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Sample records for kinesin kif1a effects

  1. Diabetes alters KIF1A and KIF5B motor proteins in the hippocampus.

    Filipa I Baptista

    Full Text Available Diabetes mellitus is the most common metabolic disorder in humans. Diabetic encephalopathy is characterized by cognitive and memory impairments, which have been associated with changes in the hippocampus, but the mechanisms underlying those impairments triggered by diabetes, are far from being elucidated. The disruption of axonal transport is associated with several neurodegenerative diseases and might also play a role in diabetes-associated disorders affecting nervous system. We investigated the effect of diabetes (2 and 8 weeks duration on KIF1A, KIF5B and dynein motor proteins, which are important for axonal transport, in the hippocampus. The mRNA expression of motor proteins was assessed by qRT-PCR, and also their protein levels by immunohistochemistry in hippocampal slices and immunoblotting in total extracts of hippocampus from streptozotocin-induced diabetic and age-matched control animals. Diabetes increased the expression and immunoreactivity of KIF1A and KIF5B in the hippocampus, but no alterations in dynein were detected. Since hyperglycemia is considered a major player in diabetic complications, the effect of a prolonged exposure to high glucose on motor proteins, mitochondria and synaptic proteins in hippocampal neurons was also studied, giving particular attention to changes in axons. Hippocampal cell cultures were exposed to high glucose (50 mM or mannitol (osmotic control; 25 mM plus 25 mM glucose for 7 days. In hippocampal cultures incubated with high glucose no changes were detected in the fluorescence intensity or number of accumulations related with mitochondria in the axons of hippocampal neurons. Nevertheless, high glucose increased the number of fluorescent accumulations of KIF1A and synaptotagmin-1 and decreased KIF5B, SNAP-25 and synaptophysin immunoreactivity specifically in axons of hippocampal neurons. These changes suggest that anterograde axonal transport mediated by these kinesins may be impaired in hippocampal

  2. The Drosophila KIF1A homolog unc-104 is important for site-specific active zone maturation

    Yao V. Zhang

    2016-09-01

    Full Text Available Abstract Mutations in the kinesin-3 family member KIF1A have been associated with hereditary spastic paraplegia, hereditary sensory and autonomic neuropathy type 2 and intellectual disability. Both autosomal recessive and autosomal dominant forms of inheritance have been reported. Loss of KIF1A or its homolog unc-104 causes early postnatal or embryonic lethality in mice and Drosophila, respectively. In this study we use a previously described hypomorphic allele of unc-104, unc-104bris, to investigate the impact of partial loss-of-function of kinesin-3 function on active zone formation at the Drosophila neuromuscular junction. unc-104bris mutants exhibit synaptic defects where a subset of synapses at the neuromuscular junction lack the key active zone organizer protein Bruchpilot. Modulating synaptic Bruchpilot levels by ectopic overexpression or RNAi-mediated knockdown suggests that the loss of active zone components such as Ca2+ channel and Liprin-α from these synapses is caused by impaired kinesin-3 transport rather than due to the absence of Bruchpilot at these synapses. In addition to defects in active zone maturation, unc-104bris mutants display impaired transport of dense core vesicles and synaptic vesicle associated proteins, among which Rab3 has been shown to regulate the distribution of Bruchpilot to active zones. Overexpression of Rab3 partially ameliorates synaptic phenotypes of unc-104bris neuromuscular junction, suggesting that lack of presynaptic Rab3 may contribute to defects in synapse maturation.

  3. Structure-based molecular simulations reveal the enhancement of biased Brownian motions in single-headed kinesin.

    Kanada, Ryo; Kuwata, Takeshi; Kenzaki, Hiroo; Takada, Shoji

    2013-01-01

    Kinesin is a family of molecular motors that move unidirectionally along microtubules (MT) using ATP hydrolysis free energy. In the family, the conventional two-headed kinesin was experimentally characterized to move unidirectionally through "walking" in a hand-over-hand fashion by coordinated motions of the two heads. Interestingly a single-headed kinesin, a truncated KIF1A, still can generate a biased Brownian movement along MT, as observed by in vitro single molecule experiments. Thus, KIF1A must use a different mechanism from the conventional kinesin to achieve the unidirectional motions. Based on the energy landscape view of proteins, for the first time, we conducted a set of molecular simulations of the truncated KIF1A movements over an ATP hydrolysis cycle and found a mechanism exhibiting and enhancing stochastic forward-biased movements in a similar way to those in experiments. First, simulating stand-alone KIF1A, we did not find any biased movements, while we found that KIF1A with a large friction cargo-analog attached to the C-terminus can generate clearly biased Brownian movements upon an ATP hydrolysis cycle. The linked cargo-analog enhanced the detachment of the KIF1A from MT. Once detached, diffusion of the KIF1A head was restricted around the large cargo which was located in front of the head at the time of detachment, thus generating a forward bias of the diffusion. The cargo plays the role of a diffusional anchor, or cane, in KIF1A "walking."

  4. Structure-based molecular simulations reveal the enhancement of biased Brownian motions in single-headed kinesin.

    Ryo Kanada

    Full Text Available Kinesin is a family of molecular motors that move unidirectionally along microtubules (MT using ATP hydrolysis free energy. In the family, the conventional two-headed kinesin was experimentally characterized to move unidirectionally through "walking" in a hand-over-hand fashion by coordinated motions of the two heads. Interestingly a single-headed kinesin, a truncated KIF1A, still can generate a biased Brownian movement along MT, as observed by in vitro single molecule experiments. Thus, KIF1A must use a different mechanism from the conventional kinesin to achieve the unidirectional motions. Based on the energy landscape view of proteins, for the first time, we conducted a set of molecular simulations of the truncated KIF1A movements over an ATP hydrolysis cycle and found a mechanism exhibiting and enhancing stochastic forward-biased movements in a similar way to those in experiments. First, simulating stand-alone KIF1A, we did not find any biased movements, while we found that KIF1A with a large friction cargo-analog attached to the C-terminus can generate clearly biased Brownian movements upon an ATP hydrolysis cycle. The linked cargo-analog enhanced the detachment of the KIF1A from MT. Once detached, diffusion of the KIF1A head was restricted around the large cargo which was located in front of the head at the time of detachment, thus generating a forward bias of the diffusion. The cargo plays the role of a diffusional anchor, or cane, in KIF1A "walking."

  5. KIF1A, an axonal transporter of synaptic vesicles, is mutated in hereditary sensory and autonomic neuropathy type 2.

    Rivière, Jean-Baptiste; Ramalingam, Siriram; Lavastre, Valérie; Shekarabi, Masoud; Holbert, Sébastien; Lafontaine, Julie; Srour, Myriam; Merner, Nancy; Rochefort, Daniel; Hince, Pascale; Gaudet, Rébecca; Mes-Masson, Anne-Marie; Baets, Jonathan; Houlden, Henry; Brais, Bernard; Nicholson, Garth A; Van Esch, Hilde; Nafissi, Shahriar; De Jonghe, Peter; Reilly, Mary M; Timmerman, Vincent; Dion, Patrick A; Rouleau, Guy A

    2011-08-12

    Hereditary sensory and autonomic neuropathy type II (HSANII) is a rare autosomal-recessive disorder characterized by peripheral nerve degeneration resulting in a severe distal sensory loss. Although mutations in FAM134B and the HSN2 exon of WNK1 were associated with HSANII, the etiology of a substantial number of cases remains unexplained. In addition, the functions of WNK1/HSN2 and FAM134B and their role in the peripheral nervous system remain poorly understood. Using a yeast two-hybrid screen, we found that KIF1A, an axonal transporter of synaptic vesicles, interacts with the domain encoded by the HSN2 exon. In parallel to this screen, we performed genome-wide homozygosity mapping in a consanguineous Afghan family affected by HSANII and identified a unique region of homozygosity located on chromosome 2q37.3 and spanning the KIF1A gene locus. Sequencing of KIF1A in this family revealed a truncating mutation segregating with the disease phenotype. Subsequent sequencing of KIF1A in a series of 112 unrelated patients with features belonging to the clinical spectrum of ulcero-mutilating sensory neuropathies revealed truncating mutations in three additional families, thus indicating that mutations in KIF1A are a rare cause of HSANII. Similarly to WNK1 mutations, pathogenic mutations in KIF1A were almost exclusively restricted to an alternatively spliced exon. This study provides additional insights into the molecular pathogenesis of HSANII and highlights the potential biological relevance of alternative splicing in the peripheral sensory nervous system. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  6. The Molecular Motor KIF1A Transports the TrkA Neurotrophin Receptor and Is Essential for Sensory Neuron Survival and Function.

    Tanaka, Yosuke; Niwa, Shinsuke; Dong, Ming; Farkhondeh, Atena; Wang, Li; Zhou, Ruyun; Hirokawa, Nobutaka

    2016-06-15

    KIF1A is a major axonal transport motor protein, but its functional significance remains elusive. Here we show that KIF1A-haploinsufficient mice developed sensory neuropathy. We found progressive loss of TrkA(+) sensory neurons in Kif1a(+/-) dorsal root ganglia (DRGs). Moreover, axonal transport of TrkA was significantly disrupted in Kif1a(+/-) neurons. Live imaging and immunoprecipitation assays revealed that KIF1A bound to TrkA-containing vesicles through the adaptor GTP-Rab3, suggesting that TrkA is a cargo of the KIF1A motor. Physiological measurements revealed a weaker capsaicin response in Kif1a(+/-) DRG neurons. Moreover, these neurons were hyposensitive to nerve growth factor, which could explain the reduced neuronal survival and the functional deficiency of the pain receptor TRPV1. Because phosphatidylinositol 3-kinase (PI3K) signaling significantly rescued these phenotypes and also increased Kif1a mRNA, we propose that KIF1A is essential for the survival and function of sensory neurons because of the TrkA transport and its synergistic support of the NGF/TrkA/PI3K signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Kinesin-8 effects on mitotic microtubule dynamics contribute to spindle function in fission yeast

    Gergely, Zachary R.; Crapo, Ammon; Hough, Loren E.; McIntosh, J. Richard; Betterton, Meredith D.

    2016-01-01

    Kinesin-8 motor proteins destabilize microtubules. Their absence during cell division is associated with disorganized mitotic chromosome movements and chromosome loss. Despite recent work studying effects of kinesin-8s on microtubule dynamics, it remains unclear whether the kinesin-8 mitotic phenotypes are consequences of their effect on microtubule dynamics, their well-established motor activity, or additional, unknown functions. To better understand the role of kinesin-8 proteins in mitosis, we studied the effects of deletion of the fission yeast kinesin-8 proteins Klp5 and Klp6 on chromosome movements and spindle length dynamics. Aberrant microtubule-driven kinetochore pushing movements and tripolar mitotic spindles occurred in cells lacking Klp5 but not Klp6. Kinesin-8–deletion strains showed large fluctuations in metaphase spindle length, suggesting a disruption of spindle length stabilization. Comparison of our results from light microscopy with a mathematical model suggests that kinesin-8–induced effects on microtubule dynamics, kinetochore attachment stability, and sliding force in the spindle can explain the aberrant chromosome movements and spindle length fluctuations seen. PMID:27146110

  8. De novo mutations in the motor domain of KIF1A cause cognitive impairment, spastic paraparesis, axonal neuropathy, and cerebellar atrophy

    Lee, Jae Ran; Srour, Myriam; Kim, Doyoun; Hamdan, Fadi F.; Lim, So Hee; Brunel-Guitton, Catherine; Décarie, Jean Claude; Rossignol, Elsa; Mitchell, Grant A.; Schreiber, Allison; Moran, Rocio; Van Haren, Keith; Richardson, Randal; Nicolai, Joost; Oberndorff, Karin M E J; Wagner, Justin D.; Boycott, Kym M.; Rahikkala, Elisa; Junna, Nella; Tyynismaa, Henna; Cuppen, Inge; Verbeek, Nienke E.; Stumpel, Connie T R M; Willemsen, Michel A.; de Munnik, Sonja A.; Rouleau, Guy A.; Kim, Eunjoon; Kamsteeg, Erik Jan; Kleefstra, Tjitske; Michaud, Jacques L.

    2015-01-01

    KIF1A is a neuron-specific motor protein that plays important roles in cargo transport along neurites. Recessive mutations in KIF1A were previously described in families with spastic paraparesis or sensory and autonomic neuropathy type-2. Here, we report 11 heterozygous de novo missense mutations

  9. Intracellular Transport and Kinesin Superfamily Proteins: Structure, Function and Dynamics

    Hirokawa, N.; Takemura, R.

    Using various molecular cell biological and molecular genetic approaches, we identified kinesin superfamily proteins (KIFs) and characterized their significant functions in intracellular transport, which is fundamental for cellular morphogenesis, functioning, and survival. We showed that KIFs not only transport various membranous organelles, proteins complexes and mRNAs fundamental for cellular functions but also play significant roles in higher brain functions such as memory and learning, determination of important developmental processes such as left-right asymmetry formation and brain wiring. We also elucidated that KIFs recognize and bind to their specific cargoes using scaffolding or adaptor protein complexes. Concerning the mechanism of motility, we discovered the simplest unique monomeric motor KIF1A and determined by molecular biophysics, cryoelectron microscopy and X-ray crystallography that KIF1A can move on a microtubule processively as a monomer by biased Brownian motion and by hydolyzing ATP.

  10. BORC Functions Upstream of Kinesins 1 and 3 to Coordinate Regional Movement of Lysosomes along Different Microtubule Tracks.

    Guardia, Carlos M; Farías, Ginny G; Jia, Rui; Pu, Jing; Bonifacino, Juan S

    2016-11-15

    The multiple functions of lysosomes are critically dependent on their ability to undergo bidirectional movement along microtubules between the center and the periphery of the cell. Centrifugal and centripetal movement of lysosomes is mediated by kinesin and dynein motors, respectively. We recently described a multi-subunit complex named BORC that recruits the small GTPase Arl8 to lysosomes to promote their kinesin-dependent movement toward the cell periphery. Here, we show that BORC and Arl8 function upstream of two structurally distinct kinesin types: kinesin-1 (KIF5B) and kinesin-3 (KIF1Bβ and KIF1A). Remarkably, KIF5B preferentially moves lysosomes on perinuclear tracks enriched in acetylated α-tubulin, whereas KIF1Bβ and KIF1A drive lysosome movement on more rectilinear, peripheral tracks enriched in tyrosinated α-tubulin. These findings establish BORC as a master regulator of lysosome positioning through coupling to different kinesins and microtubule tracks. Common regulation by BORC enables coordinate control of lysosome movement in different regions of the cell. Published by Elsevier Inc.

  11. Effects of Obstacles on the Dynamics of Kinesins, Including Velocity and Run Length, Predicted by a Model of Two Dimensional Motion.

    Woochul Nam

    Full Text Available Kinesins are molecular motors which walk along microtubules by moving their heads to different binding sites. The motion of kinesin is realized by a conformational change in the structure of the kinesin molecule and by a diffusion of one of its two heads. In this study, a novel model is developed to account for the 2D diffusion of kinesin heads to several neighboring binding sites (near the surface of microtubules. To determine the direction of the next step of a kinesin molecule, this model considers the extension in the neck linkers of kinesin and the dynamic behavior of the coiled-coil structure of the kinesin neck. Also, the mechanical interference between kinesins and obstacles anchored on the microtubules is characterized. The model predicts that both the kinesin velocity and run length (i.e., the walking distance before detaching from the microtubule are reduced by static obstacles. The run length is decreased more significantly by static obstacles than the velocity. Moreover, our model is able to predict the motion of kinesin when other (several motors also move along the same microtubule. Furthermore, it suggests that the effect of mechanical interaction/interference between motors is much weaker than the effect of static obstacles. Our newly developed model can be used to address unanswered questions regarding degraded transport caused by the presence of excessive tau proteins on microtubules.

  12. Kinesin-73 is a processive motor that localizes to Rab5-containing organelles.

    Huckaba, Thomas M; Gennerich, Arne; Wilhelm, James E; Chishti, Athar H; Vale, Ronald D

    2011-03-04

    Drosophila Kinesin-73 (Khc-73), which plays a role in mitotic spindle polarity in neuroblasts, is a metazoan-specific member of the Kinesin-3 family of motors, which includes mammalian KIF1A and Caenorhabditis elegans Unc-104. The mechanism of Kinesin-3 motors has been controversial because some studies have reported that they transport cargo as monomers whereas other studies have suggested a dimer mechanism. Here, we have performed single-molecule motility and cell biological studies of Khc-73. We find that constructs containing the motor and the conserved short stretches of putative coiled-coil-forming regions are predominantly monomeric in vitro, but that dimerization allows for fast, processive movement and high force production (7 piconewtons). In Drosophila cell lines, we present evidence that Khc-73 can dimerize in vivo. We also show that Khc-73 is recruited specifically to Rab5-containing endosomes through its "tail" domain. Our results suggest that the N-terminal half of Khc-73 can undergo a monomer-dimer transition to produce a fast processive motor and that its C-terminal half possesses a specific Rab5-vesicle binding domain.

  13. Highly loaded behavior of kinesins increases the robustness of transport under high resisting loads.

    Woochul Nam

    2015-03-01

    Full Text Available Kinesins are nano-sized biological motors which walk by repeating a mechanochemical cycle. A single kinesin molecule is able to transport its cargo about 1 μm in the absence of external loads. However, kinesins perform much longer range transport in cells by working collectively. This long range of transport by a team of kinesins is surprising because the motion of the cargo in cells can be hindered by other particles. To reveal how the kinesins are able to accomplish their tasks of transport in harsh intracellular circumstances, stochastic studies on the kinesin motion are performed by considering the binding and unbinding of kinesins to microtubules and their dependence on the force acting on kinesin molecules. The unbinding probabilities corresponding to each mechanochemical state of kinesin are modeled. The statistical characterization of the instants and locations of binding are captured by computing the probability of unbound kinesin being at given locations. It is predicted that a group of kinesins has a more efficient transport than a single kinesin from the perspective of velocity and run length. Particularly, when large loads are applied, the leading kinesin remains bound to the microtubule for long time which increases the chances of the other kinesins to bind to the microtubule. To predict effects of this behavior of the leading kinesin under large loads on the collective transport, the motion of the cargo is studied when the cargo confronts obstacles. The result suggests that the behavior of kinesins under large loads prevents the early termination of the transport which can be caused by the interference with the static or moving obstacles.

  14. Heterogeneity in kinesin function

    Reddy, Babu J N; Tripathy, Suvranta; Vershinin, Michael; Tanenbaum, Marvin E; Xu, Jing; Mattson-Hoss, Michelle; Arabi, Karim; Chapman, Dail; Doolin, Tory; Hyeon, Changbong; Gross, Steven P

    2017-01-01

    The kinesin family proteins are often studied as prototypical molecular motors; a deeper understanding of them can illuminate regulation of intracellular transport. It is typically assumed that they function identically. Here we find that this assumption of homogeneous function appears incorrect:

  15. Heterotrimeric Kinesin II Is the Microtubule Motor Protein Responsible for Pigment Dispersion in Xenopus Melanophores

    Tuma, M. Carolina; Zill, Andrew; Le Bot, Nathalie; Vernos, Isabelle; Gelfand, Vladimir

    1998-01-01

    Melanophores move pigment organelles (melanosomes) from the cell center to the periphery and vice-versa. These bidirectional movements require cytoplasmic microtubules and microfilaments and depend on the function of microtubule motors and a myosin. Earlier we found that melanosomes purified from Xenopus melanophores contain the plus end microtubule motor kinesin II, indicating that it may be involved in dispersion (Rogers, S.L., I.S. Tint, P.C. Fanapour, and V.I. Gelfand. 1997. Proc. Natl. Acad. Sci. USA. 94: 3720–3725). Here, we generated a dominant-negative construct encoding green fluorescent protein fused to the stalk-tail region of Xenopus kinesin-like protein 3 (Xklp3), the 95-kD motor subunit of Xenopus kinesin II, and introduced it into melanophores. Overexpression of the fusion protein inhibited pigment dispersion but had no effect on aggregation. To control for the specificity of this effect, we studied the kinesin-dependent movement of lysosomes. Neither dispersion of lysosomes in acidic conditions nor their clustering under alkaline conditions was affected by the mutant Xklp3. Furthermore, microinjection of melanophores with SUK4, a function-blocking kinesin antibody, inhibited dispersion of lysosomes but had no effect on melanosome transport. We conclude that melanosome dispersion is powered by kinesin II and not by conventional kinesin. This paper demonstrates that kinesin II moves membrane-bound organelles. PMID:9852150

  16. Chlorpyrifos, chlorpyrifos-oxon, and diisopropylfluorophosphate inhibit kinesin-dependent microtubule motility

    Gearhart, Debra A.; Sickles, Dale W.; Buccafusco, Jerry J.; Prendergast, Mark A.; Terry, Alvin V.

    2007-01-01

    Diisopropylfluorophosphate, originally developed as a chemical warfare agent, is structurally similar to nerve agents, and chlorpyrifos has extensive worldwide use as an agricultural pesticide. While inhibition of cholinesterases underlies the acute toxicity of these organophosphates, we previously reported impaired axonal transport in the sciatic nerves from rats treated chronically with subthreshold doses of chlorpyrifos. Those data indicate that chlorpyrifos (and/or its active metabolite, chlorpyrifos-oxon) might directly affect the function of kinesin and/or microtubules-the principal proteins that mediate anterograde axonal transport. The current report describes in vitro assays to assess the concentration-dependent effects of chlorpyrifos (0-10 μM), chlorpyrifos-oxon (0-10 μM), and diisopropylfluorophosphate (0-0.59 nM) on kinesin-dependent microtubule motility. Preincubating bovine brain microtubules with the organophosphates did not alter kinesin-mediated microtubule motility. In contrast, preincubation of bovine brain kinesin with diisopropylfluorophosphate, chlorpyrifos, or chlorpyrifos-oxon produced a concentration-dependent increase in the number of locomoting microtubules that detached from the kinesin-coated glass cover slip. Our data suggest that the organophosphates-chlorpyrifos-oxon, chlorpyrifos, and diisopropylfluorophosphate-directly affect kinesin, thereby disrupting kinesin-dependent transport on microtubules. Kinesin-dependent movement of vesicles, organelles, and other cellular components along microtubules is fundamental to the organization of all eukaryotic cells, especially in neurons where organelles and proteins synthesized in the cell body must move down long axons to pre-synaptic sites in nerve terminals. We postulate that disruption of kinesin-dependent intracellular transport could account for some of the long-term effects of organophosphates on the peripheral and central nervous system

  17. Experimental protocols for and studies of the effects of surface passivation and water isotopes on the gliding speed of microtubules propelled by kinesin-1

    Maloney, Roger Andrew

    This dissertation explores how the kinesin-1 and microtubule system is affected by surface passivation and water isotopes. Surface passivation was found to affect the gliding speed that microtubules exhibit in the gliding motility assay and the lengths of microtubules supported by the passivation. It was also found that gliding speeds of microtubules are very sensitive to temperature changes. Studies changing the water isotope were a first attempt to investigate if changing the solvent changed the osmotic pressure of the solution kinesin and microtubules were in. No osmotic pressure changes were observed, however, the experiments using different isotopes of water did illuminate the possibility that kinesin may be sensitive to viscosity changes in the solvent. This experiment also suggests further experiments that can be specifically designed to probe osmotic pressure changes. This thesis was also the first thesis ever, to the best of the author's knowledge, to be done in a completely open format. All information and notebook entries that are related to it, as well as the thesis itself, can be found on the website OpenWetWare. The thesis can also be found there including all the different versions that went into its editing. The philosophy and process of making data open and accessible to every one is also discussed.

  18. Glycogen synthase kinase 3 phosphorylates kinesin light chains and negatively regulates kinesin-based motility

    Morfini, Gerardo; Szebenyi, Gyorgyi; Elluru, Ravindhra; Ratner, Nancy; Brady, Scott T.

    2002-01-01

    Membrane-bounded organelles (MBOs) are delivered to different domains in neurons by fast axonal transport. The importance of kinesin for fast antero grade transport is well established, but mechanisms for regulating kinesin-based motility are largely unknown. In this report, we provide biochemical and in vivo evidence that kinesin light chains (KLCs) interact with and are in vivo substrates for glycogen synthase kinase 3 (GSK3). Active GSK3 inhibited anterograde, but not retrograde, transport in squid axoplasm and reduced the amount of kinesin bound to MBOs. Kinesin microtubule binding and microtubule-stimulated ATPase activities were unaffected by GSK3 phosphorylation of KLCs. Active GSK3 was also localized preferentially to regions known to be sites of membrane delivery. These data suggest that GSK3 can regulate fast anterograde axonal transport and targeting of cargos to specific subcellular domains in neurons.

  19. Reversible control of kinesin activity and microtubule gliding speeds by switching the doping states of a conducting polymer support

    Martin, Brett D [US Naval Research Laboratory, Code 6930, Washington, DC 20375 (United States); Velea, Luminita M [US Naval Research Laboratory, Code 6930, Washington, DC 20375 (United States); Soto, Carissa M [US Naval Research Laboratory, Code 6930, Washington, DC 20375 (United States); Whitaker, Craig M [US Naval Academy, Department of Chemistry, Annapolis, MD 21402 (United States); Gaber, Bruce P [US Naval Research Laboratory, Code 6930, Washington, DC 20375 (United States); Ratna, Banahalli [US Naval Research Laboratory, Code 6930, Washington, DC 20375 (United States)

    2007-02-07

    We describe a method for reversibly controlling the ATPase activity of streptavidin-linked kinesin by changing the doping states of a conducting polymer support. When the polymer (poly(CH{sub 2}OH-EDOT)) was electrochemically switched from its dedoped (semiconducting) state to its doped (conducting) state, the ATPase activity of the adsorbed kinesin complex decreased by 35% with a concomitant decrease in the gliding speeds of kinesin-driven microtubules. When the polymer was switched back to its original dedoped state, nearly identical increases were observed in the kinesin ATPase activity and microtubule speeds. Use of a fluorescent ATP substrate analogue showed that the total amount of kinesin adsorbed on the poly(CH{sub 2}OH-EDOT) surface remained constant as the doping state of the polymer was switched. The microtubules exhibited nearly identical speed differences on the doped and dedoped surfaces for both chemical and electrochemical doping methods. Michaelis-Menten modelling suggests that the doped surface acts as an 'uncompetitive inhibitor' of kinesin. This work represents an investigation into the phenomenon of an electrically switchable surface exerting a moderating effect on the activity of an adsorbed protein that does not contain a bound, electroactive metal ion.

  20. A hereditary spastic paraplegia mutation in kinesin-1A/KIF5A disrupts neurofilament transport

    Brown Anthony

    2010-11-01

    Full Text Available Abstract Background Hereditary spastic paraplegias are a group of neurological disorders characterized by progressive distal degeneration of the longest ascending and descending axons in the spinal cord, leading to lower limb spasticity and weakness. One of the dominantly inherited forms of this disease (spastic gait type 10, or SPG10 is caused by point mutations in kinesin-1A (also known as KIF5A, which is thought to be an anterograde motor for neurofilaments. Results We investigated the effect of an SPG10 mutation in kinesin-1A (N256S-kinesin-1A on neurofilament transport in cultured mouse cortical neurons using live-cell fluorescent imaging. N256S-kinesin-1A decreased both anterograde and retrograde neurofilament transport flux by decreasing the frequency of anterograde and retrograde movements. Anterograde velocity was not affected, whereas retrograde velocity actually increased. Conclusions These data reveal subtle complexities to the functional interdependence of the anterograde and retrograde neurofilament motors and they also raise the possibility that anterograde and retrograde neurofilament transport may be disrupted in patients with SPG10.

  1. Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2

    Ruane, Peter T; Gumy, Laura F; Bola, Becky; Anderson, Beverley; Wozniak, Marcin J; Hoogenraad, Casper C; Allan, Victoria J

    2016-01-01

    Microtubules and their associated proteins (MAPs) underpin the polarity of specialised cells. Adenomatous polyposis coli (APC) is one such MAP with a multifunctional agenda that requires precise intracellular localisations. Although APC has been found to associate with kinesin-2 subfamily members,

  2. Monte Carlo analysis of neck linker extension in kinesin molecular motors.

    Matthew L Kutys

    2010-11-01

    Full Text Available Kinesin stepping is thought to involve both concerted conformational changes and diffusive movement, but the relative roles played by these two processes are not clear. The neck linker docking model is widely accepted in the field, but the remainder of the step--diffusion of the tethered head to the next binding site--is often assumed to occur rapidly with little mechanical resistance. Here, we investigate the effect of tethering by the neck linker on the diffusive movement of the kinesin head, and focus on the predicted behavior of motors with naturally or artificially extended neck linker domains. The kinesin chemomechanical cycle was modeled using a discrete-state Markov chain to describe chemical transitions. Brownian dynamics were used to model the tethered diffusion of the free head, incorporating resistive forces from the neck linker and a position-dependent microtubule binding rate. The Brownian dynamics and chemomechanical cycle were coupled to model processive runs consisting of many 8 nm steps. Three mechanical models of the neck linker were investigated: Constant Stiffness (a simple spring, Increasing Stiffness (analogous to a Worm-Like Chain, and Reflecting (negligible stiffness up to a limiting contour length. Motor velocities and run lengths from simulated paths were compared to experimental results from Kinesin-1 and a mutant containing an extended neck linker domain. When tethered by an increasingly stiff spring, the head is predicted to spend an unrealistically short amount of time within the binding zone, and extending the neck is predicted to increase both the velocity and processivity, contrary to experiments. These results suggest that the Worm-Like Chain is not an adequate model for the flexible neck linker domain. The model can be reconciled with experimental data if the neck linker is either much more compliant or much stiffer than generally assumed, or if weak kinesin-microtubule interactions stabilize the diffusing

  3. Kinesin expands and stabilizes the GDP-microtubule lattice

    Peet, Daniel R.; Burroughs, Nigel J.; Cross, Robert A.

    2018-05-01

    Kinesin-1 is a nanoscale molecular motor that walks towards the fast-growing (plus) ends of microtubules, hauling molecular cargo to specific reaction sites in cells. Kinesin-driven transport is central to the self-organization of eukaryotic cells and shows great promise as a tool for nano-engineering1. Recent work hints that kinesin may also play a role in modulating the stability of its microtubule track, both in vitro2,3 and in vivo4, but the results are conflicting5-7 and the mechanisms are unclear. Here, we report a new dimension to the kinesin-microtubule interaction, whereby strong-binding state (adenosine triphosphate (ATP)-bound and apo) kinesin-1 motor domains inhibit the shrinkage of guanosine diphosphate (GDP) microtubules by up to two orders of magnitude and expand their lattice spacing by 1.6%. Our data reveal an unexpected mechanism by which the mechanochemical cycles of kinesin and tubulin interlock, and so allow motile kinesins to influence the structure, stability and mechanics of their microtubule track.

  4. Small Molecule Screen for Candidate Antimalarials Targeting Plasmodium Kinesin-5*

    Liu, Liqiong; Richard, Jessica; Kim, Sunyoung; Wojcik, Edward J.

    2014-01-01

    Plasmodium falciparum and vivax are responsible for the majority of malaria infections worldwide, resulting in over a million deaths annually. Malaria parasites now show measured resistance to all currently utilized drugs. Novel antimalarial drugs are urgently needed. The Plasmodium Kinesin-5 mechanoenzyme is a suitable “next generation” target. Discovered via small molecule screen experiments, the human Kinesin-5 has multiple allosteric sites that are “druggable.” One site in particular, unique in its sequence divergence across all homologs in the superfamily and even within the same family, exhibits exquisite drug specificity. We propose that Plasmodium Kinesin-5 shares this allosteric site and likewise can be targeted to uncover inhibitors with high specificity. To test this idea, we performed a screen for inhibitors selective for Plasmodium Kinesin-5 ATPase activity in parallel with human Kinesin-5. Our screen of nearly 2000 compounds successfully identified compounds that selectively inhibit both P. vivax and falciparum Kinesin-5 motor domains but, as anticipated, do not impact human Kinesin-5 activity. Of note is a candidate drug that did not biochemically compete with the ATP substrate for the conserved active site or disrupt the microtubule-binding site. Together, our experiments identified MMV666693 as a selective allosteric inhibitor of Plasmodium Kinesin-5; this is the first identified protein target for the Medicines of Malaria Venture validated collection of parasite proliferation inhibitors. This work demonstrates that chemical screens against human kinesins are adaptable to homologs in disease organisms and, as such, extendable to strategies to combat infectious disease. PMID:24737313

  5. The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma

    Hernández-García, Susana; San-Segundo, Laura; González-Méndez, Lorena; Corchete, Luis A; Misiewicz-Krzeminska, Irena; Martín-Sánchez, Montserrat; López-Iglesias, Ana-Alicia; Algarín, Esperanza Macarena; Mogollón, Pedro; Díaz-Tejedor, Andrea; Paíno, Teresa; Tunquist, Brian; Mateos, María-Victoria; Gutiérrez, Norma C; Díaz-Rodriguez, Elena

    2017-01-01

    [EN]Kinesin spindle protein inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (ARRY-520), an inhibitor of this protein, has demonstrated activity in heavily pre-treated multiple myeloma patients. The aim of the work herein was to investigate the activity of filanesib in combination with pomalidomide plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect. The ability of filanesib to enhance the activity of pomali...

  6. Loading direction regulates the affinity of ADP for kinesin.

    Uemura, Sotaro; Ishiwata, Shin'ichi

    2003-04-01

    Kinesin is an ATP-driven molecular motor that moves processively along a microtubule. Processivity has been explained as a mechanism that involves alternating single- and double-headed binding of kinesin to microtubules coupled to the ATPase cycle of the motor. The internal load imposed between the two bound heads has been proposed to be a key factor regulating the ATPase cycle in each head. Here we show that external load imposed along the direction of motility on a single kinesin molecule enhances the binding affinity of ADP for kinesin, whereas an external load imposed against the direction of motility decreases it. This coupling between loading direction and enzymatic activity is in accord with the idea that the internal load plays a key role in the unidirectional and cooperative movement of processive motors.

  7. A Mechanism for Cytoplasmic Streaming: Kinesin-Driven Alignment of Microtubules and Fast Fluid Flows.

    Monteith, Corey E; Brunner, Matthew E; Djagaeva, Inna; Bielecki, Anthony M; Deutsch, Joshua M; Saxton, William M

    2016-05-10

    The transport of cytoplasmic components can be profoundly affected by hydrodynamics. Cytoplasmic streaming in Drosophila oocytes offers a striking example. Forces on fluid from kinesin-1 are initially directed by a disordered meshwork of microtubules, generating minor slow cytoplasmic flows. Subsequently, to mix incoming nurse cell cytoplasm with ooplasm, a subcortical layer of microtubules forms parallel arrays that support long-range, fast flows. To analyze the streaming mechanism, we combined observations of microtubule and organelle motions with detailed mathematical modeling. In the fast state, microtubules tethered to the cortex form a thin subcortical layer and undergo correlated sinusoidal bending. Organelles moving in flows along the arrays show velocities that are slow near the cortex and fast on the inward side of the subcortical microtubule layer. Starting with fundamental physical principles suggested by qualitative hypotheses, and with published values for microtubule stiffness, kinesin velocity, and cytoplasmic viscosity, we developed a quantitative coupled hydrodynamic model for streaming. The fully detailed mathematical model and its simulations identify key variables that can shift the system between disordered (slow) and ordered (fast) states. Measurements of array curvature, wave period, and the effects of diminished kinesin velocity on flow rates, as well as prior observations on f-actin perturbation, support the model. This establishes a concrete mechanistic framework for the ooplasmic streaming process. The self-organizing fast phase is a result of viscous drag on kinesin-driven cargoes that mediates equal and opposite forces on cytoplasmic fluid and on microtubules whose minus ends are tethered to the cortex. Fluid moves toward plus ends and microtubules are forced backward toward their minus ends, resulting in buckling. Under certain conditions, the buckling microtubules self-organize into parallel bending arrays, guiding varying directions

  8. A coordinated molecular 'fishing' mechanism in heterodimeric kinesin

    Hou, Ruizheng; Wang, Zhisong

    2010-01-01

    Kar3 is a kinesin motor that facilitates chromosome segregation during cell division. Unlike many members of the kinesin superfamily, Kar3 forms a heterodimer with non-motor protein Vik1 or Cik1 in vivo. The heterodimers show ATP-driven minus-end directed motility along a microtubule (MT) lattice, and also serve as depolymerase at the MT ends. The molecular mechanisms behind this dual functionality remain mysterious. Here, a molecular mechanical model for the Kar3/Vik1 heterodimer based on structural, kinetic and motility data reveals a long-range chemomechanical transmission mechanism that resembles a familiar fishing tactic. By this molecular 'fishing', ATP-binding to Kar3 dissociates catalytically inactive Vik1 off MT to facilitate minus-end sliding of the dimer on the MT lattice. When the dimer binds the frayed ends of MT, the fishing channels ATP hydrolysis energy into MT deploymerization by a mechanochemical effect. The molecular fishing thus provides a unified mechanistic ground for Kar3's dual functionality. The fishing-promoted depolymerization differs from the depolymerase mechanisms found in homodimeric kinesins. The fishing also enables intermolecular coordination with a chemomechanical coupling feature different from the paradigmatic pattern of homodimeric motors. This study rationalizes some puzzling experimental observation, and suggests new experiments for further elucidation of the fishing mechanism

  9. Shaping the tracks : Regulation of microtubule dynamics by kinesins KIF21A and KIF21B

    van Riel, W.E.|info:eu-repo/dai/nl/338772634

    2016-01-01

    Control of microtubule dynamics is important for cell morphogenesis. Kinesins, motor proteins known to function in cargo transport, were recently also implicated in altering the microtubule network. Several kinesins are described to cause microtubule network reorganization or stabilization, either

  10. Kinesin-1 and mitochondrial motility control by discrimination of structurally equivalent but distinct subdomains in Ran-GTP-binding domains of Ran-binding protein 2.

    Patil, Hemangi; Cho, Kyoung-in; Lee, James; Yang, Yi; Orry, Andrew; Ferreira, Paulo A

    2013-03-27

    The pleckstrin homology (PH) domain is a versatile fold that mediates a variety of protein-protein and protein-phosphatidylinositol lipid interactions. The Ran-binding protein 2 (RanBP2) contains four interspersed Ran GTPase-binding domains (RBD(n = 1-4)) with close structural homology to the PH domain of Bruton's tyrosine kinase. The RBD2, kinesin-binding domain (KBD) and RBD3 comprise a tripartite domain (R2KR3) of RanBP2 that causes the unfolding, microtubule binding and biphasic activation of kinesin-1, a crucial anterograde motor of mitochondrial motility. However, the interplay between Ran GTPase and R2KR3 of RanBP2 in kinesin-1 activation and mitochondrial motility is elusive. We use structure-function, biochemical, kinetic and cell-based assays with time-lapse live-cell microscopy of over 260,000 mitochondrial-motility-related events to find mutually exclusive subdomains in RBD2 and RBD3 towards Ran GTPase binding, kinesin-1 activation and mitochondrial motility regulation. The RBD2 and RBD3 exhibit Ran-GTP-independent, subdomain and stereochemical-dependent discrimination on the biphasic kinetics of kinesin-1 activation or regulation of mitochondrial motility. Further, KBD alone and R2KR3 stimulate and suppress, respectively, multiple biophysical parameters of mitochondrial motility. The regulation of the bidirectional transport of mitochondria by either KBD or R2KR3 is highly coordinated, because their kinetic effects are accompanied always by changes in mitochondrial motile events of either transport polarity. These studies uncover novel roles in Ran GTPase-independent subdomains of RBD2 and RBD3, and KBD of RanBP2, that confer antagonizing and multi-modal mechanisms of kinesin-1 activation and regulation of mitochondrial motility. These findings open new venues towards the pharmacological harnessing of cooperative and competitive mechanisms regulating kinesins, RanBP2 or mitochondrial motility in disparate human disorders.

  11. Bidirectional motility of the fission yeast kinesin-5, Cut7

    Edamatsu, Masaki, E-mail: cedam@mail.ecc.u-tokyo.ac.jp

    2014-03-28

    Highlights: • Motile properties of Cut7 (fission yeast kinesin-5) were studied for the first time. • Half-length Cut7 moved toward plus-end direction of microtubule. • Full-length Cut7 moved toward minus-end direction of microtubule. • N- and C-terminal microtubule binding sites did not switch the motile direction. - Abstract: Kinesin-5 is a homotetrameric motor with its motor domain at the N-terminus. Kinesin-5 crosslinks microtubules and functions in separating spindle poles during mitosis. In this study, the motile properties of Cut7, fission yeast kinesin-5, were examined for the first time. In in vitro motility assays, full-length Cut7 moved toward minus-end of microtubules, but the N-terminal half of Cut7 moved toward the opposite direction. Furthermore, additional truncated constructs lacking the N-terminal or C-terminal regions, but still contained the motor domain, did not switch the motile direction. These indicated that Cut7 was a bidirectional motor, and microtubule binding regions at the N-terminus and C-terminus were not involved in its directionality.

  12. Tau excess impairs mitosis and kinesin-5 function, leading to aneuploidy and cell death.

    Bougé, Anne-Laure; Parmentier, Marie-Laure

    2016-03-01

    In neurodegenerative diseases such as Alzheimer's disease (AD), cell cycle defects and associated aneuploidy have been described. However, the importance of these defects in the physiopathology of AD and the underlying mechanistic processes are largely unknown, in particular with respect to the microtubule (MT)-binding protein Tau, which is found in excess in the brain and cerebrospinal fluid of affected individuals. Although it has long been known that Tau is phosphorylated during mitosis to generate a lower affinity for MTs, there is, to our knowledge, no indication that an excess of this protein could affect mitosis. Here, we studied the effect of an excess of human Tau (hTau) protein on cell mitosis in vivo. Using the Drosophila developing wing disc epithelium as a model, we show that an excess of hTau induces a mitotic arrest, with the presence of monopolar spindles. This mitotic defect leads to aneuploidy and apoptotic cell death. We studied the mechanism of action of hTau and found that the MT-binding domain of hTau is responsible for these defects. We also demonstrate that the effects of hTau occur via the inhibition of the function of the kinesin Klp61F, the Drosophila homologue of kinesin-5 (also called Eg5 or KIF11). We finally show that this deleterious effect of hTau is also found in other Drosophila cell types (neuroblasts) and tissues (the developing eye disc), as well as in human HeLa cells. By demonstrating that MT-bound Tau inhibits the Eg5 kinesin and cell mitosis, our work provides a new framework to consider the role of Tau in neurodegenerative diseases. © 2016. Published by The Company of Biologists Ltd.

  13. Motoring through: the role of kinesin superfamily proteins in female meiosis.

    Camlin, Nicole J; McLaughlin, Eileen A; Holt, Janet E

    2017-07-01

    The kinesin motor protein family consists of 14 distinct subclasses and 45 kinesin proteins in humans. A large number of these proteins, or their orthologues, have been shown to possess essential function(s) in both the mitotic and the meiotic cell cycle. Kinesins have important roles in chromosome separation, microtubule dynamics, spindle formation, cytokinesis and cell cycle progression. This article contains a review of the literature with respect to the role of kinesin motor proteins in female meiosis in model species. Throughout, we discuss the function of each class of kinesin proteins during oocyte meiosis, and where such data are not available their role in mitosis is considered. Finally, the review highlights the potential clinical importance of this family of proteins for human oocyte quality. To examine the role of kinesin motor proteins in oocyte meiosis. A search was performed on the Pubmed database for journal articles published between January 1970 and February 2017. Search terms included 'oocyte kinesin' and 'meiosis kinesin' in addition to individual kinesin names with the terms oocyte or meiosis. Within human cells 45 kinesin motor proteins have been discovered, with the role of only 13 of these proteins, or their orthologues, investigated in female meiosis. Furthermore, of these kinesins only half have been examined in mammalian oocytes, despite alterations occurring in gene transcripts or protein expression with maternal ageing, cryopreservation or behavioral conditions, such as binge drinking, for many of them. Kinesin motor proteins have distinct and important roles throughout oocyte meiosis in many non-mammalian model species. However, the functions these proteins have in mammalian meiosis, particularly in humans, are less clear owing to lack of research. This review brings to light the need for more experimental investigation of kinesin motor proteins, particularly those associated with maternal ageing, cryopreservation or exposure to

  14. Engineering of a novel Ca2+-regulated kinesin molecular motor using a calmodulin dimer linker

    Shishido, Hideki; Maruta, Shinsaku

    2012-01-01

    Highlights: ► Engineered kinesin–M13 and calmodulin involving single cysteine were prepared. ► CaM mutant was cross-linked to dimer by bifunctional thiol reactive reagent. ► Kinesin–M13 was dimerized via CaM dimer in the presence of calcium. ► Function of the engineered kinesin was regulated by a Ca 2+ -calmodulin dimer linker. -- Abstract: The kinesin–microtubule system holds great promise as a molecular shuttle device within biochips. However, one current barrier is that such shuttles do not have “on–off” control of their movement. Here we report the development of a novel molecular motor powered by an accelerator and brake system, using a kinesin monomer and a calmodulin (CaM) dimer. The kinesin monomer, K355, was fused with a CaM target peptide (M13 peptide) at the C-terminal part of the neck region (K355–M13). We also prepared CaM dimers using CaM mutants (Q3C), (R86C), or (A147C) and crosslinkers that react with cysteine residues. Following induction of K355–M13 dimerization with CaM dimers, we measured K355–M13 motility and found that it can be reversibly regulated in a Ca 2+ -dependent manner. We also found that velocities of K355–M13 varied depending on the type and crosslink position of the CaM dimer used; crosslink length also had a moderate effect on motility. These results suggest Ca 2+ -dependent dimerization of K355–M13 could be used as a novel molecular shuttle, equipped with an accelerator and brake system, for biochip applications.

  15. Coupling of kinesin ATP turnover to translocation and microtubule regulation: one engine, many machines.

    Friel, Claire T; Howard, Jonathon

    2012-12-01

    The cycle of ATP turnover is integral to the action of motor proteins. Here we discuss how variation in this cycle leads to variation of function observed amongst members of the kinesin superfamily of microtubule associated motor proteins. Variation in the ATP turnover cycle among superfamily members can tune the characteristic kinesin motor to one of the range of microtubule-based functions performed by kinesins. The speed at which ATP is hydrolysed affects the speed of translocation. The ratio of rate constants of ATP turnover in relation to association and dissociation from the microtubule influence the processivity of translocation. Variation in the rate-limiting step of the cycle can reverse the way in which the motor domain interacts with the microtubule producing non-motile kinesins. Because the ATP turnover cycle is not fully understood for the majority of kinesins, much work remains to show how the kinesin engine functions in such a wide variety of molecular machines.

  16. Casein Kinase 2 Reverses Tail-Independent Inactivation of Kinesin-1

    Xu, Jing

    2013-03-01

    Kinesin-1 is a plus-end microtubule-based motor, and defects in kinesin-based transport are linked to diseases including neurodegeneration. Kinesin can auto-inhibit via a head-tail interaction, but is believed to be active otherwise. Here we report a tail-independent inactivation of kinesin, reversible by the disease-relevant signalling protein, casein kinase 2 (CK2). The majority of initially active kinesin (native or tail-less) loses its ability to interact with microtubules in vitro, and CK2 reverses this inactivation (approximately fourfold) without altering kinesin's single motor properties. This activation pathway does not require motor phosphorylation, and is independent of head-tail auto-inhibition. In cultured mammalian cells, reducing CK2 expression, but not its kinase activity, decreases the force required to stall lipid droplet transport, consistent with a decreased number of active kinesin motors. Our results (Nat. Commun., 3:754, 2012) provide the first direct evidence of a protein kinase upregulating kinesin-based transport, and suggest a novel pathway for regulating the activity of cargo-bound kinesin. Work supported by NIGMS grants GM64624 to SPG, GM74830-06A1 to LH, GM76516 to LB, NS048501 to SJK, and AHA grant 825278F to JX.

  17. Initial conformation of kinesin's neck linker

    Geng Yi-Zhao; Yan Shi-Wei; Ji Qing; Liu Shu-Xia

    2014-01-01

    How ATP binding initiates the docking process of kinesin's neck linker is a key question in understanding kinesin mechanisms. By exploiting a molecular dynamics method, we investigate the initial conformation of kinesin's neck linker in its docking process. We find that, in the initial conformation, the neck linker has interactions with β0 and forms a ‘cover-neck bundle’ structure with β0. From this initial structure, the formation of extra turns and the docking of the cover-neck bundle structure can be achieved. The motor head provides a forward force on the initial cover-neck bundle structure through ATP-induced rotation. This force, together with the hydrophobic interaction of ILE327 with the hydrophobic pocket on the motor head, drives the formation of the extra turn and initiates the neck linker docking process. Based on these findings, a pathway from ATP binding-induced motor head rotation to neck linker docking is proposed. (interdisciplinary physics and related areas of science and technology)

  18. Activity of the kinesin spindle protein inhibitor ispinesib (SB-715992) in models of breast cancer

    Purcell, James W; Davis, Jefferson; Reddy, Mamatha; Martin, Shamra; Samayoa, Kimberly; Vo, Hung; Thomsen, Karen; Bean, Peter; Kuo, Wen Lin; Ziyad, Safiyyah; Billig, Jessica; Feiler, Heidi S; Gray, Joe W; Wood, Kenneth W; Cases, Sylvaine

    2009-06-10

    Ispinesib (SB-715992) is a potent inhibitor of kinesin spindle protein (KSP), a kinesin motor protein essential for the formation of a bipolar mitotic spindle and cell cycle progression through mitosis. Clinical studies of ispinesib have demonstrated a 9% response rate in patients with locally advanced or metastatic breast cancer, and a favorable safety profile without significant neurotoxicities, gastrointestinal toxicities or hair loss. To better understand the potential of ispinesib in the treatment of breast cancer we explored the activity of ispinesib alone and in combination several therapies approved for the treatment of breast cancer. We measured the ispinesib sensitivity and pharmacodynamic response of breast cancer cell lines representative of various subtypes in vitro and as xenografts in vivo, and tested the ability of ispinesib to enhance the anti-tumor activity of approved therapies. In vitro, ispinesib displayed broad anti-proliferative activity against a panel of 53 breast cell-lines. In vivo, ispinesib produced regressions in each of five breast cancer models, and tumor free survivors in three of these models. The effects of ispinesib treatment on pharmacodynamic markers of mitosis and apoptosis were examined in vitro and in vivo, revealing a greater increase in both mitotic and apoptotic markers in the MDA-MB-468 model than in the less sensitive BT-474 model. In vivo, ispinesib enhanced the anti-tumor activity of trastuzumab, lapatinib, doxorubicin, and capecitabine, and exhibited activity comparable to paclitaxel and ixabepilone. These findings support further clinical exploration of KSP inhibitors for the treatment of breast cancer.

  19. Functional characterisation and drug target validation of a mitotic kinesin-13 in Trypanosoma brucei.

    Kuan Yoow Chan

    2010-08-01

    Full Text Available Mitotic kinesins are essential for faithful chromosome segregation and cell proliferation. Therefore, in humans, kinesin motor proteins have been identified as anti-cancer drug targets and small molecule inhibitors are now tested in clinical studies. Phylogenetic analyses have assigned five of the approximately fifty kinesin motor proteins coded by Trypanosoma brucei genome to the Kinesin-13 family. Kinesins of this family have unusual biochemical properties because they do not transport cargo along microtubules but are able to depolymerise microtubules at their ends, therefore contributing to the regulation of microtubule length. In other eukaryotic genomes sequenced to date, only between one and three Kinesin-13s are present. We have used immunolocalisation, RNAi-mediated protein depletion, biochemical in vitro assays and a mouse model of infection to study the single mitotic Kinesin-13 in T. brucei. Subcellular localisation of all five T. brucei Kinesin-13s revealed distinct distributions, indicating that the expansion of this kinesin family in kinetoplastids is accompanied by functional diversification. Only a single kinesin (TbKif13-1 has a nuclear localisation. Using active, recombinant TbKif13-1 in in vitro assays we experimentally confirm the depolymerising properties of this kinesin. We analyse the biological function of TbKif13-1 by RNAi-mediated protein depletion and show its central role in regulating spindle assembly during mitosis. Absence of the protein leads to abnormally long and bent mitotic spindles, causing chromosome mis-segregation and cell death. RNAi-depletion in a mouse model of infection completely prevents infection with the parasite. Given its essential role in mitosis, proliferation and survival of the parasite and the availability of a simple in vitro activity assay, TbKif13-1 has been identified as an excellent potential drug target.

  20. A Kinesin-Related Protein Required for the Mitotic Spindle Assembly

    1999-05-01

    A. Pereira, P. Pesavento , Y. Yannoni, A.C. Spralding, and L.S.B. Goldstein. 1993. The kinesin-like protein KLP61F is essential for mitosis in...1169. 30. Heck MM, Pereira A, Pesavento P, Yannoni Y, Spradling AC, Goldstein LS: The kinesin-like protein KLP61F is essential for mitosis in

  1. FRET measurements of kinesin neck orientation reveal a structural basis for processivity and asymmetry.

    Martin, Douglas S; Fathi, Reza; Mitchison, Timothy J; Gelles, Jeff

    2010-03-23

    As the smallest and simplest motor enzymes, kinesins have served as the prototype for understanding the relationship between protein structure and mechanochemical function of enzymes in this class. Conventional kinesin (kinesin-1) is a motor enzyme that transports cargo toward the plus end of microtubules by a processive, asymmetric hand-over-hand mechanism. The coiled-coil neck domain, which connects the two kinesin motor domains, contributes to kinesin processivity (the ability to take many steps in a row) and is proposed to be a key determinant of the asymmetry in the kinesin mechanism. While previous studies have defined the orientation and position of microtubule-bound kinesin motor domains, the disposition of the neck coiled-coil remains uncertain. We determined the neck coiled-coil orientation using a multidonor fluorescence resonance energy transfer (FRET) technique to measure distances between microtubules and bound kinesin molecules. Microtubules were labeled with a new fluorescent taxol donor, TAMRA-X-taxol, and kinesin derivatives with an acceptor fluorophore attached at positions on the motor and neck coiled-coil domains were used to reconstruct the positions and orientations of the domains. FRET measurements to positions on the motor domain were largely consistent with the domain orientation determined in previous studies, validating the technique. Measurements to positions on the neck coiled-coil were inconsistent with a radial orientation and instead demonstrated that the neck coiled-coil is parallel to the microtubule surface. The measured orientation provides a structural explanation for how neck surface residues enhance processivity and suggests a simple hypothesis for the origin of kinesin step asymmetry and "limping."

