Kinematics of electromigration-driven sliding of Co nanorod fillers inside multi-walled carbon nanotubes.

The movement of Co nanorods driven by electromigration inside multi-walled carbon nanotubes was observed using in situ transmission electron microscopy. This study provides a unique method of experimental determination of both the electromigration force strength and sliding friction. When the tip of a biased electrode was located within the portion of a Co nanorod filler and an electric current was applied to push a part of the Co filler along the flow of electrons, the Co filler showed a trigonometric motion. Both the electromigration force strength and sliding friction were determined by analysis of the trigonometric movements. When a reversed electric current was applied to pull a part of the Co nanorod filler, its motion was hyperbolic-cosine like, and the motion was not suitable to determine the strengths of the two forces. Our method and the results would be useful for the development of the methods to precisely control mass transfer at the nanoscale.

Analyzing the synchronism of stacking-fault formation in side-by-side SiC nanowire pairs using the Levenshtein distance: stochastic versus deterministic processes.

Pairs of silicon carbide nanowires were grown side by side synchronously from the same metal catalyst nanoparticles. The stacking sequences of each pair were read by high-resolution transmission electron microscopy, and the similarity of each stacking sequence was measured using the Levenshtein distance. No synchronism was detected in the pairs of stacking sequences, and the results indicated that the formation of stacking faults in silicon carbide nanowires was not deterministic, but purely stochastic.

Comparative Analysis of Serum microRNA in Diagnosed Ocular Sarcoidosis versus Idiopathic Uveitis with Ocular Manifestations of Sarcoidosis.

"Idiopathic" is the most common category of uveitis, representing cases in which a specific diagnosis has not been established despite work-up. Sarcoidosis is a systemic granulomatous disorder affecting multiple organs including the lungs, skin, kidneys, and eyes. We used microRNA (miRNA) microarrays to investigate serum miRNA profiles of patients with ocular sarcoidosis as diagnosed by specific criteria (diagnosed ocular sarcoidosis), and patients with idiopathic uveitis characterized by ocular manifestations of sarcoidosis (suspected ocular sarcoidosis). Principal component analysis (PCA) and hierarchical clustering showed that serum miRNA profiles of diagnosed ocular sarcoidosis and suspected ocular sarcoidosis were both clearly distinguishable from healthy controls. Furthermore, comparative analysis of the miRNA profiles showed highly similar patterns between diagnosed ocular sarcoidosis and suspected ocular sarcoidosis. Pathway analysis revealed common pathways were involved in the two groups, including those of WNT signaling and TGF-beta signaling. Our study demonstrated a high overlap of differentially expressed serum miRNAs in patients with diagnosed ocular sarcoidosis and suspected ocular sarcoidosis, suggesting that these groups share a similar underlying pathology and may represent possible variants of the disease. Characterization of serum miRNA profiles may provide an opportunity for earlier diagnosis and treatment, and may inform more accurate clinical prognosis in patients with an ocular sarcoidosis phenotype.

Effect of Lecithin-Bound Iodine Treatment on Inherited Retinal Degeneration in Mice.

