Adaptive Dynamics for Interacting Markovian Processes

Dynamics of information flow in adaptively interacting stochastic processes is studied. We give an extended form of game dynamics for Markovian processes and study its behavior to observe information flow through the system. Examples of the adaptive dynamics for two stochastic processes interacting through matching pennies game interaction are exhibited along with underlying causal structure

Inducible mouse model of skeletal muscle specific deletion of the Vitamin D Receptor (VDR)

Fil: Centeno, Viviana Andrea. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra Química Biológica A; Argentina.Fil: Sato, AY. Indiana University School of Medicine. Department of Anatomy & Cell Biology; United States.Fil: Cregor, M. Indiana University School of Medicine. Department of Anatomy & Cell Biology; United States.Fil: Akel, NS. Indiana University School of Medicine. Department of Anatomy & Cell Biology; United States.Fil: Bellido, T.. Indiana University School of Medicine. Department of Anatomy & Cell Biology; United States.Vitamin D3 has beneficial effects on skeletal muscle and can prevent falls leading to reduced bone fracture risk. Excess of glucocorticoids (GC), either endogenous as in aging or due to glucocorticoid administration as immunosuppressants, leads to muscle loss mass and increases the risk of bone fractures. Earlier findings showed that 1,25(OH)2 vitamin D3 (1,25D3) prevents GC-induced skeletal muscle atrophy in vivo, in muscle organ cultures ex vivo, and in C2C12 myoblasts/ myotubes in vitro. Based on these findings, we formulated the hypothesis that the beneficial actions of Vitamin D3 are mediated by direct hormonal effects on skeletal muscle cells. The purpose of this work was to generate mice lacking the receptor for Vitamin D (VDR) in skeletal muscle and test their response to Vitamin D3 signaling. Towards this end, we crossed transgenic mice expressing a tamoxifen-inducible Mer-Cre-Mer driven by Human skeletal muscle alfa actin promoter with mice whose Receptor for Vitamin D, VDR, was flanked with LoxP sites at the exon 3 locus of the gene. So, tamoxifen-induced specific activation of Cre, produces a new genomic structure of VDR. Males and females 3 months old mice VDRf/f;human skeletal muscle α-actin (HSA)-Cre+/- and their littermate control VDRf/f;HSA-Cre-/- mice (C) were injected with tamoxifen for 5 days (2mg/d 1x/d for 5d). In some experiments, vehicle was injected to check the effects of tamoxifen. Fifteen days after the last tamoxifen injection, at 4months old mice, animals were implanted with slow-release pellets of 2.1mg/kg/d prednisolone or placebo and were treated with 50ng/kg/d 1,25D3 or vehicle 5x/wk for 4wks. Mice were fed a regular Vitamin D3-containing diet and maintained in a 12h light/dark cycle. First, we confirmed tissue-specific VDR deletion. HSA-CRE was present in gDNA of CRE positive mice. Also, we confirmed the deletion of VDR only in induced by tamoxifen in CRE-positive mice. The excised form of the VDR is only detected in skeletal muscle (plantaris and tibialis anterior), but not in kidney, intestine, or bone, of Cre positive mice (VDR f/f;HSA-Cre +/-) treated with tamoxifen. VDR deletion induced by tamoxifen is only detected in CRE positive mice (VDR f/f;HSA-Cre +/-), but not in any tissues from control littermate mice (VDR fl/fl;HSA-Cre -/-). In conclusion this model achieves adult-onset deletion of the VDR in skeletal muscle (Cre and tamoxifen dependent) and thus it will allow its use to determine the direct effects of vitamin D3 signaling in this tissue.Fil: Centeno, Viviana Andrea. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra Química Biológica A; Argentina.Fil: Sato, AY. Indiana University School of Medicine. Department of Anatomy & Cell Biology; United States.Fil: Cregor, M. Indiana University School of Medicine. Department of Anatomy & Cell Biology; United States.Fil: Akel, NS. Indiana University School of Medicine. Department of Anatomy & Cell Biology; United States.Fil: Bellido, T.. Indiana University School of Medicine. Department of Anatomy & Cell Biology; United States.Bioquímica y Biología Molecular (ídem 1.6.3

