bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review
Authors: Poggesi Anna , Pasi Marco , Pescini Francesca , Pantoni Leonardo , Inzitari Domenico
Published: June 2015

The term cerebral small vessel disease (SVD) refers to a group of pathologic processes with various etiologies that affect small arteries, arterioles, venules, and capillaries of the brain. Magnetic resonance imaging (MRI) correlates of SVD are lacunes, recent small subcortical infarcts, white-matter hyperintensities, enlarged perivascular spaces, microbleeds, and brain atrophy. Endothelial dysfunction is thought to have a role in the mechanisms leading to SVD-related brain changes, and the study of endothelial dysfunction has been proposed as an important step for a better comprehension of cerebral SVD. Among available methods to assess endothelial function in vivo, measurement of molecules of endothelial origin in peripheral blood is currently receiving selective attention. These molecules include products of endothelial cells that change when the endothelium is activated, as well as molecules that reflect endothelial damage and repair. This review examines the main molecular factors involved in both endothelial function and dysfunction, and the evidence linking endothelial dysfunction with cerebral SVD, and gives an overview of clinical studies that have investigated the possible association between endothelial circulating biomarkers and SVD-related brain changes.
Sirtuin 3 Mediates Neuroprotection of Ketones against Ischemic Stroke
Authors: Yin Junxiang , Han Pengcheng , Tang Zhiwei , Liu Qingwei , Shi Jiong
Published: June 2015

Stroke is one of the leading causes of death. Growing evidence indicates that ketone bodies have beneficial effects in treating stroke, but their underlying mechanism remains unclear. Our previous study showed ketone bodies reduced reactive oxygen species by using NADH as an electron donor, thus increasing the NAD+/NADH ratio. In this study, we investigated whether mitochondrial NAD+-dependent Sirtuin 3 (SIRT3) could mediate the neuroprotective effects of ketone bodies after ischemic stroke. We injected mice with either normal saline or ketones (beta-hydroxybutyrate and acetoacetate) at 30 minutes after ischemia induced by transient middle cerebral artery (MCA) occlusion. We found that ketone treatment enhanced mitochondria function, reduced oxidative stress, and therefore reduced infarct volume. This led to improved neurologic function after ischemia, including the neurologic score and the performance in Rotarod and open field tests. We further showed that ketones' effects were achieved by upregulating NAD+-dependent SIRT3 and its downstream substrates forkhead box O3a (FoxO3a) and superoxide dismutase 2 (SOD2) in the penumbra region since knocking down SIRT3 in vitro diminished ketones' beneficial effects. These results provide us a foundation to develop novel therapeutics targeting this SIRT3-FoxO3a-SOD2 pathway.
Exendin-4-Loaded PLGA Microspheres Relieve Cerebral Ischemia/Reperfusion Injury and Neurologic Deficits through Long-Lasting Bioactivity-Mediated Phosphorylated Akt/eNOS Signaling in Rats
Authors: Chien Chiang-Ting , Jou Ming-Jia , Cheng Tai-Yu , Yang Chih-Hui , Yu Tzu-Ying , Li Ping-Chia
Published: June 2015

Glucagon-like peptide-1 (GLP-1) receptor activation in the brain provides neuroprotection. Exendin-4 (Ex-4), a GLP-1 analog, has seen limited clinical usage because of its short half-life. We developed long-lasting Ex-4-loaded poly(D,L-lactide-co-glycolide) microspheres (PEx-4) and explored its neuroprotective potential against cerebral ischemia in diabetic rats. Compared with Ex-4, PEx-4 in the gradually degraded microspheres sustained higher Ex-4 levels in the plasma and cerebrospinal fluid for at least 2 weeks and improved diabetes-induced glycemia after a single subcutaneous administration (20 μg/day). Ten minutes of bilateral carotid artery occlusion (CAO) combined with hemorrhage-induced hypotension (around 30 mm Hg) significantly decreased cerebral blood flow and microcirculation in male Wistar rats subjected to streptozotocin-induced diabetes. CAO increased cortical O2– levels by chemiluminescence amplification and prefrontal cortex edema by T2-weighted magnetic resonance imaging analysis. CAO significantly increased aquaporin 4 and glial fibrillary acidic protein expression and led to cognition deficits. CAO downregulated phosphorylated Akt/endothelial nitric oxide synthase (p-Akt/p-eNOS) signaling and enhanced nuclear factor (NF)-κBp65/ intercellular adhesion molecule-1 (ICAM-1) expression, endoplasmic reticulum (ER) stress, and apoptosis in the cerebral cortex. PEx-4 was more effective than Ex-4 to improve CAO-induced oxidative injury and cognitive deficits. The neuroprotection provided by PEx-4 was through p-Akt/p-eNOS pathways, which suppressed CAO-enhanced NF- κB/ICAM-1 signaling, ER stress, and apoptosis.
Levo-tetrahydropalmatine attenuates mouse blood-brain barrier injury induced by focal cerebral ischemia and reperfusion: Involvement of Src kinase
Authors: Mao Xiao-Wei , Pan Chun-Shui , Huang Ping , Liu Yu-Ying , Wang Chuan-She , Yan Li , Hu Bai-He , Chang Xin , He Ke , Mu Huan-Na , Li Quan , Sun Kai , Fan Jing-Yu , Han Jing-Yan
Published: June 2015

