Balanced Active Core in Heterogeneous Neuronal Networks

It is hypothesized that cortical neuronal circuits operate in a global balanced state, i.e., the majority of neurons fire irregularly by receiving balanced inputs of excitation and inhibition. Meanwhile, it has been observed in experiments that sensory information is often sparsely encoded by only a small set of firing neurons, while neurons in the rest of the network are silent. The phenomenon of sparse coding challenges the hypothesis of a global balanced state in the brain. To reconcile this, here we address the issue of whether a balanced state can exist in a small number of firing neurons by taking account of the heterogeneity of network structure such as scale-free and small-world networks. We propose necessary conditions and show that, under these conditions, for sparsely but strongly connected heterogeneous networks with various types of single-neuron dynamics, despite the fact that the whole network receives external inputs, there is a small active subnetwork (active core) inherently embedded within it. The neurons in this active core have relatively high firing rates while the neurons in the rest of the network are quiescent. Surprisingly, although the whole network is heterogeneous and unbalanced, the active core possesses a balanced state and its connectivity structure is close to a homogeneous Erdös-Rényi network. The dynamics of the active core can be well-predicted using the Fokker-Planck equation. Our results suggest that the balanced state may be maintained by a small group of spiking neurons embedded in a large heterogeneous network in the brain. The existence of the small active core reconciles the balanced state and the sparse coding, and also provides a potential dynamical scenario underlying sparse coding in neuronal networks

The Dynamics of Balanced Spiking Neuronal Networks Under Poisson Drive Is Not Chaotic

Some previous studies have shown that chaotic dynamics in the balanced state, i.e., one with balanced excitatory and inhibitory inputs into cortical neurons, is the underlying mechanism for the irregularity of neural activity. In this work, we focus on networks of current-based integrate-and-fire neurons with delta-pulse coupling. While we show that the balanced state robustly persists in this system within a broad range of parameters, we mathematically prove that the largest Lyapunov exponent of this type of neuronal networks is negative. Therefore, the irregular firing activity can exist in the system without the chaotic dynamics. That is the irregularity of balanced neuronal networks need not arise from chaos

Conductivity of twin walls - surface junctions in ferroelastics: interplay of deformation potential, octahedral rotations, improper ferroelectricity and flexoelectric coupling

Electronic and structural phenomena at the twin domain wall-surface junctions in the ferroelastic materials are analyzed. Carriers accumulation caused by the strain-induced band structure changes originated via the deformation potential mechanism, structural order parameter gradient, rotostriction and flexoelectric coupling is explored. Approximate analytical results show that inhomogeneous elastic strains, which exist in the vicinity of the twin walls - surface junctions due to the rotostriction coupling, decrease the local band gap via the deformation potential and flexoelectric coupling mechanisms. This is the direct mechanism of the twin walls static conductivity in ferroelastics and, by extension, in multiferroics and ferroelectrics. On the other hand, flexoelectric and rotostriction coupling leads to the appearance of the improper polarization and electric fields proportional to the structural order parameter gradient in the vicinity of the twin walls - surface junctions. The "flexo-roto" fields leading to the carrier accumulation are considered as indirect mechanism of the twin walls conductivity. Comparison of the direct and indirect mechanisms illustrates complex range of phenomena directly responsible for domain walls static conductivity in materials with multiple order parameters.Comment: 35 pages, 11 figures, 3 table, 3 appendices Improved set of rotostriction coefficients are used in calculation

Two Mode Photon Bunching Effect as Witness of Quantum Criticality in Circuit QED

We suggest a scheme to probe critical phenomena at a quantum phase transition (QPT) using the quantum correlation of two photonic modes simultaneously coupled to a critical system. As an experimentally accessible physical implementation, a circuit QED system is formed by a capacitively coupled Josephson junction qubit array interacting with one superconducting transmission line resonator (TLR). It realizes an Ising chain in the transverse field (ICTF) which interacts with the two magnetic modes propagating in the TLR. We demonstrate that in the vicinity of criticality the originally independent fields tend to display photon bunching effects due to their interaction with the ICTF. Thus, the occurrence of the QPT is reflected by the quantum characteristics of the photonic fields.Comment: 7 pages, 4 figure

Competitions of magnetism and superconductivity in FeAs-based materials

Using the numerical unrestricted Hartree-Fock approach, we study the ground state of a two-orbital model describing newly discovered FeAs-based superconductors. We observe the competition of a $(0, \pi)$ mode spin-density wave and the superconductivity as the doping concentration changes. There might be a small region in the electron-doping side where the magnetism and superconductivity coexist. The superconducting pairing is found to be spin singlet, orbital even, and mixed s$_{xy}$ + d$_{x^{2}-y^{2}}$ wave (even parity).Comment: 5 pages, 3 figure

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival