the channel-like subunit KdpA. A first crystal structure uncovered its overall topology, suggesting such a spatial separation of energizing and transporting units. Here, we report two cryo-EM structures of the 157 kDa, asymmetric KdpFABC complex at 3.7 Å and 4.0 Å resolution in an E1 and an E2 state, respectively. Unexpectedly, the structures suggest a translocation pathway through two half-channels along KdpA and KdpB, uniting the alternating-access mechanism of actively pumping P-type ATPases with the high affinity and selectivity of K+ channels. This way, KdpFABC would function as a true chimeric complex, synergizing the best features of otherwise separately evolved transport mechanisms.
Systematic review of indoor residual spray efficacy and effectiveness against Plasmodium falciparum in Africa
Authors: Sherrard-Smith Ellie , Griffin Jamie T. , Winskill Peter , Corbel Vincent , Pennetier Cédric , Djénontin Armel , Moore Sarah , Richardson Jason H. , Müller Pie , Edi Constant , Protopopoff Natacha , Oxborough Richard , Agossa Fiacre , N’Guessan Raphael , Rowland Mark , Churcher Thomas S.
Published: November 2018

Indoor residual spraying (IRS) is an important part of malaria control. There is a growing list of insecticide classes; pyrethroids remain the principal insecticide used in bednets but recently, novel non-pyrethroid IRS products, with contrasting impacts, have been introduced. There is an urgent need to better assess product efficacy to help decision makers choose effective and relevant tools for mosquito control. Here we use experimental hut trial data to characterise the entomological efficacy of widely-used, novel IRS insecticides. We quantify their impact against pyrethroid-resistant mosquitoes and use a Plasmodium falciparum transmission model to predict the public health impact of different IRS insecticides. We report that long-lasting IRS formulations substantially reduce malaria, though their benefit over cheaper, shorter-lived formulations depends on local factors including bednet use, seasonality, endemicity and pyrethroid resistance status of local mosquito populations. We provide a framework to help decision makers evaluate IRS product effectiveness.
Exchange coupling torque in ferrimagnetic Co/Gd bilayer maximized near angular momentum compensation temperature
Authors: Bläsing Robin , Ma Tianping , Yang See-Hun , Garg Chirag , Dejene Fasil Kidane , N’Diaye Alpha T , Chen Gong , Liu Kai , Parkin Stuart S. P.
Published: November 2018

Highly efficient current-induced motion of chiral domain walls was recently demonstrated in synthetic antiferromagnetic (SAF) structures due to an exchange coupling torque (ECT). The ECT derives from the antiferromagnetic exchange coupling through a ruthenium spacer layer between the two perpendicularly magnetized layers that comprise the SAF. Here we report that the same ECT mechanism applies to ferrimagnetic bi-layers formed from adjacent Co and Gd layers. In particular, we show that the ECT is maximized at the temperature TA where the Co and Gd angular momenta balance each other, rather than at their magnetization compensation temperature TM. The current induced velocity of the domain walls is highly sensitive to longitudinal magnetic fields but we show that this not the case near TA. Our studies provide new insight into the ECT mechanism for ferrimagnetic systems. The high efficiency of the ECT makes it important for advanced domain wall based spintronic devices.
Characterisation of the British honey bee metagenome
Authors: Regan Tim , Barnett Mark W. , Laetsch Dominik R. , Bush Stephen J. , Wragg David , Budge Giles E. , Highet Fiona , Dainat Benjamin , de Miranda Joachim R. , Watson Mick , Blaxter Mark , Freeman Tom C.
Published: November 2018

The European honey bee (Apis mellifera) plays a major role in pollination and food production. Honey bee health is a complex product of the environment, host genetics and associated microbes (commensal, opportunistic and pathogenic). Improved understanding of these factors will help manage modern challenges to bee health. Here we used DNA sequencing to characterise the genomes and metagenomes of 19 honey bee colonies from across Britain. Low heterozygosity was observed in many Scottish colonies which had high similarity to the native dark bee. Colonies exhibited high diversity in composition and relative abundance of individual microbiome taxa. Most non-bee sequences were derived from known honey bee commensal bacteria or pathogens. However, DNA was also detected from additional fungal, protozoan and metazoan species. To classify cobionts lacking genomic information, we developed a novel network analysis approach for clustering orphan DNA contigs. Our analyses shed light on microbial communities associated with honey bees and demonstrate the power of high-throughput, directed metagenomics for identifying novel biological threats in agroecosystems.
Unicolored phosphor-sensitized fluorescence for efficient and stable blue OLEDs
Authors: Heimel Paul , Mondal Anirban , May Falk , Kowalsky Wolfgang , Lennartz Christian , Andrienko Denis , Lovrincic Robert
Published: November 2018

