Orphan receptor GPR179 forms macromolecular complexes with components of metabotropic signaling cascade in retina ON-bipolar neurons.

PubMed

Orlandi, Cesare; Cao, Yan; Martemyanov, Kirill A

2013-10-29

In the mammalian retina, synaptic transmission between light-excited rod photoreceptors and downstream ON-bipolar neurons is indispensable for dim vision, and disruption of this process leads to congenital stationary night blindness in human patients. The ON-bipolar neurons use the metabotropic signaling cascade, initiated by the mGluR6 receptor, to generate depolarizing responses to light-induced changes in neurotransmitter glutamate release from the photoreceptor axonal terminals. Evidence for the identity of the components involved in transducing these signals is growing rapidly. Recently, the orphan receptor, GPR179, a member of the G protein-coupled receptor (GPCR) superfamily, has been shown to be indispensable for the synaptic responses of ON-bipolar cells. In our study, we investigated the interaction of GPR179 with principle components of the signal transduction cascade. We used immunoprecipitation and proximity ligation assays in transfected cells and native retinas to characterize the protein-protein interactions involving GPR179. The influence of cascade components on GPR179 localization was examined through immunohistochemical staining of the retinas from genetic mouse models. We demonstrated that, in mouse retinas, GPR179 forms physical complexes with the main components of the metabotropic cascade, recruiting mGluR6, TRPM1, and the RGS proteins. Elimination of mGluR6 or RGS proteins, but not TRPM1, detrimentally affects postsynaptic targeting or GPR179 expression. These observations suggest that the mGluR6 signaling cascade is scaffolded as a macromolecular complex in which the interactions between the components ensure the optimal spatiotemporal characteristics of signal transduction.

Photoexcitation cascade and quantum-relativistic jet formation in graphene

NASA Astrophysics Data System (ADS)

Lewandowski, Cyprian; Levitov, Leonid

Interactions between ultra-relativistic particles can lead to striking behavior in which a high-energy particle creates showers of softer particles characterized by a collimated angular distribution aligned with the particle velocity. These showers, known as jets, are a generic phenomenon relevant for all quantum cascades of linearly dispersing particles. This talk will discuss jets formed upon photoexcitation in graphene, which due to its linear dispersion provides an appealing medium for exploring quantum-relativistic phenomena. We will study the cascade generated by carrier-carrier collisions in photon absorption, wherein a single photon creates an electron-hole (e-h) excitation that decays producing multiple near-collinear secondary e-h excitations. We will argue that the cascade can occur through an off-shell mechanism such that all the particles and holes involved reside outside the energy-momentum dispersion manifold, relieving the bottleneck arising in the on-shell process due to energy and momentum conservation. The characteristics of the jets such as the angular and energy distribution of the particles will be discussed. Photogenerated jets provide an interesting setting to investigate the carrier-carrier collision processes in graphene and other Dirac materials. We acknowledge support of the Center for Integrated Quantum Materials (CIQM) under NSF award DMR-1231319.

Mathematical modeling of filling of gas centrifuge cascade for nickel isotope separation by various feed flow rate

NASA Astrophysics Data System (ADS)

Ushakov, Anton; Orlov, Alexey; Sovach, Victor P.

2018-03-01

This article presents the results of research filling of gas centrifuge cascade for separation of the multicomponent isotope mixture with process gas by various feed flow rate. It has been used mathematical model of the nonstationary hydraulic and separation processes occurring in the gas centrifuge cascade. The research object is definition of the regularity transient of nickel isotopes into cascade during filling of the cascade. It is shown that isotope concentrations into cascade stages after its filling depend on variable parameters and are not equal to its concentration on initial isotope mixture (or feed flow of cascade). This assumption is used earlier any researchers for modeling such nonstationary process as set of steady-state concentration of isotopes into cascade. Article shows physical laws of isotope distribution into cascade stage after its filling. It's shown that varying each parameters of cascade (feed flow rate, feed stage number or cascade stage number) it is possible to change isotope concentration on output cascade flows (light or heavy fraction) for reduction of duration of further process to set of steady-state concentration of isotopes into cascade.

Mechanism of short-term ERK activation by electromagnetic fields at mobile phone frequencies.

PubMed

Friedman, Joseph; Kraus, Sarah; Hauptman, Yirmi; Schiff, Yoni; Seger, Rony

2007-08-01

The exposure to non-thermal microwave electromagnetic fields generated by mobile phones affects the expression of many proteins. This effect on transcription and protein stability can be mediated by the MAPK (mitogen-activated protein kinase) cascades, which serve as central signalling pathways and govern essentially all stimulated cellular processes. Indeed, long-term exposure of cells to mobile phone irradiation results in the activation of p38 as well as the ERK (extracellular-signal-regulated kinase) MAPKs. In the present study, we have studied the immediate effect of irradiation on the MAPK cascades, and found that ERKs, but not stress-related MAPKs, are rapidly activated in response to various frequencies and intensities. Using signalling inhibitors, we delineated the mechanism that is involved in this activation. We found that the first step is mediated in the plasma membrane by NADH oxidase, which rapidly generates ROS (reactive oxygen species). These ROS then directly stimulate MMPs (matrix metalloproteinases) and allow them to cleave and release Hb-EGF [heparin-binding EGF (epidermal growth factor)]. This secreted factor activates the EGF receptor, which in turn further activates the ERK cascade. Thus this study demonstrates for the first time a detailed molecular mechanism by which electromagnetic irradiation from mobile phones induces the activation of the ERK cascade and thereby induces transcription and other cellular processes.

Segregation of the Anodic Microbial Communities in a Microbial Fuel Cell Cascade

PubMed Central

Hodgson, Douglas M.; Smith, Ann; Dahale, Sonal; Stratford, James P.; Li, Jia V.; Grüning, André; Bushell, Michael E.; Marchesi, Julian R.; Avignone Rossa, C.

2016-01-01

Metabolic interactions within microbial communities are essential for the efficient degradation of complex organic compounds, and underpin natural phenomena driven by microorganisms, such as the recycling of carbon-, nitrogen-, and sulfur-containing molecules. These metabolic interactions ultimately determine the function, activity and stability of the community, and therefore their understanding would be essential to steer processes where microbial communities are involved. This is exploited in the design of microbial fuel cells (MFCs), bioelectrochemical devices that convert the chemical energy present in substrates into electrical energy through the metabolic activity of microorganisms, either single species or communities. In this work, we analyzed the evolution of the microbial community structure in a cascade of MFCs inoculated with an anaerobic microbial community and continuously fed with a complex medium. The analysis of the composition of the anodic communities revealed the establishment of different communities in the anodes of the hydraulically connected MFCs, with a decrease in the abundance of fermentative taxa and a concurrent increase in respiratory taxa along the cascade. The analysis of the metabolites in the anodic suspension showed a metabolic shift between the first and last MFC, confirming the segregation of the anodic communities. Those results suggest a metabolic interaction mechanism between the predominant fermentative bacteria at the first stages of the cascade and the anaerobic respiratory electrogenic population in the latter stages, which is reflected in the observed increase in power output. We show that our experimental system represents an ideal platform for optimization of processes where the degradation of complex substrates is involved, as well as a potential tool for the study of metabolic interactions in complex microbial communities. PMID:27242723

Genetic control of an epigenetic cell degeneration syndrome in Podospora anserina.

PubMed

Haedens, Vicki; Malagnac, Fabienne; Silar, Philippe

2005-06-01

Filamentous fungi frequently present degenerative processes, whose molecular basis is very often unknown. Here, we present three mutant screens that result in the identification of 29 genes that directly or indirectly control Crippled Growth (CG), an epigenetic cell degeneration of the filamentous ascomycete Podospora anserina. Two of these genes were previously shown to encode a MAP kinase kinase kinase and an NADPH oxidase involved in a signal transduction cascade that participates in stationary phase differentiations, fruiting body development and defence against fungal competitors. The numerous genes identified can be incorporated in a model in which CG results from the sustained activation of the MAP kinase cascade. Our data also emphasize the complex regulatory network underlying three interconnected processes in P. anserina: sexual reproduction, defence against competitors, and cell degeneration.

High-performance recombinant protein production with Escherichia coli in continuously operated cascades of stirred-tank reactors.

PubMed

Schmideder, Andreas; Weuster-Botz, Dirk

2017-07-01

The microbial expression of intracellular, recombinant proteins in continuous bioprocesses suffers from low product concentrations. Hence, a process for the intracellular production of photoactivatable mCherry with Escherichia coli in a continuously operated cascade of two stirred-tank reactors was established to separate biomass formation (first reactor) and protein expression (second reactor) spatially. Cascades of miniaturized stirred-tank reactors were implemented, which enable the 24-fold parallel characterization of cascade processes and the direct scale-up of results to the liter scale. With PAmCherry concentrations of 1.15 g L -1 cascades of stirred-tank reactors improved the process performance significantly compared to production processes in chemostats. In addition, an optimized fed-batch process was outperformed regarding space-time yield (149 mg L -1  h -1 ). This study implicates continuous cascade processes to be a promising alternative to fed-batch processes for microbial protein production and demonstrates that miniaturized stirred-tank reactors can reduce the timeline and costs for cascade process characterization.

Hypertonicity-induced transmitter release at Drosophila neuromuscular junctions is partly mediated by integrins and cAMP/protein kinase A

NASA Technical Reports Server (NTRS)

Suzuki, Kazuhiro; Grinnell, Alan D.; Kidokoro, Yoshiaki

2002-01-01

The frequency of quantal transmitter release increases upon application of hypertonic solutions. This effect bypasses the Ca(2+) triggering step, but requires the presence of key molecules involved in vesicle fusion, and hence could be a useful tool for dissecting the molecular process of vesicle fusion. We have examined the hypertonicity response at neuromuscular junctions of Drosophila embryos in Ca(2+)-free saline. Relative to wild-type, the response induced by puff application of hypertonic solution was enhanced in a mutant, dunce, in which the cAMP level is elevated, or in wild-type embryos treated with forskolin, an activator of adenylyl cyclase, while protein kinase A (PKA) inhibitors decreased it. The response was also smaller in a mutant, DC0, which lacks the major subunit of PKA. Thus the cAMP/PKA cascade is involved in the hypertonicity response. Peptides containing the sequence Arg-Gly-Asp (RGD), which inhibit binding of integrins to natural ligands, reduced the response, whereas a peptide containing the non-binding sequence Arg-Gly-Glu (RGE) did not. A reduced response persisted in a mutant, myospheroid, which expresses no integrins, and the response in DC0 was unaffected by RGD peptides. These data indicate that there are at lease two components in the hypertonicity response: one that is integrin mediated and involves the cAMP/PKA cascade, and another that is not integrin mediated and does not involve the cAMP/PKA cascade.

Three Pairs of Protease-Serpin Complexes Cooperatively Regulate the Insect Innate Immune Responses*

PubMed Central

Jiang, Rui; Kim, Eun-Hye; Gong, Ji-Hee; Kwon, Hyun-Mi; Kim, Chan-Hee; Ryu, Kyoung-Hwa; Park, Ji-Won; Kurokawa, Kenji; Zhang, Jinghai; Gubb, David; Lee, Bok-Luel

2009-01-01

Serpins are known to be necessary for the regulation of several serine protease cascades. However, the mechanisms of how serpins regulate the innate immune responses of invertebrates are not well understood due to the uncertainty of the identity of the serine proteases targeted by the serpins. We recently reported the molecular activation mechanisms of three serine protease-mediated Toll and melanin synthesis cascades in a large beetle, Tenebrio molitor. Here, we purified three novel serpins (SPN40, SPN55, and SPN48) from the hemolymph of T. molitor. These serpins made specific serpin-serine protease pairs with three Toll cascade-activating serine proteases, such as modular serine protease, Spätzle-processing enzyme-activating enzyme, and Spätzle-processing enzyme and cooperatively blocked the Toll signaling cascade and β-1,3-glucan-mediated melanin biosynthesis. Also, the levels of SPN40 and SPN55 were dramatically increased in vivo by the injection of a Toll ligand, processed Spätzle, into Tenebrio larvae. This increase in SPN40 and SPN55 levels indicates that these serpins function as inducible negative feedback inhibitors. Unexpectedly, SPN55 and SPN48 were cleaved at Tyr and Glu residues in reactive center loops, respectively, despite being targeted by trypsin-like Spätzle-processing enzyme-activating enzyme and Spätzle-processing enzyme. These cleavage patterns are also highly similar to those of unusual mammalian serpins involved in blood coagulation and blood pressure regulation, and they may contribute to highly specific and timely inactivation of detrimental serine proteases during innate immune responses. Taken together, these results demonstrate the specific regulatory evidences of innate immune responses by three novel serpins. PMID:19858208

Random cascade model in the limit of infinite integral scale as the exponential of a nonstationary 1/f noise: Application to volatility fluctuations in stock markets

NASA Astrophysics Data System (ADS)

Muzy, Jean-François; Baïle, Rachel; Bacry, Emmanuel

2013-04-01

In this paper we propose a new model for volatility fluctuations in financial time series. This model relies on a nonstationary Gaussian process that exhibits aging behavior. It turns out that its properties, over any finite time interval, are very close to continuous cascade models. These latter models are indeed well known to reproduce faithfully the main stylized facts of financial time series. However, it involves a large-scale parameter (the so-called “integral scale” where the cascade is initiated) that is hard to interpret in finance. Moreover, the empirical value of the integral scale is in general deeply correlated to the overall length of the sample. This feature is precisely predicted by our model, which, as illustrated by various examples from daily stock index data, quantitatively reproduces the empirical observations.

Linear models of activation cascades: analytical solutions and coarse-graining of delayed signal transduction

PubMed Central

Desikan, Radhika

2016-01-01

Cellular signal transduction usually involves activation cascades, the sequential activation of a series of proteins following the reception of an input signal. Here, we study the classic model of weakly activated cascades and obtain analytical solutions for a variety of inputs. We show that in the special but important case of optimal gain cascades (i.e. when the deactivation rates are identical) the downstream output of the cascade can be represented exactly as a lumped nonlinear module containing an incomplete gamma function with real parameters that depend on the rates and length of the cascade, as well as parameters of the input signal. The expressions obtained can be applied to the non-identical case when the deactivation rates are random to capture the variability in the cascade outputs. We also show that cascades can be rearranged so that blocks with similar rates can be lumped and represented through our nonlinear modules. Our results can be used both to represent cascades in computational models of differential equations and to fit data efficiently, by reducing the number of equations and parameters involved. In particular, the length of the cascade appears as a real-valued parameter and can thus be fitted in the same manner as Hill coefficients. Finally, we show how the obtained nonlinear modules can be used instead of delay differential equations to model delays in signal transduction. PMID:27581482

Upstream paths for Hippo signaling in Drosophila organ development.

PubMed

Choi, Kwang-Wook

2018-03-01

Organ growth is fundamental to animal development. One of major mechanisms for growth control is mediated by the conserved Hippo signaling pathway initially identified in Drosophila. The core of this pathway in Drosophila consists of a cascade of protein kinases Hippo and Warts that negatively regulate transcriptional coactivator Yorkie (Yki). Activation of Yki promotes cell survival and proliferation to induce organ growth. A key issue in Hippo signaling is to understand how core kinase cascade is activated. Activation of Hippo kinase cascade is regulated in the upstream by at least two transmembrane proteins Crumbs and Fat that act in parallel. These membrane proteins interact with additional factors such as FERM-domain proteins Expanded and Merlin to modulate subcellular localization and function of the Hippo kinase cascade. Hippo signaling is also influenced by cytoskeletal networks and cell tension in epithelia of developing organs. These upstream events in the regulation of Hippo signaling are only partially understood. This review focuses on our current understanding of some upstream processes involved in Hippo signaling in developing Drosophila organs. [BMB Reports 2018; 51(3): 134-142].

Oxygen-sensitive potassium channels in chemoreceptor cell physiology: making a virtue of necessity.

PubMed

Gonzalez, Constancio; Vaquero, Luis M; López-López, José Ramón; Pérez-García, M Teresa

2009-10-01

The characterization of the molecular mechanisms involved in low-oxygen chemotransduction has been an active field of research since the first description of an oxygen-sensitive K(+) channel in rabbit carotid body (CB) chemoreceptor cells. As a result, a large number of components of the transduction cascade, from O(2) sensors to O(2)-sensitive ion channels, have been found. Although the endpoints of the process are analogous, the heterogeneity of the elements involved in the different chemoreceptor tissues precludes a unifying theory of hypoxic signaling, and it has been a source of controversy. However, when these molecular constituents of the hypoxic cascade are brought back to their physiological context, it becomes clear that the diversity of mechanisms is necessary to build up an integrated cellular response that demands the concerted action of several O(2) sensors and several effectors.

Mechanism of short-term ERK activation by electromagnetic fields at mobile phone frequencies

PubMed Central

Friedman, Joseph; Kraus, Sarah; Hauptman, Yirmi; Schiff, Yoni; Seger, Rony

2007-01-01

The exposure to non-thermal microwave electromagnetic fields generated by mobile phones affects the expression of many proteins. This effect on transcription and protein stability can be mediated by the MAPK (mitogen-activated protein kinase) cascades, which serve as central signalling pathways and govern essentially all stimulated cellular processes. Indeed, long-term exposure of cells to mobile phone irradiation results in the activation of p38 as well as the ERK (extracellular-signal-regulated kinase) MAPKs. In the present study, we have studied the immediate effect of irradiation on the MAPK cascades, and found that ERKs, but not stress-related MAPKs, are rapidly activated in response to various frequencies and intensities. Using signalling inhibitors, we delineated the mechanism that is involved in this activation. We found that the first step is mediated in the plasma membrane by NADH oxidase, which rapidly generates ROS (reactive oxygen species). These ROS then directly stimulate MMPs (matrix metalloproteinases) and allow them to cleave and release Hb-EGF [heparin-binding EGF (epidermal growth factor)]. This secreted factor activates the EGF receptor, which in turn further activates the ERK cascade. Thus this study demonstrates for the first time a detailed molecular mechanism by which electromagnetic irradiation from mobile phones induces the activation of the ERK cascade and thereby induces transcription and other cellular processes. PMID:17456048

Distinguishing graded and ultrasensitive signalling cascade kinetics by the shape of morphogen gradients in Drosophila.

PubMed

MacNamara, Shev; Baker, Ruth E; Maini, Philip K

2011-09-21

Recently, signalling gradients in cascades of two-state reaction-diffusion systems were described as a model for understanding key biochemical mechanisms that underlie development and differentiation processes in the Drosophila embryo. Diffusion-trapping at the exterior of the cell membrane triggers the mitogen-activated protein kinase (MAPK) cascade to relay an appropriate signal from the membrane to the inner part of the cytosol, whereupon another diffusion-trapping mechanism involving the nucleus reads out this signal to trigger appropriate changes in gene expression. Proposed mathematical models exhibit equilibrium distributions consistent with experimental measurements of key spatial gradients in these processes. A significant property of the formulation is that the signal is assumed to be relayed from one system to the next in a linear fashion. However, the MAPK cascade often exhibits nonlinear dose-response properties and the final remark of Berezhkovskii et al. (2009) is that this assumption remains an important property to be tested experimentally, perhaps via a new quantitative assay across multiple genetic backgrounds. In anticipation of the need to be able to sensibly interpret data from such experiments, here we provide a complementary analysis that recovers existing formulae as a special case but is also capable of handling nonlinear functional forms. Predictions of linear and nonlinear signal relays and, in particular, graded and ultrasensitive MAPK kinetics, are compared. Copyright © 2011 Elsevier Ltd. All rights reserved.

Techno-environmental assessment of the green biorefinery concept: Combining process simulation and life cycle assessment at an early design stage.

PubMed

Corona, Andrea; Ambye-Jensen, Morten; Vega, Giovanna Croxatto; Hauschild, Michael Zwicky; Birkved, Morten

2018-09-01

The Green biorefinery (GBR) is a biorefinery concept that converts fresh biomass into value-added products. The present study combines a Process Flowsheet Simulation (PFS) and Life Cycle Assessment (LCA) to evaluate the technical and environmental performance of different GBR configurations and the cascading utilization of the GBR output. The GBR configurations considered in this study, test alternatives in the three main steps of green-biorefining: fractionation, precipitation, and protein separation. The different cascade utilization alternatives analyse different options for press-pulp utilization, and the LCA results show that the environmental profile of the GBR is highly affected by the utilization of the press-pulp and thus by the choice of conventional product replaced by the press-pulp. Furthermore, scenario analysis of different GBR configurations shows that higher benefits can be achieved by increasing product yields rather than lowering energy consumption. Green biorefining is shown to be an interesting biorefining concept, especially in a Danish context. Biorefining of green biomass is technically feasible and can bring environmental savings, when compared to conventional production methods. However, the savings will be determined by the processing involved in each conversion stage and on the cascade utilization of the different platform products. Copyright © 2018 Elsevier B.V. All rights reserved.

"Silent" Priming of Translation-Dependent LTP by [Beta]-Adrenergic Receptors Involves Phosphorylation and Recruitment of AMPA Receptors

ERIC Educational Resources Information Center

Tenorio, Gustavo; Connor, Steven A.; Guevremont, Diane; Abraham, Wickliffe C.; Williams, Joanna; O'Dell, Thomas J.; Nguyen, Peter V.

2010-01-01

The capacity for long-term changes in synaptic efficacy can be altered by prior synaptic activity, a process known as "metaplasticity." Activation of receptors for modulatory neurotransmitters can trigger downstream signaling cascades that persist beyond initial receptor activation and may thus have metaplastic effects. Because activation of…

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geiger, K.; Longacre, R.; Srivastava, D.K.

VNI is a general-purpose Monte-Carlo event-generator, which includes the simulation of lepton-lepton, lepton-hadron, lepton-nucleus, hadron-hadron, hadron-nucleus, and nucleus-nucleus collisions. It uses the real-time evolution of parton cascades in conjunction with a self-consistent hadronization scheme, as well as the development of hadron cascades after hadronization. The causal evolution from a specific initial state (determined by the colliding beam particles) is followed by the time-development of the phase-space densities of partons, pre-hadronic parton clusters, and final-state hadrons, in position-space, momentum-space and color-space. The parton-evolution is described in terms of a space-time generalization of the familiar momentum-space description of multiple (semi)hard interactions inmore » QCD, involving 2 {r_arrow} 2 parton collisions, 2 {r_arrow} 1 parton fusion processes, and 1 {r_arrow} 2 radiation processes. The formation of color-singlet pre-hadronic clusters and their decays into hadrons, on the other hand, is treated by using a spatial criterion motivated by confinement and a non-perturbative model for hadronization. Finally, the cascading of produced prehadronic clusters and of hadrons includes a multitude of 2 {r_arrow} n processes, and is modeled in parallel to the parton cascade description. This paper gives a brief review of the physics underlying VNI, as well as a detailed description of the program itself. The latter program description emphasizes easy-to-use pragmatism and explains how to use the program (including simple examples), annotates input and control parameters, and discusses output data provided by it.« less

Local cascades induced global contagion: How heterogeneous thresholds, exogenous effects, and unconcerned behaviour govern online adoption spreading

NASA Astrophysics Data System (ADS)

Karsai, Márton; Iñiguez, Gerardo; Kikas, Riivo; Kaski, Kimmo; Kertész, János

2016-06-01

Adoption of innovations, products or online services is commonly interpreted as a spreading process driven to large extent by social influence and conditioned by the needs and capacities of individuals. To model this process one usually introduces behavioural threshold mechanisms, which can give rise to the evolution of global cascades if the system satisfies a set of conditions. However, these models do not address temporal aspects of the emerging cascades, which in real systems may evolve through various pathways ranging from slow to rapid patterns. Here we fill this gap through the analysis and modelling of product adoption in the world’s largest voice over internet service, the social network of Skype. We provide empirical evidence about the heterogeneous distribution of fractional behavioural thresholds, which appears to be independent of the degree of adopting egos. We show that the structure of real-world adoption clusters is radically different from previous theoretical expectations, since vulnerable adoptions—induced by a single adopting neighbour—appear to be important only locally, while spontaneous adopters arriving at a constant rate and the involvement of unconcerned individuals govern the global emergence of social spreading.

Local cascades induced global contagion: How heterogeneous thresholds, exogenous effects, and unconcerned behaviour govern online adoption spreading

PubMed Central

Karsai, Márton; Iñiguez, Gerardo; Kikas, Riivo; Kaski, Kimmo; Kertész, János

2016-01-01

Adoption of innovations, products or online services is commonly interpreted as a spreading process driven to large extent by social influence and conditioned by the needs and capacities of individuals. To model this process one usually introduces behavioural threshold mechanisms, which can give rise to the evolution of global cascades if the system satisfies a set of conditions. However, these models do not address temporal aspects of the emerging cascades, which in real systems may evolve through various pathways ranging from slow to rapid patterns. Here we fill this gap through the analysis and modelling of product adoption in the world’s largest voice over internet service, the social network of Skype. We provide empirical evidence about the heterogeneous distribution of fractional behavioural thresholds, which appears to be independent of the degree of adopting egos. We show that the structure of real-world adoption clusters is radically different from previous theoretical expectations, since vulnerable adoptions—induced by a single adopting neighbour—appear to be important only locally, while spontaneous adopters arriving at a constant rate and the involvement of unconcerned individuals govern the global emergence of social spreading. PMID:27272744

Selective Production of Renewable para-Xylene by Tungsten Carbide Catalyzed Atom-Economic Cascade Reactions.

PubMed

Dai, Tao; Li, Changzhi; Li, Lin; Zhao, Zongbao Kent; Zhang, Bo; Cong, Yu; Wang, Aiqin

2018-02-12

Tungsten carbide was employed as the catalyst in an atom-economic and renewable synthesis of para-xylene with excellent selectivity and yield from 4-methyl-3-cyclohexene-1-carbonylaldehyde (4-MCHCA). This intermediate is the product of the Diels-Alder reaction between the two readily available bio-based building blocks acrolein and isoprene. Our results suggest that 4-MCHCA undergoes a novel dehydroaromatization-hydrodeoxygenation cascade process by intramolecular hydrogen transfer that does not involve an external hydrogen source, and that the hydrodeoxygenation occurs through the direct dissociation of the C=O bond on the W 2 C surface. Notably, this process is readily applicable to the synthesis of various (multi)methylated arenes from bio-based building blocks, thus potentially providing a petroleum-independent solution to valuable aromatic compounds. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tc-99 Decontamination From Heat Treated Gaseous Diffusion Membrane -Phase I

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oji, L.; Wilmarth, B.; Restivo, M.

2017-03-13

Uranium gaseous diffusion cascades represent a significant environmental challenge to dismantle, containerize and dispose as low-level radioactive waste. Baseline technologies rely on manual manipulations involving direct access to technetium-contaminated piping and materials. There is a potential to utilize novel thermal decontamination technologies to remove the technetium and allow for on-site disposal of the very large uranium converters. Technetium entered these gaseous diffusion cascades as a hexafluoride complex in the same fashion as uranium. Technetium, as the isotope Tc-99, is an impurity that follows uranium in the first cycle of the Plutonium and Uranium Extraction (PUREX) process. The technetium speciation ormore » exact form in the gas diffusion cascades is not well defined. Several forms of Tc-99 compounds, mostly the fluorinated technetium compounds with varying degrees of volatility have been speculated by the scientific community to be present in these cascades. Therefore, there may be a possibility of using thermal desorption, which is independent of the technetium oxidation states, to perform an in situ removal of the technetium as a volatile species and trap the radionuclide on sorbent traps which could be disposed as low-level waste.« less

A source, a cascade, a schizoid: a heuristic proposal from the Longitudinal Study of Personality Disorders.

PubMed

Lenzenweger, Mark F

2010-11-01

It is argued that personality pathology represents the final emergent product of a complex interaction of underlying neurobehavioral systems as well as environment inputs. A number of factors may be involved in the developmental pathway and a cascading of effects is plausible, although a unifying cascade for all personality disorders is not likely. The present study suggests a possible cascade relevant to one personality disorder: schizoid personality disorder in emerging adulthood. In brief, it is hypothesized that the absence of a relationship characterized by a rich degree of psychological proximal process in early childhood, which is associated with nurturance and the facilitation of more complex development, predicts impairment in the actualization of the affiliation system (i.e., that system that facilitates interpersonal connectedness and social bonds in human beings and is under substantial genetic influence), and this impairment in the affiliation system predicts the appearance of schizoid personality disorder symptoms in emerging adulthood (late teens/early 20s), which persists over time into emerging adulthood. The impairment in the affiliation system is argued to proceed through childhood sociality as reflected in temperament on through adult personality as reflected in communal positive emotion. Furthermore, it is also hypothesized that the relationship between proximal processes and the affiliation system maintains irrespective of other childhood temperament factors that might adversely impact early parent/caregiver and child relations. The data for a preliminary illustration of this possible cascade are drawn from The Longitudinal Study of Personality Disorders, which is a prospective, multiwave study of personality disorders, personality, and temperament in a large sample of adults drawn from a nonclinical population.

Theory of invasion extinction dynamics in minimal food webs

NASA Astrophysics Data System (ADS)

Haerter, Jan O.; Mitarai, Namiko; Sneppen, Kim

2018-02-01

When food webs are exposed to species invasion, secondary extinction cascades may be set off. Although much work has gone into characterizing the structure of food webs, systematic predictions on their evolutionary dynamics are still scarce. Here we present a theoretical framework that predicts extinctions in terms of an alternating sequence of two basic processes: resource depletion by or competitive exclusion between consumers. We first propose a conceptual invasion extinction model (IEM) involving random fitness coefficients. We bolster this IEM by an analytical, recursive procedure for calculating idealized extinction cascades after any species addition and simulate the long-time evolution. Our procedure describes minimal food webs where each species interacts with only a single resource through the generalized Lotka-Volterra equations. For such food webs ex- tinction cascades are determined uniquely and the system always relaxes to a stable steady state. The dynamics and scale invariant species life time resemble the behavior of the IEM, and correctly predict an upper limit for trophic levels as observed in the field.

Theory of invasion extinction dynamics in minimal food webs.

PubMed

Haerter, Jan O; Mitarai, Namiko; Sneppen, Kim

2018-02-01

When food webs are exposed to species invasion, secondary extinction cascades may be set off. Although much work has gone into characterizing the structure of food webs, systematic predictions on their evolutionary dynamics are still scarce. Here we present a theoretical framework that predicts extinctions in terms of an alternating sequence of two basic processes: resource depletion by or competitive exclusion between consumers. We first propose a conceptual invasion extinction model (IEM) involving random fitness coefficients. We bolster this IEM by an analytical, recursive procedure for calculating idealized extinction cascades after any species addition and simulate the long-time evolution. Our procedure describes minimal food webs where each species interacts with only a single resource through the generalized Lotka-Volterra equations. For such food webs ex- tinction cascades are determined uniquely and the system always relaxes to a stable steady state. The dynamics and scale invariant species life time resemble the behavior of the IEM, and correctly predict an upper limit for trophic levels as observed in the field.

Slow relaxation of cascade-induced defects in Fe

DOE PAGES

Béland, Laurent Karim; Osetsky, Yuri N.; Stoller, Roger E.; ...

2015-02-17

On-the-fly kinetic Monte Carlo (KMC) simulations are performed to investigate slow relaxation of non-equilibrium systems. Point defects induced by 25 keV cascades in α -Fe are shown to lead to a characteristic time-evolution, described by the replenish and relax mechanism. Then, we produce an atomistically-based assessment of models proposed to explain the slow structural relaxation by focusing on the aggregation of 50 vacancies and 25 self-interstital atoms (SIA) in 10-lattice-parameter α-Fe boxes, two processes that are closely related to cascade annealing and exhibit similar time signature. Four atomistic effects explain the timescales involved in the evolution: defect concentration heterogeneities, concentration-enhancedmore » mobility, cluster-size dependent bond energies and defect-induced pressure. In conclusion, these findings suggest that the two main classes of models to explain slow structural relaxation, the Eyring model and the Gibbs model, both play a role to limit the rate of relaxation of these simple point-defect systems.« less

High-Efficiency and High-Power Mid-Wave Infrared Cascade Lasers

DTIC Science & Technology

2012-10-01

internal quantum efficiency () and factor (2) is usually called the optical extraction efficiency (). The optical extraction efficiency ... quantum efficiency involves more fundamental parameters corresponding to the microscopic processes of the device operation, nevertheless, it can be...deriving parameters such as the internal quantum efficiency of a QC laser, the entire injector miniband can be treated as a single virtual state

Evidence of an evolutionary hourglass pattern in herbivory-induced transcriptomic responses.

PubMed

Durrant, Matthew; Boyer, Justin; Zhou, Wenwu; Baldwin, Ian T; Xu, Shuqing

2017-08-01

Herbivory-induced defenses are specific and activated in plants when elicitors, frequently found in the herbivores' oral secretions, are introduced into wounds during attack. While complex signaling cascades are known to be involved, it remains largely unclear how natural selection has shaped the evolution of these induced defenses. We analyzed herbivory-induced transcriptomic responses in wild tobacco, Nicotiana attenuata, using a phylotranscriptomic approach that measures the origin and sequence divergence of herbivory-induced genes. Highly conserved and evolutionarily ancient genes of primary metabolism were activated at intermediate time points (2-6 h) after elicitation, while less constrained and young genes associated with defense signaling and biosynthesis of specialized metabolites were activated at early (before 2 h) and late (after 6 h) stages of the induced response, respectively - a pattern resembling the evolutionary hourglass pattern observed during embryogenesis in animals and the developmental process in plants and fungi. The hourglass patterns found in herbivory-induced defense responses and developmental process are both likely to be a result of signaling modularization and differential evolutionary constraints on the modules involved in the signaling cascade. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Physiology of Calcium, Phosphate, Magnesium and Vitamin D.

PubMed

Allgrove, Jeremy

2015-01-01

The physiology of calcium and the other minerals involved in its metabolism is complex and intimately linked to the physiology of bone. Five principal humoral factors are involved in maintaining plasma concentrations of calcium, magnesium and phosphate and in coordinating the balance between their content in bone. The transmembrane transport of these elements is dependent on a series of complex mechanisms that are partly controlled by these hormones. The plasma concentration of calcium is initially sensed by a calcium-sensing receptor, which then sets up a cascade of events that initially determines parathyroid hormone secretion and eventually results in a specific action within the target organs, mainly bone and kidney. This chapter describes the physiology of these humoral factors and relates them to the pathological processes that give rise to disorders of calcium, phosphate and magnesium metabolism as well as of bone metabolism. This chapter also details the stages in the calcium cascade, describes the effects of calcium on the various target organs, gives details of the processes by which phosphate and magnesium are controlled and summarises the metabolism of vitamin D. The pathology of disorders of bone and calcium metabolism is described in detail in the relevant chapters. © 2015 S. Karger AG, Basel.

How does the interaction between spelling and motor processes build up during writing acquisition?

PubMed

Kandel, Sonia; Perret, Cyril

2015-03-01

How do we recall a word's spelling? How do we produce the movements to form the letters of a word? Writing involves several processing levels. Surprisingly, researchers have focused either on spelling or motor production. However, these processes interact and cannot be studied separately. Spelling processes cascade into movement production. For example, in French, producing letters PAR in the orthographically irregular word PARFUM (perfume) delays motor production with respect to the same letters in the regular word PARDON (pardon). Orthographic regularity refers to the possibility of spelling a word correctly by applying the most frequent sound-letter conversion rules. The present study examined how the interaction between spelling and motor processing builds up during writing acquisition. French 8-10 year old children participated in the experiment. This is the age handwriting skills start to become automatic. The children wrote regular and irregular words that could be frequent or infrequent. They wrote on a digitizer so we could collect data on latency, movement duration and fluency. The results revealed that the interaction between spelling and motor processing was present already at age 8. It became more adult-like at ages 9 and 10. Before starting to write, processing irregular words took longer than regular words. This processing load spread into movement production. It increased writing duration and rendered the movements more dysfluent. Word frequency affected latencies and cascaded into production. It modulated writing duration but not movement fluency. Writing infrequent words took longer than frequent words. The data suggests that orthographic regularity has a stronger impact on writing than word frequency. They do not cascade in the same extent. Copyright © 2014 Elsevier B.V. All rights reserved.

Toward a Symphony of Reactivity: Cascades Involving Catalysis and Sigmatropic Rearrangements

PubMed Central

Jones, Amanda C.; May, Jeremy A.; Sarpong, Richmond; Stoltz, Brian M.

2014-01-01

Catalysis and synthesis are intimately linked in modern organic chemistry. The synthesis of complex molecules is an ever evolving area of science. In many regards, the inherent beauty associated with a synthetic sequence can be linked to a certain combination of the creativity with which a sequence is designed and the overall efficiency with which the ultimate process is performed. In synthesis, as in other endeavors, beauty is very much in the eyes of the beholder.[**] It is with this in mind that we will attempt to review an area of synthesis that has fascinated us and that we find extraordinarily beautiful, namely the combination of catalysis and sigmatropic rearrangements in consecutive and cascade sequences. PMID:24677683

Differentiation of neuroblastoma cell line N1E-115 involves several signaling cascades.

PubMed

Oh, Ji-eun; Karlmark, Karlin Raja; Shin, Joo-ho; Pollak, Arnold; Freilinger, Angelika; Hengstschläger, Markus; Lubec, Gert

2005-03-01

No systematic searches for differential expression of signaling proteins (SP) in undifferentiated vs. differentiated cell lineages were published and herein we used protein profiling for this purpose. The NIE-115 cell line was cultivated and an aliquot was differentiated with dimethylsulfoxide (DMSO), that is known to lead to a neuronal phenotype. Cell lysates were prepared, run on two-dimensional gel electrophoresis followed by MALDI-TOF-TOF identification of proteins and maps of identified SPs were generated. Seven SPs were comparable, 27 SPs: GTP-binding/Ras-related proteins, kinases, growth factors, calcium binding proteins, phosphatase-related proteins were observed in differentiated NIE-115 cells and eight SPs of the groups mentioned above were observed in undifferentiated cells only. Switching-on/off of several individual SPs from different signaling cascades during the differentiation process is a key to understand mechanisms involved. The findings reported herein are challenging in vitro and in vivo studies to confirm a functional role for deranged SPs.

Fast quantification of bovine milk proteins employing external cavity-quantum cascade laser spectroscopy.

PubMed

Schwaighofer, Andreas; Kuligowski, Julia; Quintás, Guillermo; Mayer, Helmut K; Lendl, Bernhard

2018-06-30

Analysis of proteins in bovine milk is usually tackled by time-consuming analytical approaches involving wet-chemical, multi-step sample clean-up procedures. The use of external cavity-quantum cascade laser (EC-QCL) based IR spectroscopy was evaluated as an alternative screening tool for direct and simultaneous quantification of individual proteins (i.e. casein and β-lactoglobulin) and total protein content in commercial bovine milk samples. Mid-IR spectra of protein standard mixtures were used for building partial least squares (PLS) regression models. A sample set comprising different milk types (pasteurized; differently processed extended shelf life, ESL; ultra-high temperature, UHT) was analysed and results were compared to reference methods. Concentration values of the QCL-IR spectroscopy approach obtained within several minutes are in good agreement with reference methods involving multiple sample preparation steps. The potential application as a fast screening method for estimating the heat load applied to liquid milk is demonstrated. Copyright © 2018 Elsevier Ltd. All rights reserved.

Agent-based modeling of endotoxin-induced acute inflammatory response in human blood leukocytes.

PubMed

Dong, Xu; Foteinou, Panagiota T; Calvano, Steven E; Lowry, Stephen F; Androulakis, Ioannis P

2010-02-18

Inflammation is a highly complex biological response evoked by many stimuli. A persistent challenge in modeling this dynamic process has been the (nonlinear) nature of the response that precludes the single-variable assumption. Systems-based approaches offer a promising possibility for understanding inflammation in its homeostatic context. In order to study the underlying complexity of the acute inflammatory response, an agent-based framework is developed that models the emerging host response as the outcome of orchestrated interactions associated with intricate signaling cascades and intercellular immune system interactions. An agent-based modeling (ABM) framework is proposed to study the nonlinear dynamics of acute human inflammation. The model is implemented using NetLogo software. Interacting agents involve either inflammation-specific molecules or cells essential for the propagation of the inflammatory reaction across the system. Spatial orientation of molecule interactions involved in signaling cascades coupled with the cellular heterogeneity are further taken into account. The proposed in silico model is evaluated through its ability to successfully reproduce a self-limited inflammatory response as well as a series of scenarios indicative of the nonlinear dynamics of the response. Such scenarios involve either a persistent (non)infectious response or innate immune tolerance and potentiation effects followed by perturbations in intracellular signaling molecules and cascades. The ABM framework developed in this study provides insight on the stochastic interactions of the mediators involved in the propagation of endotoxin signaling at the cellular response level. The simulation results are in accordance with our prior research effort associated with the development of deterministic human inflammation models that include transcriptional dynamics, signaling, and physiological components. The hypothetical scenarios explored in this study would potentially improve our understanding of how manipulating the behavior of the molecular species could manifest into emergent behavior of the overall system.

Efficient collective influence maximization in cascading processes with first-order transitions

PubMed Central

Pei, Sen; Teng, Xian; Shaman, Jeffrey; Morone, Flaviano; Makse, Hernán A.

2017-01-01

In many social and biological networks, the collective dynamics of the entire system can be shaped by a small set of influential units through a global cascading process, manifested by an abrupt first-order transition in dynamical behaviors. Despite its importance in applications, efficient identification of multiple influential spreaders in cascading processes still remains a challenging task for large-scale networks. Here we address this issue by exploring the collective influence in general threshold models of cascading process. Our analysis reveals that the importance of spreaders is fixed by the subcritical paths along which cascades propagate: the number of subcritical paths attached to each spreader determines its contribution to global cascades. The concept of subcritical path allows us to introduce a scalable algorithm for massively large-scale networks. Results in both synthetic random graphs and real networks show that the proposed method can achieve larger collective influence given the same number of seeds compared with other scalable heuristic approaches. PMID:28349988

Efficient collective influence maximization in cascading processes with first-order transitions

NASA Astrophysics Data System (ADS)

Pei, Sen; Teng, Xian; Shaman, Jeffrey; Morone, Flaviano; Makse, Hernán A.

2017-03-01

In many social and biological networks, the collective dynamics of the entire system can be shaped by a small set of influential units through a global cascading process, manifested by an abrupt first-order transition in dynamical behaviors. Despite its importance in applications, efficient identification of multiple influential spreaders in cascading processes still remains a challenging task for large-scale networks. Here we address this issue by exploring the collective influence in general threshold models of cascading process. Our analysis reveals that the importance of spreaders is fixed by the subcritical paths along which cascades propagate: the number of subcritical paths attached to each spreader determines its contribution to global cascades. The concept of subcritical path allows us to introduce a scalable algorithm for massively large-scale networks. Results in both synthetic random graphs and real networks show that the proposed method can achieve larger collective influence given the same number of seeds compared with other scalable heuristic approaches.

Mothers’ Power Assertion, Children’s Negative, Adversarial Orientation, and Future Behavior Problems in Low-Income Families: Early Maternal Responsiveness as a Moderator of the Developmental Cascade

PubMed Central

Kim, Sanghag; Kochanska, Grazyna

2014-01-01

Parental power assertion, a key dimension of family environment, generally sets in motion detrimental developmental cascades; however, evidence suggests that other qualities of parenting, such as responsiveness, can significantly moderate those processes. Mechanisms that account for such moderating effects are not fully understood. We propose a conceptual model of processes linking parental power assertion, parental responsiveness, children’s negative, adversarial, rejecting orientation toward the parent, and behavior problems. We test that model in a short-term longitudinal design involving 186 low-income, ethnically diverse mothers and their toddlers. When children were 30 months, the dyads were observed in multiple, lengthy, naturalistic laboratory interactions to assess behaviorally mothers’ responsiveness and their power-assertive control style. At 33 months, we observed behavioral indicators of children’s negative, adversarial, rejecting orientation toward the mothers in several naturalistic and standardized paradigms. At 40 months, mothers rated children’s behavior problems. The proposed moderated mediation sequence, tested using a new approach, PROCESS (Hayes, 2013), was supported. The indirect effect from maternal power assertion to children’s negative, adversarial orientation to future behavior problems was present when mothers’ responsiveness was either low or average but absent when mothers were highly responsive. This study elucidates a potential process that may link parental power assertion with behavior problems and highlights how positive aspects of parenting can moderate this process and defuse maladaptive developmental cascades. It also suggests possible targets for parenting intervention and prevention efforts. PMID:25401483

Mothers' power assertion; children's negative, adversarial orientation; and future behavior problems in low-income families: early maternal responsiveness as a moderator of the developmental cascade.

PubMed

Kim, Sanghag; Kochanska, Grazyna

2015-02-01

Parental power assertion, a key dimension of family environment, generally sets in motion detrimental developmental cascades; however, evidence suggests that other qualities of parenting, such as responsiveness, can significantly moderate those processes. Mechanisms that account for such moderating effects are not fully understood. We propose a conceptual model of processes linking parental power assertion, parental responsiveness, children's negative, adversarial, rejecting orientation toward the parent, and behavior problems. We test that model in a short-term longitudinal design involving 186 low-income, ethnically diverse mothers and their toddlers. When children were 30 months, the dyads were observed in multiple, lengthy, naturalistic laboratory interactions to assess behaviorally mothers' responsiveness and their power-assertive control style. At 33 months, we observed behavioral indicators of children's negative, adversarial, rejecting orientation toward the mothers in several naturalistic and standardized paradigms. At 40 months, mothers rated children's behavior problems. The proposed moderated mediation sequence, tested using a new approach, PROCESS (Hayes, 2013), was supported. The indirect effect from maternal power assertion to children's negative, adversarial orientation to future behavior problems was present when mothers' responsiveness was either low or average but absent when mothers were highly responsive. This study elucidates a potential process that may link parental power assertion with behavior problems and highlights how positive aspects of parenting can moderate this process and defuse maladaptive developmental cascades. It also suggests possible targets for parenting intervention and prevention efforts. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Mathematical Model of Nonstationary Separation Processes Proceeding in the Cascade of Gas Centrifuges in the Process of Separation of Multicomponent Isotope Mixtures

NASA Astrophysics Data System (ADS)

Orlov, A. A.; Ushakov, A. A.; Sovach, V. P.

2017-03-01

We have developed and realized on software a mathematical model of the nonstationary separation processes proceeding in the cascades of gas centrifuges in the process of separation of multicomponent isotope mixtures. With the use of this model the parameters of the separation process of germanium isotopes have been calculated. It has been shown that the model adequately describes the nonstationary processes in the cascade and is suitable for calculating their parameters in the process of separation of multicomponent isotope mixtures.

[Clinical and etiopathogenetic role of plasminogen and metaloproteinase systems in the tumor growth. Pericellular proteolysis of extracellular matrix and tumor growth].

PubMed

Cosić, Sanda Jelisavac; Kovac, Zdenko

2011-01-01

Pericellular proteolysis is a cascade process involved in degradation of extracellular matrix. This process is included in various physiological and pathological processes. Pericellullar proteolysis has major functions like degradation of tissue stroma and weakening of intercellular connections but it also has a function in the synthesis of bioactive molecules (cytokines, growth factors and inhibitory factors). Plasminogen system is involved in fibrinolysis and starts metalloproteinase activation. Activity of proteolytic molecules is controlled by the rate of zymogenic activation, half-life of molecules, and action of inhibitory molecules. Inhibition is achieved through direct binding of inhibitor and enzyme and takes a few steps. Pericellular proteolysis is involved in tumor invasion and metastasis, inflammatory reaction, degenerative diseases and other diseases. Pathophysiological regulation of pericellular proteolysis in mentioned diseases contributes to clinical properties of diseases and has diagnostic and therapeutic importance.

Theoretical analysis of terahertz generation from a compact optical parametric oscillator based on adhesive-free-bonded periodically inverted KTiOPO4 plates

NASA Astrophysics Data System (ADS)

Li, Zhongyang; Wang, Silei; Wang, Mengtao; Yuan, Bin; Wang, Weishu

2017-10-01

Terahertz (THz) generation by difference frequency generation (DFG) processes with dual signal waves is theoretically analyzed. The dual signal waves are generated by an optical parametric oscillator (OPO) with periodically inverted KTiOPO4 (KTP) plates based on adhesive-free-bonded (AFB) technology. The phase-matching conditions in a same AFB KTP composite for the OPO generating signals and idlers and for the DFG generating THz wave can be simultaneously satisfied by selecting the thickness of each KTP plate. Moreover, 4-order cascaded DFG processes can be realized in the same AFB KTP composite. The cascaded Stokes interaction processes generating THz photons and the cascaded anti-Stokes interaction processes consuming THz photons are investigated from coupled wave equations. Take an example of 3.106 THz which locates in the vicinity of polariton resonances, THz intensities and quantum conversion efficiencies are calculated. Compared with non-cascaded DFG processes, THz intensities of 3.106 THz in 4-order cascaded DFG processes increase to 5.56 times. When the pump intensity equals 20 MW mm-2, the quantum conversion efficiency of 259% in 4-order cascaded DFG processes can be realized, which exceeds the Manley-Rowe limit.

