Digital contact tracing and network theory to stop the spread of COVID-19 using big-data on human mobility geolocalization.

The spread of COVID-19 caused by the SARS-CoV-2 virus has become a worldwide problem with devastating consequences. Here, we implement a comprehensive contact tracing and network analysis to find an optimized quarantine protocol to dismantle the chain of transmission of coronavirus with minimal disruptions to society. We track billions of anonymized GPS human mobility datapoints to monitor the evolution of the contact network of disease transmission before and after mass quarantines. As a consequence of the lockdowns, people's mobility decreases by 53%, which results in a drastic disintegration of the transmission network by 90%. However, this disintegration did not halt the spreading of the disease. Our analysis indicates that superspreading k-core structures persist in the transmission network to prolong the pandemic. Once the k-cores are identified, an optimized strategy to break the chain of transmission is to quarantine a minimal number of 'weak links' with high betweenness centrality connecting the large k-cores.

Fast algorithm to identify minimal patterns of synchrony through fibration symmetries in large directed networks.

Recent studies have revealed the interplay between the structure of network circuits with fibration symmetries and the functionality of biological networks within which they have been identified. The presence of these symmetries in complex networks predicts the phenomenon of cluster synchronization, which produces patterns of a synchronized group of nodes. Here, we present a fast, and memory efficient, algorithm to identify fibration symmetries in networks. The algorithm is particularly suitable for large networks since it has a runtime of complexity O(Mlog⁡N) and requires O(M+N) of memory resources, where N and M are the number of nodes and edges in the network, respectively. The algorithm is a modification of the so-called refinement paradigm to identify circuits that are symmetrical to information flow (i.e., fibers) by finding the coarsest refinement partition over the network. Finally, we show that the algorithm provides an optimal procedure for identifying fibers, overcoming current approaches used in the literature.

Morphological Transition between Patterns Formed by Threads of Magnetic Beads.

Magnetic beads attract each other, forming chains. We push such chains into an inclined Hele-Shaw cell and discover that they spontaneously form self-similar patterns. Depending on the angle of inclination of the cell, two completely different situations emerge; namely, above the static friction angle the patterns resemble the stacking of a rope and below they look similar to a fortress from above. Moreover, locally the first pattern forms a square lattice, while the second pattern exhibits triangular symmetry. For both patterns, the size distributions of enclosed areas follow power laws. We characterize the morphological transition between the two patterns experimentally and numerically and explain the change in polarization as a competition between friction-induced buckling and gravity.

Circuits with broken fibration symmetries perform core logic computations in biological networks.

We show that logic computational circuits in gene regulatory networks arise from a fibration symmetry breaking in the network structure. From this idea we implement a constructive procedure that reveals a hierarchy of genetic circuits, ubiquitous across species, that are surprising analogues to the emblematic circuits of solid-state electronics: starting from the transistor and progressing to ring oscillators, current-mirror circuits to toggle switches and flip-flops. These canonical variants serve fundamental operations of synchronization and clocks (in their symmetric states) and memory storage (in their broken symmetry states). These conclusions introduce a theoretically principled strategy to search for computational building blocks in biological networks, and present a systematic route to design synthetic biological circuits.

Elastic Backbone Defines a New Transition in the Percolation Model.

The elastic backbone is the set of all shortest paths. We found a new phase transition at p_{eb} above the classical percolation threshold at which the elastic backbone becomes dense. At this transition in 2D, its fractal dimension is 1.750±0.003, and one obtains a novel set of critical exponents ß_{eb}=0.50±0.02, γ_{eb}=1.97±0.05, and ν_{eb}=2.00±0.02, fulfilling consistent critical scaling laws. Interestingly, however, the hyperscaling relation is violated. Using Binder's cumulant, we determine, with high precision, the critical probabilities p_{eb} for the triangular and tilted square lattice for site and bond percolation. This transition describes a sudden rigidification as a function of density when stretching a damaged tissue.

Tryptophan overloading activates brain regions involved with cognition, mood and anxiety.

