bluuebunny/crossref_metadata_2025 huggingface dataset:
Phytochemical and Antinociceptive Investigations of Anemone coronaria Active Part Ameliorating Diabetic Neuropathy Pain
Authors: Raafat Karim , El-Lakany Abdalla
Published: February 2018

Phytochemicals might offer economic therapies, which are an alternative especially for low-income developing countries. Anemone coronaria has been used extensively as antineuralgic and antirheumatic in the folk medicine of Lebanon. Thus, the aim of this study was to investigate the antinociceptive potential of A. coronaria and its active principles against diabetic-neuropathy pain in a mouse-model. The study also aimed to achieve a bio-guided fractionation and to isolate the most active principles in A. coronaria herb. Bio-guided fractionation used reversed phase-HPLC, and 1H and 13C NMR for the identification of the most active fraction of A. coronaria, which was rich in alkaloids. This isolated alkaloid rich fraction contained catalin (21.1%), thaliporphine (14.1%), and glaucine (compound 3) (63.4%). A. coronaria extract (50, 100, and 200 mg/kg), the isolated alkaloid rich fraction (70 mg/kg), and glaucine (25, 50, and 100 mg/kg) showed significant reduction in acute and subchronic hyperglycemia, with significant increase in glutathione and catalase levels, along with normalization of HbA1c and LPO levels (n=7 per group, p≤0.05). A. coronaria extract (50, 100, and 200 mg/kg), the isolated alkaloid rich fraction (70 mg/kg), and glaucine (25, 50, and 100 mg/kg) also showed significant antinociceptive amelioration in thermal hyperalgesia pain latencies utilizing hot plate and tail flick tests. The highest doses of A. coronaria extract (200 mg/kg), isolated alkaloid rich fraction (70 mg/kg), and glaucine (100 mg/kg) showed a significant elevation in mechanical allodynia pain thresholds using Von-Frey-filaments. The results revealed that A. coronaria herb along with its most active alkaloid rich fraction and constituent (glaucine) possessed significant antihyperglycemic and antinociceptive potentials. These findings may lead to a future use of A. coronaria in the management of diabetic-neuropathy pain.
Pyrrolopyrimidine, A Multifaceted Scaffold in Cancer Targeted Therapy
Authors: Adel Mai , Serya Rabah , Lasheen Deena , Abouzid Khaled
Published: February 2018

Pyrrolopyrimidine derivatives represent a class of biologically active heterocyclic compounds which can serve as promising scaffolds that display remarkable biological activities, such as anti-inflammatory, antimicrobial, antiviral and anticancer. In the last few years, several pyrrolopyrimidine derivatives have been approved by the US FDA and in other countries for the treatment of different diseases or are currently in phase I/II clinical trials. Due to their inimitable antioxidant and anti-tumor properties, researchers were inspired to develop novel derivatives for the treatment of different types of cancer. The present review summarizes recent literature up to 2017 on the most recent development in the medicinal chemistry of pyrrolopyrimidine derivatives and their potential as anticancer therapeutics, especially compounds acting as kinase inhibitors.
A robust cloud registration method based on redundant data reduction using backpropagation neural network and shift window
Authors: Xin Meiting , Li Bing , Yan Xiao , Chen Lei , Wei Xiang
Published: February 2018

A robust coarse-to-fine registration method based on the backpropagation (BP) neural network and shift window technology is proposed in this study. Specifically, there are three steps: coarse alignment between the model data and measured data, data simplification based on the BP neural network and point reservation in the contour region of point clouds, and fine registration with the reweighted iterative closest point algorithm. In the process of rough alignment, the initial rotation matrix and the translation vector between the two datasets are obtained. After performing subsequent simplification operations, the number of points can be reduced greatly. Therefore, the time and space complexity of the accurate registration can be significantly reduced. The experimental results show that the proposed method improves the computational efficiency without loss of accuracy.
Joint excitation synchronization characteristics of fatigue test for offshore wind turbine blade
Authors: Zhang Lei-an , Yu Xiang-yong , Wei Xiu-ting , Liu Wei-sheng
Published: February 2018

In the case of the stiffness of offshore wind turbine blade is relatively large, the joint excitation device solves the problem of low accuracy of bending moment distribution, insufficient driving ability and long fatigue test period in single-point loading. In order to study the synchronous characteristics of joint excitation system, avoid blade vibration disturbance. First, on the base of a Lagrange equation, a mathematical model of combined excitation is formulated, and a numerical analysis of vibration synchronization is performed. Then, the model is constructed via MATLAB/Simulink, and the effect of the phase difference on the vibration synchronization characteristics is obtained visually. Finally, a set of joint excitation platform for the fatigue test of offshore wind turbine blades are built. The parameter measurement scheme is given and the correctness of the joint excitation synchronization in the simulation model is verified. The results show that when the rotational speed difference is 2 r/min, 30 r/min, the phase difference is 0, π/20, π/8 and π/4, as the rotational speed difference and the phase difference increase, the time required for the blade to reach a steady state is longer. When the phase difference is too large, the electromechanical coupling can no longer make the joint excitation device appear self-synchronizing phenomenon, so that the value of the phase difference develops toward a fixed value (not equal to 0), and the blade vibration disorder is serious, at this time, the effect of electromechanical coupling must be eliminated. The research results provide theoretical basis for the subsequent decoupling control algorithm and synchronization control strategy, and have good application value.
Epitaxial contact Andreev reflection spectroscopy of NbN/Co2FeSi layered devices
Authors: Shigeta Iduru , Kubota Takahide , Sakuraba Yuya , Molenaar Cor G. , Beukers Joost N. , Kimura Shojiro , Golubov Alexander A. , Brinkman Alexander , Awaji Satoshi , Takanashi Koki , Hiroi Masahiko
Published: February 2018

