Change in thermal transitions and water uptakes of poly(l-lactic acid) blends upon hydrolytic degradation

AbstractThis article reports experimental data related to the research article entitled “Poly(malic acid-co-l-lactide) as a Superb Degradation Accelerator for Poly(l-lactic acid) at Physiological Conditions” (H.T. Oyama, D. Tanishima, S. Maekawa, 2016) [1]. Hydrolytic degradation of poly(l-lactic acid) (PLLA) blends with poly(aspartic acid-co-l-lactide) (PAL) and poly(malic acid-co-l-lactide) (PML) oligomers was investigated in a phosphate buffer solution at 40°C. It was found in the differential scanning calorimetry measurements that upon hydrolysis the cold crystallization temperature (Tc) and the melting temperature (Tm) significantly shifted to lower temperature. Furthermore, the hydrolysis significantly promoted water sorption in both blends

Triple-helix potential of the mouse genome

Certain DNA sequences, including mirror-symmetric polypyrimidine•polypurine runs, are capable of folding into a triple-helix–containing non–B-form DNA structure called H-DNA. Such H-DNA–forming sequences occur frequently in many eukaryotic genomes, including in mammals, and multiple lines of evidence indicate that these motifs are mutagenic and can impinge on DNA replication, transcription, and other aspects of genome function. In this study, we show that the triplex-forming potential of H-DNA motifs in the mouse genome can be evaluated using S1-sequencing (S1-seq), which uses the single-stranded DNA (ssDNA)–specific nuclease S1 to generate deep-sequencing libraries that report on the position of ssDNA throughout the genome. When S1-seq was applied to genomic DNA isolated from mouse testis cells and splenic B cells, we observed prominent clusters of S1-seq reads that appeared to be independent of endogenous double-strand breaks, that coincided with H-DNA motifs, and that correlated strongly with the triplex-forming potential of the motifs. Fine-scale patterns of S1-seq reads, including a pronounced strand asymmetry in favor of centrally positioned reads on the pyrimidine-containing strand, suggested that this S1-seq signal is specific for one of the four possible isomers of H-DNA (H-y5). By leveraging the abundance and complexity of naturally occurring H-DNA motifs across the mouse genome, we further defined how polypyrimidine repeat length and the presence of repeat-interrupting substitutions modify the structure of H-DNA. This study provides an approach for studying DNA secondary structure genome-wide at high spatial resolution

光学材料および生体材料評価に関する第一原理計算法の研究

筑波大学 (University of Tsukuba)201

Efficacy of salvage therapies for advanced acral melanoma after anti-PD-1 monotherapy failure: a multicenter retrospective study of 108 Japanese patients

BackgroundAnti-programmed cell death protein 1 (PD-1) monotherapy is one of the standard systemic therapies for advanced melanoma; however, the efficacy of salvage systemic therapies after PD-1 monotherapy failure (PD-1 MF), particularly in acral melanoma (AM), the main clinical melanoma type in Japanese patients, is unclear. This study aimed to investigate the efficacy of salvage systemic therapies in Japanese patients with AM after PD-1 MF.Patients and methodsThe study included 108 patients with advanced AM (palm and sole, 72; nail apparatus, 36) who underwent salvage systemic therapy at 24 Japanese institutions. We mainly assessed the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).ResultsThirty-six (33%) patients received ipilimumab, 23 (21%) received nivolumab and ipilimumab (nivo/ipi), 10 (9%) received cytotoxic chemotherapy, 4 (4%) received BRAF and MEK inhibitors (BRAFi/MEKi), and the remaining 35 (32%) continued with PD-1 monotherapy after disease progression. The ORRs in the ipilimumab, nivo/ipi, cytotoxic chemotherapy, and BRAFi/MEKi groups were 8, 17, 0, and 100%, respectively. The nivo/ipi group showed the longest OS (median, 18.9 months); however, differences in ORR, PFS, and OS between the groups were insignificant. The OS in the nivo/ipi group was higher in the palm and sole groups than in the nail apparatus group (median: not reached vs. 8.7 months, p < 0.001). Cox multivariate analysis demonstrated that nail apparatus melanoma independently predicted unfavorable PFS and OS (p = 0.006 and 0.001). The total OS (from PD-1 monotherapy initiation to death/last follow-up) was insignificant between the groups.ConclusionNivo/ipi was not more effective than cytotoxic chemotherapy and ipilimumab after PD-1 MF in patients with advanced AM. The prognosis after PD-1 MF would be poorer for nail apparatus melanoma than for palm and sole melanoma

Polarizabilities from Long-Range Corrected DFT Calculations

The long-range corrected DFT functionals, LC-BLYP, LC-PBE and CAM-B3LYP with the augmented Dunning-type triple-ζ basis sets represent dynamical polarizabilities at λ = 589.3 nm of 105 medium-sized organic compounds containing C, H, O, N, S, P, F, Cl, Br and I elements with the root mean squared deviations (RMSD) of about 0.34, 0.35, and 0.42 ų, respectively. These errors do not change appreciably when the augmented double-ζ basis sets are used. The functionals with 100% of Hartree–Fock (HF) exchange at long-range perform best for aromatic compounds and the CAM-B3LYP or B3LYP functionals for fully saturated compounds. The degrees of HF exchange in mid- and long-range affect strongly the shape and location of the distributions of absolute errors in polarizability, <i>P</i>(Δα). The differences between functionals belonging to the BLYP and PBE families, and having the same degree of HF exchange, have much smaller effect on the <i>P</i>(Δα) distributions

Necroptosis of neuronal cells is related to the neuropathology of tick-borne encephalitis

Tick-borne encephalitis virus (TBEV) is a zoonotic virus that causes tick-borne encephalitis (TBE) in humans. Infections of Sapporo-17-Io1 (Sapporo) and Oshima 5-10 (Oshima) TBEV strains showed different pathogenic effects in mice. However, the differences between the two strains are unknown. In this study, we examined neuronal degeneration and death, and activation of glial cells in mice inoculated with each strain to investigate the pathogenesis of TBE. Viral growth was similar between Sapporo and Oshima, but neuronal degeneration and death, and activation of glial cells, was more prominent with Oshima. In human neuroblastoma cells, apoptosis and pyroptosis were not observed after TBEV infection. However, the expression of the necroptosis marker, mixed lineage kinase domain-like (MLKL) protein, was upregulated by TBEV infection, and this upregulation was more pronounced in Oshima than Sapporo infections. As necroptosis is a pro-inflammatory type of cell death, differences in necroptosis induction might be involved in the differences in neuropathogenicity of TBE