Statistical models for assessing agreement in method comparison studies with replicate measurements

Abstract Method comparison studies are usually analyzed by computing limits of agreement. It is recommended that replicate measurements be taken by each method, but the resulting data are more cumbersome to analyze. We discuss the statistical model underlying the classical limits of agreement and extend it to the case with replicate measurements. As the required code to fit the models is non-trivial, we provide example computer code to fit the models, and show how to use the output to derive measures of repeatability and limits of agreement. KEYWORDS: method comparison, Bland-Altman plot, mixed models * We are grateful to Peter Dalgaard for (much needed) advice on the lme syntax

Interspecific analysis of diurnal gene regulation in panicoid grasses identifies known and novel regulatory motifs

Background: The circadian clock drives endogenous 24-h rhythms that allow organisms to adapt and prepare for predictable and repeated changes in their environment throughout the day-night (diurnal) cycle. Many components of the circadian clock in Arabidopsis thaliana have been functionally characterized, but comparatively little is known about circadian clocks in grass species including major crops like maize and sorghum. Results: Comparative research based on protein homology and diurnal gene expression patterns suggests the function of some predicted clock components in grasses is conserved with their Arabidopsis counterparts, while others have diverged in function. Our analysis of diurnal gene expression in three panicoid grasses sorghum, maize, and foxtail millet revealed conserved and divergent evolution of expression for core circadian clock genes and for the overall transcriptome. We find that several classes of core circadian clock genes in these grasses differ in copy number compared to Arabidopsis, but mostly exhibit conservation of both protein sequence and diurnal expression pattern with the notable exception of maize paralogous genes. We predict conserved cis-regulatory motifs shared between maize, sorghum, and foxtail millet through identification of diurnal co-expression clusters for a subset of 27,196 orthologous syntenic genes. In this analysis, a Cochran– Mantel–Haenszel based method to control for background variation identified significant enrichment for both expected and novel 6–8 nucleotide motifs in the promoter regions of genes with shared diurnal regulation predicted to function in common physiological activities. Conclusions: This study illustrates the divergence and conservation of circadian clocks and diurnal regulatory networks across syntenic orthologous genes in panacoid grass species. Further, conserved local regulatory sequences contribute to the architecture of these diurnal regulatory networks that produce conserved patterns of diurnal gene expression

PT-symmetry breaking and maximal chirality in a nonuniform PT-symmetric ring

We study the properties of an N-site tight-binding ring with parity and time-reversal (PT) symmetric, Hermitian, site-dependent tunneling and a pair of non-Hermitian, PT-symmetric, loss and gain impurities $\pm i\gamma$. The properties of such lattices with open boundary conditions have been intensely explored over the past two years. We numerically investigate the PT-symmetric phase in a ring with a position-dependent tunneling function $t_\alpha(k)=[k(N-k)]^{\alpha/2}$ that, in an open lattice, leads to a strengthened PT-symmetric phase, and study the evolution of the PT-symmetric phase from the open chain to a ring. We show that, generally, periodic boundary conditions weaken the PT-symmetric phase, although for experimentally relevant lattice sizes $N \sim 50$, it remains easily accessible. We show that the chirality, quantified by the (magnitude of the) average transverse momentum of a wave packet, shows a maximum at the PT-symmetric threshold. Our results show that although the wavepacket intensity increases monotonically across the PT-breaking threshold, the average momentum decays monotonically on both sides of the threshold.Comment: 11 pages, 5 figures, preprin

PT-Symmetric Electronics

We show both theoretically and experimentally that a pair of inductively coupled active LRC circuits (dimer), one with amplification and another with an equivalent amount of attenuation, display all the features which characterize a wide class of non-Hermitian systems which commute with the joint parity-time PT operator: typical normal modes, temporal evolution, and scattering processes. Utilizing a Liouvilian formulation, we can define an underlying PT-symmetric Hamiltonian, which provides important insight for understanding the behavior of the system. When the PT-dimer is coupled to transmission lines, the resulting scattering signal reveals novel features which reflect the PT-symmetry of the scattering target. Specifically we show that the device can show two different behaviors simultaneously, an amplifier or an absorber, depending on the direction and phase relation of the interrogating waves. Having an exact theory, and due to its relative experimental simplicity, PT-symmetric electronics offers new insights into the properties of PT-symmetric systems which are at the forefront of the research in mathematical physics and related fields.Comment: 17 pages, 7 figure

