Photonic chip-based low-noise microwave oscillator.

Numerous modern technologies are reliant on the low-phase noise and exquisite timing stability of microwave signals. Substantial progress has been made in the field of microwave photonics, whereby low-noise microwave signals are generated by the down-conversion of ultrastable optical references using a frequency comb1-3. Such systems, however, are constructed with bulk or fibre optics and are difficult to further reduce in size and power consumption. In this work we address this challenge by leveraging advances in integrated photonics to demonstrate low-noise microwave generation via two-point optical frequency division4,5. Narrow-linewidth self-injection-locked integrated lasers6,7 are stabilized to a miniature Fabry-Pérot cavity8, and the frequency gap between the lasers is divided with an efficient dark soliton frequency comb9. The stabilized output of the microcomb is photodetected to produce a microwave signal at 20 GHz with phase noise of -96 dBc Hz-1 at 100 Hz offset frequency that decreases to -135 dBc Hz-1 at 10 kHz offset-values that are unprecedented for an integrated photonic system. All photonic components can be heterogeneously integrated on a single chip, providing a significant advance for the application of photonics to high-precision navigation, communication and timing systems.

Upconversion time-stretch infrared spectroscopy.

High-speed measurement confronts the extreme speed limit when the signal becomes comparable to the noise level. In the context of broadband mid-infrared spectroscopy, state-of-the-art ultrafast Fourier-transform infrared spectrometers, in particular dual-comb spectrometers, have improved the measurement rate up to a few MSpectra s-1, which is limited by the signal-to-noise ratio. Time-stretch infrared spectroscopy, an emerging ultrafast frequency-swept mid-infrared spectroscopy technique, has shown a record-high rate of 80 MSpectra s-1 with an intrinsically higher signal-to-noise ratio than Fourier-transform spectroscopy by more than the square-root of the number of spectral elements. However, it can measure no more than ~30 spectral elements with a low resolution of several cm-1. Here, we significantly increase the measurable number of spectral elements to more than 1000 by incorporating a nonlinear upconversion process. The one-to-one mapping of a broadband spectrum from the mid-infrared to the near-infrared telecommunication region enables low-loss time-stretching with a single-mode optical fiber and low-noise signal detection with a high-bandwidth photoreceiver. We demonstrate high-resolution mid-infrared spectroscopy of gas-phase methane molecules with a high resolution of 0.017 cm-1. This unprecedentedly high-speed vibrational spectroscopy technique would satisfy various unmet needs in experimental molecular science, e.g., measuring ultrafast dynamics of irreversible phenomena, statistically analyzing a large amount of heterogeneous spectral data, or taking broadband hyperspectral images at a high frame rate.

Early high-dose intravenous immunoglobulin for refractory heparin-induced thrombocytopenia with stroke: Two case reports.

BACKGROUND: High-dose intravenous immunoglobulin (IVIg) can be effective for patients with refractory autoimmune heparin-induced thrombocytopenia (HIT). We report two patients with autoimmune HIT (aHIT) successfully treated with early high-dose IVIg. CASE DESCRIPTION: Case 1 was a 48-year-old male who had persisting HIT with recurrent ischemic stroke after mitral valve replacement. Case 2 was a 71-year-old male who had flush heparin HIT with cerebral venous thrombosis after total hip arthroplasty. High-dose IVIg was administered 6 and 4 days after starting argatroban due to non-improved thrombocytopenia and persistently high D-dimer values, respectively. Both patients achieved favorable functional recovery at discharge as well as improvements of thrombocytopenia and hypercoagulation. CONCLUSIONS: Early high-dose IVIg may be effective for patients with aHIT and hypercoagulability.

Simple approach to broadband mid-infrared pulse generation with a mode-locked Yb-doped fiber laser.

