bluuebunny/crossref_metadata_2025 huggingface dataset:
‘What Does This Mean?’: How UK Companies Make Sense of Human Rights
Authors: OBARA Louise J
Published: May 2017

How do companies understand and talk about human rights? Do they consider human rights a moral, legal or political construct? What type of responsibility do they assume in respect of human rights (e.g., direct/indirect, narrow/broad)? Is the language and label of human rights used within day-to-day practice? This article attempts to address these questions by drawing on empirical data collected as part of an in-depth, qualitative study on the development of human rights within 22 UK companies. Through an analysis based on sensemaking, the article explores the meaning of human rights, the grounds used to justify corporate responsibility, and the human rights terminology and labels employed within the corporate setting. It then analyses what this understanding and discourse means for the debate about the role of private entities for the protection of human rights.
Real-time modelling of wavepackets in turbulent jets
Authors: Sasaki Kenzo , Piantanida Selene , Cavalieri André V. G. , Jordan Peter
Published: May 2017

Three methods are considered for estimating the downstream evolution of wavepackets in turbulent jets based on upstream measurements. The parabolised stability equations are used to compute a transfer function between axially and radially separated points in the flow, and the performance of this theoretical model is compared with that of two empirical approaches, direct transfer function calculation and autoregressive moving-average exogenous system identification, both of which require unsteady experimental data. The three approaches, which perform equally well, prove suitable for estimation of the downstream evolution of wavepackets using pressure data measured in the near-nozzle region. Over distances of the order of a couple of jet diameters, correlations of up to 80 % are observed between estimation and measurement. The performance deteriorates as axial separation between input and output is increased. While the two empirical approaches are limited in terms of both the number of input–output pairs and the number of flow variables that can be reasonably considered, the parabolised stability equations-based approach has no such limitation and can be used to perform full-field estimates comprising all of the dependent variables; in this it constitutes a potentially formidable means by which to perform single-input–multiple-output estimation. It has the further advantage of not requiring unsteady data for its construction, the only necessary ingredients being the mean flow and the linearised equations of motion.
Laminar hypersonic leading edge separation – a numerical study
Authors: Khraibut Amna , Gai S. L. , Brown L. M. , Neely A. J.
Published: May 2017

This paper describes laminar hypersonic leading edge separation. Such a configuration of separated flow was originally studied by Chapman et al. (NACA Tech. Rep. 1356, 1958) at supersonic Mach numbers as it is particularly amenable to theoretical analysis and assumes no pre-existing boundary layer. It can be considered as a limiting case of much studied generic configurations such as separation at a compression corner and separated flow behind a base. A numerical investigation is described using a compressible Navier–Stokes solver assuming perfect gas air, no slip boundary condition and a non-catalytic surface. A moderate enthalpy flow of $3.1\times 10^{6}~\text{J}~\text{kg}^{-1}$ with a unit Reynolds number of $1.34\times 10^{6}~\text{ m}^{-1}$ and a Mach number of 9.66 was considered. The resulting separated flow is analysed in the context of viscous–inviscid interaction and interpreted in terms of ‘triple-deck’ concepts. Particular emphasis is given to wall temperature effects. The effects of strong to moderate wall cooling on flow in the separated region as well as on processes of separation, reattachment and separation length, are highlighted. The numerical simulations have also shown the existence of a secondary eddy embedded within the primary recirculation region, with its size, shape and position, being strongly affected by the wall temperature.
Thermo-Mechanical Multiscale Modeling in Plasticity of Metals Using Small Strain Theory
Authors: Munjas N. , Čanađija M. , Brnić J.
Published: May 2017

A numerical coupled thermoplasticity multiscale procedure for small strain analysis is developed in the finite element environment. It is suitable for simulation of thermo-mechanical behavior and overall response of metallic materials, using standard approximation method based on the concept of representative volume element (RVE). The local level isothermal analysis that models the micro-scale, is fully coupled to the global level non-isothermal analysis. The global macro-scale tangent stiffness operator is obtained using numerical differentiation procedure using the forward difference scheme. The numerical procedure is developed for two-dimensional problems, using Abaqus user-defined subroutines. Applicability of the proposed framework is presented on several representative examples.
A HARMONIZED EUROPEAN COMPANY LAW: ARE WE THERE ALREADY?
Authors: Enriques Luca
Published: May 2017

To what extent is EU company law harmonized? This article first makes the point that little progress has been made in the direction of company law uniformity within the EU. It then argues that, even leaving aside the question of whether it would be desirable to have a uniform EU company law, that outcome is simply impossible to achieve, due to interest group resistance and the variety in national meta-rules. Yet it concludes that, in a narrow meaning, European company laws have indeed been harmonized: European Member States company laws fit together, which may well be what harmonization, not only etymologically, is all about.
The demographics and morphometries of biogenic reefs: important considerations in conservation management
Authors: Brash Jenna M. , Cook Robert L. , Mackenzie Clara L. , Sanderson William G.
Published: May 2017