Purpose: Although lecithin-bound iodine (LBI) has been administered orally for retinal diseases, a lack of clinical studies and obscure action mechanism of LBI hinder its large-scale prescription. LBI treatment suppresses chemokine (C-C motif) ligand 2 (CCL2) secretion from retinal pigment epithelial cells in vitro. Herein, we assessed the in vivo effect of LBI treatment on retinal degeneration (RD) in mice. Methods: Mertk-/-Cx3cr1GFP/+Ccr2RFP/+ mice-a model for RD-demonstrate fluorescein-labeled microglia/macrophage to facilitate visualization of CX3CR1-green fluorescent protein (GFP) and CCR2-red fluorescent protein (RFP). An LBI-containing mouse diet was provided to Mertk-/-Cx3cr1GFP/+Ccr2RFP/+ mice ad libitum from postnatal day (POD) 28. CX3CR1-GFP and CCR2-RFP expression was assessed at POD 56 using retinal sectioning and flat mounting. RD severity was assessed at POD 84. Retinal RNA was extracted from the mice of each group to measure chemokine expression. Electroretinography was performed to assess retinal function. Results: CCR2-RFP expression in the retina and retinal pigment epithelial cells was suppressed by LBI treatment compared with that in the control at POD 56. The number of outer nuclear layer nuclei was higher in the group fed with LBI-containing diet than in the control mice at POD 84. Ccl2 and Ccr2 RNA expression was suppressed by LBI intake. Electroretinography showed the LBI-treated group to have a high b-wave amplitude compared with the control group. Conclusions: Suppressing CCR2-RFP-positive macrophage invasion into the retina and CCL2 and CCR2 expression is a potential mechanism underlying LBI-mediated attenuation of RD. Translational Relevance: Life-long LBI administration may become a candidate for treating RD.

Minocycline decreases CCR2-positive monocytes in the retina and ameliorates photoreceptor degeneration in a mouse model of retinitis pigmentosa.

Retinal inflammation accelerates photoreceptor cell death caused by retinal degeneration. Minocycline, a semisynthetic broad-spectrum tetracycline antibiotic, has been previously reported to rescue photoreceptor cell death in retinal degeneration. We examined the effect of minocycline on retinal photoreceptor degeneration using c-mer proto-oncogene tyrosine kinase (Mertk)-/-Cx3cr1GFP/+Ccr2RFP/+ mice, which enabled the observation of CX3CR1-green fluorescent protein (GFP)- and CCR2-red fluorescent protein (RFP)-positive macrophages by fluorescence. Retinas of Mertk-/-Cx3cr1GFP/+Ccr2RFP/+ mice showed photoreceptor degeneration and accumulation of GFP- and RFP-positive macrophages in the outer retina and subretinal space at 6 weeks of age. Mertk-/-Cx3cr1GFP/+Ccr2RFP/+ mice were intraperitoneally administered minocycline. The number of CCR2-RFP positive cells significantly decreased after minocycline treatment. Furthermore, minocycline administration resulted in partial reversal of the thinning of the outer nuclear layer and decreased the number of apoptotic cells, as assessed by the TUNEL assay, in Mertk-/-Cx3cr1GFP/+Ccr2RFP/+ mice. In conclusion, we found that minocycline ameliorated photoreceptor cell death in an inherited photoreceptor degeneration model due to Mertk gene deficiency and has an inhibitory effect on CCR2 positive macrophages, which is likely to be a neuroprotective mechanism of minocycline.

In situ scanning electron microscopy observations of filler material transport in branched carbon microtubes by Joule heating.

Y-branched or side-by-side-branched carbon microtubes with metal filler material were fabricated, and material transport in the branched microtubes with Joule heating was investigated using in situ scanning electron microscopy with micro-electrode probes. When a voltage and electric current were applied, the material enclosed in the microtubes moved from its original position. The movement was not related to the direction of the electric current; therefore, it is concluded that the movement was not due to electromigration, but rather a temperature gradient, volume expansion and increased vapor pressure by Joule heating. In Y-branched microtubes, a part of the metal filler material moved from one branch to another branch, which would be useful for microfluidic flow switching. A cylindrical filler material was also observed to be expelled from a branch while its shape was maintained, and this phenomenon is presumably caused by vaporization-induced high pressure and could find application in micro-mechanical manipulators such as punching needles. In side-by-side-branched carbon microtubes, Joule heating caused thermal volume expansion to fill the spaces in the branches that were initially empty. The microtubes then reverted to a state almost identical to the initial state with empty spaces when the electric current was turned off. These results suggest that thermal volume expansion could be employed for flow switching.

Similarity analysis of stacking sequences in a SiC nanowire pair grown from the same catalyst nanoparticle using Levenshtein distance.