Broadband mid-infrared (MIR) molecular spectroscopy demands a bright and broadband light source in the molecular fingerprint region. To this end, intra-pulse difference frequency generation (IDFG) has shown excellent properties among various techniques. Although IDFG systems pumped with 1.5- or 2-µm ultrashort pulsed lasers have been extensively developed, few systems have been demonstrated with 1-µm lasers, which use bulky 100-W-class high-power Yb thin-disk lasers. In this work, we demonstrate a simple and robust approach of 1-µm-pumped broadband IDFG with a conventional mode-locked Yb-doped fiber laser. We first generate 3.3-W, 12.1-fs ultrashort pulses at 50 MHz by a simple combination of spectral broadening with a short single-mode fiber and pulse compression with chirped mirrors. Then, we use them for pumping a thin orientation-patterned gallium phosphide crystal, generating 1.2-mW broadband MIR pulses with the -20-dB bandwidth of 480 cm-1 in the fingerprint region (760-1240 cm-1, 8.1-13.1 µm). The 1-µm-based IDFG system allows for additional generations of ultrashort pulses in the ultraviolet and visible regions, enabling, for example, 50-MHz-level high-repetition-rate vibrational sum-frequency generation spectroscopy or pump-probe spectroscopy.

Nutrients exported from upland stream water enlarge perennial biomass crops.

Rawanbuki, a variety of Japanese butterbur (Petasites japonicus subsp. giganteus), grow naturally along the Rawan River, Hokkaido, northern Japan. Most plants reach 2-3 m in height and 10 cm in diameter in 2 months and are much larger than those grown along other rivers. We examined the hypothesis that nutrients exported from upland streams enhance the growth of the Rawanbuki. Nutrient concentrations, including nitrogen, phosphorus, and base cations, in the Rawan River were much higher than those in rivers of adjacent watersheds. High nutrient concentrations and moisture contents were found in soil along the Rawan River and a significant relationship was found between physicochemical soil conditions and aboveground biomass of butterburs. This indicates that extremely large Rawanbuki plants could be caused by these high nutrient concentrations and moisture contents in the soils. A manipulation experiment showed that fertilization simulated the growth environment along the Rawan River and enhanced the stem height and stem diameter of butterburs. This study concluded that the extremely large butterburs are caused by a large amount of nutrients exported from upland areas. These results are the first demonstration of the role of stream water nutrients in enlarging agricultural crops.

Piezo-electric transducer actuated mirror with a servo bandwidth beyond 500 kHz.

We demonstrate a novel system that uses a piezoelectric transducer (PZT)-actuated mirror for laser stabilization. A combination of a simple mechanical design and electronic circuits is used to realize an ultra-flat frequency response, which enables an effective feedback bandwidth of 500 kHz. The PZT also performed well when used in a mode-locked laser with a GHz repetition rate, to which it is difficult to apply an electro-optic modulator (EOM).

Coherent optical clock down-conversion for microwave frequencies with 10-18 instability.

Optical atomic clocks are poised to redefine the Système International (SI) second, thanks to stability and accuracy more than 100 times better than the current microwave atomic clock standard. However, the best optical clocks have not seen their performance transferred to the electronic domain, where radar, navigation, communications, and fundamental research rely on less stable microwave sources. By comparing two independent optical-to-electronic signal generators, we demonstrate a 10-gigahertz microwave signal with phase that exactly tracks that of the optical clock phase from which it is derived, yielding an absolute fractional frequency instability of 1 × 10-18 in the electronic domain. Such faithful reproduction of the optical clock phase expands the opportunities for optical clocks both technologically and scientifically for time dissemination, navigation, and long-baseline interferometric imaging.

Structure of the Current Sheet in the 11 July 2017 Electron Diffusion Region Event.

The structure of the current sheet along the Magnetospheric Multiscale (MMS) orbit is examined during the 11 July 2017 Electron Diffusion Region (EDR) event. The location of MMS relative to the X-line is deduced and used to obtain the spatial changes in the electron parameters. The electron velocity gradient values are used to estimate the reconnection electric field sustained by nongyrotropic pressure. It is shown that the observations are consistent with theoretical expectations for an inner EDR in 2-D reconnection. That is, the magnetic field gradient scale, where the electric field due to electron nongyrotropic pressure dominates, is comparable to the gyroscale of the thermal electrons at the edge of the inner EDR. Our approximation of the MMS observations using a steady state, quasi-2-D, tailward retreating X-line was valid only for about 1.4 s. This suggests that the inner EDR is localized; that is, electron outflow jet braking takes place within an ion inertia scale from the X-line. The existence of multiple events or current sheet processes outside the EDR may play an important role in the geometry of reconnection in the near-Earth magnetotail.

