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In this study, we compared the effects of cooperative flipped learning (CFL) on science achievement and learning motivation with those of simple flipped learning (SFL) and traditional lecture (TL) ...

The multiply Type-II hybrid censoring scheme is disadvantaged by an experiment time that is too long. To overcome this limitation, we propose a generalized multiply Type-II hybrid censoring scheme. Some estimators of the scale parameter of the exponential distribution are derived under a generalized multiply Type-II hybrid censoring scheme. First, the maximum likelihood estimator of the scale parameter of the exponential distribution is obtained under the proposed censoring scheme. Second, we obtain the Bayes estimators under different loss functions with a noninformative prior and an informative prior. We approximate the Bayes estimators by Lindleys approximation and the Tierney-Kadane method since the posterior distributions obtained by the two priors are complicated. In addition, the Bayes estimators are obtained by using the Markov Chain Monte Carlo samples. Finally, all proposed estimators are compared in the sense of the mean squared error through the Monte Carlo simulation and applied to real data.

In recent years, the supply of electric vehicles, which are eco-friendly cars that use electric energy rather than fossil fuels, which cause air pollution, is increasing. Accordingly, it is emerging as an urgent task to predict the charging demand for the smooth supply of electric energy required to charge electric vehicle batteries. In this paper, to predict the charging demand, time series analysis is performed based on two types of frames: One is using traditional time series techniques such as dynamic harmonic regression, seasonal and trend decomposition using Loess, and Bayesian structural time series. The other is the most widely used machine learning techniques, including random forest and extreme gradient boosting. However, the tree-based machine learning approaches have the disadvantage of not being able to capture the trend, so a hybrid strategy is proposed to overcome this problem. In addition, the seasonal variation is reflected as the feature by using the Fourier transform which is useful in the case of describing the seasonality patterns of time series data with multiple seasonality. The considered time series models are compared and evaluated through various accuracy measures. The experimental results show that the machine learning approach based on the hybrid strategy generally achieves significant improvements in predicting the charging demand. Moreover, when compared with the original machine learning method, the prediction based on the proposed hybrid strategy is more accurate than that based on the original machine learning method. Based on these results, it can find out that the proposed hybrid strategy is useful for smoothly planning future power supply and demand and efficiently managing electricity grids.

As the semiconductor industry has advanced, precisely patterned wafers of the sub-nanometer scale have been produced; hence, the development of cleaning reagents to remove contaminants from such wafers has received increasing attention. However, conventional cleaning solutions have significant drawbacks, including high cost and toxicity to both humans and the environment. In this work, we developed an eco-friendly cleaning reagent containing cellulose nanocrystals (CNCs) and a biodegradable amphoteric surfactant, cocamidopropyl betaine (CAPB), at optimal concentrations. The proposed system was applicable to both bare and patterned wafers, achieving a contaminant removal efficiency of ca. 100% without wafer damage. After investigating the cleaning mechanism utilizing different analytical techniques, we determined that the synergistic effect of the CNC/CAPB and free CAPB that includes the physical bombardment, electrostatic repulsion, and the adsorption inhibition of contaminants, contribute to the effective cleaning process. We expect this eco-friendly and cost-effective cleaning reagent to be readily adopted in the production of semiconductor products, as it could reduce the overall cost of producing electronics.

In this paper, we derive some estimators of the scale parameter of the exponentiated half-logistic distribution based on the multiply Type-I hybrid censoring scheme. We assume that the shape parameter λ is known. We obtain the maximum likelihood estimator of the scale parameter σ. The scale parameter is estimated by approximating the given likelihood function using two different Taylor series expansions since the likelihood equation is not explicitly solved. We also obtain Bayes estimators using prior distribution. To obtain the Bayes estimators, we use the squared error loss function and general entropy loss function (shape parameter q = -0.5, 1.0). We also derive interval estimation such as the asymptotic confidence interval, the credible interval, and the highest posterior density interval. Finally, we compare the proposed estimators in the sense of the mean squared error through Monte Carlo simulation. The average length of 95% intervals and the corresponding coverage probability are also obtained.

