Bulk Photovoltaic Effect Along the Nonpolar Axis in Organic-Inorganic Hybrid Perovskites.

The origin of the bulk photovoltaic effect (BPVE) was considered as a built-in electric field formed by the macroscopic polarization of materials. Alternatively, the "shift current mechanism" has been gradually accepted as the more appropriate description of the BPVE. This mechanism implies that the photocurrent generated by the BPVE is a topological current featuring an ultrafast response and dissipation-less nature, which is very attractive for photodetector applications. Meanwhile, the origin of the BPVE in organic-inorganic hybrid perovskites (OIHPs) has not been discussed and is still widely accepted as the classical mechanism without any experimental evidence. Herein, we observed the BPVE along the nonpolar axis in OIHPs, which is inconsistent with the classical explanation. Furthermore, based on the nonlinear optical tensor correlation, we substantiated that the BPVE in OIHPs is originated in the shift current mechanism.

Efficient Endocytosis of the Human Lactoferrin N-Lobe Enhances Its Antiproliferative Activity against Human Cancer Cells.

Human lactoferrin (hLF) is a glycosylated globular iron-binding protein with high functional versatility that elicits anticancer, neuroprotective, and anti-inflammatory effects. Some of the diverse functions of hLF are induced after its internalization into various cells via cell surface endocytosis receptors, such as proteoglycans, which contain glycosaminoglycan (GAG) chains. We have previously demonstrated that an hLF derivative comprising the N-terminal half of hLF (referred to as the N-lobe) is internalized by intestinal enterocyte Caco-2 cells. However, the relationship between the intracellular uptake of the N-lobe and its pharmacological activity remains poorly understood. Here, we report that the N-lobe is efficiently internalized by lung cancer cells via endocytic pathways, suppressing their proliferation. Moreover, the N-lobe showed higher intracellular uptake than hLF. We found that the N-lobe was internalized into the human lung cancer cell lines PC-14 and PC-3 via clathrin- and/or caveolae-mediated endocytosis. Intracellular uptake of the N-lobe was inhibited when an equimolar concentration of chondroitin sulfate (CS)-E, a GAG subtype involved in malignant transformation and tumor metastasis, was added. The inhibitory effect of the N-lobe on PC-14 cell proliferation decreased with the addition of CS-E in a dose-dependent manner, suggesting that the CS-recognizing sequence on the N-lobe is necessary for its internalization or that the CS proteoglycan on cancer cells acts as an endocytosis receptor. These results suggest that the efficient endocytic uptake of the N-lobe is important for its antiproliferation effects on lung cancer cell lines. Thus, the N-lobe presents a promising drug candidate for cancer treatment.

Photovoltaic effect by soft phonon excitation.

SignificanceThe quantum-mechanical geometric phase of electrons provides various phenomena such as the dissipationless photocurrent generation through the shift current mechanism. So far, the photocurrent generations are limited to above or near the band-gap photon energy, which contradicts the increasing demand of the low-energy photonic functionality. We demonstrate the photocurrent through the optical phonon excitations in ferroelectric BaTiO3 by using the terahertz light with photon energy far below the band gap. This photocurrent without electron-hole pair generation is never explained by the semiclassical treatment of electrons and only arises from the quantum-mechanical geometric phase. The observed photon-to-current conversion efficiency is as large as that for electronic excitation, which can be well accounted for by newly developed theoretical formulation of shift current.

Real-space observations of 60-nm skyrmion dynamics in an insulating magnet under low heat flow.

Thermal-current induced electron and spin dynamics in solids -dubbed "caloritronics"- have generated widespread interest in both fundamental physics and spintronics applications. Here, we examine the dynamics of nanometric topological spin textures, skyrmions driven by a temperature gradient ∇T or heat flow, that are evaluated through in-situ real-space observations in an insulating helimagnet Cu2OSeO3. We observe increases of the skyrmion velocity and the Hall angle with increasing ∇T above a critical value of ~ 13 mK/mm, which is two orders of magnitude lower than the ∇T required to drive ferromagnetic domain walls. A comparable magnitude of ∇T is also observed to move the domain walls between a skyrmion domain and the non-topological conical-spin domain from cold to hot regions. Our results demonstrate the efficient manipulation of skyrmions by temperature gradients, a promising step towards energy-efficient "green" spintronics.

