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Sample records for channelopathies increase resurgent

  1. Super-resurgence: ABA renewal increases resurgence.

    PubMed

    Kincaid, Stephanie L; Lattal, Kennon A; Spence, Jake

    2015-06-01

    Previously extinguished operant responding recurs under both resurgence and renewal procedures, but the effects of combining these procedures on recurrence has not been studied. Because renewal and resurgence are known to independently produce response recurrence, we examined whether greater resurgence would occur if the resurgence procedure was combined with an ABA renewal procedure, relative to a resurgence procedure without contextual changes. Three pigeons were exposed to a concurrent resurgence procedure in which key colors served as contextual stimuli. In the Training phase, reinforcement for pecking two keys was scheduled on concurrent variable-interval (VI) 120-s VI 120-s schedules, each correlated with different key colors. In the Alternative Reinforcement phase, reinforcement occurred when neither key was pecked for 20-s (a differential-reinforcement-of-other-behavior [DRO] 20-s schedule). During this phase, one of the key colors was changed (ABA key), while the other key color remained as in the Training phase (AAA key). In the third phase, reinforcement was not provided and the color of the ABA key was changed back to the color in effect during the Training phase while the same color remained in effect on the other key. Greater resurgence occurred on the ABA renewal key with each pigeon, demonstrating that a superimposed ABA renewal procedure increases resurgence. PMID:25712040

  2. Channelopathies

    PubMed Central

    Kim, June-Bum

    2014-01-01

    Channelopathies are a heterogeneous group of disorders resulting from the dysfunction of ion channels located in the membranes of all cells and many cellular organelles. These include diseases of the nervous system (e.g., generalized epilepsy with febrile seizures plus, familial hemiplegic migraine, episodic ataxia, and hyperkalemic and hypokalemic periodic paralysis), the cardiovascular system (e.g., long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia), the respiratory system (e.g., cystic fibrosis), the endocrine system (e.g., neonatal diabetes mellitus, familial hyperinsulinemic hypoglycemia, thyrotoxic hypokalemic periodic paralysis, and familial hyperaldosteronism), the urinary system (e.g., Bartter syndrome, nephrogenic diabetes insipidus, autosomal-dominant polycystic kidney disease, and hypomagnesemia with secondary hypocalcemia), and the immune system (e.g., myasthenia gravis, neuromyelitis optica, Isaac syndrome, and anti-NMDA [N-methyl-D-aspartate] receptor encephalitis). The field of channelopathies is expanding rapidly, as is the utility of molecular-genetic and electrophysiological studies. This review provides a brief overview and update of channelopathies, with a focus on recent advances in the pathophysiological mechanisms that may help clinicians better understand, diagnose, and develop treatments for these diseases. PMID:24578711

  3. Channelopathies.

    PubMed

    Kim, June-Bum

    2014-01-01

    Channelopathies are a heterogeneous group of disorders resulting from the dysfunction of ion channels located in the membranes of all cells and many cellular organelles. These include diseases of the nervous system (e.g., generalized epilepsy with febrile seizures plus, familial hemiplegic migraine, episodic ataxia, and hyperkalemic and hypokalemic periodic paralysis), the cardiovascular system (e.g., long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia), the respiratory system (e.g., cystic fibrosis), the endocrine system (e.g., neonatal diabetes mellitus, familial hyperinsulinemic hypoglycemia, thyrotoxic hypokalemic periodic paralysis, and familial hyperaldosteronism), the urinary system (e.g., Bartter syndrome, nephrogenic diabetes insipidus, autosomal-dominant polycystic kidney disease, and hypomagnesemia with secondary hypocalcemia), and the immune system (e.g., myasthenia gravis, neuromyelitis optica, Isaac syndrome, and anti-NMDA [N-methyl-D-aspartate] receptor encephalitis). The field of channelopathies is expanding rapidly, as is the utility of molecular-genetic and electrophysiological studies. This review provides a brief overview and update of channelopathies, with a focus on recent advances in the pathophysiological mechanisms that may help clinicians better understand, diagnose, and develop treatments for these diseases. PMID:24578711

  4. Neurological channelopathies

    PubMed Central

    Graves, T; Hanna, M

    2005-01-01

    Ion channels are membrane-bound proteins that perform key functions in virtually all human cells. Such channels are critically important for the normal function of the excitable tissues of the nervous system, such as muscle and brain. Until relatively recently it was considered that dysfunction of ion channels in the nervous system would be incompatible with life. However, an increasing number of human diseases associated with dysfunctional ion channels are now recognised. Such neurological channelopathies are frequently genetically determined but may also arise through autoimmune mechanisms. In this article clinical, genetic, immunological, and electrophysiological aspects of this expanding group of neurological disorders are reviewed. Clinical situations in which a neurological channelopathy should enter into the differential diagnosis are highlighted. Some practical guidance on how to investigate and treat this complex group of disorders is also included. PMID:15640425

  5. Pain channelopathies

    PubMed Central

    Cregg, Roman; Momin, Aliakmal; Rugiero, Francois; Wood, John N; Zhao, Jing

    2010-01-01

    Pain remains a major clinical challenge, severely afflicting around 6% of the population at any one time. Channelopathies that underlie monogenic human pain syndromes are of great clinical relevance, as cell surface ion channels are tractable drug targets. The recent discovery that loss-of-function mutations in the sodium channel Nav1.7 underlie a recessive pain-free state in otherwise normal people is particularly significant. Deletion of channel-encoding genes in mice has also provided insights into mammalian pain mechanisms. Ion channels expressed by immune system cells (e.g. P2X7) have been shown to play a pivotal role in changing pain thresholds, whilst channels involved in sensory transduction (e.g. TRPV1), the regulation of neuronal excitability (potassium channels), action potential propagation (sodium channels) and neurotransmitter release (calcium channels) have all been shown to be potentially selective analgesic drug targets in some animal pain models. Migraine and visceral pain have also been associated with voltage-gated ion channel mutations. Insights into such channelopathies thus provide us with a number of potential targets to control pain. PMID:20142270

  6. CRAC channelopathies

    PubMed Central

    2010-01-01

    Store-operated Ca2+ entry (SOCE) is an important Ca2+ influx pathway in many non-excitable and some excitable cells. It is regulated by the filling state of intracellular Ca2+ stores, notably the endoplasmic reticulum (ER). Reduction in [Ca2+]ER results in activation of plasma membrane Ca2+ channels that mediate sustained Ca2+ influx which is required for many cell functions as well as refilling of Ca2+ stores. The Ca2+ release activated Ca2+ (CRAC) channel is the best characterized SOC channel with well-defined electrophysiological properties. In recent years, the molecular components of the CRAC channel, long mysterious, have been defined. ORAI1 (or CRACM1) acts as the pore-forming subunit of the CRAC channel in the plasma membrane. Stromal interaction molecule (STIM) 1 is localized in the ER, senses [Ca2+]ER, and activates the CRAC channel upon store depletion by binding to ORAI1. Both proteins are widely expressed in many tissues in both human and mouse consistent with the widespread prevalence of SOCE and CRAC channel currents in many cells types. CRAC channelopathies in human patients with mutations in STIM1 and ORAI1 are characterized by abolished CRAC channel currents, lack of SOCE and—clinically—immunodeficiency, congenital myopathy, and anhydrotic ectodermal dysplasia. This article reviews the role of ORAI and STIM proteins for SOCE and CRAC channel function in a variety of cell types and tissues and compares the phenotypes of ORAI1 and STIM1-deficient human patients and mice with targeted deletion of Orai and Stim genes. PMID:20111871

  7. Resurgence of target responding does not exceed increases in inactive responding in a forced-choice alternative reinforcement procedure in humans.

    PubMed

    Sweeney, Mary M; Shahan, Timothy A

    2016-03-01

    Resurgence following removal of alternative reinforcement has been studied in non-human animals, children with developmental disabilities, and typically functioning adults. Adult human laboratory studies have included responses without a controlled history of reinforcement, included only two response options, or involved extensive training. Arbitrary responses allow for control over history of reinforcement. Including an inactive response never associated with reinforcement allows the conclusion that resurgence exceeds extinction-induced variability. Although procedures with extensive training produce reliable resurgence, a brief procedure with the same experimental control would allow more efficient examination of resurgence in adult humans. We tested the acceptability of a brief, single-session, three-alternative forced-choice procedure as a model of resurgence in undergraduates. Selecting a shape was the target response (reinforced in Phase I), selecting another shape was the alternative response (reinforced in Phase II), and selecting a third shape was never reinforced. Despite manipulating number of trials and probability of reinforcement, resurgence of the target response did not consistently exceed increases in the inactive response. Our findings reiterate the importance of an inactive control response and call for reexamination of resurgence studies using only two response options. We discuss potential approaches to generate an acceptable, brief human laboratory resurgence procedure. PMID:26724752

  8. Genetic neurological channelopathies: molecular genetics and clinical phenotypes

    PubMed Central

    Spillane, J; Kullmann, D M; Hanna, M G

    2016-01-01

    Evidence accumulated over recent years has shown that genetic neurological channelopathies can cause many different neurological diseases. Presentations relating to the brain, spinal cord, peripheral nerve or muscle mean that channelopathies can impact on almost any area of neurological practice. Typically, neurological channelopathies are inherited in an autosomal dominant fashion and cause paroxysmal disturbances of neurological function, although the impairment of function can become fixed with time. These disorders are individually rare, but an accurate diagnosis is important as it has genetic counselling and often treatment implications. Furthermore, the study of less common ion channel mutation-related diseases has increased our understanding of pathomechanisms that is relevant to common neurological diseases such as migraine and epilepsy. Here, we review the molecular genetic and clinical features of inherited neurological channelopathies. PMID:26558925

  9. Genetic neurological channelopathies: molecular genetics and clinical phenotypes.

    PubMed

    Spillane, J; Kullmann, D M; Hanna, M G

    2016-01-01

    Evidence accumulated over recent years has shown that genetic neurological channelopathies can cause many different neurological diseases. Presentations relating to the brain, spinal cord, peripheral nerve or muscle mean that channelopathies can impact on almost any area of neurological practice. Typically, neurological channelopathies are inherited in an autosomal dominant fashion and cause paroxysmal disturbances of neurological function, although the impairment of function can become fixed with time. These disorders are individually rare, but an accurate diagnosis is important as it has genetic counselling and often treatment implications. Furthermore, the study of less common ion channel mutation-related diseases has increased our understanding of pathomechanisms that is relevant to common neurological diseases such as migraine and epilepsy. Here, we review the molecular genetic and clinical features of inherited neurological channelopathies. PMID:26558925

  10. [Potassium channelopathies and Morvan's syndromes].

    PubMed

    Serratrice, Georges; Pellissier, Jean-François; Serra-Trice, Jacques; Weiller, Pierre-Jean

    2010-02-01

    Interest in Morvan's disease or syndrome has grown, owing to its close links with various potassium channelopathies. Potassium is crucial for gating mechanisms (channel opening and closing), and especially for repolarization. Defective potassium regulation can lead to neuronal hyperexcitability. There are three families of potassium channels: voltage-gated potassium channels or VGKC (Kv1.1-Kv1.8), inward rectifier K+ channels (Kir), and two-pore channels (K2p). VGK channels are the commonest, and especially those belonging to the Shaker group (neuromyotonia and Morvan's syndrome, limbic encephalitis, and type 1 episodic ataxia). Brain and heart K+ channelopathies are a separate group due to KCNQ1 mutation (severe type 2 long QT syndrome). Kv7 channel mutations (in KNQ2 and KCNQ3) are responsible for benign familial neonatal seizures. Mutation of the Ca+ activated K+ channel gene causes epilepsy and paroxysmal dyskinesia. Inward rectifier K+ channels regulate intracellular potassium levels. The DEND syndrome, a treatable channelopathy of the brain and pancreas, is due to KCNJ1 mutation. Andersen's syndrome, due to KCNJ2 mutation, is characterized by periodic paralysis, cardiac arrythmia, and dysmorphia. Voltage-insensitive K2p channelopathies form a final group. PMID:21166127

  11. HERG1 channelopathies

    PubMed Central

    2009-01-01

    Human ether a go-go-related gene type 1 (hERG1) K+ channels conduct the rapid delayed rectifier K+ current and mediate action potential repolarization in the heart. Mutations in KCNH2 (the gene that encodes hERG1) causes LQT2, one of the most common forms of long QT syndrome, a disorder of cardiac repolarization that predisposes affected subjects to ventricular arrhythmia and increases the risk of sudden cardiac death. Hundreds of LQT2-associated mutations have been described, and most cause a loss of function by disrupting subunit folding, assembly, or trafficking of the channel to the cell surface. Loss-of-function mutations in hERG1 channels have also recently been implicated in epilepsy. A single gain-of-function mutation has been described that causes short QT syndrome and cardiac arrhythmia. In addition, up-regulation of hERG1 channel expression has been demonstrated in specific tumors and has been associated with skeletal muscle atrophy in mice. PMID:20544339

  12. Exercise test in muscle channelopathies and other muscle disorders.

    PubMed

    Kuntzer, T; Flocard, F; Vial, C; Kohler, A; Magistris, M; Labarre-Vila, A; Gonnaud, P M; Ochsner, F; Soichot, P; Chan, V; Monnier, G

    2000-07-01

    We studied the percentage change in compound muscle action potential (CMAP) amplitude and area during and after a 5-min maximal contraction of the muscle. The exercise test (ET) was performed on 64 patients with different muscle disorders and on 46 normal controls. The range of normal ET values was defined as the mean + 2 SD of the control values. The mean sensitivity of the test was 63% in the whole group with ion channel muscle disorders, the highest sensitivity being seen in primary periodic paralysis (81%) and the lowest in chloride channelopathies (17%). In thyrotoxic periodic paralysis, the ET was abnormal in the three of the four patients studied. In patients with myotonic dystrophy, a smaller than normal increase in CMAP amplitude occurred during and after exercise, whereas in proximal myotonic myopathy a normal initial increase in CMAP amplitude was followed by an abnormal decrement. We conclude that the ET can be of use in confirming abnormal muscle membrane excitability in patients with calcium and sodium channelopathies and thyrotoxic periodic paralysis. In chloride channelopathy, the test may also be abnormal, but shows no, or only a small, increase in amplitude or area in the immediate postexercise period. The test may also be abnormal in proximal myotonic myopathy, but is normal in myotonic dystrophy. PMID:10883004

  13. Channelopathies: Summary of the hot topic keynotes session

    EPA Science Inventory

    The "Hot Topic Keynotes: Channelopathies" session of the 26th International Neurotoxicology Conference brought together toxicologists studying interactions of environmental toxicants with ion channels, to review the state of the science of channelopathies and to discuss the poten...

  14. Inherited arrhythmias: The cardiac channelopathies

    PubMed Central

    Behere, Shashank P; Weindling, Steven N

    2015-01-01

    Ion channels in the myocardial cellular membrane are responsible for allowing the cardiac action potential. Genetic abnormalities in these channels can predispose to life-threatening arrhythmias. We discuss the basic science of the cardiac action potential; outline the different clinical entities, including information regarding overlapping diagnoses, touching upon relevant genetics, new innovations in screening, diagnosis, risk stratification, and management. The special considerations of sudden unexplained death and sudden infant death syndrome are discussed. Scientists and clinicians continue to reconcile the rapidly growing body of knowledge regarding the molecular mechanisms and genetics while continuing to improve our understanding of the various clinical entities and their diagnosis and management in clinical setting. Two separate searches were run on the National Center for Biotechnology Information's website. The first using the term cardiac channelopathies was run on the PubMed database using filters for time (published in past 5 years) and age (birth-18 years), yielding 47 results. The second search using the medical subject headings (MeSH) database with the search terms “Long QT Syndrome” (MeSH) and “Short QT Syndrome” (MeSH) and “Brugada Syndrome” (MeSH) and “Catecholaminergic Polymorphic Ventricular Tachycardia” (MeSH), applying the same filters yielded 467 results. The abstracts of these articles were studied, and the articles were categorized and organized. Articles of relevance were read in full. As and where applicable, relevant references and citations from the primary articles where further explored and read in full. PMID:26556967

  15. Inherited arrhythmias: The cardiac channelopathies.

    PubMed

    Behere, Shashank P; Weindling, Steven N

    2015-01-01

    Ion channels in the myocardial cellular membrane are responsible for allowing the cardiac action potential. Genetic abnormalities in these channels can predispose to life-threatening arrhythmias. We discuss the basic science of the cardiac action potential; outline the different clinical entities, including information regarding overlapping diagnoses, touching upon relevant genetics, new innovations in screening, diagnosis, risk stratification, and management. The special considerations of sudden unexplained death and sudden infant death syndrome are discussed. Scientists and clinicians continue to reconcile the rapidly growing body of knowledge regarding the molecular mechanisms and genetics while continuing to improve our understanding of the various clinical entities and their diagnosis and management in clinical setting. Two separate searches were run on the National Center for Biotechnology Information's website. The first using the term cardiac channelopathies was run on the PubMed database using filters for time (published in past 5 years) and age (birth-18 years), yielding 47 results. The second search using the medical subject headings (MeSH) database with the search terms "Long QT Syndrome" (MeSH) and "Short QT Syndrome" (MeSH) and "Brugada Syndrome" (MeSH) and "Catecholaminergic Polymorphic Ventricular Tachycardia" (MeSH), applying the same filters yielded 467 results. The abstracts of these articles were studied, and the articles were categorized and organized. Articles of relevance were read in full. As and where applicable, relevant references and citations from the primary articles where further explored and read in full. PMID:26556967

  16. Hydrodynamics, resurgence, and transasymptotics

    NASA Astrophysics Data System (ADS)

    Başar, Gökçe; Dunne, Gerald V.

    2015-12-01

    The second order hydrodynamical description of a homogeneous conformal plasma that undergoes a boost-invariant expansion is given by a single nonlinear ordinary differential equation, whose resurgent asymptotic properties we study, developing further the recent work of Heller and Spalinski [Phys. Rev. Lett. 115, 072501 (2015)]. Resurgence clearly identifies the nonhydrodynamic modes that are exponentially suppressed at late times, analogous to the quasinormal modes in gravitational language, organizing these modes in terms of a trans-series expansion. These modes are analogs of instantons in semiclassical expansions, where the damping rate plays the role of the instanton action. We show that this system displays the generic features of resurgence, with explicit quantitative relations between the fluctuations about different orders of these nonhydrodynamic modes. The imaginary part of the trans-series parameter is identified with the Stokes constant, and the real part with the freedom associated with initial conditions.

  17. Action potential broadening in a presynaptic channelopathy.

    PubMed

    Begum, Rahima; Bakiri, Yamina; Volynski, Kirill E; Kullmann, Dimitri M

    2016-01-01

    Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca(2+) influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction. PMID:27381274

  18. Action potential broadening in a presynaptic channelopathy

    NASA Astrophysics Data System (ADS)

    Begum, Rahima; Bakiri, Yamina; Volynski, Kirill E.; Kullmann, Dimitri M.

    2016-07-01

    Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca2+ influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction.

  19. Action potential broadening in a presynaptic channelopathy

    PubMed Central

    Begum, Rahima; Bakiri, Yamina; Volynski, Kirill E.; Kullmann, Dimitri M.

    2016-01-01

    Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca2+ influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction. PMID:27381274

  20. Resurgent deformation quantisation

    SciTech Connect

    Garay, Mauricio; Goursac, Axel de; Straten, Duco van

    2014-03-15

    We construct a version of the complex Heisenberg algebra based on the idea of endless analytic continuation. The algebra would be large enough to capture quantum effects that escape ordinary formal deformation quantisation. -- Highlights: •We construct resurgent deformation quantisation. •We give integral formulæ. •We compute examples which show that hypergeometric functions appear naturally in quantum computations.

  1. Concurrent Resurgence and Behavioral History

    ERIC Educational Resources Information Center

    da Silva, Stephanie P.; Maxwell, Megan E.; Lattal, Kennon A.

    2008-01-01

    The contribution of past experiences to concurrent resurgence was investigated in three experiments. In Experiment 1, resurgence was related to the length of reinforcement history as well as the reinforcement schedule that previously maintained responding. Specifically, more resurgence occurred when key pecks had been reinforced on a…

  2. Therapeutic Approaches to Genetic Ion Channelopathies and Perspectives in Drug Discovery

    PubMed Central

    Imbrici, Paola; Liantonio, Antonella; Camerino, Giulia M.; De Bellis, Michela; Camerino, Claudia; Mele, Antonietta; Giustino, Arcangela; Pierno, Sabata; De Luca, Annamaria; Tricarico, Domenico; Desaphy, Jean-Francois; Conte, Diana

    2016-01-01

    In the human genome more than 400 genes encode ion channels, which are transmembrane proteins mediating ion fluxes across membranes. Being expressed in all cell types, they are involved in almost all physiological processes, including sense perception, neurotransmission, muscle contraction, secretion, immune response, cell proliferation, and differentiation. Due to the widespread tissue distribution of ion channels and their physiological functions, mutations in genes encoding ion channel subunits, or their interacting proteins, are responsible for inherited ion channelopathies. These diseases can range from common to very rare disorders and their severity can be mild, disabling, or life-threatening. In spite of this, ion channels are the primary target of only about 5% of the marketed drugs suggesting their potential in drug discovery. The current review summarizes the therapeutic management of the principal ion channelopathies of central and peripheral nervous system, heart, kidney, bone, skeletal muscle and pancreas, resulting from mutations in calcium, sodium, potassium, and chloride ion channels. For most channelopathies the therapy is mainly empirical and symptomatic, often limited by lack of efficacy and tolerability for a significant number of patients. Other channelopathies can exploit ion channel targeted drugs, such as marketed sodium channel blockers. Developing new and more specific therapeutic approaches is therefore required. To this aim, a major advancement in the pharmacotherapy of channelopathies has been the discovery that ion channel mutations lead to change in biophysics that can in turn specifically modify the sensitivity to drugs: this opens the way to a pharmacogenetics strategy, allowing the development of a personalized therapy with increased efficacy and reduced side effects. In addition, the identification of disease modifiers in ion channelopathies appears an alternative strategy to discover novel druggable targets. PMID:27242528

  3. Resurgence in extended hydrodynamics

    NASA Astrophysics Data System (ADS)

    Aniceto, Inês; Spaliński, Michał

    2016-04-01

    It has recently been understood that the hydrodynamic series generated by the Müller-Israel-Stewart theory is divergent and that this large-order behavior is consistent with the theory of resurgence. Furthermore, it was observed that the physical origin of this is the presence of a purely damped nonhydrodynamic mode. It is very interesting to ask whether this picture persists in cases where the spectrum of nonhydrodynamic modes is richer. We take the first step in this direction by considering the simplest hydrodynamic theory which, instead of the purely damped mode, contains a pair of nonhydrodynamic modes of complex conjugate frequencies. This mimics the pattern of black brane quasinormal modes which appear on the gravity side of the AdS/CFT description of N =4 supersymmetric Yang-Mills plasma. We find that the resulting hydrodynamic series is divergent in a way consistent with resurgence and precisely encodes information about the nonhydrodynamic modes of the theory.

  4. The puzzle of TRPV4 channelopathies

    PubMed Central

    Nilius, Bernd; Voets, Thomas

    2013-01-01

    Hereditary channelopathies, that is, mutations in channel genes that alter channel function and are causal for the pathogenesis of the disease, have been described for several members of the transient receptor potential channel family. Mutations in the TRPV4 gene, encoding a polymodal Ca2+ permeable channel, are causative for several human diseases, which affect the skeletal system and the peripheral nervous system, with highly variable phenotypes. In this review, we describe the phenotypes of TRPV4 channelopathies and overlapping symptoms. Putative mechanisms to explain the puzzle, and how mutations in the same region of the channel cause different diseases, are discussed and experimental approaches to tackle this surprising problem are suggested. PMID:23306656

  5. Channelopathies linked to plasma membrane phosphoinositides

    PubMed Central

    Logothetis, Diomedes E.; Petrou, Vasileios I.; Adney, Scott K.; Mahajan, Rahul

    2014-01-01

    The plasma membrane phosphoinositide phosphatidylinositol 4,5-bisphosphate (PIP2) controls the activity of most ion channels tested thus far through direct electrostatic interactions. Mutations in channel proteins that change their apparent affinity to PIP2 can lead to channelopathies. Given the fundamental role that membrane phosphoinositides play in regulating channel activity, it is surprising that only a small number of channelopathies have been linked to phosphoinositides. This review proposes that for channels whose activity is PIP2-dependent and for which mutations can lead to channelopathies, the possibility that the mutations alter channel-PIP2 interactions ought to be tested. Similarly, diseases that are linked to disorders of the phosphoinositide pathway result in altered PIP2 levels. In such cases, it is proposed that the possibility for a concomitant dysregulation of channel activity also ought to be tested. The ever-growing list of ion channels whose activity depends on interactions with PIP2 promises to provide a mechanism by which defects on either the channel protein or the phosphoinositide levels can lead to disease. PMID:20396900

  6. Autoimmune AQP4 channelopathies and neuromyelitis optica spectrum disorders.

    PubMed

    Hinson, Shannon R; Lennon, Vanda A; Pittock, Sean J

    2016-01-01

    Neuromyelitis optica (NMO) spectrum disorders (SD) represent an evolving group of central nervous system (CNS)-inflammatory autoimmune demyelinating diseases unified by a pathogenic autoantibody specific for the aquaporin-4 (AQP4) water channel. It was historically misdiagnosed as multiple sclerosis (MS), which lacks a distinguishing biomarker. The discovery of AQP4-IgG moved the focus of CNS demyelinating disease research from emphasis on the oligodendrocyte and myelin to the astrocyte. NMO is recognized today as a relapsing disease, extending beyond the optic nerves and spinal cord to include brain (especially in children) and skeletal muscle. Brain magnetic resonance imaging abnormalities, identifiable in 60% of patients at the second attack, are consistent with MS in 10% of cases. NMOSD-typical lesions (another 10%) occur in AQP4-enriched regions: circumventricular organs (causing intractable nausea and vomiting) and the diencephalon (causing sleep disorders, endocrinopathies, and syndrome of inappropriate antidiuresis). Advances in understanding the immunobiology of AQP4 autoimmunity have necessitated continuing revision of NMOSD clinical diagnostic criteria. Assays that selectively detect pathogenic AQP4-IgG targeting extracellular epitopes of AQP4 are promising prognostically. When referring to AQP4 autoimmunity, we suggest substituting the term "autoimmune aquaporin-4 channelopathy" for the term "NMO spectrum disorders." Randomized clinical trials are currently assessing the efficacy and safety of newer immunotherapies. Increasing therapeutic options based on understanding the molecular pathogenesis is anticipated to improve the outcome for patients with AQP4 channelopathy. PMID:27112688

  7. Channelopathy pathogenesis in autism spectrum disorders

    PubMed Central

    Schmunk, Galina; Gargus, J. Jay

    2013-01-01

    Autism spectrum disorder (ASD) is a syndrome that affects normal brain development and is characterized by impaired social interaction as well as verbal and non-verbal communication and by repetitive, stereotypic behavior. ASD is a complex disorder arising from a combination of multiple genetic and environmental factors that are independent from racial, ethnic and socioeconomical status. The high heritability of ASD suggests a strong genetic basis for the disorder. Furthermore, a mounting body of evidence implies a role of various ion channel gene defects (channelopathies) in the pathogenesis of autism. Indeed, recent genome-wide association, and whole exome- and whole-genome resequencing studies linked polymorphisms and rare variants in calcium, sodium and potassium channels and their subunits with susceptibility to ASD, much as they do with bipolar disorder, schizophrenia and other neuropsychiatric disorders. Moreover, animal models with these genetic variations recapitulate endophenotypes considered to be correlates of autistic behavior seen in patients. An ion flux across the membrane regulates a variety of cell functions, from generation of action potentials to gene expression and cell morphology, thus it is not surprising that channelopathies have profound effects on brain functions. In the present work, we summarize existing evidence for the role of ion channel gene defects in the pathogenesis of autism with a focus on calcium signaling and its downstream effects. PMID:24204377

  8. Ion channels, channelopathies, and tooth formation.

    PubMed

    Duan, X

    2014-02-01

    The biological functions of ion channels in tooth development vary according to the nature of their gating, the species of ions passing through those gates, the number of gates, localization of channels, tissue expressing the channel, and interactions between cells and microenvironment. Ion channels feature unique and specific ion flux in ameloblasts, odontoblasts, and other tooth-specific cell lineages. Both enamel and dentin have active chemical systems orchestrating a variety of ion exchanges and demineralization and remineralization processes in a stage-dependent manner. An important role for ion channels is to regulate and maintain the calcium and pH homeostasis that are critical for proper enamel and dentin biomineralization. Specific functions of chloride channels, TRPVs, calcium channels, potassium channels, and solute carrier superfamily members in tooth formation have been gradually clarified in recent years. Mutations in these ion channels or transporters often result in disastrous changes in tooth development. The channelopathies of tooth include altered eruption (CLCN7, KCNJ2, TRPV3), root dysplasia (CLCN7, KCNJ2), amelogenesis imperfecta (KCNJ1, CFTR, AE2, CACNA1C, GJA1), dentin dysplasia (CLCN5), small teeth (CACNA1C, GJA1), tooth agenesis (CLCN7), and other impairments. The mechanisms leading to tooth channelopathies are primarily related to pH regulation, calcium homeostasis, or other alterations of the niche for tooth eruption and development. PMID:24076519

  9. Mechanisms of resurgence of an extinguished instrumental behavior.

    PubMed

    Winterbauer, Neil E; Bouton, Mark E

    2010-07-01

    Four experiments examined "resurgence" of an instrumental behavior after extinction. All experiments involved three phases in which rats were (1) trained to press one lever for food reward, (2) trained to press a second lever while the first leverpress was extinguished, and (3) tested under conditions in which neither leverpress was rewarded. In each experiment, the first leverpress recovered (resurged) in Phase 3, when the second leverpress was extinguished. The results demonstrated that resurgence occurred when the schedules of reinforcement employed in Phases 1 and 2 yielded either an upshift, downshift, or no change in the rate of reward delivery between those phases. They also demonstrated that initial training on the first lever was required to observe a robust increase in pressing at test (resurgence is thus an associative effect). Resurgence was shown to occur over a wide variety of schedules of reinforcement in Phase 2 (including ratio, interval, and leverpress-independent schedules). Finally, the results do not support the view that resurgence occurs because response competition suppresses leverpressing of the first lever during extinction. Overall, they are consistent with the view that resurgence is a renewal effect in which extinction of an instrumental behavior is specific to the context provided by rewarded leverpressing during the extinction phase. PMID:20658865

  10. Resurgence in Siamese fighting fish, Betta splendens.

    PubMed

    da Silva, Stephanie P; Cançado, Carlos R X; Lattal, Kennon A

    2014-03-01

    Resurgence of previously reinforced responding was investigated in male Siamese fighting fish (Betta splendens). Swimming through a ring produced 15-s mirror presentations according to, with different fish, either a fixed-ratio 1 or a variable-interval 60-s schedule of reinforcement. When responding was stable, a differential-reinforcement-of-other-behavior schedule was substituted for the mirror-presentation schedule. Following this, mirror presentations were discontinued (extinction). During this latter phase, there were transient increases in the ring-swim response relative to the frequency of such responding during the differential-reinforcement-of-other behavior schedule. Resurgence was similar for the fish exposed previously to the fixed-ratio or to the variable-interval schedule. These results extend to Siamese fighting fish a well-established behavioral phenomenon previously not observed in this species or with this response topography, and only rarely reported following the removal of a non-consumable reinforcer. PMID:24462710

  11. Molecular genetics of infantile nervous system channelopathies.

    PubMed

    Gardiner, Mark

    2006-12-01

    Inherited or de novo mutations in at least a dozen genes encoding ion channels may present as paroxysmal disorders during the neonatal period or first year of life. These channelopathies include genes encoding voltage-gated channels specific for sodium (SCN1A, SCN2A, SCN1B, SCN9A) and potassium (KCNQ2, KCNQ3) which account for a variety of epilepsy phenotypes ranging from mild, such as Benign familial neonatal seizures (BFNS) to severe, such as Dravet syndrome (severe myoclonic epilepsy of infancy, SMEI) and the rare and unusual syndrome paroxysmal extreme pain disorder (PEPD). Ligand-gated channels involved include the GABA(A) receptor in a variety of epilepsy phenotypes and the human glycine receptor. Mutations in five genes encoding subunits of this receptor and accessory molecules underlie hyperekplexia or stiff-baby syndrome. All these conditions are rare but correct diagnosis is of value not only for genetic counselling but to allow the specific treatment which is available. PMID:17049761

  12. Chloride Channelopathies of ClC-2

    PubMed Central

    Bi, Miao Miao; Hong, Sen; Zhou, Hong Yan; Wang, Hong Wei; Wang, Li Na; Zheng, Ya Juan

    2014-01-01

    Chloride channels (ClCs) have gained worldwide interest because of their molecular diversity, widespread distribution in mammalian tissues and organs, and their link to various human diseases. Nine different ClCs have been molecularly identified and functionally characterized in mammals. ClC-2 is one of nine mammalian members of the ClC family. It possesses unique biophysical characteristics, pharmacological properties, and molecular features that distinguish it from other ClC family members. ClC-2 has wide organ/tissue distribution and is ubiquitously expressed. Published studies consistently point to a high degree of conservation of ClC-2 function and regulation across various species from nematodes to humans over vast evolutionary time spans. ClC-2 has been intensively and extensively studied over the past two decades, leading to the accumulation of a plethora of information to advance our understanding of its pathophysiological functions; however, many controversies still exist. It is necessary to analyze the research findings, and integrate different views to have a better understanding of ClC-2. This review focuses on ClC-2 only, providing an analytical overview of the available literature. Nearly every aspect of ClC-2 is discussed in the review: molecular features, biophysical characteristics, pharmacological properties, cellular function, regulation of expression and function, and channelopathies. PMID:24378849

  13. The resurgence of tuberculosis.

    PubMed

    Parry, C; Davies, P D

    1996-01-01

    A lack of reliable statistics makes tuberculosis (TB) trends in developing countries difficult to estimate. Nonetheless, the World Health Organization and the International Union against Tuberculosis and Lung Disease estimated in 1990 that one-third of the world's population was infected with the tubercle bacillus and that there were 7-8 million new cases of TB annually. 95% of the new cases occurred in the developing world, with more than 5 million in Asia and the Western Pacific and more than 1 million in sub-Saharan Africa. Almost 80% of TB cases in developing countries occur among those under age 50 years. The global annual mortality was estimated at 2.5 million, with 98% of deaths occurring in developing countries. Worldwide, TB is believed to be responsible for 25% of avoidable deaths in young adults. There has been no significant decline in the average annual risk of infection in most developing countries due to incomplete coverage by control programs and inadequate cure rates. The interaction of HIV infection with TB is another factor which contributes to the deteriorating TB situation in many developing countries. Countries with a high population growth rate and little decline in the annual risk of infection should expect either a static or increasing level of TB disease. Immigration from developing countries, HIV infection, poverty, unemployment, homelessness, overcrowding, and population aging contribute to the spread of TB in developed countries. Drug resistance thwarts the control of TB worldwide. PMID:8972116

  14. Resurgent current of voltage-gated Na+ channels

    PubMed Central

    Lewis, Amanda H; Raman, Indira M

    2014-01-01

    Resurgent Na+ current results from a distinctive form of Na+ channel gating, originally identified in cerebellar Purkinje neurons. In these neurons, the tetrodotoxin-sensitive voltage-gated Na+ channels responsible for action potential firing have specialized mechanisms that reduce the likelihood that they accumulate in fast inactivated states, thereby shortening refractory periods and permitting rapid, repetitive, and/or burst firing. Under voltage clamp, step depolarizations evoke transient Na+ currents that rapidly activate and quickly decay, and step repolarizations elicit slower channel reopening, or a ‘resurgent’ current. The generation of resurgent current depends on a factor in the Na+ channel complex, probably a subunit such as NaVβ4 (Scn4b), which blocks open Na+ channels at positive voltages, competing with the fast inactivation gate, and unblocks at negative voltages, permitting recovery from an open channel block along with a flow of current. Following its initial discovery, resurgent Na+ current has been found in nearly 20 types of neurons. Emerging research suggests that resurgent current is preferentially increased in a variety of clinical conditions associated with altered cellular excitability. Here we review the biophysical, molecular and structural mechanisms of resurgent current and their relation to the normal functions of excitable cells as well as pathophysiology. PMID:25172941

