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Sample records for channelopathies increase resurgent

  1. 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

  2. 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

  3. 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

  4. Resurgence as Choice.

    PubMed

    Shahan, Timothy A; Craig, Andrew R

    2016-10-26

    Resurgence is typically defined as an increase in a previously extinguished target behavior when a more recently reinforced alternative behavior is later extinguished. Some treatments of the phenomenon have suggested that it might also extend to circumstances where either the historic or more recently reinforced behavior is reduced by other non-extinction related means (e.g., punishment, decreases in reinforcement rate, satiation, etc.). Here we present a theory of resurgence suggesting that the phenomenon results from the same basic processes governing choice. In its most general form, the theory suggests that resurgence results from changes in the allocation of target behavior driven by changes in the values of the target and alternative options across time. Specifically, resurgence occurs when there is an increase in the relative value of an historically effective target option as a result of a subsequent devaluation of a more recently effective alternative option. We develop a more specific quantitative model of how extinction of the target and alternative responses in a typical resurgence paradigm might produce such changes in relative value across time using a temporal weighting rule. The example model does a good job in accounting for the effects of reinforcement rate and related manipulations on resurgence in simple schedules where Behavioral Momentum Theory has failed. We also discuss how the general theory might be extended to other parameters of reinforcement (e.g., magnitude, quality), other means to suppress target or alternative behavior (e.g., satiation, punishment, differential reinforcement of other behavior), and other factors (e.g., non- contingent versus contingent alternative reinforcement, serial alternative reinforcement, and multiple schedules).

  5. A model for caldera resurgence

    NASA Astrophysics Data System (ADS)

    Stix, J.; kennedy, B.; Wilcock, J.

    2011-12-01

    A key question in volcanology is the driving mechanisms of resurgence at active, recently active, and ancient calderas. Valles caldera in New Mexico and Lake City caldera in Colorado are well-studied resurgent structures which provide two crucial clues for understanding the resurgence process. (1) Within the limits of 40Ar/39Ar dating techniques, resurgence at both calderas occurred very quickly after the caldera-forming eruptions (tens of thousands of years or less). (2) Immediately before and during resurgence, dacite magma was intruded and/or erupted; this magma is chemically distinct from rhyolite magma erupted from the shallow magma chamber as ignimbrite. These observations demonstrate that resurgence is temporally linked to caldera subsidence, with the dacite magma as the driver of resurgence. Recharge of dacite magma occurs as a response to loss of lithostatic load during the caldera-forming eruption. Flow of dacite into the shallow magmatic system is facilitated by regional faults which provide pathways for magma ascent. Once the dacite enters the system, it is able to heat and remobilize residual crystal-rich rhyolite remaining in the shallow magma chamber. Surface resurgent uplift is produced by dacite and remobilized rhyolite rising through buoyancy, and by roof blocks sinking partway into the magma chamber. The resurgent deformation caused by magma ascent fractures the chamber roof, increasing its structural permeability and allowing both rhyolite and dacite magma to be intruded and/or erupted together. These same processes facilitate mingling and mixing of the dacite and rhyolite magmas. This sequence of events also promotes the development of magmatic-hydrothermal systems and ore deposits. Injection of dacite magma into the shallow rhyolite magma chamber provides a source of heat and magmatic volatiles, while resurgent deformation and fracturing increase the permeability of the system. These changes allow magmatic volatiles to rise and meteoric fluids

  6. 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.

  7. 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

  8. Mumps resurgence in Denmark.

    PubMed

    St-Martin, Gry; Knudsen, Lisbet Krause; Engsig, Frederik Neess; Panum, Inge; Andersen, Peter H S; Rønn, Jesper; Fonager, Jannik; Fischer, Thea Kølsen

    2014-11-01

    The past decade has witnessed a resurgence of parotitisvirus (mumps) in several countries where seemingly good mumps control otherwise had been achieved through vaccination. Recently detection of mumps has increased in Denmark. To describe the age-specific changes and time trends of parotitisvirus detection in Denmark over a 10 year period. Retrospective cohort study based on national laboratory data for parotitisvirus typing surveillance and national epidemiology data for mumps reporting. The parotitisvirus detection rate has increased almost 10 times during the past 10 years from an incidence <0.1 per 100,000 in 2003 to 0.96 per 100,000 in 2013. The age distribution has shifted from children to young adults, and most cases are unvaccinated (54%) or vaccinated once (41%). The increase is due mainly to the existence of cohorts with low MMR vaccine coverage. Analysis of mumps surveillance data from Denmark documents that the incidence of mumps is increasing, and that the resurgence of parotitisvirus is primarily occurring among young Danish adults. Almost half of the infected clinical mumps cases had received the first dose of MMR. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Potassium Channelopathies and Gastrointestinal Ulceration

    PubMed Central

    Han, Jaeyong; Lee, Seung Hun; Giebisch, Gerhard; Wang, Tong

    2016-01-01

    Potassium channels and transporters maintain potassium homeostasis and play significant roles in several different biological actions via potassium ion regulation. In previous decades, the key revelations that potassium channels and transporters are involved in the production of gastric acid and the regulation of secretion in the stomach have been recognized. Drugs used to treat peptic ulceration are often potassium transporter inhibitors. It has also been reported that potassium channels are involved in ulcerative colitis. Direct toxicity to the intestines from nonsteroidal anti-inflammatory drugs has been associated with altered potassium channel activities. Several reports have indicated that the long-term use of the antianginal drug Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, increases the chances of ulceration and perforation from the oral to anal regions throughout the gastrointestinal (GI) tract. Several of these drug features provide further insights into the role of potassium channels in the occurrence of ulceration in the GI tract. The purpose of this review is to investigate whether potassium channelopathies are involved in the mechanisms responsible for ulceration that occurs throughout the GI tract. PMID:27784845

  10. Behavioral momentum and resurgence: Effects of time in extinction and repeated resurgence tests

    PubMed Central

    Shahan, Timothy A.

    2014-01-01

    Resurgence is an increase in a previously extinguished operant response that occurs if an alternative reinforcement introduced during extinction is removed. Shahan and Sweeney (2011) developed a quantitative model of resurgence based on behavioral momentum theory that captures existing data well and predicts that resurgence should decrease as time in extinction and exposure to the alternative reinforcement increases. Two experiments tested this prediction. The data from Experiment 1 suggested that without a return to baseline, resurgence decreases with increased exposure to alternative reinforcement and to extinction of the target response. Experiment 2 tested the predictions of the model across two conditions, one with constant alternative reinforcement for five sessions, and the other with alternative reinforcement removed three times. In both conditions, the alternative reinforcement was removed for the final test session. Experiment 2 again demonstrated a decrease in relapse across repeated resurgence tests. Furthermore, comparably little resurgence was observed at the same time point in extinction in the final test, despite dissimilar previous exposures to alternative reinforcement removal. The quantitative model provided a good description of the observed data in both experiments. More broadly, these data suggest that increased exposure to extinction may be a successful strategy to reduce resurgence. The relationship between these data and existing tests of the effect of time in extinction on resurgence is discussed. PMID:23982985

  11. Behavioral momentum and resurgence: Effects of time in extinction and repeated resurgence tests.

    PubMed

    Sweeney, Mary M; Shahan, Timothy A

    2013-12-01

    Resurgence is an increase in a previously extinguished operant response that occurs if an alternative reinforcement introduced during extinction is removed. Shahan and Sweeney (2011) developed a quantitative model of resurgence based on behavioral momentum theory that captures existing data well and predicts that resurgence should decrease as time in extinction and exposure to the alternative reinforcement increases. Two experiments tested this prediction. The data from Experiment 1 suggested that without a return to baseline, resurgence decreases with increased exposure to alternative reinforcement and to extinction of the target response. Experiment 2 tested the predictions of the model across two conditions, one with constant alternative reinforcement for five sessions, and the other with alternative reinforcement removed three times. In both conditions, the alternative reinforcement was removed for the final test session. Experiment 2 again demonstrated a decrease in relapse across repeated resurgence tests. Furthermore, comparably little resurgence was observed at the same time point in extinction in the final test, despite dissimilar previous exposures to alternative reinforcement removal. The quantitative model provided a good description of the observed data in both experiments. More broadly, these data suggest that increased exposure to extinction may be a successful strategy to reduce resurgence. The relationship between these data and existing tests of the effect of time in extinction on resurgence is discussed.

  12. Resurgence and alternative-reinforcer magnitude.

    PubMed

    Craig, Andrew R; Browning, Kaitlyn O; Nall, Rusty W; Marshall, Ciara M; Shahan, Timothy A

    2017-03-01

    Resurgence is defined as an increase in the frequency of a previously reinforced target response when an alternative source of reinforcement is suspended. Despite an extensive body of research examining factors that affect resurgence, the effects of alternative-reinforcer magnitude have not been examined. Thus, the present experiments aimed to fill this gap in the literature. In Experiment 1, rats pressed levers for single-pellet reinforcers during Phase 1. In Phase 2, target-lever pressing was extinguished, and alternative-lever pressing produced either five-pellet, one-pellet, or no alternative reinforcement. In Phase 3, alternative reinforcement was suspended to test for resurgence. Five-pellet alternative reinforcement produced faster elimination and greater resurgence of target-lever pressing than one-pellet alternative reinforcement. In Experiment 2, effects of decreasing alternative-reinforcer magnitude on resurgence were examined. Rats pressed levers and pulled chains for six-pellet reinforcers during Phases 1 and 2, respectively. In Phase 3, alternative reinforcement was decreased to three pellets for one group, one pellet for a second group, and suspended altogether for a third group. Shifting from six-pellet to one-pellet alternative reinforcement produced as much resurgence as suspending alternative reinforcement altogether, while shifting from six pellets to three pellets did not produce resurgence. These results suggest that alternative-reinforcer magnitude has effects on elimination and resurgence of target behavior that are similar to those of alternative-reinforcer rate. Thus, both suppression of target behavior during alternative reinforcement and resurgence when conditions of alternative reinforcement are altered may be related to variables that affect the value of the alternative-reinforcement source.

  13. [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.

  14. Muscle Channelopathies: the Nondystrophic Myotonias and Periodic Paralyses

    PubMed Central

    Statland, Jeffrey M.; Barohn, Richard J.

    2013-01-01

    Purpose of Review The muscle channelopathies are a group of rare inherited diseases caused by mutations in muscle ion channels. Mutations cause an increase or decrease in muscle membrane excitability, leading to a spectrum of related clinical disorders: the nondystrophic myotonias are characterized by delayed relaxation after muscle contraction, causing muscle stiffness and pain; the periodic paralyses are characterized by episodes of flaccid muscle paralysis. This review describes the clinical characteristics, molecular pathogenesis, and treatments of the nondystrophic myotonias and periodic paralyses. Recent Findings Advances have been made in both the treatment and our understanding of the molecular pathophysiology of muscle channelopathies: (1) a recent controlled trial showed that mexiletine was effective for reducing symptoms and signs of myotonia in nondystrophic myotonia; (2) the mechanisms by which hypokalemic periodic paralysis leads to a depolarized but unexcitable sarcolemma membrane have been traced to a novel gating pore current; and (3) an association was demonstrated between mutations in a potassium inward rectifier and patients with thyrotoxic periodic paralysis. Summary The muscle channelopathies are an expanding group of muscle diseases caused by mutations in sodium, chloride, potassium, and calcium ion channels that result in increased or decreased muscle membrane excitability. Recognizing patients with channelopathies and confirming the diagnosis is important, as treatment and management strategies differ based on mutation and clinical phenotype. PMID:24305449

  15. 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.

  16. Autoimmune channelopathies of the nervous system.

    PubMed

    Kleopa, Kleopas A

    2011-09-01

    Ion channels are complex transmembrane proteins that orchestrate the electrical signals necessary for normal function of excitable tissues, including the central nervous system, peripheral nerve, and both skeletal and cardiac muscle. Progress in molecular biology has allowed cloning and expression of genes that encode channel proteins, while comparable advances in biophysics, including patch-clamp electrophysiology and related techniques, have made the functional assessment of expressed proteins at the level of single channel molecules possible. The role of ion channel defects in the pathogenesis of numerous disorders has become increasingly apparent over the last two decades. Neurological channelopathies are frequently genetically determined but may also be acquired through autoimmune mechanisms. All of these autoimmune conditions can arise as paraneoplastic syndromes or independent from malignancies. The pathogenicity of autoantibodies to ion channels has been demonstrated in most of these conditions, and patients may respond well to immunotherapies that reduce the levels of the pathogenic autoantibodies. Autoimmune channelopathies may have a good prognosis, especially if diagnosed and treated early, and if they are non-paraneoplastic. This review focuses on clinical, pathophysiologic and therapeutic aspects of autoimmune ion channel disorders of the nervous system.

  17. Ion channelopathies in functional GI disorders.

    PubMed

    Beyder, Arthur; Farrugia, Gianrico

    2016-10-01

    In the gastrointestinal (GI) tract, abnormalities in secretion, absorption, motility, and sensation have been implicated in functional gastrointestinal disorders (FGIDs). Ion channels play important roles in all these GI functions. Disruptions of ion channels' ability to conduct ions can lead to diseases called ion channelopathies. Channelopathies can result from changes in ion channel biophysical function or expression due to mutations, posttranslational modification, and accessory protein malfunction. Channelopathies are strongly established in the fields of cardiology and neurology, but ion channelopathies are only beginning to be recognized in gastroenterology. In this review, we describe the state of the emerging field of GI ion channelopathies. Several recent discoveries show that channelopathies result in alterations in GI motility, secretion, and sensation. In the epithelium, mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) or CFTR-associating proteins result in channelopathies with constipation or diarrhea as phenotypes. In the muscle, mutations in the SCN5A-encoded voltage-gated sodium channel NaV1.5 are associated with irritable bowel syndrome. In the sensory nerves, channelopathies of voltage-gated sodium channels NaV1.7 and NaV1.9 (encoded by SCN9A, SCN11A, respectively) manifest by either GI hyper- or hyposensation. Recent advances in structural biology and ion channel biophysics, coupled with personalized medicine, have fueled rapid discoveries of novel channelopathies and direct drug targeting of specific channelopathies. In summary, the emerging field of GI ion channelopathies has significant implications for functional GI disease stratification, diagnosis, and treatment. Copyright © 2016 the American Physiological Society.

  18. 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.

  19. 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…

  20. 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…

  1. 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.

  2. Resurgence matches quantization

    NASA Astrophysics Data System (ADS)

    Couso-Santamaría, Ricardo; Mariño, Marcos; Schiappa, Ricardo

    2017-04-01

    The quest to find a nonperturbative formulation of topological string theory has recently seen two unrelated developments. On the one hand, via quantization of the mirror curve associated to a toric Calabi–Yau background, it has been possible to give a nonperturbative definition of the topological-string partition function. On the other hand, using techniques of resurgence and transseries, it has been possible to extend the string (asymptotic) perturbative expansion into a transseries involving nonperturbative instanton sectors. Within the specific example of the local {{{P}}2} toric Calabi–Yau threefold, the present work shows how the Borel–Padé–Écalle resummation of this resurgent transseries, alongside occurrence of Stokes phenomenon, matches the string-theoretic partition function obtained via quantization of the mirror curve. This match is highly non-trivial, given the unrelated nature of both nonperturbative frameworks, signaling at the existence of a consistent underlying structure.

  3. Extinction-Induced Response Resurgence: A Selective Review

    ERIC Educational Resources Information Center

    Doughty, Adam H.; Oken, Gabriella

    2008-01-01

    Resurgence refers to the recovery of previously extinguished responding when a recently reinforced response is extinguished. Although the topic of resurgence has received limited experimental attention, there recently have been an increased number of investigations involving the topic. This increased experimental attention also has been…

  4. Painful Na-channelopathies: an expanding universe.

    PubMed

    Waxman, Stephen G

    2013-07-01

    The universe of painful Na-channelopathies--human disorders caused by mutations in voltage-gated sodium channels--has recently expanded in three dimensions. We now know that mutations of sodium channels cause not only rare genetic 'model disorders' such as inherited erythromelalgia and channelopathy-associated insensitivity to pain but also common painful neuropathies. We have learned that mutations of NaV1.8, as well as mutations of NaV1.7, can cause painful Na-channelopathies. Moreover, recent studies combining atomic level structural models and pharmacogenomics suggest that the goal of genomically guided pain therapy may not be unrealistic.

  5. Ion channelopathies and migraine pathogenesis.

    PubMed

    Albury, Cassie L; Stuart, Shani; Haupt, Larisa M; Griffiths, Lyn R

    2017-08-01

    Migraine is a common neurological disorder that affects approximately 12-20% of the general adult population. Migraine pathogenesis is complex and not wholly understood. Molecular genetic investigations, imaging and biochemical studies, have unveiled a number of interconnected neurological pathways which seem to have a cause and effect component integral to its cause. Much weight of migraine attack initiation can be placed on the initial trigger and the pathways involved in its neuronal counter reaction. Ion channels play a large role in the generation, portrayal and mitigation of the brains response to external triggers. Several genetic studies have identified and implicated a number of ion channelopathy genes which may contribute to this generalised process. This review will focus on the genetics of migraine with particular emphasis placed on the potentially important role genes HEPH (responsible for iron transport and homeostasis) and KCNK18 (important for the transport and homeostasis of potassium) play in migraine cause.

  6. Resurgence of Infant Caregiving Responses

    ERIC Educational Resources Information Center

    Bruzek, Jennifer L.; Thompson, Rachel H.; Peters, Lindsay C.

    2009-01-01

    Two experiments were conducted to identify the conditions likely to produce resurgence among adult human participants. The preparation was a simulated caregiving context, wherein a recorded infant cry sounded and was terminated contingent upon targeted caregiving responses. Results of Experiment 1 demonstrated resurgence with human participants in…

  7. 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

  8. 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...

  9. 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...

  10. 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.

  11. 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

  12. 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

  13. Action potential broadening in a presynaptic channelopathy.

    PubMed

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

    2016-07-06

    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.

  14. 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.

  15. 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

  16. Resurgence of Mumps in Korea

    PubMed Central

    2015-01-01

    Routine vaccination against mumps has markedly reduced its incidence. However, the incidence of mumps continuously has increased since 2007. In 2013, a large mumps epidemic occurred in Korea, and this epidemic is still an ongoing problem. This epidemic occurred primarily in school settings and affected vaccinated adolescents, predominantly male students. The recent resurgence of mumps is caused by multiple factors: suboptimal effectiveness of the current mumps vaccines, use of the Rubini strain vaccine, waning immunity in the absence of natural boosting due to the marked reduction in the mumps incidence, genotype mismatch between the vaccine and circulating mumps virus strains, and environmental conditions that foster intense exposures. Containment of mumps outbreaks is challenging because the sensitivity of diagnostic tests is low among vaccinees and control measures are less efficient because of the inherent nature of the mumps virus. Despite the suboptimal vaccine effectiveness in outbreak settings, maintaining the high vaccine coverage is an important strategy to prevent mumps outbreaks, given that the routine use of mumps vaccines has substantially reduced the incidence of mumps and its complications as compared with that in the pre-vaccine era. In order to control the current mumps epidemic and prevent further outbreaks, we need to better understand the dynamics of mumps among vaccinated populations and the changing epidemiology in Korea. Concerted efforts should be made to systematically monitor the immunization status of the Korean population and to improve diagnosis efficiency. Furthermore, more effective mumps vaccines need to be developed in the future. PMID:25844258

  17. Introduction to the Special Section on Resurgence

    ERIC Educational Resources Information Center

    Kestner, Kathryn M.; Peterson, Stephanie M.; Wacker, David P.

    2017-01-01

    In this introduction, the editors provide an overview of resurgence and its importance to practitioners. They also provide an overview of the four articles contained in this special section focusing on the applied implications of resurgence.

  18. Dendritic ion channelopathy in acquired epilepsy

    PubMed Central

    Poolos, Nicholas P.; Johnston, Daniel

    2012-01-01

    Summary Ion channel dysfunction or “channelopathy” is a proven cause of epilepsy in the relatively uncommon genetic epilepsies with Mendelian inheritance. But numerous examples of acquired channelopathy in experimental animal models of epilepsy following brain injury have also been demonstrated. Our understanding of channelopathy has grown due to advances in electrophysiology techniques that have allowed the study of ion channels in the dendrites of pyramidal neurons in cortex and hippocampus. The apical dendrites of pyramidal neurons comprise the vast majority of neuronal surface membrane area, and thus the majority of the neuronal ion channel population. Investigation of dendritic ion channels has demonstrated remarkable plasticity in ion channel localization and biophysical properties in epilepsy, many of which produce hyperexcitability and may contribute to the development and maintenance of the epileptic state. Here we review recent advances in dendritic physiology and cell biology, and their relevance to epilepsy. PMID:23216577

  19. 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

  20. Autoimmune channelopathies in paraneoplastic neurological syndromes.

    PubMed

    Joubert, Bastien; Honnorat, Jérôme

    2015-10-01

    Paraneoplastic neurological syndromes and autoimmune encephalitides are immune neurological disorders occurring or not in association with a cancer. They are thought to be due to an autoimmune reaction against neuronal antigens ectopically expressed by the underlying tumour or by cross-reaction with an unknown infectious agent. In some instances, paraneoplastic neurological syndromes and autoimmune encephalitides are related to an antibody-induced dysfunction of ion channels, a situation that can be labelled as autoimmune channelopathies. Such functional alterations of ion channels are caused by the specific fixation of an autoantibody upon its target, implying that autoimmune channelopathies are usually highly responsive to immuno-modulatory treatments. Over the recent years, numerous autoantibodies corresponding to various neurological syndromes have been discovered and their mechanisms of action partially deciphered. Autoantibodies in neurological autoimmune channelopathies may target either directly ion channels or proteins associated to ion channels and induce channel dysfunction by various mechanisms generally leading to the reduction of synaptic expression of the considered channel. The discovery of those mechanisms of action has provided insights on the regulation of the synaptic expression of the altered channels as well as the putative roles of some of their functional subdomains. Interestingly, patients' autoantibodies themselves can be used as specific tools in order to study the functions of ion channels. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.

  1. A Model of Resurgence Based on Behavioral Momentum Theory

    PubMed Central

    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 model of resurgence based on the augmented model of extinction provided by behavioral momentum theory. The model suggests that alternative reinforcement during extinction of a target response acts as both an additional source of disruption during extinction and as a source of reinforcement in the context that increases the future strength of the target response. The model does a good job accounting for existing data in the resurgence literature and makes novel and testable predictions. Thus, the model appears to provide a framework for understanding resurgence and serves to integrate the phenomenon into the existing theoretical account of persistence provided by behavioral momentum theory. In addition, we discuss some potential implications of the model for further development of behavioral momentum theory. PMID:21541118

  2. A model of resurgence based on behavioral momentum theory.

    PubMed

    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 model of resurgence based on the augmented model of extinction provided by behavioral momentum theory. The model suggests that alternative reinforcement during extinction of a target response acts as both an additional source of disruption during extinction and as a source of reinforcement in the context that increases the future strength of the target response. The model does a good job accounting for existing data in the resurgence literature and makes novel and testable predictions. Thus, the model appears to provide a framework for understanding resurgence and serves to integrate the phenomenon into the existing theoretical account of persistence provided by behavioral momentum theory. In addition, we discuss some potential implications of the model for further development of behavioral momentum theory.

  3. 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

  4. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Life threatening causes of syncope: channelopathies and cardiomyopathies.

    PubMed

    Herman, Adam; Bennett, Matthew T; Chakrabarti, Santabhanu; Chakrabarti, Santabahnu; Krahn, Andrew D

    2014-09-01

    Syncope is common, has a high recurrence rate and carries a risk of morbidity and, dependent on the cause, mortality. Although the majority of patients with syncope have a benign prognosis, syncope as a result of cardiomyopathy or channelopathy carries a poor prognosis. In addition, the identification of these disorders allows for the institution of treatments, which are effective at reducing the risk of both syncope and mortality. It is for these reasons that the identification of a cardiomyopathy or channelopathy in patients with syncope is crucial. This review article will describe the characteristics of common cardiomyopathies and channelopathies and their investigation. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Human K(ATP) channelopathies: diseases of metabolic homeostasis.

    PubMed

    Olson, Timothy M; Terzic, Andre

    2010-07-01

    Assembly of an inward rectifier K+ channel pore (Kir6.1/Kir6.2) and an adenosine triphosphate (ATP)-binding regulatory subunit (SUR1/SUR2A/SUR2B) forms ATP-sensitive K+ (KATP) channel heteromultimers, widely distributed in metabolically active tissues throughout the body. KATP channels are metabolism-gated biosensors functioning as molecular rheostats that adjust membrane potential-dependent functions to match cellular energetic demands. Vital in the adaptive response to (patho)physiological stress, KATP channels serve a homeostatic role ranging from glucose regulation to cardioprotection. Accordingly, genetic variation in KATP channel subunits has been linked to the etiology of life-threatening human diseases. In particular, pathogenic mutations in KATP channels have been identified in insulin secretion disorders, namely, congenital hyperinsulinism and neonatal diabetes. Moreover, KATP channel defects underlie the triad of developmental delay, epilepsy, and neonatal diabetes (DEND syndrome). KATP channelopathies implicated in patients with mechanical and/or electrical heart disease include dilated cardiomyopathy (with ventricular arrhythmia; CMD1O) and adrenergic atrial fibrillation. A common Kir6.2 E23K polymorphism has been associated with late-onset diabetes and as a risk factor for maladaptive cardiac remodeling in the community-at-large and abnormal cardiopulmonary exercise stress performance in patients with heart failure. The overall mutation frequency within KATP channel genes and the spectrum of genotype-phenotype relationships remain to be established, while predicting consequences of a deficit in channel function is becoming increasingly feasible through systems biology approaches. Thus, advances in molecular medicine in the emerging field of human KATP channelopathies offer new opportunities for targeted individualized screening, early diagnosis, and tailored therapy.

  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. 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

  9. Tuberculous otitis media: a resurgence?

    PubMed

    Kameswaran, M; Natarajan, K; Parthiban, M; Krishnan, P V; Raghunandhan, S

    2017-09-01

    Tuberculosis is a global health problem that is especially prevalent in developing countries such as India. Recently, atypical presentation has become more common and a high index of suspicion is essential. This study analysed the various presenting symptoms and signs of tuberculous otitis media and the role of diagnostic tests, with the aim of formulating criteria for the diagnosis. A total of 502 patients underwent tympanomastoidectomy over a two-year period. Microbiological and histopathological examinations and polymerase chain reaction analysis of tissue taken during tympanomastoidectomy were performed. A total of 25 patients (5 per cent) were diagnosed with tuberculous otitis media. Severe mixed hearing loss, facial palsy, labyrinthine fistula, post-aural fistula, perichondritis and extradural abscess were noted. There seems to be a resurgence in tuberculous otitis media in India. Microbiological, histopathological and polymerase chain reaction tests for tuberculosis are helpful for its diagnosis.

  10. Gene therapy and editing: Novel potential treatments for neuronal channelopathies.

    PubMed

    Wykes, R C; Lignani, G

    2017-05-28

    Pharmaceutical treatment can be inadequate, non-effective, or intolerable for many people suffering from a neuronal channelopathy. Development of novel treatment options, particularly those with the potential to be curative is warranted. Gene therapy approaches can permit cell-specific modification of neuronal and circuit excitability and have been investigated experimentally as a therapy for numerous neurological disorders, with clinical trials for several neurodegenerative diseases ongoing. Channelopathies can arise from a wide array of gene mutations; however they usually result in periods of aberrant network excitability. Therefore gene therapy strategies based on up or downregulation of genes that modulate neuronal excitability may be effective therapy for a wide range of neuronal channelopathies. As many channelopathies are paroxysmal in nature, optogenetic or chemogenetic approaches may be well suited to treat the symptoms of these diseases. Recent advances in gene-editing technologies such as the CRISPR-Cas9 system could in the future result in entirely novel treatment for a channelopathy by repairing disease-causing channel mutations at the germline level. As the brain may develop and wire abnormally as a consequence of an inherited or de novo channelopathy, the choice of optimal gene therapy or gene editing strategy will depend on the time of intervention (germline, neonatal or adult). Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Channelopathies in children and adults.

    PubMed

    Wilde, Arthur A M

    2008-02-01

    In the last decade, pediatric cardiologists have witnessed a revolution in the knowledge of the pathophysiology of rare arrhythmias. The identification of the molecular basis of several hereditary arrhythmia syndromes has been instrumental in this development. Within 12 years the number of causal genes has increased from two in 1995 to at least 24 early 2007 (Table I). Based on this knowledge, established treatment strategies in the 1990s have been modified during the most recent years. This leads to timely and tailored treatment of (asymptomatic) gene carriers, both through personalized lifestyle advices and pharmacologically. At the same time and of equal importance, unaffected family members (noncarriers) can be reassured.

  12. Malaria resurgence: a systematic review and assessment of its causes

    PubMed Central

    2012-01-01

    Background Considerable declines in malaria have accompanied increased funding for control since the year 2000, but historical failures to maintain gains against the disease underscore the fragility of these successes. Although malaria transmission can be suppressed by effective control measures, in the absence of active intervention malaria will return to an intrinsic equilibrium determined by factors related to ecology, efficiency of mosquito vectors, and socioeconomic characteristics. Understanding where and why resurgence has occurred historically can help current and future malaria control programmes avoid the mistakes of the past. Methods A systematic review of the literature was conducted to identify historical malaria resurgence events. All suggested causes of these events were categorized according to whether they were related to weakened malaria control programmes, increased potential for malaria transmission, or technical obstacles like resistance. Results The review identified 75 resurgence events in 61 countries, occurring from the 1930s through the 2000s. Almost all resurgence events (68/75 = 91%) were attributed at least in part to the weakening of malaria control programmes for a variety of reasons, of which resource constraints were the most common (39/68 = 57%). Over half of the events (44/75 = 59%) were attributed in part to increases in the intrinsic potential for malaria transmission, while only 24/75 (32%) were attributed to vector or drug resistance. Conclusions Given that most malaria resurgences have been linked to weakening of control programmes, there is an urgent need to develop practical solutions to the financial and operational threats to effectively sustaining today’s successful malaria control programmes. PMID:22531245

  13. [Ion channel abnormalities ("channelopathies") in neurologic diseases].

    PubMed

    Masson, C

    2002-02-16

    THE ROLE OF IONIC CHANNEL DYSFUNCTION: During various neurological diseases has been evoked for many years on electro-physiological data. Molecular biology has led to great progress in neurology, and can be considered "functional" since it is surpasses the classical anatomo-clinical methods. IONIC CHANNEL DYSFUNCTION: Can be determined genetically, resulting from the mutation of a gene code of a channel sub-unit. CHANNELOPATHIES ARE RESPONSIBLE: For muscular diseases (myotonia, familial periodic paralysis, malignant hyperthermia and congenital myasthenia), but also for central nervous system disorders such as familial hemiplegic migraine, hereditary paroxystic ataxia and certain forms of Mendel's law hereditary epilepsy. ACQUIRED IONIC CHANNEL DYSFUNCTION: Resulting from auto-immune aggression is implied in diseases such as Lambert-Eaton's myasthenic syndrome and Isaac's neuromyotonia syndrome. It probably plays a part in the clinical, and particularly the sensitive expression (paresthesia and pain) of some peripheral neuropathies and certain central nervous system affections, such as multiple sclerosis.

  14. Effects of high, low, and thinning rates of alternative reinforcement on response elimination and resurgence.

    PubMed

    Sweeney, Mary M; Shahan, Timothy A

    2013-07-01

    A common treatment for operant problem behavior is alternative reinforcement. When alternative reinforcement is removed or reduced, however, resurgence of the target behavior can occur. Shahan and Sweeney (2011) developed a quantitative model of resurgence based on behavioral momentum theory that suggests higher rates of alternative reinforcement result in faster response elimination and greater resurgence when removed, whereas lower rates of alternative reinforcement result in slower response elimination but are followed by less resurgence. Thus, the present study was designed to examine whether faster target response elimination and less resurgence could be achieved by beginning with a high rate of alternative reinforcement and gradually thinning it such that a low rate is ultimately removed during a simulated treatment lapse. Results showed that high rates of alternative reinforcement were more effective than low or thinning rates at target response suppression but resulted in resurgence when discontinued. Low and thinning rates, on the other hand, were less effective at response suppression but target responding did not increase when alternative reinforcement was discontinued. The quantitative model cannot currently account for the finding that lower-rate alternative reinforcement may not effectively disrupt behavior relative to an extinction only control. Relative advantages of high, low, thinning, or no alternative reinforcement are discussed with respect to suppression of target response rate during treatment, resurgence when alternative reinforcement is removed, and alternative response persistence, while taking into account differences between this animal model and modern applied behavior analytic treatments.

  15. Myotonic discharges discriminate chloride from sodium muscle channelopathies.

    PubMed

    Drost, Gea; Stunnenberg, Bas C; Trip, Jeroen; Borm, George; McGill, Kevin C; Ginjaar, Ieke H B; van der Kooi, Arendina W; Zwarts, Machiel J; van Engelen, Baziel G M; Faber, Catharina G; Stegeman, Dick F; Lateva, Zoia

    2015-01-01

    Non-dystrophic myotonic syndromes represent a heterogeneous group of clinically quite similar diseases sharing the feature of myotonia. These syndromes can be separated into chloride and sodium channelopathies, with gene-defects in chloride or sodium channel proteins of the sarcolemmal membrane. Myotonia has its basis in an electrical instability of the sarcolemmal membrane. In the present study we examine the discriminative power of the resulting myotonic discharges for these disorders. Needle electromyography was performed by an electromyographer blinded for genetic diagnosis in 66 non-dystrophic myotonia patients (32 chloride and 34 sodium channelopathy). Five muscles in each patient were examined. Individual trains of myotonic discharges were extracted and analyzed with respect to firing characteristics. Myotonic discharge characteristics in the rectus femoris muscle almost perfectly discriminated chloride from sodium channelopathy patients. The first interdischarge interval as a single variable was longer than 30 ms in all but one of the chloride channelopathy patients and shorter than 30 ms in all of the sodium channelopathy patients. This resulted in a detection rate of over 95%. Myotonic discharges of a single muscle can be used to better guide toward a molecular diagnosis in non-dystrophic myotonic syndromes.

  16. The resurgence of tuberculosis in Russia.

    PubMed

    Shilova, M V; Dye, C

    2001-07-29

    This paper documents and attempts to explain the epidemic spread of tuberculosis (TB) in Russia during the 1990s. After several decades of decline, the notification rate of all new TB cases among permanent residents increased by 7.5% per year from 1991-1999 and the death rate by 11% per year. Growth was quickest from 1993-1995 but increased again after the economic crisis of August 1998. Approximately 120 000 new cases and 30 000 deaths were reported in 1999. Case detection and cure rates have fallen in Russia since the mid-1980s; the fall has been accompanied by a higher frequency of severe disease among cases, and higher death and case fatality rates. With a mathematical model describing the deterioration in case finding and cure rates we could replicate the average rate of increase in incidence 1991-1999 but not the precise timing of the observed changes. Other factors that probably helped to shape the observed rise in caseload include enhanced transmission due to the mixing of prison and civilian populations, an increase in susceptibility to disease, and changes in the proportion of cases detected by surveillance. Although our explanation for the resurgence of TB is incomplete, we have identified a set of measures that can be implemented now to cut transmission, incidence and deaths.

  17. The resurgence of tuberculosis in Russia.

    PubMed Central

    Shilova, M V; Dye, C

    2001-01-01

    This paper documents and attempts to explain the epidemic spread of tuberculosis (TB) in Russia during the 1990s. After several decades of decline, the notification rate of all new TB cases among permanent residents increased by 7.5% per year from 1991-1999 and the death rate by 11% per year. Growth was quickest from 1993-1995 but increased again after the economic crisis of August 1998. Approximately 120 000 new cases and 30 000 deaths were reported in 1999. Case detection and cure rates have fallen in Russia since the mid-1980s; the fall has been accompanied by a higher frequency of severe disease among cases, and higher death and case fatality rates. With a mathematical model describing the deterioration in case finding and cure rates we could replicate the average rate of increase in incidence 1991-1999 but not the precise timing of the observed changes. Other factors that probably helped to shape the observed rise in caseload include enhanced transmission due to the mixing of prison and civilian populations, an increase in susceptibility to disease, and changes in the proportion of cases detected by surveillance. Although our explanation for the resurgence of TB is incomplete, we have identified a set of measures that can be implemented now to cut transmission, incidence and deaths. PMID:11516384

  18. Gene replacement therapy for retinal CNG channelopathies.

    PubMed

    Schön, Christian; Biel, Martin; Michalakis, Stylianos

    2013-10-01

    Visual phototransduction relies on the function of cyclic nucleotide-gated channels in the rod and cone photoreceptor outer segment plasma membranes. The role of these ion channels is to translate light-triggered changes in the second messenger cyclic guanosine 3'-5'-monophosphate levels into an electrical signal that is further processed within the retinal network and then sent to higher visual centers. Rod and cone photoreceptors express distinct CNG channels. The rod photoreceptor CNG channel is composed of one CNGB1 and three CNGA1 subunits, whereas the cone channel is formed by one CNGB3 and three CNGA3 subunits. Mutations in any of these channel subunits result in severe and currently untreatable retinal degenerative diseases like retinitis pigmentosa or achromatopsia. In this review, we provide an overview of the human diseases and relevant animal models of CNG channelopathies. Furthermore, we summarize recent results from preclinical gene therapy studies using adeno-associated viral vectors and discuss the efficacy and translational potential of these gene therapeutic approaches.

  19. Chloride channelopathies of ClC-2.

    PubMed

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

    2013-12-27

    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.

  20. 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

  1. Gauge hierarchy problem in asymptotically safe gravity - The resurgence mechanism

    NASA Astrophysics Data System (ADS)

    Wetterich, Christof; Yamada, Masatoshi

    2017-07-01

    The gauge hierarchy problem could find a solution within the scenario of asymptotic safety for quantum gravity. We discuss a ;resurgence mechanism; where the running dimensionless coupling responsible for the Higgs scalar mass first decreases in the ultraviolet regime and subsequently increases in the infrared regime. A gravity induced large anomalous dimension plays a crucial role for the required ;self-tuned criticality; in the ultraviolet regime beyond the Planck scale.

  2. Climatic factors in resurgence of Mediterranean spotted fever

    SciTech Connect

    Arenas, E.E.; Creus, B.F.; Cueto, F.B.; Porta, F.S.

    1986-06-07

    There has been a recent resurgence of Mediterranean spotted fever in areas bordering the Mediterranean Sea. This disease is caused by Rickettsia conorii, the dog tick being the vector and main reservoir. Ticks prefer warm weather and their activity increases with rising temperature. In the Valles Occidental, Spain, the incidence of the disease is correlated with hotter and drier summers in the past ten years.

  3. Recency, repeatability, and reinforcer retrenchment: an experimental analysis of resurgence.

    PubMed

    Lieving, Gregory A; Lattal, Kennon A

    2003-09-01

    Four experiments were conducted with pigeons to assess the experimental conditions necessary for the occurrence of resurgence. The general procedure consisted of the following conditions: Condition 1--reinforcement of key pecking; Condition 2--reinforcement of treadle pressing and concurrent extinction of key pecking; and Condition 3--the resurgence condition wherein resurgence was defined as the recovery of key pecking. In Experiments 1 and 2, the resurgence condition was conventional extinction. The effect of recency on resurgence magnitude was examined in Experiment 1 by manipulating the number of sessions of Condition 2, above. Resurgence was not a function of recency with the parameters used. Repeating the three conditions revealed resurgence to be a repeatable effect in Experiment 2. In Experiment 3, a variable-time schedule was in effect for the resurgence condition. Resurgence was not produced by response-independent food delivery. In Experiment 4, the resurgence condition was a variable-interval schedule for treadle pressing that arranged a lower reinforcement rate than in Condition 2 (92% reduction in reinforcers per minute). Resurgence was lower in magnitude relative to conventional extinction, although resurgence was obtained with 2 out of 3 pigeons. The results are discussed in terms of the variables controlling resurgence and the relations between behavioral history, resurgence, and other forms of response recovery.

  4. 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.

  5. Renewal, Resurgence, and Alternative Reinforcement Context

    PubMed Central

    Sweeney, Mary M.; Shahan, Timothy A.

    2015-01-01

    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

  6. 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.

  7. 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

  8. Microbialite resurgence after the Late Ordovician extinction.

    PubMed

    Sheehan, Peter M; Harris, Mark T

    2004-07-01

    Microbialites, including biogenic stromatolites, thrombolites and dendrolites, were formed by various microbial mats that trapped and bound sediments or formed the locus of mineral precipitation. Microbialites were common and diverse during the Proterozoic, but declined in abundance and morphological diversity when multicellular life diversified during the Cambrian Radiation. A second decline occurred during the Ordovician Radiation of marine animals, and from then until the present microbialites have been confined largely to high-stress environments where multicellular organisms are rare. The microbialite declines in the Phanerozoic are attributed to disruption of the mats by animals. A resurgence of stromatolite abundance and size during reduced animal diversity after the Permian extinction has been documented anecdotally. Here we show, with statistical support, that a microbialite resurgence also occurred after the Late Ordovician extinction event in western North America. The resurgences were associated with loss of mat-inhibiting animals, providing insights into shallow-water community structures after extinction events.

  9. The resurgence of the cusp anomalous dimension

    NASA Astrophysics Data System (ADS)

    Aniceto, Inês

    2016-02-01

    This work addresses the resurgent properties of the cusp anomalous dimension’s strong coupling expansion, obtained from the integral Beisert-Eden-Staudacher (BES) equation. This expansion is factorially divergent, and its first non-perturbative corrections are related to the mass gap of the O(6)σ -model. The factorial divergence can also be analyzed from a resurgence perspective. Building on the work of Basso and Korchemsky, a transseries ansatz for the cusp anomalous dimension is proposed and the corresponding expected large-order behaviour studied. One finds non-perturbative phenomena in both the positive and negative real coupling directions, which need to be included to address the analyticity conditions coming from the BES equation. After checking the resurgence structure of the proposed transseries, it is shown that it naturally leads to an unambiguous resummation procedure, furthermore allowing for a strong/weak coupling interpolation.

  10. 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

  11. Cardiac Channelopathies and Sudden Death: Recent Clinical and Genetic Advances

    PubMed Central

    Fernández-Falgueras, Anna; Sarquella-Brugada, Georgia; Brugada, Josep; Brugada, Ramon; Campuzano, Oscar

    2017-01-01

    Sudden cardiac death poses a unique challenge to clinicians because it may be the only symptom of an inherited heart condition. Indeed, inherited heart diseases can cause sudden cardiac death in older and younger individuals. Two groups of familial diseases are responsible for sudden cardiac death: cardiomyopathies (mainly hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic cardiomyopathy) and channelopathies (mainly long QT syndrome, Brugada syndrome, short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia). This review focuses on cardiac channelopathies, which are characterized by lethal arrhythmias in the structurally normal heart, incomplete penetrance, and variable expressivity. Arrhythmias in these diseases result from pathogenic variants in genes encoding cardiac ion channels or associated proteins. Due to a lack of gross structural changes in the heart, channelopathies are often considered as potential causes of death in otherwise unexplained forensic autopsies. The asymptomatic nature of channelopathies is cause for concern in family members who may be carrying genetic risk factors, making the identification of these genetic factors of significant clinical importance. PMID:28146053

  12. Resurgence: The Unintended Maintenance of Problem Behavior

    ERIC Educational Resources Information Center

    Ringdahl, Joel E.; St. Peter, Claire

    2017-01-01

    Researchers, teachers, practitioners, and parents are often concerned with how to program for and achieve the maintenance of appropriate behavior. The unintended maintenance of problem behavior is less often evaluated. This article describes a behavioral phenomenon, resurgence, that may result in the unintended maintenance of problem behavior.…

  13. 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…

  14. Caldera resurgence during magma replenishment and rejuvenation at Valles and Lake City calderas

    NASA Astrophysics Data System (ADS)

    Kennedy, Ben; Wilcock, Jack; Stix, John

    2012-10-01

    A key question in volcanology is the driving mechanisms of resurgence at active, recently active, and ancient calderas. Valles caldera in New Mexico and Lake City caldera in Colorado are well-studied resurgent structures which provide three crucial clues for understanding the resurgence process. (1) Within the limits of 40Ar/39Ar dating techniques, resurgence and hydrothermal alteration at both calderas occurred very quickly after the caldera-forming eruptions (tens of thousands of years or less). (2) Immediately before and during resurgence, dacite magma was intruded and/or erupted into each system; this magma is chemically distinct from rhyolite magma which was resident in each system. (3) At least 1 km of structural uplift occurred along regional and subsidence faults which were closely associated with shallow intrusions or lava domes of dacite magma. These observations demonstrate that resurgence at these two volcanoes is temporally linked to caldera subsidence, with the upward migration of dacite magma as the driver of resurgence. Recharge of dacite magma occurs as a response to loss of lithostatic load during the caldera-forming eruption. Flow of dacite into the shallow magmatic system is facilitated by regional fault systems which provide pathways for magma ascent. Once the dacite enters the system, it is able to heat, remobilize, and mingle with residual crystal-rich rhyolite remaining in the shallow magma chamber. Dacite and remobilized rhyolite rise buoyantly to form laccoliths by lifting the chamber roof and producing surface resurgent uplift. The resurgent deformation caused by magma ascent fractures the chamber roof, increasing its structural permeability and allowing both rhyolite and dacite magmas to intrude and/or erupt together. This sequence of events also promotes the development of magmatic-hydrothermal systems and ore deposits. Injection of dacite magma into the shallow rhyolite magma chamber provides a source of heat and magmatic volatiles

  15. Unsteady resurgence flows in karstic media

    NASA Astrophysics Data System (ADS)

    Adler, Pierre; Drygas, Piotr; Mityushev, Vladimir

    2017-04-01

    Geological porous media are heterogeneous materials which in addition contain discontinuities such as fractures and conduits which facilitate fluid transport. Fractures are relatively plane objects which strongly interact with the surrounding porous medium because of their large contact surface. A different situation occurs in karsts where distant regions of the medium can be connected by relatively thin conduits which have little if any hydrodynamic interaction with the porous medium that they cross, except at their ends. This phenomenon is called resurgence because of the obvious analogy with rivers which suddenly disappear underground and go out at the ground surface again. Similar ideas have already been developed in other fields, such as Physics with random networks and Geophysics with electrical tomography. Media with resurgences are addressed in the following way. They consist of a double structure. The first one is the continuous porous medium described by the classical Darcy law. The second one is composed by the resurgences modeled by conduits with impermeable walls which relate distant points of the continuous medium. When non steady regimes are considered, it appears necessary to confer a capacity to these conduits in addition to their hydrodynamic resistance. Therefore, the conduits are able to store some quantity of fluid. In addition, two kinds of resurgence are addressed, namely punctual and extended; in the second case, the dimensions of the ends of the conduit are not negligible compared to the characteristic length scales of the embedding porous medium. Capacities and extended resurgences are new features which were not taken into account in our previous studies. The punctual resurgence is described by a spatial network with a finite number of conduits embedded in a continuous porous medium. The flow in the network is described by the classical Kirchhoff law (including capacities). The equations for flow in the network and in the continuous

  16. Disease emergence and resurgence: Chapter 2 in Disease emergence and resurgence: The wildlife-human connection

    USGS Publications Warehouse

    Friend, Milton

    2006-01-01

    A profusion of emerging diseases has affected humans since the early 1980s, and pathogens of animal origin or products of animal origin cause many of these.2 Some of these diseases had not been established previously, such as AIDS, and others are a resurgence of diseases thought to have been controlled, such as tuberculosis in developed nations. This change in the status of diseases affecting humans has resulted in emerging infections becoming a focus for national and global attention (Box 2–1).Emerging and reemerging diseases have generally been defined as infectious diseases of humans whose occurrence during the past two decades has substantially increased or threatens to increase in the near future relative to populations affected, geographic distribution, or magnitude of impacts.3–5 This concept has been expanded to also include other species and noninfectious diseases.6–8 Disease emergence and reemergence are affecting a wide variety of species on a global scale. An overview of the scope of this problem is provided to increase awareness of the role of wildlife in the ecology of emerging/reemerging diseases and to explore some of the primary factors involved.

  17. Avoiding sports-related sudden cardiac death in children with congenital channelopathy : Recommendations for sports activities.

    PubMed

    Lang, C N; Steinfurt, J; Odening, K E

    2017-04-01

    For the past few years, children affected by an inherited channelopathy have been counseled to avoid (recreational) sports activities and all competitive sports so as to prevent exercise-induced arrhythmia and sudden cardiac death. An increased understanding of the pathophysiological mechanisms, better anti-arrhythmic strategies, and, in particular, more epidemiological data on exercise-induced arrhythmia in active athletes with channelopathies have changed the universal recommendation of "no sports," leading to revised, less strict, and more differentiated guidelines (published by the American Heart Association/American College of Cardiology in 2015). In this review, we outline the disease- and genotype-specific mechanisms of exercise-induced arrhythmia; give an overview of trigger-, symptom-, and genotype-dependent guidance in sports activities for children with long QT syndrome (LQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), or short QT syndrome (SQTS); and highlight the novelties in the current guidelines compared with previous versions. While it is still recommended for patients with LQT1 and CPVT (even when asymptomatic) and all symptomatic LQTS patients (independent of genotype) to avoid any competitive and high-intensity sports, other LQTS patients successfully treated with anti-arrhythmic therapies and phenotype-negative genotype-positive patients may be allowed to perform sports at different activity levels - provided they undergo regular, sophisticated evaluations to detect any changes in arrhythmogenic risk.

  18. The resurgence of lymphatic filariasis in the Nile delta.

    PubMed Central

    Harb, M.; Faris, R.; Gad, A. M.; Hafez, O. N.; Ramzy, R.; Buck, A. A.

    1993-01-01

    A study of 325,000 residents of 314 villages in six governorates of the Nile delta area of Egypt revealed that the prevalence of lymphatic filariasis increased from < 1% in 1965 to > 20% in 1991, especially in the governorates of Qalyubiya, Monufiya, Dakhaliya, and Giza. The distribution of the communites with endemic filariasis is focal. Clusters of villages with high prevalences are surrounded by others in which the disease is absent, although their environmental, social, and agricultural features appear similar. The article analyses why the significant decline in filariasis between 1945 and 1965 in Egypt has been followed by a resurgence of the disease. PMID:8440037

  19. Channelopathies: ion channel defects linked to heritable clinical disorders

    PubMed Central

    Felix, R.