The unique Escherichia coli GTPase Der (double Era-like GTPase), which contains tandemly repeated GTP-binding domains, has been shown to play an essential role in 50S ribosomal subunit biogenesis. The depletion of Der results in the accumulation of precursors of 50S ribosomal subunits that are structurally unstable at low Mg 2+ concentrations. Der homologs are ubiquitously found in eubacteria. Conversely, very few are conserved in eukaryotes, and none is conserved in archaea. In the present study, to verify their conserved role in bacterial 50S ribosomal subunit biogenesis, we cloned Der homologs from two gammaproteobacteria, Klebsiella pneumoniae and Salmonella enterica serovar Typhimurium; two pathogenic bacteria, Staphylococcus aureus and Neisseria gonorrhoeae ; and the extremophile Deinococcus radiodurans and then evaluated whether they could functionally complement the E. coli der -null phenotype. Only K. pneumoniae and S . Typhimurium Der proteins enabled the E. coli der -null strain to grow under nonpermissive conditions. Sucrose density gradient experiments revealed that the expression of K. pneumoniae and S . Typhimurium Der proteins rescued the structural instability of 50S ribosomal subunits, which was caused by E. coli Der depletion. To determine what allows their complementation, we constructed Der chimeras. We found that only Der chimeras harboring both the linker and long C-terminal regions could reverse the growth defects of the der -null strain. Our findings suggest that ubiquitously conserved essential GTPase Der is involved in 50S ribosomal subunit biosynthesis in various bacteria and that the linker and C-terminal regions may participate in species-specific recognition or interaction with the 50S ribosomal subunit. IMPORTANCE In Escherichia coli , Der (double Era-like GTPase) is an essential GTPase that is important for the production of mature 50S ribosomal subunits. However, to date, its precise role in ribosome biogenesis has not been clarified. In this study, we used five Der homologs from gammaproteobacteria, pathogenic bacteria, and an extremophile to elucidate their conserved function in 50S ribosomal subunit biogenesis. Among them, Klebsiella pneumoniae and Salmonella enterica serovar Typhimurium Der homologs implicated the participation of Der in ribosome assembly in E. coli . Our results show that the linker and C-terminal regions of Der homologs are correlated with its functional complementation in E. coli der mutants, suggesting that they are involved in species-specific recognition or interaction with 50S ribosomal subunits.

In this paper, some estimators of the scale parameter of the half-logistic distribution are derived under the multiply Type-II hybrid censoring scheme. We propose three methods. First, we obtain the maximum likelihood estimator of the scale parameter of the half-logistic distribution. Second, we propose some approximate maximum likelihood estimators of the scale parameter by employing three different types of Taylor series expansions. Lastly, we obtain the Bayes estimators by employing some prior distributions and loss functions. The interval estimations such as the asymptotic confidence interval and the credible interval and the highest posterior density interval are obtained. To assess the performance of the proposed estimators, we obtain the mean squared error, average length of 95% interval and coverage probability through Monte Carlo simulation and applies to the real dataset.

Highlight Plant NSN1 has GTPase and RNA-binding activities. In the nucleolus, NSN1 is involved in rRNA maturation and ribosome biogenesis through interaction with PES, EBP2, and several ribosomal proteins., Nucleostemin is a nucleolar GTP-binding protein that is involved in stem cell proliferation, embryonic development, and ribosome biogenesis in mammals. Plant nucleostemin-like 1 (NSN1) plays a role in embryogenesis, and apical and floral meristem development. In this study, a nucleolar function of NSN1 in the regulation of ribosome biogenesis was identified. Green fluorescent protein (GFP)-fused NSN1 localized to the nucleolus, which was primarily determined by its N-terminal domain. Recombinant NSN1 and its N-terminal domain (NSN1-N) bound to RNA in vitro. Recombinant NSN1 expressed GTPase activity in vitro. NSN1 silencing in Arabidopsis thaliana and Nicotiana benthamiana led to growth retardation and premature senescence. NSN1 interacted with Pescadillo and EBNA1 binding protein 2 (EBP2), which are nucleolar proteins involved in ribosome biogenesis, and with several ribosomal proteins. NSN1, NSN1-N, and EBP2 co-fractionated primarily with the 60S ribosomal large subunit in vivo. Depletion of NSN1 delayed 25S rRNA maturation and biogenesis of the 60S ribosome subunit, and repressed global translation. NSN1-deficient plants exhibited premature leaf senescence, excessive accumulation of reactive oxygen species, and senescence-related gene expression. Taken together, these results suggest that NSN1 plays a crucial role in plant growth and senescence by modulating ribosome biogenesis.

