A Variational Approach for Minimizing Lennard-Jones Energies

A variational method for computing conformational properties of molecules with Lennard-Jones potentials for the monomer-monomer interactions is presented. The approach is tailored to deal with angular degrees of freedom, {\it rotors}, and consists in the iterative solution of a set of deterministic equations with annealing in temperature. The singular short-distance behaviour of the Lennard-Jones potential is adiabatically switched on in order to obtain stable convergence. As testbeds for the approach two distinct ensembles of molecules are used, characterized by a roughly dense-packed ore a more elongated ground state. For the latter, problems are generated from natural frequencies of occurrence of amino acids and phenomenologically determined potential parameters; they seem to represent less disorder than was previously assumed in synthetic protein studies. For the dense-packed problems in particular, the variational algorithm clearly outperforms a gradient descent method in terms of minimal energies. Although it cannot compete with a careful simulating annealing algorithm, the variational approach requires only a tiny fraction of the computer time. Issues and results when applying the method to polyelectrolytes at a finite temperature are also briefly discussed.Comment: 14 pages, uuencoded compressed postscript fil

Work-related airway symptoms, nasal reactivity and health-related quality of life in female hairdressers: a follow-up study during exposure.

OBJECTIVES: Hairdressers often complain of work-related rhinitis (WR). They are infrequently sensitized to persulphates. The cause and mechanism of the symptoms and the effects on their health-related quality of life (HRQoL) remains unclear. The objectives were to follow female hairdressers with WR mainly from bleaching powder regarding nasal reactivity to persulphate and to evaluate symptoms, HRQoL and inflammatory markers in nasal lavage during a working period after vacation and compared with hairdressers without symptoms and pollen allergic women. METHODS: Skin prick tests to persulphate were performed in the hairdressers. Participants kept a diary of symptoms and of work tasks (hairdressers only). They completed HRQoL questionnaires. Eosinophil cationic protein (ECP) in nasal lavage fluid was examined. The symptomatic hairdressers performed nasal challenges with persulphate before and after the exposure. RESULTS: Skin prick tests were negative. Although the nasal reactivity to persulphate did not change a steady increase in nasal symptoms, especially blockage, and in ECP was noticed in the symptomatic hairdressers. The HRQoL deteriorated in the symptomatic hairdressers indicating an effect on their working situation and daily life. The atopics had more, but varying symptoms (itching, sneezing and secretion). CONCLUSIONS: The difference in the clinical picture between the symptomatic hairdressers and the pollen allergic women, the increase in symptoms and ECP in the nasal lavage support the view that a sensitization to hairdresser chemicals by a mechanism not yet understood is operating. The deterioration of the HRQoL in the symptomatic hairdressers indicates a considerable effect on their life

Incorporation of excluded volume correlations into Poisson-Boltzmann theory

We investigate the effect of excluded volume interactions on the electrolyte distribution around a charged macroion. First, we introduce a criterion for determining when hard-core effects should be taken into account beyond standard mean field Poisson-Boltzmann (PB) theory. Next, we demonstrate that several commonly proposed local density functional approaches for excluded volume interactions cannot be used for this purpose. Instead, we employ a non-local excess free energy by using a simple constant weight approach. We compare the ion distribution and osmotic pressure predicted by this theory with Monte Carlo simulations. They agree very well for weakly developed correlations and give the correct layering effect for stronger ones. In all investigated cases our simple weighted density theory yields more realistic results than the standard PB approach, whereas all local density theories do not improve on the PB density profiles but on the contrary, deviate even more from the simulation results.Comment: 23 pages, 7 figures, 1 tabl

Advanced therapy medicinal products and health technology assessment principles and practices for value-based and sustainable healthcare

