1,156 research outputs found

    Rottlerin stimulates apoptosis in pancreatic cancer cells through interactions with proteins of the Bcl-2 family

    Get PDF
    Rottlerin is a polyphenolic compound derived from Mallotus philipinensis. In the present study, we show that rottlerin decreased tumor size and stimulated apoptosis in an orthotopic model of pancreatic cancer with no effect on normal tissues in vivo. Rottlerin also induced apoptosis in pancreatic cancer (PaCa) cell lines by interacting with mitochondria and stimulating cytochrome c release. Immunoprecipitation results indicated that rottlerin disrupts complexes of prosurvival Bcl-xL with Bim and Puma. Furthermore, siRNA knockdown showed that Bim and Puma are necessary for rottlerin to stimulate apoptosis. We also showed that rottlerin and Bcl-2 and Bcl-xL inhibitor BH3I-2' stimulate apoptosis through a common mechanism. They both directly interact with mitochondria, causing increased cytochrome c release and mitochondrial depolarization, and both decrease sequestration of BH3-only proteins by Bcl-xL. However, the effects of rottlerin and BH3I-2' on the complex formation between Bcl-xL and BH3-only proteins are different. BH3I-2' disrupts complexes of Bcl-xL with Bad but not with Bim or Puma, whereas rottlerin had no effect on the Bcl-xL interaction with Bad. Also BH3I-2', but not rottlerin, required Bad to stimulate apoptosis. In conclusion, our results demonstrate that rottlerin has a potent proapoptotic and antitumor activity in pancreatic cancer, which is mediated by disrupting the interaction between prosurvival Bcl-2 proteins and proapoptotic BH3-only proteins. Thus rottlerin represents a promising novel agent for pancreatic cancer treatment

    Strong subadditivity inequality for quantum entropies and four-particle entanglement

    Get PDF
    Strong subadditivity inequality for a three-particle composite system is an important inequality in quantum information theory which can be studied via a four-particle entangled state. We use two three-level atoms in Λ\Lambda configuration interacting with a two-mode cavity and the Raman adiabatic passage technique for the production of the four-particle entangled state. Using this four-particle entanglement, we study for the first time various aspects of the strong subadditivity inequality.Comment: 5 pages, 3 figures, RevTeX4, submitted to PR

    Fertility and gonadal function in female survivors after treatment of early unfavorable Hodgkin lymphoma (HL) within the German Hodgkin Study Group HD14 trial

    Get PDF
    Background In the HD14 trial, 2× BEACOPPescalated+2× ABVD (2+2) has improved the primary outcome. Compared with 4× ABVD, this benefit might be compromised by more infertility in women. Therefore, we analyzed gonadal function and fertility. Patients and methods Women ≤45 years in ongoing remission at least 1 year after therapy were included. Hormone parameters, menopausal symptoms, measures to preserve fertility, menstrual cycle, pregnancies, and offspring were evaluated. Results Three hundred and thirty one of 579 women addressed participated (57.2%) and 263 per-protocol treated patients qualified (A=ABVD: 137, B=2+2: 126, mean time after therapy 42 and 43 months, respectively). Regular menstrual cycle after treatment (A: 87%, B: 83%) and time to recovery (≤12 months) were not different. Follicle-stimulating hormone and anti-Muellerian hormone were significantly better in arm A. However, pregnancies after therapy favored arm B (A: 15%, B: 26%, P=0.043) and motherhood rates were equivalent to the German normal population. Multivariate analysis revealed prophylactic use of gonadotropin-releasing hormone (GnRH) analogues as highly significant prognostic factor for preservation of fertility (odds ratio=12.87, P=0.001). Severe menopausal symptoms were frequent in women ≥30 years (A: 21%, B: 25%). Conclusions Hormonal levels after 2+2 indicate a reduced ovarian reserve. However, 2+2 in combination with GnRH analogues does not compromise fertility within the evaluated observation tim

    Testing foundations of quantum mechanics with photons

    Full text link
    The foundational ideas of quantum mechanics continue to give rise to counterintuitive theories and physical effects that are in conflict with a classical description of Nature. Experiments with light at the single photon level have historically been at the forefront of tests of fundamental quantum theory and new developments in photonics engineering continue to enable new experiments. Here we review recent photonic experiments to test two foundational themes in quantum mechanics: wave-particle duality, central to recent complementarity and delayed-choice experiments; and Bell nonlocality where recent theoretical and technological advances have allowed all controversial loopholes to be separately addressed in different photonics experiments.Comment: 10 pages, 5 figures, published as a Nature Physics Insight review articl