Cascade catalysis in membranes with enzyme immobilization for multi-enzymatic conversion of CO2 to methanol.

PubMed

Luo, Jianquan; Meyer, Anne S; Mateiu, R V; Pinelo, Manuel

2015-05-25

Facile co-immobilization of enzymes is highly desirable for bioconversion methods involving multi-enzymatic cascade reactions. Here we show for the first time that three enzymes can be immobilized in flat-sheet polymeric membranes simultaneously or separately by simple pressure-driven filtration (i.e. by directing membrane fouling formation), without any addition of organic solvent. Such co-immobilization and sequential immobilization systems were examined for the production of methanol from CO2 with formate dehydrogenase (FDH), formaldehyde dehydrogenase (FaldDH) and alcohol dehydrogenase (ADH). Enzyme activity was fully retained by this non-covalent immobilization strategy. The two immobilization systems had similar catalytic efficiencies because the second reaction (formic acid→formaldehyde) catalyzed by FaldDH was found to be the cascade bottleneck (a threshold substrate concentration was required). Moreover, the trade-off between the mitigation of product inhibition and low substrate concentration for the adjacent enzymes probably made the co-immobilization meaningless. Thus, sequential immobilization could be used for multi-enzymatic cascade reactions, as it allowed the operational conditions for each single step to be optimized, not only during the enzyme immobilization but also during the reaction process, and the pressure-driven mass transfer (flow-through mode) could overcome the diffusion resistance between enzymes. This study not only offers a green and facile immobilization method for multi-enzymatic cascade systems, but also reveals the reaction bottleneck and provides possible solutions for the bioconversion of CO2 to methanol. Copyright © 2015 Elsevier B.V. All rights reserved.

Bistable metamaterial for switching and cascading elastic vibrations

PubMed Central

Foehr, André; Daraio, Chiara

2017-01-01

The realization of acoustic devices analogous to electronic systems, like diodes, transistors, and logic elements, suggests the potential use of elastic vibrations (i.e., phonons) in information processing, for example, in advanced computational systems, smart actuators, and programmable materials. Previous experimental realizations of acoustic diodes and mechanical switches have used nonlinearities to break transmission symmetry. However, existing solutions require operation at different frequencies or involve signal conversion in the electronic or optical domains. Here, we show an experimental realization of a phononic transistor-like device using geometric nonlinearities to switch and amplify elastic vibrations, via magnetic coupling, operating at a single frequency. By cascading this device in a tunable mechanical circuit board, we realize the complete set of mechanical logic elements and interconnect selected ones to execute simple calculations. PMID:28416663

Interoception and stress

PubMed Central

Schulz, André; Vögele, Claus

2015-01-01

Afferent neural signals are continuously transmitted from visceral organs to the brain. Interoception refers to the processing of visceral-afferent neural signals by the central nervous system, which can finally result in the conscious perception of bodily processes. Interoception can, therefore, be described as a prominent example of information processing on the ascending branch of the brain–body axis. Stress responses involve a complex neuro-behavioral cascade, which is elicited when the organism is confronted with a potentially harmful stimulus. As this stress cascade comprises a range of neural and endocrine pathways, stress can be conceptualized as a communication process on the descending branch of the brain–body axis. Interoception and stress are, therefore, associated via the bi-directional transmission of information on the brain–body axis. It could be argued that excessive and/or enduring activation (e.g., by acute or chronic stress) of neural circuits, which are responsible for successful communication on the brain–body axis, induces malfunction and dysregulation of these information processes. As a consequence, interoceptive signal processing may be altered, resulting in physical symptoms contributing to the development and/or maintenance of body-related mental disorders, which are associated with stress. In the current paper, we summarize findings on psychobiological processes underlying acute and chronic stress and their interaction with interoception. While focusing on the role of the physiological stress axes (hypothalamic-pituitary-adrenocortical axis and autonomic nervous system), psychological factors in acute and chronic stress are also discussed. We propose a positive feedback model involving stress (in particular early life or chronic stress, as well as major adverse events), the dysregulation of physiological stress axes, altered perception of bodily sensations, and the generation of physical symptoms, which may in turn facilitate stress. PMID:26257668

Ocean Dynamics: Vietnam DRI

DTIC Science & Technology

2014-09-30

floor. OBJECTIVES To identify the phenomena involved in the cascade of energy from mesoscales to turbulent scales. In particular, we wish to quantify the...data from the profiler to the surface buoy. The WW Iridium telemetry system was tested on the WW moored over the continental shelf. Telemetry...2580 email: ajlucas@ucsd.edu Award: N00014-12-1-0635 LONG-TERM GOALS To gain a more complete understanding of ocean dynamical processes

Palladium-Catalyzed Atom-Transfer Radical Cyclization at Remote Unactivated C(sp3 )-H Sites: Hydrogen-Atom Transfer of Hybrid Vinyl Palladium Radical Intermediates.

PubMed

Ratushnyy, Maxim; Parasram, Marvin; Wang, Yang; Gevorgyan, Vladimir

2018-03-01

A novel mild, visible-light-induced palladium-catalyzed hydrogen atom translocation/atom-transfer radical cyclization (HAT/ATRC) cascade has been developed. This protocol involves a 1,5-HAT process of previously unknown hybrid vinyl palladium radical intermediates, thus leading to iodomethyl carbo- and heterocyclic structures. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Investigation of the role of plasma wave cascading processes in the formation of midlatitude irregularities utilizing GPS and radar observations

NASA Astrophysics Data System (ADS)

Eltrass, A.; Scales, W. A.; Erickson, P. J.; Ruohoniemi, J. M.; Baker, J. B. H.

2016-06-01

Recent studies reveal that midlatitude ionospheric irregularities are less understood due to lack of models and observations that can explain the characteristics of the observed wave structures. In this paper, the cascading processes of both the temperature gradient instability (TGI) and the gradient drift instability (GDI) are investigated as the cause of these irregularities. Based on observations obtained during a coordinated experiment between the Millstone Hill incoherent scatter radar and the Blackstone Super Dual Auroral Radar Network radar, a time series for the growth rate of both TGI and GDI is calculated for observations in the subauroral ionosphere under both quiet and disturbed geomagnetic conditions. Recorded GPS scintillation data are analyzed to monitor the amplitude scintillations and to obtain the spectral characteristics of irregularities producing ionospheric scintillations. Spatial power spectra of the density fluctuations associated with the TGI from nonlinear plasma simulations are compared with both the GPS scintillation spectral characteristics and previous in situ satellite spectral measurements. The spectral comparisons suggest that initially, TGI or/and GDI irregularities are generated at large-scale size (kilometer scale), and the dissipation of the energy associated with these irregularities occurs by generating smaller and smaller (decameter scale) irregularities. The alignment between experimental, theoretical, and computational results of this study suggests that in spite of expectations from linear growth rate calculations, cascading processes involving TGI and GDI are likely responsible for the midlatitude ionospheric irregularities associated with GPS scintillations during disturbed times.

Integrated Broadband Quantum Cascade Laser

NASA Technical Reports Server (NTRS)

Mansour, Kamjou (Inventor); Soibel, Alexander (Inventor)

2016-01-01

A broadband, integrated quantum cascade laser is disclosed, comprising ridge waveguide quantum cascade lasers formed by applying standard semiconductor process techniques to a monolithic structure of alternating layers of claddings and active region layers. The resulting ridge waveguide quantum cascade lasers may be individually controlled by independent voltage potentials, resulting in control of the overall spectrum of the integrated quantum cascade laser source. Other embodiments are described and claimed.

Why pleiotropic interventions are needed for Alzheimer's disease.

PubMed

Frautschy, Sally A; Cole, Greg M

2010-06-01

Alzheimer's disease (AD) involves a complex pathological cascade thought to be initially triggered by the accumulation of beta-amyloid (Abeta) peptide aggregates or aberrant amyloid precursor protein (APP) processing. Much is known of the factors initiating the disease process decades prior to the onset of cognitive deficits, but an unclear understanding of events immediately preceding and precipitating cognitive decline is a major factor limiting the rapid development of adequate prevention and treatment strategies. Multiple pathways are known to contribute to cognitive deficits by disruption of neuronal signal transduction pathways involved in memory. These pathways are altered by aberrant signaling, inflammation, oxidative damage, tau pathology, neuron loss, and synapse loss. We need to develop stage-specific interventions that not only block causal events in pathogenesis (aberrant tau phosphorylation, Abeta production and accumulation, and oxidative damage), but also address damage from these pathways that will not be reversed by targeting prodromal pathways. This approach would not only focus on blocking early events in pathogenesis, but also adequately correct for loss of synapses, substrates for neuroprotective pathways (e.g., docosahexaenoic acid), defects in energy metabolism, and adverse consequences of inappropriate compensatory responses (aberrant sprouting). Monotherapy targeting early single steps in this complicated cascade may explain disappointments in trials with agents inhibiting production, clearance, or aggregation of the initiating Abeta peptide or its aggregates. Both plaque and tangle pathogenesis have already reached AD levels in the more vulnerable brain regions during the "prodromal" period prior to conversion to "mild cognitive impairment (MCI)." Furthermore, many of the pathological events are no longer proceeding in series, but are going on in parallel. By the MCI stage, we stand a greater chance of success by considering pleiotropic drugs or cocktails that can independently limit the parallel steps of the AD cascade at all stages, but that do not completely inhibit the constitutive normal functions of these pathways. Based on this hypothesis, efforts in our laboratories have focused on the pleiotropic activities of omega-3 fatty acids and the anti-inflammatory, antioxidant, and anti-amyloid activity of curcumin in multiple models that cover many steps of the AD pathogenic cascade (Cole and Frautschy, Alzheimers Dement 2:284-286, 2006).

Evidence of Facilitation Cascade Processes as Drivers of Successional Patterns of Ecosystem Engineers at the Upper Altitudinal Limit of the Dry Puna.

PubMed

Malatesta, Luca; Tardella, Federico Maria; Piermarteri, Karina; Catorci, Andrea

2016-01-01

Facilitation processes constitute basic elements of vegetation dynamics in harsh systems. Recent studies in tropical alpine environments demonstrated how pioneer plant species defined as "ecosystem engineers" are capable of enhancing landscape-level richness by adding new species to the community through the modification of microhabitats, and also provided hints about the alternation of different ecosystem engineers over time. Nevertheless, most of the existing works analysed different ecosystem engineers separately, without considering the interaction of different ecosystem engineers. Focusing on the altitudinal limit of Peruvian Dry Puna vegetation, we hypothesized that positive interactions structure plant communities by facilitation cascades involving different ecosystem engineers, determining the evolution of the microhabitat patches in terms of abiotic resources and beneficiary species hosted. To analyze successional mechanisms, we used a "space-for-time" substitution to account for changes over time, and analyzed data on soil texture, composition, and temperature, facilitated species and their interaction with nurse species, and surface area of engineered patches by means of chemical analyses, indicator species analysis, and rarefaction curves. A successional process, resulting from the dynamic interaction of different ecosystem engineers, which determined a progressive amelioration of soil conditions (e.g. nitrogen and organic matter content, and temperature), was the main driver of species assemblage at the community scale, enhancing species richness. Cushion plants act as pioneers, by starting the successional processes that continue with shrubs and tussocks. Tussock grasses have sometimes been found to be capable of creating microhabitat patches independently. The dynamics of species assemblage seem to follow the nested assemblage mechanism, in which the first foundation species to colonize a habitat provides a novel substrate for colonization by other foundation species through a facilitation cascade process.

Evidence of Facilitation Cascade Processes as Drivers of Successional Patterns of Ecosystem Engineers at the Upper Altitudinal Limit of the Dry Puna

PubMed Central

2016-01-01

Facilitation processes constitute basic elements of vegetation dynamics in harsh systems. Recent studies in tropical alpine environments demonstrated how pioneer plant species defined as “ecosystem engineers” are capable of enhancing landscape-level richness by adding new species to the community through the modification of microhabitats, and also provided hints about the alternation of different ecosystem engineers over time. Nevertheless, most of the existing works analysed different ecosystem engineers separately, without considering the interaction of different ecosystem engineers. Focusing on the altitudinal limit of Peruvian Dry Puna vegetation, we hypothesized that positive interactions structure plant communities by facilitation cascades involving different ecosystem engineers, determining the evolution of the microhabitat patches in terms of abiotic resources and beneficiary species hosted. To analyze successional mechanisms, we used a “space-for-time” substitution to account for changes over time, and analyzed data on soil texture, composition, and temperature, facilitated species and their interaction with nurse species, and surface area of engineered patches by means of chemical analyses, indicator species analysis, and rarefaction curves. A successional process, resulting from the dynamic interaction of different ecosystem engineers, which determined a progressive amelioration of soil conditions (e.g. nitrogen and organic matter content, and temperature), was the main driver of species assemblage at the community scale, enhancing species richness. Cushion plants act as pioneers, by starting the successional processes that continue with shrubs and tussocks. Tussock grasses have sometimes been found to be capable of creating microhabitat patches independently. The dynamics of species assemblage seem to follow the nested assemblage mechanism, in which the first foundation species to colonize a habitat provides a novel substrate for colonization by other foundation species through a facilitation cascade process. PMID:27902757

Critical behavior in the inverse to forward energy transition in two-dimensional magnetohydrodynamic flow.

PubMed

Seshasayanan, Kannabiran; Alexakis, Alexandros

2016-01-01

We investigate the critical transition from an inverse cascade of energy to a forward energy cascade in a two-dimensional magnetohydrodynamic flow as the ratio of magnetic to mechanical forcing amplitude is varied. It is found that the critical transition is the result of two competing processes. The first process is due to hydrodynamic interactions and cascades the energy to the large scales. The second process couples small-scale magnetic fields to large-scale flows, transferring the energy back to the small scales via a nonlocal mechanism. At marginality the two cascades are both present and cancel each other. The phase space diagram of the transition is sketched.

Cytokine Involvement in Biological Inflammation Related to Degenerative Disorders of the Intervertebral Disk: A Narrative Review.

PubMed

De Geer, Christopher M

2018-03-01

The purpose of this narrative literature review is to discuss the literature regarding the potential role that cytokines play in degenerative disk disease. The inclusion criteria were studies that used inflammatory mediators in advancing disk disease processes. Research studies were limited to the last 3 decades that had free full-text available online in English. Exclusion criteria were review articles and articles pertaining to temporomandibular joints and other joints of the body other than the intervertebral disk. The following databases were searched: PubMed, EBSCOhost, and Google Scholar through March 13, 2017. A total of 82 studies were included in this review. The papers were reviewed for complex mechanisms behind the degenerative cascade, emphasizing the role of proinflammatory cytokines, which may be instrumental in processes of inflammation, neurologic pain, and disk degeneration. Interleukin-1β and tumor necrosis factor α were among the more notable cytokines involved in this cascade. Because monocyte chemoattractant protein-1 stimulates and activates macrophages in the event of infiltration, additional proinflammatory cytokines are released to act on molecules to promote blood and nerve ingrowth, resulting in pain signaling and tissue degradation. Excessive inflammation and/or tissue damage initiates a pathologic imbalance between anabolic and catabolic processes. This literature review describes how inflammatory and biochemical changes may trigger disk degeneration. Proinflammatory cytokines stimulate microvascular blood and nerve ingrowth, resulting in pain signaling and tissue degradation. This may sensitize a person to chemical and/or mechanical stimuli, contributing to severe low back pain.

Ruthenium-Catalyzed Cascade Annulation of Indole with Propargyl Alcohols.

PubMed

Kaufmann, Julia; Jäckel, Elisabeth; Haak, Edgar

2018-05-14

Cascade transformations forming multiple bonds and one-pot procedures provide rapid access to natural-product-like scaffolds from simple precursors. These atom-economic processes are valuable tools in organic synthesis and drug discovery. Herein, we report on ruthenium-catalyzed cascade annulations of indole with readily available propargyl alcohols. These provide rapid access to diverse carbazoles, cyclohepta[b]indoles, and further fused polycycles with high selectivity. A bifunctional ruthenium complex featuring a redox-coupled cyclopentadienone ligand acts as a common catalyst for the different cascade processes. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Relaxation oscillations and hierarchy of feedbacks in MAPK signaling

NASA Astrophysics Data System (ADS)

Kochańczyk, Marek; Kocieniewski, Paweł; Kozłowska, Emilia; Jaruszewicz-Błońska, Joanna; Sparta, Breanne; Pargett, Michael; Albeck, John G.; Hlavacek, William S.; Lipniacki, Tomasz

2017-01-01

We formulated a computational model for a MAPK signaling cascade downstream of the EGF receptor to investigate how interlinked positive and negative feedback loops process EGF signals into ERK pulses of constant amplitude but dose-dependent duration and frequency. A positive feedback loop involving RAS and SOS, which leads to bistability and allows for switch-like responses to inputs, is nested within a negative feedback loop that encompasses RAS and RAF, MEK, and ERK that inhibits SOS via phosphorylation. This negative feedback, operating on a longer time scale, changes switch-like behavior into oscillations having a period of 1 hour or longer. Two auxiliary negative feedback loops, from ERK to MEK and RAF, placed downstream of the positive feedback, shape the temporal ERK activity profile but are dispensable for oscillations. Thus, the positive feedback introduces a hierarchy among negative feedback loops, such that the effect of a negative feedback depends on its position with respect to the positive feedback loop. Furthermore, a combination of the fast positive feedback involving slow-diffusing membrane components with slower negative feedbacks involving faster diffusing cytoplasmic components leads to local excitation/global inhibition dynamics, which allows the MAPK cascade to transmit paracrine EGF signals into spatially non-uniform ERK activity pulses.

Cascading second-order nonlinear processes in a lithium niobate-on-insulator microdisk.

PubMed

Liu, Shijie; Zheng, Yuanlin; Chen, Xianfeng

2017-09-15

Whispering-gallery-mode (WGM) microcavities are very important in both fundamental science and practical applications, among which on-chip second-order nonlinear microresonators play an important role in integrated photonic functionalities. Here we demonstrate resonant second-harmonic generation (SHG) and cascaded third-harmonic generation (THG) in a lithium niobate-on-insulator (LNOI) microdisk resonator. Efficient SHG in the visible range was obtained with only several mW input powers at telecom wavelengths. THG was also observed through a cascading process, which reveals simultaneous phase matching and strong mode coupling in the resonator. Cascading of second-order nonlinear processes gives rise to an effectively large third-order nonlinearity, which makes on-chip second-order nonlinear microresonators a promising frequency converter for integrated nonlinear photonics.

Receptor signaling clusters in the immune synapse(in eng)

DOE PAGES

Dustin, Michael L.; Groves, Jay T.

2012-02-23

Signaling processes between various immune cells involve large-scale spatial reorganization of receptors and signaling molecules within the cell-cell junction. These structures, now collectively referred to as immune synapses, interleave physical and mechanical processes with the cascades of chemical reactions that constitute signal transduction systems. Molecular level clustering, spatial exclusion, and long-range directed transport are all emerging as key regulatory mechanisms. The study of these processes is drawing researchers from physical sciences to join the effort and represents a rapidly growing branch of biophysical chemistry. Furthermore, recent advances in physical and quantitative analyses of signaling within the immune synapses are reviewedmore » here.« less

Receptor signaling clusters in the immune synapse (in eng)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dustin, Michael L.; Groves, Jay T.

2012-02-23

Signaling processes between various immune cells involve large-scale spatial reorganization of receptors and signaling molecules within the cell-cell junction. These structures, now collectively referred to as immune synapses, interleave physical and mechanical processes with the cascades of chemical reactions that constitute signal transduction systems. Molecular level clustering, spatial exclusion, and long-range directed transport are all emerging as key regulatory mechanisms. The study of these processes is drawing researchers from physical sciences to join the effort and represents a rapidly growing branch of biophysical chemistry. Furthermore, recent advances in physical and quantitative analyses of signaling within the immune synapses are reviewedmore » here.« less

SUMCOR: Cascade summing correction for volumetric sources applying MCNP6.

PubMed

Dias, M S; Semmler, R; Moreira, D S; de Menezes, M O; Barros, L F; Ribeiro, R V; Koskinas, M F

2018-04-01

The main features of code SUMCOR developed for cascade summing correction for volumetric sources are described. MCNP6 is used to track histories starting from individual points inside the volumetric source, for each set of cascade transitions from the radionuclide. Total and FEP efficiencies are calculated for all gamma-rays and X-rays involved in the cascade. Cascade summing correction is based on the matrix formalism developed by Semkow et al. (1990). Results are presented applying the experimental data sent to the participants of two intercomparisons organized by the ICRM-GSWG and coordinated by Dr. Marie-Cristine Lépy from the Laboratoire National Henri Becquerel (LNE-LNHB), CEA, in 2008 and 2010, respectively and compared to the other participants in the intercomparisons. Copyright © 2017 Elsevier Ltd. All rights reserved.

Second order nonlinear QED processes in ultra-strong laser fields

NASA Astrophysics Data System (ADS)

Mackenroth, Felix

2017-10-01

In the interaction of ultra-intense laser fields with matter the ever increasing peak laser intensities render nonlinear QED effects ever more important. For long, ultra-intense laser pulses scattering large systems, like a macroscopic plasma, the interaction time can be longer than the scattering time, leading to multiple scatterings. These are usually approximated as incoherent cascades of single-vertex processes. Under certain conditions, however, this common cascade approximation may be insufficient, as it disregards several effects such as coherent processes, quantum interferences or pulse shape effects. Quantifying deviations of the full amplitude of multiple scatterings from the commonly employed cascade approximations is a formidable, yet unaccomplished task. In this talk we are going to discuss how to compute second order nonlinear QED amplitudes and relate them to the conventional cascade approximation. We present examples for typical second order processes and benchmark the full result against common approximations. We demonstrate that the approximation of multiple nonlinear QED scatterings as a cascade of single interactions has certain limitations and discuss these limits in light of upcoming experimental tests.

Ca2+ conduction by plant cyclic nucleotide gated channels and associated signaling components in pathogen defense signal transduction cascades.

PubMed

Ma, Wei; Berkowitz, Gerald A

2011-05-01

Ca(2+) elevation in the cytosol is an essential early event during pathogen response signaling cascades. However, the specific ion channels involved in Ca(2+) influx into plant cells, and how Ca(2+) signals are initiated and regulate downstream events during pathogen defense responses, are at present unclear. Plant cyclic nucleotide gated ion channels (CNGCs) provide a pathway for Ca(2+) conductance across the plasma membrane (PM) and facilitate cytosolic Ca(2+) elevation in response to pathogen signals. Recent studies indicate that the recognition of pathogens results in cyclic nucleotide production and the activation of CNGCs, which leads to downstream generation of pivotal signaling molecules (such as nitric oxide (NO)). Calmodulins (CaMs) and CaM-like proteins (CMLs) are also involved in this signaling, functioning as Ca(2+) sensors and mediating the synthesis of NO during the plant pathogen response signaling cascade. In this article, these and other pivotal signaling components downstream from the Ca(2+) signal, such as Ca(2+)-dependent protein kinases (CDPKs) and CaM-binding transcription activators (CAMTAs), are discussed in terms of their involvement in the pathogen response signal transduction cascade. © 2010 The Authors. New Phytologist © 2010 New Phytologist Trust.

Organization of cis-acting regulatory elements in osmotic- and cold-stress-responsive promoters.

PubMed

Yamaguchi-Shinozaki, Kazuko; Shinozaki, Kazuo

2005-02-01

cis-Acting regulatory elements are important molecular switches involved in the transcriptional regulation of a dynamic network of gene activities controlling various biological processes, including abiotic stress responses, hormone responses and developmental processes. In particular, understanding regulatory gene networks in stress response cascades depends on successful functional analyses of cis-acting elements. The ever-improving accuracy of transcriptome expression profiling has led to the identification of various combinations of cis-acting elements in the promoter regions of stress-inducible genes involved in stress and hormone responses. Here we discuss major cis-acting elements, such as the ABA-responsive element (ABRE) and the dehydration-responsive element/C-repeat (DRE/CRT), that are a vital part of ABA-dependent and ABA-independent gene expression in osmotic and cold stress responses.

Introducing fluorescence resonance energy transfer-based biosensors for the analysis of cAMP-PKA signalling in the fungal pathogen Candida glabrata.

PubMed

Demuyser, Liesbeth; Van Genechten, Wouter; Mizuno, Hideaki; Colombo, Sonia; Van Dijck, Patrick

2018-05-29

The cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) pathway is central to signal transduction in many organisms. In pathogenic fungi such as Candida albicans, this signalling cascade has proven to be involved in several processes, such as virulence, indicating its potential importance in antifungal drug discovery. Candida glabrata is an upcoming pathogen of the same species, yet information regarding the role of cAMP-PKA signalling in virulence is largely lacking. To enable efficient monitoring of cAMP-PKA activity in this pathogen, we here present the usage of two FRET-based biosensors. Both variations in the activity of PKA and the quantity of cAMP can be detected in a time-resolved manner, as we exemplify by glucose-induced activation of the pathway. We also present information on how to adequately process and analyse the data in a mathematically correct and physiologically relevant manner. These sensors will be of great benefit for scientists interested in linking the cAMP-PKA signalling cascade to downstream processes, such as virulence, possibly in a host environment. © 2018 John Wiley & Sons Ltd.

Artificial concurrent catalytic processes involving enzymes.

PubMed

Köhler, Valentin; Turner, Nicholas J

2015-01-11

The concurrent operation of multiple catalysts can lead to enhanced reaction features including (i) simultaneous linear multi-step transformations in a single reaction flask (ii) the control of intermediate equilibria (iii) stereoconvergent transformations (iv) rapid processing of labile reaction products. Enzymes occupy a prominent position for the development of such processes, due to their high potential compatibility with other biocatalysts. Genes for different enzymes can be co-expressed to reconstruct natural or construct artificial pathways and applied in the form of engineered whole cell biocatalysts to carry out complex transformations or, alternatively, the enzymes can be combined in vitro after isolation. Moreover, enzyme variants provide a wider substrate scope for a given reaction and often display altered selectivities and specificities. Man-made transition metal catalysts and engineered or artificial metalloenzymes also widen the range of reactivities and catalysed reactions that are potentially employable. Cascades for simultaneous cofactor or co-substrate regeneration or co-product removal are now firmly established. Many applications of more ambitious concurrent cascade catalysis are only just beginning to appear in the literature. The current review presents some of the most recent examples, with an emphasis on the combination of transition metal with enzymatic catalysis and aims to encourage researchers to contribute to this emerging field.

Turbulent cascade in a two-ion plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu, Xin; Faculty of Information Engineering, Jiangxi University of Science and Technology, Ganzhou 341000; Liu, San-Qiu, E-mail: sqlgroup@ncu.edu.cn

2014-11-15

It is shown that small but finite-amplitude drift wave turbulence in a two-ion-species plasma can be modeled by a Hasegawa-Mima equation. The mode cascade process and resulting turbulent spectrum are investigated. The spectrum is found to be similar to that of a two-component plasma, but the space and time scales of the turbulent cascade process can be quite different since they are rescaled by the presence of the second ion species.

Quantum-electrodynamic cascades in intense laser fields

NASA Astrophysics Data System (ADS)

Narozhny, N. B.; Fedotov, A. M.

2015-01-01

It is shown that in an intense laser field, along with cascades similar to extensive air showers, self-sustaining field-energized cascades can develop. For intensities of 1024~ \\text {W cm}-2 or higher, such cascades can even be initiated by a particle at rest in the focal area of a tightly focused laser pulse. The cascade appearance effect can considerably alter the progression of any process occurring in a high-intensity laser field. At very high intensities, the evolvement of such cascades can lead to the depletion of the laser field. This paper presents a design of an experiment to observe these two cascade types simultaneously already in next-generation laser facilities.

Dependence of quantitative accuracy of CT perfusion imaging on system parameters

NASA Astrophysics Data System (ADS)

Li, Ke; Chen, Guang-Hong

2017-03-01

Deconvolution is a popular method to calculate parametric perfusion parameters from four dimensional CT perfusion (CTP) source images. During the deconvolution process, the four dimensional space is squeezed into three-dimensional space by removing the temporal dimension, and a prior knowledge is often used to suppress noise associated with the process. These additional complexities confound the understanding about deconvolution-based CTP imaging system and how its quantitative accuracy depends on parameters and sub-operations involved in the image formation process. Meanwhile, there has been a strong clinical need in answering this question, as physicians often rely heavily on the quantitative values of perfusion parameters to make diagnostic decisions, particularly during an emergent clinical situation (e.g. diagnosis of acute ischemic stroke). The purpose of this work was to develop a theoretical framework that quantitatively relates the quantification accuracy of parametric perfusion parameters with CTP acquisition and post-processing parameters. This goal was achieved with the help of a cascaded systems analysis for deconvolution-based CTP imaging systems. Based on the cascaded systems analysis, the quantitative relationship between regularization strength, source image noise, arterial input function, and the quantification accuracy of perfusion parameters was established. The theory could potentially be used to guide developments of CTP imaging technology for better quantification accuracy and lower radiation dose.

Compact, High Power, Multi-Spectral Mid-Infrared Semiconductor Laser Package

NASA Astrophysics Data System (ADS)

Guo, Bujin; Hwang, Wen-Yen; Lin, Chich-Hsiang

2001-10-01

Through a vertically integrated effort involving atomic level material engineering, advanced device processing development, state-of-the-art optomechanical packaging, and thermal management, Applied Optoelectronics, Inc. (AOI), University of Houston (U H), and Physical Science, Inc. (PSI) have made progress in both Sb-based type-II semiconductor material and in P-based type-I laser device development. We have achieved record performance on inP based quantum cascade continuous wave (CW) laser (with more than 5 mW CW power at 210 K). Grating-coupled external-cavity quantum cascade lasers were studied for temperatures from 20 to 230 K. A tuning range of 88 nm has been obtained at 80 K. The technology can be made commercially available and represents a significant milestone with regard to the Dual Use Science and Technology (DUST) intention of fostering dual use commercial technology for defense need. AOI is the first commercial company to ship products of this licensed technology.

Terahertz generation by difference frequency generation from a compact optical parametric oscillator

NASA Astrophysics Data System (ADS)

Li, Zhongyang; Wang, Silei; Wang, Mengtao; Wang, Weishu

2017-11-01

Terahertz (THz) generation by difference frequency generation (DFG) processes with dual idler waves is theoretically analyzed. The dual idler waves are generated by a compact optical parametric oscillator (OPO) with periodically poled lithium niobate (PPLN). The phase-matching conditions in a same PPLN for the optical parametric oscillation generating signal and idler waves and for the DFG generating THz waves can be simultaneously satisfied by selecting the poling period of PPLN. Moreover, 3-order cascaded DFG processes generating THz waves can be realized in the same PPLN. To take an example of 8.341 THz which locates in the vicinity of polariton resonances, THz intensities and quantum conversion efficiencies are calculated. Compared with non-cascaded DFG processes, THz intensities of 8.341 THz in 3-order cascaded DFG processes increase to 2.57 times. When the pump intensity equals to 20 MW/mm2, the quantum conversion efficiency of 106% in 3-order cascaded DFG processes can be realized, which exceeds the Manley-Rowe limit.

Determining the Specificity of Cascade Binding, Interference, and Primed Adaptation In Vivo in the Escherichia coli Type I-E CRISPR-Cas System

PubMed Central

Cooper, Lauren A.; Stringer, Anne M.

2018-01-01

ABSTRACT In clustered regularly interspaced short palindromic repeat (CRISPR)-Cas (CRISPR-associated) immunity systems, short CRISPR RNAs (crRNAs) are bound by Cas proteins, and these complexes target invading nucleic acid molecules for degradation in a process known as interference. In type I CRISPR-Cas systems, the Cas protein complex that binds DNA is known as Cascade. Association of Cascade with target DNA can also lead to acquisition of new immunity elements in a process known as primed adaptation. Here, we assess the specificity determinants for Cascade-DNA interaction, interference, and primed adaptation in vivo, for the type I-E system of Escherichia coli. Remarkably, as few as 5 bp of crRNA-DNA are sufficient for association of Cascade with a DNA target. Consequently, a single crRNA promotes Cascade association with numerous off-target sites, and the endogenous E. coli crRNAs direct Cascade binding to >100 chromosomal sites. In contrast to the low specificity of Cascade-DNA interactions, >18 bp are required for both interference and primed adaptation. Hence, Cascade binding to suboptimal, off-target sites is inert. Our data support a model in which the initial Cascade association with DNA targets requires only limited sequence complementarity at the crRNA 5′ end whereas recruitment and/or activation of the Cas3 nuclease, a prerequisite for interference and primed adaptation, requires extensive base pairing. PMID:29666291

TC-99 Decontaminant from heat treated gaseous diffusion membrane -Phase I, Part B

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oji, L.; Restivo, M.; Duignan, M.

2017-11-01

Uranium gaseous diffusion cascades represent a significant environmental challenge to dismantle, containerize and dispose as low-level radioactive waste. Baseline technologies rely on manual manipulations involving direct access to technetium-contaminated piping and materials. There is a potential to utilize novel decontamination technologies to remove the technetium and allow for on-site disposal of the very large uranium converters. Technetium entered these gaseous diffusion cascades as a hexafluoride complex in the same fashion as uranium. Technetium, as the isotope Tc-99, is an impurity that follows uranium in the first cycle of the Plutonium and Uranium Extraction (PUREX) process. The technetium speciation or exactmore » form in the gaseous diffusion cascades is not well defined. Several forms of Tc-99 compounds, mostly the fluorinated technetium compounds with varying degrees of volatility have been speculated by the scientific community to be present in these cascades. Therefore, there may be a possibility of using thermal or leaching desorption, which is independent of the technetium oxidation states, to perform an insitu removal of the technetium as a volatile species and trap the radionuclide on sorbent traps which could be disposed as low-level waste. Based on the positive results of the first part of this work1 the use of steam as a thermal decontamination agent was further explored with a second piece of used barrier material from a different location. This new series of tests included exposing more of the material surface to the flow of high temperature steam through the change in the reactor design, subjecting it to alternating periods of stream and vacuum, as well as determining if a lower temperature steam, i.e., 121°C (250°F) would be effective, too. Along with these methods, one other simpler method involving the leaching of the Tc-99 contaminated barrier material with a 1.0 M aqueous solution of ammonium carbonate, with and without sonication, was evaluated.« less

(dis)connectivity in Catchment-Scale Sediment Cascades: Forecasting Responses in Sediment Flux Associated with Various Forms of Environmental Change

NASA Astrophysics Data System (ADS)

Fryirs, K.

2010-12-01

Fluvial systems are key elements that drive Earth surface change because they convey most of the global fluxes of water and sediment from land to oceans. Fluvial fluxes of water and sediment also drive a significant proportion of the terrestrial biochemical cycling of carbon, nutrients and pollutants. Understanding the internal dynamics of the sediment cascade is therefore critical to forecasting how environmental change, whether driven by extrinsic climate change, or intrinsic human-disturbance, might affect biochemical fluxes. To understand the internal dynamics of sediment flux requires a framework that can incorporate the various processes involved in the movement of sediment from the source area through the basin system to the outlet, and can take account of spatial variability within the system and the timeframes over which these processes operate. Traditionally a sediment budget approach has been used to quantify the sediment being supplied, transported and stored in various parts of catchments. In more recent years, a more sophisticated approach to analysis of catchment linkages and (dis)connectivity has been developed that incorporates both spatial and temporal variability in the operation of the sediment cascade. This framework is based on an understanding of longitudinal, lateral and vertical linkages in sediment flux in catchments, and where blockages occur to disrupt these linkages. These blockages have been termed buffers, barriers and blankets (Fryirs et al 2007). Depending on the position of these blockages, and their sediment residence time, various parts of catchment may be actively contributing sediment to the catchment sediment cascade and be switched on, or inactive and switched off. The degree of spatial connectivity determines the effective catchment area. The breaching capacity of buffers, barriers and blankets determines the effective timescale over which certain parts of a catchment are switched on. The sediment residence time and thresholds of stability dictate the timeframe over which certain parts of catchments are actively contributing sediment to the cascade. The manifestation of geomorphic change, and response times to disturbance can be modeled within such a framework. The notion that certain sediment sources and transport mechanisms may be switched on or switched off under various climate change scenarios can also be examined using this framework. Fryirs, K., Brierley, G. J., Preston, N. J. and Kasai, M. 2007. Buffers, barriers and blankets: The (dis)connectivity of catchment-scale sediment cascades. Catena, 70, 49-67

Transcriptional master regulator analysis in breast cancer genetic networks.

PubMed

Tovar, Hugo; García-Herrera, Rodrigo; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique

2015-12-01

Gene regulatory networks account for the delicate mechanisms that control gene expression. Under certain circumstances, gene regulatory programs may give rise to amplification cascades. Such transcriptional cascades are events in which activation of key-responsive transcription factors called master regulators trigger a series of gene expression events. The action of transcriptional master regulators is then important for the establishment of certain programs like cell development and differentiation. However, such cascades have also been related with the onset and maintenance of cancer phenotypes. Here we present a systematic implementation of a series of algorithms aimed at the inference of a gene regulatory network and analysis of transcriptional master regulators in the context of primary breast cancer cells. Such studies were performed in a highly curated database of 880 microarray gene expression experiments on biopsy-captured tissue corresponding to primary breast cancer and healthy controls. Biological function and biochemical pathway enrichment analyses were also performed to study the role that the processes controlled - at the transcriptional level - by such master regulators may have in relation to primary breast cancer. We found that transcription factors such as AGTR2, ZNF132, TFDP3 and others are master regulators in this gene regulatory network. Sets of genes controlled by these regulators are involved in processes that are well-known hallmarks of cancer. This kind of analyses may help to understand the most upstream events in the development of phenotypes, in particular, those regarding cancer biology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neuroendocrinology briefings 12: The maternal brain.

PubMed

Russell, J A

2000-12-01

The mother's brain is prepared by the hormones of pregnancy to show the strong maternal feelings that ensure the newborn is cared for. These hormones induce a cascade of changes in the brain, reducing stress reactions, evoking maternal behaviour and preparing the neuroendocrine circuits that drive the birth process and ensure that the suckling infant gets milk. The nerve cells that make oxytocin are involved in all of these aspects of motherhood, and details are emerging of how their performance is adapted by pregnancy.

Catalyzed and Electrocatalyzed Oxidation of l-Tyrosine and l-Phenylalanine to Dopachrome by Nanozymes.

PubMed

Hou, Jianwen; Vázquez-González, Margarita; Fadeev, Michael; Liu, Xia; Lavi, Ronit; Willner, Itamar

2018-06-13

Catalyzed oxygen insertion into C-H bonds represents a continuous challenge in chemistry. Particularly, driving this process at ambient temperature and aqueous media represents a "holy grail" in catalysis. We report on the catalyzed cascade transformations of l-tyrosine or l-phenylalanine to dopachrome in the presence of l-ascorbic acid/H 2 O 2 as oxidizing mixture and CuFe-Prussian Blue-like nanoparticles, Fe 3 O 4 nanoparticles or Au nanoparticles as catalysts. The process involves the primary transformation of l-tyrosine to l-DOPA that is further oxidized to dopachrome. The transformation of l-phenylalanine to dopachrome in the presence of CuFe-Prussian Blue-like nanoparticles and l-ascorbic acid/H 2 O 2 involves in the first step the formation of l-tyrosine and, subsequently, the operation of the catalytic oxidation cascade of l-tyrosine to l-DOPA and dopachrome. Electron spin resonance experiments demonstrate that ascorbate radicals and hydroxyl radicals play cooperative functions in driving the different oxygen-insertion processes. In addition, the aerobic elecrocatalyzed oxidation of l-tyrosine to dopachrome in the presence of naphthoquinone-modified Fe 3 O 4 nanoparticles and l-ascorbic acid is demonstrated. In this system, magnetic-field attraction of the naphthoquinone-modified Fe 3 O 4 nanoparticles onto the electrode allows the quinone-mediated electrocatalyzed reduction of O 2 to H 2 O 2 (bias potential -0.5 V vs SCE). The electrogenerated H 2 O 2 is then utilized to promote the transformation of l-tyrosine to dopachrome in the presence of l-ascorbic acid and Fe 3 O 4 catalyst.

A matter of hierarchy: activation of orfamide production by the post-transcriptional Gac-Rsm cascade of Pseudomonas protegens CHA0 through expression upregulation of the two dedicated transcriptional regulators.

PubMed

Sobrero, Patricio Martín; Muzlera, Andrés; Frescura, Julieta; Jofré, Edgardo; Valverde, Claudio

2017-10-01

In this work, we surveyed the genome of P. protegens CHA0 in order to identify novel mRNAs possibly under the control of the Gac-Rsm cascade that might, for their part, serve to elucidate as-yet-unknown functions involved in the biocontrol of plant pathogens and/or in cellular processes required for fitness in natural environments. In view of the experimental evidence from former studies on the Gac-Rsm cascade, we developed a computational screen supported by a combination of sequence, structural and evolutionary constraints that led to a dataset of 43 potential novel mRNA targets. We then confirmed several mRNA targets experimentally and next focused on two of the respective genes that are physically linked to the orfamide biosynthetic gene cluster and whose predicted open-reading frames resembled cognate LuxR-type transcriptional regulators of cyclic lipopeptide clusters in related pseudomonads. In this report, we demonstrate that in strain CHA0, orfamide production is stringently dependent on a functional Gac-Rsm cascade and that both mRNAs encoding transcriptional regulatory proteins are under direct translational control of the RsmA/E proteins. Our results have thus revealed a hierarchical control over the expression of orfamide biosynthetic genes with the final transcriptional control subordinated to the global Gac-Rsm post-transcriptional regulatory system. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Cascade process modeling with mechanism-based hierarchical neural networks.

PubMed

Cong, Qiumei; Yu, Wen; Chai, Tianyou

2010-02-01

Cascade process, such as wastewater treatment plant, includes many nonlinear sub-systems and many variables. When the number of sub-systems is big, the input-output relation in the first block and the last block cannot represent the whole process. In this paper we use two techniques to overcome the above problem. Firstly we propose a new neural model: hierarchical neural networks to identify the cascade process; then we use serial structural mechanism model based on the physical equations to connect with neural model. A stable learning algorithm and theoretical analysis are given. Finally, this method is used to model a wastewater treatment plant. Real operational data of wastewater treatment plant is applied to illustrate the modeling approach.

Hybrid Cascading Outage Analysis of Extreme Events with Optimized Corrective Actions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vallem, Mallikarjuna R.; Vyakaranam, Bharat GNVSR; Holzer, Jesse T.

2017-10-19

Power system are vulnerable to extreme contingencies (like an outage of a major generating substation) that can cause significant generation and load loss and can lead to further cascading outages of other transmission facilities and generators in the system. Some cascading outages are seen within minutes following a major contingency, which may not be captured exclusively using the dynamic simulation of the power system. The utilities plan for contingencies either based on dynamic or steady state analysis separately which may not accurately capture the impact of one process on the other. We address this gap in cascading outage analysis bymore » developing Dynamic Contingency Analysis Tool (DCAT) that can analyze hybrid dynamic and steady state behavior of the power system, including protection system models in dynamic simulations, and simulating corrective actions in post-transient steady state conditions. One of the important implemented steady state processes is to mimic operator corrective actions to mitigate aggravated states caused by dynamic cascading. This paper presents an Optimal Power Flow (OPF) based formulation for selecting corrective actions that utility operators can take during major contingency and thus automate the hybrid dynamic-steady state cascading outage process. The improved DCAT framework with OPF based corrective actions is demonstrated on IEEE 300 bus test system.« less

Atomistic material behavior at extreme pressures

DOE PAGES

Beland, Laurent K.; Osetskiy, Yury N.; Stoller, Roger E.

2016-08-05

Computer simulations are routinely performed to model the response of materials to extreme environments, such as neutron (or ion) irradiation. The latter involves high-energy collisions from which a recoiling atom creates a so-called atomic displacement cascade. These cascades involve coordinated motion of atoms in the form of supersonic shockwaves. These shockwaves are characterized by local atomic pressures >15 GPa and interatomic distances <2 Å. Similar pressures and interatomic distances are observed in other extreme environment, including short-pulse laser ablation, high-impact ballistic collisions and diamond anvil cells. Displacement cascade simulations using four different force fields, with initial kinetic energies ranging frommore » 1 to 40 keV, show that there is a direct relationship between these high-pressure states and stable defect production. An important shortcoming in the modeling of interatomic interactions at these short distances, which in turn determines final defect production, is brought to light.« less

Combined cross-linked enzyme aggregates of horseradish peroxidase and glucose oxidase for catalyzing cascade chemical reactions.

PubMed

Nguyen, Le Truc; Yang, Kun-Lin

2017-05-01

Cascade reactions involved unstable intermediates are often encountered in biological systems. In this study, we developed combined cross-linked enzyme aggregates (combi-CLEA) to catalyze a cascade reaction which involves unstable hydrogen peroxide as an intermediate. The combi-CLEA contains two enzymes̶ glucose oxidase (GOx) and horseradish peroxidase (HRP) which are cross-linked together as solid aggregates. The first enzyme GOx catalyzes the oxidation of glucose and produces hydrogen peroxide, which is used by the second enzyme HRP to oxidize 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS). The apparent reaction rate of the cascade reaction reaches 10.5±0.5μM/min when the enzyme ratio is 150:1 (GOx:HRP). Interestingly, even in the presence of catalase, an enzyme that quickly decomposes hydrogen peroxide, the reaction rate only decreases by 18.7% to 8.3±0.3μM/min. This result suggests that the intermediate hydrogen peroxide is not decomposed by catalase due to a short diffusion distance between GOx and HRP in the combi-CLEA. Scanning electron microscopy images suggest that combi-CLEA particles are hollow spheres and have an average diameter around 250nm. Because of their size, combi-CLEA particles can be entrapped inside a nylon membrane for detecting glucose by using the cascade reaction. Copyright © 2017 Elsevier Inc. All rights reserved.

Self-referenced processing, neurodevelopment and joint attention in autism.

PubMed

Mundy, Peter; Gwaltney, Mary; Henderson, Heather

2010-09-01

This article describes a parallel and distributed processing model (PDPM) of joint attention, self-referenced processing and autism. According to this model, autism involves early impairments in the capacity for rapid, integrated processing of self-referenced (proprioceptive and interoceptive) and other-referenced (exteroceptive) information. Measures of joint attention have proven useful in research on autism because they are sensitive to the early development of the 'parallel' and integrated processing of self- and other-referenced stimuli. Moreover, joint attention behaviors are a consequence, but also an organizer of the functional development of a distal distributed cortical system involving anterior networks including the prefrontal and insula cortices, as well as posterior neural networks including the temporal and parietal cortices. Measures of joint attention provide early behavioral indicators of atypical development in this parallel and distributed processing system in autism. In addition it is proposed that an early, chronic disturbance in the capacity for integrating self- and other-referenced information may have cascading effects on the development of self awareness in autism. The assumptions, empirical support and future research implications of this model are discussed.

Three-beam double stimulated Raman scatterings: Cascading configuration

NASA Astrophysics Data System (ADS)

Rao, B. Jayachander; Cho, Minhaeng

2018-03-01

Two-beam stimulated Raman scattering (SRS) has been used in diverse label-free spectroscopy and imaging applications of live cells, biological tissues, and functional materials. Recently, we developed a theoretical framework for the three-beam double SRS processes that involve pump, Stokes, and depletion beams, where the pump-Stokes and pump-depletion SRS processes compete with each other. It was shown that the net Stokes gain signal can be suppressed by increasing the depletion beam intensity. The theoretical prediction has been experimentally confirmed recently. In the previous scheme for a selective suppression of one SRS by making it compete with another SRS, the two SRS processes occur in a parallel manner. However, there is another possibility of three-beam double SRS scheme that can be of use to suppress either Raman gain of the Stokes beam or Raman loss of the pump beam by depleting the Stokes photons with yet another SRS process induced by the pair of Stokes and another (second) Stokes beam. This three-beam double SRS process resembles a cascading energy transfer process from the pump beam to the first Stokes beam (SRS-1) and subsequently from the first Stokes beam to the second Stokes beam (SRS-2). Here, the two stimulated Raman gain-loss processes are associated with two different Raman-active vibrational modes of solute molecule. In the present theory, both the radiation and the molecules are treated quantum mechanically. We then show that the cascading-type three-beam double SRS can be described by coupled differential equations for the photon numbers of the pump and Stokes beams. From the approximate solutions as well as exact numerical calculation results for the coupled differential equations, a possibility of efficiently suppressing the stimulated Raman loss of the pump beam by increasing the second Stokes beam intensity is shown and discussed. To further prove a potential use of this scheme for developing a super-resolution SRS microscopy, we present a theoretical expression and numerical simulation results for the full-width-at-half-maximum of SRS imaging point spread function, assuming that the pump and Stokes beam profiles are Gaussian and the second Stokes beam has a doughnut-shaped spatial profile. It is clear that the spatial resolution with the present 3-beam cascading SRS method can be enhanced well beyond the diffraction limit. We anticipate that the present work will provide a theoretical framework for a super-resolution stimulated Raman scattering microscopy that is currently under investigation.

