Hydrogen effects on nanoindentation behavior of metallic glass ribbons

Recently, metallic glass (MG) membranes that are permeable to hydrogen have gained interest due to the increasing importance of hydrogen separation in a number of applications, e.g., hydrogen-powered fuel cells. An important issue in the context of MG membranes is the hydrogen-induced embrittlement and efforts to understand the role played by hydrogen in the mechanical properties, especially yielding and plastic deformation behavior, of MGs are being made. In this study, therefore, an attempt was made by performing nanoindentation tests with cube-corner and spherical indenter tips on a series of Ni–Nb–Zr amorphous alloy ribbons to investigate the hydrogen effects on nanohardness and pop-in behavior (Figure 1). Weight gain measurements after hydrogen charging and thermal desorption spectroscopy (TDS) studies (Figure 2) were utilized to identify how the total hydrogen is partitioned into mobile and immobile parts. These, in turn, indicate the significant role of hydrogen mobility in the amorphous structure on the mechanical properties. In high-Zr alloys containing immobile H, both hardness (H) and shear yielding stress (τmax) increase significantly; while in low-Zr alloys having only mobile hydrogen, decrease in hardness and τmax were noted (Figure 1). The changes in shear transformation zone (STZ) volume, estimated through cumulative analysis of τmax, caused by hydrogen absorption were also found to depend on hydrogen mobility such that immobile hydrogen reduces the STZ volume while mobile hydrogen increases it. *This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2013R1A1A2A10058551)

An Evaluation of the Weibull and the Logistic Models for Cox's Proportional Hazards Model

Cox's proportional hazards model has been widely used in medical researches to evaluate the relationship between prognostic factors of a disease and the occurrence of outcome event. On a theoretical basis, regression coefficient estimated from Cox's proportional hazards model could be approximated by using the Weibull and the logistic model. Breast cancer cases (n=86) diagnosed at the Seoul National University Hospital were selected to evaluate the possibility of some accelerated models as an approximate model to Cox's proportional hazards model. Age at operation, tumor size and lymph node metastasis were the variables concerned in this study. Parameter estimates of two variables from the Weibull model, which seemed not to violate the proportionality assumption of Cox's model, showed almost identical values to those from Cox's proportional hazards model. However, there was a substantial degree of discrepancy in the parameter estimate of another variable, which showed an apparent unproportionality. This study confirmed that both the Weibull and the logistic models could be used as approximate methods to the estimates from Cox's proportional hazards model. Particularly noteworthy was the fact that the PC-SAS system could be successfully applied to survival analysis when the parameters were going to be estimated using Cox's model

Effects of warming and eutrophication on coastal phytoplankton production

Phytoplankton production in coastal waters influences seafood production and human health and can lead to harmful algal blooms. Water temperature and eutrophication are critical factors affecting phytoplankton production, although the combined effects of warming and nutrient changes on phytoplankton production in coastal waters are not well understood. To address this, phytoplankton production changes in natural waters were investigated using samples collected over eight months, and under 64 different initial conditions, established by combining four different water temperatures (i.e., ambient T, + 2, + 4, and + 6 degrees C), and two different nutrient conditions (i.e., non-enriched and enriched). Under the non-enriched conditions, the effect of warming on phytoplankton production was significantly positive in some months, significantly negative in others, or had no effect. However, under enriched conditions, warming affected phytoplankton production positively in all months except one, when the salinity was as low as 6.5. These results suggest that nutrient conditions can alter the effects of warming on phytoplankton production. Of several parameters, the ratio of initial nitrate concentration to chlorophyll a concentration [NCCA, mu M (pg L-1)(-1))] was one of the most critical factors determining the directionality of the warming effects. In laboratory experiments, when NCCA in the ambient or nutrient-enriched waters was >= 1.2, warming increased or did not change phytoplankton production with one exception; however, when NCCA was < 1.2, warming did not change or decreased production. In the time series data obtained from the coastal waters of four target countries, when NCCA was 1.5 or more, warming increased phytoplankton production, whereas when NCCA was lower than 1.5, warming lowered phytoplankton production, Thus, it is suggested that NCCA could be used as an index for predicting future phytoplankton production changes in coastal waters.11Ysciescopu