Background Advanced therapy medicinal products (ATMPs) are beginning to reach European markets, and questions are being asked about their value for patients and how healthcare systems should pay for them. Objectives To identify and discuss potential challenges of ATMPs in view of current health technology assessment (HTA) methodology—specifically economic evaluation methods—in Europe as it relates to ATMPs, and to suggest potential solutions to these challenges. Methods An Expert Panel reviewed current HTA principles and practices in relation to the specific characteristics of ATMPs. Results Three key topics were identified and prioritised for discussion—uncertainty, discounting, and health outcomes and value. The panel discussed that evidence challenges linked to increased uncertainty may be mitigated by collection of follow-on data, use of value of information analysis, and/or outcomes-based contracts. For discount rates, an international, multi-disciplinary forum should be established to consider the economic, social and ethical implications of the choice of rate. Finally, consideration of the feasibility of assessing the value of ATMPs beyond health gain may also be key for decision-making. Conclusions ATMPs face a challenge in demonstrating their value within current HTA frameworks. Consideration of current HTA principles and practices with regards to the specific characteristics of ATMPs and continued dialogue will be key to ensuring appropriate market access. Classification code I

Exploring Biorthonormal Transformations of Pair-Correlation Functions in Atomic Structure Variational Calculations

Multiconfiguration expansions frequently target valence correlation and correlation between valence electrons and the outermost core electrons. Correlation within the core is often neglected. A large orbital basis is needed to saturate both the valence and core-valence correlation effects. This in turn leads to huge numbers of CSFs, many of which are unimportant. To avoid the problems inherent to the use of a single common orthonormal orbital basis for all correlation effects in the MCHF method, we propose to optimize independent MCHF pair-correlation functions (PCFs), bringing their own orthonormal one-electron basis. Each PCF is generated by allowing single- and double- excitations from a multireference (MR) function. This computational scheme has the advantage of using targeted and optimally localized orbital sets for each PCF. These pair-correlation functions are coupled together and with each component of the MR space through a low dimension generalized eigenvalue problem. Nonorthogonal orbital sets being involved, the interaction and overlap matrices are built using biorthonormal transformation of the coupled basis sets followed by a counter-transformation of the PCF expansions. Applied to the ground state of beryllium, the new method gives total energies that are lower than the ones from traditional CAS-MCHF calculations using large orbital active sets. It is fair to say that we now have the possibility to account for, in a balanced way, correlation deep down in the atomic core in variational calculations

Monoamine related functional gene variants and relationships to monoamine metabolite concentrations in CSF of healthy volunteers

BACKGROUND: Concentrations of monoamine metabolites in human cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. CSF monoamine metabolite concentrations are partly determined by genetic influences. METHODS: We investigated possible relationships between DNA polymorphisms in the serotonin 2C receptor (HTR2C), the serotonin 3A receptor (HTR3A), the dopamine D(4 )receptor (DRD4), and the dopamine β-hydroxylase (DBH) genes and CSF concentrations of 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = 90). RESULTS: The HTR3A 178 C/T variant was associated with 5-HIAA levels (p = 0.02). The DBH-1021 heterozygote genotype was associated with 5-HIAA (p = 0.0005) and HVA (p = 0.009) concentrations. Neither the HTR2C Cys23Ser variant, nor the DRD4 -521 C/T variant were significantly associated with any of the monoamine metabolites. CONCLUSIONS: The present results suggest that the HTR3A and DBH genes may participate in the regulation of dopamine and serotonin turnover rates in the central nervous system

Thin superconducting disk with B-dependent Jc: Flux and current distributions

The critical state in a superconducting thin circular disk with an arbitrary magnetic field dependence of the critical sheet current, Jc(B), is analyzed. With an applied field Ba perpendicular to the disk, a set of coupled integral equations for the flux and current distributions is derived. The equations are solved numerically, and flux and current profiles are presented graphically for several commonly used Jc(B) dependences. It is shown that for small Ba the flux penetration depth can be described by an effective Bean model with a renormalized Jc entering the leading term. We argue that these results are qualitatively correct for thin superconductors of any shape. The results contrast the parallel geometry behavior, where at small Ba the B-dependence of the critical current can be ignored.Comment: RevTeX, 7 pages including 8 figure

Optogalvanic Spectroscopy of Metastable States in Yb^{+}

The metastable ^{2}F_{7/2} and ^{2}D_{3/2} states of Yb^{+} are of interest for applications in metrology and quantum information and also act as dark states in laser cooling. These metastable states are commonly repumped to the ground state via the 638.6 nm ^{2}F_{7/2} -- ^{1}D[5/2]_{5/2} and 935.2 nm ^{2}D_{3/2} -- ^{3}D[3/2]_{1/2} transitions. We have performed optogalvanic spectroscopy of these transitions in Yb^{+} ions generated in a discharge. We measure the pressure broadening coefficient for the 638.6 nm transition to be 70 \pm 10 MHz mbar^{-1}. We place an upper bound of 375 MHz/nucleon on the 638.6 nm isotope splitting and show that our observations are consistent with theory for the hyperfine splitting. Our measurements of the 935.2 nm transition extend those made by Sugiyama et al, showing well-resolved isotope and hyperfine splitting. We obtain high signal to noise, sufficient for laser stabilisation applications.Comment: 8 pages, 5 figure

A comprehensive comparison between APOGEE and LAMOST: Radial Velocities and Atmospheric Stellar Parameters

We undertake a critical and comprehensive comparison of the radial velocities and the main stellar atmospheric parameters for stars in common between the latest data releases from the APOGEE and the LAMOST surveys. There is a total of 42,420 dwarfs/giants stars in common between the APOGEE DR14 - LAMOST DR3 stellar catalogs. A comparison between the RVs shows an offset of 4.54 $\pm$ 0.03 km/s, with a dispersion of 5.8 km/s, in the sense that APOGEE RVs are larger. We observe a small offset in the Teff of about 13 K, with a scatter of 155 K. Small offset in [Fe/H] of about 0.06 dex together with a scatter of 0.13 dex is also observed. We notice that the largest offset between the surveys occurs in the surface gravities. Using only surface gravities in calibrated red giants from APOGEE DR14, where there are 24,074 stars in common, a deviation of 0.14 dex is found with substantial scatter. There are 17,482 red giant stars in common between APOGEE DR14 and those in LAMOST tied to APOGEE DR12 via the Cannon. There is generally good agreement between the two data-sets. However, we find dependencies of the differences of the stellar parameters on effective temperature. For metal-rich stars, a different trend for the [Fe/H] discrepancies is found. Surprisingly, we see no correlation between the internal APOGEE DR14 - DR12 differences in Teff and those in DR14 - LAMOST tied to DR12, where a correlation should be expected since LAMOST has been calibrated to APOGEE DR12. We also find no correlation between the [Fe/H] discrepancies, suggesting that LAMOST/Cannon is not well coupled to the APOGEE DR12 stellar parameters scale. A [Fe/H] dependence between the stellar parameters in APOGEE DR12 and those in DR14 is reported. We find a weak correlation in the differences between APOGEE DR14 - DR12 and LAMOST on DR12 surface gravity for stars hotter than 4800 K and in the log g range between 2.0 and 2.8.Comment: 14 pages, 20 figures. Accepted for publication in Astronomy & Astrophysics (A&A

Natural history of Arabidopsis thaliana and oomycete symbioses

Molecular ecology of plant–microbe interactions has immediate significance for filling a gap in knowledge between the laboratory discipline of molecular biology and the largely theoretical discipline of evolutionary ecology. Somewhere in between lies conservation biology, aimed at protection of habitats and the diversity of species housed within them. A seemingly insignificant wildflower called Arabidopsis thaliana has an important contribution to make in this endeavour. It has already transformed botanical research with deepening understanding of molecular processes within the species and across the Plant Kingdom; and has begun to revolutionize plant breeding by providing an invaluable catalogue of gene sequences that can be used to design the most precise molecular markers attainable for marker-assisted selection of valued traits. This review describes how A. thaliana and two of its natural biotrophic parasites could be seminal as a model for exploring the biogeography and molecular ecology of plant–microbe interactions, and specifically, for testing hypotheses proposed from the geographic mosaic theory of co-evolution