The restoration of blood flow following thrombolytic therapy causes ischemia and reperfusion (I/R) injury leading to blood-brain barrier (BBB) disruption and subsequent brain edema in patients of ischemic stroke. Levo-tetrahydropalmatine (l-THP) occurs in Corydalis genus and some other plants. However, whether l-THP exerts protective role on BBB disrpution following cerebral I/R remains unclear. Male C57BL/6N mice (23 to 28 g) were subjected to 90 min middle cerebral artery occlusion, followed by reperfusion for 24 h. l-THP (10, 20, 40 mg/kg) was administrated by gavage 60 min before ischemia. We found I/R evoked Evans blue extravasation, albumin leakage, brain water content increase, cerebral blood flow decrease, cerebral infarction and neurological deficits, all of which were attenuated by l-THP treatment. Meanwhile, l-THP inhibited tight junction (TJ) proteins down-expression, Src kinase phosphorylation, matrix metalloproteinases-2/9 (MMP-2/9) and caveolin-1 activation. In addition, surface plasmon resonance revealed binding of l-THP to Src kinase with high affinity. Then we found Src kinase inhibitor PP2 could attenuate Evans blue dye extravasation and inhibit the caveolin-1, MMP-9 activation, occludin down-expression after I/R, respectively. In conclusion, l-THP attenuated BBB injury and brain edema, which were correlated with inhibiting the Src kinase phosphorylation.
Facile formation of ZIF-8 thin films on ZnO nanorods
Authors: Al-Kutubi Hanan , Dikhtiarenko Alla , Zafarani Hamid Reza , Sudhölter Ernst J. R. , Gascon Jorge , Rassaei Liza
Published: June 2015

Thin films of ZIF-8 on ZnO nanorods were synthesized by casting a thin linker film followed by heating for less than an hour.
A vascular injury model using focal heat-induced activation of endothelial cells
Authors: Sylman J. L. , Artzer D. T. , Rana K. , Neeves K. B.
Published: June 2015

Focal heating of endothelial cells with a surface microelectrode induces secretion of vWF, expression of P-selectin, and recession of cell–cell junctions to reveal a subendothelial matrix that supports platelet adhesion and aggregation.
Resonant dielectrophoresis and electrohydrodynamics for high-sensitivity impedance detection of whole-cell bacteria
Authors: Couniot Numa , Francis Laurent A. , Flandre Denis
Published: June 2015

We present an innovative electrode design which uses multi-range electrokinetics with impedance spectroscopy, reaching a detection limit of 105 CFU mL−1 of bacteria.
Assembly of multiple cell gradients directed by three-dimensional microfluidic channels
Authors: Li Yiwei , Feng Xiaojun , Wang Yachao , Du Wei , Chen Peng , Liu Chao , Liu Bi-Feng
Published: June 2015

A simple and versatile 3D microfluidic strategy, enabling directed assembly of multiple gradients in cell density with user-defined designs for reconstitution of the functionality of tissues and cell density-dependant nano-cytotoxicity assay.
Molecular amorphous glasses toward large azomethine crystals with aggregation-induced emission
Authors: Marin Luminita , van der Lee Arie , Shova Sergiu , Arvinte Adina , Barboiu Mihail
Published: June 2015

Imine compounds containing rigid cores and soft aliphatic tails have been designed to generate molecular glasses and large crystals displaying aggregation-induced emission, which makes them interesting candidates for optoelectronic applications.
Combinatorial chemistry in nematodes: modular assembly of primary metabolism-derived building blocks
Authors: von Reuss Stephan H. , Schroeder Frank C.
Published: June 2015

Nematodes are amazingly skilled chemists: using simple building blocks from conserved primary metabolism and a strategy of modular assembly,C. elegansand other nematode species create complex molecular architectures to regulate their development and behaviour.
A green, simple and cost-effective approach to synthesize high quality graphene by electrochemical exfoliation via process optimization
Authors: Chuang Chung-Hsien , Su Ching-Yuan , Hsu Kuei-Ting , Chen Chia-Hsuan , Huang Chia-Hung , Chu Chi-Wen , Liu Wei-Ren
Published: June 2015

High-quality graphene was successfully manufactured by electrochemical exfoliation methodviatuning the synthetic parameters of electrolyte composition and current density.
A functionalized graphene oxide and nano-zeolitic imidazolate framework composite as a highly active and reusable catalyst for [3 + 3] formal cycloaddition reactions
Authors: Wei Yongyi , Hao Zhongkai , Zhang Fang , Li Hexing
Published: June 2015

A SO3H-functionalized graphene oxide and nano-ZIF-8 composite was used as an efficient catalyst for [3 + 3] formal cycloaddition reactions with pyranyl heterocycles.
Floating car data‐based method for detecting flooding incident under grade separation bridges in Beijing
Authors: Song Guohua , Zhang Fan , Liu Jun , Yu Liu , Gao Yong , Yu Lei
Published: June 2015

The congestion caused by a special type of incident that is different from a normal incident, namely the flooding incident under grade separation bridges, has shown to be a serious issue in Beijing because of several horrible recent experiences. To investigate the characteristics of the congestion, this study strives to develop a floating car data (FCD)‐based method for detecting the flooding incident under grade separation bridges. The study first examines the applicability of using an improved cumulative sum (CUSUM) method. However, it is found that the improved CUSUM method does not function properly when all lanes are blocked by the flooding under bridges. Then, the study proposes an analytical method by analysing characteristics of FCD. Three decision parameters, sample losing rate, speed and accumulated discrepancy, are proposed, which play a synergistic effect in the detection. It is shown from case studies that the proposed method performs satisfactorily for detecting flooding incidents under grade separation bridges. The proposed method can be used to further investigate the congestion spreading regularities to develop quick and real‐time response process to mitigating the congestion triggered by the flooding.
Experimental studies of coherent structures in an advection-reaction-diffusion system
Authors: Gowen Savannah , Solomon Tom
Published: June 2015