Modiolus modiolus L. (horse mussel) reefs are a priority marine habitat of high conservation value that is currently listed as endangered and/or threatened across its European distribution. Population structure, density or shell morphology may influence the biodiversity of a reef, either directly or indirectly. Thus, such metrics are important considerations for successful conservation management of these biodiversity hotspots. Population structure, shell morphology and growth rates were examined in M. modiolus reefs across the UK range of the habitat to examine differences between key populations, including those near the Lleyn Peninsula in Wales (southern range), off Port Appin in Western Scotland (mid-range) and in Scapa Flow in the Orkney Isles, Scotland (northern range). Additionally, the influence of physical conditions (temperature and tidal flow) to growth rate and predicted maximum shell length for each population was examined. Growth rates were determined using acetate peels of sectioned shells. Lower juvenile abundance was observed in Scapa Flow. Small, narrow-shaped shells were found to be characteristic of North Lleyn mussels, and larger, globular-shaped shells were characteristic of mussels in Scapa Flow and off Port Appin. Mussels in Scapa Flow were slower growing, yet reached a longer asymptotic length (L∞) than mussels of Port Appin and North Lleyn. Growth curves from sites within this study were analysed with other published data. A trend of higher L∞ at higher latitudes and at lower flow rates was observed. Variations in growth and age are discussed in relation to flow regimes, connectivity to other reefs, density and latitude.
Mixing for three-term progressions in finite simple groups
Authors: PELUSE SARAH
Published: May 2017

Answering a question of Gowers, Tao proved that anyA×B×C⊂ SLd(𝔽q)3contains |A||B||C|/|SLd(𝔽q)| +Od(|SLd(𝔽q)|2/qmin(d−1,2)/8) three-term progressions (x,xy,xy2). Using a modification of Tao's argument, we prove such a mixing result for three-term progressions in all nonabelian finite simple groups except for PSL2(𝔽q) with an error term that depends on the degree of quasirandomness of the group. This argument also gives an alternative proof of Tao's result whend> 2, but with the error termO(|SLd(𝔽q)|2/q(d−1)/24).
Modeling the Social Dynamics of Moral Enhancement
Authors: SANDBERG ANDERS , FABIANO JOAO
Published: May 2017

How individuals tend to evaluate the combination of their own and other’s payoffs—social value orientations—is likely to be a potential target of future moral enhancers. However, the stability of cooperation in human societies has been buttressed by evolved mildly prosocial orientations. If they could be changed, would this destabilize the cooperative structure of society? We simulate a model of moral enhancement in which agents play games with each other and can enhance their orientations based on maximizing personal satisfaction. We find that given the assumption that very low payoffs lead agents to be removed from the population, there is a broadly stable prosocial attractor state. However, the balance between prosociality and individual payoff-maximization is affected by different factors. Agents maximizing their own satisfaction can produce emergent shifts in society that reduce everybody’s satisfaction. Moral enhancement considerations should take the issues of social emergence into account.
Human Enhancement and the Story of Job
Authors: AGAR NICHOLAS , MCDONALD JOHNNY
Published: May 2017

This article explores some implications of the concept of transformative change for the debate about human enhancement. A transformative change is understood to be one that significantly alters the value an individual places on his or her experiences or achievements. The clearest examples of transformative change come from science fiction, but the concept can be illuminatingly applied to the enhancement debate. We argue that it helps to expose a threat from too much enhancement to many of the things that make human lives valuable. Among the things threated by enhancement are our relationships with other human beings. The potential to lose these relationships provides a compelling reason for almost all humans to reject too much enhancement.
Enhancing a Person, Enhancing a Civilization: A Research Program at the Intersection of Bioethics, Future Studies, and Astrobiology
Authors: ĆIRKOVIĆ MILAN M.
Published: May 2017

There are manifold intriguing issues located within largely unexplored borderlands of bioethics, future studies (including global risk analysis), and astrobiology. Human enhancement has for quite some time been among the foci of bioethical debates, but the same cannot be said about its global, transgenerational, and even cosmological consequences. In recent years, discussions of posthuman and, in general terms, postbiological civilization(s) have slowly gained a measure of academic respect, in parallel with the renewed interest in the entire field of future studies and the great strides made in understanding of the origin and evolution of life and intelligence in their widest, cosmic context. These developments promise much deeper synergic answers to questions regarding the long-term future of enhancement: how far can it go? Is human enhancement a further step toward building a true postbiological civilization? Should we actively participate and help shape this process? Is the future of humanity “typical” in the same Copernican sense as our location in space and time is typical in the galaxy, and if so, can we derive important insights about the evolutionary pathways of postbiological evolution from astrobiological and Search for ExtraTerrestrial Intelligence (SETI) studies? These and similar questions could be understood as parts of a possible unifying research program attempting to connect cultural and moral evolution with what we know and understand about their cosmological and biological counterparts.
Simulated Mortality—We Can Do More
Authors: GOLDBERG ANDREW T. , HELLER BENJAMIN J. , HOCHKEPPEL JESSE , LEVINE ADAM I. , DEMARIA SAMUEL
Published: May 2017

High-fidelity simulation (HFS) is a relatively new teaching modality, which is gaining widespread acceptance in medical education. To date, dozens of studies have proven the usefulness of HFS in improving student, resident, and attending physician performance, with similar results in the allied health fields. Although many studies have analyzed the utility of simulation, few have investigated why it works. A recent study illustrated that permissive failure, leading to simulated mortality, is one HFS method that can improve long-term performance. Critics maintain, however, that the use of simulated death is troubling and excessive. Given the controversy regarding simulated death, we consider the data about the educational value and the emotional harms associated with them, expecting that evidence could be useful in resolving the question. The goal of this narrative review is to explore the argument against simulated mortality and provide educators with an imperative as to why it can be safely utilized.
An aneurysmal right coronary artery fistula draining into the left ventricle
Authors: Li Dongxu , Wang Yabo , An Qi
Published: May 2017