  15. Follistatin in chondrocytes: the link between TRPV4 channelopathies and skeletal malformations

    PubMed Central

    Leddy, Holly A.; McNulty, Amy L.; Lee, Suk Hee; Rothfusz, Nicole E.; Gloss, Bernd; Kirby, Margaret L.; Hutson, Mary R.; Cohn, Daniel H.; Guilak, Farshid; Liedtke, Wolfgang

    2014-01-01

    Point mutations in the calcium-permeable TRPV4 ion channel have been identified as the cause of autosomal-dominant human motor neuropathies, arthropathies, and skeletal malformations of varying severity. The objective of this study was to determine the mechanism by which TRPV4 channelopathy mutations cause skeletal dysplasia. The human TRPV4V620I channelopathy mutation was transfected into primary porcine chondrocytes and caused significant (2.6-fold) up-regulation of follistatin (FST) expression levels. Pore altering mutations that prevent calcium influx through the channel prevented significant FST up-regulation (1.1-fold). We generated a mouse model of theTRPV4V620I mutation, and found significant skeletal deformities (e.g., shortening of tibiae and digits, similar to the human disease brachyolmia) and increases in Fst/TRPV4 mRNA levels (2.8-fold). FST was significantly up-regulated in primary chondrocytes transfected with 3 different dysplasia-causing TRPV4 mutations (2- to 2.3-fold), but was not affected by an arthropathy mutation (1.1-fold). Furthermore, FST-loaded microbeads decreased bone ossification in developing chick femora (6%) and tibiae (11%). FST gene and protein levels were also increased 4-fold in human chondrocytes from an individual natively expressing the TRPV4T89I mutation. Taken together, these data strongly support that up-regulation of FST in chondrocytes by skeletal dysplasia-inducing TRPV4 mutations contributes to disease pathogenesis.—Leddy, H. A., McNulty, A. L., Lee, S. H., Rothfusz, N. E., Gloss, B., Kirby, M. L., Hutson, M. R., Cohn, D. H., Guilak, F., Liedtke, W. Follistatin in chondrocytes: the link between TRPV4 channelopathies and skeletal malformations. PMID:24577120

  16. Effects of Response Effort on Resurgence.

    PubMed

    Wilson, Alyssa N; Glassford, Tyler S; Koerkenmeier, Sarah M

    2016-06-01

    The present study examined response effort during resurgence tests. Six children were trained to place balls in baskets that were placed either close (.0254 m) or far away (1.829 m or .9 m). Resurgence was assessed using a linear strip design, where responses were reinforced on a variable-interval 10-s schedule or put on extinction. During resurgence tests, minimal to low rates of resurgence associated with the greater response effort (i.e., placing a ball in the basket further way) were observed across all six participants, regardless of distance. PMID:27606253

  17. Resurgence of Integrated Behavioral Units

    PubMed Central

    Bachá-Méndez, Gustavo; Reid, Alliston K; Mendoza-Soylovna, Adela

    2007-01-01

    Two experiments with rats examined the dynamics of well-learned response sequences when reinforcement contingencies were changed. Both experiments contained four phases, each of which reinforced a 2-response sequence of lever presses until responding was stable. The contingencies then were shifted to a new reinforced sequence until responding was again stable. Extinction-induced resurgence of previously reinforced, and then extinguished, heterogeneous response sequences was observed in all subjects in both experiments. These sequences were demonstrated to be integrated behavioral units, controlled by processes acting at the level of the entire sequence. Response-level processes were also simultaneously operative. Errors in sequence production were strongly influenced by the terminal, not the initial, response in the currently reinforced sequence, but not by the previously reinforced sequence. These studies demonstrate that sequence-level and response-level processes can operate simultaneously in integrated behavioral units. Resurgence and the development of integrated behavioral units may be dissociated; thus the observation of one does not necessarily imply the other. PMID:17345948

  18. Determining the Pathogenicity of Genetic Variants Associated with Cardiac Channelopathies

    PubMed Central

    Campuzano, Oscar; Allegue, Catarina; Fernandez, Anna; Iglesias, Anna; Brugada, Ramon

    2015-01-01

    Advancements in genetic screening have generated massive amounts of data on genetic variation; however, a lack of clear pathogenic stratification has left most variants classified as being of unknown significance. This is a critical limitation for translating genetic data into clinical practice. Genetic screening is currently recommended in the guidelines for diagnosis and treatment of cardiac channelopathies, which are major contributors to sudden cardiac death in young people. We propose to characterize the pathogenicity of genetic variants associated with cardiac channelopathies using a stratified scoring system. The development of this system was considered by using all of the tools currently available to define pathogenicity. The use of this scoring system could help clinicians to understand the limitations of genetic associations with a disease, and help them better define the role that genetics can have in their clinical routine. PMID:25608792

  19. Pathophysiological Role of Omega Pore Current in Channelopathies

    PubMed Central

    Jurkat-Rott, Karin; Groome, James; Lehmann-Horn, Frank

    2012-01-01

    In voltage-gated cation channels, a recurrent pattern for mutations is the neutralization of positively charged residues in the voltage-sensing S4 transmembrane segments. These mutations cause dominant ion channelopathies affecting many tissues such as brain, heart, and skeletal muscle. Recent studies suggest that the pathogenesis of associated phenotypes is not limited to alterations in the gating of the ion-conducting alpha pore. Instead, aberrant so-called omega currents, facilitated by the movement of mutated S4 segments, also appear to contribute to symptoms. Surprisingly, these omega currents conduct cations with varying ion selectivity and are activated in either a hyperpolarized or depolarized voltage range. This review gives an overview of voltage sensor channelopathies in general and focuses on pathogenesis of skeletal muscle S4 disorders for which current knowledge is most advanced. PMID:22701429

  20. Clinical Features of Genetic Cardiac Diseases Related to Potassium Channelopathies.

    PubMed

    Adler, Arnon; Viskin, Sami

    2016-06-01

    Genetic cardiac diseases related to potassium channelopathies are a group of relatively rare syndromes that includes long QT syndrome, short QT syndrome, Brugada syndrome, and early repolarization syndrome. Patients with these syndromes share a propensity for the development of life-threatening ventricular arrhythmias in the absence of significant cardiac structural abnormalities. Familial atrial fibrillation has also been associated with potassium channel dysfunction but differs from the other syndromes by being a rare cause of a common condition. This article focuses on the clinical features, diagnosis, and management of these syndromes. PMID:27261827

  1. Finite N from resurgent large N

    NASA Astrophysics Data System (ADS)

    Couso-Santamaría, Ricardo; Schiappa, Ricardo; Vaz, Ricardo

    2015-05-01

    Due to instanton effects, gauge-theoretic large N expansions yield asymptotic series, in powers of 1 /N2. The present work shows how to generically make such expansions meaningful via their completion into resurgent transseries, encoding both perturbative and nonperturbative data. Large N resurgent transseries compute gauge-theoretic finite N results nonperturbatively (no matter how small N is). Explicit calculations are carried out within the gauge theory prototypical example of the quartic matrix model. Due to integrability in the matrix model, it is possible to analytically compute (fixed integer) finite N results. At the same time, the large N resurgent transseries for the free energy of this model was recently constructed. Together, it is shown how the resummation of the large N resurgent transseries matches the analytical finite N results up to remarkable numerical accuracy. Due to lack of Borel summability, Stokes phenomena has to be carefully taken into account, implying that instantons play a dominant role in describing the finite N physics. The final resurgence results can be analytically continued, defining gauge theory for any complex value of N.

  2. Renewal, resurgence, and alternative reinforcement context.

    PubMed

    Sweeney, Mary M; Shahan, Timothy A

    2015-07-01

    Resurgence, relapse induced by the removal of alternative reinforcement, and renewal, relapse induced by a change in contextual stimuli, are typically studied separately in operant conditioning paradigms. In analogous treatments of operant problem behavior, aspects of both relapse phenomena can operate simultaneously. Therefore, the purpose of this study was to examine a novel method for studying resurgence and renewal in the same experimental preparation. An alternative source of reinforcement was available during extinction for one group of rats (a typical resurgence preparation). Another group experienced an operant renewal preparation in which the extinction context was distinguished via olfactory and visual stimuli. A third group experienced alternative reinforcement delivery in the new context, a novel combination of typical resurgence and renewal preparations. Removal of alternative reinforcement and/or a change in context induced relapse relative to an extinction-only control group. When alternative reinforcement was delivered in a novel context, the alternative response was less persistent relative to when extinction of the alternative response took place in the context in which it was trained. This methodology might be used to illustrate shared (or distinct) mechanisms of resurgence and renewal, and to determine how delivering alternative reinforcement in another context may affect persistence and relapse. PMID:25936876

  3. Genetics of channelopathies associated with sudden cardiac death

    PubMed Central

    Campuzano, Oscar; Sarquella-Brugada, Georgia; Brugada, Ramon; Brugada, Josep

    2015-01-01

    Recent technological advances in cardiology have resulted in new guidelines for the diagnosis, treatment and prevention of diseases. Despite these improvements, sudden death remains one of the main challenges to clinicians because the majority of diseases associated with sudden cardiac death are characterized by incomplete penetrance and variable expressivity. Hence, patients may be unaware of their illness, and physical activity can be the trigger for syncope as first symptom of the disease. Most common causes of sudden cardiac death are congenital alterations and structural heart diseases, although a significant number remain unexplained after comprehensive autopsy. In these unresolved cases, channelopathies are considered the first potential cause of death. Since all these diseases are of genetic origin, family members could be at risk, despite being asymptomatic. Genetics has also benefited from technological advances, and genetic testing has been incorporated into the sudden death field, identifying the cause in clinically affected patients, asymptomatic family members and post-mortem cases without conclusive diagnosis. This review focuses on recent advances in the genetics of channelopathies associated with sudden cardiac death. PMID:26566530

  4. RESURGENCE OF MANDS FOLLOWING FUNCTIONAL COMMUNICATION TRAINING

    PubMed Central

    BERG, WENDY K.; RINGDAHL, JOEL E.; RYAN, STEPHEN E.; ING, ANNA D.; LUSTIG, NICOLE; ROMANI, PATRICK; WACKER, DAVID P.; ANDERSEN, JENNIFER K.; DURAKO, EMILY

    2015-01-01

    Experimental conditions similar to those described by Lieving and Lattal (2003) were used within two experiments to evaluate the resurgence of mands with humans. Two mands from the same operant class were trained with three participants with developmental disabilities during Experiment 1 and with two participants with developmental disabilities and a history of problem behavior during Experiment 2. The two mands were then placed on extinction. Both persisted, but showed different response strength during extinction. The mand with the weaker response strength was targeted for additional functional communication training and the alternative mand was placed on extinction. Following steady levels of occurrence of the targeted mand and no occurrences of the alternative mand, both mands were placed on extinction again. At least one instance of resurgence of the alternative mand occurred with every participant and resurgence of problem behavior occurred for both participants during Experiment 2. PMID:26640311

  5. Computational tools to investigate genetic cardiac channelopathies

    PubMed Central

    Abriel, Hugues; de Lange, Enno; Kucera, Jan P.; Loussouarn, Gildas; Tarek, Mounir

    2013-01-01

    The aim of this perspective article is to share with the community of ion channel scientists our thoughts and expectations regarding the increasing role that computational tools will play in the future of our field. The opinions and comments detailed here are the result of a 3-day long international exploratory workshop that took place in October 2013 and that was supported by the Swiss National Science Foundation. PMID:24421770

  6. Resurgence of Temporal Patterns of Responding

    ERIC Educational Resources Information Center

    Cancado, Carlos R. X.; Lattal, Kennon A.

    2011-01-01

    The resurgence of temporal patterns of key pecking by pigeons was investigated in two experiments. In Experiment 1, positively accelerated and linear patterns of responding were established on one key under a discrete-trial multiple fixed-interval variable-interval schedule. Subsequently, only responses on a second key produced reinforcers…

  7. Focus on Kir7.1: physiology and channelopathy

    PubMed Central

    Kumar, Mohit; Pattnaik, Bikash R

    2014-01-01

    Genetic studies have linked alterations in Kir7.1 channel to diverse pathologies. We summarize functional relevance of Kir7.1 channel in retinal pigment epithelium (RPE), regulation of channel function by various cytoplasmic metabolites, and mutations that cause channelopathies. At the apical membrane of RPE, K+ channels contribute to subretinal K+ homeostasis and support Na+/K+ pump and Na+-K+-2Cl− cotransporter function by providing a pathway for K+ secretion. Electrophysiological studies have established that barium- and cesium-sensitive inwardly rectifying K+ (Kir) channels make up a major component of the RPE apical membrane K+ conductance. Native human RPE expresses transcripts for Kir1.1, Kir2.1, Kir2.2, Kir3.1, Kir3.4, Kir4.2, and Kir6.1, albeit at levels at least 50-fold lower than Kir7.1. Kir7.1 is structurally similar to other Kir channels, consisting of 2 trans-membrane domains, a pore-forming loop that contains the selectivity filter, and 2 cytoplasmic polar tails. Within the cytoplasmic structure, clusters of amino acid sequences form regulatory domains that interact with cellular metabolites and control the opening and closing of the channel. Recent evidence indicated that intrinsic sequence motifs present in Kir7.1 control surface expression. Mutant Kir7.1 channels are associated with inherited eye pathologies such as Snowflake Vitreoretinal Degeneration (SVD) and Lebers Congenital Amaurosis (LCA16). Based on the current evidence, mutations implicated in channelopathies have the potential to be used for genetic testing to diagnose blindness due to Kir7.1. PMID:25558901

  8. The resurgence of mumps and pertussis.

    PubMed

    Sabbe, Martine; Vandermeulen, Corinne

    2016-04-01

    Vaccines and extended vaccination programs have had an extensive impact on morbidity and mortality rates due to infectious diseases. Because of the continuous and extensive use of vaccines in industrialized countries, many infectious diseases such as poliomyelitis, diphtheria and measles have been reduced to near-extinction. However, in recent years, many countries including the United States of America, the United Kingdom and Belgium, have been confronted with a resurgence of mumps and pertussis, despite high vaccination coverage for both vaccines. In this commentary, possible causes of this resurgence will be discussed, such as the occurrence of adapted microbes, failure to vaccinate and primary and secondary vaccine failure. Additional research of the immunological mechanisms is clearly needed to support the development of possible new and more immunogenic vaccines against mumps and pertussis. Meanwhile, extensive vaccination campaigns with both vaccines remain necessary. PMID:26751186

  9. The resurgence of mumps and pertussis

    PubMed Central

    Sabbe, Martine; Vandermeulen, Corinne

    2016-01-01

    ABSTRACT Vaccines and extended vaccination programs have had an extensive impact on morbidity and mortality rates due to infectious diseases. Because of the continuous and extensive use of vaccines in industrialized countries, many infectious diseases such as poliomyelitis, diphtheria and measles have been reduced to near-extinction. However, in recent years, many countries including the United States of America, the United Kingdom and Belgium, have been confronted with a resurgence of mumps and pertussis, despite high vaccination coverage for both vaccines. In this commentary, possible causes of this resurgence will be discussed, such as the occurrence of adapted microbes, failure to vaccinate and primary and secondary vaccine failure. Additional research of the immunological mechanisms is clearly needed to support the development of possible new and more immunogenic vaccines against mumps and pertussis. Meanwhile, extensive vaccination campaigns with both vaccines remain necessary. PMID:26751186

  10. Bordetella pertussis epidemiology and evolution in the light of pertussis resurgence.

    PubMed

    Sealey, Katie L; Belcher, Thomas; Preston, Andrew

    2016-06-01

    Whooping cough, or pertussis, is resurgent in many countries world-wide. This is linked to switching from the use of whole cell vaccines to acellular vaccines in developed countries. Current evidence suggests that this has resulted in the earlier waning of vaccine-induced immunity, an increase in asymptomatic infection with concomitant increases in transmission and increased selection pressure for Bordetellapertussis variants that are better able to evade vaccine-mediated immunity than older isolates. This review discusses recent findings in B. pertussis epidemiology and evolution in the light of pertussis resurgence, and highlights the important role for genomics-based studies in monitoring B. pertussis adaptation. PMID:26932577

  11. Fish faunal resurgence in Lake Nabugabo, East Africa

    USGS Publications Warehouse

    Chapman, L.J.; Chapman, Colin A.; Schofield, P.J.; Olowo, J.P.; Kaufman, L.S.; Seehausen, O.; Ogutu-Ohwayo., R.

    2003-01-01

     In Lake Nabugabo, Uganda, a small satellite of the equatorial Lake Victoria, approximately 50% of the indigenous fish species disappeared from the open waters subsequent to establishment of the introduced predatory Nile perch (   Lates niloticus ). However, several of these species persisted in wetland refugia. Over the past decade, Nile perch in Lake Nabugabo have been intensively fished. Herein we report a resurgence of some indigenous species in open waters. In a multiyear study, we used annual transects in inshore and offshore waters of exposed ( no wetland ) and wetland habitats to document the pattern of resurgence. In 1995, haplochromine cichlids were largely confined to inshore areas, particularly wetland ecotones, and were rare in Nile perch stomachs, as were most other indigenous species. By 2000 haplochromine cichlids were abundant in inshore and offshore areas of both exposed and wetland transects. Several indigenous noncichlids also reappeared in the main lake, including three of the four original mormyrid species. Between 1995 and 1999, there was a dramatic increase in the proportion of haplochromines in the diet of Nile perch. When haplochromines were rare ( 1995 ), Nile perch switched from an invertebrate-dominated diet to piscivory at a large size ( 30 cm total length ). In 2000, however, Nile perch were strongly piscivorous by 5–10 cm total length. The pattern of faunal loss and recovery in Lake Nabugabo demonstrates the importance of refugia in providing the seeds of resurgence and provides a model with which to understand some changes in Lake Victoria.

  12. Voltage-Gated Sodium Channels: Biophysics, Pharmacology, and Related Channelopathies

    PubMed Central

    Savio-Galimberti, Eleonora; Gollob, Michael H.; Darbar, Dawood

    2012-01-01

    Voltage-gated sodium channels (VGSC) are multi-molecular protein complexes expressed in both excitable and non-excitable cells. They are primarily formed by a pore-forming multi-spanning integral membrane glycoprotein (α-subunit) that can be associated with one or more regulatory β-subunits. The latter are single-span integral membrane proteins that modulate the sodium current (INa) and can also function as cell adhesion molecules. In vitro some of the cell-adhesive functions of the β-subunits may play important physiological roles independently of the α-subunits. Other endogenous regulatory proteins named “channel partners” or “channel interacting proteins” (ChiPs) like caveolin-3 and calmodulin/calmodulin kinase II (CaMKII) can also interact and modulate the expression and/or function of VGSC. In addition to their physiological roles in cell excitability and cell adhesion, VGSC are the site of action of toxins (like tetrodotoxin and saxitoxin), and pharmacologic agents (like antiarrhythmic drugs, local anesthetics, antiepileptic drugs, and newly developed analgesics). Mutations in genes that encode α- and/or β-subunits as well as the ChiPs can affect the structure and biophysical properties of VGSC, leading to the development of diseases termed sodium “channelopathies”.  This review will outline the structure, function, and biophysical properties of VGSC as well as their pharmacology and associated channelopathies and highlight some of the recent advances in this field. PMID:22798951

  13. Hot topic or hot air? Climate change and malaria resurgence in East African highlands

    PubMed Central

    Hay, Simon I.; Rogers, David J.; Randolph, Sarah E.; Stern, David I.; Cox, Jonathan; Shanks, G. Dennis; Snow, Robert W.

    2011-01-01

    Climate has a significant impact on malaria incidence and we have predicted that forecast climate changes might cause some modifications to the present global distribution of malaria close to its present boundaries. However, it is quite another matter to attribute recent resurgences of malaria in the highlands of East Africa to climate change. Analyses of malaria time-series at such sites have shown that malaria incidence has increased in the absence of co-varying changes in climate. We find the widespread increase in resistance of the malaria parasite to drugs and the decrease in vector control activities to be more likely driving forces behind the malaria resurgence. PMID:12482536

  14. Alternative paradigms for ion channelopathies: disorders of ion channel membrane trafficking and posttranslational modification.

    PubMed

    Curran, Jerry; Mohler, Peter J

    2015-01-01

    Channelopathies are a diverse set of disorders associated with defects in ion channel (and transporter) function. Although the vast majority of channelopathies are linked with inherited mutations that alter ion channel biophysical properties, another group of similar disorders has emerged that alter ion channel synthesis, membrane trafficking, and/or posttranslational modifications. In fact, some electrical and episodic disorders have now been identified that are not defects in the ion channel but instead reflect dysfunction in an ion channel (or transporter) regulatory protein. This review focuses on alternative paradigms for physiological disorders associated with protein biosynthesis, folding, trafficking, and membrane retention. Furthermore, the review highlights the role of aberrant posttranslational modifications in acquired channelopathies. PMID:25293528

  15. Neural network modelling of the influence of channelopathies on reflex visual attention.

    PubMed

    Gravier, Alexandre; Quek, Chai; Duch, Włodzisław; Wahab, Abdul; Gravier-Rymaszewska, Joanna

    2016-02-01

    This paper introduces a model of Emergent Visual Attention in presence of calcium channelopathy (EVAC). By modelling channelopathy, EVAC constitutes an effort towards identifying the possible causes of autism. The network structure embodies the dual pathways model of cortical processing of visual input, with reflex attention as an emergent property of neural interactions. EVAC extends existing work by introducing attention shift in a larger-scale network and applying a phenomenological model of channelopathy. In presence of a distractor, the channelopathic network's rate of failure to shift attention is lower than the control network's, but overall, the control network exhibits a lower classification error rate. The simulation results also show differences in task-relative reaction times between control and channelopathic networks. The attention shift timings inferred from the model are consistent with studies of attention shift in autistic children. PMID:26834861

  16. Resurgence: Response competition, stimulus control, and reinforcer control.

    PubMed

    Podlesnik, Christopher A; Kelley, Michael E

    2014-09-01

    Resurgence is the relapse of a previously reinforced and then extinguished target response when extinguishing a more recently reinforced alternative response. We designed the present study to assess the contribution of stimulus-control and reinforcer-control processes in determining resurgence. In a modified resurgence procedure, we removed the alternative discriminative stimulus signaling alternative reinforcement when extinguishing the alternative response. This produced more abrupt resurgence of target responding than in a typical resurgence procedure maintaining the alternative discriminative stimulus when extinguishing the alternative response. The overall amount of resurgence did not differ. Importantly, a "renewal" control added and removed the alternative stimulus during extinction, identically as in the modified resurgence procedure. However, alternative responding was never reinforced, which produced no relapse of target responding. Therefore, the more abrupt resurgence with the modified procedure than with the typical procedure suggests removing the alternative stimulus reduced the competition between alternative and target responding. These findings revealed the importance of adding and removing alternative reinforcement in producing resurgence (reinforcer control) but little influence of simply adding and removing the alternative stimulus (stimulus control). These data suggest that clinicians should consider the long-term availability of the alternative response option when developing differential-reinforcement interventions. PMID:25125267

  17. Painful neuropathies: the emerging role of sodium channelopathies.

    PubMed

    Brouwer, Brigitte A; Merkies, Ingemar S J; Gerrits, Monique M; Waxman, Stephen G; Hoeijmakers, Janneke G J; Faber, Catharina G

    2014-06-01

    Pain is a frequent debilitating feature reported in peripheral neuropathies with involvement of small nerve (Aδ and C) fibers. Voltage-gated sodium channels are responsible for the generation and conduction of action potentials in the peripheral nociceptive neuronal pathway where NaV 1.7, NaV 1.8, and NaV 1.9 sodium channels (encoded by SCN9A, SCN10A, and SCN11A) are preferentially expressed. The human genetic pain conditions inherited erythromelalgia and paroxysmal extreme pain disorder were the first to be linked to gain-of-function SCN9A mutations. Recent studies have expanded this spectrum with gain-of-function SCN9A mutations in patients with small fiber neuropathy and in a new syndrome of pain, dysautonomia, and small hands and small feet (acromesomelia). In addition, painful neuropathies have been recently linked to SCN10A mutations. Patch-clamp studies have shown that the effect of SCN9A mutations is dependent upon the cell-type background. The functional effects of a mutation in dorsal root ganglion (DRG) neurons and sympathetic neuron cells may differ per mutation, reflecting the pattern of expression of autonomic symptoms in patients with painful neuropathies who carry the mutation in question. Peripheral neuropathies may not always be length-dependent, as demonstrated in patients with initial facial and scalp pain symptoms with SCN9A mutations showing hyperexcitability in both trigeminal ganglion and DRG neurons. There is some evidence suggesting that gain-of-function SCN9A mutations can lead to degeneration of peripheral axons. This review will focus on the emerging role of sodium channelopathies in painful peripheral neuropathies, which could serve as a basis for novel therapeutic strategies. PMID:25250524

  18. A Model of Resurgence Based on Behavioral Momentum Theory

    ERIC Educational Resources Information Center

    Shahan, Timothy A.; Sweeney, Mary M.

    2011-01-01

    Resurgence is the reappearance of an extinguished behavior when an alternative behavior reinforced during extinction is subsequently placed on extinction. Resurgence is of particular interest because it may be a source of relapse to problem behavior following treatments involving alternative reinforcement. In this article we develop a quantitative…

  19. Resurgence of the cusp anomalous dimension

    NASA Astrophysics Data System (ADS)

    Dorigoni, Daniele; Hatsuda, Yasuyuki

    2015-09-01

    We revisit the strong coupling limit of the cusp anomalous dimension in planar N=4 super Yang-Mills theory. It is known that the strong coupling expansion is asymptotic and non-Borel summable. As a consequence, the cusp anomalous dimension receives non-perturbative corrections, and the complete strong coupling expansion should be a resurgent transseries. We reveal that the perturbative and non-perturbative parts in the transseries are closely interrelated. Solving the Beisert-Eden-Staudacher equation systematically, we analyze in detail the large order behavior in the strong coupling pertur- bative expansion and show that the non-perturbative information is indeed encoded there. An ambiguity of (lateral) Borel resummations of the perturbative expansion is precisely canceled by the contributions from the non-perturbative sectors, and the final result is real and unambiguous.

  20. Alabama's Appalachian overthrust amid exploratory drilling resurgence

    SciTech Connect

    Taylor, J.D. ); Epsman, M.L.

    1991-06-24

    Oil and gas exploration has been carried out sporadically in the Appalachian overthrust region of Alabama for years, but recently interest in the play has had a major resurgence. The Appalachian overthrust region of Alabama is best exposed in the valley and ridge physiographic province in the northeast part of the state. Resistant ridges of sandstone and chert and valleys of shales and carbonate have been thrust toward the northwest. Seismic data show that this structural style continues under the Cretaceous overlap. The surface and subsurface expression of the Alabama overthrust extends for more than 4,000 sq miles. Oil and gas have been produced for many years from Cambro-Ordovician, Ordovician, Mississippian, and Pennsylvanian rocks in the nearby Black Warrior basin in Alabama and Mississippi and the Cumberland plateau in Tennessee. The same zones are also potential producing horizons in the Alabama overthrust region.

  1. Resurgent transseries & Dyson-Schwinger equations

    NASA Astrophysics Data System (ADS)

    Klaczynski, Lutz

    2016-09-01

    We employ resurgent transseries as algebraic tools to investigate two self-consistent Dyson-Schwinger equations, one in Yukawa theory and one in quantum electrodynamics. After a brief but pedagogical review, we derive fixed point equations for the associated anomalous dimensions and insert a moderately generic log-free transseries ansatz to study the possible strictures imposed. While proceeding in various stages, we develop an algebraic method to keep track of the transseries' coefficients. We explore what conditions must be violated in order to stay clear of fixed point theorems to eschew a unique solution, if so desired, as we explain. An interesting finding is that the flow of data between the different sectors of the transseries shows a pattern typical of resurgence, i.e. the phenomenon that the perturbative sector of the transseries talks to the nonperturbative ones in a one-way fashion. However, our ansatz is not exotic enough as it leads to trivial solutions with vanishing nonperturbative sectors, even when logarithmic monomials are included. We see our result as a harbinger of what future work might reveal about the transseries representations of observables in fully renormalised four-dimensional quantum field theories and adduce a tentative yet to our mind weighty argument as to why one should not expect otherwise. This paper is considerably self-contained. Readers with little prior knowledge are let in on the basic reasons why perturbative series in quantum field theory eventually require an upgrade to transseries. Furthermore, in order to acquaint the reader with the language utilised extensively in this work, we also provide a concise mathematical introduction to grid-based transseries.

  2. Fosfomycin: Resurgence of an old companion.

    PubMed

    Sastry, Sangeeta; Doi, Yohei

    2016-05-01

    Fosfomycin was discovered over four decades ago, yet has drawn renewed interest as an agent active against a range of multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens. Its unique mechanism of action and broad spectrum of activity makes it a promising candidate in the treatment of various MDR/XDR infections. There has been a surge of in vitro data on its activity against MDR/XDR organisms, both when used as a single agent and in combination with other agents. In the United States, fosfomycin is only approved in an oral formulation for the treatment of acute uncomplicated urinary tract infections (UTIs), whereas in some countries both oral and intravenous formulations are available for various indications. Fosfomycin has minimal interactions with other medications and has a relatively favorable safety profile, with diarrhea being the most common adverse reaction. Fosfomycin has low protein binding and is excreted primarily unchanged in the urine. The clinical outcomes of patients treated with fosfomycin are favorable for uncomplicated UTIs, but data are limited for use in other conditions. Fosfomycin maintains activity against most Enterobacteriaceae including Escherichia coli, but plasmid-mediated resistance due to inactivation have appeared in recent years, which has the potential to compromise its use in the future. In this review, we summarize the current knowledge of this resurgent agent and its role in our antimicrobial armamentarium. PMID:26923259

  3. Studying channelopathies at the functional level using a system identification approach

    NASA Astrophysics Data System (ADS)

    Faisal, A. Aldo

    2007-09-01

    The electrical activity of our brain's neurons is controlled by voltage-gated ion channels. Mutations in these ion channels have been recently associated with clinical conditions, so called channelopathies. The involved ion channels have been well characterised at a molecular and biophysical level. However, the impact of these mutations on neuron function have been only rudimentary studied. It remains unclear how operation and performance (in terms of input-output characteristics and reliability) are affected. Here, I show how system identification techniques provide neuronal performance measures which allow to quantitatively asses the impact of channelopathies by comparing whole cell input-output relationships. I illustrate the feasibility of this approach by comparing the effects on neuronal signalling of two human sodium channel mutations (NaV 1.1 W1204R, R1648H), linked to generalized epilepsy with febrile seizures, to the wild-type NaV 1.1 channel.

  4. [Postmortem genetic testing in sudden cardiac death due to ion channelopathies].

    PubMed

    Guan, Da-wei; Zhao, Rui

    2010-04-01

    Sudden cardiac death accounts for majority of deaths in human. Evident cardiac lesions that may explain the cause of death can be detected in comprehensive postmortem investigation in most sudden cardiac death. However, no cardiac morphological abnormality is found in a considerable number of cases although the death is highly suspected from cardiac anomaly. With the advances in the modern molecular biology techniques, it has been discovered that many of these sudden deaths are caused by congenital ion channelopathies in myocardial cell, i.e., Brugada syndrome, long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and short QT syndrome, etc. This article presents the molecular genetics, electrocardiographic abnormalities, clinical manifestations, and mechanisms leading to sudden cardiac death with emphasis on the role of postmortem genetic testing in certification of cause of death. It may provide helpful information in investigating sudden cardiac death due to ion channelopathies in medico-legal practice. PMID:20653139

  5. Rare neurological channelopathies--networks to study patients, pathogenesis and treatment.

    PubMed

    Jen, Joanna C; Ashizawa, Tetsuo; Griggs, Robert C; Waters, Michael F

    2016-04-01

    Each of the thousands of rare neurological diseases requires a widely distributed network of centres, investigators and patients, so as to foster multidisciplinary investigations and involve sufficient numbers of patients in the discovery of disease pathogenesis and novel treatment. In this Review, we highlight the value of this collaborative approach in patient-oriented research into rare neurological channelopathies. Two networks, the Consortium for Clinical Investigations of Neurological Channelopathies (CINCH) and the Clinical Research Consortium for Studies of Cerebellar Ataxias (CRC-SCA), provide a link between patients with rare channelopathies and investigators who are studying disease pathogenesis and developing novel treatments. Interactions between patients, researchers and advocacy groups promote shared agendas that benefit patient education and recruitment, research collaboration and funding, and training and mentoring of junior investigators who are attracted to the study of the diseases that provide the focus for the two networks. Here, we discuss how linkage of national and international centres has enabled recruitment of study participants, provided opportunities for novel studies of pathogenesis, and facilitated successful clinical trials. PMID:26943780

  6. Role of the discriminative properties of the reinforcer in resurgence.

    PubMed

    Bouton, Mark E; Trask, Sydney

    2016-06-01

    In three experiments with rat subjects, we examined the effects of the discriminative effects of reinforcers that were presented during or after operant extinction. Experiments 1 and 2 examined resurgence, in which an extinguished operant response (R1) recovers when a second behavior (R2) that has been reinforced to replace it is also placed in extinction. The results of Experiment 1 suggest that the amount of R1's resurgence is a decreasing linear function of the interreinforcement interval used during the reinforcement of R2. In Experiment 2, R1 was reinforced with one outcome (O1), and R2 was then reinforced with a second outcome (O2) while R1 was extinguished. In resurgence tests, response-independent (noncontingent) presentations of O2 prevented resurgence of R1, which otherwise occurred when testing was conducted with either no reinforcers or noncontingent presentations of O1. In Experiment 3, we then examined the effects of noncontingent O1 and O2 presentations after simple extinction in either the presence or the absence of noncontingent presentations of O2. Overall, the results are consistent with a role for the discriminative properties of the reinforcer in controlling operant behavior. In resurgence, the reinforcer used during response elimination provides a distinct context that controls the inhibition of R1. The results are less consistent with an alternative view emphasizing the disrupting effects of alternative reinforcement. PMID:26486932

  7. Pertussis: the resurgence of a public health threat.

    PubMed

    Torre, Jackeline Aparecida Grando Della; Benevides, Gabriel Nuncio; de Melo, Ana Maria Andrello Gonçalves Pereira; Ferreira, Cristiane Rúbia

    2015-01-01

    Pertussis is an acute and very contagious pulmonary disease, clinically characterized by periods of coughing and paroxysms that may cause death. The disease afflicts mainly the pediatric population and is life threatening to children under the age of 1 year. Since the beginning of the second millennium, the number of cases of pertussis has increased, menacing public health, despite the availability of the pertussis vaccine. The resurgence of the disease among adults and older children creates a reservoir of infection that will afflict the unimmunized or incompletely immunized children. As newborns and infants show the highest mortality rate, immunization during pregnancy is a new strategy to reduce the burden of pertussis. The authors report the case of a newborn that presented respiratory distress accompanied by marked leukocytosis. Bronchiolitis was the initial diagnostic hypothesis, but the clinical picture became typical of pertussis when paroxysmal coughing ensued. Isolation of the Bordetella pertussis and antigenic demonstration by polymerase chain reaction were positive from respiratory secretion. Despite appropriate antibiotic therapy and intensive care management the child died and the autopsy showed characteristic diagnostic findings. The authors call attention to this diagnosis when facing respiratory failure among young children, mainly in the presence of marked leukocytosis. Thorough research on the immunization status of the patient's social environment is of crucial importance. PMID:26484329

  8. Resurgence of leptospirosis in dogs in Ontario: recent findings.

    PubMed

    Prescott, John F; McEwen, Beverly; Taylor, Judith; Woods, J Paul; Abrams-Ogg, Anthony; Wilcock, Brian

    2002-12-01

    A marked increase in leptospirosis in dogs was observed in 2000, part of an increasing trend observed in previous years in Ontario. The highest frequency of seropositive cases occurred from September to December 2000, with the peak in November. Large breed dogs were particularly affected. Clinical and clinicopathological data for 31 dogs admitted between 1998 and 2000 to the Ontario Veterinary College Veterinary Teaching Hospital were analyzed. Major clinical presenting features were acute onset of anorexia, depression, fever, and vomiting. Ninety percent of dogs, on admission, showed biochemical evidence of injury to several organs, notably combinations in the order of kidney, muscle, pancreas, and liver. Almost all dogs showed increased serum urea and creatinine levels, and the majority had increased total creatine kinase, bilirubin, alkaline phosphatase, and leukocytosis with neutrophilia. One-third were thrombocytopenic. Of dogs with liver-related abnormalities, most had evidence of cholestasis, with or without hepatocellular damage. Based on serologic studies, in the year 2000, the major serovar involved was autumnalis, but bratislava, grippotyphosa, and pomona were also implicated. The microscopic agglutination test often gave a confusing pattern of reactivities to the serovars that were tested. The high reactivity to serovar autumnalis may represent an erroneous or "paradoxical" reaction typical of early leptospiral serology. The year 2000 was the warmest in Ontario in each of the 4 fall months (September-December) of the previous decade, as well as being the third wettest in the fall period in the last decade. The increase in canine leptospirosis, therefore, may, in part, reflect climate change. The number of positive cases declined in 2001 by about one-third of those in 2000, but the number of submissions of sera for diagnosis increased markedly over previous years. Further work is required to isolate and to identify definitively serovars involved in

  9. Resurgence and holomorphy: From weak to strong coupling

    SciTech Connect

    Cherman, Aleksey; Koroteev, Peter; Ünsal, Mithat

    2015-05-15

    We analyze the resurgence properties of finite-dimensional exponential integrals which are prototypes for partition functions in quantum field theories. In these simple examples, we demonstrate that perturbation theory, even at arbitrarily weak coupling, fails as the argument of the coupling constant is varied. It is well-known that perturbation theory also fails at stronger coupling. We show that these two failures are actually intimately related. The formalism of resurgent transseries, which takes into account global analytic continuation properties, fixes both problems and provides an arbitrarily accurate description of exact result for any value of coupling. This means that strong coupling results can be deduced by using merely weak coupling data. Finally, we give another perspective on resurgence theory by showing that the monodromy properties of the weak coupling results are in precise agreement with the monodromy properties of the strong-coupling expansions, obtained using analysis of the holomorphy structure of Picard-Fuchs equations.