We present experimental studies of reaction front propagation in a single vortex flow with an imposed external wind. The fronts are produced by the excitable, ferroin-catalyzed Belousov-Zhabotinsky chemical reaction. The flow is generated using an electromagnetic forcing technique: an almost-radial electrical current interacts with a magnetic field from a magnet below the fluid layer to produce the vortex. The magnet is mounted on crossed translation stages allowing for movement of the vortex through the flow. Reaction fronts triggered in or in front of the moving vortex form persistent structures that are seen experimentally for time-independent (constant motion), time-periodic, and time-aperiodic flows. These results are examined with the use of burning invariant manifolds that act as one-way barriers to front motion in the flows. We also explore the usefulness of finite-time Lyapunov exponent fields as an instrument for analyzing front propagation behavior in a fluid flow.
Theoretical study of electronic transport properties of a graphene-silicene bilayer
Authors: Berdiyorov G. R. , Bahlouli H. , Peeters F. M.
Published: June 2015

Electronic transport properties of a graphene-silicene bilayer system are studied using density-functional theory in combination with the nonequilibrium Green's function formalism. Depending on the energy of the electrons, the transmission can be larger in this system as compared to the sum of the transmissions of separated graphene and silicene monolayers. This effect is related to the increased electron density of states in the bilayer sample. At some energies, the electronic states become localized in one of the layers, resulting in the suppression of the electron transmission. The effect of an applied voltage on the transmission becomes more pronounced in the layered sample as compared to graphene due to the larger variation of the electrostatic potential profile. Our findings will be useful when creating hybrid nanoscale devices where enhanced transport properties will be desirable.
Direct numerical simulation of turbulent flow in a rotating square duct
Authors: Dai Yi-Jun , Huang Wei-Xi , Xu Chun-Xiao , Cui Gui-Xiang
Published: June 2015

A fully developed turbulent flow in a rotating straight square duct is simulated by direct numerical simulations at Reτ = 300 and 0 ≤ Roτ ≤ 40. The rotating axis is parallel to two opposite walls of the duct and normal to the main flow. Variations of the turbulence statistics with the rotation rate are presented, and a comparison with the rotating turbulent channel flow is discussed. Rich secondary flow patterns in the cross section are observed by varying the rotation rate. The appearance of a pair of additional vortices above the pressure wall is carefully examined, and the underlying mechanism is explained according to the budget analysis of the mean momentum equations.
Enhancement in magnetic properties of magnesium substituted bismuth ferrite nanoparticles
Authors: Xu Jianlong , Xie Dan , Teng Changjiu , Zhang Xiaowen , Zhang Cheng , Sun Yilin , Ren Tian-Ling , Zeng Min , Gao Xingsen , Zhao Yonggang
Published: June 2015

We report a potential way to effectively improve the magnetic properties of BiFeO3 (BFO) nanoparticles through Mg2+ ion substitution at the Fe-sites of BFO lattice. The high purity and structural changes induced by Mg doping are confirmed by X-ray powder diffractometer and Raman spectra. Enhanced magnetic properties are observed in Mg substituted samples, which simultaneously exhibit ferromagnetic and superparamagnetic properties at room temperature. A physical model is proposed to support the observed ferromagnetism of Mg doped samples, and the superparamagnetic properties are revealed by the temperature dependent magnetization measurements. The improved magnetic properties and soft nature obtained by Mg doping in BFO nanoparticles demonstrate the possibility of BFO nanoparticles to practical applications.
Experimental assessment of presumed filtered density function models
Authors: Stetsyuk V. , Soulopoulos N. , Hardalupas Y. , Taylor A. M. K. P.
Published: June 2015

Measured filtered density functions (FDFs) as well as assumed beta distribution model of mixture fraction and “subgrid” scale (SGS) scalar variance z′′2¯, used typically in large eddy simulations, were studied by analysing experimental data, obtained from two-dimensional planar, laser induced fluorescence measurements in isothermal swirling turbulent flows at a constant Reynolds number of 29 000 for different swirl numbers (0.3, 0.58, and 1.07). Two-dimensional spatial filtering, by using a box filter, was performed in order to obtain the filtered variables, namely, resolved mean and “subgrid” scale scalar variance. These were used as inputs for assumed beta distribution of mixture fraction and top-hat FDF shape estimates. The presumed beta distribution model, top-hat FDF, and the measured filtered density functions were used to integrate a laminar flamelet solution in order to calculate the corresponding resolved temperature. The experimentally measured FDFs varied with the flow swirl number and both axial and radial positions in the flow. The FDFs were unimodal at flow regions with low SGS scalar variance, z′′2¯< 0.01, and bimodal at regions with high SGS variance, z′′2¯> 0.02. Bimodal FDF could be observed for a filter size of approximately 1.5-2 times the Batchelor scale. Unimodal FDF could be observed for a filter size as large as four times the Batchelor scale under well-mixed conditions. In addition, two common computational models (a gradient assumption and a scale similarity model) for the SGS scalar variance were used with the aim to evaluate their validity through comparison with the experimental data. It was found that the gradient assumption model performed generally better than the scale similarity one.
Ultra-low threshold gallium nitride photonic crystal nanobeam laser
Authors: Niu Nan , Woolf Alexander , Wang Danqing , Zhu Tongtong , Quan Qimin , Oliver Rachel A. , Hu Evelyn L.
Published: June 2015

