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Sample records for homeostatic immune oscillations

  1. Macrophages in homeostatic immune function

    PubMed Central

    Jantsch, Jonathan; Binger, Katrina J.; Müller, Dominik N.; Titze, Jens

    2014-01-01

    Macrophages are not only involved in inflammatory and anti-infective processes, but also play an important role in maintaining tissue homeostasis. In this review, we summarize recent evidence investigating the role of macrophages in controlling angiogenesis, metabolism as well as salt and water balance. Particularly, we summarize the importance of macrophage tonicity enhancer binding protein (TonEBP, also termed nuclear factor of activated T-cells 5 [NFAT5]) expression in the regulation of salt and water homeostasis. Further understanding of homeostatic macrophage function may lead to new therapeutic approaches to treat ischemia, hypertension and metabolic disorders. PMID:24847274

  2. Harmonic Oscillations in Homeostatic Controllers: Dynamics of the p53 Regulatory System

    PubMed Central

    Jolma, Ingunn W.; Ni, Xiao Yu; Rensing, Ludger; Ruoff, Peter

    2010-01-01

    Abstract Homeostatic mechanisms are essential for the protection and adaptation of organisms in a changing and challenging environment. Previously, we have described molecular mechanisms that lead to robust homeostasis/adaptation under inflow or outflow perturbations. Here we report that harmonic oscillations occur in models of such homeostatic controllers and that a close relationship exists between the control of the p53/Mdm2 system and that of a homeostatic inflow controller. This homeostatic control model of the p53 system provides an explanation why large fluctuations in the amplitude of p53/Mdm2 oscillations may arise as part of the homeostatic regulation of p53 by Mdm2 under DNA-damaging conditions. In the presence of DNA damage p53 is upregulated, but is subject to a tight control by Mdm2 and other factors to avoid a premature apoptotic response of the cell at low DNA damage levels. One of the regulatory steps is the Mdm2-mediated degradation of p53 by the proteasome. Oscillations in the p53/Mdm2 system are considered to be part of a mechanism by which a cell decides between cell cycle arrest/DNA repair and apoptosis. In the homeostatic inflow control model, harmonic oscillations in p53/Mdm2 levels arise when the binding strength of p53 to degradation complexes increases. Due to the harmonic character of the oscillations rapid fluctuating noise can lead, as experimentally observed, to large variations in the amplitude of the oscillation but not in their period, a behavior which has been difficult to simulate by deterministic limit-cycle models. In conclusion, the oscillatory response of homeostatic controllers may provide new insights into the origin and role of oscillations observed in homeostatically controlled molecular networks. PMID:20197027

  3. Differential modulation of global and local neural oscillations in REM sleep by homeostatic sleep regulation

    PubMed Central

    Kim, Bowon; Kocsis, Bernat; Hwang, Eunjin; Kim, Youngsoo; Strecker, Robert E.; McCarley, Robert W.; Choi, Jee Hyun

    2017-01-01

    Homeostatic rebound in rapid eye movement (REM) sleep normally occurs after acute sleep deprivation, but REM sleep rebound settles on a persistently elevated level despite continued accumulation of REM sleep debt during chronic sleep restriction (CSR). Using high-density EEG in mice, we studied how this pattern of global regulation is implemented in cortical regions with different functions and network architectures. We found that across all areas, slow oscillations repeated the behavioral pattern of persistent enhancement during CSR, whereas high-frequency oscillations showed progressive increases. This pattern followed a common rule despite marked topographic differences. The findings suggest that REM sleep slow oscillations may translate top-down homeostatic control to widely separated brain regions whereas fast oscillations synchronizing local neuronal ensembles escape this global command. These patterns of EEG oscillation changes are interpreted to reconcile two prevailing theories of the function of sleep, synaptic homeostasis and sleep dependent memory consolidation. PMID:28193862

  4. Exploring the Homeostatic and Sensory Roles of the Immune System

    PubMed Central

    Marques, Rafael Elias; Marques, Pedro Elias; Guabiraba, Rodrigo; Teixeira, Mauro Martins

    2016-01-01

    Immunology developed under the notion of the immune system exists to fight pathogens. Recently, the discovery of interactions with commensal microbiota that are essential to human health initiated a change in this old paradigm. Here, we argue that the immune system has major physiological roles extending far beyond defending the host. Immune and inflammatory responses share the core property of sensing, defining the immune system also as a sensory system. The inference with the immune system collects, interprets, and stores information, while creating an identity of self, places it in close relationship to the nervous system, which suggests that these systems may have a profound evolutionary connection. PMID:27065209

  5. Exploring the Homeostatic and Sensory Roles of the Immune System.

    PubMed

    Marques, Rafael Elias; Marques, Pedro Elias; Guabiraba, Rodrigo; Teixeira, Mauro Martins

    2016-01-01

    Immunology developed under the notion of the immune system exists to fight pathogens. Recently, the discovery of interactions with commensal microbiota that are essential to human health initiated a change in this old paradigm. Here, we argue that the immune system has major physiological roles extending far beyond defending the host. Immune and inflammatory responses share the core property of sensing, defining the immune system also as a sensory system. The inference with the immune system collects, interprets, and stores information, while creating an identity of self, places it in close relationship to the nervous system, which suggests that these systems may have a profound evolutionary connection.

  6. EEG delta oscillations as a correlate of basic homeostatic and motivational processes.

    PubMed

    Knyazev, Gennady G

    2012-01-01

    Functional significance of delta oscillations is not fully understood. One way to approach this question would be from an evolutionary perspective. Delta oscillations dominate the EEG of waking reptiles. In humans, they are prominent only in early developmental stages and during slow-wave sleep. Increase of delta power has been documented in a wide array of developmental disorders and pathological conditions. Considerable evidence on the association between delta waves and autonomic and metabolic processes hints that they may be involved in integration of cerebral activity with homeostatic processes. Much evidence suggests the involvement of delta oscillations in motivation. They increase during hunger, sexual arousal, and in substance users. They also increase during panic attacks and sustained pain. In cognitive domain, they are implicated in attention, salience detection, and subliminal perception. This evidence shows that delta oscillations are associated with evolutionary old basic processes, which in waking adults are overshadowed by more advanced processes associated with higher frequency oscillations. The former processes rise in activity, however, when the latter are dysfunctional.

  7. The homeostatic role of neuropeptide Y in immune function and its impact on mood and behaviour.

    PubMed

    Farzi, A; Reichmann, F; Holzer, P

    2015-03-01

    Neuropeptide Y (NPY), one of the most abundant peptides in the nervous system, exerts its effects via five receptor types, termed Y1, Y2, Y4, Y5 and Y6. NPY's pleiotropic functions comprise the regulation of brain activity, mood, stress coping, ingestion, digestion, metabolism, vascular and immune function. Nerve-derived NPY directly affects immune cells while NPY also acts as a paracrine and autocrine immune mediator, because immune cells themselves are capable of producing and releasing NPY. NPY is able to induce immune activation or suppression, depending on a myriad of factors such as the Y receptors activated and cell types involved. There is an intricate relationship between psychological stress, mood disorders and the immune system. While stress represents a risk factor for the development of mood disorders, it exhibits diverse actions on the immune system as well. Conversely, inflammation is regarded as an internal stressor and is increasingly recognized to contribute to the pathogenesis of mood and metabolic disorders. Intriguingly, the cerebral NPY system has been found to protect against distinct disturbances in response to immune challenge, attenuating the sickness response and preventing the development of depression. Thus, NPY plays an important homeostatic role in balancing disturbances of physiological systems caused by peripheral immune challenge. This implication is particularly evident in the brain in which NPY counteracts the negative impact of immune challenge on mood, emotional processing and stress resilience. NPY thus acts as a unique signalling molecule in the interaction of the immune system with the brain in health and disease.

  8. The homeostatic role of neuropeptide Y in immune function and its impact on mood and behaviour

    PubMed Central

    Farzi, Aitak; Reichmann, Florian; Holzer, Peter

    2015-01-01

    Neuropeptide Y (NPY), one of the most abundant peptides in the nervous system, exerts its effects via 5 receptor types, termed Y1, Y2, Y4, Y5 and y6. NPY’s pleiotropic functions comprise the regulation of brain activity, mood, stress coping, ingestion, digestion, metabolism, vascular and immune function. Nerve-derived NPY directly affects immune cells while NPY also acts as a paracrine and autocrine immune mediator, since immune cells themselves are capable of producing and releasing NPY. NPY is able to induce immune activation or suppression, depending on a myriad of factors such as the Y receptors activated and cell types involved. There is an intricate relationship between psychological stress, mood disorders and the immune system. While stress represents a risk factor for the development of mood disorders, it exhibits diverse actions on the immune system as well. Conversely, inflammation is regarded as an internal stressor and is increasingly recognized to contribute to the pathogenesis of mood and metabolic disorders. Intriguingly, the cerebral NPY system has been found to protect against distinct disturbances in response to immune challenge, attenuating the sickness response and preventing the development of depression. Thus, NPY plays an important homeostatic role in balancing disturbances of physiological systems caused by peripheral immune challenge. This implication is particularly evident in the brain in which NPY counteracts the negative impact of immune challenge on mood, emotional processing and stress resilience. NPY thus acts as a unique signalling molecule in the interaction of the immune system with the brain in health and disease. PMID:25545642

  9. Physiological organization of immune response based on the homeostatic mechanism of matrix reprogramming: implication in tumor and biotechnology.

    PubMed

    Malyshev, Igor Yu; Manukhina, Eugenia B; Malyshev, Yuri I

    2014-06-01

    It is accepted that the immune system responds to pathogens with activation of antigen-independent innate and antigen-dependent adaptive immunity. However many immune events do not fit or are even inconsistent with this notion. We developed a new homeostatic model of the immune response. This model consists of four units: a sensor, a regulator, an effector and a rehabilitator. The sensor, macrophages or lymphocytes, recognize pathogenic cells and generate alarm signals. The regulator, antigen-presenting cells, Тregs and myeloid-derived suppressor cells, evaluate the signals and together with sensor cells program the effector. The effector, programmed macrophages and lymphocytes, eliminate the pathogenic cells. The rehabilitator, M2 macrophages, restrict inflammation, provide angiogenesis and reparation of tissue damage, and restore the homeostasis. We suggest the terms "immune matrix" for a biological template of immune responses to pathogens and "matrix reprogramming" for the interdependent reprogramming of different cells in the matrix. In an adequate immune response, the matrix forms a negative feedback mechanism to support the homeostasis. We defined the cellular and phenotypic composition of a tumor immune matrix. A tumor reprograms the homeostatic negative feedback mechanism of matrix into a pathogenic positive feedback mechanism. M2 macrophages play a key role in this transformation. Therefore, macrophages are an attractive target for biotechnology. Based on our hypotheses, we are developing a cell biotechnology method for creation of macrophages with a stable antitumor phenotype. We have shown that such macrophages almost doubled the survival time of mice with tumor.

  10. Mast cell, the peculiar member of the immune system: A homeostatic aspect.

    PubMed

    Csaba, György

    2015-09-01

    The mast cell is a member of the immune system having a basic role in allergic (anaphylactic) reactions. However, it contains, synthesizes, stores and secretes lots of substances, which initiates other reactions or participates in them. These are in connection with the deterioration of tissue correlation, as malignant tumors, angiogenesis, wound healing, pregnancy and different pathological conditions. In addition - as other members of the immune system - mast cells can synthesize, store and secrete hormones characteristic to the endocrine glands and can transport them to the site of requirement (packed transport), or produce and employ them locally. The effect of mast cells is controversial and frequently dual, stimulatory or inhibitory to the same organ or process. This is likely due to the heterogeneity of the mast cells, in morphology and cell content alike and dependent on the actual condition of the targeted tissue. The cells are transported in an unmatured form by the blood circulation and are exposed to microenvironmental effects, which influence their maturation. Their enrichment around tumors suggested using them as targets for tumor therapy more than fifty years ago (by the author), however, this idea lives its renaissance now. The review discusses the facts and ideas critically.

  11. Photonic homeostatics

    NASA Astrophysics Data System (ADS)

    Liu, Timon C.; Li, Fan-Hui

    2010-11-01

    Photonic homeostatics is a discipline to study the establishment, maintenance, decay, upgrading and representation of function-specific homoestasis (FSH) by using photonics. FSH is a negative-feedback response of a biosystem to maintain the function-specific fluctuations inside the biosystem so that the function is perfectly performed. A stress may increase sirtuin 1 (SIRT1) activities above FSH-specific SIRT1 activity to induce a function far from its FSH. On the one hand, low level laser irradiation or monochromatic light (LLL) can not modulate a function in its FSH or a stress in its stress-specific homeostasis (StSH), but modulate a function far from its FSH or a stress far from its StSH. On the other hand, the biophotons from a biosystem with its function in its FSH should be less than the one from the biosystem with its function far from its FSH. The non-resonant interaction of low intensity laser irradiation or monochromatic light (LIL) and a kind of membrane protein can be amplified by all the membrane proteins if the function is far from its FSH. This amplification might hold for biophoton emission of the membrane protein so that the photonic spectroscopy can be used to represent the function far from its FSH, which is called photonomics.

  12. Stability of Neuronal Networks with Homeostatic Regulation

    PubMed Central

    Harnack, Daniel; Pelko, Miha; Chaillet, Antoine; Chitour, Yacine; van Rossum, Mark C.W.

    2015-01-01

    Neurons are equipped with homeostatic mechanisms that counteract long-term perturbations of their average activity and thereby keep neurons in a healthy and information-rich operating regime. While homeostasis is believed to be crucial for neural function, a systematic analysis of homeostatic control has largely been lacking. The analysis presented here analyses the necessary conditions for stable homeostatic control. We consider networks of neurons with homeostasis and show that homeostatic control that is stable for single neurons, can destabilize activity in otherwise stable recurrent networks leading to strong non-abating oscillations in the activity. This instability can be prevented by slowing down the homeostatic control. The stronger the network recurrence, the slower the homeostasis has to be. Next, we consider how non-linearities in the neural activation function affect these constraints. Finally, we consider the case that homeostatic feedback is mediated via a cascade of multiple intermediate stages. Counter-intuitively, the addition of extra stages in the homeostatic control loop further destabilizes activity in single neurons and networks. Our theoretical framework for homeostasis thus reveals previously unconsidered constraints on homeostasis in biological networks, and identifies conditions that require the slow time-constants of homeostatic regulation observed experimentally. PMID:26154297

  13. Neuroimmune regulation of homeostatic synaptic plasticity.

    PubMed

    Pribiag, Horia; Stellwagen, David

    2014-03-01

    Homeostatic synaptic plasticity refers to a set of negative-feedback mechanisms that are used by neurons to maintain activity within a functional range. While it is becoming increasingly clear that homeostatic regulation of synapse function is a key principle in the nervous system, the molecular details of this regulation are only beginning to be uncovered. Recent evidence implicates molecules classically associated with the peripheral immune system in the modulation of homeostatic synaptic plasticity. In particular, the pro-inflammatory cytokine TNFα, class I major histocompatibility complex, and neuronal pentraxin 2 are essential in the regulation of the compensatory synaptic response that occurs in response to prolonged neuronal inactivity. This review will present and discuss current evidence implicating neuroimmune molecules in the homeostatic regulation of synapse function. This article is part of the Special Issue entitled 'Homeostatic Synaptic Plasticity'.

  14. Immune Homeostatic Macrophages Programmed by the Bacterial Surface Protein NhhA Potentiate Nasopharyngeal Carriage of Neisseria meningitidis

    PubMed Central

    Wang, Xiao; Sjölinder, Mikael; Gao, Yumin; Wan, Yi

    2016-01-01

    ABSTRACT Neisseria meningitidis colonizes the nasopharyngeal mucosa of healthy populations asymptomatically, although the bacterial surface is rich in motifs that activate the host innate immunity. What determines the tolerant host response to this bacterium in asymptomatic carriers is poorly understood. We demonstrated that the conserved meningococcal surface protein NhhA orchestrates monocyte (Mo) differentiation specifically into macrophage-like cells with a CD200Rhi phenotype (NhhA-Mφ). In response to meningococcal stimulation, NhhA-Mφ failed to produce proinflammatory mediators. Instead, they upregulated interleukin-10 (IL-10) and Th2/regulatory T cell (Treg)-attracting chemokines, such as CCL17, CCL18, and CCL22. Moreover, NhhA-Mφ were highly efficient in eliminating bacteria. The in vivo validity of these findings was corroborated using a murine model challenged with N. meningitidis systematically or intranasally. The NhhA-modulated immune response protected mice from septic shock; Mo/Mφ depletion abolished this protective effect. Intranasal administration of NhhA induced an anti-inflammatory response, which was associated with N. meningitidis persistence at the nasopharynx. In vitro studies demonstrated that NhhA-triggered Mo differentiation occurred upon engaged Toll-like receptor 1 (TLR1)/TLR2 signaling and extracellular signal-regulated kinase (ERK) and Jun N-terminal protein kinase (JNK) activation and required endogenously produced IL-10 and tumor necrosis factor alpha (TNF-α). Our findings reveal a strategy that might be adopted by N. meningitidis to maintain asymptomatic nasopharyngeal colonization. PMID:26884432

  15. Immune network behavior: Oscillations, chaos and stationary states

    SciTech Connect

    De Boer, R.J.; Perelson, A.S.; Kevrekidis, I.G.

    1994-04-01

    The authors report two types of behavior in models of immune networks. The typical behavior of simple models, which involve B cells only, consists of several coexisting steady states. Finite amplitude perturbations may cause the model to switch between different equilibria. The typical behavior of more realistic models, which involve both B cells and antibody, consists of autonomous oscillations and/or chaos. While steady-state behavior leads to easy interpretations in terms of immune memory, oscillatory behavior seems to be in better agreement with experimental data obtained in unimmunized animals. The stability of the steady states, and the structure and interactions of the stable and unstable manifolds of the saddle-type equilibria turn out to be factors influencing the model`s behavior. Whether or not the model is able to attain any form of sustained oscillatory behavior, i.e., limit cycles or chaos, seems to be determined by (global) bifurcations involving the stable and unstable manifolds of the steady states.

  16. Allergic Inflammation—Innately Homeostatic

    PubMed Central

    Cheng, Laurence E.; Locksley, Richard M.

    2015-01-01

    Allergic inflammation is associated closely with parasite infection but also asthma and other common allergic diseases. Despite the engagement of similar immunologic pathways, parasitized individuals often show no outward manifestations of allergic disease. In this perspective, we present the thesis that allergic inflammatory responses play a primary role in regulating circadian and environmental inputs involved with tissue homeostasis and metabolic needs. Parasites feed into these pathways and thus engage allergic inflammation to sustain aspects of the parasitic life cycle. In response to parasite infection, an adaptive and regulated immune response is layered on the host effector response, but in the setting of allergy, the effector response remains unregulated, thus leading to the cardinal features of disease. Further understanding of the homeostatic pressures driving allergic inflammation holds promise to further our understanding of human health and the treatment of these common afflictions. PMID:25414367

  17. Robust Concentration and Frequency Control in Oscillatory Homeostats

    PubMed Central

    Thorsen, Kristian; Agafonov, Oleg; Selstø, Christina H.; Jolma, Ingunn W.; Ni, Xiao Y.; Drengstig, Tormod; Ruoff, Peter

    2014-01-01

    Homeostatic and adaptive control mechanisms are essential for keeping organisms structurally and functionally stable. Integral feedback is a control theoretic concept which has long been known to keep a controlled variable robustly (i.e. perturbation-independent) at a given set-point by feeding the integrated error back into the process that generates . The classical concept of homeostasis as robust regulation within narrow limits is often considered as unsatisfactory and even incompatible with many biological systems which show sustained oscillations, such as circadian rhythms and oscillatory calcium signaling. Nevertheless, there are many similarities between the biological processes which participate in oscillatory mechanisms and classical homeostatic (non-oscillatory) mechanisms. We have investigated whether biological oscillators can show robust homeostatic and adaptive behaviors, and this paper is an attempt to extend the homeostatic concept to include oscillatory conditions. Based on our previously published kinetic conditions on how to generate biochemical models with robust homeostasis we found two properties, which appear to be of general interest concerning oscillatory and homeostatic controlled biological systems. The first one is the ability of these oscillators (“oscillatory homeostats”) to keep the average level of a controlled variable at a defined set-point by involving compensatory changes in frequency and/or amplitude. The second property is the ability to keep the period/frequency of the oscillator tuned within a certain well-defined range. In this paper we highlight mechanisms that lead to these two properties. The biological applications of these findings are discussed using three examples, the homeostatic aspects during oscillatory calcium and p53 signaling, and the involvement of circadian rhythms in homeostatic regulation. PMID:25238410

  18. Homeostatic theory of obesity

    PubMed Central

    2015-01-01

    Health is regulated by homeostasis, a property of all living things. Homeostasis maintains equilibrium at set-points using feedback loops for optimum functioning of the organism. Imbalances in homeostasis causing overweight and obesity are evident in more than 1 billion people. In a new theory, homeostatic obesity imbalance is attributed to a hypothesized ‘Circle of Discontent’, a system of feedback loops linking weight gain, body dissatisfaction, negative affect and over-consumption. The Circle of Discontent theory is consistent with an extensive evidence base. A four-armed strategy to halt the obesity epidemic consists of (1) putting a stop to victim-blaming, stigma and discrimination; (2) devalorizing the thin-ideal; (3) reducing consumption of energy-dense, low-nutrient foods and drinks; and (4) improving access to plant-based diets. If fully implemented, interventions designed to restore homeostasis have the potential to halt the obesity epidemic. PMID:28070357

  19. Homeostatic theory of obesity.

    PubMed

    Marks, David F

    2015-01-01

    Health is regulated by homeostasis, a property of all living things. Homeostasis maintains equilibrium at set-points using feedback loops for optimum functioning of the organism. Imbalances in homeostasis causing overweight and obesity are evident in more than 1 billion people. In a new theory, homeostatic obesity imbalance is attributed to a hypothesized 'Circle of Discontent', a system of feedback loops linking weight gain, body dissatisfaction, negative affect and over-consumption. The Circle of Discontent theory is consistent with an extensive evidence base. A four-armed strategy to halt the obesity epidemic consists of (1) putting a stop to victim-blaming, stigma and discrimination; (2) devalorizing the thin-ideal; (3) reducing consumption of energy-dense, low-nutrient foods and drinks; and (4) improving access to plant-based diets. If fully implemented, interventions designed to restore homeostasis have the potential to halt the obesity epidemic.

  20. Periodic and chaotic oscillations in a tumor and immune system interaction model with three delays

    SciTech Connect

    Bi, Ping; Ruan, Shigui; Zhang, Xinan

    2014-06-15

    In this paper, a tumor and immune system interaction model consisted of two differential equations with three time delays is considered in which the delays describe the proliferation of tumor cells, the process of effector cells growth stimulated by tumor cells, and the differentiation of immune effector cells, respectively. Conditions for the asymptotic stability of equilibria and existence of Hopf bifurcations are obtained by analyzing the roots of a second degree exponential polynomial characteristic equation with delay dependent coefficients. It is shown that the positive equilibrium is asymptotically stable if all three delays are less than their corresponding critical values and Hopf bifurcations occur if any one of these delays passes through its critical value. Numerical simulations are carried out to illustrate the rich dynamical behavior of the model with different delay values including the existence of regular and irregular long periodic oscillations.

  1. Drug abuse: hedonic homeostatic dysregulation.

    PubMed

    Koob, G F; Le Moal, M

    1997-10-03

    Understanding the neurobiological mechanisms of addiction requires an integration of basic neuroscience with social psychology, experimental psychology, and psychiatry. Addiction is presented as a cycle of spiralling dysregulation of brain reward systems that progressively increases, resulting in compulsive drug use and a loss of control over drug-taking. Sensitization and counteradaptation are hypothesized to contribute to this hedonic homeostatic dysregulation, and the neurobiological mechanisms involved, such as the mesolimbic dopamine system, opioid peptidergic systems, and brain and hormonal stress systems, are beginning to be characterized. This framework provides a realistic approach to identifying the neurobiological factors that produce vulnerability to addiction and to relapse in individuals with a history of addiction.

  2. Bidirectional homeostatic plasticity induced by interneuron cell death and transplantation in vivo.

    PubMed

    Howard, MacKenzie Allen; Rubenstein, John L R; Baraban, Scott C

    2014-01-07

    Chronic changes in excitability and activity can induce homeostatic plasticity. These perturbations may be associated with neurological disorders, particularly those involving loss or dysfunction of GABA interneurons. In distal-less homeobox 1 (Dlx1(-/-)) mice with late-onset interneuron loss and reduced inhibition, we observed both excitatory synaptic silencing and decreased intrinsic neuronal excitability. These homeostatic changes do not fully restore normal circuit function, because synaptic silencing results in enhanced potential for long-term potentiation and abnormal gamma oscillations. Transplanting medial ganglionic eminence interneuron progenitors to introduce new GABAergic interneurons, we demonstrate restoration of hippocampal function. Specifically, miniature excitatory postsynaptic currents, input resistance, hippocampal long-term potentiation, and gamma oscillations are all normalized. Thus, in vivo homeostatic plasticity is a highly dynamic and bidirectional process that responds to changes in inhibition.

  3. Homeostatic plasticity at the Drosophila neuromuscular junction.

    PubMed

    Frank, C Andrew

    2014-03-01

    In biology, homeostasis refers to how cells maintain appropriate levels of activity. This concept underlies a balancing act in the nervous system. Synapses require flexibility (i.e. plasticity) to adjust to environmental challenges. Yet there must also exist regulatory mechanisms that constrain activity within appropriate physiological ranges. An abundance of evidence suggests that homeostatic regulation is critical in this regard. In recent years, important progress has been made toward identifying molecules and signaling processes required for homeostatic forms of neuroplasticity. The Drosophila melanogaster third instar larval neuromuscular junction (NMJ) has been an important experimental system in this effort. Drosophila neuroscientists combine genetics, pharmacology, electrophysiology, imaging, and a variety of molecular techniques to understand how homeostatic signaling mechanisms take shape at the synapse. At the NMJ, homeostatic signaling mechanisms couple retrograde (muscle-to-nerve) signaling with changes in presynaptic calcium influx, changes in the dynamics of the readily releasable vesicle pool, and ultimately, changes in presynaptic neurotransmitter release. Roles in these processes have been demonstrated for several molecules and signaling systems discussed here. This review focuses primarily on electrophysiological studies or data. In particular, attention is devoted to understanding what happens when NMJ function is challenged (usually through glutamate receptor inhibition) and the resulting homeostatic responses. A significant area of study not covered in this review, for the sake of simplicity, is the homeostatic control of synapse growth, which naturally, could also impinge upon synapse function in myriad ways. This article is part of the Special Issue entitled 'Homeostatic Synaptic Plasticity'.

  4. Premetastatic milieu explained by TLR4 agonist-mediated homeostatic inflammation.

    PubMed

    Maru, Yoshiro

    2010-03-01

    Accumulating evidence suggests that Toll-like receptor 4 (TLR4), a sensor for danger signals, is expressed not only in immune cells, but also in resident epithelial cells, and appears to participate in tissue homeostasis. To explain the premetastatic microenvironment created by the newly discovered endogenous TLR4 ligands, I propose a hypothesis of homeostatic inflammation that includes the classical danger hypothesis.

  5. Homeostatic plasticity mechanisms in mouse V1.

    PubMed

    Kaneko, Megumi; Stryker, Michael P

    2017-03-05

    Mechanisms thought of as homeostatic must exist to maintain neuronal activity in the brain within the dynamic range in which neurons can signal. Several distinct mechanisms have been demonstrated experimentally. Three mechanisms that act to restore levels of activity in the primary visual cortex of mice after occlusion and restoration of vision in one eye, which give rise to the phenomenon of ocular dominance plasticity, are discussed. The existence of different mechanisms raises the issue of how these mechanisms operate together to converge on the same set points of activity.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity'.

  6. Metabotropic glutamate receptor 5 modulates calcium oscillation and innate immune response induced by lipopolysaccharide in microglial cell.

    PubMed

    Liu, F; Zhou, R; Yan, H; Yin, H; Wu, X; Tan, Y; Li, L

    2014-12-05

    Microglia, the primary immune cells in the brain, have been implicated as the predominant cells governing inflammation-mediated neuronal damage. In response to immunological challenges such as lipopolysaccharide (LPS), microglia are activated and subsequently inflammatory process is initiated as evidenced by the release of pro-inflammatory chemokines and cytokines. Here we show that Group I metabotropic glutamate receptor 5 (mGluR5) is involved in LPS-induced microglia activation. LPS triggered a similar pattern of [Ca2+]i oscillation in N9, Toll-like receptor 4 (TLR4)-mutant EOC 20, TLR4-wild-type and TLR4-deficient primary mouse microglia, suggesting that LPS-induced [Ca2+]i oscillation is independent of TLR4. The characteristics of [Ca2+]i oscillation induced by LPS are consistent with those observed in mGluR5 activation. In addition, mGluR5 antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) abolished LPS-induced [Ca2+]i oscillation. Immunocytochemistry demonstrated that LPS colocalizes with mGluR5 in microglia and the direct binding of LPS and mGluR5 was further validated by antibody-based fluorescence resonance energy transfer (FRET) technology. Activation of mGluR5 using a selective agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) significantly expanded LPS-induced nuclear factor-kappa B (NF-κB) activity and CHPG alone increased NF-κB activity as well. But, mGluR5 antagonist MTEP attenuated the actions of LPS, CHPG and the additive effect of LPS and CHPG in microglia. LPS induced tumor necrosis factor-α (TNF-α) secretion in N9 microglia, but not in TLR4-mutant EOC 20 and TLR4-deficient primary mouse microglia. CHPG reduced LPS-caused TNF-α production, but MTEP increased LPS-induced TNF-α production and blocked the effect of CHPG in N9 microglia. These data demonstrate that mGluR5 and TLR4 are two critical receptors that mediate microglia activation in response to LPS, suggesting that mGluR5 may represent a novel target for modulating

  7. Integrating Hebbian and homeostatic plasticity: introduction

    PubMed Central

    2017-01-01

    Hebbian plasticity is widely considered to be the mechanism by which information can be coded and retained in neurons in the brain. Homeostatic plasticity moves the neuron back towards its original state following a perturbation, including perturbations produced by Hebbian plasticity. How then does homeostatic plasticity avoid erasing the Hebbian coded information? To understand how plasticity works in the brain, and therefore to understand learning, memory, sensory adaptation, development and recovery from injury, requires development of a theory of plasticity that integrates both forms of plasticity into a whole. In April 2016, a group of computational and experimental neuroscientists met in London at a discussion meeting hosted by the Royal Society to identify the critical questions in the field and to frame the research agenda for the next steps. Here, we provide a brief introduction to the papers arising from the meeting and highlight some of the themes to have emerged from the discussions. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’. PMID:28093560

  8. Integrating Hebbian and homeostatic plasticity: introduction.

    PubMed

    Fox, Kevin; Stryker, Michael

    2017-03-05

    Hebbian plasticity is widely considered to be the mechanism by which information can be coded and retained in neurons in the brain. Homeostatic plasticity moves the neuron back towards its original state following a perturbation, including perturbations produced by Hebbian plasticity. How then does homeostatic plasticity avoid erasing the Hebbian coded information? To understand how plasticity works in the brain, and therefore to understand learning, memory, sensory adaptation, development and recovery from injury, requires development of a theory of plasticity that integrates both forms of plasticity into a whole. In April 2016, a group of computational and experimental neuroscientists met in London at a discussion meeting hosted by the Royal Society to identify the critical questions in the field and to frame the research agenda for the next steps. Here, we provide a brief introduction to the papers arising from the meeting and highlight some of the themes to have emerged from the discussions.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity'.

  9. Immunizations

    MedlinePlus

    ... Get Weight Loss Surgery? A Week of Healthy Breakfasts Shyness Immunizations KidsHealth > For Teens > Immunizations Print A A A What's in this article? Why Are Vaccinations Important? Why Do I Need Shots? Which Vaccinations Do ...

  10. Circadian and homeostatic variation in sustained attention.

    PubMed

    Valdez, Pablo; Ramírez, Candelaria; García, Aída; Talamantes, Javier; Cortez, Juventino

    2010-01-01

    Human performance is modulated by circadian rhythms and homeostatic changes. Changes in efficiency in the performance of many tasks might be produced by variation in a basic cognitive process, such as sustained attention. This cognitive process is the capacity to respond efficiently to the environment during prolonged periods (from minutes to hours). There are three indices of sustained attention: general stability of efficiency, time on task stability, and short-term stability. The objective of this work was to analyze circadian and homeostatic influences on the indices of sustained attention. Participants were nine undergraduate female student volunteers (mean age 17.67 yrs, SD = 1.00, range 16-19 yrs) who attended school from 07:00-13:30 h, Monday to Friday. They were assessed while adhering to a modified 28 h constant-routine protocol during which feeding, room temperature, motor activity, and room illumination were controlled. Rectal temperature was recorded each minute, and indices of sustained attention were assessed hourly through a continuous performance task (CPT). General stability was measured as standard deviation of correct responses and reaction time, time on task stability was measured as the linear regression of correct responses and reaction time throughout the task, and short-term stability was measured as hit runs and error runs. Rectal temperature showed circadian variation; subjective somnolence and tiredness increased, while general performance and all indices of sustained attention declined throughout the 28 h recording session. General stability exhibited circadian variation, whereas time on task did not. Short-term stability showed circadian variations in short-error runs, long-error runs, and short-hit runs, but long-hit runs did not. There was a 26 sec short interval at the beginning of the task, characterized by a very high efficiency level of performance. Execution during this safe period was not affected by time awake and did not show

  11. Integrating intervention targets offered by homeostatic theory

    PubMed Central

    Annunziato, Rachel A; Grossman, Stephanie L

    2016-01-01

    Marks presents “homeostatic theory” which proposes that weight gain is fostered by a “Circle of Discontent” consisting of body dissatisfaction, negative affect, and overconsumption. This innovative framework offers potential intervention approaches, including victim-blaming, stigma, and discrimination, as well as devalorizing the thin-ideal. Our article discusses possible ways that clinical health psychologists based in university settings may be uniquely positioned to consider and implement large-scale programs that have shown great promise for addressing these core issues. PMID:28070390

  12. Molecular Substrates of Schizophrenia: Homeostatic Signaling to Connectivity

    PubMed Central

    Landek-Salgado, Melissa A.; Faust, Travis E.; Sawa, Akira

    2015-01-01

    Schizophrenia (SZ) is a devastating psychiatric condition affecting numerous brain systems. Recent studies have identified genetic factors that confer an increased risk of SZ and participate in the disease etiopathogenesis. In parallel to such bottom-up approaches, other studies have extensively reported biological changes in patients by brain imaging, neurochemical and pharmacological approaches. This review highlights the molecular substrates identified through studies with SZ patients, namely those using top-down approaches, while also referring to the fruitful outcomes of recent genetic studies. We have sub-classified the molecular substrates by system, focusing on elements of neurotransmission, targets in white matter-associated connectivity, immune/inflammatory and oxidative stress-related substrates, and molecules in endocrine and metabolic cascades. We further touch on crosstalk among these systems and comment on the utility of animal models in charting the developmental progression and interaction of these substrates. Based on this comprehensive information, we propose a framework for SZ research based on the hypothesis of an imbalance in homeostatic signaling from immune/inflammatory, oxidative stress, endocrine and metabolic cascades that, at least in part, underlies deficits in neural connectivity relevant to SZ. Thus, this review aims to provide information that is translationally useful and complementary to pathogenic hypotheses that have emerged from genetic studies. Based on such advances in SZ research, it is highly expected that we will discover biomarkers that may help in the early intervention, diagnosis or treatment of SZ. PMID:26390828

  13. Moving HAIRS: Towards adaptive, homeostatic materials

    NASA Astrophysics Data System (ADS)

    Aizenberg, Joanna

    Dynamic structures that respond reversibly to changes in their environment are central to self-regulating thermal and lighting systems, targeted drug delivery, sensors, and self-propelled locomotion. Since an adaptive change requires energy input, an ideal strategy would be to design materials that harvest energy directly from the environment and use it to drive an appropriate response. This lecture will present the design of a novel class of reconfigurable materials that use surfaces bearing arrays of nanostructures put in motion by environment-responsive gels. Their unique hybrid architecture, and chemical and mechanical properties can be optimized to confer a wide range of adaptive behaviors. Using both experimental and modeling approaches, we are developing these hydrogel-actuated integrated responsive systems (HAIRS) as new materials with reversible optical and wetting properties, as a multifunctional platform for controlling cell differentiation and function, and as a first homeostatic system with autonomous self-regulation.

  14. Homeostatic Fluctuations of a Tissue Surface

    NASA Astrophysics Data System (ADS)

    Risler, Thomas; Peilloux, Aurélien; Prost, Jacques

    2015-12-01

    We study the surface fluctuations of a tissue with a dynamics dictated by cell-rearrangement, cell-division, and cell-death processes. Surface fluctuations are calculated in the homeostatic state, where cell division and cell death equilibrate on average. The obtained fluctuation spectrum can be mapped onto several other spectra such as those characterizing incompressible fluids, compressible Maxwell elastomers, or permeable membranes in appropriate asymptotic regimes. Since cell division and cell death are out-of-equilibrium processes, detailed balance is broken, but a generalized fluctuation-response relation is satisfied in terms of appropriate observables. Our work is a first step toward the description of the out-of-equilibrium fluctuations of the surface of a thick epithelium and its dynamical response to external perturbations.

  15. Roles for BLyS family members in meeting the distinct homeostatic demands of innate and adaptive B cells

    PubMed Central

    Sindhava, Vishal J.; Scholz, Jean L.; Cancro, Michael P.

    2013-01-01

    B-1 and B-2 B cell populations have different progenitors, receptor diversity, anatomic location, and functions – suggesting vastly differing requisites for homeostatic regulation. There is evidence that the B lymphocyte stimulator (BLyS) family of cytokines and receptors, key factors in the homeostatic regulation of B-2 B cell subsets, is also a major player in the B-1 compartment. Here we review the development and differentiation of these two primary B cell lineages and their immune functions. We discuss evidence that BLyS or a proliferation-inducing ligand (APRIL) availability in different anatomic sites, coupled with signature BLyS receptor expression patterns on different B cell subsets, may be important for homeostatic regulation of B-1 as well as B-2 populations. Finally, we extend our working model of B cell homeostasis to integrate B-1s. PMID:23443938

  16. Immunization

    MedlinePlus

    ... remembers" the germ and can fight it again. Vaccines contain germs that have been killed or weakened. When given to a healthy person, the vaccine triggers the immune system to respond and thus ...

  17. Homeostatic Disinhibition in the Aging Brain and Alzheimer’s Disease

    PubMed Central

    Gleichmann, Marc; Chow, Vivian W.; Mattson, Mark P.

    2015-01-01

    In this article we propose that impaired efficiency of glutamatergic synaptic transmission and a compensatory reduction in inhibitory neurotransmission, a process called homeostatic dishinhibition, occurs in the aging brain and more dramatically in Alzheimer’s disease (AD). Homeostatic disinhibition may help understand certain features of the aging brain and AD including: 1) the increased risk for epileptic seizures, especially in the early phase of the disease; 2) the reduced ability to generate γ-oscillations and 3) the increase in neuronal activity as measured by functional MRI. Homeostatic disinhibition may be the major mechanism that activates cognitive reserve. Modulating neuronal activity may therefore be a viable therapeutic strategy in AD that can complement existing anti-amyloid strategies. Specifically, enhancing endogenous glutamatergic synaptic transmission through increased co-agonist signaling or through positive allosteric modulation of metabotropic glutamatergic receptors appears as an attractive strategy. Alternatively, further reduction of GABAergic signaling may work as well, although care has to be taken to prevent epileptic seizures. PMID:21187584

  18. A Role for Homeostatic Drive in the Perpetuation of Complex Chronic Illness: Gulf War Illness and Chronic Fatigue Syndrome

    PubMed Central

    Craddock, Travis J. A.; Fritsch, Paul; Rice, Mark A.; del Rosario, Ryan M.; Miller, Diane B.; Fletcher, Mary Ann; Klimas, Nancy G.; Broderick, Gordon

    2014-01-01

    A key component in the body's stress response, the hypothalamic-pituitary-adrenal (HPA) axis orchestrates changes across a broad range of major biological systems. Its dysfunction has been associated with numerous chronic diseases including Gulf War Illness (GWI) and chronic fatigue syndrome (CFS). Though tightly coupled with other components of endocrine and immune function, few models of HPA function account for these interactions. Here we extend conventional models of HPA function by including feed-forward and feedback interaction with sex hormone regulation and immune response. We use this multi-axis model to explore the role of homeostatic regulation in perpetuating chronic conditions, specifically GWI and CFS. An important obstacle in building these models across regulatory systems remains the scarcity of detailed human in vivo kinetic data as its collection can present significant health risks to subjects. We circumvented this using a discrete logic representation based solely on literature of physiological and biochemical connectivity to provide a qualitative description of system behavior. This connectivity model linked molecular variables across the HPA axis, hypothalamic-pituitary-gonadal (HPG) axis in men and women, as well as a simple immune network. Inclusion of these interactions produced multiple alternate homeostatic states and sexually dimorphic responses. Experimental data for endocrine-immune markers measured in male GWI subjects showed the greatest alignment with predictions of a naturally occurring alternate steady state presenting with hypercortisolism, low testosterone and a shift towards a Th1 immune response. In female CFS subjects, expression of these markers aligned with an alternate homeostatic state displaying hypocortisolism, high estradiol, and a shift towards an anti-inflammatory Th2 activation. These results support a role for homeostatic drive in perpetuating dysfunctional cortisol levels through persistent interaction with the

  19. Immunization.

    ERIC Educational Resources Information Center

    Guerin, Nicole; And Others

    1986-01-01

    Contents of this double journal issue concern immunization and primary health care of children. The issue decribes vaccine storage and sterilization techniques, giving particular emphasis to the role of the cold chain, i.e., the maintenance of a specific temperature range to assure potency of vaccines as they are moved from a national storage…

  20. Transcription factor KLF2 regulates homeostatic NK cell proliferation and survival.

    PubMed

    Rabacal, Whitney; Pabbisetty, Sudheer K; Hoek, Kristen L; Cendron, Delphine; Guo, Yin; Maseda, Damian; Sebzda, Eric

    2016-05-10

    Natural killer (NK) cells are innate lymphocytes that recognize and lyse virally infected or transformed cells. This latter property is being pursued in clinics to treat leukemia with the hope that further breakthroughs in NK cell biology can extend treatments to other cancers. At issue is the ability to expand transferred NK cells and prolong their functionality within the context of a tumor. In terms of NK cell expansion and survival, we now report that Kruppel-like factor 2 (KLF2) is a key transcription factor that underpins both of these events. Excision of Klf2 using gene-targeted mouse models promotes spontaneous proliferation of immature NK cells in peripheral tissues, a phenotype that is replicated under ex vivo conditions. Moreover, KLF2 imprints a homeostatic migration pattern on mature NK cells that allows these cells to access IL-15-rich microenvironments. KLF2 accomplishes this feat within the mature NK cell lineage via regulation of a subset of homing receptors that respond to homeostatic ligands while leaving constitutively expressed receptors that recognize inflammatory cytokines unperturbed. Under steady-state conditions, KLF2-deficient NK cells alter their expression of homeostatic homing receptors and subsequently undergo apoptosis due to IL-15 starvation. This novel mechanism has implications regarding NK cell contraction following the termination of immune responses including the possibility that retention of an IL-15 transpresenting support system is key to extending NK cell activity in a tumor environment.

  1. Reversible Recruitment of a Homeostatic Reserve Pool of Synaptic Vesicles Underlies Rapid Homeostatic Plasticity of Quantal Content

    PubMed Central

    Pinter, Martin J.; Rich, Mark M.

    2016-01-01

    Homeostatic regulation is essential for the maintenance of synaptic strength within the physiological range. The current study is the first to demonstrate that both induction and reversal of homeostatic upregulation of synaptic vesicle release can occur within seconds of blocking or unblocking acetylcholine receptors at the mouse neuromuscular junction. Our data suggest that the homeostatic upregulation of release is due to Ca2+-dependent increase in the size of the readily releasable pool (RRP). Blocking vesicle refilling prevented upregulation of quantal content (QC), while leaving baseline release relatively unaffected. This suggested that the upregulation of QC was due to mobilization of a distinct pool of vesicles that were rapidly recycled and thus were dependent on continued vesicle refilling. We term this pool the “homeostatic reserve pool.” A detailed analysis of the time course of vesicle release triggered by a presynaptic action potential suggests that the homeostatic reserve pool of vesicles is normally released more slowly than other vesicles, but the rate of their release becomes similar to that of the major pool during homeostatic upregulation of QC. Remarkably, instead of finding a generalized increase in the recruitment of vesicles into RRP, we identified a distinct homeostatic reserve pool of vesicles that appear to only participate in synchronized release following homeostatic upregulation of QC. Once this small pool of vesicles is depleted by the block of vesicle refilling, homeostatic upregulation of QC is no longer observed. This is the first identification of the population of vesicles responsible for the blockade-induced upregulation of release previously described. SIGNIFICANCE STATEMENT The current study is the first to demonstrate that both the induction and reversal of homeostatic upregulation of synaptic vesicle release can occur within seconds. Our data suggest that homeostatic upregulation of release is due to Ca2+-dependent

  2. Serotonin as a homeostatic regulator of lactation.

    PubMed

    Collier, R J; Hernandez, L L; Horseman, N D

    2012-08-01

    Serotonin (5-HT), a neurotransmitter produced in mammary epithelial cells (MECs), acts via autocrine-paracrine mechanisms on MECs to regulate milk secretion in a variety of species. Recent studies in dairy cows reported that 5-HT ligands affect milk yield and composition. We determined the mRNA expression of bovine 5-HT receptor (5-HTR) subtypes in bovine mammary tissue (BMT) and cultured bovine MECs. We then used pharmacologic agents to evaluate functional activities of 5-HTR subtypes. The mRNAs for five receptor isoforms (5-HTR1B, 5-HTR2A, 5-HTR2B, 5-HTR4, and 5-HTR7) were identified by conventional reverse transcription PCR, real-time PCR, and in situ hybridization in BMT. In addition to luminal MEC expression, 5-HTR4 was expressed in myoepithelium, and 5-HTR1B, HTR2A, and HTR2B were expressed in small mammary blood vessels. Studies to date report that there are multiple 5-HTR isoforms in mammary tissue of rodents, humans, and cattle. Inhibition of the 5-HT reuptake transporter with selective 5-HT reuptake inhibitors (SSRIs) disrupted tight junctions and decreased milk protein mRNA expression in mouse, human, and bovine mammary cells. Selective 5-HT reuptake inhibitors act to increase the cellular exposure to 5-HT by preventing reuptake of 5-HT by the cell and eventual degradation. Increasing 5-HT concentration in milk via inhibiting its reuptake (SSRI), or by increasing the precursor for 5-HT synthesis 5-hydroxytryptophan, accelerated decline in milk synthesis at dry-off. We conclude that the 5-HT system in mammary tissue acts as a homeostatic regulator of lactation.

  3. Transcription factor repertoire of homeostatic eosinophilopoiesis

    PubMed Central

    Bouffi, Carine; Kartashov, Andrey V.; Schollaert, Kaila L.; Chen, Xiaoting; Bacon, W. Clark; Weirauch, Matthew T.; Barski, Artem; Fulkerson, Patricia C.

    2015-01-01

    The production of mature eosinophils is a tightly orchestrated process with the aim to sustain normal eosinophil levels in tissues while also maintaining low numbers of these complex and sensitive cells in the blood. To identify regulators of homeostatic eosinophilopoiesis in mice, we took a global approach to identify genome-wide transcriptome and epigenome changes that occur during homeostasis at critical developmental stages, including eosinophil-lineage commitment and lineage maturation. Our analyses revealed a markedly greater number of transcriptome alterations associated with eosinophil maturation (1199 genes) than with eosinophil-lineage commitment (490 genes), highlighting the greater transcriptional investment necessary for differentiation. Eosinophil progenitors (EoPs) were noted to express high levels of granule proteins and contain granules with an ultrastructure distinct from that of mature resting eosinophils. Our analyses also delineated a 976-gene eosinophil-lineage transcriptome that included a repertoire of 56 transcription factors, many of which have never previously been associated with eosinophils. EoPs and eosinophils, but not granulocyte-monocyte progenitors (GMPs) or neutrophils, expressed Helios and Aiolos, members of the Ikaros family of transcription factors, which regulate gene expression via modulation of chromatin structure and DNA accessibility. Epigenetic studies revealed a distinct distribution of active chromatin marks between genes induced with lineage commitment and genes induced with cell maturation during eosinophil development. In addition, Aiolos and Helios binding sites were significantly enriched in genes expressed by EoPs and eosinophils with active chromatin, highlighting a potential novel role for Helios and Aiolos in regulating gene expression during eosinophil development. PMID:26268651

  4. Active Inference, homeostatic regulation and adaptive behavioural control.

    PubMed

    Pezzulo, Giovanni; Rigoli, Francesco; Friston, Karl

    2015-11-01

    We review a theory of homeostatic regulation and adaptive behavioural control within the Active Inference framework. Our aim is to connect two research streams that are usually considered independently; namely, Active Inference and associative learning theories of animal behaviour. The former uses a probabilistic (Bayesian) formulation of perception and action, while the latter calls on multiple (Pavlovian, habitual, goal-directed) processes for homeostatic and behavioural control. We offer a synthesis these classical processes and cast them as successive hierarchical contextualisations of sensorimotor constructs, using the generative models that underpin Active Inference. This dissolves any apparent mechanistic distinction between the optimization processes that mediate classical control or learning. Furthermore, we generalize the scope of Active Inference by emphasizing interoceptive inference and homeostatic regulation. The ensuing homeostatic (or allostatic) perspective provides an intuitive explanation for how priors act as drives or goals to enslave action, and emphasises the embodied nature of inference.

  5. Active Inference, homeostatic regulation and adaptive behavioural control

    PubMed Central

    Pezzulo, Giovanni; Rigoli, Francesco; Friston, Karl

    2015-01-01

    We review a theory of homeostatic regulation and adaptive behavioural control within the Active Inference framework. Our aim is to connect two research streams that are usually considered independently; namely, Active Inference and associative learning theories of animal behaviour. The former uses a probabilistic (Bayesian) formulation of perception and action, while the latter calls on multiple (Pavlovian, habitual, goal-directed) processes for homeostatic and behavioural control. We offer a synthesis these classical processes and cast them as successive hierarchical contextualisations of sensorimotor constructs, using the generative models that underpin Active Inference. This dissolves any apparent mechanistic distinction between the optimization processes that mediate classical control or learning. Furthermore, we generalize the scope of Active Inference by emphasizing interoceptive inference and homeostatic regulation. The ensuing homeostatic (or allostatic) perspective provides an intuitive explanation for how priors act as drives or goals to enslave action, and emphasises the embodied nature of inference. PMID:26365173

  6. The Structural Connectome of the Human Central Homeostatic Network.

    PubMed

    Edlow, Brian L; McNab, Jennifer A; Witzel, Thomas; Kinney, Hannah C

    2016-04-01

    Homeostatic adaptations to stress are regulated by interactions between the brainstem and regions of the forebrain, including limbic sites related to respiratory, autonomic, affective, and cognitive processing. Neuroanatomic connections between these homeostatic regions, however, have not been thoroughly identified in the human brain. In this study, we perform diffusion spectrum imaging tractography using the MGH-USC Connectome MRI scanner to visualize structural connections in the human brain linking autonomic and cardiorespiratory nuclei in the midbrain, pons, and medulla oblongata with forebrain sites critical to homeostatic control. Probabilistic tractography analyses in six healthy adults revealed connections between six brainstem nuclei and seven forebrain regions, several over long distances between the caudal medulla and cerebral cortex. The strongest evidence for brainstem-homeostatic forebrain connectivity in this study was between the brainstem midline raphe and the medial temporal lobe. The subiculum and amygdala were the sampled forebrain nodes with the most extensive brainstem connections. Within the human brainstem-homeostatic forebrain connectome, we observed that a lateral forebrain bundle, whose connectivity is distinct from that of rodents and nonhuman primates, is the primary conduit for connections between the brainstem and medial temporal lobe. This study supports the concept that interconnected brainstem and forebrain nodes form an integrated central homeostatic network (CHN) in the human brain. Our findings provide an initial foundation for elucidating the neuroanatomic basis of homeostasis in the normal human brain, as well as for mapping CHN disconnections in patients with disorders of homeostasis, including sudden and unexpected death, and epilepsy.

  7. Emerging links between homeostatic synaptic plasticity and neurological disease.

    PubMed

    Wondolowski, Joyce; Dickman, Dion

    2013-11-21

    Homeostatic signaling systems are ubiquitous forms of biological regulation, having been studied for hundreds of years in the context of diverse physiological processes including body temperature and osmotic balance. However, only recently has this concept been brought to the study of excitatory and inhibitory electrical activity that the nervous system uses to establish and maintain stable communication. Synapses are a primary target of neuronal regulation with a variety of studies over the past 15 years demonstrating that these cellular junctions are under bidirectional homeostatic control. Recent work from an array of diverse systems and approaches has revealed exciting new links between homeostatic synaptic plasticity and a variety of seemingly disparate neurological and psychiatric diseases. These include autism spectrum disorders, intellectual disabilities, schizophrenia, and Fragile X Syndrome. Although the molecular mechanisms through which defective homeostatic signaling may lead to disease pathogenesis remain unclear, rapid progress is likely to be made in the coming years using a powerful combination of genetic, imaging, electrophysiological, and next generation sequencing approaches. Importantly, understanding homeostatic synaptic plasticity at a cellular and molecular level may lead to developments in new therapeutic innovations to treat these diseases. In this review we will examine recent studies that demonstrate homeostatic control of postsynaptic protein translation, retrograde signaling, and presynaptic function that may contribute to the etiology of complex neurological and psychiatric diseases.

  8. Operation of a Homeostatic Sleep Switch

    PubMed Central

    Talbot, Clifford B.; Song, Seoho M.; Thurston, Alexander J. F.; Miesenböck, Gero

    2016-01-01

    Sleep disconnects animals from the external world, at considerable risks and costs that must be offset by a vital benefit. Insight into this mysterious benefit will come from understanding sleep homeostasis: to monitor sleep need, an internal bookkeeper must track physiological changes that are linked to the core function of sleep1. In Drosophila, a crucial component of the machinery for sleep homeostasis is a cluster of neurons innervating the dorsal fan-shaped body (dFB) of the central complex2,3. Artificial activation of these cells induces sleep2, whereas reductions in excitability cause insomnia3,4. dFB neurons in sleep-deprived flies tend to be electrically active, with high input resistances and long membrane time constants, while neurons in rested flies tend to be electrically silent3. Correlative evidence thus supports the simple view that homeostatic sleep control works by switching sleep-promoting neurons between active and quiescent states3. Here we demonstrate state switching by dFB neurons, identify dopamine as a neuromodulator that operates the switch, and delineate the switching mechanism. Arousing dopamine4–8 caused transient hyperpolarization of dFB neurons within tens of milliseconds and lasting excitability suppression within minutes. Both effects were transduced by Dop1R2 receptors and mediated by potassium conductances. The switch to electrical silence involved the downregulation of voltage-gated A-type currents carried by Shaker and Shab and the upregulation of voltage-independent leak currents through a two-pore domain potassium channel we term Sandman. Sandman is encoded by the CG8713 gene and translocates to the plasma membrane in response to dopamine. dFB-restricted interference with the expression of Shaker or Sandman decreased or increased sleep, respectively, by slowing the repetitive discharge of dFB neurons in the ON state or blocking their entry into the OFF state. Biophysical changes in a small population of neurons are thus

  9. Calcineurin mediates homeostatic synaptic plasticity by regulating retinoic acid synthesis

    PubMed Central

    Arendt, Kristin L.; Zhang, Zhenjie; Ganesan, Subhashree; Hintze, Maik; Shin, Maggie M.; Tang, Yitai; Cho, Ahryon; Graef, Isabella A.; Chen, Lu

    2015-01-01

    Homeostatic synaptic plasticity is a form of non-Hebbian plasticity that maintains stability of the network and fidelity for information processing in response to prolonged perturbation of network and synaptic activity. Prolonged blockade of synaptic activity decreases resting Ca2+ levels in neurons, thereby inducing retinoic acid (RA) synthesis and RA-dependent homeostatic synaptic plasticity; however, the signal transduction pathway that links reduced Ca2+-levels to RA synthesis remains unknown. Here we identify the Ca2+-dependent protein phosphatase calcineurin (CaN) as a key regulator for RA synthesis and homeostatic synaptic plasticity. Prolonged inhibition of CaN activity promotes RA synthesis in neurons, and leads to increased excitatory and decreased inhibitory synaptic transmission. These effects of CaN inhibitors on synaptic transmission are blocked by pharmacological inhibitors of RA synthesis or acute genetic deletion of the RA receptor RARα. Thus, CaN, acting upstream of RA, plays a critical role in gating RA signaling pathway in response to synaptic activity. Moreover, activity blockade-induced homeostatic synaptic plasticity is absent in CaN knockout neurons, demonstrating the essential role of CaN in RA-dependent homeostatic synaptic plasticity. Interestingly, in GluA1 S831A and S845A knockin mice, CaN inhibitor- and RA-induced regulation of synaptic transmission is intact, suggesting that phosphorylation of GluA1 C-terminal serine residues S831 and S845 is not required for CaN inhibitor- or RA-induced homeostatic synaptic plasticity. Thus, our study uncovers an unforeseen role of CaN in postsynaptic signaling, and defines CaN as the Ca2+-sensing signaling molecule that mediates RA-dependent homeostatic synaptic plasticity. PMID:26443861

  10. Doppler-broadened mid-infrared noise-immune cavity-enhanced optical heterodyne molecular spectrometry based on an optical parametric oscillator for trace gas detection.

    PubMed

    Silander, Isak; Hausmaninger, Thomas; Ma, Weiguang; Harren, Frans J M; Axner, Ove

    2015-02-15

    An optical parametric oscillator based Doppler-broadened (Db) noise-immune cavity-enhanced optical heterodyne molecular spectrometry (NICE-OHMS) system suitable for addressing fundamental vibrational transitions in the 3.2-3.9 μm mid-infrared (MIR) region has been realized. An Allan-Werle analysis provides a detection sensitivity of methane of 1.5×10(-9)  cm(-1) with a 20 s integration time, which corresponds to 90 ppt of CH4 if detected at the strongest transition addressed at 40 Torr. This supersedes that of previous Db MIR NICE-OHMS demonstrations and suggests that the technique can be suitable for detection of both the environmentally important (13)CH(4) and CH3D isotopologues. It also opens up for detection of many other molecular species at ppt and sub-ppt concentration levels.

  11. Molecular mechanisms driving homeostatic plasticity of neurotransmitter release

    PubMed Central

    Lazarevic, Vesna; Pothula, Santosh; Andres-Alonso, Maria; Fejtova, Anna

    2013-01-01

    Homeostatic plasticity is a process by which neurons adapt to the overall network activity to keep their firing rates in a reasonable range. At the cellular level this kind of plasticity comprises modulation of cellular excitability and tuning of synaptic strength. In this review we concentrate on presynaptic homeostatic plasticity controlling the efficacy of neurotransmitter release from presynaptic boutons. While morphological and electrophysiological approaches were successful to describe homeostatic plasticity-induced changes in the presynaptic architecture and function, cellular and molecular mechanisms underlying those modifications remained largely unknown for a long time. We summarize the latest progress made in the understanding of homeostasis-induced regulation of different steps of the synaptic vesicle cycle and the molecular machineries involved in this process. We particularly focus on the role of presynaptic scaffolding proteins, which functionally and spatially organize synaptic vesicle clusters, neurotransmitter release sites and the associated endocytic machinery. These proteins turned out to be major presynaptic substrates for remodeling during homeostatic plasticity. Finally, we discuss cellular processes and signaling pathways acting during homeostatic molecular remodeling and their potential involvement in the maladaptive plasticity occurring in multiple neuropathologic conditions such as neurodegeneration, epilepsy and neuropsychiatric disorders. PMID:24348337

  12. Dystroglycan mediates homeostatic synaptic plasticity at GABAergic synapses.

    PubMed

    Pribiag, Horia; Peng, Huashan; Shah, Waris Ali; Stellwagen, David; Carbonetto, Salvatore

    2014-05-06

    Dystroglycan (DG), a cell adhesion molecule well known to be essential for skeletal muscle integrity and formation of neuromuscular synapses, is also present at inhibitory synapses in the central nervous system. Mutations that affect DG function not only result in muscular dystrophies, but also in severe cognitive deficits and epilepsy. Here we demonstrate a role of DG during activity-dependent homeostatic regulation of hippocampal inhibitory synapses. Prolonged elevation of neuronal activity up-regulates DG expression and glycosylation, and its localization to inhibitory synapses. Inhibition of protein synthesis prevents the activity-dependent increase in synaptic DG and GABAA receptors (GABAARs), as well as the homeostatic scaling up of GABAergic synaptic transmission. RNAi-mediated knockdown of DG blocks homeostatic scaling up of inhibitory synaptic strength, as does knockdown of like-acetylglucosaminyltransferase (LARGE)--a glycosyltransferase critical for DG function. In contrast, DG is not required for the bicuculline-induced scaling down of excitatory synaptic strength or the tetrodotoxin-induced scaling down of inhibitory synaptic strength. The DG ligand agrin increases GABAergic synaptic strength in a DG-dependent manner that mimics homeostatic scaling up induced by increased activity, indicating that activation of this pathway alone is sufficient to regulate GABAAR trafficking. These data demonstrate that DG is regulated in a physiologically relevant manner in neurons and that DG and its glycosylation are essential for homeostatic plasticity at inhibitory synapses.

  13. Cocaine addiction as a homeostatic reinforcement learning disorder.

    PubMed

    Keramati, Mehdi; Durand, Audrey; Girardeau, Paul; Gutkin, Boris; Ahmed, Serge H

    2017-03-01

    Drug addiction implicates both reward learning and homeostatic regulation mechanisms of the brain. This has stimulated 2 partially successful theoretical perspectives on addiction. Many important aspects of addiction, however, remain to be explained within a single, unified framework that integrates the 2 mechanisms. Building upon a recently developed homeostatic reinforcement learning theory, the authors focus on a key transition stage of addiction that is well modeled in animals, escalation of drug use, and propose a computational theory of cocaine addiction where cocaine reinforces behavior due to its rapid homeostatic corrective effect, whereas its chronic use induces slow and long-lasting changes in homeostatic setpoint. Simulations show that our new theory accounts for key behavioral and neurobiological features of addiction, most notably, escalation of cocaine use, drug-primed craving and relapse, individual differences underlying dose-response curves, and dopamine D2-receptor downregulation in addicts. The theory also generates unique predictions about cocaine self-administration behavior in rats that are confirmed by new experimental results. Viewing addiction as a homeostatic reinforcement learning disorder coherently explains many behavioral and neurobiological aspects of the transition to cocaine addiction, and suggests a new perspective toward understanding addiction. (PsycINFO Database Record

  14. Modeling the dynamic interaction of Hebbian and homeostatic plasticity

    PubMed Central

    Toyoizumi, Taro; Kaneko, Megumi; Stryker, Michael P.; Miller, Kenneth D.

    2014-01-01

    Summary Hebbian and homeostatic plasticity together refine neural circuitry, but their interactions are unclear. In most existing models, each form of plasticity directly modifies synaptic strength. Equilibrium is reached when the two are inducing equal and opposite changes. We show that such models cannot reproduce ocular dominance plasticity (ODP) because negative feedback from the slow homeostatic plasticity observed in ODP cannot stabilize the positive feedback of fast Hebbian plasticity. We propose a new model in which synaptic strength is the product of a synapse-specific Hebbian factor and a postsynaptic-cell-specific homeostatic factor, with each factor separately arriving at a stable inactive state. This model captures ODP dynamics and has plausible biophysical substrates. We experimentally confirm model predictions that plasticity is inactive at stable states and that synaptic strength overshoots during recovery from visual deprivation. These results highlight the importance of multiple regulatory pathways for interactions of plasticity mechanisms operating over separate timescales. PMID:25374364

  15. Original hypothesis: Extracorporeal shockwaves as a homeostatic autoimmune restorative treatment (HART) for Type 1 diabetes mellitus.

    PubMed

    Craig, Kenneth; d'Agostino, Cristina; Poratt, Daniel; Walker, Marjorie

    2014-09-01

    Mononuclear invasion of Langerhans islet and the ensuing insulitis triggers signal-transduction for the autoimmune mediated pancreatic beta-cell (β-cell) apoptosis that severely disrupts insulin production resulting in hyperglycemia associated with Type-1 diabetes (T1DM). Today extensive global research is being conducted to eliminate the need for insulin, and even prevent or find a cure for T1DM. The multifactorial combination of autoimmune dysfunction, Langerhans islet hypoxia, and bio-chemical disruption are seen to be contributory factors for β-cell destruction and the consequential disruption to insulin production. Regeneration of β-cells back to physiological levels may restore homeostatic insulin levels, reversing T1DM. Evidence suggests that there are still functioning pancreatic β-cells even in long standing T1DM providing the potential for their regeneration. Although the exact mechanism of extracorporeal shockwaves (ESW) is yet to be fully elucidated, it is seen to influence a complex spectrum of bio-chemical, cellular and neuronal functions (i.e. suppression of pro-inflammatory immune response, improved tissue hemodynamics, anti-microbial properties, and the induction of progenitor cell expression including proangiogenic factors and nitric oxide syntheses). The rationale for the use of ESW as a therapeutic modality in this instance is attributed to its restorative properties and safety profile demonstrated in urology, cardiology, chronic wounds, osteogenesis, complex pain syndromes, and tendinopathies. ESW may restore autoimmune homeostasis creating a suitable environment for pancreatic β-cell proliferation which in-turn may significantly increase or normalize endogenous insulin secretion reducing or totally eliminating dependency of exogenous insulin. The devastating complications, morbidity and mortality associated with T1DM warrants the exploration of homeostatic autoimmune restorative treatment (HART) modalities that may partially or fully

  16. Traditional Chinese medicine and the positive correlation with homeostatic evolution of human being: based on medical perspective.

    PubMed

    Wang, Jie-Hua

    2012-08-01

    Adaptation is an eternal theme of biological evolution. The paper aims at exploring the conception of positive correlation between traditional Chinese medicine (TCM) and human homeostatic evolution based on medical perspective. Discussions mainly involve TCM conforming to natural laws and natural evolution of life, spontaneous harmonization of yin and yang and operating system of human self-healing, modern human immunology and human endogenous immune function in TCM, self-homeostasis of human micro-ecological state and balance mechanism on regulating base in TCM, as well as adaptation-eternal theme of biological evolution and safeguarding adaptability-value of TCM. In perspective of medicine, theory and practice of TCM are in positive correlation with human homeostatic evolution, and what TCM tries to maintain is human intrinsic adaptive capability to disease and nature. Therefore, it is the core value of TCM, which is to be further studied, explored, realized and known to the world.

  17. Homeostatic plasticity: comparing and contrasting cortical and hippocampal studies. A review.

    PubMed

    Leininger, Eric; Belousov, Andrei B

    2006-01-01

    Homeostatic plasticity is an important physiological process in the mammalian nervous system. In this review, we discuss methodological and mechanistic similarities and differences in cortical and hippocampal studies of homeostatic plasticity. Although there are many similarities, there are also region-specific differences in the effects and/or mechanisms that regulate homeostatic plasticity in these two regions. In this review, we propose a new experimental paradigm to study homeostatic plasticity that may address some unanswered questions in the field.