    2000-01-01

    Electrical signals are critical for the function of neurones, muscle cells, and cardiac myocytes. Proteins that regulate electrical signalling in these cells, including voltage gated ion channels, are logical sites where abnormality might lead to disease. Genetic and biophysical approaches are being used to show that several disorders result from mutations in voltage gated ion channels. Understanding gained from early studies on the pathogenesis of a group of muscle diseases that are similar in their episodic nature (periodic paralysis) showed that these disorders result from mutations in a gene encoding a voltage gated Na+ channel. Their characterisation as channelopathies has served as a paradigm for other episodic disorders. For example, migraine headache and some forms of epilepsy have been shown to result from mutations in voltage gated Ca2+ channel genes, while long QT syndrome is known to result from mutations in either K+ or Na+ channel genes. This article reviews progress made in the complementary fields of molecular genetics and cellular electrophysiology which has led to a better understanding of voltage gated ion channelopathies in humans and mice.


Keywords: ion channel genetics; ion channel physiopathology; channelopathies; hereditary diseases PMID:11015449

  20. Channeling studies in yeast: yeast as a model for channelopathies?

    PubMed

    Wolfe, Devin M; Pearce, David A

    2006-01-01

    Regulation of the concentration of ions within a cell is mediated by their specific transport and sequestration across cellular membranes. This regulation constitutes a major factor in the maintenance of correct cellular homeostasis, with the transport occurring through the action of a large number of different channel proteins localized to the plasma membrane as well as to various organelles. These ion channels vary in specificity from broad (cationic vs anionic) to highly selective (chloride vs sodium). Mutations in many of these channels result in a large number of human diseases, collectively termed channelopathies. Characterization of many of these channels has been undertaken in a variety of both prokaryotic and eukaryotic organisms. Among these organisms is the budding yeast Saccharomyces cerevisiae. Possessing a fully annotated genome, S. cerevisiae would appear to be an ideal organism in which to study this class of proteins associated to diseases. We have compiled and reviewed a list of yeast ion channels, each possessing a human homolog implicated in a channelopathy. Although yeast has been used for the study of other human disease, it has been under utilized for channelopathy research. The utility of using yeast as a model system for studying ion channels associated to human disease is illustrated using yeast lacking the GEF1 gene product that encodes the human homolog to the chloride channel CLC-3.

  1. Personalized medicine: genetic diagnosis for inherited cardiomyopathies/channelopathies.

    PubMed

    Ackerman, Michael J; Marcou, Cherisse A; Tester, David J

    2013-04-01

    Major advances in the field of molecular genetics have expanded our ability to identify genetic substrates underlying the pathogenesis of various disorders that follow Mendelian inheritance patterns. Included among these disorders are the potentially lethal and heritable channelopathies and cardiomyopathies for which the underlying genetic basis has been identified and is now better understood. Clinical and genetic heterogeneity are hallmark features of these disorders, with thousands of gene mutations being implicated within these divergent cardiovascular diseases. Genetic testing for several of these heritable channelopathies and cardiomyopathies has matured from discovery to research-based genetic testing to clinically/commercially available diagnostic tests. The purpose of this review is to provide the reader with a basic understanding of human medical genetics and genetic testing in the context of cardiovascular diseases of the heart. We review the state of clinical genetic testing for the more common channelopathies and cardiomyopathies, discuss some of the pertinent issues that arise from genetic testing, and discuss the future of personalized medicine in cardiovascular disease. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  2. 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.

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

    PubMed

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

    2002-12-01

    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.

  4. Indian Ocean Dipole drives malaria resurgence in East African highlands.

    PubMed

    Hashizume, Masahiro; Chaves, Luis Fernando; Minakawa, Noboru

    2012-01-01

    Malaria resurgence in African highlands in the 1990s has raised questions about the underlying drivers of the increase in disease incidence including the role of El-Niño-Southern Oscillation (ENSO). However, climatic anomalies other than the ENSO are clearly associated with malaria outbreaks in the highlands. Here we show that the Indian Ocean Dipole (IOD), a coupled ocean-atmosphere interaction in the Indian Ocean, affected highland malaria re-emergence. Using cross-wavelet coherence analysis, we found four-year long coherent cycles between the malaria time series and the dipole mode index (DMI) in the 1990s in three highland localities. Conversely, we found a less pronounced coherence between malaria and DMI in lowland localities. The highland/lowland contrast can be explained by the effects of mesoscale systems generated by Lake Victoria on its climate basin. Our results support the need to consider IOD as a driving force in the resurgence of malaria in the East African highlands.

  5. Implications for practice: Resurgence and differential reinforcement of alternative responding.

    PubMed

    Bloom, Sarah E; Lambert, Joseph M

    2015-12-01

    During the maintenance stages of differential reinforcement of alternative responding (DRA), failure to reinforce alternative responses could result in a resurgence of problem behavior. However, translational work done with arbitrary human responses suggests that teaching individuals to emit multiple alternative responses in sequential order may facilitate the resurgence of appropriate, rather than problem, behavior. This paper discusses the practical implications of serial DRA training on problem and appropriate behavior resurgence, as presented in the preceding article, "Serial Alternative Response Training As Intervention for Target Response Resurgence." Clinical scenarios as well as implications for self-advocacy and acceptability of behavioral interventions are considered.

  6. 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.

  7. Genetic aspects of sodium channelopathy in small fiber neuropathy.

    PubMed

    Hoeijmakers, J G J; Merkies, I S J; Gerrits, M M; Waxman, S G; Faber, C G

    2012-10-01

    Small fiber neuropathy (SFN) is a disorder typically dominated by neuropathic pain and autonomic dysfunction, in which the thinly myelinated Aδ-fibers and unmyelinated C-fibers are selectively injured. The diagnosis SFN is based on a reduced intraepidermal nerve fiber density and/or abnormal thermal thresholds in quantitative sensory testing. The etiologies of SFN are diverse, although no apparent cause is frequently seen. Recently, SCN9A-gene variants (single amino acid substitutions) have been found in ∼30% of a cohort of idiopathic SFN patients, producing gain-of-function changes in sodium channel Na(V)1.7, which is preferentially expressed in small diameter peripheral axons. Functional testing showed that these variants altered fast inactivation, slow inactivation or resurgent current and rendered dorsal root ganglion neurons hyperexcitable. In this review, we discuss the role of Na(V)1.7 in pain and highlight the molecular genetics and pathophysiology of SCN9A-gene variants in SFN. With increasing knowledge regarding the underlying pathophysiology in SFN, the development of specific treatment in these patients seems a logical target for future studies.

  8. 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…

  9. 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…

  10. 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

  11. Channelopathies and Dendritic Dysfunction in Fragile X syndrome

    PubMed Central

    Brager, Darrin H.; Johnston, Daniel

    2014-01-01

    Dendritic spine abnormalities and the metabotropic glutamate receptor theory put the focus squarely on synapses and protein synthesis as the cellular locus of Fragile X syndrome. Synapses however, are only partly responsible for information processing in neuronal networks. Neurotransmitter triggered excitatory postsynaptic potentials (EPSPs) are shaped and integrated by dendritic voltage-gated ion channels. These EPSPs, and in some cases the resultant dendritic spikes, are further modified by dendritic voltage-gated ion channels as they propagate to the soma. If the resultant somatic depolarization is large enough, action potential(s) will be triggered and propagate both orthodromically down the axon, where it may trigger neurotransmitter release, and antidromically back into the dendritic tree, where it can activate and modify dendritic voltage-gated and receptor activated ion channels. Several channelopathies, both soma-dendritic (L-type calcium channels, Slack potassium channels, h-channels, A-type potassium channels) and axo-somatic (BK channels and delayed rectifier potassium channels) were identified in the fmr1-/y mouse model of Fragile X syndrome. Pathological function of these channels will strongly influence the excitability of individual neurons as well as overall network function. In this chapter we discuss the role of voltage-gated ion channels in neuronal processing and describe how identified channelopathies in models of Fragile X syndrome may play a role in dendritic pathophysiology. PMID:24462643

  12. Voltage-gated sodium channels: biophysics, pharmacology, and related channelopathies.

    PubMed

    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 (I(Na)) 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.

  13. Deconstructing zero: resurgence, supersymmetry and complex saddles

    NASA Astrophysics Data System (ADS)

    Dunne, Gerald V.; Ünsal, Mithat

    2016-12-01

    We explain how a vanishing, or truncated, perturbative expansion, such as often arises in semi-classically tractable supersymmetric theories, can nevertheless be related to fluctuations about non-perturbative sectors via resurgence. We also demonstrate that, in the same class of theories, the vanishing of the ground state energy (unbroken supersymmetry) can be attributed to the cancellation between a real saddle and a complex saddle (with hidden topological angle π), and positivity of the ground state energy (broken supersymmetry) can be interpreted as the dominance of complex saddles. In either case, despite the fact that the ground state energy is zero to all orders in perturbation theory, all orders of fluctuations around non-perturbative saddles are encoded in the perturbative E ( N, g). We illustrate these ideas with examples from supersymmetric quantum mechanics and quantum field theory.

  14. Deconstructing zero: resurgence, supersymmetry and complex saddles

    DOE PAGES

    Dunne, Gerald V.; Ünsal, Mithat

    2016-12-01

    We explain how a vanishing, or truncated, perturbative expansion, such as often arises in semi-classically tractable supersymmetric theories, can nevertheless be related to fluctuations about non-perturbative sectors via resurgence. We also demonstrate that, in the same class of theories, the vanishing of the ground state energy (unbroken supersymmetry) can be attributed to the cancellation between a real saddle and a complex saddle (with hidden topological angle π), and positivity of the ground state energy (broken supersymmetry) can be interpreted as the dominance of complex saddles. In either case, despite the fact that the ground state energy is zero to allmore » orders in perturbation theory, all orders of fluctuations around non-perturbative saddles are encoded in the perturbative E (N, g). Finally, we illustrate these ideas with examples from supersymmetric quantum mechanics and quantum field theory.« less

  15. 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.

  16. 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.

  17. Deconstructing zero: resurgence, supersymmetry and complex saddles

    SciTech Connect

    Dunne, Gerald V.; Ünsal, Mithat

    2016-12-01

    We explain how a vanishing, or truncated, perturbative expansion, such as often arises in semi-classically tractable supersymmetric theories, can nevertheless be related to fluctuations about non-perturbative sectors via resurgence. We also demonstrate that, in the same class of theories, the vanishing of the ground state energy (unbroken supersymmetry) can be attributed to the cancellation between a real saddle and a complex saddle (with hidden topological angle π), and positivity of the ground state energy (broken supersymmetry) can be interpreted as the dominance of complex saddles. In either case, despite the fact that the ground state energy is zero to all orders in perturbation theory, all orders of fluctuations around non-perturbative saddles are encoded in the perturbative E (N, g). Finally, we illustrate these ideas with examples from supersymmetric quantum mechanics and quantum field theory.

  18. Resurgent transseries & Dyson–Schwinger equations

    SciTech Connect

    Klaczynski, Lutz

    2016-09-15

    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.

  19. 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.

  20. Resurgence of instrumental behavior after an abstinence contingency.

    PubMed

    Bouton, Mark E; Schepers, Scott T

    2014-06-01

    In resurgence, an extinguished instrumental behavior (R1) recovers when a behavior that has replaced it (R2) is also extinguished. The phenomenon may be relevant to understanding relapse that can occur after the termination of "contingency management" treatments, in which an unwanted behavior (e.g., substance abuse) is reduced by reinforcing an alternative behavior. When reinforcement is discontinued, the unwanted behavior might resurge. However, unlike most resurgence experiments, contingency management treatments also introduce a negative contingency, in which reinforcers are not delivered unless the client has abstained from the unwanted behavior. In two experiments with rats, we therefore examined the effects of adding a negative "abstinence" contingency to the resurgence design. During response elimination, R2 was not reinforced unless R1 had not been emitted for a minimum period of time (45, 90, or 135 s). In both experiments, adding such a contingency to simple R1 extinction reduced, but did not eliminate, resurgence. In Experiment 2, we found the same effect in a yoked group that could earn reinforcers for R2 at the same points in time as the negative-contingency group, but without the requirement to abstain from R1. Thus, the negative contingency per se did not contribute to the reduction in resurgence. These results suggest that the contingency reduced resurgence by making reinforcers more difficult to earn and more widely spaced in time. This could have allowed the animal to learn that R1 was extinguished in the "context" of infrequent reinforcement-a context more like that of resurgence testing. The results are thus consistent with a contextual (renewal) account of resurgence. The method might provide a better model of relapse after termination of a contingency management treatment.

  1. Autoimmune Voltage-Gated Potassium Channelopathy Presenting With Catecholamine Excess.

    PubMed

    Stepp, K Amy; Folker, Christin; Tanzer, Marie; Hayman, Jennifer; Reynolds, Thomas; Mallory, Leah

    2017-07-01

    Autoimmune voltage-gated potassium channelopathies have been associated with a range of neurological presenting symptoms, including central, peripheral, and autonomic dysfunction. We describe a 12-year-old boy who presented with nine months of pain, anxiety, and 30-pound weight loss. He was admitted for failure to thrive, then noted to be persistently hypertensive and tachycardic. Plasma metanephrines and urine metanephrines and catecholamines were elevated. Extensive investigation for causes of elevated catecholamines, such as hyperthyroidism or catecholamine-secreting tumor, was negative. A paraneoplastic panel was positive for voltage-gated potassium channel antibodies. Treatment with intravenous immunoglobulin and pulse methylprednisolone led to complete resolution of symptoms, weight gain, and normalization of vital signs and plasma metanephrines. Voltage-gated potassium channel antibodies should be considered as part of the differential in patients presenting with elevated metanephrine and catecholamine secretion. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Nav1.7 mutations associated with paroxysmal extreme pain disorder, but not erythromelalgia, enhance Navβ4 peptide-mediated resurgent sodium currents

    PubMed Central

    Theile, Jonathan W; Jarecki, Brian W; Piekarz, Andrew D; Cummins, Theodore R

    2011-01-01

    Inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEPD) are inherited pain syndromes predominantly caused by missense mutations in the peripheral neuronal voltage-gated sodium channel (Nav) isoform Nav1.7. While both IEM and PEPD mutations increase neuronal excitability, IEM mutations primarily enhance activation and PEPD mutations impair inactivation. In addition, one PEPD mutation, Nav1.7-I1461T, has been shown to increase resurgent sodium currents in dorsal root ganglion (DRG) neurons. Because resurgent currents have been implicated in increased neuronal excitability, we asked whether (1) additional PEPD mutations located within the putative inactivation gate and docking sites and (2) IEM mutations might also increase these unusual currents. Resurgent currents are generated following open-channel block at positive potentials by an endogenous blocking particle and subsequent expulsion of this blocker upon repolarization to moderately negative potentials. Here we used a mimetic of the putative blocking particle, the Navβ4 peptide, to determine if enhanced resurgent currents are induced by three distinct PEPD mutations and two IEM mutations in stably transfected HEK293 cells. We demonstrate that (1) Nav1.7-mediated resurgent currents are observed in HEK293 cells with the Navβ4 peptide in the recording pipette, (2) while the PEPD mutants M1627K, T1464I and V1299F exhibit enhanced resurgent current amplitudes compared to wild-type, the IEM mutants I848T and L858H do not, and (3) there is a strong correlation between the decay time constant of open-channel fast inactivation and resurgent current amplitude. These data suggest that resurgent currents may play a role in the neuronal hyperexcitability associated with PEPD, but not IEM, mutations. PMID:21115638

  3. Skeletal Muscle Channelopathies: New insights into the periodic paralyses and nondystrophic myotonias

    PubMed Central

    Platt, Daniel; Griggs, Robert

    2009-01-01

    Purpose of Review To summarize advances in our understanding of the clinical phenotypes, genetics, and molecular pathophysiology of the periodic paralyses, the nondystrophic myotonias, and other muscle channelopathies. Recent findings The number of pathogenic mutations causing periodic paralysis, nondystrophic myotonias, and ryanodinopathies continues to grow with the advent of exon hierarchy analysis strategies for genetic screening and better understanding and recognition of disease phenotypes. Recent studies have expanded and clarified the role of gating pore current in channelopathy pathogenesis. It has been shown that the gating pore current can account for the molecular and phenotypic pathology observed in the muscle sodium channelopathies, and, given that homologous residues are affected in mutations of calcium channels, it is possible that pore leak represents a pathomechanism applicable to many channel diseases. Improvements in treatment of the muscle channelopathies are on the horizon. A randomized controlled trial has been initiated for the study of mexiletine in nondystrophic myotonias. The class IC anti-arrhythmia drug flecainide has been shown to depress ventricular ectopy and improve exercise capacity in patients with Andersen-Tawil syndrome. Summary Recent studies have expanded our understanding of gating pore current as a disease-causing mechanism in the muscle channelopathies and have allowed new correlations to be drawn between disease genotype and phenotype. PMID:19571750

  4. Self-purification ability of a resurgence stream.

    PubMed

    Vagnetti, Roberta; Miana, Paola; Fabris, Mario; Pavoni, Bruno

    2003-09-01

    The self-purification ability of a resurgence stream has been investigated by taking samples along the course of a channeled tract made up of a first part in beaten soil (3.3 km) and a second in concrete (7.2 km). The study has been conducted by statistically processing pre-existent data, acquired monthly by analyzing waters at the beginning and at the end of the whole canal for 6 years, from 1995 to 2000 (historic data), and by performing specific experiments (recent data) to evaluate differently the self-purification capacity of the beaten soil section and that in concrete. A significant abatement of concentrations has been observed from historic data for ammonium, phosphates, turbidity, heavy metals and bacteria. From the recent data, all these parameters seem to decrease in the beaten soil tract. Whereas significant further decreases in the concrete tract were observed only for ammonium, phosphates and bacteria. For other parameters, e.g. pH, dissolved oxygen, chlorides, fluorides, sodium, and sulfates, a significant increase was observed from the historic data.

  5. Structural Insight into KCNQ (Kv7) Channel Assembly and Channelopathy

    PubMed Central

    Howard, Rebecca J.; Clark, Kimberly A.; Holton, James M.; Minor, Daniel L.

    2010-01-01

    Summary Kv7.x (KCNQ) voltage-gated potassium channels form the cardiac and auditory IKs current and the neuronal M-current. The five Kv7 subtypes have distinct assembly preferences encoded by a C-terminal cytoplasmic assembly domain, the A-domain Tail. Here, we present the high-resolution structure of the Kv7.4 A-domain Tail together with biochemical experiments that show that the domain is a self-assembling, parallel, four-stranded coiled coil. Structural analysis and biochemical studies indicate conservation of the coiled coil in all Kv7 subtypes and that a limited set of interactions encode assembly specificity determinants. Kv7 mutations have prominent roles in arrhythmias, deafness, and epilepsy. The structure together with biochemical data indicate that A-domain Tail arrhythmia mutations cluster on the solvent-accessible surface of the subunit interface at a likely site of action for modulatory proteins. Together, the data provide a framework for understanding Kv7 assembly specificity and the molecular basis of a distinct set of Kv7 channelopathies. PMID:17329207

  6. 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.

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

    PubMed Central

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

    2002-01-01

    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

  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. In Silico Evaluation of the Potential Antiarrhythmic Effect of Epigallocatechin-3-Gallate on Cardiac Channelopathies

    PubMed Central

    Boukhabza, Maroua; El Hilaly, Jaouad; Attiya, Nourdine; El-Haidani, Ahmed; Filali-Zegzouti, Younes; Mazouzi, Driss

    2016-01-01

    Ion channels are transmembrane proteins that allow the passage of ions according to the direction of their electrochemical gradients. Mutations in more than 30 genes encoding ion channels have been associated with an increasingly wide range of inherited cardiac arrhythmias. In this line, ion channels become one of the most important molecular targets for several classes of drugs, including antiarrhythmics. Nevertheless, antiarrhythmic drugs are usually accompanied by some serious side effects. Thus, developing new approaches could offer added values to prevent and treat the episodes of arrhythmia. In this sense, green tea catechins seem to be a promising alternative because of the significant effect of Epigallocatechin-3-Gallate (E3G) on the electrocardiographic wave forms of guinea pig hearts. Thus, the aim of this study was to evaluate the benefits-risks balance of E3G consumption in the setting of ion channel mutations linked with aberrant cardiac excitability phenotypes. Two gain-of-function mutations, Nav1.5-p.R222Q and Nav1.5-p.I141V, which are linked with cardiac hyperexcitability phenotypes were studied. Computer simulations of action potentials (APs) show that 30 μM E3G reduces and suppresses AP abnormalities characteristics of these phenotypes. These results suggest that E3G may have a beneficial effect in the setting of cardiac sodium channelopathies displaying a hyperexcitability phenotype. PMID:27882075

  10. Measuring quality of life impairment in skeletal muscle channelopathies

    PubMed Central

    Sansone, V A; Ricci, C; Montanari, M; Apolone, G; Rose, M; Meola, G

    2012-01-01

    Background and purpose Fatigue and pain have been previously shown to be important determinants for decreasing quality of life (QoL) in one report in patients with non-dystrophic myotonia. The aims of our study were to assess QoL in skeletal muscle channelopathies (SMC) using INQoL (individualized QoL) and SF-36 questionnaires. Methods We administered INQoL and SF-36 to 66 Italian patients with SMC (26: periodic paralysis, 36: myotonia congenita and 4: Andersen-Tawil) and compared the results in 422 patients with myotonic dystrophies (DM1: 382; and DM2: 40). Results (i) INQoL index in SMC is similar to that in DMs (P = 0.79). (ii) Patients with myotonia congenita have the worst perception of QoL. (iii) Myotonia has the most detrimental effect on patients with myotonia congenita, followed by patients with DM2 and then by patients with DM1 and hyperkalemic periodic paralysis. (iv) Pain is a significant complaint in patients with myotonia congenita, hypokalemic periodic paralysis and DM2 but not in DM1. (v) Fatigue has a similar detrimental effect on all patient groups except for patients with hyperkalemic periodic paralysis in whom muscle weakness and myotonia more than fatigue affect QoL perception. (vi) Muscle symptoms considered in INQoL correlate with physical symptoms assessed by SF-36 (R from −0.34 to −0.76). Conclusions QoL perception in patients with SMC is similar to that of patients with DMs, chronic multisystem disabling conditions. Our results provide information to target treatment and health care of these patients. The sensitivity of INQoL to changes in QoL in the SMC needs to be further explored in longitudinal studies. PMID:22607270

  11. 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.

  12. Resurgence of malaria in Bombay (Mumbai) in the 1990s: a historical perspective.

    PubMed

    Kamat, V

    2000-06-01

    Bombay has achieved extraordinary success in controlling its malaria problem for nearly six decades by relying primarily on legislative measures and non-insecticidal methods of mosquito abatement. In 1992, however, malaria reemerged in Bombay with a vengeance. During 1992-1997, the city witnessed a manifold increase in the number of malaria cases diagnosed and treated by the public health system. The large number of malaria patients treated by private practitioners was not recorded by the municipal malaria surveillance system during this period. In 1995, at the peak of the resurgence, public health officials of the Municipal Corporation of Greater Bombay (MCGB) confirmed that 170 persons in the city had died due to malaria. The crisis was unprecedented in Bombay's modern public health history. In response to intense criticism from the media, the city's public health officials attributed the resurgence to the global phenomenon of mosquito-vector resistance to insecticides, and Plasmodium resistance to antimalarial chemoprophylaxis and treatment. Local scientists who investigated the problem offered no support to this explanation. So what might explain the resurgence? What factors led the problem to reach an epidemic level in a matter of two or three years? In addressing the above principal questions, this paper adopts a historical perspective and argues that in the resurgence of malaria in Bombay in the 1990s, there is an element of the 'presence of the past'. In many ways the present public health crisis in Bombay resembles the health scenario that characterized the city at the turn of the 19th century. It is possible to draw parallels between the early public health history of malaria control in Bombay, which was punctuated by events that followed the bubonic plague epidemic of 1896, and the present-day malaria epidemic punctuated by the threat of a plague epidemic in 1994. As such, the paper covers a long period, of almost 100 years. This time-depth is used to

  13. 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…

  14. Teach or No Teach: Is Large System Education Resurging?

    ERIC Educational Resources Information Center

    Sharma, Aditya; Murphy, Marianne C.

    2011-01-01

    Legacy or not, mainframe education is being taught at many U.S. universities. Some computer science programs have always had some large system content but there does appear to be resurgence of mainframe related content in business programs such as Management Information Systems (MIS) and Computer Information Systems (CIS). Many companies such as…

  15. 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…

  16. 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

  17. Estimation of magma depth for resurgent domes: An experimental approach

    NASA Astrophysics Data System (ADS)

    Brothelande, Elodie; Merle, Olivier

    2015-02-01

    Post-collapse resurgence is a phenomenon affecting many calderas. Attributed to a renewed magma rise, the process is still poorly understood and the associated source parameters remain poorly constrained. A set of experiments has been conducted to gain insight into the structural evolution of caldera resurgent domes. A sand-plaster mixture was chosen as an analogue for the brittle pile of volcanic rocks, and silicone putty simulates the ductile behavior of the intruding magma. Resurgence is driven by the vertical uplift of the silicone, with variable shape and depth. Similarity conditions are achieved through eight dimensionless numbers, which are of the same order of magnitude in both nature and experiments. Results show that extension due to doming is, in many cases, accommodated by one axial graben. Opposite master faults of this graben intersect at depth at the junction with the rising viscous silicone. The simplicity of the geometry of the whole analogue system provides equations which allow the estimation of the silicone depth from surface parameters. These equations are then used in some field examples to assess the magma depth beneath natural resurgent domes.

  18. Malaria transmission in Bissau, Guinea-Bissau between 1995 and 2012: malaria resurgence did not negatively affect mortality.

    PubMed

    Ursing, Johan; Rombo, Lars; Rodrigues, Amabelia; Aaby, Peter; Kofoed, Poul-Erik

    2014-01-01

    As Plasmodium falciparum prevalence decreases in many parts of Sub-Saharan Africa, so does immunity resulting in larger at risk populations and increased risk of malaria resurgence. In Bissau, malaria prevalence decreased from ∼50% to 3% between 1995 and 2003. The epidemiological characteristics of P. falciparum malaria within Bandim health and demographic surveillance site (population ∼100,000) between 1995 and 2012 are described. The population was determined by census. 3603 children aged <15 years that were enrolled in clinical trials at the Bandim health centre (1995-2012) were considered incident cases. The mean annual malaria incidence per thousand children in 1995-1997, 1999-2003, 2007, 2011, 2012 were as follows; age <5 years 22→29→4→9→3, age 5-9 years 15→28→4→33→12, age 10-14 years 9→15→1→45→19. There were 4 campaigns (2003-2010) to increase use of insecticide treated bed nets (ITN) amongst children <5 years. An efficacious high-dose chloroquine treatment regime was routinely used until artemisinin based combination therapy (ACT) was introduced in 2008. Long lasting insecticide treated bed nets (LLIN) were distributed in 2011. By 2012 there was 1 net per 2 people and 97% usage. All-cause mortality decreased from post-war peaks in 1999 until 2012 in all age groups and was not negatively affected by malaria resurgence. The cause of decreasing malaria incidence (1995-2007) was probably multifactorial and coincident with the use of an efficacious high-dose chloroquine treatment regime. Decreasing malaria prevalence created a susceptible group of older children in which malaria resurged, highlighting the need to include all age groups in malaria interventions. ACT did not hinder malaria resurgence. Mass distribution of LLINs probably curtailed malaria epidemics. All-cause mortality was not negatively affected by malaria resurgence.

  19. Magmatic recharge during formation and resurgence of the Valles caldera, New Mexico, USA: evidence from quartz compositional zoning and geothermometry

    NASA Astrophysics Data System (ADS)

    Wilcock, Jack

    The Valles caldera complex in north-central New Mexico, USA, represents the type example of resurgent caldera system, characterised by eruption of two voluminous high-silica rhyolite ignimbrites (the Otowi and Tshirege Members of the Bandelier Tuff) at 1.608 +/- 0.010 Ma and 1.256 +/- 0.010 Ma, respectively. Refined dating has shown that resurgence occurred shortly after eruption of the Tshirege, or Upper Bandelier Tuff (UBT). Central resurgence of ~1000 m was accompanied by small-volume eruptions of the Deer Canyon Rhyolite, followed closely by the Redondo Creek Rhyodacite. The Cerro del Medio Rhyolite lava dome complex is a product of ring fracture volcanism following resurgence, erupting at 1.229 +/- 0.017 Ma. A central aim of this study was to find evidence for magmatic recharge during this geologically short (~ 27 ka) time period. We have combined cathodoluminescence (CL) imaging and titanium-in-quartz geothermometry techniques to individual quartz crystals from 1) different stratigraphic horizons of the UBT ignimbrite, 2) samples of the Deer Canyon Rhyolite and 3) the Cerro del Medio Rhyolite lavas. CL imaging reveals that ~80% of the erupted volume UBT ignimbrite contains unzoned quartz crystals (average concentration = 28 +/- 2 ppm Ti), recording relatively isothermal temperatures of 647-696°C. An abrupt occurrence of compositionally zoned quartz crystals) within the mid-to-late erupted UBT ignimbrite units 3-5 reveals evidence for interaction with hotter magma. Corresponding titanium-in-quartz measurements of outer, bright CL rims (71 +/- 9 ppm Ti) reveal temperature increases of ~100°C relative to the start of the UBT eruption. We have discovered an interesting heterogeneity within the Deer Canyon Rhyolite lavas, with strong spatial control on eruption of porphyritic lavas containing complexly zoned quartz crystals onto the western regions of the resurgent dome. Conversely, crystal-poor to aphyric lavas containing small, unzoned quartz crystals are

  20. Cancer as a channelopathy: ion channels and pumps in tumor development and progression.

    PubMed

    Litan, Alisa; Langhans, Sigrid A

    2015-01-01

    Increasing evidence suggests that ion channels and pumps not only regulate membrane potential, ion homeostasis, and electric signaling in excitable cells but also play important roles in cell proliferation, migration, apoptosis and differentiation. Consistent with a role in cell signaling, channel proteins and ion pumps can form macromolecular complexes with growth factors, and cell adhesion and other signaling molecules. And while cancer is still not being cataloged as a channelopathy, as the non-traditional roles of ion pumps and channels are being recognized, it is increasingly being suggested that ion channels and ion pumps contribute to cancer progression. Cancer cell migration requires the regulation of adhesion complexes between migrating cells and surrounding extracellular matrix (ECM) proteins. Cell movement along solid surfaces requires a sequence of cell protrusions and retractions that mainly depend on regulation of the actin cytoskeleton along with contribution of microtubules and molecular motor proteins such as mysoin. This process is triggered and modulated by a combination of environmental signals, which are sensed and integrated by membrane receptors, including integrins and cadherins. Membrane receptors transduce these signals into downstream signaling pathways, often involving the Rho GTPase protein family. These pathways regulate the cytoskeletal rearrangements necessary for proper timing of adhesion, contraction and detachment of cells in order to find their way through extracellular spaces. Migration and adhesion involve continuous modulation of cell motility, shape and volume, in which ion channels and pumps play major roles. Research on cancer cells suggests that certain ion channels may be involved in aberrant tumor growth and channel inhibitors often lead to growth arrest. This review will describe recent research into the role of ion pumps and ion channels in cell migration and adhesion, and how they may contribute to tumor development.

  1. Antecedent causes of a measles resurgence in the Democratic Republic of the Congo

    PubMed Central

    Scobie, Heather Melissa; Ilunga, Benoît Kebela; Mulumba, Audry; Shidi, Calixte; Coulibaly, Tiekoura; Obama, Ricardo; Tamfum, Jean-Jacques Muyembe; Simbu, Elisabeth Pukuta; Smit, Sheilagh Brigitte; Masresha, Balcha; Perry, Robert Tyrrell; Alleman, Mary Margaret; Kretsinger, Katrina; Goodson, James

    2015-01-01

    Introduction Despite accelerated measles control efforts, a massive measles resurgence occurred in the Democratic Republic of the Congo (DRC) starting in mid-2010, prompting an investigation into likely causes. Methods We conducted a descriptive epidemiological analysis using measles immunization and surveillance data to understand the causes of the measles resurgence and to develop recommendations for elimination efforts in DRC. Results During 2004-2012, performance indicator targets for case-based surveillance and routine measles vaccination were not met. Estimated coverage with the routine first dose of measles-containing vaccine (MCV1) increased from 57% to 73%. Phased supplementary immunization activities (SIAs) were conducted starting in 2002, in some cases with sub-optimal coverage (≤95%). In 2010, SIAs in five of 11 provinces were not implemented as planned, resulting in a prolonged interval between SIAs, and a missed birth cohort in one province. During July 1, 2010-December 30, 2012, high measles attack rates (>100 cases per 100,000 population) occurred in provinces that had estimated MCV1 coverage lower than the national estimate and did not implement planned 2010 SIAs. The majority of confirmed case-patients were aged <10 years (87%) and unvaccinated or with unknown vaccination status (75%). Surveillance detected two genotype B3 and one genotype B2 measles virus strains that were previously identified in the region. Conclusion The resurgence was likely caused by an accumulation of unvaccinated, measles-susceptible children due to low MCV1 coverage and suboptimal SIA implementation. To achieve the regional goal of measles elimination by 2020, efforts are needed in DRC to improve case-based surveillance and increase two-dose measles vaccination coverage through routine services and SIAs. PMID:26401224

  2. Resurgence of derived stimulus relations: replication and extensions.

    PubMed

    Doughty, Adam H; Kastner, Rebecca M; Bismark, Bryan D

    2011-01-01

    Resurgence typically refers to the recovery of a previously reinforced response when a more recently reinforced response is extinguished. Under conditions of punishment, Wilson and Hayes (1996) observed the recovery of derived stimulus relations that never had been correlated with differential consequences. The present study systematically replicated the findings of Wilson and Hayes by observing the recovery of derived stimulus relations under extinction conditions and with an additional equivalence class. College students received arbitrary-matching-to-sample training in Phase 1 that resulted in four 4-member stimulus-equivalence classes. These derived relations were not correlated with differential consequences. In Phase 2, with the same stimuli, the students received training that resulted in four different 4-member stimulus-equivalence classes. After the emergence and reinforcement of the latter derived relations, their extinction generated the recurrence of the derived relations from Phase 1. The implications of these findings for conceptualizing resurgence are discussed.

  3. Resurgent Toba - field, chronologic, and model constraints on time scales and mechanisms of resurgence at large calderas

    NASA Astrophysics Data System (ADS)

    De Silva, Shanaka; Mucek, Adonara; Gregg, Patricia; Pratomo, Indyo

    2015-06-01

    New data reveal details of the post-caldera history at the Earth’s youngest resurgent supervolcano, Toba caldera in Sumatra. Resurgence after the caldera-forming ~74 ka Youngest Toba Tuff eruption uplifted the caldera floor as a resurgent dome, Samosir Island, capped with 100m of lake sediments. 14C age data from the uppermost datable sediments reveal that Samosir Island was submerged beneath lake level (~900m a.s.l) ~33.7 ky. Since then, Samosir experienced 700m of uplift as a tilted block dipping to the west. Using 14C ages and elevations of sediment along a transect of Samosir reveal that minimum uplift rates were ~4.9 cm/yr from ~33.7 to 22.5 ka, but diminished to ~0.7 cm/yr after 22.5ka. Thermo-mechanical models informed by these rates reveal that detumescence does not produce the uplift nor the uplift rates estimated for Samosir. However, models calculating the effect of volume change of the magma reservoir within a temperature-dependent viscoelastic host rock reveal that a single pulse of ~475 km3 of magma produces a better fit to the uplift data than a constant flux. Reproducing the uplift rates require more sophisticated models. Motivation for resurgent uplift of the caldera floor is rebound of remnant magma as the system re-established magmastatic and isostatic equilibrium after the caldera collapse. Previous assertions that the caldera floor was apparently at 400m a.s.l or lower requires that uplift must have initiated between sometime between 33.7 ka and 74 ka at a minimum average uplift rate of ~1.1 cm/ year. The change in uplift rate from pre-33.7 ka to immediately post-33.7 ka suggests a role for deep recharge augmenting rebound. Average minimum rates of resurgent uplift at Toba are at least an order of magnitude slower than net rates of "restlessness" at currently active calderas. This connotes a distinction between resurgence and “restlessness” controlled by different processes, scales of process, and controlling variables.

  4. Response elimination, reinforcement rate and resurgence of operant behavior.

    PubMed

    Cançado, Carlos R X; Lattal, Kennon A

    2013-11-01

    The effects of reinforcement rate of alternative responding on resurgence were studied in six experiments with pigeons. In Experiment 1A, key pecking was maintained on a multiple variable-interval (VI) VI schedule in the Training phase. In the Response-Elimination phase, a variable differential-reinforcement-of-other-behavior (DRO) schedule was in effect in each component. Reinforcement rates were equal and then, higher in one (rich) component, and lower in the other (lean), than in the Training phase. More resurgence occurred in the lean component, but this could have resulted from response-rate differences between components in the Training-phase. Experiment 1B was a replication of Experiment 1A, but with experimentally-naïve pigeons. Response-Elimination phase reinforcement rates were manipulated systematically in subsequent experiments: In Experiment 2, reinforcement rate was equal, in one component, and lower or higher in the other, than in the Training phase. In Experiment 3, reinforcers were discontinued before differential reinforcement rates were effected. In Experiment 4, reinforcement rates first were differential and, then, equal to those in the Training phase. In Experiments 5 and 6, differential reinforcement rates were arranged by using fixed-DROs and VIs for pecking a different key, respectively. Even though resurgence was not obtained with every pigeon, at least some small-magnitude resurgence occurred in each experiment and was not related systematically to reinforcement rates of alternative responding. Schedule differences, response topography, order of conditions and the length of each phase were not sufficient to account for these results.

  5. A review of dengue fever: a resurging tropical disease.

    PubMed

    Mangold, Karen A; Reynolds, Sally L

    2013-05-01

    Dengue is a resurging mosquito-borne disease that is often contracted in U.S. travelers to Latin America, Asia, and the Caribbean. The clinical symptoms range from a simple febrile illness to hemorrhagic fever or shock. The clinical course has a wide range of outcomes, and adequate supportive care can reduce mortality rates dramatically. Repeated exposures to the virus can lead to a more complicated clinical course.

  6. 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

  7. A resurgence analysis for cubic and quartic anharmonic potentials

    NASA Astrophysics Data System (ADS)

    Gahramanov, Ilmar; Tezgin, Kemal

    2017-02-01

    In this work, we explicitly show resurgence relations between perturbative and one instanton sectors of the resonance energy levels for cubic and quartic anharmonic potentials in one-dimensional quantum mechanics. Both systems satisfy the Dunne-Ünsal relation and hence we are able to derive one-instanton nonperturbative contributions with the fluctuation terms to the energy merely from the perturbative data. We confirm our results with previous results obtained in the literature.

  8. The effect of mindfulness on extinction and behavioral resurgence.

    PubMed

    McHugh, Louise; Procter, Jonathan; Herzog, Michaela; Schock, Anne-Kathrin; Reed, Phil

    2012-12-01

    In the present experiments, we investigated the effects of mindfulness on behavioral extinction and resurgence. Participants received instrumental training; either they received FI training (Experiment 1), or they were trained to emit high rates and low rates of response via exposure to a multiple VR yoked-VI schedule prior to exposure to a multiple FI FI schedule in order to alter their rates of responding learned during Experiment 2. Participants were then exposed to either a focused- (mindfulness) or an unfocused-attention induction task. All participants were finally exposed to an extinction schedule in order to determine whether a mindfulness induction task presented immediately prior to extinction training affected extinction (Experiment 1) and behavioral resurgence (Experiment 2). During the extinction phase, the rates of responding were higher in the control group than in the mindfulness group, indicating that the mindfulness group was more sensitive to the contingencies and, thus, their prior performance extinguished more readily (Experiment 1). Moreover, rates of response in the extinction components less precisely reflected previous training in the mindfulness group, suggesting less resurgence of past behaviors after the mindfulness induction (Experiment 2).

  9. Neonicotinoid-induced resurgence of rice leaffolder, Cnaphalocrocis medinalis (Guénee).

    PubMed

    Chintalapati, Padmavathi; Katti, Gururaj; Puskur, Raghuveer Rao; Nagella Venkata, Krishnaiah

    2016-01-01

    Among the neonicotinoids, imidacloprid and thiamethoxam have been frequently used in planthopper endemic areas. Wherever leaffolder incidence occurs along with planthoppers in rice fields, use of neonicotinoids has resulted in increase in leaffolder population. The present study was carried out to verify and confirm the resurgence, as well as to identify factors contributing to resurgence. In imidacloprid- and thiamethoxam-applied plots, a 17.5-217.5% increase in leaffolder population over the untreated control was observed. Neonicotinoids showed moderate toxicity to eggs with <50% hatching, and less toxicity to first instars with >60% survival, while 37-60% of larvae reached adult stage. The larval duration was also reduced. Fecundity was stimulated, with a 6.2-37.21% increase over the untreated control. A significant positive correlation was observed between larval population and total soluble sugars in thiamethoxam treatment (r = 0.9984, P ≤ 0.01). Stimulated fecundity on neonicotinoid-sprayed plants, coupled with reduced larval duration and low egg toxicity, could be the major factors contributing to the upsurge of leaffolder. This study aids in cautioning farmers to be more vigilant while using imidacloprid and thiamethoxam, particularly in rice fields where leaffolder exists alongside planthoppers. © 2015 Society of Chemical Industry.

  10. Investigating the pertussis resurgence in England and Wales, and options for future control.

    PubMed

    Choi, Yoon Hong; Campbell, Helen; Amirthalingam, Gayatri; van Hoek, Albert Jan; Miller, Elizabeth

    2016-09-01

    In 2012 England and Wales experienced a resurgence of pertussis and an increase in infant deaths. This occurred 8 years after acellular pertussis (aP) vaccine replaced whole cell (wP) primary vaccine despite continued high coverage for the primary series and pre-school aP booster. We developed a mathematical model to describe pertussis transmission dynamics in England and Wales since the 1950s and used it to investigate the cause of the resurgence and the potential impact of additional vaccination strategies. An age-structured, compartmental, deterministic model of the pertussis transmission dynamics was fitted to 60 continuous years of age-stratified pertussis notification data in England and Wales. The model incorporated vaccine-induced and natural immunity and differentiated between vaccine-induced protection against clinical disease and infection. The degree of protection of wP vaccine against infection was estimated to be higher than that of aP vaccine. Furthermore, the duration of protection for natural and wP-induced immunity was likely to be at least 15 years, but for aP vaccine it could be as low as 5 years. Model results indicated that the likely cause of the resurgence was the replacement of wP by less efficacious aP vaccine and that an elevated level of pertussis would continue. The collapse in wP vaccine coverage in the 1970s and resultant outbreaks in the late 1970s and early 1980s could not explain the resurgence. Addition of an adolescent or toddler booster was predicted to have little impact on the disease in infants. Our findings support the recent recommendation by the World Health Organisation that countries currently using wP vaccine for primary immunisation should not change to aP vaccine unless additional strategies to control infant disease such as maternal immunisation can be assured. Improved pertussis vaccines that provide better protection against infection are needed.

  11. 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

  12. Resurgence of cholera in Hong Kong.

    PubMed Central

    Lee, S. H.; Lai, S. T.; Lai, J. Y.; Leung, N. K.

    1996-01-01

    Cholera is one of the three diseases subject to the International Health Regulations. After a period of over 30 years, the seventh pandemic of cholera, which started in South East Asia in 1961, still shows no sign of a decline. On the contrary, it has increased its severity and invaded many other countries in Africa and Latin America. In the last two years, there has been a recrudescence of the disease in South East Asia and Western Pacific Regions. The discovery of a new strain of Vibrio cholerae 0139 in these regions is causing concern in view of its potential to cause major epidemics and higher mortality. Hong Kong had two intensive outbreaks of cholera in the last two years. The cause of these outbreaks was not clear, but adverse environmental conditions and increasing pollution of coastal waters have been implicated. The spread of cholera knows no geographical boundaries. There is a need for intensified efforts among health authorities in the affected areas to prevent the international spread of the disease. PMID:8760949

  13. 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.

  14. Resurgence of cholera in Hong Kong.

    PubMed

    Lee, S H; Lai, S T; Lai, J Y; Leung, N K

    1996-08-01

    Cholera is one of the three diseases subject to the International Health Regulations. After a period of over 30 years, the seventh pandemic of cholera, which started in South East Asia in 1961, still shows no sign of a decline. On the contrary, it has increased its severity and invaded many other countries in Africa and Latin America. In the last two years, there has been a recrudescence of the disease in South East Asia and Western Pacific Regions. The discovery of a new strain of Vibrio cholerae 0139 in these regions is causing concern in view of its potential to cause major epidemics and higher mortality. Hong Kong had two intensive outbreaks of cholera in the last two years. The cause of these outbreaks was not clear, but adverse environmental conditions and increasing pollution of coastal waters have been implicated. The spread of cholera knows no geographical boundaries. There is a need for intensified efforts among health authorities in the affected areas to prevent the international spread of the disease.

  15. 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.

  16. 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.

  17. 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.

  18. Some aspects of epidemiology of resurgent malaria in Turkey.

    PubMed

    Ramsdale, C D; Haas, E

    1978-01-01

    The resurgence of autochthonous Plasmodium vivax malaria in Turkey is a matter of considerable concern. Anopheles sacharovi is the important vector but other species, notably A. superpictus, may play a role in transmission. The epidemiology is discussed in terms of factors related to the mosquito, factors related to the human host and human ecology as it affects dispersal of the parasite. Although the development of insecticide resistance is grave, the present situation is mainly attributable to operational deficiencies stemming from administrative and financial constraints.

  19. Interaction of Kv3 potassium channels and resurgent sodium current influences the rate of spontaneous firing of Purkinje neurons.

    PubMed

    Akemann, Walther; Knöpfel, Thomas

    2006-04-26

    Purkinje neurons spontaneously generate action potentials in the absence of synaptic drive and thereby exert a tonic, yet plastic, input to their target cells in the deep cerebellar nuclei. Purkinje neurons express two ionic currents with biophysical properties that are specialized for high-frequency firing: resurgent sodium currents and potassium currents mediated by Kv3.3. How these ionic currents determine the intrinsic activity of Purkinje neurons has only partially been understood. Purkinje neurons from mutant mice lacking Kv3.3 have a reduced rate of spontaneous firing. Dynamic-clamp recordings demonstrated that normal firing rates are rescued by inserting artificial Kv3 currents into Kv3.3 knock-out Purkinje neurons. Numerical simulations indicated that Kv3.3 increases the spontaneous firing rate via cooperation with resurgent sodium currents. We conclude that the rate of spontaneous action potential firing of Purkinje neurons is controlled by the interaction of Kv3.3 potassium currents and resurgent sodium currents.

  20. 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.; 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.

  1. 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…

  2. A Preliminary Investigation on Improving Functional Communication Training by Mitigating Resurgence of Destructive Behavior

    ERIC Educational Resources Information Center

    Fuhrman, Ashley M.; Fisher, Wayne W.; Greer, Brian D.

    2016-01-01

    Despite the effectiveness and widespread use of functional communication training (FCT), resurgence of destructive behavior can occur if the functional communication response (FCR) contacts a challenge, such as lapses in treatment integrity. We evaluated a method to mitigate resurgence by conducting FCT using a multiple schedule of reinforcement…

  3. A Preliminary Investigation on Improving Functional Communication Training by Mitigating Resurgence of Destructive Behavior

    ERIC Educational Resources Information Center

    Fuhrman, Ashley M.; Fisher, Wayne W.; Greer, Brian D.

    2016-01-01

    Despite the effectiveness and widespread use of functional communication training (FCT), resurgence of destructive behavior can occur if the functional communication response (FCR) contacts a challenge, such as lapses in treatment integrity. We evaluated a method to mitigate resurgence by conducting FCT using a multiple schedule of reinforcement…

  4. 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…

  5. Current Indications for Implantable Cardioverter Defibrillators in Non-Ischemic Cardiomyopathies and Channelopathies.

    PubMed

    González-Torrecilla, Esteban; Arenal, Angel; Atienza, Felipe; Datino, Tomás; Bravo, Loreto; Ruiz, Pablo; Ávila, Pablo; Fernández-Avilés, Francisco

    2015-01-01

    Current indications for implantable cardioverter defibrillators (ICDs) in patients with channelopathies and cardiomyopathies of non-ischemic origin are mainly based on non-randomized evidence. In patients with nonischemic dilated cardiomyopathy (NIDCM), there is a tendency towards a beneficial effect on total mortality of ICD therapy in patients with significant left ventricular (LV) dysfunction. Although an important reduction in sudden cardiac death (SCD) seems to be clearly demonstrated in these patients, a net beneficial effect on total mortality is unclear mostly in cases with good functional status. Risk stratification has been changing over the last two decades in patients with hypertrophic cardiomyopathy (HCM). Its risk profile has been delineated in parallel with the beneficial effect of ICD in high risk patients. Observational results based on "appropriate" ICD interventions do support its usefulness both in primary and secondary SCD prevention in these patients. Novel risk models quantify the rate of sudden cardiac death in these patients on individual basis. Less clear risk stratification is available for cases of arrhythmogenic right ventricular cardiomyopathy (ARVC) and in other uncommon familiar cardiomyopathies. Main features of risk stratification vary among the different channelopathies (long QT syndrome -LQTS-, Brugada syndrome, etc) with great debate on the management of asymptomatic patients. For most familiar cardiomyopathies, ICD therapy is the only accepted strategy in the prevention of SCD. So far, genetic testing has a limited role in risk evaluation and management of the individual patient. This review aims to summarize these criticisms and to refine the current indications of ICD implantation in patients with cardiomyopathies and major channelopathies.

