Plasmonic topological quasiparticle on the nanometre and femtosecond scales.

At the interface of classical and quantum physics, the Maxwell and Schrödinger equations describe how optical fields drive and control electronic phenomena to enable lightwave electronics at terahertz or petahertz frequencies and on ultrasmall scales1-5. The electric field of light striking a metal interacts with electrons and generates light-matter quasiparticles, such as excitons6 or plasmons7, on an attosecond timescale. Here we create and image a quasiparticle of topological plasmonic spin texture in a structured silver film. The spin angular momentum components of linearly polarized light interacting with an Archimedean coupling structure with a designed geometric phase generate plasmonic waves with different orbital angular momenta. These plasmonic fields undergo spin-orbit interaction and their superposition generates an array of plasmonic vortices. Three of these vortices can form spin textures that carry non-trivial topological charge8 resembling magnetic meron quasiparticles9. These spin textures are localized within a half-wavelength of light, and exist on the timescale of the plasmonic field. We use ultrafast nonlinear coherent photoelectron microscopy to generate attosecond videos of the spatial evolution of the vortex fields; electromagnetic simulations and analytic theory confirm the presence of plasmonic meron quasiparticles. The quasiparticles form a chiral field, which breaks the time-reversal symmetry on a nanometre spatial scale and a 20-femtosecond timescale (the 'nano-femto scale'). This transient creation of non-trivial spin angular momentum topology pertains to cosmological structure creation and topological phase transitions in quantum matter10-12, and may transduce quantum information on the nano-femto scale13,14.

Exciting space-time surface plasmon polaritons by irradiating a nanoslit structure.

Space-time (ST) wave packets are propagation-invariant pulsed optical beams that travel freely in dielectrics at a tunable group velocity without diffraction or dispersion. Because ST wave packets maintain these characteristics even when only one transverse dimension is considered, they can realize surface-bound waves (e.g., surface plasmon polaritons at a metal-dielectric interface, which we call ST-SPPs) that have the same unique characteristics as their freely propagating counterparts. However, because the spatiotemporal spectral structure of ST-SPPs is key to their propagation invariance on the metal surface, their excitation methodology must be considered carefully. Using finite-difference time-domain simulations, we show that an appropriately synthesized ST wave packet in free space can be coupled to an ST-SPP via a single nanoscale slit inscribed in the metal surface. Our calculations confirm that this excitation methodology yields surface-bound ST-SPPs that are localized in all dimensions (and can thus be considered as plasmonic "bullets"), which travel rigidly at the metal-dielectric interface without diffraction or dispersion at a tunable group velocity.

The regulatory pathway from genes directly activated by maternal factors to muscle structural genes in ascidian embryos.

Striated muscle cells in the tail of ascidian tadpole larvae differentiate cell-autonomously. Although several key regulatory factors have been identified, the genetic regulatory pathway is not fully understood; comprehensive understanding of the regulatory pathway is essential for accurate modeling in order to deduce principles for gene regulatory network dynamics, and for comparative analysis on how ascidians have evolved the cell-autonomous gene regulatory mechanism. Here, we reveal regulatory interactions among three key regulatory factors, Zic-r.b, Tbx6-r.b and Mrf, and elucidate the mechanism by which these factors activate muscle structural genes. We reveal a cross-regulatory circuit among these regulatory factors, which maintains the expression of Tbx6-r.b and Mrf during gastrulation. Although these two factors combinatorially activate muscle structural genes in late-stage embryos, muscle structural genes are activated mainly by Tbx6-r.b before gastrulation. Time points when expression of muscle structural genes become first detectable are strongly correlated with the degree of Tbx6-r.b occupancy. Thus, the genetic pathway, starting with Tbx6-r.b and Zic-r.b, which are activated by maternal factors, and ending with expression of muscle structural genes, has been revealed.

Resonance-order-dependent plasmon-induced transparency in orthogonally arranged nanocavities.