Stacking faults are easily formed in silicon carbide (SiC) crystals, and this is also the case for SiC nanowires. The stacking faults exercise influences on SiC's properties, therefore it is important to understand their formation mechanism and to control their formation for applications of SiC and its nanowires. In this study, we propose a method for investigating stacking faults' formation mechanism in nanowires and provide its proof of concept. Stacking sequences in a pair of SiC nanowires that were grown from the same metal catalyst nanoparticle were quantified as a pair of binary sequences, and Levenshtein distances between partial sequences extracted from the two sequences were measured to detect similarity between them, and the result was compared with that obtained using a surrogate data of one sequence. The similarity analysis using Levenshtein distances works as a probe for investigating possible influences of some phenomena in the catalyst nanoparticle on the formation of stacking faults. The analysis did not detect a correlation between the two sequences. Although a possibility that the formation of stacking faults in the nanowires were owing to some phenomena in the catalyst nanoparticle cannot be denied, the extrinsic cause in the catalyst nanoparticle was not detected through our analysis in this case.

Diameter-Modulated Multi-Walled Carbon Nanotubes Without Bamboo-Like Partitions: Growth, Structure and Deformation Behaviors.

Periodically diameter-modulated stack-type-multi-walled carbon nanotubes are grown from Fe-Ga catalyst nanoparticles using palmitic acid as a carbon source. A model for their formation mechanism is proposed: stick-slip motion of a catalyst nanoparticle in the growing nanotube results in periodic changes of diameter and wall thickness, and formation of inner partitions is suppressed when the degree of supersaturation is low. In addition, behaviors of nanotubes in Joule heating, bending, and under a tensile load were observed in-situ by scanning electron microscopy using micro-manipurators.

In-Situ Scanning Electron Microscopy of Individual Carbon Nanotetrahedron/Nanoribbon Structures Under a Tensile Load.

Flattening of a carbon nanotube with a switching of the flattening direction results in the formation of a nanotetrahedron/nanoribbon structure. In this study, behavior of individual carbon nanotetra-hedron/nanoribbon structures under a tensile load is observed by means of in-situ scanning electron microscopy using micro-manipulators. Positions of breakage caused by a tensile load are not necessarily at a nanotetrahedron/nanoribbon junction. The results indicate that the nanotetrahedron/nanoribbon junctions are not mechanical weak points under a tensile load, and the nanotetra-hedron/nanoribbon structures are as strong as simple multi-walled carbon nanotubes. In addition, the nanostructures maintain their shape and do not transformed to a tubular form.

Verification of Mechanism for the Formation of Carbon Nanotetrahedra Using Electron Beam Tomography.

When a carbon nanotube is flattened in two different directions, a nanotetrahedron is formed between the two nanoribbons. The distribution of the angles between the nanoribbons provides a clue to understanding the mechanism for the formation of nanotetrahedra. In this study, the angles between nanoribbons are measured using transmission electron microscopy-based electron beam tomography. The results are consistent with the proposed origami mechanism, in which the direction of flattening changes by approximately 90° during the growth of multi-walled carbon nanotubes.

Revealing the heterogeneous contamination process in metal nanoparticulate catalysts in CO gas without purification by in situ environmental transmission electron microscopy.

It is known that samples become contaminated in CO gas of high pressure unless care is taken with the gas supply line to an environmental transmission electron microscope. This technical note reveals the heterogeneous formation process of contamination in situ on a nanoparticulate catalyst sample. It is shown that the surface of metal nanoparticles is preferentially contaminated, while the surface of metal oxide supports remains uncontaminated. It is also demonstrated that the contamination is suppressed by introducing a gas purifier in a gas supply line.

Three-year visual outcomes of intravitreal ranibizumab with or without photodynamic therapy for polypoidal choroidal vasculopathy.