Harnessing the chondroitin sulfate-binding characteristics of human lactoferrin to neutralize neurite outgrowth inhibition.

Human lactoferrin (hLF) is a glycosaminoglycan (GAG)-binding protein involved in various biological functions. It consists of two globular functional domains, referred to as the N- and C-lobes. Both heparin (HP) and heparan sulfate (HS) bind to the N-lobe domain of hLF. Although some biological functions of hLF such as neuroprotective effects and cancer growth inhibition are regulated by its binding to HS, the binding characteristics of hLF with other GAG subtypes, and their effects on biological activities are still poorly understood. Here, we report that hLF binds to chondroitin sulfate (CS)-E, a GAG subtype involved in various neurodegenerative diseases. The α-helical content of hLF, which is an indicator of changes in the secondary structure of hLF, increased in the presence of CS-C, CS-D, or CS-E, but not in the presence of HP, HS, CS-A, or CS-B. This structural change was also observed in the N-lobe, the N-terminal half region of the hLF. Additionally, the thermal stability of the N-lobe showed a dose-dependent improvement in the presence of CS-E, but not in the presence of HP. This indicates that the binding mode of hLF/N-lobe to CS-E may differ from that of HP. hLF was also found to neutralize CS-E-induced inhibition of neurite outgrowth and neuronal growth cone collapse, which are neurodegenerative responses to spinal cord injury, in cultured dorsal root ganglion neurons. Thus, hLF is a promising drug candidate for the treatment of CS-E-induced neurodegenerative diseases such as spinal cord injury.

Albumin fusion at the N-terminus or C-terminus of human lactoferrin leads to improved pharmacokinetics and anti-proliferative effects on cancer cell lines.

Human lactoferrin (hLF), a soluble factor of the innate immune system, exhibits various biological functions and therefore has potential as a therapeutic protein. However, the clinical applications of hLF are limited by its low stability in blood. We therefore attempted to resolve this by producing recombinant hLF fused to human serum albumin (HSA). Two HSA-fused hLFs with different fusion orientations (hLF-HSA and HSA-hLF) were produced in Chinese hamster ovary (CHO) DG44 cells. hLF-HSA revealed higher thermal stability, resistance to peptic degradation, and stability during the process of cellular uptake and release in an intestinal enterocyte model (Caco-2 cells) than HSA-hLF. The lower stability of HSA-hLF is presumably due to the steric hindrance imposed by HSA fusion to the N-terminus of hLF. Both HSA fusion proteins, especially HSA-hLF, displayed improved pharmacokinetic properties despite the lower protein stability of HSA-hLF. hLF-HSA and HSA-hLF exhibited approximately 3.3- and 20.7-fold longer half-lives (64.0 and 403.6 min), respectively, than holo-rhLF (19.5 min). Both HSA fusion proteins were found to exert enhanced growth inhibition effects on cancer cells in vitro, but not normal cells. Their enhanced growth inhibitory activities were considered to be due to the synergetic effects of hLF and HSA because hLF alone or HSA alone failed to exert such an effect. Altogether, Fusion of HSA to hLF yielded superior pharmacokinetics and anti-proliferative activities against cancer cells. HSA-fused hLF is a novel candidate for further application of hLF as biopharmaceuticals for intravenous administration.

Defect tolerant zero-bias topological photocurrent in a ferroelectric semiconductor.

Lattice defect is a major cause of energy dissipation in conventional electric current due to the drift and diffusion motions of electrons. Different nature of current emerges when noncentrosymmetric materials are excited by light. This current, called the shift current, originates from the change in the Berry connection of electrons' wave functions during the interband optical transition. Here, we demonstrate the defect tolerance of shift current using single crystals of ferroelectric semiconductor antimony sulfoiodide (SbSI). Although the dark conductance spreads over several orders of magnitude in each crystal due to the difference in the density of defect levels, the observed shift current converges to an identical value. We also reveal that the shift current is scarcely disturbed by the surface defects while they drastically suppress the conventional photocurrent. The defect tolerance is a manifestation of the topological nature of shift current, which will be a crucial advantage in optoelectronic applications.