  6. Strategies for suppression, containment, and eradication of resurgent tuberculosis.

    PubMed

    Young, R C; Rachal, R E; Bailey, S B; Tate, H L; Nelson-Knuckles, B

    1997-11-01

    This review provides strategies for the suppression, containment, and eventual eradication of resurgent tuberculosis. Some ethnic minority communities are at greatest risk because of the prevalence of human immunodeficiency virus/acquired immunodeficiency syndrome, poverty and malnutrition, congregate living situations, aberrant lifestyles, illegal immigration, and underemployment among these populations. Proposed strategies include the education of the population at risk as well as health care providers to permit the optimization of preventive, diagnostic, and therapeutic technologies. Also necessary is the development of effective, safe, newer medications to enhance patient compliance and decrease drug resistance. Strategic planning embraces national socioeconomic policy to permit adequate resources to combat poverty and malnutrition, to rebuild the infrastructure of the public health system, and to improve access to health care among rural and urban dwellers. It is concluded that these efforts must continue to ensure the eradication of tuberculosis.

  7. [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. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  8. 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

  9. Preparedness for malaria resurgence in China: case study on imported cases in 2000-2012.

    PubMed

    Feng, Jun; Xia, Zhi-Gui; Vong, Sirenda; Yang, Wei-Zhong; Zhou, Shui-Sen; Xiao, Ning

    2014-01-01

    Malaria is the most important parasitic protozoan infection that has caused serious threats to human health globally. China has had success in reducing the morbidity and mortality of malaria to the lowest level through sustained and large-scale interventions. Although the total number of malaria cases declined gradually, the burden of the imported malaria cases mainly from Southeast Asian and African countries has increased substantially since 2000, posing a severe threat to public health in China. This review explores and analyses the epidemiological characteristics of the imported malaria based on data from 2000 to 2012, in order to provide theoretical bases and insights into effective prevention, avoid the resurgence of malaria in malaria-susceptible areas and develop appropriate strategies to protect people's health in China. This review also intends to offer the useful information of innovative approaches and tools that are required for malaria elimination in various settings.

  10. Pathophysiology of movement disorders due to gravity transitions: the channelopathy linkage in human balance and locomotion.

    PubMed

    Rizzo-Sierra, Carlos V; Leon-Sarmiento, Fidias E

    2011-07-01

    Despite theoretical and experimental efforts to understand the space adaptation syndrome (SAS), which is responsible for spatial disorientation that severely affects physical and cognitive performance in astronauts, most of its pathophysiology is still unknown. As a consequence, countermeasures for SAS are not completely effective. Accordingly, in addition to the sensory-motor conflict theories, we propose that microgravity would affect the potassium channels of inner ear hair cells that would result in a temporal channelopathy as the most likely molecular origin for SAS, as well as being responsible for perpetuating movement disorders in gravity transition environments including those to be experienced by people visiting or living on the earth, moon, mars and beyond.

  11. Effects of differential rates of alternative reinforcement on resurgence of human behavior.

    PubMed

    Smith, Brooke M; Smith, Gregory S; Shahan, Timothy A; Madden, Gregory J; Twohig, Michael P

    2017-01-01

    Despite the success of exposure-based psychotherapies in anxiety treatment, relapse remains problematic. Resurgence, the return of previously eliminated behavior following the elimination of an alternative source of reinforcement, is a promising model of operant relapse. Nonhuman resurgence research has shown that higher rates of alternative reinforcement result in faster, more comprehensive suppression of target behavior, but also in greater resurgence when alternative reinforcement is eliminated. This study investigated rich and lean rates of alternative reinforcement on response suppression and resurgence in typically developing humans. In Phase 1, three groups (Rich, n = 18; Lean, n = 18; Control, n = 10) acquired the target response. In Phase 2, target responding was extinguished and alternative reinforcement delivered on RI 1 s, RI 3 s, and extinction schedules, respectively. Resurgence was assessed during Phase 3 under extinction conditions for all groups. Target responding was suppressed most thoroughly in Rich and partially in Lean. Target responding resurged in the Rich and Lean groups, but not in the Control group. Between groups, resurgence was more pronounced in the Rich group than the Lean and Control groups. Clinical implications of these findings, including care on the part of clinicians when identifying alternative sources of reinforcement, are discussed.

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

    PubMed Central

    Schepers, Scott T.; Bouton, Mark E.

    2015-01-01

    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 to 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

  13. Sea-anemone toxin ATX-II elicits A-fiber-dependent pain and enhances resurgent and persistent sodium currents in large sensory neurons

    PubMed Central

    2012-01-01

    Background Gain-of-function mutations of the nociceptive voltage-gated sodium channel Nav1.7 lead to inherited pain syndromes, such as paroxysmal extreme pain disorder (PEPD). One characteristic of these mutations is slowed fast-inactivation kinetics, which may give rise to resurgent sodium currents. It is long known that toxins from Anemonia sulcata, such as ATX-II, slow fast inactivation and skin contact for example during diving leads to various symptoms such as pain and itch. Here, we investigated if ATX-II induces resurgent currents in sensory neurons of the dorsal root ganglion (DRGs) and how this may translate into human sensations. Results In large A-fiber related DRGs ATX-II (5 nM) enhances persistent and resurgent sodium currents, but failed to do so in small C-fiber linked DRGs when investigated using the whole-cell patch-clamp technique. Resurgent currents are thought to depend on the presence of the sodium channel β4-subunit. Using RT-qPCR experiments, we show that small DRGs express significantly less β4 mRNA than large sensory neurons. With the β4-C-terminus peptide in the pipette solution, it was possible to evoke resurgent currents in small DRGs and in Nav1.7 or Nav1.6 expressing HEK293/N1E115 cells, which were enhanced by the presence of extracellular ATX-II. When injected into the skin of healthy volunteers, ATX-II induces painful and itch-like sensations which were abolished by mechanical nerve block. Increase in superficial blood flow of the skin, measured by Laser doppler imaging is limited to the injection site, so no axon reflex erythema as a correlate for C-fiber activation was detected. Conclusion ATX-II enhances persistent and resurgent sodium currents in large diameter DRGs, whereas small DRGs depend on the addition of β4-peptide to the pipette recording solution for ATX-II to affect resurgent currents. Mechanical A-fiber blockade abolishes all ATX-II effects in human skin (e.g. painful and itch-like paraesthesias), suggesting that

  14. Two patterns of ion channelopathy in the myocardium: perspectives for development of anti-arrhythmic agents.

    PubMed

    Dai, De-Zai

    2005-03-01

    Cardiac arrhythmia remains a significant problem, due to the high morbidity and mortality associated with cardiovascular diseases with prominent cardiac remodeling. There is still a lack of effective drugs with which to combat this life-threatening disorder. The abnormal electrophysiological properties of the heart can be explained in terms of ion channels and channelopathy and, in recent years, advances have been made in understanding these properties. There are two patterns of ion channelopathies in the diseased heart: Single insufficiency disorder, which is attributed to mutations in genes, and a multiple derangement of channels. Malignant arrhythmias in a diseased heart usually occur when ventricular hypertrophy is evident, and when they are associated with abnormal repolarization. Abnormalities in the ryanodine receptor-calcium release channel complex (RyR)2, FK-506 binding protein (FKBP 12.6), cardiac sarcoplasmic reticulum calcium ATPase (SERCA2a) and phospholamban (PLB) are involved in the initiation of cardiac arrhythmias, and can be identified as targets for therapeutic interventions.

  15. A preliminary investigation on improving functional communication training by mitigating resurgence of destructive behavior.

    PubMed

    Fuhrman, Ashley M; Fisher, Wayne W; Greer, Brian D

    2016-12-01

    Despite the effectiveness and widespread use of functional communication training (FCT), resurgence of destructive behavior can occur if the functional communication response (FCR) contacts a challenge, such as lapses in treatment integrity. We evaluated a method to mitigate resurgence by conducting FCT using a multiple schedule of reinforcement prior to extinction. After functional analyses of 2 boys' destructive behavior and treatment with FCT (Study 1), we compared levels of resurgence during an extinction challenge either after a typical FCT sequence or after exposure to schedule thinning in the context of a multiple-schedule arrangement (Study 2). Results for both participants suggested that schedule thinning using discriminative stimuli in a multiple schedule mitigated the resurgence of destructive behavior.

  16. 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.

  17. Super Bugs, Resurgent and Emerging Diseases, and Pandemics: A National Security Perspective

    DTIC Science & Technology

    2008-01-01

    1 - SUPERBUGS , RESURGENT AND EMERGING DISEASES, AND PANDEMICS: A NATIONAL SECURITY PERSPECTIVE By Frances T. Pilch and 2nd Lt Kenneth...in reality, ― superbugs ‖ (those bacteria that have developed immunity to a wide number of antibiotics), emergent and resurgent diseases, and pandemics...release; distribution is unlimited. While not often considered, ― superbugs ‖ may pose a greater threat to U.S. national security than terrorists or WMDs

  18. Magmatic resurgence in Long Valley Caldera, California: possible cause of the 1980 Mammoth Lakes earthquakes

    SciTech Connect

    Savage, J.C.; Clark, M.M.

    1982-08-06

    Changes in elevation between 1975 and October 1980 along a leveling line across the Long Valley caldera indicate a broad (half-width, 15 kilometers) uplift (maximum, 0.25 meter) centered on the old resurgent dome. This uplift is consistent with reinflation of a magma reservoir at a depth of about 10 kilometers. Stresses generated by this magmatic resurgence may have caused the sequence of four magnitude 6 earthquakes near Mammoth Lakes in May 1980.

  19. Magmatic resurgence in Long Valley caldera, California: Possible cause of the 1980 Mammoth Lakes earthquakes

    USGS Publications Warehouse

    Savage, J.C.; Clark, M.M.

    1982-01-01

    Changes in elevation between 1975 and October 1980 along a leveling line across the Long Valley caldera indicate a broad (half-width, 15 kilometers) uplift (maximum, 0.25 meter) centered on the old resurgent dome. This uplift is consistent with reinflation of a magma reservoir at a depth of about 10 kilometers. Stresses generated by this magmatic resurgence may have caused the sequence of four magnitude 6 earthquakes near Mammoth Lakes in May 1980. Copyright ?? 1982 AAAS.

  20. A New Kv1.2 Channelopathy Underlying Cerebellar Ataxia*

    PubMed Central

    Xie, Gang; Harrison, John; Clapcote, Steven J.; Huang, Yun; Zhang, Jin-Yi; Wang, Lu-Yang; Roder, John C.

    2010-01-01

    A forward genetic screen of mice treated with the mutagen ENU identified a mutant mouse with chronic motor incoordination. This mutant, named Pingu (Pgu), carries a missense mutation, an I402T substitution in the S6 segment of the voltage-gated potassium channel Kcna2. The gene Kcna2 encodes the voltage-gated potassium channel α-subunit Kv1.2, which is abundantly expressed in the large axon terminals of basket cells that make powerful axo-somatic synapses onto Purkinje cells. Patch clamp recordings from cerebellar slices revealed an increased frequency and amplitude of spontaneous GABAergic inhibitory postsynaptic currents and reduced action potential firing frequency in Purkinje cells, suggesting that an increase in GABA release from basket cells is involved in the motor incoordination in Pgu mice. In line with immunochemical analyses showing a significant reduction in the expression of Kv1 channels in the basket cell terminals of Pgu mice, expression of homomeric and heteromeric channels containing the Kv1.2(I402T) α-subunit in cultured CHO cells revealed subtle changes in biophysical properties but a dramatic decrease in the amount of functional Kv1 channels. Pharmacological treatment with acetazolamide or transgenic complementation with wild-type Kcna2 cDNA partially rescued the motor incoordination in Pgu mice. These results suggest that independent of known mutations in Kcna1 encoding Kv1.1, Kcna2 mutations may be important molecular correlates underlying human cerebellar ataxic disease. PMID:20696761

  1. A new Kv1.2 channelopathy underlying cerebellar ataxia.

    PubMed

    Xie, Gang; Harrison, John; Clapcote, Steven J; Huang, Yun; Zhang, Jin-Yi; Wang, Lu-Yang; Roder, John C

    2010-10-15

    A forward genetic screen of mice treated with the mutagen ENU identified a mutant mouse with chronic motor incoordination. This mutant, named Pingu (Pgu), carries a missense mutation, an I402T substitution in the S6 segment of the voltage-gated potassium channel Kcna2. The gene Kcna2 encodes the voltage-gated potassium channel α-subunit Kv1.2, which is abundantly expressed in the large axon terminals of basket cells that make powerful axo-somatic synapses onto Purkinje cells. Patch clamp recordings from cerebellar slices revealed an increased frequency and amplitude of spontaneous GABAergic inhibitory postsynaptic currents and reduced action potential firing frequency in Purkinje cells, suggesting that an increase in GABA release from basket cells is involved in the motor incoordination in Pgu mice. In line with immunochemical analyses showing a significant reduction in the expression of Kv1 channels in the basket cell terminals of Pgu mice, expression of homomeric and heteromeric channels containing the Kv1.2(I402T) α-subunit in cultured CHO cells revealed subtle changes in biophysical properties but a dramatic decrease in the amount of functional Kv1 channels. Pharmacological treatment with acetazolamide or transgenic complementation with wild-type Kcna2 cDNA partially rescued the motor incoordination in Pgu mice. These results suggest that independent of known mutations in Kcna1 encoding Kv1.1, Kcna2 mutations may be important molecular correlates underlying human cerebellar ataxic disease.

  2. Diagnostics and Therapy of Muscle Channelopathies – Guidelines of the Ulm Muscle Centre

    PubMed Central

    Lehmann-Horn, F; Jurkat-Rott, K; Rüdel, R

    2008-01-01

    Summary This article is dedicated to our teacher, Prof. Erich Kuhn, Heidelberg, on the occasion of his 88th birthday on 23th November 2008. In contrast to muscular dystrophies, the muscle channelopathies, a group of diseases characterised by impaired muscle excitation or excitation-contraction coupling, can fairly well be treated with a whole series of pharmacological drugs. However, for a proper treatment proper diagnostics are essential. This article lists state-of-the-art diagnostics and therapies for the two types of myotonic dystrophies, for recessive and dominant myotonia congenita, for the sodium channel myotonias, for the primary dyskalemic periodic paralyses, for central core disease and for malignant hyperthermia susceptibility in detail. In addition, for each disorder a short summary of aetiology, symptomatology, and pathogenesis is provided. PMID:19472919

  3. 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

  4. 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

    2016-05-06

    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.

  5. 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.

  6. Tuberculosis in New Zealand, 1992–2001: a resurgence

    PubMed Central

    Howie, S; Voss, L; Baker, M; Calder, L; Grimwood, K; Byrnes, C

    2005-01-01

    Objective: To describe the recent epidemiology and clinical features of paediatric tuberculosis (TB) in New Zealand (NZ). Methods: A retrospective review was conducted of clinical, laboratory, and radiology records of children <16 years old diagnosed with TB between January 1992 and June 2001 in nine NZ health districts. Results: A total of 274 patients <16 years old were identified; the average annual TB rate was 4.8 per 100 000. Rates rose over time reaching a peak of 10.1 in 1999. Rates were highest in under-5 year olds, at 6.2 per 100 000, and varied by ethnicity: African 575.2, Pacific Island 15.2, Maori 6.4, Asian 5.6, and European 0.6. Seventy two cases (26%) were foreign born. Thirty six per cent of cases were not detected until they presented with symptoms and of these 44% had no known TB contact. Most cases were identified by contact tracing (48%) or immigrant screening (11%); 43% were part of outbreaks. Miliary TB or meningitis occurred in 8% of patients, two of whom died. Drug resistance was found in 7% of culture positive cases and no HIV co-infection was found. Conclusions: A resurgence of TB occurred among children in NZ between 1992 and 2001 predominantly involving non-European and immigrant groups. Despite established contact tracing and immigrant screening programmes, many cases were part of outbreaks, remained unidentified until symptoms arose, or had no known TB contact. These findings point to an unrecognised burden of adult disease, ongoing community transmission, and missed opportunities for prevention. Further study is required to confirm these hypotheses. PMID:16243871

  7. Cardiac channelopathies associated with infantile fatal ventricular arrhythmias: from the cradle to the bench.

    PubMed

    Kato, Koichi; Makiyama, Takeru; Wu, Jie; Ding, Wei-Guang; Kimura, Hiromi; Naiki, Nobu; Ohno, Seiko; Itoh, Hideki; Nakanishi, Toshio; Matsuura, Hiroshi; Horie, Minoru

    2014-01-01

    Fatal ventricular arrhythmias in the early period of life have been associated with cardiac channelopathies for decades, and postmortem analyses in SIDS victims have provided evidence of this association. However, the prevalence and functional properties of cardiac ion channel mutations in infantile fatal arrhythmia cases are not clear. Seven infants with potentially lethal arrhythmias at age < 1 year (5 males, age of onset 44.1 ± 72.1 days) were genetically analyzed for KCNQ1, KCNH2, KCNE1-5, KCNJ2, SCN5A, GJA5, and CALM1 by using denaturing high-performance liquid chromatography and direct sequencing. Whole-cell currents of wildtype and mutant channels were recorded and analyzed in Chinese hamster ovary cells transfected with SCN5A and KCNH2 cDNA. In 5 of 7 patients, we identified 4 mutations (p.N1774D, p.T290fsX53, p.F1486del and p.N406K) in SCN5A, and 1 mutation (p.G628D) in KCNH2. N1774D, F1486del, and N406K in SCN5A displayed tetrodotoxin-sensitive persistent late Na(+) currents. By contrast, SCN5A-T290fsX53 was nonfunctional. KCNH2-G628D exhibited loss of channel function. Genetic screening of 7 patients was used to demonstrate the high prevalence of cardiac channelopathies. Functional assays revealed both gain and loss of channel function in SCN5A mutations, as well as loss of function associated with the KCNH2 mutation. © 2014 Wiley Periodicals, Inc.

  8. 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

  9. 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.

  10. HCN channelopathies: pathophysiology in genetic epilepsy and therapeutic implications.

    PubMed

    Reid, Christopher A; Phillips, A Marie; Petrou, Steven

    2012-01-01

    Hyperpolarization-activated cyclic nucleotide-gated channels (HCN) can act as pacemakers in the brain making them strong candidates for driving aberrant hypersynchronous network activity seen in epilepsy. Transcriptional changes in HCN channels occur in several animal models of epilepsy. However, only recently have genetic studies demonstrated sequence variation in HCN1 and HCN2 genes associated with human epilepsy. These include a triple proline deletion in HCN2 that increases channel function and occurs more often in patients with febrile seizure syndromes. Other HCNx gene variants have been described in idiopathic generalized epilepsy although the functional consequence of these remains unclear. In this review we explore potential cellular and network mechanisms involving HCN channels in the genetic epilepsies. We suggest how new genetic sequencing technology, medium-throughput functional assays and the ability to develop syndrome-specific animal models will provide a more comprehensive understanding of how I(h) contributes to pathogenic mechanisms underlying human genetic epilepsy. We also discuss what is known about the pharmacological manipulation of HCN channels in the context of epilepsy and how this may help future efforts in developing HCN-channel-based therapy. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  11. The clinical approach to small fibre neuropathy and painful channelopathy

    PubMed Central

    Themistocleous, Andreas C; Ramirez, Juan D; Serra, Jordi; Bennett, David L H

    2014-01-01

    Small fibre neuropathy (SFN) is characterised by structural injury selectively affecting small diameter sensory and/or autonomic axons. The clinical presentation is dominated by pain. SFN complicates a number of common diseases such as diabetes mellitus and is likely to be increasingly encountered. The diagnosis of SFN is demanding as clinical features can be vague and nerve conduction studies normal. New diagnostic techniques, in particular measurement of intraepidermal nerve fibre density, have significantly improved the diagnostic efficiency of SFN. Management is focused on the treatment of the underlying cause and analgesia, as there is no neuroprotective therapy. A recent and significant advance is the finding that a proportion of cases labelled as idiopathic SFN are in fact associated with gain of function mutations of the voltage-gated sodium channels Nav1.7 and Nav1.8 (encoded by the genes SCN9A and SCN10A, respectively). There is a further group of heritable painful conditions in which gain of function mutations in ion channels alter excitability of sensory neurones but do not cause frank axon degeneration; these include mutations in Nav1.7 (causing erythromelalgia and paroxysmal extreme pain disorder) and TRPA1 (resulting in familial episodic pain disorder). These conditions are exceptionally rare but have provided great insight into the nociceptive system as well as yielding potential analgesic drug targets. In patients with no pre-existing risk factor, the investigation of an underlying cause of SFN should be systematic and appropriate for the patient population. In this review, we focus on how to incorporate recent developments in the diagnosis and pathophysiology of SFN into clinical practice. PMID:24778270

  12. Neighborhood poverty and the resurgence of tuberculosis in New York City, 1984-1992.

    PubMed

    Barr, R G; Diez-Roux, A V; Knirsch, C A; Pablos-Méndez, A

    2001-09-01

    The resurgence of tuberculosis (TB) in NewYork City has been attributed to AIDS and immigration; however, the role of poverty in the epidemic is unclear. We assessed the relation between neighborhood poverty and TB at the height of the epidemic and longitudinally from 1984 through 1992. Census block groups were used as proxies for neighborhoods. For each neighborhood, we calculated TB and AIDS incidence in 1984 and 1992 with data from the Bureaus of Tuberculosis Control and AIDS Surveillance and obtained poverty rates from the census. For 1992, 3,343 TB cases were mapped to 5,482 neighborhoods, yielding a mean incidence of 46.5 per 100,000. Neighborhood poverty was associated with TB (relative risk = 1.33; 95% confidence interval = 1.30, 1.36 per 10% increase in poverty). This association persisted after adjustment for AIDS, proportion foreign born, and race/ethnicity. Neighborhoods with declining income from 1980 to 1990 had larger increases in TB incidence than did neighborhoods with increasing income. Leading up to and at the height of the TB epidemic in New York City, neighborhood poverty was strongly associated with TB incidence. Public health interventions should target impoverished areas.

  13. Resurgent sodium current and action potential formation in dissociated cerebellar Purkinje neurons.

    PubMed

    Raman, I M; Bean, B P

    1997-06-15

    Voltage-dependent sodium channels were studied in dissociated cerebellar Purkinje neurons from rats. In whole-cell recordings, a tetrodotoxin (TTX)-sensitive inward current was elicited when the membrane was repolarized to voltages between -60 and -20 mV after depolarizations to +30 mV long enough to produce maximal inactivation. At -40 mV, this "resurgent" current peaked in 8 msec and decayed with a time constant of 30 msec. With 50 mM sodium as a charge carrier, the resurgent current was on average approximately 120 pA. CA3 pyramidal neurons had no such current. The current may reflect recovery of inactivated channels through open states, because in Purkinje neurons (but not CA3 neurons) there was partial recovery from inactivation at -40 mV, coinciding with the rise of resurgent current. In single-channel recordings, individual channels gave openings corresponding to resurgent and conventional transient current. Action potentials were recorded from dissociated neurons under current clamp to investigate the role of the resurgent current in action potential formation. Purkinje neurons fired spontaneously at approximately 30 Hz. Hyperpolarization to -85 mV prevented spontaneous firing, and brief depolarization then induced all-or-none firing of conglomerate action potentials comprising three to four spikes. When conglomerate action potentials were used as command voltages in voltage-clamp experiments, TTX-sensitive sodium current was elicited between spikes. The falling phase of an action potential is similar to voltage patterns that activate resurgent sodium current, and thus, resurgent sodium current likely contributes to the formation of conglomerate action potentials in Purkinje neurons.

  14. Interactions among DIV voltage-sensor movement, fast inactivation, and resurgent Na current induced by the NaVβ4 open-channel blocking peptide

    PubMed Central

    Lewis, Amanda H.

    2013-01-01

    Resurgent Na current flows as voltage-gated Na channels recover through open states from block by an endogenous open-channel blocking protein, such as the NaVβ4 subunit. The open-channel blocker and fast-inactivation gate apparently compete directly, as slowing the onset of fast inactivation increases resurgent currents by favoring binding of the blocker. Here, we tested whether open-channel block is also sensitive to deployment of the DIV voltage sensor, which facilitates fast inactivation. We expressed NaV1.4 channels in HEK293t cells and assessed block by a free peptide replicating the cytoplasmic tail of NaVβ4 (the “β4 peptide”). Macroscopic fast inactivation was disrupted by mutations of DIS6 (L443C/A444W; “CW” channels), which reduce fast-inactivation gate binding, and/or by the site-3 toxin ATX-II, which interferes with DIV movement. In wild-type channels, the β4 peptide competed poorly with fast inactivation, but block was enhanced by ATX. With the CW mutation, large peptide-induced resurgent currents were present even without ATX, consistent with increased open-channel block upon depolarization and slower deactivation after blocker unbinding upon repolarization. The addition of ATX greatly increased transient current amplitudes and further enlarged resurgent currents, suggesting that pore access by the blocker is actually decreased by full deployment of the DIV voltage sensor. ATX accelerated recovery from block at hyperpolarized potentials, however, suggesting that the peptide unbinds more readily when DIV voltage-sensor deployment is disrupted. These results are consistent with two open states in Na channels, dependent on the DIV voltage-sensor position, which differ in affinity for the blocking protein. PMID:23940261

  15. NALCN channelopathies

    PubMed Central

    Bend, Eric G.; Si, Yue; Stevenson, David A.; Bayrak-Toydemir, Pinar; Newcomb, Tara M.

    2016-01-01

    Objective: To perform genotype–phenotype analysis in an infant with congenital arthrogryposis due to a de novo missense mutation in the NALCN ion channel and explore the mechanism of pathogenicity using a Caenorhabditis elegans model. Methods: We performed whole-exome sequencing in a preterm neonate with congenital arthrogryposis and a severe life-threatening clinical course. We examined the mechanism of pathogenicity of the associated NALCN mutation by engineering the orthologous mutation into the nematode C elegans using CRISPR-Cas9. Results: We identified a de novo missense mutation in NALCN, c.1768C>T, in an infant with a severe neonatal lethal form of the recently characterized CLIFAHDD syndrome (congenital contractures of the limbs and face with hypotonia and developmental delay). We report novel phenotypic features including prolonged episodes of stimulus-sensitive sustained muscular contraction associated with life-threatening episodes of desaturation and autonomic instability, extending the severity of previously described phenotypes associated with mutations in NALCN. When engineered into the C elegans ortholog, this mutation results in a severe gain-of-function phenotype, with hypercontraction and uncoordinated movement. We engineered 6 additional CLIFAHDD syndrome mutations into C elegans and the mechanism of action could be divided into 2 categories: half phenocopied gain-of-function mutants and half phenocopied loss-of-function mutants. Conclusions: The clinical phenotype of our patient and electrophysiologic studies show sustained muscular contraction in response to transient sensory stimuli. In C elegans, this mutation causes neuronal hyperactivity via a gain-of-function NALCN ion channel. Testing human variants of NALCN in C elegans demonstrates that CLIFAHDD can be caused by dominant loss- or gain-of-function mutations in ion channel function. PMID:27558372

  16. 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.

  17. Resurgence structure to all orders of multi-bions in deformed SUSY quantum mechanics

    NASA Astrophysics Data System (ADS)

    Fujimori, Toshiaki; Kamata, Syo; Misumi, Tatsuhiro; Nitta, Muneto; Sakai, Norisuke

    2017-08-01

    We investigate the resurgence structure in quantum mechanical models originating in 2d nonlinear sigma models with emphasis on nearly supersymmetric and quasi-exactly solvable parameter regimes. By expanding the ground state energy in powers of a supersymmetry-breaking deformation parameter δ ɛ, we derive exact results for the expansion coefficients. In the class of models described by real multiplets, the O(δɛ) ground state energy has a non-Borel summable asymptotic series, which gives rise to imaginary ambiguities leading to rich resurgence structure. We discuss sine-Gordon quantum mechanics (QM) as an example and show that the semiclassical contributions from complex multi-bion solutions correctly reproduce the corresponding part in the exact result including the imaginary ambiguities. As a typical model described by chiral multiplets, we discuss CP^{N-1} QM and show that the exact O(δɛ) ground state energy can be completely reconstructed from the semiclassical multi-bion contributions. Although the O(δɛ) ground state energy has trivial resurgence structure, a simple but rich resurgence structure appears at O(δɛ2). We show the complete cancelation between the O(δɛ2) imaginary ambiguities arising from the non-Borel summable perturbation series and those in the semiclassical contributions of N-1 complex bion solutions. We also discuss the resurgence structure of a squashed {C}P^1 QM.

  18. Measles Resurgence Associated with Continued Circulation of Genotype H1 Viruses in China, 2005

    PubMed Central

    Ji, Yixin; Zhang, Yan; Xu, Songtao; Zhu, Zhen; Zuo, Shuyan; Jiang, Xiaohong; Lu, Peishan; Wang, Changyin; Liang, Yong; Zheng, Huanying; Liu, Yang; Mao, Naiying; Liang, Xiaofeng; Featherstone, David Alexander; Rota, Paul A; Bellini, William J; Xu, Wenbo

    2009-01-01

    Measles morbidity and mortality decreased significantly after measles vaccine was introduced into China in 1965. From 1995 to 2004, average annual measles incidence decreased to 5.6 cases per 100,000 population following the establishment of a national two-dose regimen. Molecular characterization of wild-type measles viruses demonstrated that genotype H1 was endemic and widely distributed throughout the country in China during 1995-2004. A total of 124,865 cases and 55 deaths were reported from the National Notifiable Diseases Reporting System (NNDRS) in 2005, which represented a 69.05% increase compared with 2004. Over 16,000 serum samples obtained from 914 measles outbreaks and the measles IgM positive rate was 81%. 213 wild-type measles viruses were isolated from 18 of 31 provinces in China during 2005, and all of the isolates belonged to genotype H1. The ranges of the nucleotide sequence and predicted amino acid sequence homologies of the 213 genotype H1 strains were 93.4%-100% and 90.0%-100%, respectively. H1-associated cases and outbreaks caused the measles resurgence in China in 2005. H1 genotype has the most inner variation within genotype, it could be divided into 2 clusters, and cluster 1 viruses were predominant in China throughout 2005. PMID:19737391

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

    NASA Astrophysics Data System (ADS)

    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.

  20. Combating pertussis resurgence: One booster vaccination schedule does not fit all.

    PubMed

    Riolo, Maria A; Rohani, Pejman

    2015-02-03

    Pertussis has reemerged as a major public health concern in many countries where it was once considered well controlled. Although the mechanisms responsible for continued pertussis circulation and resurgence remain elusive and contentious, many countries have nevertheless recommended booster vaccinations, the timing and number of which vary widely. Here, using a stochastic, age-stratified transmission model, we searched for cost-effective booster vaccination strategies using a genetic algorithm. We did so assuming four hypothesized mechanisms underpinning contemporary pertussis epidemiology: (I) insufficient coverage, (II) frequent primary vaccine failure, (III) waning of vaccine-derived protection, and (IV) vaccine "leakiness." For scenarios I-IV, successful booster strategies were identified and varied considerably by mechanism. Especially notable is the inability of booster schedules to alleviate resurgence when vaccines are leaky. Critically, our findings argue that the ultimate effectiveness of vaccine booster schedules will likely depend on correctly pinpointing the causes of resurgence, with misdiagnosis of the problem epidemiologically ineffective and economically costly.

  1. Agricultural development, migrant labor and the resurgence of malaria in Swaziland.

    PubMed

    Packard, R M

    1986-01-01

    Much of the research on the recent resurgence of malaria in Third World areas has focused on the problem of vector resistance arising out of the widespread use of pesticides in conjunction with the development of large-scale agricultural projects. Evidence from southern Africa, and particularly from Swaziland, where a resurgence of malaria has occurred in the absence of pesticide-resistant strains of Anopheles mosquitoes, suggests that changes in agroecosystems, labor utilization and settlement patterns, which are also associated with large-scale agricultural development, may play an equally important role in the resurgence of malaria. Renewed efforts to control malaria must, therefore, take account of the social and economic, as well as the biological determinants of this disease.

  2. 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.

  3. 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.

  4. Behavioral Momentum Theory Fails to Account for the Effects of Reinforcement Rate on Resurgence

    PubMed Central

    Craig, Andrew R.; Shahan, Timothy A.

    2017-01-01

    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 rein-forcer rates on persistence and resurgence of operant behavior. PMID:27193242

  5. Implantable cardioverter defibrillator therapy in young patients with cardiomyopathies and channelopathies: a single Italian centre experience.

    PubMed

    Migliore, Federico; Silvano, Maria; Zorzi, Alessandro; Bertaglia, Emanuele; Siciliano, Mariachiara; Leoni, Loira; De Franceschi, Pietro; Iliceto, Sabino; Corrado, Domenico

    2016-07-01

    This study was designed to prospectively evaluate the risk-benefit ratio of implantable cardioverter defibrillator (ICD) therapy in young patients with cardiomyopathies and channelopathies. The study population included 96 consecutive patients [68 men, median age 27 (22-32) years] with cardiomyopathies, such as arrhythmogenic right ventricular cardiomyopathy (n = 35), dilated cardiomyopathy (n = 17), hypertrophic cardiomyopathy (n = 15), Brugada syndrome (n = 14), idiopathic ventricular fibrillation (n = 5), left ventricular noncompaction (n = 4), long-QT syndrome (n = 4) and short-QT syndrome (n = 2), who were 18-35 years old at the time of ICD implantation. During a mean follow-up of 72.6 ± 53.3 months, one patient with end-stage hypertrophic cardiomyopathy died because of acute heart failure, and 11 patients underwent orthotopic heart transplantation. Twenty patients (20.8%) had a total of 38 appropriate ICD interventions (4%/year), and 26 patients (27.1%) experienced a total of 49 adverse ICD-related events (5.4%/year), including 23 inappropriate ICD interventions occurring in nine patients (9.4%) and 26 device-related complications requiring surgical revision occurring in 20 patients (20.8%). Lead failure/fracture requiring lead extraction was the most common complication (n = 9). A threshold for ICD therapy less than 300 ms was associated with a borderline significant lower probability of inappropriate ICD interventions (hazard ratio = 0.2; 95% confidence interval 0.02-1.2; P = 0.07), whereas underweight status was an independent predictor of device-related complications (hazard ratio = 5.4; 95% confidence interval 1.5-19.4; P = 0.01). In young patients with cardiomyopathies and channelopathies, ICD therapy provided life-saving protection by effectively terminating life-threatening ventricular arrhythmias. However, because ICD-related adverse events are common, the risk/benefit ratio should be

  6. Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies: a decade later.

    PubMed

    Pittock, Sean J; Lucchinetti, Claudia F

    2016-02-01

    The discovery of AQP4-IgG (a pathogenic antibody that targets the astrocytic water channel aquaporin-4), as the first sensitive and specific biomarker for any inflammatory central nervous system demyelinating disease (IDD), has shifted emphasis from the oligodendrocyte and myelin to the astrocyte as a central immunopathogenic player. Neuromyelitis optica (NMO) spectrum disorders (SDs) represent an evolving spectrum of IDDs extending beyond the optic nerves and spinal cord to include the brain (especially in children) and, rarely, muscle. NMOSD typical brain lesions are located in areas that highly express the target antigen, AQP4, including the circumventricular organs (accounting for intractable nausea and vomiting) and the diencephalon (accounting for sleep disorders, endocrinopathies, and syndrome of inappropriate antidiuresis). Magnetic resonance imaging brain abnormalities fulfill Barkoff criteria for multiple sclerosis in up to 10% of patients. As the spectrum broadens, the importance of highly specific assays that detect pathogenic AQP4-IgG targeting extracellular epitopes of AQP4 cannot be overemphasized. The rapid evolution of our understanding of the immunobiology of AQP4 autoimmunity necessitates continuing revision of NMOSD diagnostic criteria. Here, we describe scientific advances that have occurred since the discovery of NMO-IgG in 2004 and review novel targeted immunotherapies. We also suggest that NMOSDs should now be considered under the umbrella term autoimmune aquaporin-4 channelopathy. © 2015 New York Academy of Sciences.

  7. Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies: a decade later

    PubMed Central

    Pittock, Sean J.; Lucchinetti, Claudia F.

    2015-01-01

    The discovery of AQP4-IgG (a pathogenic antibody that targets the astrocytic water channel aquaporin-4) as the first sensitive and specific biomarker for any inflammatory central nervous system demyelinating disease, has shifted emphasis from the oligodendrocyte and myelin to the astrocyte as a central immunopathogenic player. Neuromyelitis optica (NMO) spectrum disorders (SD) represent an evolving spectrum of IDDs extending beyond the optic nerves and spinal cord to include the brain (especially in children) and, rarely, muscle. NMOSD typical brain lesions are located in areas that highly express the target antigen, AQP4, including the circumventricular organs (accounting for intractable nausea and vomiting) and the diencephalon (accounting for sleep disorders, endocrinopathies, and syndrome of inappropriate antidiuresis). Magnetic resonance imaging (MRI) brain abnormalities fulfill Barkoff criteria for multiple sclerosis in up to 10% of patients. As the spectrum broadens, the importance of highly specific assays that detect pathogenic AQP4-IgG targeting extracellular epitopes of AQP4 cannot be overemphasized. The rapid evolution of our understanding of the immunobiology of AQP4 autoimmunity necessitates continuing revision of NMOSD diagnostic criteria. Here, we describe scientific advances that have occurred since the discovery of NMO-IgG in 2004 and review novel targeted immunotherapies. We also suggest that NMOSDs should now be considered under the umbrella term autoimmune aquaporin-4 channelopathy. PMID:26096370

  8. Stochastic spontaneous calcium release events and sodium channelopathies promote ventricular arrhythmias

    NASA Astrophysics Data System (ADS)

    Campos, Fernando O.; Shiferaw, Yohannes; Vigmond, Edward J.; Plank, Gernot

    2017-09-01

    Premature ventricular complexes (PVCs), the first initiating beats of a variety of cardiac arrhythmias, have been associated with spontaneous calcium release (SCR) events at the cell level. However, the mechanisms underlying the degeneration of such PVCs into arrhythmias are not fully understood. The objective of this study was to investigate the conditions under which SCR-mediated PVCs can lead to ventricular arrhythmias. In particular, we sought to determine whether sodium (Na+) current loss-of-function in the structurally normal ventricles provides a substrate for unidirectional conduction block and reentry initiated by SCR-mediated PVCs. To achieve this goal, a stochastic model of SCR was incorporated into an anatomically accurate compute model of the rabbit ventricles with the His-Purkinje system (HPS). Simulations with reduced Na+ current due to a negative-shift in the steady-state channel inactivation showed that SCR-mediated delayed afterdepolarizations led to PVC formation in the HPS, where the electrotonic load was lower, conduction block, and reentry in the 3D myocardium. Moreover, arrhythmia initiation was only possible when intrinsic electrophysiological heterogeneity in action potential within the ventricles was present. In conclusion, while benign in healthy individuals SCR-mediated PVCs can lead to life-threatening ventricular arrhythmias when combined with Na+ channelopathies.

  9. Divalent cation-responsive myotonia and muscle paralysis in skeletal muscle sodium channelopathy.

    PubMed

    Mankodi, Ami; Grunseich, Christopher; Skov, Martin; Cook, Lisa; Aue, Georg; Purev, Enkhtsetseg; Bakar, Dara; Lehky, Tanya; Jurkat-Rott, Karin; Pedersen, Thomas H; Childs, Richard W

    2015-11-01

    We report a patient with paramyotonia congenita/hyperkalemic periodic paralysis due to Nav1.4 I693T mutation who had worsening of myotonia and muscle weakness in the setting of hypomagnesemia and hypocalcemia with marked recovery after magnesium administration. Computer simulations of the effects of the I693T mutation were introduced in the muscle fiber model by both hyperpolarizing shifts in the Nav1.4 channel activation and a faster recovery from slow channel inactivation. A further shift in the Nav1.4 channel activation in the hyperpolarizing direction as expected with low divalent cations resulted in myotonia that progressed to membrane inexcitability. Shifting the channel activation in the depolarizing direction as would be anticipated from magnesium supplementation abolished the myotonia. These observations provide clinical and biophysical evidence that the muscle symptoms in sodium channelopathy are sensitive to divalent cations. Exploration of the role of magnesium administration in therapy or prophylaxis is warranted with a randomized clinical trial.

  10. Stochastic spontaneous calcium release events and sodium channelopathies promote ventricular arrhythmias

    PubMed Central

    Campos, Fernando O.; Shiferaw, Yohannes

    2017-01-01

    Premature ventricular complexes (PVCs), the first initiating beats of a variety of cardiac arrhythmias, have been associated with spontaneous calcium release (SCR) events at the cell level. However, the mechanisms underlying the degeneration of such PVCs into arrhythmias are not fully understood. The objective of this study was to investigate the conditions under which SCR-mediated PVCs can lead to ventricular arrhythmias. In particular, we sought to determine whether sodium (Na+) current loss-of-function in the structurally normal ventricles provides a substrate for unidirectional conduction block and reentry initiated by SCR-mediated PVCs. To achieve this goal, a stochastic model of SCR was incorporated into an anatomically accurate compute model of the rabbit ventricles with the His-Purkinje system (HPS). Simulations with reduced Na+ current due to a negative-shift in the steady-state channel inactivation showed that SCR-mediated delayed afterdepolarizations led to PVC formation in the HPS, where the electrotonic load was lower, conduction block, and reentry in the 3D myocardium. Moreover, arrhythmia initiation was only possible when intrinsic electrophysiological heterogeneity in action potential within the ventricles was present. In conclusion, while benign in healthy individuals SCR-mediated PVCs can lead to life-threatening ventricular arrhythmias when combined with Na+ channelopathies. PMID:28964108

  11. Stochastic spontaneous calcium release events and sodium channelopathies promote ventricular arrhythmias.

    PubMed

    Campos, Fernando O; Shiferaw, Yohannes; Vigmond, Edward J; Plank, Gernot

    2017-09-01

    Premature ventricular complexes (PVCs), the first initiating beats of a variety of cardiac arrhythmias, have been associated with spontaneous calcium release (SCR) events at the cell level. However, the mechanisms underlying the degeneration of such PVCs into arrhythmias are not fully understood. The objective of this study was to investigate the conditions under which SCR-mediated PVCs can lead to ventricular arrhythmias. In particular, we sought to determine whether sodium (Na(+)) current loss-of-function in the structurally normal ventricles provides a substrate for unidirectional conduction block and reentry initiated by SCR-mediated PVCs. To achieve this goal, a stochastic model of SCR was incorporated into an anatomically accurate compute model of the rabbit ventricles with the His-Purkinje system (HPS). Simulations with reduced Na(+) current due to a negative-shift in the steady-state channel inactivation showed that SCR-mediated delayed afterdepolarizations led to PVC formation in the HPS, where the electrotonic load was lower, conduction block, and reentry in the 3D myocardium. Moreover, arrhythmia initiation was only possible when intrinsic electrophysiological heterogeneity in action potential within the ventricles was present. In conclusion, while benign in healthy individuals SCR-mediated PVCs can lead to life-threatening ventricular arrhythmias when combined with Na(+) channelopathies.

  12. 'Gardos Channelopathy': a variant of hereditary Stomatocytosis with complex molecular regulation.

    PubMed

    Fermo, Elisa; Bogdanova, Anna; Petkova-Kirova, Polina; Zaninoni, Anna; Marcello, Anna Paola; Makhro, Asya; Hänggi, Pascal; Hertz, Laura; Danielczok, Jens; Vercellati, Cristina; Mirra, Nadia; Zanella, Alberto; Cortelezzi, Agostino; Barcellini, Wilma; Kaestner, Lars; Bianchi, Paola

    2017-05-11

    The Gardos channel is a Ca(2+) sensitive, K(+) selective channel present in several tissues including RBCs, where it is involved in cell volume regulation. Recently, mutations at two different aminoacid residues in KCNN4 have been reported in patients with hereditary xerocytosis. We identified by whole exome sequencing a new family with two members affected by chronic hemolytic anemia carrying mutation R352H in the KCNN4 gene. No additional mutations in genes encoding for RBCs cytoskeletal, membrane or channel proteins were detected. We performed functional studies on patients' RBCs to evaluate the effects of R352H mutation on the cellular properties and eventually on the clinical phenotype. Gardos channel hyperactivation was demonstrated in circulating erythrocytes and erythroblasts differentiated ex-vivo from peripheral CD34+ cells. Pathological alterations in the function of multiple ion transport systems were observed, suggesting the presence of compensatory effects ultimately preventing cellular dehydration in patient's RBCs; moreover, flow cytometry and confocal fluorescence live-cell imaging showed Ca(2+) overload in the RBCs of both patients and hypersensitivity of Ca(2+) uptake by RBCs to swelling. Altogether these findings suggest that the 'Gardos channelopathy' is a complex pathology, to some extent different from the common hereditary xerocytosis.

  13. Biowarfare, bioterrorism, and animal diseases as bioweapons: Chapter 6 in Disease emergence and resurgence: The wildlife-human connection

    USGS Publications Warehouse

    Friend, Milton

    2006-01-01

    Linkages between disease in humans and the maladies of animals continue to be a focus for those concerned with disease effects on human health. References to animal diseases, particularly zoonoses such as rabies and glanders, are found in the writings of Greek (Hippocrates, Democritus, Aristotle, Galen, Dioscorides), Byzantine (Oribasius, Actius of Amida), and Roman (Pliny the Elder, Celsus) physicians and naturalists.3 Also, early advances in disease knowledge were closely associated with the study of contagions in animals to the extent that “The most complete ancient accounts of the concepts of contagion and contamination are found in treatises on veterinary medicine.”4,5Opportunities for disease transfer between animals and humans have increased during modern times, partly because of advances in animal husbandry and intensive agriculture that result in increased contacts among humans, domestic animals, and wildlife. Infectious pathogens exploit these contacts, and must be considered in this era of increased world tensions and international terrorism (Fig. 6.1).Disease emergence and resurgence are generally associated with natural processes and unanticipated outcomes related to human behavior and actions. That perspective has been broadened by recent acts of bioterrorism. A new category of deliberately emerging diseases contains emerging microbes that are developed by humans, usually for nefarious use.211 Included are naturally occurring microbial agents and those altered by bioengineering.This chapter highlights the wildlife component of the pathogen-host-environment triad to focus attention on the potential for bioterrorists to use wildlife as a means for infectious disease attacks against society. The value of this focus is that the underlying causes of disease emergence and the optimal prevention or control response frequently differ for disease emergence, resurgence, and deliberately emerging diseases.211 Differences also exist relative to the potential

  14. 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…

  15. 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,…

  16. 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,…

  17. 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.

  18. 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…

  19. 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…

  20. Resistance to change and resurgence in humans engaging in a computer task.

    PubMed

    Kuroda, Toshikazu; Cançado, Carlos R X; Podlesnik, Christopher A

    2016-04-01

    The relation between persistence, as measured by resistance to change, and resurgence has been examined with nonhuman animals but not systematically with humans. The present study examined persistence and resurgence with undergraduate students engaging in a computer task for points exchangeable for money. In Phase 1, a target response was maintained on a multiple variable-interval (VI) 15-s (Rich) VI 60-s (Lean) schedule of reinforcement. In Phase 2, the target response was extinguished while an alternative response was reinforced at equal rates in both schedule components. In Phase 3, the target and the alternative responses were extinguished. In an additional test of persistence (Phase 4), target responding was reestablished as in Phase 1 and then disrupted by access to videos in both schedule components. In Phases 2 and 4, target responding was more persistent in the Rich than in the Lean component. Also, resurgence generally was greater in the Rich than in the Lean component in Phase 3. The present findings with humans extend the generality of those obtained with nonhuman animals showing that higher reinforcement rates produce both greater persistence and resurgence, and suggest that common processes underlie response persistence and relapse. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Megabreccias, Early Lakes, and Duration of Resurgence Recorded in Valles Caldera, New Mexico

    NASA Astrophysics Data System (ADS)

    Goff, F.; Goff, C. J.; Phillips, E. H.; Kyle, P. R.; McIntosh, W. C.; Chipera, S.; Gardner, J. N.