We investigated the spin polarization P of Co-based Heusler alloy Co2FeSi by epitaxial contact Andreev reflection (ECAR) spectroscopy using epitaxially grown superconductor NbN and Heusler alloy Co2FeSi layered devices. Ferromagnetic Co2FeSi possesses the highest Curie temperature (TC ≈ 1100 K) and the largest spontaneous magnetic moment (ps ≈ 6 μB) in the class of Heusler alloys. The ECAR measurements revealed that the P value of Co2FeSi was 54 ± 2% with a finite barrier parameter Z, indicating that an intrinsic P value in ECAR spectroscopy would exceed reported values in point-contact Andreev reflection spectroscopy. We therefore established not only the epitaxial integration of ferromagnetic Co2FeSi with superconductor NbN on an MgO substrate but also the fabrication and evaluation techniques of their ECAR devices. This highly versatile superconducting spintronic system enables fundamental superconducting spintronic studies, and it is also a candidate for practical superconducting spintronic devices.
Mobility spectrum analytical approach for the type-II Weyl semimetal Td-MoTe2
Authors: Pei Q. L. , Luo X. , Chen F. C. , Lv H. Y. , Sun Y. , Lu W. J. , Tong P. , Sheng Z. G. , Han Y. Y. , Song W. H. , Zhu X. B. , Sun Y. P.
Published: February 2018

The extreme magnetoresistance (XMR) in orthorhombic W/MoTe2 arises from the combination of the perfect electron-hole (e-h) compensation effect and the unique orbital texture topology, which have comprised an intriguing research field in materials physics. Herein, we apply a special analytical approach as a function of mobility (μ-spectrum) without any hypothesis. Based on the interpretations of longitudinal and transverse electric transport of Td-MoTe2, the types and the numbers of carriers can be obtained. There are three observations: the large residual resistivity ratio can be observed in the MoTe2 single crystal sample, which indicates that the studied crystal is of high quality; we observed three electron-pockets and three hole-ones from the μ-spectrum and that the ratio of h/e is much less than 1, which shows that MoTe2 is more e-like; different from the separated peaks obtained from the hole-like μ-spectrum, those of the electron-like one are continuous, which may indicate the topological feature of electron-pockets in Td-MoTe2. The present results may provide an important clue to understanding the mechanism of the XMR effect in Td-MoTe2.
Effects of a GaSb buffer layer on an InGaAs overlayer grown on Ge(111) substrates: Strain, twin generation, and surface roughness
Authors: Kajikawa Y. , Nishigaichi M. , Tenma S. , Kato K. , Katsube S.
Published: February 2018

InGaAs layers were grown by molecular-beam epitaxy on nominal and vicinal Ge(111) substrates with inserting GaSb buffer layers. High-resolution X-ray diffraction using symmetric 333 and asymmetric 224 reflections was employed to analyze the crystallographic properties of the grown layers. By using the two reflections, we determined the lattice constants (the unit cell length a and the angle α between axes) of the grown layers with taking into account the rhombohedral distortion of the lattices of the grown layers. This allowed us the independent determination of the strain components (perpendicular and parallel components to the substrate surface, ε⊥ and ε//) and the composition x of the InxGa1-xAs layers by assuming the distortion coefficient D, which is defined as the ratio of ε⊥ against ε//. Furthermore, the twin ratios were determined for the GaSb and the InGaAs layers by comparing asymmetric 224 reflections from the twin domain with that from the normal domain of the layers. As a result, it has been shown that the twin ratio in the InGaAs layer can be decreased to be less than 0.1% by the use of the vicinal substrate together with annealing the GaSb buffer layer during the growth interruption before the InGaAs overgrowth.
Pressure control in interfacial systems: Atomistic simulations of vapor nucleation
Authors: Marchio S. , Meloni S. , Giacomello A. , Valeriani C. , Casciola C. M.
Published: February 2018

A large number of phenomena of scientific and technological interest involve multiple phases and occur at constant pressure of one of the two phases, e.g., the liquid phase in vapor nucleation. It is therefore of great interest to be able to reproduce such conditions in atomistic simulations. Here we study how popular barostats, originally devised for homogeneous systems, behave when applied straightforwardly to heterogeneous systems. We focus on vapor nucleation from a super-heated Lennard-Jones liquid, studied via hybrid restrained Monte Carlo simulations. The results show a departure from the trends predicted for the case of constant liquid pressure, i.e., from the conditions of classical nucleation theory. Artifacts deriving from standard (global) barostats are shown to depend on the size of the simulation box. In particular, for Lennard-Jones liquid systems of 7000 and 13 500 atoms, at conditions typically found in the literature, we have estimated an error of 10–15 kBT on the free-energy barrier, corresponding to an error of 104–106 s−1σ−3 on the nucleation rate. A mechanical (local) barostat is proposed which heals the artifacts for the considered case of vapor nucleation.
A novel method to hit the limit temperature of Stirling-type cryocooler
Authors: Wang Jue , Pan Changzhao , Zhang Tong , Luo Kaiqi , Zhou Yuan , Wang Junjie
Published: February 2018