Noncentrosymmetric Columnar Liquid Crystals with the Bulk Photovoltaic Effect for Organic Photodetectors.

The bulk photovoltaic effect (BPVE) has drawn intensive attention due to its unique features that cannot be accessed with the conventional photovoltaic effect. However, the BPVE is observed in noncentrosymmetric materials and has been studied mainly for inorganic materials. Here, we report a simple subphthalocyanine (SubPc) derivative that assembles into a noncentrosymmetric columnar liquid crystal with the help of a DC E-field. These columnar assemblies exhibit the BPVE over a wide range of wavelengths up to 650 nm. Furthermore, just by sandwiching this columnar assembly between two ITO electrodes, the resultant device reaches a light-on/off ratio, Ilight/Idark, as high as 6.6 × 103, indicating that the polar columnar assemblies with SubPcs are promising for photodetectors.

Cellular Uptake and Release of Intact Lactoferrin and Its Derivatives in an Intestinal Enterocyte Model of Caco-2 Cells.

An Intact form of lactoferrin (LF) is known to be absorbed from the small intestine and transported into the blood circulation. We reevaluated the cellular uptake and release of LF using an enterocyte model of human small intestinal cells derived from the Caco-2 cell line. In contrast to a previous report, we observed that intact bovine LF was taken up into seven and 21 d-cultured Caco-2 cells and successfully released back into the culture medium, even though the human intestinal LF receptor, intelectin-1, was not immunochemically detectable. Similar observations were made for human LF and its derivatives (the N-terminal half of LF designated N-lobe and Fc fusions). These observations regarding the uptake and release of intact LF in Caco-2 cells were consistent with in vivo observations. Therefore, we propose that the uptake and release of intact LF by Caco-2 cells should be assessed as a potential in vitro model of in vivo LF absorption in human intestines.

Reproductive interference by alien hornet Vespa velutina threatens the native populations of Vespa simillima in Japan.

The yellow-legged hornet Vespa velutina has become one of the major alien species in European and East Asian countries. As in its homeland, the invading V. velutina is reported as the major predator of honeybees and is becoming a threat to beekeeping in Europe. However, it remains unknown how V. velutina might affect native hornets when it invades Asia, where a large number of Vespa species are distributed. Thus, by analyzing the mitochondrial cytochrome c oxidase subunit I gene, we investigated whether interspecific mating occurs between V. velutina and Japanese native Vespa spp. Our results showed that the alien V. velutina causes reproductive interference in Japanese native hornet Vespa simillima. Forty-three percent of native V. simillima queens had the sperm of V. velutina males, and among the all V. simillima queens analyzed, 28% only had V. velutina sperm. We did not find evidence of V. velutina queens having the sperm of V. simillima males. These findings suggest that reproductive interference by V. velutina males poses a threat to the native V. simillima populations. A decline of V. simillima may also negatively affect other insects that interact with V. simillima.

Visualization of Electronic Multiple Ordering and Its Dynamics in High Magnetic Field: Evidence of Electronic Multiple Ordering Crystals.

Constituent atoms and electrons determine matter properties together, and they can form long-range ordering respectively. Distinguishing and isolating the electronic ordering out from the lattice crystal is a crucial issue in contemporary materials science. However, the intrinsic structure of a long-range electronic ordering is difficult to observe because it can be easily affected by many external factors. Here, we present the observation of electronic multiple ordering (EMO) and its dynamics at the micrometer scale in a manganite thin film. The strong internal couplings among multiple electronic degrees of freedom in the EMO make its morphology robust against external factors and visible via well-defined boundaries along specific axes and cleavage planes, which behave like a multiple-ordered electronic crystal. A strong magnetic field up to 17.6 T is needed to completely melt such EMO at 7 K, and the corresponding formation, motion, and annihilation dynamics are imaged utilizing a home-built high-field magnetic force microscope. The EMO is parasitic within the lattice crystal house, but its dynamics follows its own rules of electronic correlation, therefore becoming distinguishable and isolatable as the electronic ordering. Our work provides a microscopic foundation for the understanding and control of the electronic ordering and the designs of the corresponding devices.