  2. Potential involvement of kinesin-1 in the regulation of subcellular localization of Girdin

    Muramatsu, Aya [Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Enomoto, Atsushi, E-mail: enomoto@iar.nagoya-u.ac.jp [Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Kato, Takuya; Weng, Liang [Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Kuroda, Keisuke [Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Asai, Naoya; Asai, Masato; Mii, Shinji [Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Takahashi, Masahide, E-mail: mtakaha@med.nagoya-u.ac.jp [Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan)

    2015-08-07

    Girdin is an actin-binding protein that has multiple functions in postnatal neural development and cancer progression. We previously showed that Girdin is a regulator of migration for neuroblasts born from neural stem cells in the subventricular zone (SVZ) and the dentate gyrus of the hippocampus in the postnatal brain. Despite a growing list of Girdin-interacting proteins, the mechanism of Girdin-mediated migration has not been fully elucidated. Girdin interacts with Disrupted-In-Schizophrenia 1 and partitioning-defective 3, both of which have been shown to interact with the kinesin microtubule motor proteins. Based on this, we have identified that Girdin also interacts with kinesin-1, a member of neuronal kinesin proteins. Although a direct interaction of Girdin and kinesin-1 has not been determined, it is of interest to find that Girdin loss-of-function mutant mice with the mutation of a basic amino acid residue-rich region (Basic mut mice) exhibit limited interaction with kinesin-1. Furthermore, expression of a kinesin-1 mutant with motor defects, leads to Girdin mislocalization. Finally, consistent with previous studies on the role of kinesin proteins in trafficking a cell–cell adhesion molecule N-cadherin, Basic mut mice showed an aberrant expression pattern of N-cadherin in migrating SVZ neuroblasts. These findings suggest a potential role of Girdin/kinesin-1 interaction in the regulation of neuroblast migration in the postnatal brain. - Highlights: • Girdin is a regulator of migration for neuroblasts in the postnatal brain. • Girdin interacts with kinesin-1, a member of neuronal kinesin proteins. • Girdin mutant mice showed an aberrant expression of N-cadherin in neuroblasts.

  3. Mapping the structural and dynamical features of kinesin motor domains.

    Guido Scarabelli

    Full Text Available Kinesin motor proteins drive intracellular transport by coupling ATP hydrolysis to conformational changes that mediate directed movement along microtubules. Characterizing these distinct conformations and their interconversion mechanism is essential to determining an atomic-level model of kinesin action. Here we report a comprehensive principal component analysis of 114 experimental structures along with the results of conventional and accelerated molecular dynamics simulations that together map the structural dynamics of the kinesin motor domain. All experimental structures were found to reside in one of three distinct conformational clusters (ATP-like, ADP-like and Eg5 inhibitor-bound. These groups differ in the orientation of key functional elements, most notably the microtubule binding α4-α5, loop8 subdomain and α2b-β4-β6-β7 motor domain tip. Group membership was found not to correlate with the nature of the bound nucleotide in a given structure. However, groupings were coincident with distinct neck-linker orientations. Accelerated molecular dynamics simulations of ATP, ADP and nucleotide free Eg5 indicate that all three nucleotide states could sample the major crystallographically observed conformations. Differences in the dynamic coupling of distal sites were also evident. In multiple ATP bound simulations, the neck-linker, loop8 and the α4-α5 subdomain display correlated motions that are absent in ADP bound simulations. Further dissection of these couplings provides evidence for a network of dynamic communication between the active site, microtubule-binding interface and neck-linker via loop7 and loop13. Additional simulations indicate that the mutations G325A and G326A in loop13 reduce the flexibility of these regions and disrupt their couplings. Our combined results indicate that the reported ATP and ADP-like conformations of kinesin are intrinsically accessible regardless of nucleotide state and support a model where neck

  4. Structural insights into human Kif7, a kinesin involved in Hedgehog signalling

    Klejnot, Marta, E-mail: m.klejnot@beatson.gla.ac.uk; Kozielski, Frank, E-mail: m.klejnot@beatson.gla.ac.uk [The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, Scotland (United Kingdom)

    2012-02-01

    The human Kif7 motor domain structure provides insights into a kinesin of medical significance. Kif7, a member of the kinesin 4 superfamily, is implicated in a variety of diseases including Joubert, hydrolethalus and acrocallosal syndromes. It is also involved in primary cilium formation and the Hedgehog signalling pathway and may play a role in cancer. Its activity is crucial for embryonic development. Kif7 and Kif27, a closely related kinesin in the same subfamily, are orthologues of the Drosophila melano@@gaster kinesin-like protein Costal-2 (Cos2). In vertebrates, they work together to fulfil the role of the single Cos2 gene in Drosophila. Here, the high-resolution structure of the human Kif7 motor domain is reported and is compared with that of conventional kinesin, the founding member of the kinesin superfamily. These data are a first step towards structural characterization of a kinesin-4 family member and of this interesting molecular motor of medical significance.

  5. Kinesin and Dynein Mechanics: Measurement Methods and Research Applications.

    Abraham, Zachary; Hawley, Emma; Hayosh, Daniel; Webster-Wood, Victoria A; Akkus, Ozan

    2018-02-01

    Motor proteins play critical roles in the normal function of cells and proper development of organisms. Among motor proteins, failings in the normal function of two types of proteins, kinesin and dynein, have been shown to lead many pathologies, including neurodegenerative diseases and cancers. As such, it is critical to researchers to understand the underlying mechanics and behaviors of these proteins, not only to shed light on how failures may lead to disease, but also to guide research toward novel treatment and nano-engineering solutions. To this end, many experimental techniques have been developed to measure the force and motility capabilities of these proteins. This review will (a) discuss such techniques, specifically microscopy, atomic force microscopy (AFM), optical trapping, and magnetic tweezers, and (b) the resulting nanomechanical properties of motor protein functions such as stalling force, velocity, and dependence on adenosine triphosophate (ATP) concentrations will be comparatively discussed. Additionally, this review will highlight the clinical importance of these proteins. Furthermore, as the understanding of the structure and function of motor proteins improves, novel applications are emerging in the field. Specifically, researchers have begun to modify the structure of existing proteins, thereby engineering novel elements to alter and improve native motor protein function, or even allow the motor proteins to perform entirely new tasks as parts of nanomachines. Kinesin and dynein are vital elements for the proper function of cells. While many exciting experiments have shed light on their function, mechanics, and applications, additional research is needed to completely understand their behavior.

  6. A Trypanosoma brucei kinesin heavy chain promotes parasite growth by triggering host arginase activity.

    Géraldine De Muylder

    2013-10-01

    Full Text Available In order to promote infection, the blood-borne parasite Trypanosoma brucei releases factors that upregulate arginase expression and activity in myeloid cells.By screening a cDNA library of T. brucei with an antibody neutralizing the arginase-inducing activity of parasite released factors, we identified a Kinesin Heavy Chain isoform, termed TbKHC1, as responsible for this effect. Following interaction with mouse myeloid cells, natural or recombinant TbKHC1 triggered SIGN-R1 receptor-dependent induction of IL-10 production, resulting in arginase-1 activation concomitant with reduction of nitric oxide (NO synthase activity. This TbKHC1 activity was IL-4Rα-independent and did not mirror M2 activation of myeloid cells. As compared to wild-type T. brucei, infection by TbKHC1 KO parasites was characterized by strongly reduced parasitaemia and prolonged host survival time. By treating infected mice with ornithine or with NO synthase inhibitor, we observed that during the first wave of parasitaemia the parasite growth-promoting effect of TbKHC1-mediated arginase activation resulted more from increased polyamine production than from reduction of NO synthesis. In late stage infection, TbKHC1-mediated reduction of NO synthesis appeared to contribute to liver damage linked to shortening of host survival time.A kinesin heavy chain released by T. brucei induces IL-10 and arginase-1 through SIGN-R1 signaling in myeloid cells, which promotes early trypanosome growth and favors parasite settlement in the host. Moreover, in the late stage of infection, the inhibition of NO synthesis by TbKHC1 contributes to liver pathogenicity.

  7. Localization of the kinesin adaptor proteins trafficking kinesin proteins 1 and 2 in primary cultures of hippocampal pyramidal and cortical neurons.

    Loss, Omar; Stephenson, F Anne

    2015-07-01

    Neuronal function requires regulated anterograde and retrograde trafficking of mitochondria along microtubules by using the molecular motors kinesin and dynein. Previous work has established that trafficking kinesin proteins (TRAKs),TRAK1 and TRAK2, are kinesin adaptor proteins that link mitochondria to kinesin motor proteins via an acceptor protein in the mitochondrial outer membrane, etc. the Rho GTPase Miro. Recent studies have shown that TRAK1 preferentially controls mitochondrial transport in axons of hippocampal neurons by virtue of its binding to both kinesin and dynein motor proteins, whereas TRAK2 controls mitochondrial transport in dendrites resulting from its binding to dynein. This study further investigates the subcellular localization of TRAK1 and TRAK2 in primary cultures of hippocampal and cortical neurons by using both commercial antibodies and anti-TRAK1 and anti-TRAK2 antibodies raised in our own laboratory (in-house). Whereas TRAK1 was prevalently localized in axons of hippocampal and cortical neurons, TRAK2 was more prevalent in dendrites of hippocampal neurons. In cortical neurons, TRAK2 was equally distributed between axons and dendrites. Some qualitative differences were observed between commercial and in-house-generated antibody immunostaining. © 2015 Wiley Periodicals, Inc.

  8. Kinesin-2 KIF3AB exhibits novel ATPase characteristics.

    Albracht, Clayton D; Rank, Katherine C; Obrzut, Steven; Rayment, Ivan; Gilbert, Susan P

    2014-10-03

    KIF3AB is an N-terminal processive kinesin-2 family member best known for its role in intraflagellar transport. There has been significant interest in KIF3AB in defining the key principles that underlie the processivity of KIF3AB in comparison with homodimeric processive kinesins. To define the ATPase mechanism and coordination of KIF3A and KIF3B stepping, a presteady-state kinetic analysis was pursued. For these studies, a truncated murine KIF3AB was generated. The results presented show that microtubule association was fast at 5.7 μm(-1) s(-1), followed by rate-limiting ADP release at 12.8 s(-1). ATP binding at 7.5 μm(-1) s(-1) was followed by an ATP-promoted isomerization at 84 s(-1) to form the intermediate poised for ATP hydrolysis, which then occurred at 33 s(-1). ATP hydrolysis was required for dissociation of the microtubule·KIF3AB complex, which was observed at 22 s(-1). The dissociation step showed an apparent affinity for ATP that was very weak (K½,ATP at 133 μm). Moreover, the linear fit of the initial ATP concentration dependence of the dissociation kinetics revealed an apparent second-order rate constant at 0.09 μm(-1) s(-1), which is inconsistent with fast ATP binding at 7.5 μm(-1) s(-1) and a Kd ,ATP at 6.1 μm. These results suggest that ATP binding per se cannot account for the apparent weak K½,ATP at 133 μm. The steady-state ATPase Km ,ATP, as well as the dissociation kinetics, reveal an unusual property of KIF3AB that is not yet well understood and also suggests that the mechanochemistry of KIF3AB is tuned somewhat differently from homodimeric processive kinesins. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Mechanical splitting of microtubules into protofilament bundles by surface-bound kinesin-1.

    VanDelinder, Virginia; Adams, Peter G; Bachand, George D

    2016-12-21

    The fundamental biophysics of gliding microtubule (MT) motility by surface-tethered kinesin-1 motor proteins has been widely studied, as well as applied to capture and transport analytes in bioanalytical microdevices. In these systems, phenomena such as molecular wear and fracture into shorter MTs have been reported due the mechanical forces applied on the MT during transport. In the present work, we show that MTs can be split longitudinally into protofilament bundles (PFBs) by the work performed by surface-bound kinesin motors. We examine the properties of these PFBs using several techniques (e.g., fluorescence microscopy, SEM, AFM), and show that the PFBs continue to be mobile on the surface and display very high curvature compared to MT. Further, higher surface density of kinesin motors and shorter kinesin-surface tethers promote PFB formation, whereas modifying MT with GMPCPP or higher paclitaxel concentrations did not affect PFB formation.

  10. ATP-binding motifs play key roles in Krp1p, kinesin-related protein 1, function for bi-polar growth control in fission yeast

    Rhee, Dong Keun; Cho, Bon A; Kim, Hyong Bai

    2005-01-01

    Kinesin is a microtubule-based motor protein with various functions related to the cell growth and division. It has been reported that Krp1p, kinesin-related protein 1, which belongs to the kinesin heavy chain superfamily, localizes on microtubules and may play an important role in cytokinesis. However, the function of Krp1p has not been fully elucidated. In this study, we overexpressed an intact form and three different mutant forms of Krp1p in fission yeast constructed by site-directed mutagenesis in two ATP-binding motifs or by truncation of the leucine zipper-like motif (LZiP). We observed hyper-extended microtubules and the aberrant nuclear shape in Krp1p-overexpressed fission yeast. As a functional consequence, a point mutation of ATP-binding domain 1 (G89E) in Krp1p reversed the effect of Krp1p overexpression in fission yeast, whereas the specific mutation in ATP-binding domain 2 (G238E) resulted in the altered cell polarity. Additionally, truncation of the leucine zipper-like domain (LZiP) at the C-terminal of Krp1p showed a normal nuclear division. Taken together, we suggest that krp1p is involved in regulation of cell-polarized growth through ATP-binding motifs in fission yeast

  11. A smart dust biosensor powered by kinesin motors.

    Fischer, Thorsten; Agarwal, Ashutosh; Hess, Henry

    2009-03-01

    Biosensors can be miniaturized by either injecting smaller volumes into micro- and nanofluidic devices or immersing increasingly sophisticated particles known as 'smart dust' into the sample. The term 'smart dust' originally referred to cubic-millimetre wireless semiconducting sensor devices that could invisibly monitor the environment in buildings and public spaces, but later it also came to include functional micrometre-sized porous silicon particles used to monitor yet smaller environments. The principal challenge in designing smart dust biosensors is integrating transport functions with energy supply into the device. Here, we report a hybrid microdevice that is powered by ATP and relies on antibody-functionalized microtubules and kinesin motors to transport the target analyte into a detection region. The transport step replaces the wash step in traditional double-antibody sandwich assays. Owing to their small size and autonomous function, we envision that large numbers of such smart dust biosensors could be inserted into organisms or distributed into the environment for remote sensing.

  12. Kinesin-3 and dynein cooperate in long-range retrograde endosome motility along a nonuniform microtubule array

    Schuster, M.; Kilaru, S.; Fink, G.; Collemare, J.A.R.; Roger, Y.; Steinberg, G.

    2011-01-01

    The polarity of microtubules (MTs) determines the motors for intracellular motility, with kinesins moving to plus ends and dynein to minus ends. In elongated cells of Ustilago maydis, dynein is thought to move early endosomes (EEs) toward the septum (retrograde), whereas kinesin-3 transports them to

  13. Dauer pheromone and G-protein signaling modulate the coordination of intraflagellar transport kinesin motor proteins in C. elegans

    J.A. Burghoorn (Jan); M.P.J. Dekkers (Martijn); S. Rademakers (Suzanne); A.A.W. de Jong (Ton); R. Willemsen (Rob); P. Swoboda (Peter); J. McCafferty (Gert)

    2010-01-01

    textabstractCilia length and function are dynamically regulated by modulation of intraflagellar transport (IFT). The cilia of C. elegans amphid channel neurons provide an excellent model to study this process, since they use two different kinesins for anterograde transport: kinesin-II and OSM-3

  14. Kinesin-1 plays a role in transport of SNAP-25 to the plasma membrane

    Morton, April M.; Cunningham, Anthony L. [Centre for Virus Research, Westmead Millennium Institute, The University of Sydney and Westmead Hospital, Westmead, NSW 2145 (Australia); Diefenbach, Russell J., E-mail: russell_diefenbach@wmi.usyd.edu.au [Centre for Virus Research, Westmead Millennium Institute, The University of Sydney and Westmead Hospital, Westmead, NSW 2145 (Australia)

    2010-01-01

    The cellular molecular motor kinesin-1 mediates the microtubule-dependent transport of a range of cargo. We have previously identified an interaction between the cargo-binding domain of kinesin-1 heavy chain KIF5B and the membrane-associated SNARE proteins SNAP-25 and SNAP-23. In this study we further defined the minimal SNAP-25 binding domain in KIF5B to residues 874-894. Overexpression of a fragment of KIF5B (residues 594-910) resulted in significant colocalization with SNAP-25 with resulting blockage of the trafficking of SNAP-25 to the periphery of cells. This indicates that kinesin-1 facilitates the transport of SNAP-25 containing vesicles as a prerequisite to SNAP-25 driven membrane fusion events.

  15. The mechanochemical cycle of mammalian kinesin-2 KIF3A/B under load

    Andreasson, Johan O.L.; Shastry, Shankar; Hancock, William O.; Block, Steven M.

    2015-01-01

    Summary The response of motor proteins to external loads underlies their ability to work in teams and determines the net speed and directionality of cargo transport. The mammalian kinesin-2, KIF3A/B, is a heterotrimeric motor involved in intraflagellar transport and vesicle motility in neurons. Bidirectional cargo transport is known to result from the opposing activities of KIF3A/B and dynein bound to the same cargo, but the load-dependent properties of kinesin-2 are poorly understood. We used a feedback-controlled optical trap to probe the velocity, run length and unbinding kinetics of mouse KIF3A/B under various loads and nucleotide conditions. The kinesin-2 motor velocity is less sensitive than kinesin-1 to external forces, but its processivity diminishes steeply with load, and the motor was observed occasionally to slip and reattach. Each motor domain was characterized by studying homodimeric constructs, and a global fit to the data resulted in a comprehensive pathway that quantifies the principal force-dependent kinetic transitions. The properties of the KIF3A/B heterodimer are intermediate between the two homodimers, and the distinct load-dependent behavior is attributable to the properties of the motor domains, and not to the neck-linkers or the coiled-coil stalk. We conclude that the force-dependent movement of KIF3A/B differs significantly from conventional kinesin-1. Against opposing dynein forces, KIF3A/B motors are predicted to rapidly unbind and rebind, resulting in qualitatively different transport behavior from kinesin-1. PMID:25866395

  16. Deletion of the Tail Domain of the Kinesin-5 Cin8 Affects Its Directionality*

    Düselder, André; Fridman, Vladimir; Thiede, Christina; Wiesbaum, Alice; Goldstein, Alina; Klopfenstein, Dieter R.; Zaitseva, Olga; Janson, Marcel E.; Gheber, Larisa; Schmidt, Christoph F.

    2015-01-01

    The bipolar kinesin-5 motors are one of the major players that govern mitotic spindle dynamics. Their bipolar structure enables them to cross-link and slide apart antiparallel microtubules (MTs) emanating from the opposing spindle poles. The budding yeast kinesin-5 Cin8 was shown to switch from fast minus-end- to slow plus-end-directed motility upon binding between antiparallel MTs. This unexpected finding revealed a new dimension of cellular control of transport, the mechanism of which is unknown. Here we have examined the role of the C-terminal tail domain of Cin8 in regulating directionality. We first constructed a stable dimeric Cin8/kinesin-1 chimera (Cin8Kin), consisting of head and neck linker of Cin8 fused to the stalk of kinesin-1. As a single dimeric motor, Cin8Kin switched frequently between plus and minus directionality along single MTs, demonstrating that the Cin8 head domains are inherently bidirectional, but control over directionality was lost. We next examined the activity of a tetrameric Cin8 lacking only the tail domains (Cin8Δtail). In contrast to wild-type Cin8, the motility of single molecules of Cin8Δtail in high ionic strength was slow and bidirectional, with almost no directionality switches. Cin8Δtail showed only a weak ability to cross-link MTs in vitro. In vivo, Cin8Δtail exhibited bias toward the plus-end of the MTs and was unable to support viability of cells as the sole kinesin-5 motor. We conclude that the tail of Cin8 is not necessary for bidirectional processive motion, but is controlling the switch between plus- and minus-end-directed motility. PMID:25991727

  17. Anomalous inhibition of c-Met by the kinesin inhibitor aurintricarboxylic acid.

    Milanovic, Mina; Radtke, Simone; Peel, Nick; Howell, Michael; Carrière, Virginie; Joffre, Carine; Kermorgant, Stéphanie; Parker, Peter J

    2012-03-01

    c-Met [the hepatocyte growth factor (HGF) receptor] is a receptor tyrosine kinase playing a role in various biological events. Overexpression of the receptor has been observed in a number of cancers, correlating with increased metastatic tendency and poor prognosis. Additionally, activating mutations in c-Met kinase domain have been reported in a subset of familial cancers causing resistance to treatment. Receptor trafficking, relying on the integrity of the microtubule network, plays an important role in activation of downstream targets and initiation of signalling events. Aurintricarboxylic acid (ATA) is a triphenylmethane derivative that has been reported to inhibit microtubule motor proteins kinesins. Additional reported properties of this inhibitor include inhibition of protein tyrosine phosphatases, nucleases and members of the Jak family. Here we demonstrate that ATA prevents HGF-induced c-Met phosphorylation, internalisation, subsequent receptor trafficking and degradation. In addition, ATA prevented HGF-induced downstream signalling which also affected cellular function, as assayed by collective cell migration of A549 cells. Surprisingly, the inhibitory effect of ATA on HGF-induced phosphorylation and signalling in vivo was associated with an increase in basal c-Met kinase activity in vitro. It is concluded that the inhibitory effects of ATA on c-Met in vivo is an allosteric effect mediated through the kinase domain of the receptor. As the currently tested adenosine triphosphate competitive tyrosine kinase inhibitors (TKIs) may lead to tumor resistance (McDermott U, et al., Cancer Res 2010;70:1625-34), our findings suggest that novel anti-c-Met therapies could be developed in the future for cancer treatment. Copyright © 2011 UICC.

  18. Detectable states, cycle fluxes, and motility scaling of molecular motor kinesin: An integrative kinetic graph theory analysis

    Ren, Jie

    2017-12-01

    The process by which a kinesin motor couples its ATPase activity with concerted mechanical hand-over-hand steps is a foremost topic of molecular motor physics. Two major routes toward elucidating kinesin mechanisms are the motility performance characterization of velocity and run length, and single-molecular state detection experiments. However, these two sets of experimental approaches are largely uncoupled to date. Here, we introduce an integrative motility state analysis based on a theorized kinetic graph theory for kinesin, which, on one hand, is validated by a wealth of accumulated motility data, and, on the other hand, allows for rigorous quantification of state occurrences and chemomechanical cycling probabilities. An interesting linear scaling for kinesin motility performance across species is discussed as well. An integrative kinetic graph theory analysis provides a powerful tool to bridge motility and state characterization experiments, so as to forge a unified effort for the elucidation of the working mechanisms of molecular motors.

  19. S. pombe kinesins-8 promote both nucleation and catastrophe of microtubules.

    Muriel Erent

    Full Text Available The kinesins-8 were originally thought to be microtubule depolymerases, but are now emerging as more versatile catalysts of microtubule dynamics. We show here that S. pombe Klp5-436 and Klp6-440 are non-processive plus-end-directed motors whose in vitro velocities on S. pombe microtubules at 7 and 23 nm s(-1 are too slow to keep pace with the growing tips of dynamic interphase microtubules in living S. pombe. In vitro, Klp5 and 6 dimers exhibit a hitherto-undescribed combination of strong enhancement of microtubule nucleation with no effect on growth rate or catastrophe frequency. By contrast in vivo, both Klp5 and Klp6 promote microtubule catastrophe at cell ends whilst Klp6 also increases the number of interphase microtubule arrays (IMAs. Our data support a model in which Klp5/6 bind tightly to free tubulin heterodimers, strongly promoting the nucleation of new microtubules, and then continue to land as a tubulin-motor complex on the tips of growing microtubules, with the motors then dissociating after a few seconds residence on the lattice. In vivo, we predict that only at cell ends, when growing microtubule tips become lodged and their growth slows down, will Klp5/6 motor activity succeed in tracking growing microtubule tips. This mechanism would allow Klp5/6 to detect the arrival of microtubule tips at cells ends and to amplify the intrinsic tendency for microtubules to catastrophise in compression at cell ends. Our evidence identifies Klp5 and 6 as spatial regulators of microtubule dynamics that enhance both microtubule nucleation at the cell centre and microtubule catastrophe at the cell ends.

  20. Protein friction limits diffusive and directed movements of kinesin motors on microtubules.

    Bormuth, Volker; Varga, Vladimir; Howard, Jonathon; Schäffer, Erik

    2009-08-14

    Friction limits the operation of macroscopic engines and is critical to the performance of micromechanical devices. We report measurements of friction in a biological nanomachine. Using optical tweezers, we characterized the frictional drag force of individual kinesin-8 motor proteins interacting with their microtubule tracks. At low speeds and with no energy source, the frictional drag was related to the diffusion coefficient by the Einstein relation. At higher speeds, the frictional drag force increased nonlinearly, consistent with the motor jumping 8 nanometers between adjacent tubulin dimers along the microtubule, and was asymmetric, reflecting the structural polarity of the microtubule. We argue that these frictional forces arise from breaking bonds between the motor domains and the microtubule, and they limit the speed and efficiency of kinesin.

  1. Kinesin-dependent mechanism for controlling triglyceride secretion from the liver.

    Rai, Priyanka; Kumar, Mukesh; Sharma, Geetika; Barak, Pradeep; Das, Saumitra; Kamat, Siddhesh S; Mallik, Roop

    2017-12-05

    Despite massive fluctuations in its internal triglyceride content, the liver secretes triglyceride under tight homeostatic control. This buffering function is most visible after fasting, when liver triglyceride increases manyfold but circulating serum triglyceride barely fluctuates. How the liver controls triglyceride secretion is unknown, but is fundamentally important for lipid and energy homeostasis in animals. Here we find an unexpected cellular and molecular mechanism behind such control. We show that kinesin motors are recruited to triglyceride-rich lipid droplets (LDs) in the liver by the GTPase ARF1, which is a key activator of lipolysis. This recruitment is activated by an insulin-dependent pathway and therefore responds to fed/fasted states of the animal. In fed state, ARF1 and kinesin appear on LDs, consequently transporting LDs to the periphery of hepatocytes where the smooth endoplasmic reticulum (sER) is present. Because the lipases that catabolize LDs in hepatocytes reside on the sER, LDs can now be catabolized efficiently to provide triglyceride for lipoprotein assembly and secretion from the sER. Upon fasting, insulin is lowered to remove ARF1 and kinesin from LDs, thus down-regulating LD transport and sER-LD contacts. This tempers triglyceride availabiity for very low density lipoprotein assembly and allows homeostatic control of serum triglyceride in a fasted state. We further show that kinesin knockdown inhibits hepatitis-C virus replication in hepatocytes, likely because translated viral proteins are unable to transfer from the ER to LDs. Copyright © 2017 the Author(s). Published by PNAS.

  2. In vivo collection of rare proteins using kinesin-based "nano-harvesters".

    Bachand, Marlene; Bachand, George David; Greene, Adrienne Celeste; Carroll-Portillo, Amanda

    2008-11-01

    In this project, we have developed a novel platform for capturing, transport, and separating target analytes using the work harnessed from biomolecular transport systems. Nanoharvesters were constructed by co-organizing kinesin motor proteins and antibodies on a nanocrystal quantum dot (nQD) scaffold. Attachment of kinesin and antibodies to the nQD was achieved through biotin-streptavidin non-covalent bonds. Assembly of the nanoharvesters was characterized using a modified enzyme-linked immunosorbent assay (ELISA) that confirmed attachment of both proteins. Nanoharvesters selective against tumor necrosis factor-{alpha} (TNF-{alpha}) and nuclear transcription factor-{kappa}B (NF-{kappa}B) were capable of detecting target antigens at <100 ng/mL in ELISAs. A motility-based assay was subsequently developed using an antibody-sandwich approach in which the target antigen (TNF-{alpha}) formed a sandwich with the red-emitting nanoharvester and green-emitting detection nQD. In this format, successful sandwich formation resulted in a yellow emission associated with surface-bound microtubules. Step-wise analysis of sandwich formation suggested that the motility function of the kinesin motors was not adversely affected by either antigen capture or the subsequent binding of the detection nQDs. TNF-{alpha} was detected as low as {approx}1.5 ng/mL TNF-{alpha}, with 5.2% of the nanoharvesters successfully capturing the target analyte and detection nQDs. Overall, these results demonstrate the ability to capture target protein analytes in vitro using the kinesin-based nanoharvesters in nanofluidic environments. This system has direct relevance for lab-on-a-chip applications where pressure-driven or electrokinetic movement of fluids is impractical, and offers potential application for in vivo capture of rare proteins within the cytoplasmic domain of live cells.

  3. Microtubule–microtubule sliding by kinesin-1 is essential for normal cytoplasmic streaming in Drosophila oocytes

    Lu, Wen; Winding, Michael; Lakonishok, Margot; Wildonger, Jill

    2016-01-01

    Cytoplasmic streaming in Drosophila oocytes is a microtubule-based bulk cytoplasmic movement. Streaming efficiently circulates and localizes mRNAs and proteins deposited by the nurse cells across the oocyte. This movement is driven by kinesin-1, a major microtubule motor. Recently, we have shown that kinesin-1 heavy chain (KHC) can transport one microtubule on another microtubule, thus driving microtubule–microtubule sliding in multiple cell types. To study the role of microtubule sliding in oocyte cytoplasmic streaming, we used a Khc mutant that is deficient in microtubule sliding but able to transport a majority of cargoes. We demonstrated that streaming is reduced by genomic replacement of wild-type Khc with this sliding-deficient mutant. Streaming can be fully rescued by wild-type KHC and partially rescued by a chimeric motor that cannot move organelles but is active in microtubule sliding. Consistent with these data, we identified two populations of microtubules in fast-streaming oocytes: a network of stable microtubules anchored to the actin cortex and free cytoplasmic microtubules that moved in the ooplasm. We further demonstrated that the reduced streaming in sliding-deficient oocytes resulted in posterior determination defects. Together, we propose that kinesin-1 slides free cytoplasmic microtubules against cortically immobilized microtubules, generating forces that contribute to cytoplasmic streaming and are essential for the refinement of posterior determinants. PMID:27512034

  4. Cytoplasmic streaming in Drosophila oocytes varies with kinesin activity and correlates with the microtubule cytoskeleton architecture.

    Ganguly, Sujoy; Williams, Lucy S; Palacios, Isabel M; Goldstein, Raymond E

    2012-09-18

    Cells can localize molecules asymmetrically through the combined action of cytoplasmic streaming, which circulates their fluid contents, and specific anchoring mechanisms. Streaming also contributes to the distribution of nutrients and organelles such as chloroplasts in plants, the asymmetric position of the meiotic spindle in mammalian embryos, and the developmental potential of the zygote, yet little is known quantitatively about the relationship between streaming and the motor activity which drives it. Here we use Particle Image Velocimetry to quantify the statistical properties of Kinesin-dependent streaming during mid-oogenesis in Drosophila. We find that streaming can be used to detect subtle changes in Kinesin activity and that the flows reflect the architecture of the microtubule cytoskeleton. Furthermore, based on characterization of the rheology of the cytoplasm in vivo, we establish estimates of the number of Kinesins required to drive the observed streaming. Using this in vivo data as the basis of a model for transport, we suggest that the disordered character of transport at mid-oogenesis, as revealed by streaming, is an important component of the localization dynamics of the body plan determinant oskar mRNA.

  5. Vaccinia protein F12 has structural similarity to kinesin light chain and contains a motor binding motif required for virion export.

    Gareth W Morgan

    2010-02-01

    Full Text Available Vaccinia virus (VACV uses microtubules for export of virions to the cell surface and this process requires the viral protein F12. Here we show that F12 has structural similarity to kinesin light chain (KLC, a subunit of the kinesin-1 motor that binds cargo. F12 and KLC share similar size, pI, hydropathy and cargo-binding tetratricopeptide repeats (TPRs. Moreover, molecular modeling of F12 TPRs upon the crystal structure of KLC2 TPRs showed a striking conservation of structure. We also identified multiple TPRs in VACV proteins E2 and A36. Data presented demonstrate that F12 is critical for recruitment of kinesin-1 to virions and that a conserved tryptophan and aspartic acid (WD motif, which is conserved in the kinesin-1-binding sequence (KBS of the neuronal protein calsyntenin/alcadein and several other cellular kinesin-1 binding proteins, is essential for kinesin-1 recruitment and virion transport. In contrast, mutation of WD motifs in protein A36 revealed they were not required for kinesin-1 recruitment or IEV transport. This report of a viral KLC-like protein containing a KBS that is conserved in several cellular proteins advances our understanding of how VACV recruits the kinesin motor to virions, and exemplifies how viruses use molecular mimicry of cellular components to their advantage.

  6. Delivery of kinesin spindle protein targeting siRNA in solid lipid nanoparticles to cellular models of tumor vasculature

    Ying, Bo; Campbell, Robert B.

    2014-01-01

    Highlights: • siRNA-lipid nanoparticles are solid particles not lipid bilayers with aqueous core. • High, but not low, PEG content can prevent nanoparticle encapsulation of siRNA. • PEG reduces cellular toxicity of cationic nanoparticles in vitro. • PEG reduces zeta potential while improving gene silencing of siRNA nanoparticles. • Kinesin spindle protein can be an effective target for tumor vascular targeting. - Abstract: The ideal siRNA delivery system should selectively deliver the construct to the target cell, avoid enzymatic degradation, and evade uptake by phagocytes. In the present study, we evaluated the importance of polyethylene glycol (PEG) on lipid-based carrier systems for encapsulating, and delivering, siRNA to tumor vessels using cellular models. Lipid nanoparticles containing different percentage of PEG were evaluated based on their physical chemical properties, density compared to water, siRNA encapsulation, toxicity, targeting efficiency and gene silencing in vitro. siRNA can be efficiently loaded into lipid nanoparticles (LNPs) when DOTAP is included in the formulation mixture. However, the total amount encapsulated decreased with increase in PEG content. In the presence of siRNA, the final formulations contained a mixed population of particles based on density. The major population which contains the majority of siRNA exhibited a density of 4% glucose, and the minor fraction associated with a decreased amount of siRNA had a density less than PBS. The inclusion of 10 mol% PEG resulted in a greater amount of siRNA associated with the minor fraction. Finally, when kinesin spindle protein (KSP) siRNA was encapsulated in lipid nanoparticles containing a modest amount of PEG, the proliferation of endothelial cells was inhibited due to the efficient knock down of KSP mRNA. The presence of siRNA resulted in the formation of solid lipid nanoparticles when prepared using the thin film and hydration method. LNPs with a relatively modest amount of

  7. Distribution of tubulin, kinesin, and dynein in light- and dark-adapted octopus retinas.

    Martinez, J M; Elfarissi, H; De Velasco, B; Ochoa, G H; Miller, A M; Clark, Y M; Matsumoto, B; Robles, L J

    2000-01-01

    Cephalopod retinas exhibit several responses to light and dark adaptation, including rhabdom size changes, photopigment movements, and pigment granule migration. Light- and dark-directed rearrangements of microfilament and microtubule cytoskeletal transport pathways could drive these changes. Recently, we localized actin-binding proteins in light-/dark-adapted octopus rhabdoms and suggested that actin cytoskeletal rearrangements bring about the formation and degradation of rhabdomere microvilli subsets. To determine if the microtubule cytoskeleton and associated motor proteins control the other light/dark changes, we used immunoblotting and immunocytochemical procedures to map the distribution of tubulin, kinesin, and dynein in dorsal and ventral halves of light- and dark-adapted octopus retinas. Immunoblots detected alpha- and beta-tubulin, dynein intermediate chain, and kinesin heavy chain in extracts of whole retinas. Epifluorescence and confocal microscopy showed that the tubulin proteins were distributed throughout the retina with more immunoreactivity in retinas exposed to light. Kinesin localization was heavy in the pigment layer of light- and dark-adapted ventral retinas but was less prominent in the dorsal region. Dynein distribution also varied in dorsal and ventral retinas with more immunoreactivity in light- and dark-adapted ventral retinas and confocal microscopy emphasized the granular nature of this labeling. We suggest that light may regulate the distribution of microtubule cytoskeletal proteins in the octopus retina and that position, dorsal versus ventral, also influences the distribution of motor proteins. The microtubule cytoskeleton is most likely involved in pigment granule migration in the light and dark and with the movement of transport vesicles from the photoreceptor inner segments to the rhabdoms.

  8. Changes in microtubule overlap length regulate kinesin-14-driven microtubule sliding

    Braun, Marcus; Lánský, Zdeněk; Szuba, A.; Schwarz, F. W.; Mitra, A.; Gao, M.; Luedecke, A.; ten Wolde, P.R.; Diez, S.

    2017-01-01

    Roč. 13, č. 12 (2017), s. 1245-1252 ISSN 1552-4450 R&D Projects: GA ČR(CZ) GA15-17488S; GA ČR(CZ) GA17-12496Y; GA ČR(CZ) GJ17-12496Y; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : SPINDLE ELONGATION * MITOTIC SPINDLE * KINESIN-5 CIN8 * CROSS-LINKERS Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biophysics Impact factor: 15.066, year: 2016

  9. Xenopus laevis Kif18A is a highly processive kinesin required for meiotic spindle integrity

    Martin M. Möckel

    2017-04-01

    Full Text Available The assembly and functionality of the mitotic spindle depends on the coordinated activities of microtubule-associated motor proteins of the dynein and kinesin superfamily. Our current understanding of the function of motor proteins is significantly shaped by studies using Xenopus laevis egg extract as its open structure allows complex experimental manipulations hardly feasible in other model systems. Yet, the Kinesin-8 orthologue of human Kif18A has not been described in Xenopus laevis so far. Here, we report the cloning and characterization of Xenopus laevis (Xl Kif18A. Xenopus Kif18A is expressed during oocyte maturation and its depletion from meiotic egg extract results in severe spindle defects. These defects can be rescued by wild-type Kif18A, but not Kif18A lacking motor activity or the C-terminus. Single-molecule microscopy assays revealed that Xl_Kif18A possesses high processivity, which depends on an additional C-terminal microtubule-binding site. Human tissue culture cells depleted of endogenous Kif18A display mitotic defects, which can be rescued by wild-type, but not tail-less Xl_Kif18A. Thus, Xl_Kif18A is the functional orthologue of human Kif18A whose activity is essential for the correct function of meiotic spindles in Xenopus oocytes.

  10. ATPase Cycle of the Nonmotile Kinesin NOD Allows Microtubule End Tracking and Drives Chromosome Movement

    Cochran, J.; Sindelar, C; Mulko, N; Collins, K; Kong, S; Hawley, R; Kull, F

    2009-01-01

    Segregation of nonexchange chromosomes during Drosophila melanogaster meiosis requires the proper function of NOD, a nonmotile kinesin-10. We have determined the X-ray crystal structure of the NOD catalytic domain in the ADP- and AMPPNP-bound states. These structures reveal an alternate conformation of the microtubule binding region as well as a nucleotide-sensitive relay of hydrogen bonds at the active site. Additionally, a cryo-electron microscopy reconstruction of the nucleotide-free microtubule-NOD complex shows an atypical binding orientation. Thermodynamic studies show that NOD binds tightly to microtubules in the nucleotide-free state, yet other nucleotide states, including AMPPNP, are weakened. Our pre-steady-state kinetic analysis demonstrates that NOD interaction with microtubules occurs slowly with weak activation of ADP product release. Upon rapid substrate binding, NOD detaches from the microtubule prior to the rate-limiting step of ATP hydrolysis, which is also atypical for a kinesin. We propose a model for NOD's microtubule plus-end tracking that drives chromosome movement.

  11. The Kinesin Adaptor Calsyntenin-1 Organizes Microtubule Polarity and Regulates Dynamics during Sensory Axon Arbor Development

    Mary C. Halloran

    2017-04-01

    Full Text Available Axon growth and branching, and development of neuronal polarity are critically dependent on proper organization and dynamics of the microtubule (MT cytoskeleton. MTs must organize with correct polarity for delivery of diverse cargos to appropriate subcellular locations, yet the molecular mechanisms regulating MT polarity remain poorly understood. Moreover, how an actively branching axon reorganizes MTs to direct their plus ends distally at branch points is unknown. We used high-speed, in vivo imaging of polymerizing MT plus ends to characterize MT dynamics in developing sensory axon arbors in zebrafish embryos. We find that axonal MTs are highly dynamic throughout development, and that the peripheral and central axons of sensory neurons show differences in MT behaviors. Furthermore, we show that Calsyntenin-1 (Clstn-1, a kinesin adaptor required for sensory axon branching, also regulates MT polarity in developing axon arbors. In wild type neurons the vast majority of MTs are directed in the correct plus-end-distal orientation from early stages of development. Loss of Clstn-1 causes an increase in MTs polymerizing in the retrograde direction. These misoriented MTs most often are found near growth cones and branch points, suggesting Clstn-1 is particularly important for organizing MT polarity at these locations. Together, our results suggest that Clstn-1, in addition to regulating kinesin-mediated cargo transport, also organizes the underlying MT highway during axon arbor development.

  12. Parsing the roles of neck-linker docking and tethered head diffusion in the stepping dynamics of kinesin.

    Zhang, Zhechun; Goldtzvik, Yonathan; Thirumalai, D

    2017-11-14

    Kinesin walks processively on microtubules (MTs) in an asymmetric hand-over-hand manner consuming one ATP molecule per 16-nm step. The individual contributions due to docking of the approximately 13-residue neck linker to the leading head (deemed to be the power stroke) and diffusion of the trailing head (TH) that contributes in propelling the motor by 16 nm have not been quantified. We use molecular simulations by creating a coarse-grained model of the MT-kinesin complex, which reproduces the measured stall force as well as the force required to dislodge the motor head from the MT, to show that nearly three-quarters of the step occurs by bidirectional stochastic motion of the TH. However, docking of the neck linker to the leading head constrains the extent of diffusion and minimizes the probability that kinesin takes side steps, implying that both the events are necessary in the motility of kinesin and for the maintenance of processivity. Surprisingly, we find that during a single step, the TH stochastically hops multiple times between the geometrically accessible neighboring sites on the MT before forming a stable interaction with the target binding site with correct orientation between the motor head and the [Formula: see text] tubulin dimer.

  13. Crystal structure of the Candida albicans Kar3 kinesin motor domain fused to maltose-binding protein

    Delorme, Caroline; Joshi, Monika; Allingham, John S.

    2012-01-01

    Highlights: ► The Candida albicans Kar3 motor domain structure was solved as a maltose-binding protein fusion. ► The electrostatic surface and part of the ATPase pocket of the motor domain differs markedly from other kinesins. ► The MBP–Kar3 interface highlights a new site for intramolecular or intermolecular interactions. -- Abstract: In the human fungal pathogen Candida albicans, the Kinesin-14 motor protein Kar3 (CaKar3) is critical for normal mitotic division, nuclear fusion during mating, and morphogenic transition from the commensal yeast form to the virulent hyphal form. As a first step towards detailed characterization of this motor of potential medical significance, we have crystallized and determined the X-ray structure of the motor domain of CaKar3 as a maltose-binding protein (MBP) fusion. The structure shows strong conservation of overall motor domain topology to other Kar3 kinesins, but with some prominent differences in one of the motifs that compose the nucleotide-binding pocket and the surface charge distribution. The MBP and Kar3 modules are arranged such that MBP interacts with the Kar3 motor domain core at the same site where the neck linker of conventional kinesins docks during the “ATP state” of the mechanochemical cycle. This site differs from the Kar3 neck–core interface in the recent structure of the ScKar3Vik1 heterodimer. The position of MBP is also completely distinct from the Vik1 subunit in this complex. This may suggest that the site of MBP interaction on the CaKar3 motor domain provides an interface for the neck, or perhaps a partner subunit, at an intermediate state of its motile cycle that has not yet been observed for Kinesin-14 motors.

  14. Crystal structure of the Candida albicans Kar3 kinesin motor domain fused to maltose-binding protein

    Delorme, Caroline; Joshi, Monika [Department of Biomedical and Molecular Sciences, Queen' s University, Kingston, ON, Canada K7L 3N6 (Canada); Allingham, John S., E-mail: allinghj@queensu.ca [Department of Biomedical and Molecular Sciences, Queen' s University, Kingston, ON, Canada K7L 3N6 (Canada)

    2012-11-30

    Highlights: Black-Right-Pointing-Pointer The Candida albicans Kar3 motor domain structure was solved as a maltose-binding protein fusion. Black-Right-Pointing-Pointer The electrostatic surface and part of the ATPase pocket of the motor domain differs markedly from other kinesins. Black-Right-Pointing-Pointer The MBP-Kar3 interface highlights a new site for intramolecular or intermolecular interactions. -- Abstract: In the human fungal pathogen Candida albicans, the Kinesin-14 motor protein Kar3 (CaKar3) is critical for normal mitotic division, nuclear fusion during mating, and morphogenic transition from the commensal yeast form to the virulent hyphal form. As a first step towards detailed characterization of this motor of potential medical significance, we have crystallized and determined the X-ray structure of the motor domain of CaKar3 as a maltose-binding protein (MBP) fusion. The structure shows strong conservation of overall motor domain topology to other Kar3 kinesins, but with some prominent differences in one of the motifs that compose the nucleotide-binding pocket and the surface charge distribution. The MBP and Kar3 modules are arranged such that MBP interacts with the Kar3 motor domain core at the same site where the neck linker of conventional kinesins docks during the 'ATP state' of the mechanochemical cycle. This site differs from the Kar3 neck-core interface in the recent structure of the ScKar3Vik1 heterodimer. The position of MBP is also completely distinct from the Vik1 subunit in this complex. This may suggest that the site of MBP interaction on the CaKar3 motor domain provides an interface for the neck, or perhaps a partner subunit, at an intermediate state of its motile cycle that has not yet been observed for Kinesin-14 motors.

  15. BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon.

    Farías, Ginny G; Guardia, Carlos M; De Pace, Raffaella; Britt, Dylan J; Bonifacino, Juan S

    2017-04-04

    The ability of lysosomes to move within the cytoplasm is important for many cellular functions. This ability is particularly critical in neurons, which comprise vast, highly differentiated domains such as the axon and dendrites. The mechanisms that control lysosome movement in these domains, however, remain poorly understood. Here we show that an ensemble of BORC, Arl8, SKIP, and kinesin-1, previously shown to mediate centrifugal transport of lysosomes in nonneuronal cells, specifically drives lysosome transport into the axon, and not the dendrites, in cultured rat hippocampal neurons. This transport is essential for maintenance of axonal growth-cone dynamics and autophagosome turnover. Our findings illustrate how a general mechanism for lysosome dispersal in nonneuronal cells is adapted to drive polarized transport in neurons, and emphasize the importance of this mechanism for critical axonal processes.

  16. BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon

    Farías, Ginny G.; Guardia, Carlos M.; De Pace, Raffaella; Britt, Dylan J.; Bonifacino, Juan S.

    2017-01-01

    The ability of lysosomes to move within the cytoplasm is important for many cellular functions. This ability is particularly critical in neurons, which comprise vast, highly differentiated domains such as the axon and dendrites. The mechanisms that control lysosome movement in these domains, however, remain poorly understood. Here we show that an ensemble of BORC, Arl8, SKIP, and kinesin-1, previously shown to mediate centrifugal transport of lysosomes in nonneuronal cells, specifically drives lysosome transport into the axon, and not the dendrites, in cultured rat hippocampal neurons. This transport is essential for maintenance of axonal growth-cone dynamics and autophagosome turnover. Our findings illustrate how a general mechanism for lysosome dispersal in nonneuronal cells is adapted to drive polarized transport in neurons, and emphasize the importance of this mechanism for critical axonal processes. PMID:28320970

  17. Role of kinesin heavy chain in Crumbs localization along the rhabdomere elongation in Drosophila photoreceptor.

    Garrett P League

    Full Text Available BACKGROUND: Crumbs (Crb, a cell polarity gene, has been shown to provide a positional cue for the extension of the apical membrane domain, adherens junction (AJ, and rhabdomere along the growing proximal-distal axis during Drosophila photoreceptor morphogenesis. In developing Drosophila photoreceptors, a stabilized microtubule structure was discovered and its presence was linked to polarity protein localization. It was therefore hypothesized that the microtubules may provide trafficking routes for the polarity proteins during photoreceptor morphogenesis. This study has examined whether Kinesin heavy chain (Khc, a subunit of the microtubule-based motor Kinesin-1, is essential in polarity protein localization in developing photoreceptors. METHODOLOGY/PRINCIPAL FINDINGS: Because a genetic interaction was found between crb and khc, Crb localization was examined in the developing photoreceptors of khc mutants. khc was dispensable during early eye differentiation and development. However, khc mutant photoreceptors showed a range of abnormalities in the apical membrane domain depending on the position along the proximal-distal axis in pupal photoreceptors. The khc mutant showed a progressive mislocalization in the apical domain along the distal-proximal axis during rhabdomere elongation. The khc mutation also led to a similar progressive defect in the stabilized microtubule structures, strongly suggesting that Khc is essential for microtubule structure and Crb localization during distal to proximal rhabdomere elongation in pupal morphogenesis. This role of Khc in apical domain control was further supported by khc's gain-of-function phenotype. Khc overexpression in photoreceptors caused disruption of the apical membrane domain and the stabilized microtubules in the developing photoreceptors. CONCLUSIONS/SIGNIFICANCE: In summary, we examined the role of khc in the regulation of the apical Crb domain in developing photoreceptors. Since the rhabdomeres in

  18. Human kidney anion exchanger 1 interacts with kinesin family member 3B (KIF3B)

    Duangtum, Natapol [Medical Molecular Biology Unit, Office for Research and Development Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Junking, Mutita; Sawasdee, Nunghathai [Medical Molecular Biology Unit, Office for Research and Development Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Cheunsuchon, Boonyarit [Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Limjindaporn, Thawornchai, E-mail: limjindaporn@yahoo.com [Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Yenchitsomanus, Pa-thai, E-mail: grpye@mahidol.ac.th [Medical Molecular Biology Unit, Office for Research and Development Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand)

    2011-09-16

    Highlights: {yields} Impaired trafficking of kAE1 causes distal renal tubular acidosis (dRTA). {yields} The interaction between kAE1 and kinesin family member 3B (KIF3B) is reported. {yields} The co-localization between kAE and KIF3B was detected in human kidney tissues. {yields} A marked reduction of kAE1 on the cell membrane was observed when KIF3B was knockdown. {yields} KFI3B plays an important role in trafficking of kAE1 to the plasma membrane. -- Abstract: Impaired trafficking of human kidney anion exchanger 1 (kAE1) to the basolateral membrane of {alpha}-intercalated cells of the kidney collecting duct leads to the defect of the Cl{sup -}/HCO{sub 3}{sup -} exchange and the failure of proton (H{sup +}) secretion at the apical membrane of these cells, causing distal renal tubular acidosis (dRTA). In the sorting process, kAE1 interacts with AP-1 mu1A, a subunit of AP-1A adaptor complex. However, it is not known whether kAE1 interacts with motor proteins in its trafficking process to the plasma membrane or not. We report here that kAE1 interacts with kinesin family member 3B (KIF3B) in kidney cells and a dileucine motif at the carboxyl terminus of kAE1 contributes to this interaction. We have also demonstrated that kAE1 co-localizes with KIF3B in human kidney tissues and the suppression of endogenous KIF3B in HEK293T cells by small interfering RNA (siRNA) decreases membrane localization of kAE1 but increases its intracellular accumulation. All results suggest that KIF3B is involved in the trafficking of kAE1 to the plasma membrane of human kidney {alpha}-intercalated cells.

  19. Human kidney anion exchanger 1 interacts with kinesin family member 3B (KIF3B)

    Duangtum, Natapol; Junking, Mutita; Sawasdee, Nunghathai; Cheunsuchon, Boonyarit; Limjindaporn, Thawornchai; Yenchitsomanus, Pa-thai

    2011-01-01

    Highlights: → Impaired trafficking of kAE1 causes distal renal tubular acidosis (dRTA). → The interaction between kAE1 and kinesin family member 3B (KIF3B) is reported. → The co-localization between kAE and KIF3B was detected in human kidney tissues. → A marked reduction of kAE1 on the cell membrane was observed when KIF3B was knockdown. → KFI3B plays an important role in trafficking of kAE1 to the plasma membrane. -- Abstract: Impaired trafficking of human kidney anion exchanger 1 (kAE1) to the basolateral membrane of α-intercalated cells of the kidney collecting duct leads to the defect of the Cl - /HCO 3 - exchange and the failure of proton (H + ) secretion at the apical membrane of these cells, causing distal renal tubular acidosis (dRTA). In the sorting process, kAE1 interacts with AP-1 mu1A, a subunit of AP-1A adaptor complex. However, it is not known whether kAE1 interacts with motor proteins in its trafficking process to the plasma membrane or not. We report here that kAE1 interacts with kinesin family member 3B (KIF3B) in kidney cells and a dileucine motif at the carboxyl terminus of kAE1 contributes to this interaction. We have also demonstrated that kAE1 co-localizes with KIF3B in human kidney tissues and the suppression of endogenous KIF3B in HEK293T cells by small interfering RNA (siRNA) decreases membrane localization of kAE1 but increases its intracellular accumulation. All results suggest that KIF3B is involved in the trafficking of kAE1 to the plasma membrane of human kidney α-intercalated cells.

  20. Crystal Structures of the Tetratricopeptide Repeat Domains of Kinesin Light Chains: Insight into Cargo Recognition Mechanisms

    Zhu, Haizhong; Lee, Han Youl; Tong, Yufeng; Hong, Bum-Soo; Kim, Kyung-Phil; Shen, Yang; Lim, Kyung Jik; Mackenzie, Farrell; Tempel, Wolfram; Park, Hee-Won (SGC-Toronto); (PPCS); (Toronto)

    2012-10-23

    Kinesin-1 transports various cargos along the axon by interacting with the cargos through its light chain subunit. Kinesin light chains (KLC) utilize its tetratricopeptide repeat (TPR) domain to interact with over 10 different cargos. Despite a high sequence identity between their TPR domains (87%), KLC1 and KLC2 isoforms exhibit differential binding properties towards some cargos. We determined the structures of human KLC1 and KLC2 tetratricopeptide repeat (TPR) domains using X-ray crystallography and investigated the different mechanisms by which KLCs interact with their cargos. Using isothermal titration calorimetry, we attributed the specific interaction between KLC1 and JNK-interacting protein 1 (JIP1) cargo to residue N343 in the fourth TRP repeat. Structurally, the N343 residue is adjacent to other asparagines and lysines, creating a positively charged polar patch within the groove of the TPR domain. Whereas, KLC2 with the corresponding residue S328 did not interact with JIP1. Based on these finding, we propose that N343 of KLC1 can form 'a carboxylate clamp' with its neighboring asparagine to interact with JIP1, similar to that of HSP70/HSP90 organizing protein-1's (HOP1) interaction with heat shock proteins. For the binding of cargos shared by KLC1 and KLC2, we propose a different site located within the groove but not involving N343. We further propose a third binding site on KLC1 which involves a stretch of polar residues along the inter-TPR loops that may form a network of hydrogen bonds to JIP3 and JIP4. Together, these results provide structural insights into possible mechanisms of interaction between KLC TPR domains and various cargo proteins.

