283 research outputs found

    Optimal financial and ordering decisions of a firm with insurance contract

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    This paper examines the impact of a bank’s risk limit on the financial and ordering decisions of a capital-constrained firm with insurance contract. All our major results can be computed via explicit expressions. It is shown that the bank will control its risk to be below the risk limit through setting a loan limit and the firm can make the loan limit increase by buying a deductible insurance policy. It is also shown that the repayment demand level needed to avoid bankruptcy will not be affected by the insurance policy. We derive the firm’s optimal ordering quantity and insurance coverage level under a downside risk measurement and a variance risk measurement separately. It is shown that the firm should pay more attention to whether to buy insurance or not under the downside risk measurement and how much insurance coverage to buy under the variance risk measurement. Under the downside risk measurement, once the firm decides to buy insurance, the optimal coverage level is independent of the bank’s risk limit. We also show that the insurance contract has a more obvious effect on the profit increases when the selling price is high or the bank’s risk limit is low. First published online: 18 Jun 201

    Weaning Induced Hepatic Oxidative Stress, Apoptosis, and Aminotransferases through MAPK Signaling Pathways in Piglets

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    This study investigated the effects of weaning on the hepatic redox status, apoptosis, function, and the mitogen-activated protein kinase (MAPK) signaling pathways during the first week after weaning in piglets. A total of 12 litters of piglets were weaned at d 21 and divided into the weaning group (WG) and the control group (CG). Six piglets from each group were slaughtered at d 0 (d 20, referred to weaning), d 1, d 4, and d 7 after weaning. Results showed that weaning significantly increased the concentrations of hepatic free radicals H2O2 and NO, malondialdehyde (MDA), and 8-hydroxy-2′-deoxyguanosine (8-OHdG), while significantly decreasing the inhibitory hydroxyl ability (IHA) and glutathione peroxidase (GSH-Px), and altered the level of superoxide dismutase (SOD). The apoptosis results showed that weaning increased the concentrations of caspase-3, caspase-8, caspase-9 and the ratio of Bax/Bcl-2. In addition, aspartate aminotransferase transaminase (AST) and alanine aminotransferase (ALT) in liver homogenates increased after weaning. The phosphorylated JNK and ERK1/2 increased, while the activated p38 initially decreased and then increased. Our results suggested that weaning increased the hepatic oxidative stress and aminotransferases and initiated apoptosis, which may be related to the activated MAPK pathways in postweaning piglets

    Optimization of fluorescence in situ hybridization (FISH) for the identification of two polar coccoid green algae species

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    Standard FISH protocols using fluorochrome-labeled oligonucleotide probes have been successfully applied for in situ detection. However, optimized protocols of FISH for specific eukaryotes in marine environments are often not developed. This study optimized the conditions of fluorescence in situ hybridization(FISH) by using two polar isolated microalgae. The modified conditions were as follows: (1)10mg·mL-1 lysozyme solution pretreatment at 37°C for 30 min; (2)the hybridization buffer including 20% formamide; (3)the hybridization condition was 47°C for 6h. The cells enumerated by FISH were compared with those enumerated by flow cytometry(FCM) and DAPI to confirm the cell loss and hybridization efficiency. The optimized protocol was also successfully applied to Arctic Ocean samples, which were found to be dominated by Micromonas sp. The modified protocol showed a high relative efficiency and could be successfully applied for the detection of specific microbial eukaryotes in environmental samples

    Based on Network Pharmacology and Molecular Docking to Discuss the Mechanism of Antitussive and Expectorant Action of Ruanerli