Escort Evolutionary Game Theory

A family of replicator-like dynamics, called the escort replicator equation, is constructed using information-geometric concepts and generalized information entropies and diverenges from statistical thermodynamics. Lyapunov functions and escort generalizations of basic concepts and constructions in evolutionary game theory are given, such as an escorted Fisher's Fundamental theorem and generalizations of the Shahshahani geometry.Comment: Minor typo correctio

Derivative pricing under the possibility of long memory in the supOU stochastic volatility model

We consider the supOU stochastic volatility model which is able to exhibit long-range dependence. For this model we give conditions for the discounted stock price to be a martingale, calculate the characteristic function, give a strip where it is analytic and discuss the use of Fourier pricing techniques. Finally, we present a concrete specification with polynomially decaying autocorrelations and calibrate it to observed market prices of plain vanilla options

Absence of system xc⁻ on immune cells invading the central nervous system alleviates experimental autoimmune encephalitis

Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System x(c)- or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration. Methods: Semi-quantitative Western blotting served to study protein expression of xCT, the specific subunit of system x(c)-, as well as of regulators of xCT transcription, in the normal appearing white matter (NAWM) of MS patients and in the CNS and spleen of mice exposed to experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS. We next compared the clinical course of the EAE disease, the extent of demyelination, the infiltration of immune cells and microglial activation in xCT-knockout (xCT(-/-)) mice and irradiated mice reconstituted in xCT(-/-) bone marrow (BM), to their proper wild type (xCT(+/+)) controls. Results: xCT protein expression levels were upregulated in the NAWM of MS patients and in the brain, spinal cord, and spleen of EAE mice. The pathways involved in this upregulation in NAWM of MS patients remain unresolved. Compared to xCT(+/+) mice, xCT(-/-) mice were equally susceptible to EAE, whereas mice transplanted with xCT(-/-) BM, and as such only exhibiting loss of xCT in their immune cells, were less susceptible to EAE. In none of the above-described conditions, demyelination, microglial activation, or infiltration of immune cells were affected. Conclusions: Our findings demonstrate enhancement of xCT protein expression in MS pathology and suggest that system x(c)- on immune cells invading the CNS participates to EAE. Since a total loss of system x(c)- had no net beneficial effects, these results have important implications for targeting system x(c)- for treatment of MS

Topological orbital ladders

We unveil a topological phase of interacting fermions on a two-leg ladder of unequal parity orbitals, derived from the experimentally realized double-well lattices by dimension reduction. $Z_2$ topological invariant originates simply from the staggered phases of $sp$-orbital quantum tunneling, requiring none of the previously known mechanisms such as spin-orbit coupling or artificial gauge field. Another unique feature is that upon crossing over to two dimensions with coupled ladders, the edge modes from each ladder form a parity-protected flat band at zero energy, opening the route to strongly correlated states controlled by interactions. Experimental signatures are found in density correlations and phase transitions to trivial band and Mott insulators.Comment: 12 pages, 5 figures, Revised title, abstract, and the discussion on Majorana numbe

Non-Abelian statistics and topological quantum information processing in 1D wire networks