  1. Dynamic microtubule organization and mitochondrial transport are regulated by distinct Kinesin-1 pathways

    Anna Melkov

    2015-12-01

    Full Text Available The microtubule (MT plus-end motor kinesin heavy chain (Khc is well known for its role in long distance cargo transport. Recent evidence showed that Khc is also required for the organization of the cellular MT network by mediating MT sliding. We found that mutations in Khc and the gene of its adaptor protein, kinesin light chain (Klc resulted in identical bristle morphology defects, with the upper part of the bristle being thinner and flatter than normal and failing to taper towards the bristle tip. We demonstrate that bristle mitochondria transport requires Khc but not Klc as a competing force to dynein heavy chain (Dhc. Surprisingly, we demonstrate for the first time that Dhc is the primary motor for both anterograde and retrograde fast mitochondria transport. We found that the upper part of Khc and Klc mutant bristles lacked stable MTs. When following dynamic MT polymerization via the use of GFP-tagged end-binding protein 1 (EB1, it was noted that at Khc and Klc mutant bristle tips, dynamic MTs significantly deviated from the bristle parallel growth axis, relative to wild-type bristles. We also observed that GFP-EB1 failed to concentrate as a focus at the tip of Khc and Klc mutant bristles. We propose that the failure of bristle tapering is due to defects in directing dynamic MTs at the growing tip. Thus, we reveal a new function for Khc and Klc in directing dynamic MTs during polarized cell growth. Moreover, we also demonstrate a novel mode of coordination in mitochondrial transport between Khc and Dhc.

  2. Lemur tyrosine kinase-2 signalling regulates kinesin-1 light chain-2 phosphorylation and binding of Smad2 cargo.

    Manser, C

    2012-05-31

    A recent genome-wide association study identified the gene encoding lemur tyrosine kinase-2 (LMTK2) as a susceptibility gene for prostate cancer. The identified genetic alteration is within intron 9, but the mechanisms by which LMTK2 may impact upon prostate cancer are not clear because the functions of LMTK2 are poorly understood. Here, we show that LMTK2 regulates a known pathway that controls phosphorylation of kinesin-1 light chain-2 (KLC2) by glycogen synthase kinase-3β (GSK3β). KLC2 phosphorylation by GSK3β induces the release of cargo from KLC2. LMTK2 signals via protein phosphatase-1C (PP1C) to increase inhibitory phosphorylation of GSK3β on serine-9 that reduces KLC2 phosphorylation and promotes binding of the known KLC2 cargo Smad2. Smad2 signals to the nucleus in response to transforming growth factor-β (TGFβ) receptor stimulation and transport of Smad2 by kinesin-1 is required for this signalling. We show that small interfering RNA loss of LMTK2 not only reduces binding of Smad2 to KLC2, but also inhibits TGFβ-induced Smad2 signalling. Thus, LMTK2 may regulate the activity of kinesin-1 motor function and Smad2 signalling.

  3. The kinesin AtPSS1 promotes synapsis and is required for proper crossover distribution in meiosis.

    Yann Duroc

    2014-10-01

    Full Text Available Meiotic crossovers (COs shape genetic diversity by mixing homologous chromosomes at each generation. CO distribution is a highly regulated process. CO assurance forces the occurrence of at least one obligatory CO per chromosome pair, CO homeostasis smoothes out the number of COs when faced with variation in precursor number and CO interference keeps multiple COs away from each other along a chromosome. In several organisms, it has been shown that cytoskeleton forces are transduced to the meiotic nucleus via KASH- and SUN-domain proteins, to promote chromosome synapsis and recombination. Here we show that the Arabidopsis kinesin AtPSS1 plays a major role in chromosome synapsis and regulation of CO distribution. In Atpss1 meiotic cells, chromosome axes and DNA double strand breaks (DSBs appear to form normally but only a variable portion of the genome synapses and is competent for CO formation. Some chromosomes fail to form the obligatory CO, while there is an increased CO density in competent regions. However, the total number of COs per cell is unaffected. We further show that the kinesin motor domain of AtPSS1 is required for its meiotic function, and that AtPSS1 interacts directly with WIP1 and WIP2, two KASH-domain proteins. Finally, meiocytes missing AtPSS1 and/or SUN proteins show similar meiotic defects suggesting that AtPSS1 and SUNs act in the same pathway. This suggests that forces produced by the AtPSS1 kinesin and transduced by WIPs/SUNs, are required to authorize complete synapsis and regulate maturation of recombination intermediates into COs. We suggest that a form of homeostasis applies, which maintains the total number of COs per cell even if only a part of the genome is competent for CO formation.

  4. Conventional kinesin KIF5B mediates adiponectin secretion in 3T3-L1 adipocytes

    Cui, Ju, E-mail: juzi.cui@gmail.com [The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Beijing (China); Pang, Jing; Lin, Ya-Jun; Jiang, Ping; Gong, Huan [The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Beijing (China); Wang, Zai [Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing (China); Li, Jian; Cai, Jian-Ping [The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Beijing (China); Huang, Jian-Dong, E-mail: jdhuang@hku.hk [School of Biomedical Sciences and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Pokfulam (Hong Kong); The Centre for Synthetic Biology Engineering Research, Shenzhen Institutes of Advanced Technology, Shenzhen (China); Zhang, Tie-Mei, E-mail: tmzhang126@126.com [The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Beijing (China)

    2016-08-05

    Insulin stimulates adiponectin secretion and glucose transporter type 4 (GLUT4) translocation in adipocyte to regulate metabolism homeostasis. Similar to GLUT4 translocation, intracellular trafficking and release of adiponectin in adipocytes relies on the trans-Golgi network and endosomal system. Recent studies show that the heavy chain of conventional kinesin (KIF5B) mediates GLUT4 translocation in murine 3T3-L1 adipocytes, however, the motor machinery involved in mediating intracellular trafficking and release of adiponectin is unknown. Here, we examined the role of KIF5B in the regulation of adiponectin secretion. The KIF5B level was up-regulated during 3T3-L1 adipogenesis. This increase in cytosolic KIF5B was synchronized with the induction of adiponectin. Endogenous KIF5B and adiponectin were partially colocalized at the peri-nuclear and cytosolic regions. In addition, adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. Knockdown of KIF5B resulted in a marked inhibition of adiponectin secretion and overexpression of KIF5B enhanced adiponectin release, whereas leptin secretion was not affected by changes in KIF5B expression. These data suggest that the secretion of adiponectin, but not leptin, is dependent on functional KIF5B. - Highlights: • The KIF5B level was up regulated during 3T3-L1 adipogenesis. • Endogenous KIF5B and adiponectin were partially colicalized. • Adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. • The secretion of adiponectin, but not leptin, is dependent on functional KIF5B.

  5. Conventional kinesin KIF5B mediates adiponectin secretion in 3T3-L1 adipocytes

    Cui, Ju; Pang, Jing; Lin, Ya-Jun; Jiang, Ping; Gong, Huan; Wang, Zai; Li, Jian; Cai, Jian-Ping; Huang, Jian-Dong; Zhang, Tie-Mei

    2016-01-01

    Insulin stimulates adiponectin secretion and glucose transporter type 4 (GLUT4) translocation in adipocyte to regulate metabolism homeostasis. Similar to GLUT4 translocation, intracellular trafficking and release of adiponectin in adipocytes relies on the trans-Golgi network and endosomal system. Recent studies show that the heavy chain of conventional kinesin (KIF5B) mediates GLUT4 translocation in murine 3T3-L1 adipocytes, however, the motor machinery involved in mediating intracellular trafficking and release of adiponectin is unknown. Here, we examined the role of KIF5B in the regulation of adiponectin secretion. The KIF5B level was up-regulated during 3T3-L1 adipogenesis. This increase in cytosolic KIF5B was synchronized with the induction of adiponectin. Endogenous KIF5B and adiponectin were partially colocalized at the peri-nuclear and cytosolic regions. In addition, adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. Knockdown of KIF5B resulted in a marked inhibition of adiponectin secretion and overexpression of KIF5B enhanced adiponectin release, whereas leptin secretion was not affected by changes in KIF5B expression. These data suggest that the secretion of adiponectin, but not leptin, is dependent on functional KIF5B. - Highlights: • The KIF5B level was up regulated during 3T3-L1 adipogenesis. • Endogenous KIF5B and adiponectin were partially colicalized. • Adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. • The secretion of adiponectin, but not leptin, is dependent on functional KIF5B.

  6. Crystallization and X-ray diffraction analysis of the CH domain of the cotton kinesin GhKCH2

    Qin, Xinghua [China Agricultural University, No. 2 Yuanmingyuanxilu, Haidian District, Beijing 100094, People’s Republic of (China); The Fourth Military Medical University, No. 169 Changlexi Road, Xincheng District, Xi’an 710032, People’s Republic of (China); Chen, Ziwei; Li, Ping; Liu, Guoqin, E-mail: liu@cau.edu.cn [China Agricultural University, No. 2 Yuanmingyuanxilu, Haidian District, Beijing 100094, People’s Republic of (China)

    2016-02-19

    The cloning, expression, purification and crystallization of the CH domain of the plant-specific kinesin GhKCH2 is reported. GhKCH2 belongs to a group of plant-specific kinesins (KCHs) containing an actin-binding calponin homology (CH) domain in the N-terminus. Previous studies revealed that the GhKCH2 CH domain (GhKCH2-CH) had a higher affinity for F-actin (K{sub d} = 0.42 ± 0.02 µM) than most other CH-domain-containing proteins. To understand the underlying mechanism, prokaryotically expressed GhKCH2-CH (amino acids 30–166) was purified and crystallized. Crystals were grown by the sitting-drop vapour-diffusion method using 0.1 M Tris–HCl pH 7.0, 20%(w/v) PEG 8000 as a precipitant. The crystals diffracted to a resolution of 2.5 Å and belonged to space group P2{sub 1}, with unit-cell parameters a = 41.57, b = 81.92, c = 83.00 Å, α = 90.00, β = 97.31, γ = 90.00°. Four molecules were found in the asymmetric unit with a Matthews coefficient of 2.22 Å{sup 3} Da{sup −1}, corresponding to a solvent content of 44.8%.

  7. Identification of Orch3, a locus controlling dominant resistance to autoimmune orchitis, as kinesin family member 1C.

    Roxana del Rio

    Full Text Available Experimental autoimmune orchitis (EAO, the principal model of non-infectious testicular inflammatory disease, can be induced in susceptible mouse strains by immunization with autologous testicular homogenate and appropriate adjuvants. As previously established, the genome of DBA/2J mice encodes genes that are capable of conferring dominant resistance to EAO, while the genome of BALB/cByJ mice does not and they are therefore susceptible to EAO. In a genome scan, we previously identified Orch3 as the major quantitative trait locus controlling dominant resistance to EAO and mapped it to chromosome 11. Here, by utilizing a forward genetic approach, we identified kinesin family member 1C (Kif1c as a positional candidate for Orch3 and, using a transgenic approach, demonstrated that Kif1c is Orch3. Mechanistically, we showed that the resistant Kif1c(D2 allele leads to a reduced antigen-specific T cell proliferative response as a consequence of decreased MHC class II expression by antigen presenting cells, and that the L(578 → P(578 and S(1027 → P(1027 polymorphisms distinguishing the BALB/cByJ and DBA/2J alleles, respectively, can play a role in transcriptional regulation. These findings may provide mechanistic insight into how polymorphism in other kinesins such as KIF21B and KIF5A influence susceptibility and resistance to human autoimmune diseases.

  8. Structural plasticity of the N-terminal capping helix of the TPR domain of kinesin light chain.

    The Quyen Nguyen

    Full Text Available Kinesin1 plays a major role in neuronal transport by recruiting many different cargos through its kinesin light chain (KLC. Various structurally unrelated cargos interact with the conserved tetratricopeptide repeat (TPR domain of KLC. The N-terminal capping helix of the TPR domain exhibits an atypical sequence and structural features that may contribute to the versatility of the TPR domain to bind different cargos. We determined crystal structures of the TPR domain of both KLC1 and KLC2 encompassing the N-terminal capping helix and show that this helix exhibits two distinct and defined orientations relative to the rest of the TPR domain. Such a difference in orientation gives rise, at the N-terminal part of the groove, to the formation of one hydrophobic pocket, as well as to electrostatic variations at the groove surface. We present a comprehensive structural analysis of available KLC1/2-TPR domain structures that highlights that ligand binding into the groove can be specific of one or the other N-terminal capping helix orientations. Further, structural analysis reveals that the N-terminal capping helix is always involved in crystal packing contacts, especially in a TPR1:TPR1' contact which highlights its propensity to be a protein-protein interaction site. Together, these results underline that the structural plasticity of the N-terminal capping helix might represent a structural determinant for TPR domain structural versatility in cargo binding.

  9. The actin-binding protein capulet genetically interacts with the microtubule motor kinesin to maintain neuronal dendrite homeostasis.

    Paul M B Medina

    Full Text Available BACKGROUND: Neurons require precise cytoskeletal regulation within neurites, containing microtubule tracks for cargo transport in axons and dendrites or within synapses containing organized actin. Due to the unique architecture and specialized function of neurons, neurons are particularly susceptible to perturbation of the cytoskeleton. Numerous actin-binding proteins help maintain proper cytoskeletal regulation. METHODOLOGY/PRINCIPAL FINDINGS: From a Drosophila forward genetic screen, we identified a mutation in capulet--encoding a conserved actin-binding protein--that causes abnormal aggregates of actin within dendrites. Through interaction studies, we demonstrate that simultaneous genetic inactivation of capulet and kinesin heavy chain, a microtubule motor protein, produces elongate cofilin-actin rods within dendrites but not axons. These rods resemble actin-rich structures induced in both mammalian neurodegenerative and Drosophila Alzheimer's models, but have not previously been identified by loss of function mutations in vivo. We further demonstrate that mitochondria, which are transported by Kinesin, have impaired distribution along dendrites in a capulet mutant. While Capulet and Cofilin may biochemically cooperate in certain circumstances, in neuronal dendrites they genetically antagonize each other. CONCLUSIONS/SIGNIFICANCE: The present study is the first molecularly defined loss of function demonstration of actin-cofilin rods in vivo. This study suggests that simultaneous, seemingly minor perturbations in neuronal dendrites can synergize producing severe abnormalities affecting actin, microtubules and mitochondria/energy availability in dendrites. Additionally, as >90% of Alzheimer's and Parkinson's cases are sporadic this study suggests mechanisms by which multiple mutations together may contribute to neurodegeneration instead of reliance on single mutations to produce disease.

  10. Unc-51/ATG1 controls axonal and dendritic development via kinesin-mediated vesicle transport in the Drosophila brain.

    Hiroaki Mochizuki

    2011-05-01

    Full Text Available Members of the evolutionary conserved Ser/Thr kinase Unc-51 family are key regulatory proteins that control neural development in both vertebrates and invertebrates. Previous studies have suggested diverse functions for the Unc-51 protein, including axonal elongation, growth cone guidance, and synaptic vesicle transport.In this work, we have investigated the functional significance of Unc-51-mediated vesicle transport in the development of complex brain structures in Drosophila. We show that Unc-51 preferentially accumulates in newly elongating axons of the mushroom body, a center of olfactory learning in flies. Mutations in unc-51 cause disintegration of the core of the developing mushroom body, with mislocalization of Fasciclin II (Fas II, an IgG-family cell adhesion molecule important for axonal guidance and fasciculation. In unc-51 mutants, Fas II accumulates in the cell bodies, calyx, and the proximal peduncle. Furthermore, we show that mutations in unc-51 cause aberrant overshooting of dendrites in the mushroom body and the antennal lobe. Loss of unc-51 function leads to marked accumulation of Rab5 and Golgi components, whereas the localization of dendrite-specific proteins, such as Down syndrome cell adhesion molecule (DSCAM and No distributive disjunction (Nod, remains unaltered. Genetic analyses of kinesin light chain (Klc and unc-51 double heterozygotes suggest the importance of kinesin-mediated membrane transport for axonal and dendritic development. Moreover, our data demonstrate that loss of Klc activity causes similar axonal and dendritic defects in mushroom body neurons, recapitulating the salient feature of the developmental abnormalities caused by unc-51 mutations.Unc-51 plays pivotal roles in the axonal and dendritic development of the Drosophila brain. Unc-51-mediated membrane vesicle transport is important in targeted localization of guidance molecules and organelles that regulate elongation and compartmentalization of

  11. Diffusion as a Ruler: Modeling Kinesin Diffusion as a Length Sensor for Intraflagellar Transport.

    Hendel, Nathan L; Thomson, Matthew; Marshall, Wallace F

    2018-02-06

    An important question in cell biology is whether cells are able to measure size, either whole cell size or organelle size. Perhaps cells have an internal chemical representation of size that can be used to precisely regulate growth, or perhaps size is just an accident that emerges due to constraint of nutrients. The eukaryotic flagellum is an ideal model for studying size sensing and control because its linear geometry makes it essentially one-dimensional, greatly simplifying mathematical modeling. The assembly of flagella is regulated by intraflagellar transport (IFT), in which kinesin motors carry cargo adaptors for flagellar proteins along the flagellum and then deposit them at the tip, lengthening the flagellum. The rate at which IFT motors are recruited to begin transport into the flagellum is anticorrelated with the flagellar length, implying some kind of communication between the base and the tip and possibly indicating that cells contain some mechanism for measuring flagellar length. Although it is possible to imagine many complex scenarios in which additional signaling molecules sense length and carry feedback signals to the cell body to control IFT, might the already-known components of the IFT system be sufficient to allow length dependence of IFT? Here we investigate a model in which the anterograde kinesin motors unbind after cargo delivery, diffuse back to the base, and are subsequently reused to power entry of new IFT trains into the flagellum. By mathematically modeling and simulating such a system, we are able to show that the diffusion time of the motors can in principle be sufficient to serve as a proxy for length measurement. We found that the diffusion model can not only achieve a stable steady-state length without the addition of any other signaling molecules or pathways, but also is able to produce the anticorrelation between length and IFT recruitment rate that has been observed in quantitative imaging studies. Copyright © 2017 Biophysical

  12. A cAMP/PKA/Kinesin-1 Axis Promotes the Axonal Transport of Mitochondria in Aging Drosophila Neurons.

    Vagnoni, Alessio; Bullock, Simon L

    2018-04-23

    Mitochondria play fundamental roles within cells, including energy provision, calcium homeostasis, and the regulation of apoptosis. The transport of mitochondria by microtubule-based motors is critical for neuronal structure and function. This process allows local requirements for mitochondrial functions to be met and also facilitates recycling of these organelles [1, 2]. An age-related reduction in mitochondrial transport has been observed in neurons of mammalian and non-mammalian organisms [3-6], and has been proposed to contribute to the broader decline in neuronal function that occurs during aging [3, 5-7]. However, the factors that influence mitochondrial transport in aging neurons are poorly understood. Here we provide evidence using the tractable Drosophila wing nerve system that the cyclic AMP/protein kinase A (cAMP/PKA) pathway promotes the axonal transport of mitochondria in adult neurons. The level of the catalytic subunit of PKA decreases during aging, and acute activation of the cAMP/PKA pathway in aged flies strongly stimulates mitochondrial motility. Thus, the age-related impairment of transport is reversible. The expression of many genes is increased by PKA activation in aged flies. However, our results indicate that elevated mitochondrial transport is due in part to upregulation of the heavy chain of the kinesin-1 motor, the level of which declines during aging. Our study identifies evolutionarily conserved factors that can strongly influence mitochondrial motility in aging neurons. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  13. Photocontrol of the mitotic kinesin Eg5 using a novel S-trityl-L-cysteine analogue as a photochromic inhibitor.

    Ishikawa, Kumiko; Tohyama, Kanako; Mitsuhashi, Shinya; Maruta, Shinsaku

    2014-04-01

    Because the mitotic kinesin Eg5 is essential for the formation of bipolar spindles during eukaryotic cell division, it has been considered as a potential target for cancer treatment. A number of specific and potent inhibitors of Eg5 are known. S-trityl-L-cysteine is one of the inhibitors of Eg5 whose molecular mechanism of inhibition was well studied. The trityl group of S-trityl-L-cysteine was shown to be a key moiety required for potent inhibition. In this study, we synthesized a novel photochromic S-trityl-L-cysteine analogue, 4-(N-(2-(N-acetylcysteine-S-yl) acetyl) amino)-4'- (N-(2-(N-(triphenylmethyl)amino)acetyl)amino)azobenzene (ACTAB), composed of a trityl group, azobenzene and N-acetyl-L-cysteine, which exhibits cis-trans photoisomerization in order to photocontrol the function of Eg5. ACTAB exhibited cis-trans photoisomerization upon alternating irradiation at two different wavelengths in the visible range, 400 and 480 nm. ACTAB induced reversible changes in the inhibitory activity of ATPase and motor activities correlating with the cis-trans photoisomerization. Compared with cis-ACTAB, trans-ACTAB reduced ATPase activity and microtubule gliding velocity more significantly. These results suggest that ACTAB could be used as photochromic inhibitor of Eg5 to achieve photocontrol of living cells.

  14. Structural analysis of intermolecular interactions in the kinesin adaptor complex fasciculation and elongation protein zeta 1/ short coiled-coil protein (FEZ1/SCOCO.

    Marcos Rodrigo Alborghetti

    Full Text Available Cytoskeleton and protein trafficking processes, including vesicle transport to synapses, are key processes in neuronal differentiation and axon outgrowth. The human protein FEZ1 (fasciculation and elongation protein zeta 1 / UNC-76, in C. elegans, SCOCO (short coiled-coil protein / UNC-69 and kinesins (e.g. kinesin heavy chain / UNC116 are involved in these processes. Exploiting the feature of FEZ1 protein as a bivalent adapter of transport mediated by kinesins and FEZ1 protein interaction with SCOCO (proteins involved in the same path of axonal growth, we investigated the structural aspects of intermolecular interactions involved in this complex formation by NMR (Nuclear Magnetic Resonance, cross-linking coupled with mass spectrometry (MS, SAXS (Small Angle X-ray Scattering and molecular modelling. The topology of homodimerization was accessed through NMR (Nuclear Magnetic Resonance studies of the region involved in this process, corresponding to FEZ1 (92-194. Through studies involving the protein in its monomeric configuration (reduced and dimeric state, we propose that homodimerization occurs with FEZ1 chains oriented in an anti-parallel topology. We demonstrate that the interaction interface of FEZ1 and SCOCO defined by MS and computational modelling is in accordance with that previously demonstrated for UNC-76 and UNC-69. SAXS and literature data support a heterotetrameric complex model. These data provide details about the interaction interfaces probably involved in the transport machinery assembly and open perspectives to understand and interfere in this assembly and its involvement in neuronal differentiation and axon outgrowth.

  15. Loss of function of Saccharomyces cerevisiae kinesin-related CIN8 and KIP1 is suppressed by KAR3 motor domain mutations.

    Hoyt, M A; He, L; Totis, L; Saunders, W S

    1993-09-01

    The kinesin-related products of the CIN8 and KIP1 genes of Saccharomyces cerevisiae redundantly perform an essential function in mitosis. The action of either gene-product is required for an outwardly directed force that acts upon the spindle poles. We have selected mutations that suppress the temperature-sensitivity of a cin8-temperature-sensitive kip1-delta strain. The extragenic suppressors analyzed were all found to be alleles of the KAR3 gene. KAR3 encodes a distinct kinesin-related protein whose action antagonizes Cin8p/Kip1p function. All seven alleles analyzed were altered within the region of KAR3 that encodes the putative force-generating (or "motor") domain. These mutations also suppressed the inviability associated with the cin8-delta kip1-delta genotype, a property not shared by a deletion of KAR3. Other properties of the suppressing alleles revealed that they were not null for function. Six of the seven were unaffected for the essential karyogamy and meiosis properties of KAR3 and the seventh was dominant for the suppressing trait. Our findings suggest that despite an antagonistic relationship between Cin8p/Kip1p and Kar3p, aspects of their mitotic roles may be similar.

  16. The kinesin-3 family motor KLP-4 regulates anterograde trafficking of GLR-1 glutamate receptors in the ventral nerve cord of Caenorhabditis elegans.

    Monteiro, Michael I; Ahlawat, Shikha; Kowalski, Jennifer R; Malkin, Emily; Koushika, Sandhya P; Juo, Peter

    2012-09-01

    The transport of glutamate receptors from the cell body to synapses is essential during neuronal development and may contribute to the regulation of synaptic strength in the mature nervous system. We previously showed that cyclin-dependent kinase-5 (CDK-5) positively regulates the abundance of GLR-1 glutamate receptors at synapses in the ventral nerve cord (VNC) of Caenorhabditis elegans. Here we identify a kinesin-3 family motor klp-4/KIF13 in a cdk-5 suppressor screen for genes that regulate GLR-1 trafficking. klp-4 mutants have decreased abundance of GLR-1 in the VNC. Genetic analysis of klp-4 and the clathrin adaptin unc-11/AP180 suggests that klp-4 functions before endocytosis in the ventral cord. Time-lapse microscopy indicates that klp-4 mutants exhibit decreased anterograde flux of GLR-1. Genetic analysis of cdk-5 and klp-4 suggests that they function in the same pathway to regulate GLR-1 in the VNC. Interestingly, GLR-1 accumulates in cell bodies of cdk-5 but not klp-4 mutants. However, GLR-1 does accumulate in klp-4-mutant cell bodies if receptor degradation in the multivesicular body/lysosome pathway is blocked. This study identifies kinesin KLP-4 as a novel regulator of anterograde glutamate receptor trafficking and reveals a cellular control mechanism by which receptor cargo is targeted for degradation in the absence of its motor.

  17. A novel kinesin-like protein, KIF1Bbeta3 is involved in the movement of lysosomes to the cell periphery in non-neuronal cells.

    Matsushita, Masafumi; Tanaka, Shingo; Nakamura, Norihiro; Inoue, Hiroki; Kanazawa, Hiroshi

    2004-03-01

    The kinesin superfamily protein, KIF1Bbeta, a splice variant of KIF1B, is involved in the transport of synaptic vesicles in neuronal cells, and is also expressed in various non-neuronal tissues. To elucidate the functions of KIF1Bbeta in non-neuronal cells, we analyzed the intracellular localization of KIF1Bbeta and characterized its isoform expression profile. In COS-7 cells, KIF1B colocalized with lysosomal markers and expression of a mutant form of KIF1Bbeta, lacking the motor domain, impaired the intracellular distribution of lysosomes. A novel isoform of the kinesin-like protein, KIF1Bbeta3, was identified in rat and simian kidney. It lacks the 5th exon of the KIF1Bbeta-specific tail region. Overexpression of KIF1Bbeta3 induced the translocation of lysosomes to the cell periphery. However, overexpression of KIF1Bbeta3-Q98L, which harbors a pathogenic mutation associated with a familial neuropathy, Charcot-Marie-Tooth disease type 2 A, resulted in the abnormal perinuclear clustering of lysosomes. These results indicate that KIF1Bbeta3 is involved in the translocation of lysosomes from perinuclear regions to the cell periphery.

  18. Mutation of Rice BC12/GDD1, Which Encodes a Kinesin-Like Protein That Binds to a GA Biosynthesis Gene Promoter, Leads to Dwarfism with Impaired Cell Elongation[W][OA

    Li, Juan; Jiang, Jiafu; Qian, Qian; Xu, Yunyuan; Zhang, Cui; Xiao, Jun; Du, Cheng; Luo, Wei; Zou, Guoxing; Chen, Mingluan; Huang, Yunqing; Feng, Yuqi; Cheng, Zhukuan; Yuan, Ming; Chong, Kang

    2011-01-01

    The kinesins are a family of microtubule-based motor proteins that move directionally along microtubules and are involved in many crucial cellular processes, including cell elongation in plants. Less is known about kinesins directly regulating gene transcription to affect cellular physiological processes. Here, we describe a rice (Oryza sativa) mutant, gibberellin-deficient dwarf1 (gdd1), that has a phenotype of greatly reduced length of root, stems, spikes, and seeds. This reduced length is due to decreased cell elongation and can be rescued by exogenous gibberellic acid (GA3) treatment. GDD1 was cloned by a map-based approach, was expressed constitutively, and was found to encode the kinesin-like protein BRITTLE CULM12 (BC12). Microtubule cosedimentation assays revealed that BC12/GDD1 bound to microtubules in an ATP-dependent manner. Whole-genome microarray analysis revealed the expression of ent-kaurene oxidase (KO2), which encodes an enzyme involved in GA biosynthesis, was downregulated in gdd1. Electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that GDD1 bound to the element ACCAACTTGAA in the KO2 promoter. In addition, GDD1 was shown to have transactivation activity. The level of endogenous GAs was reduced in gdd1, and the reorganization of cortical microtubules was altered. Therefore, BC12/GDD1, a kinesin-like protein with transcription regulation activity, mediates cell elongation by regulating the GA biosynthesis pathway in rice. PMID:21325138

  19. Ribosomal protein NtRPL17 interacts with kinesin-12 family protein NtKRP and functions in the regulation of embryo/seed size and radicle growth.

    Tian, Shujuan; Wu, Jingjing; Liu, Yuan; Huang, Xiaorong; Li, Fen; Wang, Zhaodan; Sun, Meng-Xiang

    2017-11-28

    We previously reported that a novel motor protein belonging to the kinesin-12 family, NtKRP, displays critical roles in regulating embryo and seed size establishment. However, it remains unknown exactly how NtKRP contributes to this developmental process. Here, we report that a 60S ribosomal protein NtRPL17 directly interacts with NtKRP. The phenotypes of NtRPL17 RNAi lines show notable embryo and seed size reduction. Structural observations of the NtRPL17-silenced embryos/seeds reveal that the embryo size reduction is due to a decrease in cell number. In these embryos, cell division cycle progression is delayed at the G2/M transition. These phenotypes are similar to that in NtKRP-silenced embryos/seeds, indicating that NtKRP and NtRPL17 function as partners in the same regulatory pathway during seed development and specifically regulate cell cycle progression to control embryo/seed size. This work reveals that NtRPL17, as a widely distributed ribosomal protein, plays a critical role in seed development and provides a new clue in the regulation of seed size. Confirmation of the interaction between NtKRP and NtRPL17 and their co-function in the control of the cell cycle also suggests that the mechanism might be conserved in both plants and animals. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  20. Mutations in Human Tubulin Proximal to the Kinesin-Binding Site Alter Dynamic Instability at Microtubule Plus- and Minus-Ends

    Ti, Shih-Chieh; Pamula, Melissa C.; Howes, Stuart C.; Duellberg, Christian; Cade, Nicholas I.; Kleiner, Ralph E.; Forth, Scott; Surrey, Thomas; Nogales, Eva; Kapoor, Tarun M.

    2016-04-01

    The assembly of microtubule-based cellular structures depends on regulated tubulin polymerization and directional transport. In this research, we have purified and characterized tubulin heterodimers that have human β-tubulin isotype III (TUBB3), as well as heterodimers with one of two β-tubulin mutations (D417H or R262H). Both point mutations are proximal to the kinesin-binding site and have been linked to an ocular motility disorder in humans. Compared to wild-type, microtubules with these mutations have decreased catastrophe frequencies and increased average lifetimes of plus- and minus-end-stabilizing caps. Importantly, the D417H mutation does not alter microtubule lattice structure or Mal3 binding to growing filaments. Instead, this mutation reduces the affinity of tubulin for TOG domains and colchicine, suggesting that the distribution of tubulin heterodimer conformations is changed. Together, our findings reveal how residues on the surface of microtubules, distal from the GTP-hydrolysis site and inter-subunit contacts, can alter polymerization dynamics at the plus- and minus-ends of microtubules.

  1. Clinical value of Xenopus kinesin-like protein 2 as a prognostic marker in patients with digestive system cancers: a systematic review and meta-analysis.

    Wang, Gang; Wang, Qian; Li, Zhengyan; Liu, Chaoxu; He, Xianli

    2018-01-01

    Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein that plays an important role in spindle assembly and dynamics. However, the clinical and prognostic value of TPX2 in the digestive system cancers remains unclear. The objective of this review was to evaluate the association of TPX2 expression with disease-free survival (DFS), overall survival (OS), and clinicopathological features of digestive system cancers. The software Stata 12.0 was used to analyze the outcomes, including OS, disease-free survival (DFS), and clinicopathological characteristics. A total of 10 eligible studies with 906 patients were included. Elevated TPX2 expression was significantly associated with poor DFS (pooled hazard ratio [HR] =2.48, 95% confidence interval [CI]: 1.96-3.13) and OS (pooled HR =2.66, 95% CI: 2.04-3.48) of digestive system malignancies. Subgroup analyses showed that cancer type, sample size, study quality, and laboratory detection methods did not alter the significant prognostic value of TPX2. Additionally, TPX2 expression was found to be an independent predictive factor for DFS (HR =2.31, 95% CI: 1.78-3.01). TPX2 expression might be associated with TNM stage and pathological grade in digestive system cancer. In conclusion, TPX2 is an independent prognostic factor for survival of patients with digestive system cancer. Furthermore, its overexpression is associated with TNM stage and pathological grade in digestive system cancer.

  2. The KAC family of kinesin-like proteins is essential for the association of chloroplasts with the plasma membrane in land plants.

    Suetsugu, Noriyuki; Sato, Yoshikatsu; Tsuboi, Hidenori; Kasahara, Masahiro; Imaizumi, Takato; Kagawa, Takatoshi; Hiwatashi, Yuji; Hasebe, Mitsuyasu; Wada, Masamitsu

    2012-11-01

    Chloroplasts require association with the plasma membrane for movement in response to light and for appropriate positioning within the cell to capture photosynthetic light efficiently. In Arabidopsis, CHLOROPLAST UNUSUAL POSITIONING 1 (CHUP1), KINESIN-LIKE PROTEIN FOR ACTIN-BASED CHLOROPLAST MOVEMENT 1 (KAC1) and KAC2 are required for both the proper movement of chloroplasts and the association of chloroplasts with the plasma membrane, through the reorganization of short actin filaments located on the periphery of the chloroplasts. Here, we show that KAC and CHUP1 orthologs (AcKAC1, AcCHUP1A and AcCHUP1B, and PpKAC1 and PpKAC2) play important roles in chloroplast positioning in the fern Adiantum capillus-veneris and the moss Physcomitrella patens. The knockdown of AcKAC1 and two AcCHUP1 genes induced the aggregation of chloroplasts around the nucleus. Analyses of A. capillus-veneris mutants containing perinuclear-aggregated chloroplasts confirmed that AcKAC1 is required for chloroplast-plasma membrane association. In addition, P. patens lines in which two KAC genes had been knocked out showed an aggregated chloroplast phenotype similar to that of the fern kac1 mutants. These results indicate that chloroplast positioning and movement are mediated through the activities of KAC and CHUP1 proteins, which are conserved in land plants.

  3. Evolutionary analysis of the kinesin light chain genes in the yellow fever mosquito Aedes aegypti: gene duplication as a source for novel early zygotic genes.

    Biedler, James K; Tu, Zhijian

    2010-07-08

    The maternal zygotic transition marks the time at which transcription from the zygotic genome is initiated and a subset of maternal RNAs are progressively degraded in the developing embryo. A number of early zygotic genes have been identified in Drosophila melanogaster and comparisons to sequenced mosquito genomes suggest that some of these early zygotic genes such as bottleneck are fast-evolving or subject to turnover in dipteran insects. One objective of this study is to identify early zygotic genes from the yellow fever mosquito Aedes aegypti to study their evolution. We are also interested in obtaining early zygotic promoters that will direct transgene expression in the early embryo as part of a Medea gene drive system. Two novel early zygotic kinesin light chain genes we call AaKLC2.1 and AaKLC2.2 were identified by transcriptome sequencing of Aedes aegypti embryos at various time points. These two genes have 98% nucleotide and amino acid identity in their coding regions and show transcription confined to the early zygotic stage according to gene-specific RT-PCR analysis. These AaKLC2 genes have a paralogous gene (AaKLC1) in Ae. aegypti. Phylogenetic inference shows that an ortholog to the AaKLC2 genes is only found in the sequenced genome of Culex quinquefasciatus. In contrast, AaKLC1 gene orthologs are found in all three sequenced mosquito species including Anopheles gambiae. There is only one KLC gene in D. melanogaster and other sequenced holometabolous insects that appears to be similar to AaKLC1. Unlike AaKLC2, AaKLC1 is expressed in all life stages and tissues tested, which is consistent with the expression pattern of the An. gambiae and D. melanogaster KLC genes. Phylogenetic inference also suggests that AaKLC2 genes and their likely C. quinquefasciatus ortholog are fast-evolving genes relative to the highly conserved AaKLC1-like paralogs. Embryonic injection of a luciferase reporter under the control of a 1 kb fragment upstream of the AaKLC2.1 start

  4. Evolutionary analysis of the kinesin light chain genes in the yellow fever mosquito Aedes aegypti: gene duplication as a source for novel early zygotic genes

    Tu Zhijian

    2010-07-01

    Full Text Available Abstract Background The maternal zygotic transition marks the time at which transcription from the zygotic genome is initiated and a subset of maternal RNAs are progressively degraded in the developing embryo. A number of early zygotic genes have been identified in Drosophila melanogaster and comparisons to sequenced mosquito genomes suggest that some of these early zygotic genes such as bottleneck are fast-evolving or subject to turnover in dipteran insects. One objective of this study is to identify early zygotic genes from the yellow fever mosquito Aedes aegypti to study their evolution. We are also interested in obtaining early zygotic promoters that will direct transgene expression in the early embryo as part of a Medea gene drive system. Results Two novel early zygotic kinesin light chain genes we call AaKLC2.1 and AaKLC2.2 were identified by transcriptome sequencing of Aedes aegypti embryos at various time points. These two genes have 98% nucleotide and amino acid identity in their coding regions and show transcription confined to the early zygotic stage according to gene-specific RT-PCR analysis. These AaKLC2 genes have a paralogous gene (AaKLC1 in Ae. aegypti. Phylogenetic inference shows that an ortholog to the AaKLC2 genes is only found in the sequenced genome of Culex quinquefasciatus. In contrast, AaKLC1 gene orthologs are found in all three sequenced mosquito species including Anopheles gambiae. There is only one KLC gene in D. melanogaster and other sequenced holometabolous insects that appears to be similar to AaKLC1. Unlike AaKLC2, AaKLC1 is expressed in all life stages and tissues tested, which is consistent with the expression pattern of the An. gambiae and D. melanogaster KLC genes. Phylogenetic inference also suggests that AaKLC2 genes and their likely C. quinquefasciatus ortholog are fast-evolving genes relative to the highly conserved AaKLC1-like paralogs. Embryonic injection of a luciferase reporter under the control of a

  5. Discovery of (+)-N-(3-aminopropyl)-N-[1-(5-benzyl-3-methyl-4-oxo-[1,2]thiazolo[5,4-d]pyrimidin-6-yl)-2-methylpropyl]-4-methylbenzamide (AZD4877), a kinesin spindle protein inhibitor and potential anticancer agent.

    Theoclitou, Maria-Elena; Aquila, Brian; Block, Michael H; Brassil, Patrick J; Castriotta, Lillian; Code, Erin; Collins, Michael P; Davies, Audrey M; Deegan, Tracy; Ezhuthachan, Jayachandran; Filla, Sandra; Freed, Ellen; Hu, Haiqing; Huszar, Dennis; Jayaraman, Muthusamy; Lawson, Deborah; Lewis, Paula M; Nadella, Murali V P; Oza, Vibha; Padmanilayam, Maniyan; Pontz, Timothy; Ronco, Lucienne; Russell, Daniel; Whitston, David; Zheng, Xiaolan

    2011-10-13

    Structure-activity relationship analysis identified (+)-N-(3-aminopropyl)-N-[1-(5-benzyl-3-methyl-4-oxo-[1,2]thiazolo[5,4-d]pyrimidin-6-yl)-2-methylpropyl]-4-methylbenzamide (AZD4877), from a series of novel kinesin spindle protein (KSP) inhibitors, as exhibiting both excellent biochemical potency and pharmaceutical properties suitable for clinical development. The selected compound arrested cells in mitosis leading to the formation of the monopolar spindle phenotype characteristic of KSP inhibition and induction of cellular death. A favorable pharmacokinetic profile and notable in vivo efficacy supported the selection of this compound as a clinical candidate for the treatment of cancer.

  6. Chemical and thermal modulation of molecular motor activities

    Hong, Weili

    Molecular motors of kinesin and dynein families are responsible for various intracellular activities, from long distance movement of organelles, vesicles, protein complexes, and mRNAs to powering mitotic processes. They can take nanometer steps using chemical energy from the hydrolysis of ATP (adenosine triphosphate), and their dysfunction is involved in many neurodegenerative diseases that require long distance transport of cargos. Here I report on the study of the properties of molecular motors at a single-molecule level using optical trappings. I first studied the inhibition properties of kinesin motors by marine natural compound adociasulfates. I showed that adociasulfates compete with microtubules for binding to kinesins and thus inhibit kinesins' activity. Although adociasulfates are a strong inhibitor for all kinesin members, they show a much higher inhibition effect for conventional kinesins than for mitotic kinesins. Thus adociasulfates can be used to specifically inhibit conventional kinesins. By comparing the inhibition of kinesins by two structurally similar adociasulfates, one can see that the negatively charged sulfate residue of adociasulfates can be replaced by other negative residues and thus make it possible for adociasulfate-derived compounds to be more cell permeable. Kinesins and dyneins move cargos towards opposite directions along a microtubule. Cargos with both kinesins and dyneins attached often move bidirectionally due to undergoing a tug-of-war between the oppositely moving kinesin and dynein motors. Here I studied the effect of temperature on microtubule-based kinesin and dynein motor transport. While kinesins' and dyneins' velocities are closely matched above 15 °C, below this temperature the dyneins' velocity decreases much faster than the kinesins'. The kinesins' and dyneins' forces do not measurably change with temperature. The results suggest that temperature has significant effects on bidirectional transport and can be used to

  7. Effectiveness of a dynein team in a tug of war helped by reduced load sensitivity of detachment: evidence from the study of bidirectional endosome transport in D. discoideum.

    Bhat, Deepak; Gopalakrishnan, Manoj

    2012-08-01

    Bidirectional cargo transport by molecular motors in cells is a complex phenomenon in which the cargo (usually a vesicle) alternately moves in retrograde and anterograde directions. In this case, teams of oppositely pulling motors (e.g., kinesin and dynein) bind to the cargo, simultaneously, and 'coordinate' their activity such that the motion consists of spells of positively and negatively directed segments, separated by pauses of varying duration. A set of recent experiments have analyzed the bidirectional motion of endosomes in the amoeba D. discoideum in detail. It was found that in between directional switches, a team of five to six dyneins stall a cargo against a stronger kinesin in a tug of war, which lasts for almost a second. As the mean detachment time of a kinesin under its stall load was also observed to be ∼1 s, we infer that the collective detachment time of the dynein assembly must also be similar. Here, we analyze this inference from a modeling perspective, using experimentally measured single-molecule parameters as inputs. We find that the commonly assumed exponential load-dependent detachment rate is inconsistent with observations, as it predicts that a five-dynein assembly will detach under its combined stall load in less than a hundredth of a second. A modified model where the load-dependent unbinding rate is assumed to saturate at stall-force level for super-stall loads gives results which are in agreement with experimental data. Our analysis suggests that the load-dependent detachment of a dynein in a team is qualitatively different at sub-stall and super-stall loads, a conclusion which is likely to have implications in other situations involving collective effects of many motors.

  8. Dynamic expression pattern of kinesin accessory protein in Drosophila

    Unknown

    terization of the function of the DmKAP gene, we studied its expression pattern at different stages of development using the mRNA in .... region of the developing brain. ..... Kido M and Hirokawa N 1998 Randomization of left-right asymmetry ...

  9. An agent-based model contrasts opposite effects of dynamic and stable microtubules on cleavage furrow positioning.

    Odell, Garrett M; Foe, Victoria E

    2008-11-03

    From experiments by Foe and von Dassow (Foe, V.E., and G. von Dassow. 2008. J. Cell Biol. 183:457-470) and others, we infer a molecular mechanism for positioning the cleavage furrow during cytokinesis. Computer simulations reveal how this mechanism depends on quantitative motor-behavior details and explore how robustly this mechanism succeeds across a range of cell sizes. The mechanism involves the MKLP1 (kinesin-6) component of centralspindlin binding to and walking along microtubules to stimulate cortical contractility where the centralspindlin complex concentrates. The majority of astral microtubules are dynamically unstable. They bind most MKLP1 and suppress cortical Rho/myosin II activation because the tips of unstable microtubules usually depolymerize before MKLP1s reach the cortex. A subset of astral microtubules stabilizes during anaphase, becoming effective rails along which MKLP1 can actually reach the cortex. Because stabilized microtubules aim statistically at the equatorial spindle midplane, that is where centralspindlin accumulates to stimulate furrow formation.

  10. Molecular Basis of the Anti-Cancer Effects of Genistein Isoflavone in LNCaP Prostate Cancer Cells.

    Hartmann J

    2011-03-01

    Full Text Available Background: Prostate cancer is the most common form of non-skin cancer within the United States and the second leading cause of cancer deaths. Survival rates for the advanced disease remain relatively low, and conventional treatments may be accompanied by significant side effects. As a result, current research is aimed at alternative or adjuvant treatments that will target components of the signal transduction, cell-cycle and apoptosis pathways, to induce cell death with little or no toxic side effects to the patient. In this study, we investigated the effect of genistein isoflavone, a soy derivative, on expression levels of genes involved in these pathways. The mechanism of genistein-induced cell death was also investigated. The chemosensitivity of the LNCaP prostate cancer cells to genistein was investigated using ATP and MTS assays, and a caspase binding assay was used to determine apoptosis induction. Several molecular targets were determined using cDNA microarray and RT-PCR analysis.Results: The overall data revealed that genistein induces cell death in a time- and dose-dependent manner, and regulates expression levels of several genes involved in carcinogenesis and immunity. Several cell-cycle genes were down-regulated, including the mitotic kinesins, cyclins and cyclin-dependent kinases. Various members of the Bcl-2 family of apoptotic proteins were also affected. The DefB1 and the HLA membrane receptor genes involved in immunogenicity were also up-regulated.Conclusion: The results indicate that genistein inhibits growth of the hormone-dependent prostate cancer cells, LNCaP, via apoptosis induction through regulation of some of the genes involved in carcinogenesis of many tumors, and immunogenicity. This study augments the potential phytotherapeutic and immunotherapeutic significance of genistein isoflavone.

  11. Dynamic kinesin-1 clustering on microtubules due to mutually attractive interactions

    Roos, W.H.; Campas, O.; Montel, F.; Woehlke, G.; Spatz, J. P.; Bassereau, P.; Cappello, G.

    2008-01-01

    Molecular motors often work collectively inside the cell. While the properties of individual motors have been extensively studied over the last decade, much less is known on how motors coordinate their action when working in ensembles. The motor collective behaviour in conditions where they contact

  12. Coin Tossing Explains the Activity of Opposing Microtubule Motors on Phagosomes.

    Sanghavi, Paulomi; D'Souza, Ashwin; Rai, Ashim; Rai, Arpan; Padinhatheeri, Ranjith; Mallik, Roop

    2018-05-07

    How the opposing activity of kinesin and dynein motors generates polarized distribution of organelles inside cells is poorly understood and hotly debated [1, 2]. Possible explanations include stochastic mechanical competition [3, 4], coordinated regulation by motor-associated proteins [5-7], mechanical activation of motors [8], and lipid-induced organization [9]. Here, we address this question by using phagocytosed latex beads to generate early phagosomes (EPs) that move bidirectionally along microtubules (MTs) in an in vitro assay [9]. Dynein/kinesin activity on individual EPs is recorded as real-time force generation of the motors against an optical trap. Activity of one class of motors frequently coincides with, or is rapidly followed by opposite motors. This leads to frequent and rapid reversals of EPs in the trap. Remarkably, the choice between dynein and kinesin can be explained by the tossing of a coin. Opposing motors therefore appear to function stochastically and independently of each other, as also confirmed by observing no effect on kinesin function when dynein is inhibited on the EPs. A simple binomial probability calculation based on the geometry of EP-microtubule contact explains the observed activity of dynein and kinesin on phagosomes. This understanding of intracellular transport in terms of a hypothetical coin, if it holds true for other cargoes, provides a conceptual framework to explain the polarized localization of organelles inside cells. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  13. Regulation of microtubule-based transport by MAP4

    Semenova, Irina; Ikeda, Kazuho; Resaul, Karim; Kraikivski, Pavel; Aguiar, Mike; Gygi, Steven; Zaliapin, Ilya; Cowan, Ann; Rodionov, Vladimir

    2014-01-01

    Microtubule (MT)-based transport of organelles driven by the opposing MT motors kinesins and dynein is tightly regulated in cells, but the underlying molecular mechanisms remain largely unknown. Here we tested the regulation of MT transport by the ubiquitous protein MAP4 using Xenopus melanophores as an experimental system. In these cells, pigment granules (melanosomes) move along MTs to the cell center (aggregation) or to the periphery (dispersion) by means of cytoplasmic dynein and kinesin-2, respectively. We found that aggregation signals induced phosphorylation of threonine residues in the MT-binding domain of the Xenopus MAP4 (XMAP4), thus decreasing binding of this protein to MTs. Overexpression of XMAP4 inhibited pigment aggregation by shortening dynein-dependent MT runs of melanosomes, whereas removal of XMAP4 from MTs reduced the length of kinesin-2–dependent runs and suppressed pigment dispersion. We hypothesize that binding of XMAP4 to MTs negatively regulates dynein-dependent movement of melanosomes and positively regulates kinesin-2–based movement. Phosphorylation during pigment aggregation reduces binding of XMAP4 to MTs, thus increasing dynein-dependent and decreasing kinesin-2–dependent motility of melanosomes, which stimulates their accumulation in the cell center, whereas dephosphorylation of XMAP4 during dispersion has an opposite effect. PMID:25143402

  14. The SPF27 homologue Num1 connects splicing and kinesin 1-dependent cytoplasmic trafficking in Ustilago maydis.

    Nikola Kellner

    2014-01-01

    Full Text Available The conserved NineTeen protein complex (NTC is an integral subunit of the spliceosome and required for intron removal during pre-mRNA splicing. The complex associates with the spliceosome and participates in the regulation of conformational changes of core spliceosomal components, stabilizing RNA-RNA- as well as RNA-protein interactions. In addition, the NTC is involved in cell cycle checkpoint control, response to DNA damage, as well as formation and export of mRNP-particles. We have identified the Num1 protein as the homologue of SPF27, one of NTC core components, in the basidiomycetous fungus Ustilago maydis. Num1 is required for polarized growth of the fungal hyphae, and, in line with the described NTC functions, the num1 mutation affects the cell cycle and cell division. The num1 deletion influences splicing in U. maydis on a global scale, as RNA-Seq analysis revealed increased intron retention rates. Surprisingly, we identified in a screen for Num1 interacting proteins not only NTC core components as Prp19 and Cef1, but several proteins with putative functions during vesicle-mediated transport processes. Among others, Num1 interacts with the motor protein Kin1 in the cytoplasm. Similar phenotypes with respect to filamentous and polar growth, vacuolar morphology, as well as the motility of early endosomes corroborate the genetic interaction between Num1 and Kin1. Our data implicate a previously unidentified connection between a component of the splicing machinery and cytoplasmic transport processes. As the num1 deletion also affects cytoplasmic mRNA transport, the protein may constitute a novel functional interconnection between the two disparate processes of splicing and trafficking.

  15. The expression pattern of the C-terminal kinesin gene kifc1 during the spermatogenesis of Sepiella maindroni.

    Tan, Fu-Qing; Ma, Xiao-Xin; Zhu, Jun-Quan; Yang, Wan-Xi

    2013-12-10

    In this study, we investigated the gene sequence and characteristic of kifc1 in Sepiella maindroni through PCR and RACE technology. Our research aimed particularly at the spatio-temporal expression pattern of kifc1 in the developmental testis through in situ hybridization. The particular role of kifc1 in the spermatogenesis of S. maindroni was our particular interest. Based on multiple protein sequence alignments of KIFC1 homologues, kifc1 gene from the testis of S. maindroni was identified, which consisted of 2432bp including a 2109 in-frame ORF corresponding to 703 continuous amino acids. The encoded polypeptide shared highest similarity with Octopus tankahkeei. Through the prediction of the secondary and tertiary structures, the motor domain of KIFC1 was conserved at the C-terminal, having putative ATP-binding and microtubule-binding motifs, while the N-terminal was more specific to bind various cargoes for cellular events. The stalk domain connecting between the C-terminal and N-terminal determined the direction of movement. According to RT-PCR results, the kifc1 gene is not tissue-specific, commonly detected in different tissues, for example, the testis, liver, stomach, muscle, caecum and gills. Through an in situ hybridization method, the expression pattern of KIFC1 protein mimics in the spermatogenesis of S. maindroni. During the primary stage of the spermatogenesis, the kifc1 mRNA signal was barely detectable. At the early spermatids, the signal started to be present. With the elongation of spermatids, the signals increased substantially. It peaked and gathered around the acrosome area when the spermatids began to transform to spindle shape. As the spermatids developed into mature sperm, the signal vanished. In summary, the expression of kfic1 at specific stages during spermiogenesis and its distribution shed light on the potential functions of this motor in major cytological transformations. The KIFC1 homologue may provide a direct shaping force to the nucleus or influence the shaping process through indirect regulation. © 2013.

  16. Molecular characterization of a KIF3B-like kinesin gene in the testis of Octopus tankahkeei (Cephalopoda, Octopus).

    Dang, Ran; Zhu, Jun-Quan; Tan, Fu-Qing; Wang, Wei; Zhou, Hong; Yang, Wan-Xi

    2012-05-01

    KIF3B is known for maintaining and assembling cilia and flagellum. To date, the function of KIF3B and its relationship with KIF3A during spermiogenesis in the cephalopod Octopus tankahkeei remains unknown. In the present study, we characterized a gene encoding a homologue of rat KIF3B in the O. tankahkeei testis and examined its temporal and spatial expression pattern during spermiogenesis. The cDNA of KIF3B was obtained with degenerate and RACE PCR and the distribution pattern of ot-kif3b were observed with RT-PCR. The morphological development during spermiogenesis was illustrated by histological and transmission electron microscopy and mRNA expression of ot-kif3b was observed by in situ hybridization. The 2,365 nucleotides cDNA consisted of a 102 bp 5' untranslated region (UTR), a 2,208 bp open reading frame (ORF) encoding a protein of 736 amino acids, and a 55 bp 3' UTR. Multiple alignments revealed that the putative Ot-KIF3B shared 68, 68, 69, 68, and 67% identity with that of Homo sapiens, Mus musculus, Gallus gallus, Danio rerio, and Xenopus laevis, respectively, along with high identities with Ot-KIF3A in fundamental structures. Ot-kif3b transcripts appeared gradually in early spermatids, increased in intermediate spermatids and maximized in drastically remodeled and final spermatids. The kif3b gene is identified and its expression pattern is demonstrated for the first time in O. tankahkeei. Compared to ot-kif3a reported by our laboratory before, our data suggested that the putative heterodimeric motor proteins Ot-KIF3A/B may be involved in intraspermatic transport and might contribute to structural changes during spermiogenesis.

