Glutathione trisulfide prevents lipopolysaccharide-induced retinal inflammation via inhibition of proinflammatory cytokine production in glial cells.

We aimed to investigate the impact of glutathione trisulfide (GSSSG) on lipopolysaccharide (LPS)-induced inflammation in retinal glia. Inflammatory responses in mouse-derived glial cells and Wistar rat retinas were stimulated with administration of LPS. Cell survival and proinflammatory cytokine production were examined using the Calcein-AM assay, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Retinal microglia were visualized with immunohistochemistry for Iba1. Administration of LPS (10 µg/mL) or GSSSG (less than 100 µM) did not affect survival of cultured primary Müller cells and established microglial cells (BV-2). RT-qPCR and ELISA indicated that GSSSG inhibited LPS-induced gene upregulation and protein secretion of proinflammatory cytokines in these glial cells and rat retinas. GSSSG inhibited LPS-induced activation of TGF-ß-activated kinase 1 (TAK1), which is an upstream kinase of NF-κB, in BV-2 cells. Finally, in vivo experiments indicated that intravitreal administration of GSSSG but not its relative glutathione disulfide (GSSG) inhibited LPS (500 ng)-induced accumulation of Iba1-immunopositive microglia in rat retinas. Taken together, GSSSG has the potential to prevent pathogenesis of inflammation-associated ocular diseases by inhibiting proinflammatory cytokine expression in retinal glial cells.

Single and sequential double ionization of NO radical in intense laser fields.

We examine the dependences of the single and double ionization probabilities of NO radical on the angle between the NO axis and the laser polarization direction in an intense laser field (790 nm, 100 fs, 1-10 × 1014 W/cm2) and show that the double ionization is enhanced when the NO axis is parallel to the laser polarization direction. We reveal that the angular dependence of the sequential double ionization probability is determined by the shape of the 5σ orbital of NO+ from which the second photoelectron is emitted in the ionization from NO+ to NO2+. We also reveal that the fast oscillation in the probability of the tunnel ionization of NO originating from a coherent superposition of the two spin-orbit components in the electronic ground X2Π state is described well based on the molecular Ammosov-Delone-Krainov (MO-ADK) theory in which the time evolution of the electron density distribution of the 2π orbital is taken into account.

Rotational dynamics and transitions between Λ-type doubling of NO induced by an intense two-color laser field.

We numerically investigate the rotational dynamics of NO in the electronic ground X2Π state induced by an intense two-color laser field (10 TW/cm2) as a function of pulse duration (0.3-25 ps). In the short pulse duration of less than 12 ps, rotational Raman excitation is effectively induced and results in molecular orientation. On the contrary, when the pulse duration is longer than 15 ps, the rotational excitation is suppressed. In addition to the rotational excitation, we find that transitions between Λ-type doubling are induced. Significantly, the maximum coherent wave packet between Λ-type doubling in J = 0.5 is generated using the pulse duration of 19.8 ps. The wave packet changes to the eigenstates of Λ = +1 or -1 alternatively, where Λ is the projection of the electronic orbital angular momentum on the N-O axis, which is regarded as the unidirectional rotation of an unpaired 2π electron around the N-O axis in a space-fixed frame as well as in a molecule-fixed frame. The experimental method to observe the alternation of the rotational direction of the electron around the N-O axis is proposed.

3D-TEM study on the novel bicontinuous microdomain structure.

An ordered bicontinuous double-diamond (OBDD) morphology was found in polystyrene-block-(poly-4-vinylphenyldimethylvinylsilane-graft-polyisoprene), PS-b-(PVS-g-PI), block-graft copolymer. We obtained a 3D image of the microdomain structure formed in PS-b-(PVS-g-PI) using 3D-TEM. The 3D image shows that the polystyrene (PS) phase consists of two independent and interwoven networks. The structures of the two networks are identical and include tetrapod units that form planar six-membered rings. The features of the networks agree with those in the OBDD morphology, indicating that PS-b-(PVS-g-PI) exhibits ordered three-dimensional OBDD networks with the PS phase in the polyisoprene (PI) matrix phase. The grafted PI chains induce the frustration of the PS chains; thus, the effects of the specific interface are more dominant than those of packing frustration in the formation of the morphology, and the OBDD phase is stabilized.

Comparison of lesion enhancement between BB Cube and 3D-SPGR images for brain tumors with 1.5-T magnetic resonance imaging.