Multiscale Currents Observed by MMS in the Flow Braking Region.

We present characteristics of current layers in the off-equatorial near-Earth plasma sheet boundary observed with high time-resolution measurements from the Magnetospheric Multiscale mission during an intense substorm associated with multiple dipolarizations. The four Magnetospheric Multiscale spacecraft, separated by distances of about 50 km, were located in the southern hemisphere in the dusk portion of a substorm current wedge. They observed fast flow disturbances (up to about 500 km/s), most intense in the dawn-dusk direction. Field-aligned currents were observed initially within the expanding plasma sheet, where the flow and field disturbances showed the distinct pattern expected in the braking region of localized flows. Subsequently, intense thin field-aligned current layers were detected at the inner boundary of equatorward moving flux tubes together with Earthward streaming hot ions. Intense Hall current layers were found adjacent to the field-aligned currents. In particular, we found a Hall current structure in the vicinity of the Earthward streaming ion jet that consisted of mixed ion components, that is, hot unmagnetized ions, cold E × B drifting ions, and magnetized electrons. Our observations show that both the near-Earth plasma jet diversion and the thin Hall current layers formed around the reconnection jet boundary are the sites where diversion of the perpendicular currents take place that contribute to the observed field-aligned current pattern as predicted by simulations of reconnection jets. Hence, multiscale structure of flow braking is preserved in the field-aligned currents in the off-equatorial plasma sheet and is also translated to ionosphere to become a part of the substorm field-aligned current system.

High-Sensitivity and High-Resolution In Situ Hybridization of Coding and Long Non-coding RNAs in Vertebrate Ovaries and Testes.

BACKGROUND: Subcellular localization of coding and non-coding RNAs has emerged as major regulatory mechanisms of gene expression in various cell types and many organisms. However, techniques that enable detection of the subcellular distribution of these RNAs with high sensitivity and high resolution remain limited, particularly in vertebrate adult tissues and organs. In this study, we examined the expression and localization of mRNAs encoding Pou5f1/Oct4, Mos, Cyclin B1 and Deleted in Azoospermia-like (Dazl) in zebrafish and mouse ovaries by combining tyramide signal amplification (TSA)-based in situ hybridization with paraffin sections which can preserve cell morphology of tissues and organs at subcellular levels. In addition, the distribution of a long non-coding RNA (lncRNA), lncRNA-HSVIII, in mouse testes was examined by the same method. RESULTS: The mRNAs encoding Mos, Cyclin B1 and Dazl were found to assemble into distinct granules that were distributed in different subcellular regions of zebrafish and mouse oocytes, suggesting conserved and specific regulations of these mRNAs. The lncRNA-HSVIII was first detected in the nucleus of spermatocytes at prophase I of the meiotic cell cycle and was then found in the cytoplasm of round spermatids, revealing expression patterns of lncRNA during germ cell development. Collectively, the in situ hybridization method demonstrated in this study achieved the detection and comparison of precise distribution patterns of coding and non-coding RNAs at subcellular levels in single cells of adult tissues and organs. CONCLUSIONS: This high-sensitivity and high-resolution in situ hybridization is applicable to many vertebrate species and to various tissues and organs and will be useful for studies on the subcellular regulation of gene expression at the level of RNA localization.

[A case of Wernicke encephalopathy with hypoacusia and MR high intensity of the inferior colliculi that normalized after thiamine administration].

A 61-year-old man was admitted to our institution with progressive hypoacusia, double vision, and lightheadedness. Neurological examination on day 6 of his illness showed severe hypoacusia, mild confusion, ocular motility disorder, truncal ataxia and absence of a deep tendon reflex. MRI fluid-attenuated inversion recovery imaging revealed symmetrical high intensities in the tectum of the midbrain, involving the bilateral inferior colliculi and the bilateral medial thalami, which suggested Wernicke encephalopathy (WE). Thiamine was administered immediately after completion of the MRI, and the patients' hearing and other abnormal neurologic signs improved rapidly within a few days, except for the absence of the deep tendon reflex. Whole blood examination at admission revealed very low levels of vitamin B1. The patient was discharged on day 19, and MRI on day 39 showed the disappearance of the abnormal high intensities involving the bilateral inferior colliculi. The present case indicates that hypoacusia and abnormal MRI signal due to WE might be normalized by administration of thiamine a few days after the onset of symptoms.