Radical cation salts of TTF donors with XF6 (X = Re,Ta) anions

Electrocrystallization of the dianionic Re(IV)F6 species with different organic π electron donors was carried out. Depending on the first oxidation potential of the TTF derivatives this crystallization technique gave rise to various radical cations salts involving Re(IV) or Re(V) anions. With tetramethyltetrathiafulvalene (TMTTF) the (TMTTF)2Re(IV)F6  salt was obtained. However, with tetramethyltetraselenafulvalene (TMTSF) we obtained very small needles of the (TMTSeF)2Re(V)F6 system, analogue to the so called “Bechgaard salts” [1]. We present some characteristics of this new metallic phase. We compare to the diamagnetic (TMTSeF)2Ta(V)F6 obtained by the same strategy using TBATaF6 prepared according to the Browstein’s method [2] and explore electrocrystallization of the tantalum based anions [3], [4]. References: [1] K. Bechgaard, C.S. Jacobsen, K. Mortensen, H.J. Pedersen, N. Thorup, Solid State Commun. 1980, 33, 1119-1125. [2] S. Brownstein, Inorg. Chem. 1973, 12, N°3, 584-589. [3] C. Lenoir, K. Boubekeur, P. Batail, E. Canadell, P. Auban, O. Traetteberg, D. Jérome, Synth. Met. 1991, 42, 1939-1942. [4] F. Iwase, K. Sugiura, K. Furukawa, T. Nakamura, J. Phys. Soc. Jpn. 2009, 78, N°10, 104717:1-104717:7

Skin microbiota analysis in patients with anorexia nervosa and healthy-weight controls reveals microbial indicators of healthy weight and associations with the antimicrobial peptide psoriasin

Anorexia nervosa (AN), a psychiatric condition defined by low body weight for age and height, is associated with numerous dermatological conditions. Yet, clinical observations report that patients with AN do not suffer from infectious skin diseases like those associated with primary malnutrition. Cell-mediated immunity appears to be amplified in AN; however, this proinflammatory state does not sufficiently explain the lower incidence of infections. Antimicrobial peptides (AMPs) are important components of the innate immune system protecting from pathogens and shaping the microbiota. In Drosophila melanogaster starvation precedes increased AMP gene expression. Here, we analyzed skin microbiota in patients with AN and age-matched, healthy-weight controls and investigated the influence of weight gain on microbial community structure. We then correlated features of the skin microbial community with psoriasin and RNase 7, two highly abundant AMPs in human skin, to clarify whether an association between AMPs and skin microbiota exists and whether such a relationship might contribute to the resistance to cutaneous infections observed in AN. We find significant statistical correlations between Shannon diversity and the highly abundant skin AMP psoriasin and bacterial load, respectively. Moreover, we reveal psoriasin significantly associates with Abiotrophia, an indicator for the healthy-weight control group. Additionally, we observe a significant correlation between an individual’s body mass index and Lactobacillus, a microbial indicator of health. Future investigation may help clarify physiological mechanisms that link nutritional intake with skin physiology

An exactly solvable quantum-lattice model with a tunable degree of nonlocality

An array of N subsequent Laguerre polynomials is interpreted as an eigenvector of a non-Hermitian tridiagonal Hamiltonian $H$ with real spectrum or, better said, of an exactly solvable N-site-lattice cryptohermitian Hamiltonian whose spectrum is known as equal to the set of zeros of the N-th Laguerre polynomial. The two key problems (viz., the one of the ambiguity and the one of the closed-form construction of all of the eligible inner products which make $H$ Hermitian in the respective {\em ad hoc} Hilbert spaces) are discussed. Then, for illustration, the first four simplest, $k-$parametric definitions of inner products with $k=0,k=1,k=2$ and $k=3$ are explicitly displayed. In mathematical terms these alternative inner products may be perceived as alternative Hermitian conjugations of the initial N-plet of Laguerre polynomials. In physical terms the parameter $k$ may be interpreted as a measure of the "smearing of the lattice coordinates" in the model.Comment: 35 p