Developmental Cascade Model for Adolescent Substance Use from Infancy to Late Adolescence

ERIC Educational Resources Information Center

Eiden, Rina D.; Lessard, Jared; Colder, Craig R.; Livingston, Jennifer; Casey, Meghan; Leonard, Kenneth E.

2016-01-01

A developmental cascade model for adolescent substance use beginning in infancy was examined in a sample of children with alcoholic and nonalcoholic parents. The model examined the role of parents' alcohol diagnoses, depression and antisocial behavior in a cascading process of risk via 3 major hypothesized pathways: first, via parental…

Recent Advances in Dynamic Kinetic Resolution by Chiral Bifunctional (Thio)urea- and Squaramide-Based Organocatalysts.

PubMed

Li, Pan; Hu, Xinquan; Dong, Xiu-Qin; Zhang, Xumu

2016-10-14

The organocatalysis-based dynamic kinetic resolution (DKR) process has proved to be a powerful strategy for the construction of chiral compounds. In this feature review, we summarized recent progress on the DKR process, which was promoted by chiral bifunctional (thio)urea and squaramide catalysis via hydrogen-bonding interactions between substrates and catalysts. A wide range of asymmetric reactions involving DKR, such as asymmetric alcoholysis of azlactones, asymmetric Michael-Michael cascade reaction, and enantioselective selenocyclization, are reviewed and demonstrate the efficiency of this strategy. The (thio)urea and squaramide catalysts with dual activation would be efficient for more unmet challenges in dynamic kinetic resolution.

Effect of multiparticle collisions on pion production in relativistic heavy-ion reactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goncalves, M.G.; Medeiros, E.L.; Duarte, S.B.

In the present work we discuss the effect of N-body processes on pion multiplicity in relativistic heavy-ion reactions. This effect is analyzed in the energy range from the pion threshold up to 2 GeV/nucleon, for several projectile-target systems. The analysis is carried out in the context of intranuclear cascade calculations. It is shown that the inclusion of multibaryonic collisions is a crucial element in the study of the pion production mechanisms, being strongly dependent on the adopted correlation range for the particles involved in the N-body processes. {copyright} {ital 1997} {ital The American Physical Society}

Determining the Specificity of Cascade Binding, Interference, and Primed Adaptation In Vivo in the Escherichia coli Type I-E CRISPR-Cas System.

PubMed

Cooper, Lauren A; Stringer, Anne M; Wade, Joseph T

2018-04-17

In clustered regularly interspaced short palindromic repeat (CRISPR)-Cas (CRISPR-associated) immunity systems, short CRISPR RNAs (crRNAs) are bound by Cas proteins, and these complexes target invading nucleic acid molecules for degradation in a process known as interference. In type I CRISPR-Cas systems, the Cas protein complex that binds DNA is known as Cascade. Association of Cascade with target DNA can also lead to acquisition of new immunity elements in a process known as primed adaptation. Here, we assess the specificity determinants for Cascade-DNA interaction, interference, and primed adaptation in vivo , for the type I-E system of Escherichia coli Remarkably, as few as 5 bp of crRNA-DNA are sufficient for association of Cascade with a DNA target. Consequently, a single crRNA promotes Cascade association with numerous off-target sites, and the endogenous E. coli crRNAs direct Cascade binding to >100 chromosomal sites. In contrast to the low specificity of Cascade-DNA interactions, >18 bp are required for both interference and primed adaptation. Hence, Cascade binding to suboptimal, off-target sites is inert. Our data support a model in which the initial Cascade association with DNA targets requires only limited sequence complementarity at the crRNA 5' end whereas recruitment and/or activation of the Cas3 nuclease, a prerequisite for interference and primed adaptation, requires extensive base pairing. IMPORTANCE Many bacterial and archaeal species encode CRISPR-Cas immunity systems that protect against invasion by foreign DNA. In the Escherichia coli CRISPR-Cas system, a protein complex, Cascade, binds 61-nucleotide (nt) CRISPR RNAs (crRNAs). The Cascade complex is directed to invading DNA molecules through base pairing between the crRNA and target DNA. This leads to recruitment of the Cas3 nuclease, which destroys the invading DNA molecule and promotes acquisition of new immunity elements. We made the first in vivo measurements of Cascade binding to DNA targets. Thus, we show that Cascade binding to DNA is highly promiscuous; endogenous E. coli crRNAs can direct Cascade binding to >100 chromosomal locations. In contrast, we show that targeted degradation and acquisition of new immunity elements require highly specific association of Cascade with DNA, limiting CRISPR-Cas function to the appropriate targets. Copyright © 2018 Cooper et al.

Laboratory hemostasis: from biology to the bench.

PubMed

Lippi, Giuseppe; Favaloro, Emmanuel J

2018-06-27

Physiological hemostasis is an intricate biological system, where procoagulant and anticoagulant forces interplay and preserves blood fluidity when blood vessels are intact, or trigger clot formation to prevent excessive bleeding when blood vessels are injured. The modern model of hemostasis is divided into two principal phases. The first, defined as primary hemostasis, involves the platelet-vessel interplay, whilst the second, defined as secondary hemostasis, mainly involves coagulation factors, damaged cells and platelet surfaces, where the so-called coagulation cascade rapidly develops. The activation and amplification of the coagulation cascade is finely modulated by the activity of several physiological inhibitors. Once bleeding has been efficiently stopped by blood clot formation, dissolution of the thrombus is essential to restore vessel permeability. This process, known as fibrinolysis, also develops through coordinate action of a vast array of proteins and enzymes. An accurate diagnosis of hemostasis disturbance entails a multifaceted approach, encompassing family and personal history of hemostatic disorders, accurate collection of clinical signs and symptoms, integrated with laboratory hemostasis testing. Regarding laboratory testing, a reasonable approach entails classifying hemostasis testing according to cost, complexity and available clinical information. Laboratory workout may hence initiate with some rapid and inexpensive "screening" tests, characterized by high negative predictive value, then followed by second- or third-line analyses, specifically aimed to clarify the nature and severity of bleeding or thrombotic phenotype. This article aims to provide a general overview of the hemostatic process, and to provide some general suggestions to optimally facilitate laboratory hemostasis testing.

Beyond Aztec Castles: Toric Cascades in the dP 3 Quiver

NASA Astrophysics Data System (ADS)

Lai, Tri; Musiker, Gregg

2017-12-01

Given one of an infinite class of supersymmetric quiver gauge theories, string theorists can associate a corresponding toric variety (which is a Calabi-Yau 3-fold) as well as an associated combinatorial model known as a brane tiling. In combinatorial language, a brane tiling is a bipartite graph on a torus and its perfect matchings are of interest to both combinatorialists and physicists alike. A cluster algebra may also be associated to such quivers and in this paper we study the generators of this algebra, known as cluster variables, for the quiver associated to the cone over the del Pezzo surface d P 3. In particular, mutation sequences involving mutations exclusively at vertices with two in-coming arrows and two out-going arrows are referred to as toric cascades in the string theory literature. Such toric cascades give rise to interesting discrete integrable systems on the level of cluster variable dynamics. We provide an explicit algebraic formula for all cluster variables that are reachable by toric cascades as well as a combinatorial interpretation involving perfect matchings of subgraphs of the d P 3 brane tiling for these formulas in most cases.

Carotenoid Biosynthetic Pathways Are Regulated by a Network of Multiple Cascades of Alternative Sigma Factors in Azospirillum brasilense Sp7.

PubMed

Rai, Ashutosh Kumar; Dubey, Ashutosh Prakash; Kumar, Santosh; Dutta, Debashis; Mishra, Mukti Nath; Singh, Bhupendra Narain; Tripathi, Anil Kumar

2016-11-01

Carotenoids constitute an important component of the defense system against photooxidative stress in bacteria. In Azospirillum brasilense Sp7, a nonphotosynthetic rhizobacterium, carotenoid synthesis is controlled by a pair of extracytoplasmic function sigma factors (RpoEs) and their cognate zinc-binding anti-sigma factors (ChrRs). Its genome harbors two copies of the gene encoding geranylgeranyl pyrophosphate synthase (CrtE), the first critical step in the carotenoid biosynthetic pathway in bacteria. Inactivation of each of two crtE paralogs found in A. brasilense caused reduction in carotenoid content, suggesting their involvement in carotenoid synthesis. However, the effect of crtE1 deletion was more pronounced than that of crtE2 deletion. Out of the five paralogs of rpoH in A. brasilense, overexpression of rpoH1 and rpoH2 enhanced carotenoid synthesis. Promoters of crtE2 and rpoH2 were found to be dependent on RpoH2 and RpoE1, respectively. Using a two-plasmid system in Escherichia coli, we have shown that the crtE2 gene of A. brasilense Sp7 is regulated by two cascades of sigma factors: one consisting of RpoE1and RpoH2 and the other consisting of RpoE2 and RpoH1. In addition, expression of crtE1 was upregulated indirectly by RpoE1 and RpoE2. This study shows, for the first time in any carotenoid-producing bacterium, that the regulation of carotenoid biosynthetic pathway involves a network of multiple cascades of alternative sigma factors. Carotenoids play a very important role in coping with photooxidative stress in prokaryotes and eukaryotes. Although extracytoplasmic function (ECF) sigma factors are known to directly regulate the expression of carotenoid biosynthetic genes in bacteria, regulation of carotenoid biosynthesis by one or multiple cascades of sigma factors had not been reported. This study provides the first evidence of the involvement of multiple cascades of sigma factors in the regulation of carotenoid synthesis in any bacterium by showing the regulation of a gene encoding geranylgeranyl pyrophosphate synthase (crtE2) by RpoE1→RpoH2→CrtE2 and RpoE2→RpoH1→CrtE2 cascades in A. brasilense It also provides an insight into existence of an additional cascade or cascades regulating expression of another paralog of crtE. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Carotenoid Biosynthetic Pathways Are Regulated by a Network of Multiple Cascades of Alternative Sigma Factors in Azospirillum brasilense Sp7

PubMed Central

Rai, Ashutosh Kumar; Dubey, Ashutosh Prakash; Kumar, Santosh; Dutta, Debashis; Mishra, Mukti Nath; Singh, Bhupendra Narain

2016-01-01

ABSTRACT Carotenoids constitute an important component of the defense system against photooxidative stress in bacteria. In Azospirillum brasilense Sp7, a nonphotosynthetic rhizobacterium, carotenoid synthesis is controlled by a pair of extracytoplasmic function sigma factors (RpoEs) and their cognate zinc-binding anti-sigma factors (ChrRs). Its genome harbors two copies of the gene encoding geranylgeranyl pyrophosphate synthase (CrtE), the first critical step in the carotenoid biosynthetic pathway in bacteria. Inactivation of each of two crtE paralogs found in A. brasilense caused reduction in carotenoid content, suggesting their involvement in carotenoid synthesis. However, the effect of crtE1 deletion was more pronounced than that of crtE2 deletion. Out of the five paralogs of rpoH in A. brasilense, overexpression of rpoH1 and rpoH2 enhanced carotenoid synthesis. Promoters of crtE2 and rpoH2 were found to be dependent on RpoH2 and RpoE1, respectively. Using a two-plasmid system in Escherichia coli, we have shown that the crtE2 gene of A. brasilense Sp7 is regulated by two cascades of sigma factors: one consisting of RpoE1and RpoH2 and the other consisting of RpoE2 and RpoH1. In addition, expression of crtE1 was upregulated indirectly by RpoE1 and RpoE2. This study shows, for the first time in any carotenoid-producing bacterium, that the regulation of carotenoid biosynthetic pathway involves a network of multiple cascades of alternative sigma factors. IMPORTANCE Carotenoids play a very important role in coping with photooxidative stress in prokaryotes and eukaryotes. Although extracytoplasmic function (ECF) sigma factors are known to directly regulate the expression of carotenoid biosynthetic genes in bacteria, regulation of carotenoid biosynthesis by one or multiple cascades of sigma factors had not been reported. This study provides the first evidence of the involvement of multiple cascades of sigma factors in the regulation of carotenoid synthesis in any bacterium by showing the regulation of a gene encoding geranylgeranyl pyrophosphate synthase (crtE2) by RpoE1→RpoH2→CrtE2 and RpoE2→RpoH1→CrtE2 cascades in A. brasilense. It also provides an insight into existence of an additional cascade or cascades regulating expression of another paralog of crtE. PMID:27551017

The Brassinosteroid Signaling Pathway—New Key Players and Interconnections with Other Signaling Networks Crucial for Plant Development and Stress Tolerance

PubMed Central

Gruszka, Damian

2013-01-01

Brassinosteroids (BRs) are a class of steroid hormones regulating a wide range of physiological processes during the plant life cycle from seed development to the modulation of flowering and senescence. The last decades, and recent years in particular, have witnessed a significant advance in the elucidation of the molecular mechanisms of BR signaling from perception by the transmembrane receptor complex to the regulation of transcription factors influencing expression of the target genes. Application of the new approaches shed light on the molecular functions of the key players regulating the BR signaling cascade and allowed identification of new factors. Recent studies clearly indicated that some of the components of BR signaling pathway act as multifunctional proteins involved in other signaling networks regulating diverse physiological processes, such as photomorphogenesis, cell death control, stomatal development, flowering, plant immunity to pathogens and metabolic responses to stress conditions, including salinity. Regulation of some of these processes is mediated through a crosstalk between BR signalosome and the signaling cascades of other hormones, including auxin, abscisic acid, ethylene and salicylic acid. Unravelling the complicated mechanisms of BR signaling and its interconnections with other molecular networks may be of great importance for future practical applications in agriculture. PMID:23615468

Developmental Processes in Peer Problems of Children with ADHD in the MTA Study1: Developmental Cascades and Vicious Cycles

PubMed Central

Murray-Close, Dianna; Hoza, Betsy; Hinshaw, Stephen P.; Arnold, L Eugene; Swanson, James; Jensen, Peter S.; Hechtman, Lily; Wells, Karen

2010-01-01

We examined the developmental processes involved in peer problems among children (M age = 10.41 years) previously diagnosed with ADHD at study entry (N = 536) and a comparison group (N = 284). Participants were followed over a 6-year period ranging from middle childhood to adolescence. At four assessment periods, measures of aggression, social skills, positive illusory biases (in the social and behavioral domains), and peer rejection were assessed. Results indicated that children from the ADHD group exhibited difficulties in each of these areas at the first assessment. Moreover, there were vicious cycles among problems over time. For example, peer rejection was related to impaired social skills, which in turn predicted later peer rejection. Problems also tended to “spill over” into other areas, which in turn compromised functioning in additional areas across development, leading to cascading effects over time. The findings held even when controlling for age and were similar for males and females, the ADHD and comparison groups, and among ADHD treatment groups. The results suggest that the peer problems among children with and without ADHD may reflect similar processes; however, children with ADHD exhibit greater difficulties negotiating important developmental tasks. Implications for interventions are discussed. PMID:20883582

Color vision predicts processing modes of goal activation during action cascading.

PubMed

Jongkees, Bryant J; Steenbergen, Laura; Colzato, Lorenza S

2017-09-01

One of the most important functions of cognitive control is action cascading: the ability to cope with multiple response options when confronted with various task goals. A recent study implicates a key role for dopamine (DA) in this process, suggesting higher D1 efficiency shifts the action cascading strategy toward a more serial processing mode, whereas higher D2 efficiency promotes a shift in the opposite direction by inducing a more parallel processing mode (Stock, Arning, Epplen, & Beste, 2014). Given that DA is found in high concentration in the retina and modulation of retinal DA release displays characteristics of D2-receptors (Peters, Schweibold, Przuntek, & Müller, 2000), color vision discrimination might serve as an index of D2 efficiency. We used color discrimination, assessed with the Lanthony Desaturated Panel D-15 test, to predict individual differences (N = 85) in a stop-change paradigm that provides a well-established measure of action cascading. In this task it is possible to calculate an individual slope value for each participant that estimates the degree of overlap in task goal activation. When the stopping process of a previous task goal has not finished at the time the change process toward a new task goal is initiated (parallel processing), the slope value becomes steeper. In case of less overlap (more serial processing), the slope value becomes flatter. As expected, participants showing better color vision were more prone to activate goals in a parallel manner as indicated by a steeper slope. Our findings suggest that color vision might represent a predictor of D2 efficiency and the predisposed processing mode of goal activation during action cascading. Copyright © 2017 Elsevier Ltd. All rights reserved.

Aerodynamic Design of Axial-flow Compressors. Volume 2

NASA Technical Reports Server (NTRS)

1956-01-01

Available experimental two-dimensional-cascade data for conventional compressor blade sections are correlated. The two-dimensional cascade and some of the principal aerodynamic factors involved in its operation are first briefly described. Then the data are analyzed by examining the variation of cascade performance at a reference incidence angle in the region of minimum loss. Variations of reference incidence angle, total-pressure loss, and deviation angle with cascade geometry, inlet Mach number, and Reynolds number are investigated. From the analysis and the correlations of the available data, rules and relations are evolved for the prediction of the magnitude of the reference total-pressure loss and the reference deviation and incidence angles for conventional blade profiles. These relations are developed in simplified forms readily applicable to compressor design procedures.

Feeling safe in the plane: neural mechanisms underlying superior action control in airplane pilot trainees--a combined EEG/MRS study.

PubMed

Yildiz, Ali; Quetscher, Clara; Dharmadhikari, Shalmali; Chmielewski, Witold; Glaubitz, Benjamin; Schmidt-Wilcke, Tobias; Edden, Richard; Dydak, Ulrike; Beste, Christian

2014-10-01

In day-to-day life, we need to apply strategies to cascade different actions for efficient unfolding of behavior. While deficits in action cascading are examined extensively, almost nothing is known about the neuronal mechanisms mediating superior performance above the normal level. To examine this question, we investigate action control in airplane pilot trainees. We use a stop-change paradigm that is able to estimate the efficiency of action cascading on the basis of mathematical constraints. Behavioral and EEG data is analyzed along these constraints and integrated with neurochemical data obtained using Magnetic Resonance Spectroscopy (MRS) from the striatal gamma-aminobutyric acid (GABA) -ergic system. We show that high performance in action cascading, as exemplified in airplane pilot trainees, can be driven by intensified attentional processes, circumventing response selection processes. The results indicate that the efficiency of action cascading and hence the speed of responding as well as attentional gating functions are modulated by striatal GABA and Glutamate + Glutamine concentrations. In superior performance in action cascading similar increases in the concentrations of GABA and Glutamate + Glutamine lead to stronger neurophysiological and behavioral effects as compared to subjects with normal performance in action cascading. Copyright © 2014 Wiley Periodicals, Inc.

A Memory-Based Programmable Logic Device Using Look-Up Table Cascade with Synchronous Static Random Access Memories

NASA Astrophysics Data System (ADS)

Nakamura, Kazuyuki; Sasao, Tsutomu; Matsuura, Munehiro; Tanaka, Katsumasa; Yoshizumi, Kenichi; Nakahara, Hiroki; Iguchi, Yukihiro

2006-04-01

A large-scale memory-technology-based programmable logic device (PLD) using a look-up table (LUT) cascade is developed in the 0.35-μm standard complementary metal oxide semiconductor (CMOS) logic process. Eight 64 K-bit synchronous SRAMs are connected to form an LUT cascade with a few additional circuits. The features of the LUT cascade include: 1) a flexible cascade connection structure, 2) multi phase pseudo asynchronous operations with synchronous static random access memory (SRAM) cores, and 3) LUT-bypass redundancy. This chip operates at 33 MHz in 8-LUT cascades at 122 mW. Benchmark results show that it achieves a comparable performance to field programmable gate array (FPGAs).

Cascading disaster models in postburn flash flood

Treesearch

Fred May

2007-01-01

A useful method of modeling threats from hazards and documenting their disaster causation sequences is called “cascading threat modeling.” This type of modeling enables emergency planners to address hazard and risk assessments systematically. This paper describes a cascading threat modeling and analysis process. Wildfire and an associated postburn flash flood disaster...

Dynamics of homogeneous shear turbulence: A key role of the nonlinear transverse cascade in the bypass concept.

PubMed

Mamatsashvili, G; Khujadze, G; Chagelishvili, G; Dong, S; Jiménez, J; Foysi, H

2016-08-01

To understand the mechanism of the self-sustenance of subcritical turbulence in spectrally stable (constant) shear flows, we performed direct numerical simulations of homogeneous shear turbulence for different aspect ratios of the flow domain with subsequent analysis of the dynamical processes in spectral or Fourier space. There are no exponentially growing modes in such flows and the turbulence is energetically supported only by the linear growth of Fourier harmonics of perturbations due to the shear flow non-normality. This non-normality-induced growth, also known as nonmodal growth, is anisotropic in spectral space, which, in turn, leads to anisotropy of nonlinear processes in this space. As a result, a transverse (angular) redistribution of harmonics in Fourier space is the main nonlinear process in these flows, rather than direct or inverse cascades. We refer to this type of nonlinear redistribution as the nonlinear transverse cascade. It is demonstrated that the turbulence is sustained by a subtle interplay between the linear nonmodal growth and the nonlinear transverse cascade. This course of events reliably exemplifies a well-known bypass scenario of subcritical turbulence in spectrally stable shear flows. These two basic processes mainly operate at large length scales, comparable to the domain size. Therefore, this central, small wave number area of Fourier space is crucial in the self-sustenance; we defined its size and labeled it as the vital area of turbulence. Outside the vital area, the nonmodal growth and the transverse cascade are of secondary importance: Fourier harmonics are transferred to dissipative scales by the nonlinear direct cascade. Although the cascades and the self-sustaining process of turbulence are qualitatively the same at different aspect ratios, the number of harmonics actively participating in this process (i.e., the harmonics whose energies grow more than 10% of the maximum spectral energy at least once during evolution) varies, but always remains quite large (equal to 36, 86, and 209) in the considered here three aspect ratios. This implies that the self-sustenance of subcritical turbulence cannot be described by low-order models.

Dynamics of homogeneous shear turbulence: A key role of the nonlinear transverse cascade in the bypass concept

NASA Astrophysics Data System (ADS)

Mamatsashvili, G.; Khujadze, G.; Chagelishvili, G.; Dong, S.; Jiménez, J.; Foysi, H.

2016-08-01

To understand the mechanism of the self-sustenance of subcritical turbulence in spectrally stable (constant) shear flows, we performed direct numerical simulations of homogeneous shear turbulence for different aspect ratios of the flow domain with subsequent analysis of the dynamical processes in spectral or Fourier space. There are no exponentially growing modes in such flows and the turbulence is energetically supported only by the linear growth of Fourier harmonics of perturbations due to the shear flow non-normality. This non-normality-induced growth, also known as nonmodal growth, is anisotropic in spectral space, which, in turn, leads to anisotropy of nonlinear processes in this space. As a result, a transverse (angular) redistribution of harmonics in Fourier space is the main nonlinear process in these flows, rather than direct or inverse cascades. We refer to this type of nonlinear redistribution as the nonlinear transverse cascade. It is demonstrated that the turbulence is sustained by a subtle interplay between the linear nonmodal growth and the nonlinear transverse cascade. This course of events reliably exemplifies a well-known bypass scenario of subcritical turbulence in spectrally stable shear flows. These two basic processes mainly operate at large length scales, comparable to the domain size. Therefore, this central, small wave number area of Fourier space is crucial in the self-sustenance; we defined its size and labeled it as the vital area of turbulence. Outside the vital area, the nonmodal growth and the transverse cascade are of secondary importance: Fourier harmonics are transferred to dissipative scales by the nonlinear direct cascade. Although the cascades and the self-sustaining process of turbulence are qualitatively the same at different aspect ratios, the number of harmonics actively participating in this process (i.e., the harmonics whose energies grow more than 10% of the maximum spectral energy at least once during evolution) varies, but always remains quite large (equal to 36, 86, and 209) in the considered here three aspect ratios. This implies that the self-sustenance of subcritical turbulence cannot be described by low-order models.

MassCascade: Visual Programming for LC-MS Data Processing in Metabolomics.

PubMed

Beisken, Stephan; Earll, Mark; Portwood, David; Seymour, Mark; Steinbeck, Christoph

2014-04-01

Liquid chromatography coupled to mass spectrometry (LC-MS) is commonly applied to investigate the small molecule complement of organisms. Several software tools are typically joined in custom pipelines to semi-automatically process and analyse the resulting data. General workflow environments like the Konstanz Information Miner (KNIME) offer the potential of an all-in-one solution to process LC-MS data by allowing easy integration of different tools and scripts. We describe MassCascade and its workflow plug-in for processing LC-MS data. The Java library integrates frequently used algorithms in a modular fashion, thus enabling it to serve as back-end for graphical front-ends. The functions available in MassCascade have been encapsulated in a plug-in for the workflow environment KNIME, allowing combined use with e.g. statistical workflow nodes from other providers and making the tool intuitive to use without knowledge of programming. The design of the software guarantees a high level of modularity where processing functions can be quickly replaced or concatenated. MassCascade is an open-source library for LC-MS data processing in metabolomics. It embraces the concept of visual programming through its KNIME plug-in, simplifying the process of building complex workflows. The library was validated using open data.

Network-Based Methods for Identifying Key Active Proteins in the Extracellular Electron Transfer Process in Shewanella oneidensis MR-1.

PubMed

Ding, Dewu; Sun, Xiao

2018-01-16

Shewanella oneidensis MR-1 can transfer electrons from the intracellular environment to the extracellular space of the cells to reduce the extracellular insoluble electron acceptors (Extracellular Electron Transfer, EET). Benefiting from this EET capability, Shewanella has been widely used in different areas, such as energy production, wastewater treatment, and bioremediation. Genome-wide proteomics data was used to determine the active proteins involved in activating the EET process. We identified 1012 proteins with decreased expression and 811 proteins with increased expression when the EET process changed from inactivation to activation. We then networked these proteins to construct the active protein networks, and identified the top 20 key active proteins by network centralization analysis, including metabolism- and energy-related proteins, signal and transcriptional regulatory proteins, translation-related proteins, and the EET-related proteins. We also constructed the integrated protein interaction and transcriptional regulatory networks for the active proteins, then found three exclusive active network motifs involved in activating the EET process-Bi-feedforward Loop, Regulatory Cascade with a Feedback, and Feedback with a Protein-Protein Interaction (PPI)-and identified the active proteins involved in these motifs. Both enrichment analysis and comparative analysis to the whole-genome data implicated the multiheme c -type cytochromes and multiple signal processing proteins involved in the process. Furthermore, the interactions of these motif-guided active proteins and the involved functional modules were discussed. Collectively, by using network-based methods, this work reported a proteome-wide search for the key active proteins that potentially activate the EET process.

Spatiotemporal distributions of pair production and cascade in solid targets irradiated by ultra-relativistic lasers with different polarizations

NASA Astrophysics Data System (ADS)

Yuan, T.; Yu, J. Y.; Liu, W. Y.; Weng, S. M.; Yuan, X. H.; Luo, W.; Chen, M.; Sheng, Z. M.; Zhang, J.

2018-06-01

Two-dimensional particle-in-cell simulations have been performed to study electron-positron pair production and cascade development in single ultra-relativistic laser interaction with solid targets. The spatiotemporal distributions of particles produced via QED processes are illustrated and their dependence on laser polarizations is investigated. The evolution of particle generation displays clear QED cascade characters. Studies show that although a circularly polarized laser delays the QED process due to the effective ion acceleration, it can reduce the target heating and confine high-energy charged particles, which leads to deeper QED cascade order and denser pair plasma production than linearly polarized lasers. These findings may benefit the understanding of the coming experimental studies of ultra-relativistic laser target interaction in the QED dominated regime.

Uterine Wound Healing: A Complex Process Mediated by Proteins and Peptides.

PubMed

Lofrumento, Dario D; Di Nardo, Maria A; De Falco, Marianna; Di Lieto, Andrea

2017-01-01

Wound healing is the process by which a complex cascade of biochemical events is responsible of the repair the damage. In vivo, studies in humans and mice suggest that healing and post-healing heterogeneous behavior of the surgically wounded myometrium is both phenotype and genotype dependent. Uterine wound healing process involves many cells: endothelial cells, neutrophils, monocytes/macrophages, lymphocytes, fibroblasts, myometrial cells as well a stem cell population found in the myometrium, myoSP (side population of myometrial cells). Transforming growth factor beta (TGF-β) isoforms, connective tissue growth factor (CTGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and tumor necrosis factor alpha (TNF-β) are involved in the wound healing mechanisms. The increased TGF- β1/β3 ratio reduces scarring and fibrosis. The CTGF altered expression may be a factor involved in the abnormal scars formation of low uterine segment after cesarean section and of the formation of uterine dehiscence. The lack of bFGF is involved in the reduction of collagen deposition in the wound site and thicker scabs. The altered expression of TNF-β, VEGF, and PDGF in human myometrial smooth muscle cells in case of uterine dehiscence, it is implicated in the uterine healing process. The over-and under-expressions of growth factors genes involved in uterine scarring process could represent patient's specific features, increasing the risk of cesarean scar complications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

HELIUM EFFECTS ON DISPLACEMENT CASCADE IN TUNGSTEN

DOE Office of Scientific and Technical Information (OSTI.GOV)

Setyawan, Wahyu; Nandipati, Giridhar; Roche, Kenneth J.

2013-09-30

Molecular dynamics (MD) simulations were performed to investigate He effects on displacement cascades in W. Helium content, proportion of interstitial and substitutional He and temperature were varied to reveal the various effects. The effect of interstitial He on the number of self-interstitial atoms (SIAs) produced during cascade damage appears to be insignificant. However, interstitial He tends to fill a vacancy (V). Nevertheless, this process is less favorable than SIA-V recombination particularly when excess SIAs are present before a cascade. The efficiency of He filling and SIA-V recombination increases as temperature increases due to increased point defect mobility. Likewise, substitutional Hemore » is more susceptible to displacement during a collision cascade than W. This susceptibility increases towards higher temperatures. Consequently, the number of surviving V is governed by the interplay between displaced substitutional He and SIA-V recombination. The temperature dependence of these processes results in a minimum number of V reached at an intermediate temperature.« less

Tunable signal processing in synthetic MAP kinase cascades.

PubMed

O'Shaughnessy, Ellen C; Palani, Santhosh; Collins, James J; Sarkar, Casim A

2011-01-07

The flexibility of MAPK cascade responses enables regulation of a vast array of cell fate decisions, but elucidating the mechanisms underlying this plasticity is difficult in endogenous signaling networks. We constructed insulated mammalian MAPK cascades in yeast to explore how intrinsic and extrinsic perturbations affect the flexibility of these synthetic signaling modules. Contrary to biphasic dependence on scaffold concentration, we observe monotonic decreases in signal strength as scaffold concentration increases. We find that augmenting the concentration of sequential kinases can enhance ultrasensitivity and lower the activation threshold. Further, integrating negative regulation and concentration variation can decouple ultrasensitivity and threshold from the strength of the response. Computational analyses show that cascading can generate ultrasensitivity and that natural cascades with different kinase concentrations are innately biased toward their distinct activation profiles. This work demonstrates that tunable signal processing is inherent to minimal MAPK modules and elucidates principles for rational design of synthetic signaling systems. Copyright © 2011 Elsevier Inc. All rights reserved.

Crystallization and preliminary crystallographic analysis of two Streptococcus agalactiae proteins: the family II inorganic pyrophosphatase and the serine/threonine phosphatase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rantanen, Mika K.; Lehtiö, Lari; Rajagopal, Lakshmi

Two S. agalactiae proteins, the inorganic pyrophosphatase and the serine/threonine phosphatase, were crystallized and diffraction data were collected and processed from these crystals. The data from the two protein crystals extended to 2.80 and 2.65 Å, respectively. Streptococcus agalactiae, which infects human neonates and causes sepsis and meningitis, has recently been shown to possess a eukaryotic-like serine/threonine protein phosphorylation signalling cascade. Through their target proteins, the S. agalactiae Ser/Thr kinase and Ser/Thr phosphatase together control the growth as well as the morphology and virulence of this organism. One of the targets is the S. agalactiae family II inorganic pyrophosphatase. Themore » inorganic pyrophosphatase and the serine/threonine phosphatase have therefore been purified and crystallized and diffraction data have been collected from their crystals. The data were processed using XDS. The inorganic pyrosphosphatase crystals diffracted to 2.80 Å and the Ser/Thr phosphatase crystals to 2.65 Å. Initial structure-solution experiments indicate that structure solution will be successful in both cases. Solving the structure of the proteins involved in this cascade is the first step towards understanding this phenomenon in atomic detail.« less

Some conservation issues for the dynamical cores of NWP and climate models

NASA Astrophysics Data System (ADS)

Thuburn, J.

2008-03-01

The rationale for designing atmospheric numerical model dynamical cores with certain conservation properties is reviewed. The conceptual difficulties associated with the multiscale nature of realistic atmospheric flow, and its lack of time-reversibility, are highlighted. A distinction is made between robust invariants, which are conserved or nearly conserved in the adiabatic and frictionless limit, and non-robust invariants, which are not conserved in the limit even though they are conserved by exactly adiabatic frictionless flow. For non-robust invariants, a further distinction is made between processes that directly transfer some quantity from large to small scales, and processes involving a cascade through a continuous range of scales; such cascades may either be explicitly parameterized, or handled implicitly by the dynamical core numerics, accepting the implied non-conservation. An attempt is made to estimate the relative importance of different conservation laws. It is argued that satisfactory model performance requires spurious sources of a conservable quantity to be much smaller than any true physical sources; for several conservable quantities the magnitudes of the physical sources are estimated in order to provide benchmarks against which any spurious sources may be measured.

A hybrid-system model of the coagulation cascade: simulation, sensitivity, and validation.

PubMed

Makin, Joseph G; Narayanan, Srini

2013-10-01

The process of human blood clotting involves a complex interaction of continuous-time/continuous-state processes and discrete-event/discrete-state phenomena, where the former comprise the various chemical rate equations and the latter comprise both threshold-limited behaviors and binary states (presence/absence of a chemical). Whereas previous blood-clotting models used only continuous dynamics and perforce addressed only portions of the coagulation cascade, we capture both continuous and discrete aspects by modeling it as a hybrid dynamical system. The model was implemented as a hybrid Petri net, a graphical modeling language that extends ordinary Petri nets to cover continuous quantities and continuous-time flows. The primary focus is simulation: (1) fidelity to the clinical data in terms of clotting-factor concentrations and elapsed time; (2) reproduction of known clotting pathologies; and (3) fine-grained predictions which may be used to refine clinical understanding of blood clotting. Next we examine sensitivity to rate-constant perturbation. Finally, we propose a method for titrating between reliance on the model and on prior clinical knowledge. For simplicity, we confine these last two analyses to a critical purely-continuous subsystem of the model.

Nitric oxide signalling via cytoskeleton in plants.

PubMed

Yemets, Alla I; Krasylenko, Yuliya A; Lytvyn, Dmytro I; Sheremet, Yarina A; Blume, Yaroslav B

2011-11-01

Nitric oxide (NO) in plant cell mediates processes of growth and development starting from seed germination to pollination, as well as biotic and abiotic stress tolerance. However, proper understanding of the molecular mechanisms of NO signalling in plants has just begun to emerge. Accumulated evidence suggests that in eukaryotic cells NO regulates functions of proteins by their post-translational modifications, namely tyrosine nitration and S-nitrosylation. Among the candidates for NO-downstream effectors are cytoskeletal proteins because of their involvement in many processes regulated by NO. This review discusses new insights in plant NO signalling focused mainly on the involvement of cytoskeleton components into NO-cascades. Herein, examples of NO-related post-translational modifications of cytoskeletal proteins, and also indirect NO impact, are discussed. Special attention is paid to plant α-tubulin tyrosine nitration as an emerging topic in plant NO research. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Traversing the folding pathway of proteins using temperature-aided cascade molecular dynamics with conformation-dependent charges.

PubMed

Jani, Vinod; Sonavane, Uddhavesh; Joshi, Rajendra

2016-07-01

Protein folding is a multi-micro second time scale event and involves many conformational transitions. Crucial conformational transitions responsible for biological functions of biomolecules are difficult to capture using current state-of-the-art molecular dynamics (MD) simulations. Protein folding, being a stochastic process, witnesses these transitions as rare events. Many new methodologies have been proposed for observing these rare events. In this work, a temperature-aided cascade MD is proposed as a technique for studying the conformational transitions. Folding studies for Engrailed homeodomain and Immunoglobulin domain B of protein A have been carried out. Using this methodology, the unfolded structures with RMSD of 20 Å were folded to a structure with RMSD of 2 Å. Three sets of cascade MD runs were carried out using implicit solvation, explicit solvation, and charge updation scheme. In the charge updation scheme, charges based on the conformation obtained are calculated and are updated in the topology file. In all the simulations, the structure of 2 Å was reached within a few nanoseconds using these methods. Umbrella sampling has been performed using snapshots from the temperature-aided cascade MD simulation trajectory to build an entire conformational transition pathway. The advantage of the method is that the possible pathways for a particular reaction can be explored within a short duration of simulation time and the disadvantage is that the knowledge of the start and end state is required. The charge updation scheme adds the polarization effects in the force fields. This improves the electrostatic interaction among the atoms, which may help the protein to fold faster.

Spectral enstrophy budget in a shear-less flow with turbulent/non-turbulent interface

NASA Astrophysics Data System (ADS)

Cimarelli, Andrea; Cocconi, Giacomo; Frohnapfel, Bettina; De Angelis, Elisabetta

2015-12-01

A numerical analysis of the interaction between decaying shear free turbulence and quiescent fluid is performed by means of global statistical budgets of enstrophy, both, at the single-point and two point levels. The single-point enstrophy budget allows us to recognize three physically relevant layers: a bulk turbulent region, an inhomogeneous turbulent layer, and an interfacial layer. Within these layers, enstrophy is produced, transferred, and finally destroyed while leading to a propagation of the turbulent front. These processes do not only depend on the position in the flow field but are also strongly scale dependent. In order to tackle this multi-dimensional behaviour of enstrophy in the space of scales and in physical space, we analyse the spectral enstrophy budget equation. The picture consists of an inviscid spatial cascade of enstrophy from large to small scales parallel to the interface moving towards the interface. At the interface, this phenomenon breaks, leaving place to an anisotropic cascade where large scale structures exhibit only a cascade process normal to the interface thus reducing their thickness while retaining their lengths parallel to the interface. The observed behaviour could be relevant for both the theoretical and the modelling approaches to flow with interacting turbulent/nonturbulent regions. The scale properties of the turbulent propagation mechanisms highlight that the inviscid turbulent transport is a large-scale phenomenon. On the contrary, the viscous diffusion, commonly associated with small scale mechanisms, highlights a much richer physics involving small lengths, normal to the interface, but at the same time large scales, parallel to the interface.

Conveying endogenous and exogenous signals: MAPK cascades in plant growth and defense.

PubMed

Zhang, Mengmeng; Su, Jianbin; Zhang, Yan; Xu, Juan; Zhang, Shuqun

2018-05-09

Mitogen-activated protein kinase (MAPK) cascades are key signaling modules downstream of receptors/sensors that perceive endogenous and exogenous stimuli such as hormones, peptide ligands, and pathogen-derived patterns/effectors. In this review, we summarize recent advances in the establishment of MAPK cascades as unified signaling modules downstream of receptor-like kinases (RLKs) and receptor-like proteins (RLPs) in plant growth and defense, the identification of components connecting the RLK/RLP receptor complexes to the MAPK cascades, and the interactions between MAPK and hormone signaling pathways. We also propose a set of criteria for defining the physiological substrates of plant MAPKs. With only a limited number of MAPK components, multiple functional pathways often share the same MAPK cascade. As a result, understanding the signaling specificity, which requires detailed information about the spatiotemporal expression of the components involved, their complex formation, and the consequence of substrate phosphorylation, is central to our study of MAPK functions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Wastewater reuse in a cascade based system of a petrochemical industry for the replacement of losses in cooling towers.

PubMed

Hansen, Everton; Rodrigues, Marco Antônio Siqueira; Aquim, Patrice Monteiro de

2016-10-01

This article discusses the mapping of opportunities for the water reuse in a cascade based system in a petrochemical industry in southern Brazil. This industrial sector has a large demand for water for its operation. In the studied industry, for example, approximately 24 million cubic meters of water were collected directly from the source in 2014. The objective of this study was to evaluate the implementation of the reuse of water in cascade in a petrochemical industry, focusing on the reuse of aqueous streams to replenish losses in the cooling towers. This is an industrial scale case study with real data collected during the years 2014 and 2015. Water reuse was performed using heuristic approach based on the exploitation of knowledge acquired during the search process. The methodology of work consisted of the construction of a process map identifying the stages of production and water consumption, as well as the characterization of the aqueous streams involved in the process. For the application of the industrial water reuse as cooling water, mass balances were carried out considering the maximum concentration levels of turbidity, pH, conductivity, alkalinity, calcium hardness, chlorides, sulfates, silica, chemical oxygen demand and suspended solids as parameters turbidity, pH, conductivity, alkalinity, calcium hardness, chlorides, sulfates, silica, chemical oxygen demand and suspended solids as parameters. The adopted guideline was the fulfillment of the water quality criteria for each application in the industrial process. The study showed the feasibility for the reuse of internal streams as makeup water in cooling towers, and the implementation of the reuse presented in this paper totaled savings of 385,440 m(3)/year of water, which means a sufficient volume to supply 6350 inhabitants for a period of one year, considering the average water consumption per capita in Brazil; in addition to 201,480 m(3)/year of wastewater that would no longer be generated. Copyright © 2016 Elsevier Ltd. All rights reserved.

Viroid Pathogenicity: One Process, Many Faces

PubMed Central

Owens, Robert A.; Hammond, Rosemarie W.

2009-01-01

Despite the non-coding nature of their small RNA genomes, the visible symptoms of viroid infection resemble those associated with many plant virus diseases. Recent evidence indicates that viroid-derived small RNAs acting through host RNA silencing pathways play a key role in viroid pathogenicity. Host responses to viroid infection are complex, involving signaling cascades containing host-encoded protein kinases and crosstalk between hormonal and defense-signaling pathways. Studies of viroid-host interaction in the context of entire biochemical or developmental pathways are just beginning, and many working hypotheses have yet to be critically tested. PMID:21994551

Some aspects of radical cascade and relay reactions

PubMed Central

Quiclet-Sire, Béatrice; Zard, Samir Z.

2017-01-01

The ability to create carbon–carbon bonds is at the heart of organic synthesis. Radical processes are particularly apt at creating such bonds, especially in cascade or relay sequences where more than one bond is formed, allowing for a rapid assembly of complex structures. In the present brief overview, examples taken from the authors' laboratory will serve to illustrate the strategic impact of radical-based approaches on synthetic planning. Transformations involving nitrogen-centred radicals, electron transfer from metallic nickel and the reversible degenerative exchange of xanthates will be presented and discussed. The last method has proved to be a particularly powerful tool for the intermolecular creation of carbon–carbon bonds by radical additions even to unactivated alkenes. Various functional groups can be brought into the same molecule in a convergent manner and made to react together in order to further increase the structural complexity. One important benefit of this chemistry is the so-called RAFT/MADIX technology for the manufacture of block copolymers of almost any desired architecture. PMID:28484329

Influence maximization in social networks under an independent cascade-based model

NASA Astrophysics Data System (ADS)

Wang, Qiyao; Jin, Yuehui; Lin, Zhen; Cheng, Shiduan; Yang, Tan

2016-02-01

The rapid growth of online social networks is important for viral marketing. Influence maximization refers to the process of finding influential users who make the most of information or product adoption. An independent cascade-based model for influence maximization, called IMIC-OC, was proposed to calculate positive influence. We assumed that influential users spread positive opinions. At the beginning, users held positive or negative opinions as their initial opinions. When more users became involved in the discussions, users balanced their own opinions and those of their neighbors. The number of users who did not change positive opinions was used to determine positive influence. Corresponding influential users who had maximum positive influence were then obtained. Experiments were conducted on three real networks, namely, Facebook, HEP-PH and Epinions, to calculate maximum positive influence based on the IMIC-OC model and two other baseline methods. The proposed model resulted in larger positive influence, thus indicating better performance compared with the baseline methods.

Fast perceptual image hash based on cascade algorithm

NASA Astrophysics Data System (ADS)

Ruchay, Alexey; Kober, Vitaly; Yavtushenko, Evgeniya

2017-09-01

In this paper, we propose a perceptual image hash algorithm based on cascade algorithm, which can be applied in image authentication, retrieval, and indexing. Image perceptual hash uses for image retrieval in sense of human perception against distortions caused by compression, noise, common signal processing and geometrical modifications. The main disadvantage of perceptual hash is high time expenses. In the proposed cascade algorithm of image retrieval initializes with short hashes, and then a full hash is applied to the processed results. Computer simulation results show that the proposed hash algorithm yields a good performance in terms of robustness, discriminability, and time expenses.

Synergistic Diazo-OH Insertion/Conia-Ene Cascade Catalysis for the Stereoselective Synthesis of γ-Butyrolactones and Tetrahydrofurans.

PubMed

Hunter, Arianne C; Schlitzer, Steven C; Sharma, Indrajeet

2016-11-02

A novel and highly efficient diazo-OH insertion/Conia-ene cascade reaction of readily available homopropargylic acids and alcohols with diazo carbonyl compounds is described. The cascade reaction involves a synergistic Rh/Ag/Au catalyst cocktail and proceeds instantly with a variety of substituted diazo compounds and acids/alcohols to provide functionalized γ-butyrolactones and tetrahydrofurans with complete regio- and stereoselectivity. The unprecedented rate-enhancement, complete stereoselectivity, and the enabling of new Conia-ene cyclizations suggest a concerted [4+1]-cycloaddition reaction pathway under synergistic (Rh/Ag/Au)-catalysis conditions. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Three-photon states in nonlinear crystal superlattices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Antonosyan, D. A.; Kryuchkyan, G. Yu.; Institute for Physical Researches, National Academy of Sciences Ashtarak-2, 0203 Ashtarak

2011-04-15

It has been a longstanding goal in quantum optics to realize controllable sources generating joint multiphoton states, particularly photon triplet with arbitrary spectral characteristics. We demonstrate that such sources can be realized via cascaded parametric down-conversion (PDC) in superlattice structures of nonlinear and linear segments. We consider a scheme that involves two parametric processes--{omega}{sub 0{yields}{omega}1}+{omega}{sub 2}, {omega}{sub 2{yields}{omega}1}+{omega}{sub 1} under pulsed pump--and investigate the spontaneous creation of a photon triplet as well as the generation of high-intensity mode in intracavity three-photon splitting. We show the preparation of Greenberger-Horne-Zeilinger polarization-entangled states in cascaded type-II and type-I PDC in the framework ofmore » considering the dual-grid structure that involves two periodically poled crystals. We demonstrate the method of compensation of the dispersive effects in nonlinear segments by appropriately chosen linear dispersive segments of superlattice for preparation of the heralded joint states of two polarized photons. In the case of intracavity three-photon splitting, we concentrate on the investigation of photon-number distributions, third-order photon-number correlation function, as well as the Wigner functions. These quantities are observed both for short interaction time intervals and the over-transient regime, when dissipative effects are essential.« less

Phosphorylation of paxillin via the ERK mitogen-activated protein kinase cascade in EL4 thymoma cells.