    2003-12-01

    New 1:24,000 scale geologic mapping combined with previous and ongoing geoscientific studies are revealing significant new findings on intracaldera stratigraphy and structure, initial development of intracaldera lakes, and the duration of resurgence within the ca. 1.25 Myr Valles caldera. The caldera is about 22 km in diameter and contains a resurgent dome that is a northeast-trending oval roughly11 x 9 km in dimension. Maximum resurgence (uplift) was more than 1000 m, during which the dome split into three principal segments herein named the Redondo Peak, Redondo Border, and Valle San Luis segments. These segments are separated from each other by long, narrow grabens herein called the Redondo Creek, Jaramillo Creek, and San Luis Creek grabens. Differential uplift accompanied by intense faulting has exposed large, rootless megabreccia (Mbx) blocks composed of precaldera rocks submerged in densely welded, intracaldera upper Bandelier Tuff. The largest Mbx blocks are roughly 0.2 to 2.0 km long and consist primarily of Abo Fm (Permian), Gallisteo Fm (?) (Eocene), Santa Fe Group (Miocene), Paliza Canyon Fm (late Miocene) and lower Bandelier Tuff (ca. 1.62 Ma). Deep geothermal wells drilled within the Redondo Creek graben from 1970 to 1983 penetrate as much as 2032 m of intracaldera Bandelier Tuff and post-Bandelier rocks before intersecting caldera floor rocks (average = 1646 m, n = 23 wells). Evidence that a lake developed within the caldera depression is preserved in finely laminated lacustrine beds and rhyolitic, hydromagmatic tuffs that overlie intracaldera Bandelier Tuff on the resurgent dome. The lacustrine rocks contain organic remains and the hydromagmatic tuffs contain accretionary lapilli. In some locations, lacustrine and hydromagmatic rocks are interbedded. Earliest post-caldera rhyolite lavas (Deer Canyon Member) display occasional pepperite and pillow textures. Many lavas contain significant amounts of fine, opalized flow breccia indicating interaction

  2. 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

  3. Refined exercise testing can aid DNA-based diagnosis in muscle channelopathies.

    PubMed

    Tan, S Veronica; Matthews, Emma; Barber, Melissa; Burge, James A; Rajakulendran, Sanjeev; Fialho, Doreen; Sud, Richa; Haworth, Andrea; Koltzenburg, Martin; Hanna, Michael G

    2011-02-01

    To improve the accuracy of genotype prediction and guide genetic testing in patients with muscle channelopathies we applied and refined specialized electrophysiological exercise test parameters. We studied 56 genetically confirmed patients and 65 controls using needle electromyography, the long exercise test, and short exercise tests at room temperature, after cooling, and rewarming. Concordant amplitude-and-area decrements were more reliable than amplitude-only measurements when interpreting patterns of change during the short exercise tests. Concordant amplitude-and-area pattern I and pattern II decrements of >20% were 100% specific for paramyotonia congenita and myotonia congenita, respectively. When decrements at room temperature and after cooling were <20%, a repeat short exercise test after rewarming was useful in patients with myotonia congenita. Area measurements and rewarming distinguished true temperature sensitivity from amplitude reduction due to cold-induced slowing of muscle fiber conduction. In patients with negative short exercise tests, symptomatic eye closure myotonia predicted sodium channel myotonia over myotonia congenita. Distinctive "tornado-shaped" neuromyotonia-like discharges may be seen in patients with paramyotonia congenita. In the long exercise test, area decrements from pre-exercise baseline were more sensitive than amplitude decrements-from-maximum-compound muscle action potential (CMAP) in patients with Andersen-Tawil syndrome. Possible ethnic differences in the normative data of the long exercise test argue for the use of appropriate ethnically-matched controls. Concordant CMAP amplitude-and-area decrements of >20% allow more reliable interpretation of the short exercise tests and aid accurate DNA-based diagnosis. In patients with negative exercise tests, specific clinical features are helpful in differentiating sodium from chloride channel myotonia. A modified algorithm is suggested. Copyright © 2011 American Neurological

  4. Refined Exercise testing can aid DNA-based Diagnosis in Muscle Channelopathies

    PubMed Central

    Tan, S. Veronica; Matthews, Emma; Barber, Melissa; Burge, James A; Rajakulendran, Sanjeev; Fialho, Doreen; Sud, Richa; Haworth, Andrea; Koltzenburg, Martin; Hanna, Michael G

    2010-01-01

    Objective To improve the accuracy of genotype prediction and guide genetic testing in patients with muscle channelopathies we applied and refined specialised electrophysiological exercise test parameters. Methods We studied 56 genetically confirmed patients and 65 controls using needle electromyography, the long exercise test, and short exercise tests at room temperature, after cooling, and rewarming. Results Concordant amplitude-and-area decrements were more reliable than amplitude-only measurements when interpreting patterns of change during the short exercise tests. Concordant amplitude-and-area pattern I and pattern II decrements of >20% were 100% specific for PMC and MC respectively. When decrements at room temperature and after cooling were <20%, a repeat short exercise test after rewarming was useful in patients with myotonia congenita. Area measurements and rewarming distinguished true temperature sensitivity from amplitude reduction due to cold-induced slowing of muscle fibre conduction. In patients with negative short exercise tests, symptomatic eye closure myotonia predicted sodium channel myotonia over myotonia congenita. Distinctive ‘tornado-shaped’ neuromyotonia-like discharges may be seen in patients with paramyotonia congenita. In the long exercise test, area decrements from pre-exercise baseline were more sensitive than amplitude decrements-from-maximum-CMAP in patients with Andersen-Tawil syndrome. Possible ethnic differences in the normative data of the long exercise test argue for the use of appropriate ethnically-matched controls. Interpretation Concordant CMAP amplitude-and-area decrements of >20% allow more reliable interpretation of the short exercise tests and aid accurate DNA-based diagnosis. In patients with negative exercise tests, specific clinical features are helpful in differentiating sodium from chloride channel myotonia. A modified algorithm is suggested.. PMID:21387378

  5. 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.

  6. 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. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  7. Ataxia and myoclonic epilepsy due to a heterozygous new mutation in KCNA2: proposal for a new channelopathy.

    PubMed

    Pena, S D J; Coimbra, R L M

    2015-02-01

    We have recently performed exome analysis in a 7 year boy who presented in infancy with an encephalopathy characterized by ataxia and myoclonic epilepsy. Parents were not consanguineous and there was no family history of the disease. Exome analysis did not show any pathogenic variants in genes known to be associated with seizures and/or ataxia in children, including all known human channelopathies. However, we have identified a mutation in KCNA2 that we believe to be responsible for the disease in our patient. This gene, which encodes a member of the potassium channel, voltage-gated, shaker-related subfamily, has not been previously described as a cause of disease in humans, but mutations of the orthologous gene in mice (Kcna2) are known to cause both ataxia and convulsions. The mutation is c.890C>A, leading to the amino acid substitution p.Arg297Gln, which involves the second of the critical arginines in the S4 voltage sensor. This mutation is characterized as pathogenic by five different prediction programs. RFLP analysis and Sanger sequencing confirmed the presence of the mutation in the patient, but not in his parents, characterizing it as de novo. We believe that this discovery characterizes a new channelopathy. © 2014 John Wiley | Clinical Exome Genome Reports.

  8. Rapid resurgence of marine productivity after the Cretaceous-Paleogene mass extinction.

    PubMed

    Sepúlveda, Julio; Wendler, Jens E; Summons, Roger E; Hinrichs, Kai-Uwe

    2009-10-02

    The course of the biotic recovery after the impact-related disruption of photosynthesis and mass extinction event at the Cretaceous-Paleogene boundary has been intensely debated. The resurgence of marine primary production in the aftermath remains poorly constrained because of the paucity of fossil records tracing primary producers that lack skeletons. Here we present a high-resolution record of geochemical variation in the remarkably thick Fiskeler (also known as the Fish Clay) boundary layer at Kulstirenden, Denmark. Converging evidence from the stable isotopes of carbon and nitrogen and abundances of algal steranes and bacterial hopanes indicates that algal primary productivity was strongly reduced for only a brief period of possibly less than a century after the impact, followed by a rapid resurgence of carbon fixation and ecological reorganization.

  9. Persistence during and resurgence following noncontingent reinforcement implemented with and without extinction.

    PubMed

    Saini, Valdeep; Fisher, Wayne W; Pisman, Maegan D

    2017-03-09

    Noncontingent reinforcement (NCR) is typically implemented with extinction (EXT) for destructive behavior reinforced by social consequences and without EXT for destructive behavior reinforced by sensory consequences. Behavioral momentum theory (BMT) predicts that responding will be more persistent, and treatment relapse in the form of response resurgence more likely, when NCR is implemented without EXT due to the greater overall rate of reinforcement associated with this intervention. We used an analogue arrangement to test these predictions of BMT by comparing NCR implemented with and without EXT. For two of three participants, we observed more immediate reductions in responding during NCR without EXT. However, for all participants, NCR without EXT produced greater resurgence than NCR with EXT when we discontinued all reinforcers during an EXT Only phase, although there was variability in response patterns across and within participants. Implications for treatment of destructive behavior using NCR are discussed.

  10. Resurgence of Pseudoperonospora cubensis: The Causal Agent of Cucurbit Downy Mildew.

    PubMed

    Cohen, Yigal; Van den Langenberg, Kyle M; Wehner, Todd C; Ojiambo, Peter S; Hausbeck, Mary; Quesada-Ocampo, Lina M; Lebeda, Aleš; Sierotzki, Helge; Gisi, Ulrich

    2015-07-01

    The downy mildew pathogen, Pseudoperonospora cubensis, which infects plant species in the family Cucurbitaceae, has undergone major changes during the last decade. Disease severity and epidemics are far more destructive than previously reported, and new genotypes, races, pathotypes, and mating types of the pathogen have been discovered in populations from around the globe as a result of the resurgence of the disease. Consequently, disease control through host plant resistance and fungicide applications has become more complex. This resurgence of P. cubensis offers challenges to scientists in many research areas including pathogen biology, epidemiology and dispersal, population structure and population genetics, host preference, host-pathogen interactions and gene expression, genetic host plant resistance, inheritance of host and fungicide resistance, and chemical disease control. This review serves to summarize the current status of this major pathogen and to guide future management and research efforts within this pathosystem.

  11. Resurgence of yaws in Tanna, Vanuatu: time for a new approach?

    PubMed

    Fegan, David; Glennon, Mary J; Thami, Yogendra; Pakoa, George

    2010-04-01

    Recent reports from the island of Tanna in Vanuatu suggest that yaws has resurged. We carried out a serological and clinical survey to determine the prevalence and clinical presentation of yaws on the island. A total of 306 random serum samples were tested for rapid plasma reagin and rapid diagnostic determine syphilis: 31.04% were positive for one or both tests; 39.8% of children surveyed in three schools had skin lesions consistent with yaws; and there were only two cases of secondary yaws osteitis and no cases of tertiary yaws. These results confirm that the disease has resurged but appears to be attenuated. Intramuscular benzathine penicillin is the currently recommended treatment for yaws. We suggest that a stat dose of oral azithromycin would be a more accessible treatment as it could be prescribed by village health workers and therefore enable yaws control to be more easily incorporated into other primary health-care programmes.

  12. Antagonism of Lidocaine Inhibition by Open-Channel Blockers That Generate Resurgent Na Current

    PubMed Central

    Bant, Jason S.; Aman, Teresa K.; Raman, Indira M.

    2013-01-01

    Na channels that generate resurgent current express an intracellular endogenous open-channel blocking protein, whose rapid binding upon depolarization and unbinding upon repolarization minimizes fast and slow inactivation. Na channels also bind exogenous compounds, such as lidocaine, which functionally stabilize inactivation. Like the endogenous blocking protein, these use-dependent inhibitors bind most effectively at depolarized potentials, raising the question of how lidocaine-like compounds affect neurons with resurgent Na current. We therefore recorded lidocaine inhibition of voltage-clamped, tetrodotoxin-sensitive Na currents in mouse Purkinje neurons, which express a native blocking protein, and in mouse hippocampal CA3 pyramidal neurons with and without a peptide from the cytoplasmic tail of NaVβ4 (the β4 peptide), which mimics endogenous open-channel block. To control channel states during drug exposure, lidocaine was applied with rapid-solution exchange techniques during steps to specific voltages. Inhibition of Na currents by lidocaine was diminished by either the β4 peptide or the native blocking protein. In peptide-free CA3 cells, prolonging channel opening with a site-3 toxin, anemone toxin II, reduced lidocaine inhibition; this effect was largely occluded by open-channel blockers, suggesting that lidocaine binding is favored by inactivation but prevented by open-channel block. In constant 100 μM lidocaine, current-clamped Purkinje cells continued to fire spontaneously. Similarly, the β4 peptide reduced lidocaine-dependent suppression of spiking in CA3 neurons in slices. Thus, the open-channel blocking protein responsible for resurgent current acts as a natural antagonist of lidocaine. Neurons with resurgent current may therefore be less susceptible to use-dependent Na channel inhibitors used as local anesthetic, antiarrhythmic, and anticonvulsant drugs. PMID:23486968

  13. 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

    2015-12-17

    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.

  14. The Resurgence of Instantons: Multi-Cut Stokes Phases and the Painlevé II Equation

    NASA Astrophysics Data System (ADS)

    Schiappa, Ricardo; Vaz, Ricardo

    2014-09-01

    Resurgent transseries have recently been shown to be a very powerful construction for completely describing nonperturbative phenomena in both matrix models and topological or minimal strings. These solutions encode the full nonperturbative content of a given gauge or string theory, where resurgence relates every (generalized) multi-instanton sector to each other via large-order analysis. The Stokes phase is the adequate gauge theory phase where a 't Hooft large N expansion exists and where resurgent transseries are most simply constructed. This paper addresses the nonperturbative study of Stokes phases associated to multi-cut solutions of generic matrix models, constructing nonperturbative solutions for their free energies and exploring the asymptotic large-order behavior around distinct multi-instanton sectors. Explicit formulae are presented for the symmetric two-cut set-up, addressing the cases of the quartic matrix model in its two-cut Stokes phase; the "triple" Penner potential which yields four-point correlation functions in the AGT framework; and the Painlevé II equation describing minimal superstrings.

  15. Resurgence of the cotton bollworm Helicoverpa armigera in northern Greece associated with insecticide resistance.

    PubMed

    Mironidis, George K; Kapantaidaki, Despina; Bentila, Maria; Morou, Evangelia; Savopoulou-Soultani, M; Vontas, John

    2013-08-01

    Helicoverpa armigera has been controlled effectively with chemical insecticides in the major cotton crop production areas of northern Greece for many years. However, a resurgence of the pest was observed in 2010, which significantly affected crop production. During a 4-year survey (2007-2010), we examined the insecticide resistance status of H. armigera populations from two major and representative cotton production areas in northern Greece against seven insecticides (chlorpyrifos, diazinon, methomyl, alpha-cypermethrin, cypermethrin, gamma-cyhalothrin and endosulfan). Full dose-response bioassays on third instar larvae were performed by topical application. Lethal doses at 50% were estimated by probit analysis and resistance factors (RF) were calculated, compared to a susceptible laboratory reference strain. Resistance levels were relatively moderate until 2009, with resistance ratios below 10-fold for organophosphates and carbamates and up to 16-fold for the pyrethroid alpha-cypermethrin. However, resistance rose to 46- and 81-fold for chlorpyrifos and alpha-cypermethrin, respectively in 2010, when the resurgence of the pest was observed. None of the known pyrethroid resistance mutations were found in the pyrethroid-resistant insects. The possible association between resistance and H. armigera resurgence in Greece is discussed. © 2012 Institute of Zoology, Chinese Academy of Sciences.

  16. 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

  17. Examination of the role of dopamine D₂ and adrenergic α₂ receptors in resurgence of food seeking.

    PubMed

    Pyszczynski, Adam D; Shahan, Timothy A

    2014-09-01

    Resurgence refers to the reappearance of an extinguished operant behavior when reinforcement for an alternative behavior is also subsequently discontinued. Resurgence has been noted as a source of relapse to problem behavior following interventions involving alternative reinforcement, and has also been recently used as an animal model of relapse to drug seeking induced by reinforcement loss. Existing information about the neuropharmacology of resurgence is scarce, but suggests overlap between relapse observed in the resurgence model and relapse observed in reinstatement and renewal models. In the present experiment rats earned food pellets for pressing a target lever in Phase I. In Phase II lever pressing no longer produced food, but food was delivered for an alterative nose poke response. Finally in Phase III, neither response produced food deliveries. Prior to these Phase III sessions, separate groups of rats were injected with 0, 50, or 100 μg/kg of the dopamine D2 receptor antagonist raclopride or 0, 20, or 40 μg/kg of α 2 agonist clonidine. Both doses of raclopride were effective in blocking resurgence, but there was evidence that the higher dose did so via motor rather than motivational impairment. Only the higher dose of clonidine blocked resurgence, but did so with no evidence of motor impairment. Raclopride significantly impacted extinction of the alternative poke at both doses tested, whereas clonidine had no effect at either dose. The results of the present study provide additional information about the neuropharmacology of resurgence, as well as additional evidence of overlap between resurgence, reinstatement, and renewal.

  18. The resurgence of heroin abuse in the District of Columbia.

    PubMed

    Greene, M H

    1975-01-01

    Prospectively collected drug abuse trend surveillance data suggest that the rate of heroin use in Washington, D.C. is rising following a two year decline in the magnitude of this problem. Supportive data include increased potency of street level heroin, increased numbers of heroin-related deaths, increased detection of heroin positive urine specimens in the D.C. Superior Court arrestee population, increased demand for addiction treatment services and rising property crime rates. Increased prevalence of heroin use has not yet been associated with an increase in incidence, suggesting that former heroin users have begun to use once again following a period of abstinence. Analysis of heroin specimens seized across the United States suggests that cities formerly dependant upon European (white) heroin have now developed a new heroin distribution system which supplies Mexican (brown) heroin. This has offset the reduction in heroin use observed during 1972-1973 concomitant with the East Coast heroin shortage and widespread introduction of addiction treatment services.

  19. Open-channel block by the cytoplasmic tail of sodium channel beta4 as a mechanism for resurgent sodium current.

    PubMed

    Grieco, Tina M; Malhotra, Jyoti D; Chen, Chunling; Isom, Lori L; Raman, Indira M

    2005-01-20

    Voltage-gated sodium channels with "resurgent" kinetics are specialized for high-frequency firing. The alpha subunits interact with a blocking protein that binds open channels upon depolarization and unbinds upon repolarization, producing resurgent sodium current. By limiting classical inactivation, the cycle of block and unblock shortens refractory periods. To characterize the blocker in Purkinje neurons, we briefly exposed inside-out patches to substrate-specific proteases. Trypsin and chymotrypsin each removed resurgent current, consistent with established roles for positively charged and hydrophobic/aromatic groups in blocking sodium channels. In Purkinje cells, the only known sodium channel-associated subunit that has a cytoplasmic sequence with several positive charges and clustered hydrophobic/aromatic residues is beta4 (KKLITFILKKTREK; beta4(154-167)). After enzymatic removal of block, beta4(154-167) fully reconstituted resurgent current, whereas scrambled or point-mutated peptides were ineffective. In CA3 pyramidal neurons, which lack beta4 and endogenous block, beta4(154-167) generated resurgent current. Thus, beta4 may be the endogenous open-channel blocker responsible for resurgent kinetics.

  20. Anticancer drug oxaliplatin induces acute cooling-aggravated neuropathy via sodium channel subtype NaV1.6-resurgent and persistent current

    PubMed Central

    Sittl, Ruth; Lampert, Angelika; Huth, Tobias; Schuy, E. Theresa; Link, Andrea S.; Fleckenstein, Johannes; Alzheimer, Christian; Grafe, Peter; Carr, Richard W.

    2012-01-01

    Infusion of the chemotherapeutic agent oxaliplatin leads to an acute and a chronic form of peripheral neuropathy. Acute oxaliplatin neuropathy is characterized by sensory paresthesias and muscle cramps that are notably exacerbated by cooling. Painful dysesthesias are rarely reported for acute oxaliplatin neuropathy, whereas a common symptom of chronic oxaliplatin neuropathy is pain. Here we examine the role of the sodium channel isoform NaV1.6 in mediating the symptoms of acute oxaliplatin neuropathy. Compound and single-action potential recordings from human and mouse peripheral axons showed that cooling in the presence of oxaliplatin (30–100 μM; 90 min) induced bursts of action potentials in myelinated A, but not unmyelinated C-fibers. Whole-cell patch-clamp recordings from dissociated dorsal root ganglion (DRG) neurons revealed enhanced tetrodotoxin-sensitive resurgent and persistent current amplitudes in large, but not small, diameter DRG neurons when cooled (22 °C) in the presence of oxaliplatin. In DRG neurons and peripheral myelinated axons from Scn8amed/med mice, which lack functional NaV1.6, no effect of oxaliplatin and cooling was observed. Oxaliplatin significantly slows the rate of fast inactivation at negative potentials in heterologously expressed mNaV1.6r in ND7 cells, an effect consistent with prolonged NaV open times and increased resurgent and persistent current in native DRG neurons. This finding suggests that NaV1.6 plays a central role in mediating acute cooling-exacerbated symptoms following oxaliplatin, and that enhanced resurgent and persistent sodium currents may provide a general mechanistic basis for cold-aggravated symptoms of neuropathy. PMID:22493249

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

    PubMed

    Wang, Changlu; Wen, Xiujun

    2011-04-11

    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. Resurgence and trans-series in Quantum Field Theory: the {C}{{{P}}^{N-1 }} model

    NASA Astrophysics Data System (ADS)

    Dunne, Gerald V.; Ünsal, Mithat

    2012-11-01

    This work is a step towards a non-perturbative continuum definition of quantum field theory (QFT), beginning with asymptotically free two dimensional non-linear sigma-models, using recent ideas from mathematics and QFT. The ideas from mathematics are resurgence theory, the trans-series framework, and Borel-Écalle resummation. The ideas from QFT use continuity on {{{R}}^1}× {S}_L^1, i.e., the absence of any phase transition as N → ∞ or rapid-crossovers for finite- N, and the small- L weak coupling limit to render the semi-classical sector well-defined and calculable. We classify semi-classical configurations with actions 1 /N (kink-instantons), 2 /N (bions and bi-kinks), in units where the 2d instanton action is normalized to one. Perturbation theory possesses the IR-renormalon ambiguity that arises due to non-Borel summability of the large-orders perturbation series (of Gevrey-1 type), for which a microscopic cancellation mechanism was unknown. This divergence must be present because the corresponding expansion is on a singular Stokes ray in the complexified coupling constant plane, and the sum exhibits the Stokes phenomenon crossing the ray. We show that there is also a non-perturbative ambiguity inherent to certain neutral topological molecules (neutral bions and bion-anti-bions) in the semiclassical expansion. We find a set of "confluence equations" that encode the exact cancellation of the two different type of ambiguities. There exists a resurgent behavior in the semi-classical trans-series analysis of the QFT, whereby subleading orders of exponential terms mix in a systematic way, canceling all ambiguities. We show that a new notion of "graded resurgence triangle" is necessary to capture the path integral approach to resurgence, and that graded resurgence underlies a potentially rigorous definition of general QFTs. The mass gap and the Θ angle dependence of vacuum energy are calculated from first principles, and are in accord with large- N and lattice

  4. Caldera resurgence: new insights from the study of the Siwi-Yenkahe-Yasur system (Vanuatu)

    NASA Astrophysics Data System (ADS)

    Brothelande, E.; Lenat, J.; Merle, O.; Peltier, A.

    2013-12-01

    On Tanna Island (Vanuatu), the Siwi caldera hosts a complex association between a permanently active explosive volcano (Yasur) and one of the fastest growing resurgent dome on Earth (Yenkahe). Uplifted coral terraces and marine tuff indicate a very high resurgence rate over the past 1000 yrs (15.6 cm.yr-1) making the Yenkahe dome one of the most relevant example of active post-caldera resurgence, but also one of the most dangerous structure of that kind. New data acquired between 2008 and 2012 brought further constraints on resurgent processes involved. Tectonic patterns inferred from structural observations on satellite images and on the field, completed by a meticulous photogrammetry study, argue for a relatively extended and shallow source of deformation. Two different approaches, using analogue and numerical modeling, were developed to explore the doming effects of different sources within the first kilometers. These models provide the first quantitative estimations on the depth and the shape of the source (magmatic and/or hydrothermal) that generated the Yenkahe dome. Analysis of external surface features, such as faults patterns and collapse scars revealed by photogrammetry and field observations, also provided new data for proposing hypotheses of a multi-step construction of the Yenkahe and discussing the potential instabilities of the dome, notably on the shore-bordering eastern flank. Geophysical investigations, combining electrical methods (T.D.E.M., E.R.T., S.P.), gravimetry and magnetism, were performed providing a wide range of information in terms of internal structure. Lithology units can be distinguished at different scales, and tectonic features connected to the surface can be defined. Conductive bodies representing the hydrothermal system can be located in relationship with these features, broaching the question of a possible phreatic or phreato-magmatic activity in the future. The combination of a wide panel of methods brings here a new image on

  5. Resurgence of Cutaneous Leishmaniasis in Israel, 2001–2012

    PubMed Central

    Gandacu, Dan; Anis, Emilia; Karakis, Isabella; Warshavsky, Bruce; Slater, Paul; Grotto, Itamar

    2014-01-01

    Cutaneous leishmaniasis has long been endemic in Israel. After a 15-year period of moderate illness rates, reported incidence increased from 0.4 cases per 100,000 population in 2001 to 4.4 cases per 100,000 population in 2012, and the disease emerged in areas where its presence had previously been minimal. We analyzed all cases reported to the national surveillance system and found that outbreak patterns revealed an expansion of Leishmania major infections over large areas in the southern part of the country and the occurrence of spatially focused L. tropica outbreaks in the northern part of the country. Outbreaks often followed new construction in populated areas. Further study of factors affecting the transmission of cutaneous leishmaniasis is needed in Israel, as well as the development of effective methods to control the disease, an increase in awareness among health care professionals, and intensive public education regarding control measures in areas of known leishmaniasis foci. PMID:25271882

  6. 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.

  7. Resurgence of vivax malaria in Henan Province, China.

    PubMed Central

    Sleigh, A. C.; Liu, X. L.; Jackson, S.; Li, P.; Shang, L. Y.

    1998-01-01

    Henan Province (population, 90 million) in China has nonstable endemic malaria. After 1970 when 10.2 million cases of malaria were reported in the province, a huge control programme was undertaken, and in the mid-1980s indoor spraying and bednet impregnation with pyrethroids began. By 1992 only 318 cases were reported. In 1992 Henan declared "basic elimination of malaria" and in consequence spraying and bednet impregnation ceased after 1994. Subsequently, malaria broke out again in southern Henan. In 1995 we conducted a household survey for malaria transmission in southern Henan. Blood smears and serum samples for immunofluorescent antibody (IFA) testing were collected from 2329 people and 3.1% (73/2329) were positive for infection with Plasmodium vivax and 13% (301/2329) positive for malaria (titre > or = 1:20). All age groups were affected. Exophilic Anopheles sinensis occurs throughout the province; endo-anthropophilic A. anthropophagus, whose vectorial capacity is 20 times greater than that of A. sinensis, occurs mainly in southern Henan (S of latitude 33 degrees N) and was greatly reduced in numbers during 1985-92. Comparison of 1995 entomological data with historical data showed that A. anthropophagus increased in proportion to other anophelines after spraying activities and impregnation of bednets ceased. Over 10% of 9377 residents reported having malaria. The true number affected among the at-risk population of 700,000 must be larger. We conclude that impregnated bednets and malaria surveillance should continue even after an area is declared to have "basically eliminated" malaria. PMID:9744246

  8. 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

  9. Explaining the resurgent popularity of the wild: motivations for wild plant gathering in the Biosphere Reserve Grosses Walsertal, Austria.

    PubMed

    Schunko, Christoph; Grasser, Susanne; Vogl, Christian R

    2015-06-30

    Wild plant gathering becomes again a popular and fashionable activity in Europe after gathering practices have been increasingly abandoned over the last decades. Recent ethnobotanical research documented a diversity of gathering practices from people of diverse socio-economic and cultural backgrounds who gather in urban and rural areas. Few efforts were though made to study the motivations for gathering wild plants and to understand the resurgent popularity of wild plant gathering. This paper addresses the following research questions: (1) which motivations activate wild plant gatherers? (2) which motivation-types of gatherers exist in the Grosses Walsertal? (3) how do the motivations for gathering relate to the socio-demographic background of gatherers? Field research was conducted in the Grosses Walsertal, Austria in the years 2008 and 2009 in two field research periods. Thirty-six local farmers were first interviewed with semi-structured interviews. The motivations identified in these interviews were then included in a structured questionnaire, which was used to interview 353 residents of the valley. Pupils of local schools participated in the data collection as interviewers. Principal Component Analysis was used to categorize the motivations and to identify motivation-types of wild plant gatherers. Generalized Linear Models were calculated to identify relations between motivations and the socio-demographic background of gatherers. The respondents listed 13 different motivations for gathering wild plants and four motivations for not gathering. These 17 motivations were grouped in five motivation-types of wild plant gatherers, which are in decreasing importance: product quality, fun, tradition, not-gathering, income. Women, older respondents and homegardeners gather wild plants more often for fun; older respondents gather more often for maintaining traditions; non-homegardeners more frequently mention motivations for not gathering. The resurgent popularity of

  10. Three cases of ocular syphilis and the resurgence of the disease in Queensland

    PubMed Central

    Sara, Sergio A; McAllister, Andrew S

    2016-01-01

    The past few years has seen a resurgence of syphilis. It is predominantly associated within men who have sex with men and also within heterosexual Indigenous Australians. Possessing the ability to mimic a variety of ocular diseases, it typically manifests as uveitis, although it can affect any structure within the eye. Thus, a high degree of clinical suspicion by ophthalmologists is required to prevent disease progression and ocular morbidity. Patients require prolonged antibiotic treatment with intravenous benzylpenicillin and outpatient monitoring to successfully resolve the infection. We describe a case series of ocular syphilis presentations in Queensland, Australia. PMID:27672343

  11. Moving From the Old to the New: Insecticide Research on Bed Bugs since the Resurgence.

    PubMed

    Romero, Alvaro

    2011-05-05

    The scarcity of bed bugs in many countries over the last 50 years has resulted in a lack of modern research into the toxicology of this pest. Although bed bugs resurged in the late 1990s, published research related to insecticides has lagged behind and only began to appear in 2006. The difficulty in controlling bed bugs triggered the interest of both private and academic sectors to determine the value of currently available insecticides. What follows, is updated information on effectiveness of products, studies on insecticide susceptibility, identification of mechanisms of insecticide resistance and chemical strategies proposed to overcome resistance in modern bed bug populations.

  12. Moving From the Old to the New: Insecticide Research on Bed Bugs since the Resurgence

    PubMed Central

    Romero, Alvaro

    2011-01-01

    The scarcity of bed bugs in many countries over the last 50 years has resulted in a lack of modern research into the toxicology of this pest. Although bed bugs resurged in the late 1990s, published research related to insecticides has lagged behind and only began to appear in 2006. The difficulty in controlling bed bugs triggered the interest of both private and academic sectors to determine the value of currently available insecticides. What follows, is updated information on effectiveness of products, studies on insecticide susceptibility, identification of mechanisms of insecticide resistance and chemical strategies proposed to overcome resistance in modern bed bug populations. PMID:26467623

  13. 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.

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

    PubMed

    Sainz-Elipe, Sandra; Latorre, Jose Manuel; Escosa, Raul; Masià, Montserrat; Fuentes, Marius Vicent; Mas-Coma, Santiago; Bargues, Maria Dolores

    2010-07-31

    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. 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. 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. The Ebro Delta presents the ecological characteristics that favour

  15. 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

  16. Carbon Dioxide Emissions From Kill Zones Around the Resurgent Dome, Long Valley Caldera, CA

    NASA Astrophysics Data System (ADS)

    Bergfeld, D.; Evans, W. C.; Farrar, C. D.; Howle, J. F.

    2004-12-01

    An episode of seismic unrest beneath the resurgent dome at Long Valley caldera (LVC) in eastern California began in 1980 and is associated with approximately 80 cm of cumulative uplift on parts of the dome since that time. Studies of hydrologic and geochemical parameters can be useful in determining the source of uplift; and of particular relevance here, studies of diffuse soil degassing and temperature have been used to examine relations between gas emissions, uplift, and energy release. We present results from an eighteen-month investigation of soil temperature, soil-gas chemistry and CO2 efflux from fourteen discrete areas of vegetation kill that have appeared inside the caldera over the past two decades. Compared with the tree-kill around Mammoth Mountain on the southwest rim of the caldera, dead zones we studied around the resurgent dome are small. Individually the areas cover between 800 and 36,000 m2. All of the areas have some sites with elevated CO2 flux and elevated soil temperature. \\delta 13C values of CO2 from sites in eight of the studied areas are between -5.7 and -3.9\\permil, and are within the range of magmatic CO2. Results from the flux measurements indicate that on average total CO2 emissions from four of the areas sum about 10 tonnes per day. The other vegetation kill areas currently have only a few sites that exhibit anomalous soil temperatures and CO2 flux, and CO2 emissions from these areas are typically less than 0.3 of a tonne per day. The chemical composition of gas emissions from thermal ground in kill zones located 1.5 to 2 km northwest of the Casa Diablo geothermal power plant demonstrate a connection between some of the dead areas and perturbations related to geothermal fluid production. These results and estimates of thermal output from two of the high flux grids are used to evaluate the premise that the gaseous and thermal anomalies are related to magmatic intrusion beneath the resurgent dome.

  17. On the Singularity Structure of WKB Solution of the Boosted Whittaker Equation: its Relevance to Resurgent Functions with Essential Singularities

    NASA Astrophysics Data System (ADS)

    Kamimoto, Shingo; Kawai, Takahiro; Koike, Tatsuya

    2016-12-01

    Inspired by the symbol calculus of linear differential operators of infinite order applied to the Borel transformed WKB solutions of simple-pole type equation [Kamimoto et al. (RIMS Kôkyûroku Bessatsu B 52:127-146, 2014)], which is summarized in Section 1, we introduce in Section 2 the space of simple resurgent functions depending on a parameter with an infra-exponential type growth order, and then we define the assigning operator A which acts on the space and produces resurgent functions with essential singularities. In Section 3, we apply the operator A to the Borel transforms of the Voros coefficient and its exponentiation for the Whittaker equation with a large parameter so that we may find the Borel transforms of the Voros coefficient and its exponentiation for the boosted Whittaker equation with a large parameter. In Section 4, we use these results to find the explicit form of the alien derivatives of the Borel transformed WKB solutions of the boosted Whittaker equation with a large parameter. The results in this paper manifest the importance of resurgent functions with essential singularities in developing the exact WKB analysis, the WKB analysis based on the resurgent function theory. It is also worth emphasizing that the concrete form of essential singularities we encounter is expressed by the linear differential operators of infinite order.

  18. Resurgence in quantum field theory: nonperturbative effects in the principal chiral model.

    PubMed

    Cherman, Aleksey; Dorigoni, Daniele; Dunne, Gerald V; Ünsal, Mithat

    2014-01-17

    We explain the physical role of nonperturbative saddle points of path integrals in theories without instantons, using the example of the asymptotically free two-dimensional principal chiral model (PCM). Standard topological arguments based on homotopy considerations suggest no role for nonperturbative saddles in such theories. However, the resurgence theory, which unifies perturbative and nonperturbative physics, predicts the existence of several types of nonperturbative saddles associated with features of the large-order structure of the perturbation theory. These points are illustrated in the PCM, where we find new nonperturbative "fracton" saddle point field configurations, and suggest a quantum interpretation of previously discovered "uniton" unstable classical solutions. The fractons lead to a semiclassical realization of IR renormalons in the circle-compactified theory and yield the microscopic mechanism of the mass gap of the PCM.

  19. Preparation for malaria resurgence in China: approach in risk assessment and rapid response.

    PubMed

    Qian, Ying-Jun; Zhang, Li; Xia, Zhi-Gui; Vong, Sirenda; Yang, Wei-Zhong; Wang, Duo-Quan; Xiao, Ning

    2014-01-01

    With the shrinking of indigenous malaria cases and endemic areas in the People's Republic of China (P.R. China), imported malaria predominates over all reported cases accounting for more than 90% of the total. On the way to eliminate malaria, prompt detection and rapid response to the imported cases are crucial for the prevention of secondary transmission in previous endemic areas. Through a comprehensive literature review, this chapter aims to identify risk determinants of potential local transmission caused by the imported malaria cases and discusses gaps to be addressed to reach the elimination goal by 2020. Current main gaps with respect to dealing with potential malaria resurgence in P.R. China include lack of cross-sectoral cooperation, lack of rapid response and risk assessment, poor public awareness, and inadequate research and development in the national malaria elimination programme. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Entropy production, hydrodynamics, and resurgence in the primordial quark-gluon plasma from holography

    NASA Astrophysics Data System (ADS)

    Buchel, Alex; Heller, Michal P.; Noronha, Jorge

    2016-11-01

    Microseconds after the Big Bang quarks and gluons formed a strongly coupled nonconformal liquid driven out of equilibrium by the expansion of the Universe. We use holography to determine the nonequilibrium behavior of this liquid in a Friedmann-Lemaître-Robertson-Walker universe and develop an expansion for the corresponding entropy production in terms of the derivatives of the cosmological scale factor. We show that the resulting series has zero radius of convergence and we discuss its resurgent properties. Finally, we compute the resummed entropy production rate in a de Sitter universe at late times and show that the leading order approximation given by bulk viscosity effects can strongly overestimate/underestimate the rate depending on the microscopic parameters.

  1. Preliminary geologic studies of Sierra El Aguajito (Baja California, Mexico): a resurgent-type caldera

    NASA Astrophysics Data System (ADS)

    Garduño-Monroy, V. H.; Vargas-Ledezma, H.; Campos-Enriquez, J. O.

    1993-12-01

    Geologic field studies conducted in the Quaternary volcanic field of Tres Virgenes (State of Baja California Sur, Mexico) revealed the existence of a resurgent caldera. The caldera's eruptive products, the Aguajito sequence, overlie the products of the nearby Reforma caldera (Reforma sequence) whose youngest products have already been dated as Quaternary. The rim of the Aguajito caldera is inferred by the existence of an arcuate alignment of rhyolitic domes. The mean diameter of this subcircular feature is 10 km. The volume of its mapped acidic products is a minimum of 10 km 3. Several horizons within the sequence contain shells. K/Ar dates of the ignimbrites and domes of El Aguajito formation confirm that the unit are Pleistocene. The detailed stratigraphy also shows the evolution of a marine regression partly related to the caldera.

  2. 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

  3. 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.

  4. Operant models of relapse in zebrafish (Danio rerio): Resurgence, renewal, and reinstatement.

    PubMed

    Kuroda, Toshikazu; Mizutani, Yuto; Cançado, Carlos R X; Podlesnik, Christopher A

    2017-09-29

    Zebrafish are a widely used animal model in biomedical research, as an alternative to mammals, for having features such as a fully sequenced genome, high fecundity, and low-cost maintenance, but behavioral research with these fish remains scarce. The present study investigated whether zebrafish could be a new animal model for studies on the relapse of behavior (e.g., addiction and overeating) after the behavior has been extinguished. Specifically, we examined whether zebrafish would show three different types of relapse commonly studied with other species: resurgence, renewal, and reinstatement. For resurgence, a target response (i.e., approaching a sensor) was established by presenting a reinforcer (i.e., shrimp eggs) contingent upon the response in Phase 1; the target response was extinguished while introducing reinforcement for an alternative response in Phase 2; neither response produced the reinforcer in Phase 3. For renewal, a target response was established under Context A in Phase 1 and was extinguished under Context B in Phase 2; the fish were placed back in Context A in Phase 3, where extinction remained in effect. For reinstatement, a target response was established in Phase 1 and was extinguished in Phase 2; the reinforcer was presented independently of responding in Phase 3. Each type of relapse occurred in Phase 3. These results replicate and extend previous findings on relapse to a new species and suggest that zebrafish can be a useful animal model for studying the interactions of biological and environmental factors that lead to relapse. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. Early postcaldera rhyolite and structural resurgence at Long Valley Caldera, California

    NASA Astrophysics Data System (ADS)

    Hildreth, Wes; Fierstein, Judy; Calvert, Andrew

    2017-04-01

    After the 767-ka caldera-forming eruption of 650 km3 of rhyolite magma as the Bishop Tuff, 90-100 km3 of similar rhyolite erupted in the west-central part of Long Valley caldera in as many as 40 batches spread over the 110,000-year interval from 750 ka to 640 ka. Centrally, this Early Rhyolite (ER) is as thick as 622 m, but it spread radially to cover much of the caldera floor, where half its area is now concealed by post-ER sediments and lavas. At least 75% of the ER is aphyric rhyolite tuff. Drillholes encountered 22 (altered) ER lava flows intercalated in the pyroclastic pile, and another 11 units of (largely fresh) ER lava are exposed on the caldera's resurgent dome and at Lookout Mountain. Exposed units have been distinguished, mapped, studied petrographically and chemically, and radioisotopically dated; each is described in detail. Their phenocryst contents range from 0 to 2.5 wt%. All the phyric units have plagioclase, orthopyroxene, and ilmenite; most have biotite and rare tiny magnetite, and a few contain rare zircon. The compositional range of fresh obsidians is narrow-74.3-75.0% SiO2, 1.21-1.37% FeO*, and 5.12-5.26% K2O, but wider variations in Ti, Ba, Sr, and Zr permit distinction of individual units and eruptive groups. The limited chemical and petrographic variability shown by so many ER batches released episodically for 110,000 years suggests a thermally buffered and well-stirred reservoir. The ER central area, where ER eruptions had taken place, was uplifted 400 m to form a structural dome 10 km in diameter. Most of the inflation is attributable to 10 sills of ER that intrude the Bishop Tuff beneath the uplift, but other processes potentially contributing to resurgence are also considered. As shown by erratics of Mesozoic rocks ice-rafted from the Sierra Nevada and dropped on ER lavas, much of the ER had erupted early enough and at low enough elevation to be inundated by the intracaldera lake and was only later lifted by the resurgence that also

  10. Quality of life after videoscopic left cardiac sympathetic denervation in patients with potentially life-threatening cardiac channelopathies/cardiomyopathies.

    PubMed

    Antiel, Ryan M; Bos, J Martijn; Joyce, Daniel D; Owen, Heidi J; Roskos, Penny L; Moir, Christopher; Ackerman, Michael J

    2016-01-01

    Left cardiac sympathetic denervation (LCSD) provides an additive or potentially alternative treatment option for patients with life-threatening cardiac channelopathies/cardiomyopathies. We sought to examine the effects of LCSD on quality of life (QOL). From November 2005 to May 2013, 109 patients who underwent LCSD were subsequently sent postoperative QOL surveys. Of 109 patients, 8 (7%) could not be contacted. Of the remaining 101 patients, 62 returned surveys (response rate 61%). There were an average of 4.1 ± 1.8 self-reported side effects immediately after LCSD. The most common anticipated side effects included unilateral hand dryness, color or temperature variance between sides of the face, and abnormal sweating. Although parent-reported pediatric physical QOL scores were lower than national norms, there were no differences in psychosocial QOL or disability scores (P = .09 and .33, respectively). QOL scores for adult patients were not significantly different from a US normative sample. Adult LCSD patients reported less disability than a US normative sample (P < .01). There was no correlation between QOL scores and the presence of anticipated side effects. However, among the subset of pediatric patients who continued to receive ventricular fibrillation-terminating implantable cardioverter-defibrillator shocks after LCSD, there was a correlation between their disability scores and the number of reported shocks (Spearman correlation = 0.56). The majority of patients/parents reported that they were very or somewhat satisfied with their surgery (or their child's surgery) and would definitely or probably recommend LCSD to another patient. Despite the anticipated side effects associated with LCSD, patients are satisfied with their surgery and indicate that they would recommend the surgery to another patient. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  11. The relationship between mucosal immunity, nasopharyngeal carriage, asymptomatic transmission and the resurgence of Bordetella pertussis

    PubMed Central

    Gill, Christopher; Rohani, Pejman; Thea, Donald M

    2017-01-01

    The incidence of whooping cough in the US has been rising slowly since the 1970s, but the pace of this has accelerated sharply since acellular pertussis vaccines replaced the earlier whole cell vaccines in the late 1990s. A similar trend occurred in many other countries, including the UK, Canada, Australia, Ireland, and Spain, following the switch to acellular vaccines. The key question is why. Two leading theories (short duration of protective immunologic persistence and evolutionary shifts in the pathogen to evade the vaccine) explain some but not all of these shifts, suggesting that other factors may also be important. In this synthesis, we argue that sterilizing mucosal immunity that blocks or abbreviates the duration of nasopharyngeal carriage of Bordetella pertussis and impedes person-to-person transmission (including between asymptomatically infected individuals) is a critical factor in this dynamic. Moreover, we argue that the ability to induce such mucosal immunity is fundamentally what distinguishes whole cell and acellular pertussis vaccines and may be pivotal to understanding much of the resurgence of this disease in many countries that adopted acellular vaccines. Additionally, we offer the hypothesis that observed herd effects generated by acellular vaccines may reflect a modification of disease presentation leading to reduced potential for transmission by those already infected, as opposed to inducing resistance to infection among those who have been exposed. PMID:28928960

  12. The bear awakens: Resurgence of oil and gas in the former Soviet Union

    SciTech Connect

    Foreman, N.E.

    1996-12-31

    Since dissolution of the Soviet Union (USSR) in late 1991, the oil and gas industries in the 15 component nations have been in a state of turmoil stemming mainly from past communist management practices and the transition to Western-style market economies and multiparty governments. As a result, oil and gas output have fallen dramatically. This study incorporates separate oil and gas production forecasts, predicted independently by onshore and offshore sectors, for each of the producing republics of the Former Soviet Union (FSU) over the period 1996-2005. Supply--assessed by full-cycle resource analysis--and demand, estimated from available historic and projected consumption figures, are balanced to yield a coherent picture. Production of both oil and gas for the FSU is forecast to recover strongly. Oil and condensate output--led by Russia, Kazakhstan, and Azerbaijan--are forecast to rebound to 9,545 MBOPD by 2005, which will reinstate the FSU as one of the world`s premier crude exporting blocs. Natural gas output--propelled by gains in Russia, Turkmenistan, and Uzbekistan--will likewise resurge, reaching a world-leading 96,051 MMCFD level, of which a large amount will be exported.

  13. Universality of the topological string at large radius and NS-brane resurgence

    NASA Astrophysics Data System (ADS)

    Couso-Santamaría, Ricardo

    2017-02-01

    We show that there is a natural universal limit of the topological string free energies at the large radius point. The new free energies keep a nonholomorphic dependence on the complex structure moduli space and their functional form is the same for all Calabi-Yau geometries, compact and noncompact alike. The asymptotic nature of the free energy expansion changes in this limit due to a milder factorial growth of its coefficients, and this implies a transseries extension with instanton effects in exp (- 1/g_s^2), of NS-brane type, rather than exp (-1/g_s), of D-brane type. We show a relation between the instanton action of NS-brane type and the volume of the Calabi-Yau manifold which points to a possible interpretation in terms of NS5-branes. A similar rescaling limit has been considered recently leading to an Airy equation for the partition function which is here used to explain the resurgent properties of the rescaled transseries.

  14. Resurgence of Progressive Massive Fibrosis in Coal Miners - Eastern Kentucky, 2016.

    PubMed

    Blackley, David J; Crum, James B; Halldin, Cara N; Storey, Eileen; Laney, A Scott

    2016-12-16

    Coal workers' pneumoconiosis, also known as "black lung disease," is an occupational lung disease caused by overexposure to respirable coal mine dust. Inhaled dust leads to inflammation and fibrosis in the lungs, and coal workers' pneumoconiosis can be a debilitating disease. The Federal Coal Mine Health and Safety Act of 1969 (Coal Act),* amended in 1977, established dust limits for U.S. coal mines and created the National Institute for Occupational Safety and Health (NIOSH)-administered Coal Workers' Health Surveillance Program with the goal of reducing the incidence of coal workers' pneumoconiosis and eliminating its most severe form, progressive massive fibrosis (PMF),(†) which can be lethal. The prevalence of PMF fell sharply after implementation of the Coal Act and reached historic lows in the 1990s, with 31 unique cases identified by the Coal Workers' Health Surveillance Program during 1990-1999. Since then, a resurgence of the disease has occurred, notably in central Appalachia (Figure 1) (1,2). This report describes a cluster of 60 cases of PMF identified in current and former coal miners at a single eastern Kentucky radiology practice during January 2015-August 2016. This cluster was not discovered through the national surveillance program. This ongoing outbreak highlights an urgent need for effective dust control in coal mines to prevent coal workers' pneumoconiosis, and for improved surveillance to promptly identify the early stages of the disease and stop its progression to PMF.

  15. Amplitude death and resurgence of oscillation in networks of mobile oscillators

    NASA Astrophysics Data System (ADS)

    Majhi, Soumen; Ghosh, Dibakar

    2017-05-01

    The phenomenon of amplitude death has been explored using a variety of different coupling strategies in the last two decades. In most of the works, the basic coupling arrangement is considered to be static over time, although many realistic systems exhibit significant changes in the interaction pattern as time varies. In this article, we study the emergence of amplitude death in a dynamical network composed of time-varying interaction amidst a collection of random walkers in a finite region of three-dimensional space. We consider an oscillator for each walker and demonstrate that depending upon the network parameters and hence the interaction between them, the global oscillation in the network gets suppressed. In this framework, the vision range of each oscillator decides the number of oscillators with which it interacts. In addition, with the use of an appropriate feedback parameter in the coupling strategy, we articulate how the suppressed oscillation can be resurrected in the systems' parameter space. The phenomenon of amplitude death and the resurgence of oscillation is investigated taking limit cycle and chaotic oscillators for broad ranges of the parameters, like the interaction strength k between the entities, the vision range r and the speed of movement v.

  16. The lethal ovitrap: a response to the resurgence of dengue and chikungunya.

    PubMed

    Zeichner, Brian C; Debboun, Mustapha

    2011-01-01

    There has been a global resurgence in dengue fever since the 1960s and now more than one third of the world's population lives in dengue endemic areas. Chikungunya, another mosquito-borne disease, had been limited to sub-Saharan Africa and Southeast Asia, but recently spread to Italy and France, raising concerns that it could spread to many more countries in Europe and the Americas. There are currently no vaccines available to prevent infection with either virus and medical care is limited to symptomatic and supportive treatments. Suppression of the mosquito vector populations reduces disease transmission, however, the tools currently available to control the main vectors of dengue and chikungunya are inadequate. Larval control is very labor intensive and pesticide sprays do not adequately penetrate the microhabitats where adult mosquitoes are sequestered. The lethal ovitrap addresses these shortcomings by luring the potentially viremic female mosquitoes to an egg laying site where they are exposed to a toxic insecticide dose. It is a safe, environmentally sound, economical, and simple means of dengue and chikungunya vector control whose efficacy has been documented in 9 research papers. Management programs using the lethal ovitrap have been shown to halt dengue and chikungunya transmission. Efforts are underway to mass produce the lethal ovitrap under the registered trade name Trap-N-Kill which will ensure its availability to our armed forces deployed in dengue and chikungunya endemic areas.

  17. Relapse processes after the extinction of instrumental learning: Renewal, resurgence, and reacquisition

    PubMed Central

    Bouton, Mark E.; Winterbauer, Neil E.; Todd, Travis P.

    2012-01-01

    It is widely recognized that extinction (the procedure in which a Pavlovian conditioned stimulus or an instrumental action is repeatedly presented without its reinforcer) weakens behavior without erasing the original learning. Most of the experiments that support this claim have focused on several “relapse” effects that occur after Pavlovian extinction, which collectively suggest that the original learning is saved through extinction. However, although such effects do occur after instrumental extinction, they have not been explored there in as much detail. This article reviews recent research in our laboratory that has investigated three relapse effects that occur after the extinction of instrumental (operant) learning. In renewal, responding returns after extinction when the behavior is tested in a different context; in resurgence, responding recovers when a second response that has been reinforced during extinction of the first is itself put on extinction; and in rapid reacquisition, extinguished responding returns rapidly when the response is reinforced again. The results provide new insights into extinction and relapse, and are consistent with principles that have been developed to explain extinction and relapse as they occur after Pavlovian conditioning. Extinction of instrumental learning, like Pavlovian learning, involves new learning that is relatively dependent on the context for expression. PMID:22450305

  18. 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 Central

    Shahab, M.; Trujillo, M. Vargas

    2015-01-01

    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

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. Volcanic and deformation history of the Bodrum resurgent caldera system (southwestern Turkey)

    NASA Astrophysics Data System (ADS)

    Ulusoy, I.; Cubukcu, E.; Aydar, E.; Labazuy, P.; Gourgaud, A.; Vincent, P. M.