We investigate plasmon-induced transparency (PIT) in a resonator structure consisting of two orthogonally arranged metal-insulator-metal nanocavities. Finite-difference time- domain simulations reveal that when both cavities in this structure resonate at the same frequency, the PIT effect can be used to induce spectral modulation. This spectral modulation depends on the resonance order of the cavity coupled directly to the external field, as it occurs when first-order resonance is exhibited but not with second-order resonance. We confirmed that this behavior is caused by the discrepancies between odd-order and even-order resonances using classical mechanical models analogous to nanocavities. By tuning the resonance frequency and resonance order of the cavities, one can modulate the spectrum of the resonator structure in an order-selective manner. The resonant order-dependent PIT provides insight into the development of metamaterials that function only at specific resonant orders for incident waves of various bands.

Highly Dispersed Ni Nanoclusters Spontaneously Formed on Hydrogen Boride Sheets.

Hydrogen boride (HB) sheets are two-dimensional materials comprising a negatively charged hexagonal boron network and positively charged hydrogen atoms with a stoichiometric ratio of 1:1. Herein, we report the spontaneous formation of highly dispersed Ni nanoclusters on HB sheets. The spontaneous reduction reaction of Ni ions by the HB sheets was monitored by in-situ measurements with an ultraviolet-visible spectrometer. Acetonitrile solutions of Ni complexes and acetonitrile dispersions of the HB sheets were mixed in several molar ratios (the HB:Ni molar ratio was varied from 100:0.5 to 100:20), and the changes in the absorbance were measured over time. In all cases, the results suggest that Ni metal clusters grow on the HB sheets, considering the increase in absorbance with time. The absorbance peak position shifts to the higher wavelength as the Ni ion concentration increases. Transmission electron microscopy images of the post-reaction products indicate the formation of Ni nanoclusters, with sizes of a few nanometers, on the HB sheets, regardless of the preparation conditions. These highly dispersed Ni nanoclusters supported on HB sheets will be used for catalytic and plasmonic applications and as hydrogen storage materials.

Expression of Hey2 transcription factor in the early embryonic ventricles is controlled through a distal enhancer by Tbx20 and Gata transcription factors.

Development of multi-chambered heart is associated with spatio-temporal regulation of gene expression. A basic helix-loop-helix transcription factor Hey2 is specifically expressed in the embryonic mouse ventricles and is indispensable for ventricular myocyte differentiation, compartment identity and morphogenesis of the heart. However, how Hey2 transcription is precisely regulated in the heart remains unclear. In this study, we identified a distal Hey2 enhancer conserved in the mouse and human to possess specific transcriptional activity in ventricular free wall myocytes at the looping stage of cardiac development. Deletion of the enhancer significantly decreased endogenous Hey2 expression in the ventricular myocardium but not in other tissues of mouse embryos. Mutation/deletion of the conserved binding sites for T-box and Gata proteins, but not NK-2 proteins, abolished the enhancer activity, and Tbx20 null mice completely lost the enhancer activity in the embryonic ventricles. Luciferase reporter analysis suggested that the ventricular enhancer activity was controlled by Tbx20 through its DNA binding and cooperative function with cardiac Gata proteins. These results delineate a regulatory mechanism of ventricular Hey2 expression and help fully understand molecular cascades in myocardial cell differentiation and cardiac morphogenesis during embryonic development.

Importance of endothelial Hey1 expression for thoracic great vessel development and its distal enhancer for Notch-dependent endothelial transcription.

