HIV-1 DIS stem loop forms an obligatory bent kissing intermediate in the dimerization pathway.

The HIV-1 dimerization initiation sequence (DIS) is a conserved palindrome in the apical loop of a conserved hairpin motif in the 5′-untranslated region of its RNA genome. DIS hairpin plays an important role in genome dimerization by forming a ‘kissing complex’ between two complementary hairpins. Understanding the kinetics of this interaction is key to exploiting DIS as a possible human immunodeficiency virus (HIV) drug target. Here, we present a single-molecule Förster resonance energy transfer (smFRET) study of the dimerization reaction kinetics. Our data show the real-time formation and dissociation dynamics of individual kissing complexes, as well as the formation of the mature extended duplex complex that is ultimately required for virion packaging. Interestingly, the single-molecule trajectories reveal the presence of a previously unobserved bent intermediate required for extended duplex formation. The universally conserved A272 is essential for the formation of this intermediate, which is stabilized by Mg(2+), but not by K(+) cations. We propose a 3D model of a possible bent intermediate and a minimal dimerization pathway consisting of three steps with two obligatory intermediates (kissing complex and bent intermediate) and driven by Mg(2+) ions

Finite dimensional quantizations of the (q,p) plane : new space and momentum inequalities

We present a N-dimensional quantization a la Berezin-Klauder or frame quantization of the complex plane based on overcomplete families of states (coherent states) generated by the N first harmonic oscillator eigenstates. The spectra of position and momentum operators are finite and eigenvalues are equal, up to a factor, to the zeros of Hermite polynomials. From numerical and theoretical studies of the large $N$ behavior of the product $\lambda\_m(N) \lambda\_M(N)$ of non null smallest positive and largest eigenvalues, we infer the inequality $\delta\_N(Q) \Delta\_N(Q) = \sigma\_N \overset{<}{\underset{N \to \infty}{\to}} 2 \pi$ (resp. $\delta\_N(P) \Delta\_N(P) = \sigma\_N \overset{<}{\underset{N \to \infty}{\to}} 2 \pi$) involving, in suitable units, the minimal ($\delta\_N(Q)$) and maximal ($\Delta\_N(Q)$) sizes of regions of space (resp. momentum) which are accessible to exploration within this finite-dimensional quantum framework. Interesting issues on the measurement process and connections with the finite Chern-Simons matrix model for the Quantum Hall effect are discussed

Effects of halothane, sevoflurane and propofol on left ventricular diastolic function in humans during spontaneous and mechanical ventilation

Background. There is limited knowledge of the effects of anaesthetics on left ventricular (LV) diastolic function in humans. Our aim was to evaluate these effects in humans free from cardiovascular disease. Methods. Sixty patients (aged 18-47 yr) who had no history or signs of cardiovascular disease were randomized to receive general anaesthesia with halothane, sevoflurane or propofol. Echocardiography was performed at baseline and during spontaneous respiration at 1 minimum alveolar concentration (MAC) of the inhalational agents or propofol 4 µg ml−1 (step 1), and repeated during positive-pressure ventilation with 1 and 1.5 MAC of the inhalational agents or with propofol 4 and 6 µg ml−1 (steps 2a and 2b). Analysis of echocardiographic measurements focused on heart rate corrected isovolumic relaxation time (IVRTc) and early diastolic peak velocity of the lateral mitral annulus (Ea). Results. IVRTc decreased from baseline to step 1 in the halothane group (82 [95% CI, 76-88] ms and 74 [95% CI, 68-80] ms respectively; P=0.02), remained stable in the sevoflurane group (78 [95% CI, 72-83] ms and 73 [95% CI, 67-81] ms; n.s.) and increased in the propofol group (80 [95% CI, 74-86] ms and 92 [95% CI, 84-102] ms; P=0.02). Ea decreased in the propofol group only (18.8 [95% CI, 16.5-19.9] cm s−1 and 16.0 [95% CI, 14.9-17.9] cm s−1; P=0.003). From step 2a to step 2b, IVRTc increased further in the propofol group (109 [95% CI, 99-121] ms and 119 [95% CI, 99-135] ms; P=0.04) but remained stable in the other two groups. Ea did not change from step 2a to step 2b. Conclusions. Halothane and sevoflurane did not impair LV relaxation, whereas propofol caused a mild impairment. However, the impairment by propofol was of a magnitude that is unlikely to cause clinical diastolic dysfunctio