  10. Context change explains resurgence after the extinction of operant behavior

    PubMed Central

    Trask, Sydney; Schepers, Scott T.; Bouton, Mark E.

    2016-01-01

    Extinguished operant behavior can return or “resurge” when a response that has replaced it is also extinguished. Typically studied in nonhuman animals, the resurgence effect may provide insight into relapse that is seen when reinforcement is discontinued following human contingency management (CM) and functional communication training (FCT) treatments, which both involve reinforcing alternative behaviors to reduce behavioral excess. Although the variables that affect resurgence have been studied for some time, the mechanisms through which they promote relapse are still debated. We discuss three explanations of resurgence (response prevention, an extension of behavioral momentum theory, and an account emphasizing context change) as well as studies that evaluate them. Several new findings from our laboratory concerning the effects of different temporal distributions of the reinforcer during response elimination and the effects of manipulating qualitative features of the reinforcer pose a particular challenge to the momentum-based model. Overall, the results are consistent with a contextual account of resurgence, which emphasizes that reinforcers presented during response elimination have a discriminative role controlling behavioral inhibition. Changing the “reinforcer context” at the start of testing produces relapse if the organism has not learned to suppress its responding under conditions similar to the ones that prevail during testing. PMID:27429503

  11. An Evaluation of Resurgence during Treatment with Functional Communication Training

    ERIC Educational Resources Information Center

    Volkert, Valerie M.; Lerman, Dorothea C.; Call, Nathan A.; Trosclair-Lasserre, Nicole

    2009-01-01

    Extinction-induced resurgence is the recurrence of previously reinforced behavior when another behavior is placed on extinction (Lieving, Hagopian, Long, & O'Connor, 2004). This phenomenon may account for some instances of treatment relapse when problem behavior recovers during extinction-based treatments. The current study sought to determine…

  12. Response-Class Hierarchies and Resurgence of Severe Problem Behavior

    ERIC Educational Resources Information Center

    Lieving, Gregory A.; Hagopian, Louis P.; Long, Ethan S.; O'Connor, Julia

    2004-01-01

    Resurgence may be defined generally as the extinction-induced recurrence of previously learned response patterns. Understanding the conditions under which this phenomenon occurs has theoretical, clinical, and applied implications, particularly with respect to a related area of research on response-class hierarchies. In the current study, we…

  13. Resurgent vector-borne diseases as a global health problem.

    PubMed Central

    Gubler, D. J.

    1998-01-01

    Vector-borne infectious diseases are emerging or resurging as a result of changes in public health policy, insecticide and drug resistance, shift in emphasis from prevention to emergency response, demographic and societal changes, and genetic changes in pathogens. Effective prevention strategies can reverse this trend. Research on vaccines, environmentally safe insecticides, alternative approaches to vector control, and training programs for health-care workers are needed. PMID:9716967

  14. Nonperturbative Ambiguities and the Reality of Resurgent Transseries

    NASA Astrophysics Data System (ADS)

    Aniceto, Inês; Schiappa, Ricardo

    2015-04-01

    In a wide range of quantum theoretical settings—from quantum mechanics to quantum field theory, from gauge theory to string theory—singularities in the complex Borel plane, usually associated to instantons or renormalons, render perturbation theory ill-defined as they give rise to nonperturbative ambiguities. These ambiguities are associated to choices of an integration contour in the resummation of perturbation theory, along (singular) Stokes directions in the complex Borel plane (rendering perturbative expansions non-Borel summable along any Stokes line). More recently, it has been shown that the proper framework to address these issues is that of resurgent analysis and transseries. In this context, the cancelation of all nonperturbative ambiguities is shown to be a consequence of choosing the transseries median resummation as the appropriate family of unambiguous real solutions along the coupling-constant real axis. While the median resummation is easily implemented for one-parameter transseries, once one considers more general multi-parameter transseries the procedure becomes highly dependent upon properly understanding Stokes transitions in the complex Borel plane. In particular, all Stokes coefficients must now be known in order to explicitly implement multi-parameter median resummations. In the cases where quantum-theoretical physical observables are described by resurgent functions and transseries, the methods described herein show how one may cancel nonperturbative ambiguities, and define these observables nonperturbatively starting out from perturbation theory. Along the way, structural results concerning resurgent transseries are also obtained.

  15. Potassium channelopathy-like defect underlies early-stage cerebrovascular dysfunction in a genetic model of small vessel disease

    PubMed Central

    Dabertrand, Fabrice; Krøigaard, Christel; Bonev, Adrian D.; Cognat, Emmanuel; Dalsgaard, Thomas; Domenga-Denier, Valérie; Hill-Eubanks, David C.; Brayden, Joseph E.; Joutel, Anne; Nelson, Mark T.

    2015-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by dominant mutations in the NOTCH3 receptor in vascular smooth muscle, is a genetic paradigm of small vessel disease (SVD) of the brain. Recent studies using transgenic (Tg)Notch3R169C mice, a genetic model of CADASIL, revealed functional defects in cerebral (pial) arteries on the surface of the brain at an early stage of disease progression. Here, using parenchymal arterioles (PAs) from within the brain, we determined the molecular mechanism underlying the early functional deficits associated with this Notch3 mutation. At physiological pressure (40 mmHg), smooth muscle membrane potential depolarization and constriction to pressure (myogenic tone) were blunted in PAs from TgNotch3R169C mice. This effect was associated with an ∼60% increase in the number of voltage-gated potassium (KV) channels, which oppose pressure-induced depolarization. Inhibition of KV1 channels with 4-aminopyridine (4-AP) or treatment with the epidermal growth factor receptor agonist heparin-binding EGF (HB-EGF), which promotes KV1 channel endocytosis, reduced KV current density and restored myogenic responses in PAs from TgNotch3R169C mice, whereas pharmacological inhibition of other major vasodilatory influences had no effect. KV1 currents and myogenic responses were similarly altered in pial arteries from TgNotch3R169C mice, but not in mesenteric arteries. Interestingly, HB-EGF had no effect on mesenteric arteries, suggesting a possible mechanistic basis for the exclusive cerebrovascular manifestation of CADASIL. Collectively, our results indicate that increasing the number of KV1 channels in cerebral smooth muscle produces a mutant vascular phenotype akin to a channelopathy in a genetic model of SVD. PMID:25646445

  16. On the resurgent population and food debate.

    PubMed

    Johnson, D G

    1997-03-01

    During the 1980s, the European Union, the US, and Japan followed policies designed to limit the production of grain. In so doing, the production and stock of grain declined during the decade in developed countries. However, grain production increased in developing countries during the 1980s, causing the overall world supply of grain to grow faster than demand. International market prices for grain have been falling since the 1970s. Despite claims to the contrary, reputable studies of prospective food supply and demand indicate that there will be continued improvement in per capita food consumption, especially in the developing countries. It is highly unlikely that the factors which affect world food supply and demand can either stop the decline in real market prices for grain or result in more than a modest increase in world grain trade. While China may become a major grain importer, central and eastern Europe may become major net grain exporters who compete with traditional exporters. The likely future trend in real world grain prices is good news for urban consumers, but farmers in developing countries will have to continually adjust to the eroding prices of their product. The author discusses population and well-being since Malthus' first edition, the population growth rate as an unimportant factor in determining population well-being, negative population growth rates, recent world food developments, prospects for the future supply and demand of food, and implications for world trade. PMID:12348535

  17. Defining long-term drivers of pertussis resurgence, and optimal vaccine control strategies.

    PubMed

    Campbell, Patricia Therese; McCaw, James Matthew; McIntyre, Peter; McVernon, Jodie

    2015-10-26

    Pertussis resurgence has been reported from several developed countries with long-standing immunisation programs. Among these, Australia in 2003 discontinued an 18 months (fourth) booster dose in favour of an adolescent (fifth) dose. We developed a model to evaluate determinants of resurgence in Australia and alternative vaccine strategies for mitigation. Novel characteristics of our model included the use of seroepidemiologic data for calibration, and broad investigation of variables relevant to transmission of, and protection against, pertussis. We simulated multiple parameter combinations, retaining those consistent with observed data for subsequent use in predictive models comparing alternative vaccination schedules. Reproducing the early control of pertussis followed by late resurgence observed in Australia required natural immunity to last decades longer than vaccine-acquired immunity, with mean duration exceeding 50 years in almost 90% of simulations. Replacement of the dose at 18 months with an adolescent dose in 2003 resulted in a 40% increase in infections in the age group 18-47 months by 2013. A six dose strategy (2, 4, 6, 18 months, 4 and 15 years) yielded a reduction in infection incidence (pre-school 43%, infants 8%) greater than any alternative strategies considered for timing of five administered doses. Our finding that natural immunity drives long-term trends in pertussis cycles is relevant to a range of pertussis strategies and provides the necessary context in which to consider maternal vaccination. Comparatively short-lived vaccine-acquired immunity requires multiple boosters over the first two decades of life to maximise reduction in infections. PMID:26392008

  18. Carotid body overactivity induces respiratory neurone channelopathy contributing to neurogenic hypertension.

    PubMed

    Moraes, Davi J A; Machado, Benedito H; Paton, Julian F R

    2015-07-15

    Why sympathetic activity rises in neurogenic hypertension remains unknown. It has been postulated that changes in the electrical excitability of medullary pre-sympathetic neurones are the main causal mechanism for the development of sympathetic overactivity in experimental hypertension. Here we review recent data suggesting that enhanced sympathetic activity in neurogenic hypertension is, at least in part, dependent on alterations in the electrical excitability of medullary respiratory neurones and their central modulation of sympatho-excitatory networks. We also present results showing a critical role for carotid body tonicity in the aetiology of enhanced central respiratory modulation of sympathetic activity in neurogenic hypertension. We propose a novel hypothesis of respiratory neurone channelopathy induced by carotid body overactivity in neurogenic hypertension that may contribute to sympathetic excess. Moreover, our data support the notion of targeting the carotid body as a potential novel therapeutic approach for reducing sympathetic vasomotor tone in neurogenic hypertension. PMID:25900825

  19. Calcium channelopathies and Alzheimer's disease: insight into therapeutic success and failures.

    PubMed

    Chakroborty, Shreaya; Stutzmann, Grace E

    2014-09-15

    Calcium ions are versatile and universal biological signaling factors that regulate numerous cellular processes ranging from cell fertilization, to neuronal plasticity that underlies learning and memory, to cell death. For these functions to be properly executed, calcium signaling requires precise regulation, and failure of this regulation may tip the scales from a signal for life to a signal for death. Disruptions in calcium channel function can generate complex multi-system disorders collectively referred to as "calciumopathies" that can target essentially any cell type or organ. In this review, we focus on the multifaceted involvement of calcium signaling in the pathophysiology of Alzheimer's disease (AD), and summarize the various therapeutic options currently available to combat this disease. Detailing the series of disappointing AD clinical trial results on cognitive outcomes, we emphasize the urgency to design alternative therapeutic strategies if synaptic and memory functions are to be preserved. One such approach is to target early calcium channelopathies centrally linked to AD pathogenesis. PMID:24316360

  20. Autism-Associated SHANK3 Haploinsufficiency Causes Ih-Channelopathy in Human Neurons

    PubMed Central

    Yi, Fei; Danko, Tamas; Botelho, Salome Calado; Patzke, Christopher; Pak, ChangHui; Wernig, Marius; Südhof, Thomas C.

    2016-01-01

    Heterozygous SHANK3 mutations are associated with idiopathic autism and Phelan-McDermid syndrome. SHANK3 is a ubiquitously expressed scaffolding protein that is enriched in postsynaptic excitatory synapses. Here we used engineered conditional mutations in human neurons to show that heterozygous and homozygous SHANK3 mutations severely and specifically impair Ih-channels. SHANK3 mutations caused alterations in neuronal morphology and synaptic connectivity; chronic pharmacological blockage of Ih-channels reproduced these phenotypes, suggesting they may be secondary to Ih-channel impairment. Moreover, mouse Shank3-deficient neurons also exhibited severe decreases in Ih-currents. SHANK3 protein interacted with hyperpolarization-activated cyclic nucleotide-gated channel proteins (HCN proteins) forming Ih-channels, indicating that SHANK3 functions to organize HCN-channels. Our data suggest SHANK3 mutations predispose to autism, at least partially, by inducing an Ih-channelopathy that may be amenable to pharmacological intervention. PMID:26966193

  1. Autism-associated SHANK3 haploinsufficiency causes Ih channelopathy in human neurons.

    PubMed

    Yi, Fei; Danko, Tamas; Botelho, Salome Calado; Patzke, Christopher; Pak, ChangHui; Wernig, Marius; Südhof, Thomas C

    2016-05-01

    Heterozygous SHANK3 mutations are associated with idiopathic autism and Phelan-McDermid syndrome. SHANK3 is a ubiquitously expressed scaffolding protein that is enriched in postsynaptic excitatory synapses. Here, we used engineered conditional mutations in human neurons and found that heterozygous and homozygous SHANK3 mutations severely and specifically impaired hyperpolarization-activated cation (Ih) channels. SHANK3 mutations caused alterations in neuronal morphology and synaptic connectivity; chronic pharmacological blockage of Ih channels reproduced these phenotypes, suggesting that they may be secondary to Ih-channel impairment. Moreover, mouse Shank3-deficient neurons also exhibited severe decreases in Ih currents. SHANK3 protein interacted with hyperpolarization-activated cyclic nucleotide-gated channel proteins (HCN proteins) that form Ih channels, indicating that SHANK3 functions to organize HCN channels. Our data suggest that SHANK3 mutations predispose to autism, at least partially, by inducing an Ih channelopathy that may be amenable to pharmacological intervention. PMID:26966193

  2. Secondary neurotransmitter deficiencies in epilepsy caused by voltage-gated sodium channelopathies: A potential treatment target?

    PubMed

    Horvath, Gabriella A; Demos, Michelle; Shyr, Casper; Matthews, Allison; Zhang, Linhua; Race, Simone; Stockler-Ipsiroglu, Sylvia; Van Allen, Margot I; Mancarci, Ogan; Toker, Lilah; Pavlidis, Paul; Ross, Colin J; Wasserman, Wyeth W; Trump, Natalie; Heales, Simon; Pope, Simon; Cross, J Helen; van Karnebeek, Clara D M

    2016-01-01

    We describe neurotransmitter abnormalities in two patients with drug-resistant epilepsy resulting from deleterious de novo mutations in sodium channel genes. Whole exome sequencing identified a de novo SCN2A splice-site mutation (c.2379+1G>A, p.Glu717Gly.fs*30) resulting in deletion of exon 14, in a 10-year old male with early onset global developmental delay, intermittent ataxia, autism, hypotonia, epileptic encephalopathy and cerebral/cerebellar atrophy. In the cerebrospinal fluid both homovanillic acid and 5-hydroxyindoleacetic acid were significantly decreased; extensive biochemical and genetic investigations ruled out primary neurotransmitter deficiencies and other known inborn errors of metabolism. In an 8-year old female with an early onset intractable epileptic encephalopathy, developmental regression, and progressive cerebellar atrophy, a previously unreported de novo missense mutation was identified in SCN8A (c.5615G>A; p.Arg1872Gln), affecting a highly conserved residue located in the C-terminal of the Nav1.6 protein. Aside from decreased homovanillic acid and 5-hydroxyindoleacetic acid, 5-methyltetrahydrofolate was also found to be low. We hypothesize that these channelopathies cause abnormal synaptic mono-amine metabolite secretion/uptake via impaired vesicular release and imbalance in electrochemical ion gradients, which in turn aggravate the seizures. Treatment with oral 5-hydroxytryptophan, l-Dopa/Carbidopa, and a dopa agonist resulted in mild improvement of seizure control in the male case, most likely via dopamine and serotonin receptor activated signal transduction and modulation of glutamatergic, GABA-ergic and glycinergic neurotransmission. Neurotransmitter analysis in other sodium channelopathy patients will help validate our findings, potentially yielding novel treatment opportunities. PMID:26647175

  3. MLC1 protein: a likely link between leukodystrophies and brain channelopathies

    PubMed Central

    Brignone, Maria S.; Lanciotti, Angela; Camerini, Serena; De Nuccio, Chiara; Petrucci, Tamara C.; Visentin, Sergio; Ambrosini, Elena

    2015-01-01

    Megalencephalic leukoencephalopathy with subcortical cysts (MLCs) disease is a rare inherited, autosomal recessive form of childhood-onset spongiform leukodystrophy characterized by macrocephaly, deterioration of motor functions, epileptic seizures and mental decline. Brain edema, subcortical fluid cysts, myelin and astrocyte vacuolation are the histopathological hallmarks of MLC. Mutations in either the MLC1 gene (>75% of patients) or the GlialCAM gene (<20% of patients) are responsible for the disease. Recently, the GlialCAM adhesion protein was found essential for the membrane expression and function of the chloride channel ClC-2 indicating MLC disease caused by mutation in GlialCAM as the first channelopathy among leukodystrophies. On the contrary, the function of MLC1 protein, which binds GlialCAM, its functional relationship with ClC-2 and the molecular mechanisms underlying MLC1 mutation-induced functional defects are not fully understood yet. The human MLC1 gene encodes a 377-amino acid membrane protein with eight predicted transmembrane domains which shows very low homology with voltage-dependent potassium (K+) channel subunits. The high expression of MLC1 in brain astrocytes contacting blood vessels and meninges and brain alterations observed in MLC patients have led to hypothesize a role for MLC1 in the regulation of ion and water homeostasis. Recent studies have shown that MLC1 establishes structural and/or functional interactions with several ion/water channels and transporters and ion channel accessory proteins, and that these interactions are affected by MLC1 mutations causing MLC. Here, we review data on MLC1 functional properties obtained in in vitro and in vivo models and discuss evidence linking the effects of MLC1 mutations to brain channelopathies. PMID:25883547

  4. Historical Earthquakes and Expected Seismic Damage at Ischia Island, Resurgent Caldera (Southern Italy)

    NASA Astrophysics Data System (ADS)

    Carlino, S.; Cubellis, E.

    2005-05-01

    Information on the seismicity of the Ischia island spans about eight centuries, starting from 1228. This is characterized by the occurence of earthquakes with low energy and high intensity. The most recent earthquake of 1883 caused 2333 deaths and the destruction of the historical and environmental heritage of some areas of the island, specially at Casamicciola town. This event (Imax = XI degree MCS), represents an important date in the prevention of natural disasters, in that it was after this earthquake that the first Seismic Safety Act in Italy was passed. After the 1883 earthquake there was a period of seismic quiescence except for some isolated events felt at beginning of the last century and the very occasional micro-earthquakes recorded in the last 20 years in the northern part of the island. The epicenter of all known earthquakes are on the northern slope of Mt. Epomeo (787 m a. s.l.) resurgent block, while analysis of the effects of earthquakes and the geological structures allows us to evaluate the stress fields that generate the earthquakes. The Mt. Epomeo is a resurgent structure in the central sector of the island, whose uplift is correlated to the caldera resurgence process, for the increase of pressure of shallow magma reservoir. The caldera was formed after a large explosive eruption that deposited the Mt. Epomeo Green Tuff, about 55 ka B.P. The uplift, which started about 30 ka B.P., was of about 900 meters. The resurgent structure is bordered by a system of faults and fractures, with NW-SE, NE-SW and N-S strike and along these faults, in the northern sector, the seismicity has been localized. In a volcanic area, interpretation of the mechanisms of release and propagation of seismic energy is made even more complex as the stress field that acts at a regional level is compounded by that generated from migration of magmatic masses towards the surface, as well as the rheologic properties of the rocks dependent on the high geothermic gradient. Such

  5. Metal-metalloporphyrin frameworks: a resurging class of functional materials.

    PubMed

    Gao, Wen-Yang; Chrzanowski, Matthew; Ma, Shengqian

    2014-08-21

    This review presents comprehensively recent progress in metal-metalloporphyrin frameworks (MMPFs) with an emphasis on versatile functionalities. Following a brief introduction of basic concepts and the potential virtues of MMPFs, we give a snapshot of the historical perspective of MMPFs since 1991. We then summarize four effective strategies implemented frequently to construct prototypal MMPFs. MMPFs represent a resurging class of promising functional materials, highlighted with diverse applications including guest-molecule adsorption and separation, catalysis, nano-thin films and light-harvesting. PMID:24676096

  6. [Measles, mumps, and rubella vaccine. Resurgence of measles in Europe].

    PubMed

    Garcés-Sánchez, María; Renales-Toboso, María; Bóveda-García, María; Díez-Domingo, Javier

    2015-12-01

    Measles is a rash illness of moderate severity and high risk of serious complications, with recovery in several weeks. It is a viral disease caused by one of the most infectious and contagious pathogens that exists, whose only known reservoir is human. In 1998, the European Region of the WHO set a target of eliminating measles by 2010. This goal has not been achieved. Furthermore, it has been observed the resurgence of the disease in some parts of Europe. We review the disease and its vaccines as well as the epidemiological and social factors that have so far prevented the total control of the disease. PMID:26611100

  7. Hydrodynamics Beyond the Gradient Expansion: Resurgence and Resummation

    NASA Astrophysics Data System (ADS)

    Heller, Michal P.; Spaliński, Michał

    2015-08-01

    Consistent formulations of relativistic viscous hydrodynamics involve short-lived modes, leading to asymptotic rather than convergent gradient expansions. In this Letter we consider the Müller-Israel-Stewart theory applied to a longitudinally expanding quark-gluon plasma system and identify hydrodynamics as a universal attractor without invoking the gradient expansion. We give strong evidence for the existence of this attractor and then show that it can be recovered from the divergent gradient expansion by Borel summation. This requires careful accounting for the short-lived modes which leads to an intricate mathematical structure known from the theory of resurgence.

  8. Hydrodynamics Beyond the Gradient Expansion: Resurgence and Resummation.

    PubMed

    Heller, Michal P; Spaliński, Michał

    2015-08-14

    Consistent formulations of relativistic viscous hydrodynamics involve short-lived modes, leading to asymptotic rather than convergent gradient expansions. In this Letter we consider the Müller-Israel-Stewart theory applied to a longitudinally expanding quark-gluon plasma system and identify hydrodynamics as a universal attractor without invoking the gradient expansion. We give strong evidence for the existence of this attractor and then show that it can be recovered from the divergent gradient expansion by Borel summation. This requires careful accounting for the short-lived modes which leads to an intricate mathematical structure known from the theory of resurgence. PMID:26317715

  9. Resurgence of emerald shiners Notropis atherinoides in Lake Huron's main basin

    USGS Publications Warehouse

    Schaeffer, J.S.; Warner, D.M.; O'Brien, T. P.

    2008-01-01

    Emerald shiners Notropis atherinoides were formerly common in Lakes Huron and Michigan, but declined during the 1960s as the exotic alewife Alosa pseudoharengus proliferated. The Lake Huron emerald shiner population was chronically depressed through 2004; however, we detected resurgence in emerald shiner density and biomass in Lake Huron during acoustic and midwater trawl surveys conducted during 2004-2006. Emerald shiners were not found during 2004, but by 2006 main basin density exceeded 500 fish/ha, biomass estimates exceeded 0.5 kg/ha, and emerald shiners contributed more to pelagic biomass than alewives or rainbow smelt Osmerus mordax. Length frequency distributions suggested that increased density was the result of two consecutive strong year classes in 2005 and 2006. Emerald shiner distributions also expanded from a focus in western Lake Huron in 2005 to a lakewide distribution in 2006. Emerald shiners occurred offshore, but were nearly always associated with epilimnetic surface waters warmer than 19??C. Resurgence of emerald shiners was likely a consequence of reduced alewife abundance, as they declined concurrently with alewife proliferation during the early 1960s. Return of this species may benefit native nearshore piscivores; however, benefits to Pacific salmonids Oncorhynchus spp. are uncertain because emerald shiners are smaller and still less abundant than historically important prey species, and they may be thermally segregated from salmonines.

  10. Resurgence of Sucrose and Cocaine Seeking in Free-Feeding Rats

    PubMed Central

    Shahan, Timothy A.; Craig, Andrew R.; Sweeney, Mary M.

    2014-01-01

    Resurgence is relapse of an extinguished operant response following the removal of alternative reinforcement. In animal models of resurgence to date, rats have been food deprived and food is used as the source of alternative reinforcement. Thus, when the alternative reinforcer is removed, the only remaining source of food during experimental sessions is no longer available. Acute food deprivation is known to produce reinstatement of drug seeking, thus such deprivation has been suggested a potential mechanism of resurgence. The present experiments examined whether resurgence of sucrose and cocaine seeking could be obtained with rats that were not food deprived. Free feeding rats were trained to press a lever for either sucrose (Exp 1) or cocaine infusions (Exp 2). Next, lever pressing was extinguished and an alternative response (nose poking) was reinforced with sucrose. When nose poking was also placed on extinction, resurgence of both sucrose and cocaine seeking were observed. Thus, resurgence of both sucrose and cocaine seeking can be obtained in rats that are not food restricted and it appears unlikely that an acute hunger state is responsible for resurgence. In addition, the present procedures for studying resurgence in the absence of interpretive complexities introduced by the use of food-deprivation may prove useful for further investigations of the neurobiological mechanisms of resurgence. PMID:25446761

  11. Resurgence in η-deformed Principal Chiral Models

    NASA Astrophysics Data System (ADS)

    Demulder, Saskia; Dorigoni, Daniele; Thompson, Daniel C.

    2016-07-01

    We study the SU(2) Principal Chiral Model (PCM) in the presence of an integrable η-deformation. We put the theory on {R}× {S}^1 with twisted boundary conditions and then reduce the circle to obtain an effective quantum mechanics associated with the Whittaker-Hill equation. Using resurgent analysis we study the large order behaviour of perturbation theory and recover the fracton events responsible for IR renormalons. The fractons are modified from the standard PCM due to the presence of this η-deformation but they are still the constituents of uniton-like solutions in the deformed quantum field theory. We also find novel SL(2,{C}) saddles, thus strengthening the conjecture that the semi-classical expansion of the path integral gives rise to a resurgent transseries once written as a sum over Lefschetz thimbles living in a complexification of the field space. We conclude by connecting our quantum mechanics to a massive deformation of the {N} = 2 4-d gauge theory with gauge group SU(2) and N f = 2.

  12. Higher rate alternative non-drug reinforcement produces faster suppression of cocaine seeking but more resurgence when removed.

    PubMed

    Craig, Andrew R; Nall, Rusty W; Madden, Gregory J; Shahan, Timothy A

    2016-06-01

    Relapse following removal of an alternative source of reinforcement introduced during extinction of a target behavior is called resurgence. This form of relapse may be related to relapse of drug taking following loss of alternative non-drug reinforcement in human populations. Laboratory investigations of factors mediating resurgence with food-maintained behavior suggest higher rates of alternative reinforcement produce faster suppression of target behavior but paradoxically generate more relapse when alternative reinforcement is discontinued. At present, it is unknown if a similar effect occurs when target behavior is maintained by drug reinforcement and the alternative is a non-drug reinforcer. In the present experiment three groups of rats were trained to lever press for infusions of cocaine during baseline. Next, during treatment, cocaine reinforcement was suspended and an alternative response was reinforced with either high-rate, low-rate, or no alternative food reinforcement. Finally, all reinforcement was suspended to test for relapse of cocaine seeking. Higher rate alternative reinforcement produced faster elimination of cocaine seeking than lower rates or extinction alone, but when treatment was suspended resurgence of cocaine seeking occurred following only high-rate alternative reinforcement. Thus, although higher rate alternative reinforcement appears to more effectively suppress drug seeking, should it become unavailable, it can have the unfortunate effect of increasing relapse. PMID:26988268

  13. Comparison of clast frequency and size in the resurge deposits at the Chesapeake Bay impact structure (Eyreville A and Langley cores): Clues to the resurge process

    USGS Publications Warehouse

    Ormo, J.; Sturkell, E.; Horton, J.W., Jr.; Powars, D.S.; Edwards, L.E.

    2009-01-01

    Collapse and inward slumping of unconsolidated sedimentary strata expanded the Chesapeake Bay impact structure far beyond its central basement crater. During crater collapse, sediment-loaded water surged back to fill the crater. Here, we analyze clast frequency and granulometry of these resurge deposits in one core hole from the outermost part of the collapsed zone (i.e., Langley) as well as a core hole from the moat of the basement crater (i.e., Eyreville A). Comparisons of clast provenance and flow dynamics show that at both locations, there is a clear change in clast frequency and size between a lower unit, which we interpret to be dominated by slumped material, and an upper, water-transported unit, i.e., resurge deposit. The contribution of material to the resurge deposit was primarily controlled by stripping and erosion. This includes entrainment of fallback ejecta and sediments eroded from the surrounding seafloor, found to be dominant at Langley, and slumped material that covered the annular trough and basement crater, found to be dominant at Eyreville. Eyreville shows a higher content of crystalline clasts than Langley. There is equivocal evidence for an anti-resurge from a collapsing central water plume or, alternatively, a second resurge pulse, as well as a transition into oscillating resurge. The resurge material shows more of a debris-flow-like transport compared to resurge deposits at some other marine target craters, where the ratio of sediment to water has been relatively low. This result is likely a consequence of the combination of easily disaggregated host sediments and a relatively shallow target water depth. ?? 2009 The Geological Society of America.

  14. Some Factors Modulating the Strength of Resurgence after Extinction of an Instrumental Behavior

    ERIC Educational Resources Information Center

    Winterbauer, Neil E.; Lucke, Sara; Bouton, Mark E.

    2013-01-01

    In resurgence, an operant behavior that has undergone extinction can return ("resurge") when a second operant that has replaced it itself undergoes extinction. The phenomenon may provide insight into relapse that may occur after incentive or contingency management therapies in humans. Three experiments with rats examined the impact of several…

  15. Case for resurgence of radical perineal prostatecomy in Indian subcontinent

    PubMed Central

    Sood, Rajeev; Khattar, Nikhil; Nayyar, Rishi; Kathuria, Sachin; Narang, Vineet; Kaushal, Devashish

    2012-01-01

    Introduction: Radical perineal prostatectomy was the first surgery described for prostatic carcinoma (Young, 1904) but it lost its eminent status after Walsh's description in 1982 of anatomic radical retropubic prostatectomy followed by the enthusiasm in laparoscopy and now robotics. It made resurgence after it was realized in early 1990s that the pelvic lymph node dissection is needed only in selected cases. Last decade witnessed over 80 publications addressing the results and advances in the perineal approach. Strangely, centres from the subcontinent have chosen to ignore this resurgence. We describe our early experience with the technique in 35 patients and present the case for its more widespread usage. Patients and Methods: Thirty five patients of clinically localized carcinoma prostate were operated by perineal route in our institution from December 2006 onwards. All patients had serum prostate specific antigen levels less than 10 ng/ml. Results: Operating time was 2 to 3.5 hours (mean 2.5 hours). Rectal injury occurred in three patients but was closed primarily in all and none required a colostomy. Mean duration of hospital stay was four days. The disease was organ confined in 25(71%). Positive margins were seen in 5(14%) patients. Biochemical recurrence occurred in 17% patients at one year. Seventy six percent patients had achieved continence at one year. Conclusions: As the world is taking note of radical perineal prostatectomy again, with a very small learning curve, minimal invasion and good oncological control urologists from Indian subcontinent should also embrace this procedure in view of the relative limited resources available. PMID:23449760

  16. Resurgent malaria at the millennium: control strategies in crisis.

    PubMed

    Baird, J K

    2000-04-01

    Completion of the Panama Canal in 1914 marked the beginning of an era of vector control that achieved conspicuous success against malaria. In 1955 the World Health Organization (WHO) adopted the controversial Global Eradication Campaign emphasising DDT (dichlorodiphenyltrichloroethane) spraying in homes. The incidence of malaria fell sharply where the programme was implemented, but the strategy was not applied in holoendemic Africa. This, along with the failure to achieve eradication in larger tropical regions, contributed to disillusionment with the policy. The World Health Assembly abandoned the eradication strategy in 1969. A resurgence of malaria began at about that time and today reaches into areas where eradication or control had been achieved. A global malaria crisis looms. In 1993 the WHO adopted a Global Malaria Control Strategy that placed priority in control of disease rather than infection. This formalises a policy that emphasises diagnosis and treatment in a primary healthcare setting, while de-emphasising spraying of residual insecticides. The new policy explicitly stresses malaria in Africa, but expresses the intent to bring control programmes around the world into line with the strategy. This review raises the argument that a global control strategy conceived to address the extraordinary malaria situation in Africa may not be suitable elsewhere. The basis of argument lies in the accomplishments of the Global Eradication Campaign viewed in an historical and geographical context. Resurgent malaria accompanying declining vector control activities in Asia and the Americas suggests that the abandonment of residual spraying may be premature given the tools now at hand. The inadequacy of vector control as the primary instrument of malaria control in holoendemic Africa does not preclude its utility in Asia and the Americas. PMID:10804031

  17. Early malaria resurgence in pre-elimination areas in Kokap Subdistrict, Kulon Progo, Indonesia

    PubMed Central

    2014-01-01

    Background Indonesia is among those countries committed to malaria eradication, with a continuously decreasing incidence of malaria. However, at district level the situation is different. This study presents a case of malaria resurgence Kokap Subdistrict of the Kulon Progo District in Yogyakarta Province, Java after five years of low endemicity. This study also aims to describe the community perceptions and health services delivery situation that contribute to this case. Methods All malaria cases (2007–2011) in Kulon Progo District were stratified to annual parasite incidence (API). Two-hundred and twenty-six cases during an outbreak (May 2011 to April 2012) were geocoded by household addresses using a geographic information system (GIS) technique and clusters were identified by SaTScan software analysis (Arc GIS 10.1). Purposive random sampling was conducted on respondents living inside the clusters to identify community perceptions and behaviour related to malaria. Interviews were conducted with malaria health officers to understand the challenges of malaria surveillance and control. Results After experiencing three consecutive years with API less than 1 per thousand, malaria in Kokap subdistrict increased almost ten times higher than API in the district level and five times higher than national API. Malaria cases were found in all five villages in 2012. One primary and two secondary malaria clusters in Hargotirto and Kalirejo villages were identified during the 2011–2012 outbreak. Most of the respondents were positively aware with malaria signs and activities of health workers to prevent malaria, although some social economic activities could not be hindered. Return transmigrants or migrant workers entering to their villages, reduced numbers of village malaria workers and a surge in malaria cases in the neighbouring district contributed to the resurgence. Conclusion Community perception, awareness and participation could constitute a solid foundation for

  18. Effects of reinforcer distribution during response elimination on resurgence of an instrumental behavior.

    PubMed

    Schepers, Scott T; Bouton, Mark E

    2015-04-01

    Resurgence has commonly been viewed as the recovery of an extinguished instrumental behavior that occurs when an alternative behavior that has replaced it is also extinguished. Three experiments with rat subjects examined the effects on resurgence of the temporal distribution of reinforcement for the alternative behavior that is presented while the first response is being eliminated. Experiments 1 and 2 examined resurgence when rich rates of reinforcement at the onset of response elimination became leaner over sessions (i.e., forward thinning) and when lean rates became richer (i.e., reverse thinning). Both procedures weakened resurgence compared with that in a group that received the richest rate during all sessions. However, forward thinning was more effective than reverse thinning at reducing the resurgence effect. Experiment 3 found that final resurgence was eliminated when the alternative behavior was reinforced and extinguished in alternating response elimination sessions. The results are consistent with the hypothesis that reinforcer delivery during response elimination provides a contextual stimulus for the extinction of the original behavior; its removal during resurgence testing causes ABC renewal to occur. The results are less consistent with an alternative account that emphasizes the removal of response disruption caused by alternative reinforcement (Shahan & Sweeney, 2011). Other theoretical and applied implications are discussed. PMID:25798714

  19. Canine CNGA3 Gene Mutations Provide Novel Insights into Human Achromatopsia-Associated Channelopathies and Treatment.