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    The antitussive and expectorant effects of Ruanerli and its mechanism were investigated by methods of network pharmacology. The outcomes predicted were verified by molecular docking and animal experiments. The components and targets of Ruanerli were obtained by literature investigation and TCMSP database screen. Mapping with two groups of genes related to "cough" and "sputum" from GeneCards database, the target genes of antitussive and expectorant effects of Ruanerli were obtained. GO and KEGG enrichment analysis of the target genes was performed by Metascape platform. The PPI network among the target genes was constructed through STRING data platform. Cytoscape plugin CytoHubba was used to screen the Top10 genes related to antitussive and expectorant effects of Ruanerli, and KEGG pathway enrichment was performed on the Top10 genes through Metascape data platform to predict the possible signal pathways involved in antitussive and expectorant effects of Ruanerli. Autodock Vina was used for molecular docking between the predicted Top10 gene proteins and the Top 3 active ingredients of Ruanerli. Finally, the predicted results were verified by ammonia induced cough test and phenol red excretion test. According to the analysis of multiple databases, 51 chemical components and 282 corresponding targets have been reported, eighty of them were related to the antitussive and expectorant effects of Ruanerli. The Top10 genes selected by Degree value were mainly concentrated in infection and immune-related pathways. Molecular docking test showed that the Top10 genes had strong binding activity with the Top3 chemical components (Caffeic acid, Rutin and Valeraldehyde) in PPI network. Animal experiments showed that the cough induced by ammonia was significantly inhibited when treated with Ruanerli in mice. The levels of IL-6 and IL-13 in serum were reduced and the excretion of phenol red in mice trachea was increased. PCR and WB detection showed that the mRNA levels and protein expressions of inflammatory genes IL6, IL1B, VEGFA, PTGS2 and MAPK3 were decreased, suggesting that the antitussive and expectorant effects of Ruanerli might be related to decreasing the expression of inflammatory genes and the release of inflammatory factors

    The cumulative therapeutic effect of acupuncture in patients with migraine without aura: Evidence from dynamic alterations of intrinsic brain activity and effective connectivity

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    We explored the dynamic alterations of intrinsic brain activity and effective connectivity after acupuncture treatment to investigate the underlying neurological mechanism of acupuncture treatment in patients with migraine without aura (MwoA). The Functional Magnetic Resonance Imaging (fMRI) scans were separately obtained at baseline, after the first and 12th acupuncture sessions in 40 patients with MwoA. Compared with the healthy controls (HCs), patients with MwoA mostly showed a decreased dynamic amplitude of low-frequency fluctuation (dALFF) variability in the rostral ventromedial medulla (RVM), superior lobe of left cerebellum (Cerebellum_Crus1_L), right precuneus (PCUN.R), and so on. The decreased dALFF variability of RVM, Cerebellum_Crus1_L, and PCUN.R progressively recovered after the first and 12th acupuncture treatment sessions as compared to the baseline. There was gradually increased dynamic effective connectivity (DEC) variability in RVM outflow to the right middle frontal gyrus, left insula, right precentral gyrus, and right supramarginal gyrus, and gradually enhanced DEC variability from the right fusiform gyrus inflow to RVM. Furthermore, the gradually increased DEC variability was found from Cerebellum_Crus1_L outflow to the left middle occipital gyrus and the left precentral gyrus, from PCUN.R outflow to the right thalamus. These dALFF variabilities were positively correlated with the frequency of migraine attacks and negatively correlated with disease duration at baseline. The dynamic Granger causality analysis (GCA) coefficients of this DEC variability were positively correlated with Migraine-Specific Quality of Life Questionnaire scores and negatively correlated with the frequency of migraine attacks and visual analog scale (VAS) scores after 12th acupuncture sessions. Our results were analyzed by a longitudinal fMRI in the absence of a sham acupuncture control group and provided insight into the dynamic alterations of brain activity and effective connectivity in patients with MwoA after acupuncture intervention. Acupuncture might relieve MwoA by increasing the effective connectivity of RVM, Cerebellum_Crus1_L, and PCUN.R to make up for the decreased dALFF variability in these brain areas

    Clinical Efficacy of Temozolomide and Its Predictors in Aggressive Pituitary Tumors and Pituitary Carcinomas: A Systematic Review and Meta-Analysis

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    Background: A growing number of evidences suggest that TMZ applications can generate impressive benefits for APT and PC patients. However, the definite role of TMZ for individuals remains unclarified due to the variation between studies. And the predictive factors to alter its efficacy remain debatable.Objective: To evaluate the long-term effectiveness and safety profile of TMZ in the treatment of pituitary malignancies, and delineate the predictors during its clinical employment.Results: A literature retrieval was conducted from online databases for studies published up to December 31, 2020. Twenty one studies involving 429 patients were identified. TMZ exhibited 41% radiological overall response rate (rORR). The biochemical response rate was determinate in 53% of the functioning subset. Two-year and 4-year survival rate were 79 and 61%, respectively. TMZ prolonged the median PFS and OS as 20.18 and 40.24 months. TMZ-related adverse events occurred in 19% of patients. Regarding predictors of TMZ response, rORR was dramatically improved in patients with low/intermediate MGMT expression than those with high-MGMT (>50%) (p < 0.001). The benefit of TMZ varied according to functioning subtype of patients, with greater antitumor activities in functioning subgroups and fewer activities in non-functioning sets (p < 0.001). Notably, the concomitant therapy of radiotherapy and TMZ significantly increased the rORR (p = 0.007).Conclusion: TMZ elicits clinical benefits with moderate adverse events in APT and PC patients. MGMT expression and clinical subtype of secreting function might be vital predictors of TMZ efficacy. In the future, the combination of radiotherapy with TMZ may further improve the clinical outcomes than TMZ monotherapy

