Combined experimental and theoretical studies on glasslike transitions in the frustrated molecular conductors θ\theta-(BEDT-TTF)2MM′_2MM'(SCN)4_4

We present results of the coefficient of thermal expansion for the frustrated quasi-two-dimensional molecular conductor $\theta$-(BEDT-TTF)$_2$RbZn(SCN)$_4$ for temperatures 1.5 K $\leq T \leq$ 290 K. A pronounced first-order phase transition anomaly is observed at the combined charge-order/structural transition at 215 K. Furthermore, clear evidence is found for two separate glasslike transitions at $T_{\mathrm{g}}$ = 90-100 K and $T_{\mathrm{g}}^\dagger$ = 120-130 K, similar to previous findings for $\theta$-(BEDT-TTF)$_2$CsZn(SCN)$_4$ and $\theta$-(BEDT-TTF)$_2$CsCo(SCN)$_4$, reported in T. Thomas et al., Phys. Rev. B 105, L041114 (2022), both of which lack the charge-order/structural transition. Our findings indicate that these glasslike transitions are common features for the $\theta$-(BEDT-TTF)$_2MM^\prime$(SCN)$_4$ family with $M$ = (Rb, Cs) and $M^\prime$ = (Co, Zn), irrespective of the presence or absence of charge order. These results are consistent with our model calculations on the glasslike dynamics associated with the flexible ethylene endgroups of the BEDT-TTF molecules for various $\theta$-(BEDT-TTF)$_2MM^\prime$(SCN)$_4$ salts, predicting two different conformational glass transitions. Moreover, calculations of the hopping integrals show a substantial degree of dependence on the endgroups' conformation, suggesting a significant coupling to the electronic degrees of freedom. Our findings support the possibility that the glassy freezing of the ethylene endgroups could drive or enhance glassy charge dynamics.Comment: 11 pages, 10 figures, 1 tabl

Long interspersed nuclear element-1 hypomethylation is a potential biomarker for the prediction of response to oral fluoropyrimidines in microsatellite stable and CpG island methylator phenotype-negative colorectal cancer

金沢大学がん研究所We investigated the clinical value of methylation of long interspersed nuclear element-1 (LINE-1) for the prognosis of colorectal cancer (CRC) and for the survival benefit from adjuvant chemotherapy with oral fluoropyrimidines. LINE-1 methylation in tumor DNA was measured by quantitative methylation-specific PCR in 155 samples of stage II and stage III CRC. The presence of microsatellite instability and CpG island methylator phenotype (CIMP) were assessed and 131 microsatellite stable/CIMP- cases were selected for survival analysis, of which 77 patients had received postoperative adjuvant chemotherapy with oral fluoropyrimidines. The CRC cell lines were used to investigate possible mechanistic links between LINE-1 methylation and effects of 5-fluorouracil (5-FU). High LINE-1 methylation was a marker for better prognosis in patients treated by surgery alone. Patients with low LINE-1 methylation who were treated with adjuvant chemotherapy survived longer than those treated by surgery alone, suggestive of a survival benefit from the use of oral fluoropyrimidines. In contrast, a survival benefit from chemotherapy was not observed for patients with high LINE-1 methylation. The CRC cell lines treated with 5-FU showed increased expression of LINE-1 mRNA. This was associated with upregulation of the phospho-histone H2A.X in cells with low LINE-1 methylation, but not in cells with high LINE-1 methylation. The 5-FU-mediated induction of phospho-histone H2A.X, a marker of DNA damage, was inhibited by knockdown of LINE-1. These results suggest that LINE-1 methylation is a novel predictive marker for survival benefit from adjuvant chemotherapy with oral fluoropyrimidines in CRC patients. This finding could be important for achieving personalized chemotherapy. © 2010 Japanese Cancer Association

Long interspersed nuclear element 1 hypomethylation is a marker of poor prognosis in stage IA non-small cell lung cancer