PubMed

Ku, H; Meier, K E

2000-04-14

Intracellular signals can regulate cell adhesion via several mechanisms in a process referred to as "inside-out" signaling. In phorbol ester-sensitive EL4 thymoma cells, phorbol-12-myristate 13-acetate (PMA) induces activation of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases and promotes cell adhesion. In this study, clonal EL4 cell lines with varying abilities to activate ERKs in response to PMA were used to examine signaling events occurring downstream of ERK activation. Paxillin, a multifunctional docking protein involved in cell adhesion, was phosphorylated on serine/threonine residues in response to PMA treatment. This response was correlated with the extent and time course of ERK activation. PMA-induced phosphorylation of paxillin was inhibited by compounds that block the ERK activation pathway in EL4 cells, primary murine thymocytes, and primary murine splenocytes. Paxillin was phosphorylated in vitro by purified active ERK2. Two-dimensional electrophoresis revealed that PMA treatment generated a complex pattern of phosphorylated paxillin species in intact cells, some of which were generated by ERK-mediated phosphorylation in vitro. An ERK pathway inhibitor interfered with PMA-induced adhesion of sensitive EL4 cells to substrate. These findings describe a novel inside-out signaling pathway by which the ERK cascade may regulate events involved in adhesion.

Structural and Functional Characterization of an Archaeal Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated Complex for Antiviral Defense (CASCADE)*

PubMed Central

Lintner, Nathanael G.; Kerou, Melina; Brumfield, Susan K.; Graham, Shirley; Liu, Huanting; Naismith, James H.; Sdano, Matthew; Peng, Nan; She, Qunxin; Copié, Valérie; Young, Mark J.; White, Malcolm F.; Lawrence, C. Martin

2011-01-01

In response to viral infection, many prokaryotes incorporate fragments of virus-derived DNA into loci called clustered regularly interspaced short palindromic repeats (CRISPRs). The loci are then transcribed, and the processed CRISPR transcripts are used to target invading viral DNA and RNA. The Escherichia coli “CRISPR-associated complex for antiviral defense” (CASCADE) is central in targeting invading DNA. Here we report the structural and functional characterization of an archaeal CASCADE (aCASCADE) from Sulfolobus solfataricus. Tagged Csa2 (Cas7) expressed in S. solfataricus co-purifies with Cas5a-, Cas6-, Csa5-, and Cas6-processed CRISPR-RNA (crRNA). Csa2, the dominant protein in aCASCADE, forms a stable complex with Cas5a. Transmission electron microscopy reveals a helical complex of variable length, perhaps due to substoichiometric amounts of other CASCADE components. A recombinant Csa2-Cas5a complex is sufficient to bind crRNA and complementary ssDNA. The structure of Csa2 reveals a crescent-shaped structure unexpectedly composed of a modified RNA-recognition motif and two additional domains present as insertions in the RNA-recognition motif. Conserved residues indicate potential crRNA- and target DNA-binding sites, and the H160A variant shows significantly reduced affinity for crRNA. We propose a general subunit architecture for CASCADE in other bacteria and Archaea. PMID:21507944

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoller, Roger E; Nordlund, Kai; Melerba, L

The processes that give rise to changes in the microstructure and the physical and mechanical properties of materials exposed to energetic particles are initiated by essentially elastic collisions between atoms in what has been called an atomic displacement cascade. The formation and evolution of this primary radiation damage mechanism are described to provide an overview of how stable defects are formed by displacement cascades, as well as the nature and morphology of the defects themselves. The impact of the primary variables cascade energy and irradiation temperature are discussed, along with a range of secondary factors that can influence damage formation.Radiation-inducedmore » changes in microstructure and mechanical properties in structural materials are the result of a complex set of physical processes initiated by the collision between an energetic particle (neutron or ion) and an atom in the lattice. This primary damage event is called an atomic displacement cascade. The simplest description of a displacement cascade is to view it as a series of many billiard-ball-like elastic collisions among the atoms in the material. This chapter describes the formation and evolution of this primary radiation damage mechanism to provide an overview of how stable defects are formed by displacement cascades, as well as the nature and morphology of the defects themselves. The impact of the relevant variables such as cascade energy and irradiation temperature is discussed, and defect formation in different materials is compared.« less

Structural and functional characterization of an archaeal clustered regularly interspaced short palindromic repeat (CRISPR)-associated complex for antiviral defense (CASCADE).

PubMed

Lintner, Nathanael G; Kerou, Melina; Brumfield, Susan K; Graham, Shirley; Liu, Huanting; Naismith, James H; Sdano, Matthew; Peng, Nan; She, Qunxin; Copié, Valérie; Young, Mark J; White, Malcolm F; Lawrence, C Martin

2011-06-17

In response to viral infection, many prokaryotes incorporate fragments of virus-derived DNA into loci called clustered regularly interspaced short palindromic repeats (CRISPRs). The loci are then transcribed, and the processed CRISPR transcripts are used to target invading viral DNA and RNA. The Escherichia coli "CRISPR-associated complex for antiviral defense" (CASCADE) is central in targeting invading DNA. Here we report the structural and functional characterization of an archaeal CASCADE (aCASCADE) from Sulfolobus solfataricus. Tagged Csa2 (Cas7) expressed in S. solfataricus co-purifies with Cas5a-, Cas6-, Csa5-, and Cas6-processed CRISPR-RNA (crRNA). Csa2, the dominant protein in aCASCADE, forms a stable complex with Cas5a. Transmission electron microscopy reveals a helical complex of variable length, perhaps due to substoichiometric amounts of other CASCADE components. A recombinant Csa2-Cas5a complex is sufficient to bind crRNA and complementary ssDNA. The structure of Csa2 reveals a crescent-shaped structure unexpectedly composed of a modified RNA-recognition motif and two additional domains present as insertions in the RNA-recognition motif. Conserved residues indicate potential crRNA- and target DNA-binding sites, and the H160A variant shows significantly reduced affinity for crRNA. We propose a general subunit architecture for CASCADE in other bacteria and Archaea.

Nitric oxide contributes to high-salt perception in a blood-sucking insect model.

PubMed

Cano, Agustina; Pontes, Gina; Sfara, Valeria; Anfossi, Diego; Barrozo, Romina B

2017-11-14

In all organisms, salts produce either appetitive or aversive responses depending on the concentration. While low-salt concentration in food elicits positive responses to ingest, high-salt triggers aversion. Still the mechanisms involved in this dual behavior have just started to be uncovered in some organisms. In Rhodnius prolixus, using pharmacological and behavioral assays, we demonstrated that upon high-salt detection in food a nitric oxide (NO) dependent cascade is activated. This activation involves a soluble guanylate cyclase (sGC) and the production of cyclic guanosine monophosphate (cGMP). Thus, appetitive responses to low-salt diets turn to aversion whenever this cascade is activated. Conversely, insects feed over aversive high-salt solutions when it is blocked by reducing NO levels or by affecting the sGC activity. The activation of NO/sGC/cGMP cascade commands the avoidance feeding behavior in R. prolixus. Investigations in other insect species should examine the possibility that high-salt aversion is mediated by NO/sSG/cGMP signaling.

Mitogen-activated protein kinase kinase 5 (MKK5)-mediated signalling cascade regulates expression of iron superoxide dismutase gene in Arabidopsis under salinity stress

PubMed Central

Xing, Yu; Chen, Wei-hua; Jia, Wensuo; Zhang, Jianhua

2015-01-01

Superoxide dismutases (SODs) are involved in plant adaptive responses to biotic and abiotic stresses but the upstream signalling process that modulates their expression is not clear. Expression of two iron SODs, FSD2 and FSD3, was significantly increased in Arabidopsis in response to NaCl treatment but blocked in transgenic MKK5-RNAi plant, mkk5. Using an assay system for transient expression in protoplasts, it was found that mitogen-activated protein kinase kinase 5 (MKK5) was also activated in response to salt stress. Overexpression of MKK5 in wild-type plants enhanced their tolerance to salt treatments, while mkk5 mutant exhibited hypersensitivity to salt stress in germination on salt-containing media. Moreover, another kinase, MPK6, was also involved in the MKK5-mediated iron superoxide dismutase (FSD) signalling pathway in salt stress. The kinase activity of MPK6 was totally turned off in mkk5, whereas the activity of MPK3 was only partially blocked. MKK5 interacted with the MEKK1 protein that was also involved in the salt-induced FSD signalling pathway. These data suggest that salt-induced FSD2 and FSD3 expressions are influenced by MEKK1 via MKK5–MPK6-coupled signalling. This MAP kinase cascade (MEKK1, MKK5, and MPK6) mediates the salt-induced expression of iron superoxide dismutases. PMID:26136265

The ethylene response pathway in Arabidopsis

NASA Technical Reports Server (NTRS)

Kieber, J. J.; Evans, M. L. (Principal Investigator)

1997-01-01

The simple gas ethylene influences a diverse array of plant growth and developmental processes including germination, senescence, cell elongation, and fruit ripening. This review focuses on recent molecular genetic studies, principally in Arabidopsis, in which components of the ethylene response pathway have been identified. The isolation and characterization of two of these genes has revealed that ethylene sensing involves a protein kinase cascade. One of these genes encodes a protein with similarity to the ubiquitous Raf family of Ser/Thr protein kinases. A second gene shows similarity to the prokaryotic two-component histidine kinases and most likely encodes an ethylene receptor. Additional elements involved in ethylene signaling have only been identified genetically. The characterization of these genes and mutants will be discussed.

Cascading events in linked ecological and socioeconomic systems

USGS Publications Warehouse

Peters, Debra P.C.; Sala, O.E.; Allen, Craig D.; Covich, A.; Brunson, M.

2007-01-01

Cascading events that start at small spatial scales and propagate non-linearly through time to influence larger areas often have major impacts on ecosystem goods and services. Events such as wildfires and hurricanes are increasing in frequency and magnitude as systems become more connected through globalization processes. We need to improve our understanding of these events in order to predict their occurrence, minimize potential impacts, and allow for strategic recovery. Here, we synthesize information about cascading events in systems located throughout the Americas. We discuss a variety of examples of cascading events that share a common feature: they are often driven by linked ecological and human processes across scales. In this era of globalization, we recommend studies that explicitly examine connections across scales and examine the role of connectivity among non-contiguous as well as contiguous areas.

Nonword Reading: Comparing Dual-Route Cascaded and Connectionist Dual-Process Models with Human Data

ERIC Educational Resources Information Center

Pritchard, Stephen C.; Coltheart, Max; Palethorpe, Sallyanne; Castles, Anne

2012-01-01

Two prominent dual-route computational models of reading aloud are the dual-route cascaded (DRC) model, and the connectionist dual-process plus (CDP+) model. While sharing similarly designed lexical routes, the two models differ greatly in their respective nonlexical route architecture, such that they often differ on nonword pronunciation. Neither…

Cascaded Optimization for a Persistent Data Ferrying Unmanned Aircraft

NASA Astrophysics Data System (ADS)

Carfang, Anthony

This dissertation develops and assesses a cascaded method for designing optimal periodic trajectories and link schedules for an unmanned aircraft to ferry data between stationary ground nodes. This results in a fast solution method without the need to artificially constrain system dynamics. Focusing on a fundamental ferrying problem that involves one source and one destination, but includes complex vehicle and Radio-Frequency (RF) dynamics, a cascaded structure to the system dynamics is uncovered. This structure is exploited by reformulating the nonlinear optimization problem into one that reduces the independent control to the vehicle's motion, while the link scheduling control is folded into the objective function and implemented as an optimal policy that depends on candidate motion control. This formulation is proven to maintain optimality while reducing computation time in comparison to traditional ferry optimization methods. The discrete link scheduling problem takes the form of a combinatorial optimization problem that is known to be NP-Hard. A derived necessary condition for optimality guides the development of several heuristic algorithms, specifically the Most-Data-First Algorithm and the Knapsack Adaptation. These heuristics are extended to larger ferrying scenarios, and assessed analytically and through Monte Carlo simulation, showing better throughput performance in the same order of magnitude of computation time in comparison to other common link scheduling policies. The cascaded optimization method is implemented with a novel embedded software system on a small, unmanned aircraft to validate the simulation results with field experiments. To address the sensitivity of results on trajectory tracking performance, a system that combines motion and link control with waypoint-based navigation is developed and assessed through field experiments. The data ferrying algorithms are further extended by incorporating a Gaussian process to opportunistically learn the RF environment. By continuously improving RF models, the cascaded planner can continually improve the ferrying system's overall performance.

Cardiotonic steroids trigger non-classical testosterone signaling in Sertoli cells via the α4 isoform of the sodium pump.

PubMed

Konrad, Lutz; Dietze, Raimund; Kirch, Ulrike; Kirch, Herbert; Eva, Alexander; Scheiner-Bobis, Georgios

2011-12-01

The α4 isoform of the Na(+),K(+)-ATPase (sodium pump) is known to be expressed in spermatozoa and to be critical for their motility. In the investigation presented here, we find that the rat-derived Sertoli cell line 93RS2 also expresses considerable amounts of the α4 isoform in addition to the α1 isoform. Since Sertoli cells are not motile, one can assume that the function of the α4 isoform in these cells must differ from that in spermatozoa. Thus, we assessed a potential involvement of this isoform in signaling pathways that are activated by the cardiotonic steroid (CTS) ouabain, a highly specific sodium pump ligand. Treatment of 93RS2 cells with ouabain leads to activation of the c-Src/c-Raf/Erk1/2 signaling cascade. Furthermore, we show for the first time that the activation of this cascade by ouabain results in phosphorylation and activation of the transcription factor CREB. This signaling cascade is induced at low nanomolar concentrations of ouabain, consistent with the involvement of the α4 isoform. This is further supported by experiments involving siRNA: silencing of α4 expression entirely blocks ouabain-induced activation of Erk1/2 whereas silencing of α1 has no effect. The findings of this study unveil new aspects in CTS/sodium pump interactions by demonstrating for the first time ouabain-induced signaling through the α4 isoform. The c-Src/c-Raf/Erk1/2/CREB cascade activated by ouabain is identical to the so-called non-classical signaling cascade that is normally triggered in Sertoli cells by testosterone. Taking into consideration that CTS are produced endogenously, our results may help to gain new insights into the physiological mechanisms associated with male fertility and reproduction. Copyright © 2011 Elsevier B.V. All rights reserved.

Mitogen-Activated Protein Kinase Cascade MKK7-MPK6 Plays Important Roles in Plant Development and Regulates Shoot Branching by Phosphorylating PIN1 in Arabidopsis

PubMed Central

Liang, Yan; Wu, Xiaowei; Cai, Yueyue; Zhang, Yuanya; Wang, Yingchun; Li, Jiayang; Wang, Yonghong

2016-01-01

Emerging evidences exhibit that mitogen-activated protein kinase (MAPK/MPK) signaling pathways are connected with many aspects of plant development. The complexity of MAPK cascades raises challenges not only to identify the MAPK module in planta but also to define the specific role of an individual module. So far, our knowledge of MAPK signaling has been largely restricted to a small subset of MAPK cascades. Our previous study has characterized an Arabidopsis bushy and dwarf1 (bud1) mutant, in which the MAP Kinase Kinase 7 (MKK7) was constitutively activated, resulting in multiple phenotypic alterations. In this study, we found that MPK3 and MPK6 are the substrates for phosphorylation by MKK7 in planta. Genetic analysis showed that MKK7-MPK6 cascade is specifically responsible for the regulation of shoot branching, hypocotyl gravitropism, filament elongation, and lateral root formation, while MKK7-MPK3 cascade is mainly involved in leaf morphology. We further demonstrated that the MKK7-MPK6 cascade controls shoot branching by phosphorylating Ser 337 on PIN1, which affects the basal localization of PIN1 in xylem parenchyma cells and polar auxin transport in the primary stem. Our results not only specify the functions of the MKK7-MPK6 cascade but also reveal a novel mechanism for PIN1 phosphorylation, establishing a molecular link between the MAPK cascade and auxin-regulated plant development. PMID:27618482

Optical Wave Turbulence and Wave Condensation in a Nonlinear Optical Experiment

NASA Astrophysics Data System (ADS)

Laurie, Jason; Bortolozzo, Umberto; Nazarenko, Sergey; Residori, Stefania

We present theory, numerical simulations and experimental observations of a 1D optical wave system. We show that this system is of a dual cascade type, namely, the energy cascading directly to small scales, and the photons or wave action cascading to large scales. In the optical context the inverse cascade is particularly interesting because it means the condensation of photons. We show that the cascades are induced by a six-wave resonant interaction process described by weak turbulence theory. We show that by starting with weakly nonlinear randomized waves as an initial condition, there exists an inverse cascade of photons towards the lowest wavenumbers. During the cascade nonlinearity becomes strong at low wavenumbers and, due to the focusing nature of the nonlinearity, it leads to modulational instability resulting in the formation of solitons. Further interaction of the solitons among themselves and with incoherent waves leads to the final condensate state dominated by a single strong soliton. In addition, we show the existence of the direct energy cascade numerically and that it agrees with the wave turbulence prediction.

Modern collagen wound dressings: function and purpose.

PubMed

Fleck, Cynthia Ann; Simman, Richard

2010-09-01

Collagen, which is produced by fibroblasts, is the most abundant protein in the human body. A natural structural protein, collagen is involved in all 3 phases of the wound-healing cascade. It stimulates cellular migration and contributes to new tissue development. Because of their chemotactic properties on wound fibroblasts, collagen dressings encourage the deposition and organization of newly formed collagen, creating an environment that fosters healing. Collagen-based biomaterials stimulate and recruit specific cells, such as macrophages and fibroblasts, along the healing cascade to enhance and influence wound healing. These biomaterials can provide moisture or absorption, depending on the delivery system. Collagen dressings are easy to apply and remove and are conformable. Collagen dressings are usually formulated with bovine, avian, or porcine collagen. Oxidized regenerated cellulose, a plant-based material, has been combined with collagen to produce a dressing capable of binding to and protecting growth factors by binding and inactivating matrix metalloproteinases in the wound environment. The increased understanding of the biochemical processes involved in chronic wound healing allows the design of wound care products aimed at correcting imbalances in the wound microenvironment. Traditional advanced wound care products tend to address the wound's macroenvironment, including moist wound environment control, fluid management, and controlled transpiration of wound fluids. The newer class of biomaterials and wound-healing agents, such as collagen and growth factors, targets specific defects in the chronic wound environment. In vitro laboratory data point to the possibility that these agents benefit the wound healing process at a biochemical level. Considerable evidence has indicated that collagen-based dressings may be capable of stimulating healing by manipulating wound biochemistry.

Rescuing Ecosystems from Extinction Cascades

NASA Astrophysics Data System (ADS)

Sahasrabudhe, Sagar; Motter, Adilson

2010-03-01

Food web perturbations stemming from climate change, overexploitation, invasive species, and natural disasters often cause an initial loss of species that results in a cascade of secondary extinctions. Using a predictive modeling framework, here we will present a systematic network-based approach to reduce the number of secondary extinctions. We will show that the extinction of one species can often be compensated by the concurrent removal of a second specific species, which is a counter-intuitive effect not previously tested in complex food webs. These compensatory perturbations frequently involve long-range interactions that are not a priori evident from local predator-prey relationships. Strikingly, in numerous cases even the early removal of a species that would eventually be extinct by the cascade is found to significantly reduce the number of cascading extinctions. Other nondestructive interventions based on partial removals and growth suppression and/or mortality increase are shown to sometimes prevent all secondary extinctions.

Formate as a CO surrogate for cascade processes: Rh-catalyzed cooperative decarbonylation and asymmetric Pauson-Khand-type cyclization reactions.

PubMed

Lee, Hang Wai; Chan, Albert S C; Kwong, Fuk Yee

2007-07-07

A rhodium-(S)-xyl-BINAP complex-catalyzed tandem formate decarbonylation and [2 + 2 + 1] carbonylative cyclization is described; this cooperative process utilizes formate as a condensed CO source, and the newly developed cascade protocol can be extended to its enantioselective version, providing up to 94% ee of the cyclopentenone adducts.

Teaching an old hormone new tricks: cytosolic Ca2+ elevation involvement in plant brassinosteroid signal transduction cascades.

PubMed

Zhao, Yichen; Qi, Zhi; Berkowitz, Gerald A

2013-10-01

Brassinosteroids (BRs) are hormones that control many aspects of plant growth and development, acting at the cell level to promote division and expansion. BR regulation of plant and plant cell function occurs through altered expression of many genes. Transcriptional reprogramming downstream from cell perception of this hormone is currently known to be mediated by a phosphorylation/dephosphorylation ("phosphorelay") cascade that alters the stability of two master transcription regulators. Here, we provide evidence that BR perception by their receptor also causes an elevation in cytosolic Ca(2+), initiating a Ca(2+) signaling cascade in Arabidopsis (Arabidopsis thaliana) cell cytosol. BR-dependent increases in the expression of some genes (INDOLE-3-ACETIC ACID-INDUCIBLE1 and PHYTOCHROME B ACTIVATION-TAGGED SUPPRESSOR1) were impaired in wild-type plants by a Ca(2+) channel blocker and also in the defense-no-death (dnd1) mutant, which lacks a functional cyclic GMP-activated cell membrane Ca(2+)-conducting channel. Alternatively, mutations that impair the BR phosphorelay cascade did not much affect the BR-dependent expression of these genes. Similar effects of the Ca(2+) channel blocker and dnd1 mutation were observed on a BR plant growth phenotype, deetiolation of the seedling hypocotyl. Further evidence presented in this report suggests that a BR-dependent elevation in cyclic GMP may be involved in the Ca(2+) signaling cascade initiated by this hormone. The work presented here leads to a new model of the molecular steps that mediate some of the cell responses to this plant hormone.

Cascade Apartments: Deep Energy Multifamily Retrofit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gordon, A.; Mattheis, L.; Kunkle, R.

2014-02-01

In December of 2009-10, King County Housing Authority (KCHA) implemented energy retrofit improvements in the Cascade multifamily community, located in Kent, Washington (marine climate.)This research effort involved significant coordination from stakeholders KCHA, WA State Department of Commerce, utility Puget Sound Energy, and Cascade tenants. This report focuses on the following three primary BA research questions : 1. What are the modeled energy savings using DOE low income weatherization approved TREAT software? 2. How did the modeled energy savings compare with measured energy savings from aggregate utility billing analysis? 3. What is the Savings to Investment Ratio (SIR) of the retrofitmore » package after considering utility window incentives and KCHA capitol improvement funding.« less

Cascade Apartments - Deep Energy Multifamily Retrofit , Kent, Washington (Fact Sheet)

DOE Office of Scientific and Technical Information (OSTI.GOV)

None, None

2014-02-01

In December of 2009-10, King County Housing Authority (KCHA) implemented energy retrofit improvements in the Cascade multifamily community, located in Kent, Washington (marine climate.)This research effort involved significant coordination from stakeholders KCHA, WA State Department of Commerce, utility Puget Sound Energy, and Cascade tenants. This report focuses on the following three primary BA research questions : 1. What are the modeled energy savings using DOE low income weatherization approved TREAT software? 2. How did the modeled energy savings compare with measured energy savings from aggregate utility billing analysis? 3. What is the Savings to Investment Ratio (SIR) of the retrofitmore » package after considering utility window incentives and KCHA capitol improvement funding.« less

Cascade Apartments: Deep Energy Multifamily Retrofit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gordon, A.; Mattheis, L.; Kunkle, R.

2014-02-01

In December of 2009-10, King County Housing Authority (KCHA) implemented energy retrofit improvements in the Cascade multifamily community, located in Kent, Washington (marine climate.)This research effort involved significant coordination from stakeholders KCHA, WA State Department of Commerce, utility Puget Sound Energy, and Cascade tenants. This report focuses on the following three primary BA research questions: 1. What are the modeled energy savings using DOE low income weatherization approved TREAT software? 2. How did the modeled energy savings compare with measured energy savings from aggregate utility billing analysis? 3. What is the Savings to Investment Ratio (SIR) of the retrofit packagemore » after considering utility window incentives and KCHA capitol improvement funding.« less

Cascade debris overlap mechanism of 〈100〉 dislocation loop formation in Fe and FeCr

NASA Astrophysics Data System (ADS)

Granberg, F.; Byggmästar, J.; Sand, A. E.; Nordlund, K.

2017-09-01

Two types of dislocation loops are observed in irradiated α-Fe, the 1/2〈111〉 loop and the 〈100〉 loop. Atomistic simulations consistently predict that only the energetically more favourable 1/2〈111〉 loops are formed directly in cascades, leaving the formation mechanism of 〈100〉 loops an unsolved question. We show how 〈100〉 loops can be formed when cascades overlap with random pre-existing primary radiation damage in Fe and FeCr. This indicates that there are no specific constraints involved in the formation of 〈100〉 loops, and can explain their common occurrence.

Hemolymph Melanization in the Silkmoth Bombyx mori Involves Formation of a High Molecular Mass Complex That Metabolizes Tyrosine*

PubMed Central

Clark, Kevin D.; Strand, Michael R.

2013-01-01

The phenoloxidase (PO) cascade regulates the melanization of blood (hemolymph) in insects and other arthropods. Most studies indicate that microbial elicitors activate the PO cascade, which results in processing of the zymogen PPO to PO. PO is then thought to oxidize tyrosine and o-diphenols to quinones, which leads to melanin. However, different lines of investigation raise questions as to whether these views are fully correct. Here we report that hemolymph from the silkmoth, Bombyx mori, rapidly melanizes after collection from a wound site. Prior studies indicated that in vitro activated PPO hydroxylates Tyr inefficiently. Measurement of in vivo substrate titers, however, suggested that Tyr was the only PO substrate initially present in B. mori plasma and that it is rapidly metabolized by PO. Fractionation of plasma by gel filtration chromatography followed by bioassays indicated that melanization activity was primarily associated with a high mass complex (∼670 kDa) that contained PO. The prophenoloxidase-activating protease inhibitor Egf1.0 blocked formation of this complex and Tyr metabolism, but the addition of phenylthiourea to plasma before fractionation enhanced complex formation and Tyr metabolism. Mass spectrometry analysis indicated that the complex contained PO plus other proteins. Taken together, our results indicate that wounding alone activates the PO cascade in B. mori. They also suggest that complex formation is required for efficient use of Tyr as a substrate. PMID:23553628

The turbulent cascade of individual eddies

NASA Astrophysics Data System (ADS)

Huertas-Cerdeira, Cecilia; Lozano-Durán, Adrián; Jiménez, Javier

2014-11-01

The merging and splitting processes of Reynolds-stress carrying structures in the inertial range of scales are studied through their time-resolved evolution in channels at Reλ = 100 - 200 . Mergers and splits coexist during the whole life of the structures, and are responsible for a substantial part of their growth and decay. Each interaction involves two or more eddies and results in little overall volume loss or gain. Most of them involve a small eddy that merges with, or splits from, a significantly larger one. Accordingly, if merge and split indexes are respectively defined as the maximum number of times that a structure has merged from its birth or will split until its death, the mean eddy volume grows linearly with both indexes, suggesting an accretion process rather than a hierarchical fragmentation. However, a non-negligible number of interactions involve eddies of similar scale, with a second probability peak of the volume of the smaller parent or child at 0.3 times that of the resulting or preceding structure. Funded by the Multiflow project of the ERC.

LANGMUIR WAVE DECAY IN INHOMOGENEOUS SOLAR WIND PLASMAS: SIMULATION RESULTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krafft, C.; Volokitin, A. S.; Krasnoselskikh, V. V., E-mail: catherine.krafft@u-psud.fr

2015-08-20

Langmuir turbulence excited by electron flows in solar wind plasmas is studied on the basis of numerical simulations. In particular, nonlinear wave decay processes involving ion-sound (IS) waves are considered in order to understand their dependence on external long-wavelength plasma density fluctuations. In the presence of inhomogeneities, it is shown that the decay processes are localized in space and, due to the differences between the group velocities of Langmuir and IS waves, their duration is limited so that a full nonlinear saturation cannot be achieved. The reflection and the scattering of Langmuir wave packets on the ambient and randomly varying density fluctuationsmore » lead to crucial effects impacting the development of the IS wave spectrum. Notably, beatings between forward propagating Langmuir waves and reflected ones result in the parametric generation of waves of noticeable amplitudes and in the amplification of IS waves. These processes, repeated at different space locations, form a series of cascades of wave energy transfer, similar to those studied in the frame of weak turbulence theory. The dynamics of such a cascading mechanism and its influence on the acceleration of the most energetic part of the electron beam are studied. Finally, the role of the decay processes in the shaping of the profiles of the Langmuir wave packets is discussed, and the waveforms calculated are compared with those observed recently on board the spacecraft Solar TErrestrial RElations Observatory and WIND.« less

Heat shock protein 70 negatively regulates the heat-shock-induced suppression of the I{kappa}B/NF-{kappa}B cascade by facilitating I{kappa}B kinase renaturation and blocking its further denaturation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Kyoung-Hee; Lee, Choon-Taek; Kim, Young Whan

2005-07-01

Heat shock (HS) treatment has been previously shown to suppress the I{kappa}B/nuclear factor-{kappa}B (NF-{kappa}B) cascade by denaturing, and thus inactivating I{kappa}B kinase (IKK). HS is characterized by the induction of a group of heat shock proteins (HSPs). However, their role in the HS-induced suppression of the I{kappa}B/NF-{kappa}B cascade is unclear. Adenovirus-mediated HSP70 overexpression was found not to suppress the TNF-{alpha}-induced activation of the I{kappa}B/NF-{kappa}B pathway, thus suggesting that HSP70 is unlikely to suppress this pathway. When TNF-{alpha}-induced activation of the I{kappa}B/NF-{kappa}B pathway was regained 24 h after HS, HSP70 was found to be highly up-regulated. Moreover, blocking HSP70 induction delayedmore » TNF-{alpha}-induced I{kappa}B{alpha} degradation and the resolubilization of IKK. In addition, HSP70 associated physically with IKK, suggesting that HSP70 is involved in the recovery process via molecular chaperone effect. Adenovirus-mediated HSP70 overexpression prior to HS blocked the I{kappa}B{alpha} stabilizing effect of HS by suppressing IKK insolubilization. Moreover, the up-regulation of endogenous HSP70 by preheating, suppressed this subsequent HS-induced IKK insolubilization, and this effect was abrogated by blocking HSP70 induction. These findings indicate that HSP70 accumulates during HS and negatively regulates the HS-induced suppression of the I{kappa}B/NF-{kappa}B cascade by facilitating the renaturation of IKK and blocking its further denaturation.« less

Petrologic, tectonic, and metallogenic evolution of the Ancestral Cascades magmatic arc, Washington, Oregon, and northern California

USGS Publications Warehouse

du Bray, Edward A.; John, David A.

2011-01-01

Present-day High Cascades arc magmatism was preceded by ~40 m.y. of nearly cospatial magmatism represented by the ancestral Cascades arc in Washington, Oregon, and northernmost California (United States). Time-space-composition relations for the ancestral Cascades arc have been synthesized from a recent compilation of more than 4000 geochemical analyses and associated age data. Neither the composition nor distribution of ancestral Cascades magmatism was uniform along the length of the ancestral arc through time. Initial (>40 to 36 Ma) ancestral Cascades magmatism (mostly basalt and basaltic andesite) was focused at the north end of the arc between the present-day locations of Mount Rainier and the Columbia River. From 35 to 18 Ma, initial basaltic andesite and andesite magmatism evolved to include dacite and rhyolite; magmatic activity became more voluminous and extended along most of the arc. Between 17 and 8 Ma, magmatism was focused along the part of the arc coincident with the northern two-thirds of Oregon and returned to more mafic compositions. Subsequent ancestral Cascades magmatism was dominated by basaltic andesite to basalt prior to the post–4 Ma onset of High Cascades magmatism. Transitional tholeiitic to calc-alkaline compositions dominated early (before 40 to ca. 25 Ma) ancestral Cascades eruptive products, whereas the majority of the younger arc rocks have a calc-alkaline affinity. Tholeiitic compositions characteristic of the oldest ancestral arc magmas suggest development associated with thin, immature crust and slab window processes, whereas the younger, calc-alkaline magmas suggest interaction with thicker, more evolved crust and more conventional subduction-related magmatic processes. Presumed changes in subducted slab dip through time also correlate with fundamental magma composition variation. The predominance of mafic compositions during latest ancestral arc magmatism and throughout the history of modern High Cascades magmatism probably reflects extensional tectonics that dominated during these periods of arc magmatism. Mineral deposits associated with ancestral Cascades arc rocks are uncommon; most are small and low grade relative to those found in other continental magmatic arcs. The small size, low grade, and dearth of deposits, especially in the southern two-thirds of the ancestral arc, probably reflect many factors, the most important of which may be the prevalence of extensional tectonics within this arc domain during this magmatic episode. Progressive clockwise rotation of the forearc block west of the evolving Oregon part of the ancestral Cascades magmatism produced an extensional regime that did not foster significant mineral deposit formation. In contrast, the Washington arc domain developed in a transpressional to mildly compressive regime that was more conducive to magmatic processes and hydrothermal fluid channeling critical to deposit formation. Small, low-grade porphyry copper deposits in the northern third of the ancestral Cascades arc segment also may be a consequence of more mature continental crust, including a Mesozoic component, beneath Washington north of Mount St. Helens.

Functional Conservation of the Glide/Gcm Regulatory Network Controlling Glia, Hemocyte, and Tendon Cell Differentiation in Drosophila

PubMed Central

Cattenoz, Pierre B.; Popkova, Anna; Southall, Tony D.; Aiello, Giuseppe; Brand, Andrea H.; Giangrande, Angela

2016-01-01

High-throughput screens allow us to understand how transcription factors trigger developmental processes, including cell specification. A major challenge is identification of their binding sites because feedback loops and homeostatic interactions may mask the direct impact of those factors in transcriptome analyses. Moreover, this approach dissects the downstream signaling cascades and facilitates identification of conserved transcriptional programs. Here we show the results and the validation of a DNA adenine methyltransferase identification (DamID) genome-wide screen that identifies the direct targets of Glide/Gcm, a potent transcription factor that controls glia, hemocyte, and tendon cell differentiation in Drosophila. The screen identifies many genes that had not been previously associated with Glide/Gcm and highlights three major signaling pathways interacting with Glide/Gcm: Notch, Hedgehog, and JAK/STAT, which all involve feedback loops. Furthermore, the screen identifies effector molecules that are necessary for cell-cell interactions during late developmental processes and/or in ontogeny. Typically, immunoglobulin (Ig) domain–containing proteins control cell adhesion and axonal navigation. This shows that early and transiently expressed fate determinants not only control other transcription factors that, in turn, implement a specific developmental program but also directly affect late developmental events and cell function. Finally, while the mammalian genome contains two orthologous Gcm genes, their function has been demonstrated in vertebrate-specific tissues, placenta, and parathyroid glands, begging questions on the evolutionary conservation of the Gcm cascade in higher organisms. Here we provide the first evidence for the conservation of Gcm direct targets in humans. In sum, this work uncovers novel aspects of cell specification and sets the basis for further understanding of the role of conserved Gcm gene regulatory cascades. PMID:26567182

Near-bottom energy cascade from subinertial flows to ocean mixing in the northeastern South China Sea

NASA Astrophysics Data System (ADS)

Zhang, Y.; Liu, Z.; Zhao, Y.; Wang, W.; Li, J.; Xu, J.

2013-12-01

The motions with different scales in the bottom boundary layer are potentially important in controlling the water mass transportation. Many physical processes are involved in transferring energy from mesoscale to small-scale motions. Recent studies suggest that subinertial flows should be taken into account in the parameterization of deep-ocean mixing besides topography and tidal forcing. Here, we present the current velocity data obtained from 2 moored downward-looking ADCPs (Acoustic Doppler Current Profiler) and 1 RCM (Recording Current Meter) moored near the bottom boundary layer at a water depth of about 2000 m in the northeastern South China Sea from 2012 to 2013. Specifically, they include an ADCP 1200 kHz deployed at 30 m, an ADCP 300 kHz deployed at 110 m, and a RCM deployed at 40 m above the seafloor. Subinertial flows were calculated from the moored current velocity data by low-pass filtering with a cutoff frequency of 0.3 cycles per day (the local inertial period is about 35 hours). The horizontal subinertial flows were quite strong with average values of 2-5 cm/s. The strong downward vertical velocity with average values of 1-2 cm/s was observed during times of weak subinertial flows. The vertical propagation during both the times of weak and strong subinertial flows can also be shown by vector spectra of horizontal near-inertial current velocity. Turbulent kinetic energy production rate estimated indirectly with the variances of ADCP velocities will be compared with the subinertial kinetic energy to detect the processes of energy cascade from mesoscale motions to small-scale oscillations. The results presented in this study can provide an observational evidence for such energy cascade near the bottom boundary layer in the deep South China Sea.

Electrically driven nanopillars for THz quantum cascade lasers.

PubMed

Amanti, M I; Bismuto, A; Beck, M; Isa, L; Kumar, K; Reimhult, E; Faist, J

2013-05-06

In this work we present a rapid and parallel process for the fabrication of large scale arrays of electrically driven nanopillars for THz quantum cascade active media. We demonstrate electrical injection of pillars of 200 nm diameter and 2 µm height, over a surface of 1 mm(2). THz electroluminescence from the nanopillars is reported. This result is a promising step toward the realization of zero-dimensional structure for terahertz quantum cascade lasers.

Cascading process in the flute-mode turbulence of a plasma

NASA Technical Reports Server (NTRS)

Gonzalez, R.; Gomez, D.; Fontan, C. F.; Schifino, A. C. S.; Montagne, R.

1993-01-01

The cascades of ideal invariants in the flute-mode turbulence are analyzed by considering a statistics based on an elementary three-mode coupling process. The statistical dynamics of the system is investigated on the basis of the existence of the physically most important (PMI) triad. When finite ion Larmor radius effects are considered, the PMI triad describes the formation of zonal flows.

An iron/amine-catalyzed cascade process for the enantioselective functionalization of allylic alcohols.

PubMed

Quintard, Adrien; Constantieux, Thierry; Rodriguez, Jean

2013-12-02

Three is a lucky number: An enantioselective transformation of allylic alcohols into β-chiral saturated alcohols has been developed by combining two distinct metal- and organocatalyzed catalytic cycles. This waste-free triple cascade process merges an iron-catalyzed borrowing-hydrogen step with an aminocatalyzed nucleophilic addition reaction. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Conscious coupling: The challenges and opportunities of cascading enzymatic microreactors.

PubMed

Gruber, Pia; Marques, Marco P C; O'Sullivan, Brian; Baganz, Frank; Wohlgemuth, Roland; Szita, Nicolas

2017-07-01

The continuous production of high value or difficult to synthesize products is of increasing interest to the pharmaceutical industry. Cascading reaction systems have already been employed for chemical synthesis with great success, allowing a quick change in reaction conditions and addition of new reactants as well as removal of side products. A cascading system can remove the need for isolating unstable intermediates, increasing the yield of a synthetic pathway. Based on the success for chemical synthesis, the question arises how cascading systems could be beneficial to chemo-enzymatic or biocatalytic synthesis. Microreactors, with their rapid mass and heat transfer, small reaction volumes and short diffusion pathways, are promising tools for the development of such processes. In this mini-review, the authors provide an overview of recent examples of cascaded microreactors. Special attention will be paid to how microreactors are combined and the challenges as well as opportunities that arise from such combinations. Selected chemical reaction cascades will be used to illustrate this concept, before the discussion is widened to include chemo-enzymatic and multi-enzyme cascades. The authors also present the state of the art of online and at-line monitoring for enzymatic microreactor cascades. Finally, the authors review work-up and purification steps and their integration with microreactor cascades, highlighting the potential and the challenges of integrated cascades. © 2017 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Isostrychnine synthesis mediated by hypervalent iodine reagent.

PubMed

Jacquemot, Guillaume; Maertens, Gaëtan; Canesi, Sylvain

2015-05-18

Althought there are several reported synthetic routes to strychnine, one of the most widely recognized alkaloids, we report an unexplored route with an oxidative dearomatizing process mediated by hypervalent iodine as the key step. The new syntheses of isostrychnine and strychnine have been achieved from an readily available phenol in nine and ten steps. In addition to the key step, these syntheses involve an aza Michael-ether-enol tandem transformation, two heck type cyclizations, a reductive isomerization, and a double reductive amination in cascade leading to the alkaloid main core. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tandem SN2' nucleophilic substitution/oxidative radical cyclization of aryl substituted allylic alcohols with 1,3-dicarbonyl compounds.

PubMed

Zhang, Zhen; Li, Cheng; Wang, Shao-Hua; Zhang, Fu-Min; Han, Xue; Tu, Yong-Qiang; Zhang, Xiao-Ming

2017-04-11

A novel and efficient tandem S N 2' nucleophilic substitution/oxidative radical cyclization reaction of aryl substituted allylic alcohols with 1,3-dicarbonyl compounds has been developed by using Mn(OAc) 3 as an oxidant, which enables the expeditious synthesis of polysubstituted dihydrofuran (DHF) derivatives in moderate to high yields. The use of weakly acidic hexafluoroisopropanol (HFIP) as the solvent rather than AcOH has successfully improved the yields and expanded the substrate scope of this type of radical cyclization reactions. Mechanistic studies confirmed the cascade reaction process involving a final radical cyclization.

O-GlcNAc cycling: how a single sugar post-translational modification is changing the way we think about signaling networks.

PubMed

Slawson, Chad; Housley, Michael P; Hart, Gerald W

2006-01-01

O-GlcNAc is an ubiquitous post-translational protein modification consisting of a single N-acetlyglucosamine moiety linked to serine or threonine residues on nuclear and cytoplasmic proteins. Recent work has begun to uncover the functional roles of O-GlcNAc in cellular processes. O-GlcNAc modified proteins are involved in sensing the nutrient status of the surrounding cellular environment and adjusting the activity of cellular proteins accordingly. O-GlcNAc regulates cellular responses to hormones such as insulin, initiates a protective response to stress, modulates a cell's capacity to grow and divide, and regulates gene transcription. This review will focus on recent work involving O-GlcNAc in sensing the environment and regulating signaling cascades. (c) 2005 Wiley-Liss, Inc.

Frontier of Epilepsy Research - mTOR signaling pathway

PubMed Central

2011-01-01

Studies of epilepsy have mainly focused on the membrane proteins that control neuronal excitability. Recently, attention has been shifting to intracellular proteins and their interactions, signaling cascades and feedback regulation as they relate to epilepsy. The mTOR (mammalian target of rapamycin) signal transduction pathway, especially, has been suggested to play an important role in this regard. These pathways are involved in major physiological processes as well as in numerous pathological conditions. Here, involvement of the mTOR pathway in epilepsy will be reviewed by presenting; an overview of the pathway, a brief description of key signaling molecules, a summary of independent reports and possible implications of abnormalities of those molecules in epilepsy, a discussion of the lack of experimental data, and questions raised for the understanding its epileptogenic mechanism. PMID:21467839

TCP three-way handshake: linking developmental processes with plant immunity.

PubMed

Lopez, Jessica A; Sun, Yali; Blair, Peter B; Mukhtar, M Shahid

2015-04-01

The TCP gene family encodes plant-specific transcription factors involved in growth and development. Equally important are the interactions between TCP factors and other pathways extending far beyond development, as they have been found to regulate a variety of hormonal pathways and signaling cascades. Recent advances reveal that TCP factors are targets of pathogenic effectors and are likely to play a vital role in plant immunity. Our focus is on reviewing the involvement of TCP in known pathways and shedding light on other linkages in the nexus of plant immunity centered around TCP factors with an emphasis on the convergence of effectors, interconnected hormonal networks, utility of the circadian clock, and the potential mechanisms by which pathogen defense may occur. Copyright © 2015 Elsevier Ltd. All rights reserved.

A cascading failure model for analyzing railway accident causation

NASA Astrophysics Data System (ADS)

Liu, Jin-Tao; Li, Ke-Ping

2018-01-01

In this paper, a new cascading failure model is proposed for quantitatively analyzing the railway accident causation. In the model, the loads of nodes are redistributed according to the strength of the causal relationships between the nodes. By analyzing the actual situation of the existing prevention measures, a critical threshold of the load parameter in the model is obtained. To verify the effectiveness of the proposed cascading model, simulation experiments of a train collision accident are performed. The results show that the cascading failure model can describe the cascading process of the railway accident more accurately than the previous models, and can quantitatively analyze the sensitivities and the influence of the causes. In conclusion, this model can assist us to reveal the latent rules of accident causation to reduce the occurrence of railway accidents.

MtMAPKK4 is an essential gene for growth and reproduction of Medicago truncatula.

PubMed

Chen, Tao; Zhou, Bo; Duan, Liujian; Zhu, Hui; Zhang, Zhongming

2017-04-01

Mitogen-activated protein kinase (MAPK) cascades are universal signaling modules in eukaryotes, including yeasts, animals and plants. They are involved in responses to various biotic and abiotic stresses, hormones, cell division and developmental processes. A MAPK cascade is composed of three functionally tiered protein kinases, namely MAPK, MAPK kinases (MAPKKs) and MAPK kinase kinases (MAPKKKs). These kinases have been intensively studied for their roles in developmental and physiological processes in various organisms. In this study, a Medicago truncatula MtMAPKK4 mutant with the tobacco retrotransposon Tnt1 insertion was identified using reverse genetics methods. No homozygous progeny could be produced by self-pollination of mapkk4/+ heterozygotes for 5 generations. Heterozygous mapkk4/+ mutant plants exhibited growth retardation, chlorosis symptoms and significantly reduced numbers of infection threads and nodules. The interaction between MtMAPKK4 and MtMAPK3/6 occurred both in yeast and in planta. Green fluorescent protein-tagged MtMAPKK4, MtMAPK3 and MtMAPK6 were all localized to membranes, cytoplasm and nuclei. Expression of MtMAPKK4, MtMAPK3 and MtMAPK6 was detected in various tissues of M. truncatula plants at the nodule maturation stage. Transcript levels of these genes were decreased in roots at the early symbiotic stage. © 2016 Scandinavian Plant Physiology Society.

Electromagnetic cascade in high-energy electron, positron, and photon interactions with intense laser pulses

NASA Astrophysics Data System (ADS)

Bulanov, S. S.; Schroeder, C. B.; Esarey, E.; Leemans, W. P.

2013-06-01

The interaction of high-energy electrons, positrons, and photons with intense laser pulses is studied in head-on collision geometry. It is shown that electrons and/or positrons undergo a cascade-type process involving multiple emissions of photons. These photons can consequently convert into electron-positron pairs. As a result charged particles quickly lose their energy developing an exponentially decaying energy distribution, which suppresses the emission of high-energy photons, thus reducing the number of electron-positron pairs being generated. Therefore, this type of interaction suppresses the development of the electromagnetic avalanche-type discharge, i.e., the exponential growth of the number of electrons, positrons, and photons does not occur in the course of interaction. The suppression will occur when three-dimensional effects can be neglected in the transverse particle orbits, i.e., for sufficiently broad laser pulses with intensities that are not too extreme. The final distributions of electrons, positrons, and photons are calculated for the case of a high-energy e-beam interacting with a counterstreaming, short intense laser pulse. The energy loss of the e-beam, which requires a self-consistent quantum description, plays an important role in this process, as well as provides a clear experimental observable for the transition from the classical to quantum regime of interaction.

Termination of second messenger signaling in olfaction.

PubMed Central

Boekhoff, I; Breer, H

1992-01-01

By using isolated rat olfactory cilia and a fast kinetics methodology, it has been demonstrated that odorant-induced second messenger signaling in the millisecond time range is terminated via phosphorylation reactions catalyzed by specific protein kinases. The cyclic adenosine nucleotide pathway is turned off by kinase A activity, whereas the inositol trisphosphate cascade is terminated by kinase C. The data support the concept that desensitization of odorant responses involves phosphorylation of key elements in the transduction cascade. PMID:1370581

Modelling of information diffusion on social networks with applications to WeChat

NASA Astrophysics Data System (ADS)

Liu, Liang; Qu, Bo; Chen, Bin; Hanjalic, Alan; Wang, Huijuan

2018-04-01

Traces of user activities recorded in online social networks open new possibilities to systematically understand the information diffusion process on social networks. From the online social network WeChat, we collected a large number of information cascade trees, each of which tells the spreading trajectory of a message/information such as which user creates the information and which users view or forward the information shared by which neighbours. In this work, we propose two heterogeneous non-linear models, one for the topologies of the information cascade trees and the other for the stochastic process of information diffusion on a social network. Both models are validated by the WeChat data in reproducing and explaining key features of cascade trees. Specifically, we apply the Random Recursive Tree (RRT) to model the growth of cascade trees. The RRT model could capture key features, i.e. the average path length and degree variance of a cascade tree in relation to the number of nodes (size) of the tree. Its single identified parameter quantifies the relative depth or broadness of the cascade trees and indicates that information propagates via a star-like broadcasting or viral-like hop by hop spreading. The RRT model explains the appearance of hubs, thus a possibly smaller average path length as the cascade size increases, as observed in WeChat. We further propose the stochastic Susceptible View Forward Removed (SVFR) model to depict the dynamic user behaviour including creating, viewing, forwarding and ignoring a message on a given social network. Beside the average path length and degree variance of the cascade trees in relation to their sizes, the SVFR model could further explain the power-law cascade size distribution in WeChat and unravel that a user with a large number of friends may actually have a smaller probability to read a message (s)he receives due to limited attention.