  17. Opposing motor activities of dynein and kinesin determine retention and transport of MHC class II-containing compartments

    Wubbolts, R.; Fernandez-Borja, M.; Jordens, I.; Reits, E.; Dusseljee, S.; Echeverri, C.; Vallee, R. B.; Neefjes, J.

    1999-01-01

    MHC class II molecules exert their function at the cell surface by presenting to T cells antigenic fragments that are generated in the endosomal pathway. The class II molecules are targetted to early lysosomal structures, termed MIIC, where they interact with antigenic fragments and are subsequently

  18. Kinesin Khc-73/KIF13B modulates retrograde BMP signaling by influencing endosomal dynamics at the Drosophila neuromuscular junction.

    Liao, Edward H; Gray, Lindsay; Tsurudome, Kazuya; El-Mounzer, Wassim; Elazzouzi, Fatima; Baim, Christopher; Farzin, Sarah; Calderon, Mario R; Kauwe, Grant; Haghighi, A Pejmun

    2018-01-01

    Retrograde signaling is essential for neuronal growth, function and survival; however, we know little about how signaling endosomes might be directed from synaptic terminals onto retrograde axonal pathways. We have identified Khc-73, a plus-end directed microtubule motor protein, as a regulator of sorting of endosomes in Drosophila larval motor neurons. The number of synaptic boutons and the amount of neurotransmitter release at the Khc-73 mutant larval neuromuscular junction (NMJ) are normal, but we find a significant decrease in the number of presynaptic release sites. This defect in Khc-73 mutant larvae can be genetically enhanced by a partial genetic loss of Bone Morphogenic Protein (BMP) signaling or suppressed by activation of BMP signaling in motoneurons. Consistently, activation of BMP signaling that normally enhances the accumulation of phosphorylated form of BMP transcription factor Mad in the nuclei, can be suppressed by genetic removal of Khc-73. Using a number of assays including live imaging in larval motor neurons, we show that loss of Khc-73 curbs the ability of retrograde-bound endosomes to leave the synaptic area and join the retrograde axonal pathway. Our findings identify Khc-73 as a regulator of endosomal traffic at the synapse and modulator of retrograde BMP signaling in motoneurons.

  19. Modern molecular biomarkers of head and neck cancer. Part I. Epigenetic diagnostics and prognostics: Systematic review.

    Juodzbalys, Gintaras; Kasradze, David; Cicciù, Marco; Sudeikis, Aurimas; Banys, Laurynas; Galindo-Moreno, Pablo; Guobis, Zygimantas

    2016-01-01

    Nearly half of the head and neck cancer cases are diagnosed in late stages. Traditional screening modalities have many disadvantages. The aim of the present article was to review the scientific literature about novel head and neck cancer diagnostics - epigenetic biomarkers. A comprehensive review of the current literature was conducted according to the PRISMA guidelines by accessing the NCBI PubMed database. Authors conducted the search of articles in English language published from 2004 to 2015. A total of thirty three relevant studies were included in the review. Fifteen of them concerned DNA methylation alterations, nine evaluation of abundancies in histone expressions and nine miRNA expression changes in HNC. Considerable number of epigenetic biomarkers have been identified in both tumor tissue and salivary samples. Genes with best diagnostic effectiveness rates and further studying prospects were: TIMP3, DCC, DAPK, CDH1, CCNA1, AIM1, MGMT, HIC1, PAX1, PAX5, ZIC4, p16, EDNRB, KIF1A, MINT31, CD44, RARβ , ECAD. Individual histone and miRNA alterations tend to be hnc specific. Prognostic values of separate biomarkers are ambiguous. No established standards for molecular assay of head and neck cancer was found in order to elude the paradoxical results and discrepancies in separate trials.

  20. Are Effective Properties Effective?

    Han, Ru; Ingber, Marc S.; Hsiao, S.-C.

    2008-01-01

    The effective moduli (effective Young's modulus, effective Poisson's ratio, effective shear modulus, and effective bulk modulus) of dispersed-phase-reinforced composite materials are determined at the mesoscopic level using three-dimensional parallel boundary element simulations. By comparing the mesoscopic BEM results and the macroscopic results based on effective properties, limitations in the effective property approach have been examined

  1. Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice

    Judge, Adam D.; Robbins, Marjorie; Tavakoli, Iran; Levi, Jasna; Hu, Lina; Fronda, Anna; Ambegia, Ellen; McClintock, Kevin; MacLachlan, Ian

    2009-01-01

    siRNAs that specifically silence the expression of cancer-related genes offer a therapeutic approach in oncology. However, it remains critical to determine the true mechanism of their therapeutic effects. Here, we describe the preclinical development of chemically modified siRNA targeting the essential cell-cycle proteins polo-like kinase 1 (PLK1) and kinesin spindle protein (KSP) in mice. siRNA formulated in stable nucleic acid lipid particles (SNALP) displayed potent antitumor efficacy in b...

  2. In vivo control mechanisms of motor-cargo movement on microtubules

    Gunawardena, Shermali

    2014-03-01

    Within axons, molecular motors transport essential components required for neuronal growth and viability. Although many levels of regulation must exist for proper anterograde and retrograde transport of vital proteins, little is known about these mechanisms. Previous work suggested that the amyloid precursor protein (APP) functions as a kinesin-1 receptor during transport. However, how APP vesicle motility is regulated is unclear. Using genetics and in vivo imaging in Drosophila we showed that reduction of presenilin (PS) substantially increased anterograde and retrograde APP vesicle velocities. Strikingly, PS deficiency had no effect on an unrelated cargo vesicle containing synaptotagmin, which is powered by a different kinesin motor. Increased PS-mediated velocities required functional kinesin-1 and dynein motors. We also found that these PS-mediated effects on motor protein function were mediated via a pathway that involves glycogen synthase kinase-3 β (GSK-3 β) . PS genetically interacted with GSK-3 β in an activity dependent manner. Excess of active GSK-3 β perturbed transport by causing axonal blockages, which were enhanced by reduction of kinesin-1 or dynein, while excess of non-functional GSK-3 β had no effect. Strikingly, GSK-3 β-activity dependent transport defects were enhanced by reduction of PS. Collectively, our findings suggest that PS and GSK-3 β are required for normal motor protein function, and we propose a model in which PS likely regulates GSK-3 β activity during transport. These findings have important implications for our understanding of the complex regulatory machinery that must exist in vivo and how this system is coordinated during vesicle motility on microtubules.

  3. Depletion of kinesin 5B affects lysosomal distribution and stability and induces peri-nuclear accumulation of autophagosomes in cancer cells

    Cardoso, Carla M P; Groth-Pedersen, Line; Høyer-Hansen, Maria

    2009-01-01

    BACKGROUND: Enhanced lysosomal trafficking is associated with metastatic cancer. In an attempt to discover cancer relevant lysosomal motor proteins, we compared the lysosomal proteomes from parental MCF-7 breast cancer cells with those from highly invasive MCF-7 cells that express an active form...... in HeLa cervix carcinoma cells as analyzed by subcellular fractionation. The depletion of KIF5B triggered peripheral aggregations of lysosomes followed by lysosomal destabilization, and cell death in HeLa cells. Lysosomal exocytosis in response to plasma membrane damage as well as fluid phase...... cells. In KIF5B-depleted cells the autophagosomes formed and accumulated in the close proximity to the Golgi apparatus, whereas in the control cells they appeared uniformly distributed in the cytoplasm. CONCLUSIONS/SIGNIFICANCE: Our data identify KIF5B as a cancer relevant lysosomal motor protein...

  4. Multigeneration family with dominant SPG30 hereditary spastic paraplegia.

    Roda, Ricardo H; Schindler, Alice B; Blackstone, Craig

    2017-11-01

    Autosomal recessive KIF1A missense mutations cause hereditary spastic paraplegia (HSP) type SPG30, while recessive truncations lead to sensory and autonomic neuropathy (HSN2C) and many de novo missense mutations are associated with cognitive impairment. Here, we describe family members across three generations with pure HSP. A heterozygous p.Ser69Leu KIF1A mutation segregates with those afflicted. The same variant was previously reported in a Finnish father and son with pure HSP as well as four members of a Sicilian kindred with more intrafamilial phenotypic variability. This further validates the pathogenicity of the p.Ser69Leu mutation and suggests that it may represent a mutation hot spot.

  5. Side Effects

    Side effects are problems that occur when cancer treatment affects healthy tissues or organs. Learn about side effects caused by cancer treatment. Know what signs and symptoms to call your doctor about. Learn about treatments for side effects.

  6. Placebo Effect

    ... C. Spencer, MD Steven Karceski, MD The placebo effect Joseph H. Friedman, MD Richard Dubinsky, MD WHAT ... placebo: a “dummy” medication that should have no effect on the condition. Placebos are not only drugs. ...

  7. Systems effectiveness

    Habayeb, A R

    1987-01-01

    Highlights three principal applications of system effectiveness: hardware system evaluation, organizational development and evaluation, and conflict analysis. The text emphasizes the commonality of the system effectiveness discipline. The first part of the work presents a framework for system effectiveness, partitioning and hierarchy of hardware systems. The second part covers the structure, hierarchy, states, functions and activities of organizations. Contains an extended Appendix on mathematical concepts and also several project suggestions.

  8. "Further Effects"

    Kinigstein, Steven Michael

    In writing Further Effects, I intended to illustrate the benefits that are to be had from the use of effects - processing, when applied at the compositional level, rather than as a post-compositional afterthought. When effects are used creatively in the compositional stage, they will influence the very nature of a piece. They are capable of expressing rhythmic and metric ideas. They can alter the natural timbre of an instrument. This can be done on levels of abstraction ranging from discreet subtlety to disguise beyond recognition. There is one effect (known as "pitch shift.") that allows an instrument to play pitches that are well outside of its range. In Further Effects, I direct the performers to use a volume pedal (which I view as a tool, rather than an effect) for the broadened creative use of dynamics that it so efficiently grants. The use of an effects processor and volume pedal creates a need for ancillary equipment. An amplifier, cables, and an electric hook-up (a microphone or a pickup) will be required for each instrument. While an amplifier serves to project the processed sound, there must also be a device or method to suppress unprocessed sound. A great deal of thought and work goes into the use of effects; yet I feel it is wasteful to use this musical resource merely as post-compositional decoration.

  9. Greenhouse effect

    1992-01-01

    This special issue is devoted to the greenhouse effect and reviews the possible climate change by mankind, paleoclimates, climate models, measurement of terrestrial temperature, CO 2 concentration and energy policy

  10. Biological effects

    Trott, K.R.

    1973-01-01

    Following an introduction into the field of cellular radiation effect considering the most important experimental results, the biological significance of the colony formation ability is brought out. The inactivation concept of stem cells does not only prove to be good, according to the present results, in the interpretation of the pathogenesis of acute radiation effects on moult tissue, it also enables chronicle radiation injuries to be interpreted through changes in the fibrous part of the organs. Radiation therapy of tumours can also be explained to a large extent by the radiation effect on the unlimited reproductiveness of tumour cells. The more or less similar dose effect curves for healthy and tumour tissue in practice lead to intermittent irradiation. The dependence of the intermittent doses and intervals on factors such as Elkind recovery, synchronisation, redistribution, reoxygenation, repopulation and regeneration are reviewed. (ORU/LH) [de

  11. Effective Programming

    Frost, Jacob

    To investigate the use of VTLoE as a basis for formal derivation of functional programs with effects. As a part of the process, a number of issues central to effective formal programming are considered. In particular it is considered how to develop a proof system suitable for pratical reasoning......, how to implement this system in the generic proof assistant Isabelle and finally how to apply the logic and the implementation to programming....

  12. Facebook Effect

    STOICA, Anamaria

    2011-01-01

    This research paper is intended to understand the effects that Facebook, the social networking site has upon us, whether it influences our lives in a good or in a bad way. In order to understand the Facebook Effect we are trying to see how it impacts our lives at economic level,social level, political level, terminology level , psychological level and cultural level . Starting from the question : What does Facebook want? we found several answers consisting in pros and cons of this phenomenon ...

  13. Effective leadership

    Vávrová, Zuzana

    2010-01-01

    In my bachelor thesis I describe problems of effective leadership in organization in relation with organization's objectives filling. I focus here on main principles of leadership process. I characterize process of leadership and personality of leader, who is active executor of this process in organization. The effective leadership is here evaluated mainly from organization theory point of view and in relation with requirements to management, especially its relation with leadership and its de...

  14. [Effective delegation].

    Fang, Li; Hung, Chich-Hsiu

    2008-12-01

    Ninety-seven percent of middle level managers feel they face work overload. The source of this problem may lie in a failure to delegate tasks effectively. If a manager does not effectively delegate, he/she is more likely to report fatigue, stress and depression. Conversely, effectively delegating tasks will improve overall job quality, professional growth in subordinates and cooperation within the team. While it is necessary for managers to delegate tasks effectively, few can be considered to be good natural 'delegators'. Learning and training is necessary for managers to develop the necessary confidence and maturity. This article describes the definitions, purpose and benefits of delegation; factors related to effective delegation; strategies related to successful delegation and skills related to performing cross-cultural delegations. Such issues have seldom been addressed in previous articles. Moreover, nursing implications and suggested applications in nursing practice, education, management and research are mentioned. This article is intended to provide directions to nursing managers and subordinates to promote delegation knowledge and skills.

  15. Treatment Effects

    Heckman, James J.; Lopes, Hedibert F.; Piatek, Rémi

    2014-01-01

    This paper contributes to the emerging Bayesian literature on treatment effects. It derives treatment parameters in the framework of a potential outcomes model with a treatment choice equation, where the correlation between the unobservable components of the model is driven by a low-dimensional v......This paper contributes to the emerging Bayesian literature on treatment effects. It derives treatment parameters in the framework of a potential outcomes model with a treatment choice equation, where the correlation between the unobservable components of the model is driven by a low...... to observe the same person in both the treated and untreated states, but it also turns out to be straightforward to implement. Formulae are provided to compute mean treatment effects as well as their distributional versions. A Monte Carlo simulation study is carried out to illustrate how the methodology can...

  16. Genetic effects

    Kato, Hiroo

    1975-01-01

    In 1948-1953 a large scale field survey was conducted to investigate the possible genetic effects of A-bomb radiation on over 70,000 pregnancy terminations in the cities of Hiroshima and Nagasaki. The indices of possible genetic effect including sex ratio, birth weight, frequency of malformation, stillbirth, neonatal death, deaths within 9 months and anthropometric measurements at 9 months of age for these children were investigated in relation to their parent's exposure status to the A-bomb. There were no detectable genetic effects in this sample, except for a slight change in sex ratio which was in the direction to be expected if exposure had induced sex-linked lethal mutations. However, continued study of the sex ratio, based upon birth certificates in Hiroshima and Nagasaki for 1954-1962, did not confirm the earlier trend. Mortality in these children of A-bomb survivors is being followed using a cohort of 54,000 subjects. No clearly significant effect of parental exposure on survival of the children has been demonstrated up to 1972 (age 17 on the average). On the basis of the regression data, the minimal genetic doubling dose of this type of radiation for mutations resulting in death is estimated at 46 rem for the father and 125 rem for the mother. (auth.)

  17. Ventilation Effectiveness

    Mundt, M.; Mathisen, H. M.; Moser, M.

    Improving the ventilation effectiveness allows the indoor air quality to be significantly enhanced without the need for higher air changes in the building, thereby avoiding the higher costs and energy consumption associated with increasing the ventilation rates. This Guidebook provides easy-to-un...

  18. Listening Effectively.

    Freshour, Frank W.

    1987-01-01

    Research indicates that people spend roughly 45 to 65 percent of their waking moments listening to other persons. To help administrators improve their listening effectiveness, a format to develop a profile of personal listening styles is provided. The strengths and weaknesses of six different listening styles are explored along with ways to…

  19. Effective Consumerism.

    Daugherty, Mabel

    This module, consisting of materials for use in conducting a consumer education mini-course, deals with effective consumerism. Covered in the individual lessons are the following topics: being prepared with information (sources of consumer information and subscription forms); evaluating warranties and service contracts; evaluating advertising and…

  20. Health effects

    Mahieu, L

    1998-07-01

    The main objectives of research in the field of health effects at the Belgian Nuclear Research Centre SCK-CEN are: (1) to study cancer mortality and morbidity in nuclear workers in Belgium; (2) to document the feasibility of retrospective cohort studies in Belgium; (3) to participate in the IARC study; (4) to elucidate the mechanisms of the effects of ionizing radiation on the mammalian embryo during the early phases of its development; (5) to assess the genetic risks of material exposure to ionizing radiation; (6) to elucidate the cellular mechanisms leading to brain damage after prenatal irradiation; (7) to advise authorities and to provide the general population with adequate information concerning the health risk arising from radiation exposure. Progress and major achievements in these topical areas for 1997 are reported.

  1. Health effects

    Mahieu, L.

    1998-01-01

    The main objectives of research in the field of health effects at the Belgian Nuclear Research Centre SCK-CEN are: (1) to study cancer mortality and morbidity in nuclear workers in Belgium; (2) to document the feasibility of retrospective cohort studies in Belgium; (3) to participate in the IARC study; (4) to elucidate the mechanisms of the effects of ionizing radiation on the mammalian embryo during the early phases of its development; (5) to assess the genetic risks of material exposure to ionizing radiation; (6) to elucidate the cellular mechanisms leading to brain damage after prenatal irradiation; (7) to advise authorities and to provide the general population with adequate information concerning the health risk arising from radiation exposure. Progress and major achievements in these topical areas for 1997 are reported

  2. Effective interactions

    Elliott, J.P.

    1981-01-01

    This chapter attempts to describe and compare some of the more important nucleon-nucleon interactions that have been used in nuclear structure calculations, and to relate them where possible to the real nucleon-nucleon interaction. Explains that different interactions have been used depending on whether one is fitting to total binding energies and densities with a Hartree Fock (HF) calculation or fitting to spectra and spectroscopic data in a shell model calculation. Examines both types of calculation after two preliminary sections concerned with notation and with the philosophy underlying the use of model spaces and effective interactions. Discusses Skyrme interactions, finite range interactions, small model space, large model space, and the Sussex potential matrix elements. Focuses on the more empirical approaches in which a simple form is chosen for the effective interaction in a given model space and the parameters are deduced from fitting many-body data

  3. Ventilation effectiveness

    Mathisen, Hans Martin; Nielsen, Peter V; Moser, Alfred

    2004-01-01

    Improving the ventilation effectiveness allows the indoor air quality to be significantly enhanced without the need for higher air changes in the building, thereby avoiding the higher costs and energy consumption associated with increasing the ventilation rates. This Guidebook provides easy-to-understand descriptions of the indices used to mesure the performance of a ventilation system and which indices to use in different cases.

  4. Maximum power operation of interacting molecular motors

    Golubeva, Natalia; Imparato, Alberto

    2013-01-01

    , as compared to the non-interacting system, in a wide range of biologically compatible scenarios. We furthermore consider the case where the motor-motor interaction directly affects the internal chemical cycle and investigate the effect on the system dynamics and thermodynamics.......We study the mechanical and thermodynamic properties of different traffic models for kinesin which are relevant in biological and experimental contexts. We find that motor-motor interactions play a fundamental role by enhancing the thermodynamic efficiency at maximum power of the motors...

  5. Greenhouse effect

    Lepetit, J.P.

    1992-01-01

    This book speaks about the growth of greenhouse gases content in the atmosphere and try to forecast the different scenarios which may happen. But, in spite of international cooperation and coordinated research programs, nobody owns the answer. So possible future climatic changes depend on the behavior of the concerned actors. A review of energy policy driven by USA, Japan, Sweden, United Kingdom and Federal Republic of Germany is given. Political management of this file and public opinion in front of greenhouse effect are also described. 7 refs., 3 figs., 6 tabs

  6. Effective Teachers

    Beverly A. King Miller

    2015-09-01

    Full Text Available This article focuses on the educational strategies that can be used to support female students of African descent in their persistence in science, technology, engineering, and mathematics (STEM education and careers. STEM careers have historically been White male and White female dominated, which has yielded an underrepresentation of those of African descent. Drawing from a grounded qualitative case study, the data used for this article share the responses of Afro-Caribbean females in STEM who have immigrated to the United States from the country of Panama. As Latinas, they are representative of the changing face in the American educational system—bilingual, multicultural, and of African descent. The strategies offered reflect their own teaching practices, their former teachers, or experiences with their children’s teachers. What emerged were descriptions of four strategies and behaviors of effective teachers that align with Ladson-Billings’s culturally relevant pedagogy and Gay’s culturally responsive teaching. Included in the findings are the high standards and expectations embodied by effective teachers that serve to positively inspire their students. Culturally responsive teachers create an atmosphere of learning that supports academic success, conveying their belief in their students’ ability based upon their own reflectivity. As the U.S. educational system continues to become multilingual and multicultural, there is need for strategies for the successful inclusion and progression of students in STEM educational pathways and careers. This will occur as teachers challenge themselves to be the agents of change in the lives of their students.

  7. Radiation effects

    Collings, E.W.

    1986-01-01

    An important cause of deterioration in superconducting magnets intended for high-energy physics and fusion-reactor applications is radiation damage. The present chapter deals chiefly with the effects of electron, proton, gamma and neutron irradiation on the properties of stabilized Ti-Nb-base composite superconductors. The authors examine the particle-accelerator environment, electron irradiation of Ti-Nb superconductor, proton irradiation of Ti-Nb superconductor and its stabilizer, and deuteron irradiation of Ti-Nb superconductor. A section discussing the fusion reactor environment in general is presented, and the two principal classes of fusion reactor based on the magnetic-confinement concept, namely the tokamak and the mirrormachine are examined. Also discussed is neutron irradiation of Cu/TiNb composite superconductors and critical current density of neutronirradiated Ti-Nb. Finally, radiation damage to stabilizer and insulating materials is described

  8. Health effects

    Mahieu, L.

    1998-01-01

    The objectives of the research in the field of epidemiology , performed at the Belgian Nuclear Research Centre SCK-CEN are (1) to study cancer mortality and morbidity in nuclear workers in Belgium; (2) to document the feasibility of retrospective cohort studies in Belgium; (3) to participate in the IARC study. For radiobiology, the main objectives are: (1) to elucidate the mechanisms of the effects of ionizing radiation on the mammalian embryo during the early phase of its development, (2) to assess the genetic risks of maternal exposure to ionizing radiation, (3) to elucidate the mechanisms by which damage to the brain and mental retardation are caused in man after prenatal irradiation. The main achievements in these domains for 1997 are presented

  9. Condom effectiveness.

    Porche, D J

    1998-01-01

    People who choose not to abstain from sexual intercourse can use barrier contraceptive methods, such as condoms, to reduce their risk of contracting HIV and other sexually transmitted diseases (STDs). Health care providers who provide safer sex education and counseling should provide information on condoms as a way of reducing the risk of HIV/STD transmission. Since latex condoms are regulated by the US Food and Drug Administration (FDA) as medical devices, FDA regulations govern latex condom manufacturing and testing in accordance with stringent national standards. The FDA randomly tests imported condoms according to the same stringent quality control standards as US-produced condoms. Condom effectiveness, however, depends upon their correct and consistent use during every sexual act. Relevant data and guidelines are presented on the correct use of male latex and female polyurethane condoms. Both male latex and female polyurethane condoms can prevent the transmission of HIV and other STDs.

  10. Radiological effects

    Anon.

    1978-01-01

    Environmental monitoring in the vicinity of the Calvert Cliffs Nuclear Power Plant has been shown the radiation dose to the public from plant operation to be quite small. Calculations from the reported release rates yield 0.2 mrem whole body dose and 0.6 mrem skin dose for the calendar quarter of maximum release. Radioactivity discharges to the Chesapeake Bay have resulted in detectable concentrations of /sup 110m/Ag, 58 Co, and 60 Co in sediments and shellfish. The area yielding samples with detectable concentrations of plant effluents extends for roughly six miles up and down the western shore, with maximum values found at the plant discharge area. The radiation dose to an individual eating 29 doz oysters and 15 doz crabs (5 kg of each) taken from the plant discharge area would be about 4/1000 mrem whole body dose and 0.2 mrem gastrointestinal tract dose (about 0.007% and 0.5% of the applicable guidelines, respectively.) Comparison of these power plant-induced doses with the fluctuations in natural radiation dose already experienced by the public indicates that the power plant effects are insignificant. The natural variations are tens of times greater than the maximum doses resulting from Calvert Cliffs Power Plant. Although operations to date provide an insufficient basis to predict radiological impact of the Calvert Cliffs Plant over its operational lifetime, available data indicate that the plant should continue to operate with insignificant radiological impact, well within all applicable guidelines

  11. Thyroid effects

    Maxon, H.; Thomas, S.; Buncher, C.; Book, S.; Hertzberg, V.

    1985-01-01

    Risk coefficients for thyroid disorders have been developed for both 131 I and external x or gamma low-LET radiation. A linear, no-threshold model has been used for thyroid neoplasms. A linear, threshold model has been used for other thyroid disorders. Improvements since the Reactor Safety Study were made possible by relevant new animal and human data. Major changes are as follows. Animal data are used to supplement the human experience where necessary. A specific risk estimate model is used for thyroid neoplasms, which accounts for observed effects of gender and age at exposure on risk. For thyroid cancer, the basis of the risk coefficients is the experience of North Americans following x-irradiation for benign disease in childhood. This recognizes possible differences in susceptibility in people of different heritage. A minimum induction period for thyroid neoplasms following irradiation is used to define periods at risk. An upper bound risk coefficient for cancer induction following exposure to 131 I is based on human experience at relatively low dose exposures. While the overall lifetime risks of death due to thyroid cancer are consistent with projections by the ICRP, BEIR III, and UNSCEAR Reports, the current model permits greater flexibility in determining risk for population subgroups. 88 references, 8 tables

  12. Characterizing and modeling protein-surface interactions in lab-on-chip devices

    Katira, Parag

    receptors is beneficial from the point of view of signal enhancement, but has a strong mass transport limitation. To overcome this, the use of molecular shuttles has been proposed that can selectively capture analytes and actively transport them to the nanoreceptors. The effect of employing such a two-stage capture process on biosensor sensitivity is theoretically investigated and an optimum design for a kinesin-microtubule-driven hybrid biosensor is proposed.

  13. Using quantitative PCR to Identify Kinesin-3 Genes that are Upregulated During Growth Arrest in MouseNIH3T3 Cells

    Thorsteinsson, Rikke; Christensen, Søren Tvorup; Pedersen, Lotte Bang

    2009-01-01

    Most cells in our body form a single primary cilium when entering growth arrest. During the past decade, a number of studies have revealed a key role for primary cilia in coordinating a variety of signaling pathways that control important cellular and developmental processes. Consequently, signif...

  14. Effects of Anesthesia

    ... About Policymakers Media ASA Member Toolkit Anesthesia 101 Effects of Anesthesia Explore this page: Effects of Anesthesia ... the types of anesthesia and their side effects? Effects of Anesthesia If you’re having surgery, you ...

  15. Colossal magnetodielectric effect caused by magnetoelectric effect ...

    The colossal magnetodielectric effect is reported in Pb(Zr,Ti)O3/Terfenol-D laminate composite under low magnetic field. When the composite is placed in an external a.c. magnetic field, magnetoelectric effect is produced, as a result, the dielectric properties of the Pb(Zr,Ti)O3 is changed, i.e. magnetodielectric effect. Both the ...

  16. Military Effectiveness: A Reappraisal

    Bernasconi, Jeffrey J

    2007-01-01

    .... Two divergent theories cover the ground of military effectiveness. One looks at the interaction of social structures, whereas the other looks at the effect organization has on military effectiveness...

  17. Network-Based Effectiveness

    Friman, Henrik

    2006-01-01

    ...) to increase competitive advantage, innovation, and mission effectiveness. Network-based effectiveness occurs due to the influence of various factors such as people, procedures, technology, and organizations...

  18. Colossal magnetodielectric effect caused by magnetoelectric effect ...

    -D laminate composite under low magnetic field. When the composite is placed in an external a.c. magnetic field, magnetoelectric effect is produced, as a result, the dielectric properties of the Pb(Zr,Ti)O3 is changed, i.e. magnetodielectric effect ...

  19. Biological effects of radiation

    2013-01-01

    This fourth chapter presents: cell structure and metabolism; radiation interaction with biological tissues; steps of the production of biological effect of radiation; radiosensitivity of tissues; classification of biological effects; reversibility, transmissivity and influence factors; pre-natal biological effects; biological effects in therapy and syndrome of acute irradiation

  20. Casualties and threshold effects

    Mays, C.W.; National Cancer Inst., Bethesda

    1988-01-01

    Radiation effects like cancer are denoted as casualties. Other radiation effects occur almost in everyone when the radiation dose is sufficiently high. One then speaks of radiation effects with a threshold dose. In this article the author puts his doubt about this classification of radiation effects. He argues that some effects of exposure to radiation do not fit in this classification. (H.W.). 19 refs.; 2 figs.; 1 tab

  1. Arabidopsis CDS blastp result: AK287457 [KOME

    Full Text Available AK287457 J043019L17 At4g14330.1 68417.m02207 phragmoplast-associated kinesin-relate...d protein 2 (PAKRP2) identical to cDNA phragmoplast-associated kinesin-related protein 2 (PAKRP2) GI:16973450 3e-24 ...

  2. Arabidopsis CDS blastp result: AK242767 [KOME

    Full Text Available AK242767 J090053D16 At4g14330.1 68417.m02207 phragmoplast-associated kinesin-relate...d protein 2 (PAKRP2) identical to cDNA phragmoplast-associated kinesin-related protein 2 (PAKRP2) GI:16973450 1e-20 ...

  3. Arabidopsis CDS blastp result: AK242756 [KOME

    Full Text Available AK242756 J090051D19 At4g14330.1 68417.m02207 phragmoplast-associated kinesin-relate...d protein 2 (PAKRP2) identical to cDNA phragmoplast-associated kinesin-related protein 2 (PAKRP2) GI:16973450 4e-22 ...

  4. Arabidopsis CDS blastp result: AK059635 [KOME

    Full Text Available AK059635 001-031-A08 At4g14330.1 phragmoplast-associated kinesin-related protein 2 ...(PAKRP2) identical to cDNA phragmoplast-associated kinesin-related protein 2 (PAKRP2) GI:16973450 6e-18 ...

  5. DAFX Digital Audio Effects

    2011-01-01

    The rapid development in various fields of Digital Audio Effects, or DAFX, has led to new algorithms and this second edition of the popular book, DAFX: Digital Audio Effects has been updated throughout to reflect progress in the field. It maintains a unique approach to DAFX with a lecture-style introduction into the basics of effect processing. Each effect description begins with the presentation of the physical and acoustical phenomena, an explanation of the signal processing techniques to achieve the effect, followed by a discussion of musical applications and the control of effect parameter

  6. Experiences with effects specifications

    Simonsen, Jesper; Hertzum, Morten; Barlach, Anders

    2011-01-01

    We describe the effects-specification process from a project that was conducted during the fall 2010 and spring of 2011 in this chapter. The project configured and implemented an electronic patient record system at a maternity ward at a hospital located in a European region. The process comprised...... workshops with effects specification with management and end-users and an agile development process including prototypes configured from the effects specifications. We describe the project and the effects-specification process through which effects were related to the system design and instruments...... for measuring effects were designed. The project is analyzed and lessons learned are discussed....

  7. Biological effects of hyperthermia

    Okumura, Hiroshi

    1980-01-01

    Biological effects of hyperthermia and application of hyperthermia to cancer therapy were outlined. As to independent effects of hyperthermia, heat sensitivity of cancer cells, targets of hyperthermia, thermal tolerance of cancer cells, effects of pH on hyperthermic cell survival, effects of hyperthermia on normal tissues, and possibility of clinical application of hyperthermia were described. Combined effect of hyperthermia and x-irradiation to enhance radiosensitivity of cancer cells, its mechanism, effects of oxygen on cancer cells treated with hyperthermia and irradiation, and therapeutic ratio of combined hyperthermia and irradiation were also described. Finally, sensitizers were mentioned. (Tsunoda, M.)

  8. Side Effects (Management)

    ... cancer care is relieving side effects, called symptom management, palliative care, or supportive care. It is important ... treat them. To learn about the symptoms and management of the long-term side effects of cancer ...

  9. Acoustic Casimir Effect

    Homes, Christopher

    1997-01-01

    ...). When the indirect manifestations of the ZPF are interpreted as due to radiation pressure, acoustic noise can provide an excellent analog to investigate the Casimir effect as well as other effects due to the ZPF...

  10. Multipollutant health effect simulations

    U.S. Environmental Protection Agency — Resulting betas (health effects) from a variety of copollutant epidemiologic models used to analyze the impact of exposure measurement error on health effect...

  11. Characteristics of Effective Argumentation.

    Frana, Adrian W.

    1989-01-01

    Examines how the 1988 Presidential Debates provide a resource for effective instruction in public argument. Provides several examples of effective (and ineffective) argumentative speaking taken from the debates. (MM)

  12. Climate Effects on Health

    ... Guidance and Trainings Webinars Data and Tools Publications Climate Effects on Health Recommend on Facebook Tweet Share ... effects has been excerpted from the Third National Climate Assessment’s Health Chapter . Additional information regarding the health ...

  13. Skills for Effective Consultation.

    Dustin, Dick; Ehly, Stewart

    1984-01-01

    Discusses counselor skills that promote effective consultation. Reviews research on effective school consultation and presents a five-stage model which involves phasing in, problem identification, implementation, evaluation, and termination. Provides recommendations for the process and products of consultation. (JAC)

  14. Leadership Effectiveness and Gender

    Gedney, Christine

    1999-01-01

    This research paper on the subject of Leadership Effectiveness and Gender attempts to conduct a focused amount of research to answer the question about the correlation between gender and leadership effectiveness...

  15. Hormonal effects in newborns

    ... page: //medlineplus.gov/ency/article/001911.htm Hormonal effects in newborns To use the sharing features on this page, please enable JavaScript. Hormonal effects in newborns occur because in the womb, babies ...

  16. Medications and Side Effects

    ... to fully work. You might feel some side effects of your medication before your feel the benefits – ... as sleepiness, anxiety or headache) is a side effect or a symptom of your illness. Many side ...

  17. Somatic and genetic effects

    Broerse, J.J.; Barendsen, G.W.; Kal, H.B.; Kogel, A.J. van der

    1983-01-01

    This book contains the extended abstracts of the contributions of the poster workshop sessions on somatic and genetic effects of the 7th international congress of radiation research. They cover the following main topics: haematopoietic and immune systems, mechanisms of late effects in various tissues, endogenous and exogenous factors in radiation carcinogenesis, teratogenic effects, genetic effects, in vitro transformation, tumour induction in different tissues, carcinogenesis in incorporated tissues, cancer epidemology and risk assessment. refs.; figs.; tabs

  18. Habituation of reinforcer effectiveness

    David R Lloyd; David R Lloyd; Douglas J Medina; Larry W Hawk; Whitney D Fosco; Jerry B Richards

    2014-01-01

    In this paper we propose an integrative model of habituation of reinforcer effectiveness (HRE) that links behavioral and neural based explanations of reinforcement. We argue that habituation of reinforcer effectiveness (HRE) is a fundamental property of reinforcing stimuli. Most reinforcement models implicitly suggest that the effectiveness of a reinforcer is stable across repeated presentations. In contrast, an HRE approach predicts decreased effectiveness due to repeated presentation. We ar...

  19. Effects of teacher training

    Wahlgren, Bjarne; Larsen, Lea Lund

    2010-01-01

    The article gives a short overview over existing knowledge concerning the effect of teacher training in relation to adult learning. It presents a research design for measuring the effect of teacher traning.......The article gives a short overview over existing knowledge concerning the effect of teacher training in relation to adult learning. It presents a research design for measuring the effect of teacher traning....

  20. Biological radiation effects

    Kiefer, J.

    1989-01-01

    The book covers all aspects of biological radiation effects. The physical basis is dealt with in some detail, and the effects at the subcellular and the cellular level are discussed, taking into account modern developments and techniques. The effects on the human organism are reviewed, both from the point of view of applications in medicine as well as with regard to radiation hazards (teratogenic, gonadal and carcinogenic effects)

  1. Magnetic effects in electrochemistry

    NEBOJSA D. NIKOLIC

    2005-05-01

    Full Text Available The effect of imposed magnetic fields onto the electrodeposition of magnetic (nickel and non – magnetic (copper metals was analysed. Also, magnetic properties of electrochemically obtained nanocontacts were examined. An effort to establish a possible correlation between the morphologies of the nanocontacts and the effect of the very large ballistic magnetoresistance (BMR effect was made.

  2. Radiation Therapy Side Effects

    Radiation therapy has side effects because it not only kills or slows the growth of cancer cells, it can also affect nearby healthy cells. Many people who get radiation therapy experience fatigue. Other side effects depend on the part of the body that is being treated. Learn more about possible side effects.

  3. Effects of the KIF2C neck peptide on microtubules: lateral disintegration of microtubules and β-structure formation.

    Shimizu, Youské; Shimizu, Takashi; Nara, Masayuki; Kikumoto, Mahito; Kojima, Hiroaki; Morii, Hisayuki

    2013-04-01

    Members of the kinesin-13 sub-family, including KIF2C, depolymerize microtubules. The positive charge-rich 'neck' region extending from the N-terminus of the catalytic head is considered to be important in the depolymerization activity. Chemically synthesized peptides, covering the basic region (A182-E200), induced a sigmoidal increase in the turbidity of a microtubule suspension. The increase was suppressed by salt addition or by reduction of basicity by amino acid substitutions. Electron microscopic observations revealed ring structures surrounding the microtubules at high peptide concentrations. Using the peptide A182-D218, we also detected free thin straight filaments, probably protofilaments disintegrated from microtubules. Therefore, the neck region, even without the catalytic head domain, may induce lateral disintegration of microtubules. With microtubules lacking anion-rich C-termini as a result of subtilisin treatment, addition of the peptide induced only a moderate increase in turbidity, and rings and protofilaments were rarely detected, while aggregations, also thought to be caused by lateral disintegration, were often observed in electron micrographs. Thus, the C-termini are not crucial for the action of the peptides in lateral disintegration but contribute to structural stabilization of the protofilaments. Previous structural studies indicated that the neck region of KIF2C is flexible, but our IR analysis suggests that the cation-rich region (K190-A204) forms β-structure in the presence of microtubules, which may be of significance with regard to the action of the neck region. Therefore, the neck region of KIF2C is sufficient to cause disintegration of microtubules into protofilaments, and this may contribute to the ability of KIF2C to cause depolymerization of microtubules. © 2013 The Authors Journal compilation © 2013 FEBS.

  4. Almost sharp quantum effects

    Arias, Alvaro; Gudder, Stan

    2004-01-01

    Quantum effects are represented by operators on a Hilbert space satisfying 0≤A≤I, and sharp quantum effects are represented by projection operators. We say that an effect A is almost sharp if A=PQP for projections P and Q. We give simple characterizations of almost sharp effects. We also characterize effects that can be written as longer products of projections. For generality we first work in the formalism of von Neumann algebras. We then specialize to the full operator algebra B(H) and to finite dimensional Hilbert spaces

  5. Network effects in railways

    Landex, Alex

    2012-01-01

    Railway operation is often affected by network effects as a change in one part of the network can influence other parts of the network. Network effects occur because the train runs may be quite long and since the railway system has a high degree of interdependencies as trains cannot cross....../overtake each other everywhere in the network. First this paper describes network effects in general (section 1). In section 2 the network effects for trains and how they can be measured by scheduled waiting time is described. When the trains are affected by network effects the passengers are also affected....... Therefore, sections 3 and 4 describe the network effects for passengers and how they can be measured using passenger delay models. Before the concluding remarks in section 6, section 5 discusses how the operation can be improved by examining network effects in the planning process. © 2012 WIT Press....

  6. Spread effects - methodology

    2004-01-01

    Diffusion of technology, environmental effects and rebound effects are the principal effects from the funding of renewable energy and energy economising. It is difficult to estimate the impact of the spread effects both prior to the measures are implemented and after the measures are carried out. Statistical methods can be used to estimate the spread effects, but they are insecure and always need to be complemented with qualitative and subjective evaluations. It is more adequate to evaluate potential spread effects from market and market data surveillance for a selection of technologies and parties. Based on this information qualitative indicators for spread effects can be constructed and used both ex ante and ex post (ml)

  7. Biological radiation effects

    Gomes, R.A.

    1976-01-01

    The stages of processes leading to radiation damage are studied, as well as, the direct and indirect mechanics of its production. The radiation effects on nucleic acid and protein macro moleculas are treated. The physical and chemical factors that modify radiosensibility are analysed, in particular the oxygen effects, the sensibilization by analogues of nitrogen bases, post-effects, chemical protection and inherent cell factors. Consideration is given to restoration processes by excision of injured fragments, the bloching of the excision restoration processes, the restoration of lesions caused by ionizing radiations and to the restoration by genetic recombination. Referring to somatic effects of radiation, the early ones and the acute syndrome of radiation are discussed. The difference of radiosensibility observed in mammalian cells and main observable alterations in tissues and organs are commented. Referring to delayed radiation effects, carcinogeneses, alterations of life span, effects on growth and development, as well as localized effects, are also discussed [pt

  8. The kinesin–tubulin complex: considerations in structural and functional complexity

    Olmsted ZT

    2015-02-01

    Full Text Available Zachary T Olmsted, Andrew G Colliver, Janet L Paluh State University of New York Polytechnic Institute, Colleges of Nanoscale Science and Engineering, College of Nanoscale Science, Nanobioscience Constellation, Albany, NY, USA Abstract: The ability of cells to respond to external cues by appropriately manipulating their internal environment requires a dynamic microtubule cytoskeleton that is facilitated by associated kinesin motor interactions. The evolutionary adaptations of kinesins and tubulins when merged generate a highly adaptable communication and infrastructure cellular network that is important to understanding specialized cell functions, human disease, and disease therapies. Here, we review the state of the field in the complex relationship of kinesin–tubulin interactions. We propose 12 mechanistic specializations of kinesins. In one category, referred to as sortability, we describe how kinesin interactions with tubulin isoforms, isotypes, or posttranslationally modified tubulins contribute to diverse cellular roles. Fourteen kinesin families have previously been described. Here, we illustrate the great depth of functional complexity that is possible in members within a single kinesin family by mechanistic specialization through discussion of the well-studied Kinesin-14 family. This includes new roles of Kinesin-14 in regulating supramolecular structures such as the microtubule-organizing center γ-tubulin ring complex of centrosomes. We next explore the value of an improved mechanistic understanding of kinesin–tubulin interactions in regard to human development, disease mechanisms, and improving treatments that target kinesin–tubulin complexes. The ability to combine the current kinesin nomenclature along with a more precisely defined kinesin and tubulin molecular toolbox is needed to support more detailed exploration of kinesin–tubulin interaction mechanisms including functional uniqueness, redundancy, or adaptations to new

  9. Knudsen effects in a Scott effect experiment.

    Wells, C. W.; Wood, L. T.; Hildebrandt, A. F.

    1973-01-01

    A thermal torque sometimes observed in Scott effect measurements has been studied experimentally and an explanation for the thermal torque proposed. The magnitude of the thermal torque can be comparable to the Scott torque depending on geometrical and thermal anisotropies. The thermal torque is predicted to decrease with application of an axial magnetic field.

  10. The effective action

    DeWitt, B.

    1987-01-01

    The concept of the effective action in quantum field theory was introduced into physics by Julian Schwinger in 1954. The effective action summarizes, in a single functional, all the quantum properties of the fields under consideration. The functional derivative of the effective action yields the effective field equations, which replace the classical field equations as descriptors of the dynamical behavior of quantized fields. Solutions of these equations are 'in-out' matrix elements of the field operators and, when substituted back into the effective action itself, yield logarithms of the corresponding 'in-out' amplitudes. The classical field equations are gauge covariant, a fact that derives from the gauge invariance of the classical action. One has learned how to construct effective actions that are similarly gauge invariant (in each order of perturbation theory) and that yield effective field equations having the covariance properties of their classical analogs. Despite this advance, problems remain, stemming from the fact that there is not one but an infinite number of gauge invariant effective actions, one for every background-covariant choice of supplementary conditions and ghost fields. Vilkovisky (1984) has argued persuasively that by requiring additionally that the effective action be invariant under local invertible changes in the choice of basic field variables, one can construct a natural unique gauge invariant effective action. This lecture will examine Vilkovisky's ideas. 3 refs

  11. Aristotle and Double Effect

    Di Nucci, Ezio

    2014-01-01

    There are some interesting similarities between Aristotle’s ‘mixed actions’ in Book III of the Nicomachean Ethics and the actions often thought to be justifiable with the Doctrine of Double Effect. Here I analyse these similarities by comparing Aristotle’s examples of mixed actions with standard...... cases from the literature on double effect such as, amongst others, strategic bombing, the trolley problem, and craniotomy. I find that, despite some common features such as the dilemmatic structure and the inevitability of a bad effect, Aristotle’s mixed actions do not count as cases justifiable...... through application of the Doctrine of Double Effect because they fail to meet the crucial necessary condition of the Doctrine according to which the bad effect can only be a merely foreseen side- effect and not an intended means....

  12. Effective communication with seniors

    PONCAROVÁ, Ester

    2008-01-01

    My bachelor thesis is called "The Effective Communication With Seniors". The aim of this thesis is to describe communication, its various kinds and the basic principles of the effective communication. I will also describe the communication with seniors suffering from dementia. Another aim of this thesis is to find out whether workers in the senior houses know and use the principles of the effective communication.

  13. Multiphoton polarization Bremsstrahlung effect

    Golovinskij, P.A.

    2001-01-01

    A general approach to induced polarization effects was formulated on the basis of theory of many particles in a strong periodic field. Correlation with the perturbation theory is shown and the types of effective polarization potentials both for isolated atoms and ions, and for ions in plasma, are provided. State of art in the theory of forced polarization Bremsstrahlung effect is analyzed and some outlooks for further experimental and theoretical studies are outlined [ru

  14. Modeling quantization effects in field effect transistors

    Troger, C.

    2001-06-01

    Numerical simulation in the field of semiconductor device development advanced to a valuable, cost-effective and flexible facility. The most widely used simulators are based on classical models, as they need to satisfy time and memory constraints. To improve the performance of field effect transistors such as MOSFETs and HEMTs these devices are continuously scaled down in their dimensions. Consequently the characteristics of such devices are getting more and more determined by quantum mechanical effects arising from strong transversal fields in the channel. In this work an approach based on a two-dimensional electron gas is used to describe the confinement of the carriers. Quantization is considered in one direction only. For the derivation of a one-dimensional Schroedinger equation in the effective mass framework a non-parabolic correction for the energy dispersion due to Kane is included. For each subband a non-parabolic dispersion relation characterized by subband masses and subband non-parabolicity coefficients is introduced and the parameters are calculated via perturbation theory. The method described in this work has been implemented in a software tool that performs a self-consistent solution of Schroedinger- and Poisson-equation for a one-dimensional cut through a MOS structure or heterostructure. The calculation of the carrier densities is performed assuming Fermi-Dirac statistics. In the case of a MOS structure a metal or a polysilicon gate is considered and an arbitrary gate bulk voltage can be applied. This allows investigating quantum mechanical effects in capacity calculations, to compare the simulated data with measured CV curves and to evaluate the results obtained with a quantum mechanical correction for the classical electron density. The behavior of the defined subband parameters is compared to the value of the mass and the non-parabolicity coefficient from the model due to Kane. Finally the presented characterization of the subbands is applied

  15. The greenhouse effect

    Berger, A.

    1991-01-01

    The greenhouse effect on earth can be defined as the long wave energy trapped in the atmosphere. Climate forcing and climate system response within which climate feedback mechanisms are contained are determined. Quantitative examples illustrate what could happen if the greenhouse effect is perturbed by human activities, in particular if CO2 atmospheric concentration would double in the future. Recent satellite measurements of the greenhouse effect are given. The net cooling effect of clouds and whether or not there will be less cooling by clouds as the planet warms are also discussed

  16. Rectenna related atmospheric effects

    Lee, J.

    1980-01-01

    Possible meteorological effects arising from the existence and operations of a solar power satellite (SPS) system rectenna are examined. Analysis and model simulations in some chosen site situations and meteorological conditions indicate that the meteorological effects of the construction and operation of a rectenna are small, particularly outside the boundary of the structure. From weather and climate points of view, installation of an SPS rectenna seems likely to have effects comparable with those due to other nonindustrial land use changes covering the same area. The absorption and scattering of microwave radiation in the troposphere would have negligible atmospheric effects.

  17. Impedance and Collective Effects

    Metral, E; Rumolo, R; Herr, W

    2013-01-01

    This document is part of Subvolume C 'Accelerators and Colliders' of Volume 21 'Elementary Particles' of Landolt-Börnstein - Group I 'Elementary Particles, Nuclei and Atoms'. It contains the Chapter '4 Impedance and Collective Effects' with the content: 4 Impedance and Collective Effects Introduction 4.1 Space Charge 4.2 Wake Fields and Impedances 4.3 Coherent Instabilities 4.4 Landau Damping 4.5 Two-Stream Effects (Electron Cloud and Ions) 4.6 Beam-Beam Effects 4.7 Numerical Modelling

  18. Leadership Effectiveness and Gender

    Gedney, Christine

    1999-01-01

    .... It specifically looks at the current definitions of leadership and looks at some historical background information relating to the more common theories that relate to leadership and effectiveness...

  19. Effective Lagrangian of QED

    Kaminski, J.Z.

    1981-01-01

    A renormalization group equation for the effective Lagrangian of QED is obtained. Starting from this equation, perturbation theory for the renormalization group equation (PTRGE) is developed. The results are in full agreement with the standard perturbation theory. Conjecturing that the asymptotic effective coupling constant is finite, the effective Lagrangian for a strong magnetic field is obtained, which is proportional to the Maxwellian Lagrangian. For the asymptotically free theories the situation is diametrically opposed to QED. In these cases the effective Lagrangian of the Yang-Mills system tends to infinity for very strong external Yang-Mills fields. (Auth.)

  20. Impurity effect in the quantum Nernst effect

    Shirasaki, Ryoen; Nakamura, Hiroaki; Hatano, Naomichi

    2005-11-01

    We theoretically study the Nernst effect and the Seebeck effect in a two-dimensional electron ga in a strong magnetic field and a temperature gradient under adiabatic condition. We recently predicted for a pure system in the quantum Hall regime that the Nernst coefficients strongly suppressed and the thermal conductance is quantized due to quantum ballistic transport. Taking account of impurities, we here compute the Nernst coefficient and the Seebeck coefficient when the chemical potential coincides with a Landau level. We adopt the self-consistent Born approximation and consider the linear transport equations of the thermal electric transport induced by the temperature gradient. The thermal conductance and the Nernst coefficient are slightly modified from the pure case and the Seebeck coefficient newly appears because of the impurity scattering of electrons in the bulk states. (author)

  1. Binary effectivity rules

    Keiding, Hans; Peleg, Bezalel

    2006-01-01

    is binary if it is rationalized by an acyclic binary relation. The foregoing result motivates our definition of a binary effectivity rule as the effectivity rule of some binary SCR. A binary SCR is regular if it satisfies unanimity, monotonicity, and independence of infeasible alternatives. A binary...

  2. Summary of geonuclear effects

    Rawson, Donald E.

    1970-01-01

    Geonuclear effects are considered here to include all of the interactions between underground nuclear explosions and the surrounding earth material. They constitute a large spectrum of effects that starts with the complex chemistry of the explosion 'fireball' and continues in space until the teleseismic signals in the earth have attenuated and in time until the radioactive products have decayed. This paper does not treat the total spectrum but is restricted to those effects which are of direct use to possible non excavation engineering projects and the major side effects that could detract from the use of nuclear explosions for such projects. Emphasis is given to possible methods of enhancing the desired geonuclear effects and minimizing the deleterious ones. Those who have directly participated in developing nuclear explosive technology cannot help but be impressed by the terrific potential for useful work associated with this energy source. Those who have viewed this developing technology from the periphery (the potential industrial market, the concerned public, and specialists in many allied fields) are certainly interested in the potential benefits but cannot help but be impressed by the attendant risks. Some of the useful geonuclear effects balanced against the associated side effects are shown schematically. More experience and increased knowledge of these effects will affect both project costs and public opinion. These factors will determine how the balance will tilt in relation to specific nuclear explosion engineering projects

  3. The polarized EMC effect

    W. Bentz; I. C. Cloet; A. W. Thomas

    2007-02-01

    We calculate both the spin independent and spin dependent nuclear structure functions in an effective quark theory. The nucleon is described as a composite quark-diquark state, and the nucleus is treated in the mean field approximation. We predict a sizable polarized EMC effect, which could be confirmed in future experiments.

  4. Effective dose equivalent

    Huyskens, C.J.; Passchier, W.F.

    1988-01-01

    The effective dose equivalent is a quantity which is used in the daily practice of radiation protection as well as in the radiation hygienic rules as measure for the health risks. In this contribution it is worked out upon which assumptions this quantity is based and in which cases the effective dose equivalent can be used more or less well. (H.W.)

  5. Summary of geonuclear effects

    Rawson, Donald E [Explosives Engineering Services, Gulf General Atomic Incorporated, San Diego, CA (United States)

    1970-05-01

    Geonuclear effects are considered here to include all of the interactions between underground nuclear explosions and the surrounding earth material. They constitute a large spectrum of effects that starts with the complex chemistry of the explosion 'fireball' and continues in space until the teleseismic signals in the earth have attenuated and in time until the radioactive products have decayed. This paper does not treat the total spectrum but is restricted to those effects which are of direct use to possible non excavation engineering projects and the major side effects that could detract from the use of nuclear explosions for such projects. Emphasis is given to possible methods of enhancing the desired geonuclear effects and minimizing the deleterious ones. Those who have directly participated in developing nuclear explosive technology cannot help but be impressed by the terrific potential for useful work associated with this energy source. Those who have viewed this developing technology from the periphery (the potential industrial market, the concerned public, and specialists in many allied fields) are certainly interested in the potential benefits but cannot help but be impressed by the attendant risks. Some of the useful geonuclear effects balanced against the associated side effects are shown schematically. More experience and increased knowledge of these effects will affect both project costs and public opinion. These factors will determine how the balance will tilt in relation to specific nuclear explosion engineering projects.