    PubMed

    Tanaka, Naoto; Dutrow, Emily V; Miyadera, Keiko; Delemotte, Lucie; MacDermaid, Christopher M; Reinstein, Shelby L; Crumley, William R; Dixon, Christopher J; Casal, Margret L; Klein, Michael L; Aguirre, Gustavo D; Tanaka, Jacqueline C; Guziewicz, Karina E

    2015-01-01

    Cyclic nucleotide-gated (CNG) ion channels are key mediators underlying signal transduction in retinal and olfactory receptors. Genetic defects in CNGA3 and CNGB3, encoding two structurally related subunits of cone CNG channels, lead to achromatopsia (ACHM). ACHM is a congenital, autosomal recessive retinal disorder that manifests by cone photoreceptor dysfunction, severely reduced visual acuity, impaired or complete color blindness and photophobia. Here, we report the first canine models for CNGA3-associated channelopathy caused by R424W or V644del mutations in the canine CNGA3 ortholog that accurately mimic the clinical and molecular features of human CNGA3-associated ACHM. These two spontaneous mutations exposed CNGA3 residues essential for the preservation of channel function and biogenesis. The CNGA3-R424W results in complete loss of cone function in vivo and channel activity confirmed by in vitro electrophysiology. Structural modeling and molecular dynamics (MD) simulations revealed R424-E306 salt bridge formation and its disruption with the R424W mutant. Reversal of charges in a CNGA3-R424E-E306R double mutant channel rescued cGMP-activated currents uncovering new insights into channel gating. The CNGA3-V644del affects the C-terminal leucine zipper (CLZ) domain destabilizing intersubunit interactions of the coiled-coil complex in the MD simulations; the in vitro experiments showed incompetent trimeric CNGA3 subunit assembly consistent with abnormal biogenesis of in vivo channels. These newly characterized large animal models not only provide a valuable system for studying cone-specific CNG channel function in health and disease, but also represent prime candidates for proof-of-concept studies of CNGA3 gene replacement therapy for ACHM patients. PMID:26407004

  20. Canine CNGA3 Gene Mutations Provide Novel Insights into Human Achromatopsia-Associated Channelopathies and Treatment

    PubMed Central

    Miyadera, Keiko; Delemotte, Lucie; MacDermaid, Christopher M.; Reinstein, Shelby L.; Crumley, William R.; Dixon, Christopher J.; Casal, Margret L.; Klein, Michael L.; Aguirre, Gustavo D.; Tanaka, Jacqueline C.; Guziewicz, Karina E.

    2015-01-01

    Cyclic nucleotide-gated (CNG) ion channels are key mediators underlying signal transduction in retinal and olfactory receptors. Genetic defects in CNGA3 and CNGB3, encoding two structurally related subunits of cone CNG channels, lead to achromatopsia (ACHM). ACHM is a congenital, autosomal recessive retinal disorder that manifests by cone photoreceptor dysfunction, severely reduced visual acuity, impaired or complete color blindness and photophobia. Here, we report the first canine models for CNGA3-associated channelopathy caused by R424W or V644del mutations in the canine CNGA3 ortholog that accurately mimic the clinical and molecular features of human CNGA3-associated ACHM. These two spontaneous mutations exposed CNGA3 residues essential for the preservation of channel function and biogenesis. The CNGA3-R424W results in complete loss of cone function in vivo and channel activity confirmed by in vitro electrophysiology. Structural modeling and molecular dynamics (MD) simulations revealed R424-E306 salt bridge formation and its disruption with the R424W mutant. Reversal of charges in a CNGA3-R424E-E306R double mutant channel rescued cGMP-activated currents uncovering new insights into channel gating. The CNGA3-V644del affects the C-terminal leucine zipper (CLZ) domain destabilizing intersubunit interactions of the coiled-coil complex in the MD simulations; the in vitro experiments showed incompetent trimeric CNGA3 subunit assembly consistent with abnormal biogenesis of in vivo channels. These newly characterized large animal models not only provide a valuable system for studying cone-specific CNG channel function in health and disease, but also represent prime candidates for proof-of-concept studies of CNGA3 gene replacement therapy for ACHM patients. PMID:26407004

  1. Genetic purgatory and the cardiac channelopathies: Exposing the variants of uncertain/unknown significance issue.

    PubMed

    Ackerman, Michael J

    2015-11-01

    Merriam-Webster's online dictionary defines purgatory as "an intermediate state after death for expiatory purification" or more specifically as "a place or state of punishment wherein according to Roman Catholic doctrine the souls of those who die in God׳s grace may make satisfaction for past sins and so become fit for heaven." Alternatively, it is defined as "a place or state of temporary suffering or misery." Either way, purgatory is a place where you are stuck, and you don't want to be stuck there. It is in this context that the term genetic purgatory is introduced. Genetic purgatory is a place where the genetic test-ordering physician and patients and their families are stuck when a variant of uncertain/unknown significance (VUS) has been elucidated. It is in this dark place where suffering and misery are occurring because of unenlightened handling of a VUS, which includes using the VUS for predictive genetic testing and making radical treatment recommendations based on the presence or absence of a so-called maybe mutation. Before one can escape from this miserable place, one must first recognize that one is stuck there. Hence, the purpose of this review article is to fully expose the VUS issue as it relates to the cardiac channelopathies and make the cardiologists/geneticists/genetic counselors who order such genetic tests believers in genetic purgatory. Only then can one meaningfully attempt to get out of that place and seek to promote a VUS to disease-causative mutation status or demote it to an utterly innocuous and irrelevant variant. PMID:26144349

  2. Ideology: Its Resurgence in Social, Personality, and Political Psychology.

    PubMed

    Jost, John T; Nosek, Brian A; Gosling, Samuel D

    2008-03-01

    We trace the rise, fall, and resurgence of political ideology as a topic of research in social, personality, and political psychology. For over 200 years, political belief systems have been classified usefully according to a single left-right (or liberal-conservative) dimension that, we believe, possesses two core aspects: (a) advocating versus resisting social change and (b) rejecting versus accepting inequality. There have been many skeptics of the notion that most people are ideologically inclined, but recent psychological evidence suggests that left-right differences are pronounced in many life domains. Implicit as well as explicit preferences for tradition, conformity, order, stability, traditional values, and hierarchy-versus those for progress, rebelliousness, chaos, flexibility, feminism, and equality-are associated with conservatism and liberalism, respectively. Conservatives score consistently higher than liberals on measures of system justification. Furthermore, there are personality and lifestyle differences between liberals and conservatives as well as situational variables that induce either liberal or conservative shifts in political opinions. Our thesis is that ideological belief systems may be structured according to a left-right dimension for largely psychological reasons linked to variability in the needs to reduce uncertainty and threat. PMID:26158879

  3. Targeted next generation sequencing application in cardiac channelopathies: Analysis of a cohort of autopsy-negative sudden unexplained deaths.

    PubMed

    Farrugia, A; Keyser, C; Hollard, C; Raul, J S; Muller, J; Ludes, B

    2015-09-01

    Genetic testing for cardiac channelopathies in sudden unexplained death (SUD) has developed substantially over the last years. The Next Generation Sequencing (NGS) technology provides an unprecedented opportunity to screen for genetic variations underlying arrhythmogenic genes in a short period of time at a low cost. The present study aimed to perform genetic testing with NGS technologies on the Ion Torrent Personal Genome Machine™ (Ion PGM™) sequencer, in targeting a total of 23 genes reported to be associated with inherited cardiac channelopathies in order to identify the possible cause of death in a cohort of post-mortem cases. The molecular analyses focused on 16 cases of SUD, aged less than 35 years old. In all cases, the cause of death could not be determined after a rigorous autopsy associated with histopathological and toxicological analyses according to the guidelines of the Association for European Cardiovascular Pathology. DNA was extracted from fresh frozen tissue. An average of 200 variants was identified per case. However, after the prioritization process using a new scoring program (VaRank) and after the conjunction of clinical data and molecular findings, four "likely pathogenic" variants (including two undescribed variants), were identified in three cases (18.75%) of our cohort in the genes KCNH2, ANK2, SCN5A and RYR2. One case, who died during psychiatric hospitalization after administration of a QT prolonging drug, showed a double "likely pathogenic" variant in Long QT genes (ANK2 and SCN5A) which may have predisposed to drug-induced cardiac arrhythmias. Our study illustrates that the NGS approach based on AmpliSeq™ libraries and Ion Torrent PGM™ sequencing may be an efficient approach, integrated to post-mortem examination. Given the massive amount of information generated by NGS, a rigorous filtration strategy of variants coupled with multidisciplinary collaboration is crucial to determine the potential pathogenic role of identified

  4. Subsurface structure of Valles Caldera; a resurgent cauldron in northern New Mexico. [Abstract only

    SciTech Connect

    Goff, F.

    1983-03-01

    Valles Caldera is a 1.1 My old silicic cauldron lying at the intersection of the Rio Grande rift and northeast-trending Jemez Lineament. Geothermal exploration in the caldera region during the last 10 years provides subsurface data which refine our knowledge of deep caldera structure, but raise some questions concerning current models of resurgent cauldrons. For example, a detailed gravity investigation using 730 stations (Segar, 1974) shows a circular negative gravity anomaly centered over the caldera (as expected) but also indicates a strong northeast-trending grain of fault blocks in pre-caldera rocks, that are generally down-faulted to the southeast toward the Rift. Gravity data do not define a diapir structure beneath the resurgent dome attributable to tumescent magma; instead of a northeast-trending horst underlies the Redondo Peak segment of the dome. Interpretation of stratigraphy from many geothermal wells suggests that the caldera and resurgent dome are floored by untilted fault blocks (Hulen and Nielson, 1982). In addition, drilling to Precambrian basement and depths of 3.2 km has not encountered a large intrusive rhyolite that might logically produce tumescence of the dome. The new data indicate that the subsurface structural configuration of Valles Caldera is controlled by pre-caldera tectonics and that a more complicated mechanism is required to explain the resurgent dome standing high inside the caldera. A refined mechanism of resurgence might be one result of CSDP drilling at Valles Caldera.

  5. Resurgence and persistence of Dorymyrmex flavus after reduction of Solenopsis invicta buren with a broadcast bait.

    PubMed

    Calixto, Alejandro A; Harris, Marvin K; Barr, Charles

    2007-06-01

    The effects of bait treatment(s) on population dynamics of Solenopsis invicta and Dorymyrmex flavus were studied, and various factors underlying the resurgence and persistence of D. flavus to reinvasion by S. invicta were studied in more detail. Pitfall traps, bait vials, transect sampling, and direct inspections were used to monitor densities of these two species, and inspections of D. flavus midden contents, video monitoring of D. flavus colonies, and studies of the fate of marked S. invicta were used to further clarify interactions of these two species, D. flavus abundance increased after the reduction of S. invicta with baits. D. flavus was also observed to sustain higher densities for an extended period (2 yr) after cessation of bait treatment and to exhibit antagonistic behaviors toward S. invicta, showing an ability to resist reinvasion of the treated area by S. invicta. Given these findings, D. flavus may retard domination of the ant assemblage by S. invicta. Additional studies are justified regarding how to enhance the role of this species in affected ecosystems. PMID:17540063

  6. Transient scaling and resurgence of chimera states in networks of Boolean phase oscillators.

    PubMed

    Rosin, David P; Rontani, Damien; Haynes, Nicholas D; Schöll, Eckehard; Gauthier, Daniel J

    2014-09-01

    We study networks of nonlocally coupled electronic oscillators that can be described approximately by a Kuramoto-like model. The experimental networks show long complex transients from random initial conditions on the route to network synchronization. The transients display complex behaviors, including resurgence of chimera states, which are network dynamics where order and disorder coexists. The spatial domain of the chimera state moves around the network and alternates with desynchronized dynamics. The fast time scale of our oscillators (on the order of 100ns) allows us to study the scaling of the transient time of large networks of more than a hundred nodes, which has not yet been confirmed previously in an experiment and could potentially be important in many natural networks. We find that the average transient time increases exponentially with the network size and can be modeled as a Poisson process in experiment and simulation. This exponential scaling is a result of a synchronization rate that follows a power law of the phase-space volume. PMID:25314385

  7. A structural outline of the Yenkahe volcanic resurgent dome (Tanna Island, Vanuatu Arc, South Pacific)

    NASA Astrophysics Data System (ADS)

    Merle, O.; Brothelande, E.; Lénat, J.-F.; Bachèlery, P.; Garaébiti, E.

    2013-12-01

    A structural study has been conducted on the resurgent Yenkahe dome (5 km long by 3 km wide) located in the heart of the Siwi caldera of Tanna Island (Vanuatu arc, south Pacific). This spectacular resurgent dome hosts a small caldera and a very active strombolian cinder cone - the Yasur volcano - in the west and exhibits an intriguing graben in its central part. Detailed mapping and structural observations make it possible to unravel the volcano-tectonic history of the dome. It is shown that, following the early formation of a resurgent dome in the west, a complex collapse (caldera plus graben) occurred and this was associated with the recent uplift of the eastern part of the present dome. Eastward migration of the underlying magma related to regional tectonics is proposed to explain this evolution.

  8. Behavioral momentum theory fails to account for the effects of reinforcement rate on resurgence.

    PubMed

    Craig, Andrew R; Shahan, Timothy A

    2016-05-01

    The behavioral-momentum model of resurgence predicts reinforcer rates within a resurgence preparation should have three effects on target behavior. First, higher reinforcer rates in baseline (Phase 1) produce more persistent target behavior during extinction plus alternative reinforcement. Second, higher rate alternative reinforcement during Phase 2 generates greater disruption of target responding during extinction. Finally, higher rates of either reinforcement source should produce greater responding when alternative reinforcement is suspended in Phase 3. Recent empirical reports have produced mixed results in terms of these predictions. Thus, the present experiment further examined reinforcer-rate effects on persistence and resurgence. Rats pressed target levers for high-rate or low-rate variable-interval food during Phase 1. In Phase 2, target-lever pressing was extinguished, an alternative nose-poke became available, and nose-poking produced either high-rate variable-interval, low-rate variable-interval, or no (an extinction control) alternative reinforcement. Alternative reinforcement was suspended in Phase 3. For groups that received no alternative reinforcement, target-lever pressing was less persistent following high-rate than low-rate Phase-1 reinforcement. Target behavior was more persistent with low-rate alternative reinforcement than with high-rate alternative reinforcement or extinction alone. Finally, no differences in Phase-3 responding were observed for groups that received either high-rate or low-rate alternative reinforcement, and resurgence occurred only following high-rate alternative reinforcement. These findings are inconsistent with the momentum-based model of resurgence. We conclude this model mischaracterizes the effects of reinforcer rates on persistence and resurgence of operant behavior. PMID:27193242

  9. Resurgent Transseries and the Holomorphic Anomaly: Nonperturbative Closed Strings in Local

    NASA Astrophysics Data System (ADS)

    Couso-Santamaría, Ricardo; Edelstein, José D.; Schiappa, Ricardo; Vonk, Marcel

    2015-08-01

    The holomorphic anomaly equations describe B-model closed topological strings in Calabi-Yau geometries. Having been used to construct perturbative expansions, it was recently shown that they can also be extended past perturbation theory by making use of resurgent transseries. These yield formal nonperturbative solutions, showing integrability of the holomorphic anomaly equations at the nonperturbative level. This paper takes such constructions one step further by working out in great detail the specific example of topological strings in the mirror of the local toric Calabi-Yau background, and by addressing the associated (resurgent) large-order analysis of both perturbative and multi-instanton sectors. In particular, analyzing the asymptotic growth of the perturbative free energies, one finds contributions from three different instanton actions related by symmetry, alongside another action related to the Kähler parameter. Resurgent transseries methods then compute, from the extended holomorphic anomaly equations, higher instanton sectors and it is shown that these precisely control the asymptotic behavior of the perturbative free energies, as dictated by resurgence. The asymptotic large-order growth of the one-instanton sector unveils the presence of resonance, i.e., each instanton action is necessarily joined by its symmetric contribution. The structure of different resurgence relations is extensively checked at the numerical level, both in the holomorphic limit and in the general nonholomorphic case, always showing excellent agreement with transseries data computed out of the nonperturbative holomorphic anomaly equations. The resurgence relations further imply that the string free energy displays an intricate multi-branched Borel structure, and that resonance must be properly taken into account in order to describe the full transseries solution.

  10. Recent Trends in Intergovernmental Relations: The Resurgence of Local Actors in Education Policy

    ERIC Educational Resources Information Center

    Marsh, Julie A.; Wohlstetter, Priscilla

    2013-01-01

    In this essay, the authors explore trends in intergovernmental relations (IGR) by analyzing recent education policies--No Child Left Behind Act, Common Core State Standards, and local empowerment policies. Identifying a resurgent role for local actors in education policy, the authors argue that recent federal efforts to exert more control have in…

  11. Mechanisms of Resurgence II: Response-Contingent Reinforcers Can Reinstate a Second Extinguished Behavior

    ERIC Educational Resources Information Center

    Winterbauer, Neil E.; Bouton, Mark E.

    2011-01-01

    Three experiments with rat subjects examined resurgence of an extinguished instrumental response using the procedure introduced by Epstein (1983) with pigeons. There were three phases: (1) initial acquisition of pressing on a lever (L1) for pellet reward, (2) extinction of L1, and (3) a test session in which a second lever (L2) was inserted,…

  12. The Lebanese Brevet Professionnel: Resurgence of a Lower Secondary Vocational Track

    ERIC Educational Resources Information Center

    Vlaardingerbroek, Barend; Jaber, Lama Ziad; El-Masri, Yasmine Hachem

    2008-01-01

    The Lebanese Brevet Professionnel (BP) is an occupationally-specific vocational qualification at lower secondary level. Despite being on the margins of Lebanese education, the BP has been showing signs of a resurgence over the past few years. This paper discusses the structure and role of the BP in the context of the Lebanese education system and…

  13. Resurgence, operator product expansion, and remarks on renormalons in supersymmetric Yang-Mills theory

    SciTech Connect

    Shifman, M.

    2015-03-15

    We discuss similarities and differences between the resurgence program in quantum mechanics and the operator product expansion in strongly coupled Yang-Mills theories. In N = 1 super-Yang-Mills theories, renormalons are peculiar and are not quite similar to renormalons in QCD.

  14. Bonanza, an "Extreme" Resurgent Ignimbrite-Caldera Cycle in the San Juan Mountains, Colorado

    NASA Astrophysics Data System (ADS)

    Lipman, P. W.; McIntosh, W. C.; Zimmerer, M. J.

    2012-12-01

    Among large calderas associated with ignimbrite super-eruptions, the 33.2 Ma Bonanza caldera of the Southern Rocky Mountain volcanic field displays compositional and structural features that provide near-endmember examples of ignimbrite eruptive processes. Bonanza, source of a compositionally complex regional ignimbrite sheet erupted at 33.19±0.04 Ma, is a subsequent resurgently domed structure ~20 km diameter that subsided >3 km during eruption of ~1,000 km3 of ignimbrite. Among its exceptional features: (1) extreme compositional gradients in the associated Bonanza Tuff (mafic dacite to silicic rhyolite; 59-76.5% SiO2); (2) multiple alternations of mafic and silicic zones, rather than simple upward gradient from silicic to mafic; (3) similarly large compositional diversity among postcollapse caldera-fill lavas and exposed roof zones of resurgent intrusions; (4) compositional contrasts among outflow sectors (mainly rhyolite to east, dacite to west); (5) brief time span for the entire caldera cycle (33.2-32.9 Ma); (6) a uniquely steep-sided resurgent dome (dips of 40-50o on west and 70-80o on east flanks); (7) unique exposure levels due to later structural tilting and rugged present-day topography--from postcollapse lavas, to thickly ponded intracaldera ignimbrite and interleaved landslide breccia, down through precaldera volcanic floor, into underlying Paleozoic and Precambrian basement that are intruded by resurgent plutons. Some near-original caldera morphology remains defined by present-day landforms (western topographic rim, resurgent core, ring-fault valley), while tilting and deep erosion provide exceptional three-dimensional exposures of fill, floor, and resurgent structures. An ~2.5-km-thick section of intracaldera ignimbrite on the western flank of the resurgent dome is complexly compositionally zoned (up to nine gradational alternations of rhyolite and dacite, interleaved with collapse-breccia lenses), underlain by caldera-floor intermediate

  15. Profiling neuronal ion channelopathies with non-invasive brain imaging and dynamic causal models: Case studies of single gene mutations

    PubMed Central

    Gilbert, Jessica R.; Symmonds, Mkael; Hanna, Michael G.; Dolan, Raymond J.; Friston, Karl J.; Moran, Rosalyn J.

    2016-01-01

    Clinical assessments of brain function rely upon visual inspection of electroencephalographic waveform abnormalities in tandem with functional magnetic resonance imaging. However, no current technology proffers in vivo assessments of activity at synapses, receptors and ion-channels, the basis of neuronal communication. Using dynamic causal modeling we compared electrophysiological responses from two patients with distinct monogenic ion channelopathies and a large cohort of healthy controls to demonstrate the feasibility of assaying synaptic-level channel communication non-invasively. Synaptic channel abnormality was identified in both patients (100% sensitivity) with assay specificity above 89%, furnishing estimates of neurotransmitter and voltage-gated ion throughput of sodium, calcium, chloride and potassium. This performance indicates a potential novel application as an adjunct for clinical assessments in neurological and psychiatric settings. More broadly, these findings indicate that biophysical models of synaptic channels can be estimated non-invasively, having important implications for advancing human neuroimaging to the level of non-invasive ion channel assays. PMID:26342528

  16. Molecular genetic and genetic correlations in sodium channelopathies: Lack of founder effect and evidence for a second gene

    SciTech Connect

    Wang, J.; Zhou, J.; Feero, W.G.; Conwit, R.; Galloway, G.; Hoffman, E.P. ); Wessel, H.B. Univ. of Pittsburgh, PA ); Todorovic, S.M. ); Barany, F. ); Hausmanowa-Petrusewicz, I.; Fidzianska, A. ); Arahata, K. ); Sillen, A. ); Marks, H.G. ); Hartlage, P. ); Ricker, K. ); Lehmann-Horn, F. ); Hayakawa, H. )

    1993-06-01

    The authors present a correlation of molecular genetic data (mutations) and genetic data (dinucleotide-repeat polymorphisms) for a cohort of seven hyperkalemic periodic paralysis (HyperPP) and two paramyotonia congenita (PC) families from diverse ethnic backgrounds. They found that each of three previously identified point mutations of the adult skeletal muscle sodium-channel gene occurred on two different dinucleotide-repeat haplotypes. These results indicate that dinucleotide-repeat haplotypes are not predictive of allelic heterogeneity in sodium channelopathies, contrary to previous suggestions. In addition, they identified a HyperPP pedigree in which the dominant disorder was not linked to the sodium-channel gene. Thus, a second locus can give rise to a similar clinical phenotype. Some individuals in this pedigree exhibited a base change causing the nonconservative substitution of an evolutionarily conserved amino acid. Because this change was not present in 240 normal chromosomes and was near another HyperPP mutation, it fulfilled the most commonly used criteria for being a mutation rather than a polymorphism. However, linkage studies using single-strand conformation polymorphism-derived and sequence-derived haplotypes excluded this base change as a causative mutation: these data serve as a cautionary example of potential pitfalls in the delineation of change-of-function point mutations. 35 refs., 5 figs., 1 tab.

  17. Toward a thermometric method for assessment of fluviokarst properties: application to the Cent-Fonts resurgence (H

    NASA Astrophysics Data System (ADS)

    Machetel, P.; Prevot, M.; Fonzes, 0.; Segala, G.; Borg, H.

    2009-04-01

    In this work, we test the possibility of using thermometric and piezometric data for the assessment of hydrologic properties of fluviokarsts. The work relies on a classical conceptual model of karsts, whose open conduit system receives diffuse water infiltrations from a surrounding porous-fractured aquifer, direct allogenic stream intrusions from a far swallow zone and from a neighbor stream. Together with the surrounding porous-fractured rocks, this conduit system contributes to water feeding of a neighbor stream through a natural resurgence. However we will focus on the hydrological situation induced by aquifer pumping during low flow recession period. We propose that a thermometric mixing equation links the inflow and outflow discharges with the surface and underground water temperatures inside and outside of the karstic system. The application of the method to particular phases of pumping tests as: 1) pre-pumping period, 2) equilibrium pumping under severe drawdown conditions and, 3) long-duration high rate pumping, allows taking advantage of: 1) undisturbed conditions for baseflow assessment, 2) equilibrium between diffuse infiltration, allogenic intrusions, asymptotic answer of the aquifer to drawdown and pump extraction, and 3) aquifer answer to under increasing drawdown. We propose a first test of the method with thermometric, piezometric and flow discharges data sets recorded during a karstic aquifer pumping test campaign (Cent-Fonts resurgence, Hérault, France, 2005). The results allow finding again the main hydrological behaviors observed on field (spring drying, in-situ speleological observations, geochemical quantification of allogenic intrusions). The results of the paper suggest that this method could bring promising tools assessing baseflow, recession curves, allogenic intrusion discharges, and response of the porous-fractured part of the aquifer to drawdown.

  18. Computer modelling of the water resurge at a marine impact: the Lockne crater, Sweden

    NASA Astrophysics Data System (ADS)

    Ormö, Jens; Miyamoto, Hideaki

    When a cosmic impact occurs at sea, the resulting crater can form completely in the water mass or extend into the seafloor. At intermediate to great water depths, the collapse of the water cavity generates a forceful resurge of water along the seafloor towards the central part of the crater. The erosive effects as well as certain conspicuous deposits from resurge flows are known from several craters. This study uses numerical modelling to estimate the magnitude of the resurge in the case of the 455 Myr old marine-target Lockne impact crater, Sweden. The water depth at the Lockne target site was at least 200 m, possibly even as great as 1 km. Field evidence show that the resurge was strong enough to erode gullies hundreds of metres wide, tens of metres deep, and kilometres long. With computer modelling we studied the behaviour of the flow to get a notion of its magnitude. The calculations required simplification of the reality. We used a fixed seafloor topography and pure water. A rim in the water mass is expected but was neglected in the calculations. The simplification likely led to underestimation of the magnitude of the resurge. The effect of different target water depths was studied. At 200-m target water depth, about 1.2×10 11 m 3 of water were needed to fill the Lockne crater, including the water cavity. This took about 2200 s. It has been suggested that the main gully formation occurs when the resurge passes the inner rim of the crater. That phase lasts for about 700 s. With a 500-m target water depth, these processes are 3-4 times faster. The erosive force of the flow (i.e. unit stream power) is 1.9×10 5 (Wm -2) in the 200-m water depth model. This is of the same magnitude as the Lake Missoula Flood, the greatest catastrophic flooding known on Earth. At 500-m target water, the unit stream power is a magnitude greater.

  19. Kv3.1 uses a timely resurgent K(+) current to secure action potential repolarization.

    PubMed

    Labro, Alain J; Priest, Michael F; Lacroix, Jérôme J; Snyders, Dirk J; Bezanilla, Francisco

    2015-01-01

    High-frequency action potential (AP) transmission is essential for rapid information processing in the central nervous system. Voltage-dependent Kv3 channels play an important role in this process thanks to their high activation threshold and fast closure kinetics, which reduce the neuron's refractory period. However, premature Kv3 channel closure leads to incomplete membrane repolarization, preventing sustainable AP propagation. Here, we demonstrate that Kv3.1b channels solve this problem by producing resurgent K(+) currents during repolarization, thus ensuring enough repolarizing power to terminate each AP. Unlike previously described resurgent Na(+) and K(+) currents, Kv3.1b's resurgent current does not originate from recovery of channel block or inactivation but results from a unique combination of steep voltage-dependent gating kinetics and ultra-fast voltage-sensor relaxation. These distinct properties are readily transferrable onto an orthologue Kv channel by transplanting the voltage-sensor's S3-S4 loop, providing molecular insights into the mechanism by which Kv3 channels contribute to high-frequency AP transmission. PMID:26673941

  20. Kv3.1 uses a timely resurgent K+ current to secure action potential repolarization

    PubMed Central

    Labro, Alain J.; Priest, Michael F.; Lacroix, Jérôme J.; Snyders, Dirk J.; Bezanilla, Francisco

    2015-01-01

    High-frequency action potential (AP) transmission is essential for rapid information processing in the central nervous system. Voltage-dependent Kv3 channels play an important role in this process thanks to their high activation threshold and fast closure kinetics, which reduce the neuron's refractory period. However, premature Kv3 channel closure leads to incomplete membrane repolarization, preventing sustainable AP propagation. Here, we demonstrate that Kv3.1b channels solve this problem by producing resurgent K+ currents during repolarization, thus ensuring enough repolarizing power to terminate each AP. Unlike previously described resurgent Na+ and K+ currents, Kv3.1b's resurgent current does not originate from recovery of channel block or inactivation but results from a unique combination of steep voltage-dependent gating kinetics and ultra-fast voltage-sensor relaxation. These distinct properties are readily transferrable onto an orthologue Kv channel by transplanting the voltage-sensor's S3–S4 loop, providing molecular insights into the mechanism by which Kv3 channels contribute to high-frequency AP transmission. PMID:26673941

  1. Bed Bug Infestations and Control Practices in China: Implications for Fighting the Global Bed Bug Resurgence.

    PubMed

    Wang, Changlu; Wen, Xiujun

    2011-01-01

    The bed bug resurgence in North America, Europe, and Australia has elicited interest in investigating the causes of the widespread and increasing infestations and in developing more effective control strategies. In order to extend global perspectives on bed bug management, we reviewed bed bug literature in China by searching five Chinese language electronic databases. We conducted telephone interviews of staff from 77 Health and Epidemic Prevention Stations in six Chinese cities in November 2010. We also conducted telephone interviews of 68 pest control firms in two cities during March 2011. Two species of bed bugs (Cimex lectularius L. and Cimex hemipterus (F.)) are known to occur in China. These were common urban pests before the early1980s. Nationwide "Four-Pest Elimination" campaigns (bed bugs being one of the targeted pests) were implemented in China from 1960 to the early 1980s. These campaigns succeeded in the elimination of bed bug infestations in most communities. Commonly used bed bug control methods included applications of hot water, sealing of bed bug harborages, physical removal, and applications of residual insecticides (mainly organophosphate sprays or dusts). Although international and domestic travel has increased rapidly in China over the past decade (2000-2010), there have only been sporadic new infestations reported in recent years. During 1999-2009, all documented bed bug infestations were found in group living facilities (military dormitories, worker dormitories, and prisons), hotels, or trains. One city (Shenzhen city near Hong Kong) experienced significantly higher number of bed bug infestations. This city is characterized by a high concentration of migratory factory workers. Current bed bug control practices include educating residents, washing, reducing clutter, putting items under the hot sun in summer, and applying insecticides (pyrethroids or organophosphates). There have not been any studies or reports on bed bug insecticide

  2. Bed Bug Infestations and Control Practices in China: Implications for Fighting the Global Bed Bug Resurgence

    PubMed Central

    Wang, Changlu; Wen, Xiujun

    2011-01-01

    The bed bug resurgence in North America, Europe, and Australia has elicited interest in investigating the causes of the widespread and increasing infestations and in developing more effective control strategies. In order to extend global perspectives on bed bug management, we reviewed bed bug literature in China by searching five Chinese language electronic databases. We conducted telephone interviews of staff from 77 Health and Epidemic Prevention Stations in six Chinese cities in November 2010. We also conducted telephone interviews of 68 pest control firms in two cities during March 2011. Two species of bed bugs (Cimex lectularius L. and Cimex hemipterus (F.)) are known to occur in China. These were common urban pests before the early1980s. Nationwide “Four-Pest Elimination” campaigns (bed bugs being one of the targeted pests) were implemented in China from 1960 to the early 1980s. These campaigns succeeded in the elimination of bed bug infestations in most communities. Commonly used bed bug control methods included applications of hot water, sealing of bed bug harborages, physical removal, and applications of residual insecticides (mainly organophosphate sprays or dusts). Although international and domestic travel has increased rapidly in China over the past decade (2000–2010), there have only been sporadic new infestations reported in recent years. During 1999–2009, all documented bed bug infestations were found in group living facilities (military dormitories, worker dormitories, and prisons), hotels, or trains. One city (Shenzhen city near Hong Kong) experienced significantly higher number of bed bug infestations. This city is characterized by a high concentration of migratory factory workers. Current bed bug control practices include educating residents, washing, reducing clutter, putting items under the hot sun in summer, and applying insecticides (pyrethroids or organophosphates). There have not been any studies or reports on bed bug insecticide

  3. Resurgent and emergent disease in a changing world.

    PubMed

    Cohen, M L

    1998-01-01

    Emerging infectious diseases pose important public health problems for both the developed and developing world. Many new or previously unrecognized bacterial, fungal, viral, and parasitic diseases have emerged within the past two decades. At the same time, many once-controlled infections have re-emerged or become resistant to antimicrobial therapy. This emergence is the result of changes in society, technology, the environment, and the microbes themselves, and these changes have had often unpredictable consequences. Important factors influencing emergence include changes in human demographics and behaviour, changes in technology and industry, changes in economic development and land use, increasing and rapid international travel and commerce, microbial adaptation and change, and the breakdown of public health measures. Addressing emerging infectious diseases will require international and interdisciplinary partnerships to build an appropriate infrastructure to detect and respond to these often unanticipated threats to health. PMID:10326281

  4. The Role of Ceramics in a Resurgent Nuclear Industry

    SciTech Connect

    Marra, J

    2006-02-28

    With fuel oil and natural gas prices near record highs and worldwide energy demands increasing at an alarming rate, there is growing interest in revitalization of the nuclear power industry within the United States and across the globe. Ceramic materials have long played a very important part in the commercial nuclear industry with applications throughout the entire fuel cycle; from fuel fabrication to waste stabilization. As the international community begins to look at advanced fuel cycles that minimize waste and increase proliferation resistance, ceramic materials will play an even larger role. Many of the advanced reactor concepts being evaluated operate at high-temperature requiring the use of durable, heat-resistant materials. Ceramic fuels are being investigated for a variety of Generation IV reactor concepts. These include the traditional TRISO-coated particles as well as advanced inert-matrix fuels. In order to minimize wastes and legacy materials, ceramic processes are also being applied to fuel reprocessing operations. Ceramic materials continue to provide a vital contribution in ''closing the fuel cycle'' by stabilization of associated low-level and high-level wastes in highly durable grout, ceramics, and glass. In the next five years, programs that are currently in the conceptual phase will begin laboratory- and engineering-scale demonstrations. This will require production-scale demonstrations of several ceramic technologies from fuel form development to advanced stabilization methods. Within the next five to ten years, these demonstrations will move to even larger scales and will also include radioactive demonstrations of these advanced technologies. These radioactive demonstrations are critical to program success and will require advances in ceramic materials associated with nuclear energy applications.