The Stirling-type cryocooler with its compact size and high efficiency is always expected to obtain its temperature limit of below 3 K. However, the pressure drop losses caused by high-frequency oscillation create large obstacles for this objective. This paper reports a novel thermal-driven Stirling-type cryocooler to obtain the lowest temperature of a Stirling-type cryocooler. The advantages of a thermal-driven cryocooler (Vuilleumier cryocooler) and pulse tube cryocooler are combined with a new type of cryocooler, called the Vuilleumier gas-coupling pulse tube hybrid cryocooler (VM-PT). A prototype of the VM-PT was recently developed and optimized in our laboratory. By using helium-4 as the working gas and magnetic regenerative materials (HoCu2 and Er3Ni), the lowest temperature of 2.5 K was obtained, which can be regarded as an important breakthrough for the Stirling-type cryocooler to achieve its limit temperature of below 3 K. It can supply >30 mW cooling power at 4.2 K and >500 mW cooling power at 20 K simultaneously. Theoretically, it is feasible to use this VM-PT for cooling the superconducting devices in space applications.
Determination of the structural phase and octahedral rotation angle in halide perovskites
Authors: dos Reis Roberto , Yang Hao , Ophus Colin , Ercius Peter , Bizarri Gregory , Perrodin Didier , Shalapska Tetiana , Bourret Edith , Ciston Jim , Dahmen Ulrich
Published: February 2018

A key to the unique combination of electronic and optical properties in halide perovskite materials lies in their rich structural complexity. However, their radiation sensitive nature limits nanoscale structural characterization requiring dose efficient microscopic techniques in order to determine their structures precisely. In this work, we determine the space-group and directly image the Br halide sites of CsPbBr3, a promising material for optoelectronic applications. Based on the symmetry of high-order Laue zone reflections of convergent-beam electron diffraction, we identify the tetragonal (I4/mcm) structural phase of CsPbBr3 at cryogenic temperature. Electron ptychography provides a highly sensitive phase contrast measurement of the halide positions under low electron-dose conditions, enabling imaging of the elongated Br sites originating from the out-of-phase octahedral rotation viewed along the [001] direction of I4/mcm persisting at room temperature. The measurement of these features and comparison with simulations yield an octahedral rotation angle of 6.5°(±1.5°). The approach demonstrated here opens up opportunities for understanding the atomic scale structural phenomena applying advanced characterization tools on a wide range of radiation sensitive halide-based all-inorganic and hybrid organic-inorganic perovskites.
Detection of deep-level defects and reduced carrier concentration in Mg-ion-implanted GaN before high-temperature annealing
Authors: Akazawa Masamichi , Yokota Naoshige , Uetake Kei
Published: February 2018

We report experimental results for the detection of deep-level defects in GaN after Mg ion implantation before high-temperature annealing. The n-type GaN samples were grown on GaN free-standing substrates by metalorganic vapor phase epitaxy. Mg ions were implanted at 50 keV with a small dosage of 1.5×1011 cm-2, which did not change the conduction type of the n-GaN. By depositing Al2O3 and a Ni/Au electrode onto the implanted n-GaN, metal-oxide-semiconductor (MOS) diodes were fabricated and tested. The measured capacitance–voltage (C–V) characteristics showed a particular behavior with a plateau region and a region with an anomalously steep slope. Fitting to the experimental C–V curves by simulation showed the existence of deep-level defects and a reduction of the carrier concentration near the GaN surface. By annealing at 800oC, the density of the deep-level defects was reduced and the carrier concentration partially recovered.
Photopolymerization of complex emulsions with irregular shapes fabricated by multiplex coaxial flow focusing
Authors: Wu Qiang , Yang Chaoyu , Yang Jianxin , Huang Fangsheng , Liu Guangli , Zhu Zhiqiang , Si Ting , Xu Ronald X.
Published: February 2018

We fabricate complex emulsions with irregular shapes in the microscale by a simple but effective multiplex coaxial flow focusing process. A multiphase cone-jet structure is steadily formed, and the compound liquid jet eventually breaks up into Janus microdroplets due to the perturbations propagating along the jet interfaces. The microdroplet shapes can be exclusively controlled by interfacial tensions of adjacent phases. Crescent-moon-shaped microparticles and microcapsules with designated structural characteristics are further produced under ultraviolet light of photopolymerization after removing one hemisphere of the Janus microdroplets. These complex emulsions have potential applications in bioscience, food, functional materials, and controlled drug delivery.
Numerical characterization of the edge transport conditions and limiter fluxes of the HIDRA stellarator
Authors: Marcinko Steven , Curreli Davide
Published: February 2018

The Hybrid Illinois Device for Research and Applications (HIDRA) is a new device for education and Plasma-Material Interaction research at the University of Illinois at Urbana-Champaign. In advance of its first operational campaign, EMC3-EIRENE simulations have been run on the device. EMC3-EIRENE has been modified to calculate a per-plasma-cell relaxed Bohm-like diffusivity simultaneously with the electron temperature at each iteration. In our characterization, the electron temperature, diffusivity, heat fluxes, and particle fluxes have been obtained for varying power levels on a HIDRA magnetic grid, and scaling laws have been extracted, using constraints from previous experimental data taken when the device was operated in Germany (WEGA facility). Peak electron temperatures and heat fluxes were seen to follow a power-law dependence on the deposited radiofrequency (RF) power of type f(PRF)∝aPRFb, with typical exponents in the range of b ∼0.55 to 0.60. Higher magnetic fields have the tendency to linearize the heat flux dependence on the RF power, with exponents in the range of b ∼ 0.75. Particle fluxes are seen to saturate first, and then slightly decline for RF powers above 120 kW in the low-field case and 180 kW in the high-field case.
Dynamics of particles accelerated by head-on collisions of two magnetized plasma shocks
Authors: Takeuchi Satoshi
Published: February 2018