PURPOSE: To compare 3-year visual outcomes after intravitreal ranibizumab (IVR) monotherapy and combination therapy of photodynamic therapy (PDT) with IVR for polypoidal choroidal vasculopathy (PCV). METHODS: Medical records for 45 eyes in 45 patients (34 men, 11 women; mean age, 73.8 years old; range, 62-86 years old) with treatment-naïve PCV were reviewed retrospectively. Of the 45 eyes, 20 were treated with IVR monotherapy and 25 with combination therapy. Mean change in best-corrected visual acuity, numbers of injections of IVR and length of treatment-free period from baseline at month 36 were observed. Adverse events were monitored. RESULTS: The change in visual acuity after combination therapy was significantly better than that after IVR monotherapy (p = 0.0399). At 36 months, improvement in visual acuity was seen in five eyes (25.0%) in the IVR monotherapy group and 13 eyes (52.0%) in the combination therapy group. The treatment-free period was significantly longer in the combination therapy group (p = 0.0008). Additional IVR therapy was required significantly more frequently in the IVR monotherapy group (p = 0.0026). Post-treatment subretinal haemorrhage or retinal pigment epithelium tear occurred only in the IVR monotherapy group, in one eye (5.0%) and one eye (5.0%), respectively. CONCLUSION: Initial therapy consisting of a single session of PDT combined with IVR improves vision in treatment-naïve PCV. Compared with IVR monotherapy, this combination therapy may be more effective for PCV.

Expression pattern of Ccr2 and Cx3cr1 in inherited retinal degeneration.

BACKGROUND: Though accumulating evidence suggests that microglia, resident macrophages in the retina, and bone marrow-derived macrophages can cause retinal inflammation which accelerates photoreceptor cell death, the details of how these cells are activated during retinal degeneration (RD) remain uncertain. Therefore, it is important to clarify which cells play a dominant role in fueling retinal inflammation. However, distinguishing between microglia and macrophages is difficult using conventional techniques such as cell markers (e.g., Iba-1). Recently, two mouse models for visualizing chemokine receptors were established, Cx3cr1 (GFP/GFP) and Ccr2 (RFP/RFP) mice. As Cx3cr1 is expressed in microglia and Ccr2 is reportedly expressed in activated macrophages, these mice have the potential to distinguish microglia and macrophages, yielding novel information about the activation of these inflammatory cells and their individual roles in retinal inflammation. METHODS: In this study, c-mer proto-oncogene tyrosine kinase (Mertk) (-/-) mice, which show photoreceptor cell death due to defective retinal pigment epithelium phagocytosis, were employed as an animal model of RD. Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice were established by breeding Mertk (-/-) , Cx3cr1 (GFP/GFP) , and Ccr2 (RFP/RFP) mice. The retinal morphology and pattern of inflammatory cell activation and invasion of Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice were evaluated using retina and retinal pigment epithelium (RPE) flat mounts, retinal sections, and flow cytometry. RESULTS: Four-week-old Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice showed Cx3cr1-GFP-positive microglia in the inner retina. Cx3cr1-GFP and Ccr2-RFP dual positive activated microglia were observed in the outer retina and subretinal space of 6- and 8-week-old animals. Ccr2-RFP single positive bone marrow-derived macrophages were observed to migrate into the retina of Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice. These invading cells were still observed in the subretinal space in 18-week-old animals. CONCLUSIONS: Cx3cr1-GFP-positive microglia and Ccr2-RFP-positive macrophages were distinguishable in the retinas of Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice. In addition, Ccr2 expression in Cx3cr1 positive microglia is a feature of microglial activation in RD. Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice enabled observation of microglial activation over time during RD and may be useful for developing inflammation-targeted treatment strategies for RD in the future.

Multi-Walled Carbon Nanotube Growth in Multi-Walled Carbon Nanotubes by Chemical Vapor Deposition.