We describe a rare case of aneurysmal right coronary artery drainage into left ventricle in a 38-year old male with entailed coronary CT images. After median sternotomy surgery, the patient recovered well.
Anomalous left atrial drainage of the right superior caval vein with partial anomalous pulmonary venous return
Authors: Sulaiman Sherief , Nair Rajesh G.
Published: May 2017

We present a case of anomalous direct connection of the right superior caval vein to the left atrium. The diagnosis was made in a 2-year-old child with unexplained cyanosis and apparently normal heart. Corrective surgery was performed, and the child recovered completely.
Human MSCs promotes colorectal cancer epithelial–mesenchymal transition and progression via CCL5/β-catenin/Slug pathway
Authors: Chen Ke , Liu Qianqian , Tsang Lai Ling , Ye Qiao , Chan Hsiao Chang , Sun Yunwei , Jiang Xiaohua
Published: May 2017

Mesenchymal stem cells (MSCs) extensively interact with cancer cells and other stroma cells in the tumor microenvironment. However, the role of MSCs in colorectal cancer (CRC) progression and metastasis is controversial. This study was designed to identify the role of inflammation-activated-MSCs in CRC development. Our results show that tumor necrosis factor (TNF)-α-preactivated-hMSCs significantly promote the progression of colon cancer cells by enhancing cell proliferation, epithelial–mesenchymal transition, migration, and invasion. TNF-α-primed-hMSCs secrete high level of CCL5, which interacts with its receptor CCR1 expressed in colon cancer cells. Interestingly, the stimulation of colon cancer cell progression by TNF-α-primed hMSCs is associated with the upregulation ofβ-catenin signaling pathway. Blockingβ-catenin pathway significantly decreases the TNF-α-primed-conditioned medium or CCL5-mediated cancer cell progression by decreasing the enhancement of Slug, suggesting that the CCL5/β-catenin/Slug pathway plays a critical role in hMSC-mediated cancer progression. Furthermore,in vivomodel in nude mice confirms the ability of hMSCs to promote the proliferation and progression of colon cancer cells, and the upregulation of CCl5/β-catenin/Slug pathway. Taken together, the present study has demonstrated a novel pathway involving CCl5/CCR1/β-catenin/Slug, via which hMSCs promotes CRC development.
Skilful prediction of Sahel summer rainfall on inter-annual and multi-year timescales
Authors: Sheen K. L. , Smith D. M. , Dunstone N. J. , Eade R. , Rowell D. P. , Vellinga M.
Published: May 2017

Summer rainfall in the Sahel region of Africa exhibits one of the largest signals of climatic variability and with a population reliant on agricultural productivity, the Sahel is particularly vulnerable to major droughts such as occurred in the 1970s and 1980s. Rainfall levels have subsequently recovered, but future projections remain uncertain. Here we show that Sahel rainfall is skilfully predicted on inter-annual and multi-year (that is, >5 years) timescales and use these predictions to better understand the driving mechanisms. Moisture budget analysis indicates that on multi-year timescales, a warmer north Atlantic and Mediterranean enhance Sahel rainfall through increased meridional convergence of low-level, externally sourced moisture. In contrast, year-to-year rainfall levels are largely determined by the recycling rate of local moisture, regulated by planetary circulation patterns associated with the El Niño-Southern Oscillation. Our findings aid improved understanding and forecasting of Sahel drought, paramount for successful adaptation strategies in a changing climate.
miR-29b contributes to multiple types of muscle atrophy
Authors: Li Jin , Chan Mun Chun , Yu Yan , Bei Yihua , Chen Ping , Zhou Qiulian , Cheng Liming , Chen Lei , Ziegler Olivia , Rowe Glenn C. , Das Saumya , Xiao Junjie
Published: May 2017

A number of microRNAs (miRNAs, miRs) have been shown to play a role in skeletal muscle atrophy, but their role is not completely understood. Here we show that miR-29b promotes skeletal muscle atrophy in response to different atrophic stimuli in cells and in mouse models. miR-29b promotes atrophy of myotubes differentiated from C2C12 or primary myoblasts, and conversely, its inhibition attenuates atrophy induced by dexamethasone (Dex), TNF-α and H2O2 treatment. Targeting of IGF-1 and PI3K(p85α) by miR-29b is required for induction of muscle atrophy. In vivo, miR-29b overexpression is sufficient to promote muscle atrophy while inhibition of miR-29b attenuates atrophy induced by denervation and immobilization. These data suggest that miR-29b contributes to multiple types of muscle atrophy via targeting of IGF-1 and PI3K(p85α), and that suppression of miR-29b may represent a therapeutic approach for muscle atrophy induced by different stimuli.
Negative Poisson’s ratio in 1T-type crystalline two-dimensional transition metal dichalcogenides
Authors: Yu Liping , Yan Qimin , Ruzsinszky Adrienn
Published: May 2017

