Cellular O-Glycome Reporter/Amplification to explore O-glycans of living cells

Protein O-glycosylation has key roles in many biological processes, but the repertoire of O-glycans synthesized by cells is difficult to determine. Here we describe an approach termed Cellular O-Glycome Reporter/Amplification (CORA), a sensitive method used to amplify and profile mucin-type O-glycans synthesized by living cells. Cells convert added peracetylated benzyl-α-N-acetylgalactosamine to a large variety of modified O-glycan derivatives that are secreted from cells, allowing for easy purification for analysis by HPLC and mass spectrometry (MS). Relative to conventional O-glycan analyses, CORA resulted in an ∼100-1,000-fold increase in sensitivity and identified a more complex repertoire of O-glycans in more than a dozen cell types from Homo sapiens and Mus musculus. Furthermore, when coupled with computational modeling, CORA can be used for predictions about the diversity of the human O-glycome and offers new opportunities to identify novel glycan biomarkers for human diseases

Unfolding the procedure of characterizing recorded ultra low frequency, kHZ and MHz electromagetic anomalies prior to the L'Aquila earthquake as pre-seismic ones. Part I

Ultra low frequency, kHz and MHz electromagnetic anomalies were recorded prior to the L'Aquila catastrophic earthquake that occurred on April 6, 2009. The main aims of this contribution are: (i) To suggest a procedure for the designation of detected EM anomalies as seismogenic ones. We do not expect to be possible to provide a succinct and solid definition of a pre-seismic EM emission. Instead, we attempt, through a multidisciplinary analysis, to provide elements of a definition. (ii) To link the detected MHz and kHz EM anomalies with equivalent last stages of the L'Aquila earthquake preparation process. (iii) To put forward physically meaningful arguments to support a way of quantifying the time to global failure and the identification of distinguishing features beyond which the evolution towards global failure becomes irreversible. The whole effort is unfolded in two consecutive parts. We clarify we try to specify not only whether or not a single EM anomaly is pre-seismic in itself, but mainly whether a combination of kHz, MHz, and ULF EM anomalies can be characterized as pre-seismic one

A Logic of Blockchain Updates

Blockchains are distributed data structures that are used to achieve consensus in systems for cryptocurrencies (like Bitcoin) or smart contracts (like Ethereum). Although blockchains gained a lot of popularity recently, there is no logic-based model for blockchains available. We introduce BCL, a dynamic logic to reason about blockchain updates, and show that BCL is sound and complete with respect to a simple blockchain model

Weak chaos detection in the Fermi-Pasta-Ulam-α\alpha system using qq-Gaussian statistics

We study numerically statistical distributions of sums of orbit coordinates, viewed as independent random variables in the spirit of the Central Limit Theorem, in weakly chaotic regimes associated with the excitation of the first ($k=1$) and last ($k=N$) linear normal modes of the Fermi-Pasta-Ulam-$\alpha$ system under fixed boundary conditions. We show that at low energies ($E=0.19$), when the $k=1$ linear mode is excited, chaotic diffusion occurs characterized by distributions that are well approximated for long times ($t>10^9$) by a $q$-Gaussian Quasi-Stationary State (QSS) with $q\approx1.4$. On the other hand, when the $k=N$ mode is excited at the same energy, diffusive phenomena are \textit{absent} and the motion is quasi-periodic. In fact, as the energy increases to $E=0.3$, the distributions in the former case pass through \textit{shorter} $q$-Gaussian states and tend rapidly to a Gaussian (i.e. $q\rightarrow 1$) where equipartition sets in, while in the latter we need to reach to E=4 to see a \textit{sudden transition} to Gaussian statistics, without any passage through an intermediate QSS. This may be explained by different energy localization properties and recurrence phenomena in the two cases, supporting the view that when the energy is placed in the first mode weak chaos and "sticky" dynamics lead to a more gradual process of energy sharing, while strong chaos and equipartition appear abruptly when only the last mode is initially excited.Comment: 12 pages, 3 figures, submitted for publication to International Journal of Bifurcation and Chaos. In honor of Prof. Tassos Bountis' 60th birthda

Complex statistics and diffusion in nonlinear disordered particle chains.

We investigate dynamically and statistically diffusive motion in a Klein-Gordon particle chain in the presence of disorder. In particular, we examine a low energy (subdiffusive) and a higher energy (self-trapping) case and verify that subdiffusive spreading is always observed. We then carry out a statistical analysis of the motion, in both cases, in the sense of the Central Limit Theorem and present evidence of different chaos behaviors, for various groups of particles. Integrating the equations of motion for times as long as 10(9), our probability distribution functions always tend to Gaussians and show that the dynamics does not relax onto a quasi-periodic Kolmogorov-Arnold-Moser torus and that diffusion continues to spread chaotically for arbitrarily long times

Glyco-engineered MDCK cells display preferred receptors of H3N2 influenza absent in eggs used for vaccines

Evolution of human H3N2 influenza viruses driven by immune selection has narrowed the receptor specificity of the hemagglutinin (HA) to a restricted subset of human-type (Neu5Acα2-6 Gal) glycan receptors that have extended poly-LacNAc (Galβ1-4GlcNAc) repeats. This altered specificity has presented challenges for hemagglutination assays, growth in laboratory hosts, and vaccine production in eggs. To assess the impact of extended glycan receptors on virus binding, infection, and growth, we have engineered N-glycan extended (NExt) cell lines by overexpressing β3-Ν-acetylglucosaminyltransferase 2 in MDCK, SIAT, and hCK cell lines. Of these, SIAT-NExt cells exhibit markedly increased binding of H3 HAs and susceptibility to infection by recent H3N2 virus strains, but without impacting final virus titers. Glycome analysis of these cell lines and allantoic and amniotic egg membranes provide insights into the importance of extended glycan receptors for growth of recent H3N2 viruses and relevance to their production for cell- and egg-based vaccines

Successful network inference from time-series data using Mutual Information Rate

This work uses an information-based methodology to infer the connectivity of complex systems from observed time-series data. We first derive analytically an expression for the Mutual Information Rate (MIR), namely, the amount of information exchanged per unit of time, that can be used to estimate the MIR between two finite-length low-resolution noisy time-series, and then apply it after a proper normalization for the identification of the connectivity structure of small networks of interacting dynamical systems. In particular, we show that our methodology successfully infers the connectivity for heterogeneous networks, different time-series lengths or coupling strengths, and even in the presence of additive noise. Finally, we show that our methodology based on MIR successfully infers the connectivity of networks composed of nodes with different time-scale dynamics, where inference based on Mutual Information fails

A decision procedure for satisfiability in separation logic with inductive predicates

We show that the satisfiability problem for the "symbolic heap" fragment of separation logic with general inductively defined predicates - which includes most fragments employed in program verification - is decidable. Our decision procedure is based on the computation of a certain fixed point from the definition of an inductive predicate, called its "base", that exactly characterises its satisfiability. A complexity analysis of our decision procedure shows that it runs, in the worst case, in exponential time. In fact, we show that the satisfiability problem for our inductive predicates is EXPTIME-complete, and becomes NP-complete when the maximum arity over all predicates is bounded by a constant. Finally, we provide an implementation of our decision procedure, and analyse its performance both on a synthetically generated set of test formulas, and on a second test set harvested from the separation logic literature. For the large majority of these test cases, our tool reports times in the low milliseconds