金沢大学がん研究所Purpose: Global hypomethylation and the hypermethylation of gene promoter regions are common events in tumor DNA. The aim of this study was to evaluate the prognostic significance of both global hypomethylation and gene promoter hypermethylation in DNA from non-small cell lung cancer (NSCLC). Experimental Design: Genomic DNA was obtained from the tumor tissue of 379 NSCLC patients who underwent surgery. Methylation levels were measured by real-time PCR following bisulfite modification of DNA and were correlated with clinicopathologic parameters and patient prognosis. Methylation of long interspersed nuclear element 1 (LINE-1) was used as a surrogate marker for global methylation. Hypermethylation of the APC, CDH13, and RASSF1 promoter regions was also evaluated. Results: Tumor tissue showed significantly higher CDH13 and RASSF1 methylation levels compared with normal lung tissue, but lower LINE-1 methylation levels. APC, RASSF1, and LINE-1 methylation levels were significant prognostic factors in univariate analysis of an initial cohort of 234 cases. APC and LINE-1 methylation remained significant prognostic factors in multivariate analysis that included age, gender, smoking history, histologic type, and pathologic stage. LINE-1 methylation showed marginally significant prognostic value in stage IA and IB disease. Expansion of the study cohort to 364 cases revealed that LINE-1 methylation had significant prognostic value for stage IA NSCLC patients in multivariate analysis. Conclusions: LINE-1 hypomethylation was an independent marker of poor prognosis in stage IA NSCLC. Validation of this finding in additional tumor cohorts could have clinical relevance for the management of early-stage NSCLC. ©2010 AACR

Expression of human mutant cyclin dependent kinase 4, Cyclin D and telomerase extends the life span but does not immortalize fibroblasts derived from loggerhead sea turtle (Caretta caretta)

Conservation of the genetic resources of endangered animals is crucial for future generations. The loggerhead sea turtle (Caretta caretta) is a critically endangered species, because of human hunting, hybridisation with other sea turtle species, and infectious diseases. In the present study, we established primary fibroblast cell lines from the loggerhead sea turtle, and showed its species specific chromosome number is 2n = 56, which is identical to that of the hawksbill and olive ridley sea turtles. We first showed that intensive hybridization among multiple sea turtle species caused due to the identical chromosome number, which allows existence of stable hybridization among the multiple sea turtle species. Expressions of human-derived mutant Cyclin-dependent kinase 4 (CDK4) and Cyclin D dramatically extended the cell culture period, when it was compared with the cell culture period of wild type cells. The recombinant fibroblast cell lines maintained the normal chromosome condition and morphology, indicating that, at the G1/S phase, the machinery to control the cellular proliferation is evolutionally conserved among various vertebrates. To our knowledge, this study is the first to demonstrate the functional conservation to overcome the negative feedback system to limit the turn over of the cell cycle between mammalian and reptiles. Our cell culture method will enable the sharing of cells from critically endangered animals as research materials

Development of the photomultiplier tube readout system for the first Large-Sized Telescope of the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) is the next generation ground-based very high energy gamma-ray observatory. The Large-Sized Telescope (LST) of CTA targets 20 GeV -- 1 TeV gamma rays and has 1855 photomultiplier tubes (PMTs) installed in the focal plane camera. With the 23 m mirror dish, the night sky background (NSB) rate amounts to several hundreds MHz per pixel. In order to record clean images of gamma-ray showers with minimal NSB contamination, a fast sampling of the signal waveform is required so that the signal integration time can be as short as the Cherenkov light flash duration (a few ns). We have developed a readout board which samples waveforms of seven PMTs per board at a GHz rate. Since a GHz FADC has a high power consumption, leading to large heat dissipation, we adopted the analog memory ASIC "DRS4". The sampler has 1024 capacitors per channel and can sample the waveform at a GHz rate. Four channels of a chip are cascaded to obtain deeper sampling depth with 4096 capacitors. After a trigger is generated in a mezzanine on the board, the waveform stored in the capacitor array is subsequently digitized with a low speed (33 MHz) ADC and transferred via the FPGA-based Gigabit Ethernet to a data acquisition system. Both a low power consumption (2.64 W per channel) and high speed sampling with a bandwidth of $>$300 MHz have been achieved. In addition, in order to increase the dynamic range of the readout we adopted a two gain system achieving from 0.2 up to 2000 photoelectrons in total. We finalized the board design for the first LST and proceeded to mass production. Performance of produced boards are being checked with a series of quality control (QC) tests. We report the readout board specifications and QC results.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) play critical roles in induction and exacerbation of allergic airway inflammation. Thus, clarification of the mechanisms that underlie the regulation of ILC2 activation has received significant attention. Although ILCs are divided into three major subsets that mirror helper effector T-cell subsets, counterpart subsets of regulatory T (Treg) cells have not been well characterized. OBJECTIVE: We sought to determine the factors that induce regulatory ILCs (ILCregs). METHODS: IL-10+ ILCregs induced from ILC2s by retinoic acid (RA) were analyzed using RNA-sequencing and flow cytometry. ILCregs were evaluated in human nasal tissues from healthy individuals and patients with chronic rhinosinusitis with nasal polyp (CRSwNP), and in lung tissues from house dust mite (HDM)- or saline-treated mice. RESULTS: RA induced IL-10 secretion by human ILC2s, but not type-2 cytokines. IL-10+ ILCregs, converted from ILC2s by RA stimulation, expressed a Treg-like signature with the expression of IL-10, CTLA-4 and CD25, with down regulated effector type 2-related markers such as CRTH-2 and ST2, and suppressed activation of CD4+ T cells and ILC2s. ILCregs were rarely detected in human nasal tissue from healthy individuals or lung tissues from saline-treated mice, but were increased in nasal tissues from patients with CRSwNP and in lung tissues from HDM-treated mice. Enzymes for RA synthesis were up-regulated in airway epithelial cells during type-2 inflammation in vivo and by IL-13 in vitro. CONCLUSION: We have identified a unique immune regulatory and anti-inflammatory pathway by which RA converts ILC2s to ILCregs. Interactions between airway epithelial cells and ILC2s play an important roles in the generation of ILCregs

2008 Inter-laboratory Comparison Study of a Reference Material for Nutrients in Seawater

Autoclaved natural seawater collected in the North Pacific Ocean was used as a reference material for nutrients in seawater (RMNS) during an inter-laboratory comparison (I/C) study conducted in 2008. This study was a follow-up to previous studies conducted in 2003 and 2006. A set of six samples was distributed to each of 58 laboratories in 15 countries around the globe, and results were returned by 54 of those laboratories (15 countries). The homogeneities of samples used in the 2008 I/C study, based on analyses for three determinants, were improved compared to those of samples used in the 2003 and 2006 I/C studies. Results of these I/C studies indicate that most of the participating laboratories have an analytical technique for nutrients that is sufficient to provide data of high comparability. The differences between reported concentrations from the same laboratories in the 2006 and 2008 I/C studies for the same batch of RMNS indicate that most of the laboratories have been maintaining internal comparability for two years. Thus, with the current high level of performance in the participating laboratories, the use of a common reference material and the adaptation of an internationally accepted nutrient scale system would increase comparability among laboratories worldwide, and the use of a certified reference material would establish traceability. In the 2008 I/C study we observed a problem of non-linearity of the instruments of the participating laboratories similar to that observed among the laboratories in the 2006 I/C study. This problem of non-linearity should be investigated and discussed to improve comparability for the full range of nutrient concentrations. For silicate comparability in particular, we see relatively larger consensus standard deviations than those for nitrate and phosphate

Complications Associated With Spine Surgery in Patients Aged 80 Years or Older: Japan Association of Spine Surgeons with Ambition (JASA) Multicenter Study

Study Design:Retrospective study of registry data.Objectives:Aging of society and recent advances in surgical techniques and general anesthesia have increased the demand for spinal surgery in elderly patients. Many complications have been described in elderly patients, but a multicenter study of perioperative complications in spinal surgery in patients aged 80 years or older has not been reported. Therefore, the goal of the study was to analyze complications associated with spine surgery in patients aged 80 years or older with cervical, thoracic, or lumbar lesions.Methods:A multicenter study was performed in patients aged 80 years or older who underwent 262 spinal surgeries at 35 facilities. The frequency and severity of complications were examined for perioperative complications, including intraoperative and postoperative complications, and for major postoperative complications that were potentially life threatening, required reoperation in the perioperative period, or left a permanent injury.Results:Perioperative complications occurred in 75 of the 262 surgeries (29%) and 33 were major complications (13%). In multivariate logistic regression, age over 85 years (hazard ratio [HR] = 1.007, P = 0.025) and estimated blood loss ≥500 g (HR = 3.076, P = .004) were significantly associated with perioperative complications, and an operative time ≥180 min (HR = 2.78, P = .007) was significantly associated with major complications.Conclusions:Elderly patients aged 80 years or older with comorbidities are at higher risk for complications. Increased surgical invasion, and particularly a long operative time, can cause serious complications that may be life threatening. Therefore, careful decisions are required with regard to the surgical indication and procedure in elderly patients