Materials with a negative Poisson’s ratio, also known as auxetic materials, exhibit unusual and counterintuitive mechanical behaviour—becoming fatter in cross-section when stretched. Such behaviour is mostly attributed to some special re-entrant or hinged geometric structures regardless of the chemical composition and electronic structure of a material. Here, using first-principles calculations, we report a class of auxetic single-layer two-dimensional materials, namely, the 1T-type monolayer crystals of groups 6–7 transition-metal dichalcogenides, MX2(M=Mo, W, Tc, Re; X=S, Se, Te). These materials have a crystal structure distinct from all other known auxetic materials. They exhibit an intrinsic in-plane negative Poisson’s ratio, which is dominated by electronic effects. We attribute the occurrence of such auxetic behaviour to the strong coupling between the chalcogenporbitals and the intermetalt2g-bonding orbitals within the basic triangular pyramid structure unit. The unusual auxetic behaviour in combination with other remarkable properties of monolayer two-dimensional materials could lead to novel multi-functionalities.
Inverse Tunnel Magnetocapacitance in Fe/Al-oxide/Fe3O4
Authors: Kaiju Hideo , Nagahama Taro , Sasaki Shun , Shimada Toshihiro , Kitakami Osamu , Misawa Takahiro , Fujioka Masaya , Nishii Junji , Xiao Gang
Published: May 2017

Magnetocapacitance (MC) effect, observed in a wide range of materials and devices, such as multiferroic materials and spintronic devices, has received considerable attention due to its interesting physical properties and practical applications. A normal MC effect exhibits a higher capacitance when spins in the electrodes are parallel to each other and a lower capacitance when spins are antiparallel. Here we report an inverse tunnel magnetocapacitance (TMC) effect for the first time in Fe/AlOx/Fe3O4 magnetic tunnel junctions (MTJs). The inverse TMC reaches up to 11.4% at room temperature and the robustness of spin polarization is revealed in the bias dependence of the inverse TMC. Excellent agreement between theory and experiment is achieved for the entire applied frequency range and the wide bipolar bias regions using Debye-Fröhlich model (combined with the Zhang formula and parabolic barrier approximation) and spin-dependent drift-diffusion model. Furthermore, our theoretical calculations predict that the inverse TMC effect could potentially reach 150% in MTJs with a positive and negative spin polarization of 65% and −42%, respectively. These theoretical and experimental findings provide a new insight into both static and dynamic spin-dependent transports. They will open up broader opportunities for device applications, such as magnetic logic circuits and multi-valued memory devices.
UROPA: a tool for Universal RObust Peak Annotation
Authors: Kondili Maria , Fust Annika , Preussner Jens , Kuenne Carsten , Braun Thomas , Looso Mario
Published: May 2017

﻿﻿﻿﻿Abstract

The annotation of genomic ranges of interest represents a recurring task for bioinformatics analyses. These ranges can originate from various sources, including peaks called for transcription factor binding sites (TFBS) or histone modification ChIP-seq experiments, chromatin structure and accessibility experiments (such as ATAC-seq), but also from other types of predictions that result in genomic ranges. While peak annotation primarily driven by ChiP-seq was extensively explored, many approaches remain simplistic (“most closely located TSS”), rely on fixed pre-built references, or require complex scripting tasks on behalf of the user. An adaptable, fast, and universal tool, capable to annotate genomic ranges in the respective biological context is critically missing. UROPA (Universal RObust Peak Annotator) is a command line based tool, intended for universal genomic range annotation. Based on a configuration file, different target features can be prioritized with multiple integrated queries. These can be sensitive for feature type, distance, strand specificity, feature attributes (e.g. protein_coding) or anchor position relative to the feature. UROPA can incorporate reference annotation files (GTF) from different sources (Gencode, Ensembl, RefSeq), as well as custom reference annotation files. Statistics and plots transparently summarize the annotation process. UROPA is implemented in Python and R.
Mitochondrial targeting by dichloroacetate improves outcome following hemorrhagic shock
Authors: Subramani Kumar , Lu Sumin , Warren Marie , Chu Xiaogang , Toque Haroldo A. , Caldwell R. William , Diamond Michael P. , Raju Raghavan
Published: May 2017

Hemorrhagic shock is a leading cause of death in people under the age of 45 and accounts for almost half of trauma-related deaths. In order to develop a treatment strategy based on potentiating mitochondrial function, we investigated the effect of the orphan drug dichloroacetate (DCA) on survival in an animal model of hemorrhagic shock in the absence of fluid resuscitation. Hemorrhagic shock was induced in rats by withdrawing 60% of the blood volume and maintaining a hypotensive state. The studies demonstrated prolonged survival of rats subjected to hemorrhagic injury (HI) when treated with DCA. In separate experiments, using a fluid resuscitation model we studied mitochondrial functional alterations and changes in metabolic networks connected to mitochondria following HI and treatment with DCA. DCA treatment restored cardiac mitochondrial membrane potential and tissue ATP in the rats following HI. Treatment with DCA resulted in normalization of several metabolic and molecular parameters including plasma lactate and p-AMPK/AMPK, as well as Ach-mediated vascular relaxation. In conclusion we demonstrate that DCA can be successfully used in the treatment of hemorrhagic shock in the absence of fluid resuscitation; therefore DCA may be a good candidate in prolonged field care following severe blood loss.
Seismic anisotropy evidence for dehydration embrittlement triggering intermediate-depth earthquakes
Authors: Wang Jian , Zhao Dapeng , Yao Zhenxing
Published: May 2017