Toward understanding dynamic annealing processes in irradiated ceramics

NASA Astrophysics Data System (ADS)

Myers, Michael Thomas

High energy particle irradiation inevitably generates defects in solids in the form of collision cascades. The ballistic formation and thermalization of cascades occur rapidly and are believed to be reasonably well understood. However, knowledge of the evolution of defects after damage cascade thermalization, referred to as dynamic annealing, is quite limited. Unraveling the mechanisms associated with dynamic an- nealing is crucial since such processes play an important role in the formation of stable post-irradiation disorder in ion-beam-processed semiconductors and determines the "radiation tolerance" of many nuclear materials. The purpose of this dissertation is to further our understanding of the processes involved in dynamic annealing. In order to achieve this, two main tasks are undertaken. First, the effects of dynamic annealing are investigated in ZnO, a technologically relevant material that exhibits very high dynamic defect annealing at room temper- ature. Such high dynamic annealing leads to unusual defect accumulation in heavy ion bombarded ZnO. Through this work, the puzzling features that were observed more than a decade ago in ion-channeling spectra have finally been explained. We show that the presence of a polar surface substantially alters damage accumulation. Non-polar surface terminations of ZnO are shown to exhibit enhanced dynamic an- nealing compared to polar surface terminated ZnO. Additionally, we demonstrate one method to reduce radiation damage in polar surface terminated ZnO by means of a surface modification. These results advance our efforts in the long-sought-after goal of understanding complex radiation damage processes in ceramics. Second, a pulsed-ion-beam method is developed and demonstrated in the case of Si as a prototypical non-metallic target. Such a method is shown to be a novel experimental technique for direct extraction of dynamic annealing parameters. The relaxation times and effective diffusion lengths of mobile defects during the dynamic annealing process play a vital role in damage accumulation. We demonstrate that these parameters dominate the formation of stable post-irradiation disorder. In Si, a defect lifetime of ˜ 6 ms and a characteristic defect diffusion length of ˜ 30 nm are measured. These results should nucleate future pulsed-beam studies of dynamic defect interaction processes in technologically relevant materials. In particular, un- derstanding length- and time-scales of defect interactions are essential for extending laboratory findings to nuclear material lifetimes and to the time-scales of geological storage of nuclear waste.

Metabolomics for Biomarker Discovery in Gastroenterological Cancer

PubMed Central

Nishiumi, Shin; Suzuki, Makoto; Kobayashi, Takashi; Matsubara, Atsuki; Azuma, Takeshi; Yoshida, Masaru

2014-01-01

The study of the omics cascade, which involves comprehensive investigations based on genomics, transcriptomics, proteomics, metabolomics, etc., has developed rapidly and now plays an important role in life science research. Among such analyses, metabolome analysis, in which the concentrations of low molecular weight metabolites are comprehensively analyzed, has rapidly developed along with improvements in analytical technology, and hence, has been applied to a variety of research fields including the clinical, cell biology, and plant/food science fields. The metabolome represents the endpoint of the omics cascade and is also the closest point in the cascade to the phenotype. Moreover, it is affected by variations in not only the expression but also the enzymatic activity of several proteins. Therefore, metabolome analysis can be a useful approach for finding effective diagnostic markers and examining unknown pathological conditions. The number of studies involving metabolome analysis has recently been increasing year-on-year. Here, we describe the findings of studies that used metabolome analysis to attempt to discover biomarker candidates for gastroenterological cancer and discuss metabolome analysis-based disease diagnosis. PMID:25003943

Holocene volcanism of the upper McKenzie River catchment, central Oregon Cascades, USA

USGS Publications Warehouse

Deligne, Natalia I.; Conrey, Richard M.; Cashman, Katharine V.; Champion, Duane E.; Amidon, William H.

2016-01-01

To assess the complexity of eruptive activity within mafic volcanic fields, we present a detailed geologic investigation of Holocene volcanism in the upper McKenzie River catchment in the central Oregon Cascades, United States. We focus on the Sand Mountain volcanic field, which covers 76 km2 and consists of 23 vents, associated tephra deposits, and lava fields. We find that the Sand Mountain volcanic field was active for a few decades around 3 ka and involved at least 13 eruptive units. Despite the small total volume erupted (∼1 km3 dense rock equivalent [DRE]), Sand Mountain volcanic field lava geochemistry indicates that erupted magmas were derived from at least two, and likely three, different magma sources. Single units erupted from one or more vents, and field data provide evidence of both vent migration and reoccupation. Overall, our study shows that mafic volcanism was clustered in space and time, involved both explosive and effusive behavior, and tapped several magma sources. These observations provide important insights on possible future hazards from mafic volcanism in the central Oregon Cascades.

Experimental characterization of pairwise correlations from triple quantum correlated beams generated by cascaded four-wave mixing processes

NASA Astrophysics Data System (ADS)

Wang, Wei; Cao, Leiming; Lou, Yanbo; Du, Jinjian; Jing, Jietai

2018-01-01

We theoretically and experimentally characterize the performance of the pairwise correlations from triple quantum correlated beams based on the cascaded four-wave mixing (FWM) processes. The pairwise correlations between any two of the beams are theoretically calculated and experimentally measured. The experimental and theoretical results are in good agreement. We find that two of the three pairwise correlations can be in the quantum regime. The other pairwise correlation is always in the classical regime. In addition, we also measure the triple-beam correlation which is always in the quantum regime. Such unbalanced and controllable pairwise correlation structures may be taken as advantages in practical quantum communications, for example, hierarchical quantum secret sharing. Our results also open the way for the classification and application of quantum states generated from the cascaded FWM processes.

Dynamic hydro-climatic networks in pristine and regulated rivers

NASA Astrophysics Data System (ADS)

Botter, G.; Basso, S.; Lazzaro, G.; Doulatyari, B.; Biswal, B.; Schirmer, M.; Rinaldo, A.

2014-12-01

Flow patterns observed at-a-station are the dynamical byproduct of a cascade of processes involving different compartments of the hydro-climatic network (e.g., climate, rainfall, soil, vegetation) that regulates the transformation of rainfall into streamflows. In complex branching rivers, flow regimes result from the heterogeneous arrangement around the stream network of multiple hydrologic cascades that simultaneously occur within distinct contributing areas. As such, flow regimes are seen as the integrated output of a complex "network of networks", which can be properly characterized by its degree of temporal variability and spatial heterogeneity. Hydrologic networks that generate river flow regimes are dynamic in nature. In pristine rivers, the time-variance naturally emerges at multiple timescales from climate variability (namely, seasonality and inter-annual fluctuations), implying that the magnitude (and the features) of the water flow between two nodes may be highly variable across different seasons and years. Conversely, the spatial distribution of river flow regimes within pristine rivers involves scale-dependent transport features, as well as regional climatic and soil use gradients, which in small and meso-scale catchments (A < 103 km2) are usually mild enough to guarantee quite uniform flow regimes and high spatial correlations. Human-impacted rivers, instead, constitute hybrid networks where observed spatio-temporal patterns are dominated by anthropogenic shifts, such as landscape alterations and river regulation. In regulated rivers, the magnitude and the features of water flows from node to node may change significantly through time due to damming and withdrawals. However, regulation may impact river regimes in a spatially heterogeneous manner (e.g. in localized river reaches), with a significant decrease of spatial correlations and network connectivity. Provided that the spatial and temporal dynamics of flow regimes in complex rivers may strongly impact important biotic processes involved in the river food web (e.g. biofilm and riparian vegetation dynamics), the study of rivers as dynamic networks provides important clues to water management strategies and freshwater ecosystem studies.

Cascaded chirped photon acceleration for efficient frequency conversion

NASA Astrophysics Data System (ADS)

Edwards, Matthew R.; Qu, Kenan; Jia, Qing; Mikhailova, Julia M.; Fisch, Nathaniel J.

2018-05-01

A cascaded sequence of photon acceleration stages using the instantaneous creation of a plasma density gradient by flash ionization allows the generation of coherent and chirped ultraviolet and x-ray pulses with independently tunable frequency and bandwidth. The efficiency of the cascaded process scales with 1/ω in energy, and multiple stages produce significant frequency up-conversion with gas-density plasmas. Chirping permits subsequent pulse compression to few-cycle durations, and output frequencies are not limited to integer harmonics.

Multiplicative Process in Turbulent Velocity Statistics: A Simplified Analysis

NASA Astrophysics Data System (ADS)

Chillà, F.; Peinke, J.; Castaing, B.

1996-04-01

A lot of models in turbulence links the energy cascade process and intermittency, the characteristic of which being the shape evolution of the probability density functions (pdf) for longitudinal velocity increments. Using recent models and experimental results, we show that the flatness factor of these pdf gives a simple and direct estimate for what is called the deepness of the cascade. We analyse in this way the published data of a Direct Numerical Simulation and show that the deepness of the cascade presents the same Reynolds number dependence as in laboratory experiments. Plusieurs modèles de turbulence relient la cascade d'énergie et l'intermittence, caractérisée par l'évolution des densités de probabilité (pdf) des incréments longitudinaux de vitesse. Nous appuyant aussi bien sur des modèles récents que sur des résultats expérimentaux, nous montrons que la Curtosis de ces pdf permet une estimation simple et directe de la profondeur de la cascade. Cela nous permet de réanalyser les résultats publiés d'une simulation numérique et de montrer que la profondeur de la cascade y évolue de la même façon que pour les expériences de laboratoire en fonction du nombre de Reynolds.

Programmed Cell Death During Caenorhabditis elegans Development

PubMed Central

Conradt, Barbara; Wu, Yi-Chun; Xue, Ding

2016-01-01

Programmed cell death is an integral component of Caenorhabditis elegans development. Genetic and reverse genetic studies in C. elegans have led to the identification of many genes and conserved cell death pathways that are important for the specification of which cells should live or die, the activation of the suicide program, and the dismantling and removal of dying cells. Molecular, cell biological, and biochemical studies have revealed the underlying mechanisms that control these three phases of programmed cell death. In particular, the interplay of transcriptional regulatory cascades and networks involving multiple transcriptional regulators is crucial in activating the expression of the key death-inducing gene egl-1 and, in some cases, the ced-3 gene in cells destined to die. A protein interaction cascade involving EGL-1, CED-9, CED-4, and CED-3 results in the activation of the key cell death protease CED-3, which is tightly controlled by multiple positive and negative regulators. The activation of the CED-3 caspase then initiates the cell disassembly process by cleaving and activating or inactivating crucial CED-3 substrates; leading to activation of multiple cell death execution events, including nuclear DNA fragmentation, mitochondrial elimination, phosphatidylserine externalization, inactivation of survival signals, and clearance of apoptotic cells. Further studies of programmed cell death in C. elegans will continue to advance our understanding of how programmed cell death is regulated, activated, and executed in general. PMID:27516615

Learning optimal embedded cascades.

PubMed

Saberian, Mohammad Javad; Vasconcelos, Nuno

2012-10-01

The problem of automatic and optimal design of embedded object detector cascades is considered. Two main challenges are identified: optimization of the cascade configuration and optimization of individual cascade stages, so as to achieve the best tradeoff between classification accuracy and speed, under a detection rate constraint. Two novel boosting algorithms are proposed to address these problems. The first, RCBoost, formulates boosting as a constrained optimization problem which is solved with a barrier penalty method. The constraint is the target detection rate, which is met at all iterations of the boosting process. This enables the design of embedded cascades of known configuration without extensive cross validation or heuristics. The second, ECBoost, searches over cascade configurations to achieve the optimal tradeoff between classification risk and speed. The two algorithms are combined into an overall boosting procedure, RCECBoost, which optimizes both the cascade configuration and its stages under a detection rate constraint, in a fully automated manner. Extensive experiments in face, car, pedestrian, and panda detection show that the resulting detectors achieve an accuracy versus speed tradeoff superior to those of previous methods.

Spontaneous mirror-symmetry breaking induces inverse energy cascade in 3D active fluids

PubMed Central

Słomka, Jonasz; Dunkel, Jörn

2017-01-01

Classical turbulence theory assumes that energy transport in a 3D turbulent flow proceeds through a Richardson cascade whereby larger vortices successively decay into smaller ones. By contrast, an additional inverse cascade characterized by vortex growth exists in 2D fluids and gases, with profound implications for meteorological flows and fluid mixing. The possibility of a helicity-driven inverse cascade in 3D fluids had been rejected in the 1970s based on equilibrium-thermodynamic arguments. Recently, however, it was proposed that certain symmetry-breaking processes could potentially trigger a 3D inverse cascade, but no physical system exhibiting this phenomenon has been identified to date. Here, we present analytical and numerical evidence for the existence of an inverse energy cascade in an experimentally validated 3D active fluid model, describing microbial suspension flows that spontaneously break mirror symmetry. We show analytically that self-organized scale selection, a generic feature of many biological and engineered nonequilibrium fluids, can generate parity-violating Beltrami flows. Our simulations further demonstrate how active scale selection controls mirror-symmetry breaking and the emergence of a 3D inverse cascade. PMID:28193853

Functional blockade of α5β1 integrin induces scattering and genomic landscape remodeling of hepatic progenitor cells

PubMed Central

2010-01-01

Background Cell scattering is a physiological process executed by stem and progenitor cells during embryonic liver development and postnatal organ regeneration. Here, we investigated the genomic events occurring during this process induced by functional blockade of α5β1 integrin in liver progenitor cells. Results Cells treated with a specific antibody against α5β1 integrin exhibited cell spreading and scattering, over-expression of liver stem/progenitor cell markers and activation of the ERK1/2 and p38 MAPKs signaling cascades, in a similar manner to the process triggered by HGF/SF1 stimulation. Gene expression profiling revealed marked transcriptional changes of genes involved in cell adhesion and migration, as well as genes encoding chromatin remodeling factors. These responses were accompanied by conspicuous spatial reorganization of centromeres, while integrin genes conserved their spatial positioning in the interphase nucleus. Conclusion Collectively, our results demonstrate that α5β1 integrin functional blockade induces cell migration of hepatic progenitor cells, and that this involves a dramatic remodeling of the nuclear landscape. PMID:20958983

Cell Surface Translocation of Annexin A2 Facilitates Glutamate-induced Extracellular Proteolysis*

PubMed Central

Valapala, Mallika; Maji, Sayantan; Borejdo, Julian; Vishwanatha, Jamboor K.

2014-01-01

Glutamate-induced elevation in intracellular Ca2+ has been implicated in excitotoxic cell death. Neurons respond to increased glutamate levels by activating an extracellular proteolytic cascade involving the components of the plasmin-plasminogen system. AnxA2 is a Ca2+-dependent phospholipid binding protein and serves as an extracellular proteolytic center by recruiting the tissue plasminogen activator and plasminogen and mediating the localized generation of plasmin. Ratiometric Ca2+ imaging and time-lapse confocal microscopy demonstrated glutamate-induced Ca2+ influx. We showed that glutamate translocated both endogenous and AnxA2-GFP to the cell surface in a process dependent on the activity of the NMDA receptor. Glutamate-induced translocation of AnxA2 is dependent on the phosphorylation of tyrosine 23 at the N terminus, and mutation of tyrosine 23 to a non-phosphomimetic variant inhibits the translocation process. The cell surface-translocated AnxA2 forms an active plasmin-generating complex, and this activity can be neutralized by a hexapeptide directed against the N terminus. These results suggest an involvement of AnxA2 in potentiating glutamate-induced cell death processes. PMID:24742684

Coordination of gene expression of arachidonic and docosahexaenoic acid cascade enzymes during human brain development and aging.

PubMed

Ryan, Veronica H; Primiani, Christopher T; Rao, Jagadeesh S; Ahn, Kwangmi; Rapoport, Stanley I; Blanchard, Helene

2014-01-01

The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA) participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades. AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging. The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism. Expression patterns were split into Development (0 to 20 years) and Aging (21 to 78 years) intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2), cyclooxygenases (COX)-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA) and PTGS2 (COX-2) genes at 1q25, highly inter-correlated genes were at distant chromosomal loci. Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease.

A developmental cascade perspective of paediatric obesity: a conceptual model and scoping review.

PubMed

Smith, Justin D; Egan, Kaitlyn N; Montaño, Zorash; Dawson-McClure, Spring; Jake-Schoffman, Danielle E; Larson, Madeline; St George, Sara M

2018-04-05

Considering the immense challenge of preventing obesity, the time has come to reconceptualise the way we study the obesity development in childhood. The developmental cascade model offers a longitudinal framework to elucidate the way cumulative consequences and spreading effects of risk and protective factors, across and within biopsychosocial spheres and phases of development, can propel individuals towards obesity. In this article, we use a theory-driven model-building approach and a scoping review that included 310 published studies to propose a developmental cascade model of paediatric obesity. The proposed model provides a basis for testing hypothesised cascades with multiple intervening variables and complex longitudinal processes. Moreover, the model informs future research by resolving seemingly contradictory findings on pathways to obesity previously thought to be distinct (low self-esteem, consuming sugary foods, and poor sleep cause obesity) that are actually processes working together over time (low self-esteem causes consumption of sugary foods which disrupts sleep quality and contributes to obesity). The findings of such inquiries can aid in identifying the timing and specific targets of preventive interventions across and within developmental phases. The implications of such a cascade model of paediatric obesity for health psychology and developmental and prevention sciences are discussed.

Enhancement of optical Kerr effect in quantum-cascade lasers with multiple resonance levels.

PubMed

Bai, Jing; Citrin, D S

2008-08-18

In this paper, we investigated the optical Kerr lensing effect in quantum-cascade lasers with multiple resonance levels. The Kerr refractive index n2 is obtained through the third-order susceptibility at the fundamental frequency chi(3)( omega; omega, omega,-omega). Resonant two-photon processes are found to have almost equal contributions to chi(3)( omega; omega, omega,-omega) as the single-photon processes, which result in the predicted enhancement of the positive nonlinear (Kerr) refractive index, and thus may enhance mode-locking of quantum-cascade lasers. Moreover, we also demonstrate an isospectral optimization strategy for further improving n2 through the band-structure design, in order to boost the multimode performance of quantum-cascade lasers. Simulation results show that the optimized stepwise multiple-quantum-well structure has n2 approximately 10-8 cm2/W, a twofold enhancement over the original flat quantum-well structure. This leads to a refractive-index change (delta)n of about 0.01, which is at the upper bound of those reported for typical Kerr medium. This stronger Kerr refractive index may be important for quantum-cascade lasers ultimately to demonstrate self-mode-locking.

Search for Magnetically Broadened Cascade Emission from Blazars with VERITAS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Archambault, S.; Griffin, S.; Archer, A.

2017-02-01

We present a search for magnetically broadened gamma-ray emission around active galactic nuclei (AGNs), using VERITAS observations of seven hard-spectrum blazars. A cascade process occurs when multi-TeV gamma-rays from an AGN interact with extragalactic background light (EBL) photons to produce electron–positron pairs, which then interact with cosmic microwave background photons via inverse-Compton scattering to produce gamma-rays. Due to the deflection of the electron–positron pairs, a non-zero intergalactic magnetic field (IGMF) would potentially produce detectable effects on the angular distribution of the cascade emission. In particular, an angular broadening compared to the unscattered emission could occur. Through non-detection of angularly broadenedmore » emission from 1ES 1218+304, the source with the largest predicted cascade fraction, we exclude a range of IGMF strengths around 10{sup −14} G at the 95% confidence level. The extent of the exclusion range varies with the assumptions made about the intrinsic spectrum of 1ES 1218+304 and the EBL model used in the simulation of the cascade process. All of the sources are used to set limits on the flux due to extended emission.« less

Nicotiana benthamiana MAPK-WRKY pathway confers resistance to a necrotrophic pathogen Botrytis cinerea.

PubMed

Adachi, Hiroaki; Ishihama, Nobuaki; Nakano, Takaaki; Yoshioka, Miki; Yoshioka, Hirofumi

2016-06-02

MEK2-SIPK/WIPK cascade, a Nicotiana benthamiana mitogen-activated protein kinase (MAPK) cascade, is an essential signaling pathway for plant immunity and involved in hypersensitive response (HR) accompanied by cell death. WRKY transcription factors as substrates of SIPK and WIPK have been isolated and implicated in HR cell death. Here, we show virus-induced gene silencing of WRKY genes compromised constitutively active MEK2-triggered cell death in N. benthamiana leaves. In general, HR cell death enhances susceptibility to necrotrophic pathogens such as Botrytis cinerea. However, the WRKY gene silencing elevated susceptibility to B. cinerea. These findings suggest that downstream WRKYs of MEK2-SIPK/WIPK cascade are required for cell death-dependent and -independent immunities in N. benthamiana.

Disintegration of the agricultural by-product wheat bran under subcritical conditions.

PubMed

Reisinger, Michael; Tirpanalan, Özge; Pruksasri, Suwattana; Kneifel, Wolfgang; Novalin, Senad

2018-02-10

The disintegration of destarched wheat bran in water and sulfuric acid (pH 3) under subcritical conditions (275-300 °C) and at short reaction times (1-4 min) was investigated. A cascade process comprising a stepwise separation of the liquid was applied to reduce the formation of undesired degradation products. The highest degree of biomass disintegration (67% dry mass solubilization) was achieved by application of a cascade process at 275 °C (pH 3). Regarding the dissolution of carbohydrates (monomeric and oligomeric form), the total glucose yields remained below 60%, while the total xylose and arabinose yields were about 76% and 67%. Approximately 74% of the protein and 95% of the mineral fraction could be extracted. The application of the cascade process enabled a substantially reduced formation of degradation products. When operating hydrothermally and subcritically in order to avoid some problematic aspects of a biorefinery, an extensive disintegration and monomerization of wheat bran and its constituents remains difficult even under the tested conditions (300 °C, pH 3). However, the applied cascade process proved to be useful to increase the yields and to substantially reduce the formation of undesired degradation products. Despite this fact, increased water consumption has to be conceded. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Noise squeezing of fields that bichromatically excite atoms in a cavity.

PubMed

Li, Lingchao; Hu, Xiangming; Rao, Shi; Xu, Jun

2016-11-14

It is well known that bichromatic excitation on one common transition can tune the emission or absorption spectra of atoms due to the modulation frequency dependent non-linearities. However little attention has been focused on the quantum dynamics of fields under bichromatic excitation. Here we present dissipative effects on noise correlations of fields in bichromatic interactions with atoms in cavities. We first consider an ensemble of two-level atoms that interacts with the two cavity fields of different frequencies and considerable amplitudes. By transferring the atom-field nonlinearities to the dressed atoms we separate out the dissipative interactions of Bogoliubov modes with the dressed atoms. The Bogoliubov mode dissipation establishes stable two-photon processes of two involved fields and therefore leads to two-mode squeezing. As a generalization, we then consider an ensemble of three-level Λ atoms for cascade bichromatic interactions. We extract the Bogoliubov-like four-mode interactions, which establish a quadrilateral of the two-photon processes of four involved fields and thus result in four-mode squeezing.

Calcium and ROS: A mutual interplay

PubMed Central

Görlach, Agnes; Bertram, Katharina; Hudecova, Sona; Krizanova, Olga

2015-01-01

Calcium is an important second messenger involved in intra- and extracellular signaling cascades and plays an essential role in cell life and death decisions. The Ca2+ signaling network works in many different ways to regulate cellular processes that function over a wide dynamic range due to the action of buffers, pumps and exchangers on the plasma membrane as well as in internal stores. Calcium signaling pathways interact with other cellular signaling systems such as reactive oxygen species (ROS). Although initially considered to be potentially detrimental byproducts of aerobic metabolism, it is now clear that ROS generated in sub-toxic levels by different intracellular systems act as signaling molecules involved in various cellular processes including growth and cell death. Increasing evidence suggests a mutual interplay between calcium and ROS signaling systems which seems to have important implications for fine tuning cellular signaling networks. However, dysfunction in either of the systems might affect the other system thus potentiating harmful effects which might contribute to the pathogenesis of various disorders. PMID:26296072

Epithelial to mesenchymal transition inducing transcription factors and metastatic cancer.

PubMed

Tania, Mousumi; Khan, Md Asaduzzaman; Fu, Junjiang

2014-08-01

The epithelial to mesenchymal transition (EMT) is an important step for the developmental process. Recent evidences support that EMT allows the tumor cells to acquire invasive properties and to develop metastatic growth characteristics. Some of the transcription factors, which are actively involved in EMT process, have a significant role in the EMT-metastasis linkage. A number of studies have reported that EMT-inducing transcription factors (EMT-TFs), such as Twist, Snail, Slug, and Zeb, are directly or indirectly involved in cancer cell metastasis through a different signaling cascades, including the Akt, signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase (MAPK) and Wnt pathways, with the ultimate consequence of the downregulation of E-cadherin and upregulation of metastatic proteins, such as N-cadherin, vimentin, matrix metalloproteinase (MMP)-2, etc. This review summarizes the update information on the association of EMT-TFs with cancer metastasis and the possible cancer therapeutics via targeting the EMT-TFs.

Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL) Reveals the Sequential Differentiation of Sieve Element-Like Cells.

PubMed

Kondo, Yuki; Nurani, Alif Meem; Saito, Chieko; Ichihashi, Yasunori; Saito, Masato; Yamazaki, Kyoko; Mitsuda, Nobutaka; Ohme-Takagi, Masaru; Fukuda, Hiroo

2016-06-01

Cell differentiation is a complex process involving multiple steps, from initial cell fate specification to final differentiation. Procambial/cambial cells, which act as vascular stem cells, differentiate into both xylem and phloem cells during vascular development. Recent studies have identified regulatory cascades for xylem differentiation. However, the molecular mechanism underlying phloem differentiation is largely unexplored due to technical challenges. Here, we established an ectopic induction system for phloem differentiation named Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL). Our results verified similarities between VISUAL-induced Arabidopsis thaliana phloem cells and in vivo sieve elements. We performed network analysis using transcriptome data with VISUAL to dissect the processes underlying phloem differentiation, eventually identifying a factor involved in the regulation of the master transcription factor gene APL Thus, our culture system opens up new avenues not only for genetic studies of phloem differentiation, but also for future investigations of multidirectional differentiation from vascular stem cells. © 2016 American Society of Plant Biologists. All rights reserved.

PI3K{gamma} activation by CXCL12 regulates tumor cell adhesion and invasion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Monterrubio, Maria; Mellado, Mario; Carrera, Ana C.

Tumor dissemination is a complex process, in which certain steps resemble those in leukocyte homing. Specific chemokine/chemokine receptor pairs have important roles in both processes. CXCL12/CXCR4 is the most commonly expressed chemokine/chemokine receptor pair in human cancers, in which it regulates cell adhesion, extravasation, metastatic colonization, angiogenesis, and proliferation. All of these processes require activation of signaling pathways that include G proteins, phosphatidylinositol-3 kinase (PI3K), JAK kinases, Rho GTPases, and focal adhesion-associated proteins. We analyzed these pathways in a human melanoma cell line in response to CXCL12 stimulation, and found that PI3K{gamma} regulates tumor cell adhesion through mechanisms different frommore » those involved in cell invasion. Our data indicate that, following CXCR4 activation after CXCL12 binding, the invasion and adhesion processes are regulated differently by distinct downstream events in these signaling cascades.« less

Three-dimensional kinetic simulations of whistler turbulence in solar wind on parallel supercomputers

NASA Astrophysics Data System (ADS)

Chang, Ouliang

The objective of this dissertation is to study the physics of whistler turbulence evolution and its role in energy transport and dissipation in the solar wind plasmas through computational and theoretical investigations. This dissertation presents the first fully three-dimensional (3D) particle-in-cell (PIC) simulations of whistler turbulence forward cascade in a homogeneous, collisionless plasma with a uniform background magnetic field B o, and the first 3D PIC simulation of whistler turbulence with both forward and inverse cascades. Such computationally demanding research is made possible through the use of massively parallel, high performance electromagnetic PIC simulations on state-of-the-art supercomputers. Simulations are carried out to study characteristic properties of whistler turbulence under variable solar wind fluctuation amplitude (epsilon e) and electron beta (betae), relative contributions to energy dissipation and electron heating in whistler turbulence from the quasilinear scenario and the intermittency scenario, and whistler turbulence preferential cascading direction and wavevector anisotropy. The 3D simulations of whistler turbulence exhibit a forward cascade of fluctuations into broadband, anisotropic, turbulent spectrum at shorter wavelengths with wavevectors preferentially quasi-perpendicular to B o. The overall electron heating yields T ∥ > T⊥ for all epsilone and betae values, indicating the primary linear wave-particle interaction is Landau damping. But linear wave-particle interactions play a minor role in shaping the wavevector spectrum, whereas nonlinear wave-wave interactions are overall stronger and faster processes, and ultimately determine the wavevector anisotropy. Simulated magnetic energy spectra as function of wavenumber show a spectral break to steeper slopes, which scales as k⊥lambda e ≃ 1 independent of betae values, where lambdae is electron inertial length, qualitatively similar to solar wind observations. Specific spectral indices from simulated wavevector energy spectra do not match the frequency spectral indices from observations due to the inapplicability of Taylor's hypothesis. In contrast, the direct comparison of simulated frequency energy spectra and solar wind observations shows a closer similarity. Electron density fluctuations power spectra also exhibit a close similarity to solar wind observations and MHD predications, both qualitatively and quantitatively. Linear damping represents an intermediate fraction of the total dissipation of whistler turbulence over a wide range of betae and epsilone. The relative importance of linear damping by comparison to nonlinear dissipation increases with increasing beta e but decreases with increasing epsilone. Correlation coefficient calculations imply that the nonlinear dissipation processes in our simulation are primarily associated with dissipation in regions of intermittent current sheet structures. The simulation results suggest that whistler fluctuations could be the substantial constituent of solar wind turbulence at higher frequencies and short wavelengths, and support the magnetosonic-whistler interpretation of the quasilinear scenario. An even larger scale 3D whistler turbulence simulation exhibits both a forward cascade to shorter wavelengths with wavevectors preferentially k⊥ > k∥, and an inverse cascade to longer wavelengths with wavevectors k ≳ k⊥. The inverse cascade process is primarily driven by the nonlinear wave-wave interaction. It is shown that the energy inverse cascade rate is similar to the energy forward cascade rate at early times although the overall energy in the two cascades is very different. The presence of inverse cascade process does not affect qualitative conclusions established from the whistler turbulence forward cascade simulations.

A Noninvasive In Vivo Glucose Sensor Based on Mid-Infrared Quantum Cascade Laser Spectroscopy

NASA Astrophysics Data System (ADS)

Werth, Alexandra; Liakat, Sabbir; Xu, Laura; Gmachl, Claire

Diabetes affects over 387 million people worldwide; a number which grows every year. The most common method of measuring blood glucose concentration involves a finger prick which for some can be a harrowing process. Therefore, a portable, accurate, noninvasive glucose sensor can significantly improve the quality of life for many of these diabetics who draw blood multiple times a day to monitor their glucose levels. We have implemented a noninvasive, mobile glucose sensor using a mid-infrared (MIR) quantum cascade laser (QCL), integrating sphere, and thermal electrically (TE) cooled detector. The QCL is scanned from 8 - 10 microns wavelength over which are distinct absorption features of glucose molecules with little competition of absorption from other molecules found in the blood and interstitial fluid. The obtained absorption spectra are analyzed using a neural network algorithm which relates the small changes in absorption to the changing glucose concentration. The integrating sphere has increased the signal-to-noise ratio from a previous design, allowing us to use the TE-cooled detector which increases mobility without loss of accuracy.

Proteomics in investigation of cancer metastasis: functional and clinical consequences and methodological challenges.

PubMed

Maryáš, Josef; Faktor, Jakub; Dvořáková, Monika; Struhárová, Iva; Grell, Peter; Bouchal, Pavel

2014-03-01

Metastases are responsible for most of the cases of death in patients with solid tumors. There is thus an urgent clinical need of better understanding the exact molecular mechanisms and finding novel therapeutics targets and biomarkers of metastatic disease of various tumors. Metastases are formed in a complicated biological process called metastatic cascade. Up to now, proteomics has enabled the identification of number of metastasis-associated proteins and potential biomarkers in cancer tissues, microdissected cells, model systems, and secretomes. Expression profiles and biological role of key proteins were confirmed in verification and functional experiments. This communication reviews these observations and analyses the methodological aspects of the proteomics approaches used. Moreover, it reviews contribution of current proteomics in the field of functional characterization and interactome analysis of proteins involved in various events in metastatic cascade. It is evident that ongoing technical progress will further increase proteome coverage and sample capacity of proteomics technologies, giving complex answers to clinical and functional questions asked. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Network interactions: non-geniculate input to V1.

PubMed

Muckli, Lars; Petro, Lucy S

2013-04-01

The strongest connections to V1 are fed back from neighbouring area V2 and from a network of higher cortical areas (e.g. V3, V5, LOC, IPS and A1), transmitting the results of cognitive operations such as prediction, attention and imagination. V1 is therefore at the receiving end of a complex cortical processing cascade and not only at the entrance stage of cortical processing of retinal input. One elegant strategy to investigate this information-rich feedback to V1 is to eliminate feedforward input, that is, exploit V1's retinotopic organisation to isolate subregions receiving no direct bottom-up stimulation. We highlight the diverse mechanisms of cortical feedback, ranging from gain control to predictive coding, and conclude that V1 is involved in rich internal communication processes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of collision cascade density on radiation defect dynamics in 3C-SiC

PubMed Central

Bayu Aji, L. B.; Wallace, J. B.; Kucheyev, S. O.

2017-01-01

Effects of the collision cascade density on radiation damage in SiC remain poorly understood. Here, we study damage buildup and defect interaction dynamics in 3C-SiC bombarded at 100 °C with either continuous or pulsed beams of 500 keV Ne, Ar, Kr, or Xe ions. We find that bombardment with heavier ions, which create denser collision cascades, results in a decrease in the dynamic annealing efficiency and an increase in both the amorphization cross-section constant and the time constant of dynamic annealing. The cascade density behavior of these parameters is non-linear and appears to be uncorrelated. These results demonstrate clearly (and quantitatively) an important role of the collision cascade density in dynamic radiation defect processes in 3C-SiC. PMID:28304397

Effects of collision cascade density on radiation defect dynamics in 3C-SiC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bayu Aji, L. B.; Wallace, J. B.; Kucheyev, S. O.

Effects of the collision cascade density on radiation damage in SiC remain poorly understood. We study damage buildup and defect interaction dynamics in 3C-SiC bombarded at 100 °C with either continuous or pulsed beams of 500 keV Ne, Ar, Kr, or Xe ions. Here, we find that bombardment with heavier ions, which create denser collision cascades, results in a decrease in the dynamic annealing efficiency and an increase in both the amorphization cross-section constant and the time constant of dynamic annealing. The cascade density behavior of these parameters is non-linear and appears to be uncorrelated. Our results demonstrate clearly (andmore » quantitatively) an important role of the collision cascade density in dynamic radiation defect processes in 3C-SiC.« less

Displacement Cascade Damage Production in Metals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoller, Roger E; Malerba, Lorenzo; Nordlund, Kai

Radiation-induced changes in microstructure and mechanical properties in structural materials are the result of a complex set of physical processes initiated by the collision between an energetic particle (neutron or ion) and an atom in the lattice. This primary damage event is called an atomic displacement cascade. The simplest description of a displacement cascade is to view it as a series of many billiard-ball-like elastic collisions among the atoms in the material. This chapter describes the formation and evolution of this primary radiation damage mechanism to provide an overview of how stable defects are formed by displacement cascades, as wellmore » as the nature and morphology of the defects themselves. The impact of the relevant variables such as cascade energy and irradiation temperature is discussed, and defect formation in different materials is compared.« less

Effects of collision cascade density on radiation defect dynamics in 3C-SiC

DOE PAGES

Bayu Aji, L. B.; Wallace, J. B.; Kucheyev, S. O.

2017-03-17

Effects of the collision cascade density on radiation damage in SiC remain poorly understood. We study damage buildup and defect interaction dynamics in 3C-SiC bombarded at 100 °C with either continuous or pulsed beams of 500 keV Ne, Ar, Kr, or Xe ions. Here, we find that bombardment with heavier ions, which create denser collision cascades, results in a decrease in the dynamic annealing efficiency and an increase in both the amorphization cross-section constant and the time constant of dynamic annealing. The cascade density behavior of these parameters is non-linear and appears to be uncorrelated. Our results demonstrate clearly (andmore » quantitatively) an important role of the collision cascade density in dynamic radiation defect processes in 3C-SiC.« less

Mechanotransductive cascade of Myo-II-dependent mesoderm and endoderm invaginations in embryo gastrulation

PubMed Central

Mitrossilis, Démosthène; Röper, Jens-Christian; Le Roy, Damien; Driquez, Benjamin; Michel, Aude; Ménager, Christine; Shaw, Gorky; Le Denmat, Simon; Ranno, Laurent; Dumas-Bouchiat, Frédéric; Dempsey, Nora M.; Farge, Emmanuel

2017-01-01

Animal development consists of a cascade of tissue differentiation and shape change. Associated mechanical signals regulate tissue differentiation. Here we demonstrate that endogenous mechanical cues also trigger biochemical pathways, generating the active morphogenetic movements shaping animal development through a mechanotransductive cascade of Myo-II medio-apical stabilization. To mimic physiological tissue deformation with a cell scale resolution, liposomes containing magnetic nanoparticles are injected into embryonic epithelia and submitted to time-variable forces generated by a linear array of micrometric soft magnets. Periodic magnetically induced deformations quantitatively phenocopy the soft mechanical endogenous snail-dependent apex pulsations, rescue the medio-apical accumulation of Rok, Myo-II and subsequent mesoderm invagination lacking in sna mutants, in a Fog-dependent mechanotransductive process. Mesoderm invagination then activates Myo-II apical accumulation, in a similar Fog-dependent mechanotransductive process, which in turn initiates endoderm invagination. This reveals the existence of a highly dynamic self-inductive cascade of mesoderm and endoderm invaginations, regulated by mechano-induced medio-apical stabilization of Myo-II. PMID:28112149

Mechanotransductive cascade of Myo-II-dependent mesoderm and endoderm invaginations in embryo gastrulation

NASA Astrophysics Data System (ADS)

Mitrossilis, Démosthène; Röper, Jens-Christian; Le Roy, Damien; Driquez, Benjamin; Michel, Aude; Ménager, Christine; Shaw, Gorky; Le Denmat, Simon; Ranno, Laurent; Dumas-Bouchiat, Frédéric; Dempsey, Nora M.; Farge, Emmanuel

2017-01-01

Animal development consists of a cascade of tissue differentiation and shape change. Associated mechanical signals regulate tissue differentiation. Here we demonstrate that endogenous mechanical cues also trigger biochemical pathways, generating the active morphogenetic movements shaping animal development through a mechanotransductive cascade of Myo-II medio-apical stabilization. To mimic physiological tissue deformation with a cell scale resolution, liposomes containing magnetic nanoparticles are injected into embryonic epithelia and submitted to time-variable forces generated by a linear array of micrometric soft magnets. Periodic magnetically induced deformations quantitatively phenocopy the soft mechanical endogenous snail-dependent apex pulsations, rescue the medio-apical accumulation of Rok, Myo-II and subsequent mesoderm invagination lacking in sna mutants, in a Fog-dependent mechanotransductive process. Mesoderm invagination then activates Myo-II apical accumulation, in a similar Fog-dependent mechanotransductive process, which in turn initiates endoderm invagination. This reveals the existence of a highly dynamic self-inductive cascade of mesoderm and endoderm invaginations, regulated by mechano-induced medio-apical stabilization of Myo-II.

A cascade feedback control approach for hypnosis.

PubMed

Puebla, Hector; Alvarez-Ramírez, José

2005-10-01

This article studies the problem of controlling the drug administration during an anesthesia process, where muscle relaxation, analgesia, and hypnosis are regulated by means of monitored administration of specific drugs. On the basis of a seventh-order nonlinear pharmacokinetic-pharmacodynamic representation of the hypnosis process dynamics, a cascade (master/slave) feedback control structure for controlling the bispectral index (BIS) is proposed. The master controller compares the measured BIS with its reference value to provide the expired isoflurane concentration reference to the slave controller. In turn, the slave controller manipulates the anesthetic isoflurane concentration entering the anesthetic system to achieve the reference from the master controller. The advantage of the proposed cascade control structure with respect to its noncascade counterpart is that the former provides operation protection against BIS measurement failures. In fact, under a BIS measurement fault, the master control feedback is broken and the slave controller operates under a safe reference value. Extensive numerical simulations are used to illustrate the functioning of the proposed cascade control structure.

Physical Exercise Modulates L-DOPA-Regulated Molecular Pathways in the MPTP Mouse Model of Parkinson's Disease.

PubMed

Klemann, Cornelius J H M; Xicoy, Helena; Poelmans, Geert; Bloem, Bas R; Martens, Gerard J M; Visser, Jasper E

2018-07-01

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), resulting in motor and non-motor dysfunction. Physical exercise improves these symptoms in PD patients. To explore the molecular mechanisms underlying the beneficial effects of physical exercise, we exposed 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine (MPTP)-treated mice to a four-week physical exercise regimen, and subsequently explored their motor performance and the transcriptome of multiple PD-linked brain areas. MPTP reduced the number of DA neurons in the SNpc, whereas physical exercise improved beam walking, rotarod performance, and motor behavior in the open field. Further, enrichment analyses of the RNA-sequencing data revealed that in the MPTP-treated mice physical exercise predominantly modulated signaling cascades that are regulated by the top upstream regulators L-DOPA, RICTOR, CREB1, or bicuculline/dalfampridine, associated with movement disorders, mitochondrial dysfunction, and epilepsy-related processes. To elucidate the molecular pathways underlying these cascades, we integrated the proteins encoded by the exercise-induced differentially expressed mRNAs for each of the upstream regulators into a molecular landscape, for multiple key brain areas. Most notable was the opposite effect of physical exercise compared to previously reported effects of L-DOPA on the expression of mRNAs in the SN and the ventromedial striatum that are involved in-among other processes-circadian rhythm and signaling involving DA, neuropeptides, and endocannabinoids. Altogether, our findings suggest that physical exercise can improve motor function in PD and may, at the same time, counteract L-DOPA-mediated molecular mechanisms. Further, we hypothesize that physical exercise has the potential to improve non-motor symptoms of PD, some of which may be the result of (chronic) L-DOPA use.

Bears benefit plants via a cascade with both antagonistic and mutualistic interactions.

PubMed

Grinath, Joshua B; Inouye, Brian D; Underwood, Nora

2015-02-01

Predators can influence primary producers by generating cascades of effects in ecological webs. These effects are often non-intuitive, going undetected because they involve many links and different types of species interactions. Particularly, little is understood about how antagonistic (negative) and mutualistic (positive) interactions combine to create cascades. Here, we show that black bears can benefit plants by consuming ants. The ants are mutualists of herbivores and protect herbivores from other arthropod predators. We found that plants near bear-damaged ant nests had greater reproduction than those near undamaged nests, due to weaker ant protection for herbivores, which allowed herbivore suppression by arthropod predators. Our results highlight the need to integrate mutualisms into trophic cascade theory, which is based primarily on antagonistic relationships. Predators are often conservation targets, and our results suggest that bears and other predators should be managed with the understanding that they can influence primary producers through many paths. © 2014 John Wiley & Sons Ltd/CNRS.

On the investigation of cascade and turbomachinery rotor wake characteristics

NASA Technical Reports Server (NTRS)

Raj, R.; Lakshminarayana, B.

1975-01-01

The objective of the investigation reported in this thesis is to study the characteristics of a turbomachinery rotor wake, both analytically and experimentally. The constitutive equations for the rotor wake are developed using generalized tensors and a non-inertial frame of reference. Analytical and experimental investigation is carried out in two phases; the first phase involved the study of a cascade wake in the absence of rotation and three dimensionality. In the second phase the wake of a rotor is studied. Simplified two- and three-dimensional models are developed for the prediction of the mean velocity profile of the cascade and the rotor wake, respectively, using the principle of self-similarity. The effect of various major parameters of the rotor and the flow geometry is studied on the development of a rotor wake. Laws governing the decay of the wake velocity defect in a cascade and rotor wake as a function of downstream distance from the trailing edge, pressure gradient and other parameters are derived.

RNase MRP and the RNA processing cascade in the eukaryotic ancestor.

PubMed

Woodhams, Michael D; Stadler, Peter F; Penny, David; Collins, Lesley J

2007-02-08

Within eukaryotes there is a complex cascade of RNA-based macromolecules that process other RNA molecules, especially mRNA, tRNA and rRNA. An example is RNase MRP processing ribosomal RNA (rRNA) in ribosome biogenesis. One hypothesis is that this complexity was present early in eukaryotic evolution; an alternative is that an initial simpler network later gained complexity by gene duplication in lineages that led to animals, fungi and plants. Recently there has been a rapid increase in support for the complexity-early theory because the vast majority of these RNA-processing reactions are found throughout eukaryotes, and thus were likely to be present in the last common ancestor of living eukaryotes, herein called the Eukaryotic Ancestor. We present an overview of the RNA processing cascade in the Eukaryotic Ancestor and investigate in particular, RNase MRP which was previously thought to have evolved later in eukaryotes due to its apparent limited distribution in fungi and animals and plants. Recent publications, as well as our own genomic searches, find previously unknown RNase MRP RNAs, indicating that RNase MRP has a wide distribution in eukaryotes. Combining secondary structure and promoter region analysis of RNAs for RNase MRP, along with analysis of the target substrate (rRNA), allows us to discuss this distribution in the light of eukaryotic evolution. We conclude that RNase MRP can now be placed in the RNA-processing cascade of the Eukaryotic Ancestor, highlighting the complexity of RNA-processing in early eukaryotes. Promoter analyses of MRP-RNA suggest that regulation of the critical processes of rRNA cleavage can vary, showing that even these key cellular processes (for which we expect high conservation) show some species-specific variability. We present our consensus MRP-RNA secondary structure as a useful model for further searches.

A cascading failure analysis tool for post processing TRANSCARE simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

This is a MATLAB-based tool to post process simulation results in the EPRI software TRANSCARE, for massive cascading failure analysis following severe disturbances. There are a few key modules available in this tool, including: 1. automatically creating a contingency list to run TRANSCARE simulations, including substation outages above a certain kV threshold, N-k (1, 2 or 3) generator outages and branche outages; 2. read in and analyze a CKO file of PCG definition, an initiating event list, and a CDN file; 3. post process all the simulation results saved in a CDN file and perform critical event corridor analysis; 4.more » provide a summary of TRANSCARE simulations; 5. Identify the most frequently occurring event corridors in the system; and 6. Rank the contingencies using a user defined security index to quantify consequences in terms of total load loss, total number of cascades, etc.« less

Microwave-Assisted γ-Valerolactone Production for Biomass Lignin Extraction: A Cascade Protocol.

PubMed

Tabasso, Silvia; Grillo, Giorgio; Carnaroglio, Diego; Calcio Gaudino, Emanuela; Cravotto, Giancarlo

2016-03-26

The general need to slow the depletion of fossil resources and reduce carbon footprints has led to tremendous effort being invested in creating "greener" industrial processes and developing alternative means to produce fuels and synthesize platform chemicals. This work aims to design a microwave-assisted cascade process for a full biomass valorisation cycle. GVL (γ-valerolactone), a renewable green solvent, has been used in aqueous acidic solution to achieve complete biomass lignin extraction. After lignin precipitation, the levulinic acid (LA)-rich organic fraction was hydrogenated, which regenerated the starting solvent for further biomass delignification. This process does not requires a purification step because GVL plays the dual role of solvent and product, while the reagent (LA) is a product of biomass delignification. In summary, this bio-refinery approach to lignin extraction is a cascade protocol in which the solvent loss is integrated into the conversion cycle, leading to simplified methods for biomass valorisation.

Cascaded VLSI Chips Help Neural Network To Learn

NASA Technical Reports Server (NTRS)

Duong, Tuan A.; Daud, Taher; Thakoor, Anilkumar P.

1993-01-01

Cascading provides 12-bit resolution needed for learning. Using conventional silicon chip fabrication technology of VLSI, fully connected architecture consisting of 32 wide-range, variable gain, sigmoidal neurons along one diagonal and 7-bit resolution, electrically programmable, synaptic 32 x 31 weight matrix implemented on neuron-synapse chip. To increase weight nominally from 7 to 13 bits, synapses on chip individually cascaded with respective synapses on another 32 x 32 matrix chip with 7-bit resolution synapses only (without neurons). Cascade correlation algorithm varies number of layers effectively connected into network; adds hidden layers one at a time during learning process in such way as to optimize overall number of neurons and complexity and configuration of network.

