Self-adjoint Time Operator is the Rule for Discrete Semibounded Hamiltonians

We prove explicitly that to every discrete, semibounded Hamiltonian with constant degeneracy and with finite sum of the squares of the reciprocal of its eigenvalues and whose eigenvectors span the entire Hilbert space there exists a characteristic self-adjoint time operator which is canonically conjugate to the Hamiltonian in a dense subspace of the Hilbert space. Moreover, we show that each characteristic time operator generates an uncountable class of self- adjoint operators canonically conjugate with the same Hamiltonian in the same dense subspace.Comment: accepted for publication in the Proceedings of the Royal Society of London

Galactic Gamma-Ray Background Radiation from Supernova Remnants

The contribution of the Source Cosmic Rays (SCRs), confined in Supernova Remnants, to the diffuse high energy \gr emission above 1 GeV from the Galactic disk is studied. \grs produced by the SCRs have a much harder spectrum compared with those generated by the Galactic Cosmic Rays which occupy a much larger residence volume uniformly. SCRs contribute less than 10% at GeV energies and become dominant at \gr energies above 100 GeV. The contributions from $\pi^0$-decay and Inverse Compton \grs have comparable magnitude and spectral shape, whereas the Bremsstrahlung component is negligible. At TeV energies the contribution from SCRs increases the expected diffuse \gr flux almost by an order of magnitude. It is shown that for the inner Galaxy the discrepancy between the observed diffuse intensity and previous model predictions at energies above a few GeV can be attributed to the SCR contribution.Comment: 25 pages, 1 figures, to appear in Ap

The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates IRS-1 signaling via the formation of a sequestration complex

Phosphoinositide (PI) 3-kinase is required for most insulin and insulin-like growth factor (IGF) 1–dependent cellular responses. The p85 regulatory subunit of PI 3-kinase is required to mediate the insulin-dependent recruitment of PI 3-kinase to the plasma membrane, yet mice with reduced p85 expression have increased insulin sensitivity. To further understand the role of p85, we examined IGF-1–dependent translocation of p85α by using a green fluorescence protein (GFP)–tagged p85α (EGFP–p85α). In response to IGF-1, but not to PDGF signaling, EGFP–p85α translocates to discrete foci in the cell. These foci contain the insulin receptor substrate (IRS) 1 adaptor molecule, and their formation requires the binding of p85 to IRS-1. Surprisingly, monomeric p85 is preferentially localized to these foci compared with the p85–p110 dimer, and these foci are not sites of phosphatidylinositol-3,4,5-trisphosphate production. Ultrastructural analysis reveals that p85–IRS-1 foci are cytosolic protein complexes devoid of membrane. These results suggest a mechanism of signal down-regulation of IRS-1 that is mediated by monomeric p85 through the formation of a sequestration complex between p85 and IRS-1

Population-based assessment of cardiovascular complications of rheumatic heart disease in Fiji: a record-linkage analysis

Objective: To determine population-based rates of nonfatal complications of rheumatic heart disease (RHD). Design: Retrospective cohort study based on multiple sources of routine clinical and administrative data amalgamated by probabilistic record-linkage. Setting: Fiji, an upper-middle-income country, where most of the population has access to government-funded health care services. Participants: National cohort of 2,116 patients with clinically apparent RHD aged 5-69 years during 2008-2012. Primary and secondary outcome measures: The primary outcome was hospitalisation for any of heart failure, atrial fibrillation, ischaemic stroke and infective endocarditis. Secondary outcomes were first hospitalisation for each of the complications individually in the national cohort as well as in hospital (n=1300) and maternity (n=210) subsets. Information on outcomes was obtained from discharge diagnoses coded in the hospital patient information system. Population-based rates were obtained using relative survival methods with census data as the denominator. Results: Among 2,116 patients in the national cohort (median age, 23.3 years; 57.7% female), 546 (25.8%) were hospitalised for an RHD complication, a substantial proportion of all cardiovascular admissions in the country during this period in those aged 0–40 years (heart failure, 210/454, 46.2%; ischaemic stroke 31/134, 23.3%). Absolute numbers of RHD complications peaked during the third decade of life with higher population-based rates in women compared to men (incidence rate ratio 1.4, 95% CI 1.3–1.6, P<0.001). Hospitalisation for any RHD complication was associated with substantially increased risk of death (hazard ratio, 5.4, 95% CI, 3.4–8.8, P<0.001), especially after the onset of heart failure (hazard ratio, 6.6, 95% CI, 4.8–9.1, P<0.001). Conclusions: Our study defines the burden of RHD-attributable morbidity in the general population of Fiji, potentially reflecting the situation in low- and middle-income countries worldwide. Hospitalisation for an RHD complication is associated with markedly increased risk of death, re- emphasising the importance of effective early prevention

Pion-Lambda-Sigma Coupling Extracted from Hyperonic Atoms

The latest measurements of the atomic level width in Sigma-hyperonic Pb atom offer the most accurate datum in the region of low-energy Sigma-hyperon physics. Atomic widths are due to the conversion of Sigma-nucleon into Lambda-nucleon. In high angular momentum states this conversion is dominated by the one-pion exchange. A joint analysis of the data of the scattering of negative-Sigma on proton converting into a Lambda and a neutron and of the atomic widths allows to extract a pseudovector pion-hyperon-Sigma coupling constant of 0.048 with a statistical error of +-0.005 and a systematic one of +-0.004. This corresponds to a pseudoscalar coupling constant of 13.3 with a statistical uncertainty of 1.4 and a systematic one of 1.1.Comment: 12 pages, 1 figure, Use of Revtex.st