Thoracic great vessels such as the aorta and subclavian arteries are formed through dynamic remodeling of embryonic pharyngeal arch arteries (PAAs). Previous work has shown that loss of a basic helix-loop-helix transcription factor Hey1 in mice causes abnormal fourth PAA development and lethal great vessel anomalies resembling congenital malformations in humans. However, how Hey1 mediates vascular formation remains unclear. In this study, we revealed that Hey1 in vascular endothelial cells, but not in smooth muscle cells, played essential roles for PAA development and great vessel morphogenesis in mouse embryos. Tek-Cre-mediated Hey1 deletion in endothelial cells affected endothelial tube formation and smooth muscle differentiation in embryonic fourth PAAs and resulted in interruption of the aortic arch and other great vessel malformations. Cell specificity and signal responsiveness of Hey1 expression were controlled through multiple cis-regulatory regions. We found two distal genomic regions that had enhancer activity in endothelial cells and in the pharyngeal epithelium and somites, respectively. The novel endothelial enhancer was conserved across species and was specific to large-caliber arteries. Its transcriptional activity was regulated by Notch signaling in vitro and in vivo, but not by ALK1 signaling and other transcription factors implicated in endothelial cell specificity. The distal endothelial enhancer was not essential for basal Hey1 expression in mouse embryos but may likely serve for Notch-dependent transcriptional control in endothelial cells together with the proximal regulatory region. These findings help in understanding the significance and regulation of endothelial Hey1 as a mediator of multiple signaling pathways in embryonic vascular formation.

Differential gene expression along the animal-vegetal axis in the ascidian embryo is maintained by a dual functional protein Foxd.

In many animal embryos, a specific gene expression pattern is established along the animal-vegetal axis soon after zygotic transcription begins. In the embryo of the ascidian Ciona intestinalis, soon after the division that separates animal and vegetal hemispheres into distinct blastomeres, maternal Gata.a and ß-catenin activate specific genes in the animal and vegetal blastomeres, respectively. On the basis of these initial distinct gene expression patterns, gene regulatory networks promote animal cells to become ectodermal tissues and vegetal cells to become endomesodermal tissues and a part of the nerve cord. In the vegetal hemisphere, ß-catenin directly activates Foxd, an essential transcription factor gene for specifying endomesodermal fates. In the present study, we found that Foxd also represses the expression of genes that are activated specifically in the animal hemisphere, including Dmrt1, Prdm1-r.a (Bz1), Prdm1-r.b (Bz2), and Otx. A reporter assay showed that Dmrt1 expression was directly repressed by Foxd, and a chromatin immunoprecipitation assay showed that Foxd was bound to the upstream regions of Dmrt1, Prdm1-r.a, Prdm1-r.b, and Otx. Thus, Foxd has a dual function of activating specific gene expression in the vegetal hemisphere and of repressing the expression of genes that are normally expressed in the animal hemisphere. This dual function stabilizes the initial patterning along the animal-vegetal axis by ß-catenin and Gata.a.

Generation of a Quantitative Luciferase Reporter for Sox9 SUMOylation.

Sox9 is a master transcription factor for chondrogenesis, which is essential for chondrocyte proliferation, differentiation, and maintenance. Sox9 activity is regulated by multiple layers, including post-translational modifications, such as SUMOylation. A detection method for visualizing the SUMOylation in live cells is required to fully understand the role of Sox9 SUMOylation. In this study, we generated a quantitative reporter for Sox9 SUMOylation that is based on the NanoBiT system. The simultaneous expression of Sox9 and SUMO1 constructs that are conjugated with NanoBiT fragments in HEK293T cells induced luciferase activity in SUMOylation target residue of Sox9-dependent manner. Furthermore, the reporter signal could be detected from both cell lysates and live cells. The signal level of our reporter responded to the co-expression of SUMOylation or deSUMOylation enzymes by several fold, showing dynamic potency of the reporter. The reporter was active in multiple cell types, including ATDC5 cells, which have chondrogenic potential. Finally, using this reporter, we revealed a extracellular signal conditions that can increase the amount of SUMOylated Sox9. In summary, we generated a novel reporter that was capable of quantitatively visualizing the Sox9-SUMOylation level in live cells. This reporter will be useful for understanding the dynamism of Sox9 regulation during chondrogenesis.