Stable CW laser based on low thermal expansion ceramic cavity with 4.9 mHz/s frequency drift.

We describe a CW laser stabilized to a low thermal expansion ceramic cavity which has a lower frequency drift rate than cavities based on ultralow-expansion glass (ULE), which are widely used as optical references. Two identical optical cavities with spacers of different material, ceramic and ULE, were assembled and the optical frequencies locked to each of these cavities were compared. The optical frequency drifts of both CW lasers were measured to within a precision of 10-11 in one second over the course of one year. The ceramic cavity had a long-term frequency drift rate of 4.9 mHz/s and the ULE cavity had one of 23 mHz/s.

Embryonic expression of festina lente (fel), a novel maternal gene, in the oligochaete annelid Tubifex tubifex.

We have cloned and characterized the expression of a novel maternal gene festina lente (designated Ttu-fel) from the clitellate annelid Tubifex tubifex. Northern blot analyses have shown that Ttu-fel mRNA is approximately 8 kbp in length and that its expression is restricted to oocytes undergoing maturation division and early embryos up to 22-cell stage. Maternal transcripts of Ttu-fel are first detected in oocytes in the ovary of young adults (ca. 40 days after hatching); its expression continues in growing oocytes in the ovisac. Ttu-fel mRNA is distributed broadly throughout the egg undergoing maturation divisions. During the process of ooplasmic segregation that results in the pole plasm formation, Ttu-fel mRNA becomes concentrated to the animal and vegetal poles. The RNA in the animal hemisphere is distributed in a gradient with highest concentration in the cortical region. During the first two cleavages, Ttu-fel mRNA is segregated to CD cell then to D cell; it is subsequently inherited by the three D quadtrant micromeres, 1d, 2d and 3d. Around the time of transition to 22-cell stage, Ttu-fel mRNA becomes undetectable throughout the embryo.

Electron-Scale Quadrants of the Hall Magnetic Field Observed by the Magnetospheric Multiscale spacecraft during Asymmetric Reconnection.

An in situ measurement at the magnetopause shows that the quadrupole pattern of the Hall magnetic field, which is commonly observed in a symmetric reconnection, is still evident in an asymmetric component reconnection, but the two quadrants adjacent to the magnetosphere are strongly compressed into the electron scale and the widths of the remaining two quadrants are still ion scale. The bipolar Hall electric field pattern generally created in a symmetric reconnection is replaced by a unipolar electric field within the electron-scale quadrants. Furthermore, it is concluded that the spacecraft directly passed through the inner electron diffusion region based on the violation of the electron frozen-in condition, the energy dissipation, and the slippage between the electron flow and the magnetic field. Within the inner electron diffusion region, magnetic energy was released and accumulated simultaneously, and it was accumulated in the perpendicular directions while dissipated in the parallel direction. The localized thinning of the current sheet accounts for the energy accumulation in a reconnection.

Magneto-optic modulator for high bandwidth cavity length stabilization.

We propose a novel magneto-optical approach for the repetition frequency stabilization of optical frequency combs. We developed a Yb:fiber mode-locked laser with a fiber-based magneto-optic modulator used to stabilize one of the longitudinal modes to an optical reference with sub-hundred mrad residual phase noise. This modulator does not induce mechanical resonances and as such has the potential to achieve much broader feedback bandwidths than conventional modulators used for cavity length stabilization.

Near-Earth plasma sheet boundary dynamics during substorm dipolarization.