PURPOSE: This study aimed to compare the detectability of neoplastic lesion enhancement after gadolinium-based contrast media injection in three-dimensional T1-weighted black blood Cube (3D-T1W BB Cube) and three-dimensional T1-weighted fast spoiled gradient-echo (3D-T1W fast SPGR) images obtained with 1.5-T magnetic resonance imaging (MRI). MATERIALS AND METHODS: Phantom and clinical studies were performed to compare the lesion detectability and contrast ratio (CR) between 3D-T1W BB Cube and 3D-T1W fast SPGR pulse sequences. RESULTS: In the phantom study, the CRs for 3D-T1W BB Cube and 3D-T1W fast SPGR were equivalent at low gadolinium concentrations (0.125-1.25 mmol/l). In the clinical study, the detectability in the two modalities was similar for enhanced lesions ≥5 mm, but was significantly better in 3D-T1W BB Cube for lesions <5 mm (p = 0.011). Similarly, the CRs in both modalities were similar for lesions ≥5 mm (0.66 ± 0.36 vs. 0.56 ± 0.30, p = 0.153), but significantly lower in 3D-T1W BB Cube images for lesions <5 mm (0.29 ± 0.19 vs. 0.39 ± 0.21, p = 0.006). CONCLUSIONS: Contrast 3D-T1W BB Cube imaging appears more sensitive than 3D-T1W fast SPGR imaging for detecting neoplastic lesion enhancement in the clinical setting using a 1.5-T MRI scanner, particularly for lesions <5 mm in diameter.

Quantum unidirectional rotation directly imaged with molecules.

A gas-phase molecular ensemble coherently excited to have an oriented rotational angular momentum has recently emerged as an appropriate microscopic system to illustrate quantum mechanical behavior directly linked to classical rotational motion, which has a definite direction. To realize an intuitive visualization of such a unidirectional molecular rotation, we report high-resolution direct imaging of direction-controlled rotational wave packets in nitrogen molecules. The rotational direction was regulated by a pair of time-delayed, polarization-skewed laser pulses, introducing the dynamic chirality to the system. The subsequent spatiotemporal propagation was tracked by a newly developed Coulomb explosion imaging setup. From the observed molecular movie, time-dependent detailed nodal structures, instantaneous alignment, angular dispersion, and fractional revivals of the wave packet are fully characterized while the ensemble keeps rotating in one direction. The present approach, providing an accurate view on unidirectional rotation in quantum regime, will guide more sophisticated molecular manipulations by utilizing its capability in capturing highly structured spatiotemporal evolution of molecular wave packets.

Spectroscopic study on deuterated benzenes. II. High-resolution laser spectroscopy and rotational structure in the S(1) state.

High-resolution spectra of the S1←S0 transition in jet-cooled deuterated benzenes were observed using pulse dye amplification of single-mode laser light and mass-selective resonance enhanced multiphoton ionization (REMPI) detection. The vibrational and rotational structures were accurately analyzed for the vibronic levels in the S1 state. The degenerate 6(1) levels of C6H6 or C6D6 are split into 6a(1) and 6b(1) in many of deuterated benzenes. The rigid-rotor rotational constants were assessed and found to be slightly different between 6a and 6b because of different mean molecular structures. Their rotational levels are significantly shifted by Coriolis interactions. It was found that the Coriolis parameter proportionally changed with the number of substituted D atoms.

Multiple primary malignancies in patients with prostate cancer: increased risk of secondary malignancies after radiotherapy.

BACKGROUND: New treatment strategies for prostate cancer have recently been developed, but multiple malignancies remain a major concern. The aim of this study was to evaluate the characteristics of multiple malignancies and to analyze the risk of secondary malignancies after radiotherapy for prostate cancer. METHODS: From 2000 to 2011, 150 patients with prostate cancer were treated with curative radiotherapy in our department. Patient age range was 54-92 years (median, 70 years), and the follow-up period was 4-142 months (median, 48 months). The incidence of multiple primary cancers was compared with the estimated incidence. RESULTS: A total of 147 patients (98 %) survived more than 12 months (12-142 months; median, 48 months); 20/150 patients (13 %) died within 10 years. Cause of death was recurrent prostate cancer in 11 patients, other primary malignancies in 7 patients, and cardiovascular disease in 2 patients. Multiple primary cancers were present in 26 of 150 patients (17 %), including 16 subsequent malignancies (11 %) with latent periods of 13-83 months (median, 43 months). The subsequent non-prostate malignancies were lung cancer in 4 patients, urinary bladder or ureter cancer in 4, stomach cancer in 3, malignant lymphoma in 2, and other in 3. Analysis of the observed incidence of secondary malignancies compared with the estimated incidence in the general population revealed a higher incidence of ureter cancer and malignant lymphoma. CONCLUSION: Close attention should be paid to secondary malignancies after radiotherapy for prostate cancer, including malignancies occurring within 5 years, which could be attributable to radiotherapy.