Improving lifetimes and efficiencies of blue organic light-emitting diodes is clearly a scientific challenge. Towards solving this challenge, we propose a unicolored phosphor-sensitized fluorescence approach, with phosphorescent and fluorescent emitters tailored to preserve the initial color of phosphorescence. Using this approach, we design an efficient sky-blue light-emitting diode with radiative decay times in the submicrosecond regime. By changing the concentration of fluorescent emitter, we show that the lifetime is proportional to the reduction of the radiative decay time and tune the operational stability to lifetimes of up to 320 h (80% decay, initial luminance of 1000 cd/m2). Unicolored phosphor-sensitized fluorescence provides a clear path towards efficient and stable blue light-emitting diodes, helping to overcome the limitations of thermally activated delayed fluorescence.
Excess charge-carrier induced instability of hybrid perovskites
Authors: Lin Yuze , Chen Bo , Fang Yanjun , Zhao Jingjing , Bao Chunxiong , Yu Zhenhua , Deng Yehao , Rudd Peter N. , Yan Yanfa , Yuan Yongbo , Huang Jinsong
Published: November 2018

Identifying the origin of intrinsic instability for organic–inorganic halide perovskites (OIHPs) is crucial for their application in electronic devices, including solar cells, photodetectors, radiation detectors, and light-emitting diodes, as their efficiencies or sensitivities have already been demonstrated to be competitive with commercial available devices. Here we show that free charges in OIHPs, whether generated by incident light or by current-injection from electrodes, can reduce their stability, while efficient charge extraction effectively stabilizes the perovskite materials. The excess of both holes and electrons reduce the activation energy for ion migration within OIHPs, accelerating the degradation of OIHPs, while the excess holes and electrons facilitate the migration of cations or anions, respectively. OIHP solar cells capable of efficient charge-carrier extraction show improved light stability under regular operation conditions compared to an open-circuit condition where the photo-generated charges are confined in the perovskite layers.
Predicting natural language descriptions of mono-molecular odorants
Authors: Gutiérrez E. Darío , Dhurandhar Amit , Keller Andreas , Meyer Pablo , Cecchi Guillermo A.
Published: November 2018

There has been recent progress in predicting whether common verbal descriptors such as “fishy”, “floral” or “fruity” apply to the smell of odorous molecules. However, accurate predictions have been achieved only for a small number of descriptors. Here, we show that applying natural-language semantic representations on a small set of general olfactory perceptual descriptors allows for the accurate inference of perceptual ratings for mono-molecular odorants over a large and potentially arbitrary set of descriptors. This is noteworthy given that the prevailing view is that humans’ capacity to identify or characterize odors by name is poor. We successfully apply our semantics-based approach to predict perceptual ratings with an accuracy higher than 0.5 for up to 70 olfactory perceptual descriptors, a ten-fold increase in the number of descriptors from previous attempts. These results imply that the semantic distance between descriptors defines the equivalent of an odorwheel.
Amino acids stimulate the endosome-to-Golgi trafficking through Ragulator and small GTPase Arl5
Authors: Shi Meng , Chen Bing , Mahajan Divyanshu , Boh Boon Kim , Zhou Yan , Dutta Bamaprasad , Tie Hieng Chiong , Sze Siu Kwan , Wu Geng , Lu Lei
Published: November 2018