A kinetic model of the head-on collision of two magnetized plasma shocks is analyzed theoretically and in numerical calculations. When two plasmas with anti-parallel magnetic fields collide, they generate magnetic reconnection and form a motional electric field at the front of the collision region. This field accelerates the particles sandwiched between both shock fronts to extremely high energy. As they accelerate, the particles are bent by the transverse magnetic field crossing the magnetic neutral sheet, and their energy gains are reduced. In the numerical calculations, the dynamics of many test particles were modeled through the relativistic equations of motion. The attainable energy gain was obtained by multiplying three parameters: the propagation speed of the shock, the magnitude of the magnetic field, and the acceleration time of the test particle. This mechanism for generating high-energy particles is applicable over a wide range of spatial scales, from laboratory to interstellar plasmas.
Stabilization and enhanced energy gap by Mg doping in ε-phase Ga2O3 thin films
Authors: Bi Xiaoyu , Wu Zhenping , Huang Yuanqi , Tang Weihua
Published: February 2018

Mg-doped Ga2O3 thin films with different doping concentrations were deposited on sapphire substrates using laser molecular beam epitaxy (L-MBE) technique. X-ray diffraction (XRD), x-ray photoelectron spectroscopy (XPS) and ultraviolet-visible (UV-vis) absorption spectrum were used to characterize the crystal structure and optical properties of the as-grown films. Compared to pure Ga2O3 thin film, the Mg-doped thin films have transformed from the most stable β-phase into ε-phase. The absorption edge shifted to about 205 nm and the optical bandgap increased to ∼ 6 eV. These properties reveal that Mg-doped Ga2O3 films may have potential applications in the field of deep ultraviolet optoelectronic devices, such as deep ultraviolet photodetectors, short wavelength light emitting devices and so on.
Ion temperature measurements of indirect-drive implosions with the neutron time-of-flight detector on SG-III laser facility
Authors: Chen Zhongjing , Zhang Xing , Pu Yudong , Yan Ji , Huang Tianxuan , Jiang Wei , Yu Bo , Chen Bolun , Tang Qi , Song Zifeng , Chen Jiabin , Zhan Xiayu , Liu Zhongjie , Xie Xufei , Jiang Shaoen , Liu Shenye
Published: February 2018

The accuracy of the determination of the burn-averaged ion temperature of inertial confinement fusion implosions depends on the unfold process, including deconvolution and convolution methods, and the function, i.e., the detector response, used to fit the signals measured by neutron time-of-flight (nToF) detectors. The function given by Murphy et al. [Rev. Sci. Instrum. 68(1), 610–613 (1997)] has been widely used in Nova, Omega, and NIF. There are two components, i.e., fast and slow, and the contribution of scattered neutrons has not been dedicatedly considered. In this work, a new function, based on Murphy’s function has been employed to unfold nToF signals. The contribution of scattered neutrons is easily included by the convolution of a Gaussian response function and an exponential decay. The ion temperature is measured by nToF with the new function. Good agreement with the ion temperature determined by the deconvolution method has been achieved.
Enhancing antioxidant systems by exogenous spermine and spermidine in wheat (Triticum aestivum) seedlings exposed to salt stress
Authors: ElSayed Abdelaleim I. , Rafudeen Mohammed S. , El-hamahmy Mohamed A. M. , Odero Dennis C. , Hossain M. Sazzad
Published: February 2018

Plants have evolved complex mechanisms to mitigate osmotic and ionic stress caused by high salinity. The effect of exogenous spermine (Spm) and spermidine (Spd) on defence responses of wheat seedlings under NaCl stress was investigated by measuring antioxidant enzyme activities and the transcript expression of corresponding genes. Exogenous Spm and Spd decreased the level of malondialdehyde, increased chlorophyll and proline contents, and modulated PSII activity in wheat seedlings under salt stress. Spermidine alleviated negative effects on CO2 assimilation induced by salt stress in addition to significantly increasing the activity and content of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco). It appears Spd conferred salinity tolerance in wheat seedlings by enhancing photosynthetic capacity through regulation of gene expression and the activity of key CO2 assimilation enzymes. Exogenous Spm regulated activities of different antioxidant enzymes (catalase, glutathione reductase, dehydroascorbate reductase, ascorbate peroxidase, and superoxide dismutase) and efficiently modulate their transcription levels in wheat seedlings under salt stress. It is likely that Spm plays a key role in alleviating oxidative damage of salt stress by adjusting antioxidant enzyme activities in plants. In addition, exogenous Spd increased transcript level of spermine synthase under salt stress. Salinity stress also caused an increase in transcript levels of diamine oxidase (DAO) and polyamine oxidase (PAO). Exogenous Spd application resulted in a marked increase in free Spd and Spm contents under saline conditions. These results show that exogenous Spd and Spm effectively upregulated transcriptional levels of antioxidant enzyme genes and improved the defence response of plants under salt stress.
PI5P4Kγ functions in DTX1-mediated Notch signaling
Authors: Zheng Li , Conner Sean D.
Published: February 2018