  5. Are we headed for a resurgence of the HIV epidemic among men who have sex with men?

    PubMed Central

    Wolitski, R J; Valdiserri, R O; Denning, P H; Levine, W C

    2001-01-01

    HIV remains a critical health issue for men who have sex with men (MSM). In the United States, an estimated 365,000 to 535,000 MSM are living with HIV, and 42% of new HIV infections occur in this population. Recent data on sexually transmitted diseases and on sexual behavior indicate the potential for a resurgence in HIV infections among MSM. Outbreaks of gonorrhea and syphilis have been reported in a growing number of cities, and several studies have observed an increase in unprotected anal intercourse among MSM. These increases in HIV risk behavior may be attributed to several factors that have affected the sexual practices of MSM, including changes in beliefs regarding the severity of HIV disease. These emerging data have implications for surveillance and intervention research activities and indicate a need to reevaluate, refocus, and reinvigorate HIV prevention efforts for MSM. Our recommendations for addressing the HIV prevention needs of MSM include the need to consider HIV-related issues within the broader context of the physical, mental, and sexual health of MSM. PMID:11392927

  6. Ion channelopathies in human induced pluripotent stem cell derived cardiomyocytes: a dynamic clamp study with virtual IK1

    PubMed Central

    Meijer van Putten, Rosalie M. E.; Mengarelli, Isabella; Guan, Kaomei; Zegers, Jan G.; van Ginneken, Antoni C. G.; Verkerk, Arie O.; Wilders, Ronald

    2015-01-01

    Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) are widely used in studying basic mechanisms of cardiac arrhythmias that are caused by ion channelopathies. Unfortunately, the action potential profile of hiPSC-CMs—and consequently the profile of individual membrane currents active during that action potential—differs substantially from that of native human cardiomyocytes, largely due to almost negligible expression of the inward rectifier potassium current (IK1). In the present study, we attempted to “normalize” the action potential profile of our hiPSC-CMs by inserting a voltage dependent in silico IK1 into our hiPSC-CMs, using the dynamic clamp configuration of the patch clamp technique. Recordings were made from single hiPSC-CMs, using the perforated patch clamp technique at physiological temperature. We assessed three different models of IK1, with different degrees of inward rectification, and systematically varied the magnitude of the inserted IK1. Also, we modified the inserted IK1 in order to assess the effects of loss- and gain-of-function mutations in the KCNJ2 gene, which encodes the Kir2.1 protein that is primarily responsible for the IK1 channel in human ventricle. For our experiments, we selected spontaneously beating hiPSC-CMs, with negligible IK1 as demonstrated in separate voltage clamp experiments, which were paced at 1 Hz. Upon addition of in silico IK1 with a peak outward density of 4–6 pA/pF, these hiPSC-CMs showed a ventricular-like action potential morphology with a stable resting membrane potential near −80 mV and a maximum upstroke velocity >150 V/s (n = 9). Proarrhythmic action potential changes were observed upon injection of both loss-of-function and gain-of-function IK1, as associated with Andersen–Tawil syndrome type 1 and short QT syndrome type 3, respectively (n = 6). We conclude that injection of in silico IK1 makes the hiPSC-CM a more reliable model for investigating mechanisms underlying cardiac

  7. Resurgence of alcohol seeking produced by discontinuing non-drug reinforcement as an animal model of drug relapse.

    PubMed

    Podlesnik, Christopher A; Jimenez-Gomez, Corina; Shahan, Timothy A

    2006-06-01

    Findings from basic behavioral research suggest that simply discontinuing reinforcement for a recently reinforced operant response can cause the recurrence (i.e. resurgence) of a different previously reinforced response. The present experiment examined resurgence as an animal model of drug relapse. Initially, rats pressed levers to self-administer alcohol during baseline conditions. Next, alcohol self-administration was discontinued and non-drug reinforcers (food pellets) were presented contingent on an alternative response (chain pulling). Finally, when the non-drug reinforcer was discontinued, alcohol seeking recurred even though alcohol was still unavailable for lever pressing. These results suggest that simply discontinuing non-drug reinforcement for a behavior may be sufficient to produce relapse to drug seeking. The resurgence procedure could provide a method to examine environmental, pharmacological, and neurobiological factors that lead to relapse following the loss of a non-drug source of reinforcement. PMID:16914956

  8. Malaria resurgence risk in southern Europe: climate assessment in an historically endemic area of rice fields at the Mediterranean shore of Spain

    PubMed Central

    2010-01-01

    Background International travel and immigration have been related with an increase of imported malaria cases. This fact and climate change, prolonging the period favouring vector development, require an analysis of the malaria transmission resurgence risk in areas of southern Europe. Such a study is made for the first time in Spain. The Ebro Delta historically endemic area was selected due to its rice field landscape, the presence of only one vector, Anopheles atroparvus, with densities similar to those it presented when malaria was present, in a situation which pronouncedly differs from already assessed potential resurgence areas in other Mediterranean countries, such as France and Italy, where many different Anopheles species coexist and a different vector species dominates. Methods The transmission risk was assessed analysing: 1) climate diagrams including the minimum temperature for Plasmodium falciparum and Plasmodium vivax development; 2) monthly evolution of the Gradient Model Risk (GMR) index, specifying transmission risk period and number of potential Plasmodium generations; 3) ecological characteristics using remote sensing images with the Eurasia Land Cover characteristics database and the monthly evolution of the Normalized Difference Vegetation Index (NDVI); 4) evaluation of A. atroparvus population dynamics. Results Climatological analyses and GMR index show that a transmission risk presently exists, lasting from May until September for P. falciparum, and from May until October for P. vivax. The GMR index shows that the temperature increase does not actually mean a transmission risk increase if accompanied by a precipitation decrease reducing the number of parasite generations and transmission period. Nevertheless, this limitation is offset by the artificial flooding of the rice fields. Maximum NDVI values and A. atroparvus maximum abundance correspond to months with maximum growth of the rice fields. Conclusions The Ebro Delta presents the ecological

  9. The resurgence and genetic implications of New World primates in biomedical research.

    PubMed

    Ward, Joshua M; Vallender, Eric J

    2012-12-01

    There has been a recent resurgence of interest in New World monkeys within the biomedical research community, driven by both the sequencing of the common marmoset (Callithrix jacchus) genome and a growing demand for alternatives to Old World primates. New World monkeys offer attractive advantages over Old World species, including cheaper and simpler husbandry, while still maintaining a greater evolutionary proximity to humans compared with other animal models. Although numerous commonalities across primate species exist, there are also important genetic and reproductive differences that can and should play a critical role in selecting appropriate animal models. Common marmosets in particular have significantly reduced diversity at the major histocompatibility complex (MHC) loci and are born as hematopoietic chimeras. New World primates can make ideal translational models for research, but scientists must necessarily incorporate complete understandings of their genetic and phenotypic differences from humans and other model organisms. PMID:23099234

  10. Offshore oil resurgent in Gulf of Mexico, U.K. Shelf

    SciTech Connect

    Pagano, S.S.

    1995-01-01

    A resurgence of deep water activity in the US Gulf of Mexico and the ushering in of Great Britain`s west-of-Shetlands area as the next major hydrocarbon development on the UK continental shelf are notable trends unfolding in the oil and gas sector. In late 1994, Shell Oil and partners Amoco and Exxon ventured into an accord to commercially develop the US Gulf`s deepest water reserves. The project, tagged {open_quotes}Ram-Powell,{close_quotes} has been studied for years but is now moving to the forefront with major contracts to be awarded in the next six months or so. A tension-leg platform (TLP) tethered to the seafloor in some 3,220-feet waters will be used to develop the prospect. Ram-Powell`s price tag exceeds $1 billion.

  11. Tracking new coal-fired power plants: coal's resurgence in electric power generation

    SciTech Connect

    2007-05-01

    This information package is intended to provide an overview of 'Coal's resurgence in electric power generation' by examining proposed new coal-fired power plants that are under consideration in the USA. The results contained in this package are derived from information that is available from various tracking organizations and news groups. Although comprehensive, this information is not intended to represent every possible plant under consideration but is intended to illustrate the large potential that exists for new coal-fired power plants. It should be noted that many of the proposed plants are likely not to be built. For example, out of a total portfolio (gas, coal, etc.) of 500 GW of newly planned power plant capacity announced in 2001, 91 GW have been already been scrapped or delayed. 25 refs.

  12. Grizzly Peak cauldron, Colorado: structure and petrology of a deeply dissected resurgent ash-flow caldera

    SciTech Connect

    Fridrich, C.J.

    1987-01-01

    The 34-Ma-old Grizzly Peak cauldron is a deeply eroded 17- by 23-k caldera structure on the crest of the Sawatch Range in west-central Colorado. Subsidence of the cauldron along bounding ring faults resulted from eruption of the Grizzly Peak Tuff, which ponded in the caldera as it formed. An inner ring fracture zone divides the cauldron into two segments and is a growth fault in the intracaldera tuff. Following subsidence, the cauldron was uplifted to form a complexely faulted resurgent dome. Intracaldera Grizzly Peak Tuff, as thick as 2.7 km, is a single cooling unit zoned from high-silica rhyolite at the base to low-silica rhyolite at the eroded top and, further, contains dacite to mafic latite welded pumice clasts (fiamme) in two heterogeneous tuff horizons in the upper half of the unit. Tuff zoning defined by fiamme is unusually strong for a single volcanic unit: 77 to 57% SiO2. Major-element trends can be modeled by crystal fractionation using observed phenocrysts. Inflections in the trends of Zr, Hf, Th, REE, Y, Mn, and Sc correlated with changes in phenocryst mineralogy and composition, indicating control by crystal-liquid equilibria. Trends for some trace-element cannot be fit with the crystal-fractionation model; over different portions of the zonation, Zr, Hf, LREE, and Rb enrich at too high a rate, and Ta, Nb, and Ba enrich at too low a rate. Progressive batch melting of a single source can also be eliminated because Co, Cr, Eu, and Sr, and Ba are too strongly depleted over different silica intervals. The zonation must therefore be the result of a combination of processes. Compositional trends defined by a series of intracaldera intrusions can be explained by hybridization, during resurgence, of the unerupted portion of the zoned magma column sampled in the tuff eruption.

  13. The role of pre-existing tectonic structures and magma chamber shape on the geometry of resurgent blocks: Analogue models

    NASA Astrophysics Data System (ADS)

    Marotta, Enrica; de Vita, Sandro

    2014-02-01

    A set of analogue models has been carried out to understand the role of an asymmetric magma chamber on the resurgence-related deformation of a previously deformed crustal sector. The results are then compared with those of similar experiments, previously performed using a symmetric magma chamber. Two lines of experiments were performed to simulate resurgence in an area with a simple graben-like structure and resurgence in a caldera that collapsed within the previously generated graben-like structure. On the basis of commonly accepted scaling laws, we used dry-quartz sand to simulate the brittle behaviour of the crust and Newtonian silicone to simulate the ductile behaviour of the intruding magma. An asymmetric shape of the magma chamber was simulated by moulding the upper surface of the silicone. The resulting empty space was then filled with sand. The results of the asymmetric-resurgence experiments are similar to those obtained with symmetrically shaped silicone. In the sample with a simple graben-like structure, resurgence occurs through the formation of a discrete number of differentially displaced blocks. The most uplifted portion of the deformed depression floor is affected by newly formed, high-angle, inward-dipping reverse ring-faults. The least uplifted portion of the caldera is affected by normal faults with similar orientation, either newly formed or resulting from reactivation of the pre-existing graben faults. This asymmetric block resurgence is also observed in experiments performed with a previous caldera collapse. In this case, the caldera-collapse-related reverse ring-fault is completely erased along the shortened side, and enhances the effect of the extensional faults on the opposite side, so facilitating the intrusion of the silicone. The most uplifted sector, due to an asymmetrically shaped intrusion, is always in correspondence of the thickest overburden. These results suggest that the stress field induced by resurgence is likely dictated by

  14. Fluid flow in the resurgent dome of Long Valley Caldera: Implications from thermal data and deep electrical sounding

    USGS Publications Warehouse

    Pribnow, D.F.C.; Schutze, C.; Hurter, S.J.; Flechsig, C.; Sass, J.H.

    2003-01-01

    Temperatures of 100??C are measured at 3 km depth in a well located on the resurgent dome in the center of Long Valley Caldera, California, despite an assumed >800??C magma chamber at 6-8 km depth. Local downflow of cold meteoric water as a process for cooling the resurgent dome is ruled out by a Pecle??t-number analysis of temperature logs. These analyses reveal zones with fluid circulation at the upper and lower boundaries of the Bishop Tuff, and an upflow zone in the metasedimentary rocks. Vertical Darcy velocities range from 10 to 70 cm a-1. A 21-km-long geoelectrical profile across the caldera provides resistivity values to the order of 100 to >103 ??m down to a depth of 6 km, as well as variations of self-potential. Interpretation of the electrical data with respect to hydrothermal fluid movement confirms that there is no downflow beneath the resurgent dome. To explain the unexpectedly low temperatures in the resurgent dome, we challenge the common view that the caldera as a whole is a regime of high temperatures and the resurgent dome is a local cold anomaly. Instead, we suggest that the caldera was cooled to normal thermal conditions by vigorous hydrothermal activity in the past, and that a present-day hot water flow system is responsible for local hot anomalies, such as Hot Creek and the area of the Casa Diablo geothermal power plant. The source of hot water has been associated with recent shallow intrusions into the West Moat. The focus of planning for future power plants should be to locate this present-day flow system instead of relying on heat from the old magma chamber. ?? 2003 Elsevier B.V. All rights reserved.

  15. Fluid flow in the resurgent dome of Long Valley Caldera: implications from thermal data and deep electrical sounding

    NASA Astrophysics Data System (ADS)

    Pribnow, Daniel F. C.; Schütze, Claudia; Hurter, Suzanne J.; Flechsig, Christina; Sass, John H.

    2003-10-01

    Temperatures of 100°C are measured at 3 km depth in a well located on the resurgent dome in the center of Long Valley Caldera, California, despite an assumed >800°C magma chamber at 6-8 km depth. Local downflow of cold meteoric water as a process for cooling the resurgent dome is ruled out by a Peclét-number analysis of temperature logs. These analyses reveal zones with fluid circulation at the upper and lower boundaries of the Bishop Tuff, and an upflow zone in the metasedimentary rocks. Vertical Darcy velocities range from 10 to 70 cm a -1. A 21-km-long geoelectrical profile across the caldera provides resistivity values to the order of 10 0 to >10 3 Ωm down to a depth of 6 km, as well as variations of self-potential. Interpretation of the electrical data with respect to hydrothermal fluid movement confirms that there is no downflow beneath the resurgent dome. To explain the unexpectedly low temperatures in the resurgent dome, we challenge the common view that the caldera as a whole is a regime of high temperatures and the resurgent dome is a local cold anomaly. Instead, we suggest that the caldera was cooled to normal thermal conditions by vigorous hydrothermal activity in the past, and that a present-day hot water flow system is responsible for local hot anomalies, such as Hot Creek and the area of the Casa Diablo geothermal power plant. The source of hot water has been associated with recent shallow intrusions into the West Moat. The focus of planning for future power plants should be to locate this present-day flow system instead of relying on heat from the old magma chamber.

  16. The spatio-temporal dynamics of a post-vaccination resurgence of rabies in foxes and emergency vaccination planning.

    PubMed

    Thulke, H H; Tischendorf, L; Staubach, C; Selhorst, T; Jeltsch, F; Müller, T; Schlüter, H; Wissel, C

    1999-10-19

    We used a simulation model to study the spatio-temporal dynamics of a potential rabies outbreak in an immunized fox population after the termination of a long-term, large-scale vaccination program with two campaigns per year one in spring and one in autumn. The 'worst-case' scenario of rabies resurgence occurs if rabies has persisted at a low prevalence despite control and has remained undetected by a customary surveillance program or if infected individuals invade to the control area. Even if the termination of a vaccination program entails such a risk of a subsequent new outbreak, prolonged vaccination of a wild host population is expensive and the declining cost-benefit ratio over time eventually makes it uneconomic. Based on the knowledge of the spatio-temporal dynamics of a potential new outbreak gained from our modelling study, we suggest "terminating but observing" to be an appropriate strategy. Simulating the decline of population immunity without revaccination, we found that a new outbreak of rabies should be detected by customary surveillance programs within two years after the termination of the control. The time until detection does not depend on whether vaccination was terminated within the fourth, fifth or sixth years of repeated biannual campaigns. But it is faster if the program was completed with an autumn campaign (because next-year dispersal then occurs after a noticeable decrease in population immunity). Finally, if a rabid fox is detected after terminating vaccination, we determine a rule for defining a circular hazard area based on the simulated spatial spread of rabies. The radius of this area should be increased with the time since the last vaccination campaign. The trade-off between the number of foxes potentially missed by the emergency treatment and the cost for the emergency measures in an enlarged hazard area was found. PMID:11018731

  17. Studies of Resurgent Bed Bugs: Population Genetic Structure, Impact of Aggregation on Development and Molecular Screening for Bartonella

    NASA Astrophysics Data System (ADS)

    Saenz, Virna Lisa

    . Here we describe the development of 24 high resolution microsatellite markers and their application to elucidate infestation dynamics within three multistory apartment buildings in the United States. Results reveal contrasting characteristics potentially representative of geographic or locale differences. In Raleigh, NC, an infestation within an apartment building seemed to have started from a single introduction followed by extensive spread throughout the building. In Jersey City, NJ, two or more introductions followed by extensive spread. Populations within single apartments in all buildings showed low levels of genetic diversity suggesting that few individuals are starting these infestations, possibly a singly mated female or her progeny. This work is described in Chapter 3 and was published in the Journal of Medical Entomology in 2012. Third, we studied the impact of aggregation in bed bug development. Although it is well known that bed bugs live in aggregations, the adaptive benefits of this behavior are not well understood. In this study, we reared first instars either in isolation or in groups of five from hatching to adult eclosion and recorded their development time. Additionally, we investigated the effects of group-housing on same age nymphs versus nymphs reared with adults. Nymphal development was 2.2 d faster in grouped nymphs than in solitary-housed nymphs, representing 7.3% faster overall development. However, this grouping effect did not appear to be influenced by group composition (nymphs vs. adults). Thus, similar to other gregarious insect species, nymph development in bed bugs is faster in aggregations than in isolation. This work is described in Chapter 4. Fourth, we investigated the prevalence of a re-emergent bacterial pathogen in United States bed bugs populations. Because reports of both bed bugs and Bartonella have been increasing in the United States, and because their host ranges can overlap, we investigated whether the resurgence of these

  18. Spring persistence, transition, and resurgence of El Niño

    NASA Astrophysics Data System (ADS)

    Lee, Sang-Ki; DiNezio, Pedro N.; Chung, Eui-Seok; Yeh, Sang-Wook; Wittenberg, Andrew T.; Wang, Chunzai

    2014-12-01

    We present a systematic exploration of differences in the spatiotemporal sea surface temperature (SST) evolution along the equatorial Pacific among observed El Niño events. This inter-El Niño variability is captured by two leading orthogonal modes, which explain more than 60% of the interevent variance. The first mode illustrates the extent to which warm SST anomalies (SSTAs) in the eastern tropical Pacific (EP) persist into the boreal spring after the peak of El Niño. Our analysis suggests that a strong El Niño event tends to persist into the boreal spring in the EP, whereas a weak El Niño favors a rapid development of cold SSTAs in the EP shortly after its peak. The second mode captures the transition and resurgence of El Niño in the following year. An early-onset El Niño tends to favor a transition to La Niña, whereas a late-onset El Niño tends to persist long enough to produce another El Niño event. The spatiotemporal evolution of several El Niño events during 1949-2013 can be efficiently summarized in terms of these two modes, which are not mutually exclusive, but exhibit distinctive coupled atmosphere-ocean dynamics.

  19. Resurgence theory, ghost-instantons, and analytic continuation of path integrals

    NASA Astrophysics Data System (ADS)

    Basar, Gökçe; Dunne, Gerald V.; Ünsal, Mithat

    2013-10-01

    A general quantum mechanical or quantum field theoretical system in the path integral formulation has both real and complex saddles (instantons and ghost-instantons). Resurgent asymptotic analysis implies that both types of saddles contribute to physical observables, even if the complex saddles are not on the integration path i.e., the associated Stokes multipliers are zero. We show explicitly that instanton-anti-instanton and ghost-anti-ghost saddles both affect the expansion around the perturbative vacuum. We study a self-dual model in which the analytic continuation of the partition function to negative values of coupling constant gives a pathological exponential growth, but a homotopically independent combination of integration cycles (Lefschetz thimbles) results in a sensible theory. These two choices of the integration cycles are tied with a quantum phase transition. The general set of ideas in our construction may provide new insights into non-perturbative QFT, string theory, quantum gravity, and the theory of quantum phase transitions.

  20. Loss of Ca(v)1.3 (CACNA1D) function in a human channelopathy with bradycardia and congenital deafness.

    PubMed

    Baig, Shahid M; Koschak, Alexandra; Lieb, Andreas; Gebhart, Mathias; Dafinger, Claudia; Nürnberg, Gudrun; Ali, Amjad; Ahmad, Ilyas; Sinnegger-Brauns, Martina J; Brandt, Niels; Engel, Jutta; Mangoni, Matteo E; Farooq, Muhammad; Khan, Habib U; Nürnberg, Peter; Striessnig, Jörg; Bolz, Hanno J

    2011-01-01

    Deafness is genetically very heterogeneous and forms part of several syndromes. So far, delayed rectifier potassium channels have been linked to human deafness associated with prolongation of the QT interval on electrocardiograms and ventricular arrhythmia in Jervell and Lange-Nielsen syndrome. Ca(v)1.3 voltage-gated L-type calcium channels (LTCCs) translate sound-induced depolarization into neurotransmitter release in auditory hair cells and control diastolic depolarization in the mouse sinoatrial node (SAN). Human deafness has not previously been linked to defects in LTCCs. We used positional cloning to identify a mutation in CACNA1D, which encodes the pore-forming α1 subunit of Ca(v)1.3 LTCCs, in two consanguineous families with deafness. All deaf subjects showed pronounced SAN dysfunction at rest. The insertion of a glycine residue in a highly conserved, alternatively spliced region near the channel pore resulted in nonconducting calcium channels that had abnormal voltage-dependent gating. We describe a human channelopathy (termed SANDD syndrome, sinoatrial node dysfunction and deafness) with a cardiac and auditory phenotype that closely resembles that of Cacna1d(-/-) mice. PMID:21131953

  1. A Reevaluation of the Question: Is the Pubertal Resurgence in Pulsatile GnRH Release in the Male Rhesus Monkey (Macaca mulatta) Associated With a Gonad-Independent Augmentation of GH Secretion?

    PubMed

    Shahab, M; Trujillo, M Vargas; Plant, T M

    2015-10-01

    A somatic signal has been posited to trigger the pubertal resurgence in pulsatile GnRH secretion that initiates puberty in highly evolved primates. That GH might provide such a signal emerged in 2000 as a result of a study reporting that circulating nocturnal GH concentrations in castrated juvenile male monkeys increased in a 3-week period immediately preceding the pubertal resurgence of LH secretion. The present study was conducted to reexamine this intriguing relationship, again in an agonadal model. Four castrated juvenile male monkeys were implanted with indwelling jugular catheters, housed in remote sampling cages, and subjected to 24 hours of sequential blood sampling (every 30 min) every 2 weeks from 19.5 to 22 months of age. Twenty-four-hour profiles of circulating GH concentrations were analyzed using the pulse detection algorithm, PULSAR, and developmental changes in pulsatile GH release with respect to the initiation of the pubertal rise of LH secretion (week 0; observed between 22.5 and 32 mo of age) were examined for significance by a repeated-measures ANOVA. Changes in the parameters of pulsatile GH secretion, including mean 24-hour GH concentration and GH pulse frequency and pulse amplitude for 3 (n = 4) and 6 (n = 3) months before week 0 were unremarkable and nonsignificant. These findings fail to confirm those of the earlier study and lead us to conclude that the timing of the pubertal resurgence of GnRH release in the male monkey is not dictated by GH. Reasons for the discrepancy between the two studies are unclear. PMID:26181107

  2. 3D Imaging of Brittle/Ductile transition of the crust beneath the resurgent calderas

    NASA Astrophysics Data System (ADS)

    Tizzani, P.; Castaldo, R.; Pepe, S.; Solaro, G.

    2012-04-01

    Rheology is a crucial factor to understand the mechanical behaviour and evolution of the crust in young and tectonically active belts. The aim of this paper is to investigate the rheological properties of the crust beneath resurgent calderas as Long Valley caldera (California USA) and Campi Flegrei (Southern Italy). Through the rheological proprieties of the calderas area, we highlight the driving process that determine the cut off of the local seismicity [K. Ito, 1993]. In this context, we consider the thermal proprieties and mechanical heterogeneity of the crust in order to develop a 3D conductive time dependent thermal model of the upper crust beneath the two calderas. More specifically we integrate geophysical information (gravimetric, seismic and boreholes data) available for the considered area in FEM environment [Manconi A. et al., 2010]. We performed a numerical solution of Fourier equation to carry out an advance optimization of the real measured data. We produce a set of forward models and propose, in order to analyse and solve the statistical problem, the Monte Carlo optimization procedures as Genetic Algorithm [Manconi A. et al., 2009]. In particular we search for the heat production, the volume source distribution and the surface emissivity parameters that providing the best-fit of the geothermal profiles data measured at boreholes, by solving the non stationary heat flow equation (Campanian Ignimbrite eruption about 40 kyr for Campi Flegrei caldera and Bishop tuff eruption about 700 kyr for Long Valley caldera). The performed thermal fields allow us to obtain the rheological stratification of the crust beneath two resurgent calderas; the models suggest that the uprising of a ductile layer which connects the upper mantle to the volcanic feeding system could determine the stress conditions that controlled the distribution of seismicity. In fact, the computed 3D imaging of Brittle/Ductile transition well agrees with the seismic hypocentral distribution

  3. In Flanders fields: the Great War, Antoine Depage, and the resurgence of débridement.

    PubMed Central

    Helling, T S; Daon, E

    1998-01-01

    OBJECTIVE: The care of traumatic wounds has evolved over hundreds of years, largely as a result of armed conflicts. The lessons learned during World War I in the treatment of extensive soft-tissue injuries proved invaluable in reducing infection and preventing loss of limb and life. Foremost among these was the use of debridement. This report reviews the development of debridement as standard treatment of war wounds and highlights the surgeon largely responsible for its resurgence during one of this century's saddest chapters. SUMMARY BACKGROUND DATA: Before World War I, the care of wounds consisted of minimal exploration and liberal use of then-new antiseptics. For limited injuries, this approach appeared adequate. World War I saw the introduction of devastating weapons that produced injuries that caused extensive devitalization of tissue. Standard treatment of these patients proved woefully inadequate to prevent life-threatening infections. METHODS: This is a historical review of the conditions that occurred during World War I that prompted a change in wound management. One of those responsible for this change was the Belgian surgeon Antoine Depage. His life and contributions to the care of war wounds are profiled. Depage reintroduced the discarded French practice of wound incision and exploration (debridement) and combined it with excision of devitalized tissue. RESULTS: Through the use of debridement, excision, and delayed wound closure based on bacteriologic survey, Depage was able to reduce the incidence of infectious complications of soft-tissue injuries, particularly those involving fractures. CONCLUSIONS: Through his experiences in the Great War, Antoine Depage was able to formulate a treatment plan for wounds of war. All such injuries were assumed to be contaminated and, as such, they required early and careful debridement. Depage thought that wound closure should often be delayed and based his decision to close on the bacteriologic status of the wound

  4. Mumps resurgences in the United States: A historical perspective on unexpected elements.

    PubMed

    Barskey, Albert E; Glasser, John W; LeBaron, Charles W

    2009-10-19

    In 2006 the United States experienced the largest nationwide mumps epidemic in 20 years, primarily affecting college dormitory residents. Unexpected elements of the outbreak included very abrupt time course (75% of cases occurred within 90 days), geographic focality (85% of cases occurred in eight rural Midwestern states), rapid upward and downward shift in peak age-specific attack rate (5-9-year olds to 18-24-year olds, then back), and two-dose vaccine failure (63% of case-patients had received two doses). To construct a historical context in which to understand the recent outbreak, we reviewed US mumps surveillance data, vaccination coverage estimates, and relevant peer-reviewed literature for the period 1917-2008. Many of the unexpected features of the 2006 mumps outbreak had been reported several times previously in the US, e.g., the 1986-1987 mumps resurgence had extremely abrupt onset, rural geographic focality, and an upward-then-downward age shift. Evidence suggested recurrent mumps outbreak patterns were attributable to accumulation of susceptibles in dispersed situations where the risk of endemic disease exposure was low and were triggered when this susceptible population was brought together in crowded living conditions. The 2006 epidemic followed this pattern, with two unique variations: it was preceded by a period of very high vaccination rates and very low disease incidence and was characterized by two-dose failure rates among adults vaccinated in childhood. Data from the past 80 years suggest that preventing future mumps epidemics will depend on innovative measures to detect and eliminate build-up of susceptibles among highly vaccinated populations. PMID:19815120

  5. Resurgence in sine-Gordon quantum mechanics: exact agreement between multi-instantons and uniform WKB

    NASA Astrophysics Data System (ADS)

    Misumi, Tatsuhiro; Nitta, Muneto; Sakai, Norisuke

    2015-09-01

    We compute multi-instanton amplitudes in the sine-Gordon quantum mechanics (periodic cosine potential) by integrating out quasi-moduli parameters corresponding to separations of instantons and anti-instantons. We propose an extension of Bogomolnyi-Zinn-Justin prescription for multi-instanton configurations and an appropriate subtraction scheme. We obtain the multi-instanton contributions to the energy eigenvalue of the lowest band at the zeroth order of the coupling constant. For the configurations with only instantons (anti-instantons), we obtain unambiguous results. For those with both instantons and anti-instantons, we obtain results with imaginary parts, which depend on the path of analytic continuation. We show that the imaginary parts of the multi-instanton amplitudes precisely cancel the imaginary parts of the Borel resummation of the perturbation series, and verify that our results completely agree with those based on the uniform-WKB calculations, thus confirming the resurgence structure: divergent perturbation series combined with the nonperturbative multi-instanton contributions conspire to give unambiguous results. We also study the neutral bion contributions in the {C}{P}^{N-1} model on {{R}}^1× {S}^1 with a small circumference, taking account of the relative phase moduli between the fractional instanton and anti-instanton. We find that the sign of the interaction potential depends on the relative phase moduli, and that both the real and imaginary parts resulting from quasi-moduli integral of the neutral bion get quantitative corrections compared to the sine-Gordon quantum mechanics.

  6. Studies of Resurgent Bed Bugs: Population Genetic Structure, Impact of Aggregation on Development and Molecular Screening for Bartonella

    NASA Astrophysics Data System (ADS)

    Saenz, Virna Lisa

    . Here we describe the development of 24 high resolution microsatellite markers and their application to elucidate infestation dynamics within three multistory apartment buildings in the United States. Results reveal contrasting characteristics potentially representative of geographic or locale differences. In Raleigh, NC, an infestation within an apartment building seemed to have started from a single introduction followed by extensive spread throughout the building. In Jersey City, NJ, two or more introductions followed by extensive spread. Populations within single apartments in all buildings showed low levels of genetic diversity suggesting that few individuals are starting these infestations, possibly a singly mated female or her progeny. This work is described in Chapter 3 and was published in the Journal of Medical Entomology in 2012. Third, we studied the impact of aggregation in bed bug development. Although it is well known that bed bugs live in aggregations, the adaptive benefits of this behavior are not well understood. In this study, we reared first instars either in isolation or in groups of five from hatching to adult eclosion and recorded their development time. Additionally, we investigated the effects of group-housing on same age nymphs versus nymphs reared with adults. Nymphal development was 2.2 d faster in grouped nymphs than in solitary-housed nymphs, representing 7.3% faster overall development. However, this grouping effect did not appear to be influenced by group composition (nymphs vs. adults). Thus, similar to other gregarious insect species, nymph development in bed bugs is faster in aggregations than in isolation. This work is described in Chapter 4. Fourth, we investigated the prevalence of a re-emergent bacterial pathogen in United States bed bugs populations. Because reports of both bed bugs and Bartonella have been increasing in the United States, and because their host ranges can overlap, we investigated whether the resurgence of these

  7. Carbon dioxide emissions from vegetation-kill zones around the resurgent dome of Long Valley caldera, eastern California, USA

    USGS Publications Warehouse

    Bergfeld, Deborah; Evans, William C.; Howle, James F.; Farrar, Christopher D.

    2006-01-01

    A survey of diffuse CO2 efflux, soil temperature and soil-gas chemistry over areas of localized vegetation-kill on and around the resurgent dome of Long Valley caldera California was performed to evaluate the premise that gaseous and thermal anomalies are related to renewed intrusion of magma. Some kill sites are long-lived features and others have developed in the past few years. Total anomalous CO2 emissions from the thirteen areas average around 8.7 t per day; but the majority of the emissions come from four sites west of the Casa Diablo geothermal power plant. Geochemical analyses of the soil-gases from locations west and east of the plant revealed the presence of isobutane related to plant operations. The δ13C values of diffuse CO2 range from − 5.7‰ to − 3.4‰, similar to values previously reported for CO2 from hot springs and thermal wells around Long Valley.At many of the vegetation-kill sites soil temperatures reach boiling at depths ≤ 20 cm. Soil temperature/depth profiles at two of the high-emissions areas indicate that the conductive thermal gradient in the center of the areas is around 320 °C m− 1. We estimate total heat loss from the two areas to be about 6.1 and 2.3 MW. Given current thinking on the rate of hydrothermal fluid flow across the caldera and using the CO2 concentration in the thermal fluids, the heat and CO2 loss from the kill areas is easily provided by the shallow hydrothermal system, which is sourced to the west of the resurgent dome. We find no evidence that the development of new areas of vegetation kill across the resurgent dome are related to new input of magma or magmatic fluids from beneath the resurgent dome. Our findings indicate that the areas have developed as a response to changes in the shallow hydrologic system. Some of the changes are likely related to fluid production at the power plant, but at distal sites the changes are more likely related to seismicity and uplift of the dome.

  8. The role of B. pertussis vaccine antigen gene variants in pertussis resurgence and possible consequences for vaccine development.

    PubMed

    Preston, Andrew

    2016-05-01

    Whooping cough, or pertussis, caused by Bordetella pertussis is considered resurgent in a number of countries world-wide, despite continued high level vaccine coverage. Among a number of causes for this that have been proposed, is the emergence of B. pertussis strains expressing variants of the antigens contained in acellular pertussis vaccines; i.e. the evolution of B. pertussis toward vaccine escape. This commentary highlights the contradictory nature of evidence for this but also discusses the importance of understanding the role of B. pertussis adaptation to vaccine-mediated immune selection pressures for vaccine-mediated pertussis control strategies. PMID:26889694

  9. Resurgence and the Nekrasov-Shatashvili limit: connecting weak and strong coupling in the Mathieu and Lamé systems

    NASA Astrophysics Data System (ADS)

    Basar, Gökçe; Dunne, Gerald V.

    2015-02-01

    The Nekrasov-Shatashvili limit for the low-energy behavior of and supersymmetric SU(2) gauge theories is encoded in the spectrum of the Mathieu and Lamé equations, respectively. This correspondence is usually expressed via an all-orders Bohr-Sommerfeld relation, but this neglects non-perturbative effects, the nature of which is very different in the electric, magnetic and dyonic regions. In the gauge theory dyonic region the spectral expansions are divergent, and indeed are not Borel-summable, so they are more properly described by resurgent trans-series in which perturbative and non-perturbative effects are deeply entwined. In the gauge theory electric region the spectral expansions are convergent, but nevertheless there are non-perturbative effects due to poles in the expansion coefficients, and which we associate with worldline instantons. This provides a concrete analog of a phenomenon found recently by Drukker, Mariño and Putrov in the large N expansion of the ABJM matrix model, in which non-perturbative effects are related to complex space-time instantons. In this paper we study how these very different regimes arise from an exact WKB analysis, and join smoothly through the magnetic region. This approach also leads to a simple proof of a resurgence relation found recently by Dunne and Ünsal, showing that for these spectral systems all non-perturbative effects are subtly encoded in perturbation theory, and identifies this with the Picard-Fuchs equation for the quantized elliptic curve.