We report exceptionally low thresholds (9.1 μJ/cm2) for room temperature lasing at ∼450 nm in optically pumped Gallium Nitride (GaN) nanobeam cavity structures. The nanobeam cavity geometry provides high theoretical Q (>100 000) with small modal volume, leading to a high spontaneous emission factor, β = 0.94. The active layer materials are Indium Gallium Nitride (InGaN) fragmented quantum wells (fQWs), a critical factor in achieving the low thresholds, which are an order-of-magnitude lower than obtainable with continuous QW active layers. We suggest that the extra confinement of photo-generated carriers for fQWs (compared to QWs) is responsible for the excellent performance.
Dominant conduction mechanism in NiO-based resistive memories
Authors: Iwata Tatsuya , Nishi Yusuke , Kimoto Tsunenobu
Published: June 2015

The conduction characteristics of Pt/NiO/Pt resistive switching cells were investigated systematically through DC and AC conductance measurements in each of three resistance states: the initial state, the low resistance state (LRS), and the high resistance state (HRS). In the initial state, two different conduction processes are dominant, although this dominance is temperature-dependent. The activation energy (Ea) of the DC conductance was approximately 4.3 meV below 170 K. In addition to the low Ea, the frequency and temperature dependence of the AC conductance confirmed that the conduction originated from hopping between isolated sites. However, above 170 K, the Ea of the DC conductance was 330 meV, and this conductance was independent of frequency at low frequencies. The dominant conduction process above 170 K was found to be band conduction from analysis of the AC conductance. The resistance in the LRS varied linearly with temperature and was almost independent of frequency, thus representing the characteristics of metallic band conduction of conductive filaments. In the HRS, the DC conductance exhibited an Ea of 16 meV, which was higher than that in the initial state (4.3 meV), thus indicating that the dominant conduction mechanism in the HRS is different to the mechanism in the initial state. From discussions based on a filament model, it was concluded that filament conduction is dominant in the HRS. As a result, it is proposed that the resistive switching originates from changes in the conduction properties of the filaments themselves rather than from their rupture and formation.
Turbulence attenuation by large neutrally buoyant particles
Authors: Cisse M. , Saw E.-W. , Gibert M. , Bodenschatz E. , Bec J.
Published: June 2015

Turbulence modulation by inertial-range-size, neutrally buoyant particles is investigated experimentally in a von Kármán flow. Increasing the particle volume fraction Φv, maintaining constant impellers Reynolds number attenuates the fluid turbulence. The inertial-range energy transfer rate decreases as ∝Φv2/3, suggesting that only particles located on a surface affect the flow. Small-scale turbulent properties, such as structure functions or acceleration distribution, are unchanged. Finally, measurements hint at the existence of a transition between two different regimes occurring when the average distance between large particles is of the order of the thickness of their boundary layers.
Pre-breakdown processes in a dielectric fluid in inhomogeneous pulsed electric fields
Authors: Shneider Mikhail N. , Pekker Mikhail
Published: June 2015

We consider the development of pre-breakdown cavitation nanopores appearing in the dielectric fluid under the influence of the electrostrictive stresses in the inhomogeneous pulsed electric field. It is shown that three characteristic regions can be distinguished near the needle electrode. In the first region, where the electric field gradient is greatest, the cavitation nanopores, occurring during the voltage nanosecond pulse, may grow to the size at which an electron accelerated by the field inside the pores can acquire enough energy for excitation and ionization of the liquid on the opposite pore wall, i.e., the breakdown conditions are satisfied. In the second region, the negative pressure caused by the electrostriction is large enough for the cavitation initiation (which can be registered by optical methods), but, during the voltage pulse, the pores do not reach the size at which the potential difference across their borders becomes sufficient for ionization or excitation of water molecules. And, in the third, the development of cavitation is impossible, due to an insufficient level of the negative pressure: in this area, the spontaneously occurring micropores do not grow and collapse under the influence of surface tension forces. This paper discusses the expansion dynamics of the cavitation pores and their most probable shape.
Bridging and depletion mechanisms in colloid-colloid effective interactions: A reentrant phase diagram
Authors: Fantoni Riccardo , Giacometti Achille , Santos Andrés
Published: June 2015