Delivery Of Cascade Screening For Hereditary Conditions: A Scoping Review Of The Literature.

PubMed

Roberts, Megan C; Dotson, W David; DeVore, Christopher S; Bednar, Erica M; Bowen, Deborah J; Ganiats, Theodore G; Green, Ridgely Fisk; Hurst, Georgia M; Philp, Alisdair R; Ricker, Charité N; Sturm, Amy C; Trepanier, Angela M; Williams, Janet L; Zierhut, Heather A; Wilemon, Katherine A; Hampel, Heather

2018-05-01

Cascade screening is the process of contacting relatives of people who have been diagnosed with certain hereditary conditions. Its purpose is to identify, inform, and manage those who are also at risk. We conducted a scoping review to obtain a broad overview of cascade screening interventions, facilitators and barriers to their use, relevant policy considerations, and future research needs. We searched for relevant peer-reviewed literature in the period 1990-2017 and reviewed 122 studies. Finally, we described 45 statutes and regulations related to the use and release of genetic information across the fifty states. We sought standardized best practices for optimizing cascade screening across various geographic and policy contexts, but we found none. Studies in which trained providers contacted relatives directly, rather than through probands (index patients), showed greater cascade screening uptake; however, policies in some states might limit this approach. Major barriers to cascade screening delivery include suboptimal communication between the proband and family and geographic barriers to obtaining genetic services. Few US studies examined interventions for cascade screening or used rigorous study designs such as randomized controlled trials. Moving forward, there remains an urgent need to conduct rigorous intervention studies on cascade screening in diverse US populations, while accounting for state policy considerations.

Evidence of a Pivotal Role for the Distal Part of the Complement Cascade in the Diurnal Release of Hematopoietic Stem Cells Into Peripheral Blood.

PubMed

Borkowska, Sylwia; Suszynska, Malwina; Ratajczak, Janina; Ratajczak, Mariusz Z

2016-01-01

We found that diurnal activation of the three evolutionarily ancient proteolytic cascades in peripheral blood (PB), namely, the complement, coagulation, and fibrinolytic cascades, late at night or in the early morning hours, precedes the diurnal release of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM) into PB in wild-type mice. Moreover, activation of the distal part of the complement cascade (ComC), involving cleavage of the fifth component (C5), seems to play a crucial role in pharmacological mobilization of HSPCs. In order to shed more light on the role of diurnal rhythms in the egress of HSPCs, we studied diurnal changes in the number of circulating HSPCs in C5-deficient mice and did not observe diurnal changes in the number of these cells circulating in PB in C5(-/-) animals. Based on this finding, we conclude that activation of the distal part of the ComC, C5 cleavage, and release of C5a and desArgC5a are required in executing the diurnal release of HSPCs from BM into PB. Moreover, the fact that C5(-/-) mice still displayed normal activation of the coagulation and fibrinolytic cascades indicates that, of all the proteolytic cascades, the ComC is the dominant player regulating diurnal egress of HSPCs.

Cascade rainfall disaggregation application in U.S. Central Plains

USDA-ARS?s Scientific Manuscript database

Hourly rainfall are increasingly used in complex, process-based simulations of the environment. Long records of daily rainfall are common, but long continuous records of hourly rainfall are rare and must be developed. A Multiplicative Random Cascade (MRC) model is proposed to disaggregate observed d...

Systems and Cascades in Cognitive Development and Academic Achievement

ERIC Educational Resources Information Center

Bornstein, Marc H.; Hahn, Chun-Shin; Wolke, Dieter

2013-01-01

A large-scale ("N" = 552) controlled multivariate prospective 14-year longitudinal study of a developmental cascade embedded in a developmental system showed that information-processing efficiency in infancy (4 months), general mental development in toddlerhood (18 months), behavior difficulties in early childhood (36 months),…

The Interaction between Central and Peripheral Processing in Chinese Handwritten Production: Evidence from the Effect of Lexicality and Radical Complexity

PubMed Central

Zhang, Qingfang; Feng, Chen

2017-01-01

The interaction between central and peripheral processing in written word production remains controversial. This study aims to investigate whether the effects of radical complexity and lexicality in central processing cascade into peripheral processing in Chinese written word production. The participants were asked to write characters and non-characters (lexicality) with different radical complexity (few- and many-strokes). The findings indicated that regardless of the lexicality, the writing latencies were longer for characters with higher complexity (the many-strokes condition) than for characters with lower complexity (the few-strokes condition). The participants slowed down their writing execution at the radicals' boundary strokes, which indicated a radical boundary effect in peripheral processing. Interestingly, the lexicality and the radical complexity affected the pattern of shift velocity and writing velocity during the execution of writing. Lexical processing cascades into peripheral processing but only at the beginning of Chinese characters. In contrast, the radical complexity influenced the execution of handwriting movement throughout the entire character, and the pattern of the effect interacted with the character frequency. These results suggest that the processes of the lexicality and the radical complexity function during the execution of handwritten word production, which suggests that central processing cascades over peripheral processing during Chinese characters handwriting. PMID:28348536

Energy efficient engine: Low-pressure turbine subsonic cascade component development and integration program

NASA Technical Reports Server (NTRS)

Sharma, O. P.; Kopper, F. C.; Knudsen, L. K.; Yustinich, J. B.

1982-01-01

A subsonic cascade test program was conducted to provide technical data for optimizing the blade and vane airfoil designs for the Energy Efficient Engine Low-Pressure Turbine component. The program consisted of three parts. The first involved an evaluation of the low-chamber inlet guide vane. The second, was an evaluation of two candidate aerodynamic loading philosophies for the fourth blade root section. The third part consisted of an evaluation of three candidate airfoil geometries for the fourth blade mean section. The performance of each candidate airfoil was evaluated in a linear cascade configuration. The overall results of this study indicate that the aft-loaded airfoil designs resulted in lower losses which substantiated Pratt & Whitney Aircraft's design philosophy for the Energy Efficient Engine low-pressure turbine component.

Coordination of Gene Expression of Arachidonic and Docosahexaenoic Acid Cascade Enzymes during Human Brain Development and Aging

PubMed Central

Ryan, Veronica H.; Primiani, Christopher T.; Rao, Jagadeesh S.; Ahn, Kwangmi; Rapoport, Stanley I.; Blanchard, Helene

2014-01-01

Background The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA) participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades. Hypothesis AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging. Methods The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism. Results Expression patterns were split into Development (0 to 20 years) and Aging (21 to 78 years) intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2), cyclooxygenases (COX)-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA) and PTGS2 (COX-2) genes at 1q25, highly inter-correlated genes were at distant chromosomal loci. Conclusions Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease. PMID:24963629

[Impacts of hydroelectric cascade exploitation on river ecosystem and landscape: a review].

PubMed

Yang, Kun; Deng, Xi; Li, Xue-Ling; Wen, Ping

2011-05-01

Hydroelectric cascade exploitation, one of the major ways for exploiting water resources and developing hydropower, not only satisfies the needs of various national economic sectors, but also promotes the socio-economic sustainable development of river basin. unavoidable anthropogenic impacts on the entire basin ecosystem. Based on the process of hydroelectric cascade exploitation and the ecological characteristics of river basins, this paper reviewed the major impacts of hydroelectric cascade exploitation on dam-area ecosystems, river reservoirs micro-climate, riparian ecosystems, river aquatic ecosystems, wetlands, and river landscapes. Some prospects for future research were offered, e.g., strengthening the research of chain reactions and cumulative effects of ecological factors affected by hydroelectric cascade exploitation, intensifying the study of positive and negative ecological effects under the dam networks and their joint operations, and improving the research of successional development and stability of basin ecosystems at different temporal and spatial scales.

Phosphate Flow between Hybrid Histidine Kinases CheA3 and CheS3 Controls Rhodospirillum centenum Cyst Formation

PubMed Central

He, Kuang; Marden, Jeremiah N.; Quardokus, Ellen M.; Bauer, Carl E.

2013-01-01

Genomic and genetic analyses have demonstrated that many species contain multiple chemotaxis-like signal transduction cascades that likely control processes other than chemotaxis. The Che3 signal transduction cascade from Rhodospirillum centenum is one such example that regulates development of dormant cysts. This Che-like cascade contains two hybrid response regulator-histidine kinases, CheA3 and CheS3, and a single-domain response regulator CheY3. We demonstrate that cheS3 is epistatic to cheA3 and that only CheS3∼P can phosphorylate CheY3. We further show that CheA3 derepresses cyst formation by phosphorylating a CheS3 receiver domain. These results demonstrate that the flow of phosphate as defined by the paradigm E. coli chemotaxis cascade does not necessarily hold true for non-chemotactic Che-like signal transduction cascades. PMID:24367276

SPATIAL FOREST SOIL PROPERTIES FOR ECOLOGICAL MODELING IN THE WESTERN OREGON CASCADES

EPA Science Inventory

The ultimate objective of this work is to provide a spatially distributed database of soil properties to serve as inputs to model ecological processes in western forests at the landscape scale. The Central Western Oregon Cascades are rich in biodiversity and they are a fascinati...

Recovery of African wild dogs suppresses prey but does not trigger a trophic cascade

USDA-ARS?s Scientific Manuscript database

Large carnivores can powerfully shape ecosystems by directly suppressing herbivores, thereby indirectly benefitting plants in a process known as a trophic cascade. In 2002, after a 20-year absence, African wild dogs (Lycaon pictus) recolonized the Laikipia Plateau in central Kenya. We hypothesized t...

Electrically Tunable Terahertz Quantum-Cascade Lasers

NASA Technical Reports Server (NTRS)

Gunapala, Sarath; Soidel, Alexander; Mansour, Kamjou

2006-01-01

Improved quantum-cascade lasers (QCLs) are being developed as electrically tunable sources of radiation in the far infrared spectral region, especially in the frequency range of 2 to 5 THz. The structures of QCLs and the processes used to fabricate them have much in common with those of multiple- quantum-well infrared photodetectors.

Laser Doppler, velocimeter system for turbine stator cascade studies and analysis of statistical biasing errors

NASA Technical Reports Server (NTRS)

Seasholtz, R. G.

1977-01-01

A laser Doppler velocimeter (LDV) built for use in the Lewis Research Center's turbine stator cascade facilities is described. The signal processing and self contained data processing are based on a computing counter. A procedure is given for mode matching the laser to the probe volume. An analysis is presented of biasing errors that were observed in turbulent flow when the mean flow was not normal to the fringes.

Coupling Poisson rectangular pulse and multiplicative microcanonical random cascade models to generate sub-daily precipitation timeseries

NASA Astrophysics Data System (ADS)

Pohle, Ina; Niebisch, Michael; Müller, Hannes; Schümberg, Sabine; Zha, Tingting; Maurer, Thomas; Hinz, Christoph

2018-07-01

To simulate the impacts of within-storm rainfall variabilities on fast hydrological processes, long precipitation time series with high temporal resolution are required. Due to limited availability of observed data such time series are typically obtained from stochastic models. However, most existing rainfall models are limited in their ability to conserve rainfall event statistics which are relevant for hydrological processes. Poisson rectangular pulse models are widely applied to generate long time series of alternating precipitation events durations and mean intensities as well as interstorm period durations. Multiplicative microcanonical random cascade (MRC) models are used to disaggregate precipitation time series from coarse to fine temporal resolution. To overcome the inconsistencies between the temporal structure of the Poisson rectangular pulse model and the MRC model, we developed a new coupling approach by introducing two modifications to the MRC model. These modifications comprise (a) a modified cascade model ("constrained cascade") which preserves the event durations generated by the Poisson rectangular model by constraining the first and last interval of a precipitation event to contain precipitation and (b) continuous sigmoid functions of the multiplicative weights to consider the scale-dependency in the disaggregation of precipitation events of different durations. The constrained cascade model was evaluated in its ability to disaggregate observed precipitation events in comparison to existing MRC models. For that, we used a 20-year record of hourly precipitation at six stations across Germany. The constrained cascade model showed a pronounced better agreement with the observed data in terms of both the temporal pattern of the precipitation time series (e.g. the dry and wet spell durations and autocorrelations) and event characteristics (e.g. intra-event intermittency and intensity fluctuation within events). The constrained cascade model also slightly outperformed the other MRC models with respect to the intensity-frequency relationship. To assess the performance of the coupled Poisson rectangular pulse and constrained cascade model, precipitation events were stochastically generated by the Poisson rectangular pulse model and then disaggregated by the constrained cascade model. We found that the coupled model performs satisfactorily in terms of the temporal pattern of the precipitation time series, event characteristics and the intensity-frequency relationship.

A Comparative Analysis of Phase-Change Wastewater Processing Approaches for Microgravity

NASA Technical Reports Server (NTRS)

Lange, Kevin

2016-01-01

Two phase-change wastewater processing candidates, the ISS Vapor Compression Distillation (VCD) System and the Cascade Distiller System (CDS), are compared based on dynamic modeling of both technologies. Differences in fluid handling and energy recovery for the technologies are described and contrasted. Model predictions are presented showing how temperatures, pressures, and compositions vary locally within each distiller. These dynamic variations are difficult to observe experimentally and have implications regarding non-condensable buildup and salt precipitation potential. Alternative architectures involving VCD and CDS components are analyzed in terms of predicted performance and equivalent system mass (ESM). The addition of a downstream brine processor to increase water recovery is also evaluated. Options for reducing overall ESM are discussed, including the possibility of developing a single precipitation-tolerant primary wastewater processor.

Role of advanced glycation end products in cellular signaling☆

PubMed Central

Ott, Christiane; Jacobs, Kathleen; Haucke, Elisa; Navarrete Santos, Anne; Grune, Tilman; Simm, Andreas

2014-01-01

Improvements in health care and lifestyle have led to an elevated lifespan and increased focus on age-associated diseases, such as neurodegeneration, cardiovascular disease, frailty and arteriosclerosis. In all these chronic diseases protein, lipid or nucleic acid modifications are involved, including cross-linked and non-degradable aggregates, such as advanced glycation end products (AGEs). Formation of endogenous or uptake of dietary AGEs can lead to further protein modifications and activation of several inflammatory signaling pathways. This review will give an overview of the most prominent AGE-mediated signaling cascades, AGE receptor interactions, prevention of AGE formation and the impact of AGEs during pathophysiological processes. PMID:24624331

MEK5-ERK5 Signaling in Cancer: Implications for Targeted Therapy

PubMed Central

Hoang, Van T.; Yan, Thomas J.; Cavanaugh, Jane E.; Flaherty, Patrick T.; Beckman, Barbara S.; Burow, Matthew E.

2017-01-01

Mitogen-activated protein kinases (MAPKs) regulate diverse cellular processes including proliferation, cell survival, differentiation, and apoptosis. While conventional MAPK constituents have well-defined roles in oncogenesis, the MAPK kinase 5-extracellular signal-regulated kinase 5 (MEK5-ERK5) pathway has only recently emerged in cancer research. In this review, we consider the MEK5 signaling cascade, focusing specifically on its involvement in drug resistance and regulation of aggressive cancer phenotypes. Moreover, we explore the role of MEK5 in tumorigenesis and metastatic progression, discussing the discrepancies in preclinical studies and assessing its viability as a therapeutic target for anti-cancer agents. PMID:28153789

MAP kinase pathways in the yeast Saccharomyces cerevisiae

NASA Technical Reports Server (NTRS)

Gustin, M. C.; Albertyn, J.; Alexander, M.; Davenport, K.; McIntire, L. V. (Principal Investigator)

1998-01-01

A cascade of three protein kinases known as a mitogen-activated protein kinase (MAPK) cascade is commonly found as part of the signaling pathways in eukaryotic cells. Almost two decades of genetic and biochemical experimentation plus the recently completed DNA sequence of the Saccharomyces cerevisiae genome have revealed just five functionally distinct MAPK cascades in this yeast. Sexual conjugation, cell growth, and adaptation to stress, for example, all require MAPK-mediated cellular responses. A primary function of these cascades appears to be the regulation of gene expression in response to extracellular signals or as part of specific developmental processes. In addition, the MAPK cascades often appear to regulate the cell cycle and vice versa. Despite the success of the gene hunter era in revealing these pathways, there are still many significant gaps in our knowledge of the molecular mechanisms for activation of these cascades and how the cascades regulate cell function. For example, comparison of different yeast signaling pathways reveals a surprising variety of different types of upstream signaling proteins that function to activate a MAPK cascade, yet how the upstream proteins actually activate the cascade remains unclear. We also know that the yeast MAPK pathways regulate each other and interact with other signaling pathways to produce a coordinated pattern of gene expression, but the molecular mechanisms of this cross talk are poorly understood. This review is therefore an attempt to present the current knowledge of MAPK pathways in yeast and some directions for future research in this area.

Single-photon frequency conversion via cascaded quadratic nonlinear processes

NASA Astrophysics Data System (ADS)

Xiang, Tong; Sun, Qi-Chao; Li, Yuanhua; Zheng, Yuanlin; Chen, Xianfeng

2018-06-01

Frequency conversion of single photons is an important technology for quantum interface and quantum communication networks. Here, single-photon frequency conversion in the telecommunication band is experimentally demonstrated via cascaded quadratic nonlinear processes. Using cascaded quasi-phase-matched sum and difference frequency generation in a periodically poled lithium niobate waveguide, the signal photon of a photon pair from spontaneous down-conversion is precisely shifted to identically match its counterpart, i.e., the idler photon, in frequency to manifest a clear nonclassical dip in the Hong-Ou-Mandel interference. Moreover, quantum entanglement between the photon pair is maintained after the frequency conversion, as is proved in time-energy entanglement measurement. The scheme is used to switch single photons between dense wavelength-division multiplexing channels, which holds great promise in applications in realistic quantum networks.

Influence of uncertainties of isotopic composition of the reprocessed uranium on effectiveness of its enrichment in gas centrifuge cascades

NASA Astrophysics Data System (ADS)

Smirnov, A. Yu; Mustafin, A. R.; Nevinitsa, V. A.; Sulaberidze, G. A.; Dudnikov, A. A.; Gusev, V. E.

2017-01-01

The effect of the uncertainties of the isotopic composition of the reprocessed uranium on its enrichment process in gas centrifuge cascades while diluting it by adding low-enriched uranium (LEU) and waste uranium. It is shown that changing the content of 232U and 236U isotopes in the initial reprocessed uranium within 15% (rel.) can significantly change natural uranium consumption and separative work (up to 2-3%). However, even in case of increase of these parameters is possible to find the ratio of diluents, where the cascade with three feed flows (depleted uranium, LEU and reprocessed uranium) will be more effective than ordinary separation cascade with one feed point for producing LEU from natural uranium.

Possible explanation of the atmospheric kinetic and potential energy spectra.

PubMed

Vallgren, Andreas; Deusebio, Enrico; Lindborg, Erik

2011-12-23

We hypothesize that the observed wave number spectra of kinetic and potential energy in the atmosphere can be explained by assuming that there are two related cascade processes emanating from the same large-scale energy source, a downscale cascade of potential enstrophy, giving rise to the k(-3) spectrum at synoptic scales and a downscale energy cascade giving rise to the k(-5/3) spectrum at mesoscales. The amount of energy which is going into the downscale energy cascade is determined by the rate of system rotation, with negligible energy going downscale in the limit of very fast rotation. We present a set of simulations of a system with strong rotation and stratification, supporting these hypotheses and showing good agreement with observations.

Digital redesign of anti-wind-up controller for cascaded analog system.

PubMed

Chen, Y S; Tsai, J S H; Shieh, L S; Moussighi, M M

2003-01-01

The cascaded conventional anti-wind-up (CAW) design method for integral controller is discussed. Then, the prediction-based digital redesign methodology is utilized to find the new pulse amplitude modulated (PAM) digital controller for effective digital control of the analog plant with input saturation constraint. The desired digital controller is determined from existing or pre-designed CAW analog controller. The proposed method provides a novel methodology for indirect digital design of a continuous-time unity output-feedback system with a cascaded analog controller as in the case of PID controllers for industrial control processes with the presence of actuator saturations. It enables us to implement an existing or pre-designed cascaded CAW analog controller via a digital controller effectively.

Energy spectrum of cascade showers induced by cosmic ray muons in the range from 50 GeV to 5 TeV

NASA Technical Reports Server (NTRS)

Ashitkov, V. D.; Kirina, T. M.; Klimakov, A. P.; Kokoulin, R. P.; Petrukhin, A. A.; Yumatov, V. I.

1985-01-01

The energy spectrum of cascade showers induced by electromagnetic interactions of high energy muons of horizontal cosmic ray flux in iron absorber was measured. The total observation time exceeded 22,000 hours. Both the energy spectrum and angular distributions of cascade showers are fairly described in terms of the usual muon generation processes, with a single power index of the parent meson spectrum over the muon energy range from 150 GeV to 5 TeV.

Time-Resolved Quantum Cascade Laser Absorption Spectroscopy of Pulsed Plasma Assisted Chemical Vapor Deposition Processes Containing BCl3

NASA Astrophysics Data System (ADS)

Lang, Norbert; Hempel, Frank; Strämke, Siegfried; Röpcke, Jürgen

2011-08-01

In situ measurements are reported giving insight into the plasma chemical conversion of the precursor BCl3 in industrial applications of boriding plasmas. For the online monitoring of its ground state concentration, quantum cascade laser absorption spectroscopy (QCLAS) in the mid-infrared spectral range was applied in a plasma assisted chemical vapor deposition (PACVD) reactor. A compact quantum cascade laser measurement and control system (Q-MACS) was developed to allow a flexible and completely dust-sealed optical coupling to the reactor chamber of an industrial plasma surface modification system. The process under the study was a pulsed DC plasma with periodically injected BCl3 at 200 Pa. A synchronization of the Q-MACS with the process control unit enabled an insight into individual process cycles with a sensitivity of 10-6 cm-1·Hz-1/2. Different fragmentation rates of the precursor were found during an individual process cycle. The detected BCl3 concentrations were in the order of 1014 molecules·cm-3. The reported results of in situ monitoring with QCLAS demonstrate the potential for effective optimization procedures in industrial PACVD processes.

Estimating the Propagation of Interdependent Cascading Outages with Multi-Type Branching Processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qi, Junjian; Ju, Wenyun; Sun, Kai

In this paper, the multi-type branching process is applied to describe the statistics and interdependencies of line outages, the load shed, and isolated buses. The offspring mean matrix of the multi-type branching process is estimated by the Expectation Maximization (EM) algorithm and can quantify the extent of outage propagation. The joint distribution of two types of outages is estimated by the multi-type branching process via the Lagrange-Good inversion. The proposed model is tested with data generated by the AC OPA cascading simulations on the IEEE 118-bus system. The largest eigenvalues of the offspring mean matrix indicate that the system ismore » closer to criticality when considering the interdependence of different types of outages. Compared with empirically estimating the joint distribution of the total outages, good estimate is obtained by using the multitype branching process with a much smaller number of cascades, thus greatly improving the efficiency. It is shown that the multitype branching process can effectively predict the distribution of the load shed and isolated buses and their conditional largest possible total outages even when there are no data of them.« less

Spider foraging strategy affects trophic cascades under natural and drought conditions.

PubMed

Liu, Shengjie; Chen, Jin; Gan, Wenjin; Schaefer, Douglas; Gan, Jianmin; Yang, Xiaodong

2015-07-23

Spiders can cause trophic cascades affecting litter decomposition rates. However, it remains unclear how spiders with different foraging strategies influence faunal communities, or present cascading effects on decomposition. Furthermore, increased dry periods predicted in future climates will likely have important consequences for trophic interactions in detritus-based food webs. We investigated independent and interactive effects of spider predation and drought on litter decomposition in a tropical forest floor. We manipulated densities of dominant spiders with actively hunting or sit-and-wait foraging strategies in microcosms which mimicked the tropical-forest floor. We found a positive trophic cascade on litter decomposition was triggered by actively hunting spiders under ambient rainfall, but sit-and-wait spiders did not cause this. The drought treatment reversed the effect of actively hunting spiders on litter decomposition. Under drought conditions, we observed negative trophic cascade effects on litter decomposition in all three spider treatments. Thus, reduced rainfall can alter predator-induced indirect effects on lower trophic levels and ecosystem processes, and is an example of how such changes may alter trophic cascades in detritus-based webs of tropical forests.

A cascading activity-based probe sequentially targets E1–E2–E3 ubiquitin enzymes

PubMed Central

Mulder, Monique P.C.; Witting, Katharina; Berlin, Ilana; Pruneda, Jonathan N.; Wu, Kuen-Phon; Chang, Jer-Gung; Merkx, Remco; Bialas, Johanna; Groettrup, Marcus; Vertegaal, Alfred C.O.; Schulman, Brenda A.; Komander, David; Neefjes, Jacques; Oualid, Farid El; Ovaa, Huib

2016-01-01

Post-translational modifications of proteins with ubiquitin (Ub) and ubiquitin-like (Ubl) modifiers, orchestrated by a cascade of specialized E1, E2 and E3 enzymes, control a staggering breadth of cellular processes. To monitor catalysis along these complex reaction pathways, we developed a cascading activity-based probe, UbDha. Akin to the native Ub, upon ATP-dependent activation by the E1, UbDha can travel downstream to the E2 (and subsequently E3) enzymes through sequential trans-thioesterifications. Unlike the native Ub, at each step along the cascade UbDha has the option to react irreversibly with active site cysteine residues of target enzymes, thus enabling their detection. We show that our cascading probe ‘hops’ and ‘traps’ catalytically active ubiquitin-modifying enzymes (but not their substrates) by a mechanism diversifiable to Ubls. Our founder methodology, amenable to structural studies, proteome-wide profiling and monitoring of enzymatic activities in living cells, presents novel and versatile tools to interrogate the Ub/Ubl cascades. PMID:27182664

An experimental investigation of gapwise periodicity and unsteady aerodynamic response in an oscillating cascade. 1: Experimental and theoretical results. [turbine blades

NASA Technical Reports Server (NTRS)

Carta, F. O.

1982-01-01

Tests were conducted on a linear cascade of airfoils oscillating in pitch to measure the unsteady pressure response on selected blades along the leading edge plane of the cascade, over the chord of the center blade, and on the sidewall in the plane of the leading edge. The pressure data were reduced to Fourier coefficient form for direct comparison, and were also processed to yield integrated loads and, particularly, the aerodynamic damping coefficient. Results from the unsteady Verdon/Caspar theory for cascaded blades with nonzero thickness and camber were compared with the experimental measurements. The three primary results are: (1) from the leading edge plane blade data, the cascade was judged to be periodic in unsteady flow over the range of parameters tested; (2) the interblade phase angle was found to be the single most important parameter affecting the stability of the oscillating cascade blades; and (3) the real blade theory and the experiment were in excellent agreement for the several cases chosen for comparison.

Spider foraging strategy affects trophic cascades under natural and drought conditions

PubMed Central

Liu, Shengjie; Chen, Jin; Gan, Wenjin; Schaefer, Douglas; Gan, Jianmin; Yang, Xiaodong

2015-01-01

Spiders can cause trophic cascades affecting litter decomposition rates. However, it remains unclear how spiders with different foraging strategies influence faunal communities, or present cascading effects on decomposition. Furthermore, increased dry periods predicted in future climates will likely have important consequences for trophic interactions in detritus-based food webs. We investigated independent and interactive effects of spider predation and drought on litter decomposition in a tropical forest floor. We manipulated densities of dominant spiders with actively hunting or sit-and-wait foraging strategies in microcosms which mimicked the tropical-forest floor. We found a positive trophic cascade on litter decomposition was triggered by actively hunting spiders under ambient rainfall, but sit-and-wait spiders did not cause this. The drought treatment reversed the effect of actively hunting spiders on litter decomposition. Under drought conditions, we observed negative trophic cascade effects on litter decomposition in all three spider treatments. Thus, reduced rainfall can alter predator-induced indirect effects on lower trophic levels and ecosystem processes, and is an example of how such changes may alter trophic cascades in detritus-based webs of tropical forests. PMID:26202370

On the Origin of Cancer Metastasis

PubMed Central

Seyfried, Thomas N.; Huysentruyt, Leanne C.

2013-01-01

Metastasis involves the spread of cancer cells from the primary tumor to surrounding tissues and to distant organs and is the primary cause of cancer morbidity and mortality. In order to complete the metastatic cascade, cancer cells must detach from the primary tumor, intravasate into the circulatory and lymphatic systems, evade immune attack, extravasate at distant capillary beds, and invade and proliferate in distant organs. Currently, several hypotheses have been advanced to explain the origin of cancer metastasis. These involve an epithelial mesenchymal transition, an accumulation of mutations in stem cells, a macrophage facilitation process, and a macrophage origin involving either transformation or fusion hybridization with neoplastic cells. Many of the properties of metastatic cancer cells are also seen in normal macrophages. A macrophage origin of metastasis can also explain the long-standing “seed and soil” hypothesis and the absence of metastasis in plant cancers. The view of metastasis as a macrophage metabolic disease can provide novel insight for therapeutic management. PMID:23237552

The "memory kinases": roles of PKC isoforms in signal processing and memory formation.

PubMed

Sun, Miao-Kun; Alkon, Daniel L

2014-01-01

The protein kinase C (PKC) isoforms, which play an essential role in transmembrane signal conduction, can be viewed as a family of "memory kinases." Evidence is emerging that they are critically involved in memory acquisition and maintenance, in addition to their involvement in other functions of cells. Deficits in PKC signal cascades in neurons are one of the earliest abnormalities in the brains of patients suffering from Alzheimer's disease. Their dysfunction is also involved in several other types of memory impairments, including those related to emotion, mental retardation, brain injury, and vascular dementia/ischemic stroke. Inhibition of PKC activity leads to a reduced capacity of many types of learning and memory, but may have therapeutic values in treating substance abuse or aversive memories. PKC activators, on the other hand, have been shown to possess memory-enhancing and antidementia actions. PKC pharmacology may, therefore, represent an attractive area for developing effective cognitive drugs for the treatment of many types of memory disorders and dementias. © 2014 Elsevier Inc. All rights reserved.

Estradiol-dependent modulation of auditory processing and selectivity in songbirds

PubMed Central

Maney, Donna; Pinaud, Raphael

2011-01-01

The steroid hormone estradiol plays an important role in reproductive development and behavior and modulates a wide array of physiological and cognitive processes. Recently, reports from several research groups have converged to show that estradiol also powerfully modulates sensory processing, specifically, the physiology of central auditory circuits in songbirds. These investigators have discovered that (1) behaviorally-relevant auditory experience rapidly increases estradiol levels in the auditory forebrain; (2) estradiol instantaneously enhances the responsiveness and coding efficiency of auditory neurons; (3) these changes are mediated by a non-genomic effect of brain-generated estradiol on the strength of inhibitory neurotransmission; and (4) estradiol regulates biochemical cascades that induce the expression of genes involved in synaptic plasticity. Together, these findings have established estradiol as a central regulator of auditory function and intensified the need to consider brain-based mechanisms, in addition to peripheral organ dysfunction, in hearing pathologies associated with estrogen deficiency. PMID:21146556

Adoption: biological and social processes linked to adaptation.

PubMed

Grotevant, Harold D; McDermott, Jennifer M

2014-01-01

Children join adoptive families through domestic adoption from the public child welfare system, infant adoption through private agencies, and international adoption. Each pathway presents distinctive developmental opportunities and challenges. Adopted children are at higher risk than the general population for problems with adaptation, especially externalizing, internalizing, and attention problems. This review moves beyond the field's emphasis on adoptee-nonadoptee differences to highlight biological and social processes that affect adaptation of adoptees across time. The experience of stress, whether prenatal, postnatal/preadoption, or during the adoption transition, can have significant impacts on the developing neuroendocrine system. These effects can contribute to problems with physical growth, brain development, and sleep, activating cascading effects on social, emotional, and cognitive development. Family processes involving contact between adoptive and birth family members, co-parenting in gay and lesbian adoptive families, and racial socialization in transracially adoptive families affect social development of adopted children into adulthood.

The land-cover cascade: relationships coupling land and water

Treesearch

C.L. Burcher; H.M. Valett; E.F. Benfield

2007-01-01

We introduce the land-cover cascade (LCC) as a conceptual framework to quantify the transfer of land-cover-disturbance effects to stream biota. We hypothesize that disturbance is propagated through multivariate systems through key variables that transform a disturbance and pass a reorganized disturbance effect to the next hierarchical level where the process repeats...

Perspectives on climate change, mountain hydrology, and water resources in the Oregon Cascades, USA

Treesearch

A.W. Nolin

2012-01-01

From both social and environmental perspectives, water is the main connection between highland and lowland processes in mountain watersheds: Water flows downhill while human impacts flow uphill. For example, in the Oregon Cascades mountain range, geology, vegetation, and climate influence the hydrologic connections within watersheds. Geology determines which watersheds...

Cascading and Parallelising Curvilinear Inertial Focusing Systems for High Volume, Wide Size Distribution, Separation and Concentration of Particles

PubMed Central

Miller, B.; Jimenez, M.; Bridle, H.

2016-01-01

Inertial focusing is a microfluidic based separation and concentration technology that has expanded rapidly in the last few years. Throughput is high compared to other microfluidic approaches although sample volumes have typically remained in the millilitre range. Here we present a strategy for achieving rapid high volume processing with stacked and cascaded inertial focusing systems, allowing for separation and concentration of particles with a large size range, demonstrated here from 30 μm–300 μm. The system is based on curved channels, in a novel toroidal configuration and a stack of 20 devices has been shown to operate at 1 L/min. Recirculation allows for efficient removal of large particles whereas a cascading strategy enables sequential removal of particles down to a final stage where the target particle size can be concentrated. The demonstration of curved stacked channels operating in a cascaded manner allows for high throughput applications, potentially replacing filtration in applications such as environmental monitoring, industrial cleaning processes, biomedical and bioprocessing and many more. PMID:27808244

Expression of the plasminogen activator system and the inhibitors PAI-1 and PAI-2 in posttraumatic lesions of the CNS and brain injuries following dramatic circulatory arrests: an immunohistochemical study.

PubMed

Dietzmann, K; von Bossanyi, P; Krause, D; Wittig, H; Mawrin, C; Kirches, E

2000-01-01

Plasminogen activators as inducible extracellular serine proteases are involved in a variety of processes, such as the degradation of brain structures. In regions of brain degradation, an increase in the expression of genes encoding cytokines and proteinases has recently been demonstrated. We tested the hypothesis, whether the plasminogen activator system as well as the plasminogen activator inhibitors are expressed and possibly involved in a proteolytic cascade that breaks down the extracellular matrix as a result of ischemic or posttraumatic brain destructions. To study this supposition, we investigated immunohistochemically the expression of tPA, uPA and its receptor, the plasminogen activator inhibitors PAI-1 and PAI-2, tetranectin as well as the laminin breakdown as an event of secondary brain injury. Brain tissue from 21 autopsy cases with severe brain injuries, material from 14 ischemic infarcts and 11 controls with acute hypoxia were used. All components of the plasminogen activator system studied were over-expressed immunohistochemically in reactive astrocytes, microglia and endothelial cells around the lesion zone. Tetranectin showed an analogous distribution to the plasminogen activator system. A reduced immunoreactivity of laminin within the identical region of destruction was detected concomitant with laminin remnants in perivascular macrophages, so that a remarkable role of the plasmin cascade in the degradation of extracellular matrix proteins in the brain is taken into consideration.

Existing Whole-House Solutions Case Study: Cascade Apartments - Deep Energy Multifamily Retrofit

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2014-02-01

In December of 2009-10, King County Housing Authority (KCHA) implemented energy retrofit improvements in the Cascade multifamily community, located in Kent, Washington, which resulted in annual energy cost savings of 22%, improved comfort and air quality for residents, and increased durability of the units. This research effort involved significant coordination from stakeholders KCHA, WA State Department of Commerce, utility Puget Sound Energy, and Cascade tenants. This report focuses on the following three primary Building America research questions: 1. What are the modeled energy savings using DOE low income weatherization approved TREAT software? 2. How did the modeled energy savings comparemore » with measured energy savings from aggregate utility billing analysis? 3. What is the Savings to Investment Ratio of the retrofit package after considering utility window incentives and KCHA capital improvement funding.« less

Cascading off the West Greenland Shelf: A numerical perspective

NASA Astrophysics Data System (ADS)

Marson, Juliana M.; Myers, Paul G.; Hu, Xianmin; Petrie, Brian; Azetsu-Scott, Kumiko; Lee, Craig M.

2017-07-01

Cascading of dense water from the shelf to deeper layers of the adjacent ocean basin has been observed in several locations around the world. The West Greenland Shelf (WGS), however, is a region where this process has never been documented. In this study, we use a numerical model with a 1/4° resolution to determine (i) if cascading could happen from the WGS; (ii) where and when it could take place; (iii) the forcings that induce or halt this process; and (iv) the path of the dense plume. Results show cascading happening off the WGS at Davis Strait. Dense waters form there due to brine rejection and slide down the slope during spring. Once the dense plume leaves the shelf, it gradually mixes with waters of similar density and moves northward into Baffin Bay. Our simulation showed events happening between 2003-2006 and during 2014; but no plume was observed in the simulation between 2007 and 2013. We suggest that the reason why cascading was halted in this period is related to: the increased freshwater transport from the Arctic Ocean through Fram Strait; the additional sea ice melting in the region; and the reduced presence of Irminger Water at Davis Strait during fall/early winter. Although observations at Davis Strait show that our simulation usually overestimates the seasonal range of temperature and salinity, they agree with the overall variability captured by the model. This suggests that cascades have the potential to develop on the WGS, albeit less dense than the ones estimated by the simulation.

Cascade flutter analysis with transient response aerodynamics

NASA Technical Reports Server (NTRS)

Bakhle, Milind A.; Mahajan, Aparajit J.; Keith, Theo G., Jr.; Stefko, George L.

1991-01-01

Two methods for calculating linear frequency domain aerodynamic coefficients from a time marching Full Potential cascade solver are developed and verified. In the first method, the Influence Coefficient, solutions to elemental problems are superposed to obtain the solutions for a cascade in which all blades are vibrating with a constant interblade phase angle. The elemental problem consists of a single blade in the cascade oscillating while the other blades remain stationary. In the second method, the Pulse Response, the response to the transient motion of a blade is used to calculate influence coefficients. This is done by calculating the Fourier Transforms of the blade motion and the response. Both methods are validated by comparison with the Harmonic Oscillation method and give accurate results. The aerodynamic coefficients obtained from these methods are used for frequency domain flutter calculations involving a typical section blade structural model. An eigenvalue problem is solved for each interblade phase angle mode and the eigenvalues are used to determine aeroelastic stability. Flutter calculations are performed for two examples over a range of subsonic Mach numbers.

Do stage-specific functional responses of consumers dampen the effects of subsidies on trophic cascades in streams?

PubMed

Sato, Takuya; Watanabe, Katsutoshi

2014-07-01

Resource subsidies often weaken trophic cascades in recipient communities via consumers' functional response to the subsidies. Consumer populations are commonly stage-structured and may respond to the subsidies differently among the stages yet less is known about how this might impact the subsidy effects on the strength of trophic cascades in recipient systems. We show here, using a large-scale field experiment, that the stage structure of a recipient consumer would dampen the effects of terrestrial invertebrate subsidies on the strength of trophic cascade in streams. When a high input rate of the terrestrial invertebrates was available, both large and small fish stages switched their diet to the terrestrial subsidy, which weakened the trophic cascade in streams. However, when the input rate of the terrestrial invertebrates was at a moderate level, the terrestrial subsidy did not weaken the trophic cascade. This discrepancy was likely due to small fish stages being competitively excluded from feeding on the subsidy by larger stages of fish and primarily foraging on benthic invertebrates under the moderate input level. Although previous studies using single fish stages have clearly demonstrated that the terrestrial invertebrate input equivalent to our moderate input rate weakened the trophic cascade in streams, this subsidy effect might be overestimated given small fish stage may not switch their diet to the subsidy under competition with large fish stage. Given the ubiquity of consumer stage structure and interaction among consumer stages, the effects we saw might be widespread in nature, requiring future studies that explicitly involve consumer's stage structure into community ecology. © 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.

Aligning policy to promote cascade genetic screening for prevention and early diagnosis of heritable diseases.

PubMed

George, Rani; Kovak, Karen; Cox, Summer L

2015-06-01

Cascade genetic screening is a methodology for identifying and testing close blood relatives of individuals at increased risk for heritable conditions and follows a sequential process, minimizing testing costs and the number of family members who need to be tested. It offers considerable potential for cost savings and increased awareness of heritable conditions within families. CDC-classified Tier 1 genomic applications for hereditary breast and ovarian cancer syndrome (HBOC), Lynch Syndrome (LS), and familial hypercholesterolemia (FH) are recommended for clinical use and support the use of cascade genetic screening. Most individuals are unaware of their increased risk for heritable conditions such as HBOC, LS, and FH. Consistent implementation of cascade genetic screening could significantly increase awareness and prevention of heritable conditions. Limitations to effective implementation of cascade genetic screening include: insufficient genetic risk assessment and knowledge by a majority of healthcare providers without genetics credentials; a shortage of genetic specialists, especially in rural areas; a low rate of reimbursement for comprehensive genetic counseling services; and an individual focus on prevention by clinical guidelines and insurance coverage. The family-centric approach of cascade genetic screening improves prevention and early diagnosis of heritable diseases on a population health level. Cascade genetic screening could be better supported and augmented through changes in health policy.

Evolution of Mass Movements near Epicentre of Wenchuan Earthquake, the First Eight Years

PubMed Central

Zhang, Shuai; Zhang, Limin; Lacasse, Suzanne; Nadim, Farrokh

2016-01-01

It is increasingly clear that landslides represent a major cause of economic costs and deaths in earthquakes in mountains. In the Wenchuan earthquake case, post-seismic cascading landslides continue to represent a major problem eight years on. Failure to anticipate the impact of cascading landslides could lead to unexpected losses of human lives and properties. Previous studies tended to focus on separate landslide processes, with little attention paid to the quantification of long-term evolution of multiple processes or the evolution of mass movements. The very active mass movements near the epicentre of the Wenchuan earthquake provided us a unique opportunity to understand the complex processes of the evolving cascading landslides after a strong earthquake. This study budgets the mass movements on the hillslopes and in the channels in the first eight years since the Wenchuan earthquake and verify a conservation in mass movements. A system illustrating the evolution and interactions of mass movement after a strong earthquake is proposed. PMID:27824077

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shephard, Jacob J.; Vickers, Martin; Salzmann, Christoph G., E-mail: c.salzmann@ucl.ac.uk

Low-density amorphous (LDA) ice is involved in critical cosmological processes and has gained prominence as one of the at least two distinct amorphous forms of ice. Despite these accolades, we still have an incomplete understanding of the structural diversity that is encompassed within the LDA state and the dynamic processes that take place upon heating LDA. Heating the high-pressure ice VIII phase at ambient pressure is a remarkable example of temperature-induced amorphisation yielding LDA. We investigate this process in detail using X-ray diffraction and Raman spectroscopy and show that the LDA obtained from ice VIII is structurally different from themore » more “traditional” states of LDA which are approached upon thermal annealing. This new structural relaxation pathway involves an increase of structural order on the intermediate range length scale. In contrast with other LDA materials the local structure is more ordered initially and becomes slightly more disordered upon annealing. We also show that the cascade of phase transitions upon heating ice VIII at ambient pressure includes the formation of ice IX which may be connected with the structural peculiarities of LDA from ice VIII. Overall, this study shows that LDA is a structurally more diverse material than previously appreciated.« less

Cascade Helps JPL Explore the Solar System

NASA Technical Reports Server (NTRS)

Burke, G. R.

1996-01-01

At Jet Propulsion Laboratory (JPL), we are involved with the unmanned exploration of the solar system. Unmanned probes observe the planet surfaces using radar and optical cameras to take a variety of measurements.

Epigenetic mechanisms of memory formation and reconsolidation.

PubMed

Jarome, Timothy J; Lubin, Farah D

2014-11-01

Memory consolidation involves transcriptional control of genes in neurons to stabilize a newly formed memory. Following retrieval, a once consolidated memory destabilizes and again requires gene transcription changes in order to restabilize, a process referred to as reconsolidation. Understanding the molecular mechanisms of gene transcription during the consolidation and reconsolidation processes could provide crucial insights into normal memory formation and memory dysfunction associated with psychiatric disorders. In the past decade, modifications of epigenetic markers such as DNA methylation and posttranslational modifications of histone proteins have emerged as critical transcriptional regulators of gene expression during initial memory formation and after retrieval. In light of the rapidly growing literature in this exciting area of research, we here examine the most recent and latest evidence demonstrating how memory acquisition and retrieval trigger epigenetic changes during the consolidation and reconsolidation phases to impact behavior. In particular we focus on the reconsolidation process, where we discuss the already identified epigenetic regulators of gene transcription during memory reconsolidation, while exploring other potential epigenetic modifications that may also be involved, and expand on how these epigenetic modifications may be precisely and temporally controlled by important signaling cascades critical to the reconsolidation process. Finally, we explore the possibility that epigenetic mechanisms may serve to regulate a system or circuit level reconsolidation process and may be involved in retrieval-dependent memory updating. Hence, we propose that epigenetic mechanisms coordinate changes in neuronal gene transcription, not only during the initial memory consolidation phase, but are triggered by retrieval to regulate molecular and cellular processes during memory reconsolidation. Copyright © 2014 Elsevier Inc. All rights reserved.

Epigenetic Mechanisms of Memory Formation and Reconsolidation

PubMed Central

Jarome, Timothy J.; Lubin, Farah D.

2014-01-01

Memory consolidation involves transcriptional control of genes in neurons to stabilize a newly formed memory. Following retrieval, a once consolidated memory destabilizes and again requires gene transcription changes in order to restabilize, a process referred to as reconsolidation. Understanding the molecular mechanisms of gene transcription during the consolidation and reconsolidation processes could provide crucial insights into normal memory formation and memory dysfunction associated with psychiatric disorders. In the past decade, modifications of epigenetic markers such as DNA methylation and posttranslational modifications of histone proteins have emerged as critical transcriptional regulators of gene expression during initial memory formation and after retrieval. In light of the rapidly growing literature in this exciting area of research, we here examine the most recent and latest evidence demonstrating how memory acquisition and retrieval trigger epigenetic changes during the consolidation and reconsolidation phases to impact behavior. In particular we focus on the reconsolidation process, where we discuss the already identified epigenetic regulators of gene transcription during memory reconsolidation, while exploring other potential epigenetic modifications that may also be involved, and expand on how these epigenetic modifications may be precisely and temporally controlled by important signaling cascades critical to the reconsolidation process. Finally, we explore the possibility that epigenetic mechanisms may serve to regulate a system or circuit level reconsolidation process and may be involved in retrieval-dependent memory updating. Hence, we propose that epigenetic mechanisms coordinate changes in neuronal gene transcription, not only during the initial memory consolidation phase, but are triggered by retrieval to regulate molecular and cellular processes during memory reconsolidation. PMID:25130533

Cascaded Photoenhancement: Implications for Photonic Chemical and Biological Sensors

NASA Technical Reports Server (NTRS)

Fuller, Kirk A.; Smith, David D.

2006-01-01

Our analysis shows that coupling of gold nanoparticles to microspheres will evoke a cascading effect from the respective photoenhancement mechanisms. We refer to this amplification process as cascaded photoenhancement, and the resulting cavity amplification of surface-enhanced Raman scattering (SERS) and fluorescence as CASERS and CAF, respectively. Calculations, based on modal analysis of scattering and absorption by compound spheres, presented herein indicate that the absorption cross sections of metal nanoparticles immobilized onto dielectric microspheres can be greatly enhanced by cavity resonances in the microspheres without significant degradation of the resonators. Gain factors associated with CSP of 10(exp 3) - 10(exp 4) are predicted for realistic experimental conditions using homogenous microspheres. Cascaded surface photoenhancement thus has the potential of dramatically increasing the sensitivities of fluorescence and vibrational spectroscopies.

Fractality and the law of the wall

NASA Astrophysics Data System (ADS)

Xu, Haosen H. A.; Yang, X. I. A.

