Insights into the relation between noise and biological complexity

Understanding under which conditions the increase of systems complexity is evolutionary advantageous, and how this trend is related to the modulation of the intrinsic noise, are fascinating issues of utmost importance for synthetic and systems biology. To get insights into these matters, we analyzed chemical reaction networks with different topologies and degrees of complexity, interacting or not with the environment. We showed that the global level of fluctuations at the steady state, as measured by the sum of the Fano factors of the number of molecules of all species, is directly related to the topology of the network. For systems with zero deficiency, this sum is constant and equal to the rank of the network. For higher deficiencies, we observed an increase or decrease of the fluctuation levels according to the values of the reaction fluxes that link internal species, multiplied by the associated stoichiometry. We showed that the noise is reduced when the fluxes all flow towards the species of higher complexity, whereas it is amplified when the fluxes are directed towards lower complexity species.Comment: 5 pages, 3 figure

Homotopy, monopoles and 't Hooft tensor in QCD with generic gauge group

We study monopoles and corresponding 't Hooft tensor in QCD with a generic compact gauge group. This issue is relevant to the understanding of color confinement in terms of dual symmetry.Comment: 15 pages. Accepted for publication in JHE

Supersymmetric Wilson loops at two loops

We study the quantum properties of certain BPS Wilson loops in ${\cal N}=4$ supersymmetric Yang-Mills theory. They belong to a general family, introduced recently, in which the addition of particular scalar couplings endows generic loops on $S^3$ with a fraction of supersymmetry. When restricted to $S^2$, their quantum average has been further conjectured to be exactly computed by the matrix model governing the zero-instanton sector of YM$_2$ on the sphere. We perform a complete two-loop analysis on a class of cusped Wilson loops lying on a two-dimensional sphere, finding perfect agreement with the conjecture. The perturbative computation reproduces the matrix-model expectation through a highly non-trivial interplay between ladder diagrams and self-energies/vertex contributions, suggesting the existence of a localization procedure.Comment: 35 pages, 14 figures, typos corrected, references adde

Deciphering noise amplification and reduction in open chemical reaction networks

The impact of random fluctuations on the dynamical behavior a complex biological systems is a longstanding issue, whose understanding would shed light on the evolutionary pressure that nature imposes on the intrinsic noise levels and would allow rationally designing synthetic networks with controlled noise. Using the It\=o stochastic differential equation formalism, we performed both analytic and numerical analyses of several model systems containing different molecular species in contact with the environment and interacting with each other through mass-action kinetics. These systems represent for example biomolecular oligomerization processes, complex-breakage reactions, signaling cascades or metabolic networks. For chemical reaction networks with zero deficiency values, which admit a detailed- or complex-balanced steady state, all molecular species are uncorrelated. The number of molecules of each species follow a Poisson distribution and their Fano factors, which measure the intrinsic noise, are equal to one. Systems with deficiency one have an unbalanced non-equilibrium steady state and a non-zero S-flux, defined as the flux flowing between the complexes multiplied by an adequate stoichiometric coefficient. In this case, the noise on each species is reduced if the flux flows from the species of lowest to highest complexity, and is amplified is the flux goes in the opposite direction. These results are generalized to systems of deficiency two, which possess two independent non-vanishing S-fluxes, and we conjecture that a similar relation holds for higher deficiency systems

CoCoNet—boosting RNA contact prediction by convolutional neural networks

Co-evolutionary models such as direct coupling analysis (DCA) in combination with machine learning (ML) techniques based on deep neural networks are able to predict accurate protein contact or distance maps. Such information can be used as constraints in structure prediction and massively increase prediction accuracy. Unfortunately, the same ML methods cannot readily be applied to RNA as they rely on large structural datasets only available for proteins. Here, we demonstrate how the available smaller data for RNA can be used to improve prediction of RNA contact maps. We introduce an algorithm called CoCoNet that is based on a combination of a Coevolutionary model and a shallow Convolutional Neural Network. Despite its simplicity and the small number of trained parameters, the method boosts the positive predictive value (PPV) of predicted contacts by about 70% with respect to DCA as tested by cross-validation of about eighty RNA structures. However, the direct inclusion of the CoCoNet contacts in 3D modeling tools does not result in a proportional increase of the 3D RNA structure prediction accuracy. Therefore, we suggest that the field develops, in addition to contact PPV, metrics which estimate the expected impact for 3D structure modeling tools better. CoCoNet is freely available and can be found at https://github.com/KIT-MBS/coconet