Significance

The Notch signaling pathway performs a vital role in biological processes ranging from stem cell maintenance to cell viability. This highly conserved pathway must be tightly controlled, since defects in signaling can promote disease. The E3 ubiquitin ligase DTX1 has emerged as a key negative regulator of Notch signaling, where Notch ubiquitination by DTX1 is thought to control intracellular sorting decisions of the receptor. Here we show that DTX1 can regulate Notch activity independent of directly ubiquitinating the receptor, suggesting that DTX1 targets other factors involved in Notch transport. Using an activity-based screen for DTX1 substrates, we identify PI5P4Kγ, a lipid kinase, and discover that PI5P4Kγ and DTX1 have opposing activities in regulating Notch transit through recycling endosomes.
Coprolites reveal ecological interactions lost with the extinction of New Zealand birds
Authors: Boast Alexander P. , Weyrich Laura S. , Wood Jamie R. , Metcalf Jessica L. , Knight Rob , Cooper Alan
Published: February 2018

Over the past 50,000 y, biotic extinctions and declines have left a legacy of vacant niches and broken ecological interactions across global terrestrial ecosystems. Reconstructing the natural, unmodified ecosystems that preceded these events relies on high-resolution analyses of paleoecological deposits. Coprolites are a source of uniquely detailed information about trophic interactions and the behaviors, gut parasite communities, and microbiotas of prehistoric animal species. Such insights are critical for understanding the legacy effects of extinctions on ecosystems, and can help guide contemporary conservation and ecosystem restoration efforts. Here we use high-throughput sequencing (HTS) of ancient eukaryotic DNA from coprolites to reconstruct aspects of the biology and ecology of four species of extinct moa and the critically endangered kakapo parrot from New Zealand (NZ). Importantly, we provide evidence that moa and prehistoric kakapo consumed ectomycorrhizal fungi, suggesting these birds played a role in dispersing fungi that are key to NZ’s natural forest ecosystems. We also provide the first DNA-based evidence that moa frequently supplemented their broad diets with ferns and mosses. Finally, we also find parasite taxa that provide insight into moa behavior, and present data supporting the hypothesis of coextinction between moa and several parasite species. Our study demonstrates that HTS sequencing of coprolites provides a powerful tool for resolving key aspects of ancient ecosystems and may rapidly provide information not obtainable by conventional paleoecological techniques, such as fossil analyses.
Contribution of NIH funding to new drug approvals 2010–2016
Authors: Galkina Cleary Ekaterina , Beierlein Jennifer M. , Khanuja Navleen Surjit , McNamee Laura M. , Ledley Fred D.
Published: February 2018

Significance

This report shows that NIH funding contributed to published research associated with every one of the 210 new drugs approved by the Food and Drug Administration from 2010–2016. Collectively, this research involved >200,000 years of grant funding totaling more than $100 billion. The analysis shows that >90% of this funding represents basic research related to the biological targets for drug action rather than the drugs themselves. The role of NIH funding thus complements industry research and development, which focuses predominantly on applied research. This work underscores the breath and significance of public investment in the development of new therapeutics and the risk that reduced research funding would slow the pipeline for treating morbid disease.
Land-use and land-cover change shape the sustainability and impacts of protected areas
Authors: Tesfaw Anteneh T. , Pfaff Alexander , Golden Kroner Rachel E. , Qin Siyu , Medeiros Rodrigo , Mascia Michael B.
Published: February 2018

Significance

Emerging evidence shows that the boundaries of protected areas (PAs) and their level of protection regularly change, yet little is known regarding the underlying causes of these legal changes and their impacts on ecosystems. For PA degazettements (i.e., protection removals) in the state of Rondônia in the Brazilian Amazon we show that the PAs less effective in stemming deforestation are more likely to be degazetted. For those already deforested PAs degazettement had limited, if any, additional impact on deforestation. Consistent with the scientific literature recognizing that governance shapes conservation outcomes, governance that improves PA outcomes also improves their legal durability. Our evidence on such relationships suggests directions for research and the need for policymakers to reexamine conventional wisdom regarding PAs.
Epitope-specific monoclonal antibodies to FSHβ increase bone mass
Authors: Ji Yaoting , Liu Peng , Yuen Tony , Haider Shozeb , He Jiahuan , Romero Raquel , Chen Hao , Bloch Madison , Kim Se-Min , Lizneva Daria , Munshi Lubna , Zhou Chunxue , Lu Ping , Iqbal Jameel , Cheng Zhen , New Maria I. , Hsueh Aaron J. , Bian Zhuan , Rosen Clifford J. , Sun Li , Zaidi Mone
Published: February 2018

Significance

We have addressed the question whether osteoporosis and obesity, which often occur concurrently in postmenopausal women, can be targeted by a single agent. We have shown previously that the reproductive hormone FSH, the levels of which rise after menopause, regulates both body fat and bone mass. We now show that blocking FSH action using two purposefully designed epitope-specific antibodies protects against bone loss in mice. This positions both FSH antibodies as lead molecules for clinical development toward future use in people.
The ZBED6–IGF2 axis has a major effect on growth of skeletal muscle and internal organs in placental mammals
Authors: Younis Shady , Schönke Milena , Massart Julie , Hjortebjerg Rikke , Sundström Elisabeth , Gustafson Ulla , Björnholm Marie , Krook Anna , Frystyk Jan , Zierath Juleen R. , Andersson Leif
Published: February 2018