2018-05-01

Fluid motions in the inertial range of isotropic turbulence are fractal, with their space-filling capacity slightly below regular three-dimensional objects, which is a consequence of the energy cascade. Besides the energy cascade, the other often encountered cascading process is the momentum cascade in wall-bounded flows. Despite the long-existing analogy between the two processes, many of the thoroughly investigated aspects of the energy cascade have so far received little attention in studies of the momentum counterpart, e.g., the possibility of the momentum-transferring scales in the logarithmic region being fractal has not been considered. In this work, this possibility is pursued, and we discuss one of its implications. Following the same dimensional arguments that lead to the D =2.33 fractal dimension of wrinkled surfaces in isotropic turbulence, we show that the large-scale momentum-carrying eddies may also be fractal and non-space-filling, which then leads to the power-law scaling of the mean velocity profile. The logarithmic law of the wall, on the other hand, corresponds to space-filling eddies, as suggested by Townsend [The Structure of Turbulent Shear Flow (Cambridge University Press, Cambridge, 1980)]. Because the space-filling capacity is an integral geometric quantity, the analysis presented in this work provides us with a low-order quantity, with which, one would be able to distinguish between the logarithmic law and the power law.

Involvement of potato (Solanum tuberosum L.) MKK6 in response to potato virus Y.

PubMed

Lazar, Ana; Coll, Anna; Dobnik, David; Baebler, Spela; Bedina-Zavec, Apolonija; Zel, Jana; Gruden, Kristina

2014-01-01

Mitogen-activated protein kinase (MAPK) cascades have crucial roles in the regulation of plant development and in plant responses to stress. Plant recognition of pathogen-associated molecular patterns or pathogen-derived effector proteins has been shown to trigger activation of several MAPKs. This then controls defence responses, including synthesis and/or signalling of defence hormones and activation of defence related genes. The MAPK cascade genes are highly complex and interconnected, and thus the precise signalling mechanisms in specific plant-pathogen interactions are still not known. Here we investigated the MAPK signalling network involved in immune responses of potato (Solanum tuberosum L.) to Potato virus Y, an important potato pathogen worldwide. Sequence analysis was performed to identify the complete MAPK kinase (MKK) family in potato, and to identify those regulated in the hypersensitive resistance response to Potato virus Y infection. Arabidopsis has 10 MKK family members, of which we identified five in potato and tomato (Solanum lycopersicum L.), and eight in Nicotiana benthamiana. Among these, StMKK6 is the most strongly regulated gene in response to Potato virus Y. The salicylic acid treatment revealed that StMKK6 is regulated by the hormone that is in agreement with the salicylic acid-regulated domains found in the StMKK6 promoter. The involvement of StMKK6 in potato defence response was confirmed by localisation studies, where StMKK6 accumulated strongly only in Potato-virus-Y-infected plants, and predominantly in the cell nucleus. Using a yeast two-hybrid method, we identified three StMKK6 targets downstream in the MAPK cascade: StMAPK4_2, StMAPK6 and StMAPK13. These data together provide further insight into the StMKK6 signalling module and its involvement in plant defence.

Involvement of Potato (Solanum tuberosum L.) MKK6 in Response to Potato virus Y

PubMed Central

Lazar, Ana; Coll, Anna; Dobnik, David; Baebler, Špela; Bedina-Zavec, Apolonija; Žel, Jana; Gruden, Kristina

2014-01-01

Mitogen-activated protein kinase (MAPK) cascades have crucial roles in the regulation of plant development and in plant responses to stress. Plant recognition of pathogen-associated molecular patterns or pathogen-derived effector proteins has been shown to trigger activation of several MAPKs. This then controls defence responses, including synthesis and/or signalling of defence hormones and activation of defence related genes. The MAPK cascade genes are highly complex and interconnected, and thus the precise signalling mechanisms in specific plant–pathogen interactions are still not known. Here we investigated the MAPK signalling network involved in immune responses of potato (Solanum tuberosum L.) to Potato virus Y, an important potato pathogen worldwide. Sequence analysis was performed to identify the complete MAPK kinase (MKK) family in potato, and to identify those regulated in the hypersensitive resistance response to Potato virus Y infection. Arabidopsis has 10 MKK family members, of which we identified five in potato and tomato (Solanum lycopersicum L.), and eight in Nicotiana benthamiana. Among these, StMKK6 is the most strongly regulated gene in response to Potato virus Y. The salicylic acid treatment revealed that StMKK6 is regulated by the hormone that is in agreement with the salicylic acid-regulated domains found in the StMKK6 promoter. The involvement of StMKK6 in potato defence response was confirmed by localisation studies, where StMKK6 accumulated strongly only in Potato-virus-Y-infected plants, and predominantly in the cell nucleus. Using a yeast two-hybrid method, we identified three StMKK6 targets downstream in the MAPK cascade: StMAPK4_2, StMAPK6 and StMAPK13. These data together provide further insight into the StMKK6 signalling module and its involvement in plant defence. PMID:25111695

Plant Perception and Short-Term Responses to Phytophagous Insects and Mites.

PubMed

Santamaria, M Estrella; Arnaiz, Ana; Gonzalez-Melendi, Pablo; Martinez, Manuel; Diaz, Isabel

2018-05-03

Plant⁻pest relationships involve complex processes encompassing a network of molecules, signals, and regulators for overcoming defenses they develop against each other. Phytophagous arthropods identify plants mainly as a source of food. In turn, plants develop a variety of strategies to avoid damage and survive. The success of plant defenses depends on rapid and specific recognition of the phytophagous threat. Subsequently, plants trigger a cascade of short-term responses that eventually result in the production of a wide range of compounds with defense properties. This review deals with the main features involved in the interaction between plants and phytophagous insects and acari, focusing on early responses from the plant side. A general landscape of the diverse strategies employed by plants within the first hours after pest perception to block the capability of phytophagous insects to develop mechanisms of resistance is presented, with the potential of providing alternatives for pest control.

Shedding light on the role of AT-hook/PPC domain protein in Arabidopsis thaliana

PubMed Central

Ng, Kian-Hong

2010-01-01

Flower reproductive development is a complex process involving well-coordinated control of transcriptional regulation cascades. AGAMOUS (AG) plays an instrumental role in the specification and differentiation of reproductive organs in Arabidopsis thaliana. We recently characterized a downstream target gene of AG, GIANT KILLER (GIK), which encodes for an AT-hook/plants and prokaryotes conserved (PPC) domain protein. We found that overexpression of GIK leads to severe reproductive defects and downregulation of genes involved in patterning and differentiation of reproductive floral organs. We showed that GIK is a matrix protein, and GIK-mediated gene regulation requires binding of GIK to matrix associated region (MAR) of the target genes. We further showed that GIK-mediated negative regulation of one of the target genes, ETTIN (ETT), is associated with changes of chromatin histone modification at ETT promoter, suggesting that GIK acts as a gene expression modulator through chromatin organization. PMID:20173412

Mechanical forces and their second messengers in stimulating cell growth in vitro

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman H.

1992-01-01

Mechanical forces play an important role in modulating the growth of a number of different tissues including skeletal muscle, smooth muscle, cardiac muscle, bone, endothelium, epithelium, and lung. As interest increases in the molecular mechanisms by which mechanical forces are transduced into growth alterations, model systems are being developed to study these processes in tissue culture. This paper reviews the current methods available for mechanically stimulating tissue cultured cells. It then outlines some of the putative 'mechanogenic' second messengers involved in altering cell growth. Not surprisingly, many mechanogenic second messengers are the same as those involved in growth factor-induced cell growth. It is hypothesized that from an evolutionary standpoint, some second messenger systems may have initially evolved for unicellular organisms to respond to physical forces such as gravity and mechanical perturbation in their environment. As multicellular organisms came into existence, they appropriated these mechanogenic second messenger cascades for cellular regulation by growth factors.

How quantitative measures unravel design principles in multi-stage phosphorylation cascades.

PubMed

Frey, Simone; Millat, Thomas; Hohmann, Stefan; Wolkenhauer, Olaf

2008-09-07

We investigate design principles of linear multi-stage phosphorylation cascades by using quantitative measures for signaling time, signal duration and signal amplitude. We compare alternative pathway structures by varying the number of phosphorylations and the length of the cascade. We show that a model for a weakly activated pathway does not reflect the biological context well, unless it is restricted to certain parameter combinations. Focusing therefore on a more general model, we compare alternative structures with respect to a multivariate optimization criterion. We test the hypothesis that the structure of a linear multi-stage phosphorylation cascade is the result of an optimization process aiming for a fast response, defined by the minimum of the product of signaling time and signal duration. It is then shown that certain pathway structures minimize this criterion. Several popular models of MAPK cascades form the basis of our study. These models represent different levels of approximation, which we compare and discuss with respect to the quantitative measures.

Analysis of the Exhumation Pathways Experienced in the Cascades Range

NASA Astrophysics Data System (ADS)

Giles, S. M.; Pesek, M.; Perez, N. D.

2017-12-01

The Cascades volcanic arc is the result of subduction of the Juan de Fuca plate beneath North America. The Cascades trend north to south and create a modern orographic precipitation gradient that focuses precipitation along the western flank of the range. However, the deformation style changes from shortening in the north to extension in the south. This experimental design is an ideal location to test how surface and tectonic processes contribute to rock uplift in orogens. In the Oregon Cascades, zircon U-Pb geochronology, and multiple thermochronologic techniques (apatite U-Pb, zircon U-Th/He) will be applied to an intrusive rock exposed along a west-flowing river to investigate the exhumation pathway. These intrusive rocks are capped by late Miocene basalt flows, constraining the timing of surface exposure. The results of this study will define a time-temperature pathway and be compared with existing exhumation constraints from the Washington Cascades to determine whether the exhumation pathways may correspond to the changing structural regimes or consistent climate patterns along strike.

Cascades on a stochastic pulse-coupled network

NASA Astrophysics Data System (ADS)

Wray, C. M.; Bishop, S. R.

2014-09-01

While much recent research has focused on understanding isolated cascades of networks, less attention has been given to dynamical processes on networks exhibiting repeated cascades of opposing influence. An example of this is the dynamic behaviour of financial markets where cascades of buying and selling can occur, even over short timescales. To model these phenomena, a stochastic pulse-coupled oscillator network with upper and lower thresholds is described and analysed. Numerical confirmation of asynchronous and synchronous regimes of the system is presented, along with analytical identification of the fixed point state vector of the asynchronous mean field system. A lower bound for the finite system mean field critical value of network coupling probability is found that separates the asynchronous and synchronous regimes. For the low-dimensional mean field system, a closed-form equation is found for cascade size, in terms of the network coupling probability. Finally, a description of how this model can be applied to interacting agents in a financial market is provided.

Cascades on a stochastic pulse-coupled network

PubMed Central

Wray, C. M.; Bishop, S. R.

2014-01-01

While much recent research has focused on understanding isolated cascades of networks, less attention has been given to dynamical processes on networks exhibiting repeated cascades of opposing influence. An example of this is the dynamic behaviour of financial markets where cascades of buying and selling can occur, even over short timescales. To model these phenomena, a stochastic pulse-coupled oscillator network with upper and lower thresholds is described and analysed. Numerical confirmation of asynchronous and synchronous regimes of the system is presented, along with analytical identification of the fixed point state vector of the asynchronous mean field system. A lower bound for the finite system mean field critical value of network coupling probability is found that separates the asynchronous and synchronous regimes. For the low-dimensional mean field system, a closed-form equation is found for cascade size, in terms of the network coupling probability. Finally, a description of how this model can be applied to interacting agents in a financial market is provided. PMID:25213626

A note on compressibility and energy cascade in turbulent molecular clouds

NASA Technical Reports Server (NTRS)

Fleck, R. C., Jr.

1983-01-01

Observed velocity-size correlations are reexamined in the light of an improved theory of turbulent energy cascade that is developed. It is shown that observed velocity-size correlations cannot be compared with the Kolmogorov law, which is based on incompressible turbulent flow. The fact that the log v-log(l/rho) scaling law (v the turbulent velocity, l the associated region size, and rho the fluid density) predicted for compressible energy cascade is always steeper than that observed in molecular clouds indicates the injection rather than the dissipation of mechanical energy at smaller scales of motion. It is also shown that the concept of strict energy cascade may not be generally applicable in the interstellar medium. The agreement between theory and observation turns out to be best for small cool clouds and cloud cores, suggesting that, for these regions at least, the dominant process in establishing the observed v-l-rho correlation is a turbulent energy cascade.

The Futures Wheel: A method for exploring the implications of social-ecological change

Treesearch

D.N. Bengston

2015-01-01

Change in social-ecological systems often produces a cascade of unanticipated consequences. Natural resource professionals and other stakeholders need to understand the possible implications of cascading change to prepare for it. The Futures Wheel is a "smart group" method that uses a structured brainstorming process to uncover and evaluate multiple levels of...

Identification of cascade water tanks using a PWARX model

NASA Astrophysics Data System (ADS)

Mattsson, Per; Zachariah, Dave; Stoica, Petre

2018-06-01

In this paper we consider the identification of a discrete-time nonlinear dynamical model for a cascade water tank process. The proposed method starts with a nominal linear dynamical model of the system, and proceeds to model its prediction errors using a model that is piecewise affine in the data. As data is observed, the nominal model is refined into a piecewise ARX model which can capture a wide range of nonlinearities, such as the saturation in the cascade tanks. The proposed method uses a likelihood-based methodology which adaptively penalizes model complexity and directly leads to a computationally efficient implementation.

A stochastical event-based continuous time step rainfall generator based on Poisson rectangular pulse and microcanonical random cascade models

NASA Astrophysics Data System (ADS)

Pohle, Ina; Niebisch, Michael; Zha, Tingting; Schümberg, Sabine; Müller, Hannes; Maurer, Thomas; Hinz, Christoph

2017-04-01

Rainfall variability within a storm is of major importance for fast hydrological processes, e.g. surface runoff, erosion and solute dissipation from surface soils. To investigate and simulate the impacts of within-storm variabilities on these processes, long time series of rainfall with high resolution are required. Yet, observed precipitation records of hourly or higher resolution are in most cases available only for a small number of stations and only for a few years. To obtain long time series of alternating rainfall events and interstorm periods while conserving the statistics of observed rainfall events, the Poisson model can be used. Multiplicative microcanonical random cascades have been widely applied to disaggregate rainfall time series from coarse to fine temporal resolution. We present a new coupling approach of the Poisson rectangular pulse model and the multiplicative microcanonical random cascade model that preserves the characteristics of rainfall events as well as inter-storm periods. In the first step, a Poisson rectangular pulse model is applied to generate discrete rainfall events (duration and mean intensity) and inter-storm periods (duration). The rainfall events are subsequently disaggregated to high-resolution time series (user-specified, e.g. 10 min resolution) by a multiplicative microcanonical random cascade model. One of the challenges of coupling these models is to parameterize the cascade model for the event durations generated by the Poisson model. In fact, the cascade model is best suited to downscale rainfall data with constant time step such as daily precipitation data. Without starting from a fixed time step duration (e.g. daily), the disaggregation of events requires some modifications of the multiplicative microcanonical random cascade model proposed by Olsson (1998): Firstly, the parameterization of the cascade model for events of different durations requires continuous functions for the probabilities of the multiplicative weights, which we implemented through sigmoid functions. Secondly, the branching of the first and last box is constrained to preserve the rainfall event durations generated by the Poisson rectangular pulse model. The event-based continuous time step rainfall generator has been developed and tested using 10 min and hourly rainfall data of four stations in North-Eastern Germany. The model performs well in comparison to observed rainfall in terms of event durations and mean event intensities as well as wet spell and dry spell durations. It is currently being tested using data from other stations across Germany and in different climate zones. Furthermore, the rainfall event generator is being applied in modelling approaches aimed at understanding the impact of rainfall variability on hydrological processes. Reference Olsson, J.: Evaluation of a scaling cascade model for temporal rainfall disaggregation, Hydrology and Earth System Sciences, 2, 19.30

Accelerating object detection via a visual-feature-directed search cascade: algorithm and field programmable gate array implementation

NASA Astrophysics Data System (ADS)

Kyrkou, Christos; Theocharides, Theocharis

2016-07-01

Object detection is a major step in several computer vision applications and a requirement for most smart camera systems. Recent advances in hardware acceleration for real-time object detection feature extensive use of reconfigurable hardware [field programmable gate arrays (FPGAs)], and relevant research has produced quite fascinating results, in both the accuracy of the detection algorithms as well as the performance in terms of frames per second (fps) for use in embedded smart camera systems. Detecting objects in images, however, is a daunting task and often involves hardware-inefficient steps, both in terms of the datapath design and in terms of input/output and memory access patterns. We present how a visual-feature-directed search cascade composed of motion detection, depth computation, and edge detection, can have a significant impact in reducing the data that needs to be examined by the classification engine for the presence of an object of interest. Experimental results on a Spartan 6 FPGA platform for face detection indicate data search reduction of up to 95%, which results in the system being able to process up to 50 1024×768 pixels images per second with a significantly reduced number of false positives.

An improved numerical method to compute neutron/gamma deexcitation cascades starting from a high spin state

DOE PAGES

Regnier, D.; Litaize, O.; Serot, O.

2015-12-23

Numerous nuclear processes involve the deexcitation of a compound nucleus through the emission of several neutrons, gamma-rays and/or conversion electrons. The characteristics of such a deexcitation are commonly derived from a total statistical framework often called “Hauser–Feshbach” method. In this work, we highlight a numerical limitation of this kind of method in the case of the deexcitation of a high spin initial state. To circumvent this issue, an improved technique called the Fluctuating Structure Properties (FSP) method is presented. Two FSP algorithms are derived and benchmarked on the calculation of the total radiative width for a thermal neutron capture onmore » 238U. We compare the standard method with these FSP algorithms for the prediction of particle multiplicities in the deexcitation of a high spin level of 143Ba. The gamma multiplicity turns out to be very sensitive to the numerical method. The bias between the two techniques can reach 1.5 γγ/cascade. Lastly, the uncertainty of these calculations coming from the lack of knowledge on nuclear structure is estimated via the FSP method.« less

MyD88-deficient Hydra reveal an ancient function of TLR signaling in sensing bacterial colonizers

PubMed Central

Franzenburg, Sören; Fraune, Sebastian; Künzel, Sven; Baines, John F.; Domazet-Lošo, Tomislav; Bosch, Thomas C. G.

2012-01-01

Toll-like receptor (TLR) signaling is one of the most important signaling cascades of the innate immune system of vertebrates. Studies in invertebrates have focused on the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans, and there is little information regarding the evolutionary origin and ancestral function of TLR signaling. In Drosophila, members of the Toll-like receptor family are involved in both embryonic development and innate immunity. In C. elegans, a clear immune function of the TLR homolog TOL-1 is controversial and central components of vertebrate TLR signaling including the key adapter protein myeloid differentiation primary response gene 88 (MyD88) and the transcription factor NF-κB are not present. In basal metazoans such as the cnidarians Hydra magnipapillata and Nematostella vectensis, all components of the vertebrate TLR signaling cascade are present, but their role in immunity is unknown. Here, we use a MyD88 loss-of-function approach in Hydra to demonstrate that recognition of bacteria is an ancestral function of TLR signaling and that this process contributes to both host-mediated recolonization by commensal bacteria as well as to defense against bacterial pathogens. PMID:23112184

MyD88-deficient Hydra reveal an ancient function of TLR signaling in sensing bacterial colonizers.

PubMed

Franzenburg, Sören; Fraune, Sebastian; Künzel, Sven; Baines, John F; Domazet-Loso, Tomislav; Bosch, Thomas C G

2012-11-20

Toll-like receptor (TLR) signaling is one of the most important signaling cascades of the innate immune system of vertebrates. Studies in invertebrates have focused on the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans, and there is little information regarding the evolutionary origin and ancestral function of TLR signaling. In Drosophila, members of the Toll-like receptor family are involved in both embryonic development and innate immunity. In C. elegans, a clear immune function of the TLR homolog TOL-1 is controversial and central components of vertebrate TLR signaling including the key adapter protein myeloid differentiation primary response gene 88 (MyD88) and the transcription factor NF-κB are not present. In basal metazoans such as the cnidarians Hydra magnipapillata and Nematostella vectensis, all components of the vertebrate TLR signaling cascade are present, but their role in immunity is unknown. Here, we use a MyD88 loss-of-function approach in Hydra to demonstrate that recognition of bacteria is an ancestral function of TLR signaling and that this process contributes to both host-mediated recolonization by commensal bacteria as well as to defense against bacterial pathogens.

Emerging Importance of Phytochemicals in Regulation of Stem Cells Fate via Signaling Pathways.

PubMed

Dadashpour, Mehdi; Pilehvar-Soltanahmadi, Younes; Zarghami, Nosratollah; Firouzi-Amandi, Akram; Pourhassan-Moghaddam, Mohammad; Nouri, Mohammad

2017-11-01

To reach ideal therapeutic potential of stem cells for regenerative medicine purposes, it is essential to retain their self-renewal and differentiation capacities. Currently, biological factors are extensively used for stemness maintaining and differentiation induction of stem cells. However, low stability, high cost, complicated production process, and risks associated with viral/endotoxin infection hamper the widespread use of biological factors in the stem cell biology. Moreover, regarding the modulation of several signaling cascades, which lead to a distinct fate, phytochemicals are preferable in the stem cells biology because of their efficiency. Considering the issues related to the application of biological factors and potential advantages of phytochemicals in stem cell engineering, there is a considerable increasing trend in studies associated with the application of novel alternative molecules in the stem cell biology. In support of this statement, we aimed to highlight the various effects of phytochemicals on signaling cascades involved in commitment of stem cells. Hence, in this review, the current trends in the phytochemicals-based modulation of stem cell fate have been addressed. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Contribution of inflammatory pathways to Fabry disease pathogenesis.

PubMed

Rozenfeld, Paula; Feriozzi, Sandro

2017-11-01

Lysosomal storage diseases are usually considered to be pathologies in which the passive deposition of unwanted materials leads to functional changes in lysosomes. Lysosomal deposition of unmetabolized glycolipid substrates stimulates the activation of pathogenic cascades, including immunological processes, and particularly the activation of inflammation. In lysosomal storage diseases, the inflammatory response is continuously being activated because the stimulus cannot be eliminated. Consequently, inflammation becomes a chronic process. Lysosomes play a role in many steps of the immune response. Leukocyte perturbation and over-expression of immune molecules have been reported in Fabry disease. Innate immunity is activated by signals originating from dendritic cells via interactions between toll-like receptors and globotriaosylceramide (Gb3) and/or globotriaosylsphingosine (lyso-Gb3). Evidence indicates that these glycolipids can activate toll-like receptors, thus triggering inflammation and fibrosis cascades. In the kidney, Gb3 deposition is associated with the increased release of transforming growth factor beta and with epithelial-to-mesenchymal cell transition, leading to the over-expression of pro-fibrotic molecules and to renal fibrosis. Interstitial fibrosis is also a typical feature of heart involvement in Fabry disease. Endomyocardial biopsies show infiltration of lymphocytes and macrophages, suggesting a role for inflammation in causing tissue damage. Inflammation is present in all tissues and may be associated with other potentially pathologic processes such as apoptosis, impaired autophagy, and increases in pro-oxidative molecules, which could all contribute synergistically to tissue damage. In Fabry disease, the activation of chronic inflammation over time leads to organ damage. Therefore, enzyme replacement therapy must be started early, before this process becomes irreversible. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Drug delivery systems and materials for wound healing applications.

PubMed

Saghazadeh, Saghi; Rinoldi, Chiara; Schot, Maik; Kashaf, Sara Saheb; Sharifi, Fatemeh; Jalilian, Elmira; Nuutila, Kristo; Giatsidis, Giorgio; Mostafalu, Pooria; Derakhshandeh, Hossein; Yue, Kan; Swieszkowski, Wojciech; Memic, Adnan; Tamayol, Ali; Khademhosseini, Ali

2018-04-05

Chronic, non-healing wounds place a significant burden on patients and healthcare systems, resulting in impaired mobility, limb amputation, or even death. Chronic wounds result from a disruption in the highly orchestrated cascade of events involved in wound closure. Significant advances in our understanding of the pathophysiology of chronic wounds have resulted in the development of drugs designed to target different aspects of the impaired processes. However, the hostility of the wound environment rich in degradative enzymes and its elevated pH, combined with differences in the time scales of different physiological processes involved in tissue regeneration require the use of effective drug delivery systems. In this review, we will first discuss the pathophysiology of chronic wounds and then the materials used for engineering drug delivery systems. Different passive and active drug delivery systems used in wound care will be reviewed. In addition, the architecture of the delivery platform and its ability to modulate drug delivery are discussed. Emerging technologies and the opportunities for engineering more effective wound care devices are also highlighted. Copyright © 2018 Elsevier B.V. All rights reserved.

Regulatory cascade of neuronal loss and glucose metabolism.

PubMed

Hassan, Mubashir; Sehgal, Sheikh A; Rashid, Sajid

2014-01-01

During recent years, numerous lines of research including proteomics and molecular biology have highlighted multiple targets and signaling pathways involved in metabolic abnormalities and neurodegeneration. However, correlation studies of individual neurodegenerative disorders (ND) including Alzheimer, Parkinson, Huntington and Amyotrophic lateral sclerosis in association with Diabetes type 2 Mellitus (D2M) are demanding tasks. Here, we report a comprehensive mechanistic overview of major contributors involved in process-based co-regulation of D2M and NDs. D2M is linked with Alzheimer's disease through deregulation of calcium ions thereby leading to metabolic fluctuations of glucose and insulin. Parkinson-associated proteins disturb insulin level through ATP-sensitive potassium ion channels and extracellular signal-regulated kinases to enhance glucose level. Similarly, proteins which perturb carbohydrate metabolism for disturbing glucose homeostasis link Huntington, Amyotrophic lateral sclerosis and D2M. Other misleading processes which interconnect D2M and NDs include oxidative stress, mitochondrial dysfunctions and microRNAs (miRNA29a/b and miRNA-9). Overall, the collective listing of pathway-specific targets would help in establishing novel connections between NDs and D2M to explore better therapeutic interventions.

Patients' experiences of using a smartphone application to increase physical activity: the SMART MOVE qualitative study in primary care.

PubMed

Casey, Monica; Hayes, Patrick S; Glynn, Fergus; OLaighin, Gearóid; Heaney, David; Murphy, Andrew W; Glynn, Liam G

2014-08-01

Regular physical activity is known to help prevent and treat numerous non-communicable diseases. Smartphone applications (apps) have been shown to increase physical activity in primary care but little is known regarding the views of patients using such technology or how such technology may change behaviour. To explore patients' views and experiences of using smartphones to promote physical activity in primary care. This qualitative study was embedded within the SMART MOVE randomised controlled trial, which used an app (Accupedo-Pro Pedometer) to promote physical activity in three primary care centres in the west of Ireland. Taped and transcribed semi-structured interviews with a purposeful sample of 12 participants formed the basis of the investigation. Framework analysis was used to analyse the data. Four themes emerged from the analysis: transforming relationships with exercise; persuasive technology tools; usability; and the cascade effect. The app appeared to facilitate a sequential and synergistic process of positive change, which occurred in the relationship between the participants and their exercise behaviour; the study has termed this the 'Know-Check-Move' effect. Usability challenges included increased battery consumption and adjusting to carrying the smartphone on their person. There was also evidence of a cascade effect involving the families and communities of participants. Notwithstanding technological challenges, an app has the potential to positively transform, in a unique way, participants' relationships with exercise. Such interventions can also have an associated cascade effect within their wider families and communities. © British Journal of General Practice 2014.

Patients’ experiences of using a smartphone application to increase physical activity: the SMART MOVE qualitative study in primary care

PubMed Central

Casey, Monica; Hayes, Patrick S; Glynn, Fergus; ÓLaighin, Gearóid; Heaney, David; Murphy, Andrew W; Glynn, Liam G

2014-01-01

Background Regular physical activity is known to help prevent and treat numerous non-communicable diseases. Smartphone applications (apps) have been shown to increase physical activity in primary care but little is known regarding the views of patients using such technology or how such technology may change behaviour. Aim To explore patients’ views and experiences of using smartphones to promote physical activity in primary care. Design and setting This qualitative study was embedded within the SMART MOVE randomised controlled trial, which used an app (Accupedo-Pro Pedometer) to promote physical activity in three primary care centres in the west of Ireland. Method Taped and transcribed semi-structured interviews with a purposeful sample of 12 participants formed the basis of the investigation. Framework analysis was used to analyse the data. Results Four themes emerged from the analysis: transforming relationships with exercise; persuasive technology tools; usability; and the cascade effect. The app appeared to facilitate a sequential and synergistic process of positive change, which occurred in the relationship between the participants and their exercise behaviour; the study has termed this the ‘Know-Check-Move’ effect. Usability challenges included increased battery consumption and adjusting to carrying the smartphone on their person. There was also evidence of a cascade effect involving the families and communities of participants. Conclusion Notwithstanding technological challenges, an app has the potential to positively transform, in a unique way, participants’ relationships with exercise. Such interventions can also have an associated cascade effect within their wider families and communities. PMID:25071063

Is cascade reinforcement likely when sympatric and allopatric populations exchange migrants?

PubMed

Yukilevich, Roman; Aoki, Fumio

2016-04-01

When partially reproductively isolated species come back into secondary contact, these taxa may diverge in mating preferences and sexual cues to avoid maladaptive hybridization, a process known as reinforcement. This phenomenon often leads to reproductive character displacement (RCD) between sympatric and allopatric populations of reinforcing species that differ in their exposure to hybridization. Recent discussions have reinvigorated the idea that RCD may give rise to additional speciation between conspecific sympatric and allopatric populations, dubbing the concept "cascade reinforcement." Despite some empirical studies supporting cascade reinforcement, we still know very little about the conditions for its evolution. In the present article, we address this question by developing an individual-based population genetic model that explicitly simulates cascade reinforcement when one of the hybridizing species is split into sympatric and allopatric populations. Our results show that when sympatric and allopatric populations reside in the same environment and only differ in their exposure to maladaptive hybridization, migration between them generally inhibits the evolution of cascade by spreading the reinforcement alleles from sympatry into allopatry and erasing RCD. Under these conditions, cascade reinforcement only evolved when migration rate between sympatric and allopatric populations was very low. This indicates that stabilizing sexual selection in allopatry is generally ineffective in preventing the spread of reinforcement alleles. Only when sympatric and allopatric populations experienced divergent ecological selection did cascade reinforcement evolve in the presence of substantial migration. These predictions clarify the conditions for cascade reinforcement and facilitate our understanding of existing cases in nature.

Is cascade reinforcement likely when sympatric and allopatric populations exchange migrants?

PubMed Central

Yukilevich, Roman; Aoki, Fumio

2016-01-01

Abstract When partially reproductively isolated species come back into secondary contact, these taxa may diverge in mating preferences and sexual cues to avoid maladaptive hybridization, a process known as reinforcement. This phenomenon often leads to reproductive character displacement (RCD) between sympatric and allopatric populations of reinforcing species that differ in their exposure to hybridization. Recent discussions have reinvigorated the idea that RCD may give rise to additional speciation between conspecific sympatric and allopatric populations, dubbing the concept “cascade reinforcement.” Despite some empirical studies supporting cascade reinforcement, we still know very little about the conditions for its evolution. In the present article, we address this question by developing an individual-based population genetic model that explicitly simulates cascade reinforcement when one of the hybridizing species is split into sympatric and allopatric populations. Our results show that when sympatric and allopatric populations reside in the same environment and only differ in their exposure to maladaptive hybridization, migration between them generally inhibits the evolution of cascade by spreading the reinforcement alleles from sympatry into allopatry and erasing RCD. Under these conditions, cascade reinforcement only evolved when migration rate between sympatric and allopatric populations was very low. This indicates that stabilizing sexual selection in allopatry is generally ineffective in preventing the spread of reinforcement alleles. Only when sympatric and allopatric populations experienced divergent ecological selection did cascade reinforcement evolve in the presence of substantial migration. These predictions clarify the conditions for cascade reinforcement and facilitate our understanding of existing cases in nature. PMID:29491903

The emerging roles of β-arrestins in fibrotic diseases

PubMed Central

Gu, Yuan-jing; Sun, Wu-yi; Zhang, Sen; Wu, Jing-jing; Wei, Wei

2015-01-01

β-Arrestins and β-arrestin2 are important adaptor proteins and signal transduction proteins that are mainly involved in the desensitization and internalization of G-protein-coupled receptors. Fibrosis is characterized by accumulation of excess extracellular matrix (ECM) molecules caused by chronic tissue injury. If highly progressive, the fibrotic process leads to organ malfunction and, eventually, death. The incurable lung fibrosis, renal fibrosis and liver fibrosis are among the most common fibrotic diseases. Recent studies show that β-arrestins can activate signaling cascades independent of G-protein activation and scaffold many intracellular signaling networks by diverse types of signaling pathways, including the Hedgehog, Wnt, Notch and transforming growth factor-β pathways, as well as downstream kinases such as MAPK and PI3K. These signaling pathways are involved in the pathological process of fibrosis and fibrotic diseases. This β-arrestin-mediated regulation not only affects cell growth and apoptosis, but also the deposition of ECM, activation of inflammatory response and development of fibrotic diseases. In this review, we survey the involvement of β-arrestins in various signaling pathways and highlight different aspects of their regulation of fibrosis. We also discuss the important roles of β-arrestins in the process of fibrotic diseases by regulating the inflammation and deposit of ECM. It is becoming more evident that targeting β-arrestins may offer therapeutic potential for the treatment of fibrotic diseases. PMID:26388156

Polysaccharide of Black cumin (Nigella sativa) modulates molecular signaling cascade of gastric ulcer pathogenesis.

PubMed

Manjegowda, Srikanta Belagihalli; Rajagopal, Harsha Mysore; Dharmesh, Shylaja Mallaiah

2017-08-01

Gastric ulcer is a multi-step disease and healing requires a complex process including repair and re-architecture of gastric mucosa with the involvement of molecular events. Current study was designed to understand the gastric ulcer healing mechanism of rhamnogalacturonan-I type pectic polysaccharide of black cumin (BCPP) utilizing acetic acid induced gastric ulcers in rats. BCPP fed groups at 200mg/kg b.w. for 10days showed up to 85% healing of gastric ulcers with modulation of key molecular events involved in ulcer healing process such as increase in gastric mucin content, cyclooxygenase-2 (Cox-2) and prostaglandin E 2 (PGE 2 ). The increase in extracellular signal-regulated kinase-2 (ERK-2) indicated that, BCPP could induce PGE-2 synthesis by increasing ERK-2 mediated COX-2 activity. Increase in matrix metalloproteinase-2 (MMP-2) and decrease in MMP-9 levels in BCPP treated groups indicated differential regulation of MMP-2 and 9, an essential event required for gastric mucosal re-modulation. BCPP containing bound phenolics (26mg/g) might have also played a role in increasing speed and quality of ulcer healing by inhibiting H + , K + -ATPase and decreasing free radical mediated oxidation and cellular damages. Overall, studies showed that the polysaccharide can mediate ulcer healing by modulating signaling pathways involved in either ulcer aggravation or healing process. Copyright © 2017. Published by Elsevier B.V.

The locus of serial processing in reading aloud: orthography-to-phonology computation or speech planning?

PubMed

Mousikou, Petroula; Rastle, Kathleen; Besner, Derek; Coltheart, Max

2015-07-01

Dual-route theories of reading posit that a sublexical reading mechanism that operates serially and from left to right is involved in the orthography-to-phonology computation. These theories attribute the masked onset priming effect (MOPE) and the phonological Stroop effect (PSE) to the serial left-to-right operation of this mechanism. However, both effects may arise during speech planning, in the phonological encoding process, which also occurs serially and from left to right. In the present paper, we sought to determine the locus of serial processing in reading aloud by testing the contrasting predictions that the dual-route and speech planning accounts make in relation to the MOPE and the PSE. The results from three experiments that used the MOPE and the PSE paradigms in English are inconsistent with the idea that these effects arise during speech planning, and consistent with the claim that a sublexical serially operating reading mechanism is involved in the print-to-sound translation. Simulations of the empirical data on the MOPE with the dual route cascaded (DRC) and connectionist dual process (CDP++) models, which are computational implementations of the dual-route theory of reading, provide further support for the dual-route account. (c) 2015 APA, all rights reserved.

The role of cannabinoids in adult neurogenesis

PubMed Central

Prenderville, Jack A; Kelly, Áine M; Downer, Eric J

2015-01-01

The processes underpinning post-developmental neurogenesis in the mammalian brain continue to be defined. Such processes involve the proliferation of neural stem cells and neural progenitor cells (NPCs), neuronal migration, differentiation and integration into a network of functional synapses within the brain. Both intrinsic (cell signalling cascades) and extrinsic (neurotrophins, neurotransmitters, cytokines, hormones) signalling molecules are intimately associated with adult neurogenesis and largely dictate the proliferative activity and differentiation capacity of neural cells. Cannabinoids are a unique class of chemical compounds incorporating plant-derived cannabinoids (the active components of Cannabis sativa), the endogenous cannabinoids and synthetic cannabinoid ligands, and these compounds are becoming increasingly recognized for their roles in neural developmental processes. Indeed, cannabinoids have clear modulatory roles in adult neurogenesis, probably through activation of both CB1 and CB2 receptors. In recent years, a large body of literature has deciphered the signalling networks involved in cannabinoid-mediated regulation of neurogenesis. This timely review summarizes the evidence that the cannabinoid system is intricately associated with neuronal differentiation and maturation of NPCs and highlights intrinsic/extrinsic signalling mechanisms that are cannabinoid targets. Overall, these findings identify the central role of the cannabinoid system in adult neurogenesis in the hippocampus and the lateral ventricles and hence provide insight into the processes underlying post-developmental neurogenesis in the mammalian brain. PMID:25951750

The Emergence of Network Inefficiencies in Infants With Autism Spectrum Disorder.

PubMed

Lewis, John D; Evans, Alan C; Pruett, John R; Botteron, Kelly N; McKinstry, Robert C; Zwaigenbaum, Lonnie; Estes, Annette M; Collins, D Louis; Kostopoulos, Penelope; Gerig, Guido; Dager, Stephen R; Paterson, Sarah; Schultz, Robert T; Styner, Martin A; Hazlett, Heather C; Piven, Joseph

2017-08-01

Autism spectrum disorder (ASD) is a developmental disorder defined by behavioral features that emerge during the first years of life. Research indicates that abnormalities in brain connectivity are associated with these behavioral features. However, the inclusion of individuals past the age of onset of the defining behaviors complicates interpretation of the observed abnormalities: they may be cascade effects of earlier neuropathology and behavioral abnormalities. Our recent study of network efficiency in a cohort of 24-month-olds at high and low familial risk for ASD reduced this confound; we reported reduced network efficiencies in toddlers classified with ASD. The current study maps the emergence of these inefficiencies in the first year of life. This study uses data from 260 infants at 6 and 12 months of age, including 116 infants with longitudinal data. As in our earlier study, we use diffusion data to obtain measures of the length and strength of connections between brain regions to compute network efficiency. We assess group differences in efficiency within linear mixed-effects models determined by the Akaike information criterion. Inefficiencies in high-risk infants later classified with ASD were detected from 6 months onward in regions involved in low-level sensory processing. In addition, within the high-risk infants, these inefficiencies predicted 24-month symptom severity. These results suggest that infants with ASD, even before 6 months of age, have deficits in connectivity related to low-level processing, which contribute to a developmental cascade affecting brain organization and eventually higher-level cognitive processes and social behavior. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Control of radiative base recombination in the quantum cascade light-emitting transistor using quantum state overlap

NASA Astrophysics Data System (ADS)

Chen, Kanuo; Hsiao, Fu-Chen; Joy, Brittany; Dallesasse, John M.

2018-07-01

The concept of the quantum cascade light-emitting transistor (QCLET) is proposed by incorporating periodic stages of quantum wells and barriers in the completely depleted base-collector junction of a heterojunction bipolar transistor. The radiative band-to-band base recombination in the QCLET is shown to be controllable using the base-collector voltage bias for a given emitter-base biasing condition. A self-consistent Schrödinger-Poisson Equation model is built to validate the idea of the QCLET. A GaAs-based QCLET is designed and fabricated. Control of radiative band-to-band base recombination is observed and characterized. By changing the voltage across the quantum cascade region in the QCLET, the alignment of quantum states in the cascade region creates a tunable barrier for electrons that allows or suppresses emitter-injected electron flow from the p-type base through the quantum cascade region into the collector. The field-dependent electron barrier in the base-collector junction manipulates the effective minority carrier lifetime in the base and controls the radiative base recombination process. Under different quantum cascade region biasing conditions, the radiative base recombination is measured and analyzed.

Quantum Cascade Lasers Modulation and Applications

NASA Astrophysics Data System (ADS)

Luzhansky, Edward

The mid-wave IR (MWIR) spectral band, extending from 3 to 5 microns, is considered to be a low loss atmospheric window. There are several spectral sub-bands with relatively low atmospheric attenuation in this region making it popular for various commercial and military applications. Relatively low thermal and solar background emissions, effective penetration through the natural and anthropogenic obscurants and eye safety add to the long list of advantages of MWIR wavelengths. Quantum Cascade Lasers are compact semiconductor devices capable of operating in MWIR spectrum. They are based on inter-subband transitions in a multiple-quantum-well (QW) hetero-structure, designed by means of band-structure engineering. The inter-subband nature of the optical transition has several key advantages. First, the emission wavelength is primarily a function of the QW thickness. This characteristic allows choosing well-understood and reliable semiconductors for the generation of light in a wavelength range of interest. Second, a cascade process in which tens of photons are generated per injected electron. This cascading process is behind the intrinsic high-power capabilities of QCLs. This dissertation is focused on modulation properties of Quantum Cascade Lasers. Both amplitude and phase/frequency modulations were studied including modulation bandwidth, modulation efficiency and chirp linearity. Research was consisted of the two major parts. In the first part we describe the theory of frequency modulation (FM) response of Distributed Feedback Quantum Cascade Lasers (DFB QCL). It includes cascading effect on the QCL's maximum modulation frequency. The "gain levering" effect for the maximum FM response of the two section QCLs was studied as well. In the second part of research we concentrated on the Pulse Position Amplitude Modulation of a single section QCL. The low complexity, low size, weight and power Mid-Wavelength Infra-Red optical communications transceiver concept is introduced. The concept was realized and tested in the laboratory environment. The resilience to atmospheric impairments are analyzed with simulated turbulence. The performance compared to typical telecom based Short Wavelength Infra-Red transceiver.

Development of a continuous process for α-thio-β-chloroacrylamide synthesis with enhanced control of a cascade transformation

PubMed Central

Dennehy, Olga C; Cacheux, Valérie M Y; Deadman, Benjamin J; Lynch, Denis

2016-01-01

A continuous process strategy has been developed for the preparation of α-thio-β-chloroacrylamides, a class of highly versatile synthetic intermediates. Flow platforms to generate the α-chloroamide and α-thioamide precursors were successfully adopted, progressing from the previously employed batch chemistry, and in both instances afford a readily scalable methodology. The implementation of the key α-thio-β-chloroacrylamide casade as a continuous flow reaction on a multi-gram scale is described, while the tuneable nature of the cascade, facilitated by continuous processing, is highlighted by selective generation of established intermediates and byproducts. PMID:28144320

A cascade model of mentorship for frontline health workers in rural health facilities in Eastern Uganda: processes, achievements and lessons.

PubMed

Ajeani, Judith; Mangwi Ayiasi, Richard; Tetui, Moses; Ekirapa-Kiracho, Elizabeth; Namazzi, Gertrude; Muhumuza Kananura, Ronald; Namusoke Kiwanuka, Suzanne; Beyeza-Kashesya, Jolly

2017-08-01

There is increasing demand for trainers to shift from traditional didactic training to innovative approaches that are more results-oriented. Mentorship is one such approach that could bridge the clinical knowledge gap among health workers. This paper describes the experiences of an attempt to improve health-worker performance in maternal and newborn health in three rural districts through a mentoring process using the cascade model. The paper further highlights achievements and lessons learnt during implementation of the cascade model. The cascade model started with initial training of health workers from three districts of Pallisa, Kibuku and Kamuli from where potential local mentors were selected for further training and mentorship by central mentors. These local mentors then went on to conduct mentorship visits supported by the external mentors. The mentorship process concentrated on partograph use, newborn resuscitation, prevention and management of Post-Partum Haemorrhage (PPH), including active management of third stage of labour, preeclampsia management and management of the sick newborn. Data for this paper was obtained from key informant interviews with district-level managers and local mentors. Mentorship improved several aspects of health-care delivery, ranging from improved competencies and responsiveness to emergencies and health-worker professionalism. In addition, due to better district leadership for Maternal and Newborn Health (MNH), there were improved supplies/medicine availability, team work and innovative local problem-solving approaches. Health workers were ultimately empowered to perform better. The study demonstrated that it is possible to improve the competencies of frontline health workers through performance enhancement for MNH services using locally built capacity in clinical mentorship for Emergency Obstetric and Newborn Care (EmONC). The cascade mentoring process needed strong external mentorship support at the start to ensure improved capacity among local mentors to provide mentorship among local district staff.

Recent progress on gas sensor based on quantum cascade lasers and hollow fiber waveguides

NASA Astrophysics Data System (ADS)

Liu, Ningwu; Sun, Juan; Deng, Hao; Ding, Junya; Zhang, Lei; Li, Jingsong

2017-02-01

Mid-infrared laser spectroscopy provides an ideal platform for trace gas sensing applications. Despite this potential, early MIR sensing applications were limited due to the size of the involved optical components, e.g. light sources and sample cells. A potential solution to this demand is the integration of hollow fiber waveguide with novelty quantum cascade lasers.Recently QCLs had great improvements in power, efficiency and wavelength range, which made the miniaturized platforms for gas sensing maintaining or even enhancing the achievable sensitivity conceivable. So that the miniaturization of QCLs and HWGs can be evolved into a mini sensor, which may be tailored to a variety of real-time and in situ applications ranging from environmental monitoring to workplace safety surveillance. In this article, we introduce QCLs and HWGs, display the applications of HWG based on QCL gas sensing and discuss future strategies for hollow fiber coupled quantum cascade laser gas sensor technology.

The Hallmarks of Cancer from a Redox Perspective.

PubMed

Hornsveld, Marten; Dansen, Tobias B

2016-08-20

For a healthy cell to turn into a cancer cell and grow out to become a tumor, it needs to undergo a series of complex changes and acquire certain traits, summarized as "The Hallmarks of Cancer." These hallmarks can all be regarded as the result of altered signal transduction cascades and an understanding of these cascades is essential for cancer treatment. Redox signaling is a long overlooked form of signal transduction that proceeds through the reversible oxidation of cysteines in proteins and that uses hydrogen peroxide as a second messenger. In this article, we provide examples that show that redox signaling is involved in the regulation of proteins and signaling cascades that play roles in every hallmark of cancer. An understanding of how redox signaling and "classical" signal transduction are intertwined could hold promising strategies for cancer therapy in the future. Antioxid. Redox Signal. 25, 300-325.

Multi-catalysis cascade reactions based on the methoxycarbonylketene platform: diversity-oriented synthesis of functionalized non-symmetrical malonates for agrochemicals and pharmaceuticals.

PubMed

Ramachary, Dhevalapally B; Venkaiah, Chintalapudi; Reddy, Y Vijayendar; Kishor, Mamillapalli

2009-05-21

In this paper we describe new multi-catalysis cascade (MCC) reactions for the one-pot synthesis of highly functionalized non-symmetrical malonates. These metal-free reactions are either five-step (olefination/hydrogenation/alkylation/ketenization/esterification) or six-step (olefination/hydrogenation/alkylation/ketenization/esterification/alkylation), and employ aldehydes/ketones, Meldrum's acid, 1,4-dihydropyridine/o-phenylenediamine, diazomethane, alcohols and active ethylene/acetylenes, and involve iminium-, self-, self-, self- and base-catalysis, respectively. Many of the products have direct application in agricultural and pharmaceutical chemistry.

Palladium-Catalyzed [3 + 2]-C-C/N-C Bond-Forming Annulation.

PubMed

Liu, Yang; Mao, Zhongyi; Pradal, Alexandre; Huang, Pei-Qiang; Oble, Julie; Poli, Giovanni

2018-06-13

The synthesis of bi- and tricyclic structures incorporating pyrrolidone rings is disclosed, starting from resonance-stabilized acetamides and cyclic α,β-unsaturated-γ-oxycarbonyl derivatives. This process involves an intermolecular Tsuji-Trost allylation/intramolecular nitrogen 1,4-addition sequence. Crucial for the success of this bis-nucleophile/bis-electrophile [3 + 2] annulation is its well-defined step chronology in combination with the total chemoselectivity of the former step. When the newly formed annulation product carries a properly located o-haloaryl moiety at the nitrogen substituent, a further intramolecular keto α-arylation can join the cascade, thereby forming two new cycles and three new bonds in the same synthetic operation.

LCA-based optimization of wood utilization under special consideration of a cascading use of wood.