    Therapeutic Implications of PPAR γ

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    Osteosarcoma (OS) is the most common nonhematologic malignancy of bone in children and adults. Although dysregulation of tumor suppressor genes and oncogenes, such as Rb, p53, and the genes critical to cell cycle control, genetic stability, and apoptosis have been identified in OS, consensus genetic changes that lead to OS development are poorly understood. Disruption of the osteogenic differentiation pathway may be at least in part responsible for OS tumorigenesis. Current OS management involves chemotherapy and surgery. Peroxisome proliferator-activated receptor (PPAR) agonists and/or retinoids can inhibit OS proliferation and induce apoptosis and may inhibit OS growth by promoting osteoblastic terminal differentiation. Thus, safe and effective PPAR agonists and/or retinoid derivatives can be then used as adjuvant therapeutic drugs for OS therapy. Furthermore, these agents have the potential to be used as chemopreventive agents for the OS patients who undergo the resection of the primary bone tumors in order to prevent local recurrence and/or distal pulmonary metastasis

    Associations between genetic variations in the FURIN gene and hypertension

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    <p>Abstract</p> <p>Background</p> <p>Hypertension is a complex disease influenced by multiple genetic and environmental factors. The Kazakh ethnic group is characterized by a relatively high prevalence of hypertension. Previous research indicates that the FURIN gene may play a pivotal role in the renin-angiotensin system and maintaining the sodium-electrolyte balance. Because these systems influence blood pressure regulation, we considered FURIN as a candidate gene for hypertension. The purpose of this study was to systematically investigate the association between genetic variations in the FURIN gene and essential hypertension in a Xinjiang Kazakh population.</p> <p>Methods</p> <p>We sequenced all exons and the promoter regions of the FURIN gene in 94 hypertensive individuals to identify genetic variations associated with the disorder. Genotyping was performed using the TaqMan polymerase chain reaction method for four representative common single nucleotide polymorphisms (SNPs, -7315C > T, 1970C > G, 5604C > G, 6262C > T) in 934 Kazakh Chinese people. One SNP (1970C > G) was replicated in 1,219 Uygur Chinese people.</p> <p>Results</p> <p>Nine novel and seven known single nucleotide polymorphisms were identified in the FURIN gene. The results suggest that 1970C > G was associated with a hypertension phenotype in Kazakh Chinese (additive model, <it>P </it>= 0.091; dominant model, <it>P = </it>0.031, allele model, <it>P </it>= 0.030), and after adjustment with logistic regression analysis, ORs were 1.451 (95%CI 1.106-1.905, <it>P </it>= 0.008) and 1.496 (95% 1.103-2.028, <it>P </it>= 0.01) in additive and dominant models, respectively. In addition, the association between 1970C > G and hypertension was replicated in Uygur subjects (additive model, <it>P </it>= 0.042; dominant model, <it>P </it>= 0.102; allele model, <it>P </it>= 0.027) after adjustment in additive and dominant models, ORs were 1.327 (95% 1.07-1.646), <it>P </it>= 0.01 and 1.307 (95%CI 1.015-1.681, <it>P </it>= 0.038), respectively. G allele carriers exhibited significant lower urinary Na<sup>+ </sup>excretion rate than non-carriers in the Kazakh Chinese population (152.45 ± 76.04 uM/min vs 173.33 ± 90.02 uM/min, <it>P </it>= 0.007).</p> <p>Conclusion</p> <p>Our results suggest that the FURIN gene may be a candidate gene involved in human hypertension, and that the G allele of 1970C > G may be a modest risk factor for hypertension in Xinjiang Kazakh and Uygur populations.</p
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