Current-Voltage Characteristic and Shot Noise of Shift Current Photovoltaics.

We theoretically study the current-voltage relation, the I-V characteristic, of the photovoltaics due to the shift current, i.e., the photocurrent generated without the external dc electric field in noncentrosymmetric crystals through the Berry connection of the Bloch wave functions. We find that the I-V characteristic and shot noise are controlled by the difference of group velocities between conduction and valence bands, i.e., v_{11}-v_{22}, and the relaxation time τ. Since the shift current itself is independent of these quantities, there are a wide variety of possibilities to design it to maximize the energy conversion rate and also to suppress the noise. We propose that the Landau levels in noncentrosymmetric two-dimensional systems are a promising candidate for energy conversion.

Current-Induced Nucleation and Annihilation of Magnetic Skyrmions at Room Temperature in a Chiral Magnet.

A magnetic skyrmion is a nanometer-scale magnetic vortex carrying an integer topological charge. Skyrmions show a promise for potential application in low-power-consumption and high-density memory devices. To promote their use in applications, it is attempted to control the existence of skyrmions using low electric currents at room temperature (RT). This study presents real-space observations for the current-induced formation and annihilation of a skyrmion lattice (SkL) as well as isolated skyrmions in a microdevice composed of a thin chiral magnet Co8 Zn9 Mn3 with a Curie temperature, TC ≈ 325 K, above RT. It is found that the critical current for the manipulation of Bloch-type skyrmions is on the order of 108 A m-2 , approximately three orders of magnitude lower than that needed for the creation and drive of ferromagnetic (FM) domain walls in thin FM films. The in situ real-space imaging also demonstrates the dynamical topological transition from a helical or conical structure to a SkL induced by the flow of DC current, thus paving the way for the electrical control of magnetic skyrmions.

Publisher's Note: Direct Imaging of Dynamic Glassy Behavior in a Strained Manganite Film [Phys. Rev. Lett. 115, 265701 (2015)].

This corrects the article DOI: 10.1103/PhysRevLett.115.265701.

The NMatrix, a new method of presenting statistics, displays the characteristics of medicines with similar effects used in the treatment of lumbar spinal stenosis concisely and clearly, facilitating the selection of appropriate medications.

BACKGROUND: It is often difficult to compare the characteristics of a medicine with those of others based on common standards, whereas the application of rational standards would be expected to facilitate the comparison of medicines with similar effects. The present study was conducted to clarify the characteristics of individual medicines and to examine whether rational standards allow the most appropriate medicines to be chosen. METHODS: Participants diagnosed with lumbar spinal stenosis (LSS) were assessed for QOL and ADL based on the Roland-Morris Disability Questionnaire, JOA score, VAS, and the presence of intermittent claudication (IC). Four medicines--beraprost sodium, ethyl icosapentate (EPA), sarpogrelate hydrochloride, and limaprost alfadex (PGE1)--were prescribed in a random manner. These four medicines were assessed independently in four studies using the same study design and size in each case. Using the NMatrix, the characteristics of the four medicines and the results of mutual comparisons could be displayed concisely and clearly in one matrix based on significance levels. This work involved analyzing pooled data from the four studies. RESULTS: All four medicines improved IC--one of the characteristic symptoms of LSS--by 12 weeks after administration. PGE1 required more time than the other medicines to affect IC. EPA appeared to almost significantly ameliorate some items at every point, though the evidence was insufficient. CONCLUSIONS: The NMatrix concisely and clearly displays the characteristics of "medicines with similar effects" for the treatment of lumbar spinal stenosis, and can help physicians to choose the optimal medicine based on rational criteria for individual patients, according to their symptoms and progress.

Direct Imaging of Dynamic Glassy Behavior in a Strained Manganite Film.