A general class of nonadditive sticky-hard-sphere binary mixtures, where small and large spheres represent the solvent and the solute, respectively, is introduced. The solute-solute and solvent-solvent interactions are of hard-sphere type, while the solute-solvent interactions are of sticky-hard-sphere type with tunable degrees of size nonadditivity and stickiness. Two particular and complementary limits are studied using analytical and semi-analytical tools. The first case is characterized by zero nonadditivity, lending itself to a Percus–Yevick approximate solution from which the impact of stickiness on the spinodal curves and on the effective solute-solute potential is analyzed. In the opposite nonadditive case, the solvent-solvent diameter is zero and the model can then be reckoned as an extension of the well-known Asakura–Oosawa model with additional sticky solute-solvent interaction. This latter model has the property that its exact effective one-component problem involves only solute-solute pair potentials for size ratios such that a solvent particle fits inside the interstitial region of three touching solutes. In particular, we explicitly identify the three competing physical mechanisms (depletion, pulling, and bridging) giving rise to the effective interaction. Some remarks on the phase diagram of these two complementary models are also addressed through the use of the Noro–Frenkel criterion and a first-order perturbation analysis. Our findings suggest reentrance of the fluid-fluid instability as solvent density (in the first model) or adhesion (in the second model) is varied. Some perspectives in terms of the interpretation of recent experimental studies of microgels adsorbed onto large polystyrene particles are discussed.
Effective improvement in microwave absorption by uniform dispersion of nanodiamond in polyaniline through in-situ polymerization
Authors: Chen Xiangnan , Tian Xin , Zhou Zuowan , Jiang Man , Lu Jun , Wang Yong , Wang Li
Published: June 2015

Uniformly dispersed nanodiamond/polyaniline composite was synthesized by an in situ polymerization, in which the nanodiamond was non-gap combined with polyaniline. The hybrids displayed significant improvement in microwave absorption, which were due to additional and strong polarization originated from the HN-CO groups acting as asymmetric center. Besides, the individually dispersed nanodiamond and the special interface between polyaniline and nanodiamond brought out enhanced interfacial polarization loss. These results could help in understanding the nature of polarization loss, and might open path towards the design of microwave absorbing materials.
Small hole polarons in rare-earth titanates
Authors: Bjaalie L. , Ouellette D. G. , Moetakef P. , Cain T. A. , Janotti A. , Himmetoglu B. , Allen S. J. , Stemmer S. , Van de Walle C. G.
Published: June 2015

We investigate the behavior of hole polarons in rare-earth titanates by combining optical conductivity measurements with first-principles hybrid density functional calculations. Sr-doped GdTiO3 (Gd1−xSrxTiO3) was grown by molecular beam epitaxy. We show that a feature in the optical conductivity that was previously identified with the Mott-Hubbard gap is actually associated with the excitation of a small polaron. The assignment is based on an excellent match between the experimental spectra and first-principles calculations for polaron excitation mechanisms.
Wavelength dependence of femtosecond laser-induced damage threshold of optical materials
Authors: Gallais L. , Douti D.-B. , Commandré M. , Batavičiūtė G. , Pupka E. , Ščiuka M. , Smalakys L. , Sirutkaitis V. , Melninkaitis A.
Published: June 2015

An experimental and numerical study of the laser-induced damage of the surface of optical material in the femtosecond regime is presented. The objective of this work is to investigate the different processes involved as a function of the ratio of photon to bandgap energies and compare the results to models based on nonlinear ionization processes. Experimentally, the laser-induced damage threshold of optical materials has been studied in a range of wavelengths from 1030 nm (1.2 eV) to 310 nm (4 eV) with pulse durations of 100 fs with the use of an optical parametric amplifier system. Semi-conductors and dielectrics materials, in bulk or thin film forms, in a range of bandgap from 1 to 10 eV have been tested in order to investigate the scaling of the femtosecond laser damage threshold with the bandgap and photon energy. A model based on the Keldysh photo-ionization theory and the description of impact ionization by a multiple-rate-equation system is used to explain the dependence of laser-breakdown with the photon energy. The calculated damage fluence threshold is found to be consistent with experimental results. From these results, the relative importance of the ionization processes can be derived depending on material properties and irradiation conditions. Moreover, the observed damage morphologies can be described within the framework of the model by taking into account the dynamics of energy deposition with one dimensional propagation simulations in the excited material and thermodynamical considerations.
Near-field microwave imaging of inhomogeneous KxFeySe2: Separation of topographic and electric features
Authors: Takahashi Hideyuki , Imai Yoshinori , Maeda Atsutaka
Published: June 2015

It is important for modern scanning microwave microscopes (SMMs) to overcome the effect of the surface roughness. Here, we report microwave conductivity imaging of the phase-separated iron chalcogenide KxFeySe2 (x = 0.8, y = 1.6–2), in which electric conductivity-induced contrast is distinguished from topography-induced contrast using a combination of a scanning tunneling microscope and a SMM. We observed the characteristic modulation of the local electric property that originates from the mesoscopic phase separation of the metallic and semiconducting phases in two different scanning modes: constant current mode and constant Q (CQ) mode. In particular, CQ scanning is useful because we obtain a qualitative image in which the topographic contrast is largely eliminated without degradation of the spatial resolution.
Extended wavelength mid-infrared photoluminescence from type-I InAsN and InGaAsN dilute nitride quantum wells grown on InP
Authors: Wheatley R. , Kesaria M. , Mawst L. J. , Kirch J. D. , Kuech T. F. , Marshall A. , Zhuang Q. D. , Krier A.
Published: June 2015

Extended wavelength photoluminescence emission within the technologically important 2–5 μm spectral range has been demonstrated from InAs1−xNx and In1−yGayAs1−xNx type I quantum wells grown onto InP. Samples containing N ∼ 1% and 2% exhibited 4 K photoluminescence emission at 2.0 and 2.7 μm, respectively. The emission wavelength was extended out to 2.9 μm (3.3 μm at 300 K) using a metamorphic buffer layer to accommodate the lattice mismatch. The quantum wells were grown by molecular beam epitaxy and found to be of a high structural perfection as evidenced in the high resolution x-ray diffraction measurements. The photoluminescence was more intense from the quantum wells grown on the metamorphic buffer layer and persisted up to room temperature. The mid-infrared emission spectra were analysed, and the observed transitions were found to be in good agreement with the calculated emission energies.
Highly selective and responsive ultra-violet detection using an improved phototransistor
Authors: Soleimanzadeh Reza , Kolahdouz Mohammadreza , Charsooghi Mohammad A. , Kolahdouz Zahra , Zhang Kouchi
Published: June 2015