Terminal Ligand and Packing Effects on Slow Relaxation in an Isostructural Set of [Dy(H2_{2}dapp)X2_{2}]+ Single Molecule Magnets**

Three new dysprosium complexes with a pentadentate ligand occupying five equatorial sites differ only in the nature of the axial ligands. These help tune the relaxation properties as judged by an analysis of the AC susceptibility data. More in depth analysis by using two recently suggested fitting equations lead to similar outcomes for all three systems. As a further contribution to the relaxation pathway involving the phonon bath it is concluded that a short nitrate-nitrate interaction between molecules helps dampen the spin phonon coupling. We report three structurally related single ion Dy compounds using the pentadentate ligand 2,6-bis((E)-1-(2-(pyridin-2-yl)-hydrazineylidene)ethyl)pyridine (H$_{2}$dapp) [Dy(H$_{2}$dapp)(NO$_{3}$)$_{2}$]NO$_{3}$ (1), [Dy(H$_{2}$dapp)(OAc)$_{2}$]Cl (2) and [Dy(H$_{2}$dapp)(NO$_{3}$)$_{2}$]Cl$_{0.92}$(NO$_{3}$)$_{0.08}$ (3). The (H$_{2}$dapp) occupies a helical twisted pentagonal equatorial arrangement with two anionic ligands in the axial positions. Further influence on the electronic and magnetic structure is provided by a closely associated counterion interacting with the central N−H group of the (H$_{2}$dapp). The slow relaxation of the magnetisation shows that the anionic acetates give the greatest slowing down of the magnetisation reversal. Further influence on the relaxation properties of compounds1 and 2 is the presence of short nitrate-nitrate intermolecular ligand contact opening further lattice relaxation pathways

Prevention of neonatal oxygen-induced brain damage by reduction of intrinsic apoptosis

International audienceWithin the last decade, it became clear that oxygen contributes to the pathogenesis of neonatal brain damage, leading to neurocognitive impairment of prematurely born infants in later life. Recently, we have identified a critical role for receptor-mediated neuronal apoptosis in the immature rodent brain. However, the contribution of the intrinsic apoptotic pathway accompanied by activation of caspase-2 under hyperoxic conditions in the neonatal brain still remains elusive. Inhibition of caspases appears a promising strategy for neuroprotection. In order to assess the influence of specific caspases on the developing brain, we applied a recently developed pentapeptide-based group II caspase inhibitor (5-(2,6-difluorophenoxy)-3(R,S)-(2(S)-(2(S)-(3-methoxycarbonyl-2(S)-(3-m ethyl-2(S)-((quinoline-2-carbonyl)-amino)-butyrylamino)propionylamino) 3-methylbutyrylamino) propionylamino)-4-oxo-pentanoic acid methyl ester; TRP601). Here, we report that elevated oxygen (hyperoxia) triggers a marked increase in active caspase-2 expression, resulting in an initiation of the intrinsic apoptotic pathway with upregulation of key proteins, namely, cytochrome c, apoptosis protease-activating factor-1, and the caspase-independent protein apoptosis-inducing factor, whereas BH3-interacting domain death agonist and the anti-apoptotic protein B-cell lymphoma-2 are downregulated. These results coincide with an upregulation of caspase-3 activity and marked neurodegeneration. However, single treatment with TRP601 at the beginning of hyperoxia reversed the detrimental effects in this model. Hyperoxia-mediated neurodegeneration is supported by intrinsic apoptosis, suggesting that the development of highly selective caspase inhibitors will represent a potential useful therapeutic strategy in prematurely born infants. Cell Death and Disease (2012) 3, e250; doi:10.1038/cddis.2011.133; published online 12 January 201