PubMed

Höglmeier, Karin; Steubing, Bernhard; Weber-Blaschke, Gabriele; Richter, Klaus

2015-04-01

Cascading, the use of the same unit of a resource in multiple successional applications, is considered as a viable means to improve the efficiency of resource utilization and to decrease environmental impacts. Wood, as a regrowing but nevertheless limited and increasingly in demand resource, can be used in cascades, thereby increasing the potential efficiency per unit of wood. This study aims to assess the influence of cascading wood utilization on optimizing the overall environmental impact of wood utilization. By combining a material flow model of existing wood applications - both for materials provision and energy production - with an algebraic optimization tool, the effects of the use of wood in cascades can be modelled and quantified based on life cycle impact assessment results for all production processes. To identify the most efficient wood allocation, the effects of a potential substitution of non-wood products were taken into account in a part of the model runs. The considered environmental indicators were global warming potential, particulate matter formation, land occupation and an aggregated single score indicator. We found that optimizing either the overall global warming potential or the value of the single score indicator of the system leads to a simultaneous relative decrease of all other considered environmental impacts. The relative differences between the impacts of the model run with and without the possibility of a cascading use of wood were 7% for global warming potential and the single score indicator, despite cascading only influencing a small part of the overall system, namely wood panel production. Cascading led to savings of up to 14% of the annual primary wood supply of the study area. We conclude that cascading can improve the overall performance of a wood utilization system. Copyright © 2015 Elsevier Ltd. All rights reserved.

Potassium titanyl arsenate based cascaded optical parametric oscillator emit at 2.5 µm derived by neodymium-doped yttrium lithium fluoride laser

NASA Astrophysics Data System (ADS)

Duan, Yanmin; Zhang, Jing; Guo, Junhong; Zhu, Haiyong; Zhang, Yongchang; Xu, Changwen; Wang, Hongyan; Zhang, Yaoju

2018-04-01

We reported a potassium titanyl arsenate (KTA) based cascaded optical parametric oscillator (OPO). The secondary OPO signal light at 2.5 µm was obtained with two OPO processes in one non-critical phase matching cut KTA crystal. This cascaded OPO was driven by a Q-switched neodymium-doped yttrium lithium fluoride (Nd:YLF) laser at 1047 nm. Making full use of the negative thermal lens effect and long upper level fluorescence lifetime of Nd:YLF, signal power of 605 mW at 2503 nm was achieved with a pulse repetition frequency of 15 kHz and an incident diode pump power of 9.7 W. Therefore, the cascaded OPO derived by Q-switched Nd:YLF laser could provide high peak power pulsed laser emission in mid-infrared band.

Forward design of a complex enzyme cascade reaction

PubMed Central

Hold, Christoph; Billerbeck, Sonja; Panke, Sven

2016-01-01

Enzymatic reaction networks are unique in that one can operate a large number of reactions under the same set of conditions concomitantly in one pot, but the nonlinear kinetics of the enzymes and the resulting system complexity have so far defeated rational design processes for the construction of such complex cascade reactions. Here we demonstrate the forward design of an in vitro 10-membered system using enzymes from highly regulated biological processes such as glycolysis. For this, we adapt the characterization of the biochemical system to the needs of classical engineering systems theory: we combine online mass spectrometry and continuous system operation to apply standard system theory input functions and to use the detailed dynamic system responses to parameterize a model of sufficient quality for forward design. This allows the facile optimization of a 10-enzyme cascade reaction for fine chemical production purposes. PMID:27677244

Cascade control of superheated steam temperature with neuro-PID controller.

PubMed

Zhang, Jianhua; Zhang, Fenfang; Ren, Mifeng; Hou, Guolian; Fang, Fang

2012-11-01

In this paper, an improved cascade control methodology for superheated processes is developed, in which the primary PID controller is implemented by neural networks trained by minimizing error entropy criterion. The entropy of the tracking error can be estimated recursively by utilizing receding horizon window technique. The measurable disturbances in superheated processes are input to the neuro-PID controller besides the sequences of tracking error in outer loop control system, hence, feedback control is combined with feedforward control in the proposed neuro-PID controller. The convergent condition of the neural networks is analyzed. The implementation procedures of the proposed cascade control approach are summarized. Compared with the neuro-PID controller using minimizing squared error criterion, the proposed neuro-PID controller using minimizing error entropy criterion may decrease fluctuations of the superheated steam temperature. A simulation example shows the advantages of the proposed method. Copyright © 2012 ISA. Published by Elsevier Ltd. All rights reserved.

Climate change impacts on maritime mountain snowpack in the Oregon Cascades

Treesearch

E. Sproles; A.W. Nolin; K. Rittger; T.H. Painter

2013-01-01

This study investigates the effect of projected temperature increases on maritime mountain snowpack in the McKenzie River Basin (MRB; 3041 km2) in the Cascades Mountains of Oregon, USA. We simulated the spatial distribution of snow water equivalent (SWE) in the MRB for the period of 1989–2009 with SnowModel, a spatiallydistributed, process-based...

A rapid, one-pot, microwave-influenced synthesis of spiro-2,5-diketopiperazines via a cascade Ugi/6-exo-trig aza-Michael reaction.

PubMed

Santra, Soumava; Andreana, Peter R

2011-04-01

A rapid, cascade reaction process has been developed to access biologically validated spiro-2,5-diketopiperazines. The facile and environmentally benign method capitalizes on commercially available starting reagents for a sequential Ugi/6-exo-trig aza-Michael reaction, water as a solvent, and microwave irradiation without any extraneous additives.

Fire and weather disturbances in terrestrial ecosystems of the eastern Cascades.

Treesearch

James K. Agee

1994-01-01

Fire has been an important ecological process in eastside Cascade ecosystems for millennia. Fire regimes ranged from low severity to high severity, and historic fire return intervals ranged from less than a decade to greater than 300 years. Fire history and effects are described for grassland and shrubland ecosystems, and the range of forested communities by plant...

Exploring utilitarian and hedonic antecedents for adopting information from a recommendation agent and unplanned purchase behaviour

NASA Astrophysics Data System (ADS)

Huang, Li-Ting

2016-01-01

Research indicated that in order for properly utilizing recommendation agents (RAs), customers must rationally evaluate capability and suggestions of RAs during the interaction process. However, enjoying interactive processes and interface is also important. Methods for increasing user enjoyment of RAs are yet unknown. This study investigated the influences of utilitarian and hedonic factors on intention to adopt RAs suggestions and their antecedents. Involvement influences relative importance of utilitarian and hedonic factors. Contrary to common assumptions, customers may make unplanned purchases, rather than rational purchase. A field experiment with 2 × 2 × 2 factorial design reveals main findings. First, information diagnosticity and enjoyment enhance adoption intention simultaneously. Information diagnosticity is more important than enjoyment. Diagnosticity was determined by outcome similarity, and enjoyment was determined by both outcome similarity and atmospherics. The context of interacting with RAs is important. Outcome similarity even directly affects adoption intention. Second, highly involved users considered enjoyment and diagnosticity when forming adoption intentions, while users with low involvement only considered enjoyment. Third, information cascades altered the relationship between adoption intention and unplanned purchases. Most customers change selection after seeing ratings from other customers, even if they originally strongly want to adoption suggestion from RAs. Theoretical and managerial implications are proposed.

Cryptococcus neoformans Mediator Protein Ssn8 Negatively Regulates Diverse Physiological Processes and Is Required for Virulence

PubMed Central

Wang, Lin-Ing; Lin, Yu-Sheng; Liu, Kung-Hung; Jong, Ambrose Y.; Shen, Wei-Chiang

2011-01-01

Cryptococcus neoformans is a ubiquitously distributed human pathogen. It is also a model system for studying fungal virulence, physiology and differentiation. Light is known to inhibit sexual development via the evolutionarily conserved white collar proteins in C. neoformans. To dissect molecular mechanisms regulating this process, we have identified the SSN8 gene whose mutation suppresses the light-dependent CWC1 overexpression phenotype. Characterization of sex-related phenotypes revealed that Ssn8 functions as a negative regulator in both heterothallic a-α mating and same-sex mating processes. In addition, Ssn8 is involved in the suppression of other physiological processes including invasive growth, and production of capsule and melanin. Interestingly, Ssn8 is also required for the maintenance of cell wall integrity and virulence. Our gene expression studies confirmed that deletion of SSN8 results in de-repression of genes involved in sexual development and melanization. Epistatic and yeast two hybrid studies suggest that C. neoformans Ssn8 plays critical roles downstream of the Cpk1 MAPK cascade and Ste12 and possibly resides at one of the major branches downstream of the Cwc complex in the light-mediated sexual development pathway. Taken together, our studies demonstrate that the conserved Mediator protein Ssn8 functions as a global regulator which negatively regulates diverse physiological and developmental processes and is required for virulence in C. neoformans. PMID:21559476

Phase-synchronization, energy cascade, and intermittency in solar-wind turbulence.

PubMed

Perri, S; Carbone, V; Vecchio, A; Bruno, R; Korth, H; Zurbuchen, T H; Sorriso-Valvo, L

2012-12-14

The energy cascade in solar wind magnetic turbulence is investigated using MESSENGER data in the inner heliosphere. The decomposition of magnetic field time series in intrinsic functions, each characterized by a typical time scale, reveals phase reorganization. This allows for the identification of structures of all sizes generated by the nonlinear turbulent cascade, covering both the inertial and the dispersive ranges of the turbulent magnetic power spectrum. We find that the correlation (or anticorrelation) of phases occurs between pairs of neighboring time scales, whenever localized peaks of magnetic energy are present at both scales, consistent with the local character of the energy transfer process.

Renormalization of the fragmentation equation: exact self-similar solutions and turbulent cascades.

PubMed

Saveliev, V L; Gorokhovski, M A

2012-12-01

Using an approach developed earlier for renormalization of the Boltzmann collision integral [Saveliev and Nanbu, Phys. Rev. E 65, 051205 (2002)], we derive an exact divergence form for the fragmentation operator. Then we reduce the fragmentation equation to the continuity equation in size space, with the flux given explicitly. This allows us to obtain self-similar solutions and to find the integral of motion for these solutions (we call it the bare flux). We show how these solutions can be applied as a description of cascade processes in three- and two-dimensional turbulence. We also suggested an empirical cascade model of impact fragmentation of brittle materials.

Special Issue ;Sediment cascades in cold climate geosystems;

NASA Astrophysics Data System (ADS)

Morche, David; Krautblatter, Michael; Beylich, Achim A.

2017-06-01

This Editorial introduces the Special Issue on sediment cascades in cold climate geosystems that evolved from the eighth I.A.G./A.I.G. SEDIBUD (Sediment Budgets in Cold Environments; http://www.geomorph.org/sedibud-working-group/) workshop. The workshop was held from 1st to 4th September 2014 at the Environmental Research Station ;Schneefernerhaus; (http://www.schneefernerhaus.de/en/home.html) located at Mt. Zugspitze, the highest peak of Germany, (2962 m asl). Paper and poster presentations focused on observations, measurements and modeling of geomorphological processes in sediment cascades in cold climate geosystems. This resulting Special Issue brings together ten selected contributions from arctic and alpine environments.

Applications of absorption spectroscopy using quantum cascade lasers.

PubMed

Zhang, Lizhu; Tian, Guang; Li, Jingsong; Yu, Benli

2014-01-01

Infrared laser absorption spectroscopy (LAS) is a promising modern technique for sensing trace gases with high sensitivity, selectivity, and high time resolution. Mid-infrared quantum cascade lasers, operating in a pulsed or continuous wave mode, have potential as spectroscopic sources because of their narrow linewidths, single mode operation, tunability, high output power, reliability, low power consumption, and compactness. This paper reviews some important developments in modern laser absorption spectroscopy based on the use of quantum cascade laser (QCL) sources. Among the various laser spectroscopic methods, this review is focused on selected absorption spectroscopy applications of QCLs, with particular emphasis on molecular spectroscopy, industrial process control, combustion diagnostics, and medical breath analysis.

Transverse Cascade and Sustenance of Turbulence in Keplerian Disks with an Azimuthal Magnetic Field

NASA Astrophysics Data System (ADS)

Gogichaishvili, D.; Mamatsashvili, G.; Horton, W.; Chagelishvili, G.; Bodo, G.

2017-10-01

The magnetorotational instability (MRI) in the sheared rotational Keplerian explains fundamental problems for both astrophysics and toroidal laboratory plasmas. The turbulence occurs before the threshold for the linear eigen modes. The work shows the turbulence occurs in nonzero toroidal magnetic field with a sheared toroidal flow velocity. We analyze the turbulence in Fourier k-space and x-space each time step to clarify the nonlinear energy-momentum transfers that produce the sustenance in the linearly stable plasma. The nonlinear process is a type 3D angular redistribution of modes in Fourier space - a transverse cascade - rather than the direct/inverse cascades. The turbulence is sustained an interplay of the linear transient growth from the radial gradient of the toroidal velocity (which is the only energy supply for the turbulence) and the transverse cascade. There is a relatively small ``vital area in Fourier space'' is crucial for the sustenance. Outside the vital area the direct cascade dominates. The interplay of the linear and nonlinear processes is generally too intertwined in k-space for a classical turbulence characterization. Subcycles occur from the interactions that maintain self-organization nonlinear turbulence. The spectral characteristics in four simulations are similar showing the universality of the sustenance mechanism of the shear flow driven MHDs-turbulence. Funded by the US Department of Energy under Grant DE-FG02-04ER54742 and the Space and Geophysics Laboratory at the University of Texas at Austin. G. Mamatsashvili is supported by the Alexander von Humboldt Foundation, Germany.

Multiple Linear Regression for Reconstruction of Gene Regulatory Networks in Solving Cascade Error Problems

PubMed Central

Zainudin, Suhaila; Arif, Shereena M.

2017-01-01

Gene regulatory network (GRN) reconstruction is the process of identifying regulatory gene interactions from experimental data through computational analysis. One of the main reasons for the reduced performance of previous GRN methods had been inaccurate prediction of cascade motifs. Cascade error is defined as the wrong prediction of cascade motifs, where an indirect interaction is misinterpreted as a direct interaction. Despite the active research on various GRN prediction methods, the discussion on specific methods to solve problems related to cascade errors is still lacking. In fact, the experiments conducted by the past studies were not specifically geared towards proving the ability of GRN prediction methods in avoiding the occurrences of cascade errors. Hence, this research aims to propose Multiple Linear Regression (MLR) to infer GRN from gene expression data and to avoid wrongly inferring of an indirect interaction (A → B → C) as a direct interaction (A → C). Since the number of observations of the real experiment datasets was far less than the number of predictors, some predictors were eliminated by extracting the random subnetworks from global interaction networks via an established extraction method. In addition, the experiment was extended to assess the effectiveness of MLR in dealing with cascade error by using a novel experimental procedure that had been proposed in this work. The experiment revealed that the number of cascade errors had been very minimal. Apart from that, the Belsley collinearity test proved that multicollinearity did affect the datasets used in this experiment greatly. All the tested subnetworks obtained satisfactory results, with AUROC values above 0.5. PMID:28250767

Viral-induced systemic necrosis in plants involves both programmed cell death and the inhibition of viral multiplication, which are regulated by independent pathways.

PubMed

Komatsu, Ken; Hashimoto, Masayoshi; Ozeki, Johji; Yamaji, Yasuyuki; Maejima, Kensaku; Senshu, Hiroko; Himeno, Misako; Okano, Yukari; Kagiwada, Satoshi; Namba, Shigetou

2010-03-01

Resistant plants respond rapidly to invading avirulent plant viruses by triggering a hypersensitive response (HR). An HR is accompanied by a restraint of virus multiplication and programmed cell death (PCD), both of which have been observed in systemic necrosis triggered by a successful viral infection. Here, we analyzed signaling pathways underlying the HR in resistance genotype plants and those leading to systemic necrosis. We show that systemic necrosis in Nicotiana benthamiana, induced by Plantago asiatica mosaic virus (PlAMV) infection, was associated with PCD, biochemical features, and gene expression patterns that are characteristic of HR. The induction of necrosis caused by PlAMV infection was dependent on SGT1, RAR1, and the downstream mitogen-activated protein kinase (MAPK) cascade involving MAPKKKalpha and MEK2. However, although SGT1 and RAR1 silencing led to an increased accumulation of PlAMV, silencing of the MAPKKKalpha-MEK2 cascade did not. This observation indicates that viral multiplication is partly restrained even in systemic necrosis induced by viral infection, and that this restraint requires SGT1 and RAR1 but not the MAPKKKalpha-MEK2 cascade. Similarly, although both SGT1 and MAPKKKalpha were essential for the Rx-mediated HR to Potato virus X (PVX), SGT1 but not MAPKKKalpha was involved in the restraint of PVX multiplication. These results suggest that systemic necrosis and HR consist of PCD and a restraint of virus multiplication, and that the latter is induced through unknown pathways independent from the former.

Purinergic signaling modulates the cerebral inflammatory response in experimentally infected fish with Streptococcus agalactiae: an attempt to improve the immune response.

PubMed

Souza, Carine F; Baldissera, Matheus D; Bottari, Nathiele B; Moreira, Karen L S; da Rocha, Maria Izabel U M; da Veiga, Marcelo L; Santos, Roberto C V; Baldisserotto, Bernardo

2018-06-01

Appropriate control of the immune response is a critical determinant of fish health, and the purinergic cascade has an important role in the immune and inflammatory responses. This cascade regulates the levels of adenosine triphosphate (ATP), adenosine diphosphate, adenosine monophosphate and adenosine (Ado), molecules involved in physiological or pathological events as inflammatory and anti-inflammatory mediators. Thus, the aim of this study was to evaluate whether purinergic signaling, through the activities of nucleoside triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase, and adenosine deaminase (ADA), is capable of modulating the cerebral immune and inflammatory responses in silver catfish that is experimentally infected with Streptococcus agalactiae. Cerebral NTPDase (with ATP as substrate) and 5'-nucleotidase activities increased, while ADA activity decreased in silver catfish that is experimentally infected with S. agalactiae, compared to the control group. Moreover, the cerebral levels of ATP and Ado increased in infected animals compared to the uninfected control group. Brain histopathology in infected animals revealed inflammatory demyelination (the presence of occasional bubbly collections), increased cellular density in the area near to pia-mater and intercellular edema. Based on this evidence, the modulation of the purinergic cascade by the enzymes NTPDase, 5'-nucleotidase, and ADA exerts an anti-inflammatory profile due to the regulation of ATP and Ado levels. This suggests involvement of purinergic enzymes on streptococcosis pathogenesis, through regulating cerebral ATP and Ado levels, molecules known to participate in physiological or pathological events as inflammatory and anti-inflammatory mediators, respectively. In summary, the modulation of the cerebral purinergic cascade exerts an anti-inflammatory profile in an attempt to reduce inflammatory damage.

Insulin resistance: definition and consequences.

PubMed

Lebovitz, H E

2001-01-01

Insulin resistance is defined clinically as the inability of a known quantity of exogenous or endogenous insulin to increase glucose uptake and utilization in an individual as much as it does in a normal population. Insulin action is the consequence of insulin binding to its plasma membrane receptor and is transmitted through the cell by a series of protein-protein interactions. Two major cascades of protein-protein interactions mediate intracellular insulin action: one pathway is involved in regulating intermediary metabolism and the other plays a role in controlling growth processes and mitoses. The regulation of these two distinct pathways can be dissociated. Indeed, some data suggest that the pathway regulating intermediary metabolism is diminished in type 2 diabetes while that regulating growth processes and mitoses is normal.--Several mechanisms have been proposed as possible causes underlying the development of insulin resistance and the insulin resistance syndrome. These include: (1) genetic abnormalities of one or more proteins of the insulin action cascade (2) fetal malnutrition (3) increases in visceral adiposity. Insulin resistance occurs as part of a cluster of cardiovascular-metabolic abnormalities commonly referred to as "The Insulin Resistance Syndrome" or "The Metabolic Syndrome". This cluster of abnormalities may lead to the development of type 2 diabetes, accelerated atherosclerosis, hypertension or polycystic ovarian syndrome depending on the genetic background of the individual developing the insulin resistance.--In this context, we need to consider whether insulin resistance should be defined as a disease entity which needs to be diagnosed and treated with specific drugs to improve insulin action.

Dissecting Magnetar Variability with Bayesian Hierarchical Models

NASA Astrophysics Data System (ADS)

Huppenkothen, Daniela; Brewer, Brendon J.; Hogg, David W.; Murray, Iain; Frean, Marcus; Elenbaas, Chris; Watts, Anna L.; Levin, Yuri; van der Horst, Alexander J.; Kouveliotou, Chryssa

2015-09-01

Neutron stars are a prime laboratory for testing physical processes under conditions of strong gravity, high density, and extreme magnetic fields. Among the zoo of neutron star phenomena, magnetars stand out for their bursting behavior, ranging from extremely bright, rare giant flares to numerous, less energetic recurrent bursts. The exact trigger and emission mechanisms for these bursts are not known; favored models involve either a crust fracture and subsequent energy release into the magnetosphere, or explosive reconnection of magnetic field lines. In the absence of a predictive model, understanding the physical processes responsible for magnetar burst variability is difficult. Here, we develop an empirical model that decomposes magnetar bursts into a superposition of small spike-like features with a simple functional form, where the number of model components is itself part of the inference problem. The cascades of spikes that we model might be formed by avalanches of reconnection, or crust rupture aftershocks. Using Markov Chain Monte Carlo sampling augmented with reversible jumps between models with different numbers of parameters, we characterize the posterior distributions of the model parameters and the number of components per burst. We relate these model parameters to physical quantities in the system, and show for the first time that the variability within a burst does not conform to predictions from ideas of self-organized criticality. We also examine how well the properties of the spikes fit the predictions of simplified cascade models for the different trigger mechanisms.

DISSECTING MAGNETAR VARIABILITY WITH BAYESIAN HIERARCHICAL MODELS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huppenkothen, Daniela; Elenbaas, Chris; Watts, Anna L.

Neutron stars are a prime laboratory for testing physical processes under conditions of strong gravity, high density, and extreme magnetic fields. Among the zoo of neutron star phenomena, magnetars stand out for their bursting behavior, ranging from extremely bright, rare giant flares to numerous, less energetic recurrent bursts. The exact trigger and emission mechanisms for these bursts are not known; favored models involve either a crust fracture and subsequent energy release into the magnetosphere, or explosive reconnection of magnetic field lines. In the absence of a predictive model, understanding the physical processes responsible for magnetar burst variability is difficult. Here,more » we develop an empirical model that decomposes magnetar bursts into a superposition of small spike-like features with a simple functional form, where the number of model components is itself part of the inference problem. The cascades of spikes that we model might be formed by avalanches of reconnection, or crust rupture aftershocks. Using Markov Chain Monte Carlo sampling augmented with reversible jumps between models with different numbers of parameters, we characterize the posterior distributions of the model parameters and the number of components per burst. We relate these model parameters to physical quantities in the system, and show for the first time that the variability within a burst does not conform to predictions from ideas of self-organized criticality. We also examine how well the properties of the spikes fit the predictions of simplified cascade models for the different trigger mechanisms.« less

Interferon Lambda: Modulating Immunity in Infectious Diseases.

PubMed

Syedbasha, Mohammedyaseen; Egli, Adrian

2017-01-01

Interferon lambdas (IFN-λs; IFNL1-4) modulate immunity in the context of infections and autoimmune diseases, through a network of induced genes. IFN-λs act by binding to the heterodimeric IFN-λ receptor (IFNLR), activating a STAT phosphorylation-dependent signaling cascade. Thereby hundreds of IFN-stimulated genes are induced, which modulate various immune functions via complex forward and feedback loops. When compared to the well-characterized IFN-α signaling cascade, three important differences have been discovered. First, the IFNLR is not ubiquitously expressed: in particular, immune cells show significant variation in the expression levels of and susceptibilities to IFN-λs. Second, the binding affinities of individual IFN-λs to the IFNLR varies greatly and are generally lower compared to the binding affinities of IFN-α to its receptor. Finally, genetic variation in the form of a series of single-nucleotide polymorphisms (SNPs) linked to genes involved in the IFN-λ signaling cascade has been described and associated with the clinical course and treatment outcomes of hepatitis B and C virus infection. The clinical impact of IFN-λ signaling and the SNP variations may, however, reach far beyond viral hepatitis. Recent publications show important roles for IFN-λs in a broad range of viral infections such as human T-cell leukemia type-1 virus, rotaviruses, and influenza virus. IFN-λ also potentially modulates the course of bacterial colonization and infections as shown for Staphylococcus aureus and Mycobacterium tuberculosis . Although the immunological processes involved in controlling viral and bacterial infections are distinct, IFN-λs may interfere at various levels: as an innate immune cytokine with direct antiviral effects; or as a modulator of IFN-α-induced signaling via the suppressor of cytokine signaling 1 and the ubiquitin-specific peptidase 18 inhibitory feedback loops. In addition, the modulation of adaptive immune functions via macrophage and dendritic cell polarization, and subsequent priming, activation, and proliferation of pathogen-specific T- and B-cells may also be important elements associated with infectious disease outcomes. This review summarizes the emerging details of the IFN-λ immunobiology in the context of the host immune response and viral and bacterial infections.

Wnt/β-Catenin Signaling Modulates Human Airway Sensitization Induced by β2-Adrenoceptor Stimulation

PubMed Central

Faisy, Christophe; Grassin-Delyle, Stanislas; Blouquit-Laye, Sabine; Brollo, Marion; Naline, Emmanuel; Chapelier, Alain; Devillier, Philippe

2014-01-01

Background Regular use of β2-agonists may enhance non-specific airway responsiveness. The wingless/integrated (Wnt) signaling pathways are responsible for several cellular processes, including airway inflammation and remodeling while cAMP–PKA cascade can activate the Wnt signaling. We aimed to investigate whether the Wnt signaling pathways are involved in the bronchial hyperresponsiveness induced by prolonged exposure to β2-adrenoceptor agonists in human isolated airways. Methods Bronchi were surgically removed from 44 thoracic surgery patients. After preparation, bronchial rings and primary cultures of bronchial epithelial cells were incubated with fenoterol (0.1 µM, 15 hours, 37°C), a β2-agonist with high intrinsic efficacy. The effects of inhibitors/blockers of Wnt signaling on the fenoterol-induced airway sensitization were examined and the impact of fenoterol exposure on the mRNA expression of genes interacting with Wnt signaling or cAMP–PKA cascade was assessed in complete bronchi and in cultured epithelial cells. Results Compared to paired controls, fenoterol-sensitization was abolished by inhibition/blockage of the Wnt/β-catenin signaling, especially the cell-surface LRP5/6 co-receptors or Fzd receptors (1 µM SFRP1 or 1 µM DKK1) and the nuclear recruitment of TCF/LEF transcriptions factors (0.3 µM FH535). Wnt proteins secretion did not seem to be involved in the fenoterol-induced sensitization since the mRNA expression of Wnt remained low after fenoterol exposure and the inactivator of Wnt secretion (1 µM IWP2) had no effect on the fenoterol-sensitization. Fenoterol exposure did not change the mRNA expression of genes regulating Wnt signaling or cAMP–PKA cascade. Conclusions Collectively, our pharmacological investigations indicate that fenoterol-sensitization is modulated by the inhibition/blockage of canonical Wnt/β-catenin pathway, suggesting a phenomenon of biased agonism in connection with the β2-adrenoceptor stimulation. Future experiments based on the results of the present study will be needed to determine the impact of prolonged fenoterol exposure on the extra- and intracellular Wnt signaling pathways at the protein expression level. PMID:25360795

Wnt/β-catenin signaling modulates human airway sensitization induced by β2-adrenoceptor stimulation.

PubMed

Faisy, Christophe; Grassin-Delyle, Stanislas; Blouquit-Laye, Sabine; Brollo, Marion; Naline, Emmanuel; Chapelier, Alain; Devillier, Philippe

2014-01-01

Regular use of β2-agonists may enhance non-specific airway responsiveness. The wingless/integrated (Wnt) signaling pathways are responsible for several cellular processes, including airway inflammation and remodeling while cAMP-PKA cascade can activate the Wnt signaling. We aimed to investigate whether the Wnt signaling pathways are involved in the bronchial hyperresponsiveness induced by prolonged exposure to β2-adrenoceptor agonists in human isolated airways. Bronchi were surgically removed from 44 thoracic surgery patients. After preparation, bronchial rings and primary cultures of bronchial epithelial cells were incubated with fenoterol (0.1 µM, 15 hours, 37 °C), a β2-agonist with high intrinsic efficacy. The effects of inhibitors/blockers of Wnt signaling on the fenoterol-induced airway sensitization were examined and the impact of fenoterol exposure on the mRNA expression of genes interacting with Wnt signaling or cAMP-PKA cascade was assessed in complete bronchi and in cultured epithelial cells. Compared to paired controls, fenoterol-sensitization was abolished by inhibition/blockage of the Wnt/β-catenin signaling, especially the cell-surface LRP5/6 co-receptors or Fzd receptors (1 µM SFRP1 or 1 µM DKK1) and the nuclear recruitment of TCF/LEF transcriptions factors (0.3 µM FH535). Wnt proteins secretion did not seem to be involved in the fenoterol-induced sensitization since the mRNA expression of Wnt remained low after fenoterol exposure and the inactivator of Wnt secretion (1 µM IWP2) had no effect on the fenoterol-sensitization. Fenoterol exposure did not change the mRNA expression of genes regulating Wnt signaling or cAMP-PKA cascade. Collectively, our pharmacological investigations indicate that fenoterol-sensitization is modulated by the inhibition/blockage of canonical Wnt/β-catenin pathway, suggesting a phenomenon of biased agonism in connection with the β2-adrenoceptor stimulation. Future experiments based on the results of the present study will be needed to determine the impact of prolonged fenoterol exposure on the extra- and intracellular Wnt signaling pathways at the protein expression level.

Master equation for She-Leveque scaling and its classification in terms of other Markov models of developed turbulence

NASA Astrophysics Data System (ADS)

Nickelsen, Daniel

2017-07-01

The statistics of velocity increments in homogeneous and isotropic turbulence exhibit universal features in the limit of infinite Reynolds numbers. After Kolmogorov’s scaling law from 1941, many turbulence models aim for capturing these universal features, some are known to have an equivalent formulation in terms of Markov processes. We derive the Markov process equivalent to the particularly successful scaling law postulated by She and Leveque. The Markov process is a jump process for velocity increments u(r) in scale r in which the jumps occur randomly but with deterministic width in u. From its master equation we establish a prescription to simulate the She-Leveque process and compare it with Kolmogorov scaling. To put the She-Leveque process into the context of other established turbulence models on the Markov level, we derive a diffusion process for u(r) using two properties of the Navier-Stokes equation. This diffusion process already includes Kolmogorov scaling, extended self-similarity and a class of random cascade models. The fluctuation theorem of this Markov process implies a ‘second law’ that puts a loose bound on the multipliers of the random cascade models. This bound explicitly allows for instances of inverse cascades, which are necessary to satisfy the fluctuation theorem. By adding a jump process to the diffusion process, we go beyond Kolmogorov scaling and formulate the most general scaling law for the class of Markov processes having both diffusion and jump parts. This Markov scaling law includes She-Leveque scaling and a scaling law derived by Yakhot.

Cascading failures mechanism based on betweenness-degree ratio distribution with different connecting preferences

NASA Astrophysics Data System (ADS)

Wang, Xiao Juan; Guo, Shi Ze; Jin, Lei; Chen, Mo

We study the structural robustness of the scale free network against the cascading failure induced by overload. In this paper, a failure mechanism based on betweenness-degree ratio distribution is proposed. In the cascading failure model we built the initial load of an edge which is proportional to the node betweenness of its ends. During the edge random deletion, we find a phase transition. Then based on the phase transition, we divide the process of the cascading failure into two parts: the robust area and the vulnerable area, and define the corresponding indicator to measure the performance of the networks in both areas. From derivation, we find that the vulnerability of the network is determined by the distribution of betweenness-degree ratio. After that we use the connection between the node ability coefficient and distribution of betweenness-degree ratio to explain the cascading failure mechanism. In simulations, we verify the correctness of our derivations. By changing connecting preferences, we find scale free networks with a slight assortativity, which performs better both in robust area and vulnerable area.

Exact Theory of Compressible Fluid Turbulence

NASA Astrophysics Data System (ADS)

Drivas, Theodore; Eyink, Gregory

2017-11-01

We obtain exact results for compressible turbulence with any equation of state, using coarse-graining/filtering. We find two mechanisms of turbulent kinetic energy dissipation: scale-local energy cascade and ``pressure-work defect'', or pressure-work at viscous scales exceeding that in the inertial-range. Planar shocks in an ideal gas dissipate all kinetic energy by pressure-work defect, but the effect is omitted by standard LES modeling of pressure-dilatation. We also obtain a novel inverse cascade of thermodynamic entropy, injected by microscopic entropy production, cascaded upscale, and removed by large-scale cooling. This nonlinear process is missed by the Kovasznay linear mode decomposition, treating entropy as a passive scalar. For small Mach number we recover the incompressible ``negentropy cascade'' predicted by Obukhov. We derive exact Kolmogorov 4/5th-type laws for energy and entropy cascades, constraining scaling exponents of velocity, density, and internal energy to sub-Kolmogorov values. Although precise exponents and detailed physics are Mach-dependent, our exact results hold at all Mach numbers. Flow realizations at infinite Reynolds are ``dissipative weak solutions'' of compressible Euler equations, similarly as Onsager proposed for incompressible turbulence.

The definition of turbulence and the direction of the turbulence energy cascade

NASA Astrophysics Data System (ADS)

Gibson, Carl

2013-11-01

Turbulence is defined as an eddy-like state of fluid motion where the inertial-vortex forces of the eddies are larger than any other forces that tend to damp the eddies out. Because vorticity is produced at the Kolmogorov scale, turbulent kinetic energy always cascades from small scales to large. Irrotational flows that supply kinetic energy to turbulence from large scale motions are by definition non-turbulent. The Taylor-Reynolds-Lumley cascade of kinetic energy from large scales to small is therefore a non-turbulent cascade. The Reynolds turbulence poem must be revised to avoid further confusion. Little whorls on vortex sheets, merge and pair with more of, whorls that grow by vortex forces, Slava Kolmogorov! Turbulent mixing and transport processes in natural fluids depend on fossil turbulence and fossil turbulence waves, which are impossible by the TRL cascade direction. Standard models of cosmology, astronomy, oceanography, and atmospheric transport of heat, mass, momentum and chemical species must be revised. See journalofcosmology.com Volumes 21 and 22 for oceanographic and astro-biological examples.

Phonological Activation of Category Coordinates during Speech Planning is Observable in Children but Not in Adults: Evidence for Cascaded Processing

ERIC Educational Resources Information Center

Jescheniak, Jorg D.; Hahne, Anja; Hoffmann, Stefanie; Wagner, Valentin

2006-01-01

There is a long-standing debate in the area of speech production on the question of whether only words selected for articulation are phonologically activated (as maintained by serial-discrete models) or whether this is also true for their semantic competitors (as maintained by forward-cascading and interactive models). Past research has addressed…

Facile synthesis of unsymmetrical acridines and phenazines by a Rh(III)-catalyzed amination/cyclization/aromatization cascade.

PubMed

Lian, Yajing; Hummel, Joshua R; Bergman, Robert G; Ellman, Jonathan A

2013-08-28

We report formal [3 + 3] annulations of aromatic azides with aromatic imines and azobenzenes to give acridines and phenazines, respectively. These transformations proceed through a cascade process of Rh(III)-catalyzed amination followed by intramolecular electrophilic aromatic substitution and aromatization. Acridines can be directly prepared from aromatic aldehydes by in situ imine formation using catalytic benzylamine.

Interband Cascade Laser Photon Noise

DTIC Science & Technology

2008-12-01

undergo radiative or nonradiative interband transitions into the GaInSb QW, tunnel into the adjacent GaSb QW and then enter the next injection region by... interband tunneling . The laser structures were grown by molecular-beam-epitaxy and processed into mesa-stripe lasers with a mesa width of 15 1... INTERBAND CASCADE LASER PHOTON NOISE Patrick A. Folkes Army Research Laboratory Adelphi, MD 20783-1197 ABSTRACT We report

RhMKK9, a rose MAP KINASE KINASE gene, is involved in rehydration-triggered ethylene production in rose gynoecia.

PubMed

Chen, Jiwei; Zhang, Qian; Wang, Qigang; Feng, Ming; Li, Yang; Meng, Yonglu; Zhang, Yi; Liu, Guoqin; Ma, Zhimin; Wu, Hongzhi; Gao, Junping; Ma, Nan

2017-02-23

Flower opening is an important process in the life cycle of flowering plants and is influenced by various endogenous and environmental factors. Our previous work demonstrated that rose (Rosa hybrida) flowers are highly sensitive to dehydration during flower opening and the water recovery process after dehydration induced ethylene production rapidly in flower gynoecia. In addition, this temporal- and spatial-specific ethylene production is attributed to a transient but robust activation of the rose MAP KINASE6-ACC SYNTHASE1 (RhMPK6-RhACS1) cascade in gynoecia. However, the upstream component of RhMPK6-RhACS1 is unknown, although RhMKK9 (MAP KINASE KINASE9), a rose homologue of Arabidopsis MKK9, could activate RhMPK6 in vitro. In this study, we monitored RhMKK2/4/5/9 expression, the potential upstream kinase to RhMPK6, in rose gynoecia during dehydration and rehydration. We found only RhMKK9 was rapidly and strongly induced by rehydration. Silencing of RhMKK9 significantly decreased rehydration-triggered ethylene production. Consistently, the expression of several ethylene-responsive genes was down regulated in the petals of RhMKK9-silenced flowers. Moreover, we detected the DNA methylation level in the promoter and gene body of RhMKK9 by Chop-PCR. The results showed that rehydration specifically elevated the DNA methylation level on the RhMKK9 gene body, whereas it resulted in hypomethylation in its promoter. Our results showed that RhMKK9 possibly acts as the upstream component of the RhMKK9-RhMPK6-RhACS1 cascade and is responsible for water recovery-triggered ethylene production in rose gynoecia, and epigenetic DNA methylation is involved in the regulation of RhMKK9 expression by rehydration.

Robustness of Controllability for Networks Based on Edge-Attack

PubMed Central

Nie, Sen; Wang, Xuwen; Zhang, Haifeng; Li, Qilang; Wang, Binghong

2014-01-01

We study the controllability of networks in the process of cascading failures under two different attacking strategies, random and intentional attack, respectively. For the highest-load edge attack, it is found that the controllability of Erdős-Rényi network, that with moderate average degree, is less robust, whereas the Scale-free network with moderate power-law exponent shows strong robustness of controllability under the same attack strategy. The vulnerability of controllability under random and intentional attacks behave differently with the increasing of removal fraction, especially, we find that the robustness of control has important role in cascades for large removal fraction. The simulation results show that for Scale-free networks with various power-law exponents, the network has larger scale of cascades do not mean that there will be more increments of driver nodes. Meanwhile, the number of driver nodes in cascading failures is also related to the edges amount in strongly connected components. PMID:24586507

Robustness of controllability for networks based on edge-attack.

PubMed

Nie, Sen; Wang, Xuwen; Zhang, Haifeng; Li, Qilang; Wang, Binghong

2014-01-01

We study the controllability of networks in the process of cascading failures under two different attacking strategies, random and intentional attack, respectively. For the highest-load edge attack, it is found that the controllability of Erdős-Rényi network, that with moderate average degree, is less robust, whereas the Scale-free network with moderate power-law exponent shows strong robustness of controllability under the same attack strategy. The vulnerability of controllability under random and intentional attacks behave differently with the increasing of removal fraction, especially, we find that the robustness of control has important role in cascades for large removal fraction. The simulation results show that for Scale-free networks with various power-law exponents, the network has larger scale of cascades do not mean that there will be more increments of driver nodes. Meanwhile, the number of driver nodes in cascading failures is also related to the edges amount in strongly connected components.

Cascade production in the reactions γp→K+K+(X) and γp→K+K+π-(X)

NASA Astrophysics Data System (ADS)

Guo, L.; Weygand, D. P.; Battaglieri, M.; Vita, R. De; Kubarovsky, V.; Stoler, P.; Amaryan, M. J.; Ambrozewicz, P.; Anghinolfi, M.; Asryan, G.; Avakian, H.; Bagdasaryan, H.; Baillie, N.; Ball, J. P.; Baltzell, N. A.; Batourine, V.; Battaglieri, M.; Bedlinskiy, I.; Bellis, M.; Benmouna, N.; Berman, B. L.; Biselli, A. S.; Blaszczyk, L.; Bouchigny, S.; Boiarinov, S.; Bradford, R.; Branford, D.; Briscoe, W. J.; Brooks, W. K.; Bültmann, S.; Burkert, V. D.; Butuceanu, C.; Calarco, J. R.; Careccia, S. L.; Carman, D. S.; Chen, S.; Cole, P. L.; Collins, P.; Coltharp, P.; Crabb, D.; Crannell, H.; Crede, V.; Cummings, J. P.; Dashyan, N.; Masi, R. De; Vita, R. De; Sanctis, E. De; Degtyarenko, P. V.; Deur, A.; Dharmawardane, K. V.; Dickson, R.; Djalali, C.; Dodge, G. E.; Donnelly, J.; Doughty, D.; Dugger, M.; Dzyubak, O. P.; Egiyan, H.; Egiyan, K. S.; Fassi, L. El; Elouadrhiri, L.; Eugenio, P.; Fedotov, G.; Feldman, G.; Funsten, H.; Garçon, M.; Gavalian, G.; Gilfoyle, G. P.; Giovanetti, K. L.; Girod, F. X.; Goetz, J. T.; Gonenc, A.; Gordon, C. I. O.; Gothe, R. W.; Griffioen, K. A.; Guidal, M.; Guler, N.; Gyurjyan, V.; Hadjidakis, C.; Hafidi, K.; Hakobyan, H.; Hakobyan, R. S.; Hanretty, C.; Hardie, J.; Hersman, F. W.; Hicks, K.; Hleiqawi, I.; Holtrop, M.; Hyde-Wright, C. E.; Ilieva, Y.; Ireland, D. G.; Ishkhanov, B. S.; Isupov, E. L.; Ito, M. M.; Jenkins, D.; Johnstone, R.; Jo, H. S.; Joo, K.; Juengst, H. G.; Kalantarians, N.; Kellie, J. D.; Khandaker, M.; Kim, W.; Klein, A.; Klein, F. J.; Klimenko, A. V.; Kossov, M.; Krahn, Z.; Kramer, L. H.; Kuhn, J.; Kuhn, S. E.; Kuleshov, S. V.; Lachniet, J.; Laget, J. M.; Langheinrich, J.; Lawrence, D.; Lee, T.; Li, Ji; Livingston, K.; Lu, H. Y.; MacCormick, M.; Markov, N.; Mattione, P.; McKinnon, B.; Mecking, B. A.; Melone, J. J.; Mestayer, M. D.; Meyer, C. A.; Mibe, T.; Mikhailov, K.; Minehart, R.; Mirazita, M.; Miskimen, R.; Mokeev, V.; Moriya, K.; Morrow, S. A.; Moteabbed, M.; Munevar, E.; Mutchler, G. S.; Nadel-Turonski, P.; Nasseripour, R.; Niccolai, S.; Niculescu, G.; Niculescu, I.; Niczyporuk, B. B.; Niroula, M. R.; Niyazov, R. A.; Nozar, M.; Osipenko, M.; Ostrovidov, A. I.; Park, K.; Pasyuk, E.; Paterson, C.; Pereira, S. Anefalos; Pierce, J.; Pivnyuk, N.; Pocanic, D.; Pogorelko, O.; Pozdniakov, S.; Price, J. W.; Prok, Y.; Protopopescu, D.; Raue, B. A.; Riccardi, G.; Ricco, G.; Ripani, M.; Ritchie, B. G.; Ronchetti, F.; Rosner, G.; Rossi, P.; Sabatié, F.; Salamanca, J.; Salgado, C.; Santoro, J. P.; Sapunenko, V.; Schumacher, R. A.; Serov, V. S.; Sharabian, Y. G.; Sharov, D.; Shvedunov, N. V.; Smith, E. S.; Smith, L. C.; Sober, D. I.; Sokhan, D.; Stavinsky, A.; Stepanyan, S. S.; Stepanyan, S.; Stokes, B. E.; Strakovsky, I. I.; Strauch, S.; Taiuti, M.; Tedeschi, D. J.; Thoma, U.; Tkabladze, A.; Tkachenko, S.; Todor, L.; Tur, C.; Ungaro, M.; Vineyard, M. F.; Vlassov, A. V.; Watts, D. P.; Weinstein, L. B.; Williams, M.; Wolin, E.; Wood, M. H.; Yegneswaran, A.; Zana, L.; Zhang, J.; Zhao, B.; Zhao, Z. W.

2007-08-01

Photoproduction of the cascade resonances has been investigated in the reactions γp→K+K+(X) and γp→K+K+π-(X). The mass splitting of the ground state (Ξ-,Ξ0) doublet is measured to be 5.4±1.8 MeV/c2, consistent with existing measurements. The differential (total) cross sections for the Ξ- have been determined for photon beam energies from 2.75 to 3.85 (4.75) GeV and are consistent with a production mechanism of Y*→K+Ξ- through a t-channel process. The reaction γp→K+K+π-[Ξ0] has also been investigated to search of excited cascade resonances. No significant signal of excited cascade states other than the Ξ-(1530) is observed. The cross-section results of the Ξ-(1530) have also been obtained for photon beam energies from 3.35 to 4.75 GeV.

Cascade Reverse Osmosis Air Conditioning System: Cascade Reverse Osmosis and the Absorption Osmosis Cycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

BEETIT Project: Battelle is developing a new air conditioning system that uses a cascade reverse osmosis (RO)-based absorption cycle. Analyses show that this new cycle can be as much as 60% more efficient than vapor compression, which is used in 90% of air conditioners. Traditional vapor-compression systems use polluting liquids for a cooling effect. Absorption cycles use benign refrigerants such as water, which is absorbed in a salt solution and pumped as liquid—replacing compression of vapor. The refrigerant is subsequently separated from absorbing salt using heat for re-use in the cooling cycle. Battelle is replacing thermal separation of refrigerant withmore » a more efficient reverse osmosis process. Research has shown that the cycle is possible, but further investment will be needed to reduce the number of cascade reverse osmosis stages and therefore cost.« less

Universal fieldable assay with unassisted visual detection

NASA Technical Reports Server (NTRS)

Chelyapov, Nicolas (Inventor)

2012-01-01

A universal detection system based on allosteric aptamers, signal amplification cascade, and eye-detectable phrase transition. A broadly applicable homogeneous detection system is provided. It utilizes components of the blood coagulation cascade in the presence of polystyrene microspheres (MS) as a signal amplifier. Russell's viper venom factor X activator (RVV-X) triggers the cascade, which results in an eye-visible phase transition--precipitation of MS bound to clotted fibrin. An allosteric RNA aptamer, RNA132, with affinity for RVV-X and human vascular endothelial growth factor (VEGF.sub.165) was created. RNA132 inhibits enzymatic activity of RVV-X. The effector molecule, VEGF.sub.165, reverses the inhibitory activity of RNA132 on RVV-X and restores its enzymatic activity, thus triggering the cascade and enabling the phase transition. Similar results were obtained for another allosteric aptamer modulated by a protein tyrosine phosphatase. The assay is instrumentation-free for both processing and readout.

Social relevance: toward understanding the impact of the individual in an information cascade

NASA Astrophysics Data System (ADS)

Hall, Robert T.; White, Joshua S.; Fields, Jeremy

2016-05-01

Information Cascades (IC) through a social network occur due to the decision of users to disseminate content. We define this decision process as User Diffusion (UD). IC models typically describe an information cascade by treating a user as a node within a social graph, where a node's reception of an idea is represented by some activation state. The probability of activation then becomes a function of a node's connectedness to other activated nodes as well as, potentially, the history of activation attempts. We enrich this Coarse-Grained User Diffusion (CGUD) model by applying actor type logics to the nodes of the graph. The resulting Fine-Grained User Diffusion (FGUD) model utilizes prior research in actor typing to generate a predictive model regarding the future influence a user will have on an Information Cascade. Furthermore, we introduce a measure of Information Resonance that is used to aid in predictions regarding user behavior.

The Alzheimer's Disease Mitochondrial Cascade Hypothesis: Progress and Perspectives

PubMed Central

Swerdlow, Russell H.; Burns, Jeffrey M.; Khan, Shaharyar M.

2013-01-01

Ten years ago we first proposed the Alzheimer's disease (AD) mitochondrial cascade hypothesis. This hypothesis maintains gene inheritance defines an individual's