Topological quantum computation provides an elegant way around decoherence, as one encodes quantum information in a non-local fashion that the environment finds difficult to corrupt. Here we establish that one of the key operations---braiding of non-Abelian anyons---can be implemented in one-dimensional semiconductor wire networks. Previous work [Lutchyn et al., arXiv:1002.4033 and Oreg et al., arXiv:1003.1145] provided a recipe for driving semiconducting wires into a topological phase supporting long-sought particles known as Majorana fermions that can store topologically protected quantum information. Majorana fermions in this setting can be transported, created, and fused by applying locally tunable gates to the wire. More importantly, we show that networks of such wires allow braiding of Majorana fermions and that they exhibit non-Abelian statistics like vortices in a p+ip superconductor. We propose experimental setups that enable the Majorana fusion rules to be probed, along with networks that allow for efficient exchange of arbitrary numbers of Majorana fermions. This work paves a new path forward in topological quantum computation that benefits from physical transparency and experimental realism.Comment: 6 pages + 17 pages of Supp. Mat.; 10 figures. Supp. Mat. has doubled in size to establish results more rigorously; many other improvements as wel

Patterns of ambulatory care utilization in Taiwan

BACKGROUND: We used the insurance claims of a representative cohort to quantify the patterns of ambulatory care visits, especially the doctor-shopping phenomenon, in Taiwan. METHODS: The ambulatory visit files of the 200,000-person cohort datasets from the National Health Insurance Research Database in 2002 were analyzed. Only a visit with physician consultation would be considered. We computed the visit patterns both by visit count and by patient count. RESULTS: In 2002, there were 182,474 eligible people with 2,443,003 physician consultations. During the year, 87.4% of the cohort had visited physician clinics and 57.5% had visited hospital-based outpatient or emergency departments. On average, a person had 13.4 physician consultations and consulted 3.4 specialties, 5.2 physicians, and 3.9 healthcare facilities in a year. In 2002, 17.3% of the cohort had ever visited different healthcare facilities on the same day; 23.5% had ever visited physicians of the same specialty at different healthcare facilities within 7 days and the percentage of second visits was 3.8% of all visits. Besides, 7.6% of the cohort had visited two or more specialties at the same facility on the same day, and such visits make up 2.5% of all visits. CONCLUSION: The people in Taiwan did visit the physicians and outpatient departments frequently. Many patients not only consulted several physicians of different specialties and at different healthcare facilities during the year, but also switched the physicians and facilities quickly. An effective referral system with efficient data exchange between facilities might be the solution

Contribution of Cystine-Glutamate Antiporters to the Psychotomimetic Effects of Phencyclidine

Altered glutamate signaling contributes to a myriad of neural disorders, including schizophrenia. While synaptic levels are intensely studied, nonvesicular release mechanisms, including cystine–glutamate exchange, maintain high steady-state glutamate levels in the extrasynaptic space. The existence of extrasynaptic receptors, including metabotropic group II glutamate receptors (mGluR), pose nonvesicular release mechanisms as unrecognized targets capable of contributing to pathological glutamate signaling. We tested the hypothesis that activation of cystine–glutamate antiporters using the cysteine prodrug N-acetylcysteine would blunt psychotomimetic effects in the rodent phencyclidine (PCP) model of schizophrenia. First, we demonstrate that PCP elevates extracellular glutamate in the prefrontal cortex, an effect that is blocked by N-acetylcysteine pretreatment. To determine the relevance of the above finding, we assessed social interaction and found that N-acetylcysteine reverses social withdrawal produced by repeated PCP. In a separate paradigm, acute PCP resulted in working memory deficits assessed using a discrete trial t-maze task, and this effect was also reversed by N-acetylcysteine pretreatment. The capacity of N-acetylcysteine to restore working memory was blocked by infusion of the cystine–glutamate antiporter inhibitor (S)-4-carboxyphenylglycine into the prefrontal cortex or systemic administration of the group II mGluR antagonist LY341495 indicating that the effects of N-acetylcysteine requires cystine–glutamate exchange and group II mGluR activation. Finally, protein levels from postmortem tissue obtained from schizophrenic patients revealed significant changes in the level of xCT, the active subunit for cystine–glutamate exchange, in the dorsolateral prefrontal cortex. These data advance cystine–glutamate antiporters as novel targets capable of reversing the psychotomimetic effects of PCP