The endosome-to-Golgi or endocytic retrograde trafficking pathway is an important post-Golgi recycling route. Here we show that amino acids (AAs) can stimulate the retrograde trafficking and regulate the cell surface localization of certain Golgi membrane proteins. By testing components of the AA-stimulated mTORC1 signaling pathway, we demonstrate that SLC38A9, v-ATPase and Ragulator, but not Rag GTPases and mTORC1, are essential for the AA-stimulated trafficking. Arl5, an ARF-like family small GTPase, interacts with Ragulator in an AA-regulated manner and both Arl5 and its effector, the Golgi-associated retrograde protein complex (GARP), are required for the AA-stimulated trafficking. We have therefore identified a mechanistic connection between the nutrient signaling and the retrograde trafficking pathway, whereby SLC38A9 and v-ATPase sense AA-sufficiency and Ragulator might function as a guanine nucleotide exchange factor to activate Arl5, which, together with GARP, a tethering factor, probably facilitates the endosome-to-Golgi trafficking.
Heart enhancers with deeply conserved regulatory activity are established early in zebrafish development
Authors: Yuan Xuefei , Song Mengyi , Devine Patrick , Bruneau Benoit G. , Scott Ian C. , Wilson Michael D.
Published: November 2018

During the phylotypic period, embryos from different genera show similar gene expression patterns, implying common regulatory mechanisms. Here we set out to identify enhancers involved in the initial events of cardiogenesis, which occurs during the phylotypic period. We isolate early cardiac progenitor cells from zebrafish embryos and characterize 3838 open chromatin regions specific to this cell population. Of these regions, 162 overlap with conserved non-coding elements (CNEs) that also map to open chromatin regions in human. Most of the zebrafish conserved open chromatin elements tested drive gene expression in the developing heart. Despite modest sequence identity, human orthologous open chromatin regions recapitulate the spatial temporal expression patterns of the zebrafish sequence, potentially providing a basis for phylotypic gene expression patterns. Genome-wide, we discover 5598 zebrafish-human conserved open chromatin regions, suggesting that a diverse repertoire of ancient enhancers is established prior to organogenesis and the phylotypic period.
Adipocyte-secreted BMP8b mediates adrenergic-induced remodeling of the neuro-vascular network in adipose tissue
Authors: Pellegrinelli Vanessa , Peirce Vivian J. , Howard Laura , Virtue Samuel , Türei Dénes , Senzacqua Martina , Frontini Andrea , Dalley Jeffrey W. , Horton Antony R. , Bidault Guillaume , Severi Ilenia , Whittle Andrew , Rahmouni Kamal , Saez-Rodriguez Julio , Cinti Saverio , Davies Alun M. , Vidal-Puig Antonio
Published: November 2018

Activation of brown adipose tissue-mediated thermogenesis is a strategy for tackling obesity and promoting metabolic health. BMP8b is secreted by brown/beige adipocytes and enhances energy dissipation. Here we show that adipocyte-secreted BMP8b contributes to adrenergic-induced remodeling of the neuro-vascular network in adipose tissue (AT). Overexpression of bmp8b in AT enhances browning of the subcutaneous depot and maximal thermogenic capacity. Moreover, BMP8b-induced browning, increased sympathetic innervation and vascularization of AT were maintained at 28 °C, a condition of low adrenergic output. This reinforces the local trophic effect of BMP8b. Innervation and vascular remodeling effects required BMP8b signaling through the adipocytes to 1) secrete neuregulin-4 (NRG4), which promotes sympathetic axon growth and branching in vitro, and 2) induce a pro-angiogenic transcriptional and secretory profile that promotes vascular sprouting. Thus, BMP8b and NRG4 can be considered as interconnected regulators of neuro-vascular remodeling in AT and are potential therapeutic targets in obesity.
Publisher Correction: Coordinated targeting of cold and nicotinic receptors synergistically improves obesity and type 2 diabetes
Authors: Clemmensen Christoffer , Jall Sigrid , Kleinert Maximilian , Quarta Carmelo , Gruber Tim , Reber Josefine , Sachs Stephan , Fischer Katrin , Feuchtinger Annette , Karlas Angelos , Simonds Stephanie E. , Grandl Gerald , Loher Daniela , Sanchez-Quant Eva , Keipert Susanne , Jastroch Martin , Hofmann Susanna M. , Nascimento Emmani B. M. , Schrauwen Patrick , Ntziachristos Vasilis , Cowley Michael A. , Finan Brian , Müller Timo D. , Tschöp Matthias H.
Published: November 2018