Deciphering the folding kinetics of transmembrane helical proteins

Nearly a quarter of genomic sequences and almost half of all receptors that are likely to be targets for drug design are integral membrane proteins. Understanding the detailed mechanisms of the folding of membrane proteins is a largely unsolved, key problem in structural biology. Here, we introduce a general model and use computer simulations to study the equilibrium properties and the folding kinetics of a $C_{\alpha}$-based two helix bundle fragment (comprised of 66 amino-acids) of Bacteriorhodopsin. Various intermediates are identified and their free energy are calculated toghether with the free energy barrier between them. In 40% of folding trajectories, the folding rate is considerably increased by the presence of non-obligatory intermediates acting as traps. In all cases, a substantial portion of the helices is rapidly formed. This initial stage is followed by a long period of consolidation of the helices accompanied by their correct packing within the membrane. Our results provide the framework for understanding the variety of folding pathways of helical transmembrane proteins

The Role of Demography in the Transition to Sustainable Societies

Currently, although the global population has surpassed 7.5 billion and continues to increase in about 80 million each year, attention to demography is almost absent in most of the studies and publications related to the current situation of planetary emergency and the necessary transition to sustainable societies. For this reason, our first aim in this paper has been to discuss if this current lack of attention to demography is justified or not. With this purpose, we begin considering the scientific meaning of Sustainability, in order to overlay distorted and impoverish views of this concept that may hinder our study. Then, we analyse the reasons given by experts for and against the incidence of demographic growth in the current unsustainable situation of planetary emergency. Finally, we present proposals to face the ensemble of interconnected socio-environmental problems (including demographic evolution), to make possible an appropriate transition to sustainable societies. Aunque la población mundial ha sobrepasado los 7500 millones y continúa aumentando anualmente en alrededor de 80 millones, la atención a la demografía está hoy prácticamente ausente en la mayoría de los estudios y publicaciones acerca de la actual situación de emergencia planetaria y la necesidad de una transición a sociedades sostenibles. Con el propósito de analizar si esta falta de atención a la demografía está o no justificada, en esta contribución comenzamos discutiendo el significado científico de Sostenibilidad socioambiental, para evitar concepciones distorsionadas y empobrecidas de este concepto que pueden dificultar dicho análisis. A continuación estudiaremos las razones dadas por distintos expertos a favor y en contra de la incidencia del crecimiento demográfico en la insostenible situación actual de emergencia planetaria. Finalmente presentamos propuestas para hacer frente al conjunto de problemas estrechamente interconectados - incluido el problema demográfico - que caracterizan dicha situación, para hacer así posible una adecuada transición a sociedades sostenibles

First Observations of Long-Lived Meteor Trains with Resonance Lidar and Other Optical Instruments

In November 1998 the earth passed through a maximum in the cometary material responsible for the yearly Leonids meteor shower. The meteor storm event produced numerous examples of long-lived chemiluminescent trails--visible to the naked eye over New Mexico, where a major observation campaign was centered. One trail was detected for over an hour with a CCD camera employing a narrow sodium filter, and many others were observed for over ten minutes each. For the first time, sodium densities in such trails were measured while also being imaged in sodium light. We have verified one source of long-lived light emissions--a sodium-catalyzed reaction involving ozone--but it is far too weak to explain the visibility of such trails. In addition, we present a new explanation for the cylindrical shell appearance long reported for chemiluminescent trails and show that ozone depletion by chemical processes is a possible explanation for this phenomenon

Cryo-EM structure of the Rous sarcoma virus octameric cleaved synaptic complex intasome

Despite conserved catalytic integration mechanisms, retroviral intasomes composed of integrase (IN) and viral DNA possess diverse structures with variable numbers of IN subunits. To investigate intasome assembly mechanisms, we employed the Rous sarcoma virus (RSV) IN dimer that assembles a precursor tetrameric structure in transit to the mature octameric intasome. We determined the structure of RSV octameric intasome stabilized by a HIV-1 IN strand transfer inhibitor using single particle cryo-electron microscopy. The structure revealed significant flexibility of the two non-catalytic distal IN dimers along with previously unrecognized movement of the conserved intasome core, suggesting ordered conformational transitions between intermediates that may be important to capture the target DNA. Single amino acid substitutions within the IN C-terminal domain affected intasome assembly and function in vitro and infectivity of pseudotyped RSV virions. Unexpectedly, 17 C-terminal amino acids of IN were dispensable for virus infection despite regulating the transition of the tetrameric intasome to the octameric form in vitro. We speculate that this region may regulate the binding of highly flexible distal IN dimers to the intasome core to form the octameric complex. Our studies reveal key steps in the assembly of RSV intasomes

Structural Basis for Functional Tetramerization of Lentiviral Integrase

Experimental evidence suggests that a tetramer of integrase (IN) is the protagonist of the concerted strand transfer reaction, whereby both ends of retroviral DNA are inserted into a host cell chromosome. Herein we present two crystal structures containing the N-terminal and the catalytic core domains of maedi-visna virus IN in complex with the IN binding domain of the common lentiviral integration co-factor LEDGF. The structures reveal that the dimer-of-dimers architecture of the IN tetramer is stabilized by swapping N-terminal domains between the inner pair of monomers poised to execute catalytic function. Comparison of four independent IN tetramers in our crystal structures elucidate the basis for the closure of the highly flexible dimer-dimer interface, allowing us to model how a pair of active sites become situated for concerted integration. Using a range of complementary approaches, we demonstrate that the dimer-dimer interface is essential for HIV-1 IN tetramerization, concerted integration in vitro, and virus infectivity. Our structures moreover highlight adaptable changes at the interfaces of individual IN dimers that allow divergent lentiviruses to utilize a highly-conserved, common integration co-factor