  10. Late Cretaceous Middle Fork caldera and its resurgent granite porphyry intrusion, east-central Alaska

    NASA Astrophysics Data System (ADS)

    Bacon, C. R.; Dusel-Bacon, C.; Aleinikoff, J. N.; Slack, J. F.

    2012-12-01

    to have been exposed by erosion of thick intracaldera tuff from an asymmetric resurgent dome. The Middle Fork of the North Fork of the Fortymile River cuts an arcuate valley into and around the caldera on the west and north, and may have cut down from an original caldera moat. Proximal outflow tuff, and thus the 69 Ma land surface, remains at the west margin of the caldera structure. The Middle Fork caldera lies within a region of Paleozoic metamorphic rocks and Mesozoic plutons bounded by northeast-trending faults. To the northwest, Cretaceous plutonic rocks are widely exposed, indicating greater exhumation. The Middle Fork is a relatively well preserved caldera within a broad region of Alaska and adjacent Yukon that contains Late Cretaceous plutons and, in the less deeply exhumed blocks, silicic volcanic rocks.

  11. York platelet syndrome is a CRAC channelopathy due to gain-of-function mutations in STIM1.

    PubMed

    Markello, Thomas; Chen, Dong; Kwan, Justin Y; Horkayne-Szakaly, Iren; Morrison, Alan; Simakova, Olga; Maric, Irina; Lozier, Jay; Cullinane, Andrew R; Kilo, Tatjana; Meister, Lynn; Pakzad, Kourosh; Bone, William; Chainani, Sanjay; Lee, Elizabeth; Links, Amanda; Boerkoel, Cornelius; Fischer, Roxanne; Toro, Camilo; White, James G; Gahl, William A; Gunay-Aygun, Meral

    2015-03-01

    Store-operated Ca(2+) entry is the major route of replenishment of intracellular Ca(2+) in animal cells in response to the depletion of Ca(2+) stores in the endoplasmic reticulum. It is primarily mediated by the Ca(2+)-selective release-activated Ca(2+) (CRAC) channel, which consists of the pore-forming subunits ORAI1-3 and the Ca(2+) sensors, STIM1 and STIM2. Recessive loss-of-function mutations in STIM1 or ORAI1 result in immune deficiency and nonprogressive myopathy. Heterozygous gain-of-function mutations in STIM1 cause non-syndromic myopathies as well as syndromic forms of miosis and myopathy with tubular aggregates and Stormorken syndrome; some of these syndromic forms are associated with thrombocytopenia. Increased concentration of Ca(2+) as a result of store-operated Ca(2+) entry is essential for platelet activation. The York Platelet syndrome (YPS) is characterized by thrombocytopenia, striking ultrastructural platelet abnormalities including giant electron-opaque organelles and massive, multilayered target bodies and deficiency of platelet Ca(2+) storage in delta granules. We present clinical and molecular findings in 7 YPS patients from 4 families, demonstrating that YPS patients have a chronic myopathy associated with rimmed vacuoles and heterozygous gain-of-function STIM1 mutations. These findings expand the phenotypic spectrum of STIM1-related human disorders and define the molecular basis of YPS. PMID:25577287

  12. Homeostasis or channelopathy? Acquired cell type-specific ion channel changes in temporal lobe epilepsy and their antiepileptic potential

    PubMed Central

    Wolfart, Jakob; Laker, Debora

    2015-01-01

    Neurons continuously adapt the expression and functionality of their ion channels. For example, exposed to chronic excitotoxicity, neurons homeostatically downscale their intrinsic excitability. In contrast, the “acquired channelopathy” hypothesis suggests that proepileptic channel characteristics develop during epilepsy. We review cell type-specific channel alterations under different epileptic conditions and discuss the potential of channels that undergo homeostatic adaptations, as targets for antiepileptic drugs (AEDs). Most of the relevant studies have been performed on temporal lobe epilepsy (TLE), a widespread AED-refractory, focal epilepsy. The TLE patients, who undergo epilepsy surgery, frequently display hippocampal sclerosis (HS), which is associated with degeneration of cornu ammonis subfield 1 pyramidal cells (CA1 PCs). Although the resected human tissue offers insights, controlled data largely stem from animal models simulating different aspects of TLE and other epilepsies. Most of the cell type-specific information is available for CA1 PCs and dentate gyrus granule cells (DG GCs). Between these two cell types, a dichotomy can be observed: while DG GCs acquire properties decreasing the intrinsic excitability (in TLE models and patients with HS), CA1 PCs develop channel characteristics increasing intrinsic excitability (in TLE models without HS only). However, thorough examination of data on these and other cell types reveals the coexistence of protective and permissive intrinsic plasticity within neurons. These mechanisms appear differentially regulated, depending on the cell type and seizure condition. Interestingly, the same channel molecules that are upregulated in DG GCs during HS-related TLE, appear as promising targets for future AEDs and gene therapies. Hence, GCs provide an example of homeostatic ion channel adaptation which can serve as a primer when designing novel anti-epileptic strategies. PMID:26124723

  13. Channelopathies of skeletal muscle excitability

    PubMed Central

    Cannon, Stephen C.

    2016-01-01

    Familial disorders of skeletal muscle excitability were initially described early in the last century and are now known to be caused by mutations of voltage-gated ion channels. The clinical manifestations are often striking, with an inability to relax after voluntary contraction (myotonia) or transient attacks of severe weakness (periodic paralysis). An essential feature of these disorders is fluctuation of symptoms that are strongly impacted by environmental triggers such as exercise, temperature, or serum K+ levels. These phenomena have intrigued physiologists for decades, and in the past 25 years the molecular lesions underlying these disorders have been identified and mechanistic studies are providing insights for therapeutic strategies of disease modification. These familial disorders of muscle fiber excitability are “channelopathies” caused by mutations of a chloride channel (ClC-1), sodium channel (NaV1.4), calcium channel (CaV1.1) and several potassium channels (Kir2.1, Kir2.6, Kir3.4). This review provides a synthesis of the mechanistic connections between functional defects of mutant ion channels, their impact on muscle excitability, how these changes cause clinical phenotypes, and approaches toward therapeutics. PMID:25880512

  14. Outwitting dengue threat and epidemics resurgence in Asia-Pacific countries: strengthening integrated dengue surveillance, monitoring and response systems.

    PubMed

    Tambo, Ernest; Chen, Jun-Hu; Zhou, Xiao-Nong; Khater, Emad I M

    2016-01-01

    Dengue is still a substantial vector-borne viral disease threat and burden of public health importance worldwide. This situation is complicated by dengue virus unprecedented resurgence and persistence of varied serotypes in endemic-prone areas, and man-made and natural activities consequences that promote vector emergence, transmission dynamics and spread across the Asia-Pacific region. There is an urgent need to strengthen operational and contextual surveillance-response research in improving early detection of active reservoir detection, novel drug in case management and quality evidence-based response including the deployment of dengue mass vaccination. Moreover, sustained mapping and watching of dengue risk factors or determinants, performance and outcome indicators of control or elimination programs effectiveness in defining minimum effective data towards community knowledge-based decision-making policy and effective response packages is imperative. Moreover, implementation of a robust, integrated dengue early warning surveillance, monitoring and response systems metrics is required for evidence-based, timely and cost-effective contextual mitigation strategies, and innovative interventions. PMID:27233238

  15. Determining the foraging range and origin of resurgence after treatment of Argentine ant (Hymenoptera: Formicidae) in urban areas.

    PubMed

    Vega, S Y; Rust, M K

    2003-06-01

    The foraging range and distribution of Argentine ant, Linepithema humile (Mayr), colonies in urban areas of southern California extended at least 61 m (200 feet) from feeding stations and structures. Ants were fed at 25% sucrose feeding stations containing 0.01% fluorescent brighter (FB28). Within 14 d, from 77-90% of the ants sampled next to the feeding stations were positive for FB28. The percentage of ants with FB28 declined gradually to approximately 55% 61 m away from the feeding station. The percentage of marked ants in the controls didn't change over the 4-wk-test period. There were approximately 290,000 ants visiting the monitored stations each night before treatments. The 0.0001% fipronil baits and 0.06% fipronil SC sprays provided significant reductions in at least 4 wk. The percentage of ants marked with FB28 decreased significantly in both bait and spray treatments over 4 wk suggesting that the resurgence of ants in treated areas were because of immigration from untreated areas. It is likely that much larger areas will need to be treated to control Argentine ants in urban settings, especially if baits are being used. PMID:12852625

  16. Resurgence of anorexic symptoms during smoking cessation in patients with a history of anorexia nervosa: An unseen problem?--Report of two cases.

    PubMed

    Simioni, Nicolas; Cottencin, Olivier

    2015-09-01

    This report describes a resurgence of anorexic symptoms during a smoking cessation program in two patients with a history of anorexia nervosa. These two events were identified among patients lost to follow-up by using a strategy implemented to limit early drop out. In both cases, the resurgence of anorexic symptoms occurred rapidly after having reached abstinence from tobacco and was described as a response to the weight gain they had experienced just after the start of smoking cessation. The smoking cessation process itself was considered as the most plausible explanation for these two events. Given the potential serious consequences, further research is needed to determine whether such events are frequent during smoking cessation but being unseen because of being hidden in the loss to follow-up. This report also suggests that systematic screening for both binge eating and anorexic behaviors during smoking cessation is warranted. PMID:26016609

  17. Resurgence of Plasmodium vivax malaria in the Republic of Korea during 2006-2007.

    PubMed

    Jun, Gyo; Yeom, Joon-Sup; Hong, Jee-Young; Shin, E-Hyun; Chang, Kyu-Sik; Yu, Jae-Ran; Oh, Sejoong; Chung, Hyeok; Park, Jae-Won

    2009-10-01

    Plasmodium vivax malaria, which re-emerged in the Republic of Korea (ROK) in 1993, had decreased since 2001. However, case numbers began to increase again in 2005. The number of cases rose 54.0% in 2006, but the rate of increase slowed down in 2007. Among the total of 4,206 cases of P. vivax malaria during 2006-2007, 756 cases (18.0%) were ROK military personnel, 891 cases (21.2%) were veterans, and 2,559 cases (60.8%) were civilians. The rapid increase during this period was mostly contributed by the western part of the malaria-risk areas that is under the influence of adjacent North Korea. Local transmission cases in ROK have also increased gradually and the transmission period seemingly became longer. Chemoprophylaxis in the military should be re-assessed in view of chloroquine-resistance. Continuous surveillance and monitoring are warranted to prevent further expansion of P. vivax malaria caused by climate change in ROK. PMID:19815874

  18. Resurgence of duckweed research and applications: report from the 3rd International Duckweed Conference.

    PubMed

    Appenroth, Klaus-J; Sree, K Sowjanya; Fakhoorian, Tamra; Lam, Eric

    2015-12-01

    Duckweed, flowering plants in the Lemnaceae family, comprises the smallest angiosperms in the plant kingdom. They have some of the fastest biomass accumulation rates reported to date for plants and have the demonstrated ability to thrive on wastewater rich in dissolved organic compounds and thus could help to remediated polluted water resources and prevents eutrophication. With a high quality genome sequence now available and increased commercial interest worldwide to develop duckweed biomass for renewables such as protein and fuel, the 3rd International Duckweed Conference convened at Kyoto, Japan, in July of 2015, to update the community of duckweed researchers and developers on the progress in the field. In addition to sharing results and ideas, the conference also provided ample opportunities for new-comers as well as established workers in the field to network and create new aliances. We hope this meeting summary will also help to disseminate the key advances and observations that have been presented in this conference to the broader plant biology community in order to encourage increased cross-fertilization of ideas and technologies. PMID:26506824

  19. Cushing's syndrome and fetal features resurgence in adrenal cortex-specific Prkar1a knockout mice.

    PubMed

    Sahut-Barnola, Isabelle; de Joussineau, Cyrille; Val, Pierre; Lambert-Langlais, Sarah; Damon, Christelle; Lefrançois-Martinez, Anne-Marie; Pointud, Jean-Christophe; Marceau, Geoffroy; Sapin, Vincent; Tissier, Frédérique; Ragazzon, Bruno; Bertherat, Jérôme; Kirschner, Lawrence S; Stratakis, Constantine A; Martinez, Antoine

    2010-06-01

    Carney complex (CNC) is an inherited neoplasia syndrome with endocrine overactivity. Its most frequent endocrine manifestation is primary pigmented nodular adrenocortical disease (PPNAD), a bilateral adrenocortical hyperplasia causing pituitary-independent Cushing's syndrome. Inactivating mutations in PRKAR1A, a gene encoding the type 1 alpha-regulatory subunit (R1alpha) of the cAMP-dependent protein kinase (PKA) have been found in 80% of CNC patients with Cushing's syndrome. To demonstrate the implication of R1alpha loss in the initiation and development of PPNAD, we generated mice lacking Prkar1a specifically in the adrenal cortex (AdKO). AdKO mice develop pituitary-independent Cushing's syndrome with increased PKA activity. This leads to autonomous steroidogenic genes expression and deregulated adreno-cortical cells differentiation, increased proliferation and resistance to apoptosis. Unexpectedly, R1alpha loss results in improper maintenance and centrifugal expansion of cortisol-producing fetal adrenocortical cells with concomitant regression of adult cortex. Our data provide the first in vivo evidence that loss of R1alpha is sufficient to induce autonomous adrenal hyper-activity and bilateral hyperplasia, both observed in human PPNAD. Furthermore, this model demonstrates that deregulated PKA activity favors the emergence of a new cell population potentially arising from the fetal adrenal, giving new insight into the mechanisms leading to PPNAD. PMID:20548949

  20. La Pacana caldera, N. Chile: a re-evaluation of the stratigraphy and volcanology of one of the world's largest resurgent calderas

    NASA Astrophysics Data System (ADS)

    Lindsay, J. M.; de Silva, S.; Trumbull, R.; Emmermann, R.; Wemmer, K.

    2001-04-01

    La Pacana caldera in the Central Andes of northern Chile is one of the largest and best exposed resurgent calderas in the world. The caldera had previously been recognised as the source of the regionally-extensive Atana ignimbrite, but additional field and stratigraphic evidence, along with new K-Ar age determinations and geochemical data have led to a revision of the geology and development of this major Andean caldera. In particular, this information allows more realistic estimates of eruptive volumes and has implications for the style of ignimbrite eruption. Two major ignimbrites appear to have originated from La Pacana caldera, based on their thickness variations, lateral distributions and stratigraphic relations: the crystal-poor, rhyolitic Toconao ignimbrite (4-5 Ma) and the crystal-rich, dacitic Atana ignimbrite (4 Ma). Following caldera collapse and formation of the resurgent Atana block, several crystal-rich dacitic-rhyolitic domes formed along the margin of the resurgent block. New K-Ar ages show that this post-caldera volcanism continued from 4 to 2 Ma, indicating that the La Pacana magmatic system was active for at least 2 Ma after the main eruption. The Atana ignimbrite extends west, south and east of La Pacana caldera. Our work shows that the ignimbrite sequence northeast of the caldera, formerly mapped as Atana outflow, represents two new units which we name the upper and lower Tara ignimbrites. The distribution of the Tara ignimbrites points to a source to the north. The upper Tara ignimbrite comprises four flow units with interbedded surge and fall deposits and a characteristic, heterogeneous pumice population. It occurs in the La Pacana moat and onlaps the resurgent block. These field relations and a new K-Ar age of 3.8 Ma show convincingly that this ignimbrite erupted after formation of La Pacana caldera. The lower Tara ignimbrite is a single extensive flow unit, and has an age of 5.6 Ma. Two outcrops of lag breccia occur adjacent to the caldera

  1. Reappearance of deepwater sculpin in Lake Ontario: Resurgence or last gasp of a doomed population?

    USGS Publications Warehouse

    Lantry, B.F.; O'Gorman, R.; Walsh, M.G.; Casselman, J.M.; Hoyle, J.A.; Keir, M.J.; Lantry, J.R.

    2007-01-01

    Deepwater sculpin (Myoxocephalus thompsonii) were abundant in Lake Ontario in the 1920s and at least common into the 1940s. By the 1960s they were rare and, thereafter, some considered the population extirpated even though a synoptic survey of the lake in 1972 produced three, relatively large (148–165 mm total length, TL), and presumably old, specimens from the northern half of the lake. Deepwater sculpin were absent from annual survey catches in the 1980s and did not reappear until 1996, when three were caught in northern Lake Ontario. Isolated collections of deepwater sculpin continued during 1998–2004. Catches during 1996–2004 included five smaller individuals, 89–118 mm TL. In 2005, catches increased sharply, with 18 deepwater sculpin collected from southern waters and one from northern waters. Moreover, young, small sculpin were dominant in 2005—16 of the 19 sculpins averaged 68 ± 12 mm total length (± 1 s.d.). The young fish observed since 1996 could have originated from reproduction by the small in-lake population, from downstream drift of planktonic larvae from Lake Huron, or both. The presence of juveniles is a clear sign that conditions for survival of young deepwater sculpin are becoming more favorable, perhaps because of reduced abundance of alewife (Alosa pseudoharengus), a pelagic planktivore linked to depression of deepwater sculpin in Lake Michigan, and also low abundances of burbot (Lota lota) and lake trout (Salvelinus namaycush), benthic piscivores.

  2. The Oligocene Creede Formation, Colorado: The sedimentary record of a deep lake within a resurgent caldera

    SciTech Connect

    Larsen, D.; Smith, G.A. . Dept. of Earth and Planetary Sciences)

    1993-04-01

    The Oligocene Creede Formation is the sedimentary fill of the Creede caldera in the Tertiary San Juan volcanic field in southern Colorado. Scientific drill core and outcrop studies of Creede strata allow an evaluation of the post-collapse sedimentary environments present within a caldera. Although the Creede Formation is structurally disrupted, correlation of fallout tuffs in exposed strata to those in the cores has clarified stratigraphic relationships. Following ash-fallout from the caldera-forming eruption, up to 121 meters of coarse grained debris-flow strata and rockfall debris with interstratified basinward ephemeral lake deposits were deposited. The presence of pseudomorphs after ikaite and up-section increase in carbonate facies suggest that the lake water was somewhat alkaline and cold (near freezing), and evolved chemically with time. A late-stage drop in lake level combined with integration of basin-feeding drainages and decreased subsidence lead to basinward progradation of coarser deltaic and lacustrine fan deposits. Sedimentation patterns suggest that subsidence occurred largely in the northern half of the caldera, and decreased late in the lake's history allowing the basin to fill with sediment.

  3. The Late Cretaceous Middle Fork caldera, its resurgent intrusion, and enduring landscape stability in east-central Alaska

    USGS Publications Warehouse

    Bacon, Charles R.; Dusel-Bacon, Cynthia; Aleinikoff, John N.; Slack, John F.

    2014-01-01

    The Middle Fork is a relatively well preserved caldera within a broad region of Paleozoic metamorphic rocks and Mesozoic plutons bounded by northeast-trending faults. In the relatively downdropped and less deeply exhumed crustal blocks, Cretaceous–Early Tertiary silicic volcanic rocks attest to long-term stability of the landscape. Within the Middle Fork caldera, the granite porphyry is interpreted to have been exposed by erosion of thick intracaldera tuff from an asymmetric resurgent dome. The Middle Fork of the North Fork of the Fortymile River incised an arcuate valley into and around the caldera fill on the west and north and may have cut down from within an original caldera moat. The 70 Ma land surface is preserved beneath proximal outflow tuff at the west margin of the caldera structure and beneath welded outflow tuff 16–23 km east-southeast of the caldera in a paleovalley. Within ∼50 km of the Middle Fork caldera are 14 examples of Late Cretaceous (?)–Tertiary felsic volcanic and hypabyssal intrusive rocks that range in area from <1 km2 to ∼100 km2. Rhyolite dome clusters north and northwest of the caldera occupy tectonic basins associated with northeast-trending faults and are relatively little eroded. Lava of a latite complex, 12–19 km northeast of the caldera, apparently flowed into the paleovalley of the Middle Fork of the North Fork of the Fortymile River. To the northwest of the Middle Fork caldera, in the Mount Harper crustal block, mid-Cretaceous plutonic rocks are widely exposed, indicating greater total exhumation. To the southeast of the Middle Fork block, the Mount Veta block has been uplifted sufficiently to expose a ca. 68–66 Ma equigranular granitic pluton. Farther to the southeast, in the Kechumstuk block, the flat-lying outflow tuff remnant in Gold Creek and a regionally extensive high terrace indicate that the landscape there has been little modified since 70 Ma other than entrenchment of tributaries in response to post–2

  4. Reconstruction of caldera collapse and resurgence processes in the offshore sector of the Campi Flegrei caldera (Italy)

    NASA Astrophysics Data System (ADS)

    Steinmann, Lena; Spiess, Volkhard; Sacchi, Marco

    2015-04-01

    Large collapse calderas are associated with exceptionally explosive volcanic eruptions, which are capable of triggering a global catastrophe second only to that from a giant meteorite impact. Therefore, active calderas have attracted significant attention in both scientific communities and governmental institutions worldwide. One prime example of a large collapse caldera can be found in southern Italy, more precisely in the northern Bay of Naples within the Campi Flegrei Volcanic Area. The Campi Flegrei caldera covers an area of approximately 200 km² defined by a quasi-circular depression, half onland, half offshore. It is still under debate whether the caldera formation was related to only one ignimbritic eruption namely the Neapolitan Yellow Tuff (NYT) eruption at 15 ka or if it is a nested-caldera system related to the NYT and the Campanian Ignimbrite eruption at 39 ka. During the last 40 years, the Campi Flegrei caldera has experienced episodes of unrest involving significant ground deformation and seismicity, which have nevertheless not yet led to an eruption. Besides these short-term episodes of unrest, long-term ground deformation with rates of several tens of meters within a few thousand years can be observed in the central part of the caldera. The source of both short-term and long-term deformation is still under debate and possibly related to a shallow hydrothermal system and caldera resurgence attributed to a deeper magma chamber, respectively. Understanding the mechanisms for unrest and eruptions is of paramount importance as a future eruption of the Campi Flegrei caldera would expose more than 500,000 people to the risk of pyroclastic flows. This study is based on a dense grid (semi-3D) of high-resolution multi-channel seismic profiles acquired in the offshore sector of the Campi Flegrei caldera. The seismic lines show evidence for the escape of fluids and/or gases along weak zones such as faults, thereby supporting the existence of a hydrothermal

  5. Rock-avalanche and ocean-resurge deposits in the late Eocene Chesapeake Bay impact structure: Evidence from the ICDP-USGS Eyreville cores, Virginia, USA

    USGS Publications Warehouse

    Gohn, G.S.; Powars, D.S.; Dypvik, H.; Edwards, L.E.

    2009-01-01

    An unusually thick section of sedimentary breccias dominated by target-sediment clasts is a distinctive feature of the late Eocene Chesapeake Bay impact structure. A cored 1766-m-deep section recovered from the central part of this marine-target structure by the International Continental Scientific Drilling Program (ICDP)-U.S. Geological Survey (USGS) drilling project contains 678 m of these breccias and associated sediments and an intervening 275-m-thick granite slab. Two sedimentary breccia units consist almost entirely of Cretaceous nonmarine sediments derived from the lower part of the target sediment layer. These sediments are present as coherent clasts and as autoclastic matrix between the clasts. Primary (Cretaceous) sedimentary structures are well preserved in some clasts, and liquefaction and fluidization structures produced at the site of deposition occur in the clasts and matrix. These sedimentary breccias are interpreted as one or more rock avalanches from the upper part of the transient-cavity wall. The little-deformed, unshocked granite slab probably was transported as part of an extremely large slide or avalanche. Water-saturated Cretaceous quartz sand below the slab was transported into the seafloor crater prior to, or concurrently with, the granite slab. Two sedimentary breccia units consist of polymict diamictons that contain cobbles, boulders, and blocks of Cretaceous nonmarine target sediments and less common shocked-rock and melt ejecta in an unsorted, unstratified, muddy, fossiliferous, glauconitic quartz matrix. Much of the matrix material was derived from Upper Cretaceous and Paleogene marine target sediments. These units are interpreted as the deposits of debris flows initiated by the resurge of ocean water into the seafloor crater. Interlayering of avalanche and debris-flow units indicates a partial temporal overlap of the earlier avalanche and later resurge processes. A thin unit of stratified turbidite deposits and overlying laminated

  6. Bladder stones – red herring for resurgence of spasticity in a spinal cord injury patient with implantation of Medtronic Synchromed pump for intrathecal delivery of baclofen – a case report

    PubMed Central

    Vaidyanathan, Subramanian; Soni, Bakul M; Oo, Tun; Hughes, Peter L; Singh, Gurpreet; Watt, John WH; Sett, Pradipkumar

    2003-01-01

    Background Increased spasms in spinal cord injury (SCI) patients, whose spasticity was previously well controlled with intrathecal baclofen therapy, are due to (in order of frequency) drug tolerance, increased stimulus, low reservoir volume, catheter malfunction, disease progression, human error, and pump mechanical failure. We present a SCI patient, in whom bladder calculi acted as red herring for increased spasticity whereas the real cause was spontaneous extrusion of catheter from intrathecal space. Case Presentation A 44-year-old male sustained a fracture of C5/6 and incomplete tetraplegia at C-8 level. Medtronic Synchromed pump for intrathecal baclofen therapy was implanted 13 months later to control severe spasticity. The tip of catheter was placed at T-10 level. The initial dose of baclofen was 300 micrograms/day of baclofen, administered by a simple continuous infusion. During a nine-month period, he required increasing doses of baclofen (875 micrograms/day) to control spasticity. X-ray of abdomen showed multiple radio opaque shadows in the region of urinary bladder. No malfunction of the pump was detected. Therefore, increased spasticity was attributed to bladder stones. Electrohydraulic lithotripsy of bladder stones was carried out successfully. Even after removal of bladder stones, this patient required further increases in the dose of intrathecal baclofen (950, 1050, 1200 and then 1300 micrograms/day). Careful evaluation of pump-catheter system revealed that the catheter had extruded spontaneously and was lying in the paraspinal space at L-4, where the catheter had been anchored before it entered the subarachnoid space. A new catheter was passed into the subarachnoid space and the tip of catheter was located at T-8 level. The dose of intrathecal baclofen was decreased to 300 micrograms/day. Conclusion Vesical calculi acted as red herring for resurgence of spasticity. The real cause for increased spasms was spontaneous extrusion of whole length of

  7. Cell-Type Specific Channelopathies in the Prefrontal Cortex of the fmr1-/y Mouse Model of Fragile X Syndrome1,2,3

    PubMed Central

    Johnston, Daniel; Brager, Darrin H.

    2015-01-01

    Abstract Fragile X syndrome (FXS) is caused by transcriptional silencing of the fmr1 gene resulting in the loss of fragile X mental retardation protein (FMRP) expression. FXS patients display several behavioral phenotypes associated with prefrontal cortex (PFC) dysfunction. Voltage-gated ion channels, some of which are regulated by FMRP, heavily influence PFC neuron function. Although there is evidence for brain region-specific alterations to the function a single type of ion channel in FXS, it is unclear whether subtypes of principal neurons within a brain region are affected uniformly. We tested for alterations to ion channels critical in regulating neural excitability in two subtypes of prefrontal L5 pyramidal neurons. Using somatic and dendritic patch-clamp recordings, we provide evidence that the functional expression of h-channels (Ih) is down-regulated, whereas A-type K+ channel function is up-regulated in pyramidal tract-projecting (PT) neurons in the fmr1-/y mouse PFC. This is the opposite pattern of results from published findings from hippocampus where Ih is up-regulated and A-type K+ channel function is down-regulated. Additionally, we find that somatic Kv1-mediated current is down-regulated, resulting in increased excitability of fmr1-/y PT neurons. Importantly, these h- and K+ channel differences do not extend to neighboring intratelencephalic-projecting neurons. Thus, the absence of FMRP has divergent effects on the function of individual types of ion channels not only between brain regions, but also variable effects across cell types within the same brain region. Given the importance of ion channels in regulating neural circuits, these results suggest cell-type-specific phenotypes for the disease. PMID:26601124

  8. Channelopathies can cause epilepsy in man.

    PubMed

    Steinlein, Ortrud K

    2002-01-01

    Idiopathic epilepsies, which account for up to 40% of all epilepsies, are mainly caused by genetic factors. Most idiopathic epilepsies are due to oligogenic or multifactorial rather than monogenetic inheritance. Nevertheless, most of what is known today about the molecular genetics of idiopathic epilepsies has been found by analysing large families with rare monogenetic forms of the disease. For the first time, gene defects can be linked to certain epilepsies. Mutations in the CHRNA4 or CHRNB subunits of the neuronal nicotinic acetylcholine receptor lead to familial nocturnal frontal lobe epilepsy, while defects in the voltage-gated potassium channels KCNQ2 and KCNQ3 have recently been found to cause benign familial neonatal convulsions. The voltage-gated sodium channel subunits SCN1B, SCN1A and SCN2A as well as the GABRG2 subunit of the GABA(A) receptor are involved in the pathology of the newly described syndrome generalized epilepsy with febrile seizures plus. These rare monogenetic epilepsies can serve as models for further genetic analysis of the common forms of idiopathic epilepsies. PMID:11888238

  9. Arrhythmogenic mechanisms in ryanodine receptor channelopathies.

    PubMed

    Zhao, Yan-Ting; Valdivia, Carmen R; Gurrola, Georgina B; Hernández, Jonathan J; Valdivia, Héctor H

    2015-01-01

    Ryanodine receptors (RyRs) are the calcium release channels of sarcoplasmic reticulum (SR) that provide the majority of calcium ions (Ca(2+)) necessary to induce contraction of cardiac and skeletal muscle cells. In their intracellular environment, RyR channels are regulated by a variety of cytosolic and luminal factors so that their output signal (Ca(2+)) induces finely-graded cell contraction without igniting cellular processes that may lead to aberrant electrical activity (ventricular arrhythmias) or cellular remodeling. The importance of RyR dysfunction has been recently highlighted with the demonstration that point mutations in RYR2, the gene encoding for the cardiac isoform of the RyR (RyR2), are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT), an arrhythmogenic syndrome characterized by the development of adrenergically-mediated ventricular tachycardia in individuals with an apparently normal heart. Here we summarize the state of the field in regards to the main arrhythmogenic mechanisms triggered by RyR2 channels harboring mutations linked to CPVT. Most CPVT mutations characterized to date endow RyR2 channels with a gain of function, resulting in hyperactive channels that release Ca(2+) spontaneously, especially during diastole. The spontaneous Ca(2+) release is extruded by the electrogenic Na(+)/Ca(2+) exchanger, which depolarizes the external membrane (delayed afterdepolarization or DAD) and may trigger untimely action potentials. However, a rare set of CPVT mutations yield RyR2 channels that are intrinsically hypo-active and hypo-responsive to stimuli, and it is unclear whether these channels release Ca(2+) spontaneously during diastole. We discuss novel cellular mechanisms that appear more suitable to explain ventricular arrhythmias due to RyR2 loss-of-function mutations. PMID:25480325

  10. A Novel Channelopathy in Pulmonary Arterial Hypertension

    PubMed Central

    Austin, Eric D.; Eyries, Mélanie; Sampson, Kevin S.; Soubrier, Florent; Germain, Marine; Trégouët, David-Alexandre; Borczuk, Alain; Rosenzweig, Erika Berman; Girerd, Barbara; Montani, David; Humbert, Marc; Loyd, James E.; Kass, Robert S.; Chung, Wendy K.

    2013-01-01

    BACKGROUND Pulmonary arterial hypertension is a devastating disease with high mortality. Familial cases of pulmonary arterial hypertension are usually characterized by autosomal dominant transmission with reduced penetrance, and some familial cases have unknown genetic causes. METHODS We studied a family in which multiple members had pulmonary arterial hypertension without identifiable mutations in any of the genes known to be associated with the disease, including BMPR2, ALK1, ENG, SMAD9, and CAV1. Three family members were studied with whole-exome sequencing. Additional patients with familial or idiopathic pulmonary arterial hypertension were screened for the mutations in the gene that was identified on whole-exome sequencing. All variants were expressed in COS-7 cells, and channel function was studied by means of patch-clamp analysis. RESULTS We identified a novel heterozygous missense variant c.608 G→A (G203D) in KCNK3 (the gene encoding potassium channel subfamily K, member 3) as a disease-causing candidate gene in the family. Five additional heterozygous missense variants in KCNK3 were independently identified in 92 unrelated patients with familial pulmonary arterial hypertension and 230 patients with idiopathic pulmonary arterial hypertension. We used in silico bioinformatic tools to predict that all six novel variants would be damaging. Electrophysiological studies of the channel indicated that all these missense mutations resulted in loss of function, and the reduction in the potassium-channel current was remedied by the application of the phospholipase inhibitor ONO-RS-082. CONCLUSIONS Our study identified the association of a novel gene, KCNK3, with familial and idiopathic pulmonary arterial hypertension. Mutations in this gene produced reduced potassium-channel current, which was successfully remedied by pharmacologic manipulation. (Funded by the National Institutes of Health.) PMID:23883380

  11. Monitoring CO2 emissions in tree kill areas near the resurgent dome at Long Valley Caldera, California

    USGS Publications Warehouse

    Bergfeld, D.; Evans, William C.

    2011-01-01

    We report results of yearly measurements of the diffuse CO2 flux and shallow soil temperatures collected since 2006 across two sets of tree-kill areas at Long Valley Caldera, California. These data provide background information about CO2 discharge during a period with moderate seismicity, but little to no deformation. The tree kills are located at long-recognized areas of weak thermal fluid upflow, but have expanded in recent years, possibly in response to geothermal fluid production at Casa Diablo. The amount of CO2 discharged from the older kill area at Basalt Canyon is fairly constant and is around 3-5 tonnes of CO2 per day from an area of about 15,000 m2. The presence of isobutane in gas samples from sites in and around Basalt Canyon suggests that geothermal fluid production directly effects fluid upflow in the region close to the power plant. The average fluxes at Shady Rest are lower than average fluxes at Basalt Canyon, but the area affected by fluid upflow is larger. Total CO2 discharged from the central portion of the kill area at Shady Rest has been variable, ranging from 6 to11 tonnes per day across 61,000 m2. Gas collected at Shady Rest contains no detectable isobutane to link emissions chemically to geothermal fluid production, but two samples from 2009-10 have detectable H2S and suggest an increasing geothermal character of emitted gas. The appearance of this gas at the surface may signal increased drawdown of water levels near the geothermal productions wells.

  12. Pertussis: increasing disease as a consequence of reducing transmission.

    PubMed

    Aguas, Ricardo; Gonçalves, Guilherme; Gomes, M Gabriela M

    2006-02-01

    Since the 1980s, the occurrence of pertussis cases in developed countries has increased and shifted towards older age groups. This resurgence follows 30 years of intense mass vaccination, and has been attributed primarily to three factors: (1) more effective diagnosis of the disease, (2) waning of vaccine-induced immunity, and (3) loss of vaccine efficacy due to the emergence of new Bordetella pertussis strains. Here we develop and analyse a mathematical model to assess the plausibility of these hypotheses. We consider that exposure to B pertussis through natural infection or vaccination induces an immune response that prevents severe disease but does not fully prevent mild infections. We also assume that these protective effects are temporary due to waning of immunity. These assumptions, describing the mode of action of adaptive immunity, are combined with a standard transmission model. Two distinct epidemiological scenarios are detected: under low transmission, most infections lead to severe disease; under high transmission, mild infections are frequent, boosting clinical immunity and maintaining low levels of severe disease. The two behaviours are separated by a reinfection threshold in transmission. As a result, the highest incidence of severe disease is expected to occur at intermediate transmission intensities--near the reinfection threshold--suggesting that pertussis resurgence may be induced by a reduction in transmission, independently of vaccination. The model is extended to interpret the outcomes of current control measures and explore scenarios for future interventions. PMID:16439331

  13. The Resurgence of Cosmic Storytellers

    ERIC Educational Resources Information Center

    Swimme, Brian

    2013-01-01

    Brian Swimme's insights about the Story of the Universe look to the unifying impact of a "cosmic story" that speaks to all cultures and nations. Swimme suggests that humans are now able, through science and narrative, to present a story which will make us all a "cohesive tribe" while answering the universal questions of…

  14. The Resurgence of Biological Determinism.

    ERIC Educational Resources Information Center

    Segal, Elizabeth A.; Kilty, Keith M.