Factors associated with late recurrence after completion of 5-year adjuvant tamoxifen in estrogen receptor positive breast cancer

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background Recent large trials have shown the survival benefits of 10-year use of tamoxifen by reducing late recurrence compared with 5-year therapy in estrogen receptor(ER)-positive breast cancer. We tried to identify clinical factors associated with the late recurrence. Methods We reviewed our database of ER-positive patients who had received operations between 1996 and 2006 in two institutions. We selected 444 who had completed 5-year tamoxifen and were disease-free up to 10 years after the operation. Patients who had received aromatase inhibitors with any regimens were excluded. As a late recurrence group, 139 patients were identified who had completed 5-year tamoxifen, but had recurrence afterwards. Among them, 61 had local/contralateral breast recurrence and 78 had distant metastasis. The median follow-up was 9.7 years. Clinicopathological factors at the time of initial operation, such as age, menopausal status, progesterone receptor expression, HER2 status, tumor grade and Ki-67, were compared between the disease-free group and the late recurrence group. Results In a univariate analysis, tumor size (>2 cm), lymph node metastasis and high histologic grade were significantly associated with late recurrences (p < 0.05). In a multivariate analysis, only axillary lymph node metastasis was significant (p < 0.001). Late distant metastasis was significantly associated with tumor size and axillary lymph node metastasis (p = 0.038, p < 0.001,respectively). Late local/contralateral breast recurrence was associated with axillary lymph node metastasis (p = 0.042). Conclusions Our data showed axillary lymph node metastasis at initial operation was the only risk factor of late recurrence after completion of tamoxifen for 5 years. Our results can be helpful in making decisions to use extended tamoxifen beyond 5 years

Clinical Significance of a Large Difference (≥ 2 points) between Biopsy and Post-prostatectomy Pathological Gleason Scores in Patients with Prostate Cancer

We investigated the clinical significance of large difference (≥ 2 points) between biopsy-derived (bGS) and post-prostatectomy Gleason scores (pGS). At 14 medical centers in Korea, 1,582 men who underwent radical prostatectomy for prostate cancer were included. According to the difference between bGS and pGS, the patients were divided into three groups: A (decreased in pGS ≥ 2, n = 30), B (changed in pGS ≤ 1, n = 1,361; control group), and C (increased in pGS ≥ 2, n = 55). We evaluated various clinicopathological factors of prostate cancer and hazards for biochemical failure. Group A showed significantly higher mean maximal percentage of cancer in the positive cores (max%) and pathological T stage than control. In group C, the number of biopsy core was significantly smaller, however, tumor volume and max% were significantly higher and more positive biopsy cores were presented than control. Worse pathological stage and more margin-positive were observed in group A and C than in control. Hazard ratio for biochemical failure was also higher in group A and C (P = 0.001). However, the groups were not independent factors in multivariate analysis. In conclusion, large difference between bGS and pGS shows poor prognosis even in the decreased group. However it is not an independent prognostic factor for biochemical failure

TonEBP recognizes R-loops and initiates m6A RNA methylation for R-loop resolution