Spectral and temporal modulations of femtosecond SPP wave packets induced by resonant transmission/reflection interactions with metal-insulator-metal nanocavities.

To study the dynamical optical interactions of nano-scaled metal-insulator-metal (MIM) structures in temporal-frequency domain, femtosecond surface plasmon polariton (SPP) wave packets propagate over a surface with a MIM structure. The resonance nature of the SPP-cavity interaction is reflected as strong modulations in the spectra of transmitted and reflected SPP wavepackets, which show peaks and valleys, respectively, corresponding to the MIM cavity's eigenmode. These features indicate that the MIM structure acts as a Fabry-Pérot etalon-type spectrum filter. With appropriate tuning of the resonance frequency of the cavity, one can extract a wave packet with a narrower time duration and temporally shifted intensity peak.

A Maternal System Initiating the Zygotic Developmental Program through Combinatorial Repression in the Ascidian Embryo.

Maternal factors initiate the zygotic developmental program in animal embryos. In embryos of the chordate, Ciona intestinalis, three maternal factors-Gata.a, ß-catenin, and Zic-r.a-are required to establish three domains of gene expression at the 16-cell stage; the animal hemisphere, vegetal hemisphere, and posterior vegetal domains. Here, we show how the maternal factors establish these domains. First, only ß-catenin and its effector transcription factor, Tcf7, are required to establish the vegetal hemisphere domain. Second, genes specifically expressed in the posterior vegetal domain have additional repressive cis-elements that antagonize the activity of ß-catenin/Tcf7. This antagonizing activity is suppressed by Zic-r.a, which is specifically localized in the posterior vegetal domain and binds to DNA indirectly through the interaction with Tcf7. Third, Gata.a directs specific gene expression in the animal hemisphere domain, because ß-catenin/Tcf7 weakens the Gata.a-binding activity for target sites through a physical interaction in the vegetal cells. Thus, repressive regulation through protein-protein interactions among the maternal transcription factors is essential to establish the first distinct domains of gene expression in the chordate embryo.

Correction: A Maternal System Initiating the Zygotic Developmental Program through Combinatorial Repression in the Ascidian Embryo.

[This corrects the article DOI: 10.1371/journal.pgen.1006045.].

Near-field spectral properties of coupled plasmonic nanoparticle arrays.

We investigated the grating effect in complex gold dolmen structures, in which multiple plasmon modes are present due to plasmon hybridization, experimentally from both the far field and the near field. In particular, the near-field properties were investigated using photoemission electron microscopy, and it was demonstrated that two hybridized plasmon modes on the dolmen structures could be influenced by the grating effect. For comparison, we also investigated the grating effect in arrays of simple nanoblocks and heptamer structures, which were supposed to support a strong bright plasmon mode and a strong dark plasmon mode, respectively, in the near field. We found that the spectral responses of the two hybridized modes on the dolmen structures as the pitch size changed evolved in a manner similar to that of the bright dipole mode on the nanoblocks, whereas the dark mode on the heptamer structures is less sensitive to the pitch size.

Hand-Foot Syndrome and Post-Progression Treatment Are the Good Predictors of Better Survival in Advanced Hepatocellular Carcinoma Treated with Sorafenib: A Multicenter Study.

OBJECTIVE: To determine the relationship between treatment outcomes and hand-foot syndrome (HFS), and the relationship between survival rate and post-progression treatment after sorafenib therapy. METHODS: The study assessed 314 patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib at 5 general hospitals in Kagawa Prefecture, Japan. RESULTS: At the start of sorafenib therapy, 23.6% of the patients had HCC of a Child-Pugh class other than A. The initial sorafenib dose was 800 mg in 9.2% of the patients and 400 mg in 64.3%. Time to progression was 129 days (95% CI: 87.3-170.7) and the median overall survival (OS) was 392 days (95% CI: 316.0-468.0). The OS of the patients with Child-Pugh class A HCC was significantly better than that of the patients with Child-Pugh class B HCC (p < 0.0001). The survival curves for Child-Pugh class A-5 points and class A-6 points were significantly different, with that for class A-5 points being better (p < 0.0001). A significant difference was observed between the patients who exhibited HFS and those who did not, with the former exhibiting a better survival rate (p < 0.001). In addition, the survival rate of the patients who received post-progression treatment after sorafenib therapy was significantly better than that of the patients who did not (p < 0.001). CONCLUSION: In sorafenib therapy, patients with HFS and those who received post-progression treatment exhibited good OS.