Tryptophan is the only precursor of serotonin and mediates serotonergic activity in the brain. Previous studies have shown that the administration of tryptophan or tryptophan depletion significantly alters cognition, mood and anxiety. Nevertheless, the neurobiological alterations that follow these changes have not yet been fully investigated. The aim of this study was to verify the effects of a tryptophan-enriched diet on immunoreactivity to Fos-protein in the rat brain. Sixteen male Wistar rats were distributed into two groups that either received standard chow diet or a tryptophan-enriched diet for a period of thirty days. On the morning of the 31st day, animals were euthanized and subsequently analyzed for Fos-immunoreactivity (Fos-ir) in the dorsal and median raphe nuclei and in regions that receive serotonin innervation from these two brain areas. Treatment with a tryptophan-enriched diet increased Fos-ir in the prefrontal cortex, nucleus accumbens, paraventricular hypothalamus, arcuate and ventromedial hypothalamus, dorsolateral and dorsomedial periaqueductal grey and dorsal and median raphe nucleus. These observations suggest that the physiological and behavioral alterations that follow the administration of tryptophan are associated with the activation of brain regions that regulate cognition and mood/anxiety-related responses.

Itinerant Conductance in Fuse-Antifuse Networks.

We report on a novel dynamic phase in electrical networks, in which current channels perpetually change in time. This occurs when the elementary units of the network are fuse-antifuse devices, namely, become insulators within a certain finite interval of local applied voltages. As a consequence, the macroscopic current exhibits temporal fluctuations which increase with system size. We determine the conditions under which this exotic situation appears by establishing a phase diagram as a function of the applied field and the size of the insulating window. Besides its obvious application as a versatile electronic device, due to its rich variety of behaviors, this network model provides a possible description for particle-laden flow through porous media leading to dynamical clogging and reopening of the local channels in the pore space.

Explosive electric breakdown due to conducting-particle deposition on an insulating substrate.

We introduce a theoretical model to investigate the electric breakdown of a substrate on which highly conducting particles are adsorbed and desorbed with a probability that depends on the local electric field. We find that, by tuning the relative strength q of this dependence, the breakdown can change from continuous to explosive. Precisely, in the limit in which the adsorption probability is the same for any finite voltage drop, we can map our model exactly onto the q-state Potts model and thus the transition to a jump occurs at q = 4. In another limit, where the adsorption probability becomes independent of the local field strength, the traditional bond percolation model is recovered. Our model is thus an example of a possible experimental realization exhibiting a truly discontinuous percolation transition.

Enhanced flow in small-world networks.

The proper addition of shortcuts to a regular substrate can lead to the formation of a complex network with a highly efficient structure for navigation [J. M. Kleinberg, Nature 406, 845 (2000)]. Here we show that enhanced flow properties can also be observed in these small-world topologies. Precisely, our model is a network built from an underlying regular lattice over which long-range connections are randomly added according to the probability, Pij ∼ r−α ij , where rij is the Manhattan distance between nodes i and j, and the exponent α is a controlling parameter. The mean two-point global conductance of the system is computed by considering that each link has a local conductance given by gij ∝ r−C ij , where C determines the extent of the geographical limitations (costs) on the long-range connections. Our results show that the best flow conditions are obtained for C = 0 with α = 0, while for C ≫ 1 the overall conductance always increases with α. For C ≈ 1, α = d becomes the optimal exponent, where d is the topological dimension of the substrate. Interestingly, this exponent is identical to the one obtained for optimal navigation in small-world networks using decentralized algorithms.

Enhanced flow of core-softened fluids through narrow nanotubes.

We investigate through non-equilibrium molecular dynamic simulations the flow of anomalous fluids inside rigid nanotubes. Our results reveal an anomalous increase of the overall mass flux for nanotubes with sufficiently smaller radii. This is explained in terms of a transition from a single-file type of flow to the movement of an ordered-like fluid as the nanotube radius increases. The occurrence of a global minimum in the mass flux at this transition reflects the competition between the two characteristic length scales of the core-softened potential. Moreover, by increasing further the radius, another substantial change in the flow behavior, which becomes more evident at low temperatures, leads to a local minimum in the overall mass flux. Microscopically, this second transition is originated by the formation of a double-layer of flowing particles in the confined nanotube space. These nano-fluidic features give insights about the behavior of confined isotropic anomalous fluids.