Complex many-body interaction in perovskite manganites gives rise to a strong competition between ferromagnetic metallic and charge-ordered phases with nanoscale electronic inhomogeneity and glassy behaviors. Investigating this glassy state requires high-resolution imaging techniques with sufficient sensitivity and stability. Here, we present the results of a near-field microwave microscope imaging on the strain-driven glassy state in a manganite film. The high contrast between the two electrically distinct phases allows direct visualization of the phase separation. The low-temperature microscopic configurations differ upon cooling with different thermal histories. At sufficiently high temperatures, we observe switching between the two phases in either direction. The dynamic switching, however, stops below the glass transition temperature. Compared with the magnetization data, the phase separation was microscopically frozen, while spin relaxation was found in a short period of time.

Conifer-Derived Monoterpenes and Forest Walking.

Conifer and broadleaf trees emit volatile organic compounds in the summer. The major components of these emissions are volatile monoterpenes. Using solid phase microextraction fiber as the adsorbant, monoterpenes were successfully detected and identified in forest air samples. Gas chromatography/mass chromatogram of monoterpenes in the atmosphere of a conifer forest and that of serum from subjects who were walking in a forest were found to be similar each other. The amounts of α-pinene in the subjects became several folds higher after forest walking. The results indicate that monoterpenes in the atmosphere of conifer forests are transferred to and accumulate in subjects by inhalation while they are exposed to this type of environment.

Gate control of percolative conduction in strongly correlated manganite films.

Gate control of percolative conduction in a phase-separated manganite system is demonstrated in a field-effect transistor geometry, resulting in ambipolar switching from a metallic state to an insulating state.

Involvement of heparan sulfate 6-O-sulfation in the regulation of energy metabolism and the alteration of thyroid hormone levels in male mice.

Here, we report that male heparan sulfate 6-O-sulfotransferase-2 (Hs6st2) knockout mice showed increased body weight in an age-dependent manner even when fed with a normal diet and showed a phenotype of impaired glucose metabolism and insulin resistance. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that the expression of mitochondrial uncoupling proteins Ucp1 and Ucp3 was reduced in the interscapular brown adipose tissue (BAT) of male Hs6st2 knockout mice, suggesting reduced energy metabolism. The serum level of thyroid-stimulating hormone was significantly higher and that of thyroxine was lower in the knockout mice. When cultures of brown adipocytes from wild-type and Hs6st2 knockout mice isolated and differentiated in vitro were treated with FGF19 (fibroblast growth factor 19) or FGF21 in the presence or the absence of heparitinase I, phosphorylation of p42/p44 mitogen-activated protein (MAP) kinase was reduced. Heparan sulfate (HS) 6-O-sulfation was reduced not only in BAT but also in the thyroid tissue of the knockout mice. Thus, 6-O-sulfation in HS seems to play an important role in mediating energy metabolism by controlling thyroid hormone levels and signals from the FGF19 subfamily proteins, and the alteration of the HS composition may result in metabolic syndrome phenotypes such as altered glucose and insulin tolerance.

Sulfated glycosaminoglycan-assisted receptor specificity of human fibroblast growth factor (FGF) 19 signaling in a mouse system is different from that in a human system.

The endocrine action of human (h) intestine-derived fibroblast growth factor 19 (hFGF19) toward liver cells necessitates a highly specific recognition system. We previously reported that at physiological concentrations (~30 pM), hFGF19 requires sulfated glycosaminoglycans (sGAGs) for its signaling via human FGF receptor 4 (hFGFR4) in the presence of a co-receptor, human ßKlotho (hKLB), thus establishing specific targeting. Here we report that the specificity of hFGF19 signaling is greatly altered in a mouse model system. In in vitro cellular systems, at concentrations achievable in transgenic animals and in pharmacologic animal experiments (1-100 nM), hFGF19 activates mouse (m)FGFR1c, mFGFR2c, and mFGFR3c but not mFGFR4 in the presence of mKLB and nonheparin authentic sGAGs. Furthermore, in the presence of hepatic sGAGs or heparin, nanomolar hFGF19 activates mFGFR4, even in the absence of co-expressed mKLB. Taken together, these results indicate that the sGAG-assisted receptor specificity of hFGF19 signaling achieved in experimental mouse systems differs greatly from that in physiological human systems. This suggests the function and mechanism of hFGF19 signaling identified using mouse systems should be reevaluated.