Purpose This study aimed to evaluate the prognostic value of each component of the revised American Fertility Society (rAFS) classification system for the first recurrence of endometriosis after conservative laparoscopy. Materials and methods As this was a retrospective cohort study, data were collected by reviewing medical records. A total of 379 women ages 18 to 49 years were included. Women who underwent conservative laparoscopy with histologic confirmation of endometriosis at Gangnam Severance Hospital between March 2003 and May 2010 were included. Individual components of the rAFS classification system as well as preoperative serum CA-125 levels were retrospectively analyzed to assess their prognostic values for recurrence of endometriosis. Results Of 379 patients, 80 (21.2%) were found to have recurrence of endometriosis. The median duration of follow-up was 19.0 months, and the mean age at the time of surgery was 31.8±6.7 years. In endometriosis of advanced stage, younger age at the time of surgery, bilateral ovarian cysts at the time of diagnosis, a rAFS ovarian adhesion score >24, and complete cul-de-sac obliteration were independent risk factors of poor outcomes, and a rAFS ovarian adhesion score >24 had the highest risk of recurrence [hazard ratio=2.948 (95% CI: 1.116-7.789), p=0.029]. Conclusion Our results suggest that of the rAFS adnexal adhesion scores, the ovarian adhesion score rather than the tubal adhesion score was associated with a significantly increased risk of recurrent endometriosis. The preoperative serum CA-125 level may be also a significant prognostic factor for recurrence, as known. However, it seemed to only have borderline significance in affecting recurrence in the current study.

The efficacy of Aster sphathulifolius (AS) for evaluation of preventive potencies against diabetes and diabetic complications was analyzed by assessment of inhibitory effects against advanced glycation end-products (AGEs) formation, rat lens aldose reductase (RLAR), α-glucosidase activity, and scavenging effects against DPPH. The 50% ethanol extract showed the highest DPPH radical scavenging activity (82.38%) at a concentration of 100 μg/mL, exhibited the most potent AGEs formation inhibitory effect (93.88%) at a concentration of 200 μg/mL, showed the most potent RLAR inhibitory effect (86.44%) at a concentration of 11.11 μg/mL. The 95% ethanol extract showed a potent α-glucosidase inhibitory activity (19.16%) at a concentration of 1 mg/mL. The 50% ethanol extract value was 16.79%. The 50% ethanol extract exhibited the most potent antioxidant and preventive actions against diabetes and diabetic complications and can, thus, be a source of valuable compounds for prevention of diabetes and diabetic complications.

The efficacy of Ligularia fischeri (LF) for managing diabetic complications was evaluated by assessing inhibitory effects against advanced glycation end product (AGE) formation, rat lens aldose reductase (RLAR), and 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging. The ethyl acetate fraction from 70% ethanol extracts of LF showed the highest DPPH radical scavenging activity of 53.90% at a concentration of 3.3 μg/mL. The ethyl acetate fraction exhibited the most potent AGE formation inhibition of 73.57% at a concentration of 55 μg/mL and showed the most potent RLAR inhibition of 88.97% at a concentration of 11.11 μg/mL. The ethyl acetate fraction exhibited the most potent antioxidant and anti-diabetic effects. Nuclear magnetic resonance via bioactivity-guided fractionation of the LF ethyl acetate fraction revealed that 3,4-dicaffeoylquinic acid was the bioactive compound. This compound from LF can be effective for prevention or treatment of diabetic complications.

