Fleming's bound for the decay of mixed states

Fleming's inequality is generalized to the decay function of mixed states. We show that for any symmetric hamiltonian $h$ and for any density operator $\rho$ on a finite dimensional Hilbert space with the orthogonal projection $\Pi$ onto the range of $\rho$ there holds the estimate \Tr(\Pi \rme^{-\rmi ht}\rho \rme^{\rmi ht}) \geq\cos^{2}((\Delta h)_{\rho}t) for all real $t$ with $(\Delta h)_{\rho}| t| \leq\pi/2.$ We show that equality either holds for all $t\in\mathbb{R}$ or it does not hold for a single $t$ with $0<(\Delta h)_{\rho}| t| \leq\pi/2.$ All the density operators saturating the bound for all $t\in\mathbb{R},$ i.e. the mixed intelligent states, are determined.Comment: 12 page

The selective PI3Kα inhibitor BYL719 as a novel therapeutic option for neuroendocrine tumors: Results from multiple cell line models

Background/Aims The therapeutic options for metastatic neuroendocrine tumors (NETs) are limited. As PI3K signaling is often activated in NETs, we have assessed the effects of selective PI3Kp110α inhibition by the novel agent BYL719 on cell viability, colony formation, apoptosis, cell cycle, signaling pathways, differentiation and secretion in pancreatic (BON-1, QGP-1) and pulmonary (H727) NET cell lines. Methods Cell viability was investigated by WST-1 assay, colony formation by clonogenic assay, apoptosis by caspase3/7 assay, the cell cycle by FACS, cell signaling by Western blot analysis, expression of chromogranin A and somatostatin receptors 1/2/5 by RT-qPCR, and chromogranin A secretion by ELISA. Results BYL719 dose-dependently decreased cell viability and colony formation with the highest sensitivity in BON-1, followed by H727, and lowest sensitivity in QGP-1 cells. BYL719 induced apoptosis and G0/G1 cell cycle arrest associated with increased p27 expression. Western blots showed inhibition of PI3K downstream targets to a varying degree in the different cell lines, but IGF1R activation. The most sensitive BON-1 cells displayed a significant, and H727 cells a non- significant, GSK3 inhibition after BYL719 treatment, but these effects do not appear to be mediated through the IGF1R. In contrast, the most resistant QGP-1 cells showed no GSK3 inhibition, but a modest activation, which would partially counteract the other anti-proliferative effects. Accordingly, BYL719 enhanced neuroendocrine differentiation with the strongest effect in BON-1, followed by H727 cells indicated by induction of chromogranin A and somatostatin receptor 1/2 mRNA-synthesis, but not in QGP-1 cells. In BON-1 and QGP-1 cells, the BYL719/everolimus combination was synergistic through simultaneous AKT/mTORC1 inhibition, and significantly increased somatostatin receptor 2 transcription compared to each drug separately. Conclusion Our results suggest that the agent BYL719 could be a novel therapeutic approach to the treatment of NETs that may sensitize NET cells to somatostatin analogs, and that if there is resistance to its action this may be overcome by combination with everolimus

Heme oxygenase-1 genotype and restenosis after balloon angioplasty: a novel vascular protective factor

AbstractObjectivesWe investigated the association of the heme oxygenase-1 (HO-1) promoter genotype with the inflammatory response and restenosis after balloon angioplasty.BackgroundHeme oxygenase-1, which is induced by balloon angioplasty, can inhibit neointima formation and vascular remodeling. A dinucleotide repeat in the HO-1 gene promoter shows a length polymorphism that modulates HO-1 gene transcription. Short (<25 guanosine thymidine [GT]) repeats are associated with a 10-fold greater up-regulation of HO-1 than are longer repeats.MethodsWe studied 381 consecutive patients who underwent femoropopliteal balloon angioplasty (n = 210) and comparison groups with femoropopliteal stenting (n = 68) and lower limb angiography (n = 103). C-reactive protein (CRP) was measured at baseline, 24, and 48 h. We evaluated patency at six months by duplex sonography and assessed the association of the length of GT repeats in the HO-1 gene promoter with postintervention CRP and restenosis.ResultsRestenosis within six months was found in 74 patients (35%) after balloon angioplasty and in 21 patients (31%) after stenting. After balloon angioplasty, carriers of the short length (<25 GT) dinucleotide repeats had a lower postintervention CRP at 24 h (p = 0.009) and 48 h (p < 0.001) and a reduced risk for restenosis (adjusted relative risk 0.43, 95% confidence interval: 0.24 to 0.71, p < 0.001) compared with patients with longer alleles. After stenting or angiography, we found no association between the HO-1 genotype with CRP or restenosis.ConclusionsThe HO-1 promoter genotype that controls the degree of HO-1 up-regulation in response to stress stimuli is associated with the postintervention inflammatory response and the restenosis risk after balloon angioplasty

The selective PI3Kα inhibitor BYL719 as a novel therapeutic option for neuroendocrine tumors: Results from multiple cell line models

BACKGROUND/AIMS The therapeutic options for metastatic neuroendocrine tumors (NETs) are limited. As PI3K signaling is often activated in NETs, we have assessed the effects of selective PI3Kp110\textgreeka inhibition by the novel agent BYL719 on cell viability, colony formation, apoptosis, cell cycle, signaling pathways, differentiation and secretion in pancreatic (BON-1, QGP-1) and pulmonary (H727) NET cell lines. METHODS Cell viability was investigated by WST-1 assay, colony formation by clonogenic assay, apoptosis by caspase3/7 assay, the cell cycle by FACS, cell signaling by Western blot analysis, expression of chromogranin A and somatostatin receptors 1/2/5 by RT-qPCR, and chromogranin A secretion by ELISA. RESULTS BYL719 dose-dependently decreased cell viability and colony formation with the highest sensitivity in BON-1, followed by H727, and lowest sensitivity in QGP-1 cells. BYL719 induced apoptosis and G0/G1 cell cycle arrest associated with increased p27 expression. Western blots showed inhibition of PI3K downstream targets to a varying degree in the different cell lines, but IGF1R activation. The most sensitive BON-1 cells displayed a significant, and H727 cells a non-significant, GSK3 inhibition after BYL719 treatment, but these effects do not appear to be mediated through the IGF1R. In contrast, the most resistant QGP-1 cells showed no GSK3 inhibition, but a modest activation, which would partially counteract the other anti-proliferative effects. Accordingly, BYL719 enhanced neuroendocrine differentiation with the strongest effect in BON-1, followed by H727 cells indicated by induction of chromogranin A and somatostatin receptor 1/2 mRNA-synthesis, but not in QGP-1 cells. In BON-1 and QGP-1 cells, the BYL719/everolimus combination was synergistic through simultaneous AKT/mTORC1 inhibition, and significantly increased somatostatin receptor 2 transcription compared to each drug separately. CONCLUSION Our results suggest that the agent BYL719 could be a novel therapeutic approach to the treatment of NETs that may sensitize NET cells to somatostatin analogs, and that if there is resistance to its action this may be overcome by combination with everolimus

Personality traits and mental disorders

Peer reviewe