    2004-08-01

    The volcanic rocks of the Bodrum Peninsula, in SW Turkey and NE of the Hellenic Arc, outcrop over an area of 138 km 2. A monzonitic intrusion is exposed in the western part of the peninsula. Upper Miocene volcanism is represented by high-K (HK)-andesitic, andesitic lava flows and pillows, sparse HK-andesitic and dacitic lava domes and associated block-and-ash flows. A HK-andesitic ignimbrite sequence with two stratigraphic units is associated with the collapse of a complex caldera system. Breccias, formed as a result of slumping of the caldera walls are observed inside the caldera. Post-caldera activity is represented by HK-andesitic, HK-basaltic andesitic lava flows, domes and associated block-and-ash flows. Numerous dykes, HK-andesitic and shoshonitic in composition cut all volcanic units. The structure of the Bodrum caldera was investigated using SPOT image, digital elevation model (DEM), aerial photographs as well as field data. The Bodrum caldera is a NE-SW-elongated, semi-elliptical, deeply eroded caldera with dimensions of 18.7×7.7 km. It is partly submerged in the SW part. The complex caldera system can be described in terms of two structural domains. The collapse of the Dagbelen domain is interpreted as a piston type subsidence, while the Karakaya domain represents a piecemeal collapse. Both domains exhibit two separate resurgence events. The elongation of the caldera may be related to pre-existing regional tectonic structures. The caldera is also affected and cut by late stage faults related to regional extensional events. Moreover, pre-caldera volcanism is dispersed and cannot be related to a pre-existing stratovolcano. Bodrum volcanism is therefore interpreted as a complex ignimbritic shield volcano.

  4. 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

  5. Mislocalization of h channel subunits underlies h channelopathy in temporal lobe epilepsy

    PubMed Central

    Shin, Minyoung; Brager, Darrin; Jaramillo, Thomas C.; Johnston, Daniel; Chetkovich, Dane M.

    2008-01-01

    Many animal models of temporal lobe epilepsy (TLE) begin with status epilepticus (SE) followed by a latency period. Increased hippocampal pyramidal neuron excitability may contribute to seizures in TLE. Ih, mediated by h channels, regulates intrinsic membrane excitability by modulating synaptic integration and dampening dendritic calcium signaling. In a rat model of TLE, we found bidirectional changes in h channel function in CA1 pyramidal neurons. 1–2 days after SE, before onset of spontaneous seizures, physiological parameters dependent upon h channels were augmented and h channel subunit surface expression was increased. 28–30 days following SE, after onset of spontaneous seizures, h channel function in dendrites was reduced, coupled with diminished h channel subunit surface expression and relocalization of subunits from distal dendrites to soma. These results implicate h channel localization as a molecular mechanism influencing CA1 excitability in TLE. PMID:18657617

  6. Nav1.7 mutations associated with paroxysmal extreme pain disorder, but not erythromelalgia, enhance Navbeta4 peptide-mediated resurgent sodium currents.

    PubMed

    Theile, Jonathan W; Jarecki, Brian W; Piekarz, Andrew D; Cummins, Theodore R

    2011-02-01

    Abnormal pain sensitivity associated with inherited and acquired pain disorders occurs through increased excitability of peripheral sensory neurons in part due to changes in the properties of voltage-gated sodium channels (Navs). Resurgent sodium currents (I(NaR)) are atypical currents believed to be associated with increased excitability of neurons and may have implications in pain. Mutations in Nav1.7 (peripheral Nav isoform) associated with two genetic pain disorders, inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEPD), enhance Nav1.7 function via distinct mechanisms. We show that changes in Nav1.7 function due to mutations associated with PEPD, but not IEM, are important in I(NaR) generation, suggesting that I(NaR) may play a role in pain associated with PEPD. This knowledge provides us with a better understanding of the mechanism of I(NaR) generation and may lead to the development of specialized treatment for pain disorders associated with I(NaR).

  7. 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

  8. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2006-04-01

    A survey of diffuse CO 2 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 CO 2 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 CO 2 range from - 5.7‰ to - 3.4‰, similar to values previously reported for CO 2 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 CO 2 concentration in the thermal fluids, the heat and CO 2 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.

  10. Analysis of resurgent sodium-current expression in rat parahippocampal cortices and hippocampal formation.

    PubMed

    Castelli, Loretta; Nigro, Maximiliano J; Magistretti, Jacopo

    2007-08-13

    The resurgent Na(+) current (I(NaR)) is a component of neuronal voltage-dependent Na(+) currents that is activated by repolarization and is believed to result from an atypical path of Na(+)-channel recovery from inactivation. So far, I(NaR) has only been identified in a small number of central neuronal populations in the cerebellum, diencephalon, and brainstem. The possible presence and roles of I(NaR) in neurons of the cerebral cortex and temporal-lobe memory system are still uncharacterized. In this study whole-cell, patch-clamp experiments were carried out in acute rat brain slices to investigate I(NaR) expression and properties in several neuronal populations of the parahippocampal region and hippocampal formation. Specifically, we examined pyramidal neurons of perirhinal cortex areas 36 and 35 (layers II and V); neurons of superficial and deep layers of medial entorhinal cortex (mEC); dentate gyrus (DG) granule cells; and pyramidal cells of the CA3 and CA1 hippocampal fields. I(NaR) was found to be thoroughly expressed in parahippocampal cortices. The most consistent and prominent I(NaR) expression was observed in mEC layer-II cells. A vast majority of areas 36 and 35 neurons (both in layers II and V) and mEC layer-III and -V neurons were also endowed with I(NaR), although at lower amplitude levels. I(NaR) was expressed by approximately 60% of DG granule cells and approximately 35% of CA1 pyramidal cells of the ventral hippocampus, whereas it was never observed in CA3 neurons (both in the ventral and dorsal hippocampus) and CA1 neurons of the dorsal hippocampus. The biophysical properties of I(NaR) were very similar in all of the neuronal types in which the current was observed, with a peak in the current-voltage relationship at -35/-40 mV. Our results show that the parahippocampal region and part of the hippocampal formation are sites of major I(NaR) expression, and provide a new basis for further studies on the molecular correlates of I(NaR).

  11. Channelopathies, painful neuropathy, and diabetes: which way does the causal arrow point?

    PubMed

    Hoeijmakers, Janneke G J; Faber, Catharina G; Merkies, Ingemar S J; Waxman, Stephen G

    2014-10-01

    Diabetes mellitus, a major global health problem, is commonly associated with painful peripheral neuropathy, which can substantially erode quality of life. Despite its clinical importance, the pathophysiology of painful diabetic neuropathy is incompletely understood. It has traditionally been thought that diabetes may cause neuropathy in patients with appropriate genetic makeup. Here, we propose a hypothesis whereby painful neuropathy is not a complication of diabetes, but rather occurs as a result of mutations that, in parallel, confer vulnerability to injury in pancreatic β cells and pain-signaling dorsal root ganglion (DRG) neurons. We suggest that mutations of sodium channel NaV1.7, which is present in both cell types, may increase susceptibility for development of diabetes via β cell injury and produce painful neuropathy via a distinct effect on DRG neurons.

  12. Multidisciplinary study of a new ClC-1 mutation causing myotonia congenita: a paradigm to understand and treat ion channelopathies

    PubMed Central

    Imbrici, Paola; Altamura, Concetta; Camerino, Giulia Maria; Mangiatordi, Giuseppe Felice; Conte, Elena; Maggi, Lorenzo; Brugnoni, Raffaella; Musaraj, Kejla; Caloiero, Roberta; Alberga, Domenico; Marsano, Renè Massimiliano; Ricci, Giulia; Siciliano, Gabriele; Nicolotti, Orazio; Mora, Marina; Bernasconi, Pia; Desaphy, Jean-Francois; Mantegazza, Renato; Camerino, Diana Conte

    2016-01-01

    Myotonia congenita is an inherited disease that is characterized by impaired muscle relaxation after contraction caused by loss-of-function mutations in the skeletal muscle ClC-1 channel. We report a novel ClC-1 mutation, T335N, that is associated with a mild phenotype in 1 patient, located in the extracellular I-J loop. The purpose of this study was to provide a solid correlation between T335N dysfunction and clinical symptoms in the affected patient as well as to offer hints for drug development. Our multidisciplinary approach includes patch-clamp electrophysiology on T335N and ClC-1 wild-type channels expressed in tsA201 cells, Western blot and quantitative PCR analyses on muscle biopsies from patient and unaffected individuals, and molecular dynamics simulations using a homology model of the ClC-1 dimer. T335N channels display reduced chloride currents as a result of gating alterations rather than altered surface expression. Molecular dynamics simulations suggest that the I-J loop might be involved in conformational changes that occur at the dimer interface, thus affecting gating. Finally, the gene expression profile of T335N carrier showed a diverse expression of K+ channel genes, compared with control individuals, as potentially contributing to the phenotype. This experimental paradigm satisfactorily explained myotonia in the patient. Furthermore, it could be relevant to the study and therapy of any channelopathy.—Imbrici, P., Altamura, C., Camerino, G. M., Mangiatordi, G. F., Conte, E., Maggi, L., Brugnoni, R., Musaraj, K., Caloiero, R., Alberga, D., Marsano, R. M., Ricci, G., Siciliano, G., Nicolotti, O., Mora, M., Bernasconi, P., Desaphy, J.-F., Mantegazza, R., Camerino, D. C. Multidisciplinary study of a new ClC-1 mutation causing myotonia congenita: a paradigm to understand and treat ion channelopathies. PMID:27324117

  13. Multidisciplinary study of a new ClC-1 mutation causing myotonia congenita: a paradigm to understand and treat ion channelopathies.

    PubMed

    Imbrici, Paola; Altamura, Concetta; Camerino, Giulia Maria; Mangiatordi, Giuseppe Felice; Conte, Elena; Maggi, Lorenzo; Brugnoni, Raffaella; Musaraj, Kejla; Caloiero, Roberta; Alberga, Domenico; Marsano, Renè Massimiliano; Ricci, Giulia; Siciliano, Gabriele; Nicolotti, Orazio; Mora, Marina; Bernasconi, Pia; Desaphy, Jean-Francois; Mantegazza, Renato; Camerino, Diana Conte

    2016-10-01

    Myotonia congenita is an inherited disease that is characterized by impaired muscle relaxation after contraction caused by loss-of-function mutations in the skeletal muscle ClC-1 channel. We report a novel ClC-1 mutation, T335N, that is associated with a mild phenotype in 1 patient, located in the extracellular I-J loop. The purpose of this study was to provide a solid correlation between T335N dysfunction and clinical symptoms in the affected patient as well as to offer hints for drug development. Our multidisciplinary approach includes patch-clamp electrophysiology on T335N and ClC-1 wild-type channels expressed in tsA201 cells, Western blot and quantitative PCR analyses on muscle biopsies from patient and unaffected individuals, and molecular dynamics simulations using a homology model of the ClC-1 dimer. T335N channels display reduced chloride currents as a result of gating alterations rather than altered surface expression. Molecular dynamics simulations suggest that the I-J loop might be involved in conformational changes that occur at the dimer interface, thus affecting gating. Finally, the gene expression profile of T335N carrier showed a diverse expression of K(+) channel genes, compared with control individuals, as potentially contributing to the phenotype. This experimental paradigm satisfactorily explained myotonia in the patient. Furthermore, it could be relevant to the study and therapy of any channelopathy.-Imbrici, P., Altamura, C., Camerino, G. M., Mangiatordi, G. F., Conte, E., Maggi, L., Brugnoni, R., Musaraj, K., Caloiero, R., Alberga, D., Marsano, R. M., Ricci, G., Siciliano, G., Nicolotti, O., Mora, M., Bernasconi, P., Desaphy, J.-F., Mantegazza, R., Camerino, D. C. Multidisciplinary study of a new ClC-1 mutation causing myotonia congenita: a paradigm to understand and treat ion channelopathies.

  14. Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization.

    PubMed

    Vivekananda, Umesh; Novak, Pavel; Bello, Oscar D; Korchev, Yuri E; Krishnakumar, Shyam S; Volynski, Kirill E; Kullmann, Dimitri M

    2017-02-28

    Although action potentials propagate along axons in an all-or-none manner, subthreshold membrane potential fluctuations at the soma affect neurotransmitter release from synaptic boutons. An important mechanism underlying analog-digital modulation is depolarization-mediated inactivation of presynaptic Kv1-family potassium channels, leading to action potential broadening and increased calcium influx. Previous studies have relied heavily on recordings from blebs formed after axon transection, which may exaggerate the passive propagation of somatic depolarization. We recorded instead from small boutons supplied by intact axons identified with scanning ion conductance microscopy in primary hippocampal cultures and asked how distinct potassium channels interact in determining the basal spike width and its modulation by subthreshold somatic depolarization. Pharmacological or genetic deletion of Kv1.1 broadened presynaptic spikes without preventing further prolongation by brief depolarizing somatic prepulses. A heterozygous mouse model of episodic ataxia type 1 harboring a dominant Kv1.1 mutation had a similar broadening effect on basal spike shape as deletion of Kv1.1; however, spike modulation by somatic prepulses was abolished. These results argue that the Kv1.1 subunit is not necessary for subthreshold modulation of spike width. However, a disease-associated mutant subunit prevents the interplay of analog and digital transmission, possibly by disrupting the normal stoichiometry of presynaptic potassium channels.

  15. Volcano Instability Induced by Resurgence at the Ischia Island Caldera (Italy), and the Tsunamigenic Potential of the Related Debris Avalanche Deposits: a Complex Source of Hazard at Land-sea Interface

    NASA Astrophysics Data System (ADS)

    Tinti, S.; Zaniboni, F.; Pagnoni, G.; Marotta, E.; Della Seta, M.; de Vita, S.; Orsi, G.; Sansivero, F.; Fredi, P.

    2009-05-01

    Slope instability is a common feature in the evolution of active volcanic areas. The occurrence of mass movements is doubly linked to volcanism and volcano-tectonism, which act as either preparing factor (through increased topographic gradients or emplacement of unconsolidated deposits on slopes) or triggering factor (through earthquakes and/or eruptions). Debris avalanches and lahars in active volcanic areas are an additional factor of hazard, due to their high destructive power. Moreover, volcanoes located in coastal areas or on islands, may experience lateral collapses with the potential to generate large tsunamis. Ischia is an active volcanic island in the Gulf of Naples. Volcanism begun prior to 150 ka and continued, with periods of quiescence, until the last eruption in 1302 A.D. It has been dominated by a caldera-forming eruption (55 ka), which was followed by resurgence of the caldera floor. Volcanism and gravitational mass movements have been coeval to resurgence, which generated a maximum net uplift of about 900 m over the past 33 ka. Resurgence occurred through intermittent uplifting and tectonic quietness phases. During uplift, volcanism and generation of mass movements were very active. The resurgent area is composed of differentially displaced blocks and has a poligonal shape, resulting from reactivation of regional faults and activation of faults directly related to volcano-tectonism. The western sector is bordered by inward-dipping, high-angle reverse faults, cut by late outward-dipping normal faults due to gravitational readjustment of the slopes. The north-eastern and the south-western sides are bordered by vertical faults with right transtensive and left transpressive movements, respectively. The area located to the east of the most uplifted block is displaced by outward- dipping normal faults. Some giant landslides and their relationships with volcano-tectonism have been recognized at Ischia. Their deposits are intercalated with primary

  16. Resurgent-like currents in mouse vas deferens myocytes are mediated by NaV1.6 voltage-gated sodium channels.

    PubMed

    Teramoto, Noriyoshi; Zhu, Hai-Lei; Yotsu-Yamashita, Mari; Inai, Tetsuichiro; Cunnane, Thomas C

    2012-11-01

    Patch-clamp experiments were performed to investigate the molecular properties of resurgent-like currents in single smooth muscle cells dispersed from mouse vas deferens, utilizing both Na(V)1.6-null mice (Na(V)1.6(-/-)), lacking the expression of the Scn8a Na(+) channel gene, and their wild-type littermates (Na(V)1.6(+/+)). Na(V)1.6 immunoreactivity was clearly visible in dispersed smooth muscle cells obtained from Na(V)1.6(+/+), but not Na(V)1.6(-/-), vas deferens. Following a depolarization to +30 mV from a holding potential of -70 mV (to produce maximal inactivation of the Na(+) current), repolarization to voltages between -60 and +20 mV elicited a tetrodotoxin (TTX)-sensitive inward current in Na(V)1.6(+/+), but not Na(V)1.6(-/-), vas deferens myocytes. The resurgent-like current in Na(V)1.6(+/+) vas deferens myocytes peaked at approximately -20 mV in the current-voltage relationship. The peak amplitude of the resurgent-like current remained at a constant level when the membrane potential was repolarized to -20 mV following the application of depolarizing rectangular pulses to more positive potentials than +20 mV. 4,9-Anhydrotetrodotoxin (4,9-anhydroTTX), a selective Na(V)1.6 blocking toxin, purified from a crude mixture of TTX analogues by LC-FLD techniques, reversibly suppressed the resurgent-like currents. β-Pompilidotoxin, a voltage-gated Na(+) channel activator, evoked sustained resurgent-like currents in Na(V)1.6(+/+) but not Na(V)1.6(-/-) murine vas deferens myocytes. These results strongly indicate that, primarily, resurgent-like currents are generated as a result of Na(V)1.6 channel activity.

  17. Constraints on the source of resurgent doming inferred from analogue and numerical modeling - Implications on the current feeding system of the Yenkahe dome-Yasur volcano complex (Vanuatu)

    NASA Astrophysics Data System (ADS)

    Brothelande, E.; Peltier, A.; Got, J.-L.; Merle, O.; Lardy, M.; Garaebiti, E.

    2016-08-01

    Resurgence, defined as the post-collapse long-term uplift of a caldera floor, is commonly attributed to a renewed rise of magma. The Yenkahe dome (Vanuatu) exhibits a common morphology - elongated with a graben on top - among resurgent domes, and is also one of the most active structures of the kind. In this study, we performed a joint analysis based on analogue and finite element numerical models to (1) constrain the width and depth of the long-term deformation intrusive source of the Yenkahe dome and (2) discuss the close association between the Yenkahe dome and the active Yasur cone. We consider the resurgent deformation at the surface to be driven by the uplift of a magma reservoir roof in depth. As the edifice deformation response depends on the medium and the source properties, the mechanical behavior of the upper crust and the nature of the source are modeled using two very different sets of hypotheses. Analogue modeling uses silicone putty, an analogue for a large viscous magma body, intruding a sand-plaster mixture reproducing a Mohr-Coulomb behavior for the crust. Numerical models consider the vertical displacement of a rigid indenter, allowing the conservation of a flat-shaped roof, into an elastoplastic material. Numerical and analogue models show different resurgent dome structures at depth but similar dome and graben morphologies in the surface. Inverse faults - or equivalent shearing zones - delimiting the dome provide an explanation for the confined nature of resurgent doming and the persistent volcanic activity on the dome border represented by the Yasur volcano. Analogue and numerical models together provide an estimation range of 1-1.8 km for the intrusive deformation source depth, and 1.3-2 km for its width. The proposed association between the Yenkahe dome and the Yasur volcano is compatible with such a shallow depth of the magma reservoir, and argues for a discontinuous resurgence process.

  18. Negative-shift activation, current reduction and resurgent currents induced by β-toxins from Centruroides scorpions in sodium channels.

    PubMed

    Schiavon, Emanuele; Pedraza-Escalona, Martha; Gurrola, Georgina B; Olamendi-Portugal, Timoteo; Corzo, Gerardo; Wanke, Enzo; Possani, Lourival D

    2012-02-01

    The β-toxins purified from the New World scorpion venoms of the Centruroides species affect several voltage-gated sodium channels (VGSCs) and thus are essential tools not only for the discrimination of different channel sub-types but also for studying the structure-function relationship between channels and toxins. This communication reports the results obtained with four different peptides purified from three species of Centruroides scorpions and assayed on seven distinct isoforms of VGSC (Na(v)1.1-Na(v)1.7) by specific functional analysis conducted through single cell electrophysiology. The toxins studied were CssII from Centruroides suffusus suffusus, Cll1 and Cll2 from Centruroides limpidus limpidus and a novel toxin from Centruroides noxius, which was characterized for the first time here. It has 67 amino acid residues and four disulfide bridges with a molecular mass of 7626 Da. Three different functional features were identified: current reduction of macroscopic conductance, left shift of the voltage-dependent activation and induction of resurgent currents at negative voltages following brief, strong depolarizations. The isoforms which revealed to be more affected resulted to be Na(v)1.6 > 1.1 > 1.2 and, for the first time, a β-toxin is here shown to induce resurgent current also in isoforms different from Na(v)1.6. Additionally, these results were analyzed with molecular modelling. In conclusion, although the four toxins have a high degree of identity, they display tri-modal function, each of which shows selectivity among the different sub-types of Na+ -channels. Thus, they are invaluable as tools for structure-function studies of β-toxins and offer a basis for the design of novel ion channel-specific drugs.

  19. The thermal regime in the resurgent dome of Long Valley Caldera, California: Inferences from precision temperature logs in deep wells

    USGS Publications Warehouse

    Hurwitz, S.; Farrar, C.D.; Williams, C.F.

    2010-01-01

    Long Valley Caldera in eastern California formed 0.76Ma ago in a cataclysmic eruption that resulted in the deposition of 600km3 of Bishop Tuff. The total current heat flow from the caldera floor is estimated to be ~290MW, and a geothermal power plant in Casa Diablo on the flanks of the resurgent dome (RD) generates ~40MWe. The RD in the center of the caldera was uplifted by ~80cm between 1980 and 1999 and was explained by most models as a response to magma intrusion into the shallow crust. This unrest has led to extensive research on geothermal resources and volcanic hazards in the caldera. Here we present results from precise, high-resolution, temperature-depth profiles in five deep boreholes (327-1,158m) on the RD to assess its thermal state, and more specifically 1) to provide bounds on the advective heat transport as a guide for future geothermal exploration, 2) to provide constraints on the occurrence of magma at shallow crustal depths, and 3) to provide a baseline for future transient thermal phenomena in response to large earthquakes, volcanic activity, or geothermal production. The temperature profiles display substantial non-linearity within each profile and variability between the different profiles. All profiles display significant temperature reversals with depth and temperature gradients <50??C/km at their bottom. The maximum temperature in the individual boreholes ranges between 124.7??C and 129.5??C and bottom hole temperatures range between 99.4??C and 129.5??C. The high-temperature units in the three Fumarole Valley boreholes are at the approximate same elevation as the high-temperature unit in borehole M-1 in Casa Diablo indicating lateral or sub-lateral hydrothermal flow through the resurgent dome. Small differences in temperature between measurements in consecutive years in three of the wells suggest slow cooling of the shallow hydrothermal flow system. By matching theoretical curves to segments of the measured temperature profiles, we calculate

  20. The thermal regime in the resurgent dome of Long Valley Caldera, California: Inferences from precision temperature logs in deep wells

    NASA Astrophysics Data System (ADS)

    Hurwitz, Shaul; Farrar, Christopher D.; Williams, Colin F.

    2010-12-01

    Long Valley Caldera in eastern California formed 0.76 Ma ago in a cataclysmic eruption that resulted in the deposition of 600 km 3 of Bishop Tuff. The total current heat flow from the caldera floor is estimated to be ~ 290 MW, and a geothermal power plant in Casa Diablo on the flanks of the resurgent dome (RD) generates ~40 MWe. The RD in the center of the caldera was uplifted by ~ 80 cm between 1980 and 1999 and was explained by most models as a response to magma intrusion into the shallow crust. This unrest has led to extensive research on geothermal resources and volcanic hazards in the caldera. Here we present results from precise, high-resolution, temperature-depth profiles in five deep boreholes (327-1,158 m) on the RD to assess its thermal state, and more specifically 1) to provide bounds on the advective heat transport as a guide for future geothermal exploration, 2) to provide constraints on the occurrence of magma at shallow crustal depths, and 3) to provide a baseline for future transient thermal phenomena in response to large earthquakes, volcanic activity, or geothermal production. The temperature profiles display substantial non-linearity within each profile and variability between the different profiles. All profiles display significant temperature reversals with depth and temperature gradients <50 °C/km at their bottom. The maximum temperature in the individual boreholes ranges between 124.7 °C and 129.5 °C and bottom hole temperatures range between 99.4 °C and 129.5 °C. The high-temperature units in the three Fumarole Valley boreholes are at the approximate same elevation as the high-temperature unit in borehole M-1 in Casa Diablo indicating lateral or sub-lateral hydrothermal flow through the resurgent dome. Small differences in temperature between measurements in consecutive years in three of the wells suggest slow cooling of the shallow hydrothermal flow system. By matching theoretical curves to segments of the measured temperature profiles

  1. [Persistence and resurgence of sleeping sickness caused by Trypanosoma brucei gambiense in historic foci. Biomathematical approach of an epidemiologic enigma].

    PubMed

    Gouteux, J P; Artzrouni, M

    2000-04-01

    Since the end of the 19th century, historic endemic foci of Trypanosoma brucei gambiense sleeping sickness have proven very persistent. A five-compartment mathematical model with open vector populations was developed in order to study the dynamics of this disease in Central Africa. Of particular interest is the rate at which the disease spreads or goes to extinction at the beginning of an epidemic outbreak. A measure of this rate is the initial halving/doubling time T(o) of the numbers infected; T(o) is a doubling time when the basic reproduction number Ro > 1 and a halving time when Ro < 1. For realistic parameter values, T(o) can be quite large (i.e. several years or even decades) which corresponds to a persistent low-level endemic brought about by an Ro either just above 1 (slow spread) or just below 1 (slow extinction). A resurgence of historical foci can then be caused by a small shift in parameter values that brings Ro well above 1 and decreases T(o). In addition, when Ro is less than 1 (in the absence of vector migrations), simulations show that a very small percentage of infected immigrant flies can bring about high prevalence rates in the human population. The model is validated with field data from historical Congolese, Central and West African foci of the past.

  2. 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

    2016-05-27

    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.

  3. New Nonperturbative Methods in Quantum Field Theory: From Large-N Orbifold Equivalence to Bions and Resurgence

    NASA Astrophysics Data System (ADS)

    Dunne, Gerald V.; Ünsal, Mithat

    2016-10-01

    We present a broad conceptual introduction to some new ideas in nonperturbative quantum field theory (QFT) that have led to progress toward an understanding of quark confinement in gauge theories and, more broadly, toward a nonperturbative continuum definition of QFTs. We first present exact orbifold equivalences of supersymmetric and nonsupersymmetric QFTs in the large-N limit and exact equivalences of large-N theories in infinite volume to large-N theories in finite volume, or even at a single point. We discuss principles by which calculable QFTs are continuously connected to strong-coupling QFTs, allowing understanding of the physics of confinement or the absence thereof. We discuss the role of particular saddle solutions, termed bions, in weak-coupling calculable regimes. The properties of bions motivate an extension of semiclassical methods used to evaluate functional integrals to include families of complex saddles (Picard-Lefschetz theory). This analysis leads us to the resurgence program, which may provide a framework for combining divergent perturbation series with semiclassical instanton and bion/renormalon contributions. This program could provide a nonperturbative definition of the path integral.

  4. Inferences on the hydrothermal system beneath the resurgent dome in Long Valley Caldera, east-central California, USA, from recent pumping tests and geochemical sampling

    USGS Publications Warehouse

    Farrar, C.D.; Sorey, M.L.; Roeloffs, E.; Galloway, D.L.; Howle, J.F.; Jacobson, R.

    2003-01-01

    Quaternary volcanic unrest has provided heat for episodic hydrothermal circulation in the Long Valley caldera, including the present-day hydrothermal system, which has been active over the past 40 kyr. The most recent period of crustal unrest in this region of east-central California began around 1980 and has included periods of intense seismicity and ground deformation. Uplift totaling more than 0.7 m has been centered on the caldera's resurgent dome, and is best modeled by a near-vertical ellipsoidal source centered at depths of 6-7 km. Modeling of both deformation and microgravity data now suggests that (1) there are two inflation sources beneath the caldera, a shallower source 7-10 km beneath the resurgent dome and a deeper source ???15 km beneath the caldera's south moat and (2) the shallower source may contain components of magmatic brine and gas. The Long Valley Exploration Well (LVEW), completed in 1998 on the resurgent dome, penetrates to a depth of 3 km directly above this shallower source, but bottoms in a zone of 100??C fluid with zero vertical thermal gradient. Although these results preclude extrapolations of temperatures at depths below 3 km, other information obtained from flow tests and fluid sampling at this well indicates the presence of magmatic volatiles and fault-related permeability within the metamorphic basement rocks underlying the volcanic fill. In this paper, we present recently acquired data from LVEW and compare them with information from other drill holes and thermal springs in Long Valley to delineate the likely flow paths and fluid system properties under the resurgent dome. Additional information from mineralogical assemblages in core obtained from fracture zones in LVEW documents a previous period of more vigorous and energetic fluid circulation beneath the resurgent dome. Although this system apparently died off as a result of mineral deposition and cooling (and/or deepening) of magmatic heat sources, flow testing and tidal

  5. 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.

  6. Cushing's Syndrome and Fetal Features Resurgence in Adrenal Cortex–Specific Prkar1a Knockout Mice

    PubMed Central

    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

    2010-01-01

    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 α-regulatory subunit (R1α) of the cAMP–dependent protein kinase (PKA) have been found in 80% of CNC patients with Cushing's syndrome. To demonstrate the implication of R1α 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, R1α 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 R1α 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

  7. Health care professionals and bedbugs: an ethical analysis of a resurgent scourge.

    PubMed

    Laliberté, Maude; Hunt, Matthew; Williams-Jones, Bryn; Feldman, Debbie Ehrmann

    2013-09-01

    Many health care professionals (HCPs) are understandably reluctant to treat patients in environments infested with bedbugs, in part due to the risk of themselves becoming bedbug vectors to their own homes and workplaces. However, bedbugs are increasingly widespread in care settings, such as nursing homes, as well as in private homes visited by HCPs, leading to increased questions of how health care organizations and their staff ought to respond. This situation is associated with a range of ethical considerations including the duty of care, stigmatization, vulnerability, confidentiality, risks for third parties, and professional autonomy. In this article, we analyze these issues using a case study approach. We consider how patients whose living environments are infested with bedbugs can receive care in the community setting in a manner that supports their well-being, is consistent with fairness in care provision, and takes into account risks for HCPs and third parties. We also discuss limits and obstacles to the provision of care in these situations.

  8. Is this safe to eat?: Chapter 5 in Disease emergence and resurgence: The wildlife-human connection

    USGS Publications Warehouse

    Nol, Pauline; Friend, Milton

    2006-01-01

    The harvest and consumption of wildlife is as old as humankind and often has sustained human exploration into unsettled areas. Wildlife still remain a primary foodbase for many native peoples throughout the world. From shellfish to bear, humans today continue to hunt, fish, and otherwise harvest wildlife for recreation, social and cultural needs, dietary supplementation, subsistence, and other purposes that result in the consumption of game meat (Fig. 5.1).Over time, experience has taught people what food is safe to eat and how it should be prepared. This is especially true for those who subsist upon wildlife. Fortunately, the meat from wildlife generally is safe to eat when properly harvested and prepared; however, many people infrequently consume wildlife and are less experienced than subsistence users of wildlife in making judgments about what is safe to eat, how to handle the meat between the times of harvest and preparation, and how the meat should be prepared (Table 5.1). Disease emergence and resurgence has added a dimension that also must be considered for wildlife (e.g., chronic wasting disease in deer and elk) and domestic foods alike (see Chapters 2 and 3).This chapter provides guidance for sporadic consumers of wildlife because, unlike farmed food animals (domestic and captive-reared wildlife species) or commercially harvested finfish and shellfish, the meat from free-living wildlife in the USA and many other countries is not regulated and inspected by government authorities. The safe consumption of game harvested by the public in these situations depends entirely on the actions and discretion of those harvesting and preparing these food items. These individuals commonly encounter conditions in wildlife carcasses that cause them to ask the question “Is This Safe to Eat?” (Fig. 5.2) and in some situations to unnecessarily discard edible meat.

  9. The semi-classical expansion and resurgence in gauge theories: new perturbative, instanton, bion, and renormalon effects

    DOE PAGES

    Argyres, Philip C.; Uensal, Mithat

    2012-08-10

    We study the dynamics of four dimensional gauge theories with adjoint fermions for all gauge groups, both in perturbation theory and non-perturbatively, by using circle compactification with periodic boundary conditions for the fermions. There are new gauge phenomena. We show that, to all orders in perturbation theory, many gauge groups are Higgsed by the gauge holonomy around the circle to a product of both abelian and nonabelian gauge group factors. Non-perturbatively there are monopole-instantons with fermion zero modes and two types of monopole-anti-monopole molecules, called bions. One type are magnetic bions which carry net magnetic charge and induce a massmore » gap for gauge fluctuations. Another type are neutral bions which are magnetically neutral, and their understanding requires a generalization of multi-instanton techniques in quantum mechanics — which we refer to as the Bogomolny-Zinn-Justin (BZJ) prescription — to compactified field theory. The BZJ prescription applied to bion-anti-bion topological molecules predicts a singularity on the positive real axis of the Borel plane (i.e., a divergence from summing large orders in peturbation theory) which is of order N times closer to the origin than the leading 4-d BPST instanton-anti-instanton singularity, where N is the rank of the gauge group. The position of the bion-anti-bion singularity is thus qualitatively similar to that of the 4-d IR renormalon singularity, and we conjecture that they are continuously related as the compactification radius is changed. By making use of transseries and Écalle’s resurgence theory we argue that a non-perturbative continuum definition of a class of field theories which admit semi-classical expansions may be possible.« less

  10. The semi-classical expansion and resurgence in gauge theories: new perturbative, instanton, bion, and renormalon effects

    SciTech Connect

    Argyres, Philip C.; Uensal, Mithat

    2012-08-10

    We study the dynamics of four dimensional gauge theories with adjoint fermions for all gauge groups, both in perturbation theory and non-perturbatively, by using circle compactification with periodic boundary conditions for the fermions. There are new gauge phenomena. We show that, to all orders in perturbation theory, many gauge groups are Higgsed by the gauge holonomy around the circle to a product of both abelian and nonabelian gauge group factors. Non-perturbatively there are monopole-instantons with fermion zero modes and two types of monopole-anti-monopole molecules, called bions. One type are magnetic bions which carry net magnetic charge and induce a mass gap for gauge fluctuations. Another type are neutral bions which are magnetically neutral, and their understanding requires a generalization of multi-instanton techniques in quantum mechanics — which we refer to as the Bogomolny-Zinn-Justin (BZJ) prescription — to compactified field theory. The BZJ prescription applied to bion-anti-bion topological molecules predicts a singularity on the positive real axis of the Borel plane (i.e., a divergence from summing large orders in peturbation theory) which is of order N times closer to the origin than the leading 4-d BPST instanton-anti-instanton singularity, where N is the rank of the gauge group. The position of the bion-anti-bion singularity is thus qualitatively similar to that of the 4-d IR renormalon singularity, and we conjecture that they are continuously related as the compactification radius is changed. By making use of transseries and Écalle’s resurgence theory we argue that a non-perturbative continuum definition of a class of field theories which admit semi-classical expansions may be possible.

  11. Hand-held cow horn: resurgence of an old arm or apotential terrorist weapon

    PubMed Central

    Khalid, Lawal; Ahmed, Adamu

    2012-01-01

    Abstract: A 23 year old man presented with intestinal evisceration from stab injury to the left side of the abdomen with a hand-held cow horn at a local night party. He complained of severe abdominal pain and bleeding at the site of injury. He was hemodynamically stable. At emergency exploration, the eviscerated bowel was viable with no adjacent mesenteric tear. Other intra abdominal organs were normal. The eviscerated bowel was lavaged and reduced into the abdomen through the 7cm anterior abdominal wall laceration. The laceration was repaired and abdomen closed in layers. Post operative recovery was uneventful. The hand-held cow horn can easily be concealed and may pass through security checks undetected. It should be added to the ever increasing list of weapons of small scale terror. PMID:21502787

  12. Hand-held cow horn: resurgence of an old arm or a potential terrorist weapon.

    PubMed

    Khalid, Lawal; Ahmed, Adamu

    2012-01-01

    A 23 year old man presented with intestinal evisceration from stab injury to the left side of the abdomen with a hand-held cow horn at a local night party. He complained of severe abdominal pain and bleeding at the site of injury. He was hemodynamically stable. At emergency exploration, the eviscerated bowel was viable with no adjacent mesenteric tear. Other intra abdominal organs were normal. The eviscerated bowel was lavaged and reduced into the abdomen through the 7 cm anterior abdominal wall laceration. The laceration was repaired and abdomen closed in layers. Post operative recovery was uneventful. The hand-held cow horn can easily be concealed and may pass through security checks undetected. It should be added to the ever increasing list of weapons of small scale terror.

  13. Entomological investigation following the resurgence of human visceral leishmaniasis in southern Algeria.

    PubMed

    Benallal, K; Gassen, B; Bouiba, L; Depaquit, J; Harrat, Z

    2013-12-01

    Visceral and cutaneous leishmaniasis are the main endemic vector born diseases in Algeria. In the Hoggar region (extreme south of the country) human visceral leishmaniasis (HVL) is known to be sporadic but during the last decade the number of cases has increased significantly. In 2010, a peak of HVL cases was registered mostly among children. Therefore an entomological survey and a retrospective study on HVL cases were carried out in order to explore the transmission of the disease. Among the sand fly caught Phlebotomus bergeroti was the most frequent species (68%) followed by Sergentomyia schwetzi (22%). In this work we describe the presence of Phlebotomus (Paraphlebotomus) kazeruni for the first time in the Hoggar region. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Rabid epidemiologies: the emergence and resurgence of rabies in twentieth century South Africa.

    PubMed

    Brown, Karen

    2011-01-01

    This article discusses the history of rabies in South Africa since the early twentieth century. It argues that rabies is a zoonotic disease that traverses rural and urban spaces, that transfers itself between wild and domestic animals and remains a potential threat to human life in the region. Scientists discovered an indigenous form of rabies, found primarily in the yellow mongoose, after the first biomedically confirmed human fatalities in 1928. Since the 1950s canine rabies, presumed to have moved southwards from across the Zambezi River, has become endemic also. South Africa is home to a comparatively large number of rabies strains and animal carriers, making it a particularly interesting case study. Environmental changes during the colonial and apartheid periods have helped to explain the increase in rabies cases since the mid-twentieth century. Moreover, developments in the biological and ecological sciences have provided insights into why the rabies virus has become endemic in certain wildlife species.

  15. Resurgent beaver ponds in the northeastern United States: implications for greenhouse gas emissions.

    PubMed

    Lazar, Julia G; Addy, Kelly; Welsh, Molly K; Gold, Arthur J; Groffman, Peter M

    2014-11-01

    Beaver ponds, a wetland type of increasing density in the northeastern United States, vary spatially and temporally, creating high uncertainty in their impact to greenhouse gas (GHG) emissions. We used floating static gas chambers to assess diffusive fluxes of methane (CH), carbon dioxide (CO), and nitrous oxide (NO) from the air-water interface of three beaver ponds (0.05-8 ha) in Rhode Island from fall 2012 to summer 2013. Gas flux was based on linear changes of gas concentrations in chambers over 1 h. Our results show that these beaver ponds generated considerable CH and CO emissions. Methane flux (18-556 mg m d) showed no significant seasonal differences, but the shallowest pond generated significantly higher CH flux than the other ponds. Carbon dioxide flux (0.5-22.0 g m d) was not significantly different between sites, but it was significantly higher in the fall, possibly due to the degradation of fresh leaves. Nitrous oxide flux was low (0-2.4 mg m d). Overall, CH and CO comprised most of the global warming potential, 61 and 38%, respectively. The shallowness of the beaver ponds may have limited the time needed for CH oxidation to CO before CH escaped to the atmosphere. Beaver dams also increase the aerial extent of hydric soils, which may transform riparian areas from upland GHG sinks to wetland GHG sources thereby changing the net global warming potential. Further studies tracking the pattern and conditions of beaver pond creation and abandonment will be essential to understanding their role as GHG sources. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  16. [Imported malaria in Tunisia: consequences on the risk of resurgence of the disease].

    PubMed

    Aoun, K; Siala, E; Tchibkere, D; Ben Abdallah, R; Zallagua, N; Chahed, M K; Bouratbine, A

    2010-02-01

    Although malaria has been eradicated in Tunisia since 1979, the disease is still a health issue due to the persistence of mosquitoes and coexistence with a potential parasite reservoir in the form of imported cases. From 1999 to 2006, 98 cases of imported malaria were diagnosed at the Pasteur Institute in Tunis where nearly 30% of national cases are recorded. Tunisians accounted for 24.5% of these cases versus 75.5% involving foreigners. The occurrence rate has steadily increased in volunteer workers, businessmen, diplomats and athletes who together accounted for 41.7% of cases in 1995 as compared to only 17.4% in 1980 (p<0.01). Most cases (96.5%) were imported from sub-Saharan Africa. The most frequent countries involved in importation were Cote d'Ivoire (23 cases) and Mali (8 cases) that are now linked to Tunisia by regular flights. About one third of patients were asymptomatic at the time of diagnosis. This finding underlines the importance of recommending systematic screening in high-risk groups. Fever (70.6%) and gastro-intestinal manifestations (27.9%) were the most frequent clinical findings in the 69 symptomatic cases. Plasmodium falciparum (71.4%) was the most common species followed by Plasmodium ovale (19.4%). Gametocytes were detected in 9.2% of subjects, thus creating a theoretical source of infection for mosquitoes especially since 60.2% of all cases were recorded between June and October when mosquitoes are active in Tunisia. Due to increasing exchange with endemic malaria areas in Africa that has resulted in a higher incidence of imported cases and a futher risk of introduction of tropical mosquito species as well as to global warming that promotes plasmodium transmission, greater vigilance is necessary to ensure eradication of malaria in Tunisia.

  17. Job Creation Due to Nuclear Power Resurgence in The United States

    SciTech Connect

    C. R. Kenley; R. D. Klingler; C. M. Plowman; R. Soto; R. J. Turk; R. L. Baker; S. A. Close; V. L. McDonnell; S. W. Paul; L. R. Rabideau; S. S. Rao; B. P. Reilly

    2009-11-01

    The recent revival of global interest in the next generation of nuclear power reactors is causing a reexamination of the role of nuclear power in the United States. This renewed interest has led to questions regarding the capability and capacity of current U.S. industries to support a renewal of nuclear power plant deployment. Key among the many questions currently being asked is what potential exists for the creation of new jobs as a result of developing and operating these new plants? Idaho National Laboratory and Bechtel Power Corporation collaborated to perform a Department of Energy-sponsored study that evaluated the potential for job creation in the U.S. should these new next generation nuclear power plants be built. The study focused primarily on providing an initial estimate of the numbers of new manufacturing jobs that could be created, including those that could be repatriated from overseas, resulting from the construction of these new reactors. In addition to the growth in the manufacturing sector, the study attempted to estimate the potential increase in construction trades necessary to accomplish the new construction.

  18. Molecular epidemiological evaluation of the recent resurgence in mumps virus infections in Ireland.

    PubMed

    Carr, Michael J; Moss, Eibhlín; Waters, Allison; Dean, Jonathan; Jin, Li; Coughlan, Suzie; Connell, Jeff; Hall, William W; Hassan, Jaythoon

    2010-09-01

    Mumps is a vaccine-preventable disease; however, outbreaks have been reported in a number of countries with childhood immunization programs, particularly among young adults at the tertiary stage of education. We have retrospectively investigated the epidemiological, virological, and serological factors associated with mumps cases identified in Ireland from 2004 to 2009. Genetic analysis of mumps virus strain variability demonstrated that a single genotype, genotype G, was circulating, and it was also detected in cerebrospinal fluid samples obtained from patients with meningitis. We observed that younger individuals were disproportionately affected with neurological sequelae following mumps virus infection, and the average age of patients with mumps virus RNA detected in cerebrospinal fluid was 19.25 years (median, 19 years; range, 14 to 24 years). Our analysis showed a 4-fold rise in mumps cases in 2008-2009 and an increased incidence in infection in those >or=30 years of age. Over a 6-year period (2004 to 2009), a total of 7,805 serum samples were investigated; of this number, 1,813 (23%) were positive for mumps virus-specific IgM. We observed a strong bias for acute mumps virus infection in males compared to females (P < 10(-32)) that was independent of vaccination status.

  19. 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.

  20. Noninvasive assessment of right ventricular function: will there be resurgence in radionuclide imaging techniques?

    PubMed

    Ramani, Gautam V; Gurm, Gagandeep; Dilsizian, Vasken; Park, Myung H

    2010-03-01

    Right ventricular (RV) function is increasingly being recognized as an important prognostic marker in multiple cardiopulmonary disease states, including congestive heart failure, pulmonary arterial hypertension, and chronic obstructive pulmonary disease. Accurate and reproducible measures of RV function, although technically challenging, are highly relevant in the clinical setting. Radionuclide techniques (eg, first-pass radionuclide angiography for quantifying RV systolic function) were developed nearly 40 years ago. More recently, MRI and transthoracic echocardiography have become the diagnostic imaging techniques of choice for the noninvasive evaluation of RV function. However, developments in single photon emission computed tomography (SPECT), positron emission tomography (PET), and hybrid SPECT/CT and PET/CT systems have greatly improved the image quality and contrast resolution of radionuclide imaging of the heart, allowing for coregistered physiologic and anatomical information of the right ventricle in three dimensions. These improvements in cardiac imaging provide new opportunities for assessing RV myocardial perfusion, function, and anatomy in the same setting. Such imaging approaches may in the future provide assistance with proactive disease management, including early diagnosis of impending RV dysfunction in high-risk patients and for guiding decisions to initiate and/or modify treatments.

  1. 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.

  2. Why this book?: Chapter 1 in Disease emergence and resurgence: The wildlife-human connection

    USGS Publications Warehouse

    Friend, Milton

    2006-01-01

    The appearance and diagnosis in humans of various infectious diseases is a dynamic situation involving “new” diseases that continue to arise and challenge humankind, along with fluctuating levels of established diseases. Some of the agents causing these diseases originate in humans and others in animals. As a group, the zoonoses (diseases transmissible between animals and humans) are of special concern because of the close associations people have with domesticated species and free-ranging wildlife. In many areas of the world, those associations with wildlife have become greater during recent years, especially as the increasing human population results in wildlife and people sharing more of the same space (Fig. 1.1). In addition, the popularity of outdoor recreation and ecotourism results in millions of humans entering “wild places” (Fig. 1.2). During 2001, 39 percent of the USA population 16 years old and older participated in activities related to fish and wildlife. These activities generated 1.1 percent of the Nation’s gross domestic product ($110 billion).2 Because of these factors, zoonoses are the dominant type of infectious disease in the current era of disease emergence and reemergence, a situation that is likely to continue for the foreseeable future (see Chapter 2). Not only can humans contract diseases from wildlife (Fig. 1.3), but humans can introduce diseases that jeopardize wildlife.3,4 Wildlife populations that become infected by pathogens typically considered to cause human disease may then become enzootic foci for those infections. Recent infection of African wildlife with the human strain of tuberculosis (Mycobacterium tuberculosis) has been attributed to the expansion of ecotourism and is but one example of disease introduced into wildlife populations associated with human encroachment into remote areas.4–7Three basic factors can minimize the potential for diseases present in nature, such as AIDS, from becoming established as new

  3. Yaws resurgence in Bankim, Cameroon: The relative effectiveness of different means of detection in rural communities

    PubMed Central

    Boock, Alphonse Um; Awah, Paschal Kum; Mou, Ferdinand

    2017-01-01

    educational programs accompanied by school-based programs proved to be particularly effective in Bankim. Including yaws detection in a Buruli Ulcer outreach program constituted a win-win situation, as the demonstration effect of yaws treatment (rapid cure) increased confidence in early Buruli ulcer treatment. Mass outreach programs functioned as magnets for both diseases as well as other kinds of chronic wounds that future outreach programs need to address. PMID:28481900

  4. [Catatonia: resurgence of a concept. A review of the international literature].

    PubMed

    Pommepuy, N; Januel, D

    2002-01-01

    Catatonia was first described in 1874 by Kahlbaum as being a cyclic disease mixing motor features and mood variations. Because most cases ended in dementia, Kraepelin recognized catatonia as a form of dementia praecox and Bleuler included it within his wide group of schizophrenias. This view influenced the psychiatric practice for more than 70 years. But catatonia was recently reconsidered and this because of the definition of more precise diagnosis criteria, the discovery of a striking association with mood disorders, and the emphasis on effective therapeutics. Peralta et al empirically developed a performant diagnostic instrument with the 11 most discriminant signs among catatonic features. Diagnostic threshold is three or more signs with sensitivity of 100% and specificity of 99%. These signs are: immobility/stupor (extreme passivity, marked hypokinesia); mutism (includes inaudible whisper); negativism (resistance to instructions, contrary comportment to whose asked); oppositionism, other called gegenhalten (resistance to passive movement which increases with the force exerted); posturing (patient adopts spontaneously odd postures); catalepsy (patient retains limb positions passively imposed during examination; waxy flexibility); automatic obedience (exaggerated co-operation to instructed movements); echo phenomena (movements, mimic and speech of the examiner are copied with modification and amplifications); rigidity (increased muscular tone); verbigeration (continuous and directionless repetition of single words or phrases); withdrawal/refusal to eat or drink (turning away from examiner, no eye contact, refusal to take food or drink when offered). Using this diagnostic tool, prevalence of catatonic syndrome appears to be close to 8% of psychiatric admissions. Other signs are also common but less specific: staring, ambitendance, iterations, stereotypes, mannerism, overactivity/excitement, impulsivity, combativeness. Some authors complete this description by

  5. Human Nav1.6 Channels Generate Larger Resurgent Currents than Human Nav1.1 Channels, but the Navβ4 Peptide Does Not Protect Either Isoform from Use-Dependent Reduction

    PubMed Central

    Patel, Reesha R.; Barbosa, Cindy; Xiao, Yucheng; Cummins, Theodore R.