In the original PDF version of this article, affiliation 1, ‘Institute for Diabetes and Obesity, Helmholtz Diabetes Center (HDC), Helmholtz Zentrum Muenchen & German Center for Diabetes Research (DZD), Neuherberg, Germany’, was incorrectly given as ‘Institute of Diabetes and Regeneration Research, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Neuherberg, Germany ‘. This has now been corrected in the PDF version of the article; the HTML version was correct at the time of publication.
High-speed AFM height spectroscopy reveals µs-dynamics of unlabeled biomolecules
Authors: Heath George R. , Scheuring Simon
Published: November 2018

Dynamics are fundamental to the functions of biomolecules and can occur on a wide range of time and length scales. Here we develop and apply high-speed AFM height spectroscopy (HS-AFM-HS), a technique whereby we monitor the sensing of a HS-AFM tip at a fixed position to directly detect the motions of unlabeled molecules underneath. This gives Angstrom spatial and microsecond temporal resolutions. In conjunction with HS-AFM imaging modes to precisely locate areas of interest, HS-AFM-HS measures simultaneously surface concentrations, diffusion coefficients and oligomer sizes of annexin-V on model membranes to decipher key kinetics allowing us to describe the entire annexin-V membrane-association and self-assembly process in great detail and quantitatively. This work displays how HS-AFM-HS can assess the dynamics of unlabeled bio-molecules over several orders of magnitude and separate the various dynamic components spatiotemporally.
Multidirectional desymmetrization of pluripotent building block en route to diastereoselective synthesis of complex nature-inspired scaffolds
Authors: Srinivasulu Vunnam , Schilf Paul , Ibrahim Saleh , Khanfar Monther A. , Sieburth Scott McN , Omar Hany , Sebastian Anusha , AlQawasmeh Raed A. , O’Connor Matthew John , Al-Tel Taleb H.
Published: November 2018

Octahydroindolo[2,3-a]quinolizine ring system forms the basic framework comprised of more than 2000 distinct family members of natural products. Despite the potential applications of this privileged substructure in drug discovery, efficient, atom-economic and modular strategies for its assembly, is underdeveloped. Here we show a one-step build/couple/pair strategy that uniquely allows access to diverse octahydroindolo[2,3-a]quinolizine scaffolds with more than three contiguous chiral centers and broad distribution of molecular shapes via desymmetrization of the oxidative-dearomatization products of phenols. The cascade demonstrates excellent diastereoselectivity, and the enantioselectivity exceeded 99% when amino acids are used as chiral reagents. Furthermore, two diastereoselective reactions for the synthesis of oxocanes and piperazinones, is reported. Phenotypic screening of the octahydroindolo[2,3-a]quinolizine library identifies small molecule probes that selectively suppress mitochondrial membrane potential, ATP contents and elevate the ROS contents in hepatoma cells (Hepa1–6) without altering the immunological activation or reprogramming of T- and B-cells, a promising approach to cancer therapy.
Genetic variation in PTPN1 contributes to metabolic adaptation to high-altitude hypoxia in Tibetan migratory locusts
Authors: Ding Ding , Liu Guangjian , Hou Li , Gui Wanying , Chen Bing , Kang Le
Published: November 2018

Animal and human highlanders have evolved distinct traits to enhance tissue oxygen delivery and utilization. Unlike vertebrates, insects use their tracheal system for efficient oxygen delivery. However, the genetic basis of insect adaptation to high-altitude hypoxia remains unexplored. Here, we report a potential mechanism of metabolic adaptation of migratory locusts in the Tibetan Plateau, through whole-genome resequencing and functional investigation. A genome-wide scan revealed that the positively selected genes in Tibetan locusts are predominantly involved in carbon and energy metabolism. We observed a notable signal of natural selection in the gene PTPN1, which encodes PTP1B, an inhibitor of insulin signaling pathway. We show that a PTPN1 coding mutation regulates the metabolism of Tibetan locusts by mediating insulin signaling activity in response to hypoxia. Overall, our findings provide evidence for the high-altitude hypoxia adaptation of insects at the genomic level and explore a potential regulatory mechanism underlying the evolved metabolic homeostasis.
Structures of Coxsackievirus A10 unveil the molecular mechanisms of receptor binding and viral uncoating
Authors: Zhu Ling , Sun Yao , Fan Jinyan , Zhu Bin , Cao Lei , Gao Qiang , Zhang Yanjun , Liu Hongrong , Rao Zihe , Wang Xiangxi
Published: November 2018