  6. Radiation effects on polyaniline

    Oki, Yuichi; Kondo, Kenjiro; Suzuki, Takenori; Numajiri, Masaharu; Miura, Taichi; Doi, Shuji; Ohnishi, Toshihiro.

    1992-01-01

    Effects of γ-irradiation on electrical conductivity of polyaniline were investigated. A drastic increase of the conductivity due to radiation-induced doping was observed in combined systems of polyaniline films and halogen-containing polymers. This effect can be applied to measure an integrated radiation dose. (author)

  7. Isotopic effect giant resonances

    Buenerd, M.; Lebrun, D.; Martin, P.; Perrin, G.; Saintignon, P. de; Chauvin, J.; Duhamel, G.

    1981-10-01

    The systematics of the excitation energy of the giant dipole, monopole, and quadrupole resonances are shown to exhibit an isotopic effect. For a given element, the excitation energy of the transition decreases faster with the increasing neutron number than the empirical laws fitting the overall data. This effect is discussed in terms of the available models

  8. Relative Effects at Work

    Braeken, Johan; Mulder, Joris; Wood, Stephen

    2015-01-01

    Assessing the relative importance of predictors has been of historical importance in a variety of disciplines including management, medicine, economics, and psychology. When approaching hypotheses on the relative ordering of the magnitude of predicted effects (e.g., the effects of discrimination

  9. Presenting Food Science Effectively

    Winter, Carl K.

    2016-01-01

    While the need to present food science information effectively is viewed as a critical competency for food scientists by the Institute of Food Technologists, most food scientists may not receive adequate training in this area. Effective presentations combine both scientific content and delivery mechanisms that demonstrate presenter enthusiasm for…

  10. The greenhouse effect gases

    2006-06-01

    This road-map proposes by the Group Total aims to inform the public on the greenhouse effect gases. It presents the greenhouses effect as a key component of the climate system, the impacts of the human activity, the foreseeable consequences of global warming, the Kyoto protocol and Total commitment in the domain. (A.L.B.)

  11. PLEYOTROPIC EFFECTS OF METFORMIN

    L. Ju. Morgunov

    2014-01-01

    Full Text Available Metformin, traditionally used for the therapy of diabetes mellitus, possesses a number of diverse pleyotropic effects. The drug, in addition to the glucose-lowering actions, has a beneficial effect on components of the metabolic syndrome, significantly reduces body weight.

  12. Genetic effect of neutrons

    Luchnik, N.V.; Sevan'kaev, A.V.; Fesenko, Eh.V.

    1984-01-01

    Gene mutations resulting from neutron effect are considered, but attention is focused on chromosome mutations. Dose curves for different energy of neutrons obtained at different objects are obtained which makes it possible to consider RBE of neutrons depending on their energy and radiation dose and to get some information on the neutron effect on heredity

  13. Adverse Effects of Bisphosphonates

    Abrahamsen, Bo

    2010-01-01

    and are tolerated by the majority of patients, but serious adverse events have been recorded in some cases. Only the most common of adverse effects are robustly observable in clinical trials. In general, studies were not powered to detect effects that were lower in incidence than fractures. This review of adverse...

  14. Adverse effects of bisphosphonates

    Abrahamsen, Bo

    2010-01-01

    and are tolerated by the majority of patients, but serious adverse events have been recorded in some cases. Only the most common of adverse effects are robustly observable in clinical trials. In general, studies were not powered to detect effects that were lower in incidence than fractures. This review of adverse...

  15. RBE for deterministic effects

    1990-01-01

    In the present report, data on RBE values for effects in tissues of experimental animals and man are analysed to assess whether for specific tissues the present dose limits or annual limits of intake based on Q values, are adequate to prevent deterministic effects. (author)

  16. Radiation effects in space

    Fry, R.J.M.

    1987-07-01

    As more people spend more time in space, and the return to the moon and exploratory missions are considered, the risks require continuing examination. The effects of microgravity and radiation are two potential risks in space. These risks increase with increasing mission duration. This document considers the risk of radiation effects in space workers and explorers. 17 refs., 1 fig., 4 tabs

  17. Safeguards system effectiveness modeling

    Bennett, H.A.; Boozer, D.D.; Chapman, L.D.; Daniel, S.L.; Engi, D.; Hulme, B.L.; Varnado, G.B.

    1976-01-01

    A general methodology for the comparative evaluation of physical protection system effectiveness at nuclear facilities is presently under development. The approach is applicable to problems of sabotage or theft at fuel cycle facilities. The overall methodology and the primary analytic techniques used to assess system effectiveness are briefly outlined

  18. The greenhouse effect

    2004-01-01

    In the framework of the sustainable development, this paper presents the greenhouse effect and its impact on the climatic change, the world interest from Rio to Buenos Aires, the human activities producing the carbon dioxide and responsible of the greenhouse effect, the carbon dioxide emission decrease possibilities and shows the necessity of the electric power producers contribution. (A.L.B.)

  19. Safeguards system effectiveness modeling

    Boozer, D.D.; Hulme, B.L.; Daniel, S.L.; Varnado, G.B.; Bennett, H.A.; Chapman, L.D.; Engi, D.

    1976-09-01

    A general methodology for the comparative evaluation of physical protection system effectiveness at nuclear facilities is presently under development. The approach is applicable to problems of sabotage or theft at fuel cycle facilities. In this paper, the overall methodology and the primary analytic techniques used to assess system effectiveness are briefly outlined

  20. The Aid Effectiveness Literature

    Doucouliagos, Hristos; Paldam, Martin

    The AEL consists of empirical macro studies of the effects of development aid. At the end of 2004 it had reached 97 studies of three families, which we have summarized in one study each using meta-analysis. Studies of the effect on investments show that they rise by 1/3 of the aid – the rest is c...

  1. A 'Copenhagen Effect'?

    Werlauff, Erik

    2009-01-01

    On the basis of the Danish company law reform of 2009/2010, this article examines the question of whether the processes of liberalisation and internationalisation of the Danish rules on public and private companies which the reform represents are significant enough to warrant the term...... the ‘Copenhagen effect' in competition with the already established ‘London effect'....

  2. En "Copenhagen effect"?

    Werlauff, Erik

    2009-01-01

    Artiklen efterprøver på grundlag af den danske selskabsreform 2009/10, om den liberalisering og internationalisering, der herved har fundet sted af den danske lovgivning om aktie- og anpartsselskaber, er så betydningsfuld, at det fremtidigt giver mening at tale om en "Copenhagen effect" i...... konkurrence med den allerede kendte "London effect". Udgivelsesdato: Juni 2009...

  3. Safeguards system effectiveness modeling

    Bennett, H.A.; Boozer, D.D.; Chapman, L.D.; Daniel, S.L.; Engi, D.; Hulme, B.L.; Varnado, G.B.

    1976-01-01

    A general methodology for the comparative evaluation of physical protection system effectiveness at nuclear facilities is presently under development. The approach is applicable to problems of sabotage or theft at fuel cycle facilities. In this paper, the overall methodology and the primary analytic techniques used to assess system effectiveness are briefly outlined

  4. Microscopic dynamical Casimir effect

    Souza, Reinaldo de Melo e.; Impens, François; Neto, Paulo A. Maia

    2018-03-01

    We consider an atom in its ground state undergoing a nonrelativistic oscillation in free space. The interaction with the electromagnetic quantum vacuum leads to two effects to leading order in perturbation theory. When the mechanical frequency is larger than the atomic transition frequency, the dominant effect is the motion-induced transition to an excited state with the emission of a photon carrying the excess energy. We compute the angular distribution of emitted photons and the excitation rate. On the other hand, when the mechanical frequency is smaller than the transition frequency, the leading-order effect is the parametric emission of photon pairs, which constitutes the microscopic counterpart of the dynamical Casimir effect. We discuss the properties of the microscopic dynamical Casimir effect and build a connection with the photon production by an oscillating macroscopic metallic mirror.

  5. Nocebo effect in dermatology

    Sidharth Sonthalia

    2015-01-01

    Full Text Available Nocebo effect, originally denoting the negative counterpart of the placebo phenomenon, is now better defined as the occurrence of adverse effects to a therapeutic intervention because the patient expects them to develop. More commonly encountered in patients with a past negative experience, this effect stems from highly active processes in the central nervous system, mediated by specific neurotransmitters and modulated by psychological mechanisms such as expectation and conditioning. The magnitude of nocebo effect in clinical medicine is being increasingly appreciated and its relevance encompasses clinical trials as well as clinical practice. Although there is hardly any reference to the term nocebo in dermatology articles, the phenomenon is encountered routinely by dermatologists. Dermatology patients are more susceptible to nocebo responses owing to the psychological concern from visibility of skin lesions and the chronicity, unpredictable course, lack of ′permanent cure′ and frequent relapses of skin disorders. While finasteride remains the prototypical drug that displays a prominent nocebo effect in dermatologic therapeutics, other drugs such as isotretinoin are also likely inducers. This peculiar phenomenon has recently been appreciated in the modulation of itch perception and in controlled drug provocation tests in patients with a history of adverse drug reactions. Considering the conflict between patients′ right to information about treatment related adverse effects and the likelihood of nocebo effect stemming from information disclosure, the prospect of ethically minimizing nocebo effect remains daunting. In this article, we review the concept of nocebo effect, its postulated mechanism, relevance in clinical dermatology and techniques to prevent it from becoming a barrier to effective patient management.

  6. [Psychoanalysis and Side Effect].

    Shirahase, Joichiro

    2015-01-01

    A study of psychoanalysis from the perspective of side effects reveals that its history was a succession of measures to deal with its own side effects. This, however, does not merely suggest that, as a treatment method, psychoanalysis is incomplete and weak: rather, its history is a record of the growth and development of psychoanalysis that discovered therapeutic significance from phenomena that were initially regarded as side effects, made use of these discoveries, and elaborated them as a treatment method. The approach of research seen during the course of these developments is linked to the basic therapeutic approach of psychoanalysis. A therapist therefore does not draw conclusions about a patient's words and behaviors from a single aspect, but continues to make efforts to actively discover a variety of meanings and values from them, and to make the patient's life richer and more productive. This therapeutic approach is undoubtedly one of the unique aspects of psychoanalysis. I discuss the issue of psychoanalysis and side effects with the aim of clarifying this unique characteristic of psychoanalysis. The phenomenon called resistance inevitably emerges during the process of psychoanalytic treatment. Resistance can not only obstruct the progress of therapy; it also carries the risk of causing a variety of disadvantages to the patient. It can therefore be seen as an adverse effect. However, if we re-examine this phenomenon from the perspective of transference, we find that resistance is in fact a crucial tool in psychoanalysis, and included in its main effect, rather than a side effect. From the perspective of minimizing the character of resistance as a side effect and maximizing its character as a main effect, I have reviewed logical organization, dynamic evaluation, the structuring of treatment, the therapist's attitudes, and the training of therapists. I conclude by stating that psychoanalysis has aspects that do not match the perspective known as a side

  7. Electroplastic effect in metals

    Sprecher, A.F. Jr.

    1984-01-01

    This report presents the effects of single d-c current pulses (1000-6000 A/mm 2 approx.60 μs) on plastically deforming metals. Polycrystalline wire specimens (D 0 approx. 1/2 mm, L 0 approx. 50 mm) representing the three more common crystal structures were employed: Ti from the HCP structures; Fe, Nb, and W from the bcc structure; and Al, Cu, and Ni from the fcc structure. The tests were carried out under uniaxial tension with an applied strain rate of 1.7 x 10 -4 sec -1 at room temperature. Forced air cooling was employed in order to reduce the principal side effect, heating. As a result of applying a current pulse, there were significant drops in the flow stress (1-35%). These drops not only included an electron dislocation interaction but all side effects as well. The main side effect due to the temperature rise was thermal expansion and could account for 60-90% of the drops. In addition to thermal expansion, some thermally induced plastic flow occurred as indicated by computer simulations. The total side effects (thermal expansion and plastic flow) approximately accounted for the stress drops in Ti, W, and Nb. However, a strong electron dislocation (ed) interaction was observed in Cu and Al since plastic flow from thermal effects was negligible. In Ni and Fe the portion of the stress drops due to (ed) was unclear due to some dynamic aging effects present

  8. Noncovalent Hydrogen Isotope Effects

    Buchachenko, A. L.; Breslavskaya, N. N.

    2018-02-01

    Zero-point energies (ZPE) and isotope effects, induced by intermolecular, noncovalent vibrations, are computed and tested by experimental data. The ZPE differences of H- and D-complexes of water with hydrogen, methane, and water molecules are about 100-300 cal/mol; they result to isotope effects IE of 1.20-1.70. Semi-ionic bonds between metal ions and water ligands in M(H2O) 6 2+ complexes are much stronger; their ZPEs are about 12-14 kcal/mol per molecule and result to IE of 1.9-2.1 at 300 K. Protonated (deuterated) water and biwater exhibit the largest ZPE differences and isotope effects; the latter are 25-28 and 12-13 for water and biwater, respectively. Noncovalent IEs contribute markedly into the experimentally measured effects and explain many anomalous and even magic properties of the effects, such as the dependence of IE on the solvents and on the presence of the third substances, enormously large isotope effects at the mild conditions, the difference between IEs measured in the reactions of individual protiated and deuterated compounds and those measured in their mixture. Noncovalent IEs are not negligible and should be taken into account to make correct and substantiated conclusions on the reaction mechanisms. The kinetic equations are derived for the total isotope effects, which include noncovalent IEs as additive factors.

  9. Bystander effects and radiotherapy.

    Marín, Alicia; Martín, Margarita; Liñán, Olga; Alvarenga, Felipe; López, Mario; Fernández, Laura; Büchser, David; Cerezo, Laura

    2015-01-01

    Radiation-induced bystander effects are defined as biological effects expressed after irradiation by cells whose nuclei have not been directly irradiated. These effects include DNA damage, chromosomal instability, mutation, and apoptosis. There is considerable evidence that ionizing radiation affects cells located near the site of irradiation, which respond individually and collectively as part of a large interconnected web. These bystander signals can alter the dynamic equilibrium between proliferation, apoptosis, quiescence or differentiation. The aim of this review is to examine the most important biological effects of this phenomenon with regard to areas of major interest in radiotherapy. Such aspects include radiation-induced bystander effects during the cell cycle under hypoxic conditions when administering fractionated modalities or combined radio-chemotherapy. Other relevant aspects include individual variation and genetics in toxicity of bystander factors and normal tissue collateral damage. In advanced radiotherapy techniques, such as intensity-modulated radiation therapy (IMRT), the high degree of dose conformity to the target volume reduces the dose and, therefore, the risk of complications, to normal tissues. However, significant doses can accumulate out-of-field due to photon scattering and this may impact cellular response in these regions. Protons may offer a solution to reduce out-of-field doses. The bystander effect has numerous associated phenomena, including adaptive response, genomic instability, and abscopal effects. Also, the bystander effect can influence radiation protection and oxidative stress. It is essential that we understand the mechanisms underlying the bystander effect in order to more accurately assess radiation risk and to evaluate protocols for cancer radiotherapy.

  10. Effective field theories

    Mack, G.; Kalkreuter, T.; Palma, G.; Speh, M.

    1992-05-01

    Effective field theories encode the predictions of a quantum field theory at low energy. The effective theory has a fairly low utraviolet cutoff. As a result, loop corrections are small, at least if the effective action contains a term which is quadratic in the fields, and physical predictions can be read straight from the effective Lagrangean. Methods will be discussed how to compute an effective low energy action from a given fundamental action, either analytically or numerically, or by a combination of both methods. Basically, the idea is to integrate out the high frequency components of fields. This requires the choice of a 'blockspin', i.e. the specification af a low frequency field as a function of the fundamental fields. These blockspins will be fields of the effective field theory. The blockspin need not be a field of the same type as one of the fundamental fields, and it may be composite. Special features of blockspin in nonabelian gauge theories will be discussed in some detail. In analytical work and in multigrid updating schemes one needs interpolation kernels A from coarse to fine grid in addition to the averaging kernels C which determines the blockspin. A neural net strategy for finding optimal kernels is presented. Numerical methods are applicable to obtain actions of effective theories on lattices of finite volume. The special case of a 'lattice' with a single site (the constraint effective potential) is of particular interest. In a higgs model, the effective action reduces in this case to the free energy, considered as a function of a gauge covariant magnetization. Its shape determines the phase structure of the theory. Its loop expansion with and without gauge fields can be used to determine finite size corrections to numerical data. (orig.)

  11. Cohomology of Effect Algebras

    Frank Roumen

    2017-01-01

    Full Text Available We will define two ways to assign cohomology groups to effect algebras, which occur in the algebraic study of quantum logic. The first way is based on Connes' cyclic cohomology. The resulting cohomology groups are related to the state space of the effect algebra, and can be computed using variations on the Kunneth and Mayer-Vietoris sequences. The second way involves a chain complex of ordered abelian groups, and gives rise to a cohomological characterization of state extensions on effect algebras. This has applications to no-go theorems in quantum foundations, such as Bell's theorem.

  12. Creating more effective graphs

    Robbins, Naomi B

    2012-01-01

    A succinct and highly readable guide to creating effective graphs The right graph can be a powerful tool for communicating information, improving a presentation, or conveying your point in print. If your professional endeavors call for you to present data graphically, here's a book that can help you do it more effectively. Creating More Effective Graphs gives you the basic knowledge and techniques required to choose and create appropriate graphs for a broad range of applications. Using real-world examples everyone can relate to, the author draws on her years of experience in gr

  13. Ballistic missile defense effectiveness

    Lewis, George N.

    2017-11-01

    The potential effectiveness of ballistic missile defenses today remains a subject of debate. After a brief discussion of terminal and boost phase defenses, this chapter will focus on long-range midcourse defenses. The problems posed by potential countermeasures to such midcourse defenses are discussed as are the sensor capabilities a defense might have available to attempt to discriminate the actual missile warhead in a countermeasures environment. The role of flight testing in assessing ballistic missile defense effectiveness is discussed. Arguments made about effectiveness by missile defense supporters and critics are summarized.

  14. Effective career ladders.

    Bryant, B; Rabbitts, D; Shover, J; Torres, M; VanDerHeyden, B; Violand-Jones, S

    1992-01-01

    Motivation, quality improvement, productivity enhancement. These are just some of the benefits of an effective career ladder program. The key term here is effective. It is easy for laboratory personnel to stagnate professionally if they do not have a career ladder program, but it is even easier for them to become frustrated--even cynical--over a program that fails to live up to its expectations to encourage, support, and reward professional advancement. If you have been looking form some ideas to get your own career ladder program off the ground, the following responses from your colleagues may help as CLMR asks: What makes your career ladder program effective?

  15. Developing Effective Performance Measures

    2014-10-14

    University When Performance Measurement Goes Bad Laziness Vanity Narcissism Too Many Pettiness Inanity 52 Developing Effective...Kasunic, October 14, 2014 © 2014 Carnegie Mellon University Narcissism Measuring performance from the organization’s point of view, rather than from

  16. Space radiation effects

    Li Shiqing; Yan Heping

    1995-01-01

    The authors briefly discusses the radiation environment in near-earth space and it's influences on material, and electronic devices using in space airship, also, the research developments in space radiation effects are introduced

  17. Vascular Effects of Histamine

    olayemitoyin

    effects of histamine are mediated via H1 and H2 receptors and the actions are modulated by H3 receptor subtype located on presynaptic ... neurotransmittion in the central nervous system and .... Autoinhibition of brain histamine release.

  18. Side Effects: Sleep Problems

    Sleep problems are a common side effect during cancer treatment. Learn how a polysomnogram can assess sleep problems. Learn about the benefits of managing sleep disorders in men and women with cancer.

  19. Authoring Effective Demonstrations

    Fu, Dan; Jensen, Randy; Salas, Eduardo; Rosen, Michael A; Ramachandran, Sowmya; Upshaw, Christin L; Hinkelman, Elizabeth; Lampton, Don

    2007-01-01

    ... or human role-players for each training event. We report our ongoing efforts to (1) research the nature and purpose of demonstration, articulating guidelines for effective demonstration within a training context, and (2...

  20. Flexo-photovoltaic effect.

    Yang, Ming-Min; Kim, Dong Jik; Alexe, Marin

    2018-04-19

    It is highly desirable to discover photovoltaic mechanisms that enable a higher efficiency of solar cells. Here, we report that the bulk photovoltaic effect, which is free from the thermodynamic Shockley-Queisser limit but usually manifested only in noncentrosymmetric (piezoelectric or ferroelectric) materials, can be realized in any semiconductor, including silicon, by mediation of flexoelectric effect. We introduce strain gradients using either an atomic force microscope or a micron-scale indentation system, creating giant photovoltaic currents from centrosymmetric single crystals of SrTiO 3 , TiO 2 , and Si. This strain-gradient-induced bulk photovoltaic effect, which we call the flexo-photovoltaic effect, functions in the absence of a p - n junction. This finding may extend present solar cell technologies by boosting the solar energy conversion efficiency from a wide pool of established semiconductors. Copyright © 2018, American Association for the Advancement of Science.

  1. Pictorial Superiority Effect

    Nelson, Douglas L.; And Others

    1976-01-01

    Pictures generally show superior recognition relative to their verbal labels. This experiment was designed to link this pictorial superiority effect to sensory or meaning codes associated with the two types of symbols. (Editor)

  2. Network-Based Effectiveness

    Friman, Henrik

    2006-01-01

    ... (extended from Leavitt, 1965). This text identifies aspects of network-based effectiveness that can benefit from a better understanding of leadership and management development of people, procedures, technology, and organizations...

  3. Antihypertensive Effects of Probiotics.

    Robles-Vera, Iñaki; Toral, Marta; Romero, Miguel; Jiménez, Rosario; Sánchez, Manuel; Pérez-Vizcaíno, Francisco; Duarte, Juan

    2017-04-01

    The present review focuses in the hypertension-associated changes in the microbiota and the current insights regarding the impact of probiotics on blood pressure in animal models and in human hypertensive patients. Gut dysbiosis in hypertension is characterized by (i) the gut microbioma that is less diverse and less rich with an increased Firmicutes/Bacteroidetes ratio and (ii) a decrease in acetate- and butyrate-producing bacteria and an increase in lactate-producing bacterial populations. The meta-analysis of the human studies supports that supplementation with probiotics reduces blood pressure. The mechanism of this antihypertensive effect of probiotics and its protective effect on endothelial function has not been fully elucidated. Further investigations are needed to clarify if the effects of probiotic bacteria result from the changes in the gut microbiota and its metabolic by-products; the restoration of the gut barrier function; and the effects on endotoxemia, inflammation, and renal sympathetic nerve activity.

  4. Frost Effects Research Facility

    Federal Laboratory Consortium — Full-scale study in controlled conditionsThe Frost Effects Research Facility (FERF) is the largest refrigerated warehouse in the United States that can be used for a...

  5. Radiation effects in space

    Fry, R.J.M.

    1986-01-01

    The paper discusses the radiation environment in space that astronauts are likely to be exposed to. Emphasis is on proton and HZE particle effects. Recommendations for radiation protection guidelines are presented

  6. The effective nuclear potential

    Skyrme, T.H.R.

    1994-01-01

    An empirical analyses is made of the mean effective internucleon potential required in the shell-model description of nuclei, allowing for the presence of many-body effects as suggested by current theory. A consistent description is found in which the effective two-body interaction acts almost entirely in even states, and the many-body effects are simulated by a repulsive three-body contact interaction. The strength of the two-body interaction is consistent with that expressed by the free scattering matrix of the two-nucleon system, and that of the three-body interaction with the 'rearrangement energy' calculated in the many-body theory. (author). 21 refs, 2 figs, 7 tabs

  7. Greenhouse effect and climate

    Flohn, H.

    1987-01-01

    Model calculations with different marginal conditions and different physical processes do, on the basis of realistic assumptions, result in a temperature rise of 3 ± 1.5degC at doubling carbon dioxide concentrations. Temperatures are increasing even more due to the presence of trace gases contributing to the greenhouse effect. They are assumed to be having a share of 100% in the carbon dioxide effect (additive) in 30-40 years from now. According to the model calculations the CO 2 increase from about 280 ppm around 1850 to 345 ppm (1985) is equal to a globally averaged temperature rise of 0.5-0.7degC. As the data obtained before 1900 were incomplete and little representative climatic analyses cannot be considered to have been effective but after that time. However, considering the additional influence of other climatic effects such as vulcanism the temperature rise satisfactorily corresponds to the values obtained since 1900. (orig./HP) [de

  8. The Effects: Economy

    Nutrient pollution has diverse and far-reaching effects on the U.S. economy, impacting tourism, property values, commercial fishing, recreational businesses and many other sectors that depend on clean water.

  9. Conditions for Effectiveness.

    Wright, Jeannette T.

    1988-01-01

    The most effective college presidents are those whose leadership styles are dominant, decisive, and when appropriate, autocratic. The president has to believe profoundly in the intrinsic value of the college. (Author/MSE)

  10. Density dependent effective interactions

    Dortmans, P.J.; Amos, K.

    1994-01-01

    An effective nucleon-nucleon interaction is defined by an optimal fit to select on-and half-off-of-the-energy shell t-and g-matrices determined by solutions of the Lippmann-Schwinger and Brueckner-Bethe-Goldstone equations with the Paris nucleon-nucleon interaction as input. As such, it is seen to better reproduce the interaction on which it is based than other commonly used density dependent effective interactions. The new (medium modified) effective interaction when folded with appropriate density matrices, has been used to define proton- 12 C and proton- 16 O optical potentials. With them elastic scattering data are well fit and the medium effects identifiable. 23 refs., 8 figs

  11. Side Effects: Fatigue

    Fatigue is a common side effect of many cancer treatments such as chemotherapy, radiation therapy, immunotherapy, and surgery. Anemia and pain can also cause fatigue. Learn about symptoms and way to manage fatigue.

  12. Side Effects: Diarrhea

    Diarrhea, a side effect of cancer treatment, may cause symptoms such as loose, watery stools. Diarrhea can lead to dehydration and malnutrition in cancer patients. Learn about ways to treat and manage diarrhea during cancer treatment.

  13. Side Effects: Appetite Loss

    Cancer treatments may lower your appetite. Side effects such as nausea, fatigue, or mouth sores can also making eating difficult. Learn how to eat well to avoid losing weight or becoming dehydrated, so you stay strong during treatment.

  14. Side Effects: Pain

    Controlling pain is an important part of your cancer treatment plan. Learn how to track levels of pain. Find out how pain, a side effect of cancer treatment, is treated using acupuncture, biofeedback, and physical therapy.

  15. the effects of Garlic

    This study evaluated the effects of Garlic (Allium sativum) on taste responses and relative organ weights in albino rats. Graded dietary ... Allium sativum commonly known as garlic is a specie in the onion ..... nitrate induced toxicity in male mice.

  16. Deforestation Hydrological Effects

    Poveda J, G.; Mesa S, O.J.

    1995-01-01

    Deforestation causes strong disturbances in ecosystems and in hydrological cycle, increasing or reducing wealths. Particularly in this work, effects of feed back between interface processes land - atmosphere are discussed and is demonstrated that losses of water by evaporation-transpiration are thoroughly indispensable to maintain the balance of hydrological regime. It's concluded that as a rule the effect of deforestation is to reduce wealth middle and to increase extreme wealth with consequent stronger and more frequent droughts or flood effects. Other deforestation effects as increase in superficial temperature, increase in atmospherical pressure, decrease in soil moisture, decrease in evaporation-transpiration, decrease of soil ruggedness, decrease of thickness of atmospherical cap limit, decrease of clouds, decrease of rain in both medium and long term and the consequent decrease of rivers wealth middle are explained. Of other side, the basins with greater deforestation affectation in Colombia are indicated. Finally, it's demonstrated the need of implementing reforestation programs

  17. Side Effects: Anemia

    Anemia is a side effect of cancer treatments, including chemotherapy and radiation therapy. It can make women and men feel fatigued, dizzy, and short of breath. Learn how to manage fatigue caused by anemia during cancer treatment.

  18. Theory of Effectiveness Measurement

    Bullock, Richard K

    2006-01-01

    Effectiveness measures provide decision makers feedback on the impact of deliberate actions and affect critical issues such as allocation of scarce resources, as well as whether to maintain or change existing strategy...

  19. EFFECTS OF GLOBAL WARMING

    Dr. Basanti Jain

    2017-01-01

    The abnormal increase in the concentration of the greenhouse gases is resulting in higher temperatures. We call this effect is global warming. The average temperature around the world has increased about 1'c over 140 years, 75% of this has risen just over the past 30 years. The solar radiation, as it reaches the earth, produces "greenhouse effect" in the atmosphere. The thick atmospheric layers over the earth behaves as a glass surface, as it permits short wave radiations from coming in, but ...

  20. Modulational effects in accelerators

    Satogata, T.

    1997-01-01

    We discuss effects of field modulations in accelerators, specifically those that can be used for operational beam diagnostics and beam halo control. In transverse beam dynamics, combined effects of nonlinear resonances and tune modulations influence diffusion rates with applied tune modulation has been demonstrated. In the longitudinal domain, applied RF phase and voltage modulations provide mechanisms for parasitic halo transport, useful in slow crystal extraction. Experimental experiences with transverse tune and RF modulations are also discussed

  1. The quantum hall effect

    El-Arabi, N. M.

    1993-01-01

    Transport phenomena in two dimensional semiconductors have revealed unusual properties. In this thesis these systems are considered and discussed. The theories explain the Integral Quantum Hall Effect (IQHE) and the Fractional Quantum Hall Effect (FQHE). The thesis is composed of five chapters. The first and the second chapters lay down the theory of the IQHE, the third and fourth consider the theory of the FQHE. Chapter five deals with the statistics of particles in two dimension. (author). Refs

  2. Advertising Effectiveness In Events

    Jain, Sushilkumar

    2012-01-01

    Confronted with decreasing effectiveness of the classic marketing communications, events have become an increasingly popular alternative for marketers. Events constitute one of the most exciting and fastest growing forms of leisure and business. With time, the decreasing effectiveness of classical marketing communications boosted the use of events for marketing and making brand awareness. Event marketing is seen as the unique opportunity to integrate the firm’s communication activities like p...

  3. High Burnup Effects Program

    Barner, J.O.; Cunningham, M.E.; Freshley, M.D.; Lanning, D.D.

    1990-04-01

    This is the final report of the High Burnup Effects Program (HBEP). It has been prepared to present a summary, with conclusions, of the HBEP. The HBEP was an international, group-sponsored research program managed by Battelle, Pacific Northwest Laboratories (BNW). The principal objective of the HBEP was to obtain well-characterized data related to fission gas release (FGR) for light water reactor (LWR) fuel irradiated to high burnup levels. The HBEP was organized into three tasks as follows: Task 1 -- high burnup effects evaluations; Task 2 -- fission gas sampling; and Task 3 -- parameter effects study. During the course of the HBEP, a program that extended over 10 years, 82 fuel rods from a variety of sources were characterized, irradiated, and then examined in detail after irradiation. The study of fission gas release at high burnup levels was the principal objective of the program and it may be concluded that no significant enhancement of fission gas release at high burnup levels was observed for the examined rods. The rim effect, an as yet unquantified contributor to athermal fission gas release, was concluded to be the one truly high-burnup effect. Though burnup enhancement of fission gas release was observed to be low, a full understanding of the rim region and rim effect has not yet emerged and this may be a potential area of further research. 25 refs., 23 figs., 4 tabs

  4. Synchronization on effective networks

    Zhou Tao; Zhao Ming; Zhou Changsong

    2010-01-01

    The study of network synchronization has attracted increasing attentionrecently. In this paper, we strictly define a class of networks, namely effective networks, which are synchronizable and orientable networks. We can prove that all the effective networks with the same size have the same spectra, and are of the best synchronizability according to the master stability analysis. However, it is found that the synchronization time for different effective networks can be quite different. Further analysis shows that the key ingredient affecting the synchronization time is the maximal depth of an effective network: the larger depth results in a longer synchronization time. The secondary factor is the number of links. The increasing number of links connecting nodes in the same layer (horizontal links) will lead to longer synchronization time, whereas the increasing number of links connecting nodes in neighboring layers (vertical links) will accelerate the synchronization. Our analysis of the relationship between the structure and synchronization properties of the original and effective networks shows that the purely directed effective network can provide an approximation of the original weighted network with normalized input strength. Our findings provide insights into the roles of depth, horizontal and vertical links in the synchronizing process, and suggest that the spectral analysis is helpful yet insufficient for the comprehensive understanding of network synchronization.

  5. Synchronization on effective networks

    Zhou Tao [Web Sciences Center, University of Electronic Science and Technology of China, Chengdu 610054 (China); Zhao Ming [Department of Modern Physics, University of Science and Technology of China, Hefei 230026 (China); Zhou Changsong, E-mail: cszhou@hkbu.edu.h [Department of Physics, Hong Kong Baptist University, Kowloon Tong (Hong Kong)

    2010-04-15

    The study of network synchronization has attracted increasing attentionrecently. In this paper, we strictly define a class of networks, namely effective networks, which are synchronizable and orientable networks. We can prove that all the effective networks with the same size have the same spectra, and are of the best synchronizability according to the master stability analysis. However, it is found that the synchronization time for different effective networks can be quite different. Further analysis shows that the key ingredient affecting the synchronization time is the maximal depth of an effective network: the larger depth results in a longer synchronization time. The secondary factor is the number of links. The increasing number of links connecting nodes in the same layer (horizontal links) will lead to longer synchronization time, whereas the increasing number of links connecting nodes in neighboring layers (vertical links) will accelerate the synchronization. Our analysis of the relationship between the structure and synchronization properties of the original and effective networks shows that the purely directed effective network can provide an approximation of the original weighted network with normalized input strength. Our findings provide insights into the roles of depth, horizontal and vertical links in the synchronizing process, and suggest that the spectral analysis is helpful yet insufficient for the comprehensive understanding of network synchronization.

  6. The Lisse effect revisited.

    Weeks, Edwin P

    2002-01-01

    The Lisse effect is a rarely noted phenomenon occurring when infiltration caused by intense rain seals the surface soil layer to airflow, trapping air in the unsaturated zone. Compression of air by the advancing front results in a pressure increase that produces a water-level rise in an observation well screened below the water table that is several times as large as the distance penetrated by the wetting front. The effect is triggered by intense rains and results in a very rapid water-level rise, followed by a recession lasting a few days. The Lisse effect was first noted and explained by Thal Larsen in 1932 from water-level observations obtained in a shallow well in the village of Lisse, Holland. The original explanation does not account for the increased air pressure pushing up on the bottom of the wetting front. Analysis of the effect of this upward pressure indicates that a negative pressure head at the base of the wetting front, psi(f), analogous to that postulated by Green and Ampt (1911) to explain initially rapid infiltration rates into unsaturated soils, is involved in producing the Lisse effect. Analysis of recorded observations of the Lisse effect by Larsen and others indicates that the water-level rise, which typically ranges from 0.10 to 0.55 m, should be only slightly larger than psi(f) and that the depth of penetration of the wetting front is no more than several millimeters.

  7. Habituation of reinforcer effectiveness

    David R Lloyd

    2014-01-01

    Full Text Available In this paper we propose an integrative model of habituation of reinforcer effectiveness (HRE that links behavioral and neural based explanations of reinforcement. We argue that habituation of reinforcer effectiveness (HRE is a fundamental property of reinforcing stimuli. Most reinforcement models implicitly suggest that the effectiveness of a reinforcer is stable across repeated presentations. In contrast, an HRE approach predicts decreased effectiveness due to repeated presentation. We argue that repeated presentation of reinforcing stimuli decreases their effectiveness and that these decreases are described by the behavioral characteristics of habituation (McSweeney and Murphy, 2009;Rankin et al., 2009. We describe a neural model that postulates a positive association between dopamine neurotransmission and HRE. We present evidence that stimulant drugs, which artificially increase dopamine neurotransmission, disrupt (slow normally occurring HRE and also provide evidence that stimulant drugs have differential effects on operant responding maintained by reinforcers with rapid vs. slow HRE rates. We hypothesize that abnormal HRE due to genetic and/or environmental factors may underlie some behavioral disorders. For example, recent research indicates that slow-HRE is predictive of obesity. In contrast ADHD may reflect ‘accelerated-HRE’. Consideration of HRE is important for the development of effective reinforcement based treatments. Finally, we point out that most of the reinforcing stimuli that regulate daily behavior are non-consumable environmental/social reinforcers which have rapid-HRE. The almost exclusive use of consumable reinforcers with slow-HRE in pre-clinical studies with animals may have caused the importance of HRE to be overlooked. Further study of reinforcing stimuli with rapid-HRE is needed in order to understand how habituation and reinforcement interact and regulate behavior.

  8. Edge effects in composites

    Guz, A.N.; Kokhanenko, Yu.V.

    1995-01-01

    In the present article we survey papers on edge effects investigated by the rigorous approach. We interpret edge effects as stressed states created in a composite as a result of zones in which the stresses exhibit a rapidly changing behavior in comparison with the slow variation of the stresses outside such zones. Here the range of the edge effect is defined as the distance from the point of its inception to the boundary of the edge zone in a given direction. The transition of the stresses to the slowly varying state is determined within prescribed error limits. The size and configuration of the edge zone depends on the tolerated error. Clearly, the main difficulty associated with the rigorous approach is finding solutions of the elasticity problems. The finite-difference approach is suggested for the approximate solution of these problems. In light of the comparative time consumption of the finite-difference approach, it is best directed at certain classes of problems rather than at particular individual problems. Not too many papers on the investigation of edge effects by the rigorous approach have been published to date. Below, following in their footsteps, we formulate edge effect problems in composites, determine classes of problems, and investigate edge effects in composite materials and structural elements using them in Cartesian (planar and three-dimensional problems) and cylindrical (axisymmetric problems) coordinate frames. We note that the division of approaches to the study of edge effects into qualitative (nonrigorous) and quantitative (rigorous) reflects the authors own point of view. Of course, other schemes of classification of the approaches to the investigation of the regions of rapidly varying states in composites are possible

  9. Radiation effects and radioprotectors

    Purohit, R.K., E-mail: dr_rajendra_purohit@yahoo.co.in [Radiation Biology Laboratory, Department of Zoology, Govt. Dungar College, Bikaner (India); Bugalia, Saroj [Department of Zoology, S.K. Kalyan College, Sikar (India); Dakshene, Monika [Department of Chemistry, Govt. College, Kota (India)

    2012-07-01

    Radiation exposure causes damage to biological systems and these damages are mediated by the generation of free radicals and reactive oxygen species targeting vital cellular components such as DNA and membranes. DNA repair systems and the endogenous cellular biochemical defense mechanisms against reactive oxygen species and antioxidants enzymes like reduced Glutathione (GSH), Superoxide dismutase, Glutathione peroxidase catalase etc. fail upon exposures to higher as well as chronic radiation doses leading to alterations in cell functions, cell death or mutations. Radioprotectors prevent these alterations and protect cells and tissues from the deleterious effects of radiations. Radioprotectors are of great importance due to their possible and potential application during planned radiation exposures such as radiotherapy, diagnostic scanning, clean up operations in nuclear accidents, space expeditions etc. and Unplanned radiations exposures such as accidents in nuclear industry, nuclear terrorism, natural background radiation etc. Many of the available synthetic radioprotectors are toxic to mammalian system at doses required to be effective as radioprotector. Increasing uses of ionizing radiation have drawn the attention of many radiobiologists towards their undesired side effects produced in various tissues and for modifying them to facilitate the beneficial uses of radiation. Modification of radiation response is obtained by means of chemical substances that can significantly decrease the magnitude of response when present in a biological system during irradiation. Radioprotectors are chemicals that modify a cell's response to radiation. Radioprotectors are drugs that protect normal (non cancerous) cells from the damage caused by radiation therapy. These agents promote the repair of normal cells that are exposed to radiation. Various chemicals, like Cysteamine, MPG , WR-2721 have been tested for the protection against harmful effects of radiation. These radio

  10. Radiation effects and radioprotectors

    Purohit, R.K.; Bugalia, Saroj; Dakshene, Monika

    2012-01-01

    Radiation exposure causes damage to biological systems and these damages are mediated by the generation of free radicals and reactive oxygen species targeting vital cellular components such as DNA and membranes. DNA repair systems and the endogenous cellular biochemical defense mechanisms against reactive oxygen species and antioxidants enzymes like reduced Glutathione (GSH), Superoxide dismutase, Glutathione peroxidase catalase etc. fail upon exposures to higher as well as chronic radiation doses leading to alterations in cell functions, cell death or mutations. Radioprotectors prevent these alterations and protect cells and tissues from the deleterious effects of radiations. Radioprotectors are of great importance due to their possible and potential application during planned radiation exposures such as radiotherapy, diagnostic scanning, clean up operations in nuclear accidents, space expeditions etc. and Unplanned radiations exposures such as accidents in nuclear industry, nuclear terrorism, natural background radiation etc. Many of the available synthetic radioprotectors are toxic to mammalian system at doses required to be effective as radioprotector. Increasing uses of ionizing radiation have drawn the attention of many radiobiologists towards their undesired side effects produced in various tissues and for modifying them to facilitate the beneficial uses of radiation. Modification of radiation response is obtained by means of chemical substances that can significantly decrease the magnitude of response when present in a biological system during irradiation. Radioprotectors are chemicals that modify a cell's response to radiation. Radioprotectors are drugs that protect normal (non cancerous) cells from the damage caused by radiation therapy. These agents promote the repair of normal cells that are exposed to radiation. Various chemicals, like Cysteamine, MPG , WR-2721 have been tested for the protection against harmful effects of radiation. These radio

  11. Spin Hall effects

    Sinova, Jairo; Valenzuela, Sergio O.; Wunderlich, J.; Back, C. H.; Jungwirth, T.

    2015-10-01

    Spin Hall effects are a collection of relativistic spin-orbit coupling phenomena in which electrical currents can generate transverse spin currents and vice versa. Despite being observed only a decade ago, these effects are already ubiquitous within spintronics, as standard spin-current generators and detectors. Here the theoretical and experimental results that have established this subfield of spintronics are reviewed. The focus is on the results that have converged to give us the current understanding of the phenomena, which has evolved from a qualitative to a more quantitative measurement of spin currents and their associated spin accumulation. Within the experimental framework, optical-, transport-, and magnetization-dynamics-based measurements are reviewed and linked to both phenomenological and microscopic theories of the effect. Within the theoretical framework, the basic mechanisms in both the extrinsic and intrinsic regimes are reviewed, which are linked to the mechanisms present in their closely related phenomenon in ferromagnets, the anomalous Hall effect. Also reviewed is the connection to the phenomenological treatment based on spin-diffusion equations applicable to certain regimes, as well as the spin-pumping theory of spin generation used in many measurements of the spin Hall angle. A further connection to the spin-current-generating spin Hall effect to the inverse spin galvanic effect is given, in which an electrical current induces a nonequilibrium spin polarization. This effect often accompanies the spin Hall effect since they share common microscopic origins. Both can exhibit the same symmetries when present in structures comprising ferromagnetic and nonmagnetic layers through their induced current-driven spin torques or induced voltages. Although a short chronological overview of the evolution of the spin Hall effect field and the resolution of some early controversies is given, the main body of this review is structured from a pedagogical

  12. Magnetoelectric effects in manganites

    Jeen, Hyoung Jeen

    Research on manganites has been conducted for more than half century. Recent discoveries of colossal responses to external fields such as colossal magnetoresistance effects and correlation among spin, orbital, and lattice in phase separated manganites and multiferroic manganites have motivated me to understand these materials. The main purpose of this dissertation is to understand magnetoelectric effects in phase separated (La1-yPr y)1-xCaxMnO3 (LPCMO) thin films and multiferroic BiMnO3 (BMO) thin films. First, high quality phase separated manganite thin films have been successfully grown. To grow the high quality manganite thin films, extensive effort was devoted to fine tuning of oxygen pressure, temperature, and laser fluence during film growth. As-grown films were characterized with various ex-situ techniques: magnetization measurements, transport measurements, x-ray diffraction, atomic force microscopy, and/or transmission electron microscopy to remove the effects of impurities and unwanted strains except substrate induced strain. Second, three major results were obtained in high quality phase separated LPCMO thin films. These results are based on the dynamic nature of phases in LPCMO. 1) LPCMO thin films showed single domain to multi-domain transition during cooling. This transition can be tuned by substrate stress induced in-plane magnetic anisotropy. 2) Evidence for the origin of colossal electroresistance (CER) effect has been observed. The CER is triggered by dielectrophoresis, or movements of ferromagnetic metallic (FMM) phase, which is manifested in anisotropic transport properties in microfabricated LPCMO cross structures. This fluidic nature of the FMM phase in LPCMO under high electric fields lead to exotic magnetoelectric effects. 3) Electric field effects on magnetotransport properties have been observed. This phenomena can also be tuned by the combined effect of substrate strain and current flow. This combined effect of electric and magnetic

  13. Porters versus rowers: a unified stochastic model of motor proteins.

    Leibler, S; Huse, D A

    1993-06-01

    We present a general phenomenological theory for chemical to mechanical energy transduction by motor enzymes which is based on the classical "tight-coupling" mechanism. The associated minimal stochastic model takes explicitly into account both ATP hydrolysis and thermal noise effects. It provides expressions for the hydrolysis rate and the sliding velocity, as functions of the ATP concentration and the number of motor enzymes. It explains in a unified way many results of recent in vitro motility assays. More importantly, the theory provides a natural classification scheme for the motors: it correlates the biochemical and mechanical differences between "porters" such as cellular kinesins or dyneins, and "rowers" such as muscular myosins or flagellar dyneins.

  14. Silica-gel Catalyzed Facile Synthesis of 3,4-Dihydropyrimidinones

    Agarwal, Sameer; Aware, Umesh; Patil, Amit; Rohera, Vinita; Jain, Mukul; Patel, Pankaj; Ghate, Manjunath

    2012-01-01

    We have developed a mild and highly effective procedure for the one-pot synthesis of substituted dihydropyrimidinones in high yields using silica gel as a green, highly efficient and recyclable heterogeneous catalyst. Our approach can be applied to the preparation of a wide range of synthetic analogues for structure-activity studies. Investigations in this direction are ongoing. The pyrimidinone ring is a basic substructure of numerous biologically active alkaloids and pharmaceutical products. These cores are regarded as one of the most important groups of drug-like scaffolds. 3,4-dihydropyrimidinones above are known to exhibit variety of pharmacological activity such as calcium channel modulation, mitotic kinesin Eg5 inhibition, antiviral, anti-inflammatory, antibacterial activity, etc

  15. Simultaneous 3D tracking of passive tracers and microtubule bundles in an active gel

    Fan, Yi; Breuer, Kenneth S.; Fluids Team

    Kinesin-driven microtubule bundles generate a spontaneous flow in unconfined geometries. They exhibit properties of active matter, including the emergence of collective motion, reduction of apparent viscosity and consumption of local energy. Here we present results from 3D tracking of passive tracers (using Airy rings and 3D scanning) synchronized with 3D measurement of the microtubule bundles motion. This technique is applied to measure viscosity variation and collective flow in a confined geometry with particular attention paid to the self-pumping system recently reported by Wu et al. (2016). Results show that the viscosity in an equilibrium microtubule network is around half that of the isotropic unbundled microtubule solution. Cross-correlations of the active microtubule network and passive tracers define a neighborhood around microtubule bundles in which passive tracers are effectively transported. MRSEC NSF.

  16. Silica-gel Catalyzed Facile Synthesis of 3,4-Dihydropyrimidinones

    Agarwal, Sameer; Aware, Umesh; Patil, Amit; Rohera, Vinita; Jain, Mukul; Patel, Pankaj [Zydus Research Centre, Sarkhej-Bavla N.H., Ahmedabad (India); Ghate, Manjunath [Nirma University, Ahmedabad (India)

    2012-02-15

    We have developed a mild and highly effective procedure for the one-pot synthesis of substituted dihydropyrimidinones in high yields using silica gel as a green, highly efficient and recyclable heterogeneous catalyst. Our approach can be applied to the preparation of a wide range of synthetic analogues for structure-activity studies. Investigations in this direction are ongoing. The pyrimidinone ring is a basic substructure of numerous biologically active alkaloids and pharmaceutical products. These cores are regarded as one of the most important groups of drug-like scaffolds. 3,4-dihydropyrimidinones above are known to exhibit variety of pharmacological activity such as calcium channel modulation, mitotic kinesin Eg5 inhibition, antiviral, anti-inflammatory, antibacterial activity, etc.

  17. Pharmacological effects of biotin.

    Fernandez-Mejia, Cristina

    2005-07-01

    In the last few decades, more vitamin-mediated effects have been discovered at the level of gene expression. Increasing knowledge on the molecular mechanisms of these vitamins has opened new perspectives that form a connection between nutritional signals and the development of new therapeutic agents. Besides its role as a carboxylase prosthetic group, biotin regulates gene expression and has a wide repertoire of effects on systemic processes. The vitamin regulates genes that are critical in the regulation of intermediary metabolism: Biotin has stimulatory effects on genes whose action favors hypoglycemia (insulin, insulin receptor, pancreatic and hepatic glucokinase); on the contrary, biotin decreases the expression of hepatic phosphoenolpyruvate carboxykinase, a key gluconeogenic enzyme that stimulates glucose production by the liver. The findings that biotin regulates the expression of genes that are critical in the regulation of intermediary metabolism are in agreement with several observations that indicate that biotin supply is involved in glucose and lipid homeostasis. Biotin deficiency has been linked to impaired glucose tolerance and decreased utilization of glucose. On the other hand, the diabetic state appears to be ameliorated by pharmacological doses of biotin. Likewise, pharmacological doses of biotin appear to decrease plasma lipid concentrations and modify lipid metabolism. The effects of biotin on carbohydrate metabolism and the lack of toxic effects of the vitamin at pharmacological doses suggest that biotin could be used in the development of new therapeutics in the treatment of hyperglycemia and hyperlipidemia, an area that we are actively investigating.

  18. NEUROTROPHIC EFFECTS OF ETIFOXINE

    I. Yu. Torshin

    2016-01-01

    Full Text Available Higher anxiety results in the decreased levels of various neurotrophic factors and enkephalins and in impaired production of proinflammatory cytokines. The anxiolytic etifoxine is used to treat anxiety states and adjustment disorders. Etifoxine modulates the GABAergic transmission and metabolism of neurosteroids. The latter determines the unique neurotrophic and neuroprotective properties of the drug, such as increased expression of neurotrophic factors, regeneration of nerve fibers, and preservation and regeneration of myelin sheaths. Other important pharmacological effects of an etifoxine molecule have been also discovered; these are to relieve allodynia related to 3α-steroids and GABA receptors and to effectively treat cerebral edema, experimental autoimmune encephalitis, and excessive nervous excitability in the presence of alcohol withdrawal. In addition, the chemoreactome simulation of the molecule of etifoxine has established that its attenuated side effects are due to its lower interaction with serotonin, acetylcholine, adrenergic and other neurotransmitter receptors than is shown by benzodiazepines. Etifoxine has been also found to have anti-inflammatory (due to antihistamine and antileukotriene effects and antitumor activities and an ability to affect hemodynamics and vessel walls.The paper presents a systematic analysis of the results of trials of the neurotrophic properties of etifoxine. It considers how the drug stimulates the expression of neurotrophic factors, accelerates the maturation and regeneration of nerve fibers, and regenerates myelin sheaths.The neurotrophic effects of etifoxine along with its anxiolytic activity will accelerate the recovery of patients with different neurological diseases and enhance the quality of their neurorehabilitation.

  19. Pleiotropic effects of statins

    Narasaraju Kavalipati

    2015-01-01

    Full Text Available Statins or 3-hydroxy-methylglutaryl coenzyme A (HMG CoA reductase inhibitors not only prevents the synthesis of cholesterol biosynthesis but also inhibits the synthesis of essential isoprenoid intermediates such as farnesyl pyrophosphate, geranylgeranyl pyrophosphate, isopentanyl adenosine, dolichols and polyisoprenoid side chains of ubiquinone, heme A, and nuclear lamins. These isoprenoid intermediates are required for activation of various intracellular/signaling proteins- small guanosine triphosphate bound protein Ras and Ras-like proteins like Rho, Rab, Rac, Ral, or Rap which plays an indispensible role in multiple cellular processes. Reduction of circulating isoprenoids intermediates as a result of HMG CoA reductase inhibition by statins prevents activation of these signalling proteins. Hence, the multiple effects of statins such as antiinflammatory effects, antioxidant effects, antiproliferative and immunomodulatory effects, plaque stability, normalization of sympathetic outflow, and prevention of platelet aggregation are due to reduction of circulating isoprenoids and hence inactivation of signalling proteins. These multiple lipid-independent effects of statins termed as statin pleiotropy would potentially open floodgates for research in multiple treatment domains catching attentions of researchers and clinician across the globe.

  20. Heavy particle effects

    Yao, Y.P.

    1981-01-01

    There are two problems discussed, both of which have to do with dissimilar magnitudes in mass. Theoretically, we can devise the large difference in mass as observed by decreeing some vev, v/sub i/ to be much bigger than the other; or, we can assume that some couplings g/sub i/ are much stronger. These two different assumptions give rise to entirely different patterns of interaction in the resulting theory. The first way to generate a mass hierarchy can be called the soft way, because in the zeroth order, the large mass scale leaves its foot print merely in a few effective parameters of the residual theory. The effective theory is renormalizable, sans anomaly. In this limit, the heavy particles decouple. The second assumption (g/sub j/ much greater than g/sub j'/) to create mass hierarchy does a lot of violence to a theory. Effects of the large mass scale will be felt by the system left behind in many ways. An infinite number of parameters are needed to summarize the effects in this limit. This is called the hard limit. It follows that the resulting effective Lagrangian, if in fact it makes sense to construct one at all, will be non-polynomial and apparently non-renormalizable

  1. Relative age effect: implications for effective practice.

    Andronikos, Georgios; Elumaro, Adeboye Israel; Westbury, Tony; Martindale, Russell J J

    2016-01-01

    Physical and psychological differences related to birthdate amongst athletes of the same selection year have been characterised as the "relative age effects" (RAEs). RAEs have been identified in a variety of sports, both at youth and adult level, and are linked with dropout of athletes and a reduction of the talent pool. This study examined the existence, mechanisms and possible solutions to RAEs using qualitative methodology. Seven experts in the field of talent identification and development were interviewed. Inductive analysis of the data showed that, while there was mixed evidence for the existence of RAEs across sports, the eradication of RAEs was attributed to controllable features of the development environment. The factors reported included the structure of "categories" used to group athletes within the sport (e.g. age, weight, size, skills), recognition and prioritisation of long-term development over "short term win focus." Education of relevant parties (e.g. coaches, scouts, clubs) about RAEs and the nature of "talent" within a long-term context was suggested, along with careful consideration of the structure of the development environment (e.g. delayed selection, provision for late developers, focus on skills not results, use of challenge). Implications for research and practice are discussed.