Although a variety of factors have been reported as affecting pregnancy rates after intrauterine insemination (IUI), there have been conflicting results on prognostic factors. This study aimed to determine predictive factors for pregnancy in patients undergoing the first four IUI cycles.A total of 348 IUI cycles using clomiphene citrate or letrozole combined with gonadotropin, or gonadotropin only were analyzed. Baseline clinical characteristics, variables related to ovulation induction and sperm parameters were compared between pregnant (n = 54) and non-pregnant groups (n = 294). Logistic regression analysis was performed to identify factors that could predict a pregnancy.The overall clinical pregnancy rate was 15.5% (54/348) per cycle and 30.0% (54/180) per couple. During the first four IUI cycles, logistic regression analysis revealed that woman who were 39 years or older (OR: 0.263, 95% CI: 0.076-0.906, p = 0.034), longer duration of infertility (OR: 0.967, 95% CI: 0.942-0.993, p = 0.012), endometriosis (versus unexplained infertility; OR: 0.177, 95% CI: 0.040-0.775, p = 0.022) and endometrial thickness below 7 mm (OR: 0.114, 95% CI: 0.015-0.862, p = 0.035) were unfavorable factors to predict clinical pregnancy.Women with old age, longer duration of infertility, the presence of endometriosis or thin endometrium in the preovulatory phase may have unfavorable outcomes during the first four IUI cycles.

Objectives: To compare plasma kisspeptin, serum leptin, and serum retinol-binding protein 4 (RBP4) levels in women with and without polycystic ovary syndrome (PCOS) and to correlate these among each other and with clinical, hormonal, and metabolic parameters. Methods: Ninety women, including 54 women with PCOS and 36 without PCOS, participated in this study. For all patients, history and physical examinations were performed and blood samples were collected between days 3 and 8 of a spontaneous bleeding episode in the PCOS group and during normal menses of controls. Plasma kisspeptin, serum leptin, and serum RBP4 levels were measured using specific commercial assays. Results: Kisspeptin, leptin, and RBP4 levels were significantly higher in the PCOS group than in controls. Kisspeptin and RBP4 levels were significantly higher among obese PCOS patients than controls. Leptin levels were higher among obese PCOS patients than non-obese PCOS patients or controls. Kisspeptin and leptin levels of PCOS patients were significantly correlated with RBP4 levels. When only obese PCOS patients were analyzed, kisspeptin levels correlated with only the free androgen index. Conclusions: These findings suggest that kisspeptin, leptin, and RBP4 are associated with metabolic disturbances in women with PCOS.

This paper describes the design process for an automobile crumple zone for pedestrian protection. The impact load and bending moments predicted by impact analysis were used to design a plastic structure that may help reduce pedestrian injuries to the thigh area. The fracture effect was incorporated into the model by calculating the damage to the plastic material during impact, and the analysis was conducted under the European New Car Assessment Program (Euro NCAP) test conditions, using the upper legform developed by ESI Corporation. In addition, the values predicted by the analysis were validated by comparison with results of actual impact tests.

Background: Cartilage oligomeric matrix protein (COMP) is a biomarker for joint destruction and its serum levels are used for assessing therapeutic efficacy. This study aims to compare changes in serum COMP levels in postmenopausal women with osteopenia/osteoporosis receiving estrogen and alendronate. Methods: A total of 62 postmenopausal women diagnosed with osteopenia or osteoporosis were treated with either estrogen (17β-estradiol 1 mg, n = 30) or bisphosphonate (alendronate 5 mg, n = 32) for 6 months. The controls were healthy postmenopausal women (n = 30). Serum COMP and osteocalcin levels were measured at baseline and after 6 months of treatment. Results: Estrogen decreased levels of COMP at 6 months compared to baseline levels (–8.35 ± 19.38%), whereas the bisphosphonate and control groups resulted in no significant changes (–5.50 ± 18.69 and –1.49 ± 25.34%, respectively). Concentrations of osteocalcin decreased significantly in both treatment groups (estrogen –25.60 ± 24.42% and alendronate –13.76 ± 23.89%, respectively). There was a significant positive correlation between changes after 6 months in COMP and osteocalcin (R = 0.48, p = 0.002). Conclusions: Postmenopausal women treated with estrogen showed significantly decreased levels of COMP after 6 months. Estrogen might provide a further treatment modality in the prevention of joint destruction.

Prickly pear (Opuntia ficus-indica) is a longdomesticated crop plant of arid and semiarid parts of the world. The efficacy of extracts of prickly pear root for managing diabetes and diabetes complications was evaluated using a variety of in vitro bioassays. The ethyl acetate-soluble fraction was most effective in the prevention of diabetes and its complications via the inhibition of rat lens aldose reductase activity, the formation of advanced glycation end products, and α-glucosidase activity. MS and NMR were used to identify the bioactive compound from the ethyl acetate-soluble fraction as 3,5,7,4′-tetrahydroxyflavanone (aromadendrin).