It has been proposed that dehydration embrittlement of hydrous materials can trigger intermediate-depth earthquakes and form a double seismic zone in a subducting slab. Seismic anisotropy may provide a possible insight into intermediate-depth intraslab seismicity, because anisotropic properties of minerals change with varying water distribution, temperature and pressure. Here we present a high-resolution model of P-wave radial anisotropy tomography of the Japan subduction zone down to ~400 km depth, which is obtained using a large number of arrival-time data of local earthquakes and teleseismic events. Our results reveal a close correlation between the pattern of intermediate-depth seismicity and anisotropic structures. The seismicity occurs in portions of the Pacific and Philippine Sea slabs where positive radial anisotropy (i.e., horizontal velocity being faster than vertical one) dominates due to dehydration, whereas the inferred anhydrous parts of the slabs are found to be aseismic where negative radial anisotropy (i.e., vertical velocity being faster than horizontal one) dominates. Our anisotropic results suggest that intermediate-depth earthquakes in Japan could be triggered by dehydration embrittlement of hydrous minerals in the subducting slabs.
Automated screening for Fragile X premutation carriers based on linguistic and cognitive computational phenotypes
Authors: Movaghar Arezoo , Mailick Marsha , Sterling Audra , Greenberg Jan , Saha Krishanu
Published: May 2017

Millions of people globally are at high risk for neurodegenerative disorders, infertility or having children with a disability as a result of the Fragile X (FX) premutation, a genetic abnormality in FMR1 that is underdiagnosed. Despite the high prevalence of the FX premutation and its effect on public health and family planning, most FX premutation carriers are unaware of their condition. Since genetic testing for the premutation is resource intensive, it is not practical to screen individuals for FX premutation status using genetic testing. In a novel approach to phenotyping, we have utilized audio recordings and cognitive profiling assessed via self-administered questionnaires on 200 females. Machine-learning methods were developed to discriminate FX premutation carriers from mothers of children with autism spectrum disorders, the comparison group. By using a random forest classifier, FX premutation carriers could be identified in an automated fashion with high precision and recall (0.81 F1 score). Linguistic and cognitive phenotypes that were highly associated with FX premutation carriers were high language dysfluency, poor ability to organize material, and low self-monitoring. Our framework sets the foundation for computational phenotyping strategies to pre-screen large populations for this genetic variant with nominal costs.
Nutrient and herbivore alterations cause uncoupled changes in producer diversity, biomass and ecosystem function, but not in overall multifunctionality
Authors: Alberti J. , Cebrian J. , Alvarez F. , Escapa M. , Esquius K. S. , Fanjul E. , Sparks E. L. , Mortazavi B. , Iribarne O.
Published: May 2017

Altered nutrient cycles and consumer populations are among the top anthropogenic influences on ecosystems. However, studies on the simultaneous impacts of human-driven environmental alterations on ecosystem functions, and the overall change in system multifunctionality are scarce. We used estuarine tidal flats to study the effects of changes in herbivore density and nutrient availability on benthic microalgae (diversity, abundance and biomass) and ecosystem functions (N2-fixation, denitrification, extracellular polymeric substances -EPS- as a proxy for sediment cohesiveness, sediment water content as a proxy of water retention capacity and sediment organic matter). We found consistent strong impacts of modified herbivory and weak effects of increased nutrient availability on the abundance, biomass and diversity of benthic microalgae. However, the effects on specific ecosystem functions were disparate. Some functions were independently affected by nutrient addition (N2-fixation), modified herbivory (sediment organic matter and water content), or their interaction (denitrification), while others were not affected (EPS). Overall system multifunction remained invariant despite changes in specific functions. This study reveals that anthropogenic pressures can induce decoupled effects between community structure and specific ecosystem functions. Our results highlight the need to address several ecosystem functions simultaneously for better ecosystem characterization and management.
φBO1E, a newly discovered lytic bacteriophage targeting carbapenemase-producing Klebsiella pneumoniae of the pandemic Clonal Group 258 clade II lineage
Authors: D’Andrea Marco Maria , Marmo Pasquale , Henrici De Angelis Lucia , Palmieri Mattia , Ciacci Nagaia , Di Lallo Gustavo , Demattè Elisa , Vannuccini Elisa , Lupetti Pietro , Rossolini Gian Maria , Thaller Maria Cristina
Published: May 2017

The pandemic dissemination of KPC carbapenemase-producing Klebsiella pneumoniae (KPC-KP) represents a major public health problem, given their extensive multidrug resistance profiles and primary role in causing healthcare-associated infections. This phenomenon has largely been contributed by strains of Clonal Group (CG) 258, mostly of clade II, which in some areas represent the majority of KPC-KP isolates. Here we have characterized a newly discovered lytic Podoviridae, named φBO1E, targeting KPC-KP strains of clade II lineage of CG258. Genomic sequencing revealed that φBO1E belongs to the Kp34virus genus (87% nucleotide identity to vB_KpnP_SU552A). ΦBO1E was stable over a broad pH and temperature range, exhibited strict specificity for K. pneumoniae strains of clade II of CG258, and was unable to establish lysogeny. In a Galleria mellonella infection model, φBO1E was able to protect larvae from death following infection with KPC-KP strains of clade II of CG258, including one colistin resistant strain characterized by a hypermucoviscous phenotype. To our best knowledge φBO1E is the first characterized lytic phage targeting K. pneumoniae strains of this pandemic clonal lineage. As such, it could be of potential interest to develop new agents for treatment of KPC-KP infections and for decolonization of subjects chronically colonized by these resistant superbugs.
Electrically driven deep ultraviolet MgZnO lasers at room temperature
Authors: Suja Mohammad , Bashar Sunayna Binte , Debnath Bishwajit , Su Longxing , Shi Wenhao , Lake Roger , Liu Jianlin
Published: May 2017