    2015-01-01

    Voltage-gated sodium channels are responsible for the initiation and propagation of action potentials (APs). Two brain isoforms, Nav1.1 and Nav1.6, have very distinct cellular and subcellular expression. Specifically, Nav1.1 is predominantly expressed in the soma and proximal axon initial segment of fast-spiking GABAergic neurons, while Nav1.6 is found at the distal axon initial segment and nodes of Ranvier of both fast-spiking GABAergic and excitatory neurons. Interestingly, an auxiliary voltage-gated sodium channel subunit, Navβ4, is also enriched in the axon initial segment of fast-spiking GABAergic neurons. The C-terminal tail of Navβ4 is thought to mediate resurgent sodium current, an atypical current that occurs immediately following the action potential and is predicted to enhance excitability. To better understand the contribution of Nav1.1, Nav1.6 and Navβ4 to high frequency firing, we compared the properties of these two channel isoforms in the presence and absence of a peptide corresponding to part of the C-terminal tail of Navβ4. We used whole-cell patch clamp recordings to examine the biophysical properties of these two channel isoforms in HEK293T cells and found several differences between human Nav1.1 and Nav1.6 currents. Nav1.1 channels exhibited slower closed-state inactivation but faster open-state inactivation than Nav1.6 channels. We also observed a greater propensity of Nav1.6 to generate resurgent currents, most likely due to its slower kinetics of open-state inactivation, compared to Nav1.1. These two isoforms also showed differential responses to slow and fast AP waveforms, which were altered by the Navβ4 peptide. Although the Navβ4 peptide substantially increased the rate of recovery from apparent inactivation, Navβ4 peptide did not protect either channel isoform from undergoing use-dependent reduction with 10 Hz step-pulse stimulation or trains of slow or fast AP waveforms. Overall, these two channels have distinct biophysical

  6. How to find and access information on emerging infectious diseases: Chapter 7 in Disease emergence and resurgence: The wildlife-human connection

    USGS Publications Warehouse

    Wesenberg, Katherine; Friend, Milton

    2006-01-01

    During the last two decades of the 20th century, and continuing today, there has been a global emergence and resurgence of infectious disease of humans and other species. The “exotic” nature and serious consequences of many of these diseases results in media attention and public interest, in addition to the scientific exploration and efforts associated with combating these diseases. Finding and accessing information about diseases and keeping informed about current events and new discoveries is a daunting task because of the diversity of information sources and the great volume of published materials. This chapter provides guidance for effectively traveling the information highway and efficiently negotiating the information maze.

  7. Resurgence of measles in a country of elimination: interim assessment and current control measures in the Republic of Korea in early 2014.

    PubMed

    Yang, Tae Un; Kim, Ju Whi; Eom, Hye Eun; Oh, Hyun-Kyung; Kim, Eun Seong; Kang, Hae Ji; Nam, Jeong-Gu; Kim, Ki Soon; Kim, Sung Soon; Lee, Chan Kyu; Park, Young-Joon; Park, Ok

    2015-04-01

    Since the beginning of 2014, the Republic of Korea has experienced a resurgence of measles cases. Among the 220 cases confirmed as measles during epidemiological weeks 1-20 (December 29, 2013 to May 17, 2014), 10 imported cases were identified. The predominant genotype was B3, which reflects the circulating measles virus in adjacent countries. Even with the verification of measles elimination in March 2014 by the World Health Organization, recent importation has been related to international travel. Targeted control measures have been implemented in addition to proper isolation and patient care. A vigilant surveillance system and high levels of vaccine coverage should be maintained to sustain the measles elimination status.

  8. Structure and evolution of an active resurgent dome evidenced by geophysical investigations: The Yenkahe dome-Yasur volcano system (Siwi caldera, Vanuatu)

    NASA Astrophysics Data System (ADS)

    Brothelande, E.; Lénat, J.-F.; Chaput, M.; Gailler, L.; Finizola, A.; Dumont, S.; Peltier, A.; Bachèlery, P.; Barde-Cabusson, S.; Byrdina, S.; Menny, P.; Colonge, J.; Douillet, G. A.; Letort, J.; Letourneur, L.; Merle, O.; Di Gangi, F.; Nakedau, D.; Garaebiti, E.

    2016-08-01

    In this contribution, we focus on one of the most active resurgences on Earth, that of the Yenkahe dome in the Siwi caldera (Tanna Island, Vanuatu), which is associated with the persistently active Yasur volcano. Gravity and magnetic surveys have been carried out over the past few years in the area, as well as electrical methods including electrical resistivity tomography (ERT), time domain electro-magnetics (TDEM) and self-potential (SP). These investigations were completed by thermometry, CO2 soil gas measurements, field observations and sampling. This multi-method approach allows geological structures within the caldera to be identified, as well as associated hydrothermal features. The global structure of the caldera is deduced from gravity data, which shows the caldera rim as a high density structure. Large lava fields, emplaced before and after the onset of resurgence, are evidenced by combined gravity, magnetic and resistivity signals. In the middle of the caldera, the Yenkahe dome apparently results from a combination of volcanic and tectonic events, showing that lava extrusion and resurgence have been operating simultaneously or alternately during the Siwi caldera post-collapse history. There is a clear distinction between the western and eastern parts of the dome. The western part is older and records the growth of an initial volcanic cone and the formation of a small caldera. This small caldera (paleo-Yasur caldera), partially filled with lava flows, is the present-day focus of volcanic activity and associated fluid circulation and alteration. The eastern part of the dome is presumably younger, and is characterized by intense, extensive hydrothermal alteration and activity. Its northern part is covered by lava flow piles and exhibits a shallow hydrothermal zone in ERT. The southern part has hydrothermal alteration and activity extending at least down to the base of the resurgent dome. This part of the dome is built up of low cohesion rock and is thus

  9. 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

  10. Is Increased Intracellular Calcium in Red Blood Cells a Common Component in the Molecular Mechanism Causing Anemia?

    PubMed Central

    Hertz, Laura; Huisjes, Rick; Llaudet-Planas, Esther; Petkova-Kirova, Polina; Makhro, Asya; Danielczok, Jens G.; Egee, Stephane; del Mar Mañú-Pereira, Maria; van Wijk, Richard; Vives Corrons, Joan-Lluis; Bogdanova, Anna; Kaestner, Lars

    2017-01-01

    For many hereditary disorders, although the underlying genetic mutation may be known, the molecular mechanism leading to hemolytic anemia is still unclear and needs further investigation. Previous studies revealed an increased intracellular Ca2+ in red blood cells (RBCs) from patients with sickle cell disease, thalassemia, or Gardos channelopathy. Therefore we analyzed RBCs' Ca2+ content from 35 patients with different types of anemia (16 patients with hereditary spherocytosis, 11 patients with hereditary xerocytosis, 5 patients with enzymopathies, and 3 patients with hemolytic anemia of unknown cause). Intracellular Ca2+ in RBCs was measured by fluorescence microscopy using the fluorescent Ca2+ indicator Fluo-4 and subsequent single cell analysis. We found that in RBCs from patients with hereditary spherocytosis and hereditary xerocytosis the intracellular Ca2+ levels were significantly increased compared to healthy control samples. For enzymopathies and hemolytic anemia of unknown cause the intracellular Ca2+ levels in RBCs were not significantly different. These results lead us to the hypothesis that increased Ca2+ levels in RBCs are a shared component in the mechanism causing an accelerated clearance of RBCs from the blood stream in channelopathies such as hereditary xerocytosis and in diseases involving defects of cytoskeletal components like hereditary spherocytosis. Future drug developments should benefit from targeting Ca2+ entry mediating molecular players leading to better therapies for patients. PMID:28932200

  11. Is Increased Intracellular Calcium in Red Blood Cells a Common Component in the Molecular Mechanism Causing Anemia?

    PubMed

    Hertz, Laura; Huisjes, Rick; Llaudet-Planas, Esther; Petkova-Kirova, Polina; Makhro, Asya; Danielczok, Jens G; Egee, Stephane; Del Mar Mañú-Pereira, Maria; van Wijk, Richard; Vives Corrons, Joan-Lluis; Bogdanova, Anna; Kaestner, Lars

    2017-01-01

    For many hereditary disorders, although the underlying genetic mutation may be known, the molecular mechanism leading to hemolytic anemia is still unclear and needs further investigation. Previous studies revealed an increased intracellular Ca(2+) in red blood cells (RBCs) from patients with sickle cell disease, thalassemia, or Gardos channelopathy. Therefore we analyzed RBCs' Ca(2+) content from 35 patients with different types of anemia (16 patients with hereditary spherocytosis, 11 patients with hereditary xerocytosis, 5 patients with enzymopathies, and 3 patients with hemolytic anemia of unknown cause). Intracellular Ca(2+) in RBCs was measured by fluorescence microscopy using the fluorescent Ca(2+) indicator Fluo-4 and subsequent single cell analysis. We found that in RBCs from patients with hereditary spherocytosis and hereditary xerocytosis the intracellular Ca(2+) levels were significantly increased compared to healthy control samples. For enzymopathies and hemolytic anemia of unknown cause the intracellular Ca(2+) levels in RBCs were not significantly different. These results lead us to the hypothesis that increased Ca(2+) levels in RBCs are a shared component in the mechanism causing an accelerated clearance of RBCs from the blood stream in channelopathies such as hereditary xerocytosis and in diseases involving defects of cytoskeletal components like hereditary spherocytosis. Future drug developments should benefit from targeting Ca(2+) entry mediating molecular players leading to better therapies for patients.

  12. Mechanisms of sustained high firing rates in two classes of vestibular nucleus neurons: differential contributions of resurgent Na, Kv3, and BK currents.

    PubMed

    Gittis, Aryn H; Moghadam, Setareh H; du Lac, Sascha

    2010-09-01

    To fire at high rates, neurons express ionic currents that work together to minimize refractory periods by ensuring that sodium channels are available for activation shortly after each action potential. Vestibular nucleus neurons operate around high baseline firing rates and encode information with bidirectional modulation of firing rates up to several hundred Hz. To determine the mechanisms that enable these neurons to sustain firing at high rates, ionic currents were measured during firing by using the action potential clamp technique in vestibular nucleus neurons acutely dissociated from transgenic mice. Although neurons from the YFP-16 line fire at rates higher than those from the GIN line, both classes of neurons express Kv3 and BK currents as well as both transient and resurgent Na currents. In the fastest firing neurons, Kv3 currents dominated repolarization at all firing rates and minimized Na channel inactivation by rapidly transitioning Na channels from the open to the closed state. In slower firing neurons, BK currents dominated repolarization at the highest firing rates and sodium channel availability was protected by a resurgent blocking mechanism. Quantitative differences in Kv3 current density across neurons and qualitative differences in immunohistochemically detected expression of Kv3 subunits could account for the difference in firing range within and across cell classes. These results demonstrate how divergent firing properties of two neuronal populations arise through the interplay of at least three ionic currents.

  13. An ignimbrite caldera from the bottom up: Exhumed floor and fill of the resurgent Bonanza caldera, Southern Rocky Mountain volcanic field, Colorado

    USGS Publications Warehouse

    Lipman, Peter W.; Zimmerer, Matthew J.; McIntosh, William C.

    2015-01-01

    Among large ignimbrites, the Bonanza Tuff and its source caldera in the Southern Rocky Mountain volcanic field display diverse depositional and structural features that provide special insights concerning eruptive processes and caldera development. In contrast to the nested loci for successive ignimbrite eruptions at many large multicyclic calderas elsewhere, Bonanza caldera is an areally isolated structure that formed in response to a single ignimbrite eruption. The adjacent Marshall caldera, the nonresurgent lava-filled source for the 33.9-Ma Thorn Ranch Tuff, is the immediate precursor for Bonanza, but projected structural boundaries of two calderas are largely or entirely separate even though the western topographic rim of Bonanza impinges on the older caldera. Bonanza, source of a compositionally complex regional ignimbrite sheet erupted at 33.12 ± 0.03 Ma, is a much larger caldera system than previously recognized. It is a subequant structure ∼20 km in diameter that subsided at least 3.5 km during explosive eruption of ∼1000 km3 of magma, then resurgently domed its floor a similar distance vertically. Among its features: (1) varied exposure levels of an intact caldera due to rugged present-day topography—from Paleozoic and Precambrian basement rocks that are intruded by resurgent plutons, upward through precaldera volcanic floor, to a single thickly ponded intracaldera ignimbrite (Bonanza Tuff), interleaved landslide breccia, and overlying postcollapse lavas; (2) large compositional gradients in the Bonanza ignimbrite (silicic andesite to rhyolite ignimbrite; 60%–76% SiO2); (3) multiple alternations of mafic and silicic zones within a single ignimbrite, rather than simple upward gradation to more mafic compositions; (4) compositional contrasts between outflow sectors of the ignimbrite (mainly crystal-poor rhyolite to east, crystal-rich dacite to west); (5) similarly large compositional diversity among postcollapse caldera-fill lavas and resurgent

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

    PubMed Central

    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

    2015-01-01

    Store-operated Ca2+ entry is the major route of replenishment of intracellular Ca2+ in animal cells in response to depletion of Ca2+ stores in the endoplasmic reticulum. It is primarily mediated by the Ca2+ selective release-activated Ca2+ (CRAC) channel which consists of the pore-forming subunits ORAI1–3 and the Ca2+ 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 Ca2+ as a result of store-operated Ca2+ entry is essential for platelet activation. York Platelet syndrome (YPS) is characterized by thrombocytopenia, striking ultrastructural platelet abnormalities including giant electron opaque organelles and massive, multi-layered target bodies and deficiency of platelet Ca2+ 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

  15. Cell-Type Specific Channelopathies in the Prefrontal Cortex of the fmr1-/y Mouse Model of Fragile X Syndrome.

    PubMed

    Kalmbach, Brian E; Johnston, Daniel; Brager, Darrin H

    2015-01-01

    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.

  16. 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

  17. 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

  18. 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

  19. Decline in Herpes Simplex Virus Type 2 Among Non-Injecting Heroin and Cocaine Users in New York City, 2005 to 2014: Prospects for Avoiding a Resurgence of Human Immunodeficiency Virus.

    PubMed

    Des Jarlais, Don C; Arasteh, Kamyar; Feelemyer, Jonathan; McKnight, Courtney; Tross, Susan; Perlman, David C; Campbell, Aimee N C; Hagan, Holly; Cooper, Hannah L F

    2017-02-01

    Herpes simplex virus type 2 (HSV-2) infection increases both susceptibility to and transmissibility of human immunodeficiency virus (HIV), and HSV-2 and HIV are often strongly associated in HIV epidemics. We assessed trends in HSV-2 prevalence among non-injecting drug users (NIDUs) when HIV prevalence declined from 16% to 8% among NIDUs in New York City. Subjects were current non-injecting users of heroin and/or cocaine and who had never injected illicit drugs. Three thousand one hundred fifty-seven NIDU subjects were recruited between 2005 and 2014 among persons entering Mount Sinai Beth Israel substance use treatment programs. Structured interviews, HIV, and HSV-2 testing were administered. Change over time was assessed by comparing 2005 to 2010 with 2011 to 2014 periods. Herpes simplex virus type 2 incidence was estimated among persons who participated in multiple years. Herpes simplex virus type 2 prevalence was strongly associated with HIV prevalence (odds ratio, 3.9; 95% confidence interval, 2.9-5.1) from 2005 to 2014. Herpes simplex virus type 2 prevalence declined from 60% to 56% (P = 0.01). The percentage of NIDUs with neither HSV-2 nor HIV infection increased from 37% to 43%, (P < 0.001); the percentage with HSV-2/HIV coinfection declined from 13% to 6% (P < 0.001). Estimated HSV-2 incidence was 1 to 2/100 person-years at risk. There were parallel declines in HIV and HSV-2 among NIDUs in New York City from 2005 to 2014. The increase in the percentage of NIDUs with neither HSV-2 nor HIV infection, the decrease in the percentage with HSV-2/HIV coinfection, and the low to moderate HSV-2 incidence suggest some population-level protection against resurgence of HIV. Prevention efforts should be strengthened to end the combined HIV/HSV-2 epidemic among NIDUs in New York City.

  20. 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

  1. The arrhythmogenic consequences of increasing late INa in the cardiomyocyte.

    PubMed

    Shryock, John C; Song, Yejia; Rajamani, Sridharan; Antzelevitch, Charles; Belardinelli, Luiz

    2013-09-01

    This review presents the roles of cardiac sodium channel NaV1.5 late current (late INa) in generation of arrhythmic activity. The assumption of the authors is that proper Na(+) channel function is necessary to the maintenance of the transmembrane electrochemical gradient of Na(+) and regulation of cardiac electrical activity. Myocyte Na(+) channels' openings during the brief action potential upstroke contribute to peak INa and initiate excitation-contraction coupling. Openings of Na(+) channels outside the upstroke contribute to late INa, a depolarizing current that persists throughout the action potential plateau. The small, physiological late INa does not appear to be critical for normal electrical or contractile function in the heart. Late INa does, however, reduce the net repolarizing current, prolongs action potential duration, and increases cellular Na(+) loading. An increase of late INa, due to acquired conditions (e.g. heart failure) or inherited Na(+) channelopathies, facilitates the formation of early and delayed afterpolarizations and triggered arrhythmias, spontaneous diastolic depolarization, and cellular Ca(2+) loading. These in turn increase the spatial and temporal dispersion of repolarization time and may lead to reentrant arrhythmias.

  2. Spaced planar laminations formed by repetitive basal erosion and resurgence to high-sedimentation-rate regime: new insight from a bedform-like structures and laterally continuous exposures

    NASA Astrophysics Data System (ADS)

    Ishihara, Yoshiro; Yuri, Onishi; Tsuda, Keisuke; Yokokawa, Miwa

    2017-04-01

    Spaced planar laminations (SPL), or so-called traction carpet deposits, are frequently observed in deposits of sediment gravity flows. Several sedimentation models for a succession of inversely graded units have been suggested from field observations and flume experiments. The formation of the inversely graded unit could be summarized as follows: (1) abrupt sedimentation on freezing of an inversely graded layer, or (2) interruptions in flow causing a freezing of an inversely graded layer at the most basal part of flow. In either case, traction carpets as a bed load overlying the erosive boundary at the base of flow are required. Although some descriptions have reported SPLs forming antidune bedform-like structures and the association of SPLs with structureless massive deposits have not been clearly explained. In this study, we suggest a novel model of SPL formation by repetition of basal erosion and resurgence to high-sedimentation rates, based on detail examinations of SPLs both showing bedform-like structures and lateral extents of hundreds of meters. SPLs were investigated in the Mio-Pliocene Kiyosumi Formation in central Japan and the Miocene Aoshima Formation in southwest Japan. In a turbidite in the Kiyosumi Formation, SPLs show three mound-like structures, suggesting antidune bedforms with wavelengths of about 6 to 7 m. On the upcurrent flanks, SPLs show lenticular cross laminations or pinching out of units; those units do not show clear inverse grading. Rip-up mud clasts and relatively high-angle imbrications are also observed. On the other hand, SPLs on the downcurrent flanks show relatively clear inverse grading and transition downcurrent into a massive structureless bed. In the Aoshima Formation, SPLs with ca. 1 cm unit thickness continue approximately 50 m along a palaeocurrent direction without changes in thickness. These SPLs gradually transition upward into a massive structureless unit. From the observations described above, in addition to

  3. Insights into the evolution of the Yenkahe resurgent dome (Siwi caldera, Tanna Island, Vanuatu) inferred from aerial high-resolution photogrammetry

    NASA Astrophysics Data System (ADS)

    Brothelande, E.; Lénat, J.-F.; Normier, A.; Bacri, C.; Peltier, A.; Paris, R.; Kelfoun, K.; Merle, O.; Finizola, A.; Garaebiti, E.

    2016-08-01

    The Yenkahe dome (Tanna Island, Vanuatu) is one of the most spectacular examples of presently active post-caldera resurgence, exhibiting a very high uplift rate over the past 1000 years (156 mm/year on average). Although numerous inhabited areas are scattered around the dome, the dynamics of this structure and associated hazards remain poorly studied because of its remote location and dense vegetation cover. A high-resolution photogrammetric campaign was carried out in November 2011 over the dome. Georeferenced photographs were treated by "Structure from Motion" and "Multiple-view Stereophotogrammetry" methods to produce a 3D-digital surface model (DSM) of the area and its associated orthophotograph. This DSM is much more accurate than previously available SRTM and Aster digital elevation models (DEMs), particularly at minimal (coastline) and maximal altitudes (Yasur culmination point, 390 m). While previous mapping relied mostly on low resolution DEMs and satellite images, the high precision of the DSM allows for a detailed structural analysis of the Yenkahe dome, notably based on the quantification of fault displacements. The new structural map, inferred from the 3D reconstruction and morphological analysis of the dome, reveals a complex pattern of faults and destabilization scars reflecting a succession of constructive and destructive events. Numerous landslide scars directed toward the sea highlight the probable occurrence of a tsunami event affecting the south-eastern coast of Tanna. Simulations of landslide-triggered tsunamis show the short time propagation of such a wave (1-2 min), which could affect coastal localities even following relatively small destabilized volumes (a few million cubic meters).

  4. Decrease of Rotavirus Gastroenteritis to a Low Level Without Resurgence for Five Years After Universal RotaTeq Vaccination in Finland.

    PubMed

    Hemming-Harlo, Maria; Markkula, Jukka; Huhti, Leena; Salminen, Marjo; Vesikari, Timo

    2016-12-01

    Universal rotavirus (RV) vaccination with RotaTeq was introduced into National Immunization Programme (NIP) of Finland in September 2009. We have previously reported the reduction of RV gastroenteritis (GE) cases in the first 2 years after RV vaccination in NIP in Finland. In Tampere University Hospital, a 2-year survey of acute GE (AGE) in children was conducted before NIP in the years 2006 to 2008. This was followed by a similar prospective survey in years 2009 to 2011 and now extended to years 2012 to 2014. Stool samples from children examined in the hospital for AGE were analyzed by real-time polymerase chain reaction assays for RV and norovirus, and positive samples were typed by sequencing. The proportion of RVGE of all AGE cases decreased from 52% (421 of 809 cases) in pre-NIP years to 26% (86 of 330 cases) in post-NIP years 2009 to 2011 falling to 12% (40 of 347 cases) in 2012 and 2014. The hospitalizations for RVGE were reduced by 90% and the outpatient clinic visits also by 90% in 2012 to 2014, compared with pre-NIP year; all AGE cases were reduced by 59%. Norovirus was a major causative agent of AGE in the post-NIP period, accounting for 34% of the cases in 2009 to 2011 and 29% in 2012 to 2014. RV vaccination in NIP has led to a major reduction of RVGE cases seen in hospital with no resurgence in 5 years after NIP. A high coverage of RV vaccination will maintain RV activity at a low level but not eliminate wild-type RV circulation.

  5. A resurgence in field research is essential to better understand the diversity, ecology, and evolution of microbial eukaryotes.

    PubMed

    Heger, Thierry J; Edgcomb, Virginia P; Kim, Eunsoo; Lukeš, Julius; Leander, Brian S; Yubuki, Naoji

    2014-01-01

    The discovery and characterization of protist communities from diverse environments are crucial for understanding the overall evolutionary history of life on earth. However, major questions about the diversity, ecology, and evolutionary history of protists remain unanswered, notably because data obtained from natural protist communities, especially of heterotrophic species, remain limited. In this review, we discuss the challenges associated with "field protistology", defined here as the exploration, characterization, and interpretation of microbial eukaryotic diversity within the context of natural environments or field experiments, and provide suggestions to help fill this important gap in knowledge. We also argue that increased efforts in field studies that combine molecular and microscopical methods offer the most promising path toward (1) the discovery of new lineages that expand the tree of eukaryotes; (2) the recognition of novel evolutionary patterns and processes; (3) the untangling of ecological interactions and functions, and their roles in larger ecosystem processes; and (4) the evaluation of protist adaptations to a changing climate.

  6. 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.

  7. An outbreak of pertussis in rural Texas: an example of the resurgence of the disease in the United States.

    PubMed

    Eshofonie, Anthony O; Lin, Huai; Valcin, Randy P; Martin, LaTasha R; Grunenwald, Paul E

    2015-02-01

    During 2012, an increase in the number of pertussis cases or outbreaks was reported among most states within the United States. The majority of these cases included previously vaccinated children between the ages of 7-10 years. This underscores the growing concern regarding current immunization practices and vaccine efficacy, especially as it pertains to pertussis prevention within this age group. In the fall of 2012, an outbreak of pertussis occurred within a school district in a rural Texas county that was reflective of this national pattern. Our objective is to describe this outbreak, highlight the similarities with the national trend, and identify strategies for better disease prevention. The cases in this outbreak were interviewed and laboratory testing done. Information regarding exposure and immunization history among cases was obtained. Immunization audits of the affected institutions were also conducted. We performed a descriptive analysis of the collected data using EPI-INFO software v.3.5.3. A total of 34 cases were identified in this outbreak, of which 23 were PCR confirmed and 11 were epidemiologically linked. Ages ranged from 5 months to 12 years, and 62 % were among children aged 7-10 years. All cases were up-to-date on their pertussis vaccinations. Immunization coverage rate was over 90 % within each of the affected institutions. The characteristics of this outbreak bear striking similarities to the current national trend in terms of age groups and immunization status of the affected cases. Increased focus on this vulnerable target group, including heightened scrutiny of vaccine efficacy and delivery, is indicated.

  8. Resurgence of submersed aquatic macrophytes in the tidal Potomac River, Maryland, Virginia, and the District of Columbia

    USGS Publications Warehouse

    Carter, V.; Rybicki, N.

    1986-01-01

    A 1978-81 survey of submersed aquatic macrophytes in the tidal Potomac River showed that there were virtually no plants in the freshwater tidal river between Chain Bridge and Quantico, Virginia, decades after the disappearance of plants in the late 1930's. Plant populations were monitored in subsequent years (1983-85) using qualitative shoreline surveys and quantitative resampling of the original 1978-81 transects. In 1983, 12 species of submersed aquatic macrophytes were found in the tidal river. Population increases were dramatic; by fall 1985, plants had colonized all shallow areas between Alexandria and Gunston Cove, Virginia. Hydrilla verticillata dominated in Dyke Marsh-Hunting Creek and Swan Creek. Most other areas contained a variable mixture of Heteranthera dubia, Myriophyllum spicatum, Ceratophyllum demersum, Vallisneria americana, Najas guadalupensis and Hydrilla verticillata. No plants were found along the main river or in tidal embayments in the reach between Gunston Cove and Quantico, Virginia. Total dry weight collected in the upper tidal river in fall 1985 was 14.5 times that of spring 1985, and four times that of fall 1984. ?? 1986 Estuarine Research Federation.

  9. 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.

  10. Resurgent Na+ current in pyramidal neurones of rat perirhinal cortex: axonal location of channels and contribution to depolarizing drive during repetitive firing

    PubMed Central

    Castelli, Loretta; Biella, Gerardo; Toselli, Mauro; Magistretti, Jacopo

    2007-01-01

    The perirhinal cortex (PRC) is a supra-modal cortical area that collects and integrates information originating from uni- and multi-modal neocortical regions and directed to the hippocampus. The mechanisms that underlie the specific excitable properties of the different PRC neuronal types are still largely unknown, and their elucidation may be important in understanding the integrative functions of PRC. In this study we investigated the expression and properties of resurgent Na+ current (INaR) in pyramidal neurones of rat PRC area 35 (layer II). Patch-clamp experiments in acute PRC slices were first carried out. A measurable INaR was expressed by a large majority of neurones (31 out of 35 cells). INaR appeared as an inward, slowly decaying current elicited upon step repolarization after depolarizations sufficient to induce nearly complete inactivation of the transient Na+ current (INaT). INaR had a peak amplitude of ∼2.5% that of INaT, and showed the typical biophysical properties also observed in other neuronal types (i.e. cerebellar Purkinje and granule cells), including a bell-shaped current–voltage relationship with a peak at approximately −40 mV, and a characteristic acceleration of activation and decay speed at potentials negative to −45 mV. Current-clamp experiments were then carried out in which repetitive action-potential discharge at various frequencies was induced with depolarizing current injection. The voltage signals thus obtained were then used as command waveforms for voltage-clamp recordings. These experiments showed that a Na+ current identifiable as INaR activates in the early interspike phase even at relatively high firing frequencies (20 Hz), thereby contributing to the depolarizing drive and possibly enhancing repetitive discharge. In acutely dissociated area 35 layer II neurones, as well as in nucleated patches from the same neurones, INaR was never observed, despite the presence of typical INaTs. Since in both preparations neuronal

  11. 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

  12. Assessment of open thermodynamic system concepts for fluviokarst temperature calculations - an example, the Cent-Fonts resurgence (Hérault, France)

    NASA Astrophysics Data System (ADS)

    Machetel, P.; Yuen, D. A.

    2014-01-01

    approximation is presented with the data obtained from the main morphologic and hydrologic properties of the Cent-Font resurgence (Hérault, France). According to the results, the error reached at the output of the fluviokarst is 0.00613 (for Pe = 1.4993 × 108 and Red = 4.2969 × 104). When rescaled to the physical domain, this error leads to a temperature difference of 1.77 K between the CW and AW configurations.

  13. Resurgence of Integrated Behavioral Units

    ERIC Educational Resources Information Center

    Bacha-Mendez, 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…

  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. 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…

  16. 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…

  17. Cell-Type Specific Channelopathies in the Prefrontal Cortex of the fmr1-/y Mouse Model of Fragile X Syndrome123

    PubMed Central

    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

  18. Appetite - increased

    MedlinePlus

    ... Have you noticed any other symptoms such as anxiety, palpitations , increased thirst , vomiting , frequent urination , or unintentional weight gain? Tests that may be done include: Blood tests, ...

  19. Mucolipidosis type IV: the effect of increased lysosomal pH on the abnormal lysosomal storage.

    PubMed

    Kogot-Levin, Aviram; Zeigler, Marsha; Ornoy, Asher; Bach, Gideon

    2009-06-01

    Mucolipidosis type IV (MLIV) is a neurodegenerative channelopathy that is caused by the deficiency of TRPML1 activity, a nonselective cation channel. TRPML1 is a lysosomal membrane protein, and thus, MLIV is a lysosomal storage disorder. The basic, specific function of TRPML1 has not been yet clarified. A recent report (Soyombo AA, Tjon-Kon-Sang S, Rbaibi Y, Bashllari E, Bisceglia J, Muallem S, Kiselyov K: J Biol Chem 281:7294-7301, 2006) indicated that TRPML1 functions as an outwardly proton channel whose function is the prevention of overacidification of these organelles. Thus, in MLIV the lysosomal pH is lower than normal. Furthermore, attempts by these investigators to increase slightly the lysososmal pH with either Nigericin or Chloroquine suggested corrective effect of the abnormal storage in MLIV cells. We investigated this approach using these agents with cultured fibroblasts from severely affected and milder patients. Our data indicated that there was no reduction in the total number of storage vesicles by either agent, although Nigericin resulted in a change in the nature of the storage materials, reducing the presence of lamellated substances (lipids) so that the storage vesicles contained predominantly granulated substances. On the other hand, transfection with the normal MCOLN1 cDNA (the gene coding for TRPML1) resulted in the removal of almost all the storage materials.

  20. Quasi-Molecular K-H[2 ]Absorption As An Alternative To The Resurgence Of CaH Bands In The Spectra Of T-Type Dwarfs: Is The Cloud-Clearing Scheme At Stake?

    NASA Astrophysics Data System (ADS)

    Allard, F.; Allard, N. F.; Johnas, C. M. S.; Hauschildt, P. H.; Homeier, D.; Kielkopf, J. K.; Spiegelman, F.

    2007-08-01

    As brown dwarfs cool off with time, their atmospheres become denser and more transparent, allowing the emitted thermal flux to escape from deeper atmospheric layers. Burgasser et al. (2002) have investigated and classified the red spectra of T dwarfs in a spectral sequence where a resurgence of the hydride bands, after disappearing in the M to L spectral transition, occur between the late L to T before disappearing again in the late T dwarfs. CaH for example is identified in mid-T dwarfs at around 0.7μm (Burgassser 2003). The authors explain this resurgence by a cloud-clearing scheme where holes would allow to see the CaH from deeper enriched layers, while it is settled out from the uppermost atmospheric layers seen on the rest of the brown dwarf surface. We present the first synthetic spectra of T dwarfs including a semi-classical modelling of the pressure broadening of alkalis lines (Na I D, Li I, K I, Rb I, and Cs I fundamental resonance doublets) by molecular hydrogen and helium, the most important species in these atmospheres. We compare the models to the T dwarfs red optical spectra of Burgasser et al. (2003) and we find that the 0.7μm feature has been wrongly identified to CaH. In particular, the very strong KI resonance transition doublet at 0.77μm explains by itself this absorption feature by producing a quasi-molecular satellite absorption feature at this wavelength. The strength of this satellite is very sensitive to the density of perturbers in the lower photosphere and to the background opacity provided by the Na I D red wing, which explains naturally both its apparition in late L dwarfs and its vanishing in late T dwarfs. We find in conclusion that no cloud-clearing scheme or non-equilibrium processes is necessary to explain this absorption feature, and the evolution of the red optical spectrum of T dwarfs. And this should teach us caution about these atmospheres often too enthusiastly considered planetary. MHR 3D convection models are nevertheless

  1. 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.

  2. Back to the Future: The Resurgence of Community in American Society, and Community Journalism in the Newspaper Industry and Higher Education.

    ERIC Educational Resources Information Center

    Lauterer, Jock

    America is in the midst of the age of the emergent and enlightened community. Citizens increasingly demand from their newspapers high-quality, explanatory coverage of local issues. Newspapers large and small are responding. Community newspapers are growing, and many big city media outlets are rethinking their news coverage philosophy in terms of…

  3. SCN4A pore mutation pathogenetically contributes to autosomal dominant essential tremor and may increase susceptibility to epilepsy

    PubMed Central

    Bergareche, Alberto; Bednarz, Marcin; Sánchez, Elena; Krebs, Catharine E.; Ruiz-Martinez, Javier; De La Riva, Patricia; Makarov, Vladimir; Gorostidi, Ana; Jurkat-Rott, Karin; Marti-Masso, Jose Felix; Paisán-Ruiz, Coro

    2015-01-01

    Essential tremor (ET) is the most prevalent movement disorder, affecting millions of people in the USA. Although a positive family history is one of the most important risk factors for ET, the genetic causes of ET remain unknown. In an attempt to identify genetic causes for ET, we performed whole-exome sequencing analyses in a large Spanish family with ET, in which two patients also developed epilepsy. To further assess pathogenicity, site-directed mutagenesis, mouse and human brain expression analyses, and patch clamp techniques were performed. A disease-segregating mutation (p.Gly1537Ser) in the SCN4A gene was identified. Posterior functional analyses demonstrated that more rapid kinetics at near-threshold potentials altered ion selectivity and facilitated the conductance of both potassium and ammonium ions, which could contribute to tremor and increase susceptibility to epilepsy, respectively. In this report, for the first time, we associated the genetic variability of SCN4A with the development of essential tremor, which adds ET to the growing list of neurological channelopathies. PMID:26427606

  4. SCN4A pore mutation pathogenetically contributes to autosomal dominant essential tremor and may increase susceptibility to epilepsy.

    PubMed

    Bergareche, Alberto; Bednarz, Marcin; Sánchez, Elena; Krebs, Catharine E; Ruiz-Martinez, Javier; De La Riva, Patricia; Makarov, Vladimir; Gorostidi, Ana; Jurkat-Rott, Karin; Marti-Masso, Jose Felix; Paisán-Ruiz, Coro

    2015-12-15

    Essential tremor (ET) is the most prevalent movement disorder, affecting millions of people in the USA. Although a positive family history is one of the most important risk factors for ET, the genetic causes of ET remain unknown. In an attempt to identify genetic causes for ET, we performed whole-exome sequencing analyses in a large Spanish family with ET, in which two patients also developed epilepsy. To further assess pathogenicity, site-directed mutagenesis, mouse and human brain expression analyses, and patch clamp techniques were performed. A disease-segregating mutation (p.Gly1537Ser) in the SCN4A gene was identified. Posterior functional analyses demonstrated that more rapid kinetics at near-threshold potentials altered ion selectivity and facilitated the conductance of both potassium and ammonium ions, which could contribute to tremor and increase susceptibility to epilepsy, respectively. In this report, for the first time, we associated the genetic variability of SCN4A with the development of essential tremor, which adds ET to the growing list of neurological channelopathies.

  5. First record of the Asian malaria vector Anopheles stephensi and its possible role in the resurgence of malaria in Djibouti, Horn of Africa.

    PubMed

    Faulde, Michael K; Rueda, Leopoldo M; Khaireh, Bouh A

    2014-11-01

    Anopheles stephensi is an important vector of urban malaria in India and the Persian Gulf area. Its previously known geographical range includes southern Asia and the Arab Peninsula. For the first time, we report A. stephensi from the African continent, based on collections made in Djibouti, on the Horn of Africa, where this species' occurrence was linked to an unusual urban outbreak of Plasmodium falciparum malaria, with 1228 cases reported from February to May 2013, and a second, more severe epidemic that emerged in November 2013 and resulted in 2017 reported malaria cases between January and February 2014. Anopheles stephensi was initially identified using morphological identification keys, followed by sequencing of the Barcode cytochrome c-oxidase I (COI) gene and the rDNA second internal transcribed spacer (ITS2). Positive tests for P. falciparum circumsporozoite antigen in two of six female A. stephensi trapped in homes of malaria patients in March 2013 are evidence that autochthonous urban malaria transmission by A. stephensi has occurred. Concurrent with the second malaria outbreak, P. falciparum-positive A. stephensi females were detected in Djibouti City starting in November 2013. In sub-Saharan Africa, newly present A. stephensi may pose a significant future health threat because of this species' high susceptibility to P. falciparum infection and its tolerance of urban habitats. This may lead to increased malaria outbreaks in African cities. Rapid interruption of the urban malaria transmission cycle, based on integrated vector surveillance and control programs aimed at the complete eradication of A. stephensi from the African continent, is strongly recommended.

  6. Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates.

    PubMed

    Shahab, Muhammad; Mastronardi, Claudio; Seminara, Stephanie B; Crowley, William F; Ojeda, Sergio R; Plant, Tony M

    2005-02-08

    To further study the role of GPR54 signaling in the onset of primate puberty, we used the monkey to examine the ability of kisspeptin-10 to elicit the release of gonadotropin-releasing hormone (GnRH) precociously, and we describe the expression of GPR54 and KiSS-1 in the hypothalamus during the peripubertal period. Agonadal juvenile male monkeys were implanted with a lateral cerebroventricular cannula and a jugular vein catheter. The responsiveness of the juvenile pituitary to endogenous GnRH release was heightened with a chronic pulsatile i.v. infusion of synthetic GnRH before kisspeptin-10 (112-121) injection. Intracerebroventricular (30 microg or 100 microg) or i.v. (100 microg) bolus injections of kisspeptin-10 elicited a robust GnRH discharge, as reflected by luteinizing hormone secretion, which was abolished by pretreatment with a GnRH-receptor antagonist. RNA was isolated from the hypothalamus of agonadal males before (juvenile) and after (pubertal) the pubertal resurgence of pulsatile GnRH release and from juvenile, early pubertal, and midpubertal ovary-intact females. KiSS-1 mRNA levels detected by real-time PCR increased with puberty in both male and female monkeys. In intact females, but not in agonadal males, GPR54 mRNA levels in the hypothalamus increased approximately 3-fold from the juvenile to midpubertal stage. Hybridization histochemistry indicated robust KiSS-1 and GPR54 mRNA expression in the region of the arcuate nucleus. These findings are consistent with the hypothesis that GPR54 signaling by its cognate ligand in the primate hypothalamus may be activated at the end of the juvenile phase of development and may contribute to the pubertal resurgence of pulsatile GnRH release, the central drive for puberty.

  7. Obstructive Sleep Apnea in Patients with Congenital Long QT Syndrome: Implications for Increased Risk of Sudden Cardiac Death

    PubMed Central

    Shamsuzzaman, Abu S.; Somers, Virend K.; Knilans, Timothy K.; Ackerman, Michael J.; Wang, Yu; Amin, Raouf S.

    2015-01-01

    Background: Congenital long QT syndrome (LQTS) is a familial arrhythmogenic cardiac channelopathy characterized by prolonged ventricular repolarization and increased risk of torsades de pointes-mediated syncope, seizures, and sudden cardiac death (SCD). QT prolongation corrected for heart rate (QTc) is an important diagnostic and prognostic feature in LQTS. Obstructive sleep apnea (OSA) has been increasingly implicated in the pathogenesis of cardiovascular disease, including arrhythmias and SCD. We tested the hypothesis that the presence of concomitant OSA in patients with LQTS is associated with increased QT intervals, both during sleep and while awake. Methods and Results: Polysomnography with simultaneous overnight 12-lead electrocardiography (ECG) was recorded in 54 patients with congenital LQTS and 67 control subjects. OSA was diagnosed as apnea-hypopnea index (AHI) ≥ 5 events/h for adults and AHI > 1 event/h for children. RR and QT intervals were measured from the 12-lead surface ECG. QTc was determined by the Bazett formula. Respiratory disturbance index, AHI, and arousal index were significantly increased in patients with LQTS and with OSA compared to those without OSA and control subjects. QTc during different sleep stages and while awake was also significantly increased in patients with LQTS and OSA compared to those without OSA. Severity of OSA in patients with LQTS was directly associated with the degree of QTc. Conclusions: The presence and severity of obstructive sleep apnea (OSA) in patients with congenital long QT syndrome (LQTS) is associated with increased QT prolongation corrected for heart rate, which is an important biomarker of sudden cardiac death (SCD). Treatment of OSA in LQTS patients may reduce QT prolongation, thus reducing the risk of LQT-triggered SCD. Citation: Shamsuzzaman AS, Somers VK, Knilans TK, Ackerman MJ, Wang Y, Amin RS. Obstructive sleep apnea in patients with congenital long QT syndrome: implications for increased risk of

  8. 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

  9. Dolphin morbillivirus epizootic resurgence, Mediterranean Sea.

    PubMed

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

    2008-03-01

    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.

  10. 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.

  11. Dingle’s self-resurgence formula

    NASA Astrophysics Data System (ADS)

    Berry, M. V.

    2017-06-01

    If a nonlinear function F(S) depends on a function S(x) that is represented by a factorially divergent asymptotic power series in a small parameter x, each late coefficient of the power series for F(S(x)) can be represented explicitly as an asymptotic series whose terms involve balanced combinations of the late and early coefficients of the series for S(x). The formula for the late terms was first described by R B Dingle but not published by him. Numerics for a variety of functions F(S) demonstrate this ‘self-resurgence’ and the accuracy of the representation. Dedicated to the memory of R B Dingle, FRSE.

  12. The Resurgence of America's Auto Industry

    ScienceCinema

    Zimmer, Stephen; Cischke, Sue

    2016-07-12

    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.

  13. Block grants and the resurgence of federalism.

    PubMed Central

    Brandt, E N

    1981-01-01

    In an address, this past summer, to the National Convention of State Legislatures, President Reagan captured to essence of the block grant proposal in a sentence. "Our task," the President said, "is to restore the constitutional symmetry between the Central Government and the States and to re-establish the freedom and variety of federalism." Consolidating the current profusion of complex and often overlapping Federal health grants into four State-administered packages will greatly reduce administrative costs and allow us to make wise use of scarce health dollars in a time of economic trial. At the same time, these changes will give States the managerial and policy flexibility that they need, but have lacked, to respond to their own most pressing needs. Of perhaps most importance in the long run, this system of grants will return a just portion of responsibility for the preservation and improvement of our health care system to the States, their communities, and the people. It is precisely this kind of equilibrium, this symmetry, that the President had in mind and that, for too many years, the Federal-State-Private partnership in health has been without. The restoration of this equilibrium, it should be noted by all, is underway. PMID:7302102

  14. 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.

  15. 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.

  16. Evidence for a role of Nav1.6 in facilitating increases in neuronal hyperexcitability during epileptogenesis

    PubMed Central

    Hargus, Nicholas J.; Nigam, Aradhya; Bertram, Edward H.

    2013-01-01

    During epileptogenesis a series of molecular and cellular events occur, culminating in an increase in neuronal excitability, leading to seizure initiation. The entorhinal cortex has been implicated in the generation of epileptic seizures in both humans and animal models of temporal lobe epilepsy. This hyperexcitability is due, in part, to proexcitatory changes in ion channel activity. Sodium channels play an important role in controlling neuronal excitability, and alterations in their activity could facilitate seizure initiation. We sought to investigate whether medial entorhinal cortex (mEC) layer II neurons become hyperexcitable and display proexcitatory behavior of Na channels during epileptogenesis. Experiments were conducted 7 days after electrical induction of status epilepticus (SE), a time point during the latent period of epileptogenesis and before the onset of seizures. mEC layer II stellate neurons from post-SE animals were hyperexcitable, eliciting action potentials at higher frequencies compared with control neurons. Na channel currents recorded from post-SE neurons revealed increases in Na current amplitudes, particularly persistent and resurgent currents, as well as depolarized shifts in inactivation parameters. Immunocytochemical studies revealed increases in voltage-gated Na (Nav) 1.6 isoform levels. The toxin 4,9-anhydro-tetrodotoxin, which has greater selectivity for Nav1.6 over other Na channel isoforms, suppressed neuronal hyperexcitability, reduced macroscopic Na currents, persistent and resurgent Na current densities, and abolished depolarized shifts in inactivation parameters in post-SE neurons. These studies support a potential role for Nav1.6 in facilitating the hyperexcitability of mEC layer II neurons during epileptogenesis. PMID:23741036

  17. 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

  18. Albumin, in the Presence of Calcium, Elicits a Massive Increase in Extracellular Bordetella Adenylate Cyclase Toxin.

    PubMed

    Gonyar, Laura A; Gray, Mary C; Christianson, Gregory J; Mehrad, Borna; Hewlett, Erik L

    2017-06-01

    Pertussis (whooping cough), caused by Bordetella pertussis, is resurging in the United States and worldwide. Adenylate cyclase toxin (ACT) is a critical factor in establishing infection with B. pertussis and acts by specifically inhibiting the response of myeloid leukocytes to the pathogen. We report here that serum components, as discovered during growth in fetal bovine serum (FBS), elicit a robust increase in the amount of ACT, and ≥90% of this ACT is localized to the supernatant, unlike growth without FBS, in which ≥90% is associated with the bacterium. We have found that albumin, in the presence of physiological concentrations of calcium, acts specifically to enhance the amount of ACT and its localization to the supernatant. Respiratory secretions, which contain albumin, promote an increase in amount and localization of active ACT that is comparable to that elicited by serum and albumin. The response to albumin is not mediated through regulation of ACT at the transcriptional level or activation of the Bvg two-component system. As further illustration of the specificity of this phenomenon, serum collected from mice that lack albumin does not stimulate an increase in ACT. These data, demonstrating that albumin and calcium act synergistically in the host environment to increase production and release of ACT, strongly suggest that this phenomenon reflects a novel host-pathogen interaction that is central to infection with B. pertussis and other Bordetella species. Copyright © 2017 American Society for Microbiology.

  19. Increases in gonorrhea among high school students following hurricane Katrina.

    PubMed

    Nsuami, M J; Taylor, S N; Smith, B S; Martin, D H

    2009-06-01

    To determine the prevalence of Neisseria gonorrhoeae in a student population before hurricane Katrina and after their residential neighbourhoods were devastated in the wake of the hurricane. Students in a New Orleans public high school were offered urine screening for N gonorrhoeae and Chlamydia trachomatis using nucleic acid amplification tests before (n = 346) and after (n = 333) hurricane Katrina. Based on studies showing gonorrhea clustering in physically deteriorated neighbourhoods, it was hypothesised that the post-Katrina gonorrhea prevalence would be higher among students whose neighbourhoods still showed signs of deterioration in the aftermath of the hurricane. Before and after hurricane Katrina, the prevalence of gonorrhea increased from 2.3% (8/346, 95% CI 1.3% to 4.6%) to 5.1% (17/333, 95% CI 3.1% to 8.2%), respectively (one-sided p = 0.027). In logistic regression of gonorrhea controlling for gender, age, chlamydia infection and exposure to hurricane-affected residential neighbourhood conditions, gonorrhea was significantly associated with female gender (odds ratio (OR) 2.6, 95% CI 1.0 to 6.3; p = 0.04) and with chlamydia infection (OR 9.2, 95% CI 3.9 to 21.7; p<0.001). Although of weak statistical significance, there was a strong independent positive trend toward testing positive for gonorrhea after the hurricane (OR 2.2, 95% CI 0.9 to 5.4; p = 0.09). The analysis indicates that the odds of testing positive for gonorrhea more than doubled among students after the hurricane, indicating that surveillance activities should be restored to monitor sexually transmitted infections (STIs) among at-risk populations. Redoubled efforts should be put into STI screening programmes as soon as possible following natural disasters to prevent resurgent STI incidence rates.

  20. Unexplained Drownings and the Cardiac Channelopathies: A Molecular Autopsy Series

    PubMed Central

    Tester, David J.; Medeiros-Domingo, Argelia; Will, Melissa L.; Ackerman, Michael J.

    2011-01-01

    OBJECTIVE: To determine the prevalence and spectrum of mutations associated with long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) in a seemingly unexplained drowning cohort. PATIENTS AND METHODS: From September 1, 1998, through October 31, 2010, 35 unexplained drowning victims (23 male and 12 female; mean ± SD age, 17±12 years [range, 4-69 years]) were referred for a cardiac channel molecular autopsy. Of these, 28 (20 male and 8 female) drowned while swimming, and 7 (3 male and 4 female) were bathtub submersions. Polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing were used for a comprehensive mutational analysis of the 3 major LQTS-susceptibility genes (KCNQ1, KCNH2, and SCN5A), and a targeted analysis of the CPVT1-associated, RYR2-encoded cardiac ryanodine receptor was conducted. RESULTS: Of the 28 victims of swimming-related drowning, 8 (28.6%) were mutation positive, including 2 with KCNQ1 mutations (L273F, AAPdel71-73 plus V524G) and 6 with RYR2 mutations (R414C, I419F, R1013Q, V2321A, R2401H, and V2475F). None of the bathtub victims were mutation positive. Of the 28 victims who drowned while swimming, women were more likely to be mutation positive than men (5/8 [62.5%] vs 3/20 [15%]; P=.02). Although none of the mutation-positive, swimming-related drowning victims had a premortem diagnosis of LQTS or CPVT, a family history of cardiac arrest, family history of prior drowning, or QT prolongation was present in 50%. CONCLUSION: Nearly 30% of the victims of swimming-related drowning hosted a cardiac channel mutation. Genetic testing should be considered in the postmortem evaluation of an unexplained drowning, especially if a positive personal or family history is elicited. PMID:21964171

  1. TEMPORARY REMOVAL: Channelopathies, genetic testing and risk stratification.

    PubMed

    Wilde, Arthur A M; Amin, Ahmad

    2017-03-18

    The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

  2. Cardiac Ion Channelopathies and the Sudden Infant Death Syndrome

    PubMed Central

    2012-01-01

    The sudden infant death syndrome (SIDS) causes the sudden death of an apparently healthy infant, which remains unexplained despite a thorough investigation, including the performance of a complete autopsy. The triple risk model for the pathogenesis of SIDS points to the coincidence of a vulnerable infant, a critical developmental period, and an exogenous stressor. Primary electrical diseases of the heart, which may cause lethal arrhythmias as a result of dysfunctioning cardiac ion channels (“cardiac ion channelopathies”) and are not detectable during a standard postmortem examination, may create the vulnerable infant and thus contribute to SIDS. Evidence comes from clinical correlations between the long QT syndrome and SIDS as well as genetic analyses in cohorts of SIDS victims (“molecular autopsy”), which have revealed a large number of mutations in ion channel-related genes linked to inheritable arrhythmogenic syndromes, in particular the long QT syndrome, the short QT syndrome, the Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. Combining data from population-based cohort studies, it can be concluded that at least one out of five SIDS victims carries a mutation in a cardiac ion channel-related gene and that the majority of these mutations are of a known malignant phenotype. PMID:23304551

  3. 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

  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. Increased intracranial pressure

    MedlinePlus

    ... brain. Many conditions can increase intracranial pressure. Common causes include: Aneurysm rupture and subarachnoid hemorrhage Brain tumor Encephalitis Head injury Hydrocephalus (increased fluid around ...

  6. Increasing Accuracy and Increasing Tension in Ho

    NASA Astrophysics Data System (ADS)

    Freedman, Wendy L.

    2017-01-01

    The Hubble Constant, Ho, provides a measure of the current expansion rate of the universe. In recent decades, there has been a huge increase in the accuracy with which extragalactic distances, and hence Ho, can be measured. While the historical factor-of-two uncertainty in Ho has been resolved, a new discrepancy has arisen between the values of Ho measured in the local universe, and that estimated from cosmic microwave background measurements, assuming a Lambda cold dark matter model. I will review the advances that have led to the increase in accuracy in measurements of Ho, as well as describe exciting future prospects with the James Webb Space Telescope (JWST) and Gaia, which will make it feasible to measure extragalactic distances at percent-level accuracy in the next decade.

  7. 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

  8. 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 ...

  9. Increasingly minimal bias routing

    DOEpatents

    Bataineh, Abdulla; Court, Thomas; Roweth, Duncan

    2017-02-21

    A system and algorithm configured to generate diversity at the traffic source so that packets are uniformly distributed over all of the available paths, but to increase the likelihood of taking a minimal path with each hop the packet takes. This is achieved by configuring routing biases so as to prefer non-minimal paths at the injection point, but increasingly prefer minimal paths as the packet proceeds, referred to herein as Increasing Minimal Bias (IMB).

  10. Royalty Earnings Increase 12%.

    ERIC Educational Resources Information Center

    Nicklin, Julie L.

    1997-01-01

    Royalties paid to universities in 1995 increased 12% over the previous year. The increase is attributed in part to federal legislation allowing institutions to patent inventions and discoveries resulting from federally-funded research. Data are based on a survey of 127 universities holding 4,272 licenses generating royalties. Licensing income and…

  11. 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)

  12. 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.

  13. 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.

  14. Increasing rates of depression.

    PubMed

    Klerman, G L; Weissman, M M

    1989-04-21

    Several recent, large epidemiologic and family studies suggest important temporal changes in the rates of major depression: an increase in the rates in the cohorts born after World War II; a decrease in the age of onset with an increase in the late teenaged and early adult years; an increase between 1960 and 1975 in the rates of depression for all ages; a persistent gender effect, with the risk of depression consistently two to three times higher among women than men across all adult ages; a persistent family effect, with the risk about two to three times higher in first-degree relatives as compared with controls; and the suggestion of a narrowing of the differential risk to men and women due to a greater increase in risk of depression among young men. These trends, drawn from studies using comparable methods and modern diagnostic criteria, are evident in the United States, Sweden, Germany, Canada, and New Zealand, but not in comparable studies conducted in Korea and Puerto Rico and of Mexican-Americans living in the United States. These cohort changes cannot be fully attributed to artifacts of reporting, recall, mortality, or labeling and have implications for understanding the etiology of depression and for clinical practice.

  15. 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.

  16. Increasing mobile radiography productivity.

    PubMed

    Wong, Edward; Lung, Ngan Tsz; Ng, Kris; Jeor, Patrick

    2013-01-01

    Mobile radiography using computed radiography (CR) cassettes is a common equipment combination with a workflow bottleneck limited by location of CR readers. Advent of direct digital radiography (DDR) mobile x-ray machines removes this limitation by immediate image review and quality control. Through the use of key performance indicators (KPIs), the increase in efficiency can be quantified.

  17. 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.

  18. 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.

  19. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. 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.

  1. High population increase rates.

    PubMed

    1991-09-01

    In addition to its economic and ethnic difficulties, the USSR faces several pressing demographic problems, including high population increase rates in several of its constituent republics. It has now become clear that although the country's rigid centralized planning succeeded in covering the basic needs of people, it did not lead to welfare growth. Since the 1970s, the Soviet economy has remained sluggish, which as led to increase in the death and birth rates. Furthermore, the ideology that held that demography could be entirely controlled by the country's political and economic system is contradicted by current Soviet reality, which shows that religion and ethnicity also play a significant role in demographic dynamics. Currently, Soviet republics fall under 2 categories--areas with high or low natural population increase rates. Republics with low rates consist of Christian populations (Armenia, Moldavia, Georgia, Byelorussia, Russia, Lithuania, Estonia, Latvia, Ukraine), while republics with high rates are Muslim (Tadzhikistan, Uzbekistan, Turkmenistan, Kirgizia, Azerbaijan Kazakhstan). The later group has natural increase rates as high as 3.3%. Although the USSR as a whole is not considered a developing country, the later group of republics fit the description of the UNFPA's priority list. Another serious demographic issue facing the USSR is its extremely high rate of abortion. This is especially true in the republics of low birth rates, where up to 60% of all pregnancies are terminated by induced abortions. Up to 1/5 of the USSR's annual health care budget is spent on clinical abortions -- money which could be better spent on the production of contraceptives. Along with the recent political and economic changes, the USSR is now eager to deal with its demographic problems.

  2. Nifedipine increases fetoplacental perfusion.

    PubMed

    Karahanoglu, Ertugrul; Altinboga, Orhan; Akpinar, Funda; Demirdag, Erhan; Ozdemirci, Safak; Akyol, Aysegul; Yalvac, Serdar

    2017-01-01

    Our aim is to evaluate the effect of nifedipine on fetoplacental hemodynamic parameters. A retrospective study was conducted at a tertiary center with 30 patients for whom nifedipine treatment was used as a tocolytic therapy for preterm labor. Initiation of this treatment was at 31.6±2.5 weeks of gestation. We combined the pulse Doppler imaging parameters with grayscale imaging via the Bernoulli theorem, which is called the "continuity equation", to get the fetoplacental perfusion (FPP). Evaluated parameters were the resistance index (RI), the pulsatility index (PI), systole/diastole ratios (S/D), the velocity-time integral of the umbilical artery (VTI), the radius of the umbilical artery, the peak systolic velocity and the mean pressure gradient in the umbilical artery. From these parameters, the FPP was acquired. We found that the RI, the PI and the S/D ratio did not change after treatment with nifedipine. The mean pressure gradient, the VTI and the peak systolic velocity increased after treatment with nifedipine. Nifedipine increases FPP from 166±73.81 beat.cm3/min to 220±83.3 beat.cm3/min. Although nifedipine had no effect on the PI, the RI or the S/D, it increased the mean pressure gradient, the VTI and FPP.

  3. Increasing student success

    NASA Astrophysics Data System (ADS)

    Stewart, Gay; Stewart, John

    2013-03-01

    A more scientifically literate society benefits all STEM disciplines, as well as society as a whole. It is best realized by better serving all undergraduate STEM students. In better-serving all students, a physics department also benefits. The University of Arkansas, Fayetteville physics department has seen a drastic change in number of majors, the number of students active in research and the number of graduates pursuing graduate work, while also increasing the number of majors who decide to teach. Prior to our involvement with the Physics Teacher Education Coalition, graduation rates had increased by more than a factor of 4 in 4 years. After the increased efforts when we became a part of PhysTEC (http://PhysTEC.org) our graduation numbers doubled again. Specific attention to class policy to impact student learning in our introductory courses and strong preparation of the graduate teaching assistants, and quality advising were our primary areas of emphasis. What worked to build these numbers and strengthen these resources at Arkansas will be discussed. This work was supported in part by the National Science Foundation and through the Physics Teacher Education Coalition.

  4. Alarming increase in refugees.

    PubMed

    1992-01-01

    Over the past decade and half there has been an alarming worldwide increase in refugees. The total rose form 2.8 million in 1976 to 8.2 million in 1980, to 17.3 million in 1990. Africa's refugees rose from 1.2 million in 1976 to 5.6 million in 1990. Asia's increase over this period was much more rapid--from a mere 180,000 to 8 million. In the Americas the numbers more than trebled, from 770,000 to 2.7 million. Europe was the smallest increase, from 570,000 to 894,000. International law defines a refugee as someone outside of their own country, who has a well-founded fear of persecution because of their political or religious beliefs or ethnic origin, and who cannot turn to their own country for protection. Most refugees are genuine by this definition. The increase reflects, in part, fallout from the cold war. Ethiopia, Mozambique and Angola accounted for almost 1/2 of Africa's refugees; Afghanistan alone for 3/4 of Asia's total. They fled, for the most part, from 1 poor country into another, where they added to shortages of land and fuelwood, and intensified environmental pressure. Malawi, 1 of the poorest countries in the world, is sheltering perhaps as many as 750,000 refugees from the war in Mozambique. But among these refugees--especially among those who turned to the rich countries for asylum--were an increasing number of people who were not suffering political persecution. Driven out of their homes by the collapse of their environment or economic despair, and ready to take any means to get across borders, they are a new category: economic and environmental refugees. The most spectacular attempts hit the television screens: the Vietnamese boat people, ships festooned with Albanians. Behind the headlines there was a growing tide of asylum seekers. The numbers rose 10-fold in Germany from 1983 to 1990. In Switzerland they multiplied by 4 times. In Europe, as a whole, they grew from 71,000 in 1983 to an estimated 550,000 in 1990. In 1990 the numbers threatened to

  5. Flat shoes increase neurogenesis.

    PubMed

    Flensmark, J

    2016-12-01

    The impairment of the horizontal is caused by elevation of the heel of the foot from the ground. Receptors in the soles of the feet provide a mapping of body orientation to the upright, and is identical to Mittelstaedt's idiotropic tendency. Initiation of gait wearing flat shoes without elevation of the heel is sufficient to change to a truthful horizontal. Using flat shoes increases neurogenesis and leads to a decreased frequency of diseases of the nervous system. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Increased Efficiency LED

    NASA Technical Reports Server (NTRS)

    Egalon, Claudio Oliviera (Inventor); Rogowski, Robert S. (Inventor)

    1996-01-01

    In a semiconductor light emitting diode (LED) a large proportion of the light produced will be internally reflected when it strikes the end face of the LED at a semiconductor-air interface. This is due to the high index of refraction of most LED semiconductor materials. This problem may be partially overcome by modification of the shape of the LED by a reverse taper of the sides of the LED. Light is redirected by the taper to strike the interface at an angle closer to normal. This allows light to exit the LED that would be totally internally reflected in an untapered LED. The novelty of the present invention lies in the tapering of the sides of the LED for increased through transmission of light. Prior art devices have made use surface modifications such as roughening, addition of guiding layers, use of index matching materials and hemispherical shaping of the emitting end of the LED. Current technology LEDs have a transmission efficiency of only a few percent. An increase in this efficiency would be of great value to any technology that makes use of LEDs for light generation. The present invention is related to LAR 1 5050-SB, Collection of Light from Optical Fibers of NA greater than 1.

  7. 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

  8. 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

  9. 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

  10. Stress increases periodontal inflammation

    PubMed Central

    RIVERA, CÉSAR; MONSALVE, FRANCISCO; SUAZO, IVÁN; BECERRA, JAVIERA

    2012-01-01

    This study aimed to examine the effect of chronic restraint stress (RS) on the severity of experimental periodontal disease in rats. A total of 32 male Sprague Dawley (SD) rats were divided into four groups: i) Rats receiving two treatment regimens, chronic stress induced by movement restriction in acrylic cylinders for 1–1.5 h daily and induction of experimental periodontal disease, using a nylon ligature which was placed around the first left mandibular molars (n=8); ii) induction of periodontal disease, without RS (n=8); iii) RS (n=8) and iv) control (n=8). After 15 days, blood samples were obtained, and blood glucose levels and the corticosterone concentration were measured as stress markers. The severity of periodontal disease was analyzed according to the level of gingival and bone inflammation, leading to compromise of the teeth involved. Chronic stress was induced with movement restriction (P≤0.05, Mann-Whitney U-test) and increased the severity (P≤0.05, Mann-Whitney U-test) of experimental perio dontal disease in rats, according to the level of gingival and bone inflammation around the first left mandibular molars. The results of the present study showed that RS modulates periodontal inflammation and that the rat model described herein is suitable for investigating the association between stress and periodontal disease. PMID:23226743

  11. Increased mortality in narcolepsy.

    PubMed

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

    2014-03-01

    To evaluate the mortality rate in patients with narcolepsy. Data were derived from a large database representative of the US population, which contains anonymized patient-linked longitudinal claims for 173 million individuals. Symphony Health Solutions (SHS) Source Lx, an anonymized longitudinal patient dataset. All records of patients registered in the SHS database between 2008 and 2010. None. 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. 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.

  12. Increasing paternal responsibility.

    PubMed

    Cutright, P

    1985-01-01

    Increasing numbers of fathers of children born out of wedlock are not contributing to these children's economic support. In 1981, a tiny minority (14%) of the 1.7 million never-married mothers living with a child with an absent father had a child-support award, and of these, just 112,000 actually received some payment in 1981. The high rates of noncompliance, and the low level of legal efforts to enforce child support, are the result of attempts to collect payments through inefficient traditional methods, not the inability of fathers to pay, a Wisconsin study has shown. A basic problem with collecting child support under the present system is that it relies on fathers to control their expenditures and voluntarily to send the payment on a weekly, biweekly or monthly basis, year after year. As a Wisconsin study shows, full compliance with court-ordered payments dropped from 38% in the 1st year to below 20% by the 5th year among 163 ex-husbands tracked. A proposal by researchers at the University of Wisconsin's Institute for Research on Poverty calls for an "absent-parent tax." The Wisconsin Plan, as it is known, is simply a withholding tax based on the father's gross income and the number of his absent children. If his income falls below a certain level, payments will stop automatically, but will resume if and when it rises above the cutoff point. The Wisconsin plan removes all judicial discretion and lawyer's skill as factors in child-support awards, thus eliminating erratic awards. It also insures that support payments will be maintained during periods of conflict between the father and mother. However, before the Wisconsin Plan can effectively protect children both out of wedlock, a feature needs to be added that will establish paternity at birth. Imposing a real child-support obligation on fathers of children born outside of marriage will introduce a potentially powerful economic incentive for responsible male reproductive and parental behavior.

  13. Taking Sides on "Takings": Rhetorical Resurgence of the Sagebrush Rebellion.

    ERIC Educational Resources Information Center

    Chiaviello, Tony

    The "Takings Clause" of the Fifth Amendment to the United States Constitution seems clear enough: when the government takes an individual's property, it must pay him or her for it. The "Sagebrush Rebellion" refers to the numerous incarnations of a movement to privatize public lands and contain environmental regulation. This…

  14. The resurgence of botulinum toxin injection for strabismus in children.

    PubMed

    Mahan, Marielle; Engel, J Mark

    2017-09-01

    The present review discusses recent advances in the use of botulinum toxin for the management of strabismus in children. Botulinum toxin injection produces similar results compared to surgery for certain subtypes of strabismus, especially acute onset esotropia. It may be more effective in many subtypes of esotropia where surgery has been less reliable, including partially accommodative esotropia, esotropia associated with cerebral palsy, and thyroid eye disease. Small retrospective studies have demonstrated the efficacy of botulinum toxin in the treatment of many types of pediatric strabismus, providing some guidance for clinicians to determine which patients would benefit most from this intervention. Although administration of botulinum toxin is generally accepted as a reasonable option in select cases, many strabismus surgeons have not fully embraced the treatment, in part because of perceived disadvantages compared to surgery and difficulty in identifying subsets with the highest potential for therapeutic success. A recent study compared the administration of botulinum toxin in children with acute-onset esotropia to surgical correction and found botulinum toxin had a statistically equal success rate, but with the advantage of significantly less time under general anesthesia. In addition, botulinum toxin has been recently tried in patients with partially accommodative esotropia, esotropia associated with cerebral palsy, cyclic esotropia, and in patients with thyroid eye disease. The present review will discuss current clinical recommendations based on recent studies on the use of botulinum toxin in children with strabismus.

  15. The Resurgence of Naxalism: How Great a Threat to India?

    DTIC Science & Technology

    2008-06-01

    SEZ Special Economic Zone TDP Telugu Desam Party UDF United Democratic Front UCCRI Unity Center of Communist Revolutionaries of India...this phenomenon began in those areas most affected by Naxalism during the previous period, with the emergence of the Telugu Desam Party (TDP) in...www.apstatepolice.org/AboutUs/units/units_greyhounds.htm (accessed February 4, 2008). 180 K.C. Suri, “ Telugu Desam Party,” in India’s Political Parties, ed

  16. The Resurgence of Al-Qaeda in Syria and Iraq

    DTIC Science & Technology

    2014-05-01

    also spelled Al Julani). His name reflects the fact that he is probably from the Golan Heights, and is thought to have close 28 ties to Abu Musab al... ancient city of Aleppo in the northwest. The group’s social wing, Qism al-Ighatha (Relief Department), provides food and warm clothing to civilians

  17. 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.

  18. 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

  19. 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…

  20. Resurgent Ethnicity among Asian Americans: Ethnic Neighborhood Context and Health

    ERIC Educational Resources Information Center

    Walton, Emily

    2012-01-01

    In this study I investigate the associations of neighborhood socioeconomic and social environments with the health of Asian Americans living in both Asian ethnic neighborhoods and non-Asian neighborhoods. I use a sample of 1962 Asian Americans from the National Latino and Asian American Study (NLAAS, 2003-04). Three key findings emerge. First,…

  1. Resurgent Russia in 2030. Challenge for the USAF

    DTIC Science & Technology

    2009-09-01

    5 3 POLITICAL BACKGROUND . . . . . . . . . . . . . . . 15 4 ECONOMIC BACKGROUND...happening in our world. The discus- sion herein is a mix of cultural sociology, political science, econom - ics, military science (sometimes called...political, economic , cultural, and military studies. They also enrolled in specialized coursework pertaining to both Russian domestic and

  2. Measles resurgence in Argentina: 1997-8 outbreak.

    PubMed Central

    Bilkis, M. D.; Barrero, P. R.; Mistchenko, A. S.

    2000-01-01

    Epidemiological and clinical findings from 1162 serologically confirmed measles cases occurring in Buenos Aires, Argentina in 1997 and 1998 were retrospectively reviewed. From 90 hospitalized children, measles virus was detected by direct RT-PCR from nasopharyngeal secretions. Patients were grouped as follows: (i) not vaccinated: infants < 12 months; (ii) regularly vaccinated: children 1-4 years not covered by the last catch-up; (iii) catch-up vaccinated: patients 5-19 years immunized during the 1993 campaign. Most cases were recorded in non-vaccinated infants (54%), and the lowest in catch-up vaccinated children (16%). Mean age of the 90 hospitalized children was 11.3 months. Pneumonia was the major hospitalization cause followed by pneumonitis. Two children required intensive care and one died. The 1993 catch-up campaign seemed to reduce the number of cases in the 5- to 19-year-old group. Lack of timely follow-up probably led to the accumulation of susceptible individuals allowing measles re-emergence. Direct viral detection by RT-PCR proved to be a sensitive tool for molecular epidemiology surveillance. PMID:10813155

  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. Quantum geometry of resurgent perturbative/nonperturbative relations

    DOE PAGES

    Basar, Gokce; Dunne, Gerald V.; Unsal, Mithat

    2017-05-16

    For a wide variety of quantum potentials, including the textbook ‘instanton’ examples of the periodic cosine and symmetric double-well potentials, the perturbative data coming from fluctuations about the vacuum saddle encodes all non-perturbative data in all higher non-perturbative sectors. Here we unify these examples in geometric terms, arguing that the all-orders quantum action determines the all-orders quantum dual action for quantum spectral problems associated with a classical genus one elliptic curve. Furthermore, for a special class of genus one potentials this relation is particularly simple: this class includes the cubic oscillator, symmetric double-well, symmetric degenerate triple-well, and periodic cosine potential.more » These are related to the Chebyshev potentials, which are in turn related to certain N = 2 supersymmetric quantum field theories, to mirror maps for hypersurfaces in projective spaces, and also to topological c = 3 Landau-Ginzburg models and ‘special geometry’. These systems inherit a natural modular structure corresponding to Ramanujan’s theory of elliptic functions in alternative bases, which is especially important for the quantization. Insights from supersymmetric quantum field theory suggest similar structures for more complicated potentials, corresponding to higher genus. Lastly, our approach is very elementary, using basic classical geometry combined with all-orders WKB.« less

  5. Quantum geometry of resurgent perturbative/nonperturbative relations

    NASA Astrophysics Data System (ADS)

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

    2017-05-01

    For a wide variety of quantum potentials, including the textbook `instanton' examples of the periodic cosine and symmetric double-well potentials, the perturbative data coming from fluctuations about the vacuum saddle encodes all non-perturbative data in all higher non-perturbative sectors. Here we unify these examples in geometric terms, arguing that the all-orders quantum action determines the all-orders quantum dual action for quantum spectral problems associated with a classical genus one elliptic curve. Furthermore, for a special class of genus one potentials this relation is particularly simple: this class includes the cubic oscillator, symmetric double-well, symmetric degenerate triple-well, and periodic cosine potential. These are related to the Chebyshev potentials, which are in turn related to certain \\mathcal{N} = 2 supersymmetric quantum field theories, to mirror maps for hypersurfaces in projective spaces, and also to topological c = 3 Landau-Ginzburg models and `special geometry'. These systems inherit a natural modular structure corresponding to Ramanujan's theory of elliptic functions in alternative bases, which is especially important for the quantization. Insights from supersymmetric quantum field theory suggest similar structures for more complicated potentials, corresponding to higher genus. Our approach is very elementary, using basic classical geometry combined with all-orders WKB.

  6. 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.

  7. 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)

  8. 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…

  9. Polycrystalline lead selenide: the resurgence of an old infrared detector

    NASA Astrophysics Data System (ADS)

    Vergara, G.; Montojo, M. T.; Torquemada, M. C.; Rodrigo, M. T.; Sánchez, F. J.; Gómez, L. J.; Almazán, R. M.; Verdú, M.; Rodríguez, P.; Villamayor, V.; Álvarez, M.; Diezhandino, J.; Plaza, J.; Catalán, I.

    2007-06-01

    The existing technology for uncooled MWIR photon detectors based on polycrystalline lead salts is stigmatized for being a 50-year-old technology. It has been traditionally relegated to single-element detectors and relatively small linear arrays due to the limitations imposed by its standard manufacture process based on a chemical bath deposition technique (CBD) developed more than 40 years ago. Recently, an innovative method for processing detectors, based on a vapour phase deposition (VPD) technique, has allowed manufacturing the first 2D array of polycrystalline PbSe with good electro optical characteristics. The new method of processing PbSe is an all silicon technology and it is compatible with standard CMOS circuitry. In addition to its affordability, VPD PbSe constitutes a perfect candidate to fill the existing gap in the photonic and uncooled IR imaging detectors sensitive to the MWIR photons. The perspectives opened are numerous and very important, converting the old PbSe detector in a serious alternative to others uncooled technologies in the low cost IR detection market. The number of potential applications is huge, some of them with high commercial impact such as personal IR imagers, enhanced vision systems for automotive applications and other not less important in the security/defence domain such as sensors for active protection systems (APS) or low cost seekers. Despite the fact, unanimously accepted, that uncooled will dominate the majority of the future IR detection applications, today, thermal detectors are the unique plausible alternative. There is plenty of room for photonic uncooled and complementary alternatives are needed. This work allocates polycrystalline PbSe in the current panorama of the uncooled IR detectors, underlining its potentiality in two areas of interest, i.e., very low cost imaging IR detectors and MWIR fast uncooled detectors for security and defence applications. The new method of processing again converts PbSe into an emerging technology.

  10. Resurgence of HPAI in birds and mechanisms of transmission

    USDA-ARS?s Scientific Manuscript database

    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...

  11. Resurgent Ethnicity among Asian Americans: Ethnic Neighborhood Context and Health

    ERIC Educational Resources Information Center

    Walton, Emily

    2012-01-01

    In this study I investigate the associations of neighborhood socioeconomic and social environments with the health of Asian Americans living in both Asian ethnic neighborhoods and non-Asian neighborhoods. I use a sample of 1962 Asian Americans from the National Latino and Asian American Study (NLAAS, 2003-04). Three key findings emerge. First,…

  12. 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…

  13. Increasing Northern Hemisphere water deficit

    USGS Publications Warehouse

    McCabe, Gregory J.; Wolock, David M.

    2015-01-01

    A monthly water-balance model is used with CRUTS3.1 gridded monthly precipitation and potential evapotranspiration (PET) data to examine changes in global water deficit (PET minus actual evapotranspiration) for the Northern Hemisphere (NH) for the years 1905 through 2009. Results show that NH deficit increased dramatically near the year 2000 during both the cool (October through March) and warm (April through September) seasons. The increase in water deficit near 2000 coincides with a substantial increase in NH temperature and PET. The most pronounced increases in deficit occurred for the latitudinal band from 0 to 40°N. These results indicate that global warming has increased the water deficit in the NH and that the increase since 2000 is unprecedented for the 1905 through 2009 period. Additionally, coincident with the increase in deficit near 2000, mean NH runoff also increased due to increases in P. We explain the apparent contradiction of concurrent increases in deficit and increases in runoff.

  14. Increasing instruction time in school does increase learning

    PubMed Central

    Andersen, Simon Calmar; Nandrup, Anne Brink

    2016-01-01

    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

  15. Increasing instruction time in school does increase learning.

    PubMed

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

    2016-07-05

    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.

  16. Posttraumatic GABA(A)-mediated [Ca2+]i increase is essential for the induction of brain-derived neurotrophic factor-dependent survival of mature central neurons.

    PubMed

    Shulga, Anastasia; Thomas-Crusells, Judith; Sigl, Thomas; Blaesse, Anne; Mestres, Pedro; Meyer, Michael; Yan, Qiao; Kaila, Kai; Saarma, Mart; Rivera, Claudio; Giehl, Klaus M

    2008-07-02

    A shift of GABA(A)-mediated responses from hyperpolarizing to depolarizing after neuronal injury leads to GABA(A)-mediated increase in [Ca2+](i). In addition, central neurons become dependent on BDNF for survival. Whether these two mechanisms are causally interrelated is an open question. Here, we show in lesioned CA3 hippocampal neurons in vitro and in axotomized corticospinal neurons in vivo that posttraumatic downregulation of the neuron-specific K-Cl cotransporter KCC2 leads to intracellular chloride accumulation by the Na-K-2Cl cotransporter NKCC1, resulting in GABA-induced [Ca2+](i) transients. This mechanism is required by a population of neurons to survive in a BDNF-dependent manner after injury, because blocking GABA(A)-depolarization with the NKCC1 inhibitor bumetanide prevents the loss of neurons on BDNF withdrawal. The resurgence of KCC2 expression during recovery coincides with loss of BDNF dependency for survival. This is likely mediated through BDNF itself, because injured neurons reverse their response to this neurotrophin by switching the BDNF-induced downregulation of KCC2 to upregulation.

  17. Does residual force enhancement increase with increasing stretch magnitudes?

    PubMed

    Hisey, Brandon; Leonard, Tim R; Herzog, Walter

    2009-07-22

    It is generally accepted that force enhancement in skeletal muscles increases with increasing stretch magnitudes. However, this property has not been tested across supra-physiological stretch magnitudes and different muscle lengths, thus it is not known whether this is a generic property of skeletal muscle, or merely a property that holds for small stretch magnitudes within the physiological range. Six cat soleus muscles were actively stretched with magnitudes varying from 3 to 24 mm at three different parts of the force-length relationship to test the hypothesis that force enhancement increases with increasing stretch magnitude, independent of muscle length. Residual force enhancement increased consistently with stretch amplitudes on the descending limb of the force-length relationship up to a threshold value, after which it reached a plateau. Force enhancement did not increase with stretch amplitude on the ascending limb of the force-length relationship. Passive force enhancement was observed for all test conditions, and paralleled the behavior of the residual force enhancement. Force enhancement increased with stretch magnitude when stretching occurred at lengths where there was natural passive force within the muscle. These results suggest that force enhancement does not increase unconditionally with increasing stretch magnitude, as is generally accepted, and that increasing force enhancement with stretch appears to be tightly linked to that part of the force-length relationship where there is naturally occurring passive force.

  18. Sugar maple sap volume increases as vacuum level is increased

    Treesearch

    Russell S. Walters; H. Clay Smith

    1975-01-01

    Maple sap yields collected by using plastic tubing with a vacuum pump increased as the vacuum level was increased. Sap volumes collected at the 10- and 15-inch mercury vacuum levels were statistically significantly higher than volumes collected at the 5-inch level. Although the 15-inch vacuum yielded more sap than the 10-inch vacuum, the difference was not...

  19. Increased atherosclerosis in mice with increased vascular biglycan content.

    PubMed

    Thompson, Joel C; Tang, Tao; Wilson, Patricia G; Yoder, Meghan H; Tannock, Lisa R

    2014-07-01

    The response to retention hypothesis of atherogenesis proposes that atherosclerosis is initiated via the retention of atherogenic lipoproteins by vascular proteoglycans. Co-localization studies suggest that of all the vascular proteoglycans, biglycan is the one most closely co-localized with LDL. The goal of this study was to determine if over-expression of biglycan in hyperlipidemic mice would increase atherosclerosis development. Transgenic mice were developed by expressing biglycan under control of the smooth muscle actin promoter, and were crossed to the LDL receptor deficient (C57BL/6 background) atherosclerotic mouse model. Biglycan transgenic and non-transgenic control mice were fed an atherogenic Western diet for 4-12 weeks. LDL receptor deficient mice overexpressing biglycan under control of the smooth muscle alpha actin promoter had increased atherosclerosis development that correlated with vascular biglycan content. Increased vascular biglycan content predisposes to increased lipid retention and increased atherosclerosis development. Published by Elsevier Ireland Ltd.

  20. 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.

  1. Increasing diversity in radiologic technology.

    PubMed

    Carwile, Laura

    2003-01-01

    Diversity is increasingly important in the radiologic technology workplace. For significant changes to occur in work force diversity, educators must first recruit and retain students from a wide variety of backgrounds. This article examines personality, race and gender as factors affecting career choice and how educators can use these factors to increase diversity in their programs. An overview of the ASRT's efforts to improve diversity within the profession is presented, along with suggestions for developing effective recruitment and retention plans to increase diversity.

  2. Increasing detection and increasing incidence in thyroid cancer.

    PubMed

    Hall, Stephen F; Walker, Hugh; Siemens, Robert; Schneeberg, Amy

    2009-12-01

    It has been proposed that the increasing incidence of thyroid cancer is due to increasing detection. Using administrative data, we compare by year from 1993 to 2006, the rates of diagnostic imaging tests of the neck (computed axial tomography--CT, magnetic resonance imaging--MRI, and non-obstetrical ultrasound--US) to the incidence of thyroid cancer for the population of the Province of Ontario Canada. Women and men have different rates of tests, and those rates reflect the rates of new diagnoses of thyroid cancer. The rising incidence of thyroid disease in women is associated with increasing numbers of diagnostic imaging tests.

  3. Increasing point-count duration increases standard error

    USGS Publications Warehouse

    Smith, W.P.; Twedt, D.J.; Hamel, P.B.; Ford, R.P.; Wiedenfeld, D.A.; Cooper, R.J.

    1998-01-01

    We examined data from point counts of varying duration in bottomland forests of west Tennessee and the Mississippi Alluvial Valley to determine if counting interval influenced sampling efficiency. Estimates of standard error increased as point count duration increased both for cumulative number of individuals and species in both locations. Although point counts appear to yield data with standard errors proportional to means, a square root transformation of the data may stabilize the variance. Using long (>10 min) point counts may reduce sample size and increase sampling error, both of which diminish statistical power and thereby the ability to detect meaningful changes in avian populations.

  4. Sleep deprivation increases cigarette smoking.

    PubMed

    Hamidovic, Ajna; de Wit, Harriet

    2009-09-01

    Loss of sleep may impair the ability to abstain from drug use, through any of a number of mechanisms. Sleep loss may increase drug use by impairing attention and inhibitory control, increasing the value of drug rewards over other rewards, or by inducing mood states that facilitate use of a drug. In the present study, we examined whether sleep deprivation (SD) would increase smoking in cigarette smokers, and whether it would do so by impairing attention or inhibitory control. Healthy cigarette smokers (N=14) were tested in a two-session within subject study, after overnight SD or after a normal night's sleep. Subjects were tested in both conditions in randomized order, after abstaining from cigarettes for 48 hours. The procedure was designed to model the human relapse situation. On each 6-h laboratory session after sleep or no sleep, subjects completed mood and craving questionnaires, tasks measuring behavioral inhibition and attention, and a choice procedure in which they chose between money and smoking cigarettes. SD increased self-reported fatigue and decreased arousal, it increased the number of cigarettes subjects chose to smoke, impaired behavioral inhibition and attention. However, the impairments in inhibition or attention were not related to the increase in smoking. It is possible that SD increases smoking because smokers expect that it will reduce sleepiness. Thus, the findings suggest that sleep loss may increase the likelihood of smoking during abstinence not through inhibitory or attentional mechanisms but because of the potential of nicotine to reduce subjective sleepiness.

  5. Increasing Growth of Established Teak

    Treesearch

    C. B. Briscoe; Raul. Ybarra-Cornado

    1971-01-01

    Teak plantations, 3 to 16 years old, were thinned and fertilized in an effort to increase productivity. The best single method for increasing rate of tree increment was removal of competitors. Larger trees had a faster basal area increment but slower height growth than smaller trees on the same site conditions. Height growth was greater in the areas with higher...

  6. 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.

  7. 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.

  8. 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…

  9. 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.

  10. Pigmented basal cell carcinoma: increased melanin or increased melanocytes?

    PubMed

    Brankov, Nikoleta; Prodanovic, Edward M; Hurley, M Yadira

    2016-12-01

    Studies on the precise cause of increased melanization in pigmented basal cell carcinomas (BCC) are limited. We aimed to determine whether the cause of melanization is from increased number of melanocytes or increased melanin pigment, and if there is a difference in the number of melanocytes on different sun-exposed locations. A retrospective review of 45 skin biopsies from January 2011 to February 2011 was performed; 30 were diagnosed as pigmented BCC and 15 as non-pigmented BCC. Immunohistochemistry for MART-1 (melanoma-associated antigen recognized by T-cell 1)/Melan-A (clone M2-7610 + M2-9E3; Leica Microsystems Inc. Buffalo Grove, IL, USA) from Biocare Medical (Concord, CA, USA) was performed on all biopsies. Associations between histopathologic features, number of melanocytes, location, and specific diagnoses were analyzed by Mann-Whitney U test. The mean melanocyte count per high powered field in pigmented BCCs from sun-exposed skin was 101.9 and from intermittently sun-exposed skin was 122.5, as compared to the controls (nodular non-pigmented BCC) of 27.4 (p = 0.002) and 34.9 (p = 0.002), respectively. Pigmented BCCs have a higher mean melanocyte count as compared to non-pigmented BCCs irrespective of location. Therefore, the pigment is not only due to increased melanin, but also due to increased melanocytes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. 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)

  12. 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)

  13. Increasing Positive Interactive Classroom Behavior

    ERIC Educational Resources Information Center

    Kotcher, Elaine; Doremus, Richard R.

    1973-01-01

    The question examined in this study was as follows: do teachers increase their positive classroom interactive behaviors as a result of training in systematic classroom observation techniques? (Authors/JA)

  14. 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.

  15. Food allergy: is prevalence increasing?

    PubMed

    Tang, Mimi L K; Mullins, Raymond J

    2017-03-01

    It is generally accepted that the prevalence of food allergy has been increasing in recent decades, particularly in westernised countries, yet high-quality evidence that is based on challenge confirmed diagnosis of food allergy to support this assumption is lacking because of the high cost and potential risks associated with conducting food challenges in large populations. Accepting this caveat, the use of surrogate markers for diagnosis of food allergy (such as nationwide data on hospital admissions for food anaphylaxis or clinical history in combination with allergen-specific IgE (sIgE) measurement in population-based cohorts) has provided consistent evidence for increasing prevalence of food allergy at least in western countries, such as the UK, United States and Australia. Recent reports that children of East Asian or African ethnicity who are raised in a western environment (Australia and United States respectively) have an increased risk of developing food allergy compared with resident Caucasian children suggest that food allergy might also increase across Asian and African countries as their economies grow and populations adopt a more westernised lifestyle. Given that many cases of food allergy persist, mathematical principles would predict a continued increase in food allergy prevalence in the short to medium term until such time as an effective treatment is identified to allow the rate of disease resolution to be equal to or greater than the rate of new cases.

  16. Increase in lake trout reproduction in lake huron following the collapse of alewife: Relief from thiamine deficiency or larval predation?

    USGS Publications Warehouse

    Fitzsimons, J.D.; Brown, S.; Brown, L.; Honeyfield, D.; He, J.; Johnson, J.E.

    2010-01-01

    In the Great Lakes there is still uncertainty as to the population level effects of a thiamine deficiency on salmonines caused by high consumption of alewives Alosa pseudoharengus. A resurgence of lake trout Salvelinus namaycush reproduction in Lake Huron following the crash of alewife stocks between 2002 and 2004 provided an opportunity to evaluate the relative effects of this crash on reproduction through relief from either alewife mediated thiamine deficiency or alewife predation on larval lake trout relative to possible changes in the size of the lake trout spawning stock. Changes in mean lake trout egg thiamine concentration post crash at one spawning reef in Parry Sound, wheremean thiamine concentration increased by almost two fold, were consistent with diet switching from alewives to rainbow smelt Osmerus mordax, the next most abundant prey fish in Lake Huron. Although thiamine levels for lake trout collected at a second reef in Parry Sound did not change post-crash, levels both pre- and post-crash were consistent with a rainbow smelt diet. A reef specific fry emergence index was found to be positively related to reef specific egg thiamine concentration but negatively related to reef specific occurrence of EMS, a thiamine deficiency related mortality syndrome. We found little evidence for overlap between the timing of spring shoreward migration of alewives and lake trout emergence, suggesting that relief from alewife predation effects had relatively little effect on the observed increase in lake trout recruitment. Numbers of spawners in the north, north-central, and southern zones of the lake increased from 2000 onwards. Overall the abundance post-2003 was higher than from pre-2004, suggesting that spawner abundance may also have contributed to increased lake trout reproduction. However, predicted numbers of spawners and measured abundance of wild recruits in assessment gear were poorly correlated suggesting that the increase in reproduction was not totally

  17. Increased damping of irregular resonators.

    PubMed

    Russ, S; Sapoval, B

    2002-03-01

    It is shown that fractal drums and jagged geometry resonators may be more damped than ordinary Euclidean systems. Several damping mechanisms are examined and studied by numerical calculations. The results depend on the dissipation mechanisms but globally they increase with localization, frequency, and the irregularity of the resonator. The increased dissipation is due to the uneven spatial distribution of the vibrational amplitude in two different ways. First, it is related to the partial confinement of the vibrational modes. Secondly, increased dissipation may be due to singularities in the amplitude distribution. This is the case when a few points exist where the vibration is pinned to zero inducing local logarithmic singularities. This last effect can be spectacular: a single defect can dominate the surface damping by viscous forces of a square drum.

  18. Is serial homicide really increasing?

    PubMed

    Schlesinger, L B

    2001-01-01

    Close examination of the available crime data reveals little scientific support for the widely held belief that serial homicide is frequent and increasing. The author argues that the dramatic changes in homicide clearance rates, incidence of murders with unknown motives, and victim gender data point to a likely increase, not in serial murder, but in contract murder. This type of killing appears to be having a significant impact on society; yet there has been a complete absence of forensic psychiatric study of this crime, a circumstance that needs to change.

  19. Rapid increase of scrub typhus: an epidemiology and spatial-temporal cluster analysis in Guangzhou City, Southern China, 2006-2012.

    PubMed

    Wei, Yuehong; Huang, Yong; Luo, Lei; Xiao, Xincai; Liu, Lan; Yang, Zhicong

    2014-01-01

    Scrub typhus has been increasingly reported in Southern China, and public health authorities are concerned about its increased incidence. Additionally, little evidence is available on the epidemiology of scrub typhus in Southern China. This study aims to analyze the epidemiological and geographic features of ST in Guangzhou City, Southern China, to guide the future prevention efforts. Scrub typhus surveillance data in Guangzhou City during 2006-2012 were obtained from the Chinese National Communicable Disease Surveillance Network. We first conducted a descriptive analysis to analyze the epidemiological features of scrub typhus. Then we used space-time scan statistic based on a discrete Poisson model to detect and evaluate high-risk spatial-temporal clusters of scrub typhus. There were 4,001 cases of scrub typhus in Guangzhou City during the study period. The incidence of scrub typhus increased from 3.29 per 100,000 in 2006 to 9.85 per 100,000 in 2012. A summer peak was observed in June and July with a second peak in September and October except year 2009 and 2011. The majority of the cases (71.4%) were among persons aged ≥40 years, and female incidence was higher than male incidence in persons ≥50 years. In the space-time analysis, high-risk clusters were concentrated in rural areas in Guangzhou City. Over the past 7 years, Haizhu District, an urban area, was found to be a high-risk cluster for the first time in 2012. The resurgence of scrub typhus epidemics in Guangzhou population in 2012 necessitates more effective measures for minimizing future epidemics. Consideration of high-risk population and historical spatial-temporal clusters may help prevent scrub typhus. The risk of scrub typhus in urban areas should not be neglected and needs more attention from public health authorities.

  20. Rapid Increase of Scrub Typhus: An Epidemiology and Spatial-Temporal Cluster Analysis in Guangzhou City, Southern China, 2006–2012

    PubMed Central

    Wei, Yuehong; Huang, Yong; Luo, Lei; Xiao, Xincai; Liu, Lan; Yang, Zhicong

    2014-01-01

    Background Scrub typhus has been increasingly reported in Southern China, and public health authorities are concerned about its increased incidence. Additionally, little evidence is available on the epidemiology of scrub typhus in Southern China. This study aims to analyze the epidemiological and geographic features of ST in Guangzhou City, Southern China, to guide the future prevention efforts. Methods Scrub typhus surveillance data in Guangzhou City during 2006–2012 were obtained from the Chinese National Communicable Disease Surveillance Network. We first conducted a descriptive analysis to analyze the epidemiological features of scrub typhus. Then we used space-time scan statistic based on a discrete Poisson model to detect and evaluate high-risk spatial-temporal clusters of scrub typhus. Results There were 4,001 cases of scrub typhus in Guangzhou City during the study period. The incidence of scrub typhus increased from 3.29 per 100,000 in 2006 to 9.85 per 100,000 in 2012. A summer peak was observed in June and July with a second peak in September and October except year 2009 and 2011. The majority of the cases (71.4%) were among persons aged ≥40 years, and female incidence was higher than male incidence in persons ≥50 years. In the space-time analysis, high-risk clusters were concentrated in rural areas in Guangzhou City. Over the past 7 years, Haizhu District, an urban area, was found to be a high-risk cluster for the first time in 2012. Conclusion The resurgence of scrub typhus epidemics in Guangzhou population in 2012 necessitates more effective measures for minimizing future epidemics. Consideration of high-risk population and historical spatial-temporal clusters may help prevent scrub typhus. The risk of scrub typhus in urban areas should not be neglected and needs more attention from public health authorities. PMID:25006820

  1. Increased NMDA receptor inhibition at an increased Sevoflurane MAC

    PubMed Central

    2012-01-01

    Background Sevoflurane potently enhances glycine receptor currents and more modestly decreases NMDA receptor currents, each of which may contribute to immobility. This modest NMDA receptor antagonism by sevoflurane at a minimum alveolar concentration (MAC) could be reciprocally related to large potentiation of other inhibitory ion channels. If so, then reduced glycine receptor potency should increase NMDA receptor antagonism by sevoflurane at MAC. Methods Indwelling lumbar subarachnoid catheters were surgically placed in 14 anesthetized rats. Rats were anesthetized with sevoflurane the next day, and a pre-infusion sevoflurane MAC was measured in duplicate using a tail clamp method. Artificial CSF (aCSF) containing either 0 or 4 mg/mL strychnine was then infused intrathecally at 4 μL/min, and the post-infusion baseline sevoflurane MAC was measured. Finally, aCSF containing strychnine (either 0 or 4 mg/mL) plus 0.4 mg/mL dizocilpine (MK-801) was administered intrathecally at 4 μL/min, and the post-dizocilpine sevoflurane MAC was measured. Results Pre-infusion sevoflurane MAC was 2.26%. Intrathecal aCSF alone did not affect MAC, but intrathecal strychnine significantly increased sevoflurane requirement. Addition of dizocilpine significantly decreased MAC in all rats, but this decrease was two times larger in rats without intrathecal strychnine compared to rats with intrathecal strychnine, a statistically significant (P < 0.005) difference that is consistent with increased NMDA receptor antagonism by sevoflurane in rats receiving strychnine. Conclusions Glycine receptor antagonism increases NMDA receptor antagonism by sevoflurane at MAC. The magnitude of anesthetic effects on a given ion channel may therefore depend on the magnitude of its effects on other receptors that modulate neuronal excitability. PMID:22672766

  2. Increased NMDA receptor inhibition at an increased Sevoflurane MAC.

    PubMed

    Brosnan, Robert J; Thiesen, Roberto

    2012-06-06

    Sevoflurane potently enhances glycine receptor currents and more modestly decreases NMDA receptor currents, each of which may contribute to immobility. This modest NMDA receptor antagonism by sevoflurane at a minimum alveolar concentration (MAC) could be reciprocally related to large potentiation of other inhibitory ion channels. If so, then reduced glycine receptor potency should increase NMDA receptor antagonism by sevoflurane at MAC. Indwelling lumbar subarachnoid catheters were surgically placed in 14 anesthetized rats. Rats were anesthetized with sevoflurane the next day, and a pre-infusion sevoflurane MAC was measured in duplicate using a tail clamp method. Artificial CSF (aCSF) containing either 0 or 4 mg/mL strychnine was then infused intrathecally at 4 μL/min, and the post-infusion baseline sevoflurane MAC was measured. Finally, aCSF containing strychnine (either 0 or 4 mg/mL) plus 0.4 mg/mL dizocilpine (MK-801) was administered intrathecally at 4 μL/min, and the post-dizocilpine sevoflurane MAC was measured. Pre-infusion sevoflurane MAC was 2.26%. Intrathecal aCSF alone did not affect MAC, but intrathecal strychnine significantly increased sevoflurane requirement. Addition of dizocilpine significantly decreased MAC in all rats, but this decrease was two times larger in rats without intrathecal strychnine compared to rats with intrathecal strychnine, a statistically significant (P < 0.005) difference that is consistent with increased NMDA receptor antagonism by sevoflurane in rats receiving strychnine. Glycine receptor antagonism increases NMDA receptor antagonism by sevoflurane at MAC. The magnitude of anesthetic effects on a given ion channel may therefore depend on the magnitude of its effects on other receptors that modulate neuronal excitability.

  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. 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)

  5. Increasing Reservation Attendance: Ganado's Approach.

    ERIC Educational Resources Information Center

    Foster, Carl; And Others

    Based on recommendations of a District Attendance Task Force, in 1980 the Ganado School District (a Navajo Reservation District) formulated an Attendance Improvement Plan which decreased the primary school's absentee rate 37% over previous years and which dramatically increased Friday attendance. The primary school targeted "high risk"…

  6. Increased Challenge with the Elderly.

    ERIC Educational Resources Information Center

    Wilson, Helen

    Research has shown that too little stress or stimulation can increase health risks. To determine the effectiveness of mild stimulation on the depression levels and feelings of self-worth of the elderly, 24 withdrawn nursing home residents participated in a non-judgemental 6-month art expression group. Half the group were assigned to a control…

  7. 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)

  8. Increasing the Frequency of Daydreaming.

    ERIC Educational Resources Information Center

    Gold, Steven R.; Cundiff, Gary

    1980-01-01

    Studied increased self-reported daydreaming as measured by the daydreaming frequency scale of the Imaginal Processes Inventory, after treatments of being presented with either a positive or neutral talk about the value of daydreaming and training v no training in the use of imagery. (Author)

  9. Crop diversity for yield increase.

    PubMed

    Li, Chengyun; He, Xiahong; Zhu, Shusheng; Zhou, Huiping; Wang, Yunyue; Li, Yan; Yang, Jing; Fan, Jinxiang; Yang, Jincheng; Wang, Guibin; Long, Yunfu; Xu, Jiayou; Tang, Yongsheng; Zhao, Gaohui; Yang, Jianrong; Liu, Lin; Sun, Yan; Xie, Yong; Wang, Haining; Zhu, Youyong

    2009-11-26

    Traditional farming practices suggest that cultivation of a mixture of crop species in the same field through temporal and spatial management may be advantageous in boosting yields and preventing disease, but evidence from large-scale field testing is limited. Increasing crop diversity through intercropping addresses the problem of increasing land utilization and crop productivity. In collaboration with farmers and extension personnel, we tested intercropping of tobacco, maize, sugarcane, potato, wheat and broad bean--either by relay cropping or by mixing crop species based on differences in their heights, and practiced these patterns on 15,302 hectares in ten counties in Yunnan Province, China. The results of observation plots within these areas showed that some combinations increased crop yields for the same season between 33.2 and 84.7% and reached a land equivalent ratio (LER) of between 1.31 and 1.84. This approach can be easily applied in developing countries, which is crucial in face of dwindling arable land and increasing food demand.