Monopoles, abelian projection, and gauge invariance

A direct connection is proved between the Non-Abelian Bianchi Identities(NABI), and the abelian Bianchi identities for the 't Hooft tensor. As a consequence the existence of a non-zero magnetic current is related to the violation of the NABI's and is a gauge-invariant property. The construction allows to show that not all abelian projections can be used to expose monopoles in lattice configurations: each field configuration with non-zero magnetic charge identifies its natural projection, up to gauge transformations which tend to unity at large distances. It is shown that the so-called maximal-abelian gauge is a legitimate choice. It is also proved, starting from the NABI, that monopole condensation is a physical gauge invariant phenomenon, independent of the choice of the abelian projection.Comment: 9 pages, no figur

Femoral artery ultrasound examination: a new role in predicting cardiovascular risk

We compared intima-media thickness (IMT) and the prevalence of plaques in the common carotid artery (CCA) and common femoral artery (CFA) in apparently healthy participants. This multicenter study included 322 participants (59.9% female; age 20-78 years, mean 52.1 ± 15.3 years) who underwent Echo-color Doppler examination of the CCA and CFA bilaterally. Prevalence and composition of plaque were recorded. A significant ( P < .01) difference between mean CCA-IMT and mean CFA-IMT was detected (0.70 vs 0.73 mm). Plaque prevalence was significantly higher in the CFA compared to the CCA (40.7% vs 30.4%). Atherosclerotic plaques were found in both CFA and CCA in 46% of the cases, solely in CFA in 38%, and in CCA alone in 17%. The observed difference in plaque prevalence was even greater when only fibrolipid isolated plaques were considered (CFA 39.4% vs CCA 22.1%). In a healthy general population, atherosclerotic plaques were present in the CFA but not in the CCA in over one-third of the cases. Further studies must confirm whether ultrasonography of the CFA might be introduced in the screening protocols for cardiovascular risk assessment

Correlators of supersymmetric Wilson-loops, protected operators and matrix models in N=4 SYM

We study the correlators of a recently discovered family of BPS Wilson loops in ${\cal N}=4$ supersymmetric U(N) Yang-Mills theory. When the contours lie on a two-sphere in the space-time, we propose a closed expression that is valid for all values of the coupling constant $g$ and for any rank $N$, by exploiting the suspected relation with two-dimensional gauge theories. We check this formula perturbatively at order ${\cal O}(g^4)$ for two latitude Wilson loops and we show that, in the limit where one of the loops shrinks to a point, logarithmic corrections in the shrinking radius are absent at ${\cal O}(g^6)$. This last result strongly supports the validity of our general expression and suggests the existence of a peculiar protected local operator arising in the OPE of the Wilson loop. At strong coupling we compare our result to the string dual of the ${\cal N}=4$ SYM correlator in the limit of large separation, presenting some preliminary evidence for the agreement.Comment: 20 page, 8 figure

Genetic and environmental factors on heart rate, mean arterial pressure and carotid intima–media thickness: A longitudinal twin study

Background: Heart rate (HR), mean arterial pressure (MAP) and carotid intima–media thickness (cIMT) are moderately heritable cardiovascular traits, but the environmental effects on the longitudinal change of their heritability have never been investigated. Methods: 368 Italian and Hungarian twins (107 monozygotic, 77 dizygotic) underwent oscillometric measurement and B-mode sonography of bilateral carotid arteries in 2009/2010 and 2014. Within- -individual/cross-study wave, cross-twin/within-study wave and cross-twin/cross-study wave correlations were estimated, and bivariate Cholesky models were fitted to decompose the total variance at each wave and covariance between study waves into additive genetic, shared and unique environmental components. Results: For each trait, a moderate longitudinal stability was observed, with within-individual/crosswave correlations of 0.42 (95% CI: 0.33–0.51) for HR, 0.34 (95% CI: 0.24–0.43) for MAP, and 0.23 (95% CI: 0.12–0.33) for cIMT. Cross-twin/cross-wave correlations in monozygotic pairs were all significant and substantially higher than the corresponding dizygotic correlations. Genetic continuity was the main source of longitudinal stability, with across-time genetic correlations of 0.52 (95% CI: 0.29–0.71) for HR, 0.56 (95% CI: 0.31–0.81) for MAP, and 0.36 (95% CI: 0.07–0.64) for cIMT. Overlapping genetic factors explained respectively 57%, 77%, and 68% of the longitudinal covariance of the HR, MAP and cIMT traits. Conclusions: Genetic factors have a substantial role in the longitudinal change of HR, MAP and cIMT; however, the influence of unique environmental factors remains relevant. Further studies should better elucidate whether epigenetic mechanisms have a role in influencing the stability of the investigated traits over time