Statistical Verification of Anomaly in Chiral Angle Distribution of Air-Suspended Carbon Nanotubes

Single-walled carbon nanotubes (SWCNT) have long attracted attention due to their distinct physical properties, depending on their chiral structures (chiralities). Clarifying their growth mechanism is important toward perfect chirality-controlled bulk synthesis. Although a correlation between the chirality distribution and the carbon atom configuration at an open tube edge has been predicted theoretically, lack of sufficient statistical data on metallic and semiconducting SWCNTs prohibited its verification. Here, we report statistical verification of the chirality distribution of 413 as-grown individual air-suspended SWCNTs with a length of over 20 μm using broadband Rayleigh spectroscopy. After excluding the impact of the difference in the number of possible SWCNT structures per chiral angle interval, the abundance profile with chiral angle exhibits an increasing trend with a distinct anomaly at a chiral angle of approximately 20°. These results are well explained considering the growth rate depending on armchair-shaped site configurations at the catalyst–nanotube interface

An engineered chaperonin caging a guest protein: Structural insights and potential as a protein expression tool

The structure of a chaperonin caging a substrate protein is not quite clear. We made engineered group II chaperonins fused with a guest protein and analyzed their structural and functional features. Thermococcus sp. KS-1 chaperonin α-subunit (TCP) which forms an eightfold symmetric double-ring structure was used. Expression plasmids were constructed which carried two or four TCP genes ligated head to tail in phase and a target protein gene at the 3′ end of the linked TCP genes. Electron microscopy showed that the expressed gene products with the molecular sizes of ~120 kDa (di-TCP) and ~230 kDa (tetra-TCP) formed double-ring complexes similar to those of wild-type TCP. The tetra-TCP retained ATPase activity and its thermostability was significantly higher than that of the wild type. A 260-kDa fusion protein of tetra-TCP and green fluorescent protein (GFP, 27 kDa) was able to form the double-ring complexes with green fluorescence. Image analyses indicated that the GFP moiety of tetra-TCP/GFP fusion protein was accommodated in the central cavity, and tetra-TCP/GFP formed the closed-form similar to that crystallographically resolved in group II chaperonins. Furthermore, it was suggested that caging GFP expanded the cavity around the bottom. Using this tetra-TCP fusion strategy, two virus structural proteins (21–25 kDa) toxic to host cells or two antibody fragments (25–36 kDa) prone to aggregate were well expressed in the soluble fraction of Escherichia coli. These fusion products also assembled to double-ring complexes, suggesting encapsulation of the guest proteins. The antibody fragments liberated by site-specific protease digestion exhibited ligand-binding activities

Dose escalation of external beam radiotherapy for high-risk prostate cancer—Impact of multiple high-risk factor

Objective: To retrospectively investigate the treatment outcomes of external beam radiotherapy with androgen deprivation therapy (ADT) in high-risk prostate cancer in three radiotherapy dose groups. Methods: Between 1998 and 2013, patients with high-risk prostate cancer underwent three-dimensional conformal radiotherapy or intensity-modulated radiotherapy of 66 Gy, 72 Gy, or 78 Gy with ADT. Prostate-specific antigen (PSA) relapse was defined using the Phoenix definition. PSA relapse-free survival (PRFS) was evaluated in each radiotherapy dose group. Moreover, high-risk patients were divided into H-1 (patients with multiple high-risk factors) and H-2 (patients with a single high-risk factor) as risk subgroups. Results: Two hundred and eighty-nine patients with a median follow-up period of 77.3 months were analyzed in this study. The median duration of ADT was 10.1 months. Age, Gleason score, T stage, and radiotherapy dose influenced PRFS with statistical significance both in univariate and multivariate analyses. The 4-year PRFS rates in Group-66 Gy, Group-72 Gy and Group-78 Gy were 72.7%, 81.6% and 90.3%, respectively. PRFS rates in the H-1 subgroup differed with statistical significance with an increasing radiotherapy dose having a more favorable PRFS, while PRFS rates in H-2 subgroup did not differ with increase in radiotherapy dose. Conclusion: Dose escalation for high-risk prostate cancer in combination with ADT improved PRFS. PRFS for patients in the H-1 subgroup was poor, but dose escalation in those patients was beneficial, while dose escalation in the H-2 subgroup was not proven to be effective for improving PRFS. Keywords: Prostate cancer, External beam radiotherapy, Dose escalation, Biochemical contro

A hybrid technique of intracavitary and interstitial brachytherapy for locally advanced cervical cancer: initial outcomes of a single-institute experience

Abstract Background Locally advanced uterine cervical cancer (LAUCC) with lateral tumor extension may not always be covered adequately by conventional intracavitary brachytherapy (ICBT). Hybrid intracavitary and interstitial brachytherapy (HBT) seems to be an effective alternative by improving anatomy-oriented dose optimisation. The purpose of this study was to report initial clinical result for LAUCC treated by HBT. Methods Between January 2012 and November 2015, 42 patients with LAUCC (T1b2-4a) were treated with primary radiation therapy including HBT. Patients with distant metastasis other than para-aortic lymph node spread were excluded from this study. A retrospective analysis was performed for toxicity evaluation and oncological outcome calculation. Results Median follow-up was 23.2 months (range 13.2–71.4). Two-year overall survival, progression free survival, and local control rate were 81.6, 54.4, and 80.2%, respectively. Seven patients experienced local recurrence (16.6%). Of those, five were confined to the uterus and two at the parametria. Late adverse events ≥ grade 3 were seen in 3 patients. Conclusions HBT can generate favorable local control in tumors which cannot be adequately covered by ICBT

Characterization of cytoskeletal and structural effects of INF2 variants causing glomerulopathy and neuropathy

Abstract Focal segmental glomerulosclerosis (FSGS) is a common glomerular injury leading to end-stage renal disease. Monogenic FSGS is primarily ascribed to decreased podocyte integrity. Variants between residues 184 and 245 of INF2, an actin assembly factor, produce the monogenic FSGS phenotype. Meanwhile, variants between residues 57 and 184 cause a dual-faceted disease involving peripheral neurons and podocytes (Charcot–Marie–Tooth CMT/FSGS). To understand the molecular basis for INF2 disorders, we compared structural and cytoskeletal effects of INF2 variants classified into two subgroups: One (G73D, V108D) causes the CMT/FSGS phenotype, and the other (T161N, N202S) produces monogenic FSGS. Molecular dynamics analysis revealed that all INF2 variants show distinct flexibility compared to the wild-type INF2 and could affect stability of an intramolecular interaction between their N- and C-terminal segments. Immunocytochemistry of cells expressing INF2 variants showed fewer actin stress fibers, and disorganization of cytoplasmic microtubule arrays. Notably, CMT/FSGS variants caused more prominent changes in mitochondrial distribution and fragmentation than FSGS variants and these changes correlated with the severity of cytoskeletal disruption. Our results indicate that CMT/FSGS variants are associated with more severe global cellular defects caused by disrupted cytoskeleton-organelle interactions than are FSGS variants. Further study is needed to clarify tissue-specific pathways and/or cellular functions implicated in FSGS and CMT phenotype