  2. Biophysical radiation effects

    Fidorra, J.

    1982-07-01

    The biological effectiveness of ionizing radiation is based upon the absorption of energy in molecular structures of a cell. Because of the quantum nature of radiation large fluctuations of energy concentration in subcellulare regions has to be considered. In addition both the spatial distribution of a sensitive molecular target and cellulare repair processes has to be taken into consideration for an assessment of radiation action. In radiation protection the difference between the quality factor and the Relative Biological Effectiveness has a fundamental meaning and will be discussed in more detail. The present report includes a short review on some relevant models on radiation action and a short discussion on effects of low dose irradiation. (orig.) [de

  3. Improving nuclear regulatory effectiveness

    2001-01-01

    Ensuring that nuclear installations are operated and maintained in such a way that their impact on public health and safety is as low as reasonably practicable has been and will continue to be the cornerstone of nuclear regulation. In the past, nuclear incidents provided the main impetus for regulatory change. Today, economic factors, deregulation, technological advancements, government oversight and the general requirements for openness and accountability are leading regulatory bodies to review their effectiveness. In addition, seeking to enhance the present level of nuclear safety by continuously improving the effectiveness of regulatory bodies is seen as one of the ways to strengthen public confidence in the regulatory systems. This report covers the basic concepts underlying nuclear regulatory effectiveness, advances being made and future requirements. The intended audience is primarily nuclear safety regulators, but government authorities, nuclear power plant operators and the general public may also be interested. (author)

  4. Security effectiveness review (SER)

    Kouprianova, I.; Ek, D.; Showalter, R.; Bergman, M.

    1998-01-01

    As part of the on-going DOE/Russian MPC and A activities at the Institute of Physics and Power Engineering (IPPE) and in order to provide a basis for planning MPC and A enhancements, an expedient method to review the effectiveness of the MPC and A system has been adopted. These reviews involve the identification of appropriate and cost-effective enhancements of facilities at IPPE. This effort requires a process that is thorough but far less intensive than a traditional vulnerability assessment. The SER results in a quick assessment of current and needed enhancements. The process requires preparation and coordination between US and Russian analysts before, during, and after information gathering at the facilities in order that the analysis is accurate, effective, and mutually agreeable. The goal of this paper is to discuss the SER process, including the objectives, time scale, and lessons learned at IPPE

  5. Effective Nutritional Supplement Combinations

    Cooke, Matt; Cribb, Paul J.

    Few supplement combinations that are marketed to athletes are supported by scientific evidence of their effectiveness. Quite often, under the rigor of scientific investigation, the patented combination fails to provide any greater benefit than a group given the active (generic) ingredient. The focus of this chapter is supplement combinations and dosing strategies that are effective at promoting an acute physiological response that may improve/enhance exercise performance or influence chronic adaptations desired from training. In recent years, there has been a particular focus on two nutritional ergogenic aids—creatine monohydrate and protein/amino acids—in combination with specific nutrients in an effort to augment or add to their already established independent ergogenic effects. These combinations and others are discussed in this chapter.

  6. Radiomimetic effects of meclofenoxate

    Meier, K.; Mehlhorn, D.

    1990-01-01

    Meclofenoxate, a nootropic, by virtue of its chemical nature is an ester of p-chlorophenoxyacetic acid and dimethylaminoethanol. On top of its typical indications, particular attention was given to its radiomimetic effect to which evidence had been produced on tissue cultures by Sladek, 1977. Animal experiments were conducted to investigate the effect in the context of a transplantation tumour. One single locally delimited X-ray irradiation with concomitant administration of meclofenoxate was applied to the animals. 14 days after tumour transplantation. The radiomimetic effect of meclofenoxate was confirmed under the conditions chosen for the animal experiments. However, no confirmation was obtained for the assumption of p-chlorophenoxyacetic acid being the only active substance. (author)

  7. Quantum Zeno effect

    Petrosky, T.; Tasaki, S.; Prigogine, I.

    1991-01-01

    In 1977, Misra and Sudarshan showed, based on the quantum measurement theory, that an unstable particle will never be found to decay when it is continuously observed. They called it the quantum Zeno effect (or paradox). More generally the quantum Zeno effect is associated to the inhibition of transitions by frequent measurements. This possibility has attracted much interest over the last years. Recently, Itano, Heinzen, Bollinger and Wineland have reported that they succeeded in observing the quantum Zeno effect. This would indeed be an important step towards the understanding of the role of the observer in quantum mechanics. However, in the present paper, we will show that their results can be recovered through conventional quantum mechanics and do not involve a repeated reduction (or collapse) of the wave function. (orig.)

  8. Heavy rain effects

    Dunham, R. Earl, Jr.

    1994-01-01

    This paper summarizes the current state of knowledge of the effect of heavy rain on airplane performance. Although the effects of heavy rain on airplane systems and engines are generally known, only recently has the potential aerodynamic effect of heavy rain been recognized. In 1977 the United States Federal Aviation Administration (FAA) conducted a study of 25 aircraft accidents and incidents which occurred between 1964 and 1976 in which low-altitude wind shear could have been a contributing factor. Of the 25 cases (23 approach or landing and 2 take-off) in the study, ten cases had occurred in a rain environment, and in five cases these were classified as intense or heavy rain encounters. These results led to the reconsideration of high-intensity, short-duration rainfall as a potential weather-related aircraft safety hazard, particularly in the take-off and/or approach phases of flight.

  9. Biological effects of neutrons

    Ogiu, Toshiaki; Ohmachi, Yasushi; Ishida, Yuka [National Inst. of Radiological Sciences, Chiba (JP)] [and others

    2003-03-01

    Although the occasion to be exposed to neutrons is rare in our life, except for nuclear accidents like in the critical accident at Tokai-mura in 1999, countermeasures against accident should be always prepared. In the Tokai-mura accident, residents received less than 21 mSv of neutrons and gamma rays. The cancer risks and fetal effects of low doses of neutrons were matters of concern among residents. The purpose of this program is to investigate the relative biological effectiveness (RBE) for leukemias, and thereby to assess risks of neutrons. Animal experiments are planed to obtain the following RBEs: (1) RBE for the induction of leukemias in mice and (2) RBE for effects on fetuses. Cyclotron fast neutrons (10 MeV) and electrostatic accelerator-derived neutrons (2 MeV) are used for exposure in this program. Furthermore, cytological and cytogenetic analyses will be performed. (author)

  10. Stereoelectronic Substituent Effects

    Bols, Mikael; Jensen, Henrik Helligsø

    2006-01-01

    An investigation was carried Out on the influence of the stereo-chemistry of substituents, particularly hydroxyl groups, on their electronic effects in piperidines, carbohydrates (pyranosides), and related compounds. Polar groups, such as OH, OR, and F, were found in the 3 and 4 position to be much...... more electron-withdrawing when positioned equatorially rather than axially. In contrast, little difference in electronic effects was observed from apolar groups as a result of epimerization. These observations were believed to be caused by differences in charge-dipole interactions and were used...... to explain why stereoisomeric glycosides hydrolyze with different rates. The conformational changes of hydroxylated piperidines and related compounds as a function of pH were likewise explained from the different substituent effects of axial and equatorial OH groups....

  11. Bystander effects of radiation

    Umar, Neethu Fathima; Daniel, Nittu

    2013-01-01

    The Radiation-Induced Bystander Effect is the phenomenon in which unirradiated cells show irradiated effects due to the signals received from nearby irradiated cells. Evidence suggests that targeted cytoplasmic irradiation results in mutation in the nucleus of the hit cells. Cells that are not directly hit by an alpha particle, but are in the vicinity of one that is hit, also contribute to the genotoxic response of the cell population. When cells are irradiated, and the medium is transferred to unirradiated cells, these unirradiated cells show bystander responses when assayed for clonogenic survival and oncogenic transformation. The demonstration of a bystander effect in human tissues and, more recently, in whole organisms have clear implication of the potential relevance of the non-targeted response to human health. This effect may also contribute to the final biological consequences of exposure to low doses of radiation. The radiation-induced bystander effect represents a paradigm shift in our understanding of the radiobiological effects of ionizing radiation, in that extranuclear and extracellular events may also contribute to the final biological consequences of exposure to low doses of radiation. Multiple pathways are involved in the bystander phenomenon, and different cell types respond differently to bystander signalling. Using cDNA microarrays, a number of cellular signalling genes, including cyclooxygenase-2 (CQX-2), have been shown to be casually linked to the bystander phenomenon. The observation that inhibition of the phosphorylation of extracellular signal-related kinase (ERK) suppressed the bystander response further confirmed the important role of the mitogen-activated protein kinase (MAPK) signalling cascade in the bystander process. The cells deficient in mitochondrial DNA showed a significantly reduced response to bystander signalling, suggesting a functional role of mitochondria in the signalling process. (author)

  12. Habituation of reinforcer effectiveness.

    Lloyd, David R; Medina, Douglas J; Hawk, Larry W; Fosco, Whitney D; Richards, Jerry B

    2014-01-09

    In this paper we propose an integrative model of habituation of reinforcer effectiveness (HRE) that links behavioral- and neural-based explanations of reinforcement. We argue that HRE is a fundamental property of reinforcing stimuli. Most reinforcement models implicitly suggest that the effectiveness of a reinforcer is stable across repeated presentations. In contrast, an HRE approach predicts decreased effectiveness due to repeated presentation. We argue that repeated presentation of reinforcing stimuli decreases their effectiveness and that these decreases are described by the behavioral characteristics of habituation (McSweeney and Murphy, 2009; Rankin etal., 2009). We describe a neural model that postulates a positive association between dopamine neurotransmission and HRE. We present evidence that stimulant drugs, which artificially increase dopamine neurotransmission, disrupt (slow) normally occurring HRE and also provide evidence that stimulant drugs have differential effects on operant responding maintained by reinforcers with rapid vs. slow HRE rates. We hypothesize that abnormal HRE due to genetic and/or environmental factors may underlie some behavioral disorders. For example, recent research indicates that slow-HRE is predictive of obesity. In contrast ADHD may reflect "accelerated-HRE." Consideration of HRE is important for the development of effective reinforcement-based treatments. Finally, we point out that most of the reinforcing stimuli that regulate daily behavior are non-consumable environmental/social reinforcers which have rapid-HRE. The almost exclusive use of consumable reinforcers with slow-HRE in pre-clinical studies with animals may have caused the importance of HRE to be overlooked. Further study of reinforcing stimuli with rapid-HRE is needed in order to understand how habituation and reinforcement interact and regulate behavior.

  13. Greenhouse effects on Venus

    Bell, Peter M.

    Calculations that used Pioneer-Venus measurements of atmosphere composition, temperature profiles, and radiative heating predicted Venus' surface temperature ‘very precisely,’ says the Ames Research Center. The calculations predict not only Venus' surface temperature but agree with temperatures measured at various altitudes above the surface by the four Pioneer Venus atmosphere probe craft.Using Pioneer-Venus spacecraft data, a research team has virtually proved that the searing 482° C surface temperature of Venus is due to an atmospheric greenhouse effect. Until now the Venus greenhouse effect has been largely a theory.

  14. Low doses effects

    Tubiana, M.

    1997-01-01

    In this article is asked the question about a possible carcinogens effect of low dose irradiation. With epidemiological data, knowledge about the carcinogenesis, the professor Tubiana explains that in spite of experiments made on thousand or hundred of thousands animals it has not been possible to bring to the fore a carcinogens effect for low doses and then it is not reasonable to believe and let the population believe that low dose irradiation could lead to an increase of neoplasms and from this point of view any hardening of radiation protection standards could in fact, increase anguish about ionizing radiations. (N.C.)

  15. Effective quantum field theories

    Georgi, H.M.

    1993-01-01

    The most appropriate description of particle interactions in the language of quantum field theory depends on the energy at which the interactions are studied; the description is in terms of an ''effective field theory'' that contains explicit reference only to those particles that are actually important at the energy being studied. The various themes of the article are: local quantum field theory, quantum electrodynamics, new physics, dimensional parameters and renormalizability, socio-dynamics of particle theory, spontaneously broken gauge theories, scale dependence, grand unified and effective field theories. 2 figs

  16. Harnessing greenhouse effect

    Meunier, F.; Rivet, P.; Terrier, M.F.

    2005-01-01

    This book considers the energy and greenhouse effect questions in a global way. It presents the different methods of fight against the increase of the greenhouse effect (energy saving, carbon sinks, cogeneration,..), describes the main alternative energy sources to fossil fuels (biomass, wind power, solar, nuclear,..), and shows that, even worrying, the future is not so dark as it seems to be and that technical solutions exist which will allow to answer the worldwide growing up energy needs and to slow down the climatic drift. (J.S.)

  17. Nonequilibrium effects in Isoscaling

    Dorso, C. O.; Lopez, J. A.

    2007-01-01

    In this work we study within a simple model different properties of the system that allow us to understand the properties of the isoscaling observable. We first show that isoscaling is a general property of fragmenting systems. We show this by using a simple generalized percolation model. We show that the usual isoscaling property can be obtained in the case of bond percolation in bichromatic lattices with any regular topology. In this case the probabilities of each color (isospin) are independent. We then explore the effect of introducing 'non-equilibrium' effects

  18. The Lazarus effect

    Laurent Guiraud

    1998-01-01

    Members of the RD39 collaboration stage a demonstration of the Lazarus effect in the CERN cryolab. At the LHC experiments, the front-line inner detectors - trackers - will be traversed by a mammoth thousand million million passing particles per square centimetre over the lifetimes of the experiments. After long exposure to passing particles, defects appear in the silicon and the signal is destroyed. A group of physicists at Bern University have found that at temperatures below 100 K, dead detectors apparently come back to life. They're calling their discovery the Lazarus effect after the Biblical character raised from the dead by Jesus after he had been entombed for four days.

  19. Climate, greenhouse effect, energy

    Henriksen, Thormod; Kanestroem, Ingolf

    2001-01-01

    The book has sections on the sun as energy source, the earth climate and it's changes and factors influencing this, the greenhouse effect on earth and other planets, greenhouse gases and aerosols and their properties and importance, historic climate and paleoclimate, climatic models and their uses and limitations, future climate, consequences of climatic changes, uncertainties regarding the climate and measures for reducing the greenhouse effect. Finally there are sections on energy and energy resources, the use, sources such as fossil fuels, nuclear power, renewable resources, heat pumps, energy storage and environmental aspects and the earth magnetic field is briefly surveyed

  20. Shape memory effect alloys

    Koshimizu, S.

    1992-01-01

    Although the pseudo- or super-elasticity phenomena and the shape memory effect were known since the 1940's, the enormous curiosity and the great interest to their practical applications emerged with the development of the NITINOL alloy (Nickel-Titanium Naval Ordance Laboratory) by the NASA during the 1960's. This fact marked the appearance of a new class of materials, popularly known as shape memory effect alloys (SMEA). The objective of this work is to present a state-of-the-art of the development and applications for the SMEA. (E.O.)

  1. The Vampire Effect

    Erfgen, Carsten; Zenker, Sebastian; Sattler, Henrik

    2015-01-01

    Although many brand managers favor the use of celebrities in advertisements, others worry that celebrities overshadow the brand and thus impair brand recall. Practitioners refer to this overshadowing as the vampire effect, defined as a decrease in brand recall for an advertising stimulus...... that features a celebrity endorser versus the same stimulus with an unknown but equally attractive endorser. Because there is no agreement about whether this overshadowing really exists, this research analyzes the existence of the vampire effect and its moderators in a series of experiments with a total of 4...

  2. Level width broadening effect

    Zhang Jingshang

    2003-01-01

    In file-6 for double-differential cross sections, the level width broadening effect should be taken into account properly due to Heisenberg' uncertainty. Besides level width broadening effect, the energy resolution in the measurements is also needed in fitting measurement procedure. In general, the traditional normal Gaussian expansion is employed. However, to do so in this way the energy balance could not be held. For this reason, the deformed Gaussian expansion functions with exponential form for both the single energy point and continuous spectrum are introduced, with which the normalization and energy balance conditions could be held exactly in the analytical form. (author)

  3. Proactively evaluating training effectiveness

    Fetterman, Harry E.

    2003-01-01

    A common model of the five phase Systematic Approach to Training (SAT) displays the fifth phase, evaluation, feeding back into the previous four phases: analysis, design, development, and implementation. Evaluating training effectiveness in PP and L's Nuclear Department is not simply the fifth phase of the SAT. PP and L has demonstrated a more effective methodology is realized when evaluation is built into each of the other four phases. At PP and L, evaluation is conducted formatively throughout the first four phases of the SAT process and summatively after implementation. (author)

  4. The quantized Hall effect

    Klitzing von, K.

    1989-01-01

    The quantized Hall effect is theoretically explained in detail as are its basic properties. The explanation is completed with the pertinent mathematical relations and illustrative figures. Experimental data are critically assessed obtained by quantum transport measurement in a magnetic field on two-dimensional systems. The results are reported for a MOSFET silicon transistor and for GaAs-Al x Ga 1-x As heterostructures. The application is discussed of the quantized Hall effect in determining the fine structure constant or in implementing the resistance standard. (M.D.). 27 figs., 57 refs

  5. Analgesic effects of melatonin

    Wilhelmsen, Michael; Amirian, Ilda; Reiter, Russel J

    2011-01-01

    studies, melatonin shows potent analgesic effects in a dose-dependent manner. In clinical studies, melatonin has been shown to have analgesic benefits in patients with chronic pain (fibromyalgia, irritable bowel syndrome, migraine). The physiologic mechanism underlying the analgesic actions of melatonin...... has not been clarified. The effects may be linked to G(i) -coupled melatonin receptors, to G(i) -coupled opioid µ-receptors or GABA-B receptors with unknown downstream changes with a consequential reduction in anxiety and pain. Also, the repeated administration of melatonin improves sleep and thereby...

  6. Analgesic effects of melatonin

    Wilhelmsen, Michael; Amirian, Ilda; Reiter, Russel J

    2011-01-01

    studies, melatonin shows potent analgesic effects in a dose-dependent manner. In clinical studies, melatonin has been shown to have analgesic benefits in patients with chronic pain (fibromyalgia, irritable bowel syndrome, migraine). The physiologic mechanism underlying the analgesic actions of melatonin...... has not been clarified. The effects may be linked to G(i) -coupled melatonin receptors, to G(i) -coupled opioid μ-receptors or GABA-B receptors with unknown downstream changes with a consequential reduction in anxiety and pain. Also, the repeated administration of melatonin improves sleep and thereby...

  7. Solvent effects in chemistry

    Buncel, Erwin

    2015-01-01

    This book introduces the concepts, theory and experimental knowledge concerning solvent effects on the rate and equilibrium of chemical reactions of all kinds.  It begins with basic thermodynamics and kinetics, building on this foundation to demonstrate how a more detailed understanding of these effects may be used to aid in determination of reaction mechanisms, and to aid in planning syntheses. Consideration is given to theoretical calculations (quantum chemistry, molecular dynamics, etc.), to statistical methods (chemometrics), and to modern day concerns such as ""green"" chemistry, where ut

  8. Training effectiveness evaluation model

    Penrose, J.B.

    1993-01-01

    NAESCO's Training Effectiveness Evaluation Model (TEEM) integrates existing evaluation procedures with new procedures. The new procedures are designed to measure training impact on organizational productivity. TEEM seeks to enhance organizational productivity through proactive training focused on operation results. These results can be identified and measured by establishing and tracking performance indicators. Relating training to organizational productivity is not easy. TEEM is a team process. It offers strategies to assess more effectively organizational costs and benefits of training. TEEM is one organization's attempt to refine, manage and extend its training evaluation program

  9. Cortical compression rapidly trimmed transcallosal projections and altered axonal anterograde transport machinery.

    Chen, Li-Jin; Wang, Yueh-Jan; Tseng, Guo-Fang

    2017-10-24

    Trauma and tumor compressing the brain distort underlying cortical neurons. Compressed cortical neurons remodel their dendrites instantly. The effects on axons however remain unclear. Using a rat epidural bead implantation model, we studied the effects of unilateral somatosensory cortical compression on its transcallosal projection and the reversibility of the changes following decompression. Compression reduced the density, branching profuseness and boutons of the projection axons in the contralateral homotopic cortex 1week and 1month post-compression. Projection fiber density was higher 1-month than 1-week post-compression, suggesting adaptive temporal changes. Compression reduced contralateral cortical synaptophysin, vesicular glutamate transporter 1 (VGLUT1) and postsynaptic density protein-95 (PSD95) expressions in a week and the first two marker proteins further by 1month. βIII-tubulin and kinesin light chain (KLC) expressions in the corpus callosum (CC) where transcallosal axons traveled were also decreased. Kinesin heavy chain (KHC) level in CC was temporarily increased 1week after compression. Decompression increased transcallosal axon density and branching profuseness to higher than sham while bouton density returned to sham levels. This was accompanied by restoration of synaptophysin, VGLUT1 and PSD95 expressions in the contralateral cortex of the 1-week, but not the 1-month, compression rats. Decompression restored βIII-tubulin, but not KLC and KHC expressions in CC. However, KLC and KHC expressions in the cell bodies of the layer II/III pyramidal neurons partially recovered. Our results show cerebral compression compromised cortical axonal outputs and reduced transcallosal projection. Some of these changes did not recover in long-term decompression. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. The EMC effect

    Norton, P R

    2003-01-01

    The status of the EMC effect, the anomalous scattering of leptons on nuclei, is reviewed, together with models which have been formulated to explain it. The implications for other processes are discussed, in particular the relevance to problems in conventional nuclear physics

  11. The service bullwhip effect

    Akkermans, H.A.; Voss, C.

    2013-01-01

    Purpose This paper sets out to explore whether and how the bullwhip effect, as found in product supply chains, might also manifest itself in services, as well as what policies can be successful for mitigating it. Design/methodology/approach A combination of analytic methods was used—inductive case

  12. Thermosensory reversal effect quantified

    Bergmann Tiest, W.M.; Kappers, A.M.L.

    2008-01-01

    At room temperature, some materials feel colder than others due to differences in thermal conductivity, heat capacity and geometry. When the ambient temperature is well above skin temperature, the roles of 'cold' and 'warm' materials are reversed. In this paper, this effect is quantified by

  13. Thermosensory reversal effect quantified

    Bergmann Tiest, W.M.; Kappers, A.M.L.

    2008-01-01

    At room temperature, some materials feel colder than others due to differences in thermal conductivity, heat capacity and geometry. When the ambient temperature is well above skin temperature, the roles of ‘cold’ and ‘warm’ materials are reversed. In this paper, this effect is quantified by

  14. Squeezing the Efimov effect

    Sandoval, J. H.; Bellotti, F. F.; Yamashita, M. T.

    2018-01-01

    The quantum mechanical three-body problem is a source of continuing interest due to its complexity and not least due to the presence of fascinating solvable cases. The prime example is the Efimov effect where infinitely many bound states of identical bosons can arise at the threshold where the tw...

  15. Biological Effects of Radiation

    Jatau, B.D.; Garba, N.N.; Yusuf, A.M.; Yamusa, Y. A.; Musa, Y.

    2013-01-01

    In earlier studies, researchers aimed a single particle at the nucleus of the cell where DNA is located. Eighty percent of the cells shot through the nucleus survived. This contradicts the belief that if radiation slams through the nucleus, the cell will die. But the bad news is that the surviving cells contained mutations. Cells have a great capacity to repair DNA, but they cannot do it perfectly. The damage left behind in these studies from a single particle of alpha radiation doubled the damage that is already there. This proved, beyond a shadow of doubt, those there biological effects occur as a result of exposure to radiation, Radiation is harmful to living tissue because of its ionizing power in matter. This ionization can damage living cells directly, by breaking the chemical bonds of important biological molecules (particularly DNA), or indirectly, by creating chemical radicals from water molecules in the cells, which can then attack the biological molecules chemically. At some extent these molecules are repaired by natural biological processes, however, the effectiveness of this repair depends on the extent of the damage. The interaction of ionizing with the human body, arising either from external sources outside the body or from internal contamination of the body by radioactive materials, leads to the biological effects which may later show up as a clinical symptoms. Basically, this formed the baseline of this research to serve as a yardstick for creating awareness about radiation and its resulting effects.

  16. Beam-Beam Effects

    Herr, W; Pieloni, T

    2014-01-01

    One of the most severe limitations in high-intensity particle colliders is the beam-beam interaction, i.e. the perturbation of the beams as they cross the opposing beams. This introduction to beam-beam effects concentrates on a description of the phenomena that are present in modern colliding beam facilities

  17. Radiation effects on superconductivity

    Brown, B.S.

    1975-01-01

    The effect of radiation on the superconducting transition temperature (T/sub c/), upper critical field (H/sub c2/), and volume-pinning-force density (F/sub p/) were discussed for the three kinds of superconducting material (elements, alloys, and compounds). 11 figures, 3 tables, 86 references

  18. Radiation effects at ISABELLE

    Sanger, P.A.; Danby, G.T.

    1975-01-01

    Shielding, radiation damage, and radiation heating at the planned ISABELLE storage rings were considered. Radiation shielding studies were reviewed and were found to be adequate for present day dosage limits. Radiation damage could be encountered in some extreme cases, but is not expected to limit the performance of the superconducting magnets. Experiments to study the effect of radiation heating on actual magnets are recommended

  19. Pleiotropic effects of incretins

    Vishal Gupta

    2012-01-01

    Full Text Available Drugs that augment the incretin system [glucagon like peptide (GLP agonists and dipeptidyl peptidase-4 (DPP-4 inhibitors] represent a novel class of anti-hyperglycemic agents that have shown to improve the health and survival of beta-cells (improvement in postprandial hyperglycemia and suppress glucagon (improvement in fasting hyperglycemia. The incretins represent a large family of molecules referred to as the "glucagon superfamily of peptide hormones" of which more than 90% of the physiological effects of incretins are accomplished by GLP-1 7-37 and GLP1 7-36 amide and gastric insulinotropic peptide (GIP. GLP-1 mediates its effects via the GLP-1 receptor, which has a wide tissue distribution [pancreas, lung, heart, vascular smooth muscle cells, endothelial cells, macrophages and monocytes, kidney, gastrointestinal tract (stomach and intestine, central nervous system (neoortex, cerebellum, hypothalamus, hippocampus, brainstem nucleus tractus solitarius and peripheral nervous system]. This would imply that the incretin system has effects outside the pancreas. Over time data has accumulated to suggest that therapies that augment the incretin system has beneficial pleiotrophic effects. The incretins have shown to possess a cardiac-friendly profile, preserve neuronal cells and safeguard from neuronal degeneration, improve hepatic inflammation and hepatosteatosis, improve insulin resistance, promote weight loss and induce satiety. There is growing evidence that they may also be renoprotective promoting wound healing and bone health.

  20. Radiation effects on lymphocytes

    Roser, B.

    1976-01-01

    This review of the ontogeny of lymphocyte populations concentrates on sites of production, rates of production, and the factors governing the differentiation and longevity of the various lymphocyte pools. The physiology of the lymphocyte pools is described with particular emphasis on recirculation from blood to lymph through lymphoid tissues. The separate routes of recirculation of both thymus-derived and nonthymus-derived lymphocytes and the possible anatomical sites and mechanisms of lymphocyte cooperation are discussed. Radiation effects on lymphocyte populations are divided into two sections. First, the effects of whole-body irradiation on the total lymphocyte pools are discussed including the differential effects of irradiation on T lymphocytes, B lymphocytes, lymphoblasts, and plasma cells. The differential sensitivity of various types of immune response is correlated, where possible, with the differential sensitivity of the lymphocyte types involved. Second, experimental attempts to selectively deplete discrete subpopulations of the total lymphocyte pools, e.g., recirculating cells, are briefly discussed with particular emphasis on studies on the effects of the localization of radionuclides in lymphoid tissue

  1. Poetry Pages. Sound Effects.

    Fina, Allan de

    1992-01-01

    Explains how elementary teachers can help students understand onomatopoeia, suggesting that they define onomatopoeia, share examples of it, read poems and have students discuss onomatopoeic words, act out common household sounds, write about sound effects, and create choral readings of onomatopoeic poems. Two appropriate poems are included. (SM)

  2. Radioprotective effect of interferon

    Zasukhina, G.

    1984-12-18

    A cycle of experiments performed jointly with associations of the Moscow Engineering Physics Institute reportedly demonstrated that interferons protect human cells cultivated in a test tube against the action of fast neutrons and gamma radiation. Cells treated in advance with interferon not only survived irradiation but were almost totally protected against harmful effects of fast neutrons on the structure of chromosomes, according to the author. She mentions that the laboratory has also been studying effects produced on cells by compounds of heavy metals and other chemical compounds, including ones which cause breaks in the DNA molecule. Interferon's ability to protect cells against effects of chemical compounds has been studied in this connection. Another direction of the laboratory's work is research on interferon's effects on blood cells of persons suffering from certain hereditary diseases in which restorative processes of cells are impaired. The purpose of this is to develop courses of treatment which will not cause irreversible damages to chromosomes, the author explains. Interferon has been found to stimulate the reparation systems of cells in cases of Marfan's syndrome, for example.

  3. The Hawking effect

    Saffary, T.

    2001-02-01

    The subject of this diploma thesis is the Hawking effect. We study Fredenhagen and Haag's proof of the Hawking radiation in the framework of a semiclassical theory, the quantum field theory in curved spacetime. In particular we give an exact derivation for the short distance behaviour of the two-point function on the Schwarzschild radius

  4. Ensuring effective project management

    Ward, J.N.

    1980-01-01

    A brief description is given of the organisation methods employed by the Bechtel Power Corporation, in their contract with Mississippi Power and Light Company for the design, construction and procurement activities for the Grand Gulf Nuclear Station. The aim is to ensure effective management, and good communications at all stages of construction, between the project team and the client. (U.K.)

  5. Radiation effects in gases

    Leonhardt, J.W.

    1985-01-01

    Problems in the studies of radiation effects in gases are discussed. By means of ionization- excitation- and electron-capture yields various applications are characterized: ionization detectors, X-ray detectors, radionuclide battery, and radiation-induced chemical gas-phase reactions. Some new results of basic research in respect to the SO 2 oxidation are discussed. (author)

  6. Effects of pollutant metals

    Ragan, H.A.

    1983-01-01

    The in vitro cloning efficiency of granulocytic stem cells from mouse bone marrow was completely inhibited or markedly reduced by lead and by materials from shale oil and coal liquefaction processes. Effects of whole body irradiation to syngeneic mice then given DMSO-treated or SRC-injected bone marrow are now being studied

  7. The Kaye effect

    Binder, J M; Landig, A J

    2009-01-01

    The International Young Physicists' Tournament (IYPT) is a worldwide, annual competition for secondary school students. This is our solution to problem number 10, The Kaye effect, as presented in the final round of the 21st IYPT in Trogir, Croatia. The Kaye effect occurs when a thin stream of shampoo or a different adequate non-Newtonian liquid is poured onto a surface. Suddenly, a jet leaves the heap that is formed by the shampoo and begins to 'dance' around the primary jet like a lasso. The phenomenon ends when the 'dancing' jet hits the primary jet and subsequently collapses. We started our investigations based on available literature (Kaye 1963 Nature 197 1001, Versluis et al 2006 J. Stat. Mech., Collyer and Fischer 1976 Nature 261 682). We made experiments with a similar experimental set-up in which we could determine the velocities of both shampoo streams as well as the angle of the 'dancing' stream. From there on, we developed a theoretical model for the energy loss of the jet in the heap. We discovered that the air layer between the jet and the heap is a necessity for the Kaye effect to occur. At this point, our observations differ from the aforementioned literature. This also accounts for the shampoo beam acting as a light guide. Further experiments concerning the viscoelasticity of the shampoo revealed that the elastic property of the shampoo is necessary for the effect to occur.

  8. The Kaye effect

    Binder, J M; Landig, A J [Student Research Center Suedwuerttemberg, Gutenbergstrasse 18, 88348 Bad Saulgau (Germany)], E-mail: jan.binder@sfz-bw.de, E-mail: andreas.landig@sfz-bw.de

    2009-11-15

    The International Young Physicists' Tournament (IYPT) is a worldwide, annual competition for secondary school students. This is our solution to problem number 10, The Kaye effect, as presented in the final round of the 21st IYPT in Trogir, Croatia. The Kaye effect occurs when a thin stream of shampoo or a different adequate non-Newtonian liquid is poured onto a surface. Suddenly, a jet leaves the heap that is formed by the shampoo and begins to 'dance' around the primary jet like a lasso. The phenomenon ends when the 'dancing' jet hits the primary jet and subsequently collapses. We started our investigations based on available literature (Kaye 1963 Nature 197 1001, Versluis et al 2006 J. Stat. Mech., Collyer and Fischer 1976 Nature 261 682). We made experiments with a similar experimental set-up in which we could determine the velocities of both shampoo streams as well as the angle of the 'dancing' stream. From there on, we developed a theoretical model for the energy loss of the jet in the heap. We discovered that the air layer between the jet and the heap is a necessity for the Kaye effect to occur. At this point, our observations differ from the aforementioned literature. This also accounts for the shampoo beam acting as a light guide. Further experiments concerning the viscoelasticity of the shampoo revealed that the elastic property of the shampoo is necessary for the effect to occur.

  9. Camp's "Disneyland" Effect.

    Renville, Gary

    1999-01-01

    Describes the positive mental, physical, and social growth impacts that the camping experience had on the author, and urges camp program evaluation to plan and implement such changes. Sidebar lists steps of effective evaluation: program goals and objectives, goals of evaluation, implementation of evaluation, data analysis, and findings and…

  10. Multimodal news framing effects

    Powell, T.E.

    2017-01-01

    Visuals in news media play a vital role in framing citizens’ political preferences. Yet, compared to the written word, visual images are undervalued in political communication research. Using framing theory, this thesis redresses the balance by studying the combined, or multimodal, effects of visual

  11. Marijuana: respiratory tract effects.

    Owen, Kelly P; Sutter, Mark E; Albertson, Timothy E

    2014-02-01

    Marijuana is the most commonly used drug of abuse in the USA. It is commonly abused through inhalation and therefore has effects on the lung that are similar to tobacco smoke, including increased cough, sputum production, hyperinflation, and upper lobe emphysematous changes. However, at this time, it does not appear that marijuana smoke contributes to the development of chronic obstructive pulmonary disease. Marijuana can have multiple physiologic effects such as tachycardia, peripheral vasodilatation, behavioral and emotional changes, and possible prolonged cognitive impairment. The carcinogenic effects of marijuana are unclear at this time. Studies are mixed on the ability of marijuana smoke to increase the risk for head and neck squamous cell carcinoma, lung cancer, prostate cancer, and cervical cancer. Some studies show that marijuana is protective for development of malignancy. Marijuana smoke has been shown to have an inhibitory effect on the immune system. Components of cannabis are under investigation as treatment for autoimmune diseases and malignancy. As marijuana becomes legalized in many states for medical and recreational use, other forms of tetrahydrocannabinol (THC) have been developed, such as food products and beverages. As most research on marijuana at this time has been on whole marijuana smoke, rather than THC, it is difficult to determine if the currently available data is applicable to these newer products.

  12. Effects of ionizing radiations

    Gaussens, G.

    1984-08-01

    After recalling radiation-matter interaction, influence on radiation effects of chemical composition, structure, irradiation atmosphere, dose rate, temperature of organic materials and evolution of electrical, mechanical and physical properties are reviewed. Then behaviour under irradiation of main organic materials: elastomers, thermoplastics, thermosetting plastics, oils and paints are examined. 68 refs [fr

  13. Effects of elevated CO

    Xue, Sha; Yang, Xiaomei; Liu, Guobin; Gai, Lingtong; Zhang, Changsheng; Ritsema, Coen J.; Geissen, Violette

    2017-01-01

    Elevated CO2 and drought are key consequences of climate change and affect soil processes and plant growth. This study investigated the effects of elevated CO2 and drought on the microbial biomass and enzymatic activities in the rhizospheres of Bothriochloa ischaemum and

  14. Effectivity and Power

    Karos, Dominik; Peters, Hans

    2016-01-01

    We axiomatically develop a class of power indices for effectivity functions, both for the case where the set of alternatives is finite and where it is infinite. Such power indices make it possible to take the issues under consideration into account, in contrast to power indices defined just for

  15. Anomalous Hall effect

    Nagaosa, N.; Sinova, Jairo; Onoda, S.; MacDonald, A. H.; Ong, N. P.

    2010-01-01

    Roč. 82, č. 2 (2010), s. 1539-1592 ISSN 0034-6861 Institutional research plan: CEZ:AV0Z10100521 Keywords : anomalous Hall effect * spintronics Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 51.695, year: 2010

  16. Space Environmental Effects Knowledgebase

    Wood, B. E.

    2007-01-01

    This report describes the results of an NRA funded program entitled Space Environmental Effects Knowledgebase that received funding through a NASA NRA (NRA8-31) and was monitored by personnel in the NASA Space Environmental Effects (SEE) Program. The NASA Project number was 02029. The Satellite Contamination and Materials Outgassing Knowledgebase (SCMOK) was created as a part of the earlier NRA8-20. One of the previous tasks and part of the previously developed Knowledgebase was to accumulate data from facilities using QCMs to measure the outgassing data for satellite materials. The main object of this current program was to increase the number of material outgassing datasets from 250 up to approximately 500. As a part of this effort, a round-robin series of materials outgassing measurements program was also executed that allowed comparison of the results for the same materials tested in 10 different test facilities. Other programs tasks included obtaining datasets or information packages for 1) optical effects of contaminants on optical surfaces, thermal radiators, and sensor systems and 2) space environmental effects data and incorporating these data into the already existing NASA/SEE Knowledgebase.

  17. Effects of acid rain

    1976-03-01

    The ecological problems that are caused by sulfur pollution in Scandinavia are addressed. Subsequent chemical and physical transformations that the pollutants undergo in the atmosphere are included. The effects of pollutants on soil nutrients, with consequences mainly for forest production, are discussed. Other effects include acidification of lakes and rivers, resulting in decreased fish production. The size of the drop in pH is quite substantial in some of the lakes. The decreased pH has an immediate effect on the change in species composition of fish populations, such as trout and salmon. Efforts to reduce sulfur pollution are discussed. A long term program for the reduction of sulfur in fuel oil has been introduced. At present, there is a ban on the use of oil containing more then 2.5% S (by weight). A further ban on oil containing more than 1% sulfur is in effect in the three major urban areas of Sweden as well as a number of counties. It has been urged by environmental health authorities that in urban pollution control sulfur should be regarded as an indicator of pollutions and not be dealt with as an isolated problem.

  18. Unconscious advertising effects

    Moorman, M.; Belch, M.A.; Belch, G.E.

    2011-01-01

    Most traditional advertising effect models are based on the premise that advertising is attended to and processed consciously. However, recent neuroscientific research shows that most information is unconsciously attended to, processed, and stored in memory. The concept of unconscious processing is

  19. Exploring energy rebound effects

    Heijs, W.J.M.; Adrians, R.

    2011-01-01

    In the debate on sustainable energy use, one important aspect tends to be systematically overlooked. Sustainability may be increased by developing technological innovations and measures to promote energy conservation, but so-called rebound effects constitute a potential and largely underestimated

  20. Effective magnetic Hamiltonians

    Drchal, Václav; Kudrnovský, Josef; Turek, I.

    2013-01-01

    Roč. 26, č. 5 (2013), s. 1997-2000 ISSN 1557-1939 R&D Projects: GA ČR GA202/09/0775 Institutional support: RVO:68378271 Keywords : effective magnetic Hamiltonian * ab initio * magnetic structure Subject RIV: BE - Theoretical Physics Impact factor: 0.930, year: 2013

  1. Theorising EIA effectiveness

    Lyhne, Ivar; Laerhoven, van Frank; Cashmore, Matthew; Runhaar, Hens

    2017-01-01

    Considerable attention has been given to the effectiveness of environmental impact assessment (EIA) since the 1970s. Relatively few research studies, however, have approached EIA as an instrument of environmental governance, and have explored the mechanisms through which EIA influences the

  2. Effective Classroom Management

    Mansor, Azlin Norhaini; Eng, Wong Kim; Rasul, Mohamad Sattar; Hamzah, Mohd Izham Mohd; Hamid, Aida Hanim A.

    2012-01-01

    This paper attempts to explore and identify the characteristics of an effective teacher who teaches English as a second language to 10 year old students from different ethnics, various social economic background and multi-level language ability, at a private primary school in Malaysia. The study focused on classroom management using a case study…

  3. Antihypertensive effects of astaxanthin

    Hiroshi Yoshida

    2008-10-01

    Full Text Available Hidekatsu Yanai1,2, Kumie Ito1,2, Hiroshi Yoshida2,3, Norio Tada1,21Department of Internal Medicine; 2Institute of Clinical Medicine and Research; 3Department of Laboratory Medicine, The Jikei University School of Medicine, Chiba, JapanAbstract: Astaxanthin is a biological antioxidant naturally found in a wide variety of aquatic living organisms, and has shown various pharmacological activities, such as anti-inflammatory and antidiabetic activities. A recent study reported that the administration of astaxanthin induced a significant reduction in blood pressure and delayed the incidence of stroke in stroke-prone spontaneously hypertensive rats, suggesting that astaxanthin also has antihypertensive effect. In a study using aortic rings of spontaneously hypertensive rats, astaxanthin induced a significant reduction of the contractile responses of the aorta to α-adrenergic receptor agonist and angiotensin II, which may contribute to the antihypertensive effect of astaxanthin. In a histopathological study, astaxanthin decreased coronary artery wall thickness compared with the control, indicating the possibility that astaxanthin ameliorates hypertension-induced vascular remodeling. Astaxanthin has anti-inflammatory, antidiabetic, antihypertensive, and antioxidative activities; therefore, we should perform further studies to elucidate an antiatherogenic effect of astaxanthin.Keywords: astaxanthin, antioxidant, antihypertensive effect, atherosclerosis

  4. EFFECTIVE ELECTRONIC TUTORIAL

    Andrei A. Fedoseev

    2014-01-01

    Full Text Available The article analyzes effective electronic tutorials creation and application based on the theory of pedagogy. Herewith the issues of necessary electronic tutorial functional, ways of the educational process organization with the use of information and communication technologies and the logistics of electronic educational resources are touched upon. 

  5. The weapons effect

    Benjamin, Arlin James; Bushman, Brad J.

    In some societies, weapons are plentiful and highly visible. This review examines recent trends in research on the weapons effect, which is the finding that the mere presence of weapons can prime people to behave aggressively. The General Aggression Model provides a theoretical framework to explain

  6. Antioxidant effects of carotenoids

    Bast, A.; Haenen, G.R.M.M.; Berg, R. van den; Berg, H. van den

    1998-01-01

    Surprisingly, neither the precise pharmacological effect nor the toxicological profile is usually established for food components. Carotenoids are no exception in this regard. Only limited insight into the pharmacology and toxicology of carotenoids exists. It is known that the antioxidant action of

  7. Occlusion effects, Part I

    Hansen, Mie Østergaard

    annoyances and the objective measurements were analysed. Persons suffering from tinnitus behaved differently than person without tinnitus. The latter group showed significant relations between the measured occlusion effect, hearing loss and the personal of occlusion. The actual sensation level is also...

  8. Using Media Effectively.

    Danzer, Gerald A.; Newman, Mark

    1992-01-01

    Recommends that media presentations can be used effectively in the history classroom as images of reality. Suggests films and television programs and documentaries that can be utilized to show how movies play a role in shaping opinion and changing perceptions. (DK)

  9. The Multiplier Effect.

    Flowers, William L., Jr.; Harris, John B.

    1981-01-01

    The multiplier effect is discussed as it applies to the field of continuing education. The authors' main point is that one grant or contract can, and should, be used as the basis for building organizational competencies and capabilities that will secure other funds. (Author/CT)

  10. Cataloging Efficiency and Effectiveness.

    McCain, Cheryl; Shorten, Jay

    2002-01-01

    Reports on a survey of academic libraries that was conducted to supplement findings of cost studies by providing measures of efficiency and effectiveness for cataloging departments based on reported productivity, number of staff, task distribution, and quality measures including backlogs, authority control, and database maintenance. Identifies…

  11. Damping Effect of Humans

    Pedersen, Lars

    2012-01-01

    system and change its dynamic behavior and its dynamic characteristics. When predicting structural vibrations it is not common to account for the passive crowd, but the paper will illustrate effects of the presence of a passive croud on structural behavior. Numerical and experimental results...

  12. Late somatic effects

    Gilbert, E.S.

    1989-01-01

    Late effects are by definition effects that occur at least one year, and in most cases decades, after the time of exposure. The late effects considered in this chapter are limited to latent cancer incidence and mortality, and benign thyroid disease. A model is provided for estimating risks of late effects resulting from the radiation exposure likely to be received in the event of a nuclear power plant accident. It is assumed that exposure to high-LET radiation would be negligible in such an accident, and thus only risks from low-LET exposure are evaluated. Separate estimates are provided for risks of leukemia, bone cancer, lung cancer, gastrointestinal cancers, thyroid cancer, skin cancer, and the residual group of all other cancers; estimates of leukemia and other cancers due to in utero exposure are also provided. Risks are expressed in absolute terms as the number of cancer deaths (or cases) per million persons exposed to a particular dose. Because the time of death is also important in assessing the impact of an accident, and because the quality of life after the occurrence of cancer will often be reduced, the number of years of life lost and the number of years of life lived after the occurrence of cancer are also estimated

  13. Problems in photoradiation effects

    Milinchuk, V.K.

    1986-01-01

    This paper discusses the most interesting photoradiation effects observed in recent years and directs attention to problems whose solution has a bearing on progress in photoradiation chemistry, and which also are significant for divisions of modern physical chemistry such as the kinetics and mechanisms of elementary processes in solid organic materials, the radiation resistance of organic materials, and aging in polymers

  14. The Faraday effect revisited

    Cornean, Horia; Nenciu, Gheorghe

    2009-01-01

    This paper is the second in a series revisiting the (effect of) Faraday rotation. We formulate and prove the thermodynamic limit for the transverse electric conductivity of Bloch electrons, as well as for the Verdet constant. The main mathematical tool is a regularized magnetic and geometric...

  15. Cognitive Effects and Sedation.

    Dhingra, Lara; Ahmed, Ebtesam; Shin, Jae; Scharaga, Elyssa; Magun, Maximilian

    2015-10-01

    Cognitive effects and sedation (CES) are prevalent in chronic nonmalignant pain populations receiving long-term opioid therapy and are among the most common reasons patients discontinue opioid use. In this narrative review, we describe the phenomenology, epidemiology, mechanisms, assessment, and management of opioid-related CES. We reviewed the empirical and theoretical literature on CES in opioid-treated populations with chronic pain. Data on long-term opioid therapy (≥ 3 months in duration) in chronic nonmalignant pain patients were sought. The phenomenology of CES includes: inattention, concentration difficulties, memory deficits, psychomotor dysfunction, perceptual distortions, and executive dysfunction and somnolence, sleep disorders, and lethargy. Deficits may be caused by unrelieved pain or opioid therapy alone, or from a combination of these and other factors. Mechanisms include central nervous system effects, for example, direct toxic effects on neurons resulting in decreased consciousness; direct effects on processing and reaction resulting in cognitive or psychomotor impairment, and inhibitory effects on cholinergic activity. Pharmacological management approaches may include opioid dose reduction and rotation or psychostimulant use. Nonpharmacological approaches may include cognitive-behavioral therapy, mindfulness-based stress reduction, acupuncture, exercise, and yoga. The most prevalent CES include: memory deficits (73-81%), sleep disturbance (35-57%), and fatigue (10%). At its most severe, extreme cognitive dysfunction can result in frank delirium and decreased alertness can result in coma. Emotional distress, sleep disorders, and other comorbidities and treatments can worsen CES, particularly among the elderly. Conclusions about the neuropsychological domains affected by opioids are limited due to the heterogeneity of studies and methodological issues. Wiley Periodicals, Inc.

  16. Health Effects of Air Pollution

    ... Health effects of air pollution Health effects of air pollution Breathing air that is not clean can hurt ... important to know about the health effects that air pollution can have on you and others. Once you ...

  17. Effects of Medications on Voice

    ... ENTCareers Marketplace Find an ENT Doctor Near You Effects of Medications on Voice Effects of Medications on Voice Patient Health Information News ... replacement therapy post-menopause may have a variable effect. An inadequate level of thyroid replacement medication in ...

  18. Regional Healthcare Effectiveness

    Olga Vladimirovna Kudelina

    2016-03-01

    Full Text Available An evaluation of healthcare systems effectiveness of the regions of the Russian Federation (federal districts was conducted using the Minmax method based on the data available at the United Interdepartmental Statistical Information System. Four groups of components (i.e. availability of resources; use of resources; access to resources and medical effectiveness decomposed into 17 items were analyzed. The resource availability was measured by four indicators, including the provision of doctors, nurses, hospital beds; agencies providing health care to the population. Use of resources was measured by seven indicators: the average hospital stay, days; the average bed occupancy, days; the number of operations per 1 physician surgical; the cost per unit volume of medical care: in outpatient clinics, day hospitals, inpatient and emergency care. Access to the resources was measured by three indicators: the satisfaction of the population by medical care; the capacity of outpatient clinics; the average number of visits to health facility. The medical effectiveness was also measured by three indicators: incidence with the "first-ever diagnosis of malignancy"; life expectancy at birth, years; the number of days of temporary disability. The study of the dynamics of the components and indexes for 2008–2012 allows to indicate a multidirectional influence on the regional healthcare system. In some federal districts (e.g. North Caucasian, the effectiveness decreases due to resource availability, in others (South, North Caucasian — due to the use of resources, in others (Far Eastern, Ural — due to access to resources. It is found that the effectiveness of the healthcare systems of the federal districts differs significantly. In addition, the built matrix proves the variability the of effectiveness (comparison of expenditures and results of healthcare systems of the federal districts of the Russian Federation: the high results can be obtained at high costs

  19. Biological effects of ionizing radiation

    Heribanova, A.

    1995-01-01

    The basic principles and pathways of effects of ionizing radiation on living organisms and cells are outlined. The following topics are covered: effects of radiation on living matter (direct effects, radical or indirect effects, dual radiation action, and molecular biological theories); effects of radiation on cells and tissues (cell depletion, changes in the cytogenetic information, reparation mechanisms), dose-response relationship (deterministic effects, stochastic effects), and the effects of radiation on man (acute radiation sickness, acute local changes, fetus injuries, non-tumorous late injuries, malignant tumors, genetic changes). (P.A.). 3 tabs., 2 figs., 5 refs

  20. Effects of radiation on man

    Saunders, P.A.H.

    1981-01-01

    The available evidence on the effects of radiation on man and the predictions that have been made of possible low level effects are reviewed. Data from United Nations Scientific Committee of the Effects of Atomic Radiation (UNSCEAR) and the committee on the Biological Effects of Ionising Radiation (BEIR) is used to illustrate the acute, delayed and hereditary effects of high dose levels. The effects of low dose levels are discussed on the assumption that both somatic and hereditary effects can be predicted on the basis of linear extrapolation from high dose effects. (U.K.)

  1. Polarization effects. Volume 2

    Courant, E.

    1981-01-01

    The use of polarized proton beams in ISABELLE is important for several general reasons: (1) With a single longitudinally polarized proton beam, effects involving parity violation can be identified and hence processes involving weak interactions can be separated from those involving strong and electromagnetic interactions. (2) Spin effects are important in the strong interactions and can be useful for testing QCD. The technique for obtaining polarized proton beams in ISABELLE appears promising, particularly in view of the present development of a polarized proton beam for the AGS. Projections for the luminosity in ISABELLE for collisions of polarized protons - one or both beams polarized with longitudinal or transverse polarization - range from 1/100 to 1 times the luminosity for unpolarized protons.

  2. Renormalization and effective lagrangians

    Polchinski, J.

    1984-01-01

    There is a strong intuitive understanding of renormalization, due to Wilson, in terms of the scaling of effective lagrangians. We show that this can be made the basis for a proof of perturbative renormalization. We first study renormalizability in the language of renormalization group flows for a toy renormalization group equation. We then derive an exact renormalization group equation for a four-dimensional lambda PHI 4 theory with a momentum cutoff. We organize the cutoff dependence of the effective lagrangian into relevant and irrelevant parts, and derive a linear equation for the irrelevant part. A lengthy but straightforward argument establishes that the piece identified as irrelevant actually is so in perturbation theory. This implies renormalizability. The method extends immediately to any system in which a momentum-space cutoff can be used, but the principle is more general and should apply for any physical cutoff. Neither Weinberg's theorem nor arguments based on the topology of graphs are needed. (orig.)

  3. Developing Effective Clinical Trainers

    Kevin Khamarko

    2012-05-01

    Full Text Available Continuing education and training provides a means to improve performance among health care professionals (HCP. Research shows, however, that continuing professional education activities have inconsistent effects on HCP competence, performance, and patient health outcomes. Furthermore, the trainer’s role as a facilitator of knowledge translation (KT has been understudied. To understand how clinical trainers support their trainees in translating what they learned into practice, we conducted 16 in-depth interviews with expert trainers. These interviews yielded a variety of KT-enhancing strategies, including tailoring training activities to their trainees’ needs. In addition, participants recommended trainers familiarize themselves with their trainees’ work environments, be able to identify their knowledge deficits, and devote time to provide trainees with post-training support. Creating an effective training, one that leads to transfer, requires active planning, communication, and command of the training topic by skilled trainers.

  4. Transverse spin effects

    Ratcliffe, P.G.

    1993-01-01

    A discussion is presented of the role that transverse spin physics can play in providing information on the bound state dynamics in hadronic physics. Care is taken to distinguish between single- and double-spin measurements, each being discussed separately. In the case of single-spin effects it is stressed that as yet no satisfactory explanation has been provided within the framework if perturbative QCD which in fact generally predicts negligible effects. In order to clarify the situation experimental data at yet higher p T are necessary and semi-leptonic data could shed some light on the underlying scattering mechanisms. As regards double-spin correlations, the theoretical picture (although clouded by some ill-informed, often erroneous statements and even recent papers) is rather well understood and what is dearly missing is the experimental study of, for example, g 2 in deep-inelastic scattering. (author). 31 refs

  5. Radiation Effects Research Foundation

    1979-01-01

    The last day of March 1978 marked the completion of the first 3 years of operation of the Radiation Effects Research Foundation in Hiroshima and Nagasaki. RERF was established on 1 April 1975 as successor to the Atomic Bomb Casualty Commission which had been in continuous operation since 1947. This record of the first 3 years of operation consists of selected reports and other documents prepared in the course of conducting the business of RERF and includes a brief history, a late radiation effects that might be conducted at RERF. The wisdom and thought given to the research program and its operation by the Scientific Council and the Board of Directors is reflected in the minutes of their meetings which are included in the Appendix. (Mori, K.)