  18. Experience-dependent homeostatic synaptic plasticity in neocortex

    PubMed Central

    Whitt, Jessica L.; Petrus, Emily; Lee, Hey-Kyoung

    2013-01-01

    The organism’s ability to adapt to the changing sensory environment is due in part to the ability of the nervous system to change with experience. Input and synapse specific Hebbian plasticity, such as long-term potentiation (LTP) and long-term depression (LTD), are critical for sculpting the nervous system to wire its circuit in tune with the environment and for storing memories. However, these synaptic plasticity mechanisms are innately unstable and require another mode of plasticity that maintains homeostasis to allow neurons to function within a desired dynamic range. Several modes of homeostatic adaptation are known, some of which work at the synaptic level. This review will focus on the known mechanisms of experience-induced homeostatic synaptic plasticity in the neocortex and their potential function in sensory cortex plasticity. PMID:23466332

  19. Homeostatic reinforcement learning for integrating reward collection and physiological stability.

    PubMed

    Keramati, Mehdi; Gutkin, Boris

    2014-12-02

    Efficient regulation of internal homeostasis and defending it against perturbations requires adaptive behavioral strategies. However, the computational principles mediating the interaction between homeostatic and associative learning processes remain undefined. Here we use a definition of primary rewards, as outcomes fulfilling physiological needs, to build a normative theory showing how learning motivated behaviors may be modulated by internal states. Within this framework, we mathematically prove that seeking rewards is equivalent to the fundamental objective of physiological stability, defining the notion of physiological rationality of behavior. We further suggest a formal basis for temporal discounting of rewards by showing that discounting motivates animals to follow the shortest path in the space of physiological variables toward the desired setpoint. We also explain how animals learn to act predictively to preclude prospective homeostatic challenges, and several other behavioral patterns. Finally, we suggest a computational role for interaction between hypothalamus and the brain reward system.

  20. Nascent Proteome Remodeling following Homeostatic Scaling at Hippocampal Synapses.

    PubMed

    Schanzenbächer, Christoph T; Sambandan, Sivakumar; Langer, Julian D; Schuman, Erin M

    2016-10-19

    Homeostatic scaling adjusts the strength of synaptic connections up or down in response to large changes in input. To identify the landscape of proteomic changes that contribute to opposing forms of homeostatic plasticity, we examined the plasticity-induced changes in the newly synthesized proteome. Cultured rat hippocampal neurons underwent homeostatic up-scaling or down-scaling. We used BONCAT (bio-orthogonal non-canonical amino acid tagging) to metabolically label, capture, and identify newly synthesized proteins, detecting and analyzing 5,940 newly synthesized proteins using mass spectrometry and label-free quantitation. Neither up- nor down-scaling produced changes in the number of different proteins translated. Rather, up- and down-scaling elicited opposing translational regulation of several molecular pathways, producing targeted adjustments in the proteome. We discovered ∼300 differentially regulated proteins involved in neurite outgrowth, axon guidance, filopodia assembly, excitatory synapses, and glutamate receptor complexes. We also identified differentially regulated proteins that are associated with multiple diseases, including schizophrenia, epilepsy, and Parkinson's disease.

  1. GRIP1 is required for homeostatic regulation of AMPAR trafficking

    PubMed Central

    Tan, Han L.; Queenan, Bridget N.; Huganir, Richard L.

    2015-01-01

    Homeostatic plasticity is a negative feedback mechanism that stabilizes neurons during periods of perturbed activity. The best-studied form of homeostatic plasticity in the central nervous system is the scaling of excitatory synapses. Postsynaptic AMPA-type glutamate receptors (AMPARs) can be inserted into synapses to compensate for neuronal inactivity or removed to compensate for hyperactivity. However, the molecular mechanisms underlying the homeostatic regulation of AMPARs remain elusive. Here, we show that the expression of GRIP1, a multi-PDZ (postsynaptic density 95/discs large/zona occludens) domain AMPAR-binding protein, is bidirectionally altered by neuronal activity. Furthermore, we observe a subcellular redistribution of GRIP1 and a change in the binding of GRIP1 to GluA2 during synaptic scaling. Using a combination of biochemical, genetic, and electrophysiological methods, we find that loss of GRIP1 blocks the accumulation of surface AMPARs and the scaling up of synaptic strength that occur in response to chronic activity blockade. Collectively, our data point to an essential role of GRIP1-mediated AMPAR trafficking during inactivity-induced synaptic scaling. PMID:26216979

  2. Modeling circadian and sleep-homeostatic effects on short-term interval timing

    PubMed Central

    Späti, Jakub; Aritake, Sayaka; Meyer, Andrea H.; Kitamura, Shingo; Hida, Akiko; Higuchi, Shigekazu; Moriguchi, Yoshiya; Mishima, Kazuo

    2015-01-01

    Short-term interval timing i.e., perception and action relating to durations in the seconds range, has been suggested to display time-of-day as well as wake dependent fluctuations due to circadian and sleep-homeostatic changes to the rate at which an underlying pacemaker emits pulses; pertinent human data being relatively sparse and lacking in consistency however, the phenomenon remains elusive and its mechanism poorly understood. To better characterize the putative circadian and sleep-homeostatic effects on interval timing and to assess the ability of a pacemaker-based mechanism to account for the data, we measured timing performance in eighteen young healthy male subjects across two epochs of sustained wakefulness of 38.67 h each, conducted prior to (under entrained conditions) and following (under free-running conditions) a 28 h sleep-wake schedule, using the methods of duration estimation and duration production on target intervals of 10 and 40 s. Our findings of opposing oscillatory time courses across both epochs of sustained wakefulness that combine with increasing and, respectively, decreasing, saturating exponential change for the tasks of estimation and production are consistent with the hypothesis that a pacemaker emitting pulses at a rate controlled by the circadian oscillator and increasing with time awake determines human short-term interval timing; the duration-specificity of this pattern is interpreted as reflecting challenges to maintaining stable attention to the task that progressively increase with stimulus magnitude and thereby moderate the effects of pacemaker-rate changes on overt behavior. PMID:25741253

  3. Intrinsic and synaptic homeostatic plasticity in motoneurons from mice with glycine receptor mutations

    PubMed Central

    Tadros, M. A.; Farrell, K. E.; Schofield, P. R.; Brichta, A. M.; Graham, B. A.; Fuglevand, A. J.

    2014-01-01

    Inhibitory synaptic inputs to hypoglossal motoneurons (HMs) are important for modulating excitability in brainstem circuits. Here we ask whether reduced inhibition, as occurs in three murine mutants with distinct naturally occurring mutations in the glycine receptor (GlyR), leads to intrinsic and/or synaptic homeostatic plasticity. Whole cell recordings were obtained from HMs in transverse brainstem slices from wild-type (wt), spasmodic (spd), spastic (spa), and oscillator (ot) mice (C57Bl/6, approximately postnatal day 21). Passive and action potential (AP) properties in spd and ot HMs were similar to wt. In contrast, spa HMs had lower input resistances, more depolarized resting membrane potentials, higher rheobase currents, smaller AP amplitudes, and slower afterhyperpolarization current decay times. The excitability of HMs, assessed by “gain” in injected current/firing-frequency plots, was similar in all strains whereas the incidence of rebound spiking was increased in spd. The difference between recruitment and derecruitment current (i.e., ΔI) for AP discharge during ramp current injection was more negative in spa and ot. GABAA miniature inhibitory postsynaptic current (mIPSC) amplitude was increased in spa and ot but not spd, suggesting diminished glycinergic drive leads to compensatory adjustments in the other major fast inhibitory synaptic transmitter system in these mutants. Overall, our data suggest long-term reduction in glycinergic drive to HMs results in changes in intrinsic and synaptic properties that are consistent with homeostatic plasticity in spa and ot but not in spd. We propose such plasticity is an attempt to stabilize HM output, which succeeds in spa but fails in ot. PMID:24401707

  4. Consensus Paper: Probing Homeostatic Plasticity of Human Cortex With Non-invasive Transcranial Brain Stimulation.

    PubMed

    Karabanov, Anke; Ziemann, Ulf; Hamada, Masashi; George, Mark S; Quartarone, Angelo; Classen, Joseph; Massimini, Marcello; Rothwell, John; Siebner, Hartwig Roman

    2015-01-01

    Homeostatic plasticity is thought to stabilize neural activity around a set point within a physiologically reasonable dynamic range. Over the last ten years, a wide range of non-invasive transcranial brain stimulation (NTBS) techniques have been used to probe homeostatic control of cortical plasticity in the intact human brain. Here, we review different NTBS approaches to study homeostatic plasticity on a systems level and relate the findings to both, physiological evidence from in vitro studies and to a theoretical framework of homeostatic function. We highlight differences between homeostatic and other non-homeostatic forms of plasticity and we examine the contribution of sleep in restoring synaptic homeostasis. Finally, we discuss the growing number of studies showing that abnormal homeostatic plasticity may be associated to a range of neuropsychiatric diseases.

  5. Neuronal plasticity and thalamocortical sleep and waking oscillations.

    PubMed

    Timofeev, Igor

    2011-01-01

    Throughout life, thalamocortical (TC) network alternates between activated states (wake or rapid eye movement sleep) and slow oscillatory state dominating slow-wave sleep. The patterns of neuronal firing are different during these distinct states. I propose that due to relatively regular firing, the activated states preset some steady state synaptic plasticity and that the silent periods of slow-wave sleep contribute to a release from this steady state synaptic plasticity. In this respect, I discuss how states of vigilance affect short-, mid-, and long-term synaptic plasticity, intrinsic neuronal plasticity, as well as homeostatic plasticity. Finally, I suggest that slow oscillation is intrinsic property of cortical network and brain homeostatic mechanisms are tuned to use all forms of plasticity to bring cortical network to the state of slow oscillation. However, prolonged and profound shift from this homeostatic balance could lead to development of paroxysmal hyperexcitability and seizures as in the case of brain trauma.

  6. Neuronal plasticity and thalamocortical sleep and waking oscillations

    PubMed Central

    Timofeev, Igor

    2011-01-01

    Throughout life, thalamocortical (TC) network alternates between activated states (wake or rapid eye movement sleep) and slow oscillatory state dominating slow-wave sleep. The patterns of neuronal firing are different during these distinct states. I propose that due to relatively regular firing, the activated states preset some steady state synaptic plasticity and that the silent periods of slow-wave sleep contribute to a release from this steady state synaptic plasticity. In this respect, I discuss how states of vigilance affect short-, mid-, and long-term synaptic plasticity, intrinsic neuronal plasticity, as well as homeostatic plasticity. Finally, I suggest that slow oscillation is intrinsic property of cortical network and brain homeostatic mechanisms are tuned to use all forms of plasticity to bring cortical network to the state of slow oscillation. However, prolonged and profound shift from this homeostatic balance could lead to development of paroxysmal hyperexcitability and seizures as in the case of brain trauma. PMID:21854960

  7. Homeostatic regulation of memory systems and adaptive decisions.

    PubMed

    Mizumori, Sheri J Y; Jo, Yong Sang

    2013-11-01

    While it is clear that many brain areas process mnemonic information, understanding how their interactions result in continuously adaptive behaviors has been a challenge. A homeostatic-regulated prediction model of memory is presented that considers the existence of a single memory system that is based on a multilevel coordinated and integrated network (from cells to neural systems) that determines the extent to which events and outcomes occur as predicted. The "multiple memory systems of the brain" have in common output that signals errors in the prediction of events and/or their outcomes, although these signals differ in terms of what the error signal represents (e.g., hippocampus: context prediction errors vs. midbrain/striatum: reward prediction errors). The prefrontal cortex likely plays a pivotal role in the coordination of prediction analysis within and across prediction brain areas. By virtue of its widespread control and influence, and intrinsic working memory mechanisms. Thus, the prefrontal cortex supports the flexible processing needed to generate adaptive behaviors and predict future outcomes. It is proposed that prefrontal cortex continually and automatically produces adaptive responses according to homeostatic regulatory principles: prefrontal cortex may serve as a controller that is intrinsically driven to maintain in prediction areas an experience-dependent firing rate set point that ensures adaptive temporally and spatially resolved neural responses to future prediction errors. This same drive by prefrontal cortex may also restore set point firing rates after deviations (i.e. prediction errors) are detected. In this way, prefrontal cortex contributes to reducing uncertainty in prediction systems. An emergent outcome of this homeostatic view may be the flexible and adaptive control that prefrontal cortex is known to implement (i.e. working memory) in the most challenging of situations. Compromise to any of the prediction circuits should result in

  8. Homeostatic Regulation of Memory Systems and Adaptive Decisions

    PubMed Central

    Mizumori, Sheri JY; Jo, Yong Sang

    2013-01-01

    While it is clear that many brain areas process mnemonic information, understanding how their interactions result in continuously adaptive behaviors has been a challenge. A homeostatic-regulated prediction model of memory is presented that considers the existence of a single memory system that is based on a multilevel coordinated and integrated network (from cells to neural systems) that determines the extent to which events and outcomes occur as predicted. The “multiple memory systems of the brain” have in common output that signals errors in the prediction of events and/or their outcomes, although these signals differ in terms of what the error signal represents (e.g., hippocampus: context prediction errors vs. midbrain/striatum: reward prediction errors). The prefrontal cortex likely plays a pivotal role in the coordination of prediction analysis within and across prediction brain areas. By virtue of its widespread control and influence, and intrinsic working memory mechanisms. Thus, the prefrontal cortex supports the flexible processing needed to generate adaptive behaviors and predict future outcomes. It is proposed that prefrontal cortex continually and automatically produces adaptive responses according to homeostatic regulatory principles: prefrontal cortex may serve as a controller that is intrinsically driven to maintain in prediction areas an experience-dependent firing rate set point that ensures adaptive temporally and spatially resolved neural responses to future prediction errors. This same drive by prefrontal cortex may also restore set point firing rates after deviations (i.e. prediction errors) are detected. In this way, prefrontal cortex contributes to reducing uncertainty in prediction systems. An emergent outcome of this homeostatic view may be the flexible and adaptive control that prefrontal cortex is known to implement (i.e. working memory) in the most challenging of situations. Compromise to any of the prediction circuits should result

  9. Adolescent Changes in the Homeostatic and Circadian Regulation of Sleep

    PubMed Central

    Hagenauer, M.H.; Perryman, J.I.; Lee, T.M.; Carskadon, M.A.

    2009-01-01

    Sleep deprivation among adolescents is epidemic. We argue that this sleep deprivation is due in part to pubertal changes in the homeostatic and circadian regulation of sleep. These changes promote a delayed sleep phase that is exacerbated by evening light exposure and incompatible with aspects of modern society, notably early school start times. In this review of human and animal literature, we demonstrate that delayed sleep phase during puberty is likely a common phenomenon in mammals, not specific to human adolescents, and we provide insight into the mechanisms underlying this phenomenon. PMID:19546564

  10. Homeostatic control: the utility/customer marketplace for electric power

    SciTech Connect

    Schweppe, F.C.; Tabors, R.D.; Kirtley, J.L.

    1981-09-01

    A load management system is proposed in which the electric utility customer controls his on-site power demand to coincide with the lowest possible cost of power generation. Called Homeostatic Control, this method is founded on feedback between the customer and the utility and on customer independence. The utility has no control beyond the customer's meter. Computers located at the customer's site are continuously fed data on weather conditions, utility generating costs, and demand requirements for space conditioning, lighting, and appliances. The customer then directs the computer to schedule and control the power allotted for these functions. On-site generation by the customer can be incorporated in the system. It is argued that homeostatic control is technically feasible, that the level of control equipment sophistication can be adapted to the benefits received by the customer, that such a system would encourage the use of customer-site energy storage and energy conservation equipment, and that it represents a realistic method for allowing the customer to decide how he will use electric power during an era of increasing costs for power generation. (LCL)

  11. Thirst neurons anticipate the homeostatic consequences of eating and drinking

    PubMed Central

    Zimmerman, Christopher A.; Lin, Yen-Chu; Leib, David E.; Guo, Ling; Huey, Erica L.; Daly, Gwendolyn E.; Chen, Yiming; Knight, Zachary A.

    2016-01-01

    Thirst motivates animals to drink in order to maintain fluid balance. Traditionally, thirst has been viewed as a homeostatic response to changes in the blood volume or tonicity1–3. However, most drinking behavior is regulated too rapidly to be controlled by blood composition directly and instead appears to anticipate homeostatic imbalances before they arise4–11. How this is achieved remains unknown. Here we reveal an unexpected role for the subfornical organ (SFO) in the anticipatory regulation of thirst. We show by monitoring deep-brain calcium dynamics that thirst-promoting SFO neurons respond to inputs from the oral cavity during eating and drinking, which they then integrate with information about the composition of the blood. This integration allows SFO neurons to predict how ongoing food and water consumption will alter fluid balance in the future and then adjust behavior preemptively. Complementary optogenetic manipulations show that this anticipatory modulation is necessary for drinking in multiple contexts. These findings provide a neural mechanism to explain longstanding behavioral observations, including the prevalence of drinking during meals10,11, the rapid satiation of thirst7–9, and the fact that oral cooling is thirst-quenching12–14. PMID:27487211

  12. Homeostatic responses to palatable food consumption in satiated rats

    PubMed Central

    Hume, Catherine; Jachs, Barbara

    2016-01-01

    Objective Energy intake is regulated by overlapping homeostatic and hedonic systems. Consumption of palatable foods has been implicated in weight gain, but this assumes that homeostatic control systems do not accurately detect this hedonically driven energy intake. This study tested this assumption, hypothesizing that satiated rats would reduce their voluntary food intake and maintain a stable body weight after consuming a palatable food. Methods Lean rats or rats previously exposed to an obesogenic diet were schedule‐fed with fixed or varying amounts of palatable sweetened condensed milk (SCM) daily, and their voluntary energy intake and body weight were monitored. Results During scheduled feeding of SCM, rats voluntarily reduced bland food consumption and maintained a stable body weight. This behavior was also seen in rats with access to an obesogenic diet and was independent of the predictability of SCM access. However, lean rats offered large amounts of SCM showed an increase in total energy intake. To test whether a nutrient deficiency drove this under‐compensatory behavior, SCM was enriched with protein. However, no effect was seen on voluntary energy intake. Conclusions In schedule‐fed rats, compensatory reductions in voluntary energy intake were seen, but under‐compensation was observed if large amounts of SCM were consumed. PMID:27543760

  13. Systems analysis of bone remodelling as a homeostatic regulator.

    PubMed

    Chen, A; Hamamura, K; Zhang, P; Chen, Y; Yokota, H

    2010-01-01

    Bone remodelling in adult skeleton is a process of maintaining bone mass through combined activities of bone forming osteoblasts and bone resorbing osteoclasts. Focusing on a molecular pathway mediated by osteoprotegerin, the authors derived a mathematical formulation for molecular interactions and cellular behaviours. The authors also treated this remodelling process as a homeostatic regulator in a framework of linear quadratic problems. A primary question was: does a solution of a matrix Riccati equation provide a guideline for therapeutic interventions for prevention of bone loss? In order to elucidate the systems dynamics, the authors analysed the perturbed set of equations around a stable equilibrium state together with the original equations. The results demonstrate that a homeostatic regulator with the selected control variables effectively reduces bone degradation activities and restore a physiological remodelling process. To partially validate efficacy of the described intervention strategy, biological experiments were conducted with an osteoblast cell line using one of the control variables, salubrinal (chemical agent). The authors observed that administration of salubrinal activated mRNA levels of transcription factors and an osteogenic marker gene as well as enhancement of mineralisation. Taken together, the current study supports a potential usage of control theories in active regulation of bone remodelling homeostasis.

  14. Homeostatic Imbalance in Epithelial Ducts and Its Role in Carcinogenesis

    PubMed Central

    Rejniak, Katarzyna A.

    2012-01-01

    An epithelial duct is a well-defined multicellular structure composed of tightly packed cells separating and protecting body compartments that are used for enzyme secretion and its transport across the internal. The structural and functional integrity (homeostasis) of such ducts is vital in carrying many life functions (breathing, lactation, production of hormones). However, the processes involved in maintaining the homeostatic balance are not yet fully understood. On the other hand, the loss of epithelial tissue architecture, such as filled lumens or ductal disorganization, are among the first symptoms of the emerging epithelial tumors (carcinomas). Using the previously developed biomechanical model of epithelial ducts: IBCell, we investigated how different signals and mechanical stimuli imposed on individual epithelial cells can impact the homeostatic (im)balance and integrity of the whole epithelial tissue. We provide a link between erroneous responses of individual epithelial cells to specific signals and the emerging ductal morphologies characteristic for preinvasive cancers observed in pathology specimens, or characteristic for multicellular structures arising from mutated cells cultured in vitro. We summarize our finding in terms of altered properties of epithelial cell polarization, and discuss the relative importance of various polarization signals on the formation of tumor-like multicellular structures. PMID:24278670

  15. Reinforcement processes in opiate addiction: a homeostatic model.

    PubMed

    Schulteis, G; Koob, G F

    1996-11-01

    The development of tolerance and dependence has traditionally been considered an integral aspect of the drug addiction process, and opiate dependence has been studied extensively as a model system in this regard. However, recent emphasis on the positive reinforcing properties of drugs has led to the suggestion that tolerance, dependence, and withdrawal may be of secondary or even negligible importance in motivating compulsive drug use. The current article argues for an integrated view of addiction in the form of a homeostatic neuroadaptation model which emphasizes the motivational significance of both the positive affective state produced by opiates and the negative affective state characteristic of drug withdrawal. The model is supported by evidence at both the behavioral and neural systems levels of analysis. Understanding the important distinction between somatic and affective components of opiate withdrawal is key to recognizing the factors which contribute to the motivational significance of opiate dependence and withdrawal. In addition, the critical role of conditioning processes in the maintenance of compulsive drug use and relapse after periods of abstention is discussed. Finally, it is argued that both the positive reinforcement produced by acute administration of a drug and the negative affective state produced by withdrawal are common to multiple classes of abused drugs, suggesting that an understanding of homeostatic neuroadaptation within motivational systems provides a key to the etiology, treatment and prevention of drug addiction.

  16. Homeostatic reinforcement learning for integrating reward collection and physiological stability

    PubMed Central

    Keramati, Mehdi; Gutkin, Boris

    2014-01-01

    Efficient regulation of internal homeostasis and defending it against perturbations requires adaptive behavioral strategies. However, the computational principles mediating the interaction between homeostatic and associative learning processes remain undefined. Here we use a definition of primary rewards, as outcomes fulfilling physiological needs, to build a normative theory showing how learning motivated behaviors may be modulated by internal states. Within this framework, we mathematically prove that seeking rewards is equivalent to the fundamental objective of physiological stability, defining the notion of physiological rationality of behavior. We further suggest a formal basis for temporal discounting of rewards by showing that discounting motivates animals to follow the shortest path in the space of physiological variables toward the desired setpoint. We also explain how animals learn to act predictively to preclude prospective homeostatic challenges, and several other behavioral patterns. Finally, we suggest a computational role for interaction between hypothalamus and the brain reward system. DOI: http://dx.doi.org/10.7554/eLife.04811.001 PMID:25457346

  17. Parallel, redundant circuit organization for homeostatic control of feeding behavior.

    PubMed

    Betley, J Nicholas; Cao, Zhen Fang Huang; Ritola, Kimberly D; Sternson, Scott M

    2013-12-05

    Neural circuits for essential natural behaviors are shaped by selective pressure to coordinate reliable execution of flexible goal-directed actions. However, the structural and functional organization of survival-oriented circuits is poorly understood due to exceptionally complex neuroanatomy. This is exemplified by AGRP neurons, which are a molecularly defined population that is sufficient to rapidly coordinate voracious food seeking and consumption behaviors. Here, we use cell-type-specific techniques for neural circuit manipulation and projection-specific anatomical analysis to examine the organization of this critical homeostatic circuit that regulates feeding. We show that AGRP neuronal circuits use a segregated, parallel, and redundant output configuration. AGRP neuron axon projections that target different brain regions originate from distinct subpopulations, several of which are sufficient to independently evoke feeding. The concerted anatomical and functional analysis of AGRP neuron projection populations reveals a constellation of core forebrain nodes, which are part of an extended circuit that mediates feeding behavior.

  18. Brain glucose sensing in homeostatic and hedonic regulation.

    PubMed

    Steinbusch, Laura; Labouèbe, Gwenaël; Thorens, Bernard

    2015-09-01

    Glucose homeostasis as well as homeostatic and hedonic control of feeding is regulated by hormonal, neuronal, and nutrient-related cues. Glucose, besides its role as a source of metabolic energy, is an important signal controlling hormone secretion and neuronal activity, hence contributing to whole-body metabolic integration in coordination with feeding control. Brain glucose sensing plays a key, but insufficiently explored, role in these metabolic and behavioral controls, which when deregulated may contribute to the development of obesity and diabetes. The recent introduction of innovative transgenic, pharmacogenetic, and optogenetic techniques allows unprecedented analysis of the complexity of central glucose sensing at the molecular, cellular, and neuronal circuit levels, which will lead to a new understanding of the pathogenesis of metabolic diseases.

  19. A quantitative description of equilibrium and homeostatic thickness regulation in the in vivo cornea. II. Variations from the normal state.

    PubMed

    Friedman, M H

    1972-06-01

    The description of corneal mechanics and transport developed in part I and used there to describe normal corneal behavior is here applied to corneas whose properties or boundary conditions are abnormal. The predicted effects of changing intraocular pressure, aqueous concentration, and tear tonicity are examined, and these compare favorably with available experimental data. The periodic variation in tear tonicity which accompanies the sleep-wake cycle prevents the cornea from achieving a true steady state, but a time-average steady state, about which corneal behavior oscillates, can be defined. The in vivo effects of endothelial dystrophy and epithelial removal are explained, and it is suggested that the epithelial sodium pump may act homeostatically to maintain corneal thickness in the face of ambient temperature variations. Part II concludes with a discussion, from the standpoint of the present theory, of the role of metabolically coupled water transport in the maintenance of the normal corneal thickness.

  20. Neurovestibular modulation of circadian and homeostatic regulation: vestibulohypothalamic connection?

    NASA Technical Reports Server (NTRS)

    Fuller, Patrick M.; Jones, Timothy A.; Jones, Sherri M.; Fuller, Charles A.

    2002-01-01

    Chronic exposure to increased force environments (+G) has pronounced effects on the circadian and homeostatic regulation of body temperature (T(b)), ambulatory activity (Act), heart rate, feeding, and adiposity. By using the Brn 3.1 knockout mouse, which lacks vestibular hair cells, we recently described a major role of the vestibular system in mediating some of these adaptive responses. The present study used the C57BL6JEi-het mouse strain (het), which lacks macular otoconia, to elucidate the contribution of specific vestibular receptors. In this study, eight het and eight WT mice were exposed to 2G for 8 weeks by means of chronic centrifugation. In addition, eight het and eight WT mice were maintained as 1G controls in similar conditions. Upon 2G exposure, the WT exhibited a decrease in T(b) and an attenuated T(b) circadian rhythm. Act means and rhythms also were attenuated. Body mass and food intake were significantly lower than the 1G controls. After 8 weeks, percent body fat was significantly lower in the WT mice (P < 0.0001). In contrast, the het mice did not exhibit a decrease in mean T(b) and only a slight decrease in T(b) circadian amplitude. het Act levels were attenuated similarly to the WT mice. Body mass and food intake were only slightly attenuated in the het mice, and percent body fat, after 8 weeks, was not different in the 2G het group. These results link the vestibular macular receptors with specific alterations in homeostatic and circadian regulation.

  1. Homeostatic Scaling of Excitability in Recurrent Neural Networks

    PubMed Central

    Remme, Michiel W. H.; Wadman, Wytse J.

    2012-01-01

    Neurons adjust their intrinsic excitability when experiencing a persistent change in synaptic drive. This process can prevent neural activity from moving into either a quiescent state or a saturated state in the face of ongoing plasticity, and is thought to promote stability of the network in which neurons reside. However, most neurons are embedded in recurrent networks, which require a delicate balance between excitation and inhibition to maintain network stability. This balance could be disrupted when neurons independently adjust their intrinsic excitability. Here, we study the functioning of activity-dependent homeostatic scaling of intrinsic excitability (HSE) in a recurrent neural network. Using both simulations of a recurrent network consisting of excitatory and inhibitory neurons that implement HSE, and a mean-field description of adapting excitatory and inhibitory populations, we show that the stability of such adapting networks critically depends on the relationship between the adaptation time scales of both neuron populations. In a stable adapting network, HSE can keep all neurons functioning within their dynamic range, while the network is undergoing several (patho)physiologically relevant types of plasticity, such as persistent changes in external drive, changes in connection strengths, or the loss of inhibitory cells from the network. However, HSE cannot prevent the unstable network dynamics that result when, due to such plasticity, recurrent excitation in the network becomes too strong compared to feedback inhibition. This suggests that keeping a neural network in a stable and functional state requires the coordination of distinct homeostatic mechanisms that operate not only by adjusting neural excitability, but also by controlling network connectivity. PMID:22570604

  2. The Contribution of Job and Partner Satisfaction to the Homeostatic Defense of Subjective Wellbeing

    ERIC Educational Resources Information Center

    Lai, Lufanna C. H.; Cummins, Robert A.

    2013-01-01

    Two studies investigate subjective wellbeing (SWB) homeostasis. The first investigates the contribution of job satisfaction (JS) and partner satisfaction (PS) to the homeostatic defense of SWB. The extant model of homeostasis does not include either variable. The second study investigates the relationship between Homeostatically Protected Mood…

  3. Homeostatic synaptic plasticity in developing spinal networks driven by excitatory GABAergic currents

    PubMed Central

    Wenner, Peter

    2013-01-01

    Homeostatic plasticity refers to mechanisms that the cell or network engage in order to homeostatically maintain a preset level of activity. These mechanisms include compensatory changes in cellular excitability, excitatory and inhibitory synaptic strength and are typically studied at a developmental stage when GABA or glycine are inhibitory. Here we focus on the expression of homeostatic plasticity in the chick embryo spinal cord at a stage when GABA is excitatory. When spinal activity is perturbed in the living embryo there are compensatory changes in postsynaptic AMPA receptors and in the driving force for GABAergic currents. These changes are triggered by reduced GABAA receptor signaling, which appears to be part of the sensing machinery for triggering homeostatic plasticity. We compare and contrast these findings to homeostatic plasticity expressed in spinal systems at different stages of development, and to the developing retina at a stage when GABA is depolarizing. PMID:23727439

  4. STAT1 Regulates the Homeostatic Component of Visual Cortical Plasticity via an AMPA Receptor-Mediated Mechanism

    PubMed Central

    Van Wart, Audra; Petravicz, Jeremy; Tropea, Daniela

    2014-01-01

    Accumulating evidence points to a role for Janus kinase/signal transducers and activators of transcription (STAT) immune signaling in neuronal function; however, its role in experience-dependent plasticity is unknown. Here we show that one of its components, STAT1, negatively regulates the homeostatic component of ocular dominance plasticity in visual cortex. After brief monocular deprivation (MD), STAT1 knock-out (KO) mice show an accelerated increase of open-eye responses, to a level comparable with open-eye responses after a longer duration of MD in wild-type (WT) mice. Therefore, this component of plasticity is abnormally enhanced in KO mice. Conversely, increasing STAT1 signaling by IFNγ treatment in WT mice reduces the homeostatic component of plasticity by impairing open-eye responses. Enhanced plasticity in KO mice is accompanied by sustained surface levels of GluA1 AMPA receptors and increased amplitude and frequency of AMPA receptor-mediated mEPSCs, which resemble changes in WT mice after a longer duration of MD. These results demonstrate a unique role for STAT1 during visual cortical plasticity in vivo through a mechanism that includes AMPA receptors. PMID:25080587

  5. An intestinal microRNA modulates the homeostatic adaptation to chronic oxidative stress in C. elegans

    PubMed Central

    Kato, Masaomi; Kashem, Mohammed Abul; Cheng, Chao

    2016-01-01

    Adaptation to an environmental or metabolic perturbation is a feature of the evolutionary process. Recent insights into microRNA function suggest that microRNAs serve as key players in a robust adaptive response against stress in animals through their capacity to fine-tune gene expression. However, it remains largely unclear how a microRNA-modulated downstream mechanism contributes to the process of homeostatic adaptation. Here we show that loss of an intestinally expressed microRNA gene, mir-60, in the nematode C. elegans promotes an adaptive response to chronic – a mild and long-term – oxidative stress exposure. The pathway involved appears to be unique since the canonical stress-responsive factors, such as DAF-16/FOXO, are dispensable for mir-60 loss to enhance oxidative stress resistance. Gene expression profiles revealed that genes encoding lysosomal proteases and those involved in xenobiotic metabolism and pathogen defense responses are up-regulated by the loss of mir-60. Detailed genetic studies and computational microRNA target prediction suggest that endocytosis components and a bZip transcription factor gene zip-10, which functions in innate immune response, are directly modulated by miR-60 in the intestine. Our findings suggest that the mir-60 loss facilitates adaptive response against chronic oxidative stress by ensuring the maintenance of cellular homeostasis. PMID:27623524

  6. Macrophage pattern recognition receptors in immunity, homeostasis and self tolerance.

    PubMed

    Mukhopadhyay, Subhankar; Plüddemann, Annette; Gordon, Siamon

    2009-01-01

    Macrophages, a major component of innate immune defence, express a large repertoire of different classes of pattern recognition receptors and other surface antigens which determine the immunologic and homeostatic potential of these versatile cells. In the light of present knowledge ofmacrophage surface antigens, we discuss self versus nonself recognition, microbicidal effector functions and self tolerance in the innate immune system.

  7. The Dendritic Cell Response to Classic, Emerging, and Homeostatic Danger Signals. Implications for Autoimmunity

    PubMed Central

    Gallo, Paul M.; Gallucci, Stefania

    2013-01-01

    Dendritic cells (DCs) initiate and control immune responses, participate in the maintenance of immunological tolerance and are pivotal players in the pathogenesis of autoimmunity. In patients with autoimmune disease and in experimental animal models of autoimmunity, DCs show abnormalities in both numbers and activation state, expressing immunogenic levels of costimulatory molecules and pro-inflammatory cytokines. Exogenous and endogenous danger signals activate DCs to stimulate the immune response. Classic endogenous danger signals are released, activated, or secreted by host cells and tissues experiencing stress, damage, and non-physiologic cell death; and are therefore referred to as damage-associated molecular patterns (DAMPs). Some DAMPs are released from cells, where they are normally sequestered, during necrosis (e.g., heat shock proteins, uric acid, ATP, HMGB1, mitochondria-derived molecules). Others are actively secreted, like Type I Interferons. Here we discuss important DAMPs in the context of autoimmunity. For some, there is a clear pathogenic link (e.g., nucleic acids and lupus). For others, there is less evidence. Additionally, we explore emerging danger signals. These include inorganic materials and man-made technologies (e.g., nanomaterials) developed as novel therapeutic approaches. Some nanomaterials can activate DCs and may trigger unintended inflammatory responses. Finally, we will review “homeostatic danger signals,” danger signals that do not derive directly from pathogens or dying cells but are associated with perturbations of tissue/cell homeostasis and may signal pathological stress. These signals, like acidosis, hypoxia, and changes in osmolarity, also play a role in inflammation and autoimmunity. PMID:23772226

  8. Homeostatic mechanisms in dopamine synthesis and release: a mathematical model

    PubMed Central

    Best, Janet A; Nijhout, H Frederik; Reed, Michael C

    2009-01-01

    Background Dopamine is a catecholamine that is used as a neurotransmitter both in the periphery and in the central nervous system. Dysfunction in various dopaminergic systems is known to be associated with various disorders, including schizophrenia, Parkinson's disease, and Tourette's syndrome. Furthermore, microdialysis studies have shown that addictive drugs increase extracellular dopamine and brain imaging has shown a correlation between euphoria and psycho-stimulant-induced increases in extracellular dopamine [1]. These consequences of dopamine dysfunction indicate the importance of maintaining dopamine functionality through homeostatic mechanisms that have been attributed to the delicate balance between synthesis, storage, release, metabolism, and reuptake. Methods We construct a mathematical model of dopamine synthesis, release, and reuptake and use it to study homeostasis in single dopaminergic neuron terminals. We investigate the substrate inhibition of tyrosine hydroxylase by tyrosine, the consequences of the rapid uptake of extracellular dopamine by the dopamine transporters, and the effects of the autoreceoptors on dopaminergic function. The main focus is to understand the regulation and control of synthesis and release and to explicate and interpret experimental findings. Results We show that the substrate inhibition of tyrosine hydroxylase by tyrosine stabilizes cytosolic and vesicular dopamine against changes in tyrosine availability due to meals. We find that the autoreceptors dampen the fluctuations in extracellular dopamine caused by changes in tyrosine hydroxylase expression and changes in the rate of firing. We show that short bursts of action potentials create significant dopamine signals against the background of tonic firing. We explain the observed time courses of extracellular dopamine responses to stimulation in wild type mice and mice that have genetically altered dopamine transporter densities and the observed half-lives of extracellular

  9. Homeostatic plasticity for single node delay-coupled reservoir computing.

    PubMed

    Toutounji, Hazem; Schumacher, Johannes; Pipa, Gordon

    2015-06-01

    Supplementing a differential equation with delays results in an infinite-dimensional dynamical system. This property provides the basis for a reservoir computing architecture, where the recurrent neural network is replaced by a single nonlinear node, delay-coupled to itself. Instead of the spatial topology of a network, subunits in the delay-coupled reservoir are multiplexed in time along one delay span of the system. The computational power of the reservoir is contingent on this temporal multiplexing. Here, we learn optimal temporal multiplexing by means of a biologically inspired homeostatic plasticity mechanism. Plasticity acts locally and changes the distances between the subunits along the delay, depending on how responsive these subunits are to the input. After analytically deriving the learning mechanism, we illustrate its role in improving the reservoir's computational power. To this end, we investigate, first, the increase of the reservoir's memory capacity. Second, we predict a NARMA-10 time series, showing that plasticity reduces the normalized root-mean-square error by more than 20%. Third, we discuss plasticity's influence on the reservoir's input-information capacity, the coupling strength between subunits, and the distribution of the readout coefficients.

  10. Emerging Link between Alzheimer's Disease and Homeostatic Synaptic Plasticity

    PubMed Central

    Jang, Sung-Soo; Chung, Hee Jung

    2016-01-01

    Alzheimer's disease (AD) is an irreversible brain disorder characterized by progressive cognitive decline and neurodegeneration of brain regions that are crucial for learning and memory. Although intracellular neurofibrillary tangles and extracellular senile plaques, composed of insoluble amyloid-β (Aβ) peptides, have been the hallmarks of postmortem AD brains, memory impairment in early AD correlates better with pathological accumulation of soluble Aβ oligomers and persistent weakening of excitatory synaptic strength, which is demonstrated by inhibition of long-term potentiation, enhancement of long-term depression, and loss of synapses. However, current, approved interventions aiming to reduce Aβ levels have failed to retard disease progression; this has led to a pressing need to identify and target alternative pathogenic mechanisms of AD. Recently, it has been suggested that the disruption of Hebbian synaptic plasticity in AD is due to aberrant metaplasticity, which is a form of homeostatic plasticity that tunes the magnitude and direction of future synaptic plasticity based on previous neuronal or synaptic activity. This review examines emerging evidence for aberrant metaplasticity in AD. Putative mechanisms underlying aberrant metaplasticity in AD will also be discussed. We hope this review inspires future studies to test the extent to which these mechanisms contribute to the etiology of AD and offer therapeutic targets. PMID:27019755

  11. The human fetal placenta promotes tolerance against the semiallogeneic fetus by inducing regulatory T cells and homeostatic M2 macrophages.

    PubMed

    Svensson-Arvelund, Judit; Mehta, Ratnesh B; Lindau, Robert; Mirrasekhian, Elahe; Rodriguez-Martinez, Heriberto; Berg, Göran; Lash, Gendie E; Jenmalm, Maria C; Ernerudh, Jan

    2015-02-15

    A successful pregnancy requires that the maternal immune system is instructed to a state of tolerance to avoid rejection of the semiallogeneic fetal-placental unit. Although increasing evidence supports that decidual (uterine) macrophages and regulatory T cells (Tregs) are key regulators of fetal tolerance, it is not known how these tolerogenic leukocytes are induced. In this article, we show that the human fetal placenta itself, mainly through trophoblast cells, is able to induce homeostatic M2 macrophages and Tregs. Placental-derived M-CSF and IL-10 induced macrophages that shared the CD14(+)CD163(+)CD206(+)CD209(+) phenotype of decidual macrophages and produced IL-10 and CCL18 but not IL-12 or IL-23. Placental tissue also induced the expansion of CD25(high)CD127(low)Foxp3(+) Tregs in parallel with increased IL-10 production, whereas production of IFN-γ (Th1), IL-13 (Th2), and IL-17 (Th17) was not induced. Tregs expressed the suppressive markers CTLA-4 and CD39, were functionally suppressive, and were induced, in part, by IL-10, TGF-β, and TRAIL. Placental-derived factors also limited excessive Th cell activation, as shown by decreased HLA-DR expression and reduced secretion of Th1-, Th2-, and Th17-associated cytokines. Thus, our data indicate that the fetal placenta has a central role in promoting the homeostatic environment necessary for successful pregnancy. These findings have implications for immune-mediated pregnancy complications, as well as for our general understanding of tissue-induced tolerance.

  12. Cells, cancer, and rare events: Homeostatic metastability in stochastic nonlinear dynamical models of skin cell proliferation

    NASA Astrophysics Data System (ADS)

    Warren, Patrick B.

    2009-09-01

    A recently proposed model for skin cell proliferation [E. Clayton , Nature (London) 446, 185 (2007)] is extended to incorporate mitotic autoregulation, and hence homeostasis as a fixed point of the dynamics. Unlimited cell proliferation in such a model can be viewed as a model for carcinogenesis. One way in which this can arise is homeostatic metastability, in which the cell populations escape from the homeostatic basin of attraction by a large but rare stochastic fluctuation. Such an event can be viewed as the final step in a multistage model of carcinogenesis. Homeostatic metastability offers a possible explanation for the peculiar epidemiology of lung cancer in ex-smokers.

  13. Neurodynamic oscillators

    NASA Technical Reports Server (NTRS)

    Espinosa, Ismael; Gonzalez, Hortensia; Quiza, Jorge; Gonazalez, J. Jesus; Arroyo, Ruben; Lara, Ritaluz

    1995-01-01

    Oscillation of electrical activity has been found in many nervous systems, from invertebrates to vertebrates including man. There exists experimental evidence of very simple circuits with the capability of oscillation. Neurons with intrinsic oscillation have been found and also neural circuits where oscillation is a property of the network. These two types of oscillations coexist in many instances. It is nowadays hypothesized that behind synchronization and oscillation there is a system of coupled oscillators responsible for activities that range from locomotion and feature binding in vision to control of sleep and circadian rhythms. The huge knowledge that has been acquired on oscillators from the times of Lord Rayleigh has made the simulation of neural oscillators a very active endeavor. This has been enhanced with more recent physiological findings about small neural circuits by means of intracellular and extracellular recordings as well as imaging methods. The future of this interdisciplinary field looks very promising; some researchers are going into quantum mechanics with the idea of trying to provide a quantum description of the brain. In this work we describe some simulations using neuron models by means of which we form simple neural networks that have the capability of oscillation. We analyze the oscillatory activity with root locus method, cross-correlation histograms, and phase planes. In the more complicated neural network models there is the possibility of chaotic oscillatory activity and we study that by means of Lyapunov exponents. The companion paper shows an example of that kind.

  14. Immunosuppressive monocytes: possible homeostatic mechanism to restrain chronic intestinal inflammation

    PubMed Central

    Kurmaeva, Elvira; Bhattacharya, Dhruva; Goodman, Wendy; Omenetti, Sara; Merendino, Amber; Berney, Seth; Pizarro, Theresa; Ostanin, Dmitry V.

    2014-01-01

    Chronic colitis is accompanied by extensive myelopoiesis and accumulation of CD11b+Gr-1+ cells in spleens and secondary lymphoid tissues. Although cells with similar phenotype have been described in cancer, chronic infection, or autoimmunity, where they were associated with suppression of T cell responses, little is known regarding how these cells affect CD4 T cell responses in the context of chronic intestinal inflammation. Therefore, we undertook this study to characterize the interplay between colitis-induced myeloid cells and CD4 T cell. Within the CD11b+Gr-1+ population, only monocytes (Ly6GnegLy6Chigh) but not other myeloid cell subsets suppressed proliferation and production of cytokines by CD4 T cells. Suppression was mediated by cell-contact, NO and partially by IFN-γ and PGs. Interestingly, Ly6Chigh MDCs, isolated from colitic colons, showed up-regulation of iNOS and arginase-1 and were more potent suppressors than those isolated from spleen. On a single-cell level, MDCs inhibited Th1 responses but enhanced generation of foxp3+ T cells. MDCs, cocultured with activated/Teffs, isolated from inflamed colons under hypoxic (1% O2) conditions typical for the inflamed intestine, suppressed proliferation but not their production of proinflammatory cytokines and chemokines. Taken together, expansion of monocytes and MDCs and activation of their suppressive properties may represent a homeostatic mechanism aimed at restraining excessive T cell activation during chronic inflammatory settings. The contribution of immunosuppressive monocytes/MDCs to chronic colitis and their role in shaping T cell responses in vivo require further investigation. PMID:24696357

  15. Homeostatic and Circadian Abnormalities in Sleep and Arousal in Gulf War Syndrome

    DTIC Science & Technology

    2014-10-01

    Award Number: W81XWH-10-2-0129 TITLE: Homeostatic and Circadian Abnormalities in Sleep and Arousal in Gulf War Syndrome PRINCIPAL INVESTIGATOR...To) 20 Sep 2013 to 19 Sep 2014 4. TITLE AND SUBTITLE Homeostatic and Circadian Abnormalities in Sleep and Arousal 5a. CONTRACT NUMBER W81XWH-10...sleep pattern activity is altered in veterans with fatigue. Beyond the typical overnight polysomnography, this assessment includes objective wave

  16. Homeostatic and Circadian Abnormalities in Sleep and Arousal in Gulf War Syndrome

    DTIC Science & Technology

    2012-10-01

    the recovery and restorative aspects of sleep . 15. SUBJECT TERMS Dense array EEG, temperature, melatonin , vigilance 16. SECURITY CLASSIFICATION OF...Homeostatic and Circadian Abnormalities in Sleep and Arousal in Gulf War Syndrome PRINCIPAL INVESTIGATOR: Timothy M. Juergens, M.D...Sep 2011 to 19 Sep 2012 4. TITLE AND SUBTITLE Homeostatic and Circadian Abnormalities in Sleep and Arousal in Gul 5a. CONTRACT NUMBER

  17. Design principles for the analysis and construction of robustly homeostatic biological networks.

    PubMed

    Tang, Zhe F; McMillen, David R

    2016-11-07

    Homeostatic biological systems resist external disturbances, allowing cells and organisms to maintain a constant internal state despite perturbations from their surroundings. Many biological regulatory networks are known to act homeostatically, with examples including thermal adaptation, osmoregulation, and chemotaxis. Understanding the network topologies (sets of regulatory interactions) and biological parameter regimes that can yield homeostasis in a biological system is of interest both for the study of natural biological system, and in the context of designing new biological control schemes for use in synthetic biology. Here, we examine the mathematical properties of a function that maps a biological system's inputs to its outputs, we have formulated a novel criterion (the "cofactor condition") that compactly describes the conditions for homeostasis. We further analyze the problem of robust homeostasis, wherein the system is required to maintain homeostatic behavior when its parameter values are slightly altered. We use the cofactor condition to examine previously reported examples of robust homeostasis, showing that it is a useful way to unify a number of seemingly different analyses into a single framework. Based on the observation that all previous robustly homeostatic examples fall into one of three classes, we propose a "strong cofactor condition" and use it to provide an algorithm for designing new robustly homeostatic biological networks, giving both their topologies and constraints on their parameter values. Applying the design algorithm to a three-node biological network, we construct several robustly homeostatic genetic networks, uncovering network topologies not previously identified as candidates for exhibiting robust homeostasis.

  18. Socially isolated mice exhibit a blunted homeostatic sleep response to acute sleep deprivation compared to socially paired mice.

    PubMed

    Kaushal, Navita; Nair, Deepti; Gozal, David; Ramesh, Vijay

    2012-05-15

    Sleep is an important physiological process underlying maintenance of physical, mental and emotional health. Consequently, sleep deprivation (SD) is associated with adverse consequences and increases the risk for anxiety, immune, and cognitive disorders. SD is characterized by increased energy expenditure responses and sleep rebound upon recovery that are regulated by homeostatic processes, which in turn are influenced by stress. Since all previous studies on SD were conducted in a setting of social isolation, the impact of the social contextual setting is unknown. Therefore, we used a relatively stress-free SD paradigm in mice to assess the impact of social isolation on sleep, wakefulness and delta electroencephalogram (EEG) power during non-rapid eye movement (NREM) sleep. Paired or isolated C57BL/6J adult chronically-implanted male mice were exposed to SD for 6h and telemetric polygraphic recordings were conducted, including 18 h recovery. Recovery from SD in the paired group showed a significant decrease in wake and significant increase in NREM sleep and rapid eye movement (REM), and a similar, albeit less robust response occurred in the isolated mice. Delta power during NREM sleep was increased in both groups immediately following SD, but paired mice exhibited significantly higher delta power throughout the dark period. The increase in body temperature and gross motor activity observed during the SD procedure was decreased during the dark period. In both open field and elevated plus maze tests, socially isolated mice showed significantly higher anxiety than paired mice. The homeostatic processes altered by SD are differentially affected in paired and isolated mice, suggesting that the social context of isolation stress may adversely affect the quantity and quality of sleep in mice.

  19. Reconciling Homeostatic and Use-Dependent Plasticity in the Context of Somatosensory Deprivation

    PubMed Central

    Orczyk, John J.; Garraghty, Preston E.

    2015-01-01

    The concept of homeostatic plasticity postulates that neurons maintain relatively stable rates of firing despite changing inputs. Homeostatic and use-dependent plasticity mechanisms operate concurrently, although they have different requirements for induction. Depriving central somatosensory neurons of their primary activating inputs reduces activity and results in compensatory changes that favor excitation. Both a reduction of GABAergic inhibition and increase in glutamatergic excitatory transmission are observed in input-deprived cortex. Topographic reorganization of the adult somatosensory cortex is likely driven by both homeostatic and use-dependent mechanisms. Plasticity is induced by changes in the strengths of synaptic inputs, as well as changes in temporal correlation of neuronal activity. However, there is less certainty regarding the in vivo contribution of homeostatic mechanisms as in vitro experiments rely on manipulations that create states that do not normally occur in the living nervous system. Homeostatic plasticity seems to occur, but more in vivo research is needed to determine mechanisms. In vitro research is also needed but should better conform to conditions that might occur naturally in vivo. PMID:25866682

  20. Power oscillator

    DOEpatents

    Gitsevich, Aleksandr

    2001-01-01

    An oscillator includes an amplifier having an input and an output, and an impedance transformation network connected between the input of the amplifier and the output of the amplifier, wherein the impedance transformation network is configured to provide suitable positive feedback from the output of the amplifier to the input of the amplifier to initiate and sustain an oscillating condition, and wherein the impedance transformation network is configured to protect the input of the amplifier from a destructive feedback signal. One example of the oscillator is a single active element device capable of providing over 70 watts of power at over 70% efficiency. Various control circuits may be employed to match the driving frequency of the oscillator to a plurality of tuning states of the lamp.

  1. Subnetwork-Specific Homeostatic Plasticity in Mouse Visual Cortex In Vivo.

    PubMed

    Barnes, Samuel J; Sammons, Rosanna P; Jacobsen, R Irene; Mackie, Jennifer; Keller, Georg B; Keck, Tara

    2015-06-03

    Homeostatic regulation has been shown to restore cortical activity in vivo following sensory deprivation, but it is unclear whether this recovery is uniform across all cells or specific to a subset of the network. To address this issue, we used chronic calcium imaging in behaving adult mice to examine the activity of individual excitatory and inhibitory neurons in the same region of the layer 2/3 monocular visual cortex following enucleation. We found that only a fraction of excitatory neurons homeostatically recover activity after deprivation and inhibitory neurons show no recovery. Prior to deprivation, excitatory cells that did recover were more likely to have significantly correlated activity with other recovering excitatory neurons, thus forming a subnetwork of recovering neurons. These network level changes are accompanied by a reduction in synaptic inhibition onto all excitatory neurons, suggesting that both synaptic mechanisms and subnetwork activity are important for homeostatic recovery of activity after deprivation.

  2. Homeostatic regulation of AMPA receptor trafficking and degradation by light-controlled single synaptic activation

    PubMed Central

    Hou, Qingming; Gilbert, James; Man, Heng-Ye

    2011-01-01

    During homeostatic adjustment in response to alterations in neuronal activity, synaptic expression of AMPA receptors (AMPARs) is globally tuned up- or down so that the neuronal activity is restored to a physiological range. Given that a central neuron receives multiple presynaptic inputs, whether and how AMPAR synaptic expression is homeostatically regulated at individual synapses remains unclear. In cultured hippocampal neurons, we report that when activity of an individual presynaptic terminal is selectively elevated by light-controlled excitation, AMPAR abundance at the excited synapses is selectively down-regulated in an NMDAR-dependent manner. The reduction in surface AMPARs is accompanied by enhanced receptor endocytosis and dependent on proteasomal activity. Synaptic activation also leads to a site-specific increase in the ubiquitin ligase Nedd4 and polyubiquitination levels, consistent with AMPAR ubiquitination and degradation in the spine. These results indicate that AMPAR accumulation at individual synapses is subject to autonomous homeostatic regulation in response to synaptic activity. PMID:22153376

  3. Studying adaptation and homeostatic behaviors of kinetic networks by using MATLAB.

    PubMed

    Drengstig, Tormod; Kjosmoen, Thomas; Ruoff, Peter

    2011-01-01

    Organisms have the ability to counteract environmental perturbations and keep certain components within a cell homeostatically regulated. Closely related to homeostasis is the behavior of perfect adaptation where an organism responds to a step-wise perturbation by regulating some of its components, after a transient period, to their original pre-perturbation values. A particular interesting type of model relates to the so-called robust behavior where the homeostatic or perfect adaptation property is independent of the magnitude of the applied step-wise perturbation. It has been shown that this type of behavior is related to the control-theoretic concept of integral feedback (or integral control). Using downloadable MATLAB examples, we demonstrate how robust perfect adaptation sites can be identified in reaction kinetic networks by linearizing the system, applying the Laplace transform and inspecting the transfer function. We also show how the homeostatic set point in perfect adaptation is related to the presence of zero-order fluxes.

  4. A Cerebellar Framework for Predictive Coding and Homeostatic Regulation in Depressive Disorder.

    PubMed

    Schutter, Dennis J L G

    2016-02-01

    Depressive disorder is associated with abnormalities in the processing of reward and punishment signals and disturbances in homeostatic regulation. These abnormalities are proposed to impair error minimization routines for reducing uncertainty. Several lines of research point towards a role of the cerebellum in reward- and punishment-related predictive coding and homeostatic regulatory function in depressive disorder. Available functional and anatomical evidence suggests that in addition to the cortico-limbic networks, the cerebellum is part of the dysfunctional brain circuit in depressive disorder as well. It is proposed that impaired cerebellar function contributes to abnormalities in predictive coding and homeostatic dysregulation in depressive disorder. Further research on the role of the cerebellum in depressive disorder may further extend our knowledge on the functional and neural mechanisms of depressive disorder and development of novel antidepressant treatments strategies targeting the cerebellum.

  5. Integrating Hebbian and homeostatic plasticity: the current state of the field and future research directions.

    PubMed

    Keck, Tara; Toyoizumi, Taro; Chen, Lu; Doiron, Brent; Feldman, Daniel E; Fox, Kevin; Gerstner, Wulfram; Haydon, Philip G; Hübener, Mark; Lee, Hey-Kyoung; Lisman, John E; Rose, Tobias; Sengpiel, Frank; Stellwagen, David; Stryker, Michael P; Turrigiano, Gina G; van Rossum, Mark C

    2017-03-05

    We summarize here the results presented and subsequent discussion from the meeting on Integrating Hebbian and Homeostatic Plasticity at the Royal Society in April 2016. We first outline the major themes and results presented at the meeting. We next provide a synopsis of the outstanding questions that emerged from the discussion at the end of the meeting and finally suggest potential directions of research that we believe are most promising to develop an understanding of how these two forms of plasticity interact to facilitate functional changes in the brain.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity'.

  6. Homeostasis balance, homeostasis imbalance or distinct motivational processes? Comments on Marks (2015) 'Homeostatic Theory of Obesity'.

    PubMed

    Pelletier, Luc G; Guertin, Camille; Pope, J Paige; Rocchi, Meredith

    2016-01-01

    In his article, 'Homeostatic theory of obesity', Marks suggested that imbalances in homeostatic processes could explain weight gain and obesity. He proposes that over-consumption of high-caloric, low-nutrient and low satiating foods, combined with a stressful environment, is the origin of weight gain. Once weight gain occurs, individuals may develop body dissatisfaction and negative affect, leading to continued over-consumption, which sets in motion a system of feedback loops that leads to a Circle of Discontent and further weight gain. In this article, we attempt to clarify certain problematic aspects of Marks framework and identify specific directions that researchers should pursue to address these shortcomings.

  7. Requirement for Plk2 in orchestrated ras and rap signaling, homeostatic structural plasticity, and memory.

    PubMed

    Lee, Kea Joo; Lee, Yeunkum; Rozeboom, Aaron; Lee, Ji-Yun; Udagawa, Noriko; Hoe, Hyang-Sook; Pak, Daniel T S

    2011-03-10

    Ras and Rap small GTPases are important for synaptic plasticity and memory. However, their roles in homeostatic plasticity are unknown. Here, we report that polo-like kinase 2 (Plk2), a homeostatic suppressor of overexcitation, governs the activity of Ras and Rap via coordination of their regulatory proteins. Plk2 directs elimination of Ras activator RasGRF1 and Rap inhibitor SPAR via phosphorylation-dependent ubiquitin-proteasome degradation. Conversely, Plk2 phosphorylation stimulates Ras inhibitor SynGAP and Rap activator PDZGEF1. These Ras/Rap regulators perform complementary functions to downregulate dendritic spines and AMPA receptors following elevated activity, and their collective regulation by Plk2 profoundly stimulates Rap and suppresses Ras. Furthermore, perturbation of Plk2 disrupts Ras and Rap signaling, prevents homeostatic shrinkage and loss of dendritic spines, and impairs proper memory formation. Our study demonstrates a critical role of Plk2 in the synchronized tuning of Ras and Rap and underscores the functional importance of this regulation in homeostatic synaptic plasticity.

  8. Propagation of homeostatic sleep signals by segregated synaptic microcircuits of the Drosophila mushroom body

    PubMed Central

    Sitaraman, Divya; Aso, Yoshinori; Jin, Xin; Chen, Nan; Felix, Mario; Rubin, Gerald M.; Nitabach, Michael N.

    2015-01-01

    The Drosophila mushroom body (MB) is a key associative memory center that has also been implicated in the control of sleep. However, the identity of MB neurons underlying homeostatic sleep regulation, as well as the types of sleep signals generated by specific classes of MB neurons, has remained poorly understood. We recently identified two MB output neuron (MBON) classes whose axons convey sleep control signals from the MB to converge in the same downstream target region: a cholinergic sleep-promoting MBON class and a glutamatergic wake-promoting MBON class. Here we deploy a combination of neurogenetic, behavioral, and physiological approaches to identify and mechanistically dissect sleep-controlling circuits of the MB. Our studies reveal the existence of two segregated excitatory synaptic microcircuits that propagate homeostatic sleep information from different populations of intrinsic MB “Kenyon cells” (KCs) to specific sleep-regulating MBONs: sleep-promoting KCs increase sleep by preferentially activating the cholinergic MBONs, while wake-promoting KCs decrease sleep by preferentially activating the glutamatergic MBONs. Importantly, activity of the sleep-promoting MB microcircuit is increased by sleep deprivation and is necessary for homeostatic rebound sleep (i.e., the increased sleep that occurs after, and in compensation for, sleep lost during deprivation). These studies reveal for the first time specific functional connections between subsets of KCs and particular MBONs and establish the identity of synaptic microcircuits underlying transmission of homeostatic sleep signals in the MB. PMID:26455303

  9. Homeostatic Synaptic Plasticity Can Explain Post-traumatic Epileptogenesis in Chronically Isolated Neocortex

    PubMed Central

    Houweling, Arthur R.; Bazhenov, Maxim; Timofeev, Igor; Steriade, Mircea; Sejnowski, Terrence J.

    2010-01-01

    Chronically isolated neocortex develops chronic hyperexcitability and focal epileptogenesis in a period of days to weeks. The mechanisms operating in this model of post-traumatic epileptogenesis are not well understood. We hypothesized that the spontaneous burst discharges recorded in chronically isolated neocortex result from homeostatic plasticity (a mechanism generally assumed to stabilize neuronal activity) induced by low neuronal activity after deafferentation. To test this hypothesis we constructed computer models of neocortex incorporating a biologically based homeostatic plasticity rule that operates to maintain firing rates. After deafferentation, homeostatic upregulation of excitatory synapses on pyramidal cells, either with or without concurrent downregulation of inhibitory synapses or upregulation of intrinsic excitability, initiated slowly repeating burst discharges that closely resembled the epileptiform burst discharges recorded in chronically isolated neocortex. These burst discharges lasted a few hundred ms, propagated at 1–3 cm/s and consisted of large (10–15 mV) intracellular depolarizations topped by a small number of action potentials. Our results support a role for homeostatic synaptic plasticity as a novel mechanism of post-traumatic epileptogenesis. PMID:15483049

  10. Cutting edge: innate memory CD8+ T cells are distinct from homeostatic expanded CD8+ T cells and rapidly respond to primary antigenic stimuli.

    PubMed

    Huang, Weishan; Hu, Jianfang; August, Avery

    2013-03-15

    Innate memory phenotype (IMP) CD8(+) T cells are nonconventional αβ T cells exhibiting features of innate immune cells and are significantly increased in the absence of ITK. Their developmental path and function are not clear. In this study, we show hematopoietic MHC class I (MHCI)-dependent generation of Ag-specific IMP CD8(+) T cells using bone marrow chimeras. Wild-type bone marrow gives rise to IMP CD8(+) T cells in MHCI(-/-) recipients, resembling those in Itk(-/-) mice, but distinct from those derived via homeostatic proliferation, and independent of recipient thymus. In contrast, MHCI(-/-) bone marrow does not lead to IMP CD8(+) T cells in wild-type recipients. OTI IMP CD8(+) T cells generated via this method exhibited enhanced early response to Ag without prior primary stimulation. Our findings suggest a method to generate Ag-specific "naive" CD8(+) IMP T cells, as well as demonstrate that they are not homeostatic proliferation cells and can respond promptly in an Ag-specific fashion.

  11. Homeostatic Changes in GABA and Glutamate Receptors on Excitatory Cortical Neurons during Sleep Deprivation and Recovery

    PubMed Central

    del Cid-Pellitero, Esther; Plavski, Anton; Mainville, Lynda; Jones, Barbara E.

    2017-01-01

    Neuronal activity is regulated in a homeostatic manner through changes in inhibitory GABA and excitatory glutamate (Glu) AMPA (A) receptors (GluARs). Using immunofluorescent staining, we examined whether calcium/calmodulin-dependent protein kinase IIα (CaMKIIα)-labeled (+) excitatory neurons in the barrel cortex undergo such homeostatic regulation following enforced waking with associated cortical activation during the day when mice normally sleep the majority of the time. Sleep deprived mice were prevented from falling asleep by unilateral whisker stimulation and sleep recovery (SR) mice allowed to sleep freely following deprivation. In parallel with changes in c-Fos reflecting changes in activity, (β2-3 subunits of) GABAA Rs were increased on the membrane of CaMKIIα+ neurons with enforced waking and returned to baseline levels with SR in barrel cortex on sides both contra- and ipsilateral to the whisker stimulation. The GABAAR increase was correlated with increased gamma electroencephalographic (EEG) activity across conditions. On the other hand, (GluA1 subunits of) AMPA Rs were progressively removed from the membrane of CaMKIIα+ neurons by (Rab5+) early endosomes during enforced waking and returned to the membrane by (Rab11+) recycling endosomes during SR. The internalization of the GluA1Rs paralleled the expression of Arc, which mediates homeostatic regulation of AMPA receptors through an endocytic pathway. The reciprocal changes in GluA1Rs relative to GABAARs suggest homeostatic down-scaling during enforced waking and sensory stimulation and restorative up-scaling during recovery sleep. Such homeostatic changes with sleep-wake states and their associated cortical activities could stabilize excitability and activity in excitatory cortical neurons.

  12. How voltage-gated calcium channels gate forms of homeostatic synaptic plasticity

    PubMed Central

    Frank, C. Andrew

    2014-01-01

    Throughout life, animals face a variety of challenges such as developmental growth, the presence of toxins, or changes in temperature. Neuronal circuits and synapses respond to challenges by executing an array of neuroplasticity paradigms. Some paradigms allow neurons to up- or downregulate activity outputs, while countervailing ones ensure that outputs remain within appropriate physiological ranges. A growing body of evidence suggests that homeostatic synaptic plasticity (HSP) is critical in the latter case. Voltage-gated calcium channels gate forms of HSP. Presynaptically, the aggregate data show that when synapse activity is weakened, homeostatic signaling systems can act to correct impairments, in part by increasing calcium influx through presynaptic CaV2-type channels. Increased calcium influx is often accompanied by parallel increases in the size of active zones and the size of the readily releasable pool of presynaptic vesicles. These changes coincide with homeostatic enhancements of neurotransmitter release. Postsynaptically, there is a great deal of evidence that reduced network activity and loss of calcium influx through CaV1-type calcium channels also results in adaptive homeostatic signaling. Some adaptations drive presynaptic enhancements of vesicle pool size and turnover rate via retrograde signaling, as well as de novo insertion of postsynaptic neurotransmitter receptors. Enhanced calcium influx through CaV1 after network activation or single cell stimulation can elicit the opposite response—homeostatic depression via removal of excitatory receptors. There exist intriguing links between HSP and calcium channelopathies—such as forms of epilepsy, migraine, ataxia, and myasthenia. The episodic nature of some of these disorders suggests alternating periods of stable and unstable function. Uncovering information about how calcium channels are regulated in the context of HSP could be relevant toward understanding these and other disorders. PMID

  13. FEL Oscillators

    SciTech Connect

    George Neil

    2003-05-12

    FEL Oscillators have been around since 1977 providing not only a test bed for the physics of Free Electron Lasers and electron/photon interactions but as a workhorse of scientific research. More than 30 FEL oscillators are presently operating around the world spanning a wavelength range from the mm region to the ultraviolet using DC and rf linear accelerators and storage rings as electron sources. The characteristics that have driven the development of these sources are the desire for high peak and average power, high micropulse energies, wavelength tunability, timing flexibility, and wavelengths that are unavailable from more conventional laser sources. Substantial user programs have been performed using such sources encompassing medicine, biology, solid state research, atomic and molecular physics, effects of non-linear fields, surface science, polymer science, pulsed laser vapor deposition, to name just a few.