Mitigation of malicious attacks on networks.

Terrorist attacks on transportation networks have traumatized modern societies. With a single blast, it has become possible to paralyze airline traffic, electric power supply, ground transportation or Internet communication. How and at which cost can one restructure the network such that it will become more robust against a malicious attack? We introduce a new measure for robustness and use it to devise a method to mitigate economically and efficiently this risk. We demonstrate its efficiency on the European electricity system and on the Internet as well as on complex networks models. We show that with small changes in the network structure (low cost) the robustness of diverse networks can be improved dramatically whereas their functionality remains unchanged. Our results are useful not only for improving significantly with low cost the robustness of existing infrastructures but also for designing economically robust network systems.

Ising-like model replicating time-averaged spiking behaviour of in vitro neuronal networks.

We analyze time-averaged experimental data from in vitro activities of neuronal networks. Through a Pairwise Maximum-Entropy method, we identify through an inverse binary Ising-like model the local fields and interaction couplings which best reproduce the average activities of each neuron as well as the statistical correlations between the activities of each pair of neurons in the system. The specific information about the type of neurons is mainly stored in the local fields, while a symmetric distribution of interaction constants seems generic. Our findings demonstrate that, despite not being directly incorporated into the inference approach, the experimentally observed correlations among groups of three neurons are accurately captured by the derived Ising-like model. Within the context of the thermodynamic analogy inherent to the Ising-like models developed in this study, our findings additionally indicate that these models demonstrate characteristics of second-order phase transitions between ferromagnetic and paramagnetic states at temperatures above, but close to, unity. Considering that the operating temperature utilized in the Maximum-Entropy method is T o = 1 , this observation further expands the thermodynamic conceptual parallelism postulated in this work for the manifestation of criticality in neuronal network behavior.

Neuroprotective effects of platinum nanoparticle-based microreactors in bicuculline-induced seizures.

Epilepsy designates a group of chronic brain disorders, characterized by the recurrence of hypersynchronous, repetitive activity, of neuronal clusters. Epileptic seizures are the hallmark of epilepsy. The primary goal of epilepsy treatment is to eliminate seizures with minimal side effects. Nevertheless, approximately 30% of patients do not respond to the available drugs. An imbalance between excitatory/inhibitory neurotransmission, that leads to excitotoxicity, seizures, and cell death, has been proposed as an important mechanism regarding epileptogenesis. Recently, it has been shown that microreactors composed of platinum nanoparticles (Pt-NP) and glutamate dehydrogenase possess in vitro and in vivo activity against excitotoxicity. This study investigates the in vivo effects of these microreactors in an animal model of epilepsy induced by the administration of the GABAergic antagonist bicuculline. Male Wistar rats were administered intracerebroventricularly (i.c.v.) with the microreactors or saline and, five days later, injected with bicuculline or saline. Seizure severity was evaluated in an open field. Thirty min after behavioral measurements, animals were euthanized, and their brains processed for neurodegeneration evaluation and for neurogenesis. Treatment with the microreactors significantly increased the time taken for the onset of seizures and for the first tonic-clonic seizure, when compared to the bicuculline group that did not receive the microreactor. The administration of the microreactors also increased the time spent in total exploration and grooming. Treatment with the microreactors decreased bicuculline-induced neurodegeneration and increased neurogenesis in the dorsal and ventral hippocampus. These observations suggest that treatment with Pt-NP-based microreactors attenuates the behavioral and neurobiological consequences of epileptiform seizure activity.

Modularity map of the network of human cell differentiation.