Transfer of chirality from molecule to phase in self-assembled chiral block copolymers.

Here, we report the mechanisms of chiral transfer at various length scales in the self-assembly of enantiomeric chiral block copolymers (BCPs*). We show the evolution of homochirality from molecular chirality into phase chirality in the self-assembly of the BCPs*. The chirality of the molecule in the BCP* is identified from circular dichroism (CD) spectra, while the handedness of the helical conformation in the BCP* is determined from a split-type Cotton effect in vibrational circular dichroism spectra. Microphase separation of the BCP* is exploited to form a helical (H*) phase, and the handedness of helical nanostructure in the BCP* is directly visualized from transmission electron microscopy tomography. As examined by CD and fluorescence experiments, significant induced CD signals and a bathochromic shift of fluorescence emission for the achiral perylene moiety as a chemical junction of the BCPs* can be found while the concentration of the BCPs* in toluene solution is higher than the critical micelle concentration, suggesting a twisting and shifting mechanism initiating from the microphase-separated interface of the BCPs* leading to formation of the H* phase from self-assembly.

Defining the nanostructured morphology of triblock copolymers using resonant soft X-ray scattering.

The morphologies of a poly(1,4-isoprene)-block-polystyrene-block-poly(2-vinyl pyridine) (IS2VP) copolymer were investigated using resonant soft X-ray scattering (RSoXS) together with scanning force microscopy, small-angle X-ray scattering, and electron microscopy. Differences in the nanoscopic morphologies in the bulk and thin film samples were observed arising from the competition between segmental interactions between the blocks and the substrate and the surface energies of each block. Using soft X-rays at selected photon energies to isolate the scattering contribution from different polymer blocks, RSoXS unambiguously defined the complex morphology of the triblock copolymer. In the bulk sample, two nested, hexagonal arrays of P2VP and PI cylindrical microdomains residing in the PS matrix were observed. The cylindrical microdomains of one component were found to be located at the interstitial sites of the hexagonal array of the other component that has the larger d spacing. In solvent-annealed thin films with 40 nm in thickness, a hexagonal array of core-shell microdomains of P2VP cores with PS shells that reside in a PI matrix were observed.

Unveiling the nonadiabatic rotational excitation process in a symmetric-top molecule induced by two intense laser pulses.

We experimentally investigate the nonadiabatic rotational excitation process of a symmetric-top molecule, benzene, in the electronic ground state irradiated by intense nonresonant ultrafast laser fields. The initial rotational-state distribution was restricted mostly to the five lowest levels with different nuclear spin modifications by an extensive adiabatic cooling with the rotational temperature well below 1 K, and distributions after the interaction with a femtosecond double-pulse pair (3-5 TW/cm(2) each with 160 fs duration) with time delays were probed in a quantum-state resolved manner by employing resonant enhanced multiphoton ionization via the S(1) ← S(0) 6(0) (1) vibronic transition. Populations of 10 rotational levels with J ranging from 0 to 4 and K from 0 to 3 were examined to show an oscillatory dependence on the time delay between the two pulses. Fourier analysis of the beat signals provides the coupling strengths between the constituent levels of the rotational wave packets created by the nonadiabatic excitation. These data are in good agreement with the results from quantum mechanical calculations, evidencing stepwise excitation pathways in the wave packet creation with ΔJ = 2 in the K = 0 stack while ΔJ = 1 and 2 in the K > 0 stacks.

Inorganic gyroid with exceptionally low refractive index from block copolymer templating.

Nanoporous polymers with gyroid nanochannels can be fabricated from the self-assembly of degradable block copolymer, polystyrene-b-poly(l-lactide) (PS-PLLA), followed by the hydrolysis of PLLA blocks. A well-defined nanohybrid material with SiO2 gyroid nanostructure in a PS matrix can be obtained using the nanoporous PS as a template for sol-gel reaction. After subsequent UV degradation of the PS matrix, a highly porous inorganic gyroid network remains, yielding a single-component material with an exceptionally low refractive index (as low as 1.1).

Coherent correlation between nonadiabatic rotational excitation and angle-dependent ionization of NO in intense laser fields.