  14. STABILIZED OSCILLATOR

    DOEpatents

    Jessen, P.L.; Price, H.J.

    1958-03-18

    This patent relates to sine-wave generators and in particular describes a generator with a novel feedback circuit resulting in improved frequency stability. The generator comprises two triodes having a common cathode circuit connected to oscillate at a frequency and amplitude at which the loop galn of the circutt ls unity, and another pair of triodes having a common cathode circuit arranged as a conventional amplifier. A signal is conducted from the osciliator through a frequency selective network to the amplifier and fed back to the osciliator. The unique feature of the feedback circuit is the amplifier operates in the nonlinear portion of its tube characteristics thereby providing a relatively constant feedback voltage to the oscillator irrespective of the amplitude of its input signal.

  15. Adaptive Immune Regulation of Glial Homeostasis as an Immunization Strategy for Neurodegenerative Diseases

    PubMed Central

    Kosloski, Lisa M.; Ha, Duy M.; Stone, David K.; Hutter, Jessica A. L.; Pichler, Michael R.; Reynolds, Ashley D.; Gendelman, Howard E.; Mosley, R. Lee

    2010-01-01

    Neurodegenerative diseases, notably Alzheimer's and Parkinson's diseases, are amongst the most devastating disorders afflicting the elderly. Currently, no curative treatments or treatments that interdict disease progression exist. Over the past decade, immunization strategies have been proposed to combat disease progression. Such strategies induce humoral immune responses against misfolded protein aggregates to facilitate their clearance. Robust adaptive immunity against misfolded proteins, however, accelerates disease progression, precipitated by induced effector T cell responses that lead to encephalitis and neuronal death. Since then, mechanisms that attenuate such adaptive neurotoxic immune responses have been sought. We propose that shifting the balance between effector and regulatory T cell activity can attenuate neurotoxic inflammatory events. This review summarizes advances in immune regulation to achieve a homeostatic glial response for therapeutic gain. Promising new ways to optimize immunization schemes and measure their clinical efficacy are also discussed. PMID:20524958

  16. Solar Oscillations

    NASA Technical Reports Server (NTRS)

    Duvall, Thomas

    2004-01-01

    Oscillations were first detected in the solar photosphere in 1962 by Leighton and students. In 1970 it was calculated that these oscillations, with a period near five minutes, were the manifestations of acoustic waves trapped in the interior. The subsequent measurements of the frequencies of global oscillation modes from the spatio-temporal power spectrum of the waves made possible the refinement of solar interior models. Over the years, increased understanding of the nuclear reaction rates, the opacity, the equation of state, convection, and gravitational settling have resulted. Mass flows shift the frequencies of modes leading to very accurate measurements of the interior rotation as a function of radius and latitude. In recent years, analogues of terrestrial seismology have led to a tomography of the interior, including measurements of global north-south flows and flow and wave speed measurements below features such as sunspots. The future of helioseismology seems bright with the approval of NASA's Solar Dynamics Observatory mission, to be launched in 2008.

  17. Maturation of the enteric mucosal innate immune system during the postnatal period.

    PubMed

    Fulde, Marcus; Hornef, Mathias W

    2014-07-01

    The innate immune system instructs the host on microbial exposure and infection. This information is critical to mount a protective innate and adaptive host response to microbial challenge, but is also involved in homeostatic and adaptive processes that adjust the organism to meet environmental requirements. This is of particular importance for the neonatal host during the transition from the protected fetal life to the intense and dynamic postnatal interaction with commensal and pathogenic microorganisms. Here, we discuss both adaptive and developmental mechanisms of the mucosal innate immune system that prevent inappropriate stimulation and facilitate establishment of a stable homeostatic host-microbial interaction after birth.

  18. Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons.

    PubMed

    Chang, Michael C; Park, Joo Min; Pelkey, Kenneth A; Grabenstatter, Heidi L; Xu, Desheng; Linden, David J; Sutula, Thomas P; McBain, Chris J; Worley, Paul F

    2010-09-01

    Homeostatic synaptic scaling alters the strength of synapses to compensate for prolonged changes in network activity and involves both excitatory and inhibitory neurons. The immediate-early gene Narp (neuronal activity-regulated pentraxin) encodes a secreted synaptic protein that can bind to and induce clustering of AMPA receptors (AMPARs). We found that Narp prominently accumulated at excitatory synapses on parvalbumin-expressing interneurons (PV-INs). Increasing network activity resulted in a homeostatic increase of excitatory synaptic strength onto PV-INs that increased inhibitory drive and this response was absent in neurons cultured from Narp-/- mice. Activity-dependent changes in the strength of excitatory inputs on PV-INs in acute hippocampal slices were also dependent on Narp and Narp-/- mice had increased sensitivity to kindling-induced seizures. We propose that Narp recruits AMPARs at excitatory synapses onto PV-INs to rebalance network excitation/inhibition dynamics following episodes of increased circuit activity.

  19. Self-renewing diploid Axin2+ cells fuel homeostatic renewal of the liver

    PubMed Central

    Wang, Bruce; Zhao, Ludan; Fish, Matt; Logan, Catriona Y.; Nusse, Roel

    2015-01-01

    Summary The source of new hepatocytes in the uninjured liver has remained an open question. By lineage tracing using the Wnt-responsive gene Axin2, we identify a population of proliferating and self-renewing cells adjacent to the central vein in the liver lobule. These pericentral cells express the early liver progenitor marker Tbx3, are diploid, and thus differ from mature hepatocytes, which are mostly polyploid. The descendants of pericentral cells differentiate into Tbx3-negative, polyploid hepatocytes and can replace all hepatocytes along the liver lobule during homeostatic renewal. Adjacent central vein endothelial cells provide Wnt signals that maintain the pericentral cells, thereby constituting the niche. Thus, we identify a cell population in the liver that subserves homeostatic hepatocyte renewal, characterize its anatomical niche, and identify molecular signals that regulate its activity. PMID:26245375

  20. Sleep recalibrates homeostatic and associative synaptic plasticity in the human cortex

    PubMed Central

    Kuhn, Marion; Wolf, Elias; Maier, Jonathan G.; Mainberger, Florian; Feige, Bernd; Schmid, Hanna; Bürklin, Jan; Maywald, Sarah; Mall, Volker; Jung, Nikolai H.; Reis, Janine; Spiegelhalder, Kai; Klöppel, Stefan; Sterr, Annette; Eckert, Anne; Riemann, Dieter; Normann, Claus; Nissen, Christoph

    2016-01-01

    Sleep is ubiquitous in animals and humans, but its function remains to be further determined. The synaptic homeostasis hypothesis of sleep–wake regulation proposes a homeostatic increase in net synaptic strength and cortical excitability along with decreased inducibility of associative synaptic long-term potentiation (LTP) due to saturation after sleep deprivation. Here we use electrophysiological, behavioural and molecular indices to non-invasively study net synaptic strength and LTP-like plasticity in humans after sleep and sleep deprivation. We demonstrate indices of increased net synaptic strength (TMS intensity to elicit a predefined amplitude of motor-evoked potential and EEG theta activity) and decreased LTP-like plasticity (paired associative stimulation induced change in motor-evoked potential and memory formation) after sleep deprivation. Changes in plasma BDNF are identified as a potential mechanism. Our study indicates that sleep recalibrates homeostatic and associative synaptic plasticity, believed to be the neural basis for adaptive behaviour, in humans. PMID:27551934

  1. Reduction in endocannabinoid tone is a homeostatic mechanism for specific inhibitory synapses.

    PubMed

    Kim, Jimok; Alger, Bradley E

    2010-05-01

    When chronic alterations in neuronal activity occur, network gain is maintained by global homeostatic scaling of synaptic strength, but the stability of microcircuits can be controlled by unique adaptations that differ from the global changes. It is not understood how specificity of synaptic tuning is achieved. We found that, although a large population of inhibitory synapses was homeostatically scaled down after chronic inactivity, decreased endocannabinoid tone specifically strengthened a subset of GABAergic synapses that express cannabinoid receptors. In rat hippocampal slice cultures, a 3-5-d blockade of neuronal firing facilitated uptake and degradation of anandamide. The consequent reduction in basal stimulation of cannabinoid receptors augmented GABA release probability, fostering rapid depression of synaptic inhibition and on-demand disinhibition. This regulatory mechanism, mediated by activity-dependent changes in tonic endocannabinoid level, permits selective local tuning of inhibitory synapses in hippocampal networks.

  2. Blaming the brain for obesity: Integration of hedonic and homeostatic mechanisms.

    PubMed

    Berthoud, Hans-Rudolf; Münzberg, Heike; Morrison, Christopher D

    2017-02-09

    The brain plays a key role in the controls of energy intake and expenditure and many genes associated with obesity are expressed in the central nervous system. Technological and conceptual advances in both basic and clinical neurosciences have expanded the traditional view of homeostatic regulation of body weight by mainly the hypothalamus to include hedonic controls of appetite by cortical and subcortical brain areas processing external sensory information, reward, cognition, and executive functions. Thus, hedonic controls interact with homeostatic controls to regulate body weight in a flexible and adaptive manner that takes environmental conditions into account. This new conceptual framework has several important implications for the treatment of obesity. Because much of this interactive neural processing is outside awareness, cognitive restraint in a world of plenty is made difficult and prevention and treatment of obesity should be more rationally directed to the complex and often redundant mechanisms underlying this interaction.

  3. Self-renewing diploid Axin2(+) cells fuel homeostatic renewal of the liver.

    PubMed

    Wang, Bruce; Zhao, Ludan; Fish, Matt; Logan, Catriona Y; Nusse, Roel

    2015-08-13

    The source of new hepatocytes in the uninjured liver has remained an open question. By lineage tracing using the Wnt-responsive gene Axin2 in mice, we identify a population of proliferating and self-renewing cells adjacent to the central vein in the liver lobule. These pericentral cells express the early liver progenitor marker Tbx3, are diploid, and thereby differ from mature hepatocytes, which are mostly polyploid. The descendants of pericentral cells differentiate into Tbx3-negative, polyploid hepatocytes, and can replace all hepatocytes along the liver lobule during homeostatic renewal. Adjacent central vein endothelial cells provide Wnt signals that maintain the pericentral cells, thereby constituting the niche. Thus, we identify a cell population in the liver that subserves homeostatic hepatocyte renewal, characterize its anatomical niche, and identify molecular signals that regulate its activity.

  4. Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism

    PubMed Central

    Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

    2016-01-01

    Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism. PMID:26964832

  5. Homeostatic control: Economic integration of solar technologies into electric power operations and planning

    NASA Astrophysics Data System (ADS)

    Tabors, R. D.

    1981-07-01

    The economic issues associated with the interface of new energy technologies and the electric utility grid are discussed. The concept of homestatic control is introduced and the use of such an economic concept applied to the introduction of nondispatchable technologies into the existing utility system is examined. The transition and potential impact of a homeostatic control system working with the existing electric utility system is treated.

  6. Homeostatic structural plasticity increases the efficiency of small-world networks.

    PubMed

    Butz, Markus; Steenbuck, Ines D; van Ooyen, Arjen

    2014-01-01

    In networks with small-world topology, which are characterized by a high clustering coefficient and a short characteristic path length, information can be transmitted efficiently and at relatively low costs. The brain is composed of small-world networks, and evolution may have optimized brain connectivity for efficient information processing. Despite many studies on the impact of topology on information processing in neuronal networks, little is known about the development of network topology and the emergence of efficient small-world networks. We investigated how a simple growth process that favors short-range connections over long-range connections in combination with a synapse formation rule that generates homeostasis in post-synaptic firing rates shapes neuronal network topology. Interestingly, we found that small-world networks benefited from homeostasis by an increase in efficiency, defined as the averaged inverse of the shortest paths through the network. Efficiency particularly increased as small-world networks approached the desired level of electrical activity. Ultimately, homeostatic small-world networks became almost as efficient as random networks. The increase in efficiency was caused by the emergent property of the homeostatic growth process that neurons started forming more long-range connections, albeit at a low rate, when their electrical activity was close to the homeostatic set-point. Although global network topology continued to change when neuronal activities were around the homeostatic equilibrium, the small-world property of the network was maintained over the entire course of development. Our results may help understand how complex systems such as the brain could set up an efficient network topology in a self-organizing manner. Insights from our work may also lead to novel techniques for constructing large-scale neuronal networks by self-organization.

  7. Homeostatic structural plasticity can account for topology changes following deafferentation and focal stroke.

    PubMed

    Butz, Markus; Steenbuck, Ines D; van Ooyen, Arjen

    2014-01-01

    After brain lesions caused by tumors or stroke, or after lasting loss of input (deafferentation), inter- and intra-regional brain networks respond with complex changes in topology. Not only areas directly affected by the lesion but also regions remote from the lesion may alter their connectivity-a phenomenon known as diaschisis. Changes in network topology after brain lesions can lead to cognitive decline and increasing functional disability. However, the principles governing changes in network topology are poorly understood. Here, we investigated whether homeostatic structural plasticity can account for changes in network topology after deafferentation and brain lesions. Homeostatic structural plasticity postulates that neurons aim to maintain a desired level of electrical activity by deleting synapses when neuronal activity is too high and by providing new synaptic contacts when activity is too low. Using our Model of Structural Plasticity, we explored how local changes in connectivity induced by a focal loss of input affected global network topology. In accordance with experimental and clinical data, we found that after partial deafferentation, the network as a whole became more random, although it maintained its small-world topology, while deafferentated neurons increased their betweenness centrality as they rewired and returned to the homeostatic range of activity. Furthermore, deafferentated neurons increased their global but decreased their local efficiency and got longer tailed degree distributions, indicating the emergence of hub neurons. Together, our results suggest that homeostatic structural plasticity may be an important driving force for lesion-induced network reorganization and that the increase in betweenness centrality of deafferentated areas may hold as a biomarker for brain repair.

  8. Homeostatic Interplay between Bacterial Cell-Cell Signaling and Iron in Virulence

    PubMed Central

    Hazan, Ronen; He, Jianxin; Xiao, Gaoping; Dekimpe, Valérie; Apidianakis, Yiorgos; Lesic, Biliana; Astrakas, Christos; Déziel, Eric; Lépine, François; Rahme, Laurence G.

    2010-01-01

    Pathogenic bacteria use interconnected multi-layered regulatory networks, such as quorum sensing (QS) networks to sense and respond to environmental cues and external and internal bacterial cell signals, and thereby adapt to and exploit target hosts. Despite the many advances that have been made in understanding QS regulation, little is known regarding how these inputs are integrated and processed in the context of multi-layered QS regulatory networks. Here we report the examination of the Pseudomonas aeruginosa QS 4-hydroxy-2-alkylquinolines (HAQs) MvfR regulatory network and determination of its interaction with the QS acyl-homoserine-lactone (AHL) RhlR network. The aim of this work was to elucidate paradigmatically the complex relationships between multi-layered regulatory QS circuitries, their signaling molecules, and the environmental cues to which they respond. Our findings revealed positive and negative homeostatic regulatory loops that fine-tune the MvfR regulon via a multi-layered dependent homeostatic regulation of the cell-cell signaling molecules PQS and HHQ, and interplay between these molecules and iron. We discovered that the MvfR regulon component PqsE is a key mediator in orchestrating this homeostatic regulation, and in establishing a connection to the QS rhlR system in cooperation with RhlR. Our results show that P. aeruginosa modulates the intensity of its virulence response, at least in part, through this multi-layered interplay. Our findings underscore the importance of the homeostatic interplay that balances competition within and between QS systems via cell-cell signaling molecules and environmental cues in the control of virulence gene expression. Elucidation of the fine-tuning of this complex relationship offers novel insights into the regulation of these systems and may inform strategies designed to limit infections caused by P. aeruginosa and related human pathogens. PMID:20300606

  9. Synthetic homeostatic materials with chemo-mechano-chemical self-regulation.

    PubMed

    He, Ximin; Aizenberg, Michael; Kuksenok, Olga; Zarzar, Lauren D; Shastri, Ankita; Balazs, Anna C; Aizenberg, Joanna

    2012-07-11

    Living organisms have unique homeostatic abilities, maintaining tight control of their local environment through interconversions of chemical and mechanical energy and self-regulating feedback loops organized hierarchically across many length scales. In contrast, most synthetic materials are incapable of continuous self-monitoring and self-regulating behaviour owing to their limited single-directional chemomechanical or mechanochemical modes. Applying the concept of homeostasis to the design of autonomous materials would have substantial impacts in areas ranging from medical implants that help stabilize bodily functions to 'smart' materials that regulate energy usage. Here we present a versatile strategy for creating self-regulating, self-powered, homeostatic materials capable of precisely tailored chemo-mechano-chemical feedback loops on the nano- or microscale. We design a bilayer system with hydrogel-supported, catalyst-bearing microstructures, which are separated from a reactant-containing 'nutrient' layer. Reconfiguration of the gel in response to a stimulus induces the reversible actuation of the microstructures into and out of the nutrient layer, and serves as a highly precise 'on/off' switch for chemical reactions. We apply this design to trigger organic, inorganic and biochemical reactions that undergo reversible, repeatable cycles synchronized with the motion of the microstructures and the driving external chemical stimulus. By exploiting a continuous feedback loop between various exothermic catalytic reactions in the nutrient layer and the mechanical action of the temperature-responsive gel, we then create exemplary autonomous, self-sustained homeostatic systems that maintain a user-defined parameter--temperature--in a narrow range. The experimental results are validated using computational modelling that qualitatively captures the essential features of the self-regulating behaviour and provides additional criteria for the optimization of the homeostatic

  10. Rivalry of homeostatic and sensory-evoked emotions: Dehydration attenuates olfactory disgust and its neural correlates.

    PubMed

    Meier, Lea; Friedrich, Hergen; Federspiel, Andrea; Jann, Kay; Morishima, Yosuke; Landis, Basile Nicolas; Wiest, Roland; Strik, Werner; Dierks, Thomas

    2015-07-01

    Neural correlates have been described for emotions evoked by states of homeostatic imbalance (e.g. thirst, hunger, and breathlessness) and for emotions induced by external sensory stimulation (such as fear and disgust). However, the neurobiological mechanisms of their interaction, when they are experienced simultaneously, are still unknown. We investigated the interaction on the neurobiological and the perceptional level using subjective ratings, serum parameters, and functional magnetic resonance imaging (fMRI) in a situation of emotional rivalry, when both a homeostatic and a sensory-evoked emotion were experienced at the same time. Twenty highly dehydrated male subjects rated a disgusting odor as significantly less repulsive when they were thirsty. On the neurobiological level, we found that this reduction in subjective disgust during thirst was accompanied by a significantly reduced neural activity in the insular cortex, a brain area known to be considerably involved in processing of disgust. Furthermore, during the experience of disgust in the satiated condition, we observed a significant functional connectivity between brain areas responding to the disgusting odor, which was absent during the stimulation in the thirsty condition. These results suggest interference of conflicting emotions: an acute homeostatic imbalance can attenuate the experience of another emotion evoked by the sensory perception of a potentially harmful external agent. This finding offers novel insights with regard to the behavioral relevance of biologically different types of emotions, indicating that some types of emotions are more imperative for behavior than others. As a general principle, this modulatory effect during the conflict of homeostatic and sensory-evoked emotions may function to safeguard survival.

  11. A Diffusive Homeostatic Signal Maintains Neural Heterogeneity and Responsiveness in Cortical Networks

    PubMed Central

    Sweeney, Yann; Hellgren Kotaleski, Jeanette; Hennig, Matthias H.

    2015-01-01

    Gaseous neurotransmitters such as nitric oxide (NO) provide a unique and often overlooked mechanism for neurons to communicate through diffusion within a network, independent of synaptic connectivity. NO provides homeostatic control of intrinsic excitability. Here we conduct a theoretical investigation of the distinguishing roles of NO-mediated diffusive homeostasis in comparison with canonical non-diffusive homeostasis in cortical networks. We find that both forms of homeostasis provide a robust mechanism for maintaining stable activity following perturbations. However, the resulting networks differ, with diffusive homeostasis maintaining substantial heterogeneity in activity levels of individual neurons, a feature disrupted in networks with non-diffusive homeostasis. This results in networks capable of representing input heterogeneity, and linearly responding over a broader range of inputs than those undergoing non-diffusive homeostasis. We further show that these properties are preserved when homeostatic and Hebbian plasticity are combined. These results suggest a mechanism for dynamically maintaining neural heterogeneity, and expose computational advantages of non-local homeostatic processes. PMID:26158556

  12. Phosphorylation of AMPA receptors is required for sensory deprivation-induced homeostatic synaptic plasticity.

    PubMed

    Goel, Anubhuti; Xu, Linda W; Snyder, Kevin P; Song, Lihua; Goenaga-Vazquez, Yamila; Megill, Andrea; Takamiya, Kogo; Huganir, Richard L; Lee, Hey-Kyoung

    2011-03-31

    Sensory experience, and the lack thereof, can alter the function of excitatory synapses in the primary sensory cortices. Recent evidence suggests that changes in sensory experience can regulate the synaptic level of Ca(2+)-permeable AMPA receptors (CP-AMPARs). However, the molecular mechanisms underlying such a process have not been determined. We found that binocular visual deprivation, which is a well-established in vivo model to produce multiplicative synaptic scaling in visual cortex of juvenile rodents, is accompanied by an increase in the phosphorylation of AMPAR GluR1 (or GluA1) subunit at the serine 845 (S845) site and the appearance of CP-AMPARs at synapses. To address the role of GluR1-S845 in visual deprivation-induced homeostatic synaptic plasticity, we used mice lacking key phosphorylation sites on the GluR1 subunit. We found that mice specifically lacking the GluR1-S845 site (GluR1-S845A mutants), which is a substrate of cAMP-dependent kinase (PKA), show abnormal basal excitatory synaptic transmission and lack visual deprivation-induced homeostatic synaptic plasticity. We also found evidence that increasing GluR1-S845 phosphorylation alone is not sufficient to produce normal multiplicative synaptic scaling. Our study provides concrete evidence that a GluR1 dependent mechanism, especially S845 phosphorylation, is a necessary pre-requisite step for in vivo homeostatic synaptic plasticity.

  13. Structural brain correlates of human sleep oscillations.

    PubMed

    Saletin, Jared M; van der Helm, Els; Walker, Matthew P

    2013-12-01

    Sleep is strongly conserved within species, yet marked and perplexing inter-individual differences in sleep physiology are observed. Combining EEG sleep recordings and high-resolution structural brain imaging, here we demonstrate that the morphology of the human brain offers one explanatory factor of such inter-individual variability. Gray matter volume in interoceptive and exteroceptive cortices correlated with the expression of slower NREM sleep spindle frequencies, supporting their proposed role in sleep protection against conscious perception. Conversely, and consistent with an involvement in declarative memory processing, gray matter volume in bilateral hippocampus was associated with faster NREM sleep spindle frequencies. In contrast to spindles, gray matter volume in the homeostatic sleep-regulating center of the basal forebrain/hypothalamus, together with the medial prefrontal cortex, accounted for individual differences in NREM slow wave oscillations. Together, such findings indicate that the qualitative and quantitative expression of human sleep physiology is significantly related to anatomically specific differences in macroscopic brain structure.

  14. Immune System

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Immune System KidsHealth > For Teens > Immune System A A A ... could put us out of commission. What the Immune System Does The immune (pronounced: ih-MYOON) system, which ...

  15. Time-course and mechanisms of homeostatic plasticity in layers 2/3 and 5 of the barrel cortex

    PubMed Central

    2017-01-01

    Recent studies have shown that ocular dominance plasticity in layer 2/3 of the visual cortex exhibits a form of homeostatic plasticity that is related to synaptic scaling and depends on TNFα. In this study, we tested whether a similar form of plasticity was present in layer 2/3 of the barrel cortex and, therefore, whether the mechanism was likely to be a general property of cortical neurons. We found that whisker deprivation could induce homeostatic plasticity in layer 2/3 of barrel cortex, but not in a mouse strain lacking synaptic scaling. The time-course of homeostatic plasticity in layer 2/3 was similar to that of L5 regular spiking (RS) neurons (L5RS), but slower than that of L5 intrinsic bursting (IB) neurons (L5IB). In layer 5, the strength of evoked whisker responses and ex vivo miniature excitatory post-synaptic currents (mEPSCs) amplitudes showed an identical time-course for homeostatic plasticity, implying that plasticity at excitatory synapses contacting layer 5 neurons is sufficient to explain the changes in evoked responses. Spontaneous firing rate also showed homeostatic behaviour for L5IB cells, but was absent for L5RS cells over the time-course studied. Spontaneous firing rate homeostasis was found to be independent of evoked response homeostasis suggesting that the two depend on different mechanisms. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’. PMID:28093546

  16. Time-course and mechanisms of homeostatic plasticity in layers 2/3 and 5 of the barrel cortex.

    PubMed

    Glazewski, Stanislaw; Greenhill, Stuart; Fox, Kevin

    2017-03-05

    Recent studies have shown that ocular dominance plasticity in layer 2/3 of the visual cortex exhibits a form of homeostatic plasticity that is related to synaptic scaling and depends on TNFα. In this study, we tested whether a similar form of plasticity was present in layer 2/3 of the barrel cortex and, therefore, whether the mechanism was likely to be a general property of cortical neurons. We found that whisker deprivation could induce homeostatic plasticity in layer 2/3 of barrel cortex, but not in a mouse strain lacking synaptic scaling. The time-course of homeostatic plasticity in layer 2/3 was similar to that of L5 regular spiking (RS) neurons (L5RS), but slower than that of L5 intrinsic bursting (IB) neurons (L5IB). In layer 5, the strength of evoked whisker responses and ex vivo miniature excitatory post-synaptic currents (mEPSCs) amplitudes showed an identical time-course for homeostatic plasticity, implying that plasticity at excitatory synapses contacting layer 5 neurons is sufficient to explain the changes in evoked responses. Spontaneous firing rate also showed homeostatic behaviour for L5IB cells, but was absent for L5RS cells over the time-course studied. Spontaneous firing rate homeostasis was found to be independent of evoked response homeostasis suggesting that the two depend on different mechanisms.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity'.

  17. Grid oscillators

    NASA Technical Reports Server (NTRS)

    Popovic, Zorana B.; Kim, Moonil; Rutledge, David B.

    1988-01-01

    Loading a two-dimensional grid with active devices offers a means of combining the power of solid-state oscillators in the microwave and millimeter-wave range. The grid structure allows a large number of negative resistance devices to be combined. This approach is attractive because the active devices do not require an external locking signal, and the combining is done in free space. In addition, the loaded grid is a planar structure amenable to monolithic integration. Measurements on a 25-MESFET grid at 9.7 GHz show power-combining and frequency-locking without an external locking signal, with an ERP of 37 W. Experimental far-field patterns agree with theoretical results obtained using reciprocity.

  18. Oscillator detector

    SciTech Connect

    Potter, B.M.

    1980-05-13

    An alien liquid detector employs a monitoring element and an oscillatory electronic circuit for maintaining the temperature of the monitoring element substantially above ambient temperature. The output wave form, eg., frequency of oscillation or wave shape, of the oscillatory circuit depends upon the temperaturedependent electrical characteristic of the monitoring element. A predetermined change in the output waveform allows water to be discriminated from another liquid, eg., oil. Features of the invention employing two thermistors in two oscillatory circuits include positioning one thermistor for contact with water and the other thermistor above the oil-water interface to detect a layer of oil if present. Unique oscillatory circuit arrangements are shown that achieve effective thermistor action with an economy of parts and energizing power. These include an operational amplifier employed in an astable multivibrator circuit, a discrete transistor-powered tank circuit, and use of an integrated circuit chip.

  19. Hoxb4 Overexpression in CD4 Memory Phenotype T Cells Increases the Central Memory Population upon Homeostatic Proliferation

    PubMed Central

    Fournier, Marilaine; Labrecque, Nathalie; Bijl, Janet J.

    2013-01-01

    Memory T cell populations allow a rapid immune response to pathogens that have been previously encountered and thus form the basis of success in vaccinations. However, the molecular pathways underlying the development and maintenance of these cells are only starting to be unveiled. Memory T cells have the capacity to self renew as do hematopoietic stem cells, and overlapping gene expression profiles suggested that these cells might use the same self-renewal pathways. The transcription factor Hoxb4 has been shown to promote self-renewal divisions of hematopoietic stem cells resulting in an expansion of these cells. In this study we investigated whether overexpression of Hoxb4 could provide an advantage to CD4 memory phenotype T cells in engrafting the niche of T cell deficient mice following adoptive transfer. Competitive transplantation experiments demonstrated that CD4 memory phenotype T cells derived from mice transgenic for Hoxb4 contributed overall less to the repopulation of the lymphoid organs than wild type CD4 memory phenotype T cells after two months. These proportions were relatively maintained following serial transplantation in secondary and tertiary mice. Interestingly, a significantly higher percentage of the Hoxb4 CD4 memory phenotype T cell population expressed the CD62L and Ly6C surface markers, characteristic for central memory T cells, after homeostatic proliferation. Thus Hoxb4 favours the maintenance and increase of the CD4 central memory phenotype T cell population. These cells are more stem cell like and might eventually lead to an advantage of Hoxb4 T cells after subjecting the cells to additional rounds of proliferation. PMID:24324706

  20. Chemokines and immunity

    PubMed Central

    Palomino, Diana Carolina Torres; Marti, Luciana Cavalheiro

    2015-01-01

    Chemokines are a large family of small cytokines and generally have low molecular weight ranging from 7 to 15kDa. Chemokines and their receptors are able to control the migration and residence of all immune cells. Some chemokines are considered pro-inflammatory, and their release can be induced during an immune response at a site of infection, while others are considered homeostatic and are involved in controlling of cells migration during tissue development or maintenance. The physiologic importance of this family of mediators is resulting from their specificity − members of the chemokine family induce recruitment of well-defined leukocyte subsets. There are two major chemokine sub-families based upon cysteine residues position: CXC and CC. As a general rule, members of the CXC chemokines are chemotactic for neutrophils, and CC chemokines are chemotactic for monocytes and sub-set of lymphocytes, although there are some exceptions. This review discusses the potential role of chemokines in inflammation focusing on the two best-characterized chemokines: monocyte chemoattractant protein-1, a CC chemokine, and interleukin-8, a member of the CXC chemokine sub-family. PMID:26466066

  1. Oscillating Permanent Magnets.

    ERIC Educational Resources Information Center

    Michaelis, M. M.; Haines, C. M.

    1989-01-01

    Describes several ways to partially levitate permanent magnets. Computes field line geometries and oscillation frequencies. Provides several diagrams illustrating the mechanism of the oscillation. (YP)

  2. Modeling of Age-Dependent Epileptogenesis by Differential Homeostatic Synaptic Scaling.

    PubMed

    González, Oscar C; Krishnan, Giri P; Chauvette, Sylvain; Timofeev, Igor; Sejnowski, Terrence; Bazhenov, Maxim

    2015-09-30

    Homeostatic synaptic plasticity (HSP) has been implicated in the development of hyperexcitability and epileptic seizures following traumatic brain injury (TBI). Our in vivo experimental studies in cats revealed that the severity of TBI-mediated epileptogenesis depends on the age of the animal. To characterize mechanisms of these differences, we studied the properties of the TBI-induced epileptogenesis in a biophysically realistic cortical network model with dynamic ion concentrations. After deafferentation, which was induced by dissection of the afferent inputs, there was a reduction of the network activity and upregulation of excitatory connections leading to spontaneous spike-and-wave type seizures. When axonal sprouting was implemented, the seizure threshold increased in the model of young but not the older animals, which had slower or unidirectional homeostatic processes. Our study suggests that age-related changes in the HSP mechanisms are sufficient to explain the difference in the likelihood of seizure onset in young versus older animals. Significance statement: Traumatic brain injury (TBI) is one of the leading causes of intractable epilepsy. Likelihood of developing epilepsy and seizures following severe brain trauma has been shown to increase with age. Specific mechanisms of TBI-related epileptogenesis and how these mechanisms are affected by age remain to be understood. We test a hypothesis that the failure of homeostatic synaptic regulation, a slow negative feedback mechanism that maintains neural activity within a physiological range through activity-dependent modulation of synaptic strength, in older animals may augment TBI-induced epileptogenesis. Our results provide new insight into understanding this debilitating disorder and may lead to novel avenues for the development of effective treatments of TBI-induced epilepsy.

  3. Modeling of Age-Dependent Epileptogenesis by Differential Homeostatic Synaptic Scaling

    PubMed Central

    González, Oscar C.; Krishnan, Giri P.; Chauvette, Sylvain; Timofeev, Igor; Sejnowski, Terrence

    2015-01-01

    Homeostatic synaptic plasticity (HSP) has been implicated in the development of hyperexcitability and epileptic seizures following traumatic brain injury (TBI). Our in vivo experimental studies in cats revealed that the severity of TBI-mediated epileptogenesis depends on the age of the animal. To characterize mechanisms of these differences, we studied the properties of the TBI-induced epileptogenesis in a biophysically realistic cortical network model with dynamic ion concentrations. After deafferentation, which was induced by dissection of the afferent inputs, there was a reduction of the network activity and upregulation of excitatory connections leading to spontaneous spike-and-wave type seizures. When axonal sprouting was implemented, the seizure threshold increased in the model of young but not the older animals, which had slower or unidirectional homeostatic processes. Our study suggests that age-related changes in the HSP mechanisms are sufficient to explain the difference in the likelihood of seizure onset in young versus older animals. SIGNIFICANCE STATEMENT Traumatic brain injury (TBI) is one of the leading causes of intractable epilepsy. Likelihood of developing epilepsy and seizures following severe brain trauma has been shown to increase with age. Specific mechanisms of TBI-related epileptogenesis and how these mechanisms are affected by age remain to be understood. We test a hypothesis that the failure of homeostatic synaptic regulation, a slow negative feedback mechanism that maintains neural activity within a physiological range through activity-dependent modulation of synaptic strength, in older animals may augment TBI-induced epileptogenesis. Our results provide new insight into understanding this debilitating disorder and may lead to novel avenues for the development of effective treatments of TBI-induced epilepsy. PMID:26424890

  4. ERK Oscillation-Dependent Gene Expression Patterns and Deregulation by Stress-Response

    SciTech Connect

    Waters, Katrina M.; Cummings, Brian S.; Shankaran, Harish; Scholpa, Natalie E.; Weber, Thomas J.

    2014-09-15

    Studies were undertaken to determine whether ERK oscillations regulate a unique subset of genes in human keratinocytes and subsequently, whether the p38 stress response inhibits ERK oscillations. A DNA microarray identified many genes that were unique to ERK oscillations, and network reconstruction predicted an important role for the mediator complex subunit 1 (MED1) node in mediating ERK oscillation-dependent gene expression. Increased ERK-dependent phosphorylation of MED1 was observed in oscillating cells compared to non-oscillating counterparts as validation. Treatment of keratinocytes with a p38 inhibitor (SB203580) increased ERK oscillation amplitudes and MED1 and phospho-MED1 protein levels. Bromate is a probable human carcinogen that activates p38. Bromate inhibited ERK oscillations in human keratinocytes and JB6 cells and induced an increase in phospho-p38 and decrease in phospho-MED1 protein levels. Treatment of normal rat kidney cells and primary salivary gland epithelial cells with bromate decreased phospho-MED1 levels in a reversible fashion upon treatment with p38 inhibitors (SB202190; SB203580). Our results indicate that oscillatory behavior in the ERK pathway alters homeostatic gene regulation patterns and that the cellular response to perturbation may manifest differently in oscillating vs non-oscillating cells.

  5. The physiology of stress and effects on immune health in ruminants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As researchers have continued to explore the complex interactions among stress and production parameters such as growth, feed efficiency, and health, multidisciplinary efforts have emerged leading to a greater understanding of homeostatic regulation. The immune system can be regulated by several dif...

  6. Homeostasis and change: A commentary on Homeostatic Theory of Obesity by David Marks

    PubMed Central

    DiClemente, Carlo C; Delahanty, Janine

    2016-01-01

    This commentary on David Marks’ article on the Homeostatic Theory of Obesity and his Circle of Discontent mechanism for maintaining problematic eating behavior and obesity offers a perspective on the promise and potential of this theory. At the same time, we challenge the author to incorporate more of a process perspective into the theory. This would include greater exploration of how individuals enter and exit this hypothesized Circle of Discontent, how these mechanisms lead to obesity rather than other internalizing or externalizing disorders, and how the interactions among key variables differ for males and females and developmental stages. PMID:28070395

  7. C-terminal Src Kinase Gates Homeostatic Synaptic Plasticity and Regulates Fasciclin II Expression at the Drosophila Neuromuscular Junction

    PubMed Central

    Spring, Ashlyn M.; Brusich, Douglas J.; Frank, C. Andrew

    2016-01-01

    Forms of homeostatic plasticity stabilize neuronal outputs and promote physiologically favorable synapse function. A well-studied homeostatic system operates at the Drosophila melanogaster larval neuromuscular junction (NMJ). At the NMJ, impairment of postsynaptic glutamate receptor activity is offset by a compensatory increase in presynaptic neurotransmitter release. We aim to elucidate how this process operates on a molecular level and is preserved throughout development. In this study, we identified a tyrosine kinase-driven signaling system that sustains homeostatic control of NMJ function. We identified C-terminal Src Kinase (Csk) as a potential regulator of synaptic homeostasis through an RNAi- and electrophysiology-based genetic screen. We found that Csk loss-of-function mutations impaired the sustained expression of homeostatic plasticity at the NMJ, without drastically altering synapse growth or baseline neurotransmission. Muscle-specific overexpression of Src Family Kinase (SFK) substrates that are negatively regulated by Csk also impaired NMJ homeostasis. Surprisingly, we found that transgenic Csk-YFP can support homeostatic plasticity at the NMJ when expressed either in the muscle or in the nerve. However, only muscle-expressed Csk-YFP was able to localize to NMJ structures. By immunostaining, we found that Csk mutant NMJs had dysregulated expression of the Neural Cell Adhesion Molecule homolog Fasciclin II (FasII). By immunoblotting, we found that levels of a specific isoform of FasII were decreased in homeostatically challenged GluRIIA mutant animals–but markedly increased in Csk mutant animals. Additionally, we found that postsynaptic overexpression of FasII from its endogenous locus was sufficient to impair synaptic homeostasis, and genetically reducing FasII levels in Csk mutants fully restored synaptic homeostasis. Based on these data, we propose that Csk and its SFK substrates impinge upon homeostatic control of NMJ function by regulating

  8. Circadian rhythm and the immune response: a review.

    PubMed

    Habbal, O A; Al-Jabri, A A

    2009-01-01

    For long, the immune system has been thought of as an effector mechanism reacting to antigenic challenge with defensive responses designed to eliminate 'foreign' material and return to a standby or surveillance mode. However, the recent concept now supported by substantial evidence suggests that immunity is not effector biased but is also a sensory organ and forms part of an integrated homeostatic network. The bidirectional information flow between the neuroendocrine and immune systems functions to maintain and protect the internal homeostasis of the organism. The paradox of this interwined function is that homeostasis may require the neuroendocrine system to work for or against the immune system, as is the case in infection. Potential dangers necessitate activation of the immune system, and such a response may pose risks to the integrity of the host. This occurs when an overly vigorous response may be detrimental and kill the host, as is the case of toxic shock syndrome. Therefore, the constant monitoring role of the neuroendocrine system to control and, when necessary, regulate the function of the immune system is crucial for the homeostatic integrity of the host. This reciprocity of functional need determines the mode of action to determine the context of a perceived threat and the best way to respond. Any breakdown in this two-way communication may manifest itself in problems such as autoimmunity, septic shock, or chronic infection. In this article, we review our current knowledge of circadian rhythm and its relation to the immune response.

  9. Emerging roles of p53 and other tumour-suppressor genes in immune regulation

    PubMed Central

    Muñoz-Fontela, César; Mandinova, Anna; Aaronson, Stuart A.; Lee, Sam W.

    2017-01-01

    Tumour-suppressor genes are indispensable for the maintenance of genomic integrity. Recently, several of these genes, including p53, PTEN, RB1 and ARF, have been implicated in immune responses and inflammatory diseases. In particular, the p53 tumour-suppressor pathway is involved in crucial aspects of tumour immunology and in homeostatic regulation of immune responses. Other studies have identified roles for p53 in various cellular processes, including metabolism and stem cell maintenance. Here, we discuss the emerging roles of p53 and other tumour-suppressor genes in tumour immunology as well as in additional immunological settings, such as virus infection. This relatively unexplored area could yield important insights into the homeostatic control of immune cells in health and disease, and facilitate the development of more effective immunotherapies. Consequently, tumour-suppressor genes are emerging as potential guardians of immune integrity. PMID:27667712

  10. Sulfur and Nitrogen Limitation in Escherichia coli K-12: Specific Homeostatic Responses

    PubMed Central

    Gyaneshwar, Prasad; Paliy, Oleg; McAuliffe, Jon; Popham, David L.; Jordan, Michael I.; Kustu, Sydney

    2005-01-01

    We determined global transcriptional responses of Escherichia coli K-12 to sulfur (S)- or nitrogen (N)-limited growth in adapted batch cultures and cultures subjected to nutrient shifts. Using two limitations helped to distinguish between nutrient-specific changes in mRNA levels and common changes related to the growth rate. Both homeostatic and slow growth responses were amplified upon shifts. This made detection of these responses more reliable and increased the number of genes that were differentially expressed. We analyzed microarray data in several ways: by determining expression changes after use of a statistical normalization algorithm, by hierarchical and k-means clustering, and by visual inspection of aligned genome images. Using these tools, we confirmed known homeostatic responses to global S limitation, which are controlled by the activators CysB and Cbl, and found that S limitation propagated into methionine metabolism, synthesis of FeS clusters, and oxidative stress. In addition, we identified several open reading frames likely to respond specifically to S availability. As predicted from the fact that the ddp operon is activated by NtrC, synthesis of cross-links between diaminopimelate residues in the murein layer was increased under N-limiting conditions, as was the proportion of tripeptides. Both of these effects may allow increased scavenging of N from the dipeptide d-alanine-d-alanine, the substrate of the Ddp system. PMID:15659685

  11. Homeostatic Plasticity and STDP: Keeping a Neuron's Cool in a Fluctuating World

    PubMed Central

    Watt, Alanna J.; Desai, Niraj S.

    2010-01-01

    Spike-timing-dependent plasticity (STDP) offers a powerful means of forming and modifying neural circuits. Experimental and theoretical studies have demonstrated its potential usefulness for functions as varied as cortical map development, sharpening of sensory receptive fields, working memory, and associative learning. Even so, it is unlikely that STDP works alone. Unless changes in synaptic strength are coordinated across multiple synapses and with other neuronal properties, it is difficult to maintain the stability and functionality of neural circuits. Moreover, there are certain features of early postnatal development (e.g., rapid changes in sensory input) that threaten neural circuit stability in ways that STDP may not be well placed to counter. These considerations have led researchers to investigate additional types of plasticity, complementary to STDP, that may serve to constrain synaptic weights and/or neuronal firing. These are collectively known as “homeostatic plasticity” and include schemes that control the total synaptic strength of a neuron, that modulate its intrinsic excitability as a function of average activity, or that make the ability of synapses to undergo Hebbian modification depend upon their history of use. In this article, we will review the experimental evidence for homeostatic forms of plasticity and consider how they might interact with STDP during development, and learning and memory. PMID:21423491

  12. Homeostatic regulation of adult hippocampal neurogenesis in aging rats: long-term effects of early exercise

    PubMed Central

    Merkley, Christina M.; Jian, Charles; Mosa, Adam; Tan, Yao-Fang; Wojtowicz, J. Martin

    2014-01-01

    Adult neurogenesis is highly responsive to environmental and physiological factors. The majority of studies to date have examined short-term consequences of enhancing or blocking neurogenesis but long-term changes remain less well understood. Current evidence for age-related declines in neurogenesis warrant further investigation into these long-term changes. In this report we address the hypothesis that early life experience, such as a period of voluntary running in juvenile rats, can alter properties of adult neurogenesis for the remainder of the animal's life. The results indicate that the number of proliferating and differentiating neuronal precursors is not altered in runners beyond the initial weeks post-running, suggesting homeostatic regulation of these processes. However, the rate of neuronal maturation and survival during a 4 week period after cell division was enhanced up to 11 months of age (the end of the study period). This study is the first to show that a transient period of physical activity at a young age promotes changes in neurogenesis that persist over the long-term, which is important for our understanding of the modulation of neurogenesis by exercise with age. Functional integration of adult-born neurons within the hippocampus that resist homeostatic regulation with aging, rather than the absolute number of adult-born neurons, may be an essential feature of adult neurogenesis that promotes the maintenance of neural plasticity in old age. PMID:25071426

  13. Activity-dependent, homeostatic regulation of neurotransmitter release from auditory nerve fibers

    PubMed Central

    Ngodup, Tenzin; Goetz, Jack A.; McGuire, Brian C.; Sun, Wei; Lauer, Amanda M.; Xu-Friedman, Matthew A.

    2015-01-01

    Information processing in the brain requires reliable synaptic transmission. High reliability at specialized auditory nerve synapses in the cochlear nucleus results from many release sites (N), high probability of neurotransmitter release (Pr), and large quantal size (Q). However, high Pr also causes auditory nerve synapses to depress strongly when activated at normal rates for a prolonged period, which reduces fidelity. We studied how synapses are influenced by prolonged activity by exposing mice to constant, nondamaging noise and found that auditory nerve synapses changed to facilitating, reflecting low Pr. For mice returned to quiet, synapses recovered to normal depression, suggesting that these changes are a homeostatic response to activity. Two additional properties, Q and average excitatory postsynaptic current (EPSC) amplitude, were unaffected by noise rearing, suggesting that the number of release sites (N) must increase to compensate for decreased Pr. These changes in N and Pr were confirmed physiologically using the integration method. Furthermore, consistent with increased N, endbulbs in noise-reared animals had larger VGlut1-positive puncta, larger profiles in electron micrographs, and more release sites per profile. In current-clamp recordings, noise-reared BCs had greater spike fidelity even during high rates of synaptic activity. Thus, auditory nerve synapses regulate excitability through an activity-dependent, homeostatic mechanism, which could have major effects on all downstream processing. Our results also suggest that noise-exposed bushy cells would remain hyperexcitable for a period after returning to normal quiet conditions, which could have perceptual consequences. PMID:25944933

  14. Brain glycogen decreases with increased periods of wakefulness: implications for homeostatic drive to sleep.

    PubMed

    Kong, Jiming; Shepel, P Nicolas; Holden, Clark P; Mackiewicz, Mirek; Pack, Allan I; Geiger, Jonathan D

    2002-07-01

    Sleep is thought to be restorative in function, but what is restored during sleep is unclear. Here we tested the hypothesis that increased periods of wakefulness will result in decreased levels of glycogen, the principal energy store in brain, and with recovery sleep levels of glycogen will be replenished, thus representing a homeostatic component of sleep drive. Using a high-energy focused microwave irradiation method to kill animals and thereby snap-inactivate glycogen-producing and -metabolizing enzymes, we determined, with accuracy and precision, levels of brain glycogen and showed these levels to decrease significantly by approximately 40% in brains of rats deprived of sleep for 12 or 24 hr. Recovery sleep of 15 hr duration after 12 hr of sleep deprivation reversed the decreases in glycogen. Using a novel histochemical method to stain brain glycogen, we found glycogen to be concentrated in white matter; this finding was confirmed biochemically in white matter dissected from rats killed with microwave irradiation. Levels of glycogen, as determined histochemically, were significantly decreased in gray and white matter with sleep deprivation, and these decreases were reversed with recovery sleep. The observed decreases in levels of brain glycogen may be a consequence of increased wakefulness and/or a component integral to the homeostatic drive to sleep.

  15. Bassoon-disruption slows vesicle replenishment and induces homeostatic plasticity at a CNS synapse

    PubMed Central

    Mendoza Schulz, Alejandro; Jing, Zhizi; María Sánchez Caro, Juan; Wetzel, Friederike; Dresbach, Thomas; Strenzke, Nicola; Wichmann, Carolin; Moser, Tobias

    2014-01-01

    Endbulb of Held terminals of auditory nerve fibers (ANF) transmit auditory information at hundreds per second to bushy cells (BCs) in the anteroventral cochlear nucleus (AVCN). Here, we studied the structure and function of endbulb synapses in mice that lack the presynaptic scaffold bassoon and exhibit reduced ANF input into the AVCN. Endbulb terminals and active zones were normal in number and vesicle complement. Postsynaptic densities, quantal size and vesicular release probability were increased while vesicle replenishment and the standing pool of readily releasable vesicles were reduced. These opposing effects canceled each other out for the first evoked EPSC, which showed unaltered amplitude. We propose that ANF activity deprivation drives homeostatic plasticity in the AVCN involving synaptic upscaling and increased intrinsic BC excitability. In vivo recordings from individual mutant BCs demonstrated a slightly improved response at sound onset compared to ANF, likely reflecting the combined effects of ANF convergence and homeostatic plasticity. Further, we conclude that bassoon promotes vesicular replenishment and, consequently, a large standing pool of readily releasable synaptic vesicles at the endbulb synapse. PMID:24442636

  16. Loss of tolerance to amphetamine-induced hypophagia in rats: homeostatic readjustment vs. instrumental learning.

    PubMed

    Hughes, K M; Popi, L; Wolgin, D L

    1999-09-01

    According to the homeostatic model, the loss of tolerance to amphetamine-induced hypophagia requires a period of unrestricted feeding in the drug-free state, which transforms the compensatory response mediating tolerance ("hyperhunger") into a functional disturbance to homeostasis. In the absence of such a disturbance, tolerance should be retained. To test this prediction, rats tolerant to amphetamine's hypophagic effect were given a 4-week tolerance retention period during which milk intakes were restricted and deprivation levels held relatively constant. During this period the rats were assigned to one of the following drug treatment conditions: 1) saline injections both before and after daily milk tests (saline group); 2) saline injections before, and amphetamine injections after, daily milk tests (after group); 3) no injections and no milk tests (no-treatment group); or 4) amphetamine injections before, and saline injections after, milk tests (before group). Despite the restricted feeding regimen, both the saline and after groups lost tolerance. These results do not support the homeostatic model, but are consistent with the instrumental learning model, which views drinking milk in the undrugged state as analogous to receiving noncontingent reinforcement.

  17. Homeostatic control of synaptic activity by endogenous adenosine is mediated by adenosine kinase.

    PubMed

    Diógenes, Maria José; Neves-Tomé, Raquel; Fucile, Sergio; Martinello, Katiuscia; Scianni, Maria; Theofilas, Panos; Lopatár, Jan; Ribeiro, Joaquim A; Maggi, Laura; Frenguelli, Bruno G; Limatola, Cristina; Boison, Detlev; Sebastião, Ana M

    2014-01-01

    Extracellular adenosine, a key regulator of neuronal excitability, is metabolized by astrocyte-based enzyme adenosine kinase (ADK). We hypothesized that ADK might be an upstream regulator of adenosine-based homeostatic brain functions by simultaneously affecting several downstream pathways. We therefore studied the relationship between ADK expression, levels of extracellular adenosine, synaptic transmission, intrinsic excitability, and brain-derived neurotrophic factor (BDNF)-dependent synaptic actions in transgenic mice underexpressing or overexpressing ADK. We demonstrate that ADK: 1) Critically influences the basal tone of adenosine, evaluated by microelectrode adenosine biosensors, and its release following stimulation; 2) determines the degree of tonic adenosine-dependent synaptic inhibition, which correlates with differential plasticity at hippocampal synapses with low release probability; 3) modulates the age-dependent effects of BDNF on hippocampal synaptic transmission, an action dependent upon co-activation of adenosine A2A receptors; and 4) influences GABAA receptor-mediated currents in CA3 pyramidal neurons. We conclude that ADK provides important upstream regulation of adenosine-based homeostatic function of the brain and that this mechanism is necessary and permissive to synaptic actions of adenosine acting on multiple pathways. These mechanistic studies support previous therapeutic studies and implicate ADK as a promising therapeutic target for upstream control of multiple neuronal signaling pathways crucial for a variety of neurological disorders.

  18. Bassoon-disruption slows vesicle replenishment and induces homeostatic plasticity at a CNS synapse.

    PubMed

    Mendoza Schulz, Alejandro; Jing, Zhizi; Sánchez Caro, Juan María; Wetzel, Friederike; Dresbach, Thomas; Strenzke, Nicola; Wichmann, Carolin; Moser, Tobias

    2014-03-03

    Endbulb of Held terminals of auditory nerve fibers (ANF) transmit auditory information at hundreds per second to bushy cells (BCs) in the anteroventral cochlear nucleus (AVCN). Here, we studied the structure and function of endbulb synapses in mice that lack the presynaptic scaffold bassoon and exhibit reduced ANF input into the AVCN. Endbulb terminals and active zones were normal in number and vesicle complement. Postsynaptic densities, quantal size and vesicular release probability were increased while vesicle replenishment and the standing pool of readily releasable vesicles were reduced. These opposing effects canceled each other out for the first evoked EPSC, which showed unaltered amplitude. We propose that ANF activity deprivation drives homeostatic plasticity in the AVCN involving synaptic upscaling and increased intrinsic BC excitability. In vivo recordings from individual mutant BCs demonstrated a slightly improved response at sound onset compared to ANF, likely reflecting the combined effects of ANF convergence and homeostatic plasticity. Further, we conclude that bassoon promotes vesicular replenishment and, consequently, a large standing pool of readily releasable synaptic vesicles at the endbulb synapse.

  19. Immune Thrombocytopenia

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Immune Thrombocytopenia? Immune thrombocytopenia (THROM-bo-si-toe-PE-ne- ... from one person to another. Types of Immune Thrombocytopenia The two types of ITP are acute (temporary ...

  20. Reinjection laser oscillator and method

    DOEpatents

    McLellan, Edward J.

    1984-01-01

    A uv preionized CO.sub.2 oscillator with integral four-pass amplifier capable of providing 1 to 5 GW laser pulses with pulse widths from 0.1 to 0.5 ns full width at half-maximum (FWHM) is described. The apparatus is operated at any pressure from 1 atm to 10 atm without the necessity of complex high voltage electronics. The reinjection technique employed gives rise to a compact, efficient system that is particularly immune to alignment instabilities with a minimal amount of hardware and complexity.

  1. The homeostatic regulation of REM sleep: A role for localized expression of brain-derived neurotrophic factor in the brainstem.

    PubMed

    Datta, Subimal; Knapp, Clifford M; Koul-Tiwari, Richa; Barnes, Abigail

    2015-10-01

    Homeostatic regulation of REM sleep plays a key role in neural plasticity and deficits in this process are implicated in the development of many neuropsychiatric disorders. Little is known, however, about the molecular mechanisms that underlie this homeostatic regulation process. This study examined the hypothesis that, during selective REM sleep deprivation (RSD), increased brain-derived neurotrophic factor (BDNF) expression in REM sleep regulating areas is critical for the development of homeostatic drive for REM sleep, as measured by an increase in the number of REM sleep transitions. Rats were assigned to RSD, non-sleep deprived (BSL), or total sleep deprivation (TSD) groups. Physiological recordings were obtained from cortical, hippocampal, and pontine EEG electrodes over a 6h period, in which sleep deprivation occurred during the first 3h. In the RSD, but not the other conditions, homeostatic drive for REM sleep increased progressively. BDNF protein expression was significantly greater in the pedunculopontine tegmentum (PPT) and subcoeruleus nucleus (SubCD) in the RSD as compared to the TSD and BSL groups, areas that regulate REM sleep, but not in the medial preoptic area, which regulates non-REM sleep. There was a significant positive correlation between RSD-induced increases in number of REM sleep episodes and increased BDNF expression in the PPT and SubCD. These increases positively correlated with levels of homeostatic drive for REM sleep. These results, for the first time, suggest that selective RSD-induced increased expression of BDNF in the PPT and SubCD are determinant factors in the development of the homeostatic drive for REM sleep.

  2. Chemical oscillator as a generalized Rayleigh oscillator

    NASA Astrophysics Data System (ADS)

    Ghosh, Shyamolina; Ray, Deb Shankar

    2013-10-01

    We derive the conditions under which a set of arbitrary two dimensional autonomous kinetic equations can be reduced to the form of a generalized Rayleigh oscillator which admits of limit cycle solution. This is based on a linear transformation of field variables which can be found by inspection of the kinetic equations. We illustrate the scheme with the help of several chemical and bio-chemical oscillator models to show how they can be cast as a generalized Rayleigh oscillator.

  3. Allergies and Asthma: Do Atopic Disorders Result from Inadequate Immune Homeostasis arising from Infant Gut Dysbiosis?

    PubMed

    Johnson, Christine C; Ownby, Dennis R

    2016-01-01

    Our global hypothesis is that atopic conditions and asthma develop because an individual's immune system is not able to appropriately resolve inflammation resulting from allergen exposures. We propose that the failure to appropriately down-regulate inflammation and produce a toleragenic state results primarily from less robust immune homeostatic processes rather than from a tendency to over-respond to allergenic stimuli. An individual with lower immune homeostatic capacity is unable to rapidly and completely terminate, on average over time, immune responses to innocuous allergens, increasing risk of allergic disease. A lack of robust homeostasis also increases the risk of other inflammatory conditions, such as prolonged respiratory viral infections and obesity, leading to the common co-occurrence of these conditions. Further, we posit that the development of vigorous immune homeostatic mechanisms is an evolutionary adaptation strongly influenced by both 1) exposure to a diverse maternal microbiota through the prenatal period, labor and delivery, and, 2) an orderly assemblage process of the infant's gut microbiota ecosystem shaped by breastfeeding and early exposure to a wide variety of ingested foods and environmental microbes. This early succession of microbial communities together with early allergen exposures orchestrate the development of an immune system with a robust ability to optimally control inflammatory responses and a lowered risk for atopic disorders.

  4. Thymic involution and immune reconstitution

    PubMed Central

    Lynch, Heather E.; Goldberg, Gabrielle L.; Chidgey, Ann; Van den Brink, Marcel R.M.; Boyd, Richard; Sempowski, Gregory D.

    2009-01-01

    Chronic thymus involution associated with aging results in less efficient T-cell development and decreased emigration of naïve T cells to the periphery. Thymic decline in the aged is linked to increased morbidity and mortality in a wide range of clinical settings. Negative consequences of these effects on global health make it of paramount importance to understand the mechanisms driving thymic involution and homeostatic processes across the lifespan. There is growing evidence that thymus tissue is plastic and that the involution process might be therapeutically halted or reversed. We present here progress on the exploitation of thymosuppressive and thymostimulatory pathways using factors such as keratinocyte growth factor, interleukin 7 or sex steroid ablation for therapeutic thymus restoration and peripheral immune reconstitution in adults. PMID:19540807

  5. Cognitive Workload and Sleep Restriction Interact to Influence Sleep Homeostatic Responses

    PubMed Central

    Goel, Namni; Abe, Takashi; Braun, Marcia E.; Dinges, David F.

    2014-01-01

    Study Objectives: Determine the effects of high versus moderate workload on sleep physiology and neurobehavioral measures, during sleep restriction (SR) and no sleep restriction (NSR) conditions. Design: Ten-night experiment involving cognitive workload and SR manipulations. Setting: Controlled laboratory environment. Participants: Sixty-three healthy adults (mean ± standard deviation: 33.2 ± 8.7 y; 29 females), age 22–50 y. Interventions: Following three baseline 8 h time in bed (TIB) nights, subjects were randomized to one of four conditions: high cognitive workload (HW) + SR; moderate cognitive workload (MW) + SR; HW + NSR; or MW + NSR. SR entailed 5 consecutive nights at 4 h TIB; NSR entailed 5 consecutive nights at 8 h TIB. Subjects received three workload test sessions/day consisting of 15-min preworkload assessments, followed by a 60-min (MW) or 120-min (HW) workload manipulation comprised of visually based cognitive tasks, and concluding with 15-min of postworkload assessments. Experimental nights were followed by two 8-h TIB recovery sleep nights. Polysomnography was collected on baseline night 3, experimental nights 1, 4, and 5, and recovery night 1 using three channels (central, frontal, occipital [C3, Fz, O2]). Measurements and Results: High workload, regardless of sleep duration, increased subjective fatigue and sleepiness (all P < 0.05). In contrast, sleep restriction produced cumulative increases in Psychomotor Vigilance Test (PVT) lapses, fatigue, and sleepiness and decreases in PVT response speed and Maintenance of Wakefulness Test (MWT) sleep onset latencies (all P < 0.05). High workload produced longer sleep onset latencies (P < 0.05, d = 0.63) and less wake after sleep onset (P < 0.05, d = 0.64) than moderate workload. Slow-wave energy—the putative marker of sleep homeostasis—was higher at O2 than C3 only in the HW + SR condition (P < 0.05). Conclusions: High cognitive workload delayed sleep onset, but it also promoted sleep homeostatic

  6. Homeostatic Control of the Thyroid–Pituitary Axis: Perspectives for Diagnosis and Treatment

    PubMed Central

    Hoermann, Rudolf; Midgley, John E. M.; Larisch, Rolf; Dietrich, Johannes W.

    2015-01-01

    The long-held concept of a proportional negative feedback control between the thyroid and pituitary glands requires reconsideration in the light of more recent studies. Homeostatic equilibria depend on dynamic inter-relationships between thyroid hormones and pituitary thyrotropin (TSH). They display a high degree of individuality, thyroid-state-related hierarchy, and adaptive conditionality. Molecular mechanisms involve multiple feedback loops on several levels of organization, different time scales, and varying conditions of their optimum operation, including a proposed feedforward motif. This supports the concept of a dampened response and multistep regulation, making the interactions between TSH, FT4, and FT3 situational and mathematically more complex. As a homeostatically integrated parameter, TSH becomes neither normatively fixed nor a precise marker of euthyroidism. This is exemplified by the therapeutic situation with l-thyroxine (l-T4) where TSH levels defined for optimum health may not apply equivalently during treatment. In particular, an FT3–FT4 dissociation, discernible FT3–TSH disjoint, and conversion inefficiency have been recognized in l-T4-treated athyreotic patients. In addition to regulating T4 production, TSH appears to play an essential role in maintaining T3 homeostasis by directly controlling deiodinase activity. While still allowing for tissue-specific variation, this questions the currently assumed independence of the local T3 supply. Rather it integrates peripheral and central elements into an overarching control system. On l-T4 treatment, altered equilibria have been shown to give rise to lower circulating FT3 concentrations in the presence of normal serum TSH. While data on T3 in tissues are largely lacking in humans, rodent models suggest that the disequilibria may reflect widespread T3 deficiencies at the tissue level in various organs. As a consequence, the use of TSH, valuable though it is in many situations, should be scaled

  7. Synchronization of genetic oscillators

    NASA Astrophysics Data System (ADS)

    Zhou, Tianshou; Zhang, Jiajun; Yuan, Zhanjiang; Chen, Luonan

    2008-09-01

    Synchronization of genetic or cellular oscillators is a central topic in understanding the rhythmicity of living organisms at both molecular and cellular levels. Here, we show how a collective rhythm across a population of genetic oscillators through synchronization-induced intercellular communication is achieved, and how an ensemble of independent genetic oscillators is synchronized by a common noisy signaling molecule. Our main purpose is to elucidate various synchronization mechanisms from the viewpoint of dynamics, by investigating the effects of various biologically plausible couplings, several kinds of noise, and external stimuli. To have a comprehensive understanding on the synchronization of genetic oscillators, we consider three classes of genetic oscillators: smooth oscillators (exhibiting sine-like oscillations), relaxation oscillators (displaying jump dynamics), and stochastic oscillators (noise-induced oscillation). For every class, we further study two cases: with intercellular communication (including phase-attractive and repulsive coupling) and without communication between cells. We find that an ensemble of smooth oscillators has different synchronization phenomena from those in the case of relaxation oscillators, where noise plays a different but key role in synchronization. To show differences in synchronization between them, we make comparisons in many aspects. We also show that a population of genetic stochastic oscillators have their own synchronization mechanisms. In addition, we present interesting phenomena, e.g., for relaxation-type stochastic oscillators coupled to a quorum-sensing mechanism, different noise intensities can induce different periodic motions (i.e., inhomogeneous limit cycles).

  8. Holographic charge oscillations

    NASA Astrophysics Data System (ADS)

    Blake, Mike; Donos, Aristomenis; Tong, David

    2015-04-01

    The Reissner-Nordström black hole provides the prototypical description of a holographic system at finite density. We study the response of this system to the presence of a local, charged impurity. Below a critical temperature, the induced charge density, which screens the impurity, exhibits oscillations. These oscillations can be traced to the singularities in the density-density correlation function moving in the complex momentum plane. At finite temperature, the oscillations are very similar to the Friedel oscillations seen in Fermi liquids. However, at zero temperature the oscillations in the black hole background remain exponentially damped, while Friedel oscillations relax to a power-law.

  9. The Unfolded Protein Response Plays a Predominant Homeostatic Role in Response to Mitochondrial Stress in Pancreatic Stellate Cells

    PubMed Central

    Su, Hsin-Yuan; Waldron, Richard T.; Gong, Raymond; Ramanujan, V. Krishnan; Pandol, Stephen J.; Lugea, Aurelia

    2016-01-01

    Activated pancreatic stellate cells (PaSC) are key participants in the stroma of pancreatic cancer, secreting extracellular matrix proteins and inflammatory mediators. Tumors are poorly vascularized, creating metabolic stress conditions in cancer and stromal cells that necessitate adaptive homeostatic cellular programs. Activation of autophagy and the endoplasmic reticulum unfolded protein response (UPR) have been described in hepatic stellate cells, but the role of these processes in PaSC responses to metabolic stress is unknown. We reported that the PI3K/mTOR pathway, which AMPK can regulate through multiple inputs, modulates PaSC activation and fibrogenic potential. Here, using primary and immortalized mouse PaSC, we assess the relative contributions of AMPK/mTOR signaling, autophagy and the UPR to cell fate responses during metabolic stress induced by mitochondrial dysfunction. The mitochondrial uncoupler rottlerin at low doses (0.5–2.5 μM) was added to cells cultured in 10% FBS complete media. Mitochondria rapidly depolarized, followed by altered mitochondrial dynamics and decreased cellular ATP levels. This mitochondrial dysfunction elicited rapid, sustained AMPK activation, mTOR pathway inhibition, and blockade of autophagic flux. Rottlerin treatment also induced rapid, sustained PERK/CHOP UPR signaling. Subsequently, high doses (>5 μM) induced loss of cell viability and cell death. Interestingly, AMPK knock-down using siRNA did not prevent rottlerin-induced mTOR inhibition, autophagy, or CHOP upregulation, suggesting that AMPK is dispensable for these responses. Moreover, CHOP genetic deletion, but not AMPK knock-down, prevented rottlerin-induced apoptosis and supported cell survival, suggesting that UPR signaling is a major modulator of cell fate in PaSC during metabolic stress. Further, short-term rottlerin treatment reduced both PaSC fibrogenic potential and IL-6 mRNA expression. In contrast, expression levels of the angiogenic factors HGF and VEGF

  10. Long-Term Homeostatic Properties Complementary to Hebbian Rules in CuPc-Based Multifunctional Memristor

    NASA Astrophysics Data System (ADS)

    Wang, Laiyuan; Wang, Zhiyong; Lin, Jinyi; Yang, Jie; Xie, Linghai; Yi, Mingdong; Li, Wen; Ling, Haifeng; Ou, Changjin; Huang, Wei

    2016-10-01

    Most simulations of neuroplasticity in memristors, which are potentially used to develop artificial synapses, are confined to the basic biological Hebbian rules. However, the simplex rules potentially can induce excessive excitation/inhibition, even collapse of neural activities, because they neglect the properties of long-term homeostasis involved in the frameworks of realistic neural networks. Here, we develop organic CuPc-based memristors of which excitatory and inhibitory conductivities can implement both Hebbian rules and homeostatic plasticity, complementary to Hebbian patterns and conductive to the long-term homeostasis. In another adaptive situation for homeostasis, in thicker samples, the overall excitement under periodic moderate stimuli tends to decrease and be recovered under intense inputs. Interestingly, the prototypes can be equipped with bio-inspired habituation and sensitization functions outperforming the conventional simplified algorithms. They mutually regulate each other to obtain the homeostasis. Therefore, we develop a novel versatile memristor with advanced synaptic homeostasis for comprehensive neural functions.

  11. Long-Term Homeostatic Properties Complementary to Hebbian Rules in CuPc-Based Multifunctional Memristor

    PubMed Central

    Wang, Laiyuan; Wang, Zhiyong; Lin, Jinyi; Yang, Jie; Xie, Linghai; Yi, Mingdong; Li, Wen; Ling, Haifeng; Ou, Changjin; Huang, Wei

    2016-01-01

    Most simulations of neuroplasticity in memristors, which are potentially used to develop artificial synapses, are confined to the basic biological Hebbian rules. However, the simplex rules potentially can induce excessive excitation/inhibition, even collapse of neural activities, because they neglect the properties of long-term homeostasis involved in the frameworks of realistic neural networks. Here, we develop organic CuPc-based memristors of which excitatory and inhibitory conductivities can implement both Hebbian rules and homeostatic plasticity, complementary to Hebbian patterns and conductive to the long-term homeostasis. In another adaptive situation for homeostasis, in thicker samples, the overall excitement under periodic moderate stimuli tends to decrease and be recovered under intense inputs. Interestingly, the prototypes can be equipped with bio-inspired habituation and sensitization functions outperforming the conventional simplified algorithms. They mutually regulate each other to obtain the homeostasis. Therefore, we develop a novel versatile memristor with advanced synaptic homeostasis for comprehensive neural functions. PMID:27762316

  12. Homeostatic Control For A Mobile Robot: Dynamic Replanning In Hazardous Environments

    NASA Astrophysics Data System (ADS)

    Arkin, Ronald C.

    1989-03-01

    A longstanding goal of robotics has been to introduce intelligent machines into environments that are dangerous to humans. These environments also pose hazards to the robots themselves. By embedding sensing devices as a means for monitoring the internal state of the robot, dynamic plan reformulation can occur in situations that threaten the existence of the robot. A method exploiting an analogy to the endocrine control system is forwarded as the preferred method for homeostatic control - the maintenance of a safe internal environment for the machine. Examples are given describing the impact of fuel reserve depletion and global temperature stress. A methodology using signal schemas as a means to supplement the existing motor schema control found in the Autonomous Robot Architecture (AuRA) is presented.

  13. Regulation of human myometrial contractility during pregnancy and labour: are calcium homeostatic pathways important?

    PubMed

    Tribe, R M

    2001-03-01

    If we are to develop new strategies for the treatment and management of preterm and dysfunctional term labour, it is imperative that we improve current understanding of the control of human uterine activity. Despite many studies of animal pregnancy, there is a paucity of knowledge relating to the complex control of human myometrium during pregnancy. It is hypothesized that human myometrium is relatively quiescent during the majority of pregnancy and that as term approaches there is cascade of molecular events that prepare the uterus for labour. This review will consider the cellular mechanisms involved in the regulation of human myometrial activity and the modulation of these by hormonal and mechanical signals. In particular, the contribution of calcium homeostatic pathways to the control of human myometrial contractility during gestation will be discussed. Experimental Physiology (2001) 86.2, 247-254.

  14. Homeostatic study of the effects of sportswear color on the contest outcome

    NASA Astrophysics Data System (ADS)

    Yuan, Jian-Qin; Liu, Timon Cheng-Yi; Wu, Ren-Le; Ruan, Chang-Xiong; He, Li-Mei; Liu, Song-Hao

    2008-12-01

    There are effects of sportswear color on the contest outcome. It has been explained from the psychological and perceptual viewpoints, respectively. It was studied by integrating the homeostatic theory of exercise training and autonomic nervous model of color vision in this paper. It was found that the effects of sportswear color on the contest outcome depend on autonomic nervous homeostasis (ANH). Color can be classified into hot color such as red, orange and yellow and cold color such as green, blue and violet. If the athletes have been in ANH, there are no effects of sportswear color on the contest outcome. If the autonomic nervous system is far from ANH due to exercise induced fatigue, wearing cold color had no predominance for cold-hot matches, and wearing white had no predominance for white-color matches.

  15. Homeostatic regulation of copper in a marine fish simulated by a physiologically based pharmacokinetic model.

    PubMed

    Wang, Xun; Wang, Wen-Xiong

    2016-11-01

    Copper (Cu) is an essential yet potentially toxic metal, thus delicate homeostatic controls are developed in the fish. In this study, a physiologically based pharmacokinetic (PBPK) model was developed to simulate the homeostatic regulation of Cu in a marine fish (Terapon jarbua) under dietary and waterborne exposures. In this model, fish were schematized as a six-compartment model, with the intestine being divided into two sub-compartments (chyme and gut wall). The blood was assumed to be the "carrier" distributing Cu into different compartments. The transfer rates between different compartments were determined in fish during Cu exposure (20 d) and depuration (20 d). The differences in Cu transfer from chyme to gut wall between dietary and waterborne treatments suggested that the intestine regulated the dietary uptake and re-absorption of Cu from the chyme. The extremely low uptake rate constant (0.0013 d(-1)) for gills under waterborne exposure indicated that gills strongly restricted Cu uptake from the ambient water. For both treatments, the liver had considerable input rate through the enterohepatic circulation and comparably high exchange rate with the blood, suggesting that the liver can efficiently accumulate newly absorbed Cu. The differences in Cu output from the liver between dietary and waterborne treatments suggested that it can effectively regulate the redistribution of Cu. All of these observations demonstrated that the liver played the central role in Cu homeostasis by serving as the main depository and distributing center. Modeling results also indicated that renal and branchial excretion was of minor importance, whereas biliary excretion combined with defecation played the most important role in whole-body Cu elimination in marine fish. The effective regulation by the "Blood-Liver-Intestine" cycle could be the main reason for the relatively low levels of Cu in fish.

  16. Reorganization of Sleep by Temperature in Drosophila Requires Light, the Homeostat, and the Circadian Clock.

    PubMed

    Parisky, Katherine M; Agosto Rivera, José L; Donelson, Nathan C; Kotecha, Sejal; Griffith, Leslie C

    2016-04-04

    Increasing ambient temperature reorganizes the Drosophila sleep pattern in a way similar to the human response to heat, increasing daytime sleep while decreasing nighttime sleep. Mutation of core circadian genes blocks the immediate increase in daytime sleep, but not the heat-stimulated decrease in nighttime sleep, when animals are in a light:dark cycle. The ability of per(01) flies to increase daytime sleep in light:dark can be rescued by expression of PER in either LNv or DN1p clock cells and does not require rescue of locomotor rhythms. Prolonged heat exposure engages the homeostat to maintain daytime sleep in the face of nighttime sleep loss. In constant darkness, all genotypes show an immediate decrease in sleep in response to temperature shift during the subjective day, implying that the absence of light input uncovers a clock-independent pro-arousal effect of increased temperature. Interestingly, the effects of temperature on nighttime sleep are blunted in constant darkness and in cry(OUT) mutants in light:dark, suggesting that they are dependent on the presence of light the previous day. In contrast, flies of all genotypes kept in constant light sleep more at all times of day in response to high temperature, indicating that the presence of light can invert the normal nighttime response to increased temperature. The effect of temperature on sleep thus reflects coordinated regulation by light, the homeostat, and components of the clock, allowing animals to reorganize sleep patterns in response to high temperature with rough preservation of the total amount of sleep.

  17. Loss of Homeostatic Gas Exchange in Eastern Hemlock in Response to Pollution and Rising CO2?

    NASA Astrophysics Data System (ADS)

    Rayback, S. A.; Gagen, M. H.; Lini, A.; Cogbill, C. V.

    2014-12-01

    In eastern North American, multiple environmental effects, natural and anthropogenic, may impinge upon tree-ring based stable carbon isotope ratios when examined over long time periods. Investigation of relationships between a Vermont (USA) eastern hemlock δ¹³C (1849-2010) chronology and local and regional climate variables, as well as a regional sulfur dioxide time series revealed the decoupling of δ¹³C from significant climate drivers such as May-August maximum temperature (r=0.50, p<0.01) and, raise the possibility that this decoupling can be attributed to foliar and soil leaching of calcium due to acidic deposition since the 1960s. Further, investigation of derived photosynthetic isotope discrimination (Δ¹³C) time series showed an overall decreasing trend in Δ¹³C in response to rising atmospheric carbon dioxide (ca), but with a slight rise in Δ¹³C in the last decade. Comparison of time series of leaf intercellular CO2 concentration (ci), ci/ca, and intrinsic water use efficiency (iWUE) showed homeostatic maintenance of ci levels against ca until 1965 and rising iWUE. Then, ci increased proportional (1965-2000) and later at the same rate as ca (2001-2010) and iWUE leveled off indicating a potential loss of sensitivity to increasing atmospheric carbon dioxide. This more recent passive response may be an indication of a loss of homeostatic maintenance of stomatal control and/or may be linked to changing climate in the region (e.g., wetter conditions).

  18. Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia.

    PubMed

    Eisenhoffer, George T; Loftus, Patrick D; Yoshigi, Masaaki; Otsuna, Hideo; Chien, Chi-Bin; Morcos, Paul A; Rosenblatt, Jody

    2012-04-15

    For an epithelium to provide a protective barrier, it must maintain homeostatic cell numbers by matching the number of dividing cells with the number of dying cells. Although compensatory cell division can be triggered by dying cells, it is unknown how cell death might relieve overcrowding due to proliferation. When we trigger apoptosis in epithelia, dying cells are extruded to preserve a functional barrier. Extrusion occurs by cells destined to die signalling to surrounding epithelial cells to contract an actomyosin ring that squeezes the dying cell out. However, it is not clear what drives cell death during normal homeostasis. Here we show in human, canine and zebrafish cells that overcrowding due to proliferation and migration induces extrusion of live cells to control epithelial cell numbers. Extrusion of live cells occurs at sites where the highest crowding occurs in vivo and can be induced by experimentally overcrowding monolayers in vitro. Like apoptotic cell extrusion, live cell extrusion resulting from overcrowding also requires sphingosine 1-phosphate signalling and Rho-kinase-dependent myosin contraction, but is distinguished by signalling through stretch-activated channels. Moreover, disruption of a stretch-activated channel, Piezo1, in zebrafish prevents extrusion and leads to the formation of epithelial cell masses. Our findings reveal that during homeostatic turnover, growth and division of epithelial cells on a confined substratum cause overcrowding that leads to their extrusion and consequent death owing to the loss of survival factors. These results suggest that live cell extrusion could be a tumour-suppressive mechanism that prevents the accumulation of excess epithelial cells.

  19. Integrated Immune

    NASA Technical Reports Server (NTRS)

    Crucian, Brian; Mehta, Satish; Stowe, Raymond; Uchakin, Peter; Quiriarte, Heather; Pierson, Duane; Sams, Clarnece

    2010-01-01

    This slide presentation reviews the program to replace several recent studies about astronaut immune systems with one comprehensive study that will include in-flight sampling. The study will address lack of in-flight data to determine the inflight status of immune systems, physiological stress, viral immunity, to determine the clinical risk related to immune dysregulation for exploration class spaceflight, and to determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

  20. Saturation in coupled oscillators

    NASA Astrophysics Data System (ADS)

    Roman, Ahmed; Hanna, James

    2015-03-01

    We consider a weakly nonlinear system consisting of a resonantly forced oscillator coupled to an unforced oscillator. It has long been known that, for quadratic nonlinearities and a 2:1 resonance between the oscillators, a perturbative solution of the dynamics exhibits a phenomenon known as saturation. At low forcing, the forced oscillator responds, while the unforced oscillator is quiescent. Above a critical value of the forcing, the forced oscillator's steady-state amplitude reaches a plateau, while that of the unforced oscillator increases without bound. We show that, contrary to established folklore, saturation is not unique to quadratically nonlinear systems. We present conditions on the form of the nonlinear couplings and resonance that lead to saturation. Our results elucidate a mechanism for localization or diversion of energy in systems of coupled oscillators, and suggest new approaches for the control or suppression of vibrations in engineered systems.

  1. Effect of maternal exposure to ozone on reproductive outcome and immune, inflammatory, and allergic responses in the offspring

    EPA Science Inventory

    There is growing concern that exposure to air pollutants during pregnancy affects health outcomes in the offspring due to alterations in the development of immune and other homeostatic processes. To assess the risks of maternal inhalation exposure to ozone (O3), timed pregnant BA...

  2. The Algebra of Sleepiness: Investigating the Interaction of Homeostatic (S) and Circadian (C) Processes in Sleepiness Using Linear Metrics"

    ERIC Educational Resources Information Center

    Mairesse, Olivier; Hofmans, Joeri; Neu, Daniel; Dinis Monica de Oliveira, Armando Luis; Cluydts, Raymond; Theuns, Peter

    2010-01-01

    The present studies were conducted to contribute to the debate on the interaction between circadian (C) and homeostatic (S) processes in models of sleep regulation. The Two-Process Model of Sleep Regulation assumes a linear relationship between processes S and C. However, recent elaborations of the model, based on data from forced desynchrony…

  3. Tuning pathological brain oscillations with neurofeedback: a systems neuroscience framework

    PubMed Central

    Ros, Tomas; J. Baars, Bernard; Lanius, Ruth A.; Vuilleumier, Patrik

    2014-01-01

    Neurofeedback (NFB) is emerging as a promising technique that enables self-regulation of ongoing brain oscillations. However, despite a rise in empirical evidence attesting to its clinical benefits, a solid theoretical basis is still lacking on the manner in which NFB is able to achieve these outcomes. The present work attempts to bring together various concepts from neurobiology, engineering, and dynamical systems so as to propose a contemporary theoretical framework for the mechanistic effects of NFB. The objective is to provide a firmly neurophysiological account of NFB, which goes beyond traditional behaviorist interpretations that attempt to explain psychological processes solely from a descriptive standpoint whilst treating the brain as a “black box”. To this end, we interlink evidence from experimental findings that encompass a broad range of intrinsic brain phenomena: starting from “bottom-up” mechanisms of neural synchronization, followed by “top-down” regulation of internal brain states, moving to dynamical systems plus control-theoretic principles, and concluding with activity-dependent as well as homeostatic forms of brain plasticity. In support of our framework, we examine the effects of NFB in several brain disorders, including attention-deficit hyperactivity (ADHD) and post-traumatic stress disorder (PTSD). In sum, it is argued that pathological oscillations emerge from an abnormal formation of brain-state attractor landscape(s). The central thesis put forward is that NFB tunes brain oscillations toward a homeostatic set-point which affords an optimal balance between network flexibility and stability (i.e., self-organised criticality (SOC)). PMID:25566028

  4. Tuning pathological brain oscillations with neurofeedback: a systems neuroscience framework.

    PubMed

    Ros, Tomas; J Baars, Bernard; Lanius, Ruth A; Vuilleumier, Patrik

    2014-01-01

    Neurofeedback (NFB) is emerging as a promising technique that enables self-regulation of ongoing brain oscillations. However, despite a rise in empirical evidence attesting to its clinical benefits, a solid theoretical basis is still lacking on the manner in which NFB is able to achieve these outcomes. The present work attempts to bring together various concepts from neurobiology, engineering, and dynamical systems so as to propose a contemporary theoretical framework for the mechanistic effects of NFB. The objective is to provide a firmly neurophysiological account of NFB, which goes beyond traditional behaviorist interpretations that attempt to explain psychological processes solely from a descriptive standpoint whilst treating the brain as a "black box". To this end, we interlink evidence from experimental findings that encompass a broad range of intrinsic brain phenomena: starting from "bottom-up" mechanisms of neural synchronization, followed by "top-down" regulation of internal brain states, moving to dynamical systems plus control-theoretic principles, and concluding with activity-dependent as well as homeostatic forms of brain plasticity. In support of our framework, we examine the effects of NFB in several brain disorders, including attention-deficit hyperactivity (ADHD) and post-traumatic stress disorder (PTSD). In sum, it is argued that pathological oscillations emerge from an abnormal formation of brain-state attractor landscape(s). The central thesis put forward is that NFB tunes brain oscillations toward a homeostatic set-point which affords an optimal balance between network flexibility and stability (i.e., self-organised criticality (SOC)).

  5. Narrowing of the linewidth of an optical parametric oscillator by an acousto-optic modulator for the realization of mid-IR noise-immune cavity-enhanced optical heterodyne molecular spectrometry down to 10⁻¹⁰ cm⁻¹ Hz⁻¹/².

    PubMed

    Hausmaninger, Thomas; Silander, Isak; Axner, Ove

    2015-12-28

    The linewidth of a singly resonant optical parametric oscillator (OPO) has been narrowed with respect to an external cavity by the use of an acousto-optic modulator (AOM). This made possible an improvement of the sensitivity of a previously realized OPO-based noise-immune cavity-enhanced optical heterodyne molecular spectrometry instrument for the 3.2 - 3.9 µm mid-infrared region by one order of magnitude. The resulting system shows a detection sensitivity for methane of 2.4 × 10(-10) cm(-1) Hz(-1∕2) and 1.3 × 10(-10) cm(-1) at 20 s, which allows for detection of both the environmentally important (13)CH(4) and CH(3)D isotopologues in atmospheric samples.

  6. Covariant harmonic oscillators and coupled harmonic oscillators

    NASA Technical Reports Server (NTRS)

    Han, Daesoo; Kim, Young S.; Noz, Marilyn E.

    1995-01-01

    It is shown that the system of two coupled harmonic oscillators shares the basic symmetry properties with the covariant harmonic oscillator formalism which provides a concise description of the basic features of relativistic hadronic features observed in high-energy laboratories. It is shown also that the coupled oscillator system has the SL(4,r) symmetry in classical mechanics, while the present formulation of quantum mechanics can accommodate only the Sp(4,r) portion of the SL(4,r) symmetry. The possible role of the SL(4,r) symmetry in quantum mechanics is discussed.

  7. SHOCK-EXCITED OSCILLATOR

    DOEpatents

    Creveling, R.

    1957-12-17

    S> A shock-excited quartz crystal oscillator is described. The circuit was specifically designed for application in micro-time measuring work to provide an oscillator which immediately goes into oscillation upon receipt of a trigger pulse and abruptly ceases oscillation when a second pulse is received. To achieve the instant action, the crystal has a prestressing voltage applied across it. A monostable multivibrator receives the on and off trigger pulses and discharges a pulse through the crystal to initiate or terminate oscillation instantly.

  8. Immunization Coverage

    MedlinePlus

    ... and afford to pay for them. World Immunization Week The last week of April each year is marked by WHO and partners as World Immunization Week. It aims to accelerate action to increase awareness ...

  9. Nature's Autonomous Oscillators

    NASA Technical Reports Server (NTRS)

    Mayr, H. G.; Yee, J.-H.; Mayr, M.; Schnetzler, R.

    2012-01-01

    Nonlinearity is required to produce autonomous oscillations without external time dependent source, and an example is the pendulum clock. The escapement mechanism of the clock imparts an impulse for each swing direction, which keeps the pendulum oscillating at the resonance frequency. Among nature's observed autonomous oscillators, examples are the quasi-biennial oscillation and bimonthly oscillation of the Earth atmosphere, and the 22-year solar oscillation. The oscillations have been simulated in numerical models without external time dependent source, and in Section 2 we summarize the results. Specifically, we shall discuss the nonlinearities that are involved in generating the oscillations, and the processes that produce the periodicities. In biology, insects have flight muscles, which function autonomously with wing frequencies that far exceed the animals' neural capacity; Stretch-activation of muscle contraction is the mechanism that produces the high frequency oscillation of insect flight, discussed in Section 3. The same mechanism is also invoked to explain the functioning of the cardiac muscle. In Section 4, we present a tutorial review of the cardio-vascular system, heart anatomy, and muscle cell physiology, leading up to Starling's Law of the Heart, which supports our notion that the human heart is also a nonlinear oscillator. In Section 5, we offer a broad perspective of the tenuous links between the fluid dynamical oscillators and the human heart physiology.

  10. No warmup crystal oscillator

    NASA Technical Reports Server (NTRS)

    Phillips, D. H.

    1982-01-01

    During warmup, crystal oscillators often show a frequency offset as large as 1 part in 10 to the 5th power. If timing information is transferred to the oscillator and then the oscillator is allowed to warmup, a timing error greater than 1 millisecond will occur. For many applications, it is unsuitable to wait for the oscillator to warmup. For medium accuracy timing requirements where overall accuracies in the order of 1 millisecond are required, a no warmup crystal concept was developed. The concept utilizes two crystal oscillator, used sequentially to avoid using a crystal oscillator for timing much higher frequency accuracy once warmed up. The accuracy achieved with practical TCXOs at initial start over a range of temperatures is discussed. A second design utilizing two oven controlled oscillators is also discussed.

  11. Non-linear oscillations

    NASA Astrophysics Data System (ADS)

    Hagedorn, P.

    The mathematical pendulum is used to provide a survey of free and forced oscillations in damped and undamped systems. This simple model is employed to present illustrations for and comparisons between the various approximation schemes. A summary of the Liapunov stability theory is provided. The first and the second method of Liapunov are explained for autonomous as well as for nonautonomous systems. Here, a basic familiarity with the theory of linear oscillations is assumed. La Salle's theorem about the stability of invariant domains is explained in terms of illustrative examples. Self-excited oscillations are examined, taking into account such oscillations in mechanical and electrical systems, analytical approximation methods for the computation of self-excited oscillations, analytical criteria for the existence of limit cycles, forced oscillations in self-excited systems, and self-excited oscillations in systems with several degrees of freedom. Attention is given to Hamiltonian systems and an introduction to the theory of optimal control is provided.

  12. Neural reflexes in inflammation and immunity

    PubMed Central

    2012-01-01

    The mammalian immune system and the nervous system coevolved under the influence of infection and sterile injury. Knowledge of homeostatic mechanisms by which the nervous system controls organ function was originally applied to the cardiovascular, gastrointestinal, musculoskeletal, and other body systems. Development of advanced neurophysiological and immunological techniques recently enabled the study of reflex neural circuits that maintain immunological homeostasis, and are essential for health in mammals. Such reflexes are evolutionarily ancient, dating back to invertebrate nematode worms that possess primitive immune and nervous systems. Failure of these reflex mechanisms in mammals contributes to nonresolving inflammation and disease. It is also possible to target these neural pathways using electrical nerve stimulators and pharmacological agents to hasten the resolution of inflammation and provide therapeutic benefit. PMID:22665702

  13. Homeostatic Cytokines Induce CD4 Downregulation in African Green Monkeys Independently of Antigen Exposure To Generate Simian Immunodeficiency Virus-Resistant CD8αα T Cells

    PubMed Central

    Perkins, Molly R.; Briant, Judith A.; Calantone, Nina; Whitted, Sonya; Vinton, Carol L.; Klatt, Nichole R.; Ourmanov, Ilnour; Ortiz, Alexandra M.; Hirsch, Vanessa M.

    2014-01-01

    ABSTRACT African green monkeys (AGMs; genus Chlorocebus) are a natural host of simian immunodeficiency virus (SIVAGM). As they do not develop simian AIDS, there is great interest in understanding how this species has evolved to avoid immunodeficiency. Adult African green monkeys naturally have low numbers of CD4 T cells and a large population of major histocompatibility complex class II-restricted CD8αdim T cells that are generated through CD4 downregulation in CD4+ T cells. Mechanisms that drive this process of CD4 downregulation are unknown. Here, we show that juvenile AGMs accelerate CD4-to-CD8αα conversion upon SIV infection and avoid progression to AIDS. The CD4 downregulation induced by SIV infection is not limited to SIV-specific T cells, and vaccination of an adult AGM who had a negligible number of CD4 T cells demonstrated that CD4 downregulation can occur without antigenic exposure. Finally, we show that the T cell homeostatic cytokines interleukin-2 (IL-2), IL-7, and IL-15 can induce CD4 downregulation in vitro. These data identify a mechanism that allows AGMs to generate a large, diverse population of T cells that perform CD4 T cell functions but are resistant to SIV infection. A better understanding of this mechanism may allow the development of treatments to induce protective CD4 downregulation in humans. IMPORTANCE Many African primate species are naturally infected with SIV. African green monkeys, one natural host species, avoid simian AIDS by creating a population of T cells that lack CD4, the human immunodeficiency virus/SIV receptor; therefore, they are resistant to infection. However, these T cells maintain properties of CD4+ T cells even after receptor downregulation and preserve immune function. Here, we show that juvenile AGMs, who have not undergone extensive CD4 downregulation, accelerate this process upon SIV infection. Furthermore, we show that in vivo, CD4 downregulation does not occur exclusively in antigen-experienced T cells

  14. Homeostatic maintenance of ponderosa pine gas exchange in response to stand density changes.

    PubMed

    McDowell, Nate G; Adams, Henry D; Bailey, John D; Hess, Marcey; Kolb, Thomas E

    2006-06-01

    Homeostatic maintenance of gas exchange optimizes carbon gain per water loss. Homeostasis is regulated by short-term physiological and long-term structural mechanisms, both of which may respond to changes in resource availability associated with competition. Therefore, stand density regulation via silvicultural manipulations may facilitate growth and survival through mechanisms operating at both short and long timescales. We investigated the responses of ponderosa pine (Pinus ponderosa) to stand basal area manipulations in Arizona, USA. Stand basal area was manipulated to seven replicated levels in 1962 and was maintained for four decades by decadal thinning. We measured basal area increment (BAI) to assess the response and sustainability of wood growth, carbon isotope discrimination (A) inferred from annual rings to assess the response of crown gas exchange, and ratios of leaf area to sapwood area (A(l):A(s)) to assess longer term structural acclimation. Basal area treatments increased soil water potential (r2 = 0.99) but did not affect photosynthetic capacity. BAI increased within two years of thinning, and the 40-year mean BAI was negatively correlated with stand basal area (r2 = 0.98). delta was negatively correlated with stand basal area for years 5 through 12 after thinning (r2 = 0.90). However, delta was relatively invariant with basal area for the period 13-40 years after initial thinning despite maintenance of treatment basal areas via repeated decadal thinnings. Independent gas exchange measurements verified that the ratio of photosynthesis to stomatal conductance was invariant with basal area, but absolute values of both were elevated at lower basal areas. A(l):A(s) was negatively correlated with basal area (r2 = 0.93). We hypothesize that increased A(l):A(s) is a homeostatic response to increased water availability that maximizes water-use efficiency and whole-tree carbon uptake. Elevated A(l):A(s) of trees at low basal areas was associated with greater

  15. Control of local immunity by airway epithelial cells.

    PubMed

    Weitnauer, M; Mijošek, V; Dalpke, A H

    2016-03-01

    The lung is ventilated by thousand liters of air per day. Inevitably, the respiratory system comes into contact with airborne microbial compounds, most of them harmless contaminants. Airway epithelial cells are known to have innate sensor functions, thus being able to detect microbial danger. To avoid chronic inflammation, the pulmonary system has developed specific means to control local immune responses. Even though airway epithelial cells can act as proinflammatory promoters, we propose that under homeostatic conditions airway epithelial cells are important modulators of immune responses in the lung. In this review, we discuss epithelial cell regulatory functions that control reactivity of professional immune cells within the microenvironment of the airways and how these mechanisms are altered in pulmonary diseases. Regulation by epithelial cells can be divided into two mechanisms: (1) mediators regulate epithelial cells' innate sensitivity in cis and (2) factors are produced that limit reactivity of immune cells in trans.

  16. Host cell autophagy in immune response to zoonotic infections.

    PubMed

    Skendros, Panagiotis; Mitroulis, Ioannis

    2012-01-01

    Autophagy is a fundamental homeostatic process in which cytoplasmic targets are sequestered within double-membraned autophagosomes and subsequently delivered to lysosomes for degradation. Accumulating evidence supports the pivotal role of autophagy in host defense against intracellular pathogens implicating both innate and adaptive immunity. Many of these pathogens cause common zoonotic infections worldwide. The induction of the autophagic machinery by innate immune receptors signaling, such as TLRs, NOD1/2, and p62/SQSTM1 in antigen-presenting cells results in inhibition of survival and elimination of invading pathogens. Furthermore, Th1 cytokines induce the autophagic process, whereas autophagy also contributes to antigen processing and MHC class II presentation, linking innate to adaptive immunity. However, several pathogens have developed strategies to avoid autophagy or exploit autophagic machinery to their advantage. This paper focuses on the role of host cell autophagy in the regulation of immune response against intracellular pathogens, emphasizing on selected bacterial and protozoan zoonoses.

  17. Homeostatic model assessment and risk for hypertension during pregnancy: a longitudinal prospective study.

    PubMed

    Romero-Gutiérrez, Gustavo; Malacara, Juan Manuel; Amador, Norma; Fierro-Martínez, César; Muñoz-Guevara, Luis Manuel; Molina-Rodríguez, Roberto

    2004-11-01

    The purpose of this study was to determine the association between insulin resistance and hypertension during pregnancy with the homeostatic model assessment (HOMA-IR). A longitudinal prospective study was carried out. One hundred sixty normotensive pregnant women were followed from the first trimester until delivery. HOMA-IR levels were determined each trimester. Statistical analysis included one-way analysis of variance and multivariate logistic regression. At follow-up, 134 women (83.8%) remained normotensive, 18 (11.2%) developed gestational hypertension, and 8 (5%) developed preeclampsia. At first trimester, HOMA-IR levels were higher in women who developed gestational hypertension (2.1 +/- 0.2) than in women who developed preeclampsia (1.2 +/- 0.0), or remained normotensive (1.2 +/- 0.3); p < 0.01. In the logistic regression analysis, HOMA-IR levels at first trimester were statistically significant ( p = 0.03) to predict development of gestational hypertension. Our results support the use of the HOMA-IR as an alternative index for the assessment of the risk for hypertension during pregnancy.

  18. The Homeostatic Chemokine CCL21 Predicts Mortality in Aortic Stenosis Patients and Modulates Left Ventricular Remodeling

    PubMed Central

    Finsen, Alexandra Vanessa; Ueland, Thor; Sjaastad, Ivar; Ranheim, Trine; Ahmed, Mohammed S.; Dahl, Christen P.; Askevold, Erik T.; Aakhus, Svend; Husberg, Cathrine; Fiane, Arnt E.; Lipp, Martin; Gullestad, Lars; Christensen, Geir; Aukrust, Pål; Yndestad, Arne

    2014-01-01

    Background CCL21 acting through CCR7, is termed a homeostatic chemokine. Based on its role in concerting immunological responses and its proposed involvement in tissue remodeling, we hypothesized that this chemokine could play a role in myocardial remodeling during left ventricular (LV) pressure overload. Methods and Results Our main findings were: (i) Serum levels of CCL21 were markedly raised in patients with symptomatic aortic stenosis (AS, n = 136) as compared with healthy controls (n = 20). (ii) A CCL21 level in the highest tertile was independently associated with all-cause mortality in these patients. (iii) Immunostaining suggested the presence of CCR7 on macrophages, endothelial cells and fibroblasts within calcified human aortic valves. (iv). Mice exposed to LV pressure overload showed enhanced myocardial expression of CCL21 and CCR7 mRNA, and increased CCL21 protein levels. (v) CCR7−/− mice subjected to three weeks of LV pressure overload had similar heart weights compared to wild type mice, but increased LV dilatation and reduced wall thickness. Conclusions Our studies, combining experiments in clinical and experimental LV pressure overload, suggest that CCL21/CCR7 interactions might be involved in the response to pressure overload secondary to AS. PMID:25398010

  19. Retinoic acid receptor regulation of epimorphic and homeostatic regeneration in the axolotl.

    PubMed

    Nguyen, Matthew; Singhal, Pankhuri; Piet, Judith W; Shefelbine, Sandra J; Maden, Malcolm; Voss, S Randal; Monaghan, James R

    2017-02-15

    Salamanders are capable of regenerating amputated limbs by generating a mass of lineage-restricted cells called a blastema. Blastemas only generate structures distal to their origin unless treated with retinoic acid (RA), which results in proximodistal (PD) limb duplications. Little is known about the transcriptional network that regulates PD duplication. In this study, we target specific retinoic acid receptors (RARs) to either PD duplicate (RA treatment or RARγ agonist) or truncate (RARβ antagonist) regenerating limbs. RARE-EGFP reporter axolotls showed divergent reporter activity in limbs undergoing PD duplication versus truncation, suggesting differences in patterning and skeletal regeneration. Transcriptomics identified expression patterns that explain PD duplication, including upregulation of proximal homeobox gene expression and silencing of distal-associated genes, whereas limb truncation was associated with disrupted skeletal differentiation. RARβ antagonism in uninjured limbs induced a loss of skeletal integrity leading to long bone regression and loss of skeletal turnover. Overall, mechanisms were identified that regulate the multifaceted roles of RARs in the salamander limb including regulation of skeletal patterning during epimorphic regeneration, skeletal tissue differentiation during regeneration, and homeostatic regeneration of intact limbs.

  20. Adenosine A(3) receptor agonist acts as a homeostatic regulator of bone marrow hematopoiesis.

    PubMed

    Hofer, Michal; Pospísil, Milan; Znojil, Vladimír; Holá, Jirina; Vacek, Antonín; Streitová, Denisa

    2007-07-01

    The present study was performed to define the optimum conditions of the stimulatory action of the adenosine A(3) receptor agonist, N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA), on bone marrow hematopoiesis in mice. Effects of 2-day treatment with IB-MECA given at single doses of 200nmol/kg twice daily were investigated in normal mice and in mice whose femoral bone marrow cells were either depleted or regenerating after pretreatment with the cytotoxic drug 5-fluorouracil. Morphological criteria were used to determine the proliferation state of the granulocytic and erythroid cell systems. Significant negative correlation between the control proliferation state and the increase of cell proliferation after IB-MECA treatment irrespective of the cell lineage investigated was found. The results suggest the homeostatic character of the induced stimulatory effects and the need to respect the functional state of the target tissue when investigating effects of adenosine receptor agonists under in vivo conditions.

  1. Age-related regulation of genes: slow homeostatic changes and age-dimension technology

    NASA Astrophysics Data System (ADS)

    Kurachi, Kotoku; Zhang, Kezhong; Huo, Jeffrey; Ameri, Afshin; Kuwahara, Mitsuhiro; Fontaine, Jean-Marc; Yamamoto, Kei; Kurachi, Sumiko

    2002-11-01

    Through systematic studies of pro- and anti-blood coagulation factors, we have determined molecular mechanisms involving two genetic elements, age-related stability element (ASE), GAGGAAG and age-related increase element (AIE), a unique stretch of dinucleotide repeats (AIE). ASE and AIE are essential for age-related patterns of stable and increased gene expression patterns, respectively. Such age-related gene regulatory mechanisms are also critical for explaining homeostasis in various physiological reactions as well as slow homeostatic changes in them. The age-related increase expression of the human factor IX (hFIX) gene requires the presence of both ASE and AIE, which apparently function additively. The anti-coagulant factor protein C (hPC) gene uses an ASE (CAGGAG) to produce age-related stable expression. Both ASE sequences (G/CAGAAG) share consensus sequence of the transcriptional factor PEA-3 element. No other similar sequences, including another PEA-3 consensus sequence, GAGGATG, function in conferring age-related gene regulation. The age-regulatory mechanisms involving ASE and AIE apparently function universally with different genes and across different animal species. These findings have led us to develop a new field of research and applications, which we named “age-dimension technology (ADT)”. ADT has exciting potential for modifying age-related expression of genes as well as associated physiological processes, and developing novel, more effective prophylaxis or treatments for age-related diseases.

  2. Homeostatic imbalance between apoptosis and cell renewal in the liver of premature aging Xpd mice.

    PubMed

    Park, Jung Yoon; Cho, Mi-Ook; Leonard, Shanique; Calder, Brent; Mian, I Saira; Kim, Woo Ho; Wijnhoven, Susan; van Steeg, Harry; Mitchell, James; van der Horst, Gijsbertus T J; Hoeijmakers, Jan; Cohen, Pinchas; Vijg, Jan; Suh, Yousin

    2008-06-11

    Unrepaired or misrepaired DNA damage has been implicated as a causal factor in cancer and aging. Xpd(TTD) mice, harboring defects in nucleotide excision repair and transcription due to a mutation in the Xpd gene (R722W), display severe symptoms of premature aging but have a reduced incidence of cancer. To gain further insight into the molecular basis of the mutant-specific manifestation of age-related phenotypes, we used comparative microarray analysis of young and old female livers to discover gene expression signatures distinguishing Xpd(TTD) mice from their age-matched wild type controls. We found a transcription signature of increased apoptosis in the Xpd(TTD) mice, which was confirmed by in situ immunohistochemical analysis and found to be accompanied by increased proliferation. However, apoptosis rate exceeded the rate of proliferation, resulting in homeostatic imbalance. Interestingly, a metabolic response signature was observed involving decreased energy metabolism and reduced IGF-1 signaling, a major modulator of life span. We conclude that while the increased apoptotic response to endogenous DNA damage contributes to the accelerated aging phenotypes and the reduced cancer incidence observed in the Xpd(TTD) mice, the signature of reduced energy metabolism is likely to reflect a compensatory adjustment to limit the increased genotoxic stress in these mutants. These results support a general model for premature aging in DNA repair deficient mice based on cellular responses to DNA damage that impair normal tissue homeostasis.

  3. Imaging of homeostatic, neoplastic, and injured tissues by HA-based probes.

    PubMed

    Veiseh, Mandana; Breadner, Daniel; Ma, Jenny; Akentieva, Natalia; Savani, Rashmin C; Harrison, Rene; Mikilus, David; Collis, Lisa; Gustafson, Stefan; Lee, Ting-Yim; Koropatnick, James; Luyt, Leonard G; Bissell, Mina J; Turley, Eva A

    2012-01-09

    An increase in hyaluronan (HA) synthesis, cellular uptake, and metabolism occurs during the remodeling of tissue microenvironments following injury and during disease processes such as cancer. We hypothesized that multimodality HA-based probes selectively target and detectably accumulate at sites of high HA metabolism, thus providing a flexible imaging strategy for monitoring disease and repair processes. Kinetic analyses confirmed favorable available serum levels of the probe following intravenous (i.v.) or subcutaneous (s.c.) injection. Nuclear (technetium-HA, (99m)Tc-HA, and iodine-HA, (125)I-HA), optical (fluorescent Texas Red-HA, TR-HA), and magnetic resonance (gadolinium-HA, Gd-HA) probes imaged liver ((99m)Tc-HA), breast cancer cells/xenografts (TR-HA, Gd-HA), and vascular injury ((125)I-HA, TR-HA). Targeting of HA probes to these sites appeared to result from selective HA receptor-dependent localization. Our results suggest that HA-based probes, which do not require polysaccharide backbone modification to achieve favorable half-life and distribution, can detect elevated HA metabolism in homeostatic, injured, and diseased tissues.

  4. Antibody-mediated Impairment and Homeostatic Plasticity of Autonomic Ganglionic Synaptic Transmission

    PubMed Central

    Wang, Zhengbei; Low, Phillip A.; Vernino, Steven

    2010-01-01

    Antibodies against ganglionic acetylcholine receptors (AChR) are implicated as the cause of autoimmune autonomic ganglionopathy (AAG). To characterize ganglionic neurotransmission in an animal model of AAG, evoked and spontaneous excitatory post-synaptic potentials (EPSP) were recorded from neurons in isolated mouse superior cervical ganglia (SCG). In vitro exposure of ganglia to IgG from AAG patients progressively inhibited synaptic transmission. After passive transfer of antibody to mice, evoked EPSP amplitude decreased, and some neurons showed no synaptic responses. EPSP amplitude recovered by day seven despite persistence of ganglionic AChR antibody in the mouse serum. There was a more persistent (at least 14 day) reduction in miniature EPSP amplitude consistent with antibody-mediated reduction in post-synaptic AChR. Although the quantal size was reduced, a progressive increase in the frequency of spontaneous synaptic events occurred, suggesting a compensatory increase in presynaptic efficacy. The quantal size returned to baseline by 21 days while the frequency remained increased for at least four weeks. Ganglionic AChR antibodies cause an impairment of autonomic ganglionic synaptic transmission. Homeostatic plasticity in autonomic neurotransmission could help explain the spontaneous clinical recovery seen in some AAG patients and may also play an important role in regulating normal autonomic reflexes. PMID:20044994

  5. Effects of cellular homeostatic intrinsic plasticity on dynamical and computational properties of biological recurrent neural networks.

    PubMed

    Naudé, Jérémie; Cessac, Bruno; Berry, Hugues; Delord, Bruno

    2013-09-18

    Homeostatic intrinsic plasticity (HIP) is a ubiquitous cellular mechanism regulating neuronal activity, cardinal for the proper functioning of nervous systems. In invertebrates, HIP is critical for orchestrating stereotyped activity patterns. The functional impact of HIP remains more obscure in vertebrate networks, where higher order cognitive processes rely on complex neural dynamics. The hypothesis has emerged that HIP might control the complexity of activity dynamics in recurrent networks, with important computational consequences. However, conflicting results about the causal relationships between cellular HIP, network dynamics, and computational performance have arisen from machine-learning studies. Here, we assess how cellular HIP effects translate into collective dynamics and computational properties in biological recurrent networks. We develop a realistic multiscale model including a generic HIP rule regulating the neuronal threshold with actual molecular signaling pathways kinetics, Dale's principle, sparse connectivity, synaptic balance, and Hebbian synaptic plasticity (SP). Dynamic mean-field analysis and simulations unravel that HIP sets a working point at which inputs are transduced by large derivative ranges of the transfer function. This cellular mechanism ensures increased network dynamics complexity, robust balance with SP at the edge of chaos, and improved input separability. Although critically dependent upon balanced excitatory and inhibitory drives, these effects display striking robustness to changes in network architecture, learning rates, and input features. Thus, the mechanism we unveil might represent a ubiquitous cellular basis for complex dynamics in neural networks. Understanding this robustness is an important challenge to unraveling principles underlying self-organization around criticality in biological recurrent neural networks.

  6. Effects of homeostatic constraints on associative memory storage and synaptic connectivity of cortical circuits

    PubMed Central

    Chapeton, Julio; Gala, Rohan; Stepanyants, Armen

    2015-01-01

    The impact of learning and long-term memory storage on synaptic connectivity is not completely understood. In this study, we examine the effects of associative learning on synaptic connectivity in adult cortical circuits by hypothesizing that these circuits function in a steady-state, in which the memory capacity of a circuit is maximal and learning must be accompanied by forgetting. Steady-state circuits should be characterized by unique connectivity features. To uncover such features we developed a biologically constrained, exactly solvable model of associative memory storage. The model is applicable to networks of multiple excitatory and inhibitory neuron classes and can account for homeostatic constraints on the number and the overall weight of functional connections received by each neuron. The results show that in spite of a large number of neuron classes, functional connections between potentially connected cells are realized with less than 50% probability if the presynaptic cell is excitatory and generally a much greater probability if it is inhibitory. We also find that constraining the overall weight of presynaptic connections leads to Gaussian connection weight distributions that are truncated at zero. In contrast, constraining the total number of functional presynaptic connections leads to non-Gaussian distributions, in which weak connections are absent. These theoretical predictions are compared with a large dataset of published experimental studies reporting amplitudes of unitary postsynaptic potentials and probabilities of connections between various classes of excitatory and inhibitory neurons in the cerebellum, neocortex, and hippocampus. PMID:26150784

  7. Sleep inertia, sleep homeostatic, and circadian influences on higher-order cognitive functions

    PubMed Central

    Ronda, Joseph M.; Czeisler, Charles A.; Wright, Kenneth P.

    2016-01-01

    Summary Sleep inertia, sleep homeostatic, and circadian processes modulate cognition, including reaction time, memory, mood, and alertness. How these processes influence higher-order cognitive functions is not well known. Six participants completed a 73-daylong study that included two 14-daylong 28h forced desynchrony protocols, to examine separate and interacting influences of sleep inertia, sleep homeostasis, and circadian phase on higher-order cognitive functions of inhibitory control and selective visual attention. Cognitive performance for most measures was impaired immediately after scheduled awakening and improved over the first ~2-4h of wakefulness (sleep inertia); worsened thereafter until scheduled bedtime (sleep homeostasis); and was worst at ~60° and best at ~240° (circadian modulation, with worst and best phases corresponding to ~9AM and ~9PM respectively, in individuals with a habitual waketime of 7AM). The relative influences of sleep inertia, sleep homeostasis, and circadian phase depended on the specific higher-order cognitive function task examined. Inhibitory control appeared to be modulated most strongly by circadian phase, whereas selective visual attention for a spatial-configuration search task was modulated most strongly by sleep inertia. These findings demonstrate that some higher-order cognitive processes are differentially sensitive to different sleep-wake regulatory processes. Differential modulation of cognitive functions by different sleep-wake regulatory processes has important implications for understanding mechanisms contributing to performance impairments during adverse circadian phases, sleep deprivation, and/or upon awakening from sleep. PMID:25773686

  8. Differential Requirements of TCR Signaling in Homeostatic Maintenance and Function of Dendritic Epidermal T Cells.

    PubMed

    Zhang, Baojun; Wu, Jianxuan; Jiao, Yiqun; Bock, Cheryl; Dai, Meifang; Chen, Benny; Chao, Nelson; Zhang, Weiguo; Zhuang, Yuan

    2015-11-01

    Dendritic epidermal T cells (DETCs) are generated exclusively in the fetal thymus and maintained in the skin epithelium throughout postnatal life of the mouse. DETCs have restricted antigenic specificity as a result of their exclusive usage of a canonical TCR. Although the importance of the TCR in DETC development has been well established, the exact role of TCR signaling in DETC homeostasis and function remains incompletely defined. In this study, we investigated TCR signaling in fully matured DETCs by lineage-restricted deletion of the Lat gene, an essential signaling molecule downstream of the TCR. We found that Lat deletion impaired TCR-dependent cytokine gene activation and the ability of DETCs to undergo proliferative expansion. However, linker for activation of T cells-deficient DETCs were able to maintain long-term population homeostasis, although with a reduced proliferation rate. Mice with Lat deletion in DETCs exhibited delayed wound healing accompanied by impaired clonal expansion within the wound area. Our study revealed differential requirements for TCR signaling in homeostatic maintenance of DETCs and in their effector function during wound healing.

  9. A homeostatic-driven turnover remodelling constitutive model for healing in soft tissues.

    PubMed

    Comellas, Ester; Gasser, T Christian; Bellomo, Facundo J; Oller, Sergio

    2016-03-01

    Remodelling of soft biological tissue is characterized by interacting biochemical and biomechanical events, which change the tissue's microstructure, and, consequently, its macroscopic mechanical properties. Remodelling is a well-defined stage of the healing process, and aims at recovering or repairing the injured extracellular matrix. Like other physiological processes, remodelling is thought to be driven by homeostasis, i.e. it tends to re-establish the properties of the uninjured tissue. However, homeostasis may never be reached, such that remodelling may also appear as a continuous pathological transformation of diseased tissues during aneurysm expansion, for example. A simple constitutive model for soft biological tissues that regards remodelling as homeostatic-driven turnover is developed. Specifically, the recoverable effective tissue damage, whose rate is the sum of a mechanical damage rate and a healing rate, serves as a scalar internal thermodynamic variable. In order to integrate the biochemical and biomechanical aspects of remodelling, the healing rate is, on the one hand, driven by mechanical stimuli, but, on the other hand, subjected to simple metabolic constraints. The proposed model is formulated in accordance with continuum damage mechanics within an open-system thermodynamics framework. The numerical implementation in an in-house finite-element code is described, particularized for Ogden hyperelasticity. Numerical examples illustrate the basic constitutive characteristics of the model and demonstrate its potential in representing aspects of remodelling of soft tissues. Simulation results are verified for their plausibility, but also validated against reported experimental data.

  10. Deletion of a kinesin I motor unmasks a mechanism of homeostatic branching control by neurotrophin-3

    PubMed Central

    Auer, Thomas O; Xiao, Tong; Bercier, Valerie; Gebhardt, Christoph; Duroure, Karine; Concordet, Jean-Paul; Wyart, Claire; Suster, Maximiliano; Kawakami, Koichi; Wittbrodt, Joachim; Baier, Herwig; Del Bene, Filippo

    2015-01-01

    Development and function of highly polarized cells such as neurons depend on microtubule-associated intracellular transport, but little is known about contributions of specific molecular motors to the establishment of synaptic connections. In this study, we investigated the function of the Kinesin I heavy chain Kif5aa during retinotectal circuit formation in zebrafish. Targeted disruption of Kif5aa does not affect retinal ganglion cell differentiation, and retinal axons reach their topographically correct targets in the tectum, albeit with a delay. In vivo dynamic imaging showed that anterograde transport of mitochondria is impaired, as is synaptic transmission. Strikingly, disruption of presynaptic activity elicits upregulation of Neurotrophin-3 (Ntf3) in postsynaptic tectal cells. This in turn promotes exuberant branching of retinal axons by signaling through the TrkC receptor (Ntrk3). Thus, our study has uncovered an activity-dependent, retrograde signaling pathway that homeostatically controls axonal branching. DOI: http://dx.doi.org/10.7554/eLife.05061.001 PMID:26076409

  11. Circadian and homeostatic regulation of structural synaptic plasticity in hypocretin neurons.

    PubMed

    Appelbaum, Lior; Wang, Gordon; Yokogawa, Tohei; Skariah, Gemini M; Smith, Stephen J; Mourrain, Philippe; Mignot, Emmanuel

    2010-10-06

    Neurons exhibit rhythmic activity that ultimately affects behavior such as sleep. In living zebrafish larvae, we used time-lapse two-photon imaging of the presynaptic marker synaptophysin in hypocretin/orexin (HCRT) neurons to determine the dynamics of synaptic modifications during the day and night. We observed circadian rhythmicity in synapse number in HCRT axons. This rhythm is regulated primarily by the circadian clock but is also affected by sleep deprivation. Furthermore, NPTX2, a protein implicated in AMPA receptor clustering, modulates circadian synaptic changes. In zebrafish, nptx2b is a rhythmic gene that is mostly expressed in hypothalamic and pineal gland cells. Arrhythmic transgenic nptx2b overexpression (hcrt:NPTX2b) increases synapse number and abolishes rhythmicity in HCRT axons. Finally, hcrt:NPTX2b fish are resistant to the sleep-promoting effects of melatonin. This behavioral effect is consistent with NPTX2b-mediated increased activity of HCRT circuitry. These data provide real-time in vivo evidence of circadian and homeostatic regulation of structural synaptic plasticity.

  12. Identification of cutoff points for Homeostatic Model Assessment for Insulin Resistance index in adolescents: systematic review

    PubMed Central

    de Andrade, Maria Izabel Siqueira; Oliveira, Juliana Souza; Leal, Vanessa Sá; da Lima, Niedja Maria Silva; Costa, Emília Chagas; de Aquino, Nathalia Barbosa; de Lira, Pedro Israel Cabral

    2016-01-01

    Abstract Objective: To identify cutoff points of the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index established for adolescents and discuss their applicability for the diagnosis of insulin resistance in Brazilian adolescents. Data source: A systematic review was performed in the PubMed, Lilacs and SciELO databases, using the following descriptors: "adolescents", "insulin resistance" and "Receiver Operating Characteristics Curve". Original articles carried out with adolescents published between 2005 and 2015 in Portuguese, English or Spanish languages, which included the statistical analysis using Receiver Operating Characteristics Curve to determine the index cutoff (HOMA-IR) were included. Data synthesis: A total of 184 articles were identified and after the study phases were applied, seven articles were selected for the review. All selected studies established their cutoffs using a Receiver Operating Characteristics Curve, with the lowest observed cutoff of 1.65 for girls and 1.95 for boys and the highest of 3.82 for girls and 5.22 for boys. Of the studies analyzed, one proposed external validity, recommending the use of the HOMA-IR cutoff>2.5 for both genders. Conclusions: The HOMA-IR index constitutes a reliable method for the detection of insulin resistance in adolescents, as long as it uses cutoffs that are more adequate for the reality of the study population, allowing early diagnosis of insulin resistance and enabling multidisciplinary interventions aiming at health promotion of this population. PMID:26559605

  13. Homeostatic maintenance via degradation and repair of elastic fibers under tension

    PubMed Central

    Alves, Calebe; Araújo, Ascanio D.; Oliveira, Cláudio L. N.; Imsirovic, Jasmin; Bartolák-Suki, Erzsébet; Andrade, José S.; Suki, Béla

    2016-01-01

    Cellular maintenance of the extracellular matrix requires an effective regulation that balances enzymatic degradation with the repair of collagen fibrils and fibers. Here, we investigate the long-term maintenance of elastic fibers under tension combined with diffusion of general degradative and regenerative particles associated with digestion and repair processes. Computational results show that homeostatic fiber stiffness can be achieved by assuming that cells periodically probe fiber stiffness to adjust the production and release of degradative and regenerative particles. However, this mechanism is unable to maintain a homogeneous fiber. To account for axial homogeneity, we introduce a robust control mechanism that is locally governed by how the binding affinity of particles is modulated by mechanical forces applied to the ends of the fiber. This model predicts diameter variations along the fiber that are in agreement with the axial distribution of collagen fibril diameters obtained from scanning electron microscopic images of normal rat thoracic aorta. The model predictions match the experiments only when the applied force on the fiber is in the range where the variance of local stiffness along the fiber takes a minimum value. Our model thus predicts that the biophysical properties of the fibers play an important role in the long-term regulatory maintenance of these fibers. PMID:27279029

  14. Homeostatic maintenance via degradation and repair of elastic fibers under tension.

    PubMed

    Alves, Calebe; Araújo, Ascanio D; Oliveira, Cláudio L N; Imsirovic, Jasmin; Bartolák-Suki, Erzsébet; Andrade, José S; Suki, Béla

    2016-06-09

    Cellular maintenance of the extracellular matrix requires an effective regulation that balances enzymatic degradation with the repair of collagen fibrils and fibers. Here, we investigate the long-term maintenance of elastic fibers under tension combined with diffusion of general degradative and regenerative particles associated with digestion and repair processes. Computational results show that homeostatic fiber stiffness can be achieved by assuming that cells periodically probe fiber stiffness to adjust the production and release of degradative and regenerative particles. However, this mechanism is unable to maintain a homogeneous fiber. To account for axial homogeneity, we introduce a robust control mechanism that is locally governed by how the binding affinity of particles is modulated by mechanical forces applied to the ends of the fiber. This model predicts diameter variations along the fiber that are in agreement with the axial distribution of collagen fibril diameters obtained from scanning electron microscopic images of normal rat thoracic aorta. The model predictions match the experiments only when the applied force on the fiber is in the range where the variance of local stiffness along the fiber takes a minimum value. Our model thus predicts that the biophysical properties of the fibers play an important role in the long-term regulatory maintenance of these fibers.

  15. Imaging of Homeostatic, Neoplastic, and Injured Tissues by HA-Based Probes

    PubMed Central

    Veiseh, Mandana; Breadner, Daniel; Ma, Jenny; Akentieva, Natalia; Savani, Rashmin C; Harrison, Rene; Mikilus, David; Collis, Lisa; Gustafson, Stefan; Lee, Ting-Yim; Koropatnick, James; Luyt, Leonard G.; Bissell, Mina J.; Turley, Eva A.

    2013-01-01

    An increase in hyaluronan (HA) synthesis, cellular uptake, and metabolism occurs during the remodeling of tissue microenvironments following injury and during disease processes such as cancer. We hypothesized that multimodality HA-based probes selectively target and detectably accumulate at sites of high HA metabolism, thus providing a flexible imaging strategy for monitoring disease and repair processes. Kinetic analyses confirmed favorable available serum levels of the probe following intravenous (i.v.) or subcutaneous (s.c.) injection. Nuclear (technetium-HA, 99mTc-HA, and iodine-HA, 125I-HA), optical (fluorescent Texas Red-HA, TR-HA), and magnetic resonance (gadolinium-HA, Gd-HA) probes imaged liver (99mTc-HA), breast cancer cells/xenografts (TR-HA, Gd-HA), and vascular injury (125I-HA, TR-HA). Targeting of HA probes to these sites appeared to result from selective HA receptor-dependent localization. Our results suggest that HA-based probes, which do not require polysaccharide backbone modification to achieve favorable half-life and distribution, can detect elevated HA metabolism in homeostatic, injured, and diseased tissues. PMID:22066590

  16. Homeostatic maintenance via degradation and repair of elastic fibers under tension

    NASA Astrophysics Data System (ADS)

    Alves, Calebe; Araújo, Ascanio D.; Oliveira, Cláudio L. N.; Imsirovic, Jasmin; Bartolák-Suki, Erzsébet; Andrade, José S.; Suki, Béla

    2016-06-01

    Cellular maintenance of the extracellular matrix requires an effective regulation that balances enzymatic degradation with the repair of collagen fibrils and fibers. Here, we investigate the long-term maintenance of elastic fibers under tension combined with diffusion of general degradative and regenerative particles associated with digestion and repair processes. Computational results show that homeostatic fiber stiffness can be achieved by assuming that cells periodically probe fiber stiffness to adjust the production and release of degradative and regenerative particles. However, this mechanism is unable to maintain a homogeneous fiber. To account for axial homogeneity, we introduce a robust control mechanism that is locally governed by how the binding affinity of particles is modulated by mechanical forces applied to the ends of the fiber. This model predicts diameter variations along the fiber that are in agreement with the axial distribution of collagen fibril diameters obtained from scanning electron microscopic images of normal rat thoracic aorta. The model predictions match the experiments only when the applied force on the fiber is in the range where the variance of local stiffness along the fiber takes a minimum value. Our model thus predicts that the biophysical properties of the fibers play an important role in the long-term regulatory maintenance of these fibers.

  17. Paradoxes of neutrino oscillations

    SciTech Connect

    Akhmedov, E. Kh.; Smirnov, A. Yu.

    2009-08-15

    Despite the theory of neutrino oscillations being rather old, some of its basic issues are still being debated in the literature. We discuss a number of such issues, including the relevance of the 'same energy' and 'same momentum' assumptions, the role of quantum-mechanical uncertainty relations in neutrino oscillations, the dependence of the coherence and localization conditions that ensure the observability of neutrino oscillations on neutrino energy and momentum uncertainties, the question of (in)dependence of the oscillation probabilities on the neutrino production and detection processes, and the applicability limits of the stationary-source approximation. We also develop a novel approach to calculation of the oscillation probability in the wave-packet approach, based on the summation/integration conventions different from the standard one, which allows a new insight into the 'same energy' vs. 'same momentum' problem. We also discuss a number of apparently paradoxical features of the theory of neutrino oscillations.

  18. Peptidoglycan: a critical activator of the mammalian immune system during infection and homeostasis.

    PubMed

    Sorbara, Matthew T; Philpott, Dana J

    2011-09-01

    Peptidoglycan is a conserved structural component of the bacterial cell wall with molecular motifs unique to bacteria. The mammalian immune system takes advantage of these properties and has evolved to recognize this microbial associated molecular pattern. Mammals have four secreted peptidoglycan recognition proteins, PGLYRP-1-4, as well as two intracellular sensors of peptidoglycan, Nod1 and Nod2. Recognition of peptidoglycan is important in initiating and shaping the immune response under both homeostatic and infection conditions. During infection, peptidoglycan recognition drives both cell-autonomous and whole-organism defense responses. Here, we examine recent advances in the understanding of how peptidoglycan recognition shapes mammalian immune responses in these diverse contexts.

  19. Oscillations in stellar atmospheres

    NASA Technical Reports Server (NTRS)

    Costa, A.; Ringuelet, A. E.; Fontenla, J. M.

    1989-01-01

    Atmospheric excitation and propagation of oscillations are analyzed for typical pulsating stars. The linear, plane-parallel approach for the pulsating atmosphere gives a local description of the phenomenon. From the local analysis of oscillations, the minimum frequencies are obtained for radially propagating waves. The comparison of the minimum frequencies obtained for a variety of stellar types is in good agreement with the observed periods of the oscillations. The role of the atmosphere in the globar stellar pulsations is thus emphasized.

  20. Workshop on Harmonic Oscillators

    NASA Technical Reports Server (NTRS)

    Han, D. (Editor); Kim, Y. S. (Editor); Zachary, W. W. (Editor)

    1993-01-01

    Proceedings of a workshop on Harmonic Oscillators held at the College Park Campus of the University of Maryland on March 25 - 28, 1992 are presented. The harmonic oscillator formalism is playing an important role in many branches of physics. This is the simplest mathematical device which can connect the basic principle of physics with what is observed in the real world. The harmonic oscillator is the bridge between pure and applied physics.

  1. Self-oscillation

    NASA Astrophysics Data System (ADS)

    Jenkins, Alejandro

    2013-04-01

    Physicists are very familiar with forced and parametric resonance, but usually not with self-oscillation, a property of certain dynamical systems that gives rise to a great variety of vibrations, both useful and destructive. In a self-oscillator, the driving force is controlled by the oscillation itself so that it acts in phase with the velocity, causing a negative damping that feeds energy into the vibration: no external rate needs to be adjusted to the resonant frequency. The famous collapse of the Tacoma Narrows bridge in 1940, often attributed by introductory physics texts to forced resonance, was actually a self-oscillation, as was the swaying of the London Millennium Footbridge in 2000. Clocks are self-oscillators, as are bowed and wind musical instruments. The heart is a “relaxation oscillator”, i.e., a non-sinusoidal self-oscillator whose period is determined by sudden, nonlinear switching at thresholds. We review the general criterion that determines whether a linear system can self-oscillate. We then describe the limiting cycles of the simplest nonlinear self-oscillators, as well as the ability of two or more coupled self-oscillators to become spontaneously synchronized (“entrained”). We characterize the operation of motors as self-oscillation and prove a theorem about their limit efficiency, of which Carnot’s theorem for heat engines appears as a special case. We briefly discuss how self-oscillation applies to servomechanisms, Cepheid variable stars, lasers, and the macroeconomic business cycle, among other applications. Our emphasis throughout is on the energetics of self-oscillation, often neglected by the literature on nonlinear dynamical systems.

  2. Interactions between synaptic homeostatic mechanisms: an attempt to reconcile BCM theory, synaptic scaling, and changing excitation/inhibition balance.

    PubMed

    Keck, Tara; Hübener, Mark; Bonhoeffer, Tobias

    2017-02-22

    Homeostatic plasticity is proposed to be mediated by synaptic changes, such as synaptic scaling and shifts in the excitation/inhibition balance. These mechanisms are thought to be separate from the Bienenstock, Cooper, Munro (BCM) learning rule, where the threshold for the induction of long-term potentiation and long-term depression slides in response to changes in activity levels. Yet, both sets of mechanisms produce a homeostatic response of a relative increase (or decrease) in strength of excitatory synapses in response to overall activity-level changes. Here we review recent studies, with a focus on in vivo experiments, to re-examine the overlap and differences between these two mechanisms and we suggest how they may interact to facilitate firing-rate homeostasis, while maintaining functional properties of neurons.

  3. The interaction of meal-related, rhythmic and homeostatic mechanisms and the generation of thirst and drinking

    NASA Technical Reports Server (NTRS)

    Johnson, R. F.; Johnson, A. K.

    1997-01-01

    One of the primary goals of the study of thirst is to understand why drinking occurs under ad libitum or natural conditions. An appreciation of the experimental strategies applied by physiologists studying thirst from different perspectives can facilitate progress toward understanding the natural history of drinking behavior. Drinking research carried out using three separate perspectives-homeostatic, circadian rhythms, and food-associated-generates types of information about the mechanisms underlying drinking behavior. By combining research strategies and methods derived from each of these approaches, it has been possible to gain new information that increases our appreciation of the interactions between homeostatic mechanisms and circadian rhythms in the modulation of water intake and how these might be related to drinking associated with food intake under near natural conditions.

  4. C. elegans Body Cavity Neurons Are Homeostatic Sensors that Integrate Fluctuations in Oxygen Availability and Internal Nutrient Reserves.

    PubMed

    Witham, Emily; Comunian, Claudio; Ratanpal, Harkaranveer; Skora, Susanne; Zimmer, Manuel; Srinivasan, Supriya

    2016-02-23

    It is known that internal physiological state, or interoception, influences CNS function and behavior. However, the neurons and mechanisms that integrate sensory information with internal physiological state remain largely unknown. Here, we identify C. elegans body cavity neurons called URX(L/R) as central homeostatic sensors that integrate fluctuations in oxygen availability with internal metabolic state. We show that depletion of internal body fat reserves increases the tonic activity of URX neurons, which influences the magnitude of the evoked sensory response to oxygen. These responses are integrated via intracellular cGMP and Ca(2+). The extent of neuronal activity thus reflects the balance between the perception of oxygen and available fat reserves. The URX homeostatic sensor ensures that neural signals that stimulate fat loss are only deployed when there are sufficient fat reserves to do so. Our results uncover an interoceptive neuroendocrine axis that relays internal state information to the nervous system.

  5. Structural Brain Correlates of Human Sleep Oscillations

    PubMed Central

    Saletin, Jared M.; van der Helm, Els; Walker, Matthew P.

    2014-01-01

    Sleep is strongly conserved within species, yet marked and perplexing inter-individual differences in sleep physiology are observed. Combining EEG sleep recordings and high-resolution structural brain imaging, here we demonstrate that the morphology of the human brain offers one explanatory factor of such inter-individual variability. Grey matter volume in interoceptive and exteroceptive cortices correlated with the expression of slower NREM sleep spindle frequencies, supporting their proposed role in sleep protection against conscious perception. Conversely, and consistent with an involvement in declarative memory processing, grey matter volume in bilateral hippocampus was associated with faster NREM sleep spindle frequencies. In contrast to spindles, grey matter volume in the homeostatic sleep-regulating center of the basal forebrain/hypothalamus, together with the medial prefrontal cortex, accounted for individual differences in NREM slow wave oscillations. Together, such findings indicate that the qualitative and quantitative expression of human sleep physiology is significantly related to anatomically specific differences in macroscopic brain structure. PMID:23770411

  6. A role for cortical nNOS/NK1 neurons in coupling homeostatic sleep drive to EEG slow wave activity.

    PubMed

    Morairty, Stephen R; Dittrich, Lars; Pasumarthi, Ravi K; Valladao, Daniel; Heiss, Jaime E; Gerashchenko, Dmitry; Kilduff, Thomas S

    2013-12-10

    Although the neural circuitry underlying homeostatic sleep regulation is little understood, cortical neurons immunoreactive for neuronal nitric oxide synthase (nNOS) and the neurokinin-1 receptor (NK1) have been proposed to be involved in this physiological process. By systematically manipulating the durations of sleep deprivation and subsequent recovery sleep, we show that activation of cortical nNOS/NK1 neurons is directly related to non-rapid eye movement (NREM) sleep time, NREM bout duration, and EEG δ power during NREM sleep, an index of preexisting homeostatic sleep drive. Conversely, nNOS knockout mice show reduced NREM sleep time, shorter NREM bouts, and decreased power in the low δ range during NREM sleep, despite constitutively elevated sleep drive. Cortical NK1 neurons are still activated in response to sleep deprivation in these mice but, in the absence of nNOS, they are unable to up-regulate NREM δ power appropriately. These findings support the hypothesis that cortical nNOS/NK1 neurons translate homeostatic sleep drive into up-regulation of NREM δ power through an NO-dependent mechanism.

  7. Tumor necrosis factor (TNF)-receptor 1 and 2 mediate homeostatic synaptic plasticity of denervated mouse dentate granule cells

    PubMed Central

    Becker, Denise; Deller, Thomas; Vlachos, Andreas

    2015-01-01

    Neurological diseases are often accompanied by neuronal cell death and subsequent deafferentation of connected brain regions. To study functional changes after denervation we generated entorhino-hippocampal slice cultures, transected the entorhinal pathway, and denervated dentate granule cells in vitro. Our previous work revealed that partially denervated neurons respond to the loss of input with a compensatory, i.e., homeostatic, increase in their excitatory synaptic strength. TNFα maintains this denervation-induced homeostatic strengthening of excitatory synapses. Here, we used pharmacological approaches and mouse genetics to assess the role of TNF-receptor 1 and 2 in lesion-induced excitatory synaptic strengthening. Our experiments disclose that both TNF-receptors are involved in the regulation of denervation-induced synaptic plasticity. In line with this result TNF-receptor 1 and 2 mRNA-levels were upregulated after deafferentation in vitro. These findings implicate TNF-receptor signaling cascades in the regulation of homeostatic plasticity of denervated networks and suggest an important role for TNFα-signaling in the course of neurological diseases accompanied by deafferentation. PMID:26246237

  8. DNA Immunization

    PubMed Central

    Wang, Shixia; Lu, Shan

    2013-01-01

    DNA immunization was discovered in early 1990s and its use has been expanded from vaccine studies to a broader range of biomedical research, such as the generation of high quality polyclonal and monoclonal antibodies as research reagents. In this unit, three common DNA immunization methods are described: needle injection, electroporation and gene gun. In addition, several common considerations related to DNA immunization are discussed. PMID:24510291

  9. Homeostatic modulation of stimulation-dependent plasticity in human motor cortex.

    PubMed

    Ilić, N V; Milanović, S; Krstić, J; Bajec, D D; Grajić, M; Ilić, T V

    2011-01-01

    Since recently, it is possible, using noninvasive cortical stimulation, such as the protocol of paired associative stimulation (PAS), to induce the plastic changes in the motor cortex, in humans that mimic Hebb's model of learning. Application of TMS conjugated with peripheral electrical stimulation at strictly coherent temporal manner lead to convergence of inputs in the sensory-motor cortex, with the consequent synaptic potentiation or weakening, if applied repetitively. However, when optimal interstimulus interval (ISI) for induction of LTP-like effects is applied as a single pair, Motor evoked potential (MEP) amplitude inhibition is observed, the paradigm known as short-latency afferent inhibition (SLAI). Aiming to resolve this paradox, PAS protocols were applied, with 200 repetitions of TMS pulses paired with median nerve electrical stimulation, at ISI equal to individual latencies of evoked response of somatosensory cortex (N(20)) (PAS(LTP)), and at ISI of N(20) shortened for 5 msec (PAS(LTD)) - protocols that mimic LTP-like changes in the human motor cortex. MEP amplitudes before, during and after interventions were measured as an indicator based on output signals originating from the motor system. Post-intervention MEP amplitudes following the TMS protocols of PAS(LTP) and PAS(LTD) were facilitated and depressed, respectively, contrary to MEP amplitudes during intervention. During PAS(LTP) MEP amplitudes were significantly decreased in case of PAS(LTP), while in the case of PAS(LTD) an upward trend was observed. In conclusions, a possible explanation for the seemingly paradoxical effect of PAS can be found in the mechanism of homeostatic modulation of plasticity. Those findings indicate the existence of complex relationships in the development of plasticity induced by stimulation, depending on the level of the previous motor cortex excitability.

  10. Homeostatic response to hypoxia is regulated by the N-end rule pathway in plants.

    PubMed

    Gibbs, Daniel J; Lee, Seung Cho; Isa, Nurulhikma Md; Gramuglia, Silvia; Fukao, Takeshi; Bassel, George W; Correia, Cristina Sousa; Corbineau, Françoise; Theodoulou, Frederica L; Bailey-Serres, Julia; Holdsworth, Michael J

    2011-10-23

    Plants and animals are obligate aerobes, requiring oxygen for mitochondrial respiration and energy production. In plants, an unanticipated decline in oxygen availability (hypoxia), as caused by roots becoming waterlogged or foliage submergence, triggers changes in gene transcription and messenger RNA translation that promote anaerobic metabolism and thus sustain substrate-level ATP production. In contrast to animals, oxygen sensing has not been ascribed to a mechanism of gene regulation in response to oxygen deprivation in plants. Here we show that the N-end rule pathway of targeted proteolysis acts as a homeostatic sensor of severe low oxygen levels in Arabidopsis, through its regulation of key hypoxia-response transcription factors. We found that plants lacking components of the N-end rule pathway constitutively express core hypoxia-response genes and are more tolerant of hypoxic stress. We identify the hypoxia-associated ethylene response factor group VII transcription factors of Arabidopsis as substrates of this pathway. Regulation of these proteins by the N-end rule pathway occurs through a characteristic conserved motif at the amino terminus initiating with Met-Cys. Enhanced stability of one of these proteins, HRE2, under low oxygen conditions improves hypoxia survival and reveals a molecular mechanism for oxygen sensing in plants via the evolutionarily conserved N-end rule pathway. SUB1A-1, a major determinant of submergence tolerance in rice, was shown not to be a substrate for the N-end rule pathway despite containing the N-terminal motif, indicating that it is uncoupled from N-end rule pathway regulation, and that enhanced stability may relate to the superior tolerance of Sub1 rice varieties to multiple abiotic stresses.

  11. Enkephalin release promotes homeostatic increases in constitutively active mu opioid receptors during morphine withdrawal.

    PubMed

    Shoblock, J R; Maidment, N T

    2007-11-09

    We previously demonstrated that naloxone administration produces a robust conditioned place aversion (CPA) in opiate-naive rodents by blocking the action of enkephalins at mu opioid receptors (MORs). The aversive response to naloxone is potentiated by prior exposure to morphine. Morphine-induced MOR constitutive activity is hypothesized to underlie this enhanced effect of naloxone, an inverse agonist at the MOR. We sought additional evidence for the role of constitutively active MORs in this morphine-induced enhancement using the pro-enkephalin knockout (pENK(-)/(-)) mouse, which is devoid of naloxone CPA in the morphine-naive state. Naloxone, but not the neutral antagonist, 6-beta-naloxol, produced CPA and physical withdrawal signs in pENK(-)/(-) mice when administered 2 h, but not 20 h, after morphine administration. Naloxone-precipitated physical withdrawal signs were attenuated in the pENK(-)/(-) mice relative to wild-type (WT) animals. In both WT and pENK(-)/(-) mice, naloxone-precipitated withdrawal jumping was greatest when naloxone was administered 2 h after morphine treatment and diminished at 3 h, in agreement with previous estimates of the time course for morphine-induced MOR constitutive activity in vitro. However, naloxone regained an ability to precipitate physical withdrawal in the WT, but not the pENK(-)/(-) mice when administered 4.5 h after morphine administration. Taken together, the data suggest that a compensatory increase in enkephalin release during spontaneous morphine withdrawal promotes a second period of MOR constitutive activity in WT mice that is responsible for the enhanced naloxone aversion observed in such animals even when naloxone is administered 20 h after morphine. The endogenous enkephalin system and MOR constitutive activity may therefore play vital roles in hedonic homeostatic dysregulation following chronic opiate administration.

  12. Homeostatic regulation and Pavlovian conditioning in tolerance to amphetamine-induced anorexia.

    PubMed

    Poulos, C X; Wilkinson, D A; Cappell, H

    1981-10-01

    A series of experiments on the role of Pavlovian processes in tolerance to amphetamine-induced anorexia in rats was conducted. In Experiment 1A, tolerance to the suppressant effect of d-amphetamine (4.0 mg/kg) on milk consumption was substantially diminished in an environment not previously associated with drug administration. Experiment 1B supported the interpretation that Pavlovian compensatory conditioning rather than a nonassociative mechanism mediated this phenomenon. Experiment 2 examined the hypothesis that "contingent tolerance" results from an inadvertent manipulation of Pavlovian cues. As in previous research, tolerance was contingent in that it did not develop if the rats were not exposed to food under the influence of the drug. Tolerance developed only if access to food occurred under the influence of amphetamine, but as in Experiment 1A, it was substantially diminished in an environment not previously associated with drug administration. Thus, tolerance to amphetamine-induced anorexia was shown to be both contingent on previous experience with food in the drugged state and subject to Pavlovian control. No current explanation for the occurrence of contingent tolerance or for the control of tolerance by Pavlovian processes can at once account for both of these findings. Experiment 3 confirmed the hypothesis that interaction with the food stimulus would be necessary to extinguish tolerance. This finding is also problematic for any current behavioral theory of tolerance. It is proposed that interaction with food is necessary for the homeostatic regulation of disturbances in eating caused by amphetamine. When activated, this regulatory process operates by means of Pavlovian conditional compensatory processes.

  13. The Homeostatic Chemokine CCL21 Predicts Mortality and May Play a Pathogenic Role in Heart Failure

    PubMed Central

    Yndestad, Arne; Finsen, Alexandra Vanessa; Ueland, Thor; Husberg, Cathrine; Dahl, Christen P.; Øie, Erik; Vinge, Leif Erik; Sjaastad, Ivar; Sandanger, Øystein; Ranheim, Trine; Dickstein, Kenneth; Kjekshus, John; Damås, Jan Kristian; Fiane, Arnt E.; Hilfiker-Kleiner, Denise; Lipp, Martin; Gullestad, Lars; Christensen, Geir; Aukrust, Pål

    2012-01-01

    Background CCL19 and CCL21, acting through CCR7, are termed homeostatic chemokines. Based on their role in concerting immunological responses and their proposed involvement in tissue remodeling, we hypothesized that these chemokines could play a pathogenic role in heart failure (HF). Methodology/Principal Findings Our main findings were: (i) Serum levels of CCL19 and particularly CCL21 were markedly raised in patients with chronic HF (n = 150) as compared with healthy controls (n = 20). A CCL21 level above median was independently associated with all-cause mortality. (ii) In patients with HF following acute myocardial infarction (MI; n = 232), high versus low CCL21 levels 1 month post-MI were associated with cardiovascular mortality, even after adjustment for established risk factors. (iii). Explanted failing human LV tissue (n = 29) had markedly increased expression of CCL21 as compared with non-failing myocardium (n = 5). (iv) Our studies in CCR7−/− mice showed improved survival and attenuated increase in markers of myocardial dysfunction and wall stress in post-MI HF after 1 week, accompanied by increased myocardial expression of markers of regulatory T cells. (v) Six weeks post-MI, there was an increase in markers of myocardial dysfunction and wall stress in CCR7 deficient mice. Conclusions/Significance High serum levels of CCL21 are independently associated with mortality in chronic and acute post-MI HF. Our findings in CCR7 deficient mice may suggest that CCL21 is not only a marker, but also a mediator of myocardial failure. However, while short term inhibition of CCR7 may be beneficial following MI, a total lack of CCR7 during long-term follow-up could be harmful. PMID:22427939

  14. Alzheimer’s disease as homeostatic responses to age-related myelin breakdown

    PubMed Central

    Bartzokis, George

    2011-01-01

    The amyloid hypothesis (AH) of Alzheimer’s disease (AD) posits that the fundamental cause of AD is the accumulation of the peptide amyloid beta (Aβ) in the brain. This hypothesis has been supported by observations that genetic defects in amyloid precursor protein (APP) and presenilin increase Aβ production and cause familial AD (FAD). The AH is widely accepted but does not account for important phenomena including recent failures of clinical trials to impact dementia in humans even after successfully reducing Aβ deposits. Herein, the AH is viewed from the broader overarching perspective of the myelin model of the human brain that focuses on functioning brain circuits and encompasses white matter and myelin in addition to neurons and synapses. The model proposes that the recently evolved and extensive myelination of the human brain underlies both our unique abilities and susceptibility to highly prevalent age-related neuropsychiatric disorders such as late onset AD (LOAD). It regards oligodendrocytes and the myelin they produce as being both critical for circuit function and uniquely vulnerable to damage. This perspective reframes key observations such as axonal transport disruptions, formation of axonal swellings/sphenoids and neuritic plaques, and proteinaceous deposits such as Aβ and tau as by-products of homeostatic myelin repair processes. It delineates empirically testable mechanisms of action for genes underlying FAD and LOAD and provides “upstream” treatment targets. Such interventions could potentially treat multiple degenerative brain disorders by mitigating the effects of aging and associated changes in iron, cholesterol, and free radicals on oligodendrocytes and their myelin. PMID:19775776

  15. Homeostatically Maintained Resting Naive CD4+ T Cells Resist Latent HIV Reactivation

    PubMed Central

    Tsunetsugu-Yokota, Yasuko; Kobayahi-Ishihara, Mie; Wada, Yamato; Terahara, Kazutaka; Takeyama, Haruko; Kawana-Tachikawa, Ai; Tokunaga, Kenzo; Yamagishi, Makoto; Martinez, Javier P.; Meyerhans, Andreas

    2016-01-01

    Homeostatic proliferation (HSP) is a major mechanism by which long-lived naïve and memory CD4+ T cells are maintained in vivo and suggested to contribute to the persistence of the latent HIV-1 reservoir. However, while many in vitro latency models rely on CD4+ T cells that were initially differentiated via T-cell receptor (TCR) stimulation into memory/effector cells, latent infection of naïve resting CD4+ T cells maintained under HSP conditions has not been fully addressed. Here, we describe an in vitro HSP culture system utilizing the cytokines IL-7 and IL-15 that allows studying latency in naïve resting CD4+ T cells. CD4+ T cells isolated from several healthy donors were infected with HIV pseudotypes expressing GFP and cultured under HSP conditions or TCR conditions as control. Cell proliferation, phenotype, and GFP expression were analyzed by flow cytometry. RNA expression was quantified by qRT-PCR. Under HSP culture conditions, latently HIV-1 infected naïve cells are in part maintained in the non-dividing (= resting) state. Although a few HIV-1 provirus+ cells were present in these resting GFP negative cells, the estimated level of GFP transcripts per infected cell seems to indicate a block at the post-transcriptional level. Interestingly, neither TCR nor the prototypic HDAC inhibitor SAHA were able to reactivate HIV-1 provirus from these cells. This lack of reactivation was not due to methylation of the HIV LTR. These results point to a mechanism of HIV control in HSP-cultured resting naïve CD4+ T cells that may be distinct from that in TCR-stimulated memory/effector T cells. PMID:27990142

  16. Genome Sequence of “Candidatus Arthromitus” sp. Strain SFB-Mouse-NL, a Commensal Bacterium with a Key Role in Postnatal Maturation of Gut Immune Functions

    PubMed Central

    Bolotin, Alexander; de Wouters, Tomas; Schnupf, Pamela; Bouchier, Christiane; Loux, Valentin; Rhimi, Moez; Jamet, Alexandre; Dervyn, Rozenn; Boudebbouze, Samira; Blottière, Hervé M.; Sorokin, Alexei; Snel, Johannes; Cerf-Bensussan, Nadine; Gaboriau-Routhiau, Valérie; van de Guchte, Maarten

    2014-01-01

    “Candidatus Arthromitus” sp. strain SFB-mouse-NL (SFB, segmented filamentous bacteria) is a commensal bacterium necessary for inducing the postnatal maturation of homeostatic innate and adaptive immune responses in the mouse gut. Here, we report the genome sequence of this bacterium, which sets it apart from earlier sequenced mouse SFB isolates. PMID:25035333

  17. Does lymphopenia preclude restoration of immune homeostasis? The particular case of type 1 diabetes.

    PubMed

    Askenasy, Enosh M; Askenasy, Nadir; Askenasy, Jean-Jaques

    2010-08-01

    Induction of hematopoietic chimerism initiates tolerizing processes that often restore control over autoimmune reactions: graft versus autoimmunity reaction. In view of the limited capacity of autologous bone marrow transplants and some cases of persistent autoimmune diabetes after allogeneic transplants, we hypothesize that the preparative conditioning regimens adopted from the oncological setting are suboptimal approaches to rebooting the immune system. In general, homeostatic expansion under lymphopenic conditions favors the recovery and development of cytotoxic T cells. Autoimmune diabetes is a particular case in which debulking is ineffective due to resistance of the effector cells to depletion by conventional immunosuppressive therapies. Furthermore, resetting of immune activity is impaired by lymphopenia-induced proliferation of residual diabetogenic clones and delayed recovery of suppressor cells. For control of the autoimmune reaction it is essential to design immunomodulatory approaches that overcome rejection while avoiding homeostatic expansion of residual diabetogenic clones.

  18. A role for innate immunity in type 1 diabetes?

    PubMed

    Beyan, H; Buckley, L R; Yousaf, N; Londei, M; Leslie, R D G

    2003-01-01

    Two arms of the immune system, innate and adaptive immunity, differ in their mode of immune recognition. The innate immune system recognizes a few highly conserved structures on a broad range of microorganisms. On the other hand, recognition of self or autoreactivity is generally confined to the adaptive immune response. Whilst autoimmune features are relatively common, they should be distinguished from autoimmune disease that is infrequent. Type 1 diabetes is an immune-mediated disease due to the destruction of insulin secreting cells mediated by aggressive immune responses, including activation of the adaptive immune system following genetic and environmental interaction. Hypotheses for the cause of the immune dysfunction leading to type 1 diabetes include self-reactive T-cell clones that (1) escape deletion in the thymus, (2) escape from peripheral tolerance or (3) escape from homeostatic control with an alteration in the immune balance leading to autoimmunity. Evidence, outlined in this review, raises the possibility that changes in the innate immune system could lead to autoimmunity, by either priming or promoting aggressive adaptive immune responses. Hostile microorganisms are identified by genetically determined surface receptors on innate effector cells, thereby promoting clearance of these invaders. These innate effectors include a few relatively inflexible cell populations such as monocytes/macrophages, dendritic cells (DC), natural killer (NK) cells, natural killer T (NKT) cells and gammadelta T cells. Recent studies have identified abnormalities in some of these cells both in patients with type 1 diabetes and in those at risk of the disease. However, it remains unclear whether these abnormalities in innate effector cells predispose to autoimmune disease. If they were to do so, then modulation of the innate immune system could be of therapeutic value in preventing immune-mediated diseases such as type 1 diabetes.

  19. Electronically Tuned Microwave Oscillator

    NASA Technical Reports Server (NTRS)

    Lakshminarayana, Mysore

    1987-01-01

    Features include low phase noise and frequency stability. Bias-tuned, low-phase-noise microwave oscillator circuit based on npn bipolar transistor and dielectric resonator. Operating at frequency of about 8.4 GHz, oscillator adjusted to give low phase noise, relatively flat power output versus frequency, and nearly linear frequency versus bias voltage.

  20. Investigating Magnetic Oscillations.

    ERIC Educational Resources Information Center

    Brueningsen, Christopher A.

    1993-01-01

    Studies magnetic oscillation using an air track. Ceramic magnets are attached to the cart and also are used as dampeners in place of the springs. The resulting oscillations are fairly sinusoidal and is a good example of simple harmonic motion. (MVL)

  1. Active-bridge oscillator

    DOEpatents

    Wessendorf, Kurt O.

    2001-01-01

    An active bridge oscillator is formed from a differential amplifier where positive feedback is a function of the impedance of one of the gain elements and a relatively low value common emitter resistance. This use of the nonlinear transistor parameter h stabilizes the output and eliminates the need for ALC circuits common to other bridge oscillators.

  2. HIGH POWER PULSED OSCILLATOR

    DOEpatents

    Singer, S.; Neher, L.K.

    1957-09-24

    A high powered, radio frequency pulse oscillator is described for generating trains of oscillations at the instant an input direct voltage is impressed, or immediately upon application of a light pulse. In one embodiment, the pulse oscillator comprises a photo-multiplier tube with the cathode connected to the first dynode by means of a resistor, and adjacent dynodes are connected to each other through adjustable resistors. The ohmage of the resistors progressively increases from a very low value for resistors adjacent the cathode to a high value adjacent the plate, the last dynode. Oscillation occurs with this circuit when a high negative voltage pulse is applied to the cathode and the photo cathode is bombarded. Another embodiment adds capacitors at the resistor connection points of the above circuit to increase the duration of the oscillator train.

  3. Nested autoinhibitory feedbacks alter the resistance of homeostatic adaptive biochemical networks.

    PubMed

    Schaber, Jörg; Lapytsko, Anastasiya; Flockerzi, Dietrich

    2014-02-06

    Negative feedback control is a ubiquitous feature of biochemical systems, as is time delay between a signal and its response. Negative feedback in conjunction with time delay can lead to oscillations. In a cellular context, it might be beneficial to mitigate oscillatory behaviour to avoid recurring stress situations. This can be achieved by increasing the distance between the parameters of the system and certain thresholds, beyond which oscillations occur. This distance has been termed resistance. Here, we prove that in a generic three-dimensional negative feedback system the resistance of the system is modified by nested autoinhibitory feedbacks. Our system features negative feedbacks through both input-inhibition as well as output-activation, a signalling component with mass conservation and perfect adaptation. We show that these features render the system applicable to biological data, exemplified by the high osmolarity glycerol system in yeast and the mammalian p53 system. Output-activation is better supported by data than input-inhibition and also shows distinguished properties with respect to the system's stimulus. Our general approach might be useful in designing synthetic systems in which oscillations can be tuned by synthetic autoinhibitory feedbacks.

  4. Oscillators and Oscillations in the Basal Ganglia

    PubMed Central

    Wilson, Charles J.

    2015-01-01

    What is the meaning of an action potential? There must be different answers for neurons that oscillate spontaneously, firing action potentials even in the absence of any synaptic input, and those driven to fire from a resting membrane potential. In spontaneously firing neurons, the occurrence of the next action potential is guaranteed. Only variations in its timing can carry the message. Among cells of this type are all those making up the deeper nuclei of the basal ganglia, including both segments of the globus pallidus, the substantia nigra, and the subthalamic nucleus. These cells receive thousands of excitatory and inhibitory synaptic inputs, but no input is required to maintain the firing of the cells; they fire at approximately the same rate when the synapses are silenced. Instead, synaptic inputs produce brief changes in spike timing and firing rate. The interactions among oscillating cells within and among the basal ganglia nuclei produce a complex resting pattern of activity. Normally, this pattern is highly irregular and decorrelates the network, so that the firing of each cell is statistically independent of the others. This maximizes the potential information that may be transmitted by the basal ganglia to its target structures. In Parkinson’s disease, the resting pattern of activity is dominated by a slow oscillation shared by all the neurons. Treatment with deep brain stimulation may gain its therapeutic value by disrupting this shared pathological oscillation, and restoring independent action by each neuron in the network. PMID:25449134

  5. Immune System

    EPA Science Inventory

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  6. Stromal cell contributions to the homeostasis and functionality of the immune system.

    PubMed

    Mueller, Scott N; Germain, Ronald N

    2009-09-01

    A defining characteristic of the immune system is the constant movement of many of its constituent cells through the secondary lymphoid tissues, mainly the spleen and lymph nodes, where crucial interactions that underlie homeostatic regulation, peripheral tolerance and the effective development of adaptive immune responses take place. What has only recently been recognized is the role that non-haematopoietic stromal elements have in many aspects of immune cell migration, activation and survival. In this Review, we summarize our current understanding of lymphoid compartment stromal cells, examine their possible heterogeneity, discuss how these cells contribute to immune homeostasis and the efficient initiation of adaptive immune responses, and highlight how targeting of these elements by some pathogens can influence the host immune response.

  7. Trafficking receptor signatures define blood plasmablasts responding to tissue-specific immune challenge

    PubMed Central

    Seong, Yekyung; Lazarus, Nicole H.; Sutherland, Lusijah; Habtezion, Aida; Abramson, Tzvia; He, Xiao-Song; Greenberg, Harry B.

    2017-01-01

    Antibody-secreting cells are generated in regional lymphoid tissues and traffic as plasmablasts (PBs) via lymph and blood to target sites for local immunity. We used multiparameter flow cytometry to define PB trafficking programs (TPs, combinations of adhesion molecules and chemoattractant receptors) and their imprinting in patients in response to localized infection or immune insults. TPs enriched after infection or autoimmune inflammation of mucosae correlate with sites of immune response or symptoms, with different TPs imprinted during small intestinal, colon, throat, and upper respiratory immune challenge. PBs induced after intramuscular or intradermal influenza vaccination, including flu-specific antibody–secreting cells, display TPs characterized by the lack of mucosal homing receptors. PBs of healthy donors display diverse mucosa-associated TPs, consistent with homeostatic immune activity. Identification of TP signatures of PBs may facilitate noninvasive monitoring of organ-specific immune responses. PMID:28352656

  8. Ultrastable Cryogenic Microwave Oscillators

    NASA Astrophysics Data System (ADS)

    Mann, Anthony G.

    Ultrastable cryogenic microwave oscillators are secondary frequency standards in the microwave domain. The best of these oscillators have demonstrated a short term frequency stability in the range 10-14 to a few times 10-16. The main application for these oscillators is as flywheel oscillators for the next generation of passive atomic frequency standards, and as local oscillators in space telemetry ground stations to clean up the transmitter close in phase noise. Fractional frequency stabilities of passive atomic frequency standards are now approaching 3 x10^-14 /τ where τ is the measurement time, limited only by the number of atoms that are being interrogated. This requires an interrogation oscillator whose short-term stability is of the order of 10-14 or better, which cannot be provided by present-day quartz technology. Ultrastable cryogenic microwave oscillators are based on resonators which have very high electrical Q-factors. The resolution of the resonator's linewidth is typically limited by electronics noise to about 1ppm and hence Q-factors in excess of 108 are required. As these are only attained in superconducting cavities or sapphire resonators at low temperatures, use of liquid helium cooling is mandatory, which has so far restricted these oscillators to the research or metrology laboratory. Recently, there has been an effort to dispense with the need for liquid helium and make compact flywheel oscillators for the new generation of primary frequency standards. Work is under way to achieve this goal in space-borne and mobile liquid-nitrogen-cooled systems. The best cryogenic oscillators developed to date are the ``whispering gallery'' (WG) mode sapphire resonator-oscillators of NASA's Jet Propulsion Laboratory (JPL) and the University of Western Australia (UWA), as well as Stanford University's superconducting cavity stabilized oscillator (SCSO). All of these oscillators have demonstrated frequency

  9. Quasi-Fibonacci oscillators

    NASA Astrophysics Data System (ADS)

    Gavrilik, A. M.; Kachurik, I. I.; Rebesh, A. P.

    2010-06-01

    We study the properties of the sequences of the energy eigenvalues for some generalizations of q-deformed oscillators including the p, q-oscillator, and the three-, four- and five-parameter deformed oscillators given in the literature. It is shown that most of the considered models belong to the class of so-called Fibonacci oscillators for which any three consecutive energy levels satisfy the relation En + 1 = λEn + ρEn - 1 with real constants λ, ρ. On the other hand, for a certain μ-oscillator known since 1993, we prove its non-Fibonacci nature. Possible generalizations of the three-term Fibonacci relation are discussed, among which for the μ-oscillator we choose, as the most adequate, the so-called quasi-Fibonacci (or local Fibonacci) property of the energy levels. The property is encoded in the three-term quasi-Fibonacci (QF) relation with the non-constant, n-dependent coefficients λ and ρ. Various aspects of the QF relation are elaborated for the μ-oscillator and some of its extensions.

  10. Autophagy as a Stress Response Pathway in the Immune System.

    PubMed

    Bhattacharya, Abhisek; Eissa, N Tony

    2015-01-01

    Macroautophagy, hereafter, referred to as autophagy, has long been regarded as a housekeeping pathway involved in intracellular degradation and energy recycling. These housekeeping and homeostatic functions are especially important during cellular stress, such as periods of nutrient deprivation. However, importance of autophagy extends far beyond its degradative functions. Recent evidence shows that autophagy plays an essential role in development, organization and functions of the immune system, and defects in autophagy lead to several diseases, including cancer and autoimmunity. In the immune system, autophagy is important in regulation of the innate and adaptive immune responses. This review focuses on the roles of autophagy in the adaptive immune system. We first introduce the autophagy pathway and provide a brief description of the major molecular players involved in autophagy. We then discuss the importance of autophagy as a stress integrator mechanism and provide relevant examples of this role of autophagy in adaptive immune cells. Then we proceed to describe how autophagy regulates development, activation and functions of different adaptive immune cells. In these contexts, we mention both degradative and non-degradative roles of autophagy, and illustrate their importance. We also discuss role of autophagy in antigen presenting cells, which play critical roles in the activation of adaptive immune cells. Further, we describe how autophagy regulates functions of different adaptive immune cells during infection, inflammation and autoimmunity.

  11. The microbiota in adaptive immune homeostasis and disease.

    PubMed

    Honda, Kenya; Littman, Dan R

    2016-07-07

    In the mucosa, the immune system's T cells and B cells have position-specific phenotypes and functions that are influenced by the microbiota. These cells play pivotal parts in the maintenance of immune homeostasis by suppressing responses to harmless antigens and by enforcing the integrity of the barrier functions of the gut mucosa. Imbalances in the gut microbiota, known as dysbiosis, can trigger several immune disorders through the activity of T cells that are both near to and distant from the site of their induction. Elucidation of the mechanisms that distinguish between homeostatic and pathogenic microbiota-host interactions could identify therapeutic targets for preventing or modulating inflammatory diseases and for boosting the efficacy of cancer immunotherapy.

  12. Oscillation of Angiogenesis and Vascular Dropout in Progressive Human Vascular Disease. [Vascular Pattern as Useful Read-Out of Complex Molecular Signaling

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, Patricia

    2010-01-01

    When analyzed by VESsel GENeration Analysis (VESGEN) software, vascular patterns provide useful integrative read-outs of complex, interacting molecular signaling pathways. Using VESGEN, we recently discovered and published our innovative, surprising findings that angiogenesis oscillated with vascular dropout throughout progression of diabetic retinopathy, a blinding vascular disease. Our findings provide a potential paradigm shift in the current prevailing view on progression and treatment of this disease, and a new early-stage window of regenerative therapeutic opportunities. The findings also suggest that angiogenesis may oscillate with vascular disease in a homeostatic-like manner during early stages of other inflammatory progressive diseases such as cancer and coronary vascular disease.

  13. Undamped fritting oscillations

    NASA Astrophysics Data System (ADS)

    Titov, V. A.

    2013-01-01

    Fritting oscillations in a glasslike film of methane and chlorine rapidly attenuate. A change in the boundary condition makes them weakly damped, while dosed synchronized injections of vacancies with high-energy particles make it possible to obtain a self-oscillatory system. The mechanism of fritting oscillations is described in detail. An oscillating dissipative structure is formed in the active medium of nonequilibrium glass supersaturated with vacancies and exhibiting a liquid-like behavior. A capillary flow of the medium plays a special role in its evolution.

  14. Solar atmosphere neutrino oscillations

    SciTech Connect

    Fogli, G.L.; Lisi, E.; Mirizzi, A.; Montanino, D.; Serpico, P.D.; /Fermilab

    2007-02-01

    The Sun is a source of high energy neutrinos (E > 10 GeV) produced by cosmic ray interactions in the solar atmosphere. We study the impact of three-flavor oscillations on the solar atmosphere neutrino fluxes observable at Earth. We find that peculiar matter oscillation effects in the Sun do exist, but are significantly suppressed by averaging over the production region and over the neutrino and antineutrino components. In particular, the relation between the neutrino fluxes at the Sun and at the Earth can be approximately expressed in terms of phase-averaged ''vacuum'' oscillations, dominated by a single mixing parameter (the angle {theta}{sub 23}).

  15. LSND neutrino oscillation results

    SciTech Connect

    Louis, W.C.

    1996-06-01

    In the past several years, a number of experiments have searched for neutrino oscillations, where a neutrino of one type (say {bar {nu}}{sub {mu}}) spontaneously transforms into a neutrino of another type (say {bar {nu}}{sub e}). For this phenomenon to occur, neutrinos must be massive and the apparent conservation law of lepton families must be violated. In 1995 the LSND experiment published data showing candidate events that are consistent with {bar {nu}}{sub {mu}} oscillations. Additional data are reported here which provide stronger evidence for neutrino oscillations.

  16. Innate immunity.

    PubMed

    Revillard, Jean-Pierre

    2002-01-01

    For more than half a century immunological research has been almost exclusively orientated towards the acquired immune response and the mechanisms of immune tolerance. Major discoveries have enabled us to better understand the functioning of the specific immune system: the structure of antibody molecules, the genetic mechanisms leading to the molecular diversity of B (BCR) and T (TCR) lymphocyte antigen receptors, the biological function of major histocompatibility complex (MHC) molecules in the presentation of peptides to alpha/beta receptor bearing T lymphocytes, the processes of positive and negative selection of lymphocytes during the course of their differentiation. The major role of specific or acquired immunity has been shown by the rapidly lethal character of severe combined immune deficiency diseases and various alterations in the mechanisms of tolerance have been proposed to explain the chronic inflammatory illnesses which are considered to be auto-immune. Natural or innate immunity has been known since the first description of an inflammatory reaction attributed to Cornelius Celsus. It entered into the scientific era at the end of the 19th century with the discovery of phagocytes by Metchnikoff and of the properties of the complement system by Bordet [1] but due to the vastness of the field and its lack of clear definition, it failed to excite the interest of researchers. The discovery of cytokines and progress in knowledge of the mechanisms of the inflammatory reaction have certainly helped to banish preconceived ideas about natural immunity, which was wrongly labelled as non-specific. This has led to the proposition of a wider role for immune functions beyond the level of the cell or the organism [2] and to a better understanding of the importance of the immediate defence mechanisms and their role in the later orientation of the acquired response.

  17. Maternal Immunization

    PubMed Central

    Chu, Helen Y.; Englund, Janet A.

    2014-01-01

    Maternal immunization has the potential to protect the pregnant woman, fetus, and infant from vaccine-preventable diseases. Maternal immunoglobulin G is actively transported across the placenta, providing passive immunity to the neonate and infant prior to the infant's ability to respond to vaccines. Currently inactivated influenza, tetanus toxoid, and acellular pertussis vaccines are recommended during pregnancy. Several other vaccines have been studied in pregnancy and found to be safe and immunogenic and to provide antibody to infants. These include pneumococcus, group B Streptococcus, Haemophilus influenzae type b, and meningococcus vaccines. Other vaccines in development for potential maternal immunization include respiratory syncytial virus, herpes simplex virus, and cytomegalovirus vaccines. PMID:24799324

  18. Interindividual differences in the dynamics of the homeostatic process are trait-like and distinct for sleep versus wakefulness.

    PubMed

    Rusterholz, Thomas; Tarokh, Leila; Van Dongen, Hans P A; Achermann, Peter

    2017-04-01

    The sleep homeostatic Process S reflects the build-up of sleep pressure during waking and its dissipation during sleep. Process S is modelled as a saturating exponential function during waking and a decreasing exponential function during sleep. Slow wave activity is a physiological marker for non-rapid eye movement (non-REM) sleep intensity and serves as an index of Process S. There is considerable interindividual variability in the sleep homeostatic responses to sleep and sleep deprivation. The aim of this study was to investigate whether interindividual differences in Process S are trait-like. Polysomnographic recordings of 8 nights (12-h sleep opportunities, 22:00-10:00 hours) interspersed with three 36-h periods of sustained wakefulness were performed in 11 healthy young adults. Empirical mean slow wave activity per non-REM sleep episode at episode mid-points were used for parameter estimation. Parameters of Process S were estimated using different combinations of consecutive sleep recordings, resulting in two to three sets of parameters per subject. Intraclass correlation coefficients were calculated to assess whether the parameters were stable across the study protocol and they showed trait-like variability among individuals. We found that the group-average time constants of the build-up and dissipation of Process S were 19.2 and 2.7 h, respectively. Intraclass correlation coefficients ranged from 0.48 to 0.56, which reflects moderate trait variability. The time constants of the build-up and dissipation varied independently among subjects, indicating two distinct traits. We conclude that interindividual differences in the parameters of the dynamics of the sleep homeostatic Process S are trait-like.

  19. Response to Metronidazole and Oxidative Stress Is Mediated through Homeostatic Regulator HsrA (HP1043) in Helicobacter pylori

    PubMed Central

    Olekhnovich, Igor N.; Vitko, Serhiy; Valliere, Meaghan

    2014-01-01

    Metronidazole (MTZ) is often used in combination therapies to treat infections caused by the gastric pathogen Helicobacter pylori. Resistance to MTZ results from loss-of-function mutations in genes encoding RdxA and FrxA nitroreductases. MTZ-resistant strains, when cultured at sub-MICs of MTZ (5 to 20 μg/ml), show dose-dependent defects in bacterial growth; depressed activities of many Krebs cycle enzymes, including pyruvate:ferredoxin oxidoreductase (PFOR); and low transcript levels of porGDAB (primer extension), phenotypes consistent with an involvement of a transcriptional regulator. Using a combination of protein purification steps, electrophoretic mobility shift assays (EMSAs), and mass spectrometry analyses of proteins bound to porG promoter sequences, we identified HP1043, an essential homeostatic global regulator (HsrA [for homeostatic stress regulator]). Competition EMSAs and supershift analyses with HsrA-enriched protein fractions confirmed specific binding to porGDAB and hsrA promoter sequences. Exposure to MTZ resulted in >10-fold decreases in levels of HsrA and in levels of the HsrA-regulated gene products PFOR and TlpB. Exposure to paraquat (PQ), hydrogen peroxide, or organic peroxides showed near equivalence with MTZ, revealing a common oxidative stress response pathway. Finally, direct superoxide dismutase (SOD) assays showed an inverse relationship between HsrA levels and SOD activity, suggesting that HsrA may serve as a repressor of sodB. As a homeostatic sentinel, HsrA appears to be ideally positioned to enable rapid shutdown of genes associated with metabolism and growth while activating (directly or indirectly) oxidative defense genes in response to low levels of toxic metabolites (MTZ or oxygen) before they reach DNA-damaging levels. PMID:24296668

  20. Homeostatic regulation of synaptic excitability: tonic GABAA receptor currents replace Ih in cortical pyramidal neurons of HCN1 knockout mice

    PubMed Central

    Chen, Xiangdong; Shu, Shaofang; Schwartz, Lauren C.; Sun, Chengsan; Kapur, Jaideep; Bayliss, Douglas A.

    2010-01-01

    Homeostatic control of synaptic efficacy is often mediated by dynamic regulation of excitatory synaptic receptors. Here, we report a novel form of homeostatic synaptic plasticity based on regulation of shunt currents that control dendritosomatic information transfer. In cortical pyramidal neurons from wild type mice, HCN1 channels underlie a dendritic hyperpolarization-activated cationic current (Ih) that serves to limit temporal summation of synaptic inputs. In HCN1 knockout mice, as expected, Ih is reduced in pyramidal neurons and its effects on synaptic summation are strongly diminished. Unexpectedly, we found a markedly enhanced bicuculline- and L-655,708-sensitive background GABAA current in these cells that could be attributed to selective up-regulation of GABAA α5 subunit expression in the cortex of HCN1 knockout mice. Strikingly, despite diminished Ih, baseline sub-linear summation of evoked EPSPs was unchanged in pyramidal neurons from HCN1 knockout mice; however, blocking tonic GABAA currents with bicuculline enhanced synaptic summation more strongly in pyramidal cells from HCN1 knockout mice than in those cells from wild type mice. Increasing tonic GABAA receptor conductance in the context of reduced Ih, using computational or pharmacological approaches, restored normal baseline synaptic summation, as observed in neurons from HCN1 knockout mice. These data indicate that up-regulation of α5 subunit-mediated GABAA receptor tonic current compensates quantitatively for loss of dendritic Ih in cortical pyramidal neurons from HCN1 knockout mice to maintain normal synaptic summation; they further imply that dendritosomatic synaptic efficacy is a controlled variable for homeostatic regulation of cortical neuron excitability in vivo. PMID:20164346

  1. Homeostatic effects of exercise and sleep on metabolic processes in mice with an overexpressed skeletal muscle clock.

    PubMed

    Brager, Allison J; Heemstra, Lydia; Bhambra, Raman; Ehlen, J Christopher; Esser, Karyn A; Paul, Ketema N; Novak, Colleen M

    2017-01-01

    Brain and muscle-ARNT-like factor (Bmal1/BMAL1) is an essential transcriptional/translational factor of circadian clocks. Loss of function of Bmal1/BMAL1 is highly disruptive to physiological and behavioral processes. In light of these previous findings, we examined if transgenic overexpression of Bmal1/BMAL1 in skeletal muscle could alter metabolic processes. First, we characterized in vivo and ex vivo metabolic phenotypes of muscle overexpressed mice (male and female) compared to wild-type littermates (WT). Second, we examined in vivo and ex vivo metabolic processes in the presence of positive and negative homeostatic challenges: high-intensity treadmill running (positive) and acute sleep deprivation (negative). In vivo measures of metabolic processes included body composition, respiratory exchange ratio (RER; VCO2/VO2), energy expenditure, total activity counts, and food intake collected from small animal indirect calorimetry. Ex vivo measure of insulin sensitivity in skeletal muscle was determined from radioassays. RER was lower for muscle overexpressed females compared to female WTs. There were no genotype-dependent differences in metabolic phenotypes for males. With homeostatic challenges, muscle overexpressed mice had lower energy expenditure after high-intensity treadmill running. Acute sleep deprivation reduced insulin sensitivity in skeletal muscle in overexpressed male mice, but not male WTs. The present study contributes to a body of evidence showing pleiotropic, non-circadian, and homeostatic effects of altered Bmal1/BMAL1 expression on metabolic processes, demonstrating a critical need to further investigate the broad and complex actions of Bmal1/BMAL1 on physiology and behavior.

  2. Entraining synthetic genetic oscillators

    NASA Astrophysics Data System (ADS)

    Wagemakers, Alexandre; Buldú, Javier M.; Sanjuán, Miguel A. F.; de Luis, Oscar; Izquierdo, Adriana; Coloma, Antonio

    2009-09-01

    We propose a new approach for synchronizing a population of synthetic genetic oscillators, which consists in the entrainment of a colony of repressilators by external modulation. We present a model where the repressilator dynamics is affected by periodic changes in temperature. We introduce an additional plasmid in the bacteria in order to correlate the temperature variations with the enhancement of the transcription rate of a certain gene. This can be done by introducing a promoter that is related to the heat shock response. This way, the expression of that gene results in a protein that enhances the overall oscillations. Numerical results show coherent oscillations of the population for a certain range of the external frequency, which is in turn related to the natural oscillation frequency of the modified repressilator. Finally we study the transient times related with the loss of synchronization and we discuss possible applications in biotechnology of large-scale production coupled to synchronization events induced by heat shock.

  3. Oscillating fluid power generator

    DOEpatents

    Morris, David C

    2014-02-25

    A system and method for harvesting the kinetic energy of a fluid flow for power generation with a vertically oriented, aerodynamic wing structure comprising one or more airfoil elements pivotably attached to a mast. When activated by the moving fluid stream, the wing structure oscillates back and forth, generating lift first in one direction then in the opposite direction. This oscillating movement is converted to unidirectional rotational movement in order to provide motive power to an electricity generator. Unlike other oscillating devices, this device is designed to harvest the maximum aerodynamic lift forces available for a given oscillation cycle. Because the system is not subjected to the same intense forces and stresses as turbine systems, it can be constructed less expensively, reducing the cost of electricity generation. The system can be grouped in more compact clusters, be less evident in the landscape, and present reduced risk to avian species.

  4. High frequency nanotube oscillator

    DOEpatents

    Peng, Haibing [Houston, TX; Zettl, Alexander K [Kensington, TX

    2012-02-21

    A tunable nanostructure such as a nanotube is used to make an electromechanical oscillator. The mechanically oscillating nanotube can be provided with inertial clamps in the form of metal beads. The metal beads serve to clamp the nanotube so that the fundamental resonance frequency is in the microwave range, i.e., greater than at least 1 GHz, and up to 4 GHz and beyond. An electric current can be run through the nanotube to cause the metal beads to move along the nanotube and changing the length of the intervening nanotube segments. The oscillator can operate at ambient temperature and in air without significant loss of resonance quality. The nanotube is can be fabricated in a semiconductor style process and the device can be provided with source, drain, and gate electrodes, which may be connected to appropriate circuitry for driving and measuring the oscillation. Novel driving and measuring circuits are also disclosed.

  5. A novel photonic oscillator

    NASA Technical Reports Server (NTRS)

    Yao, X. S.; Maleki, L.

    1995-01-01

    We report a novel oscillator for photonic RF systems. This oscillator is capable of generating high-frequency signals up to 70 GHz in both electrical and optical domains and is a special voltage-controlled oscillator with an optical output port. It can be used to make a phase-locked loop (PLL) and perform all functions that a PLL is capable of for photonic systems. It can be synchronized to a reference source by means of optical injection locking, electrical injection locking, and PLL. It can also be self-phase locked and self-injection locked to generate a high-stability photonic RF reference. Its applications include high-frequency reference regeneration and distribution, high-gain frequency multiplication, comb-frequecy and square-wave generation, carrier recovery, and clock recovery. We anticipate that such photonic voltage-controlled oscillators (VCOs) will be as important to photonic RF systems as electrical VCOs are to electrical RF systems.

  6. Oscillating Filaments. I. Oscillation and Geometrical Fragmentation

    NASA Astrophysics Data System (ADS)

    Gritschneder, Matthias; Heigl, Stefan; Burkert, Andreas

    2017-01-01

    We study the stability of filaments in equilibrium between gravity and internal as well as external pressure using the grid-based AMR code RAMSES. A homogeneous, straight cylinder below a critical line mass is marginally stable. However, if the cylinder is bent, such as with a slight sinusoidal perturbation, an otherwise stable configuration starts to oscillate, is triggered into fragmentation, and collapses. This previously unstudied behavior allows a filament to fragment at any given scale, as long as it has slight bends. We call this process “geometrical fragmentation.” In our realization, the spacing between the cores matches the wavelength of the sinusoidal perturbation, whereas up to now, filaments were thought to be only fragmenting on the characteristic scale set by the mass-to-line ratio. Using first principles, we derive the oscillation period as well as the collapse timescale analytically. To enable a direct comparison with observations, we study the line-of-sight velocity for different inclinations. We show that the overall oscillation pattern can hide the infall signature of cores.

  7. The Neonatal Window of Opportunity: Setting the Stage for Life-Long Host-Microbial Interaction and Immune Homeostasis.

    PubMed

    Torow, Natalia; Hornef, Mathias W

    2017-01-15

    The existence of a neonatal window was first highlighted by epidemiological studies that revealed the particular importance of this early time in life for the susceptibility to immune-mediated diseases in humans. Recently, the first animal studies emerged that present examples of early-life exposure-triggered persisting immune events, allowing a detailed analysis of the factors that define this particular time period. The enteric microbiota and the innate and adaptive immune system represent prime candidates that impact on the pathogenesis of immune-mediated diseases and are known to reach a lasting homeostatic equilibrium following a dynamic priming period after birth. In this review, we outline the postnatal establishment of the microbiota and maturation of the innate and adaptive immune system and discuss examples of early-life exposure-triggered immune-mediated diseases that start to shed light on the critical importance of the early postnatal period for life-long immune homeostasis.

  8. Immune response

    MedlinePlus Videos and Cool Tools

    The immune system includes specialized white blood cells, called lymphocytes that adapt themselves to fight specific foreign invaders. These cells develop into two groups in the bone marrow. From the bone ...

  9. Current oscillations in nanopores

    NASA Astrophysics Data System (ADS)

    Hyland, Brittany

    We develop a simple phenomenological model to describe current oscillations in single, conically shaped nanopores. The model utilizes aspects of reaction rate theory, electrochemical oscillators, and nonlinear dynamical systems. Time series of experimental data were analyzed and compared to time series simulated using the model equations. There is good qualitative agreement between experiment and simulation, though the model needs to be improved in order to obtain better quantitative agreement.

  10. Ultrastable Multigigahertz Photonic Oscillator

    NASA Technical Reports Server (NTRS)

    Logan, Ronald T., Jr.

    1996-01-01

    Novel photonic oscillator developed to serve as ultrastable source of microwave and millimeter-wave signals. In system, oscillations generated photonically, then converted to electronic form. Includes self-mode-locked semiconductor laser producing stream of pulses, detected and fed back to laser as input. System also includes fiber-optic-delay-line discriminator, which detects fluctuations of self-mode-locking frequency and generates error signal used in negative-feedback loop to stabilize pulse-repetition frequency.

  11. Rocket Engine Oscillation Diagnostics

    NASA Technical Reports Server (NTRS)

    Nesman, Tom; Turner, James E. (Technical Monitor)

    2002-01-01

    Rocket engine oscillating data can reveal many physical phenomena ranging from unsteady flow and acoustics to rotordynamics and structural dynamics. Because of this, engine diagnostics based on oscillation data should employ both signal analysis and physical modeling. This paper describes an approach to rocket engine oscillation diagnostics, types of problems encountered, and example problems solved. Determination of design guidelines and environments (or loads) from oscillating phenomena is required during initial stages of rocket engine design, while the additional tasks of health monitoring, incipient failure detection, and anomaly diagnostics occur during engine development and operation. Oscillations in rocket engines are typically related to flow driven acoustics, flow excited structures, or rotational forces. Additional sources of oscillatory energy are combustion and cavitation. Included in the example problems is a sampling of signal analysis tools employed in diagnostics. The rocket engine hardware includes combustion devices, valves, turbopumps, and ducts. Simple models of an oscillating fluid system or structure can be constructed to estimate pertinent dynamic parameters governing the unsteady behavior of engine systems or components. In the example problems it is shown that simple physical modeling when combined with signal analysis can be successfully employed to diagnose complex rocket engine oscillatory phenomena.

  12. Oscillating asymmetric dark matter

    SciTech Connect

    Tulin, Sean; Yu, Hai-Bo; Zurek, Kathryn M. E-mail: haiboyu@umich.edu

    2012-05-01

    We study the dynamics of dark matter (DM) particle-antiparticle oscillations within the context of asymmetric DM. Oscillations arise due to small DM number-violating Majorana-type mass terms, and can lead to recoupling of annihilation after freeze-out and washout of the DM density. Asymmetric DM oscillations 'interpolate' between symmetric and asymmetric DM freeze-out scenarios, and allow for a larger DM model-building parameter space. We derive the density matrix equations for DM oscillations and freeze-out from first principles using nonequilibrium field theory, and our results are qualitatively different than in previous studies. DM dynamics exhibits particle-vs-antiparticle 'flavor' effects, depending on the interaction type, analogous to neutrino oscillations in a medium. 'Flavor-sensitive' DM interactions include scattering or annihilation through a new vector boson, while 'flavor-blind' interactions include scattering or s-channel annihilation through a new scalar boson. In particular, we find that flavor-sensitive annihilation does not recouple when coherent oscillations begin, and that flavor-blind scattering does not lead to decoherence.

  13. Oscillating asymmetric dark matter

    NASA Astrophysics Data System (ADS)

    Tulin, Sean; Yu, Hai-Bo; Zurek, Kathryn M.

    2012-05-01

    We study the dynamics of dark matter (DM) particle-antiparticle oscillations within the context of asymmetric DM. Oscillations arise due to small DM number-violating Majorana-type mass terms, and can lead to recoupling of annihilation after freeze-out and washout of the DM density. Asymmetric DM oscillations "interpolate" between symmetric and asymmetric DM freeze-out scenarios, and allow for a larger DM model-building parameter space. We derive the density matrix equations for DM oscillations and freeze-out from first principles using nonequilibrium field theory, and our results are qualitatively different than in previous studies. DM dynamics exhibits particle-vs-antiparticle "flavor" effects, depending on the interaction type, analogous to neutrino oscillations in a medium. "Flavor-sensitive" DM interactions include scattering or annihilation through a new vector boson, while "flavor-blind" interactions include scattering or s-channel annihilation through a new scalar boson. In particular, we find that flavor-sensitive annihilation does not recouple when coherent oscillations begin, and that flavor-blind scattering does not lead to decoherence.

  14. Stromal cell contributions to the homeostasis and functionality of the immune system

    PubMed Central

    Mueller, Scott N.; Germain, Ronald N.

    2009-01-01

    A defining characteristic of the immune system is the constant movement of many of its constituent cells through the secondary lymphoid tissues, mainly the spleen and lymph nodes, where crucial interactions that underlie homeostatic regulation, peripheral tolerance, and effective development of adaptive immunity take place. What has only recently been recognized is the role that non-haematopoietic stromal elements have in multiple aspects of immune cell migration, activation and survival. In this Review, we summarize our current understanding of lymphoid compartment stromal cells, examine their possible heterogeneity, discuss how these cells contribute to immune homeostasis and the efficient initiation of adaptive immunity, and highlight how targeting of these elements by some pathogens can influence the host response. PMID:19644499

  15. Neutrino Oscillation Physics

    SciTech Connect

    Kayser, Boris

    2012-06-01

    To complement the neutrino-physics lectures given at the 2011 International School on Astro Particle Physics devoted to Neutrino Physics and Astrophysics (ISAPP 2011; Varenna, Italy), at the 2011 European School of High Energy Physics (ESHEP 2011; Cheila Gradistei, Romania), and, in modified form, at other summer schools, we present here a written description of the physics of neutrino oscillation. This description is centered on a new way of deriving the oscillation probability. We also provide a brief guide to references relevant to topics other than neutrino oscillation that were covered in the lectures. Neutrinos and photons are by far the most abundant elementary particles in the universe. Thus, if we would like to comprehend the universe, we must understand the neutrinos. Of course, studying the neutrinos is challenging, since the only known forces through which these electrically-neutral leptons interact are the weak force and gravity. Consequently, interactions of neutrinos in a detector are very rare events, so that very large detectors and intense neutrino sources are needed to make experiments feasible. Nevertheless, we have confirmed that the weak interactions of neutrinos are correctly described by the Standard Model (SM) of elementary particle physics. Moreover, in the last 14 years, we have discovered that neutrinos have nonzero masses, and that leptons mix. These discoveries have been based on the observation that neutrinos can change from one 'flavor' to another - the phenomenon known as neutrino oscillation. We shall explain the physics of neutrino oscillation, deriving the probability of oscillation in a new way. We shall also provide a very brief guide to references that can be used to study some major neutrino-physics topics other than neutrino oscillation.

  16. A specific requirement of Arc/Arg3.1 for visual experience-induced homeostatic synaptic plasticity in mouse primary visual cortex.

    PubMed

    Gao, Ming; Sossa, Kenneth; Song, Lihua; Errington, Lauren; Cummings, Laurel; Hwang, Hongik; Kuhl, Dietmar; Worley, Paul; Lee, Hey-Kyoung

    2010-05-26

    Visual experience scales down excitatory synapses in the superficial layers of visual cortex in a process that provides an in vivo paradigm of homeostatic synaptic scaling. Experience-induced increases in neural activity rapidly upregulates mRNAs of immediate early genes involved in synaptic plasticity, one of which is Arc (activity-regulated cytoskeleton protein or Arg3.1). Cell biological studies indicate that Arc/Arg3.1 protein functions to recruit endocytic machinery for AMPA receptor internalization, and this action, together with its activity-dependent expression, rationalizes a role for Arc/Arg3.1 in homeostatic synaptic scaling. Here, we investigated the role of Arc/Arg3.1 in homeostatic scaling in vivo by examining experience-dependent development of layer 2/3 neurons in the visual cortex of Arc/Arg3.1 knock-out (KO) mice. Arc/Arg3.1 KOs show minimal changes in basal and developmental regulation of excitatory synaptic strengths but display a profound deficit in homeostatic regulation of excitatory synapses by visual experience. As additional evidence of specificity, we found that the visual experience-induced regulation of inhibitory synapses is normal, although the basal inhibitory synaptic strength is increased in the Arc/Arg3.1 KOs. Our results demonstrate that Arc/Arg3.1 plays a selective role in regulating visual experience-dependent homeostatic plasticity of excitatory synaptic transmission in vivo.

  17. Activity-Dependent Bidirectional Regulation of GAD Expression in a Homeostatic Fashion Is Mediated by BDNF-Dependent and Independent Pathways.

    PubMed

    Hanno-Iijima, Yoko; Tanaka, Masami; Iijima, Takatoshi

    2015-01-01

    Homeostatic synaptic plasticity, or synaptic scaling, is a mechanism that tunes neuronal transmission to compensate for prolonged, excessive changes in neuronal activity. Both excitatory and inhibitory neurons undergo homeostatic changes based on synaptic transmission strength, which could effectively contribute to a fine-tuning of circuit activity. However, gene regulation that underlies homeostatic synaptic plasticity in GABAergic (GABA, gamma aminobutyric) neurons is still poorly understood. The present study demonstrated activity-dependent dynamic scaling in which NMDA-R (N-methyl-D-aspartic acid receptor) activity regulated the expression of GABA synthetic enzymes: glutamic acid decarboxylase 65 and 67 (GAD65 and GAD67). Results revealed that activity-regulated BDNF (brain-derived neurotrophic factor) release is necessary, but not sufficient, for activity-dependent up-scaling of these GAD isoforms. Bidirectional forms of activity-dependent GAD expression require both BDNF-dependent and BDNF-independent pathways, both triggered by NMDA-R activity. Additional results indicated that these two GAD genes differ in their responsiveness to chronic changes in neuronal activity, which could be partially caused by differential dependence on BDNF. In parallel to activity-dependent bidirectional scaling in GAD expression, the present study further observed that a chronic change in neuronal activity leads to an alteration in neurotransmitter release from GABAergic neurons in a homeostatic, bidirectional fashion. Therefore, the differential expression of GAD65 and 67 during prolonged changes in neuronal activity may be implicated in some aspects of bidirectional homeostatic plasticity within mature GABAergic presynapses.

  18. Late evening brain activation patterns and their relation to the internal biological time, melatonin, and homeostatic sleep debt.

    PubMed

    Gorfine, Tali; Zisapel, Nava

    2009-02-01

    Sleep propensity increases sharply at night. Some evidence implicates the pineal hormone melatonin in this process. Using functional magnetic resonance imaging, brain activation during a visual search task was examined at 22:00 h (when endogenous melatonin levels normally increase). The relationships between brain activation, endogenous melatonin (measured in saliva), and self-reported fatigue were assessed. Finally, the effects of exogenous melatonin administered at 22:00 h were studied in a double blind, placebo-controlled crossover manner. We show that brain activation patterns as well as the response to exogenous melatonin significantly differ at night from those seen in afternoon hours. Thus, activation in the rostro-medial and lateral aspects of the occipital cortex and the thalamus diminished at 22:00 h. Activation in the right parietal cortex increased at night and correlated with individual fatigue levels, whereas exogenous melatonin given at 22:00 h reduced activation in this area. The right dorsolateral prefrontal cortex, an area considered to reflect homeostatic sleep debt, demonstrated increased activation at 22:00 h. Surprisingly, this increase correlated with endogenous melatonin. These results demonstrate and partially differentiate circadian effects (whether mediated by melatonin or not) and homeostatic sleep debt modulation of human brain activity associated with everyday fatigue at night.

  19. Two features of sleep slow waves: homeostatic and reactive aspects--from long term to instant sleep homeostasis.

    PubMed

    Halász, Péter; Bódizs, Róbert; Parrino, Liborio; Terzano, Mario

    2014-10-01

    In this paper we reviewed results of sleep research that have changed the views about sleep slow wave homeostasis, which involve use-dependent and experience-dependent local aspects to understand more of the physiology of plastic changes during sleep. Apart from the traditional homeostatic slow-wave economy, we also overviewed research on the existence and role of reactive aspects of sleep slow waves. Based on the results from spontaneous and artificially evoked slow waves, we offer a new hypothesis on instant slow wave homeostatic regulation. This regulation compensates for any potentially sleep-disturbing events by providing instant "delta injections" to maintain the nightly delta level, thus protecting cognitive functions located in the frontal lobe. We suggest that this double (long-term /instant) homeostasis provides double security for the frontal lobes in order to protect cognitive functions. The incorporation of reactive slow wave activity (SWA) makes sleep regulation more dynamic and provides more room for the internalization of external influences during sleep.

  20. Plasticity in respiratory motor neurons in response to reduced synaptic inputs: A form of homeostatic plasticity in respiratory control?

    PubMed

    Braegelmann, K M; Streeter, K A; Fields, D P; Baker, T L

    2017-01-01

    For most individuals, the respiratory control system produces a remarkably stable and coordinated motor output-recognizable as a breath-from birth until death. Very little is understood regarding the processes by which the respiratory control system maintains network stability in the presence of changing physiological demands and network properties that occur throughout life. An emerging principle of neuroscience is that neural activity is sensed and adjusted locally to assure that neurons continue to operate in an optimal range, yet to date, it is unknown whether such homeostatic plasticity is a feature of the neurons controlling breathing. Here, we review the evidence that local mechanisms sense and respond to perturbations in respiratory neural activity, with a focus on plasticity in respiratory motor neurons. We discuss whether these forms of plasticity represent homeostatic plasticity in respiratory control. We present new analyses demonstrating that reductions in synaptic inputs to phrenic motor neurons elicit a compensatory enhancement of phrenic inspiratory motor output, a form of plasticity termed inactivity-induced phrenic motor facilitation (iPMF), that is proportional to the magnitude of activity deprivation. Although the physiological role of iPMF is not understood, we hypothesize that it has an important role in protecting the drive to breathe during conditions of prolonged or intermittent reductions in respiratory neural activity, such as following spinal cord injury or during central sleep apnea.

  1. Circadian and homeostatic modulation of functional connectivity and regional cerebral blood flow in humans under normal entrained conditions.

    PubMed

    Hodkinson, Duncan J; O'Daly, Owen; Zunszain, Patricia A; Pariante, Carmine M; Lazurenko, Vitaly; Zelaya, Fernando O; Howard, Matthew A; Williams, Steven C R

    2014-09-01

    Diurnal rhythms have been observed in human behaviors as diverse as sleep, olfaction, and learning. Despite its potential impact, time of day is rarely considered when brain responses are studied by neuroimaging techniques. To address this issue, we explicitly examined the effects of circadian and homeostatic regulation on functional connectivity (FC) and regional cerebral blood flow (rCBF) in healthy human volunteers, using whole-brain resting-state functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). In common with many circadian studies, we collected salivary cortisol to represent the normal circadian activity and functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Intriguingly, the changes in FC and rCBF we observed indicated fundamental decreases in the functional integration of the default mode network (DMN) moving from morning to afternoon. Within the anterior cingulate cortex (ACC), our results indicate that morning cortisol levels are negatively correlated with rCBF. We hypothesize that the homeostatic mechanisms of the HPA axis has a role in modulating the functional integrity of the DMN (specifically, the ACC), and for the purposes of using fMRI as a tool to measure changes in disease processes or in response to treatment, we demonstrate that time of the day is important when interpreting resting-state data.

  2. A New Neutrino Oscillation

    SciTech Connect

    Parke, Stephen J.; /Fermilab

    2011-07-01

    Starting in the late 1960s, neutrino detectors began to see signs that neutrinos, now known to come in the flavors electron ({nu}{sub e}), muon ({nu}{sub {mu}}), and tau ({nu}{sub {tau}}), could transform from one flavor to another. The findings implied that neutrinos must have mass, since massless particles travel at the speed of light and their clocks, so to speak, don't tick, thus they cannot change. What has since been discovered is that neutrinos oscillate at two distinct scales, 500 km/GeV and 15,000 km/GeV, which are defined by the baseline (L) of the experiment (the distance the neutrino travels) divided by the neutrino energy (E). Neutrinos of one flavor can oscillate into neutrinos of another flavor at both L/E scales, but the amplitude of these oscillations is different for the two scales and depends on the initial and final flavor of the neutrinos. The neutrino states that propogate unchanged in time, the mass eigenstates {nu}1, {nu}2, {nu}3, are quantum mechanical mixtures of the electron, muon, and tau neutrino flavors, and the fraction of each flavor in a given mass eigenstate is controlled by three mixing angles and a complex phase. Two of these mixing angles are known with reasonable precision. An upper bound exists for the third angle, called {theta}{sub 13}, which controls the size of the muon neutrino to electron neutrino oscillation at an L/E of 500 km/GeV. The phase is completely unknown. The existence of this phase has important implications for the asymmetry between matter and antimatter we observe in the universe today. Experiments around the world have steadily assembled this picture of neutrino oscillation, but evidence of muon neutrino to electron neutrino oscillation at 500 km/GeV has remained elusive. Now, a paper from the T2K (Tokai to Kamioka) experiment in Japan, reports the first possible observation of muon neutrinos oscillating into electron neutrinos at 500 km/GeV. They see 6 candidate signal events, above an expected background

  3. Oscillate boiling from microheaters

    NASA Astrophysics Data System (ADS)

    Li, Fenfang; Gonzalez-Avila, S. Roberto; Nguyen, Dang Minh; Ohl, Claus-Dieter

    2017-01-01

    We report about an intriguing boiling regime occurring for small heaters embedded on the boundary in subcooled water. The microheater is realized by focusing a continuous wave laser beam to about 10 μ m in diameter onto a 165-nm-thick layer of gold, which is submerged in water. After an initial vaporous explosion a single bubble oscillates continuously and repeatedly at several 100 kHz albeit with constant laser power input. The microbubble's oscillations are accompanied with bubble pinch-off, leading to a stream of gaseous bubbles in the subcooled water. The self-driven bubble oscillation is explained with a thermally kicked oscillator caused by surface attachment and by the nonspherical collapses. Additionally, Marangoni stresses induce a recirculating streaming flow which transports cold liquid towards the microheater, reducing diffusion of heat along the substrate and therefore stabilizing the phenomenon to many million cycles. We speculate that this oscillate boiling regime may overcome the heat transfer thresholds observed during the nucleate boiling crisis and offers a new pathway for heat transfer under microgravity conditions.

  4. Oscillations following periodic reinforcement.

    PubMed

    Monteiro, Tiago; Machado, Armando

    2009-06-01

    Three experiments examined behavior in extinction following periodic reinforcement. During the first phase of Experiment 1, four groups of pigeons were exposed to fixed interval (FI 16s or FI 48s) or variable interval (VI 16s or VI 48s) reinforcement schedules. Next, during the second phase, each session started with reinforcement trials and ended with an extinction segment. Experiment 2 was similar except that the extinction segment was considerably longer. Experiment 3 replaced the FI schedules with a peak procedure, with FI trials interspersed with non-food peak interval (PI) trials that were four times longer. One group of pigeons was exposed to FI 20s PI 80s trials, and another to FI 40s PI 160s trials. Results showed that, during the extinction segment, most pigeons trained with FI schedules, but not with VI schedules, displayed pause-peck oscillations with a period close to, but slightly greater than the FI parameter. These oscillations did not start immediately after the onset of extinction. Comparing the oscillations from Experiments 1 and 2 suggested that the alternation of reconditioning and re-extinction increases the reliability and earlier onset of the oscillations. In Experiment 3 the pigeons exhibited well-defined pause-peck cycles since the onset of extinction. These cycles had periods close to twice the value of the FI and lasted for long intervals of time. We discuss some hypotheses concerning the processes underlying behavioral oscillations following periodic reinforcement.

  5. Neuroendocrine regulation and tumor immunity.

    PubMed

    Toni, R; Mirandola, P; Gobbi, G; Vitale, M

    2007-01-01

    The morphogenetic events leading to the transendothelial passage of lymphoid and tumoral cells are analyzed in light of a very recent and global theory of intercellular communication designated as the Triune Information Network (TIN). The TIN system is based on the assumption that cell-cell interactions primarily occur through cell surface informations or topobiological procesess, whose mechanisms rely upon expression of adhesion molecules, and are regulated by an array of locally-borne (autocrine/paracrine signals and autonomic inputs) and distantly-borne (endocrine secretions) messages. The final aim of the TIN is to control homeostatic functions crucial for the organism survival, like morphogenesis. Knowledge of the TIN signals involved in lymphoid and tumoral cell intravasation might offer a new perspetive to study the mechanisms of tumor immunity. Recognition of tumor target cells by immune cytotoxic effectors, in fact, can be considered a notable case of TIN-mediated cell to cell interaction. In particular, Natural Killer (NK) cells play a role in the cell-mediated control of tumor growth and metastatic spreading. Cell targeting and killing are dependent on the different NK cell receptors and on the efficacy of NK cells after cytokine and monoclonal antibody administration in cancer therapy. Since efficacy of NK cell-based immunotheraphy has been proven in KIR-mismatch regimens or in TRAIL-dependent apoptosis, the ability to manipulate the balance of activating and inhibitory receptors on NK cells and of their cognate ligands as well as the sensitivity of tumor cells to apoptosis, opens new perspectives for NK cell based immunotherapy.

  6. Digital numerically controlled oscillator

    NASA Technical Reports Server (NTRS)

    Cellier, A.; Huey, D. C.; Ma, L. N. (Inventor)

    1980-01-01

    The frequency and phase of an output signal from an oscillator circuit are controlled with accuracy by a digital input word. Positive and negative alterations in output frequency are both provided for by translating all values of input words so that they are positive. The oscillator reference frequency is corrected only in one direction, by adding phase to the output frequency of the oscillator. The input control word is translated to a single algebraic sign and the digital 1 is added thereto. The translated input control word is then accumulated. A reference clock signal having a frequency at an integer multiple of the desired frequency of the output signal is generated. The accumulated control word is then compared with a threshold level. The output signal is adjusted in a single direction by dividing the frequency of the reference clock signal by a first integer or by an integer different from the first integer.

  7. Magnetic vortex oscillators

    NASA Astrophysics Data System (ADS)

    Hrkac, Gino; Keatley, Paul S.; Bryan, Matthew T.; Butler, Keith

    2015-11-01

    The magnetic vortex has sparked the interest of the academic and industrial communities over the last few decades. From their discovery in the 1970s for bubble memory devices to their modern application as radio frequency oscillators, magnetic vortices have been adopted to modern telecommunication and sensor applications. Basic properties of vortex structures in the static and dynamic regime, from a theoretical and experimental point of view, are presented as well as their application in spin torque driven nano-pillar and magnetic tunnel junction devices. Single vortex excitations and phase locking phenomena of coupled oscillators are discussed with an outlook of vortex oscillators in magnetic hybrid structures with imprinted domain confinement and dynamic encryption devices.

  8. Chalcogenide optical parametric oscillator.

    PubMed

    Ahmad, Raja; Rochette, Martin

    2012-04-23

    We demonstrate the first optical parametric oscillator (OPO) based on chalcogenide glass. The parametric gain medium is an As(2)Se(3) chalcogenide microwire coated with a layer of polymer. The doubly-resonant OPO oscillates simultaneously at a Stokes and an anti Stokes wavelength shift of >50 nm from the pump wavelength that lies at λ(P) = 1,552 nm. The oscillator has a peak power threshold of 21.6 dBm and a conversion efficiency of >19%. This OPO experiment provides an additional application of the chalcogenide microwire technology; and considering the transparency of As(2)Se(3) glass extending far in the mid-infrared (mid-IR) wavelengths, the device holds promise for realizing mid-IR OPOs utilizing existing optical sources in the telecommunications wavelength region.

  9. Micromechanical Oscillating Mass Balance

    NASA Technical Reports Server (NTRS)

    Altemir, David A. (Inventor)

    1997-01-01

    A micromechanical oscillating mass balance and method adapted for measuring minute quantities of material deposited at a selected location, such as during a vapor deposition process. The invention comprises a vibratory composite beam which includes a dielectric layer sandwiched between two conductive layers. The beam is positioned in a magnetic field. An alternating current passes through one conductive layers, the beam oscillates, inducing an output current in the second conductive layer, which is analyzed to determine the resonant frequency of the beam. As material is deposited on the beam, the mass of the beam increases and the resonant frequency of the beam shifts, and the mass added is determined.

  10. New sensitive marginal oscillator

    NASA Astrophysics Data System (ADS)

    Rahf, L.

    1981-09-01

    A new type of a sensitive marginal oscillator has been developed for the determination of high magnetic inductions by means of nuclear magnetic resonance. Obtaining a high sensitivity with this measuring principle demands a soft behavior of the oscillator which is a particular feature of the circuit presented. It is shown that this behavior is due to the fact that a very weak positive feedback is established by the inner capacitances of the single field effect transistor used in the circuit. Optimal values for the operation parameters are calculated.

  11. Coupled opto-electronic oscillator

    NASA Technical Reports Server (NTRS)

    Yao, X. Steve (Inventor); Maleki, Lute (Inventor)

    1999-01-01

    A coupled opto-electronic oscillator that directly couples a laser oscillation with an electronic oscillation to simultaneously achieve a stable RF oscillation at a high frequency and ultra-short optical pulsation by mode locking with a high repetition rate and stability. Single-mode selection can be achieved even with a very long opto-electronic loop. A multimode laser can be used to pump the electronic oscillation, resulting in a high operation efficiency. The optical and the RF oscillations are correlated to each other.

  12. Plant Immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plants are faced with defending themselves against a multitude of pathogens, including bacteria, fungi, viruses, nematodes, etc. Immunity is multi-layered and complex. Plants can induce defenses when they recognize small peptides, proteins or double-stranded RNA associated with pathogens. Recognitio...

  13. Homeostatic and circadian control of body temperature in the fat-tailed gerbil.

    PubMed

    Refinetti, R

    1998-01-01

    The interplay of homeostasis and circadian rhythmicity in the control of body temperature was studied in the fat-tailed gerbil (Pachyuromys duprasi). In a first study, the body temperature rhythm of 8 gerbils maintained at 24 degrees C under a 14L:10D light-dark cycle was studied by telemetry. Data from 9 other species of small mammals were also obtained for comparison. The gerbils were found to exhibit a robust rhythm of body temperature (the most robust of the 10 species) with a high plateau during the dark phase of the light-dark cycle and a low plateau during the light phase. In a second experiment, 5 gerbils were allowed to select the temperature of their environment by moving along a thermal gradient. The animals consistently selected higher ambient temperatures during the light phase of the light-dark cycle (when their body temperature was at the low plateau). In a third experiment, the metabolic response of 8 gerbils to an acute cold exposure was determined by indirect calorimetry. Greater cold-induced thermogenesis was observed during the light phase. The fact that the animals selected higher ambient temperatures and displayed greater cold-induced thermogenesis when their body temperature was lower contradicts the hypothesis that the body temperature rhythm is caused by a rhythmic oscillation of the thermoregulatory set point.

  14. Oscillating Reactions: Two Analogies

    ERIC Educational Resources Information Center

    Petruševski, Vladimir M.; Stojanovska, Marina I.; Šoptrajanov, Bojan T.

    2007-01-01

    Oscillating chemical reactions are truly spectacular phenomena, and demonstrations are always appreciated by the class. However, explaining such reactions to high school or first-year university students is problematic, because it may seem that no acceptable explanation is possible unless the students have profound knowledge of both physical…

  15. Wein bridge oscillator circuit

    NASA Technical Reports Server (NTRS)

    Lipoma, P. C.

    1971-01-01

    Circuit with minimum number of components provides stable outputs of 2 to 8 volts at frequencies of .001 to 100 kHz. Oscillator exhibits low power consumption, portability, simplicity, and drive capability, it has application as loudspeaker tester and audible alarm, as well as in laboratory and test generators.

  16. A simple violin oscillator

    NASA Technical Reports Server (NTRS)

    Jones, R. T.

    1976-01-01

    For acoustic tests the violin is driven laterally at the bridge by a small speaker of the type commonly found in pocket transistor radios. An audio oscillator excites the tone which is picked up by a sound level meter. Gross patterns of vibration modes are obtained by the Chladni method.

  17. Voltage-Controlled Oscillator

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Integrated Component Systems, Inc. incorporated information from a NASA Tech Briefs article into a voltage-controlled oscillator it designed for a customer. The company then applied the technology to its series of phase-locked loop synthesizers, which offer superior phase noise performance.

  18. LSND neutrino oscillation results

    SciTech Connect

    Louis, W.C.; LSND Collaboration

    1997-06-01

    The LSND experiment at Los Alamos has conducted searches for {anti {nu}}{sub {mu}} {r_arrow} {anti {nu}}{sub e} oscillations using {anti {nu}}{sub {mu}} from U{sup +} decay at rest and for {nu}{sub {mu}} {r_arrow} {nu}{sub e} oscillations using {nu}{sub {mu}} from {pi}{sup +} decay in flight. For the {anti {nu}}{sub {mu}} {r_arrow} {anti {nu}}{sub e} search, a total excess of 51.8{sub {minus}16.9}{sup +18.7} {+-} 8.0 events is observed with e{sup +} energy between 20 and 60 MeV, while for the {nu}{sub {mu}} {r_arrow} {nu}{sub e} search, a total excess of 18.1 {+-} 6.6 {+-} 4.0 events is observed with e{sup {minus}} energy between 60 and 200 MeV. If attributed to neutrino oscillations, these excesses correspond to oscillation probabilities (averaged over the experimental energies and spatial acceptances) of (0.31 {+-} 0.12 {+-} 0.05)% and (0.26 {+-} 0.10 {+-} 0.05)%, respectively.

  19. Relativistic harmonic oscillator revisited

    SciTech Connect

    Bars, Itzhak

    2009-02-15

    The familiar Fock space commonly used to describe the relativistic harmonic oscillator, for example, as part of string theory, is insufficient to describe all the states of the relativistic oscillator. We find that there are three different vacua leading to three disconnected Fock sectors, all constructed with the same creation-annihilation operators. These have different spacetime geometric properties as well as different algebraic symmetry properties or different quantum numbers. Two of these Fock spaces include negative norm ghosts (as in string theory), while the third one is completely free of ghosts. We discuss a gauge symmetry in a worldline theory approach that supplies appropriate constraints to remove all the ghosts from all Fock sectors of the single oscillator. The resulting ghost-free quantum spectrum in d+1 dimensions is then classified in unitary representations of the Lorentz group SO(d,1). Moreover, all states of the single oscillator put together make up a single infinite dimensional unitary representation of a hidden global symmetry SU(d,1), whose Casimir eigenvalues are computed. Possible applications of these new results in string theory and other areas of physics and mathematics are briefly mentioned.

  20. Roles and regulation of gastrointestinal eosinophils in immunity and disease.

    PubMed

    Jung, YunJae; Rothenberg, Marc E

    2014-08-01

    Eosinophils have historically been considered to be destructive end-stage effector cells that have a role in parasitic infections and allergic reactions by the release of their granule-derived cytotoxic proteins. However, an increasing number of experimental observations indicate that eosinophils also are multifunctional leukocytes involved in diverse inflammatory and physiologic immune responses. Under homeostatic conditions, eosinophils are particularly abundant in the lamina propria of the gastrointestinal tract, where their involvement in various biological processes within the gastrointestinal tract has been posited. In this review, we summarize the molecular steps involved in eosinophil development and describe eosinophil trafficking to the gastrointestinal tract. We synthesize the current findings on the phenotypic and functional properties of gastrointestinal eosinophils and the accumulating evidence that they have a contributory role in gastrointestinal disorders, with a focus on primary eosinophilic gastrointestinal disorders. Finally, we discuss the potential role of eosinophils as modulators of the intestinal immune system.

  1. Monolithic Millimeter Wave Oscillator

    NASA Astrophysics Data System (ADS)

    Wang, Nan-Lei

    There is an increasing interest in the millimeter -wave spectrum for use in communications and for military and scientific applications. The concept of monolithic integration aims to produce very-high-frequency circuits in a more reliable, reproducible way than conventional electronics, and also at lower cost, with smaller size and lighter weight. In this thesis, a negative resistance device is integrated monolithically with a resonator to produce an effective oscillator. This work fills the void resulting from the exclusion of the local oscillator from the monolithic millimeter-wave integrated circuit (MMMIC) receiver design. For convenience a microwave frequency model was used to design the resonator circuit. A 5 GHz hybrid oscillator was first fabricated to test the design; the necessary GaAs process technology was developed for the fabrication. Negative resistance devices and oscillator theory were studied, and a simple but practical model of the Gunn diode was devised to solve the impedance matching problem. Monolithic oscillators at the Ka band (35 GHz) were built and refined. All devices operated in CW mode. By means of an electric-field probe, the output power was coupled into a metallic waveguide for measurement purposes. The best result was 3.63 mW of power output, the highest efficiency was 0.43% and the frequency stability was better than 10-4. In the future, an IMPATT diode could replace the Gunn device to give much higher power and efficiency. A varactor-tuned circuit also suitable for large-scale integration is under study.

  2. Orthogonal polynomials and deformed oscillators

    NASA Astrophysics Data System (ADS)

    Borzov, V. V.; Damaskinsky, E. V.

    2015-10-01

    In the example of the Fibonacci oscillator, we discuss the construction of oscillator-like systems associated with orthogonal polynomials. We also consider the question of the dimensions of the corresponding Lie algebras.

  3. Master oscillator stability requirements considerations

    SciTech Connect

    Schwarz, H.; Vancraeynest, J.

    1986-06-24

    This note attempts to point out some ideas about the required stability of the 476 MHz master oscillator, assuming that the phase noise of the oscillator is the only source of noise in the accelerator system.

  4. The role of novel and known extracellular matrix and adhesion molecules in the homeostatic and regenerative bone marrow microenvironment

    PubMed Central

    Klamer, Sofieke; Voermans, Carlijn

    2014-01-01

    Maintenance of haematopoietic stem cells and differentiation of committed progenitors occurs in highly specialized niches. The interactions of haematopoietic stem and progenitor cells (HSPCs) with cells, growth factors and extracellular matrix (ECM) components of the bone marrow (BM) microenvironment control homeostasis of HSPCs. We only start to understand the complexity of the haematopoietic niche(s) that comprises endosteal, arterial, sinusoidal, mesenchymal and neuronal components. These distinct niches produce a broad range of soluble factors and adhesion molecules that modulate HSPC fate during normal hematopoiesis and BM regeneration. Adhesive interactions between HSPCs and the microenvironment will influence their localization and differentiation potential. In this review we highlight the current understanding of the functional role of ECM- and adhesion (regulating) molecules in the haematopoietic niche during homeostatic and regenerative hematopoiesis. This knowledge may lead to the improvement of current cellular therapies and more efficient development of future cellular products. PMID:25482635

  5. Brain-derived neurotrophic factor--a major player in stimulation-induced homeostatic metaplasticity of human motor cortex?

    PubMed

    Mastroeni, Claudia; Bergmann, Til Ole; Rizzo, Vincenzo; Ritter, Christoph; Klein, Christine; Pohlmann, Ines; Brueggemann, Norbert; Quartarone, Angelo; Siebner, Hartwig Roman

    2013-01-01

    Repetitive transcranial magnetic stimulation (rTMS) of the human motor hand area (M1HAND) can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val(66)met polymorphism in the brain-derived neurotrophic factor (BDNF) gene. Here we used theta burst stimulation (TBS) to examine whether the BDNF val(66)met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS) usually inducing a lasting increase and continuous TBS (cTBS) a lasting decrease in corticospinal excitability. In three separate sessions, healthy val(66)met (n = 12) and val(66)val (n = 17) carriers received neuronavigated cTBS followed by cTBS (n = 27), cTBS followed by iTBS (n = 29), and iTBS followed by iTBS (n = 28). Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS) and increase (iTBS) in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val(66)met carriers and val(66)val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val(66)met polymorphism, our results do not support the notion that the BDNF val(66)met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND.

  6. A reappraisal of the blood glucose homeostat which comprehensively explains the type 2 diabetes mellitus–syndrome X complex

    PubMed Central

    Koeslag, Johan H; Saunders, Peter T; Terblanche, Elmarie

    2003-01-01

    Blood glucose concentrations are unaffected by exercise despite very high rates of glucose flux. The plasma ionised calcium levels are even more tightly controlled after meals and during lactation. This implies ‘integral control’. However, pairs of integral counterregulatory controllers (e.g. insulin and glucagon, or calcitonin and parathyroid hormone) cannot operate on the same controlled variable, unless there is some form of mutual inhibition. Flip-flop functional coupling between pancreatic α- and β-cells via gap junctions may provide such a mechanism. Secretion of a common inhibitory chromogranin by the parathyroids and the thyroidal C-cells provides another. Here we describe how the insulin:glucagon flip-flop controller can be complemented by growth hormone, despite both being integral controllers. Homeostatic conflict is prevented by somatostatin-28 secretion from both the hypothalamus and the pancreatic islets. Our synthesis of the information pertaining to the glucose homeostat that has accumulated in the literature predicts that disruption of the flip-flop mechanism by the accumulation of amyloid in the pancreatic islets in type 2 diabetes mellitus will lead to hyperglucagonaemia, hyperinsulinaemia, insulin resistance, glucose intolerance and impaired insulin responsiveness to elevated blood glucose levels. It explains syndrome X (or metabolic syndrome) as incipient type 2 diabetes in which the glucose control system, while impaired, can still maintain blood glucose at the desired level. It also explains why it is characterised by high plasma insulin levels and low plasma growth hormone levels, despite normoglycaemia, and how this leads to central obesity, dyslipidaemia and cardiovascular disease in both syndrome X and type 2 diabetes. PMID:12717005

  7. The homeostatic set point of the hypothalamus-pituitary-thyroid axis – maximum curvature theory for personalized euthyroid targets

    PubMed Central

    2014-01-01

    Background Despite rendering serum free thyroxine (FT4) and thyrotropin (TSH) within the normal population ranges broadly defined as euthyroidism, many patients being treated for hyperthyroidism and hypothyroidism persistently experience subnormal well-being discordant from their pre-disease healthy euthyroid state. This suggests that intra-individual physiological optimal ranges are narrower than laboratory-quoted normal ranges and implies the existence of a homeostatic set point encoded in the hypothalamic-pituitary-thyroid (HPT) axis that is unique to every individual. Methods We have previously shown that the dose–response characteristic of the hypothalamic-pituitary (HP) unit to circulating thyroid hormone levels follows a negative exponential curve. This led to the discovery that the normal reference intervals of TSH and FT4 fall within the ‘knee’ region of this curve where the maximum curvature of the exponential HP characteristic occurs. Based on this observation, we develop the theoretical framework localizing the position of euthyroid homeostasis over the point of maximum curvature of the HP characteristic. Results The euthyroid set points of patients with primary hypothyroidism and hyperthyroidism can be readily derived from their calculated HP curve parameters using the parsimonious mathematical model above. It can be shown that every individual has a euthyroid set point that is unique and often different from other individuals. Conclusions In this treatise, we provide evidence supporting a set point-based approach in tailoring euthyroid targets. Rendering FT4 and TSH within the laboratory normal ranges can be clinically suboptimal if these hormone levels are distant from the individualized euthyroid homeostatic set point. This mathematical technique permits the euthyroid set point to be realistically computed using an algorithm readily implementable for computer-aided calculations to facilitate precise targeted dosing of patients in this modern

  8. Ionization oscillations in Hall accelerators

    NASA Astrophysics Data System (ADS)

    Barral, S.; Peradzyński, Z.

    2010-01-01

    The underlying mechanism of low-frequency oscillations in Hall accelerators is investigated theoretically. It is shown that relaxation oscillations arise from a competition between avalanche ionization and the advective transport of the working gas. The model derived recovers the slow progression and fast recession of the ionization front. Analytical approximations of the shape of current pulses and of the oscillation frequency are provided for the case of large amplitude oscillations.

  9. Many-body Bloch oscillations

    NASA Astrophysics Data System (ADS)

    Haque, Masud

    2014-03-01

    We consider Bloch oscillations of interacting quantum particles in a one-dimensional lattice subject to a linear potential gradient (a tilt). For hard-core bosons and for free fermions, we show perfectly periodic behavior of density and momentum distributions. The oscillations can be predominantly position oscillations, or predominantly width oscillations, depending on the initial state. We show how the periodic behavior is modified for weak and strong interactions.

  10. Neutrino Oscillations with Reactor Neutrinos

    NASA Astrophysics Data System (ADS)

    Cabrera, Anatael

    2007-06-01

    Prospect measurements of neutrino oscillations with reactor neutrinos are reviewed in this document. The following items are described: neutrinos oscillations status, reactor neutrino experimental strategy, impact of uncertainties on the neutrino oscillation sensitivity and, finally, the experiments in the field. This is the synthesis of the talk delivered during the NOW2006 conference at Otranto (Italy) during September 2006.

  11. Immunization Schedules for Adults

    MedlinePlus

    ... ACIP Vaccination Recommendations Why Immunize? Vaccines: The Basics Immunization Schedules for Adults in Easy-to-read Formats ... previous immunizations. View or Print a Schedule Recommended Immunizations for Adults (19 Years and Older) by Age ...

  12. Immune System (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Immune System KidsHealth > For Parents > Immune System A A A ... can lead to illness and infection. About the Immune System The immune system is the body's defense against ...

  13. Immunity in Drosophila melanogaster--from microbial recognition to whole-organism physiology.

    PubMed

    Buchon, Nicolas; Silverman, Neal; Cherry, Sara

    2014-12-01

    Since the discovery of antimicrobial peptide responses 40 years ago, the fruit fly Drosophila melanogaster has proven to be a powerful model for the study of innate immunity. Early work focused on innate immune mechanisms of microbial recognition and subsequent nuclear factor-κB signal transduction. More recently, D. melanogaster has been used to understand how the immune response is regulated and coordinated at the level of the whole organism. For example, researchers have used this model in studies investigating interactions between the microbiota and the immune system at barrier epithelial surfaces that ensure proper nutritional and immune homeostasis both locally and systemically. In addition, studies in D. melanogaster have been pivotal in uncovering how the immune response is regulated by both endocrine and metabolic signalling systems, and how the immune response modifies these systems as part of a homeostatic circuit. In this Review, we briefly summarize microbial recognition and antiviral immunity in D. melanogaster, and we highlight recent studies that have explored the effects of organism-wide regulation of the immune response and, conversely, the effects of the immune response on organism physiology.

  14. Extrahepatic complications to cirrhosis and portal hypertension: haemodynamic and homeostatic aspects.

    PubMed

    Møller, Søren; Henriksen, Jens H; Bendtsen, Flemming

    2014-11-14

    In addition to complications relating to the liver, patients with cirrhosis and portal hypertension develop extrahepatic functional disturbances of multiple organ systems. This can be considered a multiple organ failure that involves the heart, lungs, kidneys, the immune systems, and other organ systems. Progressive fibrosis of the liver and subsequent metabolic impairment leads to a systemic and splanchnic arteriolar vasodilatation. This affects both the haemodynamic and functional homeostasis of many organs and largely determines the course of the disease. With the progression of the disease, the circulation becomes hyperdynamic with cardiac, pulmonary as well as renal consequences for dysfunction and reduced survival. Infections and a changed cardiac function known as cirrhotic cardiomyopathy may be involved in further aggravation of other complications such as renal failure precipitating the hepatorenal syndrome. Patients with end-stage liver disease and related complications as for example the hepatopulmonary syndrome can only radically be treated by liver transplantation. As a bridge to this treatment, knowledge on the mechanisms of the pathophysiology of complications is essential for the choice of vasoactive drugs, antibiotics, drugs with specific effects on fibrogenesis and inflammation, and drugs that target specific receptors.

  15. Peroxisome Proliferator-Activated Receptor γ 2 Modulates Late-Pregnancy Homeostatic Metabolic Adaptations

    PubMed Central

    Vivas, Yurena; Díez-Hochleitner, Monica; Izquierdo-Lahuerta, Adriana; Corrales, Patricia; Horrillo, Daniel; Velasco, Ismael; Martínez-García, Cristina; Campbell, Mark; Sevillano, Julio; Ricote, Mercedes; Ros, Manuel; Ramos, Maria Pilar; Medina-Gomez, Gema

    2016-01-01

    Pregnancy requires adaptation of maternal energy metabolism, including expansion and functional modifications of adipose tissue. Insulin resistance (IR), predominantly during late gestation, is a physiological metabolic adaptation that serves to support the metabolic demands of fetal growth. The molecular mechanisms underlying these adaptations are not fully understood and may contribute to gestational diabetes mellitus. Peroxisome proliferator-activated receptor γ (PPARγ) controls adipogenesis, glucose and lipid metabolism and insulin sensitivity. The PPARγ2 isoform is mainly expressed in adipocytes and is thus likely to contribute to adipose tissue adaptation during late pregnancy. In the present study, we investigated the contribution of PPARγ2 to the metabolic adaptations occurring during the late phase of pregnancy in the context of IR. Using a model of late pregnancy in PPARγ2 knockout (KO) mice, we found that deletion of PPARγ2 exacerbated IR in association with lower serum adiponectin levels, increased body weight and enhanced lipid accumulation in the liver. Lack of PPARγ2 provoked changes in the distribution of fat mass and preferentially prevented expansion of the perigonadal depot while at the same time exacerbating inflammation. Pregnant PPARγ2KO mice presented adipose tissue depot-dependent decreased expression of genes involved in lipid metabolism. Collectively, these data indicate that PPARγ2 is essential in promoting healthy adipose tissue expansion and immune and metabolic functionality during pregnancy, contributing to the physiological adaptations that lead gestation to term. PMID:27782293

  16. Voltage-controlled photonic oscillator.

    PubMed

    Savchenkov, A A; Ilchenko, V S; Liang, W; Eliyahu, D; Matsko, A B; Seidel, D; Maleki, L

    2010-05-15

    We report the development and demonstration of an X-band voltage-controlled photonic oscillator based on a whispering gallery mode resonator made of an electro-optic crystalline material. The oscillator has good spectral purity and wide, agile, linear tunability. We have modified the existing theoretical model of the opto-electronic oscillator to describe the performance of our tunable oscillator and have found a good agreement between the theoretical predictions and the measurement results. We show that the device is promising for higher-frequency applications where high-performance tunable oscillators with wide tunability do not exist.

  17. Stable local oscillator module.

    SciTech Connect

    Brocato, Robert Wesley

    2007-11-01

    This report gives a description of the development of a Stable Local Oscillator (StaLO) multi-chip module (MCM). It is a follow-on report to SAND2006-6414, Stable Local Oscillator Microcircuit. The StaLO accepts a 100MHz input signal and produces output signals at 1.2, 3.3, and 3.6 GHz. The circuit is built as a multi-chip module (MCM), since it makes use of integrated circuit technologies in silicon and lithium niobate as well as discrete passive components. This report describes the development of an MCM-based version of the complete StaLO, fabricated on an alumina thick film hybrid substrate.

  18. Oscillations of complex networks

    NASA Astrophysics Data System (ADS)

    Wang, Xingang; Lai, Ying-Cheng; Lai, Choy Heng

    2006-12-01

    A complex network processing information or physical flows is usually characterized by a number of macroscopic quantities such as the diameter and the betweenness centrality. An issue of significant theoretical and practical interest is how such quantities respond to sudden changes caused by attacks or disturbances in recoverable networks, i.e., functions of the affected nodes are only temporarily disabled or partially limited. By introducing a model to address this issue, we find that, for a finite-capacity network, perturbations can cause the network to oscillate persistently in the sense that the characterizing quantities vary periodically or randomly with time. We provide a theoretical estimate of the critical capacity-parameter value for the onset of the network oscillation. The finding is expected to have broad implications as it suggests that complex networks may be structurally highly dynamic.

  19. THz Local Oscillator Technology

    NASA Technical Reports Server (NTRS)

    Mehdi, Imran

    2004-01-01

    The last decade has seen a number of technological advancements that have now made it possible to implement fully solid state local oscillator chains up to 2 THz. These chains are composed of cascaded planar multiplier stages that are pumped with W-band high power sources. The high power W-band sources are achieved by power combining MMIC amplifiers and can provide in access of 150 mW with about 10% bandwidth. Planar diode technology has also enabled novel circuit topologies that can take advantage of the high input power and demonstrate significant efficiencies well into the THz range. Cascaded chains to 1.9 THz have now been demonstrated with enough output power to successfully pump hot-electron bolometer mixers in this frequency range. An overview of the current State-of-the-Art of the local oscillator technology will be presented along with highlighting future trends and challenges.

  20. Nonlinear Neural Network Oscillator.

    DTIC Science & Technology

    A nonlinear oscillator (10) includes a neural network (12) having at least one output (12a) for outputting a one dimensional vector. The neural ... neural network and the input of the input layer for modifying a magnitude and/or a polarity of the one dimensional output vector prior to the sample of...first or a second direction. Connection weights of the neural network are trained on a deterministic sequence of data from a chaotic source or may be a

  1. Millennial climate oscillation spied

    SciTech Connect

    Kerr, R.A.

    1996-01-12

    Although evaluating the effects of greenhouse gases on climatic warming has been a major growth industry, greenhouse gases are not the only effect on the global climate. Analysing climate records stored in sediments and glacial ice, researchers have detected a slow climate oscillation that has alternately warmed and cooled the world very couple of thousand years for the past hundred thousand years, perhaps millions of years. This article gives an overview of the evidence.

  2. Decay of oscillating universes

    NASA Astrophysics Data System (ADS)

    Mithani, Audrey Todhunter

    2016-08-01

    It has been suggested by Ellis et al that the universe could be eternal in the past, without beginning. In their model, the "emergent universe'' exists forever in the past, in an "eternal'' phase before inflation begins. We will show that in general, such an "eternal'' phase is not possible, because of an instability due to quantum tunneling. One candidate model, the "simple harmonic universe'' has been shown by Graham et al to be perturbatively stable; we find that it is unstable with respect to quantum tunneling. We also investigate the stability of a distinct oscillating model in loop quantum cosmology with respect to small perturbations and to quantum collapse. We find that the model has perturbatively stable and unstable solutions, with both types of solutions occupying significant regions of the parameter space. All solutions are unstable with respect to collapse by quantum tunneling to zero size. In addition, we investigate the effect of vacuum corrections, due to the trace anomaly and the Casimir effect, on the stability of an oscillating universe with respect to decay by tunneling to the singularity. We find that these corrections do not generally stabilize an oscillating universe. Finally, we determine the decay rate of the oscillating universe. Although the wave function of the universe lacks explicit time dependence in canonical quantum cosmology, time evolution may be present implicitly through the semiclassical superspace variables, which themselves depend on time in classical dynamics. Here, we apply this approach to the simple harmonic universe, by extending the model to include a massless, minimally coupled scalar field φ which has little effect on the dynamics but can play the role of a "clock''.

  3. Covariant deformed oscillator algebras

    NASA Technical Reports Server (NTRS)

    Quesne, Christiane

    1995-01-01

    The general form and associativity conditions of deformed oscillator algebras are reviewed. It is shown how the latter can be fulfilled in terms of a solution of the Yang-Baxter equation when this solution has three distinct eigenvalues and satisfies a Birman-Wenzl-Murakami condition. As an example, an SU(sub q)(n) x SU(sub q)(m)-covariant q-bosonic algebra is discussed in some detail.

  4. Oscillating stagnation point flow

    NASA Technical Reports Server (NTRS)

    Grosch, C. E.; Salwen, H.

    1982-01-01

    A solution of the Navier-Stokes equations is given for an incompressible stagnation point flow whose magnitude oscillates in time about a constant, non-zero, value (an unsteady Hiemenz flow). Analytic approximations to the solution in the low and high frequency limits are given and compared with the results of numerical integrations. The application of these results to one aspect of the boundary layer receptivity problem is also discussed.

  5. Oscillating stagnation point flow

    NASA Astrophysics Data System (ADS)

    Grosch, C. E.; Salwen, H.

    1982-11-01

    A solution of the Navier-Stokes equations is given for an incompressible stagnation point flow whose magnitude oscillates in time about a constant, non-zero, value (an unsteady Hiemenz flow). Analytic approximations to the solution in the low and high frequency limits are given and compared with the results of numerical integrations. The application of these results to one aspect of the boundary layer receptivity problem is also discussed.

  6. Biochemical Oscillations and Cellular Rhythms

    NASA Astrophysics Data System (ADS)

    Goldbeter, Albert; Berridge, Foreword by M. J.

    1997-04-01

    1. Introduction; Part I. Glycolytic Oscillations: 2. Oscillatory enzymes: simple periodic behaviour in an allosteric model for glycolytic oscillations; Part II. From Simple to Complex Oscillatory Behaviour; 3. Birhythmicity: coexistence between two stable rhythms; 4. From simple periodic behaviour to complex oscillations, including bursting and chaos; Part III. Oscillations Of Cyclic Amo In Dictyostelium Cells: 5. Models for the periodic synthesis and relay of camp signals in Dictyostelium discoideum amoebae; 6. Complex oscillations and chaos in the camp signalling system of Dictyostelium; 7. The onset of camp oscillations in Dictyostelium as a model for the ontogenesis of biological rhythms; Part IV. Pulsatile Signalling In Intercellular Communication: 8. Function of the rhythm of intercellular communication in Dictyostelium. Link with pulsatile hormone secretion; Part V. Calcium Oscillations: 9. Oscillations and waves of intracellular calcium; Part VI. The Mitotic Oscillator: 10. Modelling the mitotic oscillator driving the cell division cycle; Part VII. Circadian Rhythms: 11. Towards a model for circadian oscillations in the Drosophila period protein (PER); 12. Conclusions and perspectives; References.

  7. LSND neutrino oscillation results

    SciTech Connect

    Louis, W.C.; LSND Collaboration

    1996-10-01

    The LSND (Liquid Scintillator Neutrino Detector) experiment at Los Alamos has conducted a search for muon antineutrino {r_arrow} electron antineutrino oscillations using muon neutrinos from antimuon decay at rest. The electron antineutrinos are detected via the reaction electron antineutrino + proton {r_arrow} positron + neutron, correlated with the 2.2-MeV gamma from neutron + proton {r_arrow} deuteron + gamma. The use of tight cuts to identify positron events with correlated gamma rays yields 22 events with positron energy between 36 and 60 MeV and only 4.6 {+-} 0.6 background events. The probability that this excess is due entirely to a statistical fluctuation is 4.1 {times} 10{sup -8}. A chi-squared fit to the entire positron sample results in a total excess of 51.8 {sup +18.7}{sub -16.9} {+-} 8.0 events with positron energy between 20 and 60 MeV. If attributed to muon antineutrino {r_arrow} electron antineutrino oscillations, this corresponds to an oscillation probability (averaged over the experimental energy and spatial acceptance) of (0.31 {+-} 0.12 {+-} 0.05){percent}. 10 refs., 7 figs., 1 tab.

  8. LSND neutrino oscillation results

    SciTech Connect

    White, D.H.; LSND Collaboration

    1997-11-01

    The LSND experiment at Los Alamos has conducted a search for {anti v}{sub {mu}} {yields} {anti v}{sub e} oscillations using {anti v}{sub {mu}} from {mu}{sup +} decay at rest. The {anti v}{sub e} are detected via the reaction {anti v}{sub e} p {yields} e{sup +}n, correlated with the 2.2 MeV {gamma} from n p {yields} d {gamma}. The use of tight cuts to identify e{sup +} events with correlated {gamma} rays yielded 22 events with e{sup +} energy between 36 and 60 MeV and only 4.6 {+-} 0.6 background events. The probability that this excess is due entirely to a statistical fluctuation is 4.1 {times} 10{sup {minus}8}. A {chi}{sup 2} fit to the entire e{sup +} sample results in a total excess of 51.8{sub {minus}16.9}{sup +18.7} {+-} 8.0 events with e{sup +} energy between 20 and 60 MeV. If attributed to {anti v}{sub {mu}} {yields} {anti v}{sub e} oscillations, this corresponds to an oscillation probability (averaged over the experimental energy and spatial acceptance) of 0.31 {+-} 0.12 {+-} 0.05%.

  9. Temperature sensitive oscillator

    NASA Technical Reports Server (NTRS)

    Kleinberg, L. L. (Inventor)

    1986-01-01

    An oscillator circuit for sensing and indicating temperature by changing oscillator frequency with temperature comprises a programmable operational amplifier which is operated on the roll-off portion of its gain versus frequency curve and has its output directly connected to the inverting input to place the amplifier in a follower configuration. Its output is also connected to the non-inverting input by a capacitor with a crystal or other tuned circuit also being connected to the non-inverting input. A resistor is connected to the program input of the amplifier to produce a given set current at a given temperature, the set current varying with temperature. As the set current changes, the gain-bandwidth of the amplifier changes and, in turn, the reflected capacitance across the crystal changes, thereby providing the desired change in oscillator frequency by pulling the crystal. There is no requirement that a crystal employed with this circuit display either a linear frequency change with temperature or a substantial frequency change with temperature.

  10. Nonlinear Oscillators in Space Physics

    NASA Technical Reports Server (NTRS)

    Lester,Daniel; Thronson, Harley

    2011-01-01

    We discuss dynamical systems that produce an oscillation without an external time dependent source. Numerical results are presented for nonlinear oscillators in the Em1h's atmosphere, foremost the quasi-biennial oscillation (QBOl. These fluid dynamical oscillators, like the solar dynamo, have in common that one of the variables in a governing equation is strongly nonlinear and that the nonlinearity, to first order, has particular form. of 3rd or odd power. It is shown that this form of nonlinearity can produce the fundamental li'equency of the internal oscillation. which has a period that is favored by the dynamical condition of the fluid. The fundamental frequency maintains the oscillation, with no energy input to the system at that particular frequency. Nonlinearities of 2nd or even power could not maintain the oscillation.

  11. Innate and Adaptive Immune Response to Apoptotic Cells

    PubMed Central

    Peng, YuFeng; Martin, David A; Kenkel, Justin; Zhang, Kang; Ogden, Carol Anne; Elkon, Keith B.

    2007-01-01

    The immune system is constantly exposed to dying cells, most of which arise during central tolerance and from effete circulating immune cells. Under homeostatic conditions, phagocytes (predominantly macrophages and dendritic cells) belonging to the innate immune system, rapidly ingest cells and their debris. Apoptotic cell removal requires recognition of altered self on the apoptotic membrane, a process which is facilitated by natural antibodies and serum opsonins. Recognition, may be site and context specific. Uptake and ingestion of apoptotic cells promotes an immunosuppressive environment that avoids inflammatory responses to self antigens. However, it does not preclude a T cell response and it is likely that constant exposure to self antigen, particularly by immature dendritic cells, leads to T cell tolerance. Tolerance occurs by several different mechanisms including anergy and deletion (for CD8+ T cells) and induction of T regulatory cells (for CD4+ T cells). Failed apoptotic cell clearance promotes immune responses to self antigens, especially when the cellular contents are leaked from the cell (necrosis). Inflammatory responses may be induced by nucleic acid stimulation of toll like receptors and other immune sensors, specific intracellular proteins and non protein (uric acid) stimulation of inflammasomes. PMID:17888627

  12. Extracellular Membrane Vesicles and Immune Regulation in the Brain

    PubMed Central

    Cossetti, Chiara; Smith, Jayden A.; Iraci, Nunzio; Leonardi, Tommaso; Alfaro-Cervello, Clara; Pluchino, Stefano

    2012-01-01

    The brain is characterized by a complex and integrated network of interacting cells in which cell-to-cell communication is critical for proper development and function. Initially considered as an immune privileged site, the brain is now regarded as an immune specialized system. Accumulating evidence reveals the presence of immune components in the brain, as well as extensive bidirectional communication that takes place between the nervous and the immune system both under homeostatic and pathological conditions. In recent years the secretion of extracellular membrane vesicles (EMVs) has been described as a new and evolutionary well-conserved mechanism of cell-to-cell communication, with EMVs influencing the microenvironment through the traffic of bioactive molecules that include proteins and nucleic acids, such as DNA, protein coding, and non-coding RNAs. Increasing evidence suggests that EMVs are a promising candidate to study cross-boundary cell-to-cell communication pathways. Herein we review the role of EMVs secreted by neural cells in modulating the immune response(s) within the brain under physiological and pathological circumstances. PMID:22557978

  13. Environmentally related disorders of the hematologic and immune systems

    SciTech Connect

    Luster, M.I.; Wierda, D.; Rosenthal, G.J. )

    1990-03-01

    From observations in rodents and, to a lesser extent, in humans inadvertently or occupationally exposed, it appears that a number of xenobiotics adversely affect immune homeostatic systems, either through acting as a hapten and resulting in hypersensitivity reactions or through altering hematopoietic or immune functions. At present, however, there is no evidence that the immune or hematopoietic systems of the general population have been compromised by xenobiotics via environmental exposure. Nonetheless, these examples and our current knowledge about the pathogenesis of disease support the possibility that chemical-induced damage to the immune system may be associated with potential pathological conditions, some of which may become detectable only after a long latency. Likewise, exposure to immunotoxic xenobiotics might represent additional risk to individuals with already fragile immune systems (e.g., in malnutrition, infancy, old age). However, it is important to be cautious when attempting to extrapolate meaningful conclusions from experimental data or isolated epidemiologic studies to risk assessment for low-level human exposure.65 references.

  14. Acquisition of a Nd-Yag Pumped MOPO (Master Oscillator/Power Oscillator) Optical Parametric Oscillator

    DTIC Science & Technology

    1997-09-30

    SEP 1997 2. REPORT TYPE 3. DATES COVERED 00-00-1997 to 00-00-1997 4. TITLE AND SUBTITLE Acquisition of a Nd-Yag Pumped MOPO (Master Oscillator...unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 ACQUISITION OF A ND-YAG PUMPED MOPO (MASTER OSCILLATOR / POWER OSCILLATOR) OPTICAL...instrument is configured in a master oscillator/power oscillator configuration, hence the designation MOPO . The MOPO will be used in conjunction

  15. Glucose Oscillations Can Activate an Endogenous Oscillator in Pancreatic Islets.

    PubMed

    McKenna, Joseph P; Dhumpa, Raghuram; Mukhitov, Nikita; Roper, Michael G; Bertram, Richard

    2016-10-01

    Pancreatic islets manage elevations in blood glucose level by secreting insulin into the bloodstream in a pulsatile manner. Pulsatile insulin secretion is governed by islet oscillations such as bursting electrical activity and periodic Ca2+ entry in β-cells. In this report, we demonstrate that although islet oscillations are lost by fixing a glucose stimulus at a high concentration, they may be recovered by subsequently converting the glucose stimulus to a sinusoidal wave. We predict with mathematical modeling that the sinusoidal glucose signal's ability to recover islet oscillations depends on its amplitude and period, and we confirm our predictions by conducting experiments with islets using a microfluidics platform. Our results suggest a mechanism whereby oscillatory blood glucose levels recruit non-oscillating islets to enhance pulsatile insulin output from the pancreas. Our results also provide support for the main hypothesis of the Dual Oscillator Model, that a glycolytic oscillator endogenous to islet β-cells drives pulsatile insulin secretion.

  16. Integrated Circuit Immunity

    NASA Technical Reports Server (NTRS)

    Sketoe, J. G.; Clark, Anthony

    2000-01-01

    This paper presents a DOD E3 program overview on integrated circuit immunity. The topics include: 1) EMI Immunity Testing; 2) Threshold Definition; 3) Bias Tee Function; 4) Bias Tee Calibration Set-Up; 5) EDM Test Figure; 6) EMI Immunity Levels; 7) NAND vs. and Gate Immunity; 8) TTL vs. LS Immunity Levels; 9) TP vs. OC Immunity Levels; 10) 7805 Volt Reg Immunity; and 11) Seventies Chip Set. This paper is presented in viewgraph form.

  17. Altered gamma oscillations during pregnancy through loss of δ subunit-containing GABA(A) receptors on parvalbumin interneurons.

    PubMed

    Ferando, Isabella; Mody, Istvan

    2013-01-01

    Gamma (γ) oscillations (30-120 Hz), an emergent property of neuronal networks, correlate with memory, cognition and encoding. In the hippocampal CA3 region, locally generated γ oscillations emerge through feedback between inhibitory parvalbumin-positive basket cells (PV+BCs) and the principal (pyramidal) cells. PV+BCs express δ-subunit-containing GABA(A)Rs (δ-GABA(A)Rs) and NMDA receptors (NMDA-Rs) that balance the frequency of γ oscillations. Neuroactive steroids (NS), such as the progesterone-derived (3α,5α)-3-hydroxy-pregnan-20-one (allopregnanolone; ALLO), modulate the expression of δ-GABA(A)Rs and the tonic conductance they mediate. Pregnancy produces large increases in ALLO and brain-region-specific homeostatic changes in δ-GABA(A)Rs expression. Here we show that in CA3, where most PV+ interneurons (INs) express δ-GABA(A)Rs, expression of δ-GABA(A)Rs on INs diminishes during pregnancy, but reverts to control levels within 48 h postpartum. These anatomical findings were corroborated by a pregnancy-related increase in the frequency of kainate-induced CA3 γ oscillations in vitro that could be countered by the NMDA-R antagonists D-AP5 and PPDA. Mimicking the typical hormonal conditions during pregnancy by supplementing 100 nM ALLO lowered the γ frequencies to levels found in virgin or postpartum mice. Our findings show that states of altered NS levels (e.g., pregnancy) may provoke perturbations in γ oscillatory activity through direct effects on the GABAergic system, and underscore the importance of δ-GABA(A)Rs homeostatic plasticity in maintaining constant network output despite large hormonal changes. Inaccurate coupling of NS levels to δ-GABA(A)R expression may facilitate abnormal neurological and psychiatric conditions such as epilepsy, post-partum depression, and post-partum psychosis, thus providing insights into potential new treatments.

  18. Altered gamma oscillations during pregnancy through loss of δ subunit-containing GABAA receptors on parvalbumin interneurons

    PubMed Central

    Ferando, Isabella; Mody, Istvan

    2013-01-01

    Gamma (γ) oscillations (30–120 Hz), an emergent property of neuronal networks, correlate with memory, cognition and encoding. In the hippocampal CA3 region, locally generated γ oscillations emerge through feedback between inhibitory parvalbumin-positive basket cells (PV+BCs) and the principal (pyramidal) cells. PV+BCs express δ-subunit-containing GABAARs (δ-GABAARs) and NMDA receptors (NMDA-Rs) that balance the frequency of γ oscillations. Neuroactive steroids (NS), such as the progesterone-derived (3α,5α)-3-hydroxy-pregnan-20-one (allopregnanolone; ALLO), modulate the expression of δ-GABAARs and the tonic conductance they mediate. Pregnancy produces large increases in ALLO and brain-region-specific homeostatic changes in δ-GABAARs expression. Here we show that in CA3, where most PV+ interneurons (INs) express δ-GABAARs, expression of δ-GABAARs on INs diminishes during pregnancy, but reverts to control levels within 48 h postpartum. These anatomical findings were corroborated by a pregnancy-related increase in the frequency of kainate-induced CA3 γ oscillations in vitro that could be countered by the NMDA-R antagonists D-AP5 and PPDA. Mimicking the typical hormonal conditions during pregnancy by supplementing 100 nM ALLO lowered the γ frequencies to levels found in virgin or postpartum mice. Our findings show that states of altered NS levels (e.g., pregnancy) may provoke perturbations in γ oscillatory activity through direct effects on the GABAergic system, and underscore the importance of δ-GABAARs homeostatic plasticity in maintaining constant network output despite large hormonal changes. Inaccurate coupling of NS levels to δ-GABAAR expression may facilitate abnormal neurological and psychiatric conditions such as epilepsy, post-partum depression, and post-partum psychosis, thus providing insights into potential new treatments. PMID:24062647

  19. Nutritionally mediated programming of the developing immune system.

    PubMed

    Palmer, Amanda C

    2011-09-01

    A growing body of evidence highlights the importance of a mother's nutrition from preconception through lactation in programming the emerging organ systems and homeostatic pathways of her offspring. The developing immune system may be particularly vulnerable. Indeed, examples of nutrition-mediated immune programming can be found in the literature on intra-uterine growth retardation, maternal micronutrient deficiencies, and infant feeding. Current models of immune ontogeny depict a "layered" expansion of increasingly complex defenses, which may be permanently altered by maternal malnutrition. One programming mechanism involves activation of the maternal hypothalamic-pituitary-adrenal axis in response to nutritional stress. Fetal or neonatal exposure to elevated stress hormones is linked in animal studies to permanent changes in neuroendocrine-immune interactions, with diverse manifestations such as an attenuated inflammatory response or reduced resistance to tumor colonization. Maternal malnutrition may also have a direct influence, as evidenced by nutrient-driven epigenetic changes to developing T regulatory cells and subsequent risk of allergy or asthma. A 3rd programming pathway involves placental or breast milk transfer of maternal immune factors with immunomodulatory functions (e.g. cytokines). Maternal malnutrition can directly affect transfer mechanisms or influence the quality or quantity of transferred factors. The public health implications of nutrition-mediated immune programming are of particular importance in the developing world, where prevalent maternal undernutrition is coupled with persistent infectious challenges. However, early alterations to the immune system, resulting from either nutritional deficiencies or excesses, have broad relevance for immune-mediated diseases, such as asthma, and chronic inflammatory conditions like cardiovascular disease.

  20. Synchronous Discrete Harmonic Oscillator

    SciTech Connect

    Antippa, Adel F.; Dubois, Daniel M.

    2008-10-17

    We introduce the synchronous discrete harmonic oscillator, and present an analytical, numerical and graphical study of its characteristics. The oscillator is synchronous when the time T for one revolution covering an angle of 2{pi} in phase space, is an integral multiple N of the discrete time step {delta}t. It is fully synchronous when N is even. It is pseudo-synchronous when T/{delta}t is rational. In the energy conserving hyperincursive representation, the phase space trajectories are perfectly stable at all time scales, and in both synchronous and pseudo-synchronous modes they cycle through a finite number of phase space points. Consequently, both the synchronous and the pseudo-synchronous hyperincursive modes of time-discretization provide a physically realistic and mathematically coherent, procedure for dynamic, background independent, discretization of spacetime. The procedure is applicable to any stable periodic dynamical system, and provokes an intrinsic correlation between space and time, whereby space-discretization is a direct consequence of background-independent time-discretization. Hence, synchronous discretization moves the formalism of classical mechanics towards that of special relativity. The frequency of the hyperincursive discrete harmonic oscillator is ''blue shifted'' relative to its continuum counterpart. The frequency shift has the precise value needed to make the speed of the system point in phase space independent of the discretizing time interval {delta}t. That is the speed of the system point is the same on the polygonal (in the discrete case) and the circular (in the continuum case) phase space trajectories.

  1. Synchronous Discrete Harmonic Oscillator

    NASA Astrophysics Data System (ADS)

    Antippa, Adel F.; Dubois, Daniel M.

    2008-10-01

    We introduce the synchronous discrete harmonic oscillator, and present an analytical, numerical and graphical study of its characteristics. The oscillator is synchronous when the time T for one revolution covering an angle of 2π in phase space, is an integral multiple N of the discrete time step Δt. It is fully synchronous when N is even. It is pseudo-synchronous when T/Δt is rational. In the energy conserving hyperincursive representation, the phase space trajectories are perfectly stable at all time scales, and in both synchronous and pseudo-synchronous modes they cycle through a finite number of phase space points. Consequently, both the synchronous and the pseudo-synchronous hyperincursive modes of time-discretization provide a physically realistic and mathematically coherent, procedure for dynamic, background independent, discretization of spacetime. The procedure is applicable to any stable periodic dynamical system, and provokes an intrinsic correlation between space and time, whereby space-discretization is a direct consequence of background-independent time-discretization. Hence, synchronous discretization moves the formalism of classical mechanics towards that of special relativity. The frequency of the hyperincursive discrete harmonic oscillator is "blue shifted" relative to its continuum counterpart. The frequency shift has the precise value needed to make the speed of the system point in phase space independent of the discretizing time interval Δt. That is the speed of the system point is the same on the polygonal (in the discrete case) and the circular (in the continuum case) phase space trajectories.

  2. On particle oscillations

    NASA Astrophysics Data System (ADS)

    Góźdź, Marek; Góźdź, Andrzej

    2014-05-01

    It has been firmly established that neutrinos change their flavour during propagation. This feature is attributed to the feature that each flavour eigenstate is a superposition of three mass eigenstates, which propagate with different frequencies. This picture, although widely accepted, is wrong in the simplest approach and requires quite sophisticated treatment based on the wave-packet description within quantum field theory. In this communication we present a novel, much simpler explanation and show that oscillations among massive particles can be obtained in a natural way. We use the framework of quantum mechanics with time being a physical observable, not just a parameter.

  3. CORE SATURATION BLOCKING OSCILLATOR

    DOEpatents

    Spinrad, R.J.

    1961-10-17

    A blocking oscillator which relies on core saturation regulation to control the output pulse width is described. In this arrangement an external magnetic loop is provided in which a saturable portion forms the core of a feedback transformer used with the thermionic or semi-conductor active element. A first stationary magnetic loop establishes a level of flux through the saturation portion of the loop. A second adjustable magnet moves the flux level to select a saturation point giving the desired output pulse width. (AEC)

  4. THz Local Oscillator Sources

    NASA Astrophysics Data System (ADS)

    Mehdi, Imran; Schlecht, Erich; Chattopadhyay, Goutam; Siegel, Peter H.

    Most operational Submillimeter-wave radio telescopes, both space borne and ground based, employ local oscillator sources based on Gunn diodes followed by whisker contacted Schottky multipliers. Enough progress, however, has been made on a number of fronts to conclude that next generation of radio telescopes that become operational in the new Millennium will have a different local oscillator (LO) generation architecture. MMIC power amplifiers with impressive gain in the Ka- to-W band have enabled the use of microwave synthesizers which can then be actively multiplied to provide a frequency agile power source beyond 100 GHz. This medium power millimeter source can then be amplified to enable efficient pumping of follow-on balanced multiplier stages. Input power to the multipliers can be further enhanced by power combining to achieve close to half a Watt at W-band. An 800 GHz three-stage multiplier chain, implemented this way has demonstrated a peak output power of 1 mW. A second advance in LO generation lies in the Schottky diode varactor technology. Planar Schottky diode multipliers have now been demonstrated up to 1500 GHz and it can be assumed that most of the future multiplier chains will be based on these robust devices rather than the whisker contacted diode of the past. The ability to produce planar GaAs diode chips deep into the THz range, with submicron dimensions, has opened up a wide range of circuit design space which can be taken advantage of to improve efficiency, bandwidth, and power handling capability of the multipliers. A third breakthrough has been the demonstration of photonic based LO sources utilizing GaAs photomixers. These sources, though not yet implemented in robust space borne missions, offer a number of advantages over their electronic counterparts, including extremely broad tuning, fiber coupled components, and solid-state implementation. Another development, which holds some promise, is the use of micro-machining technology to implement

  5. Brain Oscillations, Hypnosis, and Hypnotizability.

    PubMed

    Jensen, Mark P; Adachi, Tomonori; Hakimian, Shahin

    2015-01-01

    This article summarizes the state-of-science knowledge regarding the associations between hypnosis and brain oscillations. Brain oscillations represent the combined electrical activity of neuronal assemblies, usually measured as specific frequencies representing slower (delta, theta, alpha) and faster (beta, gamma) oscillations. Hypnosis has been most closely linked to power in the theta band and changes in gamma activity. These oscillations are thought to play a critical role in both the recording and recall of declarative memory and emotional limbic circuits. The authors propose that this role may be the mechanistic link between theta (and perhaps gamma) oscillations and hypnosis, specifically, that the increases in theta oscillations and changes in gamma activity observed with hypnosis may underlie some hypnotic responses. If these hypotheses are supported, they have important implications for both understanding the effects of hypnosis and for enhancing response to hypnotic treatments.

  6. Brain Oscillations, Hypnosis, and Hypnotizability

    PubMed Central

    Jensen, Mark P.; Adachi, Tomonori; Hakimian, Shahin

    2014-01-01

    In this article, we summarize the state-of-science knowledge regarding the associations between hypnosis and brain oscillations. Brain oscillations represent the combined electrical activity of neuronal assemblies, and are usually measured as specific frequencies representing slower (delta, theta, alpha) and faster (beta, gamma) oscillations. Hypnosis has been most closely linked to power in the theta band and changes in gamma activity. These oscillations are thought to play a critical role in both the recording and recall of declarative memory and emotional limbic circuits. Here we propose that it is this role that may be the mechanistic link between theta (and perhaps gamma) oscillations and hypnosis; specifically that theta oscillations may facilitate, and that changes in gamma activity observed with hypnosis may underlie, some hypnotic responses. If these hypotheses are supported, they have important implications for both understanding the effects of hypnosis, and for enhancing response to hypnotic treatments. PMID:25792761

  7. Competing Synchronization of Nonlinear Oscillators

    NASA Astrophysics Data System (ADS)

    Rosa, Epaminondas

    2006-03-01

    Coupled nonlinear oscillators abound in nature and in man-made devices. Think for example of two neurons in the brain competing to get the attention of a third neuron, and eventually developing some sort of synchronization process. This is a common feature involving oscillators in general, and can be studied using numerical simulations and/or experimental setups. In this talk, results involving electronic circuits and plasma discharges will be presented showing interesting features related to the types of oscillators and to the types of couplings. In particular, for the case of two oscillators competing for synchronization with a third one, the target oscillator synchronizes alternately to one or the other of the competing oscillators. The time intervals of synchronous states vary in a random-like manner. Numerical and experimental results will be presented and the consistency between them will be discussed.

  8. C P -violating baryon oscillations

    NASA Astrophysics Data System (ADS)

    McKeen, David; Nelson, Ann E.

    2016-10-01

    We enumerate the conditions necessary for C P violation to be manifest in n -n ¯ oscillations and build a simple model that can give rise to such effects. We discuss a possible connection between neutron oscillations and dark matter, provided the mass of the latter lies between mp-me and mp+me. We apply our results to a possible baryogenesis scenario involving C P violation in the oscillations of the Ξ0.

  9. Localization oscillation in antidot lattices

    NASA Astrophysics Data System (ADS)

    Uryu, S.; Ando, T.

    1998-06-01

    The Anderson localization in square and hexagonal antidot lattices is numerically studied with the use of a Thouless number method. It is revealed that localization is very sensitive to the aspect ratio between the antidot diameter and the lattice constant. In a hexagonal lattice, both the Thouless number and the localization length oscillate with the period equal to the Al’tshuler-Aronov-Spivak oscillation. The oscillation is quite weak in a square lattice.

  10. Transmission-line tunnel diode oscillator: A sensitive, fast, and flexible low-temperature detection system

    SciTech Connect

    Brisson, J.G.; Silvera, I.F.

    1986-11-01

    Tunnel diode oscillators (TDO's) excel in high-resolution measurement of inductive and capacitive transducers at cryogenic temperatures. The transmission-line tunnel diode oscillator (TLTDO) discussed here combines the ease of construction of a discrete element TDO with the quick response times and immunity to stray reactances of the reentrant cavity TDO. Theory and design of four TLTDO's are discussed. Two characteristic response times for TDO's are discussed.

  11. Thymomegaly, Microsplenia, and Defective Homeostatic Proliferation of Peripheral Lymphocytes in p51-Ets1 Isoform-Specific Null Mice▿

    PubMed Central

    Higuchi, Tsukasa; Bartel, Frank O.; Masuya, Masahiro; Deguchi, Takao; Henderson, Kelly W.; Li, Runzhao; Muise-Helmericks, Robin C.; Kern, Michael J.; Watson, Dennis K.; Spyropoulos, Demetri D.

    2007-01-01

    Ets1 is a member of the Ets transcription factor family. Alternative splicing of exon VII results in two naturally occurring protein isoforms: full-length Ets1 (p51-Ets1) and Ets1ΔVII (p42-Ets1). These isoforms bear key distinctions regarding protein-protein interactions, DNA binding kinetics, and transcriptional target specificity. Disruption of both Ets1 isoforms in mice results in the loss of detectable NK and NKT cell activity and defects in B and T lymphocytes. We generated mice that express only the Ets1ΔVII isoform. Ets1ΔVII homozygous mice express no p51-Ets1 and elevated levels of the p42-Ets1 protein relative to the wild type and display increased perinatal lethality, thymomegaly, and peripheral lymphopenia. Proliferation was increased in both the thymus and the spleen, while apoptosis was decreased in the thymus and increased in the spleen of homozygotes. Significant elevations of CD8+ and CD8+CD4+ thymocytes were observed. Lymphoid cell (CD19+, CD4+, and CD8+) reductions were predominantly responsible for diminished spleen cellularity, with fewer memory cells and a failure of homeostatic proliferation to maintain peripheral lymphocytes. Collectively, the Ets1ΔVII mutants demonstrate lymphocyte maturation defects associated with misregulation of p16Ink4a, p27Kip1, and CD44. Thus, a balance in the differential regulation of Ets1 isoforms represents a potential mechanism in the control of lymphoid maturation and homeostasis. PMID:17339335

  12. Preparations of homeostatic thymus hormone consist predominantly of histones 2A and 2B and suggest additional histone functions.

    PubMed Central

    Reichhart, R; Zeppezauer, M; Jörnvall, H

    1985-01-01

    The two major constituents in preparations of the homeostatic thymus hormone (HTH) were purified. Amino acid sequence analysis showed that the components (HTH alpha and HTH beta) are identical to histones H2A and H2B, suggesting the possibility that histones might have hitherto unrecognized occurrence and functions. If the HTH activities are not ascribed to the two histones in the preparation, they could only be derived from minor constituents present in minimal amounts. Therefore, the histone structures were scrutinized for properties of relevance in relation to hormone activities and for similarities with thymic hormones. Similarities between COOH-terminal regions of histones H2A, H2B, and H3 were noticed, as well as some similarities between NH2-terminal regions of histones and parts of recognized thymus hormones and related proteins. Potential signals, resembling cleavage sites in prohormones, are present in the histone structures, and further correlations with recently discovered ubiquitin functions may explain molecular mechanisms for actions of the HTH preparations. None of the observations is significant by itself, but the combined results suggest the hypothesis of different relationships and functions, including hormone-like activities, for some histones. Images PMID:3860828

  13. Homeostatic response to blocking cell division in Drosophila imaginal discs: Role of the Fat/Dachsous (Ft/Ds) pathway.

    PubMed

    Montes, Antonio J; Morata, Ginés

    2017-03-11

    One major problem in developmental biology is the identification of the mechanisms that control the final size of tissues and organs. We are addressing this issue in the imaginal discs of Drosophila by analysing the response to blocking cell division in large domains in the wing and leg discs. The affected domains may be zones of restricted lineage like compartments, or zones of open lineage that may integrate cells from the surrounding territory. Our results reveal the existence of a powerful homeostatic mechanism that can compensate for gross differences in growth rates and builds structures of normal size. This mechanism functions at the level of whole discs, inducing additional cell proliferation to generate the cells that populate the cell division-arrested territory and generating an active recruitment process to integrate those cells. The activation of this response mechanism is mediated by alterations in the normal activity of PCP genes of the Fat/Ds system: in discs mutant for dachs, ds or four jointed the response mechanism is not activated.

  14. MicroRNA 21 Is a Homeostatic Regulator of Macrophage Polarization and Prevents Prostaglandin E2-Mediated M2 Generation

    PubMed Central

    Wang, Zhuo; Brandt, Stephanie; Medeiros, Alexandra; Wang, Soujuan; Wu, Hao; Dent, Alexander; Serezani, C. Henrique

    2015-01-01

    Macrophages dictate both initiation and resolution of inflammation. During acute inflammation classically activated macrophages (M1) predominate, and during the resolution phase alternative macrophages (M2) are dominant. The molecular mechanisms involved in macrophage polarization are understudied. MicroRNAs are differentially expressed in M1 and M2 macrophages that influence macrophage polarization. We identified a role of miR-21 in macrophage polarization, and found that cross-talk between miR-21 and the lipid mediator prostaglandin E2 (PGE2) is a determining factor in macrophage polarization. miR-21 inhibition impairs expression of M2 signature genes but not M1 genes. PGE2 and its downstream effectors PKA and Epac inhibit miR-21 expression and enhance expression of M2 genes, and this effect is more pronounced in miR-21-/- cells. Among potential targets involved in macrophage polarization, we found that STAT3 and SOCS1 were enhanced in miR-21-/- cells and further enhanced by PGE2. We found that STAT3 was a direct target of miR-21 in macrophages. Silencing the STAT3 gene abolished PGE2-mediated expression of M2 genes in miR-21-/- macrophages. These data shed light on the molecular brakes involved in homeostatic macrophage polarization and suggest new therapeutic strategies to prevent inflammatory responses. PMID:25706647

  15. IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1

    PubMed Central

    Ruckerl, Dominik; Thomas, Graham D.; Hewitson, James P.; Duncan, Sheelagh; Brombacher, Frank; Maizels, Rick M.; Hume, David A.; Allen, Judith E.

    2013-01-01

    Macrophages (MΦs) colonize tissues during inflammation in two distinct ways: recruitment of monocyte precursors and proliferation of resident cells. We recently revealed a major role for IL-4 in the proliferative expansion of resident MΦs during a Th2-biased tissue nematode infection. We now show that proliferation of MΦs during intestinal as well as tissue nematode infection is restricted to sites of IL-4 production and requires MΦ-intrinsic IL-4R signaling. However, both IL-4Rα–dependent and –independent mechanisms contributed to MΦ proliferation during nematode infections. IL-4R–independent proliferation was controlled by a rise in local CSF-1 levels, but IL-4Rα expression conferred a competitive advantage with higher and more sustained proliferation and increased accumulation of IL-4Rα+ compared with IL-4Rα− cells. Mechanistically, this occurred by conversion of IL-4Rα+ MΦs from a CSF-1–dependent to –independent program of proliferation. Thus, IL-4 increases the relative density of tissue MΦs by overcoming the constraints mediated by the availability of CSF-1. Finally, although both elevated CSF1R and IL-4Rα signaling triggered proliferation above homeostatic levels, only CSF-1 led to the recruitment of monocytes and neutrophils. Thus, the IL-4 pathway of proliferation may have developed as an alternative to CSF-1 to increase resident MΦ numbers without coincident monocyte recruitment. PMID:24101381

  16. Age-related homeostatic mid-channel proteolysis of neuronal L-type voltage-gated Ca2+ channels

    PubMed Central

    Michailidis, Ioannis E.; Abele-Henckels, Kathryn; Zhang, Wei K.; Lin, Bochao; Yu, Yong; Geyman, Larry; Ehlers, Michael D.; Pnevmatikakis, Eftychios A.; Yang, Jian

    2014-01-01

    SUMMARY Neural circuitry and brain activity depend critically on proper function of voltage-gated calcium channels (VGCCs), whose activity must be tightly controlled. We show that the main body of the pore-forming α1 subunit of neuronal L-type VGCCs, Cav1.2, is proteolytically cleaved, resulting in Cav1.2 fragment-channels that separate but remain on the plasma membrane. This “gmid-channel” proteolysis is regulated by channel activity, involves the Ca2+-dependent protease calpain and the ubiquitin-proteasome system, and causes attenuation and biophysical alterations of VGCC currents. Recombinant Cav1.2 fragment-channels mimicking the products of mid-channel proteolysis do not form active channels on their own, but when properly paired, produce currents with distinct biophysical properties. Mid-channel proteolysis increases dramatically with age and can be attenuated with an L-type VGCC blocker in vivo. Mid-channel proteolysis represents a novel form of homeostatic negative-feedback processing of VGCCs that could profoundly affect neuronal excitability, neurotransmission, neuroprotection, and calcium signaling in physiological and disease states. PMID:24908485

  17. B Cell Development in the Bone Marrow Is Regulated by Homeostatic Feedback Exerted by Mature B Cells.

    PubMed

    Shahaf, Gitit; Zisman-Rozen, Simona; Benhamou, David; Melamed, Doron; Mehr, Ramit

    2016-01-01

    Cellular homeostasis in the B cell compartment is strictly imposed to balance cell production and cell loss. However, it is not clear whether B cell development in the bone marrow is an autonomous process or subjected to regulation by the peripheral B cell compartment. To specifically address this question, we used mice transgenic for human CD20, where effective depletion of B lineage cells is obtained upon administration of mouse anti-human CD20 antibodies, in the absence of any effect on other cell lineages and/or tissues. We followed the kinetics of B cell return to equilibrium by BrdU labeling and flow cytometry and analyzed the resulting data by mathematical modeling. Labeling was much faster in depleted mice. Compared to control mice, B cell-depleted mice exhibited a higher proliferation rate in the pro-/pre-B compartment, and higher cell death and lower differentiation in the immature B cell compartment. We validated the first result by analysis of the expression of Ki67, the nuclear protein expressed in proliferating cells, and the second using Annexin V staining. Collectively, our results suggest that B lymphopoiesis is subjected to homeostatic feedback mechanisms imposed by mature B cells in the peripheral compartment.

  18. Homeostatic 'bystander' proliferation of human peripheral blood B cells in response to polyclonal T-cell stimulation in vitro.

    PubMed

    Jasiulewicz, Aleksandra; Lisowska, Katarzyna A; Pietruczuk, Krzysztof; Frąckowiak, Joanna; Fulop, Tamas; Witkowski, Jacek M

    2015-11-01

    The mechanisms of maintenance of adequate numbers of B lymphocytes and of protective levels of immunoglobulins in the absence of antigenic (re)stimulation remain not fully understood. Meanwhile, our results presented here show that both peripheral blood naive and memory B cells can be activated strongly and non-specifically (in a mitogen-like fashion) in 5-day in vitro cultures of anti-CD3- or concanavalin A (Con A)-stimulated peripheral blood mononuclear cells of healthy people. This polyclonal, bystander activation of the B cells includes multiple divisions of most of them (assessed here by the flow cytometric technique of dividing cell tracking) and significant antibody [immunoglobulin M (IgM) and IgG] secretion. Observed proliferation of the CD19(+) B cells depends on contact with stimulated T helper (Th) cells (via CD40-CD40L interaction) and on the response of B cells to secreted interleukins IL-5, IL-10 and IL-4, and is correlated with the levels of these Th-derived molecules, while it does not involve the ligation of the BCR/CD19 complex. We suggest that the effect might reflect the situation occurring in vivo as the homeostatic proliferation of otherwise non-stimulated, peripheral B lymphocytes, providing an always ready pool for efficient antibody production to any new (or cognate) antigen challenge.

  19. Critical role of quorum sensing-dependent glutamate metabolism in homeostatic osmolality and outer membrane vesiculation in Burkholderia glumae

    PubMed Central

    Kang, Yongsung; Goo, Eunhye; Kim, Jinwoo; Hwang, Ingyu

    2017-01-01

    Metabolic homeostasis in cooperative bacteria is achieved by modulating primary metabolism in a quorum sensing (QS)-dependent manner. A perturbed metabolism in QS mutants causes physiological stress in the rice bacterial pathogen Burkholderia glumae. Here, we show that increased bacterial osmolality in B. glumae is caused by unusually high cellular concentrations of glutamate and betaine generated by QS deficiencies. QS negatively controls glutamate uptake and the expression of genes involved in the glutamine synthetase and glutamine oxoglutarate aminotransferase cycles. Thus, cellular glutamate levels were significantly higher in the QS mutants than in the wild type, and they caused hyperosmotic cellular conditions. Under the hypotonic conditions of the periplasm in the QS mutants, outer membrane bulging and vesiculation were observed, although these changes were rescued by knocking out the gltI gene, which encodes a glutamate transporter. Outer membrane modifications were not detected in the wild type. These results suggest that QS-dependent glutamate metabolism is critical for homeostatic osmolality. We suggest that outer membrane bulging and vesiculation might be the outcome of a physiological adaptation to relieve hypotonic osmotic stress in QS mutants. Our findings reveal how QS functions to maintain bacterial osmolality in a cooperative population. PMID:28272446

  20. Homeostatic interactions at the front of migration control the integrity and the efficiency of a migratory glial chain.

    PubMed

    Berzsenyi, Sara; Kumar, Arun; Giangrande, Angela

    2011-09-28

    In metazoans, cell migration often occurs in a collective manner: the cells move while physically and functionally connected to their neighbors. The coordinated and timely movement of the cells eventually ensures the proper organization of tissues, and deregulation in such a process contributes to the development of severe diseases. Thus, understanding the cellular mechanisms underlying coordinated cell movement is of great interest in basic and medical science. The developing Drosophila wing provides an excellent model to follow the chain migration of glial cells in vivo. Cells at the tip of the glial collective have been shown to control the timely movement of the chain. In the present study, we show that while pioneers trigger chain migration, they cannot move as single cells. We also show that isolating cell clusters at the chain tip restores the formation of smaller migratory communities. Interestingly, the migratory efficiency of these de novo formed communities depends on the number of cells and progressively improves as the size of the cluster increases. Thus, homeostatic events at the migratory front control community integrity, efficiency, and coordination, emphasizing the importance of interactions and cell counting in fine-tuning collective processes.

  1. Critical role of quorum sensing-dependent glutamate metabolism in homeostatic osmolality and outer membrane vesiculation in Burkholderia glumae.

    PubMed

    Kang, Yongsung; Goo, Eunhye; Kim, Jinwoo; Hwang, Ingyu

    2017-03-08

    Metabolic homeostasis in cooperative bacteria is achieved by modulating primary metabolism in a quorum sensing (QS)-dependent manner. A perturbed metabolism in QS mutants causes physiological stress in the rice bacterial pathogen Burkholderia glumae. Here, we show that increased bacterial osmolality in B. glumae is caused by unusually high cellular concentrations of glutamate and betaine generated by QS deficiencies. QS negatively controls glutamate uptake and the expression of genes involved in the glutamine synthetase and glutamine oxoglutarate aminotransferase cycles. Thus, cellular glutamate levels were significantly higher in the QS mutants than in the wild type, and they caused hyperosmotic cellular conditions. Under the hypotonic conditions of the periplasm in the QS mutants, outer membrane bulging and vesiculation were observed, although these changes were rescued by knocking out the gltI gene, which encodes a glutamate transporter. Outer membrane modifications were not detected in the wild type. These results suggest that QS-dependent glutamate metabolism is critical for homeostatic osmolality. We suggest that outer membrane bulging and vesiculation might be the outcome of a physiological adaptation to relieve hypotonic osmotic stress in QS mutants. Our findings reveal how QS functions to maintain bacterial osmolality in a cooperative population.

  2. Ultraconserved elements are associated with homeostatic control of splicing regulators by alternative splicing and nonsense-mediated decay

    PubMed Central

    Ni, Julie Z.; Grate, Leslie; Donohue, John Paul; Preston, Christine; Nobida, Naomi; O’Brien, Georgeann; Shiue, Lily; Clark, Tyson A.; Blume, John E.; Ares, Manuel

    2007-01-01

    Many alternative splicing events create RNAs with premature stop codons, suggesting that alternative splicing coupled with nonsense-mediated decay (AS-NMD) may regulate gene expression post-transcriptionally. We tested this idea in mice by blocking NMD and measuring changes in isoform representation using splicing-sensitive microarrays. We found a striking class of highly conserved stop codon-containing exons whose inclusion renders the transcript sensitive to NMD. A genomic search for additional examples identified >50 such exons in genes with a variety of functions. These exons are unusually frequent in genes that encode splicing activators and are unexpectedly enriched in the so-called “ultraconserved” elements in the mammalian lineage. Further analysis show that NMD of mRNAs for splicing activators such as SR proteins is triggered by splicing activation events, whereas NMD of the mRNAs for negatively acting hnRNP proteins is triggered by splicing repression, a polarity consistent with widespread homeostatic control of splicing regulator gene expression. We suggest that the extreme genomic conservation surrounding these regulatory splicing events within splicing factor genes demonstrates the evolutionary importance of maintaining tightly tuned homeostasis of RNA-binding protein levels in the vertebrate cell. PMID:17369403

  3. The role of homeostatic regulation between tumor suppressor DAB2IP and oncogenic Skp2 in prostate cancer growth

    PubMed Central

    Tsai, Yuh-Shyan; Lai, Chen-Li; Lai, Chih-Ho; Chang, Kai-Hsiung; Wu, Kaijie; Tseng, Shu-Fen; Fazli, Ladan; Gleave, Martin; Xiao, Guanghua; Gandee, Leah; Sharifi, Nima; Moro, Loredana; Tzai, Tzong-Shin; Hsieh, Jer-Tsong

    2014-01-01

    Altered DAB2IP gene expression often detected in prostate cancer (PCa) is due to epigenetic silencing. In this study, we unveil a new mechanism leading to the loss of DAB2IP protein; an oncogenic S-phase kinase-associated protein-2 (Skp2) as E3 ubiquitin ligase plays a key regulator in DAB2IP degradation. In order to unveil the role of Skp2 in the turnover of DAB2IP protein, both prostate cell lines and prostate cancer specimens with a variety of molecular and cell biologic techniques were employed. We demonstrated that DAB2IP is regulated by Skp2-mediated proteasome degradation in the prostate cell lines. Further analyses identified the N-terminal DAB2IP containing the ubiquitination site. Immunohistochemical study exhibited an inverse correlation between DAB2IP and Skp2 protein expression in the prostate cancer tissue microarray. In contrast, DAB2IP can suppress Skp2 protein expression is mediated through Akt signaling. The reciprocal regulation between DAB2IP and Skp2 can impact on the growth of PCa cells. This reciprocal regulation between DAB2IP and Skp2 protein represents a unique homeostatic balance between tumor suppressor and oncoprotein in normal prostate epithelia, which is apparently altered in cancer cells. The outcome of this study has identified new potential targets for developing new therapeutic strategy for PCa. PMID:25115390

  4. Symmetries of coupled harmonic oscillators

    NASA Technical Reports Server (NTRS)

    Han, D.; Kim, Y. S.

    1993-01-01

    It is shown that the system of two coupled harmonic oscillators possesses many interesting symmetries. It is noted that the symmetry of a single oscillator is that of the three-parameter group Sp(2). Thus two uncoupled oscillator exhibits a direct product of two Sp(2) groups, with six parameters. The coupling can be achieved through a rotation in the two-dimensional space of two oscillator coordinates. The closure of the commutation relations for the generators leads to the ten-parameter group Sp(4) which is locally isomorphic to the deSitter group O(3,2).

  5. Dipole oscillations in fermionic mixtures

    SciTech Connect

    Chiacchiera, S.; Macri, T.; Trombettoni, A.

    2010-03-15

    We study dipole oscillations in a general fermionic mixture. Starting from the Boltzmann equation, we classify the different solutions in the parameter space through the number of real eigenvalues of the small oscillations matrix. We discuss how this number can be computed using the Sturm algorithm and its relation with the properties of the Laplace transform of the experimental quantities. After considering two components in harmonic potentials having different trapping frequencies, we study dipole oscillations in three-component mixtures. Explicit computations are done for realistic experimental setups using the classical Boltzmann equation without intraspecies interactions. A brief discussion of the application of this classification to general collective oscillations is also presented.

  6. Quartz-crystal-oscillator hygrometer

    NASA Technical Reports Server (NTRS)

    Kruger, R.

    1977-01-01

    Measuring device, which eliminates complex and expensive optical components by electronically sensing dewpoint of water vapor in gas, employs piezoelectric crystal oscillator, supportive circuitry, temperature regulators, and readout.

  7. Chemotaxis and Actin Oscillations

    NASA Astrophysics Data System (ADS)

    Bodenschatz, Eberhard; Hsu, Hsin-Fang; Negrete, Jose; Beta, Carsten; Pumir, Alain; Gholami, Azam; Tarantola, Marco; Westendorf, Christian; Zykov, Vladimir

    Recently, self-oscillations of the cytoskeletal actin have been observed in Dictyostelium, a model system for studying chemotaxis. Here we report experimental results on the self-oscillation mechanism and the role of regulatory proteins and myosin II. We stimulate cells rapidly and periodically by using photo un-caging of the chemoattractant in a micro-fluidic device and measured the cellular responses. We found that the response amplitude grows with stimulation strength only in a very narrow region of stimulation, after which the response amplitude reaches a plateau. Moreover, the frequency-response is not constant but rather varies with the strength of external stimuli. To understand the underlying mechanism, we analyzed the polymerization and de-polymerization time in the single cell level. Despite of the large cell-to-cell variability, we found that the polymerization time is independent of external stimuli and the de-polymerization time is prolonged as the stimulation strength increases. Our conclusions will be summarized and the role of noise in the signaling network will be discussed. German Science Foundation CRC 937.

  8. Neutrino oscillations refitted

    NASA Astrophysics Data System (ADS)

    Forero, D. V.; Tórtola, M.; Valle, J. W. F.

    2014-11-01

    Here, we update our previous global fit of neutrino oscillations by including the recent results that have appeared since the Neutrino 2012 conference. These include the measurements of reactor antineutrino disappearance reported by Daya Bay and RENO, together with latest T2K and MINOS data including both disappearance and appearance channels. We also include the revised results from the third solar phase of Super-Kamiokande, SK-III, as well as new solar results from the fourth phase of Super-Kamiokande, SK-IV. We find that the preferred global determination of the atmospheric angle θ23 is consistent with maximal mixing. We also determine the impact of the new data upon all the other neutrino oscillation parameters with an emphasis on the increasing sensitivity to the C P phase, thanks to the interplay between accelerator and reactor data. In the Appendix, we present the updated results obtained after the inclusion of new reactor data presented at the Neutrino 2014 conference. We discuss their impact on the global neutrino analysis.

  9. Monolithic optical parametric oscillators

    NASA Astrophysics Data System (ADS)

    Breunig, Ingo; Beckmann, Tobias; Buse, Karsten

    2012-02-01

    Stability and footprint of optical parametric oscillators (OPOs) strongly depend on the cavity used. Monolithic OPOs tend to be most stable and compact since they do not require external mirrors that have to be aligned. The most straightforward way to get rid of the mirrors is to coat the end faces of the nonlinear crystal. Whispering gallery resonators (WGRs) are a more advanced solution since they provide ultra-high reflectivity over a wide spectral range without any coating. Furthermore, they can be fabricated out of nonlinear-optical materials like lithium niobate. Thus, they are ideally suited to serve as a monolithic OPO cavity. We present the experimental realization of optical parametric oscillators based on whispering gallery resonators. Pumped at 1 μm wavelength, they generate signal and idler fields tunable between 1.8 and 2.5 μm wavelength. We explore different schemes, how to phase match the nonlinear interaction in a WGR. In particular, we show improvements in the fabrication of quasi-phase-matching structures. They enable great flexibility for the tuning and for the choice of the pump laser.

  10. Scanning for oscillations

    NASA Astrophysics Data System (ADS)

    de Cheveigné, Alain; Arzounian, Dorothée

    2015-12-01

    Objective. Oscillations are an important aspect of brain activity, but they often have a low signal-to-noise ratio (SNR) due to source-to-electrode mixing with competing brain activity and noise. Filtering can improve the SNR of narrowband signals, but it introduces ringing effects that may masquerade as genuine oscillations, leading to uncertainty as to the true oscillatory nature of the phenomena. Likewise, time-frequency analysis kernels have a temporal extent that blurs the time course of narrowband activity, introducing uncertainty as to timing and causal relations between events and/or frequency bands. Approach. Here, we propose a methodology that reveals narrowband activity within multichannel data such as electroencephalography, magnetoencephalography, electrocorticography or local field potential. The method exploits the between-channel correlation structure of the data to suppress competing sources by joint diagonalization of the covariance matrices of narrowband filtered and unfiltered data. Main results. Applied to synthetic and real data, the method effectively extracts narrowband components at unfavorable SNR. Significance. Oscillatory components of brain activity, including weak sources that are hard or impossible to observe using standard methods, can be detected and their time course plotted accurately. The method avoids the temporal artifacts of standard filtering and time-frequency analysis methods with which it remains complementary.

  11. Extinction of oscillating populations

    NASA Astrophysics Data System (ADS)

    Smith, Naftali R.; Meerson, Baruch

    2016-03-01

    Established populations often exhibit oscillations in their sizes that, in the deterministic theory, correspond to a limit cycle in the space of population sizes. If a population is isolated, the intrinsic stochasticity of elemental processes can ultimately bring it to extinction. Here we study extinction of oscillating populations in a stochastic version of the Rosenzweig-MacArthur predator-prey model. To this end we develop a WKB (Wentzel, Kramers and Brillouin) approximation to the master equation, employing the characteristic population size as the large parameter. Similar WKB theories have been developed previously in the context of population extinction from an attracting multipopulation fixed point. We evaluate the extinction rates and find the most probable paths to extinction from the limit cycle by applying Floquet theory to the dynamics of an effective four-dimensional WKB Hamiltonian. We show that the entropic barriers to extinction change in a nonanalytic way as the system passes through the Hopf bifurcation. We also study the subleading pre-exponential factors of the WKB approximation.

  12. Nanoscale relaxation oscillator

    DOEpatents

    Zettl, Alexander K.; Regan, Brian C.; Aloni, Shaul

    2009-04-07

    A nanoscale oscillation device is disclosed, wherein two nanoscale droplets are altered in size by mass transport, then contact each other and merge through surface tension. The device may also comprise a channel having an actuator responsive to mechanical oscillation caused by expansion and contraction of the droplets. It further has a structure for delivering atoms between droplets, wherein the droplets are nanoparticles. Provided are a first particle and a second particle on the channel member, both being made of a chargeable material, the second particle contacting the actuator portion; and electrodes connected to the channel member for delivering a potential gradient across the channel and traversing the first and second particles. The particles are spaced apart a specified distance so that atoms from one particle are delivered to the other particle by mass transport in response to the potential (e.g. voltage potential) and the first and second particles are liquid and touch at a predetermined point of growth, thereby causing merging of the second particle into the first particle by surface tension forces and reverse movement of the actuator. In a preferred embodiment, the channel comprises a carbon nanotube and the droplets comprise metal nanoparticles, e.g. indium, which is readily made liquid.

  13. Socially synchronized circadian oscillators.

    PubMed

    Bloch, Guy; Herzog, Erik D; Levine, Joel D; Schwartz, William J

    2013-08-22

    Daily rhythms of physiology and behaviour are governed by an endogenous timekeeping mechanism (a circadian 'clock'). The alternation of environmental light and darkness synchronizes (entrains) these rhythms to the natural day-night cycle, and underlying mechanisms have been investigated using singly housed animals in the laboratory. But, most species ordinarily would not live out their lives in such seclusion; in their natural habitats, they interact with other individuals, and some live in colonies with highly developed social structures requiring temporal synchronization. Social cues may thus be critical to the adaptive function of the circadian system, but elucidating their role and the responsible mechanisms has proven elusive. Here, we highlight three model systems that are now being applied to understanding the biology of socially synchronized circadian oscillators: the fruitfly, with its powerful array of molecular genetic tools; the honeybee, with its complex natural society and clear division of labour; and, at a different level of biological organization, the rodent suprachiasmatic nucleus, site of the brain's circadian clock, with its network of mutually coupled single-cell oscillators. Analyses at the 'group' level of circadian organization will likely generate a more complex, but ultimately more comprehensive, view of clocks and rhythms and their contribution to fitness in nature.

  14. Instant Childhood Immunization Schedule

    MedlinePlus

    ... Recommendations Why Immunize? Vaccines: The Basics Instant Childhood Immunization Schedule Recommend on Facebook Tweet Share Compartir Get ... date. See Disclaimer for additional details. Based on Immunization Schedule for Children 0 through 6 Years of ...

  15. Immune System Quiz

    MedlinePlus

    ... Room? What Happens in the Operating Room? Quiz: Immune System KidsHealth > For Kids > Quiz: Immune System A A A How much do you know about your immune system? Find out by taking this quiz! About KidsHealth ...

  16. The streptomycin mouse model for Salmonella diarrhea: functional analysis of the microbiota, the pathogen's virulence factors, and the host's mucosal immune response.

    PubMed

    Kaiser, Patrick; Diard, Médéric; Stecher, Bärbel; Hardt, Wolf-Dietrich

    2012-01-01

    The mammalian intestine is colonized by a dense microbial community, the microbiota. Homeostatic and symbiotic interactions facilitate the peaceful co-existence between the microbiota and the host, and inhibit colonization by most incoming pathogens ('colonization resistance'). However, if pathogenic intruders overcome colonization resistance, a fierce, innate inflammatory defense can be mounted within hours, the adaptive arm of the immune system is initiated, and the pathogen is fought back. The molecular nature of the homeostatic interactions, the pathogen's ability to overcome colonization resistance, and the triggering of native and adaptive mucosal immune responses are still poorly understood. To study these mechanisms, the streptomycin mouse model for Salmonella diarrhea is of great value. Here, we review how S. Typhimurium triggers mucosal immune responses by active (virulence factor elicited) and passive (MyD88-dependent) mechanisms and introduce the S. Typhimurium mutants available for focusing on either response. Interestingly, mucosal defense turns out to be a double-edged sword, limiting pathogen burdens in the gut tissue but enhancing pathogen growth in the gut lumen. This model allows not only studying the molecular pathogenesis of Salmonella diarrhea but also is ideally suited for analyzing innate defenses, microbe handling by mucosal phagocytes, adaptive secretory immunoglobulin A responses, probing microbiota function, and homeostatic microbiota-host interactions. Finally, we discuss the general need for defined assay conditions when using animal models for enteric infections and the central importance of littermate controls.

  17. The unresponsiveness of the immune system of the rat to hypergravity

    NASA Technical Reports Server (NTRS)

    Scibetta, S. M.; Caren, L. D.; Oyama, J.

    1984-01-01

    The immune response in rats exposed to simulated hypergravity (2.1 G and 3.1 G) by chronic centrifugation was assessed. Rats were immunized with sheep red blood cells (SRBC), either on the day of initial exposure to hypergravity (hyper-G), or after being centrifuged for 28 d and remaining on the centrifuge thereafter. Pair-fed and ad libitum fed noncentrifuged controls were used. Although there were some alterations in leukocyte counts, hyper-G did not systematically affect the primary or secondary anti-SRBC response, hematocrits, or the sizes of the liver, spleen, kidneys, thymus, or adrenal glands. The immune system is thus remarkably homeostatic under hypergravity conditions which do affect other physiologic parameters.

  18. The Immune System in Tissue Environments Regaining Homeostasis after Injury: Is “Inflammation” Always Inflammation?

    PubMed Central

    2016-01-01

    Inflammation is a response to infections or tissue injuries. Inflammation was once defined by clinical signs, later by the presence of leukocytes, and nowadays by expression of “proinflammatory” cytokines and chemokines. But leukocytes and cytokines often have rather anti-inflammatory, proregenerative, and homeostatic effects. Is there a need to redefine “inflammation”? In this review, we discuss the functions of “inflammatory” mediators/regulators of the innate immune system that determine tissue environments to fulfill the need of the tissue while regaining homeostasis after injury. PMID:27597803

  19. Afferent lymphatic cannulation as a model system to study innate immune responses to infection and vaccination.

    PubMed

    Neeland, Melanie R; Meeusen, Els N T; de Veer, Michael J

    2014-03-15

    The afferent lymphatics consist of the cells and immunomodulatory signals that are involved in the early response to peripheral stimuli. Examination of this compartment in both homeostatic and stimulatory conditions permits the analysis of the innate biological pathways responsible for the generation of an adaptive immune response in the lymph node. Afferent lymphatic cannulation is therefore an ideal model system to study cellular migration and antigen dispersal kinetics during infection and vaccination. Utilisation of these lymphatic cannulation models has demonstrated the ability to both increase current understanding of infectious diseases, vaccine delivery systems and has the potential to target effector cells and molecules that may be used as novel therapeutic or vaccine targets.

  20. A riot of rhythms: neuronal and glial circadian oscillators in the mediobasal hypothalamus

    PubMed Central

    Guilding, Clare; Hughes, Alun TL; Brown, Timothy M; Namvar, Sara; Piggins, Hugh D

    2009-01-01

    Background In mammals, the synchronized activity of cell autonomous clocks in the suprachiasmatic nuclei (SCN) enables this structure to function as the master circadian clock, coordinating daily rhythms in physiology and behavior. However, the dominance of this clock has been challenged by the observations that metabolic duress can over-ride SCN controlled rhythms, and that clock genes are expressed in many brain areas, including those implicated in the regulation of appetite and feeding. The recent development of mice in which clock gene/protein activity is reported by bioluminescent constructs (luciferase or luc) now enables us to track molecular oscillations in numerous tissues ex vivo. Consequently we determined both clock activities and responsiveness to metabolic perturbations of cells and tissues within the mediobasal hypothalamus (MBH), a site pivotal for optimal internal homeostatic regulation. Results Here we demonstrate endogenous circadian rhythms of PER2::LUC expression in discrete subdivisions of the arcuate (Arc) and dorsomedial nuclei (DMH). Rhythms resolved to single cells did not maintain long-term synchrony with one-another, leading to a damping of oscillations at both cell and tissue levels. Complementary electrophysiology recordings revealed rhythms in neuronal activity in the Arc and DMH. Further, PER2::LUC rhythms were detected in the ependymal layer of the third ventricle and in the median eminence/pars tuberalis (ME/PT). A high-fat diet had no effect on the molecular oscillations in the MBH, whereas food deprivation resulted in an altered phase in the ME/PT. Conclusion Our results provide the first single cell resolution of endogenous circadian rhythms in clock gene expression in any intact tissue outside the SCN, reveal the cellular basis for tissue level damping in extra-SCN oscillators and demonstrate that an oscillator in the ME/PT is responsive to changes in metabolism. PMID:19712475

  1. Stable local oscillator microcircuit.

    SciTech Connect

    Brocato, Robert Wesley

    2006-10-01

    This report gives a description of the development of a Stable Local Oscillator (StaLO) Microcircuit. The StaLO accepts a 100MHz input signal and produces output signals at 1.2, 3.3, and 3.6 GHz. The circuit is built as a multi-chip module (MCM), since it makes use of integrated circuit technologies in silicon and lithium niobate as well as discrete passive components. The StaLO uses a comb generator followed by surface acoustic wave (SAW) filters. The comb generator creates a set of harmonic components of the 100MHz input signal. The SAW filters are narrow bandpass filters that are used to select the desired component and reject all others. The resulting circuit has very low sideband power levels and low phase noise (both less than -40dBc) that is limited primarily by the phase noise level of the input signal.

  2. Galilean covariant harmonic oscillator

    NASA Technical Reports Server (NTRS)

    Horzela, Andrzej; Kapuscik, Edward

    1993-01-01

    A Galilean covariant approach to classical mechanics of a single particle is described. Within the proposed formalism, all non-covariant force laws defining acting forces which become to be defined covariantly by some differential equations are rejected. Such an approach leads out of the standard classical mechanics and gives an example of non-Newtonian mechanics. It is shown that the exactly solvable linear system of differential equations defining forces contains the Galilean covariant description of harmonic oscillator as its particular case. Additionally, it is demonstrated that in Galilean covariant classical mechanics the validity of the second Newton law of dynamics implies the Hooke law and vice versa. It is shown that the kinetic and total energies transform differently with respect to the Galilean transformations.

  3. Fano Interference in Classical Oscillators

    ERIC Educational Resources Information Center

    Satpathy, S.; Roy, A.; Mohapatra, A.

    2012-01-01

    We seek to illustrate Fano interference in a classical coupled oscillator by using classical analogues of the atom-laser interaction. We present an analogy between the dressed state picture of coherent atom-laser interaction and a classical coupled oscillator. The Autler-Townes splitting due to the atom-laser interaction is analogous to the…

  4. Oscillator With Low Phase Noise

    NASA Technical Reports Server (NTRS)

    Kleinberg, Leonard L.

    1987-01-01

    Phase errors cancelled for high frequency stability. Radio-frequency oscillator achieves high stability of frequency through parallel, two-amplifier configuration in which effects cause phase noise tend to cancel each other. Circuit includes two amplifiers with resonating elements, each constitutes part of feedback loop of other. Generate same frequency because each circuit provides other with conditions necessary for oscillation.

  5. Longitudinal oscillation of launch vehicles

    NASA Technical Reports Server (NTRS)

    Glaser, R. F.

    1973-01-01

    During powered flight a vehicle may develop longitudinal self-excited oscillations, so-called oscillations, of its structure. The energy supplying the vibration is tapped from the thrust by the activity of the system itself; that is, oscillation of the structure causes oscillation of the propellant system, especially of the pumps. In this way an oscillating thrust can be created that, by a feedback loop, may sustain the structural oscillation under certain circumstances. Two special features of the system proved to be essential for creation of instability. One is the effect of the inherent time interval that the thrust oscillation is lagging behind the structural oscillation. The other is the decreased of system mass caused by the exhausting of gas. The latter feature may cause an initially stable system to become unstable. To examine the stability of the system, a single mass-spring model, which is the result of a one-term Galerkin approach to the equation of motion, has been considered. The Nyquist stability criterion leads to a stability graph that shows the stability conditions in terms of the system parameter and also demonstrates the significance of time lag, feedback magnitude, and loss of mass. An important conclusion can be drawn from the analysis: large relative displacements of the pump-engine masses favor instability. This is also confirmed by flight measurements.

  6. Mechanical Parametric Oscillations and Waves

    ERIC Educational Resources Information Center

    Dittrich, William; Minkin, Leonid; Shapovalov, Alexander S.

    2013-01-01

    Usually parametric oscillations are not the topic of general physics courses. Probably it is because the mathematical theory of this phenomenon is relatively complicated, and until quite recently laboratory experiments for students were difficult to implement. However parametric oscillations are good illustrations of the laws of physics and can be…

  7. Investigating the interaction between the homeostatic and circadian processes of sleep-wake regulation for the prediction of waking neurobehavioural performance

    NASA Technical Reports Server (NTRS)

    Van Dongen, Hans P A.; Dinges, David F.

    2003-01-01

    The two-process model of sleep regulation has been applied successfully to describe, predict, and understand sleep-wake regulation in a variety of experimental protocols such as sleep deprivation and forced desynchrony. A non-linear interaction between the homeostatic and circadian processes was reported when the model was applied to describe alertness and performance data obtained during forced desynchrony. This non-linear interaction could also be due to intrinsic non-linearity in the metrics used to measure alertness and performance, however. Distinguishing these possibilities would be of theoretical interest, but could also have important implications for the design and interpretation of experiments placing sleep at different circadian phases or varying the duration of sleep and/or wakefulness. Although to date no resolution to this controversy has been found, here we show that the issue can be addressed with existing data sets. The interaction between the homeostatic and circadian processes of sleep-wake regulation was investigated using neurobehavioural performance data from a laboratory experiment involving total sleep deprivation. The results provided evidence of an actual non-linear interaction between the homeostatic and circadian processes of sleep-wake regulation for the prediction of waking neurobehavioural performance.

  8. Physiology and Anatomy for Nurses and Healthcare Practitioners: A Homeostatic Approach - Third edition Clancy John McVicar Andrew J Physiology and Anatomy for Nurses and Healthcare Practitioners: A Homeostatic Approach - Third edition 768pp Hodder Arnold 9780340967591 0340967595 [Formula: see text].

    PubMed

    2010-02-10

    John Clancy and Andrew McVicar give a fascinating insight into the homeostatic mechanism for health. The content focuses on the body's adaptive responses in health and the maladaptive processes in ill-health. In turn, these processes are linked to the knowledge required by healthcare professionals in restoring health or enhancing the quality of life until death.

  9. Surface acoustic wave stabilized oscillators

    NASA Technical Reports Server (NTRS)

    Parker, T. E.

    1978-01-01

    A number of 401.2 MHz surface acoustic wave (SAW) controlled oscillators were built and tested. The performance of these oscillators was evaluated for possible use as stable oscillators in communication systems. A short term frequency stability of better than 1 x 10 to the minus 9th power for one second was measured for the SAW oscillators. Long term frequency drift was measured and was found to be dependent on SAW design and packaging. Drift rates ranging from 15 ppm in twenty weeks to 2.5 ppm in twenty weeks were observed. Some further improvement was required. The temperature dependence of the saw oscillators was evaluated and it was concluded that some form of temperature compensation will be necessary to meet the requirements of some communication systems.

  10. Photoacoustic elastic oscillation and characterization.

    PubMed

    Gao, Fei; Feng, Xiaohua; Zheng, Yuanjin

    2015-08-10

    Photoacoustic imaging and sensing have been studied extensively to probe the optical absorption of biological tissue in multiple scales ranging from large organs to small molecules. However, its elastic oscillation characterization is rarely studied and has been an untapped area to be explored. In literature, photoacoustic signal induced by pulsed laser is commonly modelled as a bipolar "N-shape" pulse from an optical absorber. In this paper, the photoacoustic damped oscillation is predicted and modelled by an equivalent mass-spring system by treating the optical absorber as an elastic oscillator. The photoacoustic simulation incorporating the proposed oscillation model shows better agreement with the measured signal from an elastic phantom, than conventional photoacoustic simulation model. More interestingly, the photoacoustic damping oscillation effect could potentially be a useful characterization approach to evaluate biological tissue's mechanical properties in terms of relaxation time, peak number and ratio beyond optical absorption only, which is experimentally demonstrated in this paper.

  11. Quantum oscillations without magnetic field

    NASA Astrophysics Data System (ADS)

    Liu, Tianyu; Pikulin, D. I.; Franz, M.

    2017-01-01

    When the magnetic field B is applied to a metal, nearly all observable quantities exhibit oscillations periodic in 1 /B . Such quantum oscillations reflect the fundamental reorganization of electron states into Landau levels as a canonical response of the metal to the applied magnetic field. We predict here that, remarkably, in the recently discovered Dirac and Weyl semimetals, quantum oscillations can occur in the complete absence of magnetic field. These zero-field quantum oscillations are driven by elastic strain which, in the space of the low-energy Dirac fermions, acts as a chiral gauge potential. We propose an experimental setup in which the strain in a thin film (or nanowire) can generate a pseudomagnetic field b as large as 15 T and demonstrate the resulting de Haas-van Alphen and Shubnikov-de Haas oscillations periodic in 1 /b .

  12. Progress in optical parametric oscillators

    NASA Technical Reports Server (NTRS)

    Fan, Y. X.; Byer, R. L.

    1984-01-01

    It is pointed out that tunable coherent sources are very useful for many applications, including spectroscopy, chemistry, combustion diagnostics, and remote sensing. Compared with other tunable sources, optical parametric oscillators (OPO) offer the potential advantage of a wide wavelength operating range, which extends from 0.2 micron to 25 microns. The current status of OPO is examined, taking into account mainly advances made during the last decade. Attention is given to early LiNbO3 parametric oscillators, problems which have prevented wide use of parametric oscillators, the demonstration of OPO's using urea and AgGaS2, progress related to picosecond OPO's, a breakthrough in nanosecond parametric oscillators, the first demonstration of a waveguide and fiber parametric amplification and generation, the importance of chalcopyrite crystals, and theoretical work performed with the aim to understand the factors affecting the parametric oscillator performance.

  13. Coupled oscillators on evolving networks

    NASA Astrophysics Data System (ADS)

    Singh, R. K.; Bagarti, Trilochan

    2016-12-01

    In this work we study coupled oscillators on evolving networks. We find that the steady state behavior of the system is governed by the relative values of the spread in natural frequencies and the global coupling strength. For coupling strong in comparison to the spread in frequencies, the system of oscillators synchronize and when coupling strength and spread in frequencies are large, a phenomenon similar to amplitude death is observed. The network evolution provides a mechanism to build inter-oscillator connections and once a dynamic equilibrium is achieved, oscillators evolve according to their local interactions. We also find that the steady state properties change by the presence of additional time scales. We demonstrate these results based on numerical calculations studying dynamical evolution of limit-cycle and van der Pol oscillators.

  14. Homeostatic action of adenosine A3 and A1 receptor agonists on proliferation of hematopoietic precursor cells.

    PubMed

    Hofer, Michal; Pospísil, Milan; Znojil, Vladimír; Holá, Jirina; Streitová, Denisa; Vacek, Antonín

    2008-07-01

    Two adenosine receptor agonists, N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA) and N6-cyclopentyladenosine (CPA), which selectively activate adenosine A3 and A1 receptors, respectively, were tested for their ability to influence proliferation of granulocytic and erythroid cells in femoral bone marrow of mice using morphological criteria. Agonists were given intraperitoneally to mice in repeated isomolar doses of 200 nmol/kg. Three variants of experiments were performed to investigate the action of the agonists under normal resting state of mice and in phases of cell depletion and subsequent regeneration after treatment with the cytotoxic drug 5-fluorouracil. In the case of granulopoiesis, IB-MECA 1) increased by a moderate but significant level proliferation of cells under normal resting state; 2) strongly increased proliferation of cells in the cell depletion phase; but 3) did not influence cell proliferation in the regeneration phase. CPA did not influence cell proliferation under normal resting state and in the cell depletion phase, but strongly suppressed the overshooting cell proliferation in the regeneration phase. The stimulatory effect of IB-MECA on cell proliferation of erythroid cells was observed only when this agonist was administered during the cell depletion phase. CPA did not modulate erythroid proliferation in any of the functional states investigated, probably due to the lower demand for cell production as compared with granulopoiesis. The results indicate opposite effects of the two adenosine receptor agonists on proliferation of hematopoietic cells and suggest the plasticity and homeostatic role of the adenosine receptor expression.

  15. GABA Receptors on Orexin and Melanin-Concentrating Hormone Neurons Are Differentially Homeostatically Regulated Following Sleep Deprivation123

    PubMed Central

    Toossi, Hanieh; del Cid-Pellitero, Esther

    2016-01-01

    Abstract Though overlapping in distribution through the hypothalamus, orexin (Orx) and melanin-concentrating hormone (MCH) neurons play opposite roles in the regulation of sleep–wake states. Orx neurons discharge during waking, whereas MCH neurons discharge during sleep. In the present study, we examined in mice whether GABAA and GABAB receptors (Rs) are present on Orx and MCH neurons and might undergo differential changes as a function of their different activities following sleep deprivation (SD) and sleep recovery (SR). Applying quantitative stereological image analysis to dual-immunofluorescent stained sections, we determined that the proportion of Orx neurons positively immunostained for GABAARs was significantly higher following SD (∼48%) compared with sleep control (SC; ∼24%) and SR (∼27%), and that the luminance of the GABAARs was significantly greater. In contrast, the average proportion of the MCH neurons immunostained for GABAARs was insignificantly lower following SD (∼43%) compared with SC (∼54%) and SR (56%), and the luminance of the GABAARs was significantly less. Although, GABABRs were observed in all Orx and MCH neurons (100%), the luminance of these receptors was differentially altered following SD. The intensity of GABABRs in the Orx neurons was significantly greater after SD than after SC and SR, whereas that in the MCH neurons was significantly less. The present results indicate that GABA receptors undergo dynamic and differential changes in the wake-active Orx neurons and the sleep-active MCH neurons as a function of and homeostatic adjustment to their preceding activity and sleep–wake state. PMID:27294196

  16. BDNF contributes to both rapid and homeostatic alterations in AMPA receptor surface expression in nucleus accumbens medium spiny neurons

    PubMed Central

    Reimers, Jeremy M.; Loweth, Jessica A.; Wolf, Marina E.

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) plays a critical role in plasticity at glutamate synapses and the effects of repeated cocaine exposure. We recently showed that intracranial injection of BDNF into the rat nucleus accumbens (NAc), a key region for cocaine addiction, rapidly increases AMPA receptor (AMPAR) surface expression. To further characterize BDNF’s role in both rapid AMPAR trafficking and slower, homeostatic changes in AMPAR surface expression, we investigated the effects of acute (30 min) and long-term (24 h) treatment with BDNF on AMPAR distribution in NAc medium spiny neurons from postnatal rats co-cultured with mouse prefrontal cortex (PFC) neurons to restore excitatory inputs. Immunocytochemical studies showed that acute BDNF treatment increased cell surface GluA1 and GluA2 levels, as well as their co-localization, on NAc neurons. This effect of BDNF, confirmed using a protein crosslinking assay, was dependent on ERK but not AKT signaling. In contrast, long-term BDNF treatment decreased AMPAR surface expression on NAc neurons. Based on this latter result, we tested the hypothesis that BDNF plays a role in AMPAR “scaling down” in response to a prolonged increase in neuronal activity produced by bicuculline (24 h). Supporting this hypothesis, decreasing BDNF signaling with the extracellular BDNF scavenger TrkB-Fc prevented the scaling down of GluA1 and GluA2 surface levels in NAc neurons normally produced by bicuculline. In conclusion, BDNF exerts bidirectional effects on NAc AMPAR surface expression, depending on duration of exposure. Furthermore, BDNF’s involvement in synaptic scaling in the NAc differs from its previously described role in the visual cortex. PMID:24712995

  17. Homeostatic Imbalance and Colon Cancer: The Dynamic Epigenetic Interplay of Inflammation, Environmental Toxins, and Chemopreventive Plant Compounds

    PubMed Central

    Sokolosky, Melissa L.; Wargovich, Michael J.

    2012-01-01

    The advent of modern medicine has allowed for significant advances within the fields of emergency care, surgery, and infectious disease control. Health threats that were historically responsible for immeasurable tolls on human life are now all but eradicated within certain populations, specifically those that enjoy higher degrees of socio-economic status and access to healthcare. However, modernization and its resulting lifestyle trends have ushered in a new era of chronic illness; one in which an unprecedented number of people are estimated to contract cancer and other inflammatory diseases. Here, we explore the idea that homeostasis has been redefined within just a few generations, and that diseases such as colorectal cancer are the result of fluctuating physiological and molecular imbalances. Phytochemical-deprived, pro-inflammatory diets combined with low-dose exposures to environmental toxins, including bisphenol-A (BPA) and other endocrine disruptors, are now linked to increasing incidences of cancer in westernized societies and developing countries. There is recent evidence that disease determinants are likely set in utero and further perpetuated into adulthood dependent upon the innate and environmentally-acquired phenotype unique to each individual. In order to address a disease as multi-factorial, case-specific, and remarkably adaptive as cancer, research must focus on its root causes in order to elucidate the molecular mechanisms by which they can be prevented or counteracted via plant-derived compounds such as epigallocatechin-3-gallate (EGCG) and resveratrol. The significant role of epigenetics in the regulation of these complex processes is emphasized here to form a comprehensive view of the dynamic interactions that influence modern-day carcinogenesis, and how sensibly restoring homeostatic balance may be the key to the cancer riddle. PMID:22675672

  18. Homeostatic regulation of the PI(4,5)P2-Ca(2+) signaling system at ER-PM junctions.

    PubMed

    Chang, Chi-Lun; Liou, Jen

    2016-08-01

    The phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-Ca(2+) signaling system is important for cell activation in response to various extracellular stimuli. This signaling system is initiated by receptor-induced hydrolysis of PI(4,5)P2 in the plasma membrane (PM) to generate the soluble second messenger inositol 1,4,5-trisphosphate (IP3). IP3 subsequently triggers the release of Ca(2+) from the endoplasmic reticulum (ER) store to the cytosol to activate Ca(2+)-mediated responses, such as secretion and proliferation. The consumed PM PI(4,5)P2 and ER Ca(2+) must be quickly restored to sustain signaling responses, and to maintain the homeostasis of PI(4,5)P2 and Ca(2+). Since phosphatidylinositol (PI), the precursor lipid for PM PI(4,5)P2, is synthesized in the ER membrane, and a Ca(2+) influx across the PM is required to refill the ER Ca(2+) store, efficient communications between the ER and the PM are critical for the homeostatic regulation of the PI(4,5)P2-Ca(2+) signaling system. This review describes the major findings that established the framework of the PI(4,5)P2-Ca(2+) signaling system, and recent discoveries on feedback control mechanisms at ER-PM junctions that sustain the PI(4,5)P2-Ca(2+) signaling system. Particular emphasis is placed on the characterization of ER-PM junctions where efficient communications between the ER and the PM occur, and the activation mechanisms of proteins that dynamically localize to ER-PM junctions to provide the feedback control during PI(4,5)P2-Ca(2+) signaling, including the ER Ca(2+) sensor STIM1, the extended synaptotagmin E-Syt1, and the PI transfer protein Nir2. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon.

  19. Ghrelin Modulates the fMRI BOLD Response of Homeostatic and Hedonic Brain Centers Regulating Energy Balance in the Rat

    PubMed Central

    Deli, Levente; Gajári, Dávid; Dávid, Szabolcs; Pozsgay, Zsófia; Hegedűs, Nikolett; Tihanyi, Károly; Liposits, Zsolt

    2014-01-01

    The orexigenic gut-brain peptide, ghrelin and its G-protein coupled receptor, the growth hormone secretagogue receptor 1a (GHS-R1A) are pivotal regulators of hypothalamic feeding centers and reward processing neuronal circuits of the brain. These systems operate in a cooperative manner and receive a wide array of neuronal hormone/transmitter messages and metabolic signals. Functional magnetic resonance imaging was employed in the current study to map BOLD responses to ghrelin in different brain regions with special reference on homeostatic and hedonic regulatory centers of energy balance. Experimental groups involved male, ovariectomized female and ovariectomized estradiol-replaced rats. Putative modulation of ghrelin signaling by endocannabinoids was also studied. Ghrelin-evoked effects were calculated as mean of the BOLD responses 30 minutes after administration. In the male rat, ghrelin evoked a slowly decreasing BOLD response in all studied regions of interest (ROI) within the limbic system. This effect was antagonized by pretreatment with GHS-R1A antagonist JMV2959. The comparison of ghrelin effects in the presence or absence of JMV2959 in individual ROIs revealed significant changes in the prefrontal cortex, nucleus accumbens of the telencephalon, and also within hypothalamic centers like the lateral hypothalamus, ventromedial nucleus, paraventricular nucleus and suprachiasmatic nucleus. In the female rat, the ghrelin effects were almost identical to those observed in males. Ovariectomy and chronic estradiol replacement had no effect on the BOLD response. Inhibition of the endocannabinoid signaling by rimonabant significantly attenuated the response of the nucleus accumbens and septum. In summary, ghrelin can modulate hypothalamic and mesolimbic structures controlling energy balance in both sexes. The endocannabinoid signaling system contributes to the manifestation of ghrelin's BOLD effect in a region specific manner. In females, the estradiol milieu does

  20. Nonlinear dynamics of plasma oscillations modeled by an anharmonic oscillator

    SciTech Connect

    Enjieu Kadji, H. G.; Nana Nbendjo, B. R.; Chabi Orou, J. B.; Talla, P. K.

    2008-03-15

    This paper considers nonlinear dynamics of plasma oscillations modeled by an anharmonic oscillator. These plasma oscillations are described by a nonlinear differential equation of the form xe+{epsilon}(1+x{sup 2})x+x+{kappa}x{sup 2}+{delta}x{sup 3}=F cos {omega}t. The amplitudes of the forced harmonic, superharmonic, and subharmonic oscillatory states are obtained using the harmonic balance technique and the multiple time scales method. Admissible values of the amplitude of the external strength are derived. Bifurcation sequences displayed by the model for each type of oscillatory states are performed numerically through the fourth-order Runge-Kutta scheme.

  1. Emergence of amplitude and oscillation death in identical coupled oscillators.

    PubMed

    Zou, Wei; Senthilkumar, D V; Duan, Jinqiao; Kurths, Jürgen

    2014-09-01

    We deduce rigorous conditions for the onset of amplitude death (AD) and oscillation death (OD) in a system of identical coupled paradigmatic Stuart-Landau oscillators. A nonscalar coupling and high frequency are beneficial for the onset of AD. In strong contrast, scalar diffusive coupling and low intrinsic frequency are in favor of the emergence of OD. Our finding contributes to clearly distinguish intrinsic geneses for AD and OD, and further substantially corroborates that AD and OD are indeed two dynamically distinct oscillation quenching phenomena due to distinctly different mechanisms.

  2. Microscale Immune Studies Laboratory.

    SciTech Connect

    Poschet, Jens Fredrich; Carroll-Portillo, Amanda; Wu, Meiye; Manginell, Ronald Paul; Herr, Amy Elizabeth; Martino, Anthony A.; Perroud, Thomas D.; Branda, Catherine; Srivastava, Nimisha; Sinclair, Michael B.; Moorman, Matthew Wallace; Apblett, Christopher Alan; Sale, Kenneth L.; James, Conrad D.; Carles, Elizabeth L.; Lidke, Diane S.; Van Benthem, Mark Hilary; Rebeil, Roberto; Kaiser, Julie; Seaman, William; Rempe, Susan; Brozik, Susan Marie; Jones, Howland D. T.; Gemperline, Paul; Throckmorton, Daniel J.; Misra, Milind; Murton, Jaclyn K.; Carson, Bryan D.; Zhang, Zhaoduo; Plimpton, Steven James; Renzi, Ronald F.; Lane, Todd W.; Ndiaye-Dulac, Elsa; Singh, Anup K.; Haaland, David Michael; Faulon, Jean-Loup Michel; Davis, Ryan W.; Ricken, James Bryce; Branda, Steven S.; Patel, Kamlesh D.; Joo, Jaewook; Kubiak, Glenn D.; Brennan, James S.; Martin, Shawn Bryan; Brasier, Allan

    2009-01-01

    The overarching goal is to develop novel technologies to elucidate molecular mechanisms of the innate immune response in host cells to pathogens such as bacteria and viruses including the mechanisms used by pathogens to subvert/suppress/obfuscate the immune response to cause their harmful effects. Innate immunity is our first line of defense against a pathogenic bacteria or virus. A comprehensive 'system-level' understanding of innate immunity pathways such as toll-like receptor (TLR) pathways is the key to deciphering mechanisms of pathogenesis and can lead to improvements in early diagnosis or developing improved therapeutics. Current methods for studying signaling focus on measurements of a limited number of components in a pathway and hence, fail to provide a systems-level understanding. We have developed a systems biology approach to decipher TLR4 pathways in macrophage cell lines in response to exposure to pathogenic bacteria and their lipopolysaccharide (LPS). Our approach integrates biological reagents, a microfluidic cell handling and analysis platform, high-resolution imaging and computational modeling to provide spatially- and temporally-resolved measurement of TLR-network components. The Integrated microfluidic platform is capable of imaging single cells to obtain dynamic translocation data as well as high-throughput acquisition of quantitative protein expression and phosphorylation information of selected cell populations. The platform consists of multiple modules such as single-cell array, cell sorter, and phosphoflow chip to provide confocal imaging, cell sorting, flow cytomtery and phosphorylation assays. The single-cell array module contains fluidic constrictions designed to trap and hold single host cells. Up to 100 single cells can be trapped and monitored for hours, enabling detailed statistically-significant measurements. The module was used to analyze translocation behavior of transcription factor NF-kB in macrophages upon activation by E

  3. Immunization for Women

    MedlinePlus

    ... nfid.org/#sthash.eZ72dCSP.dpuf Diseases & Vaccines Overview Immunization Schedules Talk to you doctor about your immunization ... years Immunization Schedule for Children, 7-18 years Immunization News July 8, 2016 HPV-related cancers on ...

  4. Relaxation damping in oscillating contacts

    PubMed Central

    Popov, M.; Popov, V.L.; Pohrt, R.

    2015-01-01

    If a contact of two purely elastic bodies with no sliding (infinite coefficient of friction) is subjected to superimposed oscillations in the normal and tangential directions, then a specific damping appears, that is not dependent on friction or dissipation in the material. We call this effect “relaxation damping”. The rate of energy dissipation due to relaxation damping is calculated in a closed analytic form for arbitrary axially-symmetric contacts. In the case of equal frequency of normal and tangential oscillations, the dissipated energy per cycle is proportional to the square of the amplitude of tangential oscillation and to the absolute value of the amplitude of normal oscillation, and is dependent on the phase shift between both oscillations. In the case of low frequency tangential oscillations with superimposed high frequency normal oscillations, the dissipation is proportional to the ratio of the frequencies. Generalization of the results for macroscopically planar, randomly rough surfaces as well as for the case of finite friction is discussed. PMID:26549011

  5. Linking oscillations in cerebellar circuits

    PubMed Central

    Courtemanche, Richard; Robinson, Jennifer C.; Aponte, Daniel I.

    2013-01-01

    In many neuroscience fields, the study of local and global rhythmicity has been receiving increasing attention. These network influences could directly impact on how neuronal groups interact together, organizing for different contexts. The cerebellar cortex harbors a variety of such local circuit rhythms, from the rhythms in the cerebellar cortex per se, or those dictated from important afferents. We present here certain cerebellar oscillatory phenomena that have been recorded in rodents and primates. Those take place in a range of frequencies: from the more known oscillations in the 4–25 Hz band, such as the olivocerebellar oscillatory activity and the granule cell layer oscillations, to the more recently reported slow (<1 Hz oscillations), and the fast (>150 Hz) activity in the Purkinje cell layer. Many of these oscillations appear spontaneously in the circuits, and are modulated by behavioral imperatives. We review here how those oscillations are recorded, some of their modulatory mechanisms, and also identify some of the cerebellar nodes where they could interact. A particular emphasis has been placed on how these oscillations could be modulated by movement and certain neuropathological manifestations. Many of those oscillations could have a definite impact on the way information is processed in the cerebellum and how it interacts with other structures in a variety of contexts. PMID:23908606

  6. The transition between immune and disease states in a cellular automaton model of clonal immune response

    NASA Astrophysics Data System (ADS)

    Bezzi, Michele; Celada, Franco; Ruffo, Stefano; Seiden, Philip E.

    1997-02-01

    In this paper we extend the Celada-Seiden (CS) model of the humoral immune response to include infections virus and killer T cells (cellular response). The model represents molecules and cells with bitstrings. The response of the system to virus involves a competition between the ability of the virus to kill the host cells and the host's ability to eliminate the virus. We find two basins of attraction in the dynamics of this system, one is identified with disease and the other with the immune state. There is also an oscillating state that exists on the border of these two stable states. Fluctuations in the population of virus or antibody can end the oscillation and drive the system into one of the stable states. The introduction of mechanisms of cross-regulation between the two responses can bias the system towards one of them. We also study a mean field model, based on coupled maps, to investigate virus-like infections. This simple model reproduces the attractors for average populations observed in the cellular automaton. All the dynamical behavior connected to spatial extension is lost, as is the oscillating feature. Thus the mean field approximation introduced with coupled maps destroys oscillations.

  7. Epigenetic Control of Immunity

    PubMed Central

    Busslinger, Meinrad; Tarakhovsky, Alexander

    2014-01-01

    Immunity relies on the heterogeneity of immune cells and their ability to respond to pathogen challenges. In the adaptive immune system, lymphocytes display a highly diverse antigen receptor repertoire that matches the vast diversity of pathogens. In the innate immune system, the cell's heterogeneity and phenotypic plasticity enable flexible responses to changes in tissue homeostasis caused by infection or damage. The immune responses are calibrated by the graded activity of immune cells that can vary from yeast-like proliferation to lifetime dormancy. This article describes key epigenetic processes that contribute to the function of immune cells during health and disease. PMID:24890513

  8. Integrated Immune Experiment

    NASA Technical Reports Server (NTRS)

    Crucian, Brian

    2009-01-01

    This viewgraph presentation reviews NASA's Integrated Immune Experiment. The objectives include: 1) Address significant lack of data regarding immune status during flight; 2) Replace several recent immune studies with one comprehensive study that will include in-flight sampling; 3) Determine the in-flight status of immunity, physiological stress, viral immunity/reactivation; 4) Determine the clinical risk related to immune dysregulation for exploration class spaceflight; and 5) Determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

  9. Understanding Herd Immunity.

    PubMed

    Metcalf, C J E; Ferrari, M; Graham, A L; Grenfell, B T

    2015-12-01

    Individual immunity is a powerful force affecting host health and pathogen evolution. Importantly, the effects of individual immunity also scale up to affect pathogen transmission dynamics and the success of vaccination campaigns for entire host populations. Population-scale immunity is often termed 'herd immunity'. Here we outline how individual immunity maps to population outcomes and discuss implications for control of infectious diseases. Particular immunological characteristics may be more or less likely to result in a population level signature of herd immunity; we detail this and also discuss other population-level outcomes that might emerge from individual-level immunity.

  10. Contributions of Nonhematopoietic Cells and Mediators to Immune Responses: Implications For Immunotoxicology

    PubMed Central

    Kaplan, Barbara L. F.; Li, Jinze; LaPres, John J.; Pruett, Stephen B.; Karmaus, Peer W. F.

    2015-01-01

    Immunotoxicology assessments have historically focused on the effects that xenobiotics exhibit directly on immune cells. These studies are invaluable as they identify immune cell targets and help characterize mechanisms and/or adverse outcome pathways of xenobiotics within the immune system. However, leukocytes can receive environmental cues by cell-cell contact or via released mediators from cells of organs outside of the immune system. These organs include, but are not limited to, the mucosal areas such as the lung and the gut, the liver, and the central nervous system. Homeostatic perturbation in these organs induced directly by toxicants can initiate and alter the outcome of local and systemic immunity. This review will highlight some of the identified nonimmune influences on immune homeostasis and provide summaries of how immunotoxic mechanisms of selected xenobiotics involve nonimmune cells or mediators. Thus, this review will identify data gaps and provide possible alternative mechanisms by which xenobiotics alter immune function that could be considered during immunotoxicology safety assessment. PMID:26008184

  11. Explosive oscillation death in coupled Stuart-Landau oscillators

    NASA Astrophysics Data System (ADS)

    Bi, Hongjie; Hu, Xin; Zhang, Xiyun; Zou, Yong; Liu, Zonghua; Guan, Shuguang

    2014-12-01

    Recently, explosive phase transitions, such as explosive percolation and explosive synchronization, have attracted extensive research interest. So far, most existing works have investigated Kuramoto-type models, where only phase variables are involved. Here, we report the occurrence of explosive oscillation quenching in a system of coupled Stuart-Landau oscillators that incorporates both phase and amplitude dynamics. We observe three typical scenarios with distinct microscopic mechanism of occurrence, i.e., ordinary, hierarchical, and cluster explosive oscillation death, corresponding to different frequency distributions of oscillators. We carry out theoretical analyses and obtain the backward transition point, which is shown to be independent of the specific frequency distributions. Numerical results are consistent with the theoretical predictions.

  12. VOLTAGE-CONTROLLED TRANSISTOR OSCILLATOR

    DOEpatents

    Scheele, P.F.

    1958-09-16

    This patent relates to transistor oscillators and in particular to those transistor oscillators whose frequencies vary according to controlling voltages. A principal feature of the disclosed transistor oscillator circuit resides in the temperature compensation of the frequency modulating stage by the use of a resistorthermistor network. The resistor-thermistor network components are selected to have the network resistance, which is in series with the modulator transistor emitter circuit, vary with temperature to compensate for variation in the parameters of the transistor due to temperature change.

  13. Galactic oscillator symmetry

    NASA Technical Reports Server (NTRS)

    Rosensteel, George

    1995-01-01

    Riemann ellipsoids model rotating galaxies when the galactic velocity field is a linear function of the Cartesian coordinates of the galactic masses. In nuclear physics, the kinetic energy in the linear velocity field approximation is known as the collective kinetic energy. But, the linear approximation neglects intrinsic degrees of freedom associated with nonlinear velocity fields. To remove this limitation, the theory of symplectic dynamical symmetry is developed for classical systems. A classical phase space for a self-gravitating symplectic system is a co-adjoint orbit of the noncompact group SP(3,R). The degenerate co-adjoint orbit is the 12 dimensional homogeneous space Sp(3,R)/U(3), where the maximal compact subgroup U(3) is the symmetry group of the harmonic oscillator. The Hamiltonian equations of motion on each orbit form a Lax system X = (X,F), where X and F are elements of the symplectic Lie algebra. The elements of the matrix X are the generators of the symplectic Lie algebra, viz., the one-body collective quadratic functions of the positions and momenta of the galactic masses. The matrix F is composed from the self-gravitating potential energy, the angular velocity, and the hydostatic pressure. Solutions to the hamiltonian dynamical system on Sp(3,R)/U(3) are given by symplectic isospectral deformations. The Casimirs of Sp(3,R), equal to the traces of powers of X, are conserved quantities.

  14. Analyzing Atmospheric Neutrino Oscillations

    SciTech Connect

    Escamilla, J.; Ernst, D. J.; Latimer, D. C.

    2007-10-26

    We provide a pedagogic derivation of the formula needed to analyze atmospheric data and then derive, for the subset of the data that are fully-contained events, an analysis tool that is quantitative and numerically efficient. Results for the full set of neutrino oscillation data are then presented. We find the following preliminary results: 1.) the sub-dominant approximation provides reasonable values for the best fit parameters for {delta}{sub 32}, {theta}{sub 23}, and {theta}{sub 13} but does not quantitatively provide the errors for these three parameters; 2.) the size of the MSW effect is suppressed in the sub-dominant approximation; 3.) the MSW effect reduces somewhat the extracted error for {delta}{sub 32}, more so for {theta}{sub 23} and {theta}{sub 13}; 4.) atmospheric data alone constrains the allowed values of {theta}{sub 13} only in the sub-dominant approximation, the full three neutrino calculations requires CHOOZ to get a clean constraint; 5.) the linear in {theta}{sub 13} terms are not negligible; and 6.) the minimum value of {theta}{sub 13} is found to be negative, but at a statistically insignificant level.

  15. A Matterwave Transistor Oscillator

    NASA Astrophysics Data System (ADS)

    Caliga, Seth; Straatsma, Cameron; Anderson, Dana

    2013-05-01

    We perform experiments with an Rb87 Bose-condensed gas in a magnetic trap separated into three regions by a pair of blue-detuned optical barriers, forming a transistor-like structure having large ``source'' and ``drain'' regions separated by a narrow ``gate'' region. A condensate is produced in the source by forced RF evaporative cooling. While atom number and chemical potential of the source atoms are determined by traditional time of flight methods, we observe the flux and energy of the drain atoms emerging from the gate-drain barrier with a high resolution (NA = 0.6) in-trap absorption imaging system. Asymmetric cooling of the trap causes a thermo-mechanically induced superfluid current to flow from the source to the gate over the source-gate barrier. Feedback through superfluid coupling between the source and the gate maintains near equality of the source and gate chemical potentials while superfluid flow continues to cause atoms to emerge from the gate into the drain. A resonant ``terminator'' beam illuminating the drain region effectively couples emerging gate atoms to the vacuum. By turning off the terminator beam shortly before snapping an absorption image we determine both the atom flux and the atom energy. With an appropriate choice of cooling schedule, barrier heights, and separations, the gate emits a monoenergetic beam of atoms. We establish that this system is a superfluid analog of an antenna-coupled transistor-oscillator circuit in which the dual of the electromagnetic wave is a matterwave.

  16. Epidemics with multistrain interactions: The interplay between cross immunity and antibody-dependent enhancement

    NASA Astrophysics Data System (ADS)

    Bianco, Simone; Shaw, Leah B.; Schwartz, Ira B.

    2009-12-01

    This paper examines the interplay of the effect of cross immunity and antibody-dependent enhancement (ADE) in multistrain diseases. Motivated by dengue fever, we study a model for the spreading of epidemics in a population with multistrain interactions mediated by both partial temporary cross immunity and ADE. Although ADE models have previously been observed to cause chaotic outbreaks, we show analytically that weak cross immunity has a stabilizing effect on the system. That is, the onset of disease fluctuations requires a larger value of ADE with small cross immunity than without. However, strong cross immunity is shown numerically to cause oscillations and chaotic outbreaks even for low values of ADE.

  17. Glucose Oscillations Can Activate an Endogenous Oscillator in Pancreatic Islets

    PubMed Central

    Mukhitov, Nikita; Roper, Michael G.; Bertram, Richard

    2016-01-01

    Pancreatic islets manage elevations in blood glucose level by secreting insulin into the bloodstream in a pulsatile manner. Pulsatile insulin secretion is governed by islet oscillations such as bursting electrical activity and periodic Ca2+ entry in β-cells. In this report, we demonstrate that although islet oscillations are lost by fixing a glucose stimulus at a high concentration, they may be recovered by subsequently converting the glucose stimulus to a sinusoidal wave. We predict with mathematical modeling that the sinusoidal glucose signal’s ability to recover islet oscillations depends on its amplitude and period, and we confirm our predictions by conducting experiments with islets using a microfluidics platform. Our results suggest a mechanism whereby oscillatory blood glucose levels recruit non-oscillating islets to enhance pulsatile insulin output from the pancreas. Our results also provide support for the main hypothesis of the Dual Oscillator Model, that a glycolytic oscillator endogenous to islet β-cells drives pulsatile insulin secretion. PMID:27788129

  18. Floating Oscillator-Embedded Triboelectric Generator for Versatile Mechanical Energy Harvesting

    PubMed Central

    Seol, Myeong-Lok; Han, Jin-Woo; Jeon, Seung-Bae; Meyyappan, M.; Choi, Yang-Kyu

    2015-01-01

    A versatile vibration energy harvesting platform based on a triboelectricity is proposed and analyzed. External mechanical vibration repeats an oscillating motion of a polymer-coated metal oscillator floating inside a surrounding tube. Continuous sidewall friction at the contact interface of the oscillator induces current between the inner oscillator electrode and the outer tube electrode to convert mechanical vibrations into electrical energy. The floating oscillator-embedded triboelectric generator (FO-TEG) is applicable for both impulse excitation and sinusoidal vibration which universally exist in usual environment. For the impulse excitation, the generated current sustains and slowly decays by the residual oscillation of the floating oscillator. For the sinusoidal vibration, the output energy can be maximized by resonance oscillation. The operating frequency range can be simply optimized with high degree of freedom to satisfy various application requirements. In addition, the excellent immunity against ambient humidity is experimentally demonstrated, which stems from the inherently packaged structure of FO-TEG. The prototype device provides a peak-to-peak open-circuit voltage of 157 V and instantaneous short-circuit current of 4.6 μA, within sub-10 Hz of operating frequency. To visually demonstrate the energy harvesting behavior of FO-TEG, lighting of an array of LEDs is demonstrated using artificial vibration and human running. PMID:26553524

  19. Brain oscillations in neuropsychiatric disease.

    PubMed

    Başar, Erol

    2013-09-01

    The term "brain (or neural) oscillations" refers to the rhythmic and/or repetitive electrical activity generated spontaneously and in response to stimuli by neural tissue in the central nervous system. The importance of brain oscillations in sensory-cognitive processes has become increasingly evident. It has also become clear that event-related oscillations are modified in many types of neuropathology, in particular in cognitive impairment. This review discusses methods such as evoked/event-related oscillations and spectra, coherence analysis, and phase locking. It gives examples of applications of essential methods and concepts in bipolar disorder that provide a basis for fundamental notions regarding neurophysiologic biomarkers in cognitive impairment. The take-home message is that in the development of diagnostic and pharmacotherapeutic strategies, neurophysiologic data should be analyzed in a framework that uses a multiplicity of methods and frequency bands.

