310 research outputs found

    "This strange story of ours ought to be told" Narrative and its Production in The Moonstone

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    Relative abundances of CO2, CO, and CH4 in atmospheres of Earth-like lifeless planets

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    Carbon is an essential element for life on Earth, and the relative abundances of major carbon species (CO2, CO, and CH4) in the atmosphere exert fundamental controls on planetary climate and biogeochemistry. Here, we employed a theoretical model of atmospheric chemistry to investigate diversity in the atmospheric abundances of CO2, CO, and CH4 on Earth-like lifeless planets orbiting Sun-like (F-, G-, and K-type) stars. We focused on the conditions for the formation of a CO-rich atmosphere, which would be favorable for the origin of life. Results demonstrated that elevated atmospheric CO2 levels trigger photochemical instability of the CO budget in the atmosphere (i.e., CO runaway) owing to enhanced CO2 photolysis relative to H2O photolysis. Higher volcanic outgassing fluxes of reduced C (CO and CH4) also tend to initiate CO runaway. Our systematic examinations revealed that anoxic atmospheres of Earth-like lifeless planets could be classified in the phase space of CH4/CO2 versus CO/CO2, where a distinct gap in atmospheric carbon chemistry is expected to be observed. Our findings indicate that the gap structure is a general feature of Earth-like lifeless planets with reducing atmospheres orbiting Sun-like (F-, G-, and K-type) stars

    Drug interaction prediction using ontology-driven hypothetical assertion framework for pathway generation followed by numerical simulation

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    <p>Abstract</p> <p>Background</p> <p>In accordance with the increasing amount of information concerning individual differences in drug response and molecular interaction, the role of <it>in silico </it>prediction of drug interaction on the pathway level is becoming more and more important. However, in view of the interferences for the identification of new drug interactions, most conventional information models of a biological pathway would have limitations. As a reflection of real world biological events triggered by a stimulus, it is important to facilitate the incorporation of known molecular events for inferring (unknown) possible pathways and hypothetic drug interactions. Here, we propose a new Ontology-Driven Hypothetic Assertion (OHA) framework including pathway generation, drug interaction detection, simulation model generation, numerical simulation, and hypothetic assertion. Potential drug interactions are detected from drug metabolic pathways dynamically generated by molecular events triggered after the administration of certain drugs. Numerical simulation enables to estimate the degree of side effects caused by the predicted drug interactions. New hypothetic assertions of the potential drug interactions and simulation are deduced from the Drug Interaction Ontology (DIO) written in Web Ontology Language (OWL).</p> <p>Results</p> <p>The concept of the Ontology-Driven Hypothetic Assertion (OHA) framework was demonstrated with known interactions between irinotecan (CPT-11) and ketoconazole. Four drug interactions that involved cytochrome p450 (CYP3A4) and albumin as potential drug interaction proteins were automatically detected from Drug Interaction Ontology (DIO). The effect of the two interactions involving CYP3A4 were quantitatively evaluated with numerical simulation. The co-administration of ketoconazole may increase AUC and Cmax of SN-38(active metabolite of irinotecan) to 108% and 105%, respectively. We also estimates the potential effects of genetic variations: the AUC and Cmax of SN-38 may increase to 208% and 165% respectively with the genetic variation UGT1A1*28/*28 which reduces the expression of UGT1A1 down to 30%.</p> <p>Conclusion</p> <p>These results demonstrate that the Ontology-Driven Hypothetic Assertion framework is a promising approach for <it>in silico </it>prediction of drug interactions. The following future researches for the <it>in silico </it>prediction of individual differences in the response to the drug and drug interactions after the administration of multiple drugs: expansion of the Drug Interaction Ontology for other drugs, and incorporation of virtual population model for genetic variation analysis, as well as refinement of the pathway generation rules, the drug interaction detection rules, and the numerical simulation models.</p

    Cystatin C in children with malignancies

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    Several factors besides renal function influence serum cystatin C (CysC) levels. The present study evaluates the value of serum CysC and the equation for CysC based estimated glomerular filtration rate (CysC-eGFR) for Japanese children with malignancies.We collected information at 36 time points from 13 patients aged ≤ 17 years with malignancies. We assessed tumor activity, cell recovery phase after chemotherapy, neutropenia phase, inflammation response and medication with granulocyte-colony stimulating factor, steroid, and levothyroxine as risk factors associated with serum CysC levels. Although no 24-h creatinine clearance (CCr) data collected at 36 time points indicated renal dysfunction, serum CysC levels were above and below the reference values at four and five time points, respectively. The frequency of elevated serum CysC levels was higher in patients without therapy or with stable or progressive disease than among those with a complete or partial response (p = 0.0046). The correlation coefficient between CCr and CysC-eGFR was 0.355 (p = 0.054), but this improved to 0.663 (p = 0.0010) when restricted to patients with a complete or partial response. Levels of serum CysC might become elevated regardless of renal function, and CysC-eGFR might become unpredictable during the active phase of tumors

    A calmodulin inhibitor, W-7 influences the effect of cyclic adenosine 3', 5'-monophosphate signaling on ligninolytic enzyme gene expression in Phanerochaete chrysosporium

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    The capacity of white-rot fungi to degrade wood lignin may be highly applicable to the development of novel bioreactor systems, but the mechanisms underlying this function are not yet fully understood. Lignin peroxidase (LiP) and manganese peroxidase (MnP), which are thought to be very important for the ligninolytic property, demonstrated increased activity in Phanerochaete chrysosporium RP-78 (FGSC #9002, ATCC MYA-4764™) cultures following exposure to 5 mM cyclic adenosine 3', 5'-monophosphate (cAMP) and 500 μM 3'-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor. Real-time reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that transcription of most LiP and MnP isozyme genes was statistically significantly upregulated in the presence of the cAMP and IBMX compared to the untreated condition. However, 100 μM calmodulin (CaM) inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), which had insignificant effects on fungal growth and intracellular cAMP concentration, not only offset the increased activity and transcription induced by the drugs, but also decreased them to below basal levels. Like the isozyme genes, transcription of the CaM gene (cam) was also upregulated by cAMP and IBMX. These results suggest that cAMP signaling functions to increase the transcription of LiP and MnP through the induction of cam transcription

    Influences of protein ingestion on glucagon-like peptide (GLP)-1-immunoreactive endocrine cells in the chicken ileum

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    Influences of a specific dietary nutrient on glucagon-like peptide (GLP)-1-containing cells in the chicken intestine are not yet clear. Significance of dietary protein level on GLP-1-containing cells in the chicken ileum was investigated. Chickens fed control or experimental diets of varying protein levels were examined using immunohistochemical and morphometrical techniques. We show that the protein ingestion had an impact on the activities of GLP-1-immunoreactive cells in the chicken ileum. Weight gains declined with decreasing dietary crude protein (CP) levels, but no significant differences were detected in the daily feed intake and villous height. GLP-1-immunoreactive cells with a round or oval shape were frequently observed in the lower CP level groups (4.5% and 0%). Frequencies of occurrence of GLP-1-immunoreactive cells were 41.1 +/- 4.1, 38.5 +/- 4, 34.8 +/- 3.1 and 34.3 +/- 3.7 (cells/mm(2), mean +/- SD) for dietary CP level of 18%, 9%, 4.5% and 0% groups, respectively and significant differences were recognized between the control and lower CP level groups (P<0.05). Multiple regression analysis indicated a significant correlation between the daily protein intake and frequencies of occurrence of GLP-1-immunoreactive cells. The protein ingestion is one of the signals that influence GLP-1-containing cells in the chicken small intestine.ArticleANIMAL SCIENCE JOURNAL. 85(5):581-587 (2014)journal articl

    Efficacy and Complications of Emergent Transcatheter Arterial Embolization for the Management of Intractable Uterine Bleeding

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    Objective:Transcatheter arterial embolization(TAE), including uterine artery embolization(UAE), is effective for the management of obstetric and gynecologic hemorrhage. Some adverse effects have been reported with TAE, such as amenorrhea, endometrial trauma, and subsequent infertility. Herein we report the efficacy and complications of emergent TAE for the management of severe intractable uterine bleeding at our institute.Methods:From 2010 to 2019, thirty-eight patients underwent emergent TAE for intractable uterine bleeding. We evaluated the efficacy and complications of TAE, including a change in menstruation, fertility, and pregnancy outcomes in perinatal patients(group A;n=23), and in patients with gynecologic hemorrhage(group B;n=15).Results:In group A, 7 cases of retained placenta, 4 cases of postpartum hemorrhage, 2 cases of placenta accrete, 2 cases of uterine artery pseudoaneurysm, 2 cases of cervical pregnancy, 1 case of cesarean scar pregnancy, and 5 cases of unexplained hemorrhage were included. The median age of the group A was 37. In group B, 4 cases of uterine artery pseudoaneurysm, 2 cases of uterine arteriovenous malformation, 3 cases of uterine fibroids, 1case of adenomyosis, and 5 cases of unexplained hemorrhage were included. The median age of the group B was 39. The first attempt at TAE successfully controlled hemorrhage in 33 of 38 patients (86.8%)without major complications, and the remaining 5 patients required an additional attempt at TAE to control hemorrhage. One patient(2.6%)had transient buttock pain and foot ischemia. Among the 33 patients who had adequate follow-up care, all patients resumed regular menstruation. The median time to resume regular menstruation after TAE was 3 months (range, 1-13 months)in group A(n=20)and 1 month(range, 1-6 months)in group B(n=13). Four of patients had 6 pregnancies in total:3 full-term live births, 2 missed abortions, and 1 artificial abortion. Among the 13 patients who desired pregnancy, 3(23%)conceived spontaneously.Conclusions:This retrospective study showed that emergent TAE may be effective and safe in treating intractable uterine bleeding with a high success rate. Ovarian and endometrial function were preserved based on the relatively early return of menstruation. Further prospective investigations with large number of patients are needed to confirm the preservation of ovarian function, fertility, and pregnancy outcome in reproductive-aged women

    Bioorganic synthesis of a recombinant HIV-1 fusion inhibitor, SC35EK, with an N-terminal pyroglutamate capping group.

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    The bioorganic synthesis of an end-capped anti-HIV peptide from a recombinant protein was investigated. Cyanogen bromide-mediated cleavage of two Met-Gln sites across the target anti-HIV sequence generated an HIV-1 fusion inhibitor (SC35EK) analog bearing an N-terminal pyroglutamate (pGlu) residue and a C-terminal homoserine lactone (Hsl) residue. The end-capped peptide, pGlu-SC35EK-Hsl, had similar bioactivity and biophysical properties to the parent peptide, and an improved resistance to peptidase-mediated degradation was observed compared with the non-end-capped peptide obtained using standard recombinant technology
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