We report chemical vapor deposition (CVD) growth of a multi-walled carbon nanotube (MWCNT) inside another MWCNTs from a cementite (Fe3C) catalyst nanoparticles. The CNTs have bi or tri-layered core(s)-sheath structure with various crystallinity. The sheath grows first at a lower temperature, and then the catalyst nanoparticle works again to grow the core(s) at a higher temperature in the tip or root growth mode. Transmission electron microscopy (TEM) observation provides a clear piece of evidence of reverse-inward growth.

Flattened Multiwalled Carbon Nanotube with Multi-Layered Structure.

Fabrication of novel nanostructures based on carbon nanotubes has been a focus of recent interest since they are expected to inherit excellent properties of carbon nanotube. To find new nanotube-based nanostructures, it is important to find a new growth mode or process. This paper reports the formation of a multiwalled carbon nanotube that has bi-layered structure and is partly flattened. Transmission electron microscopy observations suggest that the outer multiwalled layer was formed first from a Fe catalyst nanoparticle, and was partly flattened during the growth. Then the catalyst nanoparticle worked again to form the inner multiwalled tube moving inside the outer tube and became flattened at the same position of the outer tube. It is likely that the inner growth gave an expansion stress against the flattened outer tube; nevertheless, the flattened part of the outer tube remained. This observation evidences that the flattening of the nanotube occurred simultaneously during the growth and was stabilized by structural defect.

Association between the major histocompatibility complex and clinical response to infliximab therapy in patients with Behçet uveitis.

PURPOSE: Our aim was to investigate whether major histocompatibility complex (MHC) polymorphisms are associated with response to infliximab therapy in Japanese patients with Behçet uveitis (BU). METHODS: We retrospectively reviewed 24 patients (17 men and seven women) treated with infliximab for BU. Of them, ten patients were genotyped as HLA A*2601, and nine as HLA B*5101. Therapeutic response levels in the two groups were compared based on ocular attacks and the Behçet disease ocular attack score 24 (BOS24) over 24 months of treatment. RESULTS: Mean frequencies of ocular attacks at 13-18 and 19-24 months after the start of treatment were significantly higher in the HLA A*2601 group (P = 0.0392 and 0.0177, respectively). Mean BOS24-6 M values for months 1-6, 7-12, 13-18, and 19-24 were also significantly higher in the HLA A*2601 group (P = 0.0459, 0.0150, 0.0394, and 0.0178, respectively). Shortening of the infusion interval was required in eight patients in the HLA A*2601 group but in one only in the HLA B*5101 group. Behçet-disease-related adverse events occurred in eight patients in the HLA A*2601 group and two in the HLA B*5101 group. Nonocular adverse events occurred in four patients in the HLA A*2601 group and none in the HLA B*5101 group. CONCLUSIONS: Although mean change from baseline in the number of ocular attack scores in the HLA A26 and HLA B51 groups seemed to be similar, the HLA-A26 group had a more severe disease course under infliximab therapy for ocular/extraocular involvement. These data suggest that response to infliximab therapy in Japanese patients with BU is partly due to genetic determinants in the HLA complex.

Chains of carbon nanotetrahedra/nanoribbons.

Flattening of a carbon nanotube results in the formation of a carbon nanoribbon with well-defined edges. In addition, a switching of the flattening direction by about a right angle yields a carbon nanotetrahedron at the switching point in a nanoribbon. Here, we report that chains of carbon nanotetrahedra/nanoribbons are formed via sequential switching of the flattening direction of multiwalled carbon nanotubes, in which neighboring two nanotetrahedra are connected by a short nanoribbon, namely a flattened nanotube. We suggest that the formation of nanotetrahedra chains is caused by a quasi-periodic instability of catalyst iron nanoparticles during the chemical vapor deposition growth. In addition, two adjoining carbon nanotetrahedra were found.

Splitting and joining in carbon nanotube/nanoribbon/nanotetrahedron growth.