  20. Transient voltage oscillations in coils

    SciTech Connect

    Chowdhuri, P.

    1985-01-01

    Magnet coils may be excited into internal voltage oscillations by transient voltages. Such oscillations may electrically stress the magnet's dielectric components to many times its normal stress. This may precipitate a dielectric failure, and the attendant prolonged loss of service and costly repair work. Therefore, it is important to know the natural frequencies of oscillations of a magnet during the design stage, and to determine whether the expected switching transient voltages can excite the magnet into high-voltage internal oscillations. The series capacitance of a winding significantly affects its natural frequencies. However, the series capacitance is difficult to calculate, because it may comprise complex capacitance network, consisting of intra- and inter-coil turn-to-turn capacitances of the coil sections. A method of calculating the series capacitance of a winding is proposed. This method is rigorous but simple to execute. The time-varying transient voltages along the winding are also calculated.

  1. Matter Effects On Neutrino Oscillations

    NASA Astrophysics Data System (ADS)

    Gordon, Michael

    An introduction to neutrino oscillations in vacuum is presented, followed by a survey of various techniques for obtaining either exact or approximate expressions for numu → nue oscillations in matter. The method developed by Arafune, Koike, and Sato uses a perturbative analysis to find an approximation for the evolution operator. The method used by Freund yields an approximate oscillation probability by diagonalizing the Hamiltonian, finding the eigenvalues and eigenvectors, and then using those to find modified mixing angles with the matter effect taken into account. The method devised by Mann, Kafka, Schneps, and Altinok produces an exact expression for the oscillation by determining explicitly the evolution operator. These methods are compared to each other using the T2K, MINOS, NOnuA, and LBNE parameters.

  2. Gamma Oscillations and Visual Binding

    NASA Astrophysics Data System (ADS)

    Robinson, Peter A.; Kim, Jong Won

    2006-03-01

    At the root of visual perception is the mechanism the brain uses to analyze features in a scene and bind related ones together. Experiments show this process is linked to oscillations of brain activity in the 30-100 Hz gamma band. Oscillations at different sites have correlation functions (CFs) that often peak at zero lag, implying simultaneous firing, even when conduction delays are large. CFs are strongest between cells stimulated by related features. Gamma oscillations are studied here by modeling mm-scale patchy interconnections in the visual cortex. Resulting predictions for gamma responses to stimuli account for numerous experimental findings, including why oscillations and zero-lag synchrony are associated, observed connections with feature preferences, the shape of the zero-lag peak, and variations of CFs with attention. Gamma waves are found to obey the Schroedinger equation, opening the possibility of cortical analogs of quantum phenomena. Gamma instabilities are tied to observations of gamma activity linked to seizures and hallucinations.

  3. Joint Replacement Surgery and the Innate Immune System

    PubMed Central

    Goodman, Stuart; Konttinen, Yrjö T.; Takagi, Michiaki

    2015-01-01

    Total joint replacement is a highly successful, cost-effective surgical procedure that relieves pain and improves function for patients with end-stage arthritis. The most commonly used materials for modern joint replacements include metal alloys such as cobalt chrome and titanium alloys, polymers including polymethylmethacrylate and polyethylene, and ceramics. Implantation of a joint prosthesis incites an acute inflammatory reaction that is regulated by the innate immune system, a preprogrammed non-antigen specific biological response composed of cells, proteins, and other factors. This “frontline” immune mechanism was originally designed to combat invading microorganisms, but now responds to both pathogen-associated molecular patterns or PAMPS (by-products from microorganisms), and damage associated molecular patterns or DAMPS (molecular by-products from cells), via pattern recognition receptors (PRRs). In this way, potentially injurious stimuli that might disrupt the normal homeostatic regulatory mechanisms of the organism are efficiently dealt with, ensuring the survival of the host. Initial surgical implantation of the joint replacement, as well as ongoing generation of wear debris and byproducts during usage of the joint, activates the innate immune system. Understanding and potentially modulating these events may lead to improved function and increased longevity of joint replacements in the future. PMID:25747028

  4. Magnetically Coupled Magnet-Spring Oscillators

    ERIC Educational Resources Information Center

    Donoso, G.; Ladera, C. L.; Martin, P.

    2010-01-01

    A system of two magnets hung from two vertical springs and oscillating in the hollows of a pair of coils connected in series is a new, interesting and useful example of coupled oscillators. The electromagnetically coupled oscillations of these oscillators are experimentally and theoretically studied. Its coupling is electromagnetic instead of…

  5. Nonlinear oscillations of coalescing magnetic flux ropes

    NASA Astrophysics Data System (ADS)

    Kolotkov, Dmitrii Y.; Nakariakov, Valery M.; Rowlands, George

    2016-05-01

    An analytical model of highly nonlinear oscillations occurring during a coalescence of two magnetic flux ropes, based upon two-fluid hydrodynamics, is developed. The model accounts for the effect of electric charge separation, and describes perpendicular oscillations of the current sheet formed by the coalescence. The oscillation period is determined by the current sheet thickness, the plasma parameter β , and the oscillation amplitude. The oscillation periods are typically greater or about the ion plasma oscillation period. In the nonlinear regime, the oscillations of the ion and electron concentrations have a shape of a narrow symmetric spikes.

  6. An extended relativistic quantum oscillator for ? particles

    NASA Astrophysics Data System (ADS)

    Nedjadi, Y.; Ait-Tahar, S.; Barrett, R. C.

    1998-04-01

    We introduce the extended Duffin-Kemmer-Petiau (DKP) oscillator obtained by combining two relativistic quantum oscillator models. In a study analogous to Kukulin, Loyola and Moshinsky's work on extended Dirac oscillators, we investigate whether this extended version has oscillator shells controllably independent from the spin-orbit coupling. This extended DKP oscillator is found to be exactly solvable for natural parity states. We calculate and discuss both the natural- and unnatural-parity eigenspectra of its spin-1 representation.

  7. Imbalanced immune homeostasis in immune thrombocytopenia.

    PubMed

    Yazdanbakhsh, Karina

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders.

  8. Imbalanced immune homeostasis in immune thrombocytopenia

    PubMed Central

    Yazdanbakhsh, Karina

    2017-01-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders. PMID:27312156

  9. Alterations in immune cells and mediators in the brain: it’s not always neuroinflammation!

    PubMed Central

    Estes, Myka L.; McAllister, A. Kimberley

    2015-01-01

    Neuroinflammation was once a clearly defined term denoting pathological immune processes within the CNS. Historically this term was used to indicate the four hallmarks of peripheral inflammation that occur following severe CNS injuries like stroke, injury or infection. Recently, however, the definition of neuroinflammation has relaxed to the point that it is often now assumed to be present when even only a single classical hallmark of inflammation is measured. As a result, a wide range of disorders, from psychiatric to degenerative diseases, are now assumed to have an integral inflammatory component. Ironically, at the same time, research has revealed unexpected non-classical immune actions of immune mediators and cells in the CNS in the absence of pathology, increasing the likelihood that homeostatic and adaptive immune processes in the CNS will be mistaken for neuroinflammation. Thus, we suggest reserving the term neuroinflammation for contexts where multiple signs of inflammation are present to avoid erroneously classifying disorders as inflammatory when they may instead be caused by non-immune etiologies or secondary immune processes that serve adaptive roles. PMID:25345893

  10. Engineering self-assembled materials to study and direct immune function.

    PubMed

    Tostanoski, Lisa H; Jewell, Christopher M

    2017-04-06

    The immune system is an awe-inspiring control structure that maintains a delicate and constantly changing balance between pro-immune functions that fight infection and cancer, regulatory or suppressive functions involved in immune tolerance, and homeostatic resting states. These activities are determined by integrating signals in space and time; thus, improving control over the densities, combinations, and durations with which immune signals are delivered is a central goal to better combat infectious disease, cancer, and autoimmunity. Self-assembly presents a unique opportunity to synthesize materials with well-defined compositions and controlled physical arrangement of molecular building blocks. This review highlights strategies exploiting these capabilities to improve the understanding of how precisely-displayed cues interact with immune cells and tissues. We present work centered on fundamental properties that regulate the nature and magnitude of immune response, highlight pre-clinical and clinical applications of self-assembled technologies in vaccines, cancer, and autoimmunity, and describe some of the key manufacturing and regulatory hurdles facing these areas.

  11. Immune Responses in Neonates

    PubMed Central

    Basha, Saleem; Surendran, Naveen; Pichichero, Michael

    2015-01-01

    Neonates have little immunological memory and a developing immune system, which increases their vulnerability to infectious agents. Recent advances in understanding of neonatal immunity indicate that both innate and adaptive responses are dependent on precursor frequency of lymphocytes, antigenic dose and mode of exposure. Studies in neonatal mouse models and human umbilical cord blood cells demonstrate the capability of neonatal immune cells to produce immune responses similar to adults in some aspects but not others. This review focuses mainly on the developmental and functional mechanisms of the human neonatal immune system. In particular, the mechanism of innate and adaptive immunity and the role of neutrophils, antigen presenting cells, differences in subclasses of T lymphocytes (Th1, Th2, Tregs) and B cells are discussed. In addition, we have included the recent developments in neonatal mouse immune system. Understanding neonatal immunity is essential to development of therapeutic vaccines to combat newly emerging infectious agents. PMID:25088080

  12. Aging changes in immunity

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/004008.htm Aging changes in immunity To use the sharing features ... cells and antibodies that destroy these harmful substances. AGING CHANGES AND THEIR EFFECTS ON THE IMMUNE SYSTEM ...

  13. Immunity to cancer

    SciTech Connect

    Reif, A.E.; Mitchell, M.S.

    1985-01-01

    This book contains five sections, each containing several papers. The section titles are: Identification and Characterization of Tumor Antigens; Immune Responses to Tumor Antigens; Regulation of the Immune Response to Tumor Cells, Immunotherapy and Biomodulators, and Immunotherapy and Immunoprophylaxis.

  14. Immune System and Disorders

    MedlinePlus

    Your immune system is a complex network of cells, tissues, and organs that work together to defend against germs. It ... t, to find and destroy them. If your immune system cannot do its job, the results can be ...

  15. [Immune system and tumors].

    PubMed

    Terme, Magali; Tanchot, Corinne

    2017-02-01

    Despite having been much debated, it is now well established that the immune system plays an essential role in the fight against cancer. In this article, we will highlight the implication of the immune system in the control of tumor growth and describe the major components of the immune system involved in the antitumoral immune response. The immune system, while exerting pressure on tumor cells, also will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as they develop. Finally, we will illustrate the numerous mechanisms of immune suppression that take place within the tumoral microenvironment which allow tumor cells to escape control from the immune system. The increasingly precise knowledge of the brakes to an effective antitumor immune response allows the development of immunotherapy strategies more and more innovating and promising of hope.

  16. Liver fibrosis and repair: immune regulation of wound healing in a solid organ.

    PubMed

    Pellicoro, Antonella; Ramachandran, Prakash; Iredale, John P; Fallowfield, Jonathan A

    2014-03-01

    Fibrosis is a highly conserved and co-ordinated protective response to tissue injury. The interaction of multiple pathways, molecules and systems determines whether fibrosis is self-limiting and homeostatic, or whether it is uncontrolled and excessive. Immune cells have been identified as key players in this fibrotic cascade, with the capacity to exert either injury-inducing or repair-promoting effects. A multi-organ approach was recently suggested to identify the core and regulatory pathways in fibrosis, with the aim of integrating the wealth of information emerging from basic fibrosis research. In this Review, we focus on recent advances in liver fibrosis research as a paradigm for wound healing in solid organs and the role of the immune system in regulating and balancing this response.

  17. Arrays of coupled chemical oscillators

    NASA Astrophysics Data System (ADS)

    Forrester, Derek Michael

    2015-11-01

    Oscillating chemical reactions result from complex periodic changes in the concentration of the reactants. In spatially ordered ensembles of candle flame oscillators the fluctuations in the ratio of oxygen atoms with respect to that of carbon, hydrogen and nitrogen produces an oscillation in the visible part of the flame related to the energy released per unit mass of oxygen. Thus, the products of the reaction vary in concentration as a function of time, giving rise to an oscillation in the amount of soot and radiative emission. Synchronisation of interacting dynamical sub-systems occurs as arrays of flames that act as master and slave oscillators, with groups of candles numbering greater than two, creating a synchronised motion in three-dimensions. In a ring of candles the visible parts of each flame move together, up and down and back and forth, in a manner that appears like a “worship”. Here this effect is shown for rings of flames which collectively empower a central flame to pulse to greater heights. In contrast, situations where the central flames are suppressed are also found. The phenomena leads to in-phase synchronised states emerging between periods of anti-phase synchronisation for arrays with different columnar sizes of candle and positioning.

  18. Arrays of coupled chemical oscillators

    PubMed Central

    Forrester, Derek Michael

    2015-01-01

    Oscillating chemical reactions result from complex periodic changes in the concentration of the reactants. In spatially ordered ensembles of candle flame oscillators the fluctuations in the ratio of oxygen atoms with respect to that of carbon, hydrogen and nitrogen produces an oscillation in the visible part of the flame related to the energy released per unit mass of oxygen. Thus, the products of the reaction vary in concentration as a function of time, giving rise to an oscillation in the amount of soot and radiative emission. Synchronisation of interacting dynamical sub-systems occurs as arrays of flames that act as master and slave oscillators, with groups of candles numbering greater than two, creating a synchronised motion in three-dimensions. In a ring of candles the visible parts of each flame move together, up and down and back and forth, in a manner that appears like a “worship”. Here this effect is shown for rings of flames which collectively empower a central flame to pulse to greater heights. In contrast, situations where the central flames are suppressed are also found. The phenomena leads to in-phase synchronised states emerging between periods of anti-phase synchronisation for arrays with different columnar sizes of candle and positioning. PMID:26582365

  19. Quantum Oscillations from Fermi Arcs

    NASA Astrophysics Data System (ADS)

    Pereg-Barnea, Tamar; Refael, Gil; Franz, Marcel; Weber, Heidi; Seradjeh, Babak

    2009-03-01

    Recent experiments[1] in a variety of High Tc superconductors revel 1/B oscillations in the vortex-liquid state. The period of oscillations in underdoped samples is short and can be translated, via the Onsager relation to an area in k-space which makes up a few percents of the Brillouin zone. Quantum oscillations are usually thought of as arising from closed orbits in momentum space along the Fermi surface and are used to measure the Fermi vector. Thus, the observation of quantum oscillations in the cuprates seems to be at odds with the observation of Fermi arcs in ARPES experiments[2] due to their fragmented Fermi surface topology. In this talk we show that quantum oscillations can arise from a partially gapped Fermi surface. We adopt a phenomenological model of arcs which terminate at a regime with a superconducting gap of d-wave symmetry to describe the pseudo gap phase. Without invoking any additional order, quantization of energy is found well below the gap maximum. Semiclassically the quantization condition arises from closed orbits in real-space. When translated to momentum space, the area enclosed by the orbits is much smaller than that of the full Fermi surface. [1]N. Doiron-Leyaraud et al. nature 447, 565 (2007) [2]Kanigel et al. Nature Physics 2 447 (2006)

  20. Large amplitude drop shape oscillations

    NASA Technical Reports Server (NTRS)

    Trinh, E. H.; Wang, T. G.

    1982-01-01

    An experimental study of large amplitude drop shape oscillation was conducted in immiscible liquids systems and with levitated free liquid drops in air. In liquid-liquid systems the results indicate the existence of familiar characteristics of nonlinear phenomena. The resonance frequency of the fundamental quadrupole mode of stationary, low viscosity Silicone oil drops acoustically levitated in water falls to noticeably low values as the amplitude of oscillation is increased. A typical, experimentally determined relative frequency decrease of a 0.5 cubic centimeters drop would be about 10% when the maximum deformed shape is characterized by a major to minor axial ratio of 1.9. On the other hand, no change in the fundamental mode frequency could be detected for 1 mm drops levitated in air. The experimental data for the decay constant of the quadrupole mode of drops immersed in a liquid host indicate a slight increase for larger oscillation amplitudes. A qualitative investigation of the internal fluid flows for such drops revealed the existence of steady internal circulation within drops oscillating in the fundamental and higher modes. The flow field configuration in the outer host liquid is also significantly altered when the drop oscillation amplitude becomes large.

  1. TRANSVERSE OSCILLATIONS IN CHROMOSPHERIC MOTTLES

    SciTech Connect

    Kuridze, D.; Mathioudakis, M.; Jess, D. B.; Keenan, F. P.; Morton, R. J.; Erdelyi, R.; Dorrian, G. D.

    2012-05-01

    A number of recent investigations have revealed that transverse waves are ubiquitous in the solar chromosphere. The vast majority of these have been reported in limb spicules and active region fibrils. We investigate long-lived, quiet-Sun, on-disk features such as chromospheric mottles (jet-like features located at the boundaries of supergranular cells) and their transverse motions. The observations were obtained with the Rapid Oscillations in the Solar Atmosphere instrument at the Dunn Solar Telescope. The data set is comprised of simultaneous imaging in the H{alpha} core, Ca II K, and G band of an on-disk quiet-Sun region. Time-distance techniques are used to study the characteristics of the transverse oscillations. We detect over 40 transverse oscillations in both bright and dark mottles, with periods ranging from 70 to 280 s, with the most frequent occurrence at {approx}165 s. The velocity amplitudes and transverse displacements exhibit characteristics similar to limb spicules. Neighboring mottles oscillating in-phase are also observed. The transverse oscillations of individual mottles are interpreted in terms of magnetohydrodynamic kink waves. Their estimated periods and damping times are consistent with phase mixing and resonant mode conversion.

  2. Your Child's Immunization Record

    MedlinePlus

    Your Child’s Immunization Record It’s important to keep up-to-date records of all your child’s immunizations, beginning at birth and continuing through ... receives a vaccination by filling in the date. Record of Immunizations Date Given: Where Given: Reaction: Hepatitis ...

  3. The Immune System Game

    ERIC Educational Resources Information Center

    Work, Kirsten A.; Gibbs, Melissa A.; Friedman, Erich J.

    2015-01-01

    We describe a card game that helps introductory biology students understand the basics of the immune response to pathogens. Students simulate the steps of the immune response with cards that represent the pathogens and the cells and molecules mobilized by the immune system. In the process, they learn the similarities and differences between the…

  4. Immune System Quiz

    MedlinePlus

    ... los dientes Video: Getting an X-ray Quiz: Immune System KidsHealth > For Kids > Quiz: Immune System Print A A A How much do you know about your immune system? Find out by taking this quiz! About KidsHealth ...

  5. Immune Disorder HSCT Protocol

    ClinicalTrials.gov

    2016-11-01

    Immune Deficiency Disorders; Severe Combined Immunodeficiency; Chronic Granulomatous Disease; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Hyper-IgM; DiGeorge Syndrome; Chediak-Higashi Syndrome; Common Variable Immune Deficiency; Immune Dysregulatory Disorders; Hemophagocytic Lymphohistiocytosis; IPEX; Autoimmune Lymphoproliferative Syndrome; X-linked Lymphoproliferative Syndrome

  6. Nonstationary oscillations in gyrotrons revisited

    SciTech Connect

    Dumbrajs, O.; Kalis, H.

    2015-05-15

    Development of gyrotrons requires careful understanding of different regimes of gyrotron oscillations. It is known that in the planes of the generalized gyrotron variables: cyclotron resonance mismatch and dimensionless current or cyclotron resonance mismatch and dimensionless interaction length complicated alternating sequences of regions of stationary, periodic, automodulation, and chaotic oscillations exist. In the past, these regions were investigated on the supposition that the transit time of electrons through the interaction space is much shorter than the cavity decay time. This assumption is valid for short and/or high diffraction quality resonators. However, in the case of long and/or low diffraction quality resonators, which are often utilized, this assumption is no longer valid. In such a case, a different mathematical formalism has to be used for studying nonstationary oscillations. One example of such a formalism is described in the present paper.

  7. Oscillations of solar atmosphere neutrinos

    SciTech Connect

    Fogli, G. L.; Lisi, E.; Mirizzi, A.; Montanino, D.; Serpico, P. D.

    2006-11-01

    The Sun is a source of high-energy neutrinos (E(greater-or-similar sign)10 GeV) produced by cosmic ray interactions in the solar atmosphere. We study the impact of three-flavor oscillations (in vacuum and in matter) on solar atmosphere neutrinos, and calculate their observable fluxes at Earth, as well as their event rates in a kilometer-scale detector in water or ice. We find that peculiar three-flavor oscillation effects in matter, which can occur in the energy range probed by solar atmosphere neutrinos, are significantly suppressed by averaging over the production region and over the neutrino and antineutrino components. In particular, we find that the relation between the neutrino fluxes at the Sun and at the Earth can be approximately expressed in terms of phase-averaged vacuum oscillations, dominated by a single mixing parameter (the angle {theta}{sub 23})

  8. Stochastic excitation of stellar oscillations

    NASA Astrophysics Data System (ADS)

    Samadi, Reza

    2001-05-01

    Since more than about thirty years, solar oscillations are thought to be excited stochastically by the turbulent motions in the solar convective zone. It is currently believed that oscillations of stars lower than 2 solar masses - which possess an upper convective zone - are excited stochastically by turbulent convection in their outer layers. Providing that accurate measurements of the oscillation amplitudes and damping rates are available it is possible to evaluate the power injected into the modes and thus - by comparison with the observations - to constrain current theories. A recent theoretical work (Samadi & Goupil, 2001; Samadi et al., 2001) supplements and reinforces the theory of stochastic excitation of star vibrations. This process was generalized to a global description of the turbulent state of their convective zone. The comparison between observation and theory, thus generalized, will allow to better know the turbulent spectrum of stars, and this in particular thanks to the COROT mission.

  9. Magnetically insulated transmission line oscillator

    DOEpatents

    Bacon, Larry D.; Ballard, William P.; Clark, M. Collins; Marder, Barry M.

    1988-01-01

    A magnetically insulated transmission line oscillator employs self-generated magnetic fields to generate microwave energy. An anode of the oscillator includes slow-wave structures which are formed of a plurality of thin conductive vanes defining cavities therebetween, and a gap is formed between the anode and a cathode of the oscillator. In response to a pulsed voltage applied to the anode and cathode, self-generated magnetic fields arfe produced in a cross-field orientation with respect to the orientation of the electric field between the anode and the cathode. The cross-field magnetic fields insulate the flow of electrons in the gap and confine the flow of electrons within the gap.

  10. Magnetically insulated transmission line oscillator

    DOEpatents

    Bacon, L.D.; Ballard, W.P.; Clark, M.C.; Marder, B.M.

    1987-05-19

    A magnetically insulated transmission line oscillator employs self-generated magnetic fields to generate microwave energy. An anode of the oscillator includes slow-wave structures which are formed of a plurality of thin conductive vanes defining cavities therebetween, and a gap is formed between the anode and a cathode of the oscillator. In response to a pulsed voltage applied to the anode and cathode, self-generated magnetic fields are produced in a cross-field orientation with respect to the orientation of the electric field between the anode and the cathode. The cross-field magnetic fields insulate the flow of electrons in the gap and confine the flow of electrons within the gap. 11 figs.

  11. THE TIME COURSE OF ADENOSINE, NITRIC OXIDE (NO) AND INDUCIBLE NO SYNTHASE CHANGES IN THE BRAIN WITH SLEEP LOSS AND THEIR ROLE IN THE NREM SLEEP HOMEOSTATIC CASCADE

    PubMed Central

    Kalinchuk, Anna V.; McCarley, Robert W.; Porkka-Heiskanen, Tarja; Basheer, Radhika

    2011-01-01

    Both adenosine and nitric oxide (NO) are known for their role in sleep homeostasis, with the basal forebrain (BF) wakefulness center as an important site of action. Previously we reported a cascade of homeostatic events, wherein sleep deprivation (SD) induces the production of inducible nitric oxide synthase (iNOS)-dependent NO in BF, leading to enhanced release of extracellular adenosine. In turn, increased BF adenosine leads to enhanced sleep intensity, as measured by increased non-rapid eye movement (NREM) EEG delta activity. However, the presence and time course of similar events in cortex has not been studied, although a frontal cortical role for the increase in NREM recovery sleep EEG delta power is known. Accordingly, we performed simultaneous hourly microdialysis sample collection from BF and frontal cortex (FC) during 11h SD. We observed that both areas showed sequential increases in iNOS and NO, followed by increases in adenosine. BF increases began at 1h SD, while FC increases began at 5h SD. iNOS and Fos-double labeling indicated that iNOS induction occurred in BF and FC wake-active neurons. These data support the role of BF adenosine and NO in sleep homeostasis and indicate the temporal and spatial sequence of sleep homeostatic cascade for NO and adenosine. PMID:21062286

  12. Multiple sclerosis immunology: The healthy immune system vs the MS immune system.

    PubMed

    Kasper, Lloyd H; Shoemaker, Jennifer

    2010-01-05

    Multiple sclerosis (MS) is a debilitating autoimmune disease characterized by both inflammation and axonal degeneration. The resulting demyelination and subsequent degeneration of axons account for the disability of patients with MS. Early investigations indicated that disease progression was driven by CD4(+) effector T cells. However, clinical therapies specifically targeting these cells have, for the most part, not been effective. Therefore, new areas of research in experimental autoimmune encephalomyelitis (the experimental model of MS) and human MS have identified previously unknown contributions to disease pathogenesis, including interleukin-17-producing T helper 17 cells, B cells, CD8(+) T cells, and both CD4(+) and CD8(+) T-regulatory cells. Research into the respective mechanisms of action of these cells has identified novel therapeutic targets to combat this devastating disease. This article reviews the autoimmune response in patients with MS compared with individuals without MS and summarizes the fundamental differences in the immunologic response between people with and without MS. Investigations into these autoimmune differences and the disruption of the homeostatic balance of the immune system will help guide future research into MS therapeutics, with particular attention to the long-term management of this disease.

  13. Whispering gallery optical parametric oscillators

    NASA Astrophysics Data System (ADS)

    Breunig, Ingo; Buse, Karsten

    2013-12-01

    Whispering gallery optical parametric oscillators (WGR OPOs) are monolithic sources for tunable coherent and non-classical light. They are based on total internal reflection. Since reflection losses are negligible, their oscillation threshold can be far below one milliwatt. With sub-millimeter diameters, they are the most compact OPOs demonstrated so far. Recent experimental results demonstrate that WGR OPOs emit coherent light tunable over hundreds of nanometers. Operation in the visible as well as in the near-infrared has been demonstrated with up to 30 % conversion efficiency. These results indicate a great potential of WGR OPOs for spectroscopic and sensing applications.

  14. Polarization mixing optical parametric oscillator.

    SciTech Connect

    Pearl, Shaul; Smith, Arlee Virgil; Arie, Ady; Blau, Pinhas; Kalmani, Gal

    2005-05-01

    We report the experimental realization of a new type of optical parametric oscillator in which oscillation is achieved by polarization rotation in a linear retarder, followed by nonlinear polarization mixing. The mixing is performed by a type II degenerate parametric downconversion in a periodically poled KTP crystal pumped by a 1064 nm pulsed Nd:YAG pump. A single, linearly polarized beam, precisely at the degenerate wavelength is generated. The output spectrum has a narrow linewidth (below the instrumentation bandwidth of 1 nm) and is highly stable with respect to variations in the crystal temperature.

  15. Primordial lepton oscillations and baryogenesis

    NASA Astrophysics Data System (ADS)

    Hamada, Yuta; Kitano, Ryuichiro

    2016-11-01

    The baryon asymmetry of the Universe should have been produced after the inflation era. We consider the possibility that the asymmetry is generated by the flavor oscillations in the reheating process after inflation, so that the baryon asymmetry is realized already at the beginning of the radiation dominated era. In the seesaw model, we show that the propagators of the left-handed leptons generically have flavor mixings in the thermal background, that can generate flavor-dependent lepton asymmetry through the CP violation in the oscillation phenomena. The flavor dependent rates for the wash-out process can leave the net asymmetry today.

  16. Magnetic Oscillations in Weyl Semimetals

    NASA Astrophysics Data System (ADS)

    Ashby, Phillip; Carbotte, Jules

    2014-03-01

    Weyl semimetals are a three-dimensional phase containing band touchings at isolated points in the Brillouin zone. A Weyl semimetal can be thought of as a higher dimensional generalization of graphene. We study the thermodynamic and transport properties of a Weyl semimetal subject to an applied magnetic field. We examine the quantum oscillations in the magnetization to look for signatures that distinguish the Weyl semimetal from conventional phases of matter. We find distinctive sawtooth-like oscillations in the magnetization that reflect the relativistic nature of the bulk bands. The effect of impurities on these signatures will also be discussed.

  17. Critical-state dynamics of avalanches and oscillations jointly emerge from balanced excitation/inhibition in neuronal networks.

    PubMed

    Poil, Simon-Shlomo; Hardstone, Richard; Mansvelder, Huibert D; Linkenkaer-Hansen, Klaus

    2012-07-18

    Criticality has gained widespread interest in neuroscience as an attractive framework for understanding the character and functional implications of variability in brain activity. The metastability of critical systems maximizes their dynamic range, storage capacity, and computational power. Power-law scaling-a hallmark of criticality-has been observed on different levels, e.g., in the distribution of neuronal avalanches in vitro and in vivo, but also in the decay of temporal correlations in behavioral performance and ongoing oscillations in humans. An unresolved issue is whether power-law scaling on different organizational levels in the brain-and possibly in other hierarchically organized systems-can be related. Here, we show that critical-state dynamics of avalanches and oscillations jointly emerge in a neuronal network model when excitation and inhibition is balanced. The oscillatory activity of the model was qualitatively similar to what is typically observed in recordings of human resting-state MEG. We propose that homeostatic plasticity mechanisms tune this balance in healthy brain networks, and that it is essential for critical behavior on multiple levels of neuronal organization with ensuing functional benefits. Based on our network model, we introduce a concept of multi-level criticality in which power-law scaling can emerge on multiple time scales in oscillating networks.

  18. Kidney and innate immunity.

    PubMed

    Wang, Ying-Hui; Zhang, Yu-Gen

    2017-03-01

    Innate immune system is an important modulator of the inflammatory response during infection and tissue injury/repair. The kidney as a vital organ with high energy demand plays a key role in regulating the disease related metabolic process. Increasing research interest has focused on the immune pathogenesis of many kidney diseases. However, innate immune cells such as dendritic cells, macrophages, NK cells and a few innate lymphocytes, as well as the complement system are essential for renal immune homeostasis and ensure a coordinated balance between tissue injury and regeneration. The innate immune response provides the first line of host defense initiated by several classes of pattern recognition receptors (PRRs), such as membrane-bound Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), together with inflammasomes responsible for early innate immune response. Although the innate immune system is well studied, the research on the detailed relationship between innate immunity and kidney is still very limited. In this review, we will focus on the innate immune sensing system in renal immune homeostasis, as well as the corresponding pathogenesis of many kidney diseases. The pivotal roles of innate immunity in renal injury and regeneration with special emphasis on kidney disease related immunoregulatory mechanism are also discussed.

  19. BLOCKING OSCILLATOR DOUBLE PULSE GENERATOR CIRCUIT

    DOEpatents

    Haase, J.A.

    1961-01-24

    A double-pulse generator, particuiarly a double-pulse generator comprising a blocking oscillator utilizing a feedback circuit to provide means for producing a second pulse within the recovery time of the blocking oscillator, is described. The invention utilized a passive network which permits adjustment of the spacing between the original pulses derived from the blocking oscillator and further utilizes the original pulses to trigger a circuit from which other pulses are initiated. These other pulses are delayed and then applied to the input of the blocking oscillator, with the result that the output from the oscillator circuit contains twice the number of pulses originally initiated by the blocking oscillator itself.

  20. Chapter 2: Innate Immunity

    PubMed Central

    Turvey, Stuart E.; Broide, David H.

    2009-01-01

    Recent years have witnessed an explosion of interest in the innate immune system. Questions about how the innate immune system senses infection and empowers a protective immune response are being answered at the molecular level. These basic science discoveries are being translated into a more complete understanding of the central role innate immunity plays in the pathogenesis of many human infectious and inflammatory diseases. It is particularly exciting that we are already seeing a return on these scientific investments with the emergence of novel therapies to harness the power of the innate immune system. In this review we explore the defining characteristics of the innate immune system, and through more detailed examples, we highlight recent breakthroughs that have advanced our understanding of the role of innate immunity in human health and disease. PMID:19932920

  1. Mutation of albedo and growth response produces oscillations in a spatial Daisyworld

    NASA Astrophysics Data System (ADS)

    Wood, A. J.; Ackland, G.; Lenton, T.

    2005-12-01

    We present an extension of a 2-dimensional cellular automata (CA) Daisyworld to include mutation of optimum growth temperature as well as mutation of albedo. It is well established for the latter case such models exhibit homeostasis of the environment -- temperature in this case. In our model the organisms (daisies) can adapt to prevailing environmental conditions or evolve to alter their environment. This setup allows us to examine whether or not the former inhibits or even destroys the homeostatic effect. We find the resulting system to be capable of regulation on average but that it oscillates with a period of hundreds of daisy generations. The ability of the daisies to alter their optimal growing temperature leads initially to a planet which is less able to sustain itself, but the planet becomes steadily more stable (on average) for greater rates of genetic drift in this characteristic. Weaker and less regular oscillations have already been predicted in Daisyworlds before but in this model they become stronger and more regular as the mutation rate of the optimum growth temperature is increased. The oscillation itself is non-trivial and is composed by a series of well defined stages: when the population is maximal, a local region of daisies may lower (raise) the local temperature and adapt to it offering them a competitive advantage. The thermal time delay means that their newly adapted offspring are more successful, spiraling the daisies away from the optimal temperature. Once the population fragments, growth occurs primarily at boundaries between daisy patches and the bare earth - so warm (cold) adapted daisies are more successful, the direction of heating changes and the cycle reverses. We have analysed in detail the dependency of the period of oscillation on the various external parameters. It is found to decrease with increasing death rate, and to increase separately with increasing heat diffusion and heat capacity. The dependence of the period is

  2. Phosphatidylserine receptor Tim-4 is essential for the maintenance of the homeostatic state of resident peritoneal macrophages.

    PubMed

    Wong, Kit; Valdez, Patricia A; Tan, Christine; Yeh, Sherry; Hongo, Jo-Anne; Ouyang, Wenjun

    2010-05-11

    Tim-4 is a phosphatidylserine (PS) receptor that is expressed on various macrophage subsets. It mediates phagocytosis of apoptotic cells by peritoneal macrophages. The in vivo functions of Tim-4 in phagocytosis and immune responses, however, are still unclear. In this study, we show that Tim-4 quickly forms punctate caps on contact with apoptotic cells, in contrast to its normal diffused expression on the surface of phagocytes. Despite its expression in marginal zone and tingible body macrophages, Tim-4 deficiency only minimally affects outcomes of several acute immune challenges, including the trapping of apoptotic cells in the marginal zone, the clearance apoptotic cells by tingible body macrophages, and the formation of germinal centers and elicitation of antibody responses against sheep red blood cells (SRBCs). In addition, Tim-4(-/-) resident peritoneal macrophages (rPMs) phagocytose necrotic cells and other opsonized targets normally. However, their ability to bind and engulf apoptotic cells is significantly compromised both in vitro and in vivo. Most importantly, Tim-4 deficiency results in increased cellularity in the peritoneum. Resting rPMs produce higher TNF-alpha in culture. Their response to LPS, on the contrary, is dampened. Our data support an indispensible role of Tim-4 in maintaining the homeostasis of rPMs.

  3. Measuring polio immunity to plan immunization activities.

    PubMed

    Voorman, Arend; Lyons, Hil M

    2016-11-21

    The Global Polio Eradication Initiative is closer than ever to achieving a polio-free world. Immunization activities must still be carried out in non-endemic countries to maintain population immunity at levels which will stop poliovirus from spreading if it is re-introduced from still-infected areas. In areas where there is no active transmission of poliovirus, programs must rely on surrogate indicators of population immunity to determine the appropriate immunization activities, typically caregiver-reported vaccination history obtained from non-polio acute flaccid paralysis patients identified through polio surveillance. We used regression models to examine the relationship between polio vaccination campaigns and caregiver-reported polio vaccination history. We find that in many countries, vaccination campaigns have a surprisingly weak impact on these commonly used indicators. We conclude that alternative criteria and data, such as routine immunization indicators from vaccination records or household surveys, should be considered for planning polio vaccination campaigns, and that validation of such surrogate indicators is necessary if they are to be used as the basis for program planning and risk assessment. We recommend that the GPEI and similar organizations consider or continue devoting additional resources to rigorously study population immunity and campaign effectiveness in at-risk countries.

  4. How do plants achieve immunity? Defence without specialized immune cells.

    PubMed

    Spoel, Steven H; Dong, Xinnian

    2012-01-25

    Vertebrates have evolved a sophisticated adaptive immune system that relies on an almost infinite diversity of antigen receptors that are clonally expressed by specialized immune cells that roam the circulatory system. These immune cells provide vertebrates with extraordinary antigen-specific immune capacity and memory, while minimizing self-reactivity. Plants, however, lack specialized mobile immune cells. Instead, every plant cell is thought to be capable of launching an effective immune response. So how do plants achieve specific, self-tolerant immunity and establish immune memory? Recent developments point towards a multilayered plant innate immune system comprised of self-surveillance, systemic signalling and chromosomal changes that together establish effective immunity.

  5. Hydrogen rotation-vibration oscillator

    DOEpatents

    Rhodes, C.K.

    1974-01-29

    A laser system is described wherein molecular species of hydrogen and hydrogen isotopes are induced to oscillate on rotational-vibrational levels by subjecting the hydrogen to a transverse beam of electrons of a narrowly defined energy between about 1 and 5 eV, thereby producing high intensity and high energy output. (Official Gazette)

  6. Compressible flow in fluidic oscillators

    NASA Astrophysics Data System (ADS)

    Graff, Emilio; Hirsch, Damian; Gharib, Mory

    2013-11-01

    We present qualitative observations on the internal flow characteristics of fluidic oscillator geometries commonly referred to as sweeping jets in active flow control applications. We also discuss the effect of the geometry on the output jet in conditions from startup to supersonic exit velocity. Supported by the Boeing Company.

  7. Covariant harmonic oscillators: 1973 revisited

    NASA Technical Reports Server (NTRS)

    Noz, M. E.

    1993-01-01

    Using the relativistic harmonic oscillator, a physical basis is given to the phenomenological wave function of Yukawa which is covariant and normalizable. It is shown that this wave function can be interpreted in terms of the unitary irreducible representations of the Poincare group. The transformation properties of these covariant wave functions are also demonstrated.

  8. Varactor tuned transistor oscillators /Survey/

    NASA Astrophysics Data System (ADS)

    Deriugin, I. A.; Kitaev, Iu. I.; Solodovnikov, N. P.

    1981-03-01

    Major developments in the theory and technology of varactor tuned solid state oscillators are surveyed on the basis of data appearing in periodical and patent literature. Attention is given to problems in general theory, modulation characteristics, transient processes occurring during tuning, stability properties, and circuit fabrication aspects.

  9. Low-Vibration Oscillating Compressor

    NASA Technical Reports Server (NTRS)

    Studer, P. A.

    1984-01-01

    Oscillating compressor momentum compensated: produces little vibration in its supporting structure. Compressure requires no lubrication and virtually free of wear. Compresses working fluids such as helium, nitrogen or chlorfluorocarbons for Stirling-cycle refrigeration or other purposes. Compressor includes two mutually opposed ferromagnetic pistons of same shape and mass. Electromagnetic flux links both pistons, causing magnetic attraction between them.

  10. Geometry of thermal plasma oscillations

    SciTech Connect

    Burton, Da; Noble, A.

    2009-01-22

    We develop a method for investigating the relationship between the shape of a 1-particle distribution and non-linear electrostatic oscillations in a collisionless plasma, incorporating transverse thermal motion. A general expression is found for the maximum sustainable electric field, and is evaluated for a particular highly anisotropic distribution.

  11. Linearization of Conservative Nonlinear Oscillators

    ERIC Educational Resources Information Center

    Belendez, A.; Alvarez, M. L.; Fernandez, E.; Pascual, I.

    2009-01-01

    A linearization method of the nonlinear differential equation for conservative nonlinear oscillators is analysed and discussed. This scheme is based on the Chebyshev series expansion of the restoring force which allows us to obtain a frequency-amplitude relation which is valid not only for small but also for large amplitudes and, sometimes, for…

  12. Cubication of Conservative Nonlinear Oscillators

    ERIC Educational Resources Information Center

    Belendez, Augusto; Alvarez, Mariela L.; Fernandez, Elena; Pascual, Immaculada

    2009-01-01

    A cubication procedure of the nonlinear differential equation for conservative nonlinear oscillators is analysed and discussed. This scheme is based on the Chebyshev series expansion of the restoring force, and this allows us to approximate the original nonlinear differential equation by a Duffing equation in which the coefficients for the linear…

  13. High Frequency Stable Oscillate boiling

    NASA Astrophysics Data System (ADS)

    Li, Fenfang; Gonzalez-Avila, Silvestre Roberto; Ohl, Claus Dieter

    2015-11-01

    We present an unexpected regime of resonant bubble oscillations on a thin metal film submerged in water, which is continuously heated with a focused CW laser. The oscillatory bubble dynamics reveals a remarkably stable frequency of several 100 kHz and is resolved from the side using video recordings at 1 million frames per second. The emitted sound is measured simultaneously and shows higher harmonics. Once the laser is switched on the water in contact with the metal layer is superheated and an explosively expanding cavitation bubble is generated. However, after the collapse a microbubble is nucleated from the bubble remains which displays long lasting oscillations. Generally, pinch-off from of the upper part of the microbubble is observed generating a continuous stream of small gas bubbles rising upwards. The cavitation expansion, collapse, and the jetting of gas bubbles are detected by the hydrophone and are correlated to the high speed video. We find the bubble oscillation frequency is dependent on the bubble size and surface tension. A preliminary model based on Marangoni flow and heat transfer can explain the high flow velocities observed, yet the origin of bubble oscillation is currently not well understood.

  14. The immune system, natural autoantibodies and general homeostasis in health and disease.

    PubMed

    Poletaev, A; Boura, P

    2011-10-01

    It is generally accepted that the destination of the immune system is not only to discriminate between self and non-self but also to mount responses against non-self. During the last decades, it became evident that weak self-reactivity is a necessary condition for immune homeostasis. Natural self reactivity and the internal image created by autoantibodies, participate greatly to the maintenance of homeostasis. Under conditions of increased or altered antigenic pressure, the homeostatic status is disrupted and the organism becomes vulnerable to the emergence of diseases. "Immunculus" is the self-reactive and interconnected entity of the immune system, provided by a complicated network of natural autoantibobies of different specificity, as a mosaic picture. Quantitative changes in each part of the image are related to variations of expression of relative antigens. The immune system takes in account image information from the continuous screening of the antigenic status and compares between presented state and the desired (optimal) one. Substantial and prolonged deviations from the optimal state, triggers the induction of compensatory and reparative processes, aiming to restore molecular and functional homeostasis. So, natural autoimmunity through the ability of natural a-Abs to induce mechanisms of natural and acquired immunity, aims to prevent pathogenic processes and maintain or restore health status.

  15. Tailoring gut immune responses with lipoteichoic acid-deficient Lactobacillus acidophilus

    PubMed Central

    Lightfoot, Yaíma L.; Mohamadzadeh, Mansour

    2013-01-01

    As highlighted by the development of intestinal autoinflammatory disorders when tolerance is lost, homeostatic interactions between gut microbiota, resident immune cells, and the gut epithelium are key in the maintenance of gastrointestinal health. Gut immune responses, whether stimulatory or regulatory, are dictated by the activated dendritic cells (DCs) that first interact with microorganisms and their gene products to then elicit T and B cell responses. Previously, we have demonstrated that treatment with genetically modified Lactobacillus acidophilus is sufficient to tilt the immune balance from proinflammatory to regulatory in experimental models of colitis and colon cancer. Given the significant role of DCs in efficiently orchestrating intestinal immune responses, characterization of the signals induced within these cells by the surface layer molecules, such as lipoteichoic acid (LTA), and proteins of L. acidophilus is critical for future treatment and prevention of gastrointestinal diseases. Here, we discuss the potential regulatory pathways involved in the downregulation of pathogenic inflammation in the gut, and explore questions regarding the immune responses to LTA-deficient L. acidophilus that require future studies. PMID:23390423

  16. The role of peripheral immune cells in the CNS in steady state and disease.

    PubMed

    Prinz, Marco; Priller, Josef

    2017-02-01

    The CNS is protected by the immune system, including cells that reside directly within the CNS and help to ensure proper neural function, as well as cells that traffic into the CNS with disease. The CNS-resident immune system is comprised mainly of innate immune cells and operates under homeostatic conditions. These myeloid cells in the CNS parenchyma and at CNS-periphery interfaces are highly specialized but also extremely plastic cells that immediately react to any changes in CNS homeostasis and become reactive in the context of neurodegenerative disorders such as Alzheimer's disease or Parkinson's disease. However, when the blood-brain barrier is impaired during CNS diseases such as multiple sclerosis or altered with cerebral ischemia, peripheral adaptive and innate immune cells, including monocytes, neutrophils, T cells and B cells, can enter the CNS, where they execute distinct cell-mediated effects. On the basis of these observations, we assess strategies for targeting peripheral immune cells to reduce CNS disease burden.

  17. Single mode pulsed dye laser oscillator

    DOEpatents

    Hackel, Richard P.

    1992-01-01

    A single mode pulsed dye laser oscillator is disclosed. The dye laser oscillator provides for improved power efficiency by reducing the physical dimensions of the overall laser cavity, which improves frequency selection capability.

  18. Single mode pulsed dye laser oscillator

    DOEpatents

    Hackel, R.P.

    1992-11-24

    A single mode pulsed dye laser oscillator is disclosed. The dye laser oscillator provides for improved power efficiency by reducing the physical dimensions of the overall laser cavity, which improves frequency selection capability. 6 figs.

  19. Opto-Electronic Oscillator and its Applications

    NASA Technical Reports Server (NTRS)

    Yao, X. S.; Maleki, L.

    1996-01-01

    We present the theoretical and experimental results of a new class of microwave oscillators called opto-electronic oscillators (OEO). We discuss techniques of achieving high stability single mode operation and demonstrate the applications of OEO in photonic communication systems.

  20. Retinoid Homeostatic Gene Expression in Liver, Lung and Kidney: Ontogeny and Response to Vitamin A-Retinoic Acid (VARA) Supplementation from Birth to Adult Age

    PubMed Central

    Owusu, Sarah A.; Ross, A. Catharine

    2016-01-01

    Vitamin A (VA, retinol) metabolism is homeostatically controlled, but little is known of its regulation in the postnatal period. Here, we determined the postnatal trajectory of VA storage and metabolism in major compartments of VA metabolism–plasma, liver, lung, and kidney from postnatal (P) day 1 to adulthood. We also investigated the response to supplementation with VARA, a combination of VA and 10% all-trans-retinoic acid that previously was shown to synergistically increase retinol uptake and storage in lung. Nursling pups of dams fed a VA-marginal diet received an oral dose of oil (placebo) or VARA on each of four neonatal days: P1, P4, P7, and P10; and again as adults. Tissues were collected 6 h after the final dosing on P1, P4, P10, and at adult age. Gene transcripts for Lrat and Rbp4 in liver and Raldh-1 and Raldh-3 in lung, did not differ in the neonatal period but were higher, P<0.05, in adults, while Cyp26B1, Stra6, megalin, and Raldh-2 in lung did not differ from perinatal to adult ages. VARA supplementation increased total retinol in plasma, liver and lung, with a dose-by-dose accumulation in neonatal liver and lung, while transcripts for Lrat in liver, megalin in kidney, Cyp26A1/B1 in liver and lung, respectively, and Stra6 in lung, were all increased, suggesting pathways of VA uptake, storage and RA oxidation were each augmented after VARA. VARA decreased hepatic expression of Rbp4, responsible for VA trafficking from liver to plasma, and, in lung, of Raldh-1 and Raldh-2, which function in RA production. Our results define retinoid homeostatic gene expression from neonatal and adult age and show that while supplementation with VARA acutely alters retinol content and retinoid homeostatic gene expression in neonatal and adult lung, liver and kidney, VARA supplementation of neonates increased adult-age VA content only in the liver. PMID:26731668

  1. Rabi-oscillation-induced π phase flip in an unbalanced Ramsey atom interferometer

    NASA Astrophysics Data System (ADS)

    Li, R. B.; Yao, Z. W.; Wang, K.; Lu, S. B.; Cao, L.; Wang, J.; Zhan, M. S.

    2016-09-01

    We present an observation of zero-to-π phase flips induced by Rabi oscillation in an unbalanced Ramsey atom interferometer. The phase shift and visibility are experimentally investigated by modulating either the polarization or duration of Raman lasers, and they are well explained by a theoretical model. In an atom interferometer, the π phase flips are caused not only by the sign of Rabi frequency but also by the Rabi oscillation. Considering the π phase flips, we propose the composite-light-pulse sequences for realizing the large-momentum-transfer beam splitter and mirror, which have the high immunity to the external phase noise in building the cold atom interferometer.

  2. Ultralow-phase-noise oscillators based on BAW resonators.

    PubMed

    Li, Mingdong; Seok, Seonho; Rolland, Nathalie; Rolland, Paul; El Aabbaoui, Hassan; de Foucauld, Emeric; Vincent, Pierre; Giordano, Vincent

    2014-06-01

    This paper presents two 2.1-GHz low-phase noise oscillators based on BAW resonators. Both a single-ended common base structure and a differential Colpitts structure have been implemented in a 0.25-μm BiCMOS process. The detailed design methods including the realization, optimization, and test are reported. The differential Colpitts structure exhibits a phase noise 6.5 dB lower than the single-ended structure because of its good performance of power noise immunity. Comparison between the two structures is also carried out. The differential Colpitts structure shows a phase noise level of -87 dBc/Hz at 1-kHz offset frequency and a phase noise floor of -162 dBc/Hz, with an output power close to -6.5 dBm and a core consumption of 21.6 mW. Furthermore, with the proposed optimization methods, both proposed devices have achieved promising phase noise performance compared with state-of-the-art oscillators described in the literature. Finally, we briefly present the application of the proposed BAW oscillator to a micro-atomic clock.

  3. Human immune system variation

    PubMed Central

    Brodin, Petter; Davis, Mark M.

    2017-01-01

    The human immune system is highly variable between individuals but relatively stable over time within a given person. Recent conceptual and technological advances have enabled systems immunology analyses, which reveal the composition of immune cells and proteins in populations of healthy individuals. The range of variation and some specific influences that shape an individual’s immune system is now becoming clearer. Human immune systems vary as a consequence of heritable and non-heritable influences, but symbiotic and pathogenic microbes and other non-heritable influences explain most of this variation. Understanding when and how such influences shape the human immune system is key for defining metrics of immunological health and understanding the risk of immune-mediated and infectious diseases. PMID:27916977

  4. Immune Regulation of Cancer

    PubMed Central

    Disis, Mary L.

    2010-01-01

    Innate and adaptive immune system cells play a major role in regulating the growth of cancer. Although it is commonly thought that an immune response localized to the tumor will inhibit cancer growth, it is clear that some types of inflammation induced in a tumor may also lead to cancer proliferation, invasion, and dissemination. Recent evidence suggests, however, that some patients with cancer can mount an antitumor immune response that has the potential to control or eliminate cancer. Indeed, a so-called “immune response” signature has been described in malignancy that is associated with improved outcomes in several tumor types. Moreover, the presence of specific subsets of T cells, which have the capability to penetrate tumor stroma and infiltrate deep into the parenchyma, identifies patients with an improved prognosis. Immune-based therapies have the potential to modulate the tumor microenvironment by eliciting immune system cells that will initiate acute inflammation that leads to tissue destruction. PMID:20516428

  5. Immunizations: vaccinations in general.

    PubMed

    Wiley, Catherine C

    2015-06-01

    The childhood immunization schedule is complex and nuanced. Although serious adverse reactions to immunizations are uncommon, clinicians must be well-versed in these reactions as well as the contraindications and precautions to each vaccine. • Conjugate vaccine technology links polysaccharide antigens to carrier proteins, triggering T-cell-dependent immunity to polysaccharides, thereby strengthening immune memory. • On the basis of some research evidence and consensus, live vaccines are generally contraindicated in immunocompromised patients and in pregnancy. Most live vaccines can be administered to household contacts of immunocompromised patients. • On the basis of some research and consensus, modified administration of meningococcal, pneumococcal, and less commonly, other vaccines may be indicated to protect immunocompromised patients. • On the basis of disease epidemiology and consensus, international travelers should be up-to-date with all routine immunizations; depending on destination, additional vaccines or immune globulin may be required.

  6. Neural circuitry and immunity.

    PubMed

    Pavlov, Valentin A; Tracey, Kevin J

    2015-12-01

    Research during the last decade has significantly advanced our understanding of the molecular mechanisms at the interface between the nervous system and the immune system. Insight into bidirectional neuro-immune communication has characterized the nervous system as an important partner of the immune system in the regulation of inflammation. Neuronal pathways, including the vagus nerve-based inflammatory reflex, are physiological regulators of immune function and inflammation. In parallel, neuronal function is altered in conditions characterized by immune dysregulation and inflammation. Here, we review these regulatory mechanisms and describe the neural circuitry modulating immunity. Understanding these mechanisms reveals possibilities to use targeted neuromodulation as a therapeutic approach for inflammatory and autoimmune disorders. These findings and current clinical exploration of neuromodulation in the treatment of inflammatory diseases define the emerging field of Bioelectronic Medicine.

  7. Origins of adaptive immunity.

    PubMed

    Liongue, Clifford; John, Liza B; Ward, Alister

    2011-01-01

    Adaptive immunity, involving distinctive antibody- and cell-mediated responses to specific antigens based on "memory" of previous exposure, is a hallmark of higher vertebrates. It has been argued that adaptive immunity arose rapidly, as articulated in the "big bang theory" surrounding its origins, which stresses the importance of coincident whole-genome duplications. Through a close examination of the key molecules and molecular processes underpinning adaptive immunity, this review suggests a less-extreme model, in which adaptive immunity emerged as part of longer evolutionary journey. Clearly, whole-genome duplications provided additional raw genetic materials that were vital to the emergence of adaptive immunity, but a variety of other genetic events were also required to generate some of the key molecules, whereas others were preexisting and simply co-opted into adaptive immunity.

  8. Squeezed states of damped oscillator chain

    NASA Technical Reports Server (NTRS)

    Manko, O. V.

    1993-01-01

    The Caldirola-Kanai model of one-dimensional damped oscillator is extended to the chain of coupled parametric oscillators with damping. The correlated and squeezed states for the chain of coupled parametric oscillators with damping are constructed. Based on the concept of the integrals of motion, it is demonstrated how squeezing phenomenon arises due to parametric excitation.

  9. Scleronomic Holonomic Constraints and Conservative Nonlinear Oscillators

    ERIC Educational Resources Information Center

    Munoz, R.; Gonzalez-Garcia, G.; Izquierdo-De La Cruz, E.; Fernandez-Anaya, G.

    2011-01-01

    A bead sliding, under the sole influence of its own weight, on a rigid wire shaped in the fashion of a plane curve, will describe (generally anharmonic) oscillations around a local minimum. For given shapes, the bead will behave as a harmonic oscillator in the whole range, such as an unforced, undamped, Duffing oscillator, etc. We also present…

  10. Propulsion of a flapping and oscillating airfoil

    NASA Technical Reports Server (NTRS)

    Garrick, I E

    1937-01-01

    Formulas are given for the propelling or drag force experience in a uniform air stream by an airfoil or an airfoil-aileron combination, oscillating in any of three degrees of freedom; vertical flapping, torsional oscillations about a fixed axis parallel to the span, and angular oscillations of the aileron about a hinge.

  11. On the excitation of Goodwin's oscillations

    NASA Astrophysics Data System (ADS)

    Antonova, A. O.; Reznik, S. N.; Todorov, M. D.

    2014-11-01

    We consider the necessary condition for excitation of long-periodic Goodwin's oscillations and short-periodic sawtooth oscillations in the Goodwin model with fixed delay in the induced investment. Also, using the method of equivalent linearization we evaluate the amplitude of steady-state oscillation.

  12. NOx Emission Reduction by Oscillating Combustion

    SciTech Connect

    2005-09-01

    This project focuses on a new technology that reduces NOx emissions while increasing furnace efficiency for both air- and oxygen-fired furnaces. Oscillating combustion is a retrofit technology that involves the forced oscillation of the fuel flow rate to a furnace. These oscillations create successive, fuel-rich and fuel-lean zones within the furnace.

  13. Fluidic Oscillator Array for Synchronized Oscillating Jet Generation

    NASA Technical Reports Server (NTRS)

    Koklu, Mehti (Inventor)

    2016-01-01

    A fluidic oscillator array includes a plurality of fluidic-oscillator main flow channels. Each main flow channel has an inlet and an outlet. Each main flow channel has first and second control ports disposed at opposing sides thereof, and has a first and a second feedback ports disposed at opposing sides thereof. The feedback ports are located downstream of the control ports with respect to a direction of a fluid flow through the main flow channel. The system also includes a first fluid accumulator in fluid communication with each first control port and each first feedback port, and a second fluid accumulator in fluid communication with each second control port and each second feedback port.

  14. [Low-Frequency Flow Oscillation

    NASA Technical Reports Server (NTRS)

    Bragg, Michael B.

    1997-01-01

    The results of the research conducted under this grant are presented in detail in three Master theses, by Heinrich, Balow, and Broeren. Additional analysis of the experimental data can be found in two AIAA Journal articles and two conference papers. Citations for all of the studies' publications can be found in the bibliography which is attached. The objective of Heinrich's study was to document the low-frequency flow oscillation on the LRN-1007 airfoil, which had been previously observed at low Reynolds number, to determine its origin, and explore the phenomenon at higher Reynolds number. Heinrich performed detailed flow visualization on the airfoil using surface fluorescent oil and laser-sheet off-body visualization. A large leading-edge separation bubble and trailing-edge separation was identified on the airfoil just prior to the onset of the unsteady stall flow oscillation. From the laser-sheet data, the unsteady flow appeared as a massive boundary-layer separation followed by flow reattachment. Hot-wire data were taken in the wake to identify the presence of the flow oscillation and the dominant frequency. The oscillation was found in the flow from a Reynolds number of 0.3 to 1.3 x 10 exp 6. The Strouhal number based on airfoil projected height was nominally 0.02 and increased slightly with increasing Reynolds number and significantly with increasing airfoil angle of attack. Balow focused his research on the leading-edge separation bubble which was hypothesized to be the origin of the low-frequency oscillation. Initially, experimental measurements in the bubble at the onset of the low-frequency oscillation were attempted to study the characteristics of the bubble and explain possible relationships to the shear-layer-flapping phenomena. Unfortunately, the bubble proved to be extremely sensitive to the probe interference and it drastically reduced the size of the bubble. These detailed measurements were then abandoned by Balow. However, this led to a series of

  15. Innate Immunity in Disease

    PubMed Central

    Elliott, David E.; Siddique, Sana S.; Weinstock, Joel V.

    2014-01-01

    Cells can innately recognize generic products of viruses, bacteria, fungi, or injured tissue by engagement of pattern recognition receptors. Innate immune cells rapidly respond to this engagement in order to control commensals, thwart pathogens and/or prompt repair. Insufficient or excessive activation of the innate immune response results in disease. This review focuses on pattern recognition receptors and cells of the innate immune system important for intestinal function. Our improving knowledge pertaining to this important aspect of our immune response is opening potential important new therapeutic opportunities for the treatment of disease. PMID:24632348

  16. Improving immunization strategies

    NASA Astrophysics Data System (ADS)

    Gallos, Lazaros K.; Liljeros, Fredrik; Argyrakis, Panos; Bunde, Armin; Havlin, Shlomo

    2007-04-01

    We introduce an immunization method where the percentage of required vaccinations for immunity are close to the optimal value of a targeted immunization scheme of highest degree nodes. Our strategy retains the advantage of being purely local, without the need for knowledge on the global network structure or identification of the highest degree nodes. The method consists of selecting a random node and asking for a neighbor that has more links than himself or more than a given threshold and immunizing him. We compare this method to other efficient strategies on three real social networks and on a scale-free network model and find it to be significantly more effective.

  17. Measuring neutrino oscillation parameters using $\

    SciTech Connect

    Backhouse, Christopher James

    2011-01-01

    MINOS is a long-baseline neutrino oscillation experiment. It consists of two large steel-scintillator tracking calorimeters. The near detector is situated at Fermilab, close to the production point of the NuMI muon-neutrino beam. The far detector is 735 km away, 716m underground in the Soudan mine, Northern Minnesota. The primary purpose of the MINOS experiment is to make precise measurements of the 'atmospheric' neutrino oscillation parameters (Δmatm2 and sin2atm). The oscillation signal consists of an energy-dependent deficit of vμ interactions in the far detector. The near detector is used to characterize the properties of the beam before oscillations develop. The two-detector design allows many potential sources of systematic error in the far detector to be mitigated by the near detector observations. This thesis describes the details of the vμ-disappearance analysis, and presents a new technique to estimate the hadronic energy of neutrino interactions. This estimator achieves a significant improvement in the energy resolution of the neutrino spectrum, and in the sensitivity of the neutrino oscillation fit. The systematic uncertainty on the hadronic energy scale was re-evaluated and found to be comparable to that of the energy estimator previously in use. The best-fit oscillation parameters of the vμ-disappearance analysis, incorporating this new estimator were: Δm2 = 2.32-0.08+0.12 x 10-3 eV2, sin 2 2θ > 0.90 (90% C.L.). A similar analysis, using data from a period of running where the NuMI beam was operated in a configuration producing a predominantly $\\bar{v}$μ beam, yielded somewhat different best-fit parameters Δ$\\bar{m}${sup 2} = (3.36-0.40+0.46(stat.) ± 0.06(syst.)) x 10-3eV2, sin2 2$\\bar{θ}$ = 0.86-0.12_0.11

  18. Restoration of oscillation in network of oscillators in presence of direct and indirect interactions

    NASA Astrophysics Data System (ADS)

    Majhi, Soumen; Bera, Bidesh K.; Bhowmick, Sourav K.; Ghosh, Dibakar

    2016-10-01

    The suppression of oscillations in coupled systems may lead to several unwanted situations, which requires a suitable treatment to overcome the suppression. In this paper, we show that the environmental coupling in the presence of direct interaction, which can suppress oscillation even in a network of identical oscillators, can be modified by introducing a feedback factor in the coupling scheme in order to restore the oscillation. We inspect how the introduction of the feedback factor helps to resurrect oscillation from various kinds of death states. We numerically verify the resurrection of oscillations for two paradigmatic limit cycle systems, namely Landau-Stuart and Van der Pol oscillators and also in generic chaotic Lorenz oscillator. We also study the effect of parameter mismatch in the process of restoring oscillation for coupled oscillators.

  19. Programmed death-1 immune checkpoint blockade in the treatment of hematological malignancies.

    PubMed

    Tsirigotis, Panagiotis; Savani, Bipin N; Nagler, Arnon

    2016-09-01

    The use of tumor-specific monoclonal antibodies (MAbs) has revolutionize the field of cancer immunotherapy. Although treatment of malignant diseases with MAbs is promising, many patients fail to respond or relapse after an initial response. Both solid tumors and hematological malignancies develop mechanisms that enable them to evade the host immune system by usurping immune checkpoint pathways such as PD-1, PD-2, PDL-1, or PDL-2 (programmed cell death protein-1 or 2 and PD-Ligand 1 or 2), which are expressed on activated T cells and on T-regulatory, B cells, natural killers, monocytes, and dendritic cells. One of the most exciting anticancer development in recent years has been the immune checkpoint blockade therapy by using MAbs against immune checkpoint receptor and/or ligands. Anti-PD1 antibodies have been tested in clinical studies that included patients with hematological malignancies and showed remarkable efficacy in Hodgkin lymphoma (HL). In our review, we will focus on the effect of PD-1 activation on hematological malignancies and its role as a therapeutic target. Key messages The programmed death 1 (PD1) immune checkpoint is an important homeostatic mechanism of the immune system that helps in preventing autoimmunity and uncontrolled inflammation in cases of chronic infections. However, PD1 pathway is also operated by a wide variety of malignancies and represents one of the most important mechanisms by which tumor cells escape from the surveillance of the immune system. Blocking of immune checkpoints by the use of monoclonal antibodies opened a new era in the field of cancer immunotherapy. Results from clinical trials are promising, and currently, this approach has been proven effective and safe in patients with solid tumors and hematological malignancies.

  20. Inflammation and Bone Destruction in Arthritis: Synergistic Activity of Immune and Mesenchymal Cells in Joints

    PubMed Central

    Komatsu, Noriko; Takayanagi, Hiroshi

    2012-01-01

    Rheumatoid arthritis (RA) is an immune-mediated disease of the joints that is characterized by chronic inflammation and synovial hyperplasia that eventually lead to cartilage and bone destruction. Synovial fibroblasts are mesenchymal cells recognized as a key cell population in RA due to their hyperproliferative and hypersensitive properties in the inflammatory milieu and hyperproduction of both inflammatory cytokines and matrix-degrading enzymes. On the immune cell side, a wealth of evidence has shown that CD4+T-cells, especially IL-17 producing helper T (Th17) cells, play a prominent role, particularly in the initiation of systemic immune response in RA. However, it is still unclear how the local chronic inflammation in the joint is elicited by a systemic immune response. Recent studies have shed light on the importance of the interaction between immune and mesenchymal cells in joints including synovial fibroblasts. In particular, mesenchymal cells contribute to the Th17-mediated chronic inflammation in RA by promoting the migration of Th17 cells to the inflamed site and then the homeostatic proliferation and concomitant increase in IL-17 production. In addition, recent progress in osteoimmunology has provided new insight into the pathogenesis of the bone destruction which takes place in RA. Th17-related cytokines have been shown to enhance osteoclastogenesis, mainly via synovial fibroblasts. Thus, mesenchymal cells are a determinant of the development of RA that links the systemic immune response and the local disorder in the joints. In addition, the interaction of immune and mesenchymal cells plays a key role in both the chronic inflammation and bone destruction seen in RA. Elucidation of the precise events involved in this interaction will lead to a better understanding of the mechanisms by which chronic inflammation and bone destruction in joint results from a systemic immune response, and also will help provide a molecular basis for novel therapeutic