Deterministic and Probabilistic Binary Search in Graphs

We consider the following natural generalization of Binary Search: in a given undirected, positively weighted graph, one vertex is a target. The algorithm's task is to identify the target by adaptively querying vertices. In response to querying a node $q$, the algorithm learns either that $q$ is the target, or is given an edge out of $q$ that lies on a shortest path from $q$ to the target. We study this problem in a general noisy model in which each query independently receives a correct answer with probability $p > \frac{1}{2}$ (a known constant), and an (adversarial) incorrect one with probability $1-p$. Our main positive result is that when $p = 1$ (i.e., all answers are correct), $\log_2 n$ queries are always sufficient. For general $p$, we give an (almost information-theoretically optimal) algorithm that uses, in expectation, no more than $(1 - \delta)\frac{\log_2 n}{1 - H(p)} + o(\log n) + O(\log^2 (1/\delta))$ queries, and identifies the target correctly with probability at leas $1-\delta$. Here, $H(p) = -(p \log p + (1-p) \log(1-p))$ denotes the entropy. The first bound is achieved by the algorithm that iteratively queries a 1-median of the nodes not ruled out yet; the second bound by careful repeated invocations of a multiplicative weights algorithm. Even for $p = 1$, we show several hardness results for the problem of determining whether a target can be found using $K$ queries. Our upper bound of $\log_2 n$ implies a quasipolynomial-time algorithm for undirected connected graphs; we show that this is best-possible under the Strong Exponential Time Hypothesis (SETH). Furthermore, for directed graphs, or for undirected graphs with non-uniform node querying costs, the problem is PSPACE-complete. For a semi-adaptive version, in which one may query $r$ nodes each in $k$ rounds, we show membership in $\Sigma_{2k-1}$ in the polynomial hierarchy, and hardness for $\Sigma_{2k-5}$

Development of the expert system prototype "medexpert" for differential disease diagnostics

The task of this article is creation a prototype of expert system "MEDExpert" which will help to doctors in the analysis of collected data about the patient and the diagnosis. The article describes the "MEDExpert" system, intended for informational support of medical solutions in medicine using modern information technologies, in particular, image recognition methods. The system uses a general decision-making technique using a differential series and the analogy method. The main problems of the field of creating medical expert systems were analyzed, and with their help the practical principle of the program part of the system was obtained. An integrated approach was proposed to analyze the data and obtain the necessary information for detecting the disease. The Visual Studio 2015 development environment and C #programming language, as well as a set of Windows Forms graphical tools and the Microsoft SQL Server 2015 database management system implemented the prototype. Computer technology intended for the classification, diagnosis, assessment of the state, analysis of the interaction of regulatory and therapeutic processes, selection, evaluation and correction of therapeutic measures. "MEDExpert" can be used for training specialists

Transient microstructural brain anomalies and epileptiform discharges in mice defective for epilepsy and language-related NMDA receptor subunit gene Grin2a

Wiley Periodicals, Inc. © 2018 International League Against Epilepsy Objective: The epilepsy-aphasia spectrum (EAS) is a heterogeneous group of age-dependent childhood disorders characterized by sleep-activated discharges associated with infrequent seizures and language, cognitive, and behavioral deficits. Defects in the GRIN2A gene, encoding a subunit of glutamate-gated N-methyl-d-aspartate (NMDA) receptors, represent the most important cause of EAS identified so far. Neocortical or thalamic lesions were detected in a subset of severe EAS disorders, and more subtle anomalies were reported in patients with so-called “benign” phenotypes. However, whether brain structural alterations exist in the context of GRIN2A defects is unknown. Methods: Magnetic resonance diffusion tensor imaging (MR-DTI) was used to perform longitudinal analysis of the brain at 3 developmental timepoints in living mice genetically knocked out (KO) for Grin2a. In addition, electroencephalography (EEG) was recorded using multisite extracellular electrodes to characterize the neocortical activity in vivo. Results: Microstructural alterations were detected in the neocortex, the corpus callosum, the hippocampus, and the thalamus of Grin2a KO mice. Most MR-DTI alterations were detected at a specific developmental stage when mice were aged 30 days, but not at earlier (15 days) or later (2 months) ages. EEG analysis detected epileptiform discharges in Grin2a KO mice in the third postnatal week. Significance: Grin2a KO mice replicated several anomalies found in patients with EAS disorders. Transient structural alterations detected by MR-DTI recalled the age-dependent course of EAS disorders, which in humans start during childhood and show variable outcome at the onset of adolescence. Together with the epileptiform discharges detected in young Grin2a KO mice, our data suggested the existence of early anomalies in the maturation of the neocortical and thalamocortical systems. Whereas the possible relationship of those anomalies with sleep warrants further investigations, our data suggest that Grin2a KO mice may serve as an animal model to study the neuronal mechanisms of EAS disorders and to design new therapeutic strategies