Coxsackievirus A10 (CVA10), a human type-A Enterovirus (HEV-A), can cause diseases ranging from hand-foot-and-mouth disease to polio-myelitis-like disease. CVA10, together with some other HEV-As, utilizing the molecule KREMEN1 as an entry receptor, constitutes a KREMEN1-dependent subgroup within HEV-As. Currently, there is no vaccine or antiviral therapy available for treating diseases caused by CVA10. The atomic-resolution structure of the CVA10 virion, which is within the KREMEN1-dependent subgroup, shows significant conformational differences in the putative receptor binding sites and serotype-specific epitopes, when compared to the SCARB2-dependent subgroup of HEV-A, such as EV71, highlighting specific differences between the sub-groups. We also report two expanded structures of CVA10, an empty particle and uncoating intermediate at atomic resolution, as well as a medium-resolution genome structure reconstructed using a symmetry-mismatch method. Structural comparisons coupled with previous results, reveal an ordered signal transmission process for enterovirus uncoating, converting exo-genetic receptor-attachment inputs into a generic RNA release mechanism.
Canopy mortality has doubled in Europe’s temperate forests over the last three decades
Authors: Senf Cornelius , Pflugmacher Dirk , Zhiqiang Yang , Sebald Julius , Knorn Jan , Neumann Mathias , Hostert Patrick , Seidl Rupert
Published: November 2018

Mortality is a key indicator of forest health, and increasing mortality can serve as bellwether for the impacts of global change on forest ecosystems. Here we analyze trends in forest canopy mortality between 1984 and 2016 over more than 30 Mill. ha of temperate forests in Europe, based on a unique dataset of 24,000 visually interpreted spectral trajectories from the Landsat archive. On average, 0.79% of the forest area was affected by natural or human-induced mortality annually. Canopy mortality increased by +2.40% year–1, doubling the forest area affected by mortality since 1984. Areas experiencing low-severity mortality increased more strongly than areas affected by stand-replacing mortality events. Changes in climate and land-use are likely causes of large-scale forest mortality increase. Our findings reveal profound changes in recent forest dynamics with important implications for carbon storage and biodiversity conservation, highlighting the importance of improved monitoring of forest mortality.
Genetic effects of BDKRB2 and KNG1 on deep venous thrombosis after orthopedic surgery and the potential mediator
Authors: Wang Qingfeng , Cheng Guoping , Wang Xiaohui , Wang Dandan , Yang Yanmei , Chen Ke , Ye Jiumin , Qing Zhong
Published: November 2018

Deep venous thrombosis (DVT) is a common complication of orthopedic surgery. Genetic risk factors and high heritability carried a substantial risk of DVT. In this study, we aimed to investigate the potential association in the Han Chinese population between the polymorphisms of BDKRB2 and KNG1 and DVT after orthopedic surgery (DVTAOS). A total of 3,010 study subjects comprising 892 DVT cases and 2,118 controls were included in the study, and 39 single nucleotide polymorphisms (SNPs) in total (30 for BDKRB2 and 9 for KNG1) were chosen for genotyping. Two SNPs, rs710446 (OR = 1.27, P = 0.00016) and rs2069588 (OR = 1.29, P = 0.00056), were identified as significantly associated with DVTAOS. After adjusting for BMI, the significance of rs2069588 decreased (P = 0.0013). Haplotype analyses showed that an LD block containing rs2069588 significantly correlated with the DVTAOS risk. Moreover, bioinformatics analysis indicated that hsa-miR-758-5p and BDKRB2 formed miRNA/SNP target duplexes if the rs2069588 allele was in the T form, suggesting that rs2069588 may alter BDKRB2 expression by affecting hsa-miR-758-5p/single-nucleotide polymorphism target duplexes. Our results demonstrate additional evidence supporting that there is an important role for the KNG1 and BDKRB2 genes in the increased susceptibility of DVTAOS.