    1998-01-01

    Addresses two areas where science has been and still is used to justify policies and attitudes that are discriminatory and oppressive: homosexuality and alcoholism. This article analyzes the debate over whether these correlations are biologically or socially determined. Of particular concern is the potential impact of biological determinism on the…

  15. Ampicillin: rise fall and resurgence.

    PubMed

    Kaushik, Dwarikadhish; Mohan, Mudit; Borade, Dhammraj M; Swami, Onkar C

    2014-05-01

    Antimicrobial resistance (AMR) is a global problem. AMR has posed new challenges in treatment of infectious diseases. Antimicrobials are losing efficacy due to development of resistant pathogens. It has lead to re-emergence of certain infectious diseases. Treatment of such diseases has undergone changes with use of alternative antimicrobials and drug combinations. Pathogens are likely to develop resistance to alternative antimicrobials also and risk of infections with nonexistent treatment is real. Salmonella showed widespread resistant to ampicillin which resulted in use of alternative antimicrobials like fluroquinolones and cephalosporins in the treatment of enteric fever in last two decades. Unfortunately there are growing reports of resistance to these antimicrobials. Interestingly there are numerous reports of ampicillin regaining activity against Salmonella. Speculatively lack of exposure of Salmonella to ampicillin for long time resulted in the loss of plasmid mediated resistance in the pathogen. There may have been emergence of de novo ampicillin susceptible strains. This is assuring in the era where problem of AMR is compounded by the scarcity of new antimicrobial development. PMID:24995206

  16. Kinetic and functional analysis of transient, persistent and resurgent sodium currents in rat cerebellar granule cells in situ: an electrophysiological and modelling study

    PubMed Central

    Magistretti, Jacopo; Castelli, Loretta; Forti, Lia; D'Angelo, Egidio

    2006-01-01

    Cerebellar neurones show complex and differentiated mechanisms of action potential generation that have been proposed to depend on peculiar properties of their voltage-dependent Na+ currents. In this study we analysed voltage-dependent Na+ currents of rat cerebellar granule cells (GCs) by performing whole-cell, patch-clamp experiments in acute rat cerebellar slices. A transient Na+ current (INaT) was always present and had the properties of a typical fast-activating/inactivating Na+ current. In addition to INaT, robust persistent (INaP) and resurgent (INaR) Na+ currents were observed. INaP peaked at ∼−40 mV, showed half-maximal activation at ∼−55 mV, and its maximal amplitude was about 1.5% of that of INaT. INaR was elicited by repolarizing pulses applied following step depolarizations able to activate/inactivate INaT, and showed voltage- and time-dependent activation and voltage-dependent decay kinetics. The conductance underlying INaR showed a bell-shaped voltage dependence, with peak at −35 mV. A significant correlation was found between GC INaR and INaT peak amplitudes; however, GCs expressing INaT of similar size showed marked variability in terms of INaR amplitude, and in a fraction of cells INaR was undetectable. INaT, INaP and INaR could be accounted for by a 13-state kinetic scheme comprising closed, open, inactivated and blocked states. Current-clamp experiments carried out to identify possible functional correlates of INaP and/or INaR revealed that in GCs single action potentials were followed by depolarizing afterpotentials (DAPs). In a majority of cells, DAPs showed properties consistent with INaR playing a role in their generation. Computer modelling showed that INaR promotes DAP generation and enhances high-frequency firing, whereas INaP boosts near-threshold firing activity. Our findings suggest that special properties of voltage-dependent Na+ currents provides GCs with mechanisms suitable for shaping activity patterns, with potentially

  17. Pharmacological approach to the treatment of long and short QT syndromes.

    PubMed

    Patel, Chinmay; Antzelevitch, Charles

    2008-04-01

    Inherited channelopathies have received increasing attention in recent years. The past decade has witnessed impressive progress in our understanding of the molecular and cellular basis of arrhythmogenesis associated with inherited channelopathies. An imbalance in ionic forces induced by these channelopathies affects the duration of ventricular repolarization and amplifies the intrinsic electrical heterogeneity of the myocardium, creating an arrhythmogenic milieu. Today, many of the channelopathies have been linked to mutations in specific genes encoding either components of ion channels or membrane or regulatory proteins. Many of the channelopathies are genetically heterogeneous with a variable degree of expression of the disease. Defining the molecular basis of channelopathies can have a profound impact on patient management, particularly in cases in which genotype-specific pharmacotherapy is available. The long QT syndrome (LQTS) is one of the first identified and most studied channelopathies where abnormal prolongation of ventricular repolarization predisposes an individual to life threatening ventricular arrhythmia called Torsade de Pointes. On the other hand of the spectrum, molecular defects favoring premature repolarization lead to Short QT syndrome (SQTS), a recently described inherited channelopathy. Both of these channelopathies are associated with a high risk of sudden cardiac death due to malignant ventricular arrhythmia. Whereas pharmacological therapy is first line treatment for LQTS, defibrillators are considered as primary treatment for SQTS. This review provides a comprehensive review of the molecular genetics, clinical features, genotype-phenotype correlations and genotype-specific approach to pharmacotherapy of these two mirror-image channelopathies, SQTS and LQTS. PMID:18378319

  18. Pharmacological approach to the treatment of long and short QT syndromes☆

    PubMed Central

    Patel, Chinmay; Antzelevitch, Charles

    2008-01-01

    Inherited channelopathies have received increasing attention in recent years. The past decade has witnessed impressive progress in our understanding of the molecular and cellular basis of arrhythmogenesis associated with inherited channelopathies. An imbalance in ionic forces induced by these channelopathies affects the duration of ventricular repolarization and amplifies the intrinsic electrical heterogeneity of the myocardium, creating an arrhythmogenic milieu. Today, many of the channelopathies have been linked to mutations in specific genes encoding either components of ion channels or membrane or regulatory proteins. Many of the channelopathies are genetically heterogeneous with a variable degree of expression of the disease. Defining the molecular basis of channelopathies can have a profound impact on patient management, particularly in cases in which genotype-specific pharmacotherapy is available. The long QT syndrome (LQTS) is one of the first identified and most studied channelopathies where abnormal prolongation of ventricular repolarization predisposes an individual to life threatening ventricular arrhythmia called Torsade de Pointes. On the other hand of the spectrum, molecular defects favoring premature repolarization lead to Short QT syndrome (SQTS), a recently described inherited channelopathy. Both of these channelopathies are associated with a high risk of sudden cardiac death due to malignant ventricular arrhythmia. Whereas pharmacological therapy is first line treatment for LQTS, defibrillators are considered as primary treatment for SQTS. This review provides a comprehensive review of the molecular genetics, clinical features, genotype–phenotype correlations and genotype-specific approach to pharmacotherapy of these two mirror-image channelopathies, SQTS and LQTS. PMID:18378319

  19. Increasing numbers of migrants challenge policymakers worldwide.

    PubMed

    Martin, P

    1996-05-01

    International migration has increased greatly in the 1990s. In the mid-1990s there were about 125 million migrants (about 2% of the world's population) not living in their country of birth or citizenship. There are 2-4 million new migrants each year. The global migrant population is concentrated in only a few countries. In many Middle Eastern countries, foreign workers make up most of the labor force (60-90%). Africa and western Asia have more than 50% of all 27 million refugees and displaced persons. Germany, France, the UK, the US, Italy, Japan, and Canada have about 33% of the migrant population. Newly arriving immigrants make up a large percentage of annual population growth in industrialized countries with low birth rates (100% in Germany and about 33% in the US). Major migration flows are from Mexico, Central America, and Asia to the US; from North Africa and eastern Europe to western Europe; and from the Philippines and India to the Middle East. Two US legalization programs contributed to a resurgence in immigration in the early 1990s. Many of the world's top economic powers are very concerned about immigration. Economic growth can cut down on economic migration. Many specialists think that freer trade, more foreign investment, and, in some cases, aid can spark economic growth. Many residents of countries receiving migrants want immigration curtailed. Many industrial democracies handle difficult migration issues by making trade-offs, particularly combine stricter immigration controls with more assistance to integrate new immigrants and liberalize trade so countries can export goods instead of people. PMID:12291192

  20. Increased aldosterone-dependent Kv1.5 recycling predisposes to pacing-induced atrial fibrillation in Kcne3-/- mice.

    PubMed

    Lisewski, Ulrike; Koehncke, Clemens; Wilck, Nicola; Buschmeyer, Bastian; Pieske, Burkert; Roepke, Torsten K

    2016-07-01

    Hyperaldosteronism is associated with an increased prevalence of atrial fibrillation (AF). Mutations in KCNE3 have been associated with AF, and Kcne3(-/-) mice exhibit hyperaldosteronism. In this study, we used recently developed Kcne3(-/-) mice to study atrial electrophysiology with respect to development of aldosterone-dependent AF. In invasive electrophysiology studies, Kcne3(-/-) mice displayed a reduced atrial effective refractory period (AERP) and inducible episodes of paroxysmal AF. The cellular arrhythmogenic correlate for AF predisposition was a significant increase in atrial Kv currents generated by the micromolar 4-aminopyridine-sensitive Kv current encoded by Kv1.5. Electrophysiological alterations in Kcne3(-/-) mice were aldosterone dependent and were associated with increased Rab4, -5, and -9-dependent recycling of Kv1.5 channels to the Z-disc/T-tubulus region and lateral membrane via activation of the Akt/AS160 pathway. Treatment with spironolactone inhibited Akt/AS160 phosphorylation, reduced Rab-dependent Kv1.5 recycling, normalized AERP and atrial Kv currents to the wild-type level, and reduced arrhythmia induction in Kcne3(-/-) mice. Kcne3 deletion in mice predisposes to AF by a heretofore unrecognized mechanism-namely, increased aldosterone-dependent Kv1.5 recycling via Rab GTPases. The findings uncover detailed molecular mechanisms underpinning a channelopathy-linked form of AF and emphasize the inevitability of considering extracardiac mechanisms in genetic arrhythmia syndromes.-Lisewski, U., Koehncke, C., Wilck, N., Buschmeyer, B., Pieske, B., Roepke, T. K. Increased aldosterone-dependent Kv1.5 recycling predisposes to pacing-induced atrial fibrillation in Kcne3(-/-) mice. PMID:26985008

  1. Private practitioners and their role in the resurgence of malaria in Mumbai (Bombay) and Navi Mumbai (New Bombay), India: serving the affected or aiding an epidemic?

    PubMed

    Kamat, V R

    2001-03-01

    The increased emphasis on privatization of the health care sector in many developing countries by international financial institutions and national governments expects an expanding role for private health care practitioners in the management of major communicable diseases such as tuberculosis, malaria, acute respiratory infections (ARIs) and sexually transmitted diseases (STDs). Largely unexamined in the Indian context, however, is the socio-cultural context, the micro-level political environment in which private practitioners carry out their activities, and the quality of care they provide to their patients. Examining these aspects is significant given the impressive growth of the country's private health sector during the past decade. This paper reports the results of an ethnographic study carried out in Mumbai (Bombay) and Nav Mumbai (New Bombay), India on private general practitioners (GPs) and their role in the management of malaria at a time when these two neighboring cities were in the midst of the worst malaria epidemic in over 60 years. Described are the characteristics of a sample of 48 private practitioners from the two cities, and their clinics. This is followed by a discussion of the data gathered through untructured interviews with practitioners and patients, and complemented by observational data on doctor-patient encounters gathered at 16 clinics over a 9-month period. The findings of the study suggest that many practitioners in Mumbai and Navi Mumbai were poorly qualified and did not play a supportive role in the two cities' public health departments to bring the epidemic under control. The majority of the practitioners adopted diagnostic and treatment practices that were not consistent with the guidelines laid down by WHO and India's National Malaria Eradication Programme. Very few practitioners, especially those practicing in low-income areas, relied on a peripheral blood-smear test to make a diagnosis. Practitioners whose clientele was mostly

  2. Channelopathies - Emerging Trends in The Management of Inherited Arrhythmias

    PubMed Central

    Chockalingam, Priya; Mizusawa, Yuka; Wilde, Arthur A.M.

    2016-01-01

    In spite of their relative rarity, inheritable arrhythmias have come to the forefront as a group of potentially fatal but preventable cause of sudden cardiac death in children and (young) adults. Comprehensive management of inherited arrhythmias includes diagnosing and treating the proband and identifying and protecting affected family members. This has been made possible by the vast advances in the field of molecular biology enabling better understanding of the genetic underpinnings of some of these disease groups, namely congenital long QT syndrome, catecholaminergic polymorphic ventricular tachycardia and Brugada syndrome. The ensuing knowledge of the genotype-phenotype correlations enables us to risk-stratify, prognosticate and treat based on the genetic test results. The various diagnostic modalities currently available to us, including clinical tools and genetic technologies, have to be applied judiciously in order to promptly identify those affected and to spare the emotional burden of a potentially lethal disease in the unaffected individuals. The therapeutic armamentarium of inherited arrhythmias includes pharmacological agents, device therapies and surgical interventions. A treatment strategy keeping in mind the risk profile of the patients, the local availability of drugs and the expertise of the treating personnel is proving effective. While opportunities for research are numerous in this expanding field of medicine, there is also tremendous scope for incorporating the emerging trends in managing patients and families with inherited arrhythmias in the Indian subcontinent. PMID:25852242

  3. Sodium channel β subunits: emerging targets in channelopathies.

    PubMed

    O'Malley, Heather A; Isom, Lori L

    2015-01-01

    Voltage-gated sodium channels (VGSCs) are responsible for the initiation and propagation of action potentials in excitable cells. VGSCs in mammalian brain are heterotrimeric complexes of α and β subunits. Although β subunits were originally termed auxiliary, we now know that they are multifunctional signaling molecules that play roles in both excitable and nonexcitable cell types and with or without the pore-forming α subunit present. β subunits function in VGSC and potassium channel modulation, cell adhesion, and gene regulation, with particularly important roles in brain development. Mutations in the genes encoding β subunits are linked to a number of diseases, including epilepsy, sudden death syndromes like SUDEP and SIDS, and cardiac arrhythmia. Although VGSC β subunit-specific drugs have not yet been developed, this protein family is an emerging therapeutic target. PMID:25668026

  4. Sodium channel β subunits: emerging targets in channelopathies

    PubMed Central

    O’Malley, Heather A.; Isom, Lori L.

    2016-01-01

    Voltage-gated sodium channels (VGSCs) are responsible for initiation and propagation of action potentials in excitable cells. VGSCs in mammalian brain are heterotrimeric complexes of α and β subunits. Originally called “auxiliary,” we now know that β subunit proteins are multifunctional signaling molecules that play roles in both excitable and non-excitable cell types, and with or without the pore-forming α subunit present. β subunits function in VGSC and potassium channel modulation, cell adhesion, and gene regulation, with particularly important roles in brain development. Mutations in the genes encoding β subunits are linked to a number of diseases, including epilepsy, sudden death syndromes like SUDEP and SIDS, and cardiac arrhythmia. While VGSC β subunit-specific drugs have not yet been developed, this protein family is an emerging therapeutic target. PMID:25668026

  5. Channelopathies - emerging trends in the management of inherited arrhythmias.

    PubMed

    Chockalingam, Priya; Mizusawa, Yuka; Wilde, Arthur Am

    2015-01-01

    In spite of their relative rarity, inheritable arrhythmias have come to the forefront as a group of potentially fatal but preventable cause of sudden cardiac death in children and (young) adults. Comprehensive management of inherited arrhythmias includes diagnosing and treating the proband and identifying and protecting affected family members. This has been made possible by the vast advances in the field of molecular biology enabling better understanding of the genetic underpinnings of some of these disease groups, namely congenital long QT syndrome, catecholaminergic polymorphic ventricular tachycardia and Brugada syndrome. The ensuing knowledge of the genotype-phenotype correlations enables us to risk-stratify, prognosticate and treat based on the genetic test results. The various diagnostic modalities currently available to us, including clinical tools and genetic technologies, have to be applied judiciously in order to promptly identify those affected and to spare the emotional burden of a potentially lethal disease in the unaffected individuals. The therapeutic armamentarium of inherited arrhythmias includes pharmacological agents, device therapies and surgical interventions. A treatment strategy keeping in mind the risk profile of the patients, the local availability of drugs and the expertise of the treating personnel is proving effective. While opportunities for research are numerous in this expanding field of medicine, there is also tremendous scope for incorporating the emerging trends in managing patients and families with inherited arrhythmias in the Indian subcontinent. PMID:25852242

  6. Novel insights into the pathomechanisms of skeletal muscle channelopathies.

    PubMed

    Burge, James A; Hanna, Michael G

    2012-02-01

    The nondystrophic myotonias and primary periodic paralyses are an important group of genetic muscle diseases characterized by dysfunction of ion channels that regulate membrane excitability. Clinical manifestations vary and include myotonia, hyperkalemic and hypokalemic periodic paralysis, progressive myopathy, and cardiac arrhythmias. The severity of myotonia ranges from severe neonatal presentation causing respiratory compromise through to mild later-onset disease. It remains unclear why the frequency of attacks of paralysis varies greatly or why many patients develop a severe permanent fixed myopathy. Recent detailed characterizations of human genetic mutations in voltage-gated muscle sodium (gene: SCN4A), chloride (gene: CLCN1), calcium (gene: CACNA1S), and inward rectifier potassium (genes: KCNJ2, KCNJ18) channels have resulted in new insights into disease mechanisms, clinical phenotypic variation, and therapeutic options. PMID:22083238

  7. The Resurgence of America's Auto Industry

    ScienceCinema

    Zimmer, Stephen; Cischke, Sue;

    2013-05-29

    A look at how strategic investments and partnerships between the Energy Department and automakers have helped the American auto industry become a leader in advanced and fuel-efficient vehicles ? creating jobs and boosting profits in the process.

  8. The Resurgence of America's Auto Industry

    SciTech Connect

    Zimmer, Stephen; Cischke, Sue

    2012-01-01

    A look at how strategic investments and partnerships between the Energy Department and automakers have helped the American auto industry become a leader in advanced and fuel-efficient vehicles — creating jobs and boosting profits in the process.

  9. Dolphin Morbillivirus Epizootic Resurgence, Mediterranean Sea

    PubMed Central

    Raga, Juan-Antonio; Domingo, Mariano; Corteyn, Mandy; Van Bressem, Marie-Françoise; Fernández, Mercedes; Aznar, Francisco-Javier; Barrett, Thomas

    2008-01-01

    In July 2007, >100 striped dolphins, Stenella coeruleoalba, were found dead along the coast of the Spanish Mediterranean. Of 10 dolphins tested, 7 were positive for a virus strain closely related to the dolphin morbillivirus that was isolated during a previous epizootic in 1990. PMID:18325265

  10. Geoscience Field Education: A Recent Resurgence

    NASA Astrophysics Data System (ADS)

    Whitmeyer, Steven J.; Mogk, David W.

    2009-10-01

    Field education traditionally has been an integral component of undergraduate geoscience curricula. Students have learned the fundamentals of field techniques during core geology courses and have honed their field credentials during class-specific field trips, semester-long field courses, and capstone summer field camps. In many geoscience departments, field camp remains a graduation requirement, and more than 100 field camps currently are offered by U.S. universities and colleges (see http://geology.com/field-camp.shtml). During the past several decades, however, many geoscience departments have moved away from traditional geologic fieldwork and toward a broader theoretical and laboratory-intensive focus that encompasses a range of subdisciplines. Trends that have influenced these shifts include (1) the decline in the late twentieth century of the petroleum and mining industries, which have consistently championed the values of fieldwork; (2) a decrease in the number of professional jobs that incorporate field mapping; (3) a decline in the number of geoscience majors nationwide [American Geological Institute (AGI), 2009]; and (4) barriers to fieldwork, including time requirements, cost, liability, and decreasing access to field sites.

  11. The resurgence of selective contracting restrictions.

    PubMed

    Marsteller, J A; Bovbjerg, R R; Nichols, L M; Verrilli, D K

    1997-10-01

    As managed care has spread, so has legislation to force plans to contract with any willing provider (AWP) and give patients freedom of choice (FOC). Managed care organizations' selective networks and provider integration reduce patient access to providers, along with provider access to paying patients, so many providers have lobbied for AWP-FOC laws. In opposition are managed care organizations (MCOs), which want full freedom to contract selectively to control prices and utilization. This article comprehensively describes laws in all fifty-one jurisdictions, classifies their relative strength, and assesses the implications of the laws. Most are relatively weak forms and all are limited in application by ERISA and the federal HMO Act. The article also uses an associative multivariate analysis to relate the selective contracting environments to HMO penetration rates, rural population, physician density, and other variables. States with weak laws also have higher HMO penetration and higher physician density, but smaller rural populations. We conclude that the strongest laws overly restrict the management of care, to the likely detriment of cost control. But where market power is rapidly concentrating, not restricting selective contracting could diminish long-term competition and patient access to care. In the face of uncertainty about the impact of these laws, an intermediate approach may be better than all or nothing. States should consider mandating that plans offer point-of-service options, for a separate premium. This option expands patient choice of plans at the time of enrollment and of providers at the time of care, yet maintains plans' ability to control core providers. PMID:9394244

  12. Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways

    PubMed Central

    Onodera, Yasuhito; Nam, Jin-Min; Bissell, Mina J.

    2013-01-01

    There is a considerable resurgence of interest in the role of aerobic glycolysis in cancer; however, increased glycolysis is frequently viewed as a consequence of oncogenic events that drive malignant cell growth and survival. Here we provide evidence that increased glycolytic activation itself can be an oncogenic event in a physiologically relevant 3D culture model. Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. Conversely, reduction of glucose uptake in malignant cells promoted the formation of organized and growth-arrested structures with basal polarity, and suppressed oncogenic pathways. Unexpectedly and importantly, we found that unlike reported literature, in 3D the differences between “normal” and malignant phenotypes could not be explained by HIF-1α/2α, AMPK, or mTOR pathways. Loss of epithelial integrity involved activation of RAP1 via exchange protein directly activated by cAMP (EPAC), involving also O-linked N-acetylglucosamine modification downstream of the hexosamine biosynthetic pathway. The former, in turn, was mediated by pyruvate kinase M2 (PKM2) interaction with soluble adenylyl cyclase. Our findings show that increased glucose uptake activates known oncogenic pathways to induce malignant phenotype, and provide possible targets for diagnosis and therapeutics. PMID:24316969

  13. Increased feelings with increased body signals

    PubMed Central

    Vianna, Eduardo P. M.; Weinstock, Joel; Elliott, David; Summers, Robert; Tranel, Daniel

    2006-01-01

    Since the beginning of psychology as a scientific endeavour, the question of whether the body plays a role in how a person experiences emotion has been the centre of emotion research. Patients with structural gastrointestinal disorders, such as Crohn's disease, provide an intriguing opportunity to study the influence of body signals on emotions and feelings. In the present study, emotionally salient films were presented to participants with Crohn's disease in either the active state (Crohn's-active, CA) or silent state (Crohn's-silent, CS), and to normal comparison (NC) participants. We hypothesized that CA participants would have increased feelings, compared with CS and NC participants, when viewing emotional films designed to elicit happiness, disgust, sadness and fear. Gastric myoelectrical activity (electrogastrogram, or EGG) was measured during the films, and after each film was presented, participants rated emotion intensity (arousal) and pleasantness (valence). All groups labelled the emotions similarly. In support of the hypothesis, CA participants showed an increase in subjective arousal for negative emotions compared with CS and NC participants. The CA participants also showed increased EGG during emotional film viewing, as well as a strong positive correlation of EGG with arousal ratings. Together, these findings can be taken as evidence that aberrant feedback from the gastrointestinal system up-regulates the intensity of feelings of negative emotions. PMID:18985099

  14. Increased head circumference

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003305.htm Increased head circumference To use the sharing features on this page, please enable JavaScript. Increased head circumference is when the measured distance around the ...

  15. Increased intracranial pressure

    MedlinePlus

    Increased intracranial pressure is a rise in the pressure inside the skull that can result from or cause brain injury. ... Increased intracranial pressure can be due to a rise in pressure of the cerebrospinal fluid. This is ...

  16. Increases in Problem Drinking

    MedlinePlus

    ... review our exit disclaimer . Subscribe Increases in Problem Drinking Alcohol use disorder is becoming more common, a ... the need to better educate people about problem drinking and its treatment. Alcohol use disorder, or AUD, ...

  17. Increasing productivity: Another approach

    SciTech Connect

    Norton, F.J.

    1996-06-10

    An engineering information (EI) and information technology (IT) organization that must improve its productivity should work to further its business goals. This paper explores a comprehensive model for increasing EI/IT productivity by supporting organizational objectives.

  18. Increasing Public Library Productivity.

    ERIC Educational Resources Information Center

    Samuelson, Howard

    1981-01-01

    Suggests ways of improving productivity for public libraries faced with increased accountability, dwindling revenues, and continuing inflation. Techniques described include work simplification, work analysis, improved management, and employee motivation. (RAA)

  19. Meeting increased demand.

    PubMed

    Blair, Andrew

    2004-07-01

    New Zealand is a little country with a little economy but with a population that's rapidly aging. New Zealand's population is only 4.3 million people. It's GDP is only $US58.6 billion (2002). New Zealand's expenditure on health as a percentage of GDP is not out of line with that of other countries. As a nation we have been increasing expenditure on health over recent years. In 1990 we spent 7% of GDP on health. In 1995 that increased to 7.65% and is now 8.3%. However, in per capita terms our expenditure on health does not compare so well with like countries. The size of New Zealand's economy is restricting what our country spends on health. Health is already the second highest demand on the New Zealand tax dollar. The tolerance of New Zealanders would be challenged if a Government attempted to increase taxes further to meet the growing demands for expenditure on health, but at the same time the population's expectations are increasing. This is the challenging situation we face today. What lies ahead? Like all industrialized countries New Zealand is facing an aging population. The population below age 40 is decreasing, but it is increasing significantly over that age. 16% of the population is currently aged over 60. By 2051 this proportion will almost double to just over 31%. Coupled with the aging population is increased awareness and expectations, as access to options for treatment and technology becomes readily accessible to the population through such media as the internet. The extent of the impact of the aging population can be clearly represented by focusing on one specialty such as orthopaedics. The New Zealand Orthopaecic Association undertook a study in July 2003 which concluded (among other things) that as a result of the projected aging of the population, over the next 50 years: Musculo-skeletal operations will increase by over 30%. The number of hip replacements will nearly double. The incidence of osteoporosis will increase by a massive 201%. The number

  20. Seismic waves increase permeability.

    PubMed

    Elkhoury, Jean E; Brodsky, Emily E; Agnew, Duncan C

    2006-06-29

    Earthquakes have been observed to affect hydrological systems in a variety of ways--water well levels can change dramatically, streams can become fuller and spring discharges can increase at the time of earthquakes. Distant earthquakes may even increase the permeability in faults. Most of these hydrological observations can be explained by some form of permeability increase. Here we use the response of water well levels to solid Earth tides to measure permeability over a 20-year period. At the time of each of seven earthquakes in Southern California, we observe transient changes of up to 24 degrees in the phase of the water level response to the dilatational volumetric strain of the semidiurnal tidal components of wells at the Piñon Flat Observatory in Southern California. After the earthquakes, the phase gradually returns to the background value at a rate of less than 0.1 degrees per day. We use a model of axisymmetric flow driven by an imposed head oscillation through a single, laterally extensive, confined, homogeneous and isotropic aquifer to relate the phase response to aquifer properties. We interpret the changes in phase response as due to changes in permeability. At the time of the earthquakes, the permeability at the site increases by a factor as high as three. The permeability increase depends roughly linearly on the amplitude of seismic-wave peak ground velocity in the range of 0.21-2.1 cm s(-1). Such permeability increases are of interest to hydrologists and oil reservoir engineers as they affect fluid flow and might determine long-term evolution of hydrological and oil-bearing systems. They may also be interesting to seismologists, as the resulting pore pressure changes can affect earthquakes by changing normal stresses on faults. PMID:16810253

  1. Increased global financings

    SciTech Connect

    Anderson, J.

    1994-10-01

    The results of a financial rankings survey for the first half of 1994 show increased financial activity over the second half of 1993. More than $10.5 billion is reported by developers and financial firms for 62 transactions during 1994`s first six months.

  2. Does salt increase thirst?

    PubMed

    Leshem, Micah

    2015-02-01

    Our diet is believed to be overly rich in sodium, and it is commonly believed that sodium intake increases drinking. Hence the concern of a possible contribution of dietary sodium to beverage intake which in turn may contribute to obesity and ill health. Here we examine whether voluntary, acute intake of a sodium load, as occurs in routine eating and snacking, increases thirst and drinking. We find that after ingesting 3.5 or 4.4 g NaCl (men) and 1.9 or 3.7 g (women) on nuts during 15 minutes, there is no increase in thirst or drinking of freely available water in the following 2 h compared with eating similar amounts of sugared or unflavored nuts. This suggests that routine ingestion of boluses of salt (~30-40% of daily intake for men, ~ 20-40% for women) does not increase drinking. Methodological concerns such as about nuts as vehicle for sodium suggest further research to establish the generalizability of this unexpected result. PMID:25447020

  3. Productivity increases in science

    SciTech Connect

    Danko, J.E.; Young, J.K.; Molton, P.M.; Dirks, J.A.

    1993-02-01

    The study quantifies the impact on the cost of experimentation of synergistic advancements in instrumentation, theory, and computation over the last two decades. The study finds that the productivity of experimental investigation (experimental results/$) is increasing as science is transformed from a linear, isolated approach to a hierarchical, multidisciplinary approach. Developments such as massively parallel processors coupled with instrumental systems with multiple probes and diverse data analysis capabilities will further this transformation and increase the productivity of scientific studies. The complexities and scale of today's scientific challenges are much greater than in the past, however, so that the costs of research are increasing. Even though science is much more productive in terms of the experimental results, the challenges facing scientific investigators are increasing at an even faster pace. New approaches to infrastructure investments must capitalize on the changing dynamics of research and allow the scientific community to maximize gains in productivity so that complex problems can be attacked cost-effectively. Research strategies that include user facilities and coordinated experimental, computational, and theoretical research are needed.

  4. Productivity increases in science

    SciTech Connect

    Danko, J.E.; Young, J.K.; Molton, P.M.; Dirks, J.A.

    1993-02-01

    The study quantifies the impact on the cost of experimentation of synergistic advancements in instrumentation, theory, and computation over the last two decades. The study finds that the productivity of experimental investigation (experimental results/$) is increasing as science is transformed from a linear, isolated approach to a hierarchical, multidisciplinary approach. Developments such as massively parallel processors coupled with instrumental systems with multiple probes and diverse data analysis capabilities will further this transformation and increase the productivity of scientific studies. The complexities and scale of today`s scientific challenges are much greater than in the past, however, so that the costs of research are increasing. Even though science is much more productive in terms of the experimental results, the challenges facing scientific investigators are increasing at an even faster pace. New approaches to infrastructure investments must capitalize on the changing dynamics of research and allow the scientific community to maximize gains in productivity so that complex problems can be attacked cost-effectively. Research strategies that include user facilities and coordinated experimental, computational, and theoretical research are needed.

  5. Designer drilling increases recovery

    SciTech Connect

    Eck-Olsen, J.; Drevdal, K.E.

    1995-04-01

    Implementation of a new designer-well profile has resulted in increased recovery and production rates. The geologically complex Gullfaks field, located in the Norwegian sector of the North Sea, required a new type of well profile to increase total recovery and production rates from Gullfaks A, B and C platforms. Advances in steerable technology and directional drilling performance enabled a 3-D horizontal, extended-reach well profile, now designated as a designer well, to penetrate multiple targets. This article presents the concept, implementation and conclusions drawn from designer well application. Gullfaks field, in Norwegian North Sea Block 34/10, is the first license ever run by a fully Norwegian joint venture corporation. The license group consists of Statoil (operator), Norsk Hydro and Saga Petroleum. The field currently produces more than 535,000 bopd from three main Jurassic reservoirs.

  6. Condom use increasing.

    PubMed

    Finger, W R

    1998-01-01

    Condom use is central to the prevention of AIDS among people at risk for contracting HIV. As such, condom use is increasing dramatically even though many men say that they do not like using them. Condom sales through social marketing campaigns have increased dramatically in some countries, where tens of millions of condoms are sold annually. For example, during the period 1991-96, annual social marketing sales increased about five-fold in Ethiopia to 21 million, and nine-fold in Brazil to 27 million. These sales reflect the success of condom social marketing campaigns in making condoms accessible and largely affordable. There is also a greater general awareness of AIDS than there used to be, and communication campaigns have shown that condoms are an effective solution. More condoms still need to be used in the ongoing struggle against HIV/AIDS. The author discusses the factors which affect the limited acceptance of condoms, condom use outside of marriage, social marketing, and family planning programs. PMID:12293530

  7. Thunder day increase

    NASA Astrophysics Data System (ADS)

    Hilberg, Steven D.

    1984-04-01

    A report issued by the Illinois State Water Survey concludes that annual values of thunder days for North America exhibited a general increase of about 15% from 1901 to 1945, followed by a general decrease of 10% from 1945 to 1980. A study of the variability of thunder days across North America showed a general decrease with time, particularly after 1940. A major finding of this study is that frequencies of thunderstorms over areas as large as the North American continent show major long-term trends.The report, “Temporal Distribution of Global Thunder Days,” summarizes the results of a 1-year study by Stanley A. Changnon, Jr., and Chin-Fei Hsu of the temporal variations of thunder-day records during 1901-1980 using quality weather records from weather stations scattered around the globe. A thunder day is recorded when one or more peals of thunder are heard anytime during the 24-hour period from midnight to midnight, which is consistent with the definition of a thunderstorm used at first-order weather stations since 1897. They found most stations in the northern hemisphere north of 45° latitude exhibited a general increase in thunder activity from 1901 to 1980. The project was funded by the National Science Foundation.

  8. China update: HIV increasing.

    PubMed

    Gil, V E

    1993-01-01

    The HIV/AIDS case rate in China increased 117% over the period 1990-1992, from 446 to 957 HIV infections. While the majority of cases in 1990 were localized in Yunnan among minority farmers and manual laborers, infection is now found in 19 provinces, counties, and urban areas over a wider spectrum of society. The concentration of cases among IV-drug users has decreased from 83.4% to 72.6%. HIV monitoring and prevention stations have been in place in the country since 1986. The government also encouraged special zones and semiautonomous cities as well as the World Health Organization to take steps to monitor and prevent the spread of HIV. While these effort have served to augment the degree of sex education previously provided, low budgets, bureaucracy, and ambivalence have impeded control efforts. Only 1.25 million of the 1.16 billion population has been serosampled over 8 years and 100,000 fewer serosamples were taken in 1992 compared to in 1991. Neither the general population nor health workers have sufficient knowledge about HIV/AIDS to prevent its continued spread. While gay men sampled in Beijing were better informed about transmission means and risk groups, over two thirds believed they were not at risk if they avoided having sex with foreigners. Recent economic reform measures allowing large movements of population from rural to urban areas, increased disposable income available for prostitutes, and greater exposure to alternative sexual norms and behaviors through the media and music further increase the risk of HIV transmission, especially among the younger generation. To counter these risks, an AIDS hotline for information and referrals has been established in Beijing which openly reaches out to the homosexual community and fields 8-12 calls/day. Training programs for doctors, counselors, professors, and social workers have been attended by people from more than 30 provinces and regions. In addition, modest research into sexual behavior is also being

  9. Core Noise - Increasing Importance

    NASA Technical Reports Server (NTRS)

    Hultgren, Lennart S.