We report a novel phenomenon for carbon nanotube growth that results in a new carbon nanotube morphology. A carbon nanotube grown via metal nanoparticle-catalyzed chemical vapor deposition splits into two flattened nanotubes during growth and the two flattened nanotubes merge to form a ring of carbon nanotube/nanoribbon. This novel process is revealed by transmission electron microscopy observations of the carbon nanostructures. We propose that the splitting-and-joining process involves only one metal catalyst nanoparticle and a self-folding mechanism that we have named the origami mechanism to explain the process and the formation of nanoribbons and nanotetrahedra.

Treatment of experimental autoimmune uveoretinitis with peroxisome proliferator-activated receptor α agonist fenofibrate.

PURPOSE: The peroxisome proliferator-activated receptor α (PPARα) agonist has been approved for treating hypercholesterolemia and lipid abnormalities. Researchers have recently discovered that an anti-inflammatory effect of PPAR agonist may have the potential to treat autoimmune disease. This study aims to investigate the therapeutic effects of fenofibrate on experimental autoimmune uveoretinitis (EAU). METHODS: EAU was induced in Lewis rats using bovine S-antigen (S-Ag) peptide. Fenofibrate was suspended in 3% arabic gum and administered orally at a high dose of 100 mg/kg and at a low dose of 20 mg/kg every day. Fenofibrate treatment was initiated after the clinical onset once daily for 14 days. The rats were examined every other day for clinical signs of EAU. The histological scores and delayed-type hypersensitivity (DTH) were evaluated on day 28 post-immunization. Morphologic and immunohistochemical examinations were performed with light and confocal microscopy, respectively. Lymphocyte proliferation was measured with [3H] thymidine incorporation into antigen-stimulated T cells from inguinal lymph nodes. RESULTS: Clinical and histological scores of EAU were decreased in the fenofibrate-treated groups. The expression of inflammatory cytokines and Müller cell proliferation were inhibited in the fenofibrate-treated groups. DTH was significantly inhibited in the fenofibrate-treated groups, compared with the vehicle-treated groups (controls). Lymphocyte proliferation assay demonstrated decreased proliferation in the presence of 25 mg/ml S-Ag peptide in the fenofibrate-treated groups compared with controls. CONCLUSIONS: The current results indicate that fenofibrate administered orally following clinical onset has therapeutic effect in EAU. Fenofibrate may be useful for treating intraocular inflammation.

Three-year visual outcome of photodynamic therapy plus intravitreal bevacizumab with or without subtenon triamcinolone acetonide injections for polypoidal choroidal vasculopathy.

PURPOSE: To compare the 3-year visual outcome after double therapy of photodynamic therapy (PDT) with intravitreal bevacizumab (IVB) and triple therapy of PDT combined with IVB and subtenon triamcinolone acetonide (STTA) injections for polypoidal choroidal vasculopathy (PCV). DESIGN: Retrospective, comparative, interventional case series. METHODS: Medical records for 36 eyes in 36 patients (33 men, 3 women; mean age 73.5 years old; range 63-82 years old) with treatment-naive subfoveal PCV were reviewed retrospectively. Of the 36 eyes, 17 were treated with double therapy and 19 with triple therapy. RESULTS: The change in visual acuity after triple therapy was significantly better than that after double therapy (p<0.05). At 36 months, improvement in visual acuity was seen in 5 eyes (29.4%) in the double therapy group and 10 eyes (52.6%) in the triple therapy group. Retreatment using the initial treatment was performed for six eyes (35.3%) in the double therapy group and five eyes (26.3%) in the triple therapy group, and treatment-free period was significantly longer in the triple therapy group (p<0.05). The mean number of additional antivascular endothelial growth factor therapy was higher in the double therapy group. Post-treatment vitreous haemorrhage or retinal pigment epithelium tear occurred only in the double therapy group, in one eye (5.9%) and one eye (5.9%), respectively. CONCLUSIONS: Initial therapy consisting of a single session of PDT combined with IVB and STTA improves vision in treatment-naive subfoveal PCV. Compared with double therapy, this triple therapy may be more effective for PCV.