On the anomaly of Balmer line profiles of A-type stars. Fundamental binary systems

In previous work, Gardiner et al. (1999) found evidence for a discrepancy between the Teff obtained from Balmer lines with that from photometry and fundamental values for A-type stars. An investigation into this anomaly is presented using Balmer line profiles of stars in binary system with fundamental values of both Teff and log g. A revision of the fundamental parameters for binary systems given by Smalley & Dworetsky (1995) is also presented. The Teff obtained by fitting Halpha and Hbeta line profiles is compared to the fundamental values and those obtained from uvby photometry. We find that the discrepancy found by Gardiner et al. (1999) for stars in the range 7000 K < Teff < 9000 K is no longer evident.Comment: 10 pages, 4 figures; Accepted by A&

Functional properties of human NMDA receptors associated with epilepsy-related mutations of GluN2A subunit

© 2017 Sibarov, Bruneau, Antonov, Szepetowski, Burnashev and Giniatullin. Genetic variants of the glutamate activated N-methyl-D-aspartate (NMDA) receptor (NMDAR) subunit GluN2A are associated with the hyperexcitable states manifested by epileptic seizures and interictal discharges in patients with disorders of the epilepsy-aphasia spectrum (EAS). The variants found in sporadic cases and families are of different types and include microdeletions encompassing the corresponding GRIN2A gene as well as nonsense, splice-site and missense GRIN2A defects. They are located at different functional domains of GluN2A and no clear genotype-phenotype correlation has emerged yet. Moreover, GluN2A variants may be associated with phenotypic pleiotropy. Deciphering the consequences of pathogenic GRIN2A variants would surely help in better understanding of the underlying mechanisms. This emphasizes the need for functional studies to unravel the basic functional properties of each specific NMDAR variant. In the present study, we have used patch-clamp recordings to evaluate kinetic changes of mutant NMDARs reconstituted after co-transfection of cultured cells with the appropriate expression vectors. Three previously identified missense variants found in patients or families with disorders of the EAS and situated in the N-terminal domain (p.Ile184Ser) or in the ligand-binding domain (p.Arg518His and p.Ala716Thr) of GluN2A were studied in both the homozygous and heterozygous conditions. Relative surface expression and current amplitude were significantly reduced for NMDARs composed of mutant p.Ile184Ser and p.Arg518His, but not p.Ala716His, as compared with wild-type (WT) NMDARs. Amplitude of whole-cell currents was still drastically decreased when WT and mutant p.Arg518His-GluN2A subunits were co-expressed, suggesting a dominant-negative mechanism. Activation times were significantly decreased in both homozygous and heterozygous conditions for the two p.Ile184Ser and p.Arg518His variants, but not for p.Ala716His. Deactivation also significantly increased for p.Ile184Ser variant in the homozygous but not the heterozygous state while it was increased for p.Arg518His in both states. Our data indicate that p.Ile184Ser and p.Arg518His GluN2A variants both impacted on NMDAR function, albeit differently, whereas p.Ala716His did not significantly influence NMDAR kinetics, hence partly questioning its direct and strong pathogenic role. This study brings new insights into the functional impact that GRIN2A variants might have on NMDAR kinetics, and provides a mechanistic explanation for the neurological manifestations seen in the corresponding human spectrum of disorders