R-loops are three-stranded, RNA???DNA hybrid, nucleic acid structures produced due to inappropriate processing of newly transcribed RNA or transcription-replication collision (TRC). Although R-loops are important for many cellular processes, their accumulation causes genomic instability and malignant diseases, so these structures are tightly regulated. It was recently reported that R-loop accumulation is resolved by methyltransferase-like 3 (METTL3)-mediated m6A RNA methylation under physiological conditions. However, it remains unclear how R-loops in the genome are recognized and induce resolution signals. Here, we demonstrate that tonicity-responsive enhancer binding protein (TonEBP) recognizes R-loops generated by DNA damaging agents such as ultraviolet (UV) or camptothecin (CPT). Single-molecule imaging and biochemical assays reveal that TonEBP preferentially binds a R-loop via both 3D collision and 1D diffusion along DNA in vitro. In addition, we find that TonEBP recruits METTL3 to R-loops through the Rel homology domain (RHD) for m6A RNA methylation. We also show that TonEBP recruits RNaseH1 to R-loops through a METTL3 interaction. Consistent with this, TonEBP or METTL3 depletion increases R-loops and reduces cell survival in the presence of UV or CPT. Collectively, our results reveal an R-loop resolution pathway by TonEBP and m6A RNA methylation by METTL3 and provide new insights into R-loop resolution processes

DNA Methylation and Expression Patterns of Key Tissue-specific Genes in Adult Stem Cells and Stomach Tissues

CpG-island margins and non-island-CpG sites round the transcription start sites of CpG-island-positive and -negative genes are methylated to various degrees in a tissue-specific manner. These methylation-variable CpG sites were analyzed to delineate a relationship between the methylation and transcription of the tissue-specific genes. The level of tissue-specific transcription was estimated by counting the number of the total transcripts in the SAGE (serial analysis of gene expression) database. The methylation status of 12 CpG-island margins and 21 non-island CpG sites near the key tissue-specific genes was examined in pluripotent stromal cells obtained from fat and bone marrow samples as well as in lineage-committed cells from marrow bulk, stomach, colon, breast, and thyroid samples. Of the 33 CpG sites examined, 10 non-island-CpG sites, but none of the CpG-island margins were undermethylated concurrent with tissue-specific expression of their nearby genes. The net methylation of the 33 CpG sites and the net amount of non-island-CpG gene transcripts were high in stomach tissues and low in stromal cells. The present findings suggest that the methylation of the non-island-CpG sites is inversely associated with the expression of the nearby genes, and the concert effect of transitional-CpG methylation is linearly associated with the stomach-specific genes lacking CpG-islands

Fimasartan versus perindopril with and without diuretics in the treatment of elderly patients with essential hypertension (Fimasartan in the Senior Subjects (FITNESS)): study protocol for a randomized controlled trial

Background Hypertension is an important risk factor for cardiovascular disease, even in the elderly. Fimasartan is a new non-peptide angiotensin II receptor blocker with a selective type I receptor blocking effect. The objective of this study is to confirm the safety and the non-inferiority of the blood pressure–lowering effect of fimasartan compared with those of perindopril, which has been proven safe and effective in elderly patients with hypertension. Methods This is a randomized, double-blind, active-controlled, two-parallel group, optional-titration, multicenter, phase 3 study comparing the efficacy and safety of fimasartan and perindopril arginine. The study population consists of individuals 70 years old or older with essential hypertension. The primary outcome will be a change in sitting systolic blood pressure from baseline after the administration of the investigational product for 8 weeks. The secondary outcomes will be a change in sitting diastolic blood pressure from baseline and changes in sitting systolic blood pressure and diastolic blood pressure from baseline after the administration of the investigational product for 4, 16, and 24 weeks. The sample size will be 119 subjects for each group to confer enough power to test for the primary outcome. Discussion Research to confirm the efficacy and safety of a new medicine compared with those of previously proven anti-hypertensive drugs is beneficial to guide physicians in the selection of therapeutic agents. If it is confirmed that the new drug is not inferior to the existing drug, the drug will be considered as an option in the treatment of hypertension in elderly patients. Trial registration ClinicalTrials.gov Identifier: NCT03246555, registered on July 25, 2017.The study is funded by Boryung Pharmaceutical Co., Ltd. The company was involved in all stages of the study conduct and design. Boryung also took responsibility for all costs associated with the development and publishing of the manuscript