Emergence of robustness against noise: A structural phase transition in evolved models of gene regulatory networks

We investigate the evolution of Boolean networks subject to a selective pressure which favors robustness against noise, as a model of evolved genetic regulatory systems. By mapping the evolutionary process into a statistical ensemble and minimizing its associated free energy, we find the structural properties which emerge as the selective pressure is increased and identify a phase transition from a random topology to a "segregated core" structure, where a smaller and more densely connected subset of the nodes is responsible for most of the regulation in the network. This segregated structure is very similar qualitatively to what is found in gene regulatory networks, where only a much smaller subset of genes --- those responsible for transcription factors --- is responsible for global regulation. We obtain the full phase diagram of the evolutionary process as a function of selective pressure and the average number of inputs per node. We compare the theoretical predictions with Monte Carlo simulations of evolved networks and with empirical data for Saccharomyces cerevisiae and Escherichia coli.Comment: 12 pages, 10 figure

Probing the loss origins of ultra-smooth Si3N4\mathrm{Si_3N_4} integrated photonic waveguides

On-chip optical waveguides with low propagation losses and precisely engineered group velocity dispersion (GVD) are important to nonlinear photonic devices such as soliton microcombs. Yet, despite intensive research efforts, nonlinear integrated photonic platforms still feature propagation losses orders of magnitude higher than in standard optical fiber. The tight confinement and high index contrast of integrated waveguides make them highly susceptible to fabrication induced surface roughness. Therefore, microresonators with ultra-high Q factors are, to date, only attainable in polished bulk crystalline, or chemically etched silica based devices, that pose however challenges for full photonic integration. Here, we demonstrate the fabrication of silicon nitride ($\mathrm{Si_3N_4}$) waveguides with unprecedentedly smooth sidewalls and tight confinement with record low propagation losses. This is achieved by combining the photonic Damascene process with a novel reflow process, which reduces etching roughness, while sufficiently preserving dimensional accuracy. This leads to previously unattainable \emph{mean} microresonator Q factors larger than $5\times10^6$ for tightly confining waveguides with anomalous dispersion. Via systematic process step variation and two independent characterization techniques we differentiate the scattering and absorption loss contributions, and reveal metal impurity related absorption to be an important loss origin. Although such impurities are known to limit optical fibers, this is the first time they are identified, and play a tangible role, in absorption of integrated microresonators. Taken together, our work provides new insights in the origins of propagation losses in $\mathrm{Si_3N_4}$ waveguides and provides the technological basis for integrated nonlinear photonics in the ultra-high Q regime

Network of recurrent events for the Olami-Feder-Christensen model

We numerically study the dynamics of a discrete spring-block model introduced by Olami, Feder and Christensen (OFC) to mimic earthquakes and investigate to which extent this simple model is able to reproduce the observed spatiotemporal clustering of seismicty. Following a recently proposed method to characterize such clustering by networks of recurrent events [Geophys. Res. Lett. {\bf 33}, L1304, 2006], we find that for synthetic catalogs generated by the OFC model these networks have many non-trivial statistical properties. This includes characteristic degree distributions -- very similar to what has been observed for real seismicity. There are, however, also significant differences between the OFC model and earthquake catalogs indicating that this simple model is insufficient to account for certain aspects of the spatiotemporal clustering of seismicity.Comment: 11 pages, 16 figure

Using Open Data to Rapidly Benchmark Biomolecular Simulations : Phospholipid Conformational Dynamics

Molecular dynamics (MD) simulations are widely used to monitor time-resolved motions of biomacromolecules, although it often remains unknown how closely the conformational dynamics correspond to those occurring in real life. Here, we used a large set of open-access MD trajectories of phosphatidylcholine (PC) lipid bilayers to benchmark the conformational dynamics in several contemporary MD models (force fields) against nuclear magnetic resonance (NMR) data available in the literature: effective correlation times and spin-lattice relaxation rates. We found none of the tested MD models to fully reproduce the conformational dynamics. That said, the dynamics in CHARMM36 and Slipids are more realistic than in the Amber Lipid14, OPLS-based MacRog, and GROMOS-based Berger force fields, whose sampling of the glycerol backbone conformations is too slow. The performance of CHARMM36 persists when cholesterol is added to the bilayer, and when the hydration level is reduced. However, for conformational dynamics of the PC headgroup, both with and without cholesterol, Slipids provides the most realistic description because CHARMM36 overestimates the relative weight of similar to 1 ns processes in the headgroup dynamics. We stress that not a single new simulation was run for the present work. This demonstrates the worth of open-access MD trajectory databanks for the indispensable step of any serious MD study: benchmarking the available force fields. We believe this proof of principle will inspire other novel applications of MD trajectory databanks and thus aid in developing biomolecular MD simulations into a true computational microscope-not only for lipid membranes but for all biomacromolecular systems.Peer reviewe

Consistent Gravitationally-Coupled Spin-2 Field Theory

Inspired by the translational gauge structure of teleparallel gravity, the theory for a fundamental massless spin-2 field is constructed. Accordingly, instead of being represented by a symmetric second-rank tensor, the fundamental spin-2 field is assumed to be represented by a spacetime (world) vector field assuming values in the Lie algebra of the translation group. The flat-space theory naturally emerges in the Fierz formalism and is found to be equivalent to the usual metric-based theory. However, the gravitationally coupled theory, with gravitation itself described by teleparallel gravity, is shown not to present the consistency problems of the spin-2 theory constructed on the basis of general relativity.Comment: 16 pages, no figures. V2: Presentation changes, including addition of a new sub-section, aiming at clarifying the text; version accepted for publication in Class. Quantum Grav