  6. [Adverse effects of oxcarbazepine].

    Fang, Shu; Gong, Zhi-Cheng

    2015-04-01

    Oxcarbazepine is a new antiepileptic drug. The results of clinical trials suggest that oxcarbazepine is well tolerated and has less drug interactions. It is being used more and more widely in clinical practice, but its adverse effects should not be ignored. The most common adverse effects of oxcarbazepine are usually related to the central nervous system and digestive system, including fatigue, drowsiness, diplopia, dizziness, nausea and vomit. The common skin adverse reaction is rash. Long-term use of oxcarbazepine may also cause hyponatremia. This article reviews the literature from China and overseas about the adverse effets of oxcarbazepine over the last 10 years in order to find information about rational clinical use of oxcarbazepine.

  7. The Creativity Passdown Effect

    Pries-Heje, Jan

    2015-01-01

    Purpose – The purpose of this paper is to suggest that translating a design theory (DT) into practice (e.g. creating an instance design artifact (IDA)) is hardly straight-forward and requires substantial creativity. Specifically the authors suggest that adopting a DT embodies a creativity passdown...... effect in which the creative thinking of a team of design theorist(s) inherent in DT invokes a creative mind of a team of artifact instance designer(s) in creating an IDA. In this study, the authors empirically investigate the creativity passdown effect through an action case in which a DT (DT nexus...... designer team introducing a previously published DT as a basis for creating an IDA. Findings – The experience in the action case suggests that using a DT in creating an IDA may encourage design thinking, and in certain way increase its power and practical relevance by fostering the creative mind...

  8. Ozone health effects

    Easterly, C.

    1994-01-01

    Ozone is a principal component of photochemical air pollution endogenous to numerous metropolitan areas. It is primarily formed by the oxidation of NOx in the presence of sunlight and reactive organic compounds. Ozone is a highly active oxidizing agent capable of causing injury to the lung. Lung injury may take the form of irritant effects on the respiratory tract that impair pulmonary function and result in subjective symptoms of respiratory discomfort. These symptoms include, but are not limited to, cough and shortness of breath, and they can limit exercise performance. The effects of ozone observed in humans have been primarily limited to alterations in respiratory function, and a range of respiratory physiological parameters have been measured as a function of ozone exposure in adults and children. These affects have been observed under widely varying (clinical experimental and environmental settings) conditions

  9. Lightning Physics and Effects

    Orville, Richard E.

    2004-03-01

    Lightning Physics and Effects is not a lightning book; it is a lightning encyclopedia. Rarely in the history of science has one contribution covered a subject with such depth and thoroughness as to set the enduring standard for years, perhaps even decades, to come. This contribution covers all aspects of lightning, including lightning physics, lightning protection, and the interaction of lightning with a variety of objects and systems as well as the environment. The style of writing is well within the ability of the technical non-expert and anyone interested in lightning and its effects. Potential readers will include physicists; engineers working in the power industry, communications, computer, and aviation industries; atmospheric scientists; geophysicists; meteorologists; atmospheric chemists; foresters; ecologists; physicians working in the area of electrical trauma; and, lastly, architects. This comprehensive reference volume contains over 300 illustrations, 70 tables with quantitative information, and over 6000 reference and bibliography entries.

  10. The QCD Effective String

    Espriu, D.

    2003-01-01

    QCD can be described in a certain kinematical regime by an effective string theory. This string must couple to background chiral fields in a chirally invariant manner, thus taking into account the true chirally non-invariant QCD vacuum. By requiring conformal symmetry of the string and the unitarity constraint on chiral fields we reconstruct the equations of motion for the latter ones. These provide a consistent background for the propagation of the string. By further requiring locality of the effective action we recover the Lagrangian of non-linear sigma model of pion interactions. The prediction is unambiguous and parameter-free. The estimated chiral structural constants of Gasser and Leutwyler fit very well the phenomenological values. (author)

  11. Electricity Distribution Effectiveness

    Waldemar Szpyra

    2015-12-01

    Full Text Available This paper discusses the basic concepts of cost accounting in the power industry and selected ways of assessing the effectiveness of electricity distribution. The results of effectiveness analysis of MV/LV distribution transformer replacement are presented, and unit costs of energy transmission through various medium-voltage line types are compared. The calculation results confirm the viability of replacing transformers manufactured before 1975. Replacing transformers manufactured after 1975 – only to reduce energy losses – is not economically justified. Increasing use of a PAS type line for energy transmission in local distribution networks is reasonable. Cabling these networks under the current calculation rules of discounts for excessive power outages is not viable, even in areas particularly exposed to catastrophic wire icing.

  12. Aid Effectiveness on Growth

    Doucouliagos, Hristos; Paldam, Martin

    The AEL (aid effectiveness literature) is econo¬metric studies of the macroeconomic effects of development aid. It contains about 100 papers of which 68 are reduced form estimates of theeffect of aid on growth in the recipient country. The raw data show that growth is unconnected to aid......, but the AEL has put so much structure on the data that all results possible have emerged. The present meta study considers both the best-set of the 68 papers and the all-set of 543 regressions published. Both sets have a positive average aid-growth elasticity, but it is small and insignificant: The AEL has...... betweenstudies is real. In particular, the aid-growth association is stronger for Asian countries, and the aid-growth association is shown to have been weaker in the 1970s....

  13. Context effects in games

    Ivo Vlaev

    2007-12-01

    Full Text Available We report an experiment exploring sequential context effects on strategy choices in one-shot Prisoner's Dilemma (PD game. Rapoport and Chammah (1965 have shown that some PDs are cooperative and lead to high cooperation rate, whereas others are uncooperative. Participants played very cooperative and very uncooperative games, against anonymous partners. The order in which these games were played affected their cooperation rate by producing perceptual contrast, which appeared only between the trials, but not between two separate sequences of games. These findings suggest that people may not have stable perceptions of absolute cooperativeness. Instead, they judge the cooperativeness of each fresh game only in relation to the previous game. The observed effects suggest that the principles underlying judgments about highly abstract magnitudes such as cooperativeness may be similar to principles governing the perception of sensory magnitudes.

  14. The effects of Chernobyl

    Lambert, B.E.

    1987-01-01

    It was concluded that the Chernobyl accident will result in an (undetectable) increase of cancer in the U.K. over the next 40-50 years-probably 400-500 cases occurring, less than half of which would be fatal. Preventive measures which could have been instigated would have had doubtful effects in terms of total health detriment in the population. The overall governmental response was marked by confusion. The need for independent monitoring and assessment, and effective public communication was highlighted by the number of unofficial bodies and 'instant experts' approached for advice and information. There is an obvious need for some consensus about intervention or action levels among European countries. (U.K.)

  15. The weapons effect.

    Benjamin, Arlin James; Bushman, Brad J

    2018-02-01

    In some societies, weapons are plentiful and highly visible. This review examines recent trends in research on the weapons effect, which is the finding that the mere presence of weapons can prime people to behave aggressively. The General Aggression Model provides a theoretical framework to explain why the weapons effect occurs. This model postulates that exposure to weapons increases aggressive thoughts and hostile appraisals, thus explaining why weapons facilitate aggressive behavior. Data from meta-analytic reviews are consistent with the General Aggression Model. These findings have important practical as well as theoretical implications. They suggest that the link between weapons and aggression is very strong in semantic memory, and that merely seeing a weapon can make people more aggressive. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Effectiveness of medical interventions.

    Stegenga, Jacob

    2015-12-01

    To be effective, a medical intervention must improve one's health by targeting a disease. The concept of disease, though, is controversial. Among the leading accounts of disease-naturalism, normativism, hybridism, and eliminativism-I defend a version of hybridism. A hybrid account of disease holds that for a state to be a disease that state must both (i) have a constitutive causal basis and (ii) cause harm. The dual requirement of hybridism entails that a medical intervention, to be deemed effective, must target either the constitutive causal basis of a disease or the harms caused by the disease (or ideally both). This provides a theoretical underpinning to the two principle aims of medical treatment: care and cure. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Susceptibility to anchoring effects

    Todd McElroy

    2007-02-01

    Full Text Available Previous research on anchoring has shown this heuristic to be a very robust psychological phenomenon ubiquitous across many domains of human judgment and decision-making. Despite the prevalence of anchoring effects, researchers have only recently begun to investigate the underlying factors responsible for how and in what ways a person is susceptible to them. This paper examines how one such factor, the Big-Five personality trait of openness-to-experience, influences the effect of previously presented anchors on participants' judgments. Our findings indicate that participants high in openness-to-experience were significantly more influenced by anchoring cues relative to participants low in this trait. These findings were consistent across two different types of anchoring tasks providing convergent evidence for our hypothesis.

  18. Measuring marketing effectiveness.

    Gluckman, J; Michaelis, T

    1987-09-01

    The most frequent question about the marketing function in hospitals today is, What are we getting for our money? To answer this, marketing directors must convince the board first of the need for marketing, then of marketing's effectiveness. To measure marketing effectiveness, some basic needs are a staff, equipment, cooperation between departments, utilization data, and a research budget. Some steps to be followed include developing a marketing data base--consisting of demographic projections, demand projections, and market share--testing a marketing strategy through experimentation, documenting the expected results and measurement techniques, and calculating the expected return on investments. In dealing with those "impossible-to-measure" cases, such as a physician who is not advertising but finds that a competitor is, a decision tree can help determine whether to advertise and how much to spend by indicating what the return on investment might be.

  19. Radiation effects in semiconductors

    2011-01-01

    There is a need to understand and combat potential radiation damage problems in semiconductor devices and circuits. Written by international experts, this book explains the effects of radiation on semiconductor devices, radiation detectors, and electronic devices and components. These contributors explore emerging applications, detector technologies, circuit design techniques, new materials, and innovative system approaches. The text focuses on how the technology is being used rather than the mathematical foundations behind it. It covers CMOS radiation-tolerant circuit implementations, CMOS pr

  20. Effective quantum field theories

    Georgi, H.M.

    1989-01-01

    Certain dimensional parameters play a crucial role in the understanding of weak and strong interactions based on SU(2) x U(1) and SU(3) symmetry group theories and of grand unified theories (GUT's) based on SU(5). These parameters are the confinement scale of quantum chromodynamics and the breaking scales of SU(2) x U(1) and SU(5). The concepts of effective quantum field theories and renormalisability are discussed with reference to the economics and ethics of research. (U.K.)

  1. Effects of low doses

    Le Guen, B.

    2001-01-01

    Actually, even though it is comfortable for the risk management, the hypothesis of the dose-effect relationship linearity is not confirmed for any model. In particular, in the area of low dose rate delivered by low let emitters. this hypothesis is debated at the light of recent observations, notably these ones relative to the mechanisms leading to genetic instability and induction eventuality of DNA repair. The problem of strong let emitters is still to solve. (N.C.)

  2. Effective Majorana neutrino decay

    Duarte, Lucia [Instituto de Fisica, Facultad de Ingenieria,Universidad de la Republica, Montevideo (Uruguay); Romero, Ismael; Peressutti, Javier; Sampayo, Oscar A. [Universidad Nacional de Mar del Plata, Departamento de Fisica, Instituto de Investigaciones Fisicas de Mar del Plata (IFIMAR) CONICET, UNMDP, Mar del Plata (Argentina)

    2016-08-15

    We study the decay of heavy sterile Majorana neutrinos according to the interactions obtained from an effective general theory. We describe the two- and three-body decays for a wide range of neutrino masses. The results obtained and presented in this work could be useful for the study of the production and detection of these particles in a variety of high energy physics experiments and astrophysical observations. We show in different figures the dominant branching ratios and the total decay width. (orig.)

  3. Radiation Bystander Effects Mechanism

    Shokohzaman Soleymanifard

    2009-06-01

    Full Text Available Introduction: Radiation Induced Bystander Effect (RIBE which cause radiation effects in non-irradiated cells, has challenged the principle according to which radiation traversal through the nucleus of a cell is necessary for producing biological responses. What is the mechanism of this phenomenon? To have a better understanding of this rather ambiguous concept substantial number of original and reviewed article were carefully examined. Results: Irradiated cells release molecules which can propagate in cell environment and/or transmit through gap junction intercellular communication. These molecules can reach to non-irradiated cells and transmit bystander signals. In many investigations, it has been confirmed that these molecules are growth factors, cytokines, nitric oxide and free radicals like reactive oxygen species (ROS. Transmission of by stander signal to neighboring cells persuades them to produce secondary growth factors which in their turn cause further cell injuries. Some investigators suggest, organelles other than nucleus (mitochondria and cell membrane are the origin of these signals.  There is another opinion which suggests double strand breaks (DSB are not directly generated in bystander cells, rather they are due to smaller damage like single strand breaks which accumulate and end up to DSB. Although bystander mechanisms have not been exactly known, it can be confirmed that multiple mechanisms and various pathways are responsible for this effect. Cell type, radiation type, experimental conditions and end points identify the dominant mechanism. Conclusion: Molecules and pathways which are responsible for RIBE, also cause systemic responses to other non-irradiation stresses. So RIBE is a kind of systemic stress or innate immune responses, which are performed by cell microenvironment. Irradiated cells and their signals are components of microenvironment for creating bystander effects.

  4. Effect of Nanotechnology

    D.Baswaraj; Vasanthi,; Sareddy Deepthi; Mohammad Zainuddin

    2012-01-01

    In this paper, we will put forward the vast effect on nanotechnology in various fields. A basic definition of Nanotechnology is the study manipulation and manufacture of extremely minute machines or devices. The future of technology at times becomes easier to predict. Computers will compute faster, materials will become stronger and medicine will cure more diseases .the technology that works at the nanometer scale of molecules and atoms will be a large part of this future, enabling great impr...

  5. Developmental effects of corruption

    Frøystad, Mona

    2007-01-01

    Traditionally, typical measures of corruption have been broad, composite indices which are often meant to measure overall corruption level in a country. In this thesis I study how different types of corruption can have different effects on development, measured by GDP growth, GDP per capita growth and GDP per capita. Thereby, I wanted to see if some types of corruption could be concluded as more damaging than others. I have discussed and empirically tested the consequences of corruption in pu...

  6. Man and radiation effects

    Rausch, L.

    1982-01-01

    The book describes the effects of ionizing radiation on man in a simple, popular, detailed and generally valid manner and gives a comprehensive picture of the concepts, elements, principles of function, and perspectives of medical radiobiology. Radiobiology in general is explained, and its application in research on the causes of radiolesions and radiation diseases as well as a radiotherapy and radiation protection is discussed in popular form. (orig./MG) [de

  7. The Leverage Ratchet Effect

    Anat R. Admati; Peter M. DeMarzo; Martin F. Hellwig; Paul Pfleiderer

    2013-01-01

    Shareholder-creditor conflicts can create leverage ratchet effects, resulting in inefficient capital structures. Once debt is in place, shareholders may inefficiently increase leverage but avoid reducing it no matter how beneficial leverage reduction might be to total firm value. We present conditions for an irrelevance result under which shareholders view asset sales, pure recapitalization and asset expansion with new equity as equally undesirable. We then analyze how seniority, asset hetero...

  8. Dark Matter Effective Theory

    Del Nobile, Eugenio; Sannino, Francesco

    2012-01-01

    We organize the effective (self)interaction terms for complex scalar dark matter candidates which are either an isosinglet, isodoublet or an isotriplet with respect to the weak interactions. The classification has been performed ordering the operators in inverse powers of the dark matter cutoff...... scale. We assume Lorentz invariance, color and charge neutrality. We also introduce potentially interesting dark matter induced flavor-changing operators. Our general framework allows for model independent investigations of dark matter properties....

  9. [Neuroprotective effects of curcumin].

    Li, Yong; Wang, Pengwen

    2009-12-01

    Traditionally, turmeric has been put to use as a food additive and herbal medicine in Asia. Curcumin is an active principle of the perennial herb curcuma longa (commonly known as turmeric). Recent evidence suggests that curcumin has activities with potential for neuroprotective efficacy, including anti-inflammatory, antioxidant, and antiprotein-aggregate activities. In the current review, we provide the newly evidence for the potential role of curcumin in the neuroprotective effects of neurodegenerative diseases like Alzheimer's disease (AD).

  10. Delegating effectively across cultures

    Sylvie Chevrier; Michaël Viegas-Pires

    2013-01-01

    International audience; This article builds on the contingency approach of global leadership to examine empowerment in a cross-cultural context. Drawing upon an ethnographic research in a French NGO settled in Madagascar, it demonstrates that effective empowerment is not so much a matter of degree -more or less delegation- than a matter of manner. Understanding the cultural representations of role and structure formalization, skill development, collective work and decision-making appeared to ...

  11. Coanda effect in valves

    Uruba Václav

    2017-01-01

    Full Text Available Coanda effect takes place in flow within valves diffuser for certain conditions. The valve plug in half-closed position forms wall-jet, which could be stable or instable, depending on geometry and other conditions. This phenomenon was subject of experimental study using time-resolved PIV technique. For the acquired data analysis the special spatio-temporal methods have been used.

  12. Filter Effectiveness Evaluation

    2013-08-01

    synthetic paraffinic kerosene (SPK), as well as Ultra Low Sulfur Diesel (ULSD) treated with mono-olein to simulate the effects of biodiesel . Results...fuel. Sufficient analysis and qualification of filter products is becoming increasingly crucial in ground transportation vehicles to promote the...well as a simulated biodiesel composed of ultra low sulfur diesel (ULSD) and mono-olein. As written in the scope of work, the alternative aviation

  13. Radiation effects in metals

    Leteurtre Jean.

    1978-01-01

    The current understanding of radiation damage in metals is reviewed, simplifying the actual complexity of the effects by considering some aspects separately. The production of point defects in metals, the primary damage state are first studied. The second part of the lecture is devoted to the evolution of this primary damage state as a function of temperature and dose: the steady state concentration of point defects, the nucleation of secondary defects and their growth are successively considered

  14. Effects and side effects of inspections and accountability in education

    de Wolff, I.; Janssens, F.

    2005-01-01

    This paper presents an overview of studies into effects and side effects of control mechanisms in education. We focus on effects and side effects of inspection visits and public performance indicators. A first conclusion is that the studies do not provide us with a clear answer to the question of

  15. Separating Gender Composition Effects from Peer Effects in Education

    Jahanshahi, Babak

    2017-01-01

    This paper aims to demonstrate the importance of controlling for endogenous peer effects in estimating the influence of gender peer effects on educational outcomes. Using Manski's linear-in-means model, this paper illustrates that the estimation of gender peer effects is potentially biased in the presence of endogenous peer effect in education.…

  16. Stringy effects in scrambling

    Shenker, Stephen H. [Stanford Institute for Theoretical Physics and Department of Physics, Stanford University Stanford, CA (United States); Stanford, Douglas [Stanford Institute for Theoretical Physics and Department of Physics, Stanford University Stanford, CA (United States); School of Natural Sciences, Institute for Advanced Study, Princeton, NJ (United States)

    2015-05-26

    In (http://dx.doi.org/10.1007/JHEP03(2014)067) we gave a precise holographic calculation of chaos at the scrambling time scale. We studied the influence of a small perturbation, long in the past, on a two-sided correlation function in the thermofield double state. A similar analysis applies to squared commutators and other out-of-time-order one-sided correlators (http://dx.doi.org/10.1007/JHEP12(2014)046, http://dx.doi.org/10.1007/JHEP03(2015)051A). The essential bulk physics is a high energy scattering problem near the horizon of an AdS black hole. The above papers used Einstein gravity to study this problem; in the present paper we consider stringy and Planckian corrections. Elastic stringy corrections play an important role, effectively weakening and smearing out the development of chaos. We discuss their signature in the boundary field theory, commenting on the extension to weak coupling. Inelastic effects, although important for the evolution of the state, leave a parametrically small imprint on the correlators that we study. We briefly discuss ways to diagnose these small corrections, and we propose another correlator where inelastic effects are order one.

  17. Understaning the "funding effect"

    Oreskes, N.

    2016-12-01

    There is a long history of industry funding of scientific and engineering research in the USA. Much of this work has been of high quality. Research demonstrates, however, that corporate funding can represent a threat to scientific independence and integrity. Studies show that sponsors' interests can affect research results, particularly when sponsors have a strong interest in a particular research outcome. The effects may occur through the impact of subconscious bias on sampling, study design, data interpretation, and/or reporting of results. Corporate funding can also skew research toward investigating certain questions at the expense of others, downplaying the significance of adverse findings, and/or failing to report adverse results. Gifts can affect behavior, even when they are unrelated to research activities. These impacts that are so substantial that they have a name: "the funding effect."[i] Evidence shows that scientists who strive to be objective and fair-minded may nonetheless fall prey to the funding effect. In many cases, the challenges of corporate gifts and funding can be addressed through education and improved self-awareness, agreements that protect researchers' freedom to publish without sponsor approval, sensible disclosure policies, and reasonable sanctions for failures of disclosure. However, in some cases, it may be appropriate for researchers and scientific societies to decline funding.

  18. Squeezing the Efimov effect

    Sandoval, J. H.; Bellotti, F. F.; Yamashita, M. T.; Frederico, T.; Fedorov, D. V.; Jensen, A. S.; Zinner, N. T.

    2018-03-01

    The quantum mechanical three-body problem is a source of continuing interest due to its complexity and not least due to the presence of fascinating solvable cases. The prime example is the Efimov effect where infinitely many bound states of identical bosons can arise at the threshold where the two-body problem has zero binding energy. An important aspect of the Efimov effect is the effect of spatial dimensionality; it has been observed in three dimensional systems, yet it is believed to be impossible in two dimensions. Using modern experimental techniques, it is possible to engineer trap geometry and thus address the intricate nature of quantum few-body physics as function of dimensionality. Here we present a framework for studying the three-body problem as one (continuously) changes the dimensionality of the system all the way from three, through two, and down to a single dimension. This is done by considering the Efimov favorable case of a mass-imbalanced system and with an external confinement provided by a typical experimental case with a (deformed) harmonic trap.

  19. Stringy effects in scrambling

    Shenker, Stephen H.; Stanford, Douglas

    2015-01-01

    In (http://dx.doi.org/10.1007/JHEP03(2014)067) we gave a precise holographic calculation of chaos at the scrambling time scale. We studied the influence of a small perturbation, long in the past, on a two-sided correlation function in the thermofield double state. A similar analysis applies to squared commutators and other out-of-time-order one-sided correlators (http://dx.doi.org/10.1007/JHEP12(2014)046, http://dx.doi.org/10.1007/JHEP03(2015)051A). The essential bulk physics is a high energy scattering problem near the horizon of an AdS black hole. The above papers used Einstein gravity to study this problem; in the present paper we consider stringy and Planckian corrections. Elastic stringy corrections play an important role, effectively weakening and smearing out the development of chaos. We discuss their signature in the boundary field theory, commenting on the extension to weak coupling. Inelastic effects, although important for the evolution of the state, leave a parametrically small imprint on the correlators that we study. We briefly discuss ways to diagnose these small corrections, and we propose another correlator where inelastic effects are order one.

  20. Inverse Faraday Effect Revisited

    Mendonça, J. T.; Ali, S.; Davies, J. R.

    2010-11-01

    The inverse Faraday effect is usually associated with circularly polarized laser beams. However, it was recently shown that it can also occur for linearly polarized radiation [1]. The quasi-static axial magnetic field by a laser beam propagating in plasma can be calculated by considering both the spin and the orbital angular momenta of the laser pulse. A net spin is present when the radiation is circularly polarized and a net orbital angular momentum is present if there is any deviation from perfect rotational symmetry. This orbital angular momentum has recently been discussed in the plasma context [2], and can give an additional contribution to the axial magnetic field, thus enhancing or reducing the inverse Faraday effect. As a result, this effect that is usually attributed to circular polarization can also be excited by linearly polarized radiation, if the incident laser propagates in a Laguerre-Gauss mode carrying a finite amount of orbital angular momentum.[4pt] [1] S. ALi, J.R. Davies and J.T. Mendonca, Phys. Rev. Lett., 105, 035001 (2010).[0pt] [2] J. T. Mendonca, B. Thidé, and H. Then, Phys. Rev. Lett. 102, 185005 (2009).

  1. Nonnutritive effects of glutamine.

    Roth, Erich

    2008-10-01

    Glutamine is the most abundant free amino acid of the human body. Besides its role as a constituent of proteins and its importance in amino acid transamination, glutamine has regulatory capacity in immune and cell modulation. Glutamine deprivation reduces proliferation of lymphocytes, influences expression of surface activation markers on lymphocytes and monocytes, affects the production of cytokines, and stimulates apoptosis. Moreover, glutamine administration seems to have a positive effect on glucose metabolism in the state of insulin resistance. Glutamine influences a variety of different molecular pathways. Glutamine stimulates the formation of heat shock protein 70 in monocytes by enhancing the stability of mRNA, influences the redox potential of the cell by enhancing the formation of glutathione, induces cellular anabolic effects by increasing the cell volume, activates mitogen-activated protein kinases, and interacts with particular aminoacyl-transfer RNA synthetases in specific glutamine-sensing metabolism. Glutamine is applied under clinical conditions as an oral, parenteral, or enteral supplement either as the single amino acid or in the form of glutamine-containing dipeptides for preventing mucositis/stomatitis and for preventing glutamine-deficiency in critically ill patients. Because of the high turnover rate of glutamine, even high amounts of glutamine up to a daily administration of 30 g can be given without any important side effects.

  2. The intention interference effect.

    Cohen, Anna-Lisa; Kantner, Justin; Dixon, Roger A; Lindsay, D Stephen

    2011-01-01

    Intentions have been shown to be more accessible (e.g., more quickly and accurately recalled) compared to other sorts of to-be-remembered information; a result termed an intention superiority effect (Goschke & Kuhl, 1993). In the current study, we demonstrate an intention interference effect (IIE) in which color-naming performance in a Stroop task was slower for words belonging to an intention that participants had to remember to carry out (Do-the-Task condition) versus an intention that did not have to be executed (Ignore-the-Task condition). In previous work (e.g., Cohen et al., 2005), having a prospective intention in mind was confounded with carrying a memory load. In Experiment 1, we added a digit-retention task to control for effects of cognitive load. In Experiment 2, we eliminated the memory confound in a new way, by comparing intention-related and control words within each trial. Results from both Experiments 1 and 2 revealed an IIE suggesting that interference is very specific to the intention, not just to a memory load.

  3. The real butterfly effect

    Palmer, T N; Döring, A; Seregin, G

    2014-01-01

    Historical evidence is reviewed to show that what Ed Lorenz meant by the iconic phrase ‘the butterfly effect’ is not at all captured by the notion of sensitive dependence on initial conditions in low-order chaos. Rather, as presented in his 1969 Tellus paper, Lorenz intended the phrase to describe the existence of an absolute finite-time predicability barrier in certain multi-scale fluid systems, implying a breakdown of continuous dependence on initial conditions for large enough forecast lead times. To distinguish from ‘mere’ sensitive dependence, the effect discussed in Lorenz's Tellus paper is referred to as ‘the real butterfly effect’. Theoretical evidence for such a predictability barrier in a fluid described by the three-dimensional Navier–Stokes equations is discussed. Whilst it is still an open question whether the Navier–Stokes equation has this property, evidence from both idealized atmospheric simulators and analysis of operational weather forecasts suggests that the real butterfly effect exists in an asymptotic sense, i.e. for initial-time atmospheric perturbations that are small in scale and amplitude compared with (weather) scales of interest, but still large in scale and amplitude compared with variability in the viscous subrange. Despite this, the real butterfly effect is an intermittent phenomenon in the atmosphere, and its presence can be signalled a priori, and hence mitigated, by ensemble forecast methods. (invited article)

  4. Effects of radiation

    Masse, R.

    2006-01-01

    The medical consequences of a whole-body irradiation come from the destruction of cells and inflammatory reactions it provokes. The most sensitive organs are the tissues that actively split. The embryo is particularly sensitive, from 200 mSv for the effects on the brain development. The reproduction functions are reached for man from 2000 mSv, the ovary sensitivity is less, the oocytes do not split after the fetus life. For adult the bone marrow outrage leads to the disappearing of blood cells (4000 mSv). The doses from 6000 to 10000 mSv lead the failure of the digestive system and lung. for the upper doses every tissue is reached, particularly by the effects on cells of blood vessels. Important brain dysfunctions appear beyond 10000 mSv. As regards the delayed effects of overexposures the epidemiology brings to light sanitary consequences of the exposure of the population to the ionizing radiations and requires that all the possible factors associated for that purpose are considered. About hereditary effects, it appears that moderate acute radiation exposures of even a relatively large human population must have little impact, in spite of the rate of spontaneous congenital deformations is of the order of 6 %. For the induction of cancers, it is not observed excess for doses lower than 200 mSv for adults and 100 mSv for children (the populations studied are survival people of hiroshima and Nagasaki, patients treated by irradiation, uranium miners, children exposed to radioactive iodine after Chernobylsk accident). To simplify an expression of the risk has been fixed to 5% of induced cancer by Sv for population and 4% by Sv for workers, the different being explained by the demography and the sensitivity of the youngest age groups. As regards the low doses of radiations, a bundle of convergent epidemiological observations notices the absence of effects of the low doses rates. Biological mechanisms, notably of repair are approached, then certain accidents (Goiania

  5. Estimation of morbidity effects

    Ostro, B.

    1994-01-01

    Many researchers have related exposure to ambient air pollution to respiratory morbidity. To be included in this review and analysis, however, several criteria had to be met. First, a careful study design and a methodology that generated quantitative dose-response estimates were required. Therefore, there was a focus on time-series regression analyses relating daily incidence of morbidity to air pollution in a single city or metropolitan area. Studies that used weekly or monthly average concentrations or that involved particulate measurements in poorly characterized metropolitan areas (e.g., one monitor representing a large region) were not included in this review. Second, studies that minimized confounding ad omitted variables were included. For example, research that compared two cities or regions and characterized them as 'high' and 'low' pollution area were not included because of potential confounding by other factors in the respective areas. Third, concern for the effects of seasonality and weather had to be demonstrated. This could be accomplished by either stratifying and analyzing the data by season, by examining the independent effects of temperature and humidity, and/or by correcting the model for possible autocorrelation. A fourth criterion for study inclusion was that the study had to include a reasonably complete analysis of the data. Such analysis would include an careful exploration of the primary hypothesis as well as possible examination of te robustness and sensitivity of the results to alternative functional forms, specifications, and influential data points. When studies reported the results of these alternative analyses, the quantitative estimates that were judged as most representative of the overall findings were those that were summarized in this paper. Finally, for inclusion in the review of particulate matter, the study had to provide a measure of particle concentration that could be converted into PM10, particulate matter below 10

  6. How molecular motors are arranged on a cargo is important for vesicular transport.

    Robert P Erickson

    2011-05-01

    Full Text Available The spatial organization of the cell depends upon intracellular trafficking of cargos hauled along microtubules and actin filaments by the molecular motor proteins kinesin, dynein, and myosin. Although much is known about how single motors function, there is significant evidence that cargos in vivo are carried by multiple motors. While some aspects of multiple motor function have received attention, how the cargo itself--and motor organization on the cargo--affects transport has not been considered. To address this, we have developed a three-dimensional Monte Carlo simulation of motors transporting a spherical cargo, subject to thermal fluctuations that produce both rotational and translational diffusion. We found that these fluctuations could exert a load on the motor(s, significantly decreasing the mean travel distance and velocity of large cargos, especially at large viscosities. In addition, the presence of the cargo could dramatically help the motor to bind productively to the microtubule: the relatively slow translational and rotational diffusion of moderately sized cargos gave the motors ample opportunity to bind to a microtubule before the motor/cargo ensemble diffuses out of range of that microtubule. For rapidly diffusing cargos, the probability of their binding to a microtubule was high if there were nearby microtubules that they could easily reach by translational diffusion. Our simulations found that one reason why motors may be approximately 100 nm long is to improve their 'on' rates when attached to comparably sized cargos. Finally, our results suggested that to efficiently regulate the number of active motors, motors should be clustered together rather than spread randomly over the surface of the cargo. While our simulation uses the specific parameters for kinesin, these effects result from generic properties of the motors, cargos, and filaments, so they should apply to other motors as well.

  7. Effects of increased biofuel utilization

    Bahr, J.; Blad, B.; Hillring, B.

    1996-01-01

    This report is a compilation of present knowledge regarding the effects of an increased use of biomass fuels. Main areas treated are: Availability of raw materials; Effects on forestry and agriculture; Transportation; Areas of use; Cost and price formation; Emission to the atmosphere, and effect on the climate; and Effect on employment and regional aspects. 29 tabs

  8. Isotope effects on nuclear shielding

    Hansen, P.E.

    1983-01-01

    This review concentrates upon empirical trends and practical uses of mostly secondary isotope effects, both of the intrinsic and equilibrium types. The text and the tables are arranged in the following fashion. The most 'popular' isotope effect is treated first, deuterium isotope effects on 13 C nuclear shielding, followed by deuterium on 1 H nuclear shieldings, etc. Focus is thus on the isotopes producing the effect rather than on the nuclei suffering the effect. After a brief treatment of each type of isotope effect, general trends are dealt with. Basic trends of intrinsic isotope effects such as additivity, solvent effects, temperature effects, steric effects, substituent effects and hyperconjugation are discussed. Uses of isotope effects for assignment purposes, in stereochemical studies, in hydrogen bonding and in isotopic tracer studies are dealt with. Kinetic studies, especially of phosphates, are frequently performed by utilizing isotope effects. In addition, equilibrium isotope effects are treated in great detail as these are felt to be new and very important and may lead to new uses of isotope effects. Techniques used to obtain isotope effects are briefly surveyed at the end of the chapter. (author)

  9. Cumulative radiation effect

    Kirk, J.; Cain, O.; Gray, W.M.

    1977-01-01

    Cumulative Radiation Effect (CRE) represents a scale of accumulative sub-tolerance radiation damage, with a unique value of the CRE describing a specific level of radiation effect. Computer calculations have been used to simplify the evaluation of problems associated with the applications of the CRE-system in radiotherapy. In a general appraisal of the applications of computers to the CRE-system, the various problems encountered in clinical radiotherapy have been categorised into those involving the evaluation of a CRE at a point in tissue and those involving the calculation of CRE distributions. As a general guide, the computer techniques adopted at the Glasgow Institute of Radiotherapeutics for the solution of CRE problems are presented, and consist basically of a package of three interactive programs for point CRE calculations and a Fortran program which calculates CRE distributions for iso-effect treatment planning. Many examples are given to demonstrate the applications of these programs, and special emphasis has been laid on the problem of treating a point in tissue with different doses per fraction on alternate treatment days. The wide range of possible clinical applications of the CRE-system has been outlined and described under the categories of routine clinical applications, retrospective and prospective surveys of patient treatment, and experimental and theoretical research. Some of these applications such as the results of surveys and studies of time optimisation of treatment schedules could have far-reaching consequences and lead to significant improvements in treatment and cure rates with the minimum damage to normal tissue. (author)

  10. Telepsychiatry: effectiveness and feasibility

    Gajaria A

    2015-04-01

    Full Text Available Amy Gajaria,1 David K Conn,1,2 Robert Madan1,2 1Department of Psychiatry, University of Toronto, Toronto, ON, Canada; 2Department of Psychiatry, Baycrest Health Sciences, Toronto, ON, Canada Abstract: Providing psychiatric services by real-time videoconferencing has been increasingly adopted as a method of reaching hard-to-serve populations since the early 1990s. As the field has expanded, a growing body of research has developed investigating both how telepsychiatry compares to in-person psychiatric care and how effectively telepsychiatry can be implemented in routine clinical care. A narrative review was performed to consider the evidence that telepsychiatry is feasible and effective across a variety of patient populations and clinical settings. There is a growing body of evidence investigating the efficacy of telepsychiatry when used for psychiatric assessment and treatment in the adult, child, and geriatric populations. Though studies vary in quality, they generally demonstrate that telepsychiatry is effective across multiple age groups and clinical settings. Telepsychiatry is generally well accepted by patients and clinicians and is feasible to implement, with the suggestion that some patients may actually prefer telepsychiatry to in-person treatment. Issues to consider in the implementation of telepsychiatry services include funding and reimbursement, medico-legal issues when provision crosses legislative boundaries, incorporation into existing health systems, and crosscultural considerations. Future directions for research and practice include a need for higher-quality efficacy studies, consideration of data security, increased attention to low- and middle-income countries, and the introduction of novel technological approaches. Keywords: efficacy, service delivery, telemental health, videoconferencing 

  11. Effectiveness of peritonaeal dialysis

    Jovanović Nataša

    2005-01-01

    Full Text Available Introduction. In the last few years, an increasing number of patients suffering from terminal renal disease of various leading causes was treated with renal replacement therapy. Peritonaeal dialysis involves an exchange of water and solutes between blood in the peritonaeal capillaries and dialysate in the peritonaeal cavum throughout the peritonaeum. Effective dialysis treatment should provide good quality of life, decrease the number of physical complaints, and bring the incidence of morbidity and mortality closer to the incidence of morbidity and mortality in the healthy population. Aim. The aim of this study was the evaluation of peritonaeal transport characteristics and dialysis effectiveness in 58 patients affected by terminal renal disease who underwent peritonaeal dialysis treatment during August 2003 at the Clinic of Nephrology of the Clinical Centre of Serbia. Method. We examined 30 male and 28 female patients, with an average age of 52 years (range 26 to 78 years. The average duration of peritoneal dialysis treatment was 20 months (ranging from 2 to 66 months, and the end-stage renal failure was caused by different leading disease in our patients. We applied different dialysis modalities: continuous ambulatory peritonaeal dialysis (CAPD with three to five 2- or 3-litre exchanges daily, cyclic peritonaeal dialysis (CCPD, intermittent peritonaeal dialysis (IPD, or automatic peritonaeal dialysis (APD, according to the transport characteristics of the peritonaeal membrane, the residual renal function (RRF, and the clinical status of the patients, in order to perform adequate depuration as suggested by the new international criteria. A peritonaeal equilibrium test (PET was performed according to the new international advice; urea and creatinine clearances (Kt/V and Ccr as well as RRF were calculated using the internationally suggested formulas. Results. Most of our patients received effective dialysis treatment, thanks to the modulation of

  12. Effecting dietary change.

    Adamson, Ashley J; Mathers, John C

    2004-11-01

    A world epidemic of diet-related chronic disease is currently being faced. In the UK incidence of obesity alone has tripled in the last 20 years and this trend is predicted to continue. Consensus exists for the urgent need for a change in diet and other lifestyle factors and for the direction and targets for this change. The evidence for how this change can be achieved is less certain. It has been established that disease processes begin in childhood. Recent evidence indicates that dietary habits too are established in childhood but that these habits are amenable to change. While establishing a healthy lifestyle in childhood is paramount, interventions have the potential to promote positive change throughout the life course. Success in reversing current trends in diet-related disease will depend on commitment from legislators, health professionals, industry and individuals, and this collaboration must seek to address not only the food choices of the individual but also the environment that influences such choices. Recent public health policy development in England, if fully supported and implemented, is a positive move towards this goal. Evidence for effective strategies to promote dietary change at the individual level is emerging and three reviews of this evidence are discussed. In addition, three recent dietary intervention studies, in three different settings and with different methods and aims, are presented to illustrate methods of effecting dietary change. Further work is required on what factors influence the eating behaviour and physical activity of individuals. There is a need for further theory-based research on which to develop more effective strategies to enable individuals to adopt healthier lifestyles.

  13. Effects of background radiation

    Knox, E.G.; Stewart, A.M.; Gilman, E.A.; Kneale, G.W.

    1987-01-01

    The primary objective of this investigation is to measure the relationship between exposure to different levels of background gamma radiation in different parts of the country, and different Relative Risks for leukaemias and cancers in children. The investigation is linked to an earlier analysis of the effects of prenatal medical x-rays upon leukaemia and cancer risk; the prior hypothesis on which the background-study was based, is derived from the earlier results. In a third analysis, the authors attempted to measure varying potency of medical x-rays delivered at different stages of gestation and the results supply a link between the other two estimates. (author)

  14. Environmental Effects of BPA

    Laura Canesi

    2015-07-01

    Full Text Available Research on bisphenol A (BPA as an environmental contaminant has now major regulatory implications toward the ecosystem health, and hence it is incumbent on scientists to do their research to the highest standards possible, in order that the most appropriate decisions are made to mitigate the impacts to aquatic wildlife. However, the contribution given so far appears rather fragmented. The present overview aims to collect available information on the effects of BPA on aquatic vertebrates and invertebrates to provide a general scenario and to suggest future developments toward more comprehensive approaches useful for aquatic species protection.

  15. Space Charge Effects

    Ferrario, M.; Palumbo, L.

    2014-12-19

    The space charge forces are those generated directly by the charge distribution, with the inclusion of the image charges and currents due to the interaction of the beam with a perfectly conducting smooth pipe. Space charge forces are responsible for several unwanted phenomena related to beam dynamics, such as energy loss, shift of the synchronous phase and frequency , shift of the betatron frequencies, and instabilities. We will discuss in this lecture the main feature of space charge effects in high-energy storage rings as well as in low-energy linacs and transport lines.

  16. The greenhouse effect

    Choudhury, A.M.

    1990-10-01

    In this paper, the effect of the increase of the temperature of the earth's atmosphere as a consequence of the increase in the CO 2 and other trace gas content has been reviewed. The results of various model studies have been included. There is the frightening prediction that global mean temperature will rise by several degrees with the consequent rise of mean sea level. Model computations also show that in the tropics rainfall will increase whereas in the subtropics and southern mid latitude, rainfall will decrease. If this happens, mankind will be faced with a major disaster in history. Agreement between theory and observations has been discussed. (author). 16 refs, 8 tabs

  17. Genetic effects of radiation

    Selby, P.B.

    1977-01-01

    Many of the most important findings concerning the genetic effects of radiation have been obtained in the Biology Division of Oak Ridge National Laboratory. The paper focuses on some of the major discoveries made in the Biology Division and on a new method of research that assesses damage to the skeletons of mice whose fathers were irradiated. The results discussed have considerable influence upon estimates of genetic risk in humans from radiation, and an attempt is made to put the estimated amount of genetic damage caused by projected nuclear power development into its proper perspective

  18. Holographic effective field theories

    Martucci, Luca [Dipartimento di Fisica ed Astronomia “Galileo Galilei' , Università di Padova,and INFN - Sezione di Padova, Via Marzolo 8, I-35131 Padova (Italy); Zaffaroni, Alberto [Dipartimento di Fisica, Università di Milano-Bicocca,and INFN - Sezione di Milano-Bicocca, I-20126 Milano (Italy)

    2016-06-28

    We derive the four-dimensional low-energy effective field theory governing the moduli space of strongly coupled superconformal quiver gauge theories associated with D3-branes at Calabi-Yau conical singularities in the holographic regime of validity. We use the dual supergravity description provided by warped resolved conical geometries with mobile D3-branes. Information on the baryonic directions of the moduli space is also obtained by using wrapped Euclidean D3-branes. We illustrate our general results by discussing in detail their application to the Klebanov-Witten model.

  19. The Policy Design Effect

    Hedegaard, Troels Fage

    2014-01-01

    attitudes have argued that this ‘policy design effect’ can be explained by a combination of self-interest patterns, public perceptions of the recipient group and whether eligibility under the policy is perceived as fair or arbitrary.The explanations, however, lack micro-level theory and testing as to why...... the design of a policy affects individual and public support. This article seeks to explain this policy design effect by theoretically outlining and testing how being proximate to recipients of a social benefit affects attitudes towards the benefit. A survey of attitudes towards spending on five social...

  20. Effective Lagrangian from superstrings

    Cvetic, M.

    1989-01-01

    This paper presents a method to calculate the structure of the effective potential for four-dimensional vacua of the heterotic superstring with the space-time supersymmetry. The authors spell out the properties of the string vertices as defined in terms of the conformal field theory, the structure of the string amplitudes, in particular those that probe the superpotential terms, and present a method to evaluate such string amplitudes. The authors illustrate the approach by presenting certain results for the (blown-up) orbifolds

  1. Modifying radionuclide effects

    Sasser, L.B.

    1983-01-01

    This project involves a study of the relationship of physiological and environmental factors to the metabolism and effects of radionuclides. We have studied placental transfer and suckling as pathways of americium entry into the newborn or juvenile rat. Rats were injected intravenously with 5 μCi of 241 Am while nulliparous (30 days prior to mating), pregnant (day 19 of gestation), or lactating (1 day after parturition), and subsequent litters were killed to determine 241 Am retention. A deficit in reproductive performance was observed in the group injected before mating, as evidenced by reduced number and weight of offspring

  2. Photochemical effects of sunlight.

    Daniels, F

    1972-07-01

    The importance of sunlight in bringing about not only photosynthesis in plants, but also other photochemical effects, is reviewed. More effort should be devoted to photochemical storage of the sun's energy without the living plant. There is no theoretical reason to believe that such reactions are impossible. Ground rules for searching for suitable solar photochemical reactions are given, and a few attempts are described, but nothing successful has yet been found. Future possibilities are suggested. Photogalvanic cells which convert sunlight into electricity deserve further research. Eugene Rabinowitch has been an active pioneer in these fields.

  3. Effective mechanic training

    Burdge, R.E.

    1979-01-01

    The need for the training of mechanics is discussed, and the increased interest within the utility industry of placing a similar importance on this training as it has traditionally placed on operator training, is expressed. Effective approaches and techniques are described. Fundamental mechanical maintenance concepts and their practical application are discussed, including the use of supporting video programs. The importance of follow-up practical shop exercise which reinforces classroom instruction is stressed, drawing from practical utility experience. Utilizing success in training as a measure of eligibility for advancement is discussed as well as the interface between training and the company bargaining unit

  4. Radiation effects on vasoproliferation

    Yamaura, Hirotsugu; Matsuzawa, Taiju

    1975-01-01

    The authors quantitatively examined radiation effects on vascular proliferarion, using the rat transparent chamber technique to observe the living microcirculation. We studied the process of vasoproliferation and revascularization from the surrounding pre-existing vessels into the surgically avascularized area in the chamber, by measuring the vascular lenght photographically. A hyper-vascularized zone, about 0.5 mm in with, was formed on the vascularizing frontier, the significance of which is so far not known. When the chambers were irradiated with various doses of 60 Co γ-rays, a dose dependent inhibition of vasoproliferation was observed. (auth.)

  5. Events and Effects

    Rytter, Mikkel

    2010-01-01

    Analyzing the period of ‘intensive transnationalism’ among Pakistani migrants in Denmark precipitated by the 2005 earthquake in Kashmir, this article explores the relationship between events and effects on a global scale. One significant initiative after the disaster was the founding of an ad hoc......, and national identity politics in Denmark. Despite the medical doctors’ efforts and intentions, the out- come was framed by 9/11, which has become the major critical event of the decade—one that has supported a developing cleavage between the Danish majority and Denmark’s Muslim immigrant minority....

  6. Genotoxic effect of alkaloids

    J. A. P. Henriques

    1991-01-01

    Full Text Available Because of the increase use of alkaloids in general medical practice in recent years, it is of interest to determine genotoxic, mutagenic and recombinogenic response to different groups of alkaloids in prokaryotic and eucaryotic organisms. Reserpine, boldine and chelerythrine did not show genotoxicity response in the SOS-Chromotest whereas skimmianine showed genotixicity in the presence of a metabolic activation mixture. Voacristine isolated fromthe leaves of Ervatamia coronaria shows in vivo cytostatic and mutagenic effects in Saccharomyces cerevisiae hapioids cells. The Rauwolfia alkaloid (reserpine was not able to induce reverse mutation and recombinational mitotic events (crossing-over and gene conversion in yeast diploid strain XS2316.

  7. Spin Hall effect transistor

    Wunderlich, Joerg; Park, B.G.; Irvine, A.C.; Zarbo, Liviu; Rozkotová, E.; Němec, P.; Novák, Vít; Sinova, Jairo; Jungwirth, Tomáš

    2010-01-01

    Roč. 330, č. 6012 (2010), s. 1801-1804 ISSN 0036-8075 R&D Projects: GA AV ČR KAN400100652; GA MŠk LC510 EU Projects: European Commission(XE) 215368 - SemiSpinNet Grant - others:AV ČR(CZ) AP0801 Program:Akademická prémie - Praemium Academiae Institutional research plan: CEZ:AV0Z10100521 Keywords : spin Hall effect * spintronics * spin transistor Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 31.364, year: 2010

  8. Heavy Quark Effective Theory

    Manohar, A. V.

    2003-02-01

    These lecture notes present some of the basic ideas of heavy quark effective theory. The topics covered include the classification of states, the derivation of the HQET Lagrangian at tree level, hadron masses, meson form factors, Luke's theorem, reparameterization invariance and inclusive decays. Radiative corrections are discussed in some detail, including an explicit computation of a matching correction for HQET. Borel summability, renormalons, and their connection with the QCD perturbation series is covered, as well as the use of the upsilon expansion to improve the convergence of the perturbation series.

  9. Higgs Effective Field Theories

    2016-01-01

    The main focus of this meeting is to present new theoretical advancements related to effective field theories, evaluate the impact of initial results from the LHC Run2, and discuss proposals for data interpretation/presentation during Run2. A crucial role of the meeting is to bring together theorists from different backgrounds and with different viewpoints and to extend bridges towards the experimental community. To this end, we would like to achieve a good balance between senior and junior speakers, enhancing the visibility of younger scientists while keeping some overview talks.

  10. Radiation effects on vasoproliferation

    Yamaura, H; Matsuzawa, T [Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis, Leprosy and Cancer

    1975-06-01

    The authors quantitatively examined radiation effects on vascular proliferarion, using the rat transparent chamber technique to observe the living microcirculation. We studied the process of vasoproliferation and revascularization from the surrounding pre-existing vessels into the surgically avascularized area in the chamber, by measuring the vascular lenght photographically. A hyper-vascularized zone, about 0.5 mm in with, was formed on the vascularizing frontier, the significance of which is so far not known. When the chambers were irradiated with various doses of /sup 60/Co ..gamma..-rays, a dose dependent inhibition of vasoproliferation was observed.

  11. Radiation. Doses, effect, risk

    Vapirev, E.; Todorov, P.

    1994-12-01

    This book outlines in a popular form the topic of ionizing radiation impacts on living organisms. It contains data gathered by ICRP for a period of 35 years. The essential dosimetry terms and units are presented. Natural and artificial sources of ionizing radiation are described. Possible biological radiation effects and diseases as a consequence of external and internal irradiation at normal and accidental conditions are considered. An assessment of genetic risk for human populations is presented and the concept of 'acceptable risk' is discussed

  12. Minimizing the Pacman effect

    Ritson, D.; Chou, W.

    1997-10-01

    The Pacman bunches will experience two deleterious effects: tune shift and orbit displacement. It is known that the tune shift can be compensated by arranging crossing planes 900 relative to each other at successive interaction points (lPs). This paper gives an analytical estimate of the Pacman orbit displacement for a single as well as for two crossings. For the latter, it can be minimized by using equal phase advances from one IP to another. In the LHC, this displacement is in any event small and can be neglected

  13. Interfacial effects in multilayers

    Barbee, T.W. Jr.

    1998-01-01

    Interfacial structure and the atomic interactions between atoms at interfaces in multilayers or nano-laminates have significant impact on the physical properties of these materials. A technique for the experimental evaluation of interfacial structure and interfacial structure effects is presented and compared to experiment. In this paper the impact of interfacial structure on the performance of x-ray, soft x-ray and extreme ultra-violet multilayer optic structures is emphasized. The paper is concluded with summary of these results and an assessment of their implications relative to multilayer development and the study of buried interfaces in solids in general

  14. Regional greenhouse climate effects

    Hansen, J.; Rind, D.; Delgenio, A.; Lacis, A.; Lebedeff, S.; Prather, M.; Ruedy, R.; Karl, T.

    1990-01-01

    The authors discuss the impact of an increasing greenhouse effect on three aspects of regional climate: droughts, storms and temperature. A continuous of current growth rates of greenhouse gases causes an increase in the frequency and severity of droughts in their climate model simulations, with the greatest impacts in broad regions of the subtropics and middle latitudes. But the greenhouse effect enhances both ends of the hydrologic cycle in the model, that is, there is an increased frequency of extreme wet situations, as well as increased drought. Model results are shown to imply that increased greenhouse warming will lead to more intense thunderstorms, that is, deeper thunderstorms with greater rainfall. Emanual has shown that the model results also imply that the greenhouse warming leads to more destructive tropical cyclones. The authors present updated records of observed temperatures and show that the observations and model results, averaged over the globe and over the US, are generally consistent. The impacts of simulated climate changes on droughts, storms and temperature provide no evidence that there will be regional winners if greenhouse gases continue to increase rapidly

  15. Piezoelectric effects in biomaterials

    Zimmerman, R.L.

    1976-03-01

    Precision methods have been developed for the simultaneous measurement of the complex piezoelectric stress constants and the electric conduction and polarization currents. Samples of Collagen, keratin, and chitin are prepared and measured in such a way to optimize the determination of the position and orientation of the electric dipole moments. The temperature and the hydration state of the samples are varied during the measurement of the piezoelectric constants in an effort to understand the role of water in biological material. Above 40 0 C, the inherent piezolectricity is enhanced by the water of hydration, in contrast to the more easily understood reduction observed at lower temperatures. Gelatin, which has no inherent piezoelectricity, displays a piezoelectricity proportional to the currents of conduction and polarization. An analysis of the new effect shows that it is a measure of the variation of the resistivity with deformation (d rho/dS - rho) in the same way that the electric field induced piezoelectricity is a measure of the variation of the dielectric constant with deformation (dk/dS + k). Both are sensitive to electric dipole relaxation effects. (Author) [pt

  16. Acrolein health effects.

    Faroon, O; Roney, N; Taylor, J; Ashizawa, A; Lumpkin, M H; Plewak, D J

    2008-08-01

    Acrolein is a chemical used as an intermediate reactive aldehyde in chemical industry. It is used for synthesis of many organic substances, methionine production, and methyl chloride refrigerant. The general population is exposed to acrolein via smoking, second-hand smoke, exposure to wood and plastic smoke. Firefighters and population living or working in areas with heavy automotive traffic may expose to higher level of acrolein via inhalation of smoke or automotive exhaust. Degradation of acrolein in all environmental media occurs rapidly, therefore, environmental accumulation is not expected. Acrolein degrade in 6A days when applied to surface water, and it has not been found as a contaminant in municipal drinking water. Acrolein vapor may cause eye, nasal and respiratory tract irritations in low level exposure. A decrease in breathing rate was reported by volunteers acutely exposed to 0.3A ppm of acrolein. At similar level, mild nasal epithelial dysplasia, necrosis, and focal basal cell metaplasia have been observed in rats. The acrolein effects on gastrointestinal mucosa in the animals include epithelial hyperplasia, ulceration, and hemorrhage. The severity of the effects is dose dependent. Acrolein induces the respiratory, ocular, and gastrointestinal irritations by inducing the release of peptides in nerve terminals innervating these systems. Levels of acrolein between 22 and 249 ppm for 10 min induced a dose-related decrease in substance P (a short-chain polypeptide that functions as a neurotransmitter or neuromodulator).