An ultra-violet (UV) phototransistor with 700 × 200 μm2 gate area decorated with vertically aligned Zinc Oxide (ZnO) nanorods to enhance UV responsivity is designed and manufactured. Spectral responsivity of the device was measured for wavelengths ranged from 200 to 1100 nm of the electromagnetic spectrum in different transistor working regions. The best responsivity was achieved at sub-threshold and very weak inversion region. In order to enhance UV range selectivity, oxygen plasma has been employed on the nanorods, and consequently, nearly 3-fold improvement in its relative sensitivity at 375 nm was achieved. The final manufactured phototransistor shows a highly selective response of 24 kA/W in the UV range.
Cytochrome
cbb
3
of
Thioalkalivibrio
is a Na
+
-pumping cytochrome oxidase
Authors: Muntyan Maria S. , Cherepanov Dmitry A. , Malinen Anssi M. , Bloch Dmitry A. , Sorokin Dimitry Y. , Severina Inna I. , Ivashina Tatiana V. , Lahti Reijo , Muyzer Gerard , Skulachev Vladimir P.
Published: June 2015

Significance

The majority of aerobic living organisms use oxygen for respiration. The key enzyme, which directly reduces oxygen to water during respiration, is the terminal cytochrome
c
oxidase. It generates a large portion of the utilizable energy provided by the respiratory chain. Accumulation of biologically available energy by means of cytochrome
c
oxidases is believed to be due to the proton-motive force across the mitochondrial or bacterial membrane. Details of this energy conversion are still unclear. Here we report the discovery of a sodium-pumping cytochrome
c
oxidase that converts energy of respiration into sodium-motive force. This finding provides clues to understanding the mechanism of cytochrome
c
oxidase that is not available when applying knowledge of the proton-pumping versions of the enzyme.
Regulation by a chaperone improves substrate selectivity during cotranslational protein targeting
Authors: Ariosa Aileen , Lee Jae Ho , Wang Shuai , Saraogi Ishu , Shan Shu-ou
Published: June 2015

Significance

Correct protein biogenesis is crucial for all cells. Numerous factors including molecular chaperones, modification enzymes, and protein-targeting machineries bind near the ribosome exit site and can access the nascent protein. How nascent proteins are accurately selected into the correct biogenesis pathway in such a crowded environment is an emerging question central to accurate protein biogenesis. Using chemical biology and biochemical and biophysical tools, we show that the major cotranslational chaperone, trigger factor, and cotranslational targeting machinery, signal recognition particle, regulate each other at multiple stages, including initial binding, ribosome delivery to the membrane, and enforcement of a timer for cotranslational protein targeting. Together, these mechanisms enhance accurate substrate selection into both cotranslational and posttranslational protein targeting pathways.
Selective buckling via states of self-stress in topological metamaterials
Authors: Paulose Jayson , Meeussen Anne S. , Vitelli Vincenzo
Published: June 2015

Significance

An ongoing challenge in modern materials science is to create artificial structures, termed metamaterials, with an unconventional response that can be programmed by suitable design of their geometry or topology. We demonstrate a novel metamaterial in which small structural variations single out regions that buckle selectively under external stresses. Surprisingly, these regions are at first glance indistinguishable from the rest of the structure. Our samples are examples of topological metamaterials that are the mechanical analogues of topologically protected electronic systems. As a result, the buckling response is robust against structural perturbations yet tunable without affecting secondary physical properties in the buckling region. This feature is desirable for optomechanical or thermomechanical metamaterials in which multiple characteristics need to be tuned simultaneously.
Gate-controlled proton diffusion and protonation-induced ratchet motion in the stator of the bacterial flagellar motor
Authors: Nishihara Yasutaka , Kitao Akio
Published: June 2015

Significance

The bacterial flagellum is a molecular machine for the locomotion of bacteria. The flagellar motor can convert the motive force of protons and other ions to molecular motor rotations. We report on the multi-ion transfer mechanism of the flagellar motor stator MotA/B in
Escherichia coli
, which primarily utilizes protons. We have identified a leucine amino acid residue as the gateway for H
3
O
+
diffusion. Mutations of a key valine residue cause a narrowing of the channel that is consistent with the size-dependent ion selectivity. We also show that the protonation/deprotonation cycle induces a ratchet motion in the stator, which can couple to the motor rotation. Ion selectivity and the ratchet motion are key to understanding the mechanism of the flagellar motor.
Leinamycin E1 acting as an anticancer prodrug activated by reactive oxygen species
Authors: Huang Sheng-Xiong , Yun Bong-Sik , Ma Ming , Basu Hirak S. , Church Dawn R. , Ingenhorst Gudrun , Huang Yong , Yang Dong , Lohman Jeremy R. , Tang Gong-Li , Ju Jianhua , Liu Tao , Wilding George , Shen Ben
Published: June 2015