Semiconductor lasers in the deep ultraviolet (UV) range have numerous potential applications ranging from water purification and medical diagnosis to high-density data storage and flexible displays. Nevertheless, very little success was achieved in the realization of electrically driven deep UV semiconductor lasers to date. In this paper, we report the fabrication and characterization of deep UV MgZnO semiconductor lasers. These lasers are operated with continuous current mode at room temperature and the shortest wavelength reaches 284 nm. The wide bandgap MgZnO thin films with various Mg mole fractions were grown on c-sapphire substrate using radio-frequency plasma assisted molecular beam epitaxy. Metal-semiconductor-metal (MSM) random laser devices were fabricated using lithography and metallization processes. Besides the demonstration of scalable emission wavelength, very low threshold current densities of 29~33 A/cm2 are achieved. Numerical modeling reveals that impact ionization process is responsible for the generation of hole carriers in the MgZnO MSM devices. The interaction of electrons and holes leads to radiative excitonic recombination and subsequent coherent random lasing.
A nucleotide-controlled conformational switch modulates the activity of eukaryotic IMP dehydrogenases
Authors: Buey Rubén M. , Fernández-Justel David , Marcos-Alcalde Íñigo , Winter Graeme , Gómez-Puertas Paulino , de Pereda José María , Luis Revuelta José
Published: May 2017

Inosine-5′-monophosphate dehydrogenase (IMPDH) is an essential enzyme for nucleotide metabolism and cell proliferation. Despite IMPDH is the target of drugs with antiviral, immunosuppressive and antitumor activities, its physiological mechanisms of regulation remain largely unknown. Using the enzyme from the industrial fungus Ashbya gossypii, we demonstrate that the binding of adenine and guanine nucleotides to the canonical nucleotide binding sites of the regulatory Bateman domain induces different enzyme conformations with significantly distinct catalytic activities. Thereby, the comparison of their high-resolution structures defines the mechanistic and structural details of a nucleotide-controlled conformational switch that allosterically modulates the catalytic activity of eukaryotic IMPDHs. Remarkably, retinopathy-associated mutations lie within the mechanical hinges of the conformational change, highlighting its physiological relevance. Our results expand the mechanistic repertoire of Bateman domains and pave the road to new approaches targeting IMPDHs.
Release of Cytochrome C from Bax Pores at the Mitochondrial Membrane
Authors: Zhang Mingzhen , Zheng Jie , Nussinov Ruth , Ma Buyong
Published: May 2017

How cytochrome C is released from the mitochondria to the cytosol via Bax oligomeric pores, a process which is required for apoptosis, is still a mystery. Based on experimentally measured residue-residue distances, we recently solved the first atomic model for Bax oligomeric pores at the membranes using computational approaches. Here, we investigate the mechanism at the microsecond time- and nanometer space- scale using MD simulations. Our free energy landscape depicts a low barrier for the permeation of cytochrome C into the Bax C-terminal mouth, with the pathway proceeding to the inner cavity and exiting via the N-terminal mouth. Release is guided by organized charged/hydrophilic surfaces. The hydrophilicity and negative charge of the pore surface gradually increase along the release pathway from the pore entry to the exit opening. Rather than inert passing of the cytochrome C through a rigid pore, the flexible pore may selectively aid the cytochrome C passage. Once the Bax pore is formed in the membrane, with a low energy barrier, the release of cytochrome C may be readily achieved through energy fluctuations. Collectively, our work provides mechanistic insight in atomic detail into the release of cytochrome C through Bax oligomeric pores.
Cognitive ability and physical health: a Mendelian randomization study
Authors: Hagenaars Saskia P. , Gale Catharine R. , Deary Ian J. , Harris Sarah E.
Published: May 2017

Causes of the association between cognitive ability and health remain unknown, but may reflect a shared genetic aetiology. This study examines the causal genetic associations between cognitive ability and physical health. We carried out two-sample Mendelian randomization analyses using the inverse-variance weighted method to test for causality between later life cognitive ability, educational attainment (as a proxy for cognitive ability in youth), BMI, height, systolic blood pressure, coronary artery disease, and type 2 diabetes using data from six independent GWAS consortia and the UK Biobank sample (N = 112 151). BMI, systolic blood pressure, coronary artery disease and type 2 diabetes showed negative associations with cognitive ability; height was positively associated with cognitive ability. The analyses provided no evidence for casual associations from health to cognitive ability. In the other direction, higher educational attainment predicted lower BMI, systolic blood pressure, coronary artery disease, type 2 diabetes, and taller stature. The analyses indicated no causal association from educational attainment to physical health. The lack of evidence for causal associations between cognitive ability, educational attainment, and physical health could be explained by weak instrumental variables, poorly measured outcomes, or the small number of disease cases.
Genome-Wide Comparative Analysis of Miniature Inverted Repeat Transposable Elements in 19 Arabidopsis thaliana Ecotype Accessions
Authors: Guo Cheng , Spinelli Matthew , Ye Congting , Li Qingshun Q. , Liang Chun
Published: May 2017