KOI-3890: A high mass-ratio asteroseismic red-giant++M-dwarf eclipsing binary undergoing heartbeat tidal interactions

KOI-3890 is a highly eccentric, 153-day period eclipsing, single-lined spectroscopic binary system containing a red-giant star showing solar-like oscillations alongside tidal interactions. The combination of transit photometry, radial velocity observations, and asteroseismology have enabled the detailed characterisation of both the red-giant primary and the M-dwarf companion, along with the tidal interaction and the geometry of the system. The stellar parameters of the red-giant primary are determined through the use of asteroseismology and grid-based modelling to give a mass and radius of $M_{\star}=1.04\pm0.06\;\textrm{M}_{\odot}$ and $R_{\star}=5.8\pm0.2\;\textrm{R}_{\odot}$ respectively. When combined with transit photometry the M-dwarf companion is found to have a mass and radius of $M_{\mathrm{c}}=0.23\pm0.01\;\textrm{M}_{\odot}$ and $R_{\mathrm{c}}=0.256\pm0.007\;\textrm{R}_{\odot}$. Moreover, through asteroseismology we constrain the age of the system through the red-giant primary to be $9.1^{+2.4}_{-1.7}\;\mathrm{Gyr}$. This provides a constraint on the age of the M-dwarf secondary, which is difficult to do for other M-dwarf binary systems. In addition, the asteroseismic analysis yields an estimate of the inclination angle of the rotation axis of the red-giant star of $i=87.6^{+2.4}_{-1.2}$ degrees. The obliquity of the system\textemdash the angle between the stellar rotation axis and the angle normal to the orbital plane\textemdash is also derived to give $\psi=4.2^{+2.1}_{-4.2}$ degrees showing that the system is consistent with alignment. We observe no radius inflation in the M-dwarf companion when compared to current low-mass stellar models.Comment: 11 pages, 5 figures, accepted for publication in MNRA

Mutations in DYNC2LI1 disrupt cilia function and cause short rib polydactyly syndrome.

The short rib polydactyly syndromes (SRPSs) are a heterogeneous group of autosomal recessive, perinatal lethal skeletal disorders characterized primarily by short, horizontal ribs, short limbs and polydactyly. Mutations in several genes affecting intraflagellar transport (IFT) cause SRPS but they do not account for all cases. Here we identify an additional SRPS gene and further unravel the functional basis for IFT. We perform whole-exome sequencing and identify mutations in a new disease-producing gene, cytoplasmic dynein-2 light intermediate chain 1, DYNC2LI1, segregating with disease in three families. Using primary fibroblasts, we show that DYNC2LI1 is essential for dynein-2 complex stability and that mutations in DYNC2LI1 result in variable length, including hyperelongated, cilia, Hedgehog pathway impairment and ciliary IFT accumulations. The findings in this study expand our understanding of SRPS locus heterogeneity and demonstrate the importance of DYNC2LI1 in dynein-2 complex stability, cilium function, Hedgehog regulation and skeletogenesis

Marine-inspired drugs and biomaterials in the perspective of pancreatic cancer therapies

Despite its low prevalence, pancreatic cancer (PC) is one of the deadliest, typically characterised as silent in early stages and with a dramatically poor prognosis when in its advanced stages, commonly associated with a high degree of metastasis. Many efforts have been made in pursuing innovative therapeutical approaches, from the search for new cytotoxic drugs and other bioactive compounds, to the development of more targeted approaches, including improved drug delivery devices. Marine biotechnology has been contributing to this quest by providing new chemical leads and materials originating from different organisms. In this review, marine biodiscovery for PC is addressed, particularly regarding marine invertebrates (namely sponges, molluscs, and bryozoans), seaweeds, fungi, and bacteria. In addition, the development of biomaterials based on marine-originating compounds, particularly chitosan, fucoidan, and alginate, for the production of advanced cancer therapies, is also discussed. The key role that drug delivery can play in new cancer treatments is highlighted, as therapeutical outcomes need to be improved to give further hope to patients.The authors would like to acknowledge the funding from the European Union Framework Program for Research and Innovation Horizon 2020 through project SponGES (H2020-BG-01-2015-679849) and from the European Regional Development Fund, through INTERREG España-Portugal 2014-2020 under BLUEBIOLAB (0474_BLUEBIOLAB_1_E) project and through NORTE2020/PT2020 Programme under ATLANTIDA (Norte-01-0145-FEDER-000040) project

Asymptotic integral kernel for ensembles of random normal matrices with radial potentials

We use the steepest descents method to study the integral kernel of a family of normal random matrix ensembles with eigenvalue distribution P_{N}(z_{1},...,z_{N}) = Z_{N}^{-1} e^{-NSigma_{i=1}^{N}V_{alpha}(z_{i})} Pi_{1leqi<jleqN}|z_{i}-z_{j}|^{2} where V_{alpha}(z)=|z|^{alpha}, z in C and alpha in ]0,infty[. Asymptotic analysis with error estimates are obtained. A corollary of this expansion is a scaling limit for the n-point function in terms of the integral kernel for the classical Segal--Bargmann space