Study of flavour dependencies in leptogenesis

We study the impact of flavours on the efficiency factors and give analytical and numerical results of the baryon asymmetry taking into account the different charged lepton Yukawa contributions and the complete (diagonal and off-diagonal) $L$ to $B-L$ conversion $A$ matrix. With this treatment we update the lower bound on the lightest right-handed neutrino mass.Comment: 13 pages, 11 figures. typos corrected, some formulae modified. 2 figures and discussion adde

Leptogenesis beyond the limit of hierarchical heavy neutrino masses

We calculate the baryon asymmetry of the Universe in thermal leptogenesis beyond the usual lightest right-handed (RH) neutrino dominated scenario (N_1DS) and in particular beyond the hierarchical limit (HL), M_1 << M_2 << M_3, for the RH neutrino mass spectrum. After providing some orientation among the large variety of models, we first revisit the central role of the N_1DS, with new insights on the dynamics of the asymmetry generation and then discuss the main routes departing from it, focusing on models beyond the HL. We study in detail two examples of `strong-strong' wash-out scenarios: one with `maximal phase' and the limit of very large M_3, studying the effects arising when delta_2=(M_2-M_1)/M_1 is small. We extend analytical methods already applied to the N_1DS showing, for example, that, in the degenerate limit (DL), the efficiency factors of the RH neutrinos become equal with the single decay parameter replaced by the sum. Both cases disprove the misconception that close RH neutrino masses necessarily lead to a final asymmetry enhancement and to a relaxation of the lower bounds on M_1 and on the initial temperature of the radiation-dominated expansion. We also explain why leptogenesis tends to favor normal hierarchy compared to inverted hierarchy for the left-handed neutrino masses.Comment: 30 pages, 8 figures; corrected typo in Eq. (67); shortened Introduction, Section 3 and Conclusions; one figure removed; added 2 references; to appear in JCA

Leptogenesis in the presence of exact flavor symmetries

In models with flavor symmetries in the leptonic sector leptogenesis can take place in a very different way compared to the standard leptogenesis scenario. We study the generation of a $B-L$ asymmetry in these kind of models in the flavor symmetric phase pointing out that successful leptogenesis requires (i) the right-handed neutrinos to lie in different representations of the flavor group; (ii) the flavons to be lighter at least that one of the right-handed neutrino representations. When these conditions are satisfied leptogenesis proceeds due to new contributions to the CP violating asymmetry and -depending on the specific model- in several stages. We demonstrate the validity of these arguments by studying in detail the generation of the $B-L$ asymmetry in a scenario of a concrete $A_4$ flavor model realization.Comment: 25 pages, 7 figures; version 2: A few clarifications added. Version matches publication in JHE

Thermomechanical Response of a Representative Porin for Biomimetics

The thermomechanical response of Omp2a, a representative porin used for the fabrication of smart biomimetic nanomembranes, has been characterized using microcantilever technology and compared with standard proteins. For this purpose, thermally induced transitions involving the conversion of stable trimers to bigger aggregates, local reorganizations based on the strengthening or weakening of intermolecular interactions, and protein denaturation have been detected by the microcantilever resonance frequency and deflection as a function of the temperature. Measurements have been carried out on arrays of 8-microcantilevers functionalized with proteins (Omp2a, lysozyme and bovine serum albumin). To interpret the measured nanofeatures, the response of proteins to temperature has been also examined using other characterization techniques, including real time wide angle X-ray diffraction. Results not only demonstrate the complex behavior of porins, which exhibit multiple local thermal transitions before undergoing denaturation at temperatures higher than 105 °C, but also suggest a posttreatment to control the orientation of immobilized Omp2a molecules in functionalized biomimetic nanomembranes and, thus, increase their efficacy in ion transport.Peer Reviewe