Physical Orbit for Lambda Virginis and a Test of Stellar Evolution Models

Lambda Virginis (LamVir) is a well-known double-lined spectroscopic Am binary with the interesting property that both stars are very similar in abundance but one is sharp-lined and the other is broad-lined. We present combined interferometric and spectroscopic studies of LamVir. The small scale of the LamVir orbit (~20 mas) is well resolved by the Infrared Optical Telescope Array (IOTA), allowing us to determine its elements as well as the physical properties of the components to high accuracy. The masses of the two stars are determined to be 1.897 Msun and 1.721 Msun, with 0.7% and 1.5% errors respectively, and the two stars are found to have the same temperature of 8280 +/- 200 K. The accurately determined properties of LamVir allow comparisons between observations and current stellar evolution models, and reasonable matches are found. The best-fit stellar model gives LamVir a subsolar metallicity of Z=0.0097, and an age of 935 Myr. The orbital and physical parameters of LamVir also allow us to study its tidal evolution time scales and status. Although currently atomic diffusion is considered to be the most plausible cause of the Am phenomenon, the issue is still being actively debated in the literature. With the present study of the properties and evolutionary status of LamVir, this system is an ideal candidate for further detailed abundance analyses that might shed more light on the source of the chemical anomalies in these A stars.Comment: 43 Pages, 13 figures. Accepted for publication in Ap

Capacity of optical reading, Part 1: Reading boundless error-free bits using a single photon

We show that nature imposes no fundamental upper limit to the number of information bits per expended photon that can, in principle, be read reliably when classical data is encoded in a medium that can only passively modulate the amplitude and phase of the probe light. We show that with a coherent-state (laser) source, an on-off (amplitude-modulation) pixel encoding, and shot-noise-limited direct detection (an overly-optimistic model for commercial CD/DVD drives), the highest photon information efficiency achievable in principle is about 0.5 bit per transmitted photon. We then show that a coherent-state probe can read unlimited bits per photon when the receiver is allowed to make joint (inseparable) measurements on the reflected light from a large block of phase-modulated memory pixels. Finally, we show an example of a spatially-entangled non-classical light probe and a receiver design---constructable using a single-photon source, beam splitters, and single-photon detectors---that can in principle read any number of error-free bits of information. The probe is a single photon prepared in a uniform coherent superposition of multiple orthogonal spatial modes, i.e., a W-state. The code, target, and joint-detection receiver complexity required by a coherent-state transmitter to achieve comparable photon efficiency performance is shown to be much higher in comparison to that required by the W-state transceiver.Comment: 11 pages, 12 figures, v3 includes a new plot characterizing the photon efficiency vs. encoding efficiency tradeoff for optical reading. The main technical body of the paper remains unaltere

Somatic Accumulation of GluA1-AMPA Receptors Leads to Selective Cognitive Impairments in Mice

© 2018 Bannerman, Borchardt, Jensen, Rozov, Haj-Yasein, Burnashev, Zamanillo, Bus, Grube, Adelmann, Rawlins and Sprengel. The GluA1 subunit of the L-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) plays a crucial, but highly selective, role in cognitive function. Here we analyzed AMPAR expression, AMPAR distribution and spatial learning in mice (Gria1R/R), expressing the “trafficking compromised” GluA1(Q600R) point mutation. Our analysis revealed somatic accumulation and reduction of GluA1(Q600R) and GluA2, but only slightly reduced CA1 synaptic localization in hippocampi of adult Gria1R/R mice. These immunohistological changes were accompanied by a strong reduction of somatic AMPAR currents in CA1, and a reduction of plasticity (short-term and long-term potentiation, STP and LTP, respectively) in the CA1 subfield following tetanic and theta-burst stimulation. Nevertheless, spatial reference memory acquisition in the Morris water-maze and on an appetitive Y-maze task was unaffected in Gria1R/R mice. In contrast, spatial working/short-term memory during both spontaneous and rewarded alternation tasks was dramatically impaired. These findings identify the GluA1(Q600R) mutation as a loss of function mutation that provides independent evidence for the selective role of GluA1 in the expression of short-term memory