Prediction of Embolization Area after Conventional Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma Using SYNAPSE VINCENT.

PURPOSE: Transcatheter arterial chemoembolization (TACE) is one of the most effective therapeutic options for hepatocellular carcinoma (HCC) and it is important to protect residual liver function after treatment as well as the effect. To reduce the liver function deterioration, we evaluated the automatic software to predict the embolization area of TACE in 3 dimensions. MATERIALS AND METHODS: Automatic prediction software of embolization area was used in chemoembolization of 7 HCCs. Embolization area of chemoembolization was evaluated within 1 week CT findings after TACE and compared simulated area using automatic prediction software. RESULTS: The maximal diameter of these tumors is in the range 12-42 mm (24.6 ± 9.5 mm). The average time for detecting tumor-feeding branches was 242 s. The total time to detect tumor-feeding branches and simulate the embolization area was 384 s. All cases could detect all tumor-feeding branches of HCC, and the expected embolization area of simulation with automatic prediction software was almost the same as the actual areas, as shown by CT after TACE. CONCLUSION: This new technology has possibilities to reduce the amount of contrast medium used, protect kidney function, decrease radiation exposure, and improve the therapeutic effect of TACE.

Efficacy of probiotic treatment with Bifidobacterium longum 536 for induction of remission in active ulcerative colitis: A randomized, double-blinded, placebo-controlled multicenter trial.

BACKGROUND AND AIM: We conducted a randomized, double-blinded, placebo-controlled trial to investigate the efficacy of Bifidobacterium longum 536 (BB536) supplementation for induction of remission in Japanese patients with active ulcerative colitis (UC). METHODS: Fifty-six patients with mild to moderate UC were enrolled. Three patients had pancolitis, 36 had left-sided colitis, and 17 had proctitis. Patients were randomly treated with 2-3 × 10(11) freeze-dried viable BB536 (28 patients) or placebo (28 patients) for 8 weeks. RESULTS: In total, 63% of patients receiving BB536 showed clinical remission (UC disease activity index [UCDAI] ≤2) at week 8 compared to 52% of those receiving placebo (P = 0.395). We observed a significant decrease of UCDAI scores (3.8 ± 0.4 at baseline to 2.6 ± 0.4 at week 8) in the BB536 group (P < 0.01), whereas there was no significant decrease in the placebo group (P = 0.88). There was also a significant decrease in the Rachmilewitz endoscopic index (EI) and the Mayo subscore at week 8 in the BB536 group, whereas there was no significant decrease in the placebo group. A single patient in the BB536 group complained of a mild side-effect, but no other adverse effects were observed. CONCLUSION: Supplementation with BB536 was well tolerated and reduced UCDAI scores, EI and Mayo subscores after 8 weeks in Japanese patients with mild to moderately active UC.

[Mechanotransduction and mechanical control of gene expression.]

Cells change gene expression when they differentiate into different cell lineages. Cells also change their gene expression profiles to adapt to altering milieus. Even physical forces(for example, forces evoked by muscle contraction or exercise)change gene expression dramatically, although the molecular mechanisms of this physico-genetic link are largely unknown. Here, we summarize several works published recently, trying to highlight the physical force as an essential parameter of gene expression and maintenance of homeostasis.

Initial Experience Performing Percutaneous Ultrasound Examination with Real-Time Virtual Sonography with Color Display.