Miniature inverted repeat transposable elements (MITEs) are prevalent in eukaryotic genomes. They are known to critically influence the process of genome evolution and play a role in gene regulation. As the first study concentrated in the transposition activities of MITEs among different ecotype accessions within a species, we conducted a genome-wide comparative analysis by characterizing and comparing MITEs in 19Arabidopsis thalianaaccessions. A total of 343485 MITE putative sequences, including canonical, diverse and partial ones, were delineated from all 19 accessions. Within the entire population of MITEs sequences, 80.7% of them were previously unclassified MITEs, demonstrating a different genomic distribution and functionality compared to the classified MITEs. The interactions between MITEs and homologous genes across 19 accessions provided a fine source for analyzing MITE transposition activities and their impacts on genome evolution. Moreover, a significant proportion of MITEs were found located in the last exon of genes besides the ordinary intron locality, thus potentially modifying the end of genes. Finally, analysis of the impact of MITEs on gene expression suggests that migrations of MITEs have no detectable effect on the expression level for host genes across accessions.
Gene-body CG methylation and divergent expression of duplicate genes in rice
Authors: Wang Xutong , Zhang Zhibin , Fu Tiansi , Hu Lanjuan , Xu Chunming , Gong Lei , Wendel Jonathan F. , Liu Bao
Published: May 2017

Gene and genome duplication fosters genetic novelty, but redundant gene copies would undergo mutational decay unless preserved via selective or neutral forces. Molecular mechanisms mediating duplicate preservation remain incompletely understood. Several recent studies showed an association between DNA methylation and expression divergence of duplicated genes and suggested a role of epigenetic mechanism in duplicate retention. Here, we compare genome-wide gene-body CG methylation (BCGM) and duplicate gene expression between a rice mutant null for OsMet1-2(a major CG methytransferase in rice) and its isogenic wild-type. We demonstrate a causal link between BCGM divergence and expression difference of duplicate copies. Interestingly, the higher- and lower-expressing copies of duplicates as separate groups show broadly different responses with respect to direction of expression alteration upon loss of BCGM. A role for BCGM in conditioning expression divergence between copies of duplicates generally holds for duplicates generated by whole genome duplication (WGD) or by small-scale duplication processes. However, differences are evident among these categories, including a higher proportion of WGD duplicates manifesting expression alteration, and differential propensities to lose BCGM by the higher- and lower-expression copies in the mutant. Together, our results support the notion that differential epigenetic marking may facilitate long-term retention of duplicate genes.
Functional analysis of the role of hydrogen sulfide in the regulation of dark-induced leaf senescence in Arabidopsis
Authors: Wei Bo , Zhang Wei , Chao Jin , Zhang Tianru , Zhao Tingting , Noctor Graham , Liu Yongsheng , Han Yi
Published: May 2017

There is growing evidence that hydrogen sulfide (H2S) is involved in many physiological processes in plants, but the role of H2S in dark-induced leaf senescence remains unknown. In this work, we found that H2S not only inhibited chlorophyll degradation but also caused the accumulation of photoreactive pheide a in detached leaves under extended darkness. Despite this, transcript levels of senescence-associated genes (SAGs) were less affected in H2S-treated detached leaves compared with those in H2S-untreated detached leaves. Furthermore, cell death/rapid bleaching occurred in both H2S-treated detached and attached leaves after transfer from extended darkness to light. Unlike the lack of effect of H2S on SAG transcripts in darkened detached leaves, exogenous H2S induced higher SAG transcript levels in attached leaves than untreated attached leaves. Genetic evidence further underlined the positive correlation between SAG expression in attached leaves and H2S. In addition, effects of H2S on SAG expression in attached leaves were compromised in the S-nitrosoglutathione reductase-deficient mutant, gsnor1. Taken together, our results suggest that H2S suppresses chlorophyll degradation of detached leaves by regulating a dark-dependent reaction, and that this gas positively modulates SAG expression in attached leaves under prolonged darkness in a GSNOR1-dependent manner.
Expression and integrated network analyses revealed functional divergence of NHX-type Na+/H+ exchanger genes in poplar
Authors: Tian Fengxia , Chang Ermei , Li Yu , Sun Pei , Hu Jianjun , Zhang Jin
Published: May 2017

The Na+/H+ antiporters (NHXs) are secondary ion transporters to exchange H+ and transfer the Na+ or K+ across membrane, they play crucial roles during plant development and stress responses. To gain insight into the functional divergence of NHX genes in poplar, eight PtNHX were identified from Populus trichocarpa genome. PtNHXs containing 10 transmembrane helices (TMH) and a hydrophilic C-terminal domain, the TMH compose a hollow cylinder to provide the channel for Na+ and H+ transport. The expression patterns and cis-acting elements showed that all the PtNHXs were response to single or multiple stresses including drought, heat, cold, salinity, MV, and ABA. Both the co-expression network and protein-protein interaction network of PtNHXs implying their functional divergence. Interestingly, although PtNHX7 and PtNHX8 were generated by whole genome duplication event, they showed significant differences in expression pattern, protein structure, co-expressed genes, and interacted proteins. Only PtNHX7 interact with CBL and CIPK, indicating PtNHX7 is the primary NHX involved in CBL-CIPK pathway during salt stress responses. Natural variation analysis based on 549 P. trichocarpa individuals indicated the frequency of SNPs in PtNHX7 was significantly higher than other PtNHXs. Our findings provide new insights into the functional divergence of NHX genes in poplar.
Application of nuclear magnetic resonance spectroscopy in food adulteration determination: the example of Sudan dye I in paprika powder
Authors: Hu Yaxi , Wang Shuo , Wang Shenlin , Lu Xiaonan
Published: May 2017