Significance

The natural product leinamycin (LNM), upon reductive activation by cellular thiols, exerts its antitumor activity by an episulfonium ion-mediated DNA alkylation. Manipulation of the LNM biosynthesis in
Streptomyces atroolivaceus
S-140 yielded a recombinant strain that produced an LNM biosynthetic intermediate, leinamycin E1 (LNM E1). Complementary to the reductive activation of LNM by cellular thiols, LNM E1 can be oxidatively activated by cellular reactive oxygen species (ROS) to generate a similar episulfonium ion intermediate, thereby alkylating DNA and leading to eventual cell death. The feasibility of exploiting LNM E1 as an anticancer prodrug activated by ROS was demonstrated in two prostate cancer cell lines, LNCaP and DU-145. The structure of LNM E1 also reveals critical new insights into LNM biosynthesis.
BMP9 and BMP10 are necessary for proper closure of the ductus arteriosus
Authors: Levet Sandrine , Ouarné Marie , Ciais Delphine , Coutton Charles , Subileau Mariela , Mallet Christine , Ricard Nicolas , Bidart Marie , Debillon Thierry , Faravelli Francesca , Rooryck Caroline , Feige Jean-Jacques , Tillet Emmanuelle , Bailly Sabine
Published: June 2015

Significance

At birth, newborns must switch from the fetal aquatic life to the aerial one, by closure of a vessel named the ductus arteriosus. During fetal life, it allows blood to bypass the lungs, and a failure of its closure at birth is a major cause of mortality, particularly in preterm neonates. This pathological condition is known as patent ductus arteriosus and occurs in approximately 60% of preterm infants born before 28 wk of gestation. Herein, we show, for the first time to our knowledge, the involvement of two circulating growth factors, bone morphogenetic proteins BMP9 and BMP10, in the anatomical closure of this vessel. This finding will have potential clinical applications in the management of this pathology.
Amelioration of toxicity in neuronal models of amyotrophic lateral sclerosis by hUPF1
Authors: Barmada Sami J. , Ju Shulin , Arjun Arpana , Batarse Anthony , Archbold Hilary C. , Peisach Daniel , Li Xingli , Zhang Yuxi , Tank Elizabeth M. H. , Qiu Haiyan , Huang Eric J. , Ringe Dagmar , Petsko Gregory A. , Finkbeiner Steven
Published: June 2015

Significance

Amyotrophic lateral sclerosis (ALS) is a devastating disorder inevitably resulting in paralysis and death. Mutations in genes encoding RNA binding proteins cause familial ALS, but wild-type (WT) versions of these proteins accumulate in sporadic disease. In this study, we identified and characterized human up-frameshift protein 1 (hUPF1) as a potent modifier of neurodegeneration in ALS models. hUPF1 dramatically reduced toxicity in primary mammalian neurons expressing WT and disease-associated mutant RNA binding proteins, demonstrating efficacy in familial and sporadic disease models, and verifying the existence of a conserved neurotoxic pathway targeted by hUPF1. The work has fundamental implications for ALS disease mechanisms and offers a novel perspective on effective therapies generalizable to both sporadic and familial disease.
The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing
Authors: Lee Soung-Hoon , Kim Mi-Yeon , Kim Hyun-Yi , Lee Young-Mi , Kim Heesu , Nam Kyoung Ae , Roh Mi Ryung , Min Do Sik , Chung Kee Yang , Choi Kang-Yell
Published: June 2015

Wnt/β-catenin signaling plays important roles in cutaneous wound healing and dermal fibrosis. However, its regulatory mechanism has not been fully elucidated, and a commercially available wound-healing agent targeting this pathway is desirable but currently unavailable. We found that CXXC-type zinc finger protein 5 (CXXC5) serves as a negative feedback regulator of the Wnt/β-catenin pathway by interacting with the Dishevelled (Dvl) protein. In humans, CXXC5 protein levels were reduced in epidermal keratinocytes and dermal fibroblasts of acute wounds. A differential regulation of β-catenin, α-smooth muscle actin (α-SMA), and collagen I by overexpression and silencing of CXXC5 in vitro indicated a critical role for this factor in myofibroblast differentiation and collagen production. In addition, CXXC5−/− mice exhibited accelerated cutaneous wound healing, as well as enhanced keratin 14 and collagen synthesis. Protein transduction domain (PTD)–Dvl-binding motif (DBM), a competitor peptide blocking CXXC5-Dvl interactions, disrupted this negative feedback loop and activated β-catenin and collagen production in vitro. Co-treatment of skin wounds with PTD-DBM and valproic acid (VPA), a glycogen synthase kinase 3β (GSK3β) inhibitor which activates the Wnt/β-catenin pathway, synergistically accelerated cutaneous wound healing in mice. Together, these data suggest that CXXC5 would represent a potential target for future therapies aimed at improving wound healing.
Analytic extensions of algebraic isomorphisms
Authors: Kaliman S.
Published: June 2015

Let

Ψ
:

X
1

→

X
2

\Psi : X_1 \to X_2

be an isomorphism of closed affine algebraic subvarieties of

C

n

\mathbb {C}^n

such that

n
>
max
(
2
dim
⁡

X
1

,
dim
⁡
T

X
1

)

n > \max (2\dim X_1, \dim TX_1)