Stable, synthetic analogs of diadenosine tetraphosphate inhibit rat and human P2X3 receptors and inflammatory pain

© 2016, © The Author(s) 2016.Background: A growing body of evidence suggests that ATP-gated P2X3 receptors (P2X3Rs) are implicated in chronic pain. We address the possibility that stable, synthetic analogs of diadenosine tetraphosphate (Ap4A) might induce antinociceptive effects by inhibiting P2X3Rs in peripheral sensory neurons. Results: The effects of two stable, synthetic Ap4A analogs (AppNHppA and AppCH2ppA) are studied firstly in vitro on HEK293 cells expressing recombinant rat P2XRs (P2X2Rs, P2X3Rs, P2X4Rs, and P2X7Rs) and then using native rat brain cells (cultured trigeminal, nodose, or dorsal root ganglion neurons). Thereafter, the action of these stable, synthetic Ap4A analogs on inflammatory pain and thermal hyperalgesia is studied through the measurement of antinociceptive effects in formalin and Hargreaves plantar tests in rats in vivo. In vitro inhibition of rat P2X3Rs (not P2X2Rs, P2X4Rs nor P2X7Rs) is shown to take place mediated by high-affinity desensitization (at low concentrations; IC50 values 100–250 nM) giving way to only weak partial agonism at much higher concentrations (EC50 values ≥ 10 µM). Similar inhibitory activity is observed with human recombinant P2X3Rs. The inhibitory effects of AppNHppA on nodose, dorsal root, and trigeminal neuron whole cell currents suggest that stable, synthetic Ap4A analogs inhibit homomeric P2X3Rs in preference to heteromeric P2X2/3Rs. Both Ap4A analogs mediate clear inhibition of pain responses in both in vivo inflammation models. Conclusions: Stable, synthetic Ap4A analogs (AppNHppA and AppCH2ppA) being weak partial agonist provoke potent high-affinity desensitization-mediated inhibition of homomeric P2X3Rs at low concentrations. Therefore, both analogs demonstrate clear potential as potent analgesic agents for use in the management of chronic pain associated with heightened P2X3R activation

CXCL12 inhibits expression of the NMDA receptor's NR2B subunit through a histone deacetylase-dependent pathway contributing to neuronal survival

Homeostatic chemokines, such as CXCL12, can affect neuronal activity by the regulation of inhibitory and excitatory neurotransmission, but the mechanisms involved are still undefined. Our previous studies have shown that CXCL12 protects cortical neurons from excitotoxicity by promoting the function of the gene-repressor protein Rb, which is involved in the recruitment of chromatin modifiers (such as histone deacetylases (HDACs)) to gene promoters. In neurons, Rb controls activity-dependent genes essential to neuronal plasticity and survival, such as the N-methyl--aspartic acid (NMDA) receptor's subunit NR2B, the expression of which in the tetrameric ion channel largely affects calcium signaling by glutamate. In this study, we report that CXCL12 differentially modulates intracellular responses after stimulation of synaptic and extrasynaptic NMDA receptors, by a specific regulation of the NR2B gene that involves HDACs. Our results show that CXCL12 selectively inhibits NR2B expression in vitro and in vivo altering NMDA-induced calcium responses associated with neuronal death, while promoting prosurvival pathways that depend on stimulation of synaptic receptors. Along with previous studies, these findings underline the role of CXCL12/CXCR4 in the regulation of crucial components of glutamatergic transmission. These novel effects of CXCL12 may be involved in the physiological function of the chemokine in both developing and mature brains