Carcinogenic Sudan I has been added illegally into spices for an apparent freshness. 1H solution and solid-state (SS) nuclear magnetic resonance (NMR) spectroscopies were applied and compared for determination of Sudan I in paprika powders (PPs). For solution NMR, PPs spiked with Sudan I were extracted with acetonitrile, centrifuged, rotor-evaporated, and re-dissolved in DMSO-d6 for spectral collection. For SSNMR, Sudan I contaminated PPs were mixed with DMSO-d6 solution and used for spectral collection. Linear regression models constructed for quantitative analyses resulted in the average accuracies for unknown samples as 98% and 105%, respectively. Limits of detection for the solution NMR and SSNMR spectrometers were 6.7 and 128.6 mg kg−1, while the limits of quantification were 22.5 and 313.7 mg kg−1. The overall analysis time required by both methods was similar (35 and 32 min). Both NMR techniques are feasible for rapid and accurate determination of Sudan I adulteration in PPs.
The Toxic Effects of Tetrachlorobisphenol A in Saccharomyces cerevisiae Cells via Metabolic Interference
Authors: Tian Juan , Ji Zhihua , Wang Fengbang , Song Maoyong , Li Hao
Published: May 2017

Tetrachlorobisphenol A (TCBPA) is a common flame retardant detected in different environments. However, its toxic effects on animals and humans are not fully understood. Here, the differential intracellular metabolites and associated gene expression were used to clarify the metabolic interference of TCBPA in Saccharomyces cerevisiae, a simple eukaryotic model organism. The results indicated that TCBPA treatment promoted the glycolysis pathway but inhibited the tricarboxylic acid (TCA) cycle, energy metabolism and the hexose monophosphate pathway (HMP) pathway. Thus, the HMP pathway produced less reducing power, leading to the accumulation of reactive oxygen species (ROS) and aggravation of oxidative damage. Accordingly, the carbon flux was channelled into the accumulation of fatty acids, amino acids and glycerol instead of biomass production and energy metabolism. The accumulation of these metabolites might serve a protective function against TCBPA stress by maintaining the cell membrane integrity or providing a stable intracellular environment in S. cerevisiae. These results enhance our knowledge of the toxic effects of TCBPA on S. cerevisiae via metabolic interference and pave the way for clarification of the mechanisms underlying TCBPA toxicity in animals and humans.
Isolated Congenital Anosmia and CNGA2 Mutation
Authors: Sailani M. Reza , Jingga Inlora , MirMazlomi Seyed Hashem , Bitarafan Fatemeh , Bernstein Jonathan A. , Snyder Michael P. , Garshasbi Masoud
Published: May 2017

Isolated congenital anosmia (ICA) is a rare condition that is associated with life-long inability to smell. Here we report a genetic characterization of a large Iranian family segregating ICA. Whole exome sequencing in five affected family members and five healthy members revealed a stop gain mutation in CNGA2 (OMIM 300338) (chrX:150,911,102; CNGA2. c.577C > T; p.Arg193*). The mutation segregates in an X-linked pattern, as all the affected family members are hemizygotes, whereas healthy family members are either heterozygote or homozygote for the reference allele. cnga2 knockout mice are congenitally anosmic and have abnormal olfactory system physiology, additionally Karstensen et al. recently reported two anosmic brothers sharing a CNGA2 truncating variant. Our study in concert with these findings provides strong support for role of CNGA2 gene with pathogenicity of ICA in humans. Together, these results indicate that mutations in key olfactory signaling pathway genes are responsible for human disease.
Ultra-large non-volatile modulation of magnetic moments in PbZr0.2Ti0.8O3/MgO/La0.7Sr0.3MnO3 heterostructure at room temperature via interfacial polarization mediation
Authors: Liu Q. , Miao J. , Reeve Robert , Meng K. K. , Xu X. G. , Wu Y. , Jiang Y.
Published: May 2017

Multiferroic hybrid structures PbZr0.2Ti0.8O3 (PZT)/La0.7Sr0.3MnO3 (LSMO) and PZT/MgO/LSMO were epitaxially deposited on (001) Nb:SrTiO3 crystals. Crystallinity and ferroelectric domain structures were investigated for the PZT/LSMO heterostructure. Interestingly, relatively high non-volatile magnetoelectric coupling effects were observed in both heterostructures at room temperature. The change of chemical valence for Mn and Ti at the PZT/MgO/LSMO interface may play a dominant role rather than external strain or orbital reconstruction, which lead to a large modulation of the magnetization. Correspondingly, the transport behavior of the PZT/MgO/LSMO heterostructure is investigated to confirm the role of oxygen vacancies motion. Our result indicates that the PZT/MgO/LSMO heterostructure have a promising application for future high-density non-volatile memories.