  10. 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…

  11. Does Canoeing Increase Streambank Erosion?

    Treesearch

    Edward A. Hansen

    1975-01-01

    Describes research on the Pine River in Michigan to determine if large increases in canoeing accelerated streambank erosion. Most erosion was natural, but people sliding and camping on streambanks created some erosion. Heavy canoe traffic was not a cause of erosion.

  12. Paraplegia increases skeletal muscle autophagy.

    PubMed

    Fry, Christopher S; Drummond, Micah J; Lujan, Heidi L; DiCarlo, Stephen E; Rasmussen, Blake B

    2012-11-01

    Paraplegia results in significant skeletal muscle atrophy through increases in skeletal muscle protein breakdown. Recent work has identified a novel SIRT1-p53 pathway that is capable of regulating autophagy and protein breakdown. Soleus muscle was collected from 6 male Sprague-Dawley rats 10 weeks after complete T4-5 spinal cord transection (paraplegia group) and 6 male sham-operated rats (control group). We utilized immunoblotting methods to measure intracellular proteins and quantitative real-time polymerase chain reaction to measure the expression of skeletal muscle microRNAs. SIRT1 protein expression was 37% lower, and p53 acetylation (LYS379) was increased in the paraplegic rats (P < 0.05). Atg7 and Beclin-1, markers of autophagy induction, were elevated in the paraplegia group compared with controls (P < 0.05). Severe muscle atrophy resulting from chronic paraplegia appears to increase skeletal muscle autophagy independent of SIRT1 signaling. We conclude that chronic paraplegia may cause an increase in autophagic cell death and negatively impact skeletal muscle protein balance. Copyright © 2012 Wiley Periodicals, Inc.

  13. Paraplegia increases skeletal muscle autophagy

    PubMed Central

    Fry, Christopher S.; Drummond, Micah J.; Lujan, Heidi L.; DiCarlo, Stephen E.; Rasmussen, Blake B.

    2012-01-01

    INTRODUCTION Paraplegia results in significant skeletal muscle atrophy through increases in skeletal muscle protein breakdown. Recent work has identified a novel SIRT1-p53 pathway that is capable of regulating autophagy and protein breakdown. METHODS Soleus muscle was collected from 6 male Sprague-Dawley rats 10 weeks following complete T(4)-T(5) spinal-cord transection (paraplegia) and 6 male sham-operated rats (control). We utilized immunoblotting methods to measure intracellular proteins and qRT-PCR to measure the expression of skeletal muscle microRNAs. RESULTS SIRT1 protein expression was 37% lower, and p53 acetylation (LYS379) was increased in the paraplegia rats (P<0.05). Atg7 and Beclin-1, markers of autophagy induction, were elevated in paraplegia compared to controls (P<0.05). DISCUSSION Severe muscle atrophy resulting from chronic paraplegia appears to increase skeletal muscle autophagy independent of SIRT1 signaling. We conclude that chronic paraplegia may cause an increase in autophagic cell-death and negatively impact skeletal muscle protein balance. PMID:23055316

  14. Increasing Positive Interactive Classroom Behavior.

    ERIC Educational Resources Information Center

    Kotcher, Elaine; Doremus, Richard R.

    During the spring of 1972 training workshops for 88 elementary and secondary teachers of the Great Neck Public Schools held to examine four hypotheses: 1) workshops in training teachers to observe classroom behavior would significantly increase these same teachers' positive classroom interactive behaviors consisting of teacher, pupil-pupil,…

  15. How To Increase Advertising Revenue.

    ERIC Educational Resources Information Center

    Mitchell, Carmen

    1995-01-01

    Describes advertising sales strategies to help faculty advisers of community college newspapers increase revenues. Argues that sales representatives should know their product well and maintain demographic information on the paper's readership. Includes strategies for organizing advertising staff, searching for potential clients, and taking charge…

  16. 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…

  17. 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.

  18. 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)

  19. How To Increase Advertising Revenue.

    ERIC Educational Resources Information Center

    Mitchell, Carmen

    1995-01-01

    Describes advertising sales strategies to help faculty advisers of community college newspapers increase revenues. Argues that sales representatives should know their product well and maintain demographic information on the paper's readership. Includes strategies for organizing advertising staff, searching for potential clients, and taking charge…

  20. High Blood Pressure Increasing Worldwide

    MedlinePlus

    ... other ways to control blood pressure, including healthy lifestyle choices and maintaining a normal weight, Roth said. Murray said some of the factors responsible for the worldwide increase in high blood pressure are unhealthy diets and obesity. In addition, in developing countries, more people are ...

  1. Increasing the Overall Quality and the Number of Women and Hispanic Geoscientists for the Workforce: Rebuilding an Undergraduate Program

    NASA Astrophysics Data System (ADS)

    Ford, M. T.; McGehee, T. L.

    2014-12-01

    Over the past ten years, the Geosciences Program at Texas A&M University-Kingsville has increased the number of Geology majors 400%, and in the past five years we have graduated 62 students, an increase of 800%. Of these graduates, 37% were Hispanic or African-American and 26% were women. Our graduates are high-achievers with 13% also graduating from the Honor's College (campus-wide rate is less than 1.5%) and that included three women and two Hispanic graduates. Two of these recent graduates are doctoral candidates and eleven are master's candidates at major universities. Of these, three master's candidates are Hispanic, including two women, and one doctoral candidate is a Hispanic woman. The recent productivity and quality changes in this program are attributed to our shift toward an undergraduate, student-centered focus. The increases in productivity resulted from the development of strong relationships with community colleges across the state and significant efforts in recruitment and retention. The major changes in quality included implementation of a strong field-oriented focus with full faculty participation, a strong undergraduate research program, a well-developed recruitment and retention plan, a GIS Certification incorporated into the geology degree, and a culture change to further student professional development. We have maintained over 50 majors in our program for the past three years through increased faculty presentations at high-schools and community colleges, a good University recruiting staff, and quarterly newsletters, focused on student achievements, sent to all prospective students and parents inquiring about the geology major. The resurgence of the oil and gas industry and the retirement of geoscientists have provided a steady stream of job opportunities for our graduates. The 79% that are not pursuing a graduate education accepted jobs after graduation. These include oil and gas entry level jobs, mining jobs, teaching jobs, and geospatial

  2. Increasing Accuracy in Environmental Measurements

    NASA Astrophysics Data System (ADS)

    Jacksier, Tracey; Fernandes, Adelino; Matthew, Matt; Lehmann, Horst

    2016-04-01

    Human activity is increasing the concentrations of green house gases (GHG) in the atmosphere which results in temperature increases. High precision is a key requirement of atmospheric measurements to study the global carbon cycle and its effect on climate change. Natural air containing stable isotopes are used in GHG monitoring to calibrate analytical equipment. This presentation will examine the natural air and isotopic mixture preparation process, for both molecular and isotopic concentrations, for a range of components and delta values. The role of precisely characterized source material will be presented. Analysis of individual cylinders within multiple batches will be presented to demonstrate the ability to dynamically fill multiple cylinders containing identical compositions without isotopic fractionation. Additional emphasis will focus on the ability to adjust isotope ratios to more closely bracket sample types without the reliance on combusting naturally occurring materials, thereby improving analytical accuracy.

  3. Lead exposure increases blood pressure by increasing angiotensinogen expression.

    PubMed

    Jiao, Jiandong; Wang, Miaomiao; Wang, Yiqing; Sun, Na; Li, Chunping

    2016-01-01

    Lead exposure can induce increased blood pressure. Several mechanisms have been proposed to explain lead-induced hypertension. Changes in angiotensinogen (AGT) expression levels or gene variants may also influence blood pressure. In this study, we hypothesized that AGT expression levels or gene variants contribute to lead-induced hypertension. A preliminary HEK293 cell model experiment was performed to analyze the association between AGT expression and lead exposure. In a population-based study, serum AGT level was measured in both lead-exposed and control populations. To further detect the influence of AGT gene single nucleotide polymorphisms (SNPs) in lead-induced hypertension, two SNPs (rs699 and rs4762) were genotyped in a case-control study including 219 lead-exposed subjects and 393 controls. Lead exposure caused an increase in AGT expression level in HEK 293 cell models (P < 0.001) compared to lead-free cells, and individuals exposed to lead had higher systolic and diastolic blood pressure (P < 0.001). Lead-exposed individuals had higher serum AGT levels compared to controls (P < 0.001). However, no association was found between AGT gene SNPs (rs699 and rs4762) and lead exposure. Nevertheless, the change in AGT expression level may play an important role in the development of lead-induced hypertension.

  4. Increased Body Mass Index Associated with Increased Risky Sexual Behaviors

    PubMed Central

    Gordon, Lonna P.; Diaz, Angela; Soghomonian, Christine; Nucci-Sack, Anne T.; Weiss, Jocelyn M.; Strickler, Howard D.; Burk, Robert D.; Schlecht, Nicolas F.; Ochner, Christopher N.

    2015-01-01

    Study Objective The increasing prevalence of adolescent obesity has led to consideration of the potential effect of obesity on risky sexual behaviors. The current study examined whether body mass index (BMI) was related to age at sexual debut, type of sexual behavior, partner number, and condom use in a population of adolescent women at high risk for obesity and risky sexual behaviors. Study Design Cross-sectional examination of 860 sexually active, predominantly minority, adolescent women who received medical care at an urban health center from 2007 – 2013. Intervention Self-reported age at sexual debut, types of sexual intercourse, number of partners and condom use was compared to clinically – assessed BMI. Results Body mass index was positively associated with number of sexual partners (p = 0.001) and history of attempted anal intercourse (p = 0.002). An inverse association was observed with age at first anal intercourse (p = 0.040). Conclusions In this sample of adolescent women, increased BMI was associated with riskier sexual practices at a younger age. This study suggests that overweight and obese adolescents are a vulnerable population who may need targeted sexual health counseling. PMID:26358938

  5. Breech presentation: increasing maternal choice.

    PubMed

    Tiran, Denise

    2004-11-01

    Pregnant women with a third trimester breech presentation are almost invariably offered Caesarean section as the mode of delivery of first choice, especially when external version has failed to turn the fetus to cephalic. However, increasingly women are resorting to alternatives, to avoid either operative delivery or manipulative intervention in late pregnancy. This paper reviews some of the options for women with breech presentation, focusing especially on integrating these options into conventional maternity care.

  6. Increasing diversity in our profession

    USGS Publications Warehouse

    Davis, Ronald D.; Diswood, Samuel; Dominguez, Annette; Engel-Wilson, Ronald W.; Jefferson, Keith; Miles, A. Keith; Moore, Elizabeth F.; Reidinger, Russell; Ruther, Sherry; Valdez, Raul; Wilson, Kenneth; Zablan, Marilet A.

    2002-01-01

    The Wildlife Society's (TWS) Ethnic and Gender Diversity Committee (previously the Minority Affairs Committee) was established in 1998 and given several charges by TWS Council. This paper responds to our original charge to consider possi- ble actions and programs that TWS might undertake to increase minority participation in the wildlife profession and TWS (R.Anthony, 13 February 1998, Memo to MinorityAffairs Committee).

  7. Increasing diversity in our profession

    USGS Publications Warehouse

    Davis, Ronald D.; Diswood, Samuel; Dominguez, Annette; Engel-Wilson, Ronald W.; Jefferson, Keith; Miles, A. Keith; Moore, Elizabeth F.; Reidinger, Russell; Ruther, Sherry; Valdez, Raul; Wilson, Kenneth; Zablan, Marilet A.

    2002-01-01

    The Wildlife Society's (TWS) Ethnic and Gender Diversity Committee (previously the Minority Affairs Committee) was established in 1998 and given several charges by TWS Council. This paper responds to our original charge to consider possi- ble actions and programs that TWS might undertake to increase minority participation in the wildlife profession and TWS (R.Anthony, 13 February 1998, Memo to MinorityAffairs Committee).

  8. Is surgical workforce diversity increasing?

    PubMed

    Andriole, Dorothy A; Jeffe, Donna B; Schechtman, Kenneth B

    2007-03-01

    We sought to determine the extent to which recent increases in levels of gender and racial diversity in the overall resident-physician workforce were evident among core-surgical specialty resident workforces. Chi-square tests for trend assessed the importance of changes from 1996 to 2004 in proportions of women and African Americans in the surgery-resident workforce. Surgery-resident trends were compared with overall resident workforce trends using two-tailed t-tests to compare regression slopes that quantified rates of change over time. Chi-square tests assessed differences between proportions of women and African Americans in the current overall board-certified workforce and their proportions in the surgery board-certified workforce. From 1996 to 2004, proportions of women increased in all seven surgical specialties studied. Compared with the overall trend toward increasing proportions of women in the resident workforce, the trend in one surgical specialty was larger (obstetrics/gynecology, p < 0.01), four were similar (each p > 0.05), and two were smaller (each p < 0.001). Proportions of African Americans increased in four specialties. Compared with the overall trend, trends in two specialties were larger (obstetrics/gynecology and neurologic surgery, each p < 0.01) and two were similar (each p > 0.05). Proportions of African Americans decreased in three specialties (each p < 0.01). Proportions of women and African Americans in every board-certified specialty workforce, except obstetrics/gynecology, remained lower than in the overall board-certified workforce (each p < 0.01). Many demographic disparities between the surgery-resident and overall-resident workforces have persisted since 1996 and will likely perpetuate ongoing surgery board-certified workforce disparities.

  9. Experiencing discrimination increases risk taking.

    PubMed

    Jamieson, Jeremy P; Koslov, Katrina; Nock, Matthew K; Mendes, Wendy Berry

    2013-02-01

    Prior research has revealed racial disparities in health outcomes and health-compromising behaviors, such as smoking and drug abuse. It has been suggested that discrimination contributes to such disparities, but the mechanisms through which this might occur are not well understood. In the research reported here, we examined whether the experience of discrimination affects acute physiological stress responses and increases risk-taking behavior. Black and White participants each received rejecting feedback from partners who were either of their own race (in-group rejection) or of a different race (out-group rejection, which could be interpreted as discrimination). Physiological (cardiovascular and neuroendocrine) changes, cognition (memory and attentional bias), affect, and risk-taking behavior were assessed. Significant participant race × partner race interactions were observed. Cross-race rejection, compared with same-race rejection, was associated with lower levels of cortisol, increased cardiac output, decreased vascular resistance, greater anger, increased attentional bias, and more risk-taking behavior. These data suggest that perceived discrimination is associated with distinct profiles of physiological reactivity, affect, cognitive processing, and risk taking, implicating direct and indirect pathways to health disparities.

  10. Heterozygosity increases microsatellite mutation rate

    PubMed Central

    Amos, William

    2016-01-01

    Whole genome sequencing of families of Arabidopsis has recently lent strong support to the heterozygote instability (HI) hypothesis that heterozygosity locally increases mutation rate. However, there is an important theoretical difference between the impact on base substitutions, where mutation rate increases in regions surrounding a heterozygous site, and the impact of HI on sequences such as microsatellites, where mutations are likely to occur at the heterozygous site itself. At microsatellite loci, HI should create a positive feedback loop, with heterozygosity and mutation rate mutually increasing each other. Direct support for HI acting on microsatellites is limited and contradictory. I therefore analysed AC microsatellites in 1163 genome sequences from the 1000 genomes project. I used the presence of rare alleles, which are likely to be very recent in origin, as a surrogate measure of mutation rate. I show that rare alleles are more likely to occur at locus-population combinations with higher heterozygosity even when all populations carry exactly the same number of alleles. PMID:26740567

  11. High Heels Increase Women's Attractiveness.

    PubMed

    Guéguen, Nicolas

    2015-11-01

    Research has found that the appearance of women's apparel helps increase their attractiveness as rated by men and that men care more about physical features in potential opposite-sex mates. However, the effect of sartorial appearance has received little interest from scientists. In a series of studies, the length of women's shoe heels was examined. A woman confederate wearing black shoes with 0, 5, or 9 cm heels asked men for help in various circumstances. In Study 1, she asked men to respond to a short survey on gender equality. In Study 2, the confederate asked men and women to participate in a survey on local food habit consumption. In Study 3, men and women in the street were observed while walking in back of the female confederate who dropped a glove apparently unaware of her loss. It was found that men's helping behavior increased as soon as heel length increased. However, heel length had no effect on women's helping behavior. It was also found that men spontaneously approached women more quickly when they wore high-heeled shoes (Study 4). Change in gait, foot-size judgment, and misattribution of sexiness and sexual intent were used as possible explanations.

  12. [How to increase food production?].

    PubMed

    Gahamanyi, L

    1984-12-01

    Pressure of population on cultivable land, serious soil erosion, and low productivity due to scarcity of inputs have hampered efforts to provide an adequate diet for the population of Rwanda. Until the present, production has increased about as rapidly as population, but Rwanda is not totally self-sufficient in food, future climatic conditions may be less favorable than those of the past, technical and resource constraints are likely to increase, and little new land will be available for cultivation. Between 1970-80, hectares devoted to bananas and beans have increased considerably, but the marginal nature of much new land has seriously lowered productivity. Sweet potatoes are more extensively grown but their productivity is limited, and productivity of manioc has stagnated despite efforts to increase it. Peas are less frequently cultivated because the fallow land on they they are grown has almost disappeared due to population pressure. Agriculture in Rwanda has always been associated with herding, but population pressure is eliminating pastureland. Firewood for cooking is also becoming more scarce and reforestation is not proceeding rapidly enough to fill projected demand. Between 1978-80 and the year 2000, preliminary goals are to increase production in tons from 2,005,900 to 3,375,000 for bananas, from 177,400 to 330,000 for beans, from 15,200 to 45,500 for ground nuts, from 4000 to 25,000 for soybeans, from 174,800 to 288,000 for sorghum, from 81,300 to 250,000 for maize, from 3700 to 45,000 for rice, from 837,100 to 2,148,000 for sweet potatoes, from 506,600 to 1,200,000 for manioc, and from 216,000 to 600,000 for potatoes. Reaching these goals will require doubling of overall productivity per hectare. Different strategies will be required for increasing the yields of the principal crops. Priority should be given to developing strains of beans that will grow well in the poor soils, dry or cold regions, and acidic soils where they are usually planted in Rwanda

  13. RANGE INCREASER FOR PNEUMATIC GAUGES

    DOEpatents

    Fowler, A.H.; Seaborn, G.B. Jr.

    1960-09-27

    An improved pneumatic gage is offered in which the linear range has been increased without excessive air consumption. This has been accomplished by providing an expansible antechamber connected to the nozzle of the gage so that the position of the nozzle with respect to the workpiece is varied automatically by variation in pressure within the antechamber. This arrangement ensures that the nozzle-to-workpiece clearance is maintained within certain limits, thus obtaining a linear relation of air flow to nozzle-to-workpiece clearance over a wider range.

  14. Supply prices to increase slightly.

    PubMed

    Hard, R

    1991-03-05

    Expect hospital supply prices to increase by about 3 percent to 4 percent during 1991, says the new economic forecast from the Joint Purchasing Corp. (JPC), New York City. JPC's report may help reduce the uncertainty for those making supply price forecasts during the current recession. The Economic Forecast and Budget Impact Report presents economic information from industry analysts and publishes the data in a single volume. The JPC forecast can be used as a guide to help determine price changes; however, it's also important to consider changes in consumption, utilization, and quality when using the report, says JPC's president.

  15. Increase Productivity Through Knowledge Management

    NASA Astrophysics Data System (ADS)

    Gavrikova, N. A.; Dolgih, I. N.; Dyrina, E. N.

    2016-04-01

    Increase in competition level requires companies to improve the efficiency of work force use characterized by labor productivity. Professional knowledge of staff and its experience play the key role in it. The results of Extrusion Line operator’s working time analysis are performed in this article. The analysis revealed that the reasons of working time ineffective use connected with inadequate information exchange and knowledge management in the company. Authors suggest the way to solve this problem: the main sources of knowledge in engineering enterprise have been defined, the conditions of success and the stages of knowledge management control have been stated.

  16. Increasing Coverage of Appropriate Vaccinations

    PubMed Central

    Jacob, Verughese; Chattopadhyay, Sajal K.; Hopkins, David P.; Morgan, Jennifer Murphy; Pitan, Adesola A.; Clymer, John

    2016-01-01

    Context Population-level coverage for immunization against many vaccine-preventable diseases remains below optimal rates in the U.S. The Community Preventive Services Task Force recently recommended several interventions to increase vaccination coverage based on systematic reviews of the evaluation literature. The present study provides the economic results from those reviews. Evidence acquisition A systematic review was conducted (search period, January 1980 through February 2012) to identify economic evaluations of 12 interventions recommended by the Task Force. Evidence was drawn from included studies; estimates were constructed for the population reach of each strategy, cost of implementation, and cost per additional vaccinated person because of the intervention. Analyses were conducted in 2014. Evidence synthesis Reminder systems, whether for clients or providers, were among the lowest-cost strategies to implement and the most cost effective in terms of additional people vaccinated. Strategies involving home visits and combination strategies in community settings were both costly and less cost effective. Strategies based in settings such as schools and managed care organizations that reached the target population achieved additional vaccinations in the middle range of cost effectiveness. Conclusions The interventions recommended by the Task Force differed in reach, cost, and cost effectiveness. This systematic review presents the economic information for 12 effective strategies to increase vaccination coverage that can guide implementers in their choice of interventions to fit their local needs, available resources, and budget. PMID:26847663

  17. Increasing crude tall oil yield

    SciTech Connect

    Gupta, J.

    1983-10-01

    In the kraft pulping process for softwoods and hardwood, tall oil recovery is an important part of making profit. During the past 10 years, crude tall oil (CTO) production in the U.S. and Canada has dropped. Estimated CTO yield from fresh Canadian pine is 36-40 lb/a.d. ton and from Southern U.S. 70-80 lb/a.d. ton, while the average yield of CTO is approximately 40% of available tall oil in pine wood. Besides low yield, many pulp mills fail to achieve a CTO quality that lives up to market expectations. The moisture content of CTO is reported to vary widely (1.5-3.5%), whereas it should not exceed 1.5% for marketable quality. The acid number of CTO varies in the range of 135 to 150, whereas industry standards are 145-150. At present the average sale price of CTO is approximately $150/ton. By upgrading existing plants, the yield can be increased, resulting in additional revenues. Thus, if a batch acidulation plant is replaced by a continuous acidulation plant, the yield will increase by approximately 15-50%. The capital required for installing a continuous system is approximately $1.1-1.5 million for a 500-a.d. ton/day pulp mill, requiring a payback period of approximatley 5-7 years. 7 references.

  18. Increasing situational awareness using smartphones

    NASA Astrophysics Data System (ADS)

    Boddhu, Sanjay K.; Williams, Robert L.; Wasser, Edward; Kode, Niranjan

    2012-06-01

    In recent years, the United States Armed Services and various law enforcement agencies have shown increasing interest in evaluating the feasibility of using smartphones and hand-held devices as part of the standard gear for its personnel, who are actively engaged on battlefield or in crime-prone areas. The primary motive driving analysis efforts to employ smartphone-based technologies is the prospect of the increased "Situational Awareness" achievable thru a digitally connected network of armed personnel. Personnel would be equipped with customized smart applications that use the device's sensors (GPS, camera, compass, etc...) to sense the hostile environments as well as enabling them to perform collaborative tasks to effectively complete a given mission. In this vein, as part of the Summer At The Edge (SATE) program, a group of student interns under the guidance of mentors from Qbase and AFRL, have employed smartphones and built three smart applications to tackle three real-world scenarios: PinPoint, IStream, and Cooperative GPS. This paper provides implementation details for these prototype applications, along with the supporting visualization and sensor cloud platforms and discusses results obtained from field testing of the same. Further, the paper concludes by providing the implications of the present work and insights into future work.

  19. Hybridization increases invasive knotweed success

    PubMed Central

    Parepa, Madalin; Fischer, Markus; Krebs, Christine; Bossdorf, Oliver

    2014-01-01

    Hybridization is one of the fundamental mechanisms by which rapid evolution can occur in exotic species. If hybrids show increased vigour, this could significantly contribute to invasion success. Here, we compared the success of the two invasive knotweeds, Fallopia japonica and F. sachalinensis, and their hybrid, F. × bohemica, in competing against experimental communities of native plants. Using plant material from multiple clones of each taxon collected across a latitudinal gradient in Central Europe, we found that knotweed hybrids performed significantly better in competition with a native community and that they more strongly reduced the growth of the native plants. One of the parental species, F. sachalinensis, regenerated significantly less well from rhizomes, and this difference disappeared if activated carbon was added to the substrate, which suggests allelopathic inhibition of F. sachalinensis regeneration by native plants. We found substantial within-taxon variation in competitive success in all knotweed taxa, but variation was generally greatest in the hybrid. Interestingly, there was also significant variation within the genetically uniform F. japonica, possibly reflecting epigenetic differences. Our study shows that invasive knotweed hybrids are indeed more competitive than their parents and that hybridization increased the invasiveness of the exotic knotweed complex. PMID:24665343

  20. Public knowledge about AIDS increasing.

    PubMed

    Campbell, M J; Waters, W E

    1987-04-04

    In response to concern over the perceived limited effectiveness of Department of Health and Social Security (UK) advertising campaigns to inform the public of the basic facts of Acquired Immunodeficiency Syndrome (AIDS), a prospective questionnaire study was undertaken in Southampton, England to test the effectiveness of government education prior to a January, 1987 government television/leaflet advertising campaign. 300 questionnaires about AIDS were mailed in December of 1986 to a sample drawn from electoral rolls. The response rate was 61%. Most of the questions were drawn from material covered in the campaign. The results seemed to indicate a small overall increase in knowledge about AIDS. Some changes from a June survey were noted, e.g.: more people were aware that AIDS is a virus for which there is no cure and that it is not readily transmitted by sharing washing, eating or drinking utensils; more people believed that the statement that women are at greater risk for catching AIDS is false. Respondents were generally favorable to the government's continued use of television, even with explicit language, and to its use of the schools, for AIDS education. Many were not aware of the dangers to intravenous drug users or of the symptoms of AIDS. Other surveys have shown an increasing knowledge of AIDS dangers. It is possible that television coverage of the problem will continue to be necessary, in order that less literate populations be reached. Further AIDS health education in general is needed.

  1. Social Power Increases Interoceptive Accuracy

    PubMed Central

    Moeini-Jazani, Mehrad; Knoeferle, Klemens; de Molière, Laura; Gatti, Elia; Warlop, Luk

    2017-01-01

    Building on recent psychological research showing that power increases self-focused attention, we propose that having power increases accuracy in perception of bodily signals, a phenomenon known as interoceptive accuracy. Consistent with our proposition, participants in a high-power experimental condition outperformed those in the control and low-power conditions in the Schandry heartbeat-detection task. We demonstrate that the effect of power on interoceptive accuracy is not explained by participants’ physiological arousal, affective state, or general intention for accuracy. Rather, consistent with our reasoning that experiencing power shifts attentional resources inward, we show that the effect of power on interoceptive accuracy is dependent on individuals’ chronic tendency to focus on their internal sensations. Moreover, we demonstrate that individuals’ chronic sense of power also predicts interoceptive accuracy similar to, and independent of, how their situationally induced feeling of power does. We therefore provide further support on the relation between power and enhanced perception of bodily signals. Our findings offer a novel perspective–a psychophysiological account–on how power might affect judgments and behavior. We highlight and discuss some of these intriguing possibilities for future research. PMID:28824501

  2. Increasing entropy for colloidal stabilization

    PubMed Central

    Mo, Songping; Shao, Xuefeng; Chen, Ying; Cheng, Zhengdong

    2016-01-01

    Stability is of paramount importance in colloidal applications. Attraction between colloidal particles is believed to lead to particle aggregation and phase separation; hence, stability improvement can be achieved through either increasing repulsion or reducing attraction by modifying the fluid medium or by using additives. Two traditional mechanisms for colloidal stability are electrostatic stabilization and steric stabilization. However, stability improvement by mixing attractive and unstable particles has rarely been considered. Here, we emphasize the function of mixing entropy in colloidal stabilization. Dispersion stability improvement is demonstrated by mixing suspensions of attractive nanosized titania spheres and platelets. A three-dimensional phase diagram is proposed to illustrate the collaborative effects of particle mixing and particle attraction on colloidal stability. This discovery provides a novel method for enhancing colloidal stability and opens a novel opportunity for engineering applications. PMID:27872473

  3. Increase in composite binder activity

    NASA Astrophysics Data System (ADS)

    Fediuk, R.; Smoliakov, A.; Stoyushko, N.

    2016-11-01

    The binder of portland cement (51-59 wt.%), fly ash of thermal power stations (3644 wt.%), limestone crushing waste (4-9 wt.%) and dry hyper plasticizer (0.2 wt.%) has been created. It can be used in the building materials industry for production of high-strength concrete. The composite binder is obtained by co-milling of the components in vario-planetary mill to a specific surface area of 550-600 m2/kg. The technical result is the possibility of obtaining a composite binder with significant replacement of cement with industrial waste, cost-effective and superior to portland cement for construction and technical properties, increased activity. This allows producing concrete for walling with a compressive strength of 100 MPa, while using more than 50% of industrial waste.

  4. Increasing entropy for colloidal stabilization

    NASA Astrophysics Data System (ADS)

    Mo, Songping; Shao, Xuefeng; Chen, Ying; Cheng, Zhengdong

    2016-11-01

    Stability is of paramount importance in colloidal applications. Attraction between colloidal particles is believed to lead to particle aggregation and phase separation; hence, stability improvement can be achieved through either increasing repulsion or reducing attraction by modifying the fluid medium or by using additives. Two traditional mechanisms for colloidal stability are electrostatic stabilization and steric stabilization. However, stability improvement by mixing attractive and unstable particles has rarely been considered. Here, we emphasize the function of mixing entropy in colloidal stabilization. Dispersion stability improvement is demonstrated by mixing suspensions of attractive nanosized titania spheres and platelets. A three-dimensional phase diagram is proposed to illustrate the collaborative effects of particle mixing and particle attraction on colloidal stability. This discovery provides a novel method for enhancing colloidal stability and opens a novel opportunity for engineering applications.

  5. Advertising increases demand for vasectomy.

    PubMed

    Mehta, M; Mckenzie, M

    1996-01-01

    The recent evaluation of a 2-year no-scalpel vasectomy (NSV) training program providing on-site, hands-on training for physicians working in 43 publicly funded health centers in 17 states found that demand for vasectomy in low-income and minority communities in the US increased following the implementation of innovative advertising strategies. The program also provided sites with surgical instruments, training materials, a press kit, and some help with public information activities. Participating clinics used a range of formal and informal advertising strategies, including radio and printed advertisements, to inform potential clients about vasectomy services. Many interested clients presented to clinics to undergo vasectomy once they had been made aware of the service and its availability. Several providers even stated that advertising caused the demand for vasectomy to exceed their capacity to provide services. The provision of low- or no-cost procedures helped to attract new clients.

  6. Increased damping in irregular resonators

    NASA Astrophysics Data System (ADS)

    Sapoval, Bernard; Asch, Mark; Felix, Simon; Filoche, Marcel

    2005-04-01

    The relation between shape and damping of shallow acoustical cavities has been studied numerically in the case where the dissipation occurs only on the cavity walls. It is first found that whatever the type of geometrical irregularity, many, but not all the modes are localized. It is shown that the localization mechanism is what is called weak localization. The more irregular, the smaller the quality factors are found. However this effect is very different for the non-localized and the localized modes. For non-localized modes the damping increases roughly proportionally to the cavity surface. The localized modes are even more damped. These results generalize the results already obtained both numerically and experimentally on prefractal acoustical cavities. [B. Sapoval, O. Haeberle, and S. Russ, J. Acoust. Soc. Am. 102, 2014-2019 (1997); B. Hebert, B. Sapoval, and S. Russ, ibid. 105, 1567-1576 (1999)].

  7. Moire interferometry with increased sensitivity

    NASA Astrophysics Data System (ADS)

    Han, Bongtae; Post, Daniel

    The basic sensitivity of moire interferometry was increased beyond the previously conceived theoretical limit. This was accomplished by creating the virtual reference grating inside a refractive medium instead of air, thus shortening the wavelength of light. A very compact four-beam moire interferometer in a refractive medium was developed for microscopic viewing, which produced a basic sensitivity of 208 nm per fringe order, corresponding to moire with 4800 lines per mm. Its configuration made it inherently stable and relatively insensitive to environmental disturbances. An optical microscope was employed as the image recording system to obtain high spatial resolution. The method was demonstrated for deformation of a thick graphite/epoxy composite at the 0/90 deg ply interface.

  8. Thunderstorms Increase Mercury Wet Deposition.

    PubMed

    Holmes, Christopher D; Krishnamurthy, Nishanth P; Caffrey, Jane M; Landing, William M; Edgerton, Eric S; Knapp, Kenneth R; Nair, Udaysankar S

    2016-09-06

    Mercury (Hg) wet deposition, transfer from the atmosphere to Earth's surface by precipitation, in the United States is highest in locations and seasons with frequent deep convective thunderstorms, but it has never been demonstrated whether the connection is causal or simple coincidence. We use rainwater samples from over 800 individual precipitation events to show that thunderstorms increase Hg concentrations by 50% relative to weak convective or stratiform events of equal precipitation depth. Radar and satellite observations reveal that strong convection reaching the upper troposphere (where high atmospheric concentrations of soluble, oxidized mercury species (Hg(II)) are known to reside) produces the highest Hg concentrations in rain. As a result, precipitation meteorology, especially thunderstorm frequency and total rainfall, explains differences in Hg deposition between study sites located in the eastern United States. Assessing the fate of atmospheric mercury thus requires bridging the scales of global transport and convective precipitation.

  9. Reflexive aerostructures: increased vehicle survivability

    NASA Astrophysics Data System (ADS)

    Margraf, Thomas W.; Hemmelgarn, Christopher D.; Barnell, Thomas J.; Franklin, Mark A.

    2007-04-01

    Aerospace systems stand to benefit significantly from the advancement of reflexive aerostructure technologies for increased vehicle survivability. Cornerstone Research Group Inc. (CRG) is developing lightweight, healable composite systems for use as primary load-bearing aircraft components. The reflexive system is comprised of piezoelectric structural health monitoring systems, localized thermal activation systems, and lightweight, healable composite structures. The reflexive system is designed to mimic the involuntary human response to damage. Upon impact, the structural health monitoring system will identify the location and magnitude of the damage, sending a signal to a discrete thermal activation control system to resistively heat the shape memory polymer (SMP) matrix composite above activation temperature, resulting in localized shape recovery and healing of the damaged areas. CRG has demonstrated SMP composites that can recover 90 percent of flexural yield stress and modulus after postfailure healing. During the development, CRG has overcome issues of discrete activation, structural health monitoring integration, and healable resin systems. This paper will address the challenges associated with development of a reflexive aerostructure, including integration of structural health monitoring, discrete healing, and healable shape memory resin systems.

  10. Vocal attractiveness increases by averaging.

    PubMed

    Bruckert, Laetitia; Bestelmeyer, Patricia; Latinus, Marianne; Rouger, Julien; Charest, Ian; Rousselet, Guillaume A; Kawahara, Hideki; Belin, Pascal

    2010-01-26

    Vocal attractiveness has a profound influence on listeners-a bias known as the "what sounds beautiful is good" vocal attractiveness stereotype [1]-with tangible impact on a voice owner's success at mating, job applications, and/or elections. The prevailing view holds that attractive voices are those that signal desirable attributes in a potential mate [2-4]-e.g., lower pitch in male voices. However, this account does not explain our preferences in more general social contexts in which voices of both genders are evaluated. Here we show that averaging voices via auditory morphing [5] results in more attractive voices, irrespective of the speaker's or listener's gender. Moreover, we show that this phenomenon is largely explained by two independent by-products of averaging: a smoother voice texture (reduced aperiodicities) and a greater similarity in pitch and timbre with the average of all voices (reduced "distance to mean"). These results provide the first evidence for a phenomenon of vocal attractiveness increases by averaging, analogous to a well-established effect of facial averaging [6, 7]. They highlight prototype-based coding [8] as a central feature of voice perception, emphasizing the similarity in the mechanisms of face and voice perception. Copyright 2010 Elsevier Ltd. All rights reserved.

  11. Scientific progress as increasing verisimilitude.

    PubMed

    Niiniluoto, Ilkka

    2014-06-01

    According to the foundationalist picture, shared by many rationalists and positivist empiricists, science makes cognitive progress by accumulating justified truths. Fallibilists, who point out that complete certainty cannot be achieved in empirical science, can still argue that even successions of false theories may progress toward the truth. This proposal was supported by Karl Popper with his notion of truthlikeness or verisimilitude. Popper's own technical definition failed, but the idea that scientific progress means increasing truthlikeness can be expressed by defining degrees of truthlikeness in terms of similarities between states of affairs. This paper defends the verisimilitude approach against Alexander Bird who argues that the "semantic" definition (in terms of truth or truthlikeness alone) is not sufficient to define progress, but the "epistemic" definition referring to justification and knowledge is more adequate. Here Bird ignores the crucial distinction between real progress and estimated progress, explicated by the difference between absolute (and usually unknown) degrees of truthlikeness and their evidence-relative expected values. Further, it is argued that Bird's idea of returning to the cumulative model of growth requires an implausible trick of transforming past false theories into true ones.

  12. R & D increases electricity markets

    SciTech Connect

    Sussman, S.S.

    1995-10-01

    As the electric utility industry moves increasingly toward open competition, sharing of information among utilities will become more restrictive. Today, the spirit of cooperation seens to be faltering, due to each companies` concerns about revealing potentially sensitive information which could be exploited by a utility`s competitors. This situation raises a serious question regarding the future of cooperative R&D. One area of R&D that will benefit all electric energy providers is that which will create new or larger markets for electricity. An R&D consortia can also help to satisfy some rather generic needs of its competitive members. Members of competitive industries have quickly and economically developed market-building technologies through their support of R&D consortium. It is very likely that as the electric utility industry undergoes restructuring, collaborative R&D will continue to produce mutually beneficial technologies. The realities of competition will require the electric R&D consortia to adjust the processes used to plan and manage R&D projects.

  13. Slow motion increases perceived intent

    PubMed Central

    Caruso, Eugene M.; Burns, Zachary C.; Converse, Benjamin A.

    2016-01-01

    To determine the appropriate punishment for a harmful action, people must often make inferences about the transgressor’s intent. In courtrooms and popular media, such inferences increasingly rely on video evidence, which is often played in “slow motion.” Four experiments (n = 1,610) involving real surveillance footage from a murder or broadcast replays of violent contact in professional football demonstrate that viewing an action in slow motion, compared with regular speed, can cause viewers to perceive an action as more intentional. This slow motion intentionality bias occurred, in part, because slow motion video caused participants to feel like the actor had more time to act, even when they knew how much clock time had actually elapsed. Four additional experiments (n = 2,737) reveal that allowing viewers to see both regular speed and slow motion replay mitigates the bias, but does not eliminate it. We conclude that an empirical understanding of the effect of slow motion on mental state attribution should inform the life-or-death decisions that are currently based on tacit assumptions about the objectivity of human perception. PMID:27482091

  14. Increased coagulation in childhood obesity.

    PubMed

    Bilge, Yildiz Dallar; Alioglu, Bulent; Simşek, Enver; Tapci, Ayse Esra; Ozen, Cınar

    2012-11-01

    This study aims to explore the relation between childhood obesity and procoagulant and anticoagulant systems. Fifty-one obese children and 32 normal-weighted children with similar age and gender distribution and between ages of 5 and 16 years were recruited to the study. Antropometric measures of all subjects, existence of any accompanying disease, and medication histories had been recorded. Full blood count, procoagulant, and anticoagulant coagulation tests were run for all subjects. When hematologic variables of obese children were compared with those of healthy controls, it was found that average erythrocyte hemoglobin concentration, erythrocyte distribution width, and platelet count of obese children are significantly higher than healthy control group. It was also found that fibrinogen, thrombin time, factor (F) VIII, FIX, FX, and von Willebrand factor levels of obese children are higher than healthy control group. By contrast, antithrombin levels of obese children are found to be lower. In our study, we found that there is a procoagulant increase in the coagulation system activity of obese children compared to non-obese healthy children, whereas there is a significant decrease in anticoagulant system. These changes occurred in obese patients, especially higher levels of plasma procoagulant factors such as fibrinogen, FVIII, FIX, and von Willebrand factor, lead us to think that there is an activity in these patients at endothelial level. Further studies are needed on endothelial activity of obese children.

  15. Elective haemodialysis increases exhaled isoprene.

    PubMed

    Lirk, Philipp; Bodrogi, Florian; Raifer, Hartmann; Greiner, Karin; Ulmer, Hanno; Rieder, Josef

    2003-05-01

    Uraemic odour is a characteristic feature of patients with end-stage renal disease (ESRD). However, few investigations have been carried out into the composition of exhaled air in ESRD patients undergoing haemodialysis (HD). Increases of exhaled isoprene levels by a factor of up to 2.7 following HD have been reported. We attempted to confirm these findings in 50 patients undergoing HD using haemophan (n=23) or polysulphone (n=27) dialysis membranes. Parallel evaluation of ambient air, calorie intake, medication and haemodynamic variables was performed. Samples were analysed using proton transfer reaction-mass spectrometry (PTR-MS). Significant changes in breath isoprene concentration were observed when comparing patients before [39.14+/-14.96 parts per billion (ppbv)] and after (63.54+/-27.59 ppbv) dialysis (P<0.001). The quotient of values before and after dialysis was 1.84 (SD 1.41). No significant differences in isoprene kinetics were found between the use of haemophan and polysulphone membranes. No significant correlations were observed between isoprene quotients and variations in blood pressure during HD, calorie intake, ingestion of lipid-lowering drugs or serum lipid levels. Isoprene concentration was higher in the exhaled air of patients after HD as compared with values before HD. Large interindividual variability existed in isoprene kinetics. Oxidative stress appears to be an unlikely cause for this rise. An alternative hypothesis is an influence of respiratory variables on isoprene exhalation based upon Henry's law constant. We therefore propose to perform online monitoring of isoprene exhalation by PTR-MS during the HD session to investigate the possible influence of respiratory variables.

  16. ClC Channels and Transporters: Structure, Physiological Functions, and Implications in Human Chloride Channelopathies

    PubMed Central

    Poroca, Diogo R.; Pelis, Ryan M.; Chappe, Valérie M.

    2017-01-01

    The discovery of ClC proteins at the beginning of the 1990s was important for the development of the Cl- transport research field. ClCs form a large family of proteins that mediate voltage-dependent transport of Cl- ions across cell membranes. They are expressed in both plasma and intracellular membranes of cells from almost all living organisms. ClC proteins form transmembrane dimers, in which each monomer displays independent ion conductance. Eukaryotic members also possess a large cytoplasmic domain containing two CBS domains, which are involved in transport modulation. ClC proteins function as either Cl- channels or Cl-/H+ exchangers, although all ClC proteins share the same basic architecture. ClC channels have two gating mechanisms: a relatively well-studied fast gating mechanism, and a slow gating mechanism, which is poorly defined. ClCs are involved in a wide range of physiological processes, including regulation of resting membrane potential in skeletal muscle, facilitation of transepithelial Cl- reabsorption in kidneys, and control of pH and Cl- concentration in intracellular compartments through coupled Cl-/H+ exchange mechanisms. Several inherited diseases result from C1C gene mutations, including myotonia congenita, Bartter’s syndrome (types 3 and 4), Dent’s disease, osteopetrosis, retinal degeneration, and lysosomal storage diseases. This review summarizes general features, known or suspected, of ClC structure, gating and physiological functions. We also discuss biophysical properties of mammalian ClCs that are directly involved in the pathophysiology of several human inherited disorders, or that induce interesting phenotypes in animal models. PMID:28386229

  17. ClC Channels and Transporters: Structure, Physiological Functions, and Implications in Human Chloride Channelopathies.

    PubMed

    Poroca, Diogo R; Pelis, Ryan M; Chappe, Valérie M

    2017-01-01

    The discovery of ClC proteins at the beginning of the 1990s was important for the development of the Cl(-) transport research field. ClCs form a large family of proteins that mediate voltage-dependent transport of Cl(-) ions across cell membranes. They are expressed in both plasma and intracellular membranes of cells from almost all living organisms. ClC proteins form transmembrane dimers, in which each monomer displays independent ion conductance. Eukaryotic members also possess a large cytoplasmic domain containing two CBS domains, which are involved in transport modulation. ClC proteins function as either Cl(-) channels or Cl(-)/H(+) exchangers, although all ClC proteins share the same basic architecture. ClC channels have two gating mechanisms: a relatively well-studied fast gating mechanism, and a slow gating mechanism, which is poorly defined. ClCs are involved in a wide range of physiological processes, including regulation of resting membrane potential in skeletal muscle, facilitation of transepithelial Cl(-) reabsorption in kidneys, and control of pH and Cl(-) concentration in intracellular compartments through coupled Cl(-)/H(+) exchange mechanisms. Several inherited diseases result from C1C gene mutations, including myotonia congenita, Bartter's syndrome (types 3 and 4), Dent's disease, osteopetrosis, retinal degeneration, and lysosomal storage diseases. This review summarizes general features, known or suspected, of ClC structure, gating and physiological functions. We also discuss biophysical properties of mammalian ClCs that are directly involved in the pathophysiology of several human inherited disorders, or that induce interesting phenotypes in animal models.

  18. Stress, caffeine and ethanol trigger transient neurological dysfunction through shared mechanisms in a mouse calcium channelopathy.

    PubMed

    Raike, Robert S; Weisz, Catherine; Hoebeek, Freek E; Terzi, Matthew C; De Zeeuw, Chris I; van den Maagdenberg, Arn M; Jinnah, H A; Hess, Ellen J

    2013-02-01

    Several episodic neurological disorders are caused by ion channel gene mutations. In patients, transient neurological dysfunction is often evoked by stress, caffeine and ethanol, but the mechanisms underlying these triggers are unclear because each has diverse and diffuse effects on the CNS. Attacks of motor dysfunction in the Ca(V)2.1 calcium channel mouse mutant tottering are also triggered by stress, caffeine and ethanol. Therefore, we used the tottering mouse attacks to explore the pathomechanisms of the triggers. Despite the diffuse physiological effects of these triggers, ryanodine receptor blockers prevented attacks induced by all of them. In contrast, compounds that potentiate ryanodine receptors triggered attacks suggesting a convergent biochemical pathway. Tottering mouse attacks were both induced and blocked within the cerebellum suggesting that the triggers act locally to instigate attacks. In fact, stress, caffeine and alcohol precipitated attacks in Ca(V)2.1 mutant mice in which genetic pathology was limited to cerebellar Purkinje cells, suggesting that the triggers initiate dysfunction within a specific brain region. The surprising biochemical and anatomical specificity of the triggers and the discovery that the triggers operate through shared mechanisms suggest that it is possible to develop targeted therapies aimed at blocking the induction of episodic neurological dysfunction, rather than treating the symptoms once provoked. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Stress, caffeine and ethanol trigger transient neurological dysfunction through shared mechanisms in a mouse calcium channelopathy

    PubMed Central

    Raike, Robert S.; Weisz, Catherine; Hoebeek, Freek E.; Terzi, Matthew C.; Zeeuw, Chris I. De; van den Maagdenberg, Arn M.; Jinnah, H.A.; Hess, Ellen J.

    2012-01-01

    Several episodic neurological disorders are caused by ion channel gene mutations. In patients, transient neurological dysfunction is often evoked by stress, caffeine and ethanol, but the mechanisms underlying these triggers are unclear because each has diverse and diffuse effects on the CNS. Attacks of motor dysfunction in the CaV2.1 calcium channel mouse mutant tottering are also triggered by stress, caffeine and ethanol. Therefore, we used the tottering mouse attacks to explore the pathomechanisms of the triggers. Despite the diffuse physiological effects of these triggers, ryanodine receptor blockers prevented attacks induced by all of them. In contrast, compounds that potentiate ryanodine receptors triggered attacks suggesting a convergent biochemical pathway. Tottering mouse attacks were both induced and blocked within the cerebellum suggesting that the triggers act locally to instigate attacks. In fact, stress, caffeine and alcohol precipitated attacks in CaV2.1 mutant mice in which genetic pathology was limited to cerebellar Purkinje cells, suggesting that the triggers initiate dysfunction within a specific brain region. The surprising biochemical and anatomical specificity of the triggers and the discovery that the triggers operate through shared mechanisms suggests that it is possible to develop targeted therapies aimed at blocking the induction of episodic neurological dysfunction, rather than treating the symptoms once provoked. PMID:23009754

  20. Dendritic channelopathies contribute to neocortical and sensory hyperexcitability in Fmr1(-/y) mice.

    PubMed

    Zhang, Yu; Bonnan, Audrey; Bony, Guillaume; Ferezou, Isabelle; Pietropaolo, Susanna; Ginger, Melanie; Sans, Nathalie; Rossier, Jean; Oostra, Ben; LeMasson, Gwen; Frick, Andreas

    2014-12-01

    Hypersensitivity in response to sensory stimuli and neocortical hyperexcitability are prominent features of Fragile X Syndrome (FXS) and autism spectrum disorders, but little is known about the dendritic mechanisms underlying these phenomena. We found that the primary somatosensory neocortex (S1) was hyperexcited in response to tactile sensory stimulation in Fmr1(-/y) mice. This correlated with neuronal and dendritic hyperexcitability of S1 pyramidal neurons, which affect all major aspects of neuronal computation, from the integration of synaptic input to the generation of action potential output. Using dendritic electrophysiological recordings, calcium imaging, pharmacology, biochemistry and a computer model, we found that this defect was, at least in part, attributable to the reduction and dysfunction of dendritic h- and BKCa channels. We pharmacologically rescued several core hyperexcitability phenomena by targeting BKCa channels. Our results provide strong evidence pointing to the utility of BKCa channel openers for the treatment of the sensory hypersensitivity aspects of FXS.