PURPOSE: We report the efficacy of percutaneous ultrasound (US) examination using a novel real-time virtual sonography (RVS) method that collates multiple Digital Imaging and Communications in Medicine (DICOM) data sources and displays reference images in color. MATERIALS AND METHODS: A total of 7 patients with 9 hepatocellular carcinomas were evaluated. Using the SYNAPSE VINCENT volume analyzer, DICOM data of the portal vein, hepatic vein, tumor, and hepatic segment were isolated from contrast-enhanced computed tomography DICOM data. Each portion of DICOM data was uploaded into an US scanner (HI VISION Ascendus, Hitachi Aloka Medical Ltd., Tokyo, Japan) and unified on a US platform to create a single reference image. Each uploaded portion of DICOM data was assigned a different color. Further, conventional RVS was performed using this information. RESULTS: The maximal tumoral diameter ranged from 6.4 to 15 mm (mean ± SD, 11.0 ± 2.8). DICOM data could be isolated, enabling the display of color RVS in all patients. Color RVS facilitated superior visibility compared with conventional grayscale RVS and facilitated the comprehension of spatial positioning. CONCLUSION: RVS with color display demonstrates utility in increasing operator comprehension of spatial and positional relationships during percutaneous US examination.

Virtual sonography for novice sonographers: usefulness of SYNAPSE VINCENT® with pre-check imaging of tumor location.

PURPOSE: To evaluate the usefulness of a virtual ultrasound (US) imaging device as a tool to assist novice sonographers. MATERIALS AND METHODS: A prospective blinded pilot study was conducted involving patients with liver lesions. Two sonographers and 2 medical doctors with less than 5 years of experience performed US examinations. The time needed to detect liver lesions on US and the success rate for detecting liver lesions with and without using the virtual US imaging device SYNAPSE VINCENT® (Fujifilm Medical Co., Tokyo, Japan) before US examination were evaluated. RESULTS: Thirty-two patients with the following 42 liver lesions were included: liver cyst (n = 24), hemangioma (n = 8), hepatocellular carcinoma (n = 6), and liver metastasis (n = 4). The maximal diameter of these lesions ranged from 0.3 to 1.5 cm (mean ± SD, 0.8 ± 0.4). The average time for detecting liver lesions on US was 47.8 s (range, 7-113) with VINCENT and 112.9 s (range, 14-313) without VINCENT before US examination. There were significant differences in the duration of US examination with and without VINCENT (p = 0.0002, Student's t test). The rates for accurately detecting liver lesions were 100 and 76.2% (16/21) in US beginners with and without VINCENT, respectively. Significantly higher detection rates were found in the US beginners who used VINCENT compared to those who did not use VINCENT (p = 0.047, Fisher's exact test). CONCLUSION: Before US examination, a reference with VINCENT could contribute to the successful detection of liver lesions and could be time-saving for US beginners.

Genomic cis-regulatory networks in the early Ciona intestinalis embryo.

Precise spatiotemporal gene expression during animal development is achieved through gene regulatory networks, in which sequence-specific transcription factors (TFs) bind to cis-regulatory elements of target genes. Although numerous cis-regulatory elements have been identified in a variety of systems, their global architecture in the gene networks that regulate animal development is not well understood. Here, we determined the structure of the core networks at the cis-regulatory level in early embryos of the chordate Ciona intestinalis by chromatin immunoprecipitation (ChIP) of 11 TFs. The regulatory systems of the 11 TF genes examined were tightly interconnected with one another. By combining analysis of the ChIP data with the results of previous comprehensive analyses of expression profiles and knockdown of regulatory genes, we found that most of the previously determined interactions are direct. We focused on cis-regulatory networks responsible for the Ciona mesodermal tissues by examining how the networks specify these tissues at the level of their cis-regulatory architecture. We also found many interactions that had not been predicted by simple gene knockdown experiments, and we showed that a significant fraction of TF-DNA interactions make major contributions to the regulatory control of target gene expression.