    2011-01-01

    This presentation is a technical summary of and outlook for NASA-internal and NASA-sponsored external research on core (combustor and turbine) noise funded by the Fundamental Aeronautics Program Subsonic Fixed Wing (SFW) Project. Sections of the presentation cover: the SFW system-level noise metrics for the 2015, 2020, and 2025 timeframes; turbofan design trends and their aeroacoustic implications; the emerging importance of core noise and its relevance to the SFW Reduced-Perceived-Noise Technical Challenge; and the current research activities in the core-noise area, with additional details given about the development of a high-fidelity combustor-noise prediction capability as well as activities supporting the development of improved reduced-order, physics-based models for combustor-noise prediction. The need for benchmark data for validation of high-fidelity and modeling work and the value of a potential future diagnostic facility for testing of core-noise-reduction concepts are indicated. The NASA Fundamental Aeronautics Program has the principal objective of overcoming today's national challenges in air transportation. The SFW Reduced-Perceived-Noise Technical Challenge aims to develop concepts and technologies to dramatically reduce the perceived aircraft noise outside of airport boundaries. This reduction of aircraft noise is critical to enabling the anticipated large increase in future air traffic. Noise generated in the jet engine core, by sources such as the compressor, combustor, and turbine, can be a significant contribution to the overall noise signature at low-power conditions, typical of approach flight. At high engine power during takeoff, jet and fan noise have traditionally dominated over core noise. However, current design trends and expected technological advances in engine-cycle design as well as noise-reduction methods are likely to reduce non-core noise even at engine-power points higher than approach. In addition, future low-emission combustor

  10. Elenoside increases intestinal motility

    PubMed Central

    Navarro, E; Alonso, SJ; Navarro, R; Trujillo, J; Jorge, E

    2006-01-01

    AIM: To study the effects of elenoside, an arylnaph-thalene lignan from Justicia hyssopifolia, on gastro-intestinal motility in vivo and in vitro in rats. METHODS: Routine in vivo experimental assessments were catharsis index, water percentage of boluses, intestinal transit, and codeine antagonism. The groups included were vehicle control (propylene glycol-ethanol-plant oil-tween 80), elenoside (i.p. 25 and 50 mg/kg), cisapride (i.p. 10 mg/kg), and codeine phosphate (intragastric route, 50 mg/kg). In vitro approaches used isolated rat intestinal tissues (duodenum, jejunum, and ileum). The effects of elenoside at concentrations of 3.2 x 10-4, 6.4 x 10-4 and 1.2 x 10-3 mol/L, and cisapride at 10-6 mol/L were investigated. RESULTS: Elenoside in vivo produced an increase in the catharsis index and water percentage of boluses and in the percentage of distance traveled by a suspension of activated charcoal. Codeine phosphate antagonized the effect of 25 mg/kg of elenoside. In vitro, elenoside in duodenum, jejunum and ileum produced an initial decrease in the contraction force followed by an increase. Elenoside resulted in decreased intestinal frequency in duodenum, jejunum, and ileum. The in vitro and in vivo effects of elenoside were similar to those produced by cisapride. CONCLUSION: Elenoside is a lignan with an action similar to that of purgative and prokinetics drugs. Elenoside, could be an alternative to cisapride in treatment of gastrointestinal diseases as well as a preventive therapy for the undesirable gastrointestinal effects produced by opioids used for mild to moderate pain. PMID:17131476

  11. Increased Mortality in Narcolepsy

    PubMed Central

    Ohayon, Maurice M.; Black, Jed; Lai, Chinglin; Eller, Mark; Guinta, Diane; Bhattacharyya, Arun

    2014-01-01

    Objective: To evaluate the mortality rate in patients with narcolepsy. Design: Data were derived from a large database representative of the US population, which contains anonymized patient-linked longitudinal claims for 173 million individuals. Setting: Symphony Health Solutions (SHS) Source Lx, an anonymized longitudinal patient dataset. Patients/Participants: All records of patients registered in the SHS database between 2008 and 2010. Interventions: None Measurements and Results: Identification of patients with narcolepsy was based on ≥ 1 medical claim with the diagnosis of narcolepsy (ICD-9 347.xx) from 2002 to 2012. Dates of death were acquired from the Social Security Administration via a third party; the third party information was encrypted in the same manner as the claims data such that anonymity is ensured prior to receipt by SHS. Annual all-cause mortality rates for 2008, 2009, and 2010 were calculated retrospectively for patients with narcolepsy and patients without narcolepsy in the database, and standardized mortality ratios (SMR) were calculated. Mortality rates were also compared with the general US population (Centers for Disease Control data). SMRs of the narcolepsy population were consistent over the 3-year period and showed an approximate 1.5-fold excess mortality relative to those without narcolepsy. The narcolepsy population had consistently higher mortality rates relative to those without narcolepsy across all age groups, stratified by age decile, from 25-34 years to 75+ years of age. The SMR for females with narcolepsy was lower than for males with narcolepsy. Conclusions: Narcolepsy was associated with approximately 1.5-fold excess mortality relative to those without narcolepsy. While the cause of this increased mortality is unknown, these findings warrant further investigation. Citation: Ohayon MM; Black J; Lai C; Eller M; Guinta D; Bhattacharyya A. Increased mortality in narcolepsy. SLEEP 2014;37(3):439-444. PMID:24587565

  12. Increasing immunization coverage.

    PubMed

    Hammer, Lawrence D; Curry, Edward S; Harlor, Allen D; Laughlin, James J; Leeds, Andrea J; Lessin, Herschel R; Rodgers, Chadwick T; Granado-Villar, Deise C; Brown, Jeffrey M; Cotton, William H; Gaines, Beverly Marie Madry; Gambon, Thresia B; Gitterman, Benjamin A; Gorski, Peter A; Kraft, Colleen A; Marino, Ronald Vincent; Paz-Soldan, Gonzalo J; Zind, Barbara

    2010-06-01

    In 1977, the American Academy of Pediatrics issued a statement calling for universal immunization of all children for whom vaccines are not contraindicated. In 1995, the policy statement "Implementation of the Immunization Policy" was published by the American Academy of Pediatrics, followed in 2003 with publication of the first version of this statement, "Increasing Immunization Coverage." Since 2003, there have continued to be improvements in immunization coverage, with progress toward meeting the goals set forth in Healthy People 2010. Data from the 2007 National Immunization Survey showed that 90% of children 19 to 35 months of age have received recommended doses of each of the following vaccines: inactivated poliovirus (IPV), measles-mumps-rubella (MMR), varicella-zoster virus (VZB), hepatitis B virus (HBV), and Haemophilus influenzae type b (Hib). For diphtheria and tetanus and acellular pertussis (DTaP) vaccine, 84.5% have received the recommended 4 doses by 35 months of age. Nevertheless, the Healthy People 2010 goal of at least 80% coverage for the full series (at least 4 doses of DTaP, 3 doses of IPV, 1 dose of MMR, 3 doses of Hib, 3 doses of HBV, and 1 dose of varicella-zoster virus vaccine) has not yet been met, and immunization coverage of adolescents continues to lag behind the goals set forth in Healthy People 2010. Despite these encouraging data, a vast number of new challenges that threaten continued success toward the goal of universal immunization coverage have emerged. These challenges include an increase in new vaccines and new vaccine combinations as well as a significant number of vaccines currently under development; a dramatic increase in the acquisition cost of vaccines, coupled with a lack of adequate payment to practitioners to buy and administer vaccines; unanticipated manufacturing and delivery problems that have caused significant shortages of various vaccine products; and the rise of a public antivaccination movement that uses the

  13. Catalyst increases COS conversion

    SciTech Connect

    Goodboy, K.P.

    1985-02-18

    Increasingly stringent air quality legislation is placing greater emphasis on conversion of COS and CS/sub 2/ in Claus plants for the maximum sulfur recovery. Overall sulfur recovery goals are dependent upon outstanding service from the Claus catalyst in each reactor because catalyst activity is a major factor influencing plant performance. Today's catalyst are much improved over those used 10 years ago for the Claus (H/sub 2/S/SO/sub 2/) reaction. Recent technical efforts have focused on the conversion of COS and CS/sub 2/. These carbon-sulfur compounds can account for as much as 50% of the sulfur going to the incinerator, which essentially converts all remaining sulfur species to SO/sub 2/ for atmospheric dispersion. Previously, the mechanism of Claus COS conversion, i.e., hydrolysis or oxidation by SO/sub 2/, was studied and the conclusion was that oxidation by SO/sub 2/ appears to be the predominate mode of COS conversion on sulfated alumina catalysts.

  14. Forced Resurgence and Targeting of Intracellular Uropathogenic Escherichia coli Reservoirs

    PubMed Central

    Blango, Matthew G.; Ott, Elizabeth M.; Erman, Andreja; Veranic, Peter; Mulvey, Matthew A.

    2014-01-01

    Intracellular quiescent reservoirs of uropathogenic Escherichia coli (UPEC), which can seed the bladder mucosa during the acute phase of a urinary tract infection (UTI), are protected from antibiotic treatments and are extremely difficult to eliminate. These reservoirs are a potential source for recurrent UTIs that affect millions annually. Here, using murine infection models and the bladder cell exfoliant chitosan, we demonstrate that intracellular UPEC populations shift within the stratified layers of the urothelium during the course of a UTI. Following invasion of the terminally differentiated superficial layer of epithelial cells that line the bladder lumen, UPEC can multiply and disseminate, eventually establishing reservoirs within underlying immature host cells. If given access, UPEC can invade the superficial and immature bladder cells equally well. As infected immature host cells differentiate and migrate towards the apical surface of the bladder, UPEC can reinitiate growth and discharge into the bladder lumen. By inducing the exfoliation of the superficial layers of the urothelium, chitosan stimulates rapid regenerative processes and the reactivation and efflux of quiescent intracellular UPEC reservoirs. When combined with antibiotics, chitosan treatment significantly reduces bacterial loads within the bladder and may therefore be of therapeutic value to individuals with chronic, recurrent UTIs. PMID:24667805

  15. Resurgence of vitamin D: Old wine in new bottle

    PubMed Central

    Vaishya, Raju; Vijay, Vipul; Agarwal, Amit Kumar; Jahangir, Jabed

    2015-01-01

    There are early references of it in ancient text and physicians have discussed its importance and features of its deficiency in the past. Vitamin D has again regained interest with recent dramatic rise in the incidence of deficiency in the developing as well as developing world. In this review article, we discuss the biochemical and role of vitamin D in the skeletal system. We also discuss the recommended dietary requirements and features of skeletal deficiency. Extra-skeletal roles of vitamin D deficiency have been a matter of debate lately and it has also been discussed in detail in this article. In conclusion, it would not be wrong to label vitamin D as one of the most important vitamin involved in the metabolism of the musculoskeletal system and any clinician, especially the orthopaedician, should be well versed with its overall mechanism and roles in the human body. PMID:26155053

  16. Disease emergence and resurgence: the wildlife-human connection

    USGS Publications Warehouse

    Friend, Milton

    2006-01-01

    In 2000, the Global Outbreak Alert and Response Network (GOARN) was organized as a global disease watchdog group to coordinate disease outbreak information and health crisis response. The World Health Organization (WHO) is the headquarters for this network.2 Understandably, the primary focus for WHO is human health. However, diseases such as the H5N1 avian influenza epizootic in Asian bird populations demonstrate the need for integrating knowledge about disease emergence in animals and in humans.

  17. Restart: The Resurgence of Computer Science in UK Schools

    ERIC Educational Resources Information Center

    Brown, Neil C. C.; Sentance, Sue; Crick, Tom; Humphreys, Simon

    2014-01-01

    Computer science in UK schools is undergoing a remarkable transformation. While the changes are not consistent across each of the four devolved nations of the UK (England, Scotland, Wales and Northern Ireland), there are developments in each that are moving the subject to become mandatory for all pupils from age 5 onwards. In this article, we…

  18. Resurgence of HPAI in birds and mechanisms of transmission

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High pathogenicity avian influenza (HPAI) viruses typically produce a similar severe, systemic disease with high mortality in chickens and other gallinaceous birds, but either no disease or only mild disease in domestic ducks and wild birds. However with emergence of H5N1 HPAI viruses and their mai...

  19. The Resurgence of U.S. Nuclear Power, 2. edition

    SciTech Connect

    2007-11-15

    The updated report provides an overview of the opportunities for nuclear power in the U.S. electric industry, including a concise look at the challenges faced by nuclear power, the ability of advanced nuclear reactors to address these challenges, and the current state of nuclear power generation. Topics covered in the report include: an overview of U.S. Nuclear Power including its history, the current market environment, and the future of nuclear power in the U.S.; an analysis of the key business factors that are driving renewed interest in nuclear power; an analysis of the barriers that are hindering the implementation of new nuclear power plants; a description of nuclear power technology including existing reactors, as well as 3rd and 4th generation reactor designs; a review of the economics of new nuclear power projects and comparison to other generation alternatives; a discussion of the key government initiatives supporting nuclear power development; profiles of the key reactor manufacturers participating in the U.S. nuclear power market; and, profiles of the leading U.S. utilities participating in the U.S. nuclear power market.

  20. Burial and resurgence of projective identification in French psychoanalysis.

    PubMed

    Widlöcher, Daniel

    2014-08-01

    Curiously enough, the concept of projective identification was ignored, and even rejected in France for at least two decades after the publication of the founding texts of Melanie Klein and Herbert Rosenfeld. This rejection was due to a critique from child psychoanalysts close to Anna Freud and also from the teaching of Lacan: the first took the real mother-child relation extensively into account, while the latter only saw the internal object as a signifier. The fact that during this period the countertransference was a concept reduced to its negative content no doubt explains this deliberate ignorance. With the dissemination of a broader and more positive conception of the countertransference, a renewal of interest could be observed in the 1980s with references to empathic listening and to the effects of thought-induction. PMID:25229546

  1. The Resurgence of Genetic Determinism: Is It a Distraction?

    ERIC Educational Resources Information Center

    Jackson, Jacquelyne F.

    1998-01-01

    Argues that there is a wealth of little known but rapidly growing evidence that contradicts the assumptions and claims of genetic determinism. Recent research showing the impacts of child maltreatment and environmental pollutants suggest interventions that might alleviate the problems sometimes attributed to genetic deficiencies. (SLD)

  2. Glycoprotein IIb/IIIa inhibitors: The resurgence of tirofiban.

    PubMed

    King, Shawn; Short, Marintha; Harmon, Cassidy

    2016-03-01

    Glycoprotein (GP) IIb/IIIa inhibitors block platelet aggregation, reducing thrombotic events in acute coronary syndrome. They are most often utilized in patients who likely have an intracoronary thrombus. Tirofiban, eptifibatide, and abciximab are the three GP IIb/IIIa inhibitors approved for use in the United States. Each agent has unique pharmacological properties. They all have a rapid onset and are most often utilized in conjunction with heparin. Tirofiban, in particular, fell out of favor due to inferior dosing with its original Food and Drug Administration (FDA) approved indication, but has re-emerged in the market with a high-dose bolus regimen that is considered equally as effective as the FDA approved dosing regimens of other GP IIb/IIIa inhibitors. This review looks at pharmacological properties of all three agents, significant clinical trials associated with their use, and their place in current guidelines. PMID:26187354

  3. An Evaluation of Resurgence during Functional Communication Training

    ERIC Educational Resources Information Center

    Wacker, David P.; Harding, Jay W.; Morgan, Theresa A.; Berg, Wendy K.; Schieltz, Kelly M.; Lee, John F.; Padilla, Yaniz C.

    2013-01-01

    Three children who displayed destructive behavior maintained by negative reinforcement received functional communication training (FCT). During FCT, the children were required to complete a demand and then to mand (touch a card attached to a microswitch, sign, or vocalize) to receive brief play breaks. Prior to and 1 to 3 times following the…

  4. Increasing instruction time in school does increase learning.

    PubMed

    Andersen, Simon Calmar; Humlum, Maria Knoth; Nandrup, Anne Brink

    2016-07-01

    Increasing instruction time in school is a central element in the attempts of many governments to improve student learning, but prior research-mainly based on observational data-disputes the effect of this approach and points out the potential negative effects on student behavior. Based on a large-scale, cluster-randomized trial, we find that increasing instruction time increases student learning and that a general increase in instruction time is at least as efficient as an expert-developed, detailed teaching program that increases instruction with the same amount of time. These findings support the value of increased instruction time. PMID:27325778

  5. Defective interactions of protein partner with ion channels and transporters as alternative mechanisms of membrane channelopathies

    PubMed Central

    Kline, Crystal F.; Mohler, Peter J.

    2013-01-01

    The past twenty years have revealed the existence of numerous ion channel mutations resulting in human pathology. Ion channels provide the basis of diverse cellular functions, ranging from hormone secretion, excitation-contraction coupling, cell signaling, immune response, and trans-epithelial transport. Therefore, the regulation of biophysical properties of channels is vital in human physiology. Only within the last decade has the role of non-ion channel components come to light in regard to ion channel spatial, temporal, and biophysical regulation in physiology. A growing number of auxiliary components have been determined to play elemental roles in excitable cell physiology, with dysfunction resulting in disorders and related manifestations. This review focuses on the broad implications of such dysfunction, focusing on disease-causing mutations that alter interactions between ion channels and auxiliary ion channel components in a diverse set of human excitable cell disease. PMID:23732236

  6. Neurological manifestations of oculodentodigital dysplasia: a Cx43 channelopathy of the central nervous system?

    PubMed Central

    De Bock, Marijke; Kerrebrouck, Marianne; Wang, Nan; Leybaert, Luc

    2013-01-01

    The coordination of tissue function is mediated by gap junctions (GJs) that enable direct cell–cell transfer of metabolic and electric signals. GJs are formed by connexins of which Cx43 is most widespread in the human body. In the brain, Cx43 GJs are mostly found in astroglia where they coordinate the propagation of Ca2+ waves, spatial K+ buffering, and distribution of glucose. Beyond its role in direct intercellular communication, Cx43 also forms unapposed, non-junctional hemichannels in the plasma membrane of glial cells. These allow the passage of several neuro- and gliotransmitters that may, combined with downstream paracrine signaling, complement direct GJ communication among glial cells and sustain glial-neuronal signaling. Mutations in the GJA1 gene encoding Cx43 have been identified in a rare, mostly autosomal dominant syndrome called oculodentodigital dysplasia (ODDD). ODDD patients display a pleiotropic phenotype reflected by eye, hand, teeth, and foot abnormalities, as well as craniofacial and bone malformations. Remarkably, neurological symptoms such as dysarthria, neurogenic bladder (manifested as urinary incontinence), spasticity or muscle weakness, ataxia, and epilepsy are other prominent features observed in ODDD patients. Over 10 mutations detected in patients diagnosed with neurological disorders are associated with altered functionality of Cx43 GJs/hemichannels, but the link between ODDD-related abnormal channel activities and neurologic phenotype is still elusive. Here, we present an overview on the nature of the mutants conveying structural and functional changes of Cx43 channels and discuss available evidence for aberrant Cx43 GJ and hemichannel function. In a final step, we examine the possibilities of how channel dysfunction may lead to some of the neurological manifestations of ODDD. PMID:24133447

  7. Increasing FCC regenerator catalyst level

    SciTech Connect

    Wong, R.F. )

    1993-11-01

    A Peruvian FCC unit's operations were improved by increasing the regenerator's catalyst level. This increase resulted in lower stack losses, an improved temperature profile, increased catalyst activity and a lower catalyst consumption rate. A more stable operation saved this Peruvian refiner over $131,000 per year in catalyst alone. These concepts and data may be suitable for your FCC unit as well.

  8. Is asthma prevalence still increasing?

    PubMed

    Lundbäck, Bo; Backman, Helena; Lötvall, Jan; Rönmark, Eva

    2016-01-01

    Increased awareness of asthma in society and altered diagnostic practices makes evaluation of data on prevalence change difficult. In most parts of the world the asthma prevalence seems to still be increasing. The increase is associated with urbanization and has been documented particularly among children and teenagers in urban areas of middle- and low-level income countries. Use of validated questionnaires has enabled comparisons of studies. Among adults there are few studies based on representative samples of the general population which allow evaluation of time trends of prevalence. This review focuses mainly on studies of asthma prevalence and symptoms among adults. Parallel with increased urbanization, we can assume that the increase in asthma prevalence in most areas of the world will continue. However, in Australia and North-West Europe studies performed, particularly among children and adolescents, indicate that the increase in asthma prevalence may now be leveling off. PMID:26610152

  9. Korea's 2015 cigarette tax increases.

    PubMed

    Cherukupalli, Rajeev

    2016-03-01

    South Korea increased tobacco taxes in 2015 after a 10-year gap. This commentary suggests two lessons for public finance practitioners. Substantive tax increases are crucial to reducing tobacco use; particularly where prices are demonstrably lower and prevalence higher in comparison to other countries ranked similarly on economic development indicators. Second, as a rule of thumb, governments cannot afford to neglect the annual increases that ensure that tobacco taxes do not lose their efficacy over time. PMID:25673328

  10. Increased airway glucose increases airway bacterial load in hyperglycaemia

    PubMed Central

    Gill, Simren K.; Hui, Kailyn; Farne, Hugo; Garnett, James P.; Baines, Deborah L.; Moore, Luke S.P.; Holmes, Alison H.; Filloux, Alain; Tregoning, John S.

    2016-01-01

    Diabetes is associated with increased frequency of hospitalization due to bacterial lung infection. We hypothesize that increased airway glucose caused by hyperglycaemia leads to increased bacterial loads. In critical care patients, we observed that respiratory tract bacterial colonisation is significantly more likely when blood glucose is high. We engineered mutants in genes affecting glucose uptake and metabolism (oprB, gltK, gtrS and glk) in Pseudomonas aeruginosa, strain PAO1. These mutants displayed attenuated growth in minimal medium supplemented with glucose as the sole carbon source. The effect of glucose on growth in vivo was tested using streptozocin-induced, hyperglycaemic mice, which have significantly greater airway glucose. Bacterial burden in hyperglycaemic animals was greater than control animals when infected with wild type but not mutant PAO1. Metformin pre-treatment of hyperglycaemic animals reduced both airway glucose and bacterial load. These data support airway glucose as a critical determinant of increased bacterial load during diabetes. PMID:27273266

  11. Increased airway glucose increases airway bacterial load in hyperglycaemia.

    PubMed

    Gill, Simren K; Hui, Kailyn; Farne, Hugo; Garnett, James P; Baines, Deborah L; Moore, Luke S P; Holmes, Alison H; Filloux, Alain; Tregoning, John S

    2016-01-01

    Diabetes is associated with increased frequency of hospitalization due to bacterial lung infection. We hypothesize that increased airway glucose caused by hyperglycaemia leads to increased bacterial loads. In critical care patients, we observed that respiratory tract bacterial colonisation is significantly more likely when blood glucose is high. We engineered mutants in genes affecting glucose uptake and metabolism (oprB, gltK, gtrS and glk) in Pseudomonas aeruginosa, strain PAO1. These mutants displayed attenuated growth in minimal medium supplemented with glucose as the sole carbon source. The effect of glucose on growth in vivo was tested using streptozocin-induced, hyperglycaemic mice, which have significantly greater airway glucose. Bacterial burden in hyperglycaemic animals was greater than control animals when infected with wild type but not mutant PAO1. Metformin pre-treatment of hyperglycaemic animals reduced both airway glucose and bacterial load. These data support airway glucose as a critical determinant of increased bacterial load during diabetes. PMID:27273266

  12. Is the Rape Rate Increasing?

    ERIC Educational Resources Information Center

    Cameron, Paul; And Others

    While it has been asserted that rape has increased in frequency over the past generation, part of this increase may be due to a greater willingness to report rape to the authorities. A study was conducted to examine the frequency of rape and to describe the characteristics of rape victims. A random questionnaire survey of 4,340 adults in five…

  13. Assessing and Increasing Physical Activity

    ERIC Educational Resources Information Center

    Van Camp, Carole M.; Hayes, Lynda B.

    2012-01-01

    Increasing physical activity is a crucial component of any comprehensive approach to combat the growing obesity epidemic. This review summarizes recent behavioral research on the measurement of physical activity and interventions aimed at increasing physical activity and provides directions for future research.

  14. Magnetic Coupling Delivers Increased Torque

    NASA Technical Reports Server (NTRS)

    Carter, Edward L.

    1989-01-01

    Fixed magnetic pins reduce reluctance of gap in magnetic coupling. Concentrate flux and increase torque transmitted. Coupling arranged as face or radial drive. Addition of flux pins to gap between magnetically coupled shafts in bioreactor experiment increases transferred torque by almost 50 percent.

  15. Extreme precipitation: Increases all round

    NASA Astrophysics Data System (ADS)

    Ingram, William

    2016-05-01

    Globally, extreme rainfall is expected to increase with warming, but regional changes over land have been less certain. Now research shows that this intense precipitation has increased across both the wetter and the drier parts of the continents, and will continue to do so as global warming continues.

  16. Shared medical appointments: increasing patient access without increasing physician hours.

    PubMed

    Bronson, David L; Maxwell, Richard A

    2004-05-01

    Shared medical visits are a new concept in patient care. Doctors perform a series of one-on-one patient encounters in a group setting during a 90-minute visit and manage and advise each patient in front of the others. Patients benefit from improved access to their physician and significantly increased education, while providers can boost their access and productivity without increasing hours. Such group visits are voluntary and for established patients only. PMID:15195773

  17. Volatiles Which Increase Magma Viscosity

    NASA Astrophysics Data System (ADS)

    Webb, S.

    2015-12-01

    The standard model of an erupting volcano is one in which the viscosity of a decompressing magma increases as the volatiles leave the melt structure to form bubbles. It has now been observed that the addition of the "volatiles" P, Cl and F result in an increase in silicate melt viscosity. This observation would mean that the viscosity of selected degassing magmas would decrease rather than increase. Here we look at P, Cl and F as three volatiles which increase viscosity through different structural mechanisms. In all three cases the volatiles increase the viscosity of peralkaline composition melts, but appear to always decrease the viscosity of peraluminous melts. Phosphorus causes the melt to unmix into a Na-P rich phase and a Na-poor silicate phase. Thus as the network modifying Na (or Ca) are removed to the phosphorus-rich melt, the matrix melt viscosity increases. With increasing amounts of added phosphorus (at network modifying Na ~ P) the addition of further phosphorus causes a decrease in viscosity. The addition of chlorine to Fe-free aluminosilicate melts results in an increase in viscosity. NMR data on these glass indicates that the chlorine sits in salt-like structures surrounded by Na and/or Ca. Such structures would remove network-modifying atoms from the melt structure and thus result in an increase in viscosity. The NMR spectra of fluorine-bearing glasses shows that F takes up at least 5 different structural positions in peralkaline composition melts. Three of these positions should result in a decrease in viscosity due to the removal of bridging oxygens. Two of the structural positons of F, however, should result in an increase in viscosity as they require the removal of network-modifying atoms from the melt structure (with one of the structures being that observed for Cl). This would imply that increasing amounts of F might result in an increase in viscosity. This proposed increase in viscosity with increasing F has now been experimentally confirmed.

  18. Increasing Learning from TV News.

    ERIC Educational Resources Information Center

    Perloff, Richard M.; And Others

    1982-01-01

    Describes an experiment that manipulated two variables, repetition and pausing for viewer "digestion" of information in a news telecast. Concludes that the use of repetition increased viewers' retention of information, but that pauses did not. (FL)

  19. Meclofenamate increases ventilation in lambs.

    PubMed

    Guerra, F A; Savich, R D; Clyman, R I; Kitterman, J A

    1989-01-01

    To investigate the effects of the prostaglandin synthetase inhibitor, meclofenamate, on postnatal ventilation, we studied 11 unanaesthetised, spontaneously-breathing lambs at an average age of 7.9 +/- 1.1 days (SEM; range 5-14 days) and an average weight of 4.9 +/- 0.5 kg (range 3.0-7.0 kg). After a 30-min control period we infused 4.23 mg/kg meclofenamate over 10 min and then gave 0.23 mg/h per kg for the remainder of the 4 h. Ventilation increased progressively from a control value of 515 +/- 72 ml/min per kg to a maximum of 753 +/- 100 ml/min per kg after 3h of infusion (P less than 0.05) due to an increased breathing rate; the effects were similar during both high- and low-voltage electrocortical activity. There were no significant changes in tidal volume, heart rate, blood pressure, arterial pH or PaCO2, the increased ventilation resulted from either an increase in dead space ventilation or an increase in CO2 production. This study indicates that meclofenamate causes an increase in ventilation in lambs but no changes in pH of PaCO2. The mechanism and site of action remain to be defined. PMID:2507622

  20. Increases in sexually transmitted infections and sexual risk behaviour without a concurrent increase in HIV incidence among men who have sex with men in San Francisco: a suggestion of HIV serosorting?

    PubMed Central

    Truong, H M; Kellogg, T; Klausner, J D; Katz, M H; Dilley, J; Knapper, K; Chen, S; Prabhu, R; Grant, R M; Louie, B; McFarland, W

    2006-01-01

    Background Sexually transmitted infections (STI) and unprotected anal intercourse (UAI) have been increasing among men who have sex with men (MSM) in San Francisco. However, HIV incidence has stabilised. Objectives To describe recent trends in sexual risk behaviour, STI, and HIV incidence among MSM in San Francisco and to assess whether increases in HIV serosorting (that is, selective unprotected sex with partners of the same HIV status) may contribute to preventing further expansion of the epidemic. Methods The study applies an ecological approach and follows the principles of second generation HIV surveillance. Temporal trends in biological and behavioural measures among MSM were assessed using multiple pre‐existing data sources: STI case reporting, prevention outreach programmatic data, and voluntary HIV counselling and testing data. Results Reported STI cases among MSM rose from 1998 through 2004, although the rate of increase slowed between 2002 and 2004. Rectal gonorrhoea cases increased from 157 to 389 while early syphilis increased from nine to 492. UAI increased overall from 1998 to 2004 (p<0.001) in community based surveys; however, UAI with partners of unknown HIV serostatus decreased overall (p<0.001) among HIV negative MSM, and among HIV positive MSM it declined from 30.7% in 2001 to a low of 21.0% in 2004 (p<0.001). Any UAI, receptive UAI, and insertive UAI with a known HIV positive partner decreased overall from 1998 to 2004 (p<0.001) among MSM seeking anonymous HIV testing and at the STI clinic testing programme. HIV incidence using the serological testing algorithm for recent HIV seroconversion (STARHS) peaked in 1999 at 4.1% at the anonymous testing sites and 4.8% at the STI clinic voluntary testing programme, with rates levelling off through 2004. Conclusions HIV incidence among MSM appears to have stabilised at a plateau following several years of resurgence. Increases in the selection of sexual partners of concordant HIV serostatus may be

  1. Pulsed electric field increases reproduction.

    PubMed

    Panagopoulos, Dimitris J

    2016-01-01

    Purpose To study the effect of pulsed electric field - applied in corona discharge photography - on Drosophila melanogaster reproduction, possible induction of DNA fragmentation, and morphological alterations in the gonads. Materials and methods Animals were exposed to different field intensities (100, 200, 300, and 400 kV/m) during the first 2-5 days of their adult lives, and the effect on reproductive capacity was assessed. DNA fragmentation during early- and mid-oogenesis was investigated by application of the TUNEL (Terminal deoxynucleotide transferase dUTP Nick End Labeling) assay. Sections of follicles after fixation and embedding in resins were observed for possible morphological/developmental abnormalities. Results The field increased reproduction by up to 30% by increasing reproductive capacity in both sexes. The effect increased with increasing field intensities. The rate of increase diminished at the strongest intensities. Slight induction of DNA fragmentation was observed exclusively in the nurse (predominantly) and follicle cells, and exclusively at the two most sensitive developmental stages, i.e., germarium and predominantly stage 7-8. Sections of follicles from exposed females at stages of early and mid-oogennesis other than germarium and stages 7-8 did not reveal abnormalities. Conclusions (1) The specific type of electric field may represent a mild stress factor, inducing DNA fragmentation and cell death in a small percentage of gametes, triggering the reaction of the animal's reproductive system to increase the rate of gametogenesis in order to compensate the loss of a small number of gametes. (2) The nurse cells are the most sensitive from all three types of egg chamber cells. (3) The mid-oogenesis checkpoint (stage 7-8) is more sensitive to this field than the early oogenesis one (germarium) in contrast to microwave exposure. (4) Possible therapeutic applications, or applications in increasing fertility, should be investigated. PMID:26651869

  2. Hydrologic effects of increased urbanization

    USGS Publications Warehouse

    Guay, Joel R.

    1995-01-01

    Urban areas in Perris Valley, California, have more than tripled during the last 20 years, resulting in increased storm-runoff volumes and peak discharges. To quantify the effects of increased urbanization, rainfall-runoff models of the basin were developed to simulate runoff for 1970-75 and 1990-93 conditions. Hourly rainfall data for 1949-93 were used with the rainfall-runoff models to simulate a long-term record of storm runoff. The hydrologic effects of increased urbanization from 1970-75 to 1990-93 conditions were analyzed by comparing the frequency of annual peak discharges and runoff volumes, and a duration analysis of storm peak discharges. The maximum annual-peak discharge for the 1990-93 model simulation was 32 percent higher than the discharge for 1970-75 model simulation. However, the frequency analysis of each time series indicated the 100-year peak discharges for each study period were identical.

  3. Fires increase Amazon forest productivity through increases in diffuse radiation

    NASA Astrophysics Data System (ADS)

    Rap, A.; Spracklen, D. V.; Mercado, L.; Reddington, C. L.; Haywood, J. M.; Ellis, R. J.; Phillips, O. L.; Artaxo, P.; Bonal, D.; Restrepo Coupe, N.; Butt, N.

    2015-06-01

    Atmospheric aerosol scatters solar radiation increasing the fraction of diffuse radiation and the efficiency of photosynthesis. We quantify the impacts of biomass burning aerosol (BBA) on diffuse radiation and plant photosynthesis across Amazonia during 1998-2007. Evaluation against observed aerosol optical depth allows us to provide lower and upper BBA emissions estimates. BBA increases Amazon basin annual mean diffuse radiation by 3.4-6.8% and net primary production (NPP) by 1.4-2.8%, with quoted ranges driven by uncertainty in BBA emissions. The enhancement of Amazon basin NPP by 78-156 Tg C a-1 is equivalent to 33-65% of the annual regional carbon emissions from biomass burning. This NPP increase occurs during the dry season and acts to counteract some of the observed effect of drought on tropical production. We estimate that 30-60 Tg C a-1 of this NPP enhancement is within woody tissue, accounting for 8-16% of the observed carbon sink across mature Amazonian forests.

  4. Increased Spreading Activation in Depression

    ERIC Educational Resources Information Center

    Foster, Paul S.; Yung, Raegan C.; Branch, Kaylei K.; Stringer, Kristi; Ferguson, Brad J.; Sullivan, William; Drago, Valeria

    2011-01-01

    The dopaminergic system is implicated in depressive disorders and research has also shown that dopamine constricts lexical/semantic networks by reducing spreading activation. Hence, depression, which is linked to reductions of dopamine, may be associated with increased spreading activation. However, research has generally found no effects of…

  5. Increasing Originality in Written Expression.

    ERIC Educational Resources Information Center

    Belasco, Jack Thomas

    This study partially replicated Moss's "A Study of the Effect of Selected Methods of Instruction Designed to Increase Originality in Written Expression," except for the fact that this investigator taught a 5th grade and an 11th grade class for most of a school year. Some of the conclusions of the study were: no particular teaching technique was…

  6. PMR Composites Of Increased Toughness

    NASA Technical Reports Server (NTRS)

    Vannucci, Raymond D.; Bowles, Kenneth J.

    1988-01-01

    Toughness increased without sacrificing processability or hot strength. Resin composition provides best overall balance of composite toughness and retention of mechanical properties at 600 degree F (316 degree C) with processability obtained by substituting 20 mole percent of diamine used in PMR-15 resins with diamine containing twice number of flexible phenyl connecting groups.

  7. Japan to increase coal imports

    SciTech Connect

    Griffin, S.

    1982-04-01

    Imports of coal into Japan are expected to increase next year. One major company is buying into a Canadian mine to obtain a long-term supply contract, and other companies are expected to follow. A feasibility study on production of methanol-coal slurry and its transportation by pipeline in Alberta, Canada (conducted by Japan and Canada) has been completed.

  8. Increasing Enrollment through Benefit Segmentation.

    ERIC Educational Resources Information Center

    Goodnow, Betty

    1982-01-01

    The applicability of benefit segmentation, a market research technique which groups people according to benefits expected from a program offering, was tested at the College of DuPage. Preferences and demographic characteristics were analyzed and program improvements adopted, increasing enrollment by 20 percent. (Author/SK)

  9. Increasing vegetable consumption in adolescents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies have demonstrated that diets rich in vegetables may protect against many chronic diseases and overweight. Despite these benefits, consumption in children and adolescents is well below recommended levels. Finding methods to increase vegetable consumption in adolescents is important. Our objec...

  10. Increasing Public Understanding of Science.

    ERIC Educational Resources Information Center

    Smith, Isobel

    1998-01-01

    The Science of Genes workshop is a program designed to increase public understanding of science by demystifying the language used to describe it. Methods include analogies, models, simple experiments, and opportunities for discussion of controversial topics such as genetic engineering. (JOW)