. We prove that

Ψ
\Psi

can be extended to a holomorphic automorphism of

C

n

\mathbb {C}^n

. Furthermore, when

Ψ
\Psi

is an isomorphism of curves, such an extension exists for every

n
≥
3

n\geq 3

even when

dim

T

X
1

=
n

\dim \,TX_1=n

.
Social genetic and social environment effects on parental and helper care in a cooperatively breeding bird
Authors: Adams Mark James , Robinson Matthew R. , Mannarelli Maria-Elena , Hatchwell Ben J.
Published: June 2015

Phenotypes expressed in a social context are not only a function of the individual, but can also be shaped by the phenotypes of social partners. These social effects may play a major role in the evolution of cooperative breeding if social partners differ in the quality of care they provide and if individual carers adjust their effort in relation to that of other carers. When applying social effects models to wild study systems, it is also important to explore sources of individual plasticity that could masquerade as social effects. We studied offspring provisioning rates of parents and helpers in a wild population of long-tailed tits
Aegithalos caudatus
using a quantitative genetic framework to identify these social effects and partition them into genetic, permanent environment and current environment components. Controlling for other effects, individuals were consistent in their provisioning effort at a given nest, but adjusted their effort based on who was in their social group, indicating the presence of social effects. However, these social effects differed between years and social contexts, indicating a current environment effect, rather than indicating a genetic or permanent environment effect. While this study reveals the importance of examining environmental and genetic sources of social effects, the framework we present is entirely general, enabling a greater understanding of potentially important social effects within any ecological population.
Cancer across the tree of life: cooperation and cheating in multicellularity
Authors: Aktipis C. Athena , Boddy Amy M. , Jansen Gunther , Hibner Urszula , Hochberg Michael E. , Maley Carlo C. , Wilkinson Gerald S.
Published: June 2015

Multicellularity is characterized by cooperation among cells for the development, maintenance and reproduction of the multicellular organism. Cancer can be viewed as cheating within this cooperative multicellular system. Complex multicellularity, and the cooperation underlying it, has evolved independently multiple times. We review the existing literature on cancer and cancer-like phenomena across life, not only focusing on complex multicellularity but also reviewing cancer-like phenomena across the tree of life more broadly. We find that cancer is characterized by a breakdown of the central features of cooperation that characterize multicellularity, including cheating in proliferation inhibition, cell death, division of labour, resource allocation and extracellular environment maintenance (which we term the five foundations of multicellularity). Cheating on division of labour, exhibited by a lack of differentiation and disorganized cell masses, has been observed in all forms of multicellularity. This suggests that deregulation of differentiation is a fundamental and universal aspect of carcinogenesis that may be underappreciated in cancer biology. Understanding cancer as a breakdown of multicellular cooperation provides novel insights into cancer hallmarks and suggests a set of assays and biomarkers that can be applied across species and characterize the fundamental requirements for generating a cancer.
The multiple facets of Peto's paradox: a life-history model for the evolution of cancer suppression
Authors: Brown Joel S. , Cunningham Jessica J. , Gatenby Robert A.
Published: June 2015

Large animals should have higher lifetime probabilities of cancer than small animals because each cell division carries an attendant risk of mutating towards a tumour lineage. However, this is not observed—a (Peto's) paradox that suggests large and/or long-lived species have evolved effective cancer suppression mechanisms. Using the Euler–Lotka population model, we demonstrate the evolutionary value of cancer suppression as determined by the ‘cost’ (decreased fecundity) of suppression verses the ‘cost’ of cancer (reduced survivorship). Body sizeper sewill not select for sufficient cancer suppression to explain the paradox. Rather, cancer suppression should be most extreme when the probability of non-cancer death decreases with age (e.g. alligators), maturation is delayed, fecundity rates are low and fecundity increases with age. Thus, the value of cancer suppression is predicted to be lowest in the vole (short lifespan, high fecundity) and highest in the naked mole rat (long lived with late female sexual maturity). The life history of pre-industrial humans likely selected for quite low levels of cancer suppression. In modern humans that live much longer, this level results in unusually high lifetime cancer risks. The model predicts a lifetime risk of 49% compared with the current empirical value of 43%.
The Golden Retriever Lifetime Study: establishing an observational cohort study with translational relevance for human health
Authors: Guy Michael K. , Page Rodney L. , Jensen Wayne A. , Olson Patricia N. , Haworth J. David , Searfoss Erin E. , Brown Diane E.
Published: June 2015

The Golden Retriever Lifetime Study (GRLS) is the first prospective longitudinal study attempted in veterinary medicine to identify the major dietary, genetic and environmental risk factors for cancer and other important diseases in dogs. The GRLS is an observational study that will follow a cohort of 3000 purebred Golden Retrievers throughout their lives via annual online questionnaires from the dog owner and annual physical examinations and collection of biological samples by the primary care veterinarian. The field of comparative medicine investigating naturally occurring disorders in pets is specifically relevant to the many diseases that have a genetic basis for disease in both animals and humans, including cancer, blindness, metabolic and behavioural disorders and some neurodegenerative disorders. The opportunity for the GRLS to provide high-quality data for translational comparative medical initiatives in several disease categories is great. In particular, the opportunity to develop a lifetime dataset of lifestyle and activity, environmental exposure and diet history combined with simultaneous annual biological sample sets and detailed health outcomes will provide disease incidence data for this cohort of geographically dispersed dogs and associations with a wide variety of potential risk factors. The GRLS will provide a lifetime historical context, repeated biological sample sets and outcomes necessary to interrogate complex associations between genes and environmental influences and cancer.