987 research outputs found

    Quantum chaos in one dimension?

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    In this work we investigate the inverse of the celebrated Bohigas-Giannoni-Schmit conjecture. Using two inversion methods we compute a one-dimensional potential whose lowest N eigenvalues obey random matrix statistics. Our numerical results indicate that in the asymptotic limit, N->infinity, the solution is nowhere differentiable and most probably nowhere continuous. Thus such a counterexample does not exist.Comment: 7 pages, 10 figures, minor correction, references extende

    Staurosporine induces necroptotic cell death under caspase-compromised conditions in U937 cells

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    For a long time necrosis was thought to be an uncontrolled process but evidences recently have revealed that necrosis can also occur in a regulated manner. Necroptosis, a type of programmed necrosis is defined as a death receptor-initiated process under caspase-compromised conditions. The process requires the kinase activity of receptor-interacting protein kinase 1 and 3 (RIPK1 and RIPK3) and mixed lineage kinase domain-like protein (MLKL), as a substrate of RIPK3. The further downstream events remain elusive. We applied known inhibitors to characterize the contributing enzymes in necroptosis and their effect on cell viability and different cellular functions were detected mainly by flow cytometry. Here we report that staurosporine, the classical inducer of intrinsic apoptotic pathway can induce necroptosis under caspase-compromised conditions in U937 cell line. This process could be hampered at least partially by the RIPK1 inhibitor necrotstin-1 and by the heat shock protein 90 kDa inhibitor geldanamycin. Moreover both the staurosporine-triggered and the classical death ligand-induced necroptotic pathway can be effectively arrested by a lysosomal enzyme inhibitor CA-074-OMe and the recently discovered MLKL inhibitor necrosulfonamide. We also confirmed that the enzymatic role of poly(ADP-ribose)polymerase (PARP) is dispensable in necroptosis but it contributes to membrane disruption in secondary necrosis. In conclusion, we identified a novel way of necroptosis induction that can facilitate our understanding of the molecular mechanisms of necroptosis. Our results shed light on alternative application of staurosporine, as a possible anticancer therapeutic agent. Furthermore, we showed that the CA-074-OMe has a target in the signaling pathway leading to necroptosis. Finally, we could differentiate necroptotic and secondary necrotic processes based on participation of PARP enzyme

    Calcaneal BMD Obtained by Dual X-Ray and Laser Predicts Future Hip Fractures—A Prospective Study on 4 398 Swedish Women

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    The predictive value of dual X-ray and laser (DXL) calcaneal BMD (BMDDXL) on hip fractures was prospectively studied in 4,398 females aged 55 to 99 years. The average follow-up period was 3 years and 11 months with a total of 17,270 person years. Fractures were identified from the national patient register. After inclusion, 130 females sustained a hip fracture. The age adjusted hazard ratio for T-score <−2.5 versus >−2.5 was 2.64. Of all patients who sustained a hip fracture 78% had a T-score of −2.5 or below. The annual hip fracture rate was 0.26% at T-scores ≥−2, but 1.5% at T-scores ≤−2.5. The area under curve for the model including calcaneal BMDDXL, follow-up time, and age to prospectively predict hip fractures was 0.84. Conclusions. Calcaneal BMDDXL obtained by DXL Calscan predicts hip fractures and may therefore be suitable for diagnosing osteoporosis and for predicting fracture risk
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