  17. Cumulative radiation effect

    Kirk, J.; Gray, W.M.; Watson, E.R.

    1977-01-01

    In five previous papers, the concept of Cumulative Radiation Effect (CRE) has been presented as a scale of accumulative sub-tolerance radiation damage, with a unique value of the CRE describing a specific level of radiation effect. Simple nomographic and tabular methods for the solution of practical problems in radiotherapy are now described. An essential feature of solving a CRE problem is firstly to present it in a concise and readily appreciated form, and, to do this, nomenclature has been introduced to describe schedules and regimes as compactly as possible. Simple algebraic equations have been derived to describe the CRE achieved by multi-schedule regimes. In these equations, the equivalence conditions existing at the junctions between schedules are not explicit and the equations are based on the CREs of the constituent schedules assessed individually without reference to their context in the regime as a whole. This independent evaluation of CREs for each schedule has resulted in a considerable simplification in the calculation of complex problems. The calculations are further simplified by the use of suitable tables and nomograms, so that the mathematics involved is reduced to simple arithmetical operations which require at the most the use of a slide rule but can be done by hand. The order of procedure in the presentation and calculation of CRE problems can be summarised in an evaluation procedure sheet. The resulting simple methods for solving practical problems of any complexity on the CRE-system are demonstrated by a number of examples. (author)

  18. Radiation effects on microelectronics

    Gover, J.E.

    1987-01-01

    Applications of radiation-hardened microelectronics in nuclear power systems include (a) light water reactor (LWR) containment building, postaccident instrumentation that can operate through the beta and gamma radiation released in a design basis loss-of-coolant accident; (b) advanced LWR instrumentation and control systems employing distributed digital integrated circuit (IC) technology to achieve a high degree of artificial intelligence and thereby reduce the probability of operator error under accident conditions; (c) instrumentation, command, control and communication systems for space nuclear power applications that must operate during the neutron and gamma-ray core leakage environments as well as the background electron, proton, and heavy charged particle environments of space; and (d) robotics systems designed for the described functions. Advanced microelectronics offer advantages in cost and reliability over alternative approaches to instrumentation and control. No semiconductor technology is hard to all classes of radiation effects phenomena. As the effects have become better understood, however, significant progress has been made in hardening IC technology. Application of hardened microelectronics to nuclear power systems has lagged military applications because of the limited market potential of hardened instruments and numerous institutional impediments

  19. The Chernobyl effect

    Opp, K.D.; Roehl, W.

    1990-01-01

    In what way and to what extent does an event like the Chernobyl reactor accident influence the citizen's attitudes and political commitment. This book evolves a number of theses on these questions dealing above all with the determinants of political protest. Two investigations are presented in order to verify those theses: in 1982 and 1987 (some nine months after the Chernobyl reactor accident), the same persons were interviewed. In addition, representative surveys in the Federal Republic of Germany are analysed, in order to assess in general the impact of Chernobyl. From the contents: explanation model for political protest; Chernobyl effect: effect of critical events on the mobilization of political protest; discontent with nuclear energy use, political alienation and protest; internal incentives for protest: norms, readiness for aggression, and entertainment quality of protest; resources as determinants of political protest; sanctions and protest; social nets and political protest; verification of a central model of political protest, and problems encountered by research. Appendix: investigation plan and random sampling of the panel of nuclear power opponents. (orig./HP) [de

  20. Meditation: Process and effects.

    Sharma, Hari

    2015-01-01

    Meditation has become popular in many Western nations, especially the USA. An increasing body of research shows various health benefits associated with meditation and these findings have sparked interest in the field of medicine. The practice of meditation originated in the ancient Vedic times of India and is described in the ancient Vedic texts. Meditation is one of the modalities used in Ayurveda (Science of Life), the comprehensive, natural health care system that originated in the ancient Vedic times of India. The term "meditation" is now loosely used to refer to a large number of diverse techniques. According to Vedic science, the true purpose of meditation is to connect oneself to one's deep inner Self. Techniques which achieve that goal serve the true purpose of meditation. Neurological and physiological correlates of meditation have been investigated previously. This article describes the process of meditation at a more fundamental level and aims to shed light on the deeper underlying mechanism of the beneficial effects associated with meditation. Research on the effects of meditation is summarized.

  1. Biological effects of tritium

    Nieto, M.

    1985-01-01

    The aim of this project is to study the thermal effects on proliferation activity in the intestinal epithelium of the goldfish acclimated at different temperatures (stationary state). The cell division occurs only at certain phases of the circadian cycle when the proliferative activity is synchronized or trained by an environmental factor such as light-dark cycle. Another aspect of the project is the study of the biological effects, non-stochastic, on cell kinetics in animals chronically exposed to low dose rates or tritium and gamma rays from 60 CO, used as a standard radiation. The influence on the accumulated dose per cell and cycle cell in function of the duration of the cell cycle at different acclimation temperatures should be considered. To calculate the risk of tritium contamination from nuclear power plants (radiation exposure), the organic tissue-bond is of decisive importance due to the long turnover of the organic tissue-bond in organisms favouring transport of tritium to other organisms of the ecosystem and to man. (author)

  2. The Creative Stereotype Effect.

    Denis Dumas

    Full Text Available Because of its fundamental relevance to scientific innovation, artistic expression, and human ingenuity, creativity has long been the subject of systematic psychological investigation. Concomitantly, the far-reaching effects of stereotypes on various cognitive and social processes have been widely researched. Bridging these two literatures, we show in a series of two studies that stereotypes related to creativity can both enhance and diminish individuals' performance on a divergent thinking task. Specifically, Study 1 demonstrated that participants asked to take on a stereotypically uninhibited perspective performed significantly better on a divergent thinking task than those participants who took on a stereotypically inhibited perspective, and a control group. Relatedly, Study 2 showed that the same effect is found within-subjects, with divergent thinking significantly improving when participants invoke an uninhibited stereotype. Moreover, we demonstrate the efficacy of Latent Semantic Analysis as an objective measure of the originality of ideas, and discuss implications of our findings for the nature of creativity. Namely, that creativity may not be best described as a stable individual trait, but as a malleable product of context and perspective.

  3. Ecotoxicological effects extrapolation models

    Suter, G.W. II

    1996-09-01

    One of the central problems of ecological risk assessment is modeling the relationship between test endpoints (numerical summaries of the results of toxicity tests) and assessment endpoints (formal expressions of the properties of the environment that are to be protected). For example, one may wish to estimate the reduction in species richness of fishes in a stream reach exposed to an effluent and have only a fathead minnow 96 hr LC50 as an effects metric. The problem is to extrapolate from what is known (the fathead minnow LC50) to what matters to the decision maker, the loss of fish species. Models used for this purpose may be termed Effects Extrapolation Models (EEMs) or Activity-Activity Relationships (AARs), by analogy to Structure-Activity Relationships (SARs). These models have been previously reviewed in Ch. 7 and 9 of and by an OECD workshop. This paper updates those reviews and attempts to further clarify the issues involved in the development and use of EEMs. Although there is some overlap, this paper does not repeat those reviews and the reader is referred to the previous reviews for a more complete historical perspective, and for treatment of additional extrapolation issues.

  4. Handbook of radiation effects

    Holmes-Siedle, A.; Adams, L.

    1993-01-01

    This handbook is intended to serve as a tool for designers of equipment and scientific instruments in cases where they are required to ensure the survival of the equipment in radiation environments. High-technology materials, especially semiconductors and optics, tend to degrade on exposure to radiation in many different ways. Intense high-energy radiation environments are found in nuclear reactors and accelerators, machines for radiation therapy, industrial sterilization, and space. Some engineers have to build equipment which will survive a nuclear explosion from a hostile source. Proper handling of a disaster with radioactive materials requires equipment which depends utterly on semiconductor microelectronics and imaging devices. Thus the technology of radiation-tolerant electronics is an instrument for good social spheres as diverse as disaster planning and the exploration of Mars. In order to design equipment for intense environments like those described above, then degradation from high-energy irradiation must be seen as a basic design parameter. The aim of this handbook is to assist the engineer or student in that thought; to make it possible to write intelligent specifications; to offer some understanding of the complex variety of effects which occur when high-technology components encounter high-energy radiation; and to go thoroughly into the balance of choices of how to alleviate the effects and hence achieve the design aims of the project. Separate abstracts were prepared for 15 chapters of this book

  5. Stochastic Effects in Microstructure

    Glicksman M.E.

    2002-01-01

    Full Text Available We are currently studying microstructural responses to diffusion-limited coarsening in two-phase materials. A mathematical solution to late-stage multiparticle diffusion in finite systems is formulated with account taken of particle-particle interactions and their microstructural correlations, or "locales". The transition from finite system behavior to that for an infinite microstructure is established analytically. Large-scale simulations of late-stage phase coarsening dynamics show increased fluctuations with increasing volume fraction, Vv, of the mean flux entering or leaving particles of a given size class. Fluctuations about the mean flux were found to depend on the scaled particle size, R/, where R is the radius of a particle and is the radius of the dispersoid averaged over the population within the microstructure. Specifically, small (shrinking particles tend to display weak fluctuations about their mean flux, whereas particles of average, or above average size, exhibit strong fluctuations. Remarkably, even in cases of microstructures with a relatively small volume fraction (Vv ~ 10-4, the particle size distribution is broader than that for the well-known Lifshitz-Slyozov limit predicted at zero volume fraction. The simulation results reported here provide some additional surprising insights into the effect of diffusion interactions and stochastic effects during evolution of a microstructure, as it approaches its thermodynamic end-state.

  6. "Metamagnetoelectric" effect in multiferroics

    Fouokeng, G. C.; Fodouop, F. Kuate; Tchoffo, M.; Fai, L. C.; Randrianantoandro, N.

    2018-05-01

    We present a theoretical calculation of magnetoelectric properties in a quasi-two dimensional spin chain externally controlled by a static electric field in y-direction and magnetic field in z-direction. Given the diversity of properties in functional materials and their applications in physics, the multiferroic model is investigated. By using the Fermi-Dirac statistics of quantum gases and the Landau theory, we assess the effects of the Dzyaloshinskii-Moriya interaction and the electric polarization on the magnetoelectric coupling that induces at low temperature the "metamagnetoelectric" effet, and likewise affects the ferroelectricity induced through symmetry mechanisms and magnetic properties of the multiferroic system. In fact, the variation of the induced polarisation due to spin arrangement through the Dzyaloshinskii-Moriya interaction gives rise to a multistep interdependent metamagnetic and metaelectric transitions which are settled up by the corresponding Dzyaloshinskii-Moriya parameter and the system then exhibits a spin gap that results from an electric and a magnetic demagnetization field range. This metamagnetoelectric effect observed in these multiferroic materials model is seem to be highly tunable via the external electric and magnetic fields and thus can be crucial in the design of new mechanisms for the processing and storage of data and other spintronic applications.

  7. Modification of radiation effects

    Lindenbaum, A.

    1975-01-01

    Results are reported from studies on the tissue distribution of 239 Pu and 241 Am in mice and beagle dogs and the effectiveness of various therapeutic treatments for decorporation. In dogs injected with monomeric Pu the value of a regimen of early and prolonged treatment with DTPA (diethylenetriaminepentaacetic acid) for minimizing the Pu burden in the soft tissues and skeleton was demonstrated. These results have immediate implication for DTPA treatment in man. New studies in mice verified the action of pyran copolymer antiviral agents in enhancing the effectiveness of DTPA for removal of polymeric Pu from the liver. Recent application of autoradiographic procedures for quantitatively comparing short- and long-term localization of monomeric and polymeric 239 Pu in dog liver showed that there is no net translocation of monomeric Pu within the liver between 6 and 90 days following injection. One of the molecular studies presently underway aims at synthesis of a variety of DTPA esters. The diethyl ester has already been prepared and tested for toxicity in mice. These compounds are designed to bring DTPA into contact with plutonium deposits unavailable to the action of ionic DTPA. (U.S.)

  8. Hydrothermal effects on montmorillonite

    Pusch, R.; Karnland, O.

    1988-06-01

    Hydrothermal effects on montmorillonite clay are usually taken to have the form of conversion of this clay mineral to other species, such as illite, disregarding microstructural alteration and cementation caused by precipitation of silica and other compounds. The report is focussed on identification of the primary processes that are involved in such alteration, the release of silica and the microstructural changes associated with heating being of major interest. In the first test phase, Na montmorillonite in distilled water was investigated by XRD, rheology tests and electron microscopy after heating to 60-225 0 C for 0.01 to 1 year. The preliminary conclusions are that heating produces contraction of the particle network to form dense 'branches', the effect being most obvious at the highest temperature but of significance even at 60-100 0 C. Release of substantial amounts of silica gas been documented for temperatures exceeding 150 0 and precipitation of silica was observed on cooling after the hydrothermal testing under the closed conditions that prevailed throughout the tests. The precipitates, which appeared to be amorphous and probably consisted of hydrous silica gels, were concluded to have increased the mechanical strength and caused some brittleness, particularly of the dense clays. The nature of the silica release, which is assumed to be associated with beidellitization, may be closely related to an unstable state of a certain fraction of tetrahedral silica at heat-inducted transfer between two different crystal modes of montmorillonite. (orig.)

  9. Low-level effects

    Devine, R.T.; Chaput, R.L.

    1987-01-01

    Risk assignments can be made to given practices involving exposure to radiation, because sufficient data are available for the effects of high-dose, low-LET radiation and because sufficient exists in the methods of extrapolation to low doses and low dose rates. The confidence in the extrapolations is based on the fact that the risk is not expected to be overestimated, using the assumptions made (as opposed to the possibility that the extrapolations represent an accurate estimate of the risk). These risk estimates have been applied to the selection of permissible exposure levels, to show that various amounts of radiation involve no greater risk to the worker than the risk expected in another industry that is generally considered safe. The setting of standards for protection from exposure to low levels of ionizing radiation is made by expert committees at the national and international levels who weigh social factors as well as scientific factors. Data on low-level effects may be applied when assigning a ''probability of causation'' to a certain exposure of radiation. This has become a prominent method for arriving at an equitable award for damages caused by such exposure. The generation of these tables requires as many (if not more) social and political considerations as does the setting up of protection criteria. It is impossible to extract a purely scientific conclusion solely from the protection standards and other legal decisions. Sufficient information exists on low-LET radiation that safety standards for exposure can be rationally (if not scientifically) agreed upon

  10. The Creative Stereotype Effect.

    Dumas, Denis; Dunbar, Kevin N

    2016-01-01

    Because of its fundamental relevance to scientific innovation, artistic expression, and human ingenuity, creativity has long been the subject of systematic psychological investigation. Concomitantly, the far-reaching effects of stereotypes on various cognitive and social processes have been widely researched. Bridging these two literatures, we show in a series of two studies that stereotypes related to creativity can both enhance and diminish individuals' performance on a divergent thinking task. Specifically, Study 1 demonstrated that participants asked to take on a stereotypically uninhibited perspective performed significantly better on a divergent thinking task than those participants who took on a stereotypically inhibited perspective, and a control group. Relatedly, Study 2 showed that the same effect is found within-subjects, with divergent thinking significantly improving when participants invoke an uninhibited stereotype. Moreover, we demonstrate the efficacy of Latent Semantic Analysis as an objective measure of the originality of ideas, and discuss implications of our findings for the nature of creativity. Namely, that creativity may not be best described as a stable individual trait, but as a malleable product of context and perspective.

  11. Nanoscale effects in interdiffusion

    Erdelyi, Z.; Langer, G.A.; Beke, D.L.; Csik, A.

    2007-01-01

    Complete text of publication follows. Diffusion on the nano/atomic scales in multilayers, thin films has many challenging features even if the role of structural defects can be neglected and 'only' the effects related to the nano/atomic scale raise. The most basic equations to describe the diffusion are Fick's equations. It is important to emphasize that the diffusion coefficient in Fick's equations is in general composition independent and Fick's classical equations do not include the stress effects, which can have important influence onto the diffusion especially on the nano/atomic scale. We illustrate that the continuum descriptions of the diffusion cannot be applied automatically on such short distances, the classical continuum approximations (Fick's laws) cannot describe correctly the atomic movements. They predict faster kinetics than the atomistic models and the interface shift is always proportional to the square root of the time. However, the kinetics can be even linear on the nano/atomic scale. We have shown from computer simulations that Fick's laws violate on the nanoscale either in completely or restricted miscible systems. This is strongly related to the discrete character of the system on the nanoscale and to the highly neglected fact in the literature that the diffusion coefficients depend on the composition. As will be seen the composition dependence of D is very important and has very significant influence on the diffusion kinetics on the nano/atomic scales. It originates from the fact that usually the diffusion coefficients are different in an A and in a B matrix. Consequently in case of a real interface, which is not atomically sharp, i.e. there is a more or less intermixed region between the pure A and B matrixes, the diffusion coefficient changes continuously while e.g. an A atom diffuses from the pure A matrix into the pure B. This feature can be also called diffusion asymmetry. We have also illustrated that in this case not only the

  12. Intentional binding of visual effects.

    Ruess, Miriam; Thomaschke, Roland; Kiesel, Andrea

    2018-04-01

    When an action produces an effect, the effect is perceived earlier in time compared to a stimulus without preceding action. This temporal bias is called intentional binding (IB) and serves as an implicit measure of sense of agency. Typically, IB is investigated by presenting a rotating clock hand while participants execute an action and perceive a resulting tone. Participants are asked to estimate the time point of tone onset by referring to the clock hand position. This time point estimate is compared to a time point estimate of a tone in a condition in which the tone occurs without preceding action. Studies employing this classic clock paradigm employed auditory action effects. We modified this paradigm to investigate potential IB of visual action effects, and, additionally, to investigate how IB differs for visual action effects (Experiment 1) in comparison to auditory action effects (Experiment 2). Our results show that, like the IB of an auditory effect, the time point of a visual action effect is shifted toward the causing action, and that the size of the IB depends on the delay duration of the effect. Comparable to auditory action effects, earlier action effects showed stronger IB compared to later action effects. Yet overall IB of the visual effects was weaker than IB of the auditory effects. As IB is seen as an indicator of sense of agency, this may have important implications for the design of human-machine interfaces.

  13. Effective Bug Finding

    Rivas, Iago Abal

    Lightweight bug finders (also known as code scanners) are becoming popular, they scale well and can find simple yet common programming errors. It is now considered a good practice to integrate these tools as part of your development process. The Linux project, for instance, has an automated testing...... service, known as the Kbuild robot, that runs a few of these code scanners. In this project, I have carefully studied tens of historical Linux bugs, and I have found that many of these bugs, despite being conceptually simple, were not caught by any code scanning tool. The reason is that, by design, code...... by matching temporal bug-patterns against the control-flow graph of this program abstraction. I have implemented a proof-of-concept bug finder based on this technique, EBA, and confirmed that it is both scalable and effective at finding bugs. On a benchmark of historical Linux double-lock bugs, EBA was able...

  14. Cumulative environmental effects. Summary

    2012-01-01

    This report presents a compilation of knowledge about the state of the environment and human activity in the Norwegian part of the North Sea and Skagerrak. The report gives an overview of pressures and impacts on the environment from normal activity and in the event of accidents. This is used to assess the cumulative environmental effects, which factors have most impact and where the impacts are greatest, and to indicate which problems are expected to be most serious in the future. The report is intended to provide relevant information that can be used in the management of the marine area in the future. It also provides input for the identification of environmental targets and management measures for the North Sea and Skagerrak.(Author)

  15. Cumulative environmental effects. Summary

    NONE

    2012-07-01

    This report presents a compilation of knowledge about the state of the environment and human activity in the Norwegian part of the North Sea and Skagerrak. The report gives an overview of pressures and impacts on the environment from normal activity and in the event of accidents. This is used to assess the cumulative environmental effects, which factors have most impact and where the impacts are greatest, and to indicate which problems are expected to be most serious in the future. The report is intended to provide relevant information that can be used in the management of the marine area in the future. It also provides input for the identification of environmental targets and management measures for the North Sea and Skagerrak.(Author)

  16. Managing intercultural conflict effectively

    Ting-Toomey, Stella

    2001-01-01

    In this volume, Ting-Toomey and Oetzel accomplish two objectives: to explain the culture-based situational conflict model, including the relationship among conflict, ethnicity, and culture; and, second, integrate theory and practice in the discussion of interpersonal conflict in culture, ethnic, and gender contexts. While the book is theoretically directed, it is also a down-to-earth practical book that contains ample examples, conflict dialogues, and critical incidents. Managing Intercultural Conflict Effectively helps to illustrate the complexity of intercultural conflict interactions and readers will gain a broad yet integrative perspective in assessing intercultural conflict situations. The book is a multidisciplinary text that draws from the research work of a variety of disciplines such as cross-cultural psychology, social psychology, sociology, marital and family studies, international management, and communication.

  17. About greenhouse effect origins

    Arrhenius, S.; Chamberlin, Th.; Croll, J.; Fourier, J.; Pouillet, C.; Tyndall, J.

    2009-01-01

    In order to understand and decipher the ecological crisis in progress, an historical prospect of its origins and evolution at the worldwide scale is necessary. This book gathers seven founder articles (including 4 original translations), harbingers of the present day climate change. Written during the 19. century by famous scientists like Joseph Fourier, Claude Pouillet, James Croll, John Tyndall, Svante Arrhenius and Thomas Chamberlin, they relate a century of major progress in the domain of Earth's sciences in praise of these scientists. This book allows to (re)discover these texts: discovery of the greenhouse effect principle (Fourier), determination of solar radiation absorption by the atmosphere (Pouillet), rivalry between the astronomical theory of glacial cycles (Croll) and the carbon dioxide climatic theory (Tyndall), influence of the CO 2 concentration in the atmosphere on the global warming (Arrhenius), and confirmation of the major role of CO 2 in the Earth's temperature regulation (Chamberlin). (J.S.)

  18. Applications of Josephson effect

    Benacka, S.

    Week coupling superconducting systems are described, such as the tunnel system, the bridge-type system, the whisker connection of two superconductors, and the Clark SLUG (Superconducting Low-Inductance Undulatory Galvanometer). The equivalent diagram is presented. If the power supply resistance is greater than the barrier resistance, the hysteresis occurs of the volt-ampere characteristics as a function of the inherent capacitance and inductance of the system. In the opposite case, hysteresis decays and the negative differential resistance region may be effective. The d.c. and high-='requency SQUID (Superconducting Quantum Interference Device) systems are described. The whisker and bridge types are mainly used in the high-frequency region. These systems may be used as sources of electromagnetic radiation of up to 10 THz. The generated out.out is in the order of 10 -10 W. (J.B.)

  19. Ground motion effects

    Blume, J A [John A. Blume and Associates, San Francisco, CA (United States)

    1969-07-01

    Ground motion caused by natural earthquakes or by nuclear explosion causes buildings and other structures to respond in such manner as possibly to have high unit stresses and to be subject to damage or-in some cases-collapse. Even minor damage may constitute a hazard to persons within or adjacent to buildings. The risk of damage may well be the governing restraint on the uses of nuclear energy for peaceful purposes. Theory is advanced regarding structural-dynamic response but real buildings and structures are complex, highly variable, and often difficult to model realistically. This paper discusses the state of knowledge, the art of damage prediction and safety precautions, and shows ground motion effects from explosions of underground nuclear devices in the continental United States including events Salmon, Gasbuggy, Boxcar, Faultless and Benham. (author)

  20. The Creativity Passdown Effect

    Pries-Heje, Jan; Lee, Jong Seok; Baskerville, Richard

    2012-01-01

    Design theory lies at the heart of information systems design science research. One concern in this area is the potential to limit the designer’s creativity by over-specifying the meta-design or the design process. This paper explains how design research encapsulates a two-person design team...... consisting of the design theorist and the artifact instance designer. Design theory embodies a creativity passdown effect in which the creative design thinking is partly executed by the design theorist and the completion of this thinking is deferred to the artifact instance designer. In fact, rather than...... limiting the instance designer’s creativity, the design theorist may create an opportunity for the instance designer to be creative by passing down a design theory. Further, the artifact instance designer operates within the problem domain defined by design theorist, and engages in design thinking...

  1. TOWARD MORE EFFECTIVE REGULATION

    J. GRAF

    2000-06-01

    This paper proposes a model relationship between the operator engaged in a hazardous activity, the regulator of that activity, and the general public. The roles and responsibilities of each entity are described in a way that allows effective communication flow. The role of the regulator is developed using the steam boiler as an example of a hazard subject to regulation; however, the model applies to any regulated activity. In this model the safety analyst has the extremely important role of communicating sometimes difficult technical information to the regulator in a way that the regulator can provide credible assurance to the general public as to the adequacy of the control of the hazardous activity. The conclusion asserts that acceptance of the model, understanding of the roles and responsibilities and definition of who communicates what information to whom will mitigate frustration on the part of each of the three entities.

  2. Performance effect of Lean

    Kristensen, Thomas Borup; Israelsen, Poul

    2016-01-01

    To understand how the practices of Lean affect performance, we tested and validated a system-wide approach using mediating relationships in a structural equation model. We used a cross-sectional survey of 200 Danish companies that indicated that they used Lean. Thus, this study is especially...... relevant to Denmark, but the approach is empirically more generalizable. We show that the effect of Lean standardized flow production practices on performance is mediated by analytical continuous improvement empowerment practices and by delegation of decision rights practices. Thus, standardized flow...... of decision rights. The paper provides evidence that supports the view that middle managers’ actions further enhance performance in Lean companies. The right Lean behavior by middle managers increases the level of analytical continuous improvement empowerment. In total, high-performing Lean companies...

  3. The Music Effect

    Ridder, Hanne Mette Ochsner

    2006-01-01

    http://www.njmt.no/bookreview_2006071.html "The music effect is not about a particular composer, musical style, geographic location, language, or performance group. It is, at once, about all of these" (p. 249). This book is written by two people with very different educational backgrounds. Dr...... into music physiology. We have already seen them working together in 2001 in Berger’s book Music Therapy, Sensory Integration and the Autistic Child published by Jessica Kingsley, and this time their collaboration results in a book that is about the attributes of scientific reality (physics) as embedded....... Schneck is a fellow of the American Institute for Medical and Biological Engineering and Dorita S. Berger, MA, is a Board Certified music therapist. They have in common that both play music and perform professionally, and together they integrate various theories from scientific reality and music aesthetic...

  4. The Effective Ambidextrous Organization

    Andersen, Torben Juul; Nielsen, Bo Bernhard

    the essence of organizational ambidexterity as the means to sustain performance over time when environmental conditions change. This paper incorporates strategic management and organization theoretical rationales in a model that combines elements of integration and experimentation in the strategy making....... Results of structural equation analyses indicate that superior performance in the ambidextrous organizations is associated with efficiencies derived from adherence to centralized strategic planning and effectiveness generated by decentralized innovative behavior through participation and autonomous...... process and thereby extends the evolving literature on the ambidextrous organization. The performance relationships of the ambidextrous integrative strategy making model are investigated on the basis of a cross-sectional sample of 185 business entities operating in different manufacturing industries...

  5. Radioactive effect of ribomunyl

    Vavrova, J.

    1994-01-01

    Ribomunyl is an immunomodulation agent used in prevention of chronic respiratory disease in man. A single s.c. and i.p. Ribomunyl administration in the dose of 50 and 125 g/mouse, resp., resulted for the non-irradiated animals in stimulation of the 125 IUdR incorporation into the spleen and the marrow. On the other hand there occurred erythropoiesis suppression in the marrow, measured by the 59 Fe incorporation. In sublethally irradiated mice Ribomunyl stimulates a faster regeneration of the 125 IUdR incorporation into the spleen. In the irradiated mice we proved a radioprotective effect of Ribomunyl in case of single i.p. and s.c. administration 24 hr before irradiation. The value of the dose reduction factor (DRF) equals to 1.2. (author)

  6. Hot chocolate effect

    Crawford, F.S.

    1982-01-01

    The ''hot chocolate effect'' was investigated quantitatively, using water. If a tall glass cylinder is filled nearly completely with water and tapped on the bottom with a softened mallet one can detect the lowest longitudinal mode of the water column, for which the height of the water column is one-quarter wavelength. If the cylinder is rapidly filled with hot tap water containing dissolved air the pitch of that mode may descend by nearly three octaves during the first few seconds as the air comes out of solution and forms bubbles. Then the pitch gradually rises as the bubbles float to the top. A simple theoretical expression for the pitch ratio is derived and compared with experiment. The agreement is good to within the 10% accuracy of the experiments

  7. Ground motion effects

    Blume, J.A.

    1969-01-01

    Ground motion caused by natural earthquakes or by nuclear explosion causes buildings and other structures to respond in such manner as possibly to have high unit stresses and to be subject to damage or-in some cases-collapse. Even minor damage may constitute a hazard to persons within or adjacent to buildings. The risk of damage may well be the governing restraint on the uses of nuclear energy for peaceful purposes. Theory is advanced regarding structural-dynamic response but real buildings and structures are complex, highly variable, and often difficult to model realistically. This paper discusses the state of knowledge, the art of damage prediction and safety precautions, and shows ground motion effects from explosions of underground nuclear devices in the continental United States including events Salmon, Gasbuggy, Boxcar, Faultless and Benham. (author)

  8. Piezotronic and Piezophototronic Effects

    Wang, Zhong Lin

    2010-05-06

    Owing to the polarization of ions in a crystal that has noncentral symmetry, a piezoelectric potential (piezopotential) is created in the material by applying a stress. The creation of piezopotential together with the presence of Schottky contacts are the fundamental physics responsible for a few important nanotechnologies. The nanogenerator is based on the piezopotential-driven transient flow of electrons in the external load. On the basis of nanomaterials in the wurtzite semiconductors, such as ZnO and GaN, electronics fabricated by using a piezopotential as a gate voltage are called piezotronics, with applications in strain/force/pressure-triggered/controlled electronic devices, sensors, and logic gates. The piezophototronic effect is a result of three-way coupling among piezoelectricity, photonic excitation, and semiconductor transport, which allows tuning and controlling of electro-optical processes by a strain-induced piezopotential. © 2010 American Chemical Society.

  9. The effective bootstrap

    Castedo Echeverri, Alejandro; Harling, Benedict von; Serone, Marco

    2016-06-01

    We study the numerical bounds obtained using a conformal-bootstrap method where different points in the plane of conformal cross ratios z and anti z are sampled. In contrast to the most used method based on derivatives evaluated at the symmetric point z= anti z=1/2, we can consistently ''integrate out'' higher-dimensional operators and get a reduced simpler, and faster to solve, set of bootstrap equations. We test this ''effective'' bootstrap by studying the 3D Ising and O(n) vector models and bounds on generic 4D CFTs, for which extensive results are already available in the literature. We also determine the scaling dimensions of certain scalar operators in the O(n) vector models, with n=2,3,4, which have not yet been computed using bootstrap techniques.

  10. Space-Charge Effect

    Chauvin, N

    2013-01-01

    First, this chapter introduces the expressions for the electric and magnetic space-charge internal fields and forces induced by high-intensity beams. Then, the root-mean-square equation with space charge is derived and discussed. In the third section, the one-dimensional Child-Langmuir law, which gives the maximum current density that can be extracted from an ion source, is exposed. Space-charge compensation can occur in the low-energy beam transport lines (located after the ion source). This phenomenon, which counteracts the spacecharge defocusing effect, is explained and its main parameters are presented. The fifth section presents an overview of the principal methods to perform beam dynamics numerical simulations. An example of a particles-in-cells code, SolMaxP, which takes into account space-charge compensation, is given. Finally, beam dynamics simulation results obtained with this code in the case of the IFMIF injector are presented. (author)

  11. Space-Charge Effect

    Chauvin, N.

    2013-12-16

    First, this chapter introduces the expressions for the electric and magnetic space-charge internal fields and forces induced by high-intensity beams. Then, the root-mean-square equation with space charge is derived and discussed. In the third section, the one-dimensional Child-Langmuir law, which gives the maximum current density that can be extracted from an ion source, is exposed. Space-charge compensation can occur in the low-energy beam transport lines (located after the ion source). This phenomenon, which counteracts the spacecharge defocusing effect, is explained and its main parameters are presented. The fifth section presents an overview of the principal methods to perform beam dynamics numerical simulations. An example of a particles-in-cells code, SolMaxP, which takes into account space-charge compensation, is given. Finally, beam dynamics simulation results obtained with this code in the case of the IFMIF injector are presented.

  12. The hot chocolate effect

    Crawford, Frank S.

    1982-05-01

    The ''hot chocolate effect'' was investigated quantitatively, using water. If a tall glass cylinder is filled nearly completely with water and tapped on the bottom with a softened mallet one can detect the lowest longitudinal mode of the water column, for which the height of the water column is one-quarter wavelength. If the cylinder is rapidly filled with hot tap water containing dissolved air the pitch of that mode may descend by nearly three octaves during the first few seconds as the air comes out of solution and forms bubbles. Then the pitch gradually rises as the bubbles float to the top. A simple theoretical expression for the pitch ratio is derived and compared with experiment. The agreement is good to within the 10% accuracy of the experiments.

  13. Hydrodynamic effects on coalescence.

    Dimiduk, Thomas G.; Bourdon, Christopher Jay; Grillet, Anne Mary; Baer, Thomas A.; de Boer, Maarten Pieter; Loewenberg, Michael (Yale University, New Haven, CT); Gorby, Allen D.; Brooks, Carlton, F.

    2006-10-01

    The goal of this project was to design, build and test novel diagnostics to probe the effect of hydrodynamic forces on coalescence dynamics. Our investigation focused on how a drop coalesces onto a flat surface which is analogous to two drops coalescing, but more amenable to precise experimental measurements. We designed and built a flow cell to create an axisymmetric compression flow which brings a drop onto a flat surface. A computer-controlled system manipulates the flow to steer the drop and maintain a symmetric flow. Particle image velocimetry was performed to confirm that the control system was delivering a well conditioned flow. To examine the dynamics of the coalescence, we implemented an interferometry capability to measure the drainage of the thin film between the drop and the surface during the coalescence process. A semi-automated analysis routine was developed which converts the dynamic interferogram series into drop shape evolution data.

  14. Haemodynamic effects of eating

    Høost, U; Kelbaek, H; Rasmusen, H

    1996-01-01

    to obtain forearm blood flow and Doppler-ultrasonography for portal vein flow. Plasma levels of catecholamines and insulin were determined by radioimmunoassay. 3. Cardiac output increased considerably after each meal, including the control meal (water) with only minor differences in extent and timing. Left......1. The purpose of this study was to investigate the effect of fractional meal stimulation on postprandial haemodynamic changes, the possible correlation between these changes and the potential mediating role of circulating catecholamines and insulin. 2. Healthy young subjects were studied before...... and after ingestion of isocaloric, isovolumetric high-protein, carbohydrate or fat meals (80-85% of total energy), 60 kJ per kg of body weight. Multigated radionuclide cardiography with autologous 99mTc-labelled erythrocytes was performed for assessment of cardiac output, venous occlusion plethysmography...

  15. Radiation effects on polyethylenes

    Suzuki, T.; Oki, Y.; Numajiri, M.; Miura, T.; Kondo, K.; Tanabe, Y.; Ishiyama, M.; Ito, Y.

    1992-01-01

    Radiation effects on four kinds of polyethylenes were studied from the viewpoints of mechanical properties, free radicals and free volumes. The samples were irradiated using a cobalt 60 gamma source to give doses up to 3MGy. The degradation of mechanical strength due to gamma-irradiation was evaluated by the elongation at break and its tensile strength. Radiation induced free radicals were measured by ESR. Free volumes observed by the o-Ps component of the positron annihilation spectrum are normally the large ones located in the amorphous regions and after irradiation these are created in crystalline regions, too. The sizes and the relative numbers of free volumes were evaluated by lifetimes and intensities of a long-lived component of positronium, respectively. Using these data, the properties of polyethylenes before and after irradiation are discussed. (author)

  16. Hepatoprotective Effects of Mushrooms

    Rosane Marina Peralta

    2013-07-01

    Full Text Available The particular characteristics of growth and development of mushrooms in nature result in the accumulation of a variety of secondary metabolites such as phenolic compounds, terpenes and steroids and essential cell wall components such as polysaccharides, b-glucans and proteins, several of them with biological activities. The present article outlines and discusses the available information about the protective effects of mushroom extracts against liver damage induced by exogenous compounds. Among mushrooms, Ganoderma lucidum is indubitably the most widely studied species. In this review, however, emphasis was given to studies using other mushrooms, especially those presenting efforts of attributing hepatoprotective activities to specific chemical components usually present in the mushroom extracts.

  17. A Moessbauer effect spectrometer

    Fayek, M.K.; Abbas, Y.M.; Bahgat, A.A.

    1983-01-01

    A Moessbauer effect spectrometer of Harwell type is installed and put in operation. The driving system is of a constant acceleration mode with a velocity range 40mm/sec. and associated to a 1024 multichannel analyser working in a multiscalar time mode. The gamma ray sources are 50 mCi Co 57 in Pd and 20 mCi Snsup(119m) in Ba Sn(O) 3 . Measurements are taken with the source kept at room temperature, while the absorber can be maintained at various temperatures. Gamma ray resonance spectra of different standard samples are obtained. Zero velocity and magnetic field calibration curves are deduced. Examples of some Moessbauer spectra for running investigated materials with a comprehensive general description are also given

  18. Late somatic effects

    Gilbert, E.

    1985-01-01

    A model is provided for estimating risks of late effects resulting from low-LET radiation exposure likely to be received in the event of a nuclear power plant accident. Separate estimates are provided for risks of leukemia, cancers of the bones, lungs, gastrointestinal tract, thyroid, skin, and the residual group of all other cancers; estimates of leukemia and other cancers due to in utero exposure are also provided. Risks are expressed in absolute terms as the number of cancer deaths (or cases) per million persons exposed to a particular dose. In addition, the number of years of life lost and the number of years of life lived after the occurrence of cancer are also estimated. The model used in the earlier Reactor Safety Study has been modified to reflect additional epidemiological data and these changes are described in detail. 37 references, 1 figure, 13 tables

  19. COSYMA: Health effects models

    Ehrhardt, J.

    1995-02-01

    As one of the main objectives of the MARIA project (''Methods for Assessing the Radiological Impact of Accidents'') initiated by the Commission of the European Communities the program package COSYMA (''COde SYstem from MARIA'') for assessing the radiological and economic off-site consequences of accidental releases of radioactive material to the atmosphere has been jointly developed by the Kernforschungszentrum Karlsruhe (KfK), FRG, and the National Radiological Protection Board (NRPB), UK. COSYMA includes models and data for assessing a broad spectrum of accident consequences, and they are implemented in independent modules. The subject of this report are those modules, which incorporate models and data for assessing individual and collective risks for deterministic and stochastic health effects. It describes the models implemented, the mathematical algorithms and the required data. Examples are given and explained for the input and output part of the modules. (orig.)

  20. The effective bootstrap

    Castedo Echeverri, Alejandro [SISSA, Trieste (Italy); INFN, Trieste (Italy); Harling, Benedict von [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Serone, Marco [SISSA, Trieste (Italy); INFN, Trieste (Italy); ICTP, Trieste (Italy)

    2016-06-15

    We study the numerical bounds obtained using a conformal-bootstrap method where different points in the plane of conformal cross ratios z and anti z are sampled. In contrast to the most used method based on derivatives evaluated at the symmetric point z= anti z=1/2, we can consistently ''integrate out'' higher-dimensional operators and get a reduced simpler, and faster to solve, set of bootstrap equations. We test this ''effective'' bootstrap by studying the 3D Ising and O(n) vector models and bounds on generic 4D CFTs, for which extensive results are already available in the literature. We also determine the scaling dimensions of certain scalar operators in the O(n) vector models, with n=2,3,4, which have not yet been computed using bootstrap techniques.

  1. Basic optics of effect materials.

    Jones, Steven A

    2010-01-01

    Effect materials derive their color and effect primarily from thin-film interference. Effect materials have evolved over the decades from simple guanine crystals to the complex multilayer optical structures of today. The development of new complex effect materials requires an understanding of the optics of effect materials. Such an understanding would also benefit the cosmetic formulator as these new effect materials are introduced. The root of this understanding begins with basic optics. This paper covers the nature of light, interference of waves, thin-film interference, color from interference, and color travel.

  2. Health effects of radon

    Easterly, C.

    1994-01-01

    Exposure of people to radon has taken on increased interest during the last decade because of the understanding that buildings can serve to trap radon and its daughters, and thereby build up undesirable concentrations of these radioactive elements. Numerous studies of underground miners (often uranium miners) have shown an increased risk of lung cancer in comparison with nonexposed populations. Laboratory animals exposed to radon daughters also develop lung cancer. The abundant epidemiological and experimental data have established the carcinogenicity of radon progeny. Those observations are of considerable importance, because uranium, from which radon and its progeny arise, is ubiquitous in the earth's crust, including coal mines. Risk estimates of the health effects of long-term exposures at relatively low levels require continued development, especially to address the potential health effects of radon and radon daughters in homes and occupational settings where the exposure levels are less than levels in underground uranium and other metal mines that have been the subject of epidemiological studies. Two approaches can be used to characterize the lung-cancer risks associated with radon-daughter exposure: mathematical representations of the respiratory tract that model radiation doses to target cells and epidemiological investigation of exposed populations, mainly underground uranium miners. The mathematically-based dosimetric approach provides an estimate of lung cancer risk related to radon-daughter exposure based specifically on modeling of the dose to target cells. The various dosimetric models all require assumptions, some of which are not subject to direct verification, as to breathing rates; the deposition of radon daughters in the respiratory tract; and the type, nature, and location of the target cells for cancer induction. The most recent large committee effort drawn together to evaluate this issue was sponsored by the National Research Council

  3. Biological radiation effects

    Sejourne, Michele.

    1977-01-01

    This work examines ionizing radiations: what they are, where they come from, their actions and consequences, finally the norms and preventive measures necessary to avoid serious contamination, whether the individual or the population in general is involved. Man has always been exposed to natural irradiation, but owing to the growing use of ionizing radiations both in medicine and in industry, not to mention nuclear tests and their use as an argument of dissuasion, the irradiation of human beings is increasing daily. Radioactive contamination does remain latent, apart from acute cases, but this is where the danger lies since the consequences may not appear until long after the irradiation. Of all biological effects due to the action of radioelements the genetic risk is one of the most important, affecting the entire population and especially the generations to come. The risk of cancer and leukemia induction plays a substantial part also since a large number of people may be concerned, depending on the mode of contamination involved. All these long-term dangers do not of course exclude the various general or local effects to which the individual alone may be exposed and which sometimes constitute a threat to life. As a result the use of ionizing radiations must be limited and should only be involved if no other process can serve instead. The regulations governing radioelements must be stringent and their application strictly supervised for the better protection of man. This protection must be not only individual but also collective since pollution exists in air, water and land passes to plants and animals and finally reaches the last link in the food chain, man [fr

  4. Psychobehavioral Effects of Meditation.

    Pokorski, Mieczyslaw; Suchorzynska, Anna

    2018-01-01

    Meditation is an increasingly popular psychobehavioral therapy. Various meditation techniques in use make it hard to objectively scrutinize the psychological benefits. Therefore, in this study we set out to examine the effects of two fundamentally different meditative techniques, Zazen, 'seated meditation', in which the body and mind are calmed, and Tai Chi, 'meditation in motion', based on energetic martial art performance. The aim was to compare the effects of both techniques on personality structure, emotional intelligence, mood, and coping with stress. The study was conducted in 48 healthy volunteers, aged 39-50, divided into those practicing Zazen, Tai Chi, and the non-meditating controls, each group consisting of 16 persons. The psychometric tools consisted of Coping Inventory for Stressful Situations (CISS), the University of Wales Institute of Science and Technology Mood Adjective Checklist (UMACL), Emotional Intelligence Inventory (INTE), and the NEO Five-Factor Inventory (NEO-FFI). We found that both Zazen and Tai Chi meditations significantly enhanced openness to experience, one of the personality dimensions of the Big Five Model. The enhanced openness was associated with improved strategies for coping with stress. The meditators had less avoidance-oriented approaches to perceived stress. They also had improved mood compared with non-meditating controls. The findings suggest that enhanced openness to experience could shape one's desire to hold onto the meditation regimen. We conclude that both, diametrically different types of meditation, are conducive to mental health by improving the general well-being, counteracting stress, and leading to a better vigor of spirit. Meditation may thus be considered a complimentary, albeit rather modestly acting, adjunct to psychotherapy.

  5. Fluorosis: halo effect

    Diaz Madriz, Jose Esteban; Granados Quesada, Maria Pamela; Lopez Chacon, Angelica Maria; Monge Cantillo, Carol Paola; Munoz Aguero, Geiner Andres; Vargas Vargas, Jorge Andres

    2013-01-01

    The halo effect was determined from the consumption of potatoes from Tierra Blanca de Cartago and Palmira de Zarcero. Seminars were held to get to know the topic of fluorosis. A mini health fair was held to explain the effects of fluoride in a population affected by it. Samples of water and forest type potato were collected in the area of Zarcero and San Juan de Chicoa. Measurements of the samples were made in the Chemistry Laboratory of the Universidad de Costa Rica. 20 mg of potato from each zone and 80 ml of distilled water were weighed and then liquefied. Each shake was dispensed in 2 clean test tubes and 7 samples were obtained, of which, 2 test tubes contained the liquefied 1, 2 tubes the liquefied 2, 1 tube with the Rio Reventado water centrifuged. 1 tube with Zarcero irrigation water and 1 tube with distilled water, for the subsequent analysis of fluoride concentration. The samples were taken to the LAMBDA Chemical Laboratory, where the ion chromatography test was performed on each of the samples. A concentration of fluorides of 0.73 ppm was obtained in the water of the Rio Reventado, while a concentration of less than 0.60 ppm was obtained in the water collected in Zarcero. The highest concentration of fluoride was presented in the potato from the area of Palmira de Zarcero with 2.41 ppm compared to that obtained in Cartago, with a lower concentration of 1.34 ppm. The maximum recommended concentration was exceeded in both results. A concentration less than 0.02 ppm was obtained in the analysis of distilled water as a control test [es

  6. Possible oxidative effects of isotretinoin and modulatory effects of ...

    ... in the treatment of nodular cystic acne and as an inhibitor of proliferation of neoplastic cells, by exerting a regulatory effect on the cell differentiation. This study aimed at investigating the possible oxidative effects of ITN and modulatory effects of vitamins A and C in mutant and non-mutant Saccharomyces cerevisiae strains.

  7. Nuclear energy and greenhouse effect

    Strub, R.A.

    1991-01-01

    The contribution of nuclear power plants against the greenhouse effects is evaluated, not only nuclear energy is unable to fight greenhouse effect increase but long life wastes endanger environment. 8 refs

  8. Effects of herbicides on fish

    Solomon, Keith R.; Dalhoff, Kristoffer; Volz, David

    2013-01-01

    Herbicides are used to control weeds and are usually targeted to processes and target sites that are specific to plants. As a result, most herbicides are not acutely toxic to fish. Exceptions to this general rule are uncouplers of oxidative phosphorylation and some herbicides that interfere...... with cell division. Chronic and sublethal effects have been studied for some herbicides, but fewer data are available for these effects than for acute effects. The sublethal effects of herbicides that have been studied include reproduction, stress, olfaction, and behavior. Although some of these responses......, and reproduction. As with all pesticides, herbicides may have indirect effects in fish. These effects are mediated by herbicide-induced changes in food webs or in the physical environment. Indirect effects can only occur if direct effects occur first and would be mediated by the killing of plants by herbicides...

  9. HIV Medicines and Side Effects

    ... medicines, talk to your health care provider about possible side effects. Tell your health care provider about your lifestyle and point out any possible side effects that would be especially hard for you to ...

  10. Effects of PTSD on Family

    ... for PTSD » Public » Effects of PTSD on Family PTSD: National Center for PTSD Menu Menu PTSD PTSD Home For the Public ... code here Enter ZIP code here Effects of PTSD on Family Public This section is for Veterans, ...

  11. Antidepressants: Can They Lose Effectiveness?

    ... t seem to be having the same effect. Can antidepressants lose effectiveness? Answers from Daniel K. Hall- ... some people and not in others. There also can be other reasons an antidepressant is no longer ...

  12. Probiotics: Safety and Side Effects

    ... of this page please turn JavaScript on. Feature: Probiotics Safety and Side Effects Past Issues / Winter 2016 ... Says About the Safety and Side Effects of Probiotics Whether probiotics are likely to be safe for ...

  13. Alcohol's Effects on the Body

    ... Effects on the Body Alcohol's Effects on the Body Drinking too much – on a single occasion or ... your health. Here’s how alcohol can affect your body: Brain: Alcohol interferes with the brain’s communication pathways, ...

  14. Transversal Doppler-Fizeau effect

    Subacius, E.

    1981-01-01

    The relativistic calculation of the Doppler-Fizeau effect foresees a second grade redshift due to the proper time dilation of a moving object. The relevance of this relativistic effect on astrophysical observation is discussed, herein. (Auhor) [pt

  15. Coping – Late Side Effects

    Cancer treatment can cause late side effects that may not show up for months or years after treatment. These late effects may include heart and lung problems, bone loss, eye and hearing changes, lymphedema, and other problems

  16. Effectiveness of Family Planning Methods

    ... women in a year Effectiveness of Family Planning Methods Implant Reversible Intrauterine Device (IUD) Permanent Male Sterilization ... 0.5 % Diaphragm 12 % How to make your method most effective After procedure, little or nothing to ...

  17. Effective action and brane running

    Brevik, Iver; Ghoroku, Kazuo; Yahiro, Masanobu

    2004-01-01

    We address the renormalized effective action for a Randall-Sundrum brane running in 5D bulk space. The running behavior of the brane action is obtained by shifting the brane position without changing the background and fluctuations. After an appropriate renormalization, we obtain an effective, low energy brane world action, in which the effective 4D Planck mass is independent of the running position. We address some implications for this effective action

  18. Quantum effects in accelerator physics

    Leinaas, J.M.

    1991-08-01

    Quantum effects for electrons in a storage ring are discussed, in particular the polarization effect due to spin flip synchrotron radiation. The electrons are treated as a simple quantum mechnical two-level system coupled to the orbital motion and the radiation field. The excitations of the spin system are then related to the Unruh effect, i.e. the effect that an accelerated radiation detector is thermally excited by vacuum fluctuations. 24 refs., 2 figs

  19. Anomalous Hall effect

    Nagaosa, Naoto; Sinova, Jairo; Onoda, Shigeki; MacDonald, A. H.; Ong, N. P.

    2010-04-01

    The anomalous Hall effect (AHE) occurs in solids with broken time-reversal symmetry, typically in a ferromagnetic phase, as a consequence of spin-orbit coupling. Experimental and theoretical studies of the AHE are reviewed, focusing on recent developments that have provided a more complete framework for understanding this subtle phenomenon and have, in many instances, replaced controversy by clarity. Synergy between experimental and theoretical works, both playing a crucial role, has been at the heart of these advances. On the theoretical front, the adoption of the Berry-phase concepts has established a link between the AHE and the topological nature of the Hall currents. On the experimental front, new experimental studies of the AHE in transition metals, transition-metal oxides, spinels, pyrochlores, and metallic dilute magnetic semiconductors have established systematic trends. These two developments, in concert with first-principles electronic structure calculations, strongly favor the dominance of an intrinsic Berry-phase-related AHE mechanism in metallic ferromagnets with moderate conductivity. The intrinsic AHE can be expressed in terms of the Berry-phase curvatures and it is therefore an intrinsic quantum-mechanical property of a perfect crystal. An extrinsic mechanism, skew scattering from disorder, tends to dominate the AHE in highly conductive ferromagnets. The full modern semiclassical treatment of the AHE is reviewed which incorporates an anomalous contribution to wave-packet group velocity due to momentum-space Berry curvatures and correctly combines the roles of intrinsic and extrinsic (skew-scattering and side-jump) scattering-related mechanisms. In addition, more rigorous quantum-mechanical treatments based on the Kubo and Keldysh formalisms are reviewed, taking into account multiband effects, and demonstrate the equivalence of all three linear response theories in the metallic regime. Building on results from recent experiment and theory, a

  20. DUBNA: Spin effects

    Anon.

    1995-01-01

    Full text: Earlier this year, a collaboration of Russian, Ukrainian and French laboratories measured the difference between the polarized neutron and proton total reaction rate (total cross section difference) at slightly higher energies than previous experiments, providing an interesting hint of an effect predicted by theory. This was measured using a beam of longitudinally polarized neutrons and a longitudinally polarized proton target with parallel and antiparallel polarization directions. The polarized neutron beam, from the break-up of polarized deuterons, was accelerated by the Synchrophasotron at the Joint Institute for Nuclear Research (JINR) Laboratory of High Energies, Dubna (Russian Federation). The polarized target, 20 cm long and 3 cm in diameter, provided by DAPNIA (Saclay, France) and Argonne (USA), had also been used in 1989-1990 at Fermilab for the E704 experiment. Equipment from Saclay and Argonne was shipped to Dubna and work started in June 1994. The International Association for the Promotion of Cooperation with Scientists from the Independent States of the Former Soviet Union (INTAS) supported the construction and improvement of the target in a suitable transportable form. The target was mounted in the JINR Laboratory of Nuclear Problems (LNP) by experts from DAPNIA (Saclay), JINR Dubna (LNP, LHE and Laboratory of Particle Physics - LPP), Gatchina (Russia), RASMoscow and the Kharkov (Ukraine) laboratories. The Saturne National Laboratory (Saclay), helped with computer programmes for the NMR target polarization measurements. Apparatus was tested in early February. The beam of 2 x 109 polarized deuterons produced 106 polarized neutrons at 3.6 GeV. The neutron beam polarization was about 52%. The new superconducting Nuclotron accelerator should allow the beam intensity to be increased and beam quality improved after an upgrade of the injection system. Preliminary results for the polarized neutron-proton cross section difference at neutron kinetic