4-point effective actions in open and closed superstring theory

Recently the effective action for the 4-point functions in abelian open superstring theory has been derived, giving an explicit construction of the bosonic and fermionic terms of this infinite $\alpha'$ series. In the present work we generalize this result to the nonabelian case. We test our result, at ${\alpha'}^3$ and ${\alpha'}^4$ order, with several existing versions for these terms, finding agreement in most of the cases. We also apply these ideas to derive the effective action for the 4-point functions of the NS-NS sector of closed superstring theory, to all order in $\alpha'$.Comment: 26 pages, 1 figure. To appear in JHE

Ellipticine cytotoxicity to cancer cell lines — a comparative study

Ellipticine is a potent antineoplastic agent exhibiting multiple mechanisms of action. This anticancer agent should be considered a pro-drug, whose pharmacological efficiency and/or genotoxic side effects are dependent on its cytochrome P450 (CYP)- and/or peroxidase-mediated activation to species forming covalent DNA adducts. Ellipticine can also act as an inhibitor or inducer of biotransformation enzymes, thereby modulating its own metabolism leading to its genotoxic and pharmacological effects. Here, a comparison of the toxicity of ellipticine to human breast adenocarcinoma MCF-7 cells, leukemia HL-60 and CCRF-CEM cells, neuroblastoma IMR-32, UKF-NB-3 and UKF-NB-4 cells and U87MG glioblastoma cells and mechanisms of its action to these cells were evaluated. Treatment of all cells tested with ellipticine resulted in inhibition of cell growth and proliferation. This effect was associated with formation of two covalent ellipticine-derived DNA adducts, identical to those formed by 13-hydroxy- and 12-hydroxyellipticine, the ellipticine metabolites generated by CYP and peroxidase enzymes, in MCF-7, HL-60, CCRF-CEM, UKF-NB-3, UKF-NB-4 and U87MG cells, but not in neuroblastoma UKF-NB-3 cells. Therefore, DNA adduct formation in most cancer cell lines tested in this comparative study might be the predominant cause of their sensitivity to ellipticine treatment, whereas other mechanisms of ellipticine action also contribute to its cytotoxicity to neuroblastoma UKF-NB-3 cells

DNA and histone deacetylases as targets for neuroblastoma treatment

Neuroblastoma, a tumor of the peripheral sympathetic nervous system, is the most frequent solid extra cranial tumor in children and is a major cause of death from neoplasia in infancy. Still little improvement in therapeutic options has been made, requiring a need for the development of new therapies. In our laboratory, we address still unsettled questions, which of mechanisms of action of DNA-damaging drugs both currently use for treatment of human neuroblastomas (doxorubicin, cis-platin, cyclophosphamide and etoposide) and another anticancer agent decreasing growth of neuroblastomas in vitro, ellipticine, are predominant mechanism(s) responsible for their antitumor action in neuroblastoma cell lines in vitro. Because hypoxia frequently occurs in tumors and strongly correlates with advanced disease and poor outcome caused by chemoresistance, the effects of hypoxia on efficiencies and mechanisms of actions of these drugs in neuroblastomas are also investigated. Since the epigenetic structure of DNA and its lesions play a role in the origin of human neuroblastomas, pharmaceutical manipulation of the epigenome may offer other treatment options also for neuroblastomas. Therefore, the effects of histone deacetylase inhibitors on growth of neuroblastoma and combination of these compounds with doxorubicin, cis-platin, etoposide and ellipticine as well as mechanisms of such effects in human neuroblastona cell lines in vitro are also investigated. Such a study will increase our knowledge to explain the proper function of these drugs on the molecular level, which should be utilized for the development of new therapies for neuroblastomas

A quantitative link between CO 2 emissions from tropical vegetation fires and the daily tropospheric excess (DTE) of CO 2 seen by NOAA-10 (1987-1991)