Beta-amyloid (Aβ) is a major pathogenic peptide for Alzheimer's disease (AD) and is generated by the processing of amyloid precursor protein (APP). The Aβ monomers aggregate into oligomeric and fibrillar forms which have been implicated as the toxic species inducing the neuronal dysfunction. Brown algae Ecklonia cava is known for its anti-oxidant and anti-inflammatory functions. Therefore, we tested the effect of E. cava extract on the production and aggregation of Aβ peptides. The butanol extract of E. cava reduced Aβ secretion from HEK293 cells expressing APP with Swedish mutation and increased soluble APPα and C-terminal fragment-α (CTFα), of which activity was similar to BACE (β-site of APP cleaving enzyme) inhibitors. Furthermore, the extract inhibited Aβ oligomerization, particularly mid-size oligomer formation, confirmed by the ultrastructural morphology. Congo red, thioflavin T assays, and electron microscopy showed that the extract inhibited Aβ fibril formation effectively. Finally, the extract protected primary cortical neurons from various Aβ-induced cell deaths, especially oligomer-induced death. Although further study is needed to test the effectiveness of the extract in vivo, our results demonstrate, for the first time, that the butanol extract of E. cava could be used as an anti-Aβ agent for AD therapeutics.

To date, protein profiles for hepatocellular carcinomas and cholangiocarcinomas have not been systematically evaluated and compared with each other in an unbiased way. Thirty-six hepatocellular carcinomas and adjacent normal tissue samples were analyzed using histology-directed, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). Four cholangiocarcinomas and adjacent normal tissue samples were also evaluated. Tissue samples were sectioned at 10 µm, with 1-3 sections thaw-mounted on a conductive indium tin oxide-coated glass slide. Sinapinic acid was manually deposited on areas of each tissue section enriched by epithelial cells, either tumor or normal, and mass spectra were acquired using a MALDI-time of flight instrument. According to class prediction analysis, average prediction accuracy in test sets (composed of 18 hepatocellular carcinoma-normal pairs) ranged from 93.0 to 95.8%. Cholangiocarcinomas and hepatocellular carcinomas had different protein profiles, as evidenced by average prediction accuracy of >95% in the test set for all classifiers. Permutation P-values for 0.632 + bootstrap cross validated misclassification rates (at feature selection P < 0.001) were less than 0.05 for predicting p53 immunostaining status. We conclude that MALDI MS profiles may be useful in assisting with the diagnosis and the differential diagnosis of primary liver cancers.

In this study, we investigated the cellular functions of nuclear localizing protein (NLP) in Nicotiana benthamiana. The GFP fusion protein of Arabidopsis NLP is mostly targeted to the nucleus and cytosol, but it infrequently targets only the nucleus. Silencing of NLP using virus-induced gene silencing caused growth retardation and abnormal leaf development in N. benthamiana. At the cellular level, downregulation of NLP expression increased the size of pavement cells and stomata in the leaf tissues. NLP suppression also increased endoreduplication in leaf cells, suggesting a role of NLP in the endocycle. NLP transcript levels in leaves were significantly increased in response to infection with the nonhost pathogens. NLP deficiency attenuated HR cell death against nonhost pathogens and in response to gene-for-gene interaction. These findings suggest that NLP plays a role in plant development and plant defense responses against pathogens.