A single nucleotide substitution in the third intron of insulin-like growth factor 2 (
IGF2
) is associated with increased muscle mass and reduced subcutaneous fat in domestic pigs. This mutation disrupts the binding of the ZBED6 transcription factor and leads to a threefold up-regulation of
IGF2
expression in pig skeletal muscle. Here, we investigated the biological significance of ZBED6–
IGF2
interaction in the growth of placental mammals using two mouse models, ZBED6 knock-out (
Zbed6
−/−
) and
Igf2
knock-in mice that carry the pig
IGF2
mutation. These transgenic mice exhibit markedly higher serum IGF2 concentrations, higher growth rate, increased lean mass, and larger heart, kidney, and liver; no significant changes were observed for white adipose tissues. The changes in body and lean mass were most pronounced in female mice. The phenotypic changes were concomitant with a remarkable up-regulation of
Igf2
expression in adult tissues. Transcriptome analysis of skeletal muscle identified differential expression of genes belonging to the extracellular region category. Expression analysis using fetal muscles indicated a minor role of ZBED6 in regulating
Igf2
expression prenatally. Furthermore, transcriptome analysis of the adult skeletal muscle revealed that this elevated expression of
Igf2
was derived from the P1 and P2 promoters. The results revealed very similar phenotypic effects in the
Zbed6
knock-out mouse and in the
Igf2
knock-in mouse, showing that the effect of ZBED6 on growth of muscle and internal organs is mediated through the binding site in the
Igf2
gene. The results explain why this ZBED6 binding site is extremely well conserved among placental mammals.
Borrowed Spanish discourse markers in narrative
Authors: Brody Mary Jill
Published: February 2018

This pilot study examines texts from three generations of speakers of Tojol-ab’al, a Mayan language that has been in long-term contact with Spanish, to determine the influence from Spanish on Tojol-ab’al narrative discourse. Discourse markers borrowed from Spanish and those indigenous to Tojol-ab’al are examined to determine discourse structure. Discourse markers borrowed from Spanish appear frequently even in the speech of the oldest, monolingual generation. Although the youngest generation uses many more words (nouns, verbs) borrowed from Spanish than do the earlier generations, narrative discourse structure, as indicated by the use of both borrowed and indigenous discourse markers, remains substantially the same through time.
El futuro es perifrástico
Authors: Kyzar Kendall
Published: February 2018

In this study of the expression of futurity in the Spanish of Mexicans residing in the Baton Rouge, Louisiana, metropolitan area, I explore the distribution of the variants of futurity – the morphological future (MF), the periphrastic future (PF) and the simple present (SP) – and the constraints conditioning their occurrence. The results indicate that the PF registers the highest rate of occurrence with a frequency of 72.0% to the detriment of the MF. In comparison with other studies (cf. Gutiérrez 1995; Orozco 2007a), the PF is the most favored variant at the expense of the others. The type of verb, as reported in previous studies (cf. Orozco 2005, 2007a), is the linguistic constraint that most strongly influences the expression of futurity. Regarding social constraints, level of education conditions the use of the future. The lack of statistical significance for gender suggests that women and men have similar sociolinguistic behaviors. This opens the possibility of exploring other linguistic variables in other bilingual Mexican communities to determine whether the social trends that are found are limited to the expression of futurity or to the communities under study.
Report on the measurement results for the EURAMET 658 extension: project to examine underlying parameters in radiance scale realisation
Authors: McEvoy Helen , Martin Maria Jose , Steiner Anton , Schreiber Ekkehard , Girard Ferruccio , Battuello Mauro , Sadli Mohamed , Ridoux Pascal , Gutschwager Berndt , Hollandt Joerg , Diril Ahmet , Pehlivan Özlem
Published: February 2018

This report describes the measurement procedures and participant results for the EURAMET project 658 extension—'project to examine underlying parameters in radiance temperature scale realisation from 156 °C to 1000 °C', with particular emphasis on the results of the variable temperature and fixed point blackbody measurements for the justification of radiation thermometry CMCs.

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCT, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Feeding habits estimated from weight-related isotope variations of mesopelagic fish larvae in the Kuroshio waters of the northeastern East China Sea
Authors: Mei Weiping , Umezawa Yu , Wan Xin , Yuan Jinghan , Sassa Chiyuki
Published: February 2018

Bulk carbon and nitrogen stable isotope (SI) ratios (δ13C and δ15N) were analysed to investigate the feeding habits of six taxa of mesopelagic fish larvae inhabiting the Kuroshio waters of the northeastern East China Sea. Large variation in tissue SI during early larval periods suggested maternal effects from parent fishes, and non-selective feeding on a variety of plankton species due to poor swimming ability. The similarity between SI ratios measured in larval tissues and those estimated for eggs of an “income breeder” in the spawning area support an “income breeder” strategy in Diaphus slender type and Vinciguerria nimbaria, while Lipolagus ochotensis seemed to show “capital breeder”-like characteristics. SI ratios of the fish larvae studied became relatively constant at species-specific body dry-weights (0.5–1.0 mg), probably due to the commencement of selective feeding, meaning SI ratios during late larval periods could be used for trophic position analysis. There was great overlap (44.6–76.5%) in trophic niche among the larval fishes within the same taxonomic family of Myctophidae. Even if principal diet components cannot be identified with gut contents analyses, diet information from other fish species occupying a similar isotopic niche can thus improve our understanding of the diets of larval fishes.
The first in situ observation of torsional Alfvén waves during the interaction of large-scale magnetic clouds
Authors: Raghav Anil N , Kule Ankita
Published: February 2018