    Mother-to-infant and father-to-infant initial emotional involvement

    Get PDF
    While infant attachment has been largely studied, parental attachment is still relatively unknown, especially when referred to fathers. However, it is mainly recognised that parents’ emotional involvement with the newborn contributes to the quality of the interaction and the care they provide. The aim of this study was to study mother-to-infant and father-to-infant initial emotional involvement; namely, differences between mothers and fathers and changes in mother’s emotions toward the neonate within the first days after delivery. The Bonding Scale, an extended Portuguese version of the ‘New Mother-to-Infant Bonding Scale’, was administered during the first two days after childbirth to a sample of 315 mothers and 141 fathers (n = 456), at the Júlio Dinis Maternity Hospital (Portugal). Most mothers and fathers show positive emotions and only a few of them showed negative emotions toward the infant. Maternal and paternal emotional involvement toward the newborn tend to be similar; nevertheless, fathers show less fear and better emotional involvement with the neonate, while mothers are sadder and show more emotions not related to bonding. During the first days following delivery, emotions not related to bonding, such as fear, seem to decrease in mothers.Bial Foundation - Grant 58/02.Human Development and Health Service of the Calouste Gulbenkian Foundation - Grant 48914

    A teleofunctional account of evolutionary mismatch.

    Get PDF
    This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10539-016-9527-1When the environment in which an organism lives deviates in some essential way from that to which it is adapted, this is described as "evolutionary mismatch," or "evolutionary novelty." The notion of mismatch plays an important role, explicitly or implicitly, in evolution-informed cognitive psychology, clinical psychology, and medicine. The evolutionary novelty of our contemporary environment is thought to have significant implications for our health and well-being. However, scientists have generally been working without a clear definition of mismatch. This paper defines mismatch as deviations in the environment that render biological traits unable, or impaired in their ability, to produce their selected effects (i.e., to perform their proper functions in Neander's sense). The machinery developed by Millikan in connection with her account of proper function, and with her related teleosemantic account of representation, is used to identify four major types, and several subtypes, of evolutionary mismatch. While the taxonomy offered here does not in itself resolve any scientific debates, the hope is that it can be used to better formulate empirical hypotheses concerning the effects of mismatch. To illustrate, it is used to show that the controversial hypothesis that general intelligence evolved as an adaptation to handle evolutionary novelty can, contra some critics, be formulated in a conceptually coherent way

    Pb0.4Bi1.6Sr2Ca1Cu2O8+xPb_{0.4}Bi_{1.6}Sr_{2}Ca_{1}Cu_{2}O_{8+x} and Oxygen Stoichiometry: Structure, Resistivity, Fermi Surface Topology and Normal State Properties

    Full text link
    Pb0.4Bi1.6Sr2CaCu2O8+xPb_{0.4}Bi_{1.6}Sr_2CaCu_2O_{8+x} (Bi(Pb)Bi(Pb)-2212) single crystal samples were studied using transmission electron microscopy (TEM), abab-plane (ρab\rho_{ab}) and cc-axis (ρc\rho_c) resistivity, and high resolution angle-resolved ultraviolet photoemission spectroscopy (ARUPS). TEM reveals that the modulation in the bb-axis for Pb(0.4)Pb(0.4)-doped Bi(Pb)Bi(Pb)-2212 is dominantly of PbPb-type that is not sensitive to the oxygen content of the system, and the system clearly shows a structure of orthorhombic symmetry. Oxygen annealed samples exhibit a much lower cc-axis resistivity and a resistivity minimum at 8013080-130K. He-annealed samples exhibit a much higher cc-axis resistivity and dρc/dT<0d\rho_c/dT<0 behavior below 300K. The Fermi surface (FS) of oxygen annealed Bi(Pb)Bi(Pb)-2212 mapped out by ARUPS has a pocket in the FS around the Mˉ\bar{M} point and exhibits orthorhombic symmetry. There are flat, parallel sections of the FS, about 60\% of the maximum possible along kx=kyk_x = k_y, and about 30\% along kx=kyk_x = - k_y. The wavevectors connecting the flat sections are about 0.72(π,π)0.72(\pi, \pi) along kx=kyk_x = k_y, and about 0.80(π,π)0.80(\pi, \pi) along kx=kyk_x = - k_y, rather than (π,π)(\pi,\pi). The symmetry of the near-Fermi-energy dispersing states in the normal state changes between oxygen-annealed and He-annealed samples.Comment: APS_REVTEX 3.0, 49 pages, including 11 figures, available upon request. Submitted to Phys. Rev. B
    corecore