Non-steroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1) is involved in cellular processes such as inflammation, apoptosis and tumorigenesis. However, little is known about the expression and function of NAG-1 in the endometrium. This study aimed to evaluate the expression of NAG-1 in the endometrium and in the absence or presence of endometriosis and to investigate the effect of celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, on NAG-1 mRNA levels and apoptosis in human endometrial stromal cells (HESCs).Eutopic endometrial samples were obtained during surgery from 40 patients with, and 40 patients without, endometriosis. Real-time PCR was used to quantify NAG-1 mRNA levels and immunohistochemistry was used to localize NAG-1 protein in the endometrium. To investigate the effects of celecoxib, HESCs were isolated and cultured with different concentrations of celecoxib or with 100 µM celecoxib at different times. Apoptosis was assessed by flow cytometry.NAG-1 mRNA levels and immunoreactivity showed cyclical changes through the menstrual cycle, increasing during the late secretory and menstrual phases. NAG-1 mRNA and protein levels were significantly lower in patients with endometriosis, compared with the control group. Celecoxib induced NAG-1 mRNA levels and apoptosis in cultured HESCs, with the effects dependent on drug concentrations and duration of treatment. Celecoxib treatment had no effect on prostaglandin E(2) levels in the culture supernatants.NAG-1 may be important in maintaining homeostasis in the normal endometrium and alterations in NAG-1 expression may be associated with the establishment of endometriosis. NAG-1 might be a therapeutic target for endometriosis.

The levonorgestrel-releasing intrauterine system (LNG-IUS) is effective in the treatment of dysmenorrhea associated with adenomyosis. However, the mechanism of pain relief of LNG-IUS in patients with adenomyosis is unclear. We aimed to investigate the effects of LNG-IUS on the expression of nerve growth factor (NGF) and its receptors, NGFR p75 and TrkA in patients with adenomyosis. Endometrial and myometrial tissues were prepared from 17 LNG-IUS-treated patients and 15 hormonally untreated patients who had undergone hysterectomies for adenomyosis. Immunohistochemistry with antibodies against NGF, NGFR p75, and TrkA, was performed. The expression of NGF, NGFR p75, and TrkA in endometrium and myometrium of LNG-IUS-treated patients was significantly decreased compared to those of hormonally untreated patients. Our findings may indicate that the suppression of NGF and its receptors by LNG-IUS is another possible mechanism of relieving pain in patients with adenomyosis.

Although the pathophysiology of adenomyosis has not been clarified, it is thought to be related to ectopic endometrium, which depends on hormonal regulation. The levonorgestrel-releasing intrauterine system (LNG-IUS) is effective for the medical treatment of adenomyosis. However, the underlying molecular mechanisms by which LNG-IUS ameliorates adenomyosis pathology remain unclear. This study was designed to compare the expression levels of steroid receptor coregulators in human endometrium of control and participants with adenomyosis and to determine whether LNG-IUS modulated their expression. Immunohistochemistry with H-scores was performed. Steroid receptor coactivators were shown to have significantly decreased expressions at the secretory phase in the LNG-IUS group when compared to the other groups. Expression of transcriptional intermediary factor 2 was lower in the LNG-IUS group than in both the control group (P = .015) and the untreated adenomyosis group (P = .019) during the secretory phase. Amplified in breast cancer 1 expression was higher in the stromal cells of the untreated adenomyosis group than in those of the controls (P = .017) during the secretory phase; however, levels were lower in the LNG-IUS group (P = .005). Nuclear receptor corepressor expression increased during the proliferative phase and decreased during the secretory phase in untreated adenomyosis; this pattern was reversed in the control and LNG-IUS groups. Thus, an altered expression of steroid receptor coregulators may play a role in adenomyosis development and treatment.

To date, protein profiles for hepatocellular carcinomas and cholangiocarcinomas have not been systematically evaluated and compared with each other in an unbiased way. Thirty-six hepatocellular carcinomas and adjacent normal tissue samples were analyzed using histology-directed, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). Four cholangiocarcinomas and adjacent normal tissue samples were also evaluated. Tissue samples were sectioned at 10 µm, with 1-3 sections thaw-mounted on a conductive indium tin oxide-coated glass slide. Sinapinic acid was manually deposited on areas of each tissue section enriched by epithelial cells, either tumor or normal, and mass spectra were acquired using a MALDI-time of flight instrument. According to class prediction analysis, average prediction accuracy in test sets (composed of 18 hepatocellular carcinoma-normal pairs) ranged from 93.0 to 95.8%. Cholangiocarcinomas and hepatocellular carcinomas had different protein profiles, as evidenced by average prediction accuracy of95% in the test set for all classifiers. Permutation P-values for 0.632 + bootstrap cross validated misclassification rates (at feature selection P0.001) were less than 0.05 for predicting p53 immunostaining status. We conclude that MALDI MS profiles may be useful in assisting with the diagnosis and the differential diagnosis of primary liver cancers.