The large-scale magnetic cloud such as coronal mass ejections (CMEs) is the fundamental driver of the space weather. The interaction of the multiple-CMEs in interplanetary space affects their dynamic evolution and geo-effectiveness. The complex and merged multiple magnetic clouds appear as the in situ signature of the interacting CMEs. The Alfvén waves are speculated to be one of the major possible energy exchange/dissipation mechanism during the interaction. However, no such observational evidence has been found in the literature. The case studies of CME–CME collision events suggest that the magnetic and thermal energy of the CME is converted into the kinetic energy. Moreover, magnetic reconnection process is justified to be responsible for merging of multiple magnetic clouds. Here, we present unambiguous evidence of sunward torsional Alfvén waves in the interacting region after the super-elastic collision of multiple CMEs. The Walén relation is used to confirm the presence of Alfvén waves in the interacting region of multiple CMEs/magnetic clouds. We conclude that Alfvén waves and magnetic reconnection are the possible energy exchange/dissipation mechanisms during large-scale magnetic clouds collisions. This study has significant implications not only in CME-magnetosphere interactions but also in the interstellar medium where interactions of large-scale magnetic clouds are possible.
Multifactorial chromosomal variants regulate polymyxin resistance in extensively drug-resistant Klebsiella pneumoniae
Authors: Pitt Miranda E. , Elliott Alysha G. , Cao Minh Duc , Ganesamoorthy Devika , Karaiskos Ilias , Giamarellou Helen , Abboud Cely S. , Blaskovich Mark A. T. , Cooper Matthew A. , Coin Lachlan J. M.
Published: February 2018

Extensively drug-resistant Klebsiella pneumoniae (XDR-KP) infections cause high mortality and are disseminating globally. Identifying the genetic basis underpinning resistance allows for rapid diagnosis and treatment. XDR isolates sourced from Greece and Brazil, including 19 polymyxin-resistant and five polymyxin-susceptible strains, were subjected to whole genome sequencing. Seventeen of the 19 polymyxin-resistant isolates harboured variations upstream or within mgrB. The most common mutation identified was an insertion at nucleotide position 75 in mgrB via an ISKpn26-like element in the ST258 lineage and ISKpn13 in one ST11 isolate. Three strains acquired an IS1 element upstream of mgrB and another strain had an ISKpn25 insertion at 133 bp. Other isolates had truncations (C28STOP, Q30STOP) or a missense mutation (D29E) affecting mgrB. Complementation assays revealed all mgrB perturbations contributed to resistance. Missense mutations in phoQ (T281M, G385C) were also found to facilitate resistance. Several variants in phoPQ co-segregating with the ISKpn26-like insertion were identified as potential partial suppressor mutations. Three ST258 samples were found to contain subpopulations with different resistance-conferring mutations, including the ISKpn26-like insertion colonizing with a novel mutation in pmrB (P158R), both confirmed via complementation assays. These findings highlight the broad spectrum of chromosomal modifications which can facilitate and regulate resistance against polymyxins in K. pneumoniae.
Characterization of missing values in untargeted MS-based metabolomics data and evaluation of missing data handling strategies
Authors: Do Kieu Trinh , Wahl Simone , Raffler Johannes , Molnos Sophie , Laimighofer Michael , Adamski Jerzy , Suhre Karsten , Strauch Konstantin , Peters Annette , Gieger Christian , Langenberg Claudia , Stewart Isobel D. , Theis Fabian J. , Grallert Harald , Kastenmüller Gabi , Krumsiek Jan
Published: February 2018

BACKGROUND

Untargeted mass spectrometry (MS)-based metabolomics data often contain missing values that reduce statistical power and can introduce bias in epidemiological studies. However, a systematic assessment of the various sources of missing values and strategies to handle these data has received little attention. Missing data can occur systematically, e.g. from run day-dependent effects due to limits of detection (LOD); or it can be random as, for instance, a consequence of sample preparation.

METHODS

We investigated patterns of missing data in an MS-based metabolomics experiment of serum samples from the German KORA F4 cohort (n = 1750). We then evaluated 31 imputation methods in a simulation framework and biologically validated the results by applying all imputation approaches to real metabolomics data. We examined the ability of each method to reconstruct biochemical pathways from data-driven correlation networks, and the ability of the method to increase statistical power while preserving the strength of established genetically metabolic quantitative trait loci.

RESULTS

Run day-dependent LOD-based missing data accounts for most missing values in the metabolomics dataset. Although multiple imputation by chained equations (MICE) performed well in many scenarios, it is computationally and statistically challenging. K-nearest neighbors (KNN) imputation on observations with variable pre-selection showed robust performance across all evaluation schemes and is computationally more tractable.

CONCLUSION

Missing data in untargeted MS-based metabolomics data occur for various reasons. Based on our results, we recommend thatKNN-based imputation is performed on observations with variable pre-selection since it showed robust results in all evaluation schemes.

Key messages

Untargeted MS-based metabolomics data show missing values due to both batch-specific LOD-based and non-LOD-based effects.

Statistical evaluation of multiple imputation methods was conducted on both simulated and real datasets.

Biological evaluation on real data assessed the ability of imputation methods to preserve statistical inference of biochemical pathways and correctly estimate effects of genetic variants on metabolite levels.