Cell differentiation in multicellular organisms is a complex process whose mechanism can be understood by a reductionist approach, in which the individual processes that control the generation of different cell types are identified. Alternatively, a large-scale approach in search of different organizational features of the growth stages promises to reveal its modular global structure with the goal of discovering previously unknown relations between cell types. Here, we sort and analyze a large set of scattered data to construct the network of human cell differentiation (NHCD) based on cell types (nodes) and differentiation steps (links) from the fertilized egg to a developed human. We discover a dynamical law of critical branching that reveals a self-similar regularity in the modular organization of the network, and allows us to observe the network at different scales. The emerging picture clearly identifies clusters of cell types following a hierarchical organization, ranging from sub-modules to super-modules of specialized tissues and organs on varying scales. This discovery will allow one to treat the development of a particular cell function in the context of the complex network of human development as a whole. Our results point to an integrated large-scale view of the network of cell types systematically revealing ties between previously unrelated domains in organ functions.

Unveiling the paths of COVID-19 in a large city based on public transportation data.

Human mobility plays a key role in the dissemination of infectious diseases around the world. However, the complexity introduced by commuting patterns in the daily life of cities makes such a role unclear, especially at the intracity scale. Here, we propose a multiplex network fed with 9 months of mobility data with more than 107 million public bus validations in order to understand the relation between urban mobility and the spreading of COVID-19 within a large city, namely, Fortaleza in the northeast of Brazil. Our results suggest that the shortest bus rides in Fortaleza, measured in the number of daily rides among all neighborhoods, decreased [Formula: see text]% more than the longest ones after an epidemic wave. Such a result is the opposite of what has been observed at the intercity scale. We also find that mobility changes among the neighborhoods are synchronous and geographically homogeneous. Furthermore, we find that the most central neighborhoods in mobility are the first targets for infectious disease outbreaks, which is quantified here in terms of the positive linear relation between the disease arrival time and the average of the closeness centrality ranking. These central neighborhoods are also the top neighborhoods in the number of reported cases at the end of an epidemic wave as indicated by the exponential decay behavior of the disease arrival time in relation to the number of accumulated reported cases with decay constant [Formula: see text] days. We believe that these results can help in the development of new strategies to impose restriction measures in the cities guiding decision-makers with smart actions in public health policies, as well as supporting future research on urban mobility and epidemiology.

Impact of CoronaVac on Covid-19 outcomes of elderly adults in a large and socially unequal Brazilian city: A target trial emulation study.

BACKGROUND: Although CoronaVac was the only Covid-19 vaccine adopted in the first months of the Brazilian vaccination campaign, randomized clinical trials to evaluate its efficacy in elderly adults were limited. In this study, we use routinely collected surveillance and SARS-CoV-2 vaccination and testing data comprising the population of the fifth largest city of Brazil to evaluate the effectiveness of CoronaVac in adults 60+ years old against severe outcomes. METHODS: Using large observational databases on vaccination and surveillance data from the city of Fortaleza, Brazil, we defined a retrospective cohort including 324,302 eligible adults aged ≥60 years to evaluate the effectiveness of the CoronaVac vaccine. The cohort included individuals vaccinated between January 21, 2021, and August 31, 2021, who were matched with unvaccinated persons at the time of rollout following a 1:1 ratio according to baseline covariates of age, sex, and Human Development Index of the neighborhood of residence. Only Covid-19-related severe outcomes were included in the analysis: hospitalization, ICU admission, and death. Vaccine effectiveness for each outcome was calculated by using the risk ratio between the two groups, with the risk obtained by the Kaplan-Meier estimator. RESULTS: We obtained 62,643 matched pairs for assessing the effectiveness of the two-dose regimen of CoronaVac. The demographic profile of the matched population was statistically representative of the population of Fortaleza. Using the cumulative incidence as the risk associated with each group, starting at day 14 since the receipt of the second dose, we found an 82.3 % (95 % CI 66.3-93.9) effectiveness against Covid-19-related death, 68.4 % (95 % CI 42.3-86.4) against ICU admission, and 55.8 % (95 % CI 42.7-68.3) against hospital admission. CONCLUSIONS: Our results show that, despite critical delays in vaccine delivery and limited evidence in efficacy trial estimates, CoronaVac contributed to preventing deaths and severe morbidity due to Covid-19 in elderly adults.