We report on the large-scale evolution of dipolarization in the near-Earth plasma sheet during an intense (AL ~ -1000 nT) substorm on August 10, 2016, when multiple spacecraft at radial distances between 4 and 15 R E were present in the night-side magnetosphere. This global dipolarization consisted of multiple short-timescale (a couple of minutes) B z disturbances detected by spacecraft distributed over 9 MLT, consistent with the large-scale substorm current wedge observed by ground-based magnetometers. The four spacecraft of the Magnetospheric Multiscale were located in the southern hemisphere plasma sheet and observed fast flow disturbances associated with this dipolarization. The high-time-resolution measurements from MMS enable us to detect the rapid motion of the field structures and flow disturbances separately. A distinct pattern of the flow and field disturbance near the plasma boundaries was found. We suggest that a vortex motion created around the localized flows resulted in another field-aligned current system at the off-equatorial side of the BBF-associated R1/R2 systems, as was predicted by the MHD simulation of a localized reconnection jet. The observations by GOES and Geotail, which were located in the opposite hemisphere and local time, support this view. We demonstrate that the processes of both Earthward flow braking and of accumulated magnetic flux evolving tailward also control the dynamics in the boundary region of the near-Earth plasma sheet.Graphical AbstractMultispacecraft observations of dipolarization (left panel). Magnetic field component normal to the current sheet (BZ) observed in the night side magnetosphere are plotted from post-midnight to premidnight region: a GOES 13, b Van Allen Probe-A, c GOES 14, d GOES 15, e MMS3, g Geotail, h Cluster 1, together with f a combined product of energy spectra of electrons from MMS1 and MMS3 and i auroral electrojet indices. Spacecraft location in the GSM X-Y plane (upper right panel). Colorcoded By disturbances around the reconnection jets from the MHD simulation of the reconnection by Birn and Hesse (1996) (lower right panel). MMS and GOES 14-15 observed disturbances similar to those at the location indicated by arrows.

Confined Singlet Oxygen in Mesoporous Silica Nanoparticles: Selective Photochemical Oxidation of Small Molecules in Living Cells.

Chemical conversion of specific bioactive molecules by external stimuli in living cells is a powerful noninvasive tool for clarification of biomolecular interactions and to control cellular functions. However, in chaotic biological environments, it has been difficult to induce arbitrary photochemical reactions on specific molecules because of their poor molecular selectivity. Here we report a selective and nontoxic photochemical reaction system utilizing photoactivated mesoporous silica nanoparticles to control biological functions. Methylene blue modification within nanoparticle pores for photosensitization produced singlet oxygen confined to the pore that could mediate selective oxidation of small molecules without any damage to living cells. This intracellular photochemical system produced bioactive molecules in situ and remotely controlled the cell cycle phase. We also confirmed that this photoreaction could be applied to control cell cycle phase in tumor tissue transplanted in mice. The cell cycle phase in the cells in mice, to which our system was administered, was arrested at the G2/M phase upon photoirradiation. We demonstrate a simple and promising method for the exogenous conversion of an intracellular biomolecule to another functional compound.

Offset-free broadband Yb:fiber optical frequency comb for optical clocks.

We demonstrate a passively offset-frequency stabilized optical frequency comb centered at 1060 nm. The offset-free comb was achieved through difference frequency generation (DFG) between two portions of a supercontinuum based on a Yb:fiber laser. As the DFG comb had only one degree of freedom, repetition frequency, full stabilization was achieved via locking one of the modes to an ultra-stable continuous wave (CW) laser. The DFG comb provided sufficient average power to enable further amplification, using Yb-doped fiber amplifier, and spectral broadening. The spectrum spanned from 690 nm to 1300 nm and the average power was of several hundred mW, which could be ideal for the comparison of optical clocks, such as optical lattice clocks operated with Sr (698 nm) and Hg (1063 nm) reference atoms.

Controlling Localization and Excretion of Nanoparticles by Click Modification of the Surface Chemical Structures inside Living Cells.

Invited for this month's cover is the group of Drs. Takeo Ito and Kazuhito Tanabe from Kyoto University, Japan. The cover image shows accumulation of silica nanoparticles on the plasma membrane by click modification of the surface in living cells. Read the full text of the article at 10.1002/cplu.201402436.

Controlling Localization and Excretion of Nanoparticles by Click Modification of the Surface Chemical Structures inside Living Cells.

Surface modification of silica nanoparticles (SiNPs) inside living cells was conducted by using the copper-free bioorthogonal click reaction to evaluate the effects of surface chemical structures on dynamic behavior and excretion of SiNPs. The results demonstrated the spatial translocation of intracellular SiNPs to the plasma membrane upon surface modification in situ with phospholipids. Moreover, the extent and kinetics of excretion of the SiNPs from inside the cell were enhanced by modification.