KNN-based imputation on observations with variable pre-selection andK= 10 showed robust performance for all data scenarios across all evaluation schemes.
Viral-mediated optogenetic stimulation of peripheral motor nerves in non-human primates
Authors: Williams Jordan J. , Watson Alan M. , Vazquez Alberto L. , Schwartz Andrew B.
Published: February 2018

Objective

Reanimation of muscles paralyzed by disease states such as spinal cord injury remains a much sought after therapeutic goal of neuroprosthetic research. Optogenetic stimulation of peripheral motor nerves expressing light-sensitive opsins is a promising approach to muscle reanimation that may overcome several drawbacks of traditional methods such as functional electrical stimulation (FES). However, the utility of these methods has only been demonstrated in rodents to date, while translation to clinical practice will likely first require demonstration and refinement of these gene therapy techniques in non-human primates.

Approach

Three rhesus macaques were injected intramuscularly with either one or both of two optogenetic constructs (AAV6-hSyn-ChR2-eYFP and/or AAV6-hSyn-Chronos-eYFP) to transduce opsin expression in the corresponding nerves. Neuromuscular junctions were targeted for virus delivery using an electrical stimulating injection technique. Functional opsin expression was periodically evaluated up to 13 weeks post-injection by optically stimulating targeted nerves with a 472 nm fiber-coupled laser while recording electromyographic (EMG) responses.

Main Results

One monkey demonstrated functional expression of ChR2 at 8 weeks post-injection in each of two injected muscles, while the second monkey briefly exhibited contractions coupled to optical stimulation in a muscle injected with the Chronos construct at 10 weeks. A third monkey injected only in one muscle with the ChR2 construct showed strong optically coupled contractions at 5 ½ weeks which then disappeared by 9 weeks. EMG responses to optical stimulation of ChR2-transduced nerves demonstrated graded recruitment relative to both stimulus pulse-width and light intensity, and were able to track stimulus trains up to 16 Hz. In addition, the EMG response to prolonged stimulation showed delayed fatigue over several minutes.

Significance

These results demonstrate the feasibility of viral transduction of peripheral motor nerves for functional optical stimulation of motor activity in non-human primates, a variable timeline of opsin expression in a primate model closer to humans, and fundamental EMG response characteristics to optical nerve stimulation. Subsequently, they represent an important step in translating these optogenetic techniques as a clinically viable gene therapy.
Neuroligins mediate presynaptic maturation through brain-derived neurotrophic factor signaling
Authors: Petkova Andoniya , Gödecke Nina , Korte Martin , Dresbach Thomas
Published: February 2018

Maturation is a process that allows synapses to acquire full functionality; failures in synaptic maturation may contribute to neurodevelopmental disorders. Neuroligins are postsynaptic cell-adhesion molecules essential for synapse maturation, but the underlying pathways are incompletely understood. Here, we show that maturational increases in active zone stability and synaptic vesicle recycling rely on the joint action of Neuroligins and brain-derived neurotrophic factor (BDNF). Applying BDNF to neuronal cultures mimicked the maturation-promoting effects of overexpressing the Neuroligin isoforms NL1 or NL2. Inhibiting BDNF signaling reduced the effects of NL1 and NL2 on presynaptic maturation and of NL2 on synapse formation. Applying BDNF to NL1-knockout mouse cultures rescued defective presynaptic maturation, indicating that BDNF acts downstream of NL1 and can restore presynaptic maturation at late stages of network development. Our data introduce BDNF as a novel and essential component in a transsynaptic pathway linking Neuroligin-mediated cell adhesion, neurotrophin action and presynaptic maturation.
A T7 phage factor required for managing RpoS inEscherichia coli
Authors: Tabib-Salazar Aline , Liu Bing , Barker Declan , Burchell Lynn , Qimron Udi , Matthews Steve J. , Wigneshweraraj Sivaramesh
Published: February 2018

T7 development inEscherichia colirequires the inhibition of the housekeeping form of the bacterial RNA polymerase (RNAP), Eσ70, by two T7 proteins: Gp2 and Gp5.7. While the biological role of Gp2 is well understood, that of Gp5.7 remains to be fully deciphered. Here, we present results from functional and structural analyses to reveal that Gp5.7 primarily serves to inhibit EσS, the predominant form of the RNAP in the stationary phase of growth, which accumulates in exponentially growingE. colias a consequence of buildup of guanosine pentaphosphate ((p)ppGpp) during T7 development. We further demonstrate a requirement of Gp5.7 for T7 development inE. colicells in the stationary phase of growth. Our finding represents a paradigm for how some lytic phages have evolved distinct mechanisms to inhibit the bacterial transcription machinery to facilitate phage development in bacteria in the exponential and stationary phases of growth.

Significance statement

Virus that infect bacteria (phages) represent the most abundant living entities on the planet and many aspects of our fundamental knowledge of phage-bacteria relationships have been derived in the context of exponentially growing bacteria. In the case of the prototypicalEscherichia coliphage T7, specific inhibition of the housekeeping form of the RNA polymerase (Eσ70) by a T7 protein, called Gp2, is essential for the development of viral progeny. We now reveal that T7 uses a second specific inhibitor that selectively inhibits the stationary phase RNAP (EσS), which enables T7 to develop well in exponentially growing and stationary phase bacteria. The results have broad implications for our understanding of phage-bacteria relationships and therapeutic application of phages.