Self-similar but not conformally invariant traces obtained by modified Loewner forces.

The two-dimensional Loewner exploration process is generalized to the case where the random force is self-similar with positively correlated increments. We model this random force by a fractional Brownian motion with Hurst exponent H≥1/2≡H_{BM}, where H_{BM} stands for the one-dimensional Brownian motion. By manipulating the deterministic force, we design a scale-invariant equation describing self-similar traces which lack conformal invariance. The model is investigated in terms of the "input diffusivity parameter" κ, which coincides with the one of the ordinary Schramm-Loewner evolution (SLE) at H=H_{BM}. In our numerical investigation, we focus on the scaling properties of the traces generated for κ=2,3, κ=4, and κ=6,8 as the representatives, respectively, of the dilute phase, the transition point, and the dense phase of the ordinary SLE. The resulting traces are shown to be scale invariant. Using two equivalent schemes, we extract the fractal dimension, D_{f}(H), of the traces which decrease monotonically with increasing H, reaching D_{f}=1 at H=1 for all κ values. The left passage probability (LPP) test demonstrates that, for H values not far from the uncorrelated case (small ε_{H}≡H-H_{BM}/H_{BM}), the prediction of the ordinary SLE is applicable with an effective diffusivity parameter κ_{eff}. Not surprisingly, the κ_{eff}'s do not fulfill the prediction of SLE for the relation between D_{f}(H) and the diffusivity parameter.

Platinum nanoparticle-based microreactors protect against the behavioral and neurobiological consequences of chronic stress exposure.

Excitotoxicity is described as the exacerbated activation of glutamate AMPA and NMDA receptors that leads to neuronal damage, and ultimately to cell death. Astrocytes are responsible for the clearance of 80-90% of synaptically released glutamate, preventing excitotoxicity. Chronic stress renders neurons vulnerable to excitotoxicity and has been associated to neuropsychiatric disorders, i.e., anxiety. Microreactors containing platinum nanoparticles (Pt-NP) and glutamate dehydrogenase have shown in vitro activity against excitotoxicity. The purpose of the present study was to investigate the in vivo effects of these microreactors on the behavioral and neurobiological effects of chronic stress exposure. Rats were either unstressed or exposed for 2 weeks to an unpredictable chronic mild stress paradigm (UCMS), administered intra-ventral hippocampus with the microreactors (with or without the blockage of astrocyte functioning), and seven days later tested in the elevated T-maze (ETM; Experiment 1). The ETM allows the measurement of two defensive responses, avoidance and escape, in terms of psychopathology respectively related to generalized anxiety and panic disorder. Locomotor activity in an open field was also measured. Since previous evidence shows that stress inhibits adult neurogenesis, we evaluated the effects of the different treatments on the number of cells expressing the marker of migrating neuroblasts doublecortin (DCX) in the dorsal and ventral hippocampus (Experiment 2). Results showed that UCMS induces anxiogenic effects, increases locomotion, and decreases the number of DCX cells in the dorsal and ventral hippocampus, effects that were counteracted by microreactor administration. This is the first study to demonstrate the in vivo efficacy of Pt-NP against the behavioral and neurobiological effects of chronic stress exposure.

Transverse instability of dunes.

The simplest type of dune is the transverse one, which propagates with invariant profile orthogonally to a fixed wind direction. Here we show, by means of numerical simulations, that transverse dunes are unstable with respect to along-axis perturbations in their profile and decay on the bedrock into barchan dunes. Any forcing modulation amplifies exponentially with growth rate determined by the dune turnover time. We estimate the distance covered by a transverse dune before fully decaying into barchans and identify the patterns produced by different types of perturbation.

Tricritical point in explosive percolation.

The suitable interpolation between classical percolation and a special variant of explosive percolation enables the explicit realization of a tricritical percolation point. With high-precision simulations of the order parameter and the second moment of the cluster size distribution a fully consistent tricritical scaling scenario emerges yielding the tricritical crossover exponent 1/φ(t)=1.8 ± 0.1.