We investigate coherent correlation between nonadiabatic rotational excitation and angle-dependent ionization of NO in intense laser fields in the state-resolved manner. When neutral NO molecules are partly ionized in intense laser fields (I(0) > 35 TW/cm(2)), a hole in the rotational wave packet of the remaining neutral NO is created because of the ionization rate depending on the alignment angle of the molecular axis with respect to the laser polarization direction. Rotational state distributions of NO are experimentally observed, and then the characteristic feature that the population at higher J levels is increased by the ionization can be identified. Numerical calculation for solving time-dependent rotational Schrödinger equations including the effect of the ionization is carried out. The numerical results suggest that NO molecules aligned perpendicular to the laser polarization direction are dominantly ionized at the peak intensity of I(0) = 42 TW/cm(2), where the multiphoton ionization is preferred rather than the tunneling ionization.

Block copolymers with a twist.

Chiral block copolymers (BCPs*) comprising chiral entities were designed to fabricate helical architectures (i.e., twisted morphologies) from self-assembly. A new helical phase (H*) with P622 symmetry was discovered in the self-assembly of poly(styrene)-b-poly(l-lactide) (PS-PLLA) BCPs*. Hexagonally packed, interdigitated PLLA helical microdomains in a PS matrix were directly visualized by electron tomography. The phase diagram of the PS-PLLA BCPs* was also established. Phase transitions from the H* phase to the stable cylinder and gyroid phases were found after long-time annealing, suggesting that the H* is a long-lived metastable phase. In contrast to racemic poly(styrene)-b-poly(d,l-lactide) BCPs, chiral interaction significantly enhances the incompatibility between achiral PS and chiral PLLA blocks in the PS-PLLA BCPs* and can be estimated through the determination of the interaction parameter.

High therapeutic effectiveness of postoperative irinotecan chemotherapy in a typical case of radiographically and pathologically diagnosed pleuropulmonary blastoma.

A 2-year 9-month-old girl with a large mass in the right chest underwent middle and inferior lobectomy, after which the mass was pathologically diagnosed as a pleuropulmonary blastoma (PPB). The clinical, radiographic, and pathologic findings were typical. Three courses of postoperative chemotherapy with 2 different regimens were ineffective in preventing multiple metastases of the lung. We then instituted a protocol with irinotecan (CPT-11) and vincristine. After the third course of this protocol the metastases disappeared and there were no recurrences. PPB is a rare pediatric malignant tumor, and no adequate therapy has been defined. This is the only case reported to have been treated with vincristine/irinotecan therapy for the treatment of PPB.

Helical nanocomposites from chiral block copolymer templates.

Three-dimensional hexagonally packed PLLA nanohelices in the PS matrix were formed in the self-assembly of PS-PLLA chiral block copolymer. After hydrolysis of the PLLA blocks, PS with hexagonally packed helical nanochannels can be fabricated and treated as the template for the following sol-gel process. Subsequently, silica precursor mixture was introduced into the PS template by a pore-filling process. Well-defined helical nanocomposites with SiO(2) inorganic nanohelices orderly dispersed in polymeric matrix can be successfully obtained after the sol-gel process. As a result, with the combination of the self-assembly of degradable block copolymers and sol-gel chemistry, we suggest a novel method for the preparation of the helical nanocomposites with ordered texture.

Ultrafast angular momentum orientation by linearly polarized laser fields.

We theoretically show and experimentally verify that a pair of linearly polarized intense femtosecond pulses can create molecular ensembles with oriented rotational angular momentum on an ultrafast (approximately ps) time scale, when the delay and the mutual polarization between them are appropriately arranged. An asymmetric distribution for +M and -M sublevels relies on quantum interference between rotational wave packets created in stimulated Raman excitation by the first and second pulses. The present approach provides spatiotemporally propagating ensembles, of which the classical perspective is molecules rotating in a clockwise or counterclockwise direction.

Quantum state reconstruction of a rotational wave packet created by a nonresonant intense femtosecond laser field.

We have experimentally determined the amplitudes and phases of a rotational wave packet in an adiabatically cooled benzene molecule, created by a nonresonant intense femtosecond laser field. In this wave-packet reconstruction, the initial wave packet is further interfered by a replica of the first laser pulse, and the resultant modulation in population is observed in a state-resolved manner. Though several states with different nuclear-spin modifications are populated in the initial condition, a single wave packet created from one of them (with J=0) is specifically reconstructed. Phase shifts characteristic of stepwise Raman excitation beyond the perturbative regime are experimentally identified.