International audience[1] Monthly mean mid-tropospheric CO 2 columns over the tropics are retrieved from evening and morning observations of NOAA-10 (1987-1991). We find that the difference between these two columns (''Daily Tropospheric Excess'', DTE) increases up to 3 ppm over regions affected by fires. At regional scale over Africa, America, and Australia, the variations of the DTE are very similar to those of independently derived biomass burning CO 2 emissions. A strong correlation (R 2 $ 0.8) is found between regional mean DTE and fire CO 2 emissions values from the Global Fire Emissions Database (GFEDv2) even though the two products span over periods ten years apart from each other. The DTE distribution over Africa indicates that the southern hemisphere experiences 20% more fire activity during El Niño conditions than during La Niña conditions and the reverse for the northern hemisphere. Such an African dipole of ENSO-related fire variability is comparable to changes analyzed from GFEDv2 CO 2 emission maps. However, the estimated one sigma uncertainty on the DTE remains close to this DTE ENSO signal. The physical mechanism linking DTE with emissions is not fully elucidated. Hot convective fire plumes injecting CO 2 into the troposphere during the afternoon peak of fire activity, seen by the satellite at 1930 LT, and then being diluted by large scale atmospheric transport, before the next satellite pass at 0730 LT, could explain the tight observed relationship between DTE and CO 2 emissions. We conclude that DTE data can be very useful to quantitatively reconstruct fire emission patterns before the ATSR and MODIS era when better quality fire count and burned area data became available. Citation: Chédin, A., N. A. Scott, R. Armante, C. Pierangelo, C. Crevoisier, O. Fossé, and P. Ciais (2008), A quantitative link between CO 2 emissions from tropical vegetation fires and the daily tropospheric excess (DTE) of CO 2 seen by NOA

Prognosis in unexplained recurrent pregnancy loss: a systematic review and quality assessment of current clinical prediction models

Objective: To identify models predicting live birth or ongoing pregnancy in couples with unexplained recurrent pregnancy loss (RPL) and evaluate the risk of bias, performance, generalizability, and applicability of these models. Evidence Review: A systematic literature search was performed in PubMed, Embase, Web of Science, and Cochrane Library until December 2020. Studies were eligible for inclusion if they were original studies predicting pregnancy outcome in patients with unexplained RPL and presented a tool that allowed for individual predictions. The risk of bias and applicability of the studies were assessed using the Prediction model Risk of Bias Assessment Tool. The Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis statement was used to assess reporting quality. Results: The search yielded 1,170 unique articles that were screened on the basis of the title and abstract. Seven studies were included: 1 prospective cohort study and 6 retrospective cohort studies. The recommended steps for the development of a prediction model were not followed by any of the studies, although 6 were published before the Prediction model Risk of Bias Assessment Tool and Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines. The included studies had a high risk of bias and were not externally validated. Conclusion: International guidelines recommend supportive care programs with prognostic counseling for couples with unexplained RPL. This information manages the expectations of couples and improves their ability to make an informed decision regarding further pregnancy attempts. On the basis of the results of this study, we cannot recommend the use of any of the studied prediction models in clinical practice to prevent overestimation of chances and false belief

Toward more accurate prediction of future pregnancy outcome in couples with unexplained recurrent pregnancy loss: taking both partners into account

Objective: To identify, besides maternal age and the number of previous pregnancy losses, additional characteristics of couples with unexplained recurrent pregnancy loss (RPL) that improve the prediction of an ongoing pregnancy. Design: Hospital-based cohort study in couples who visited specialized RPL units of two academic centers between 2012 and 2020. Setting: Two academic centers in the Netherlands. Patients: Clinical data from 526 couples with unexplained RPL were used in this study. Intervention(s): None. Main Outcome Measures: The final model to estimate the chance of a subsequent ongoing pregnancy was determined using a backward selection process and internally validated using bootstrapping. Model performance was assessed in terms of calibration and discrimination (area under the receiver operating characteristic curve). Results: Subsequent ongoing pregnancy was achieved in 345 of 526 couples (66%). The number of previous pregnancy losses, maternal age, paternal age, maternal body mass index, paternal body mass index, maternal smoking status, and previous in vitro fertilization/intracytoplasmic sperm injection treatment were predictive of the outcome. The optimism-corrected area under the receiver operating characteristic curve was 0.63 compared with 0.57 when using only the number of previous pregnancy losses and maternal age. Conclusions: The identification of additional predictors of a subsequent ongoing pregnancy after RPL, including male characteristics, is significant for both clinicians and couples with RPL. At the same time, we showed that the predictive ability of the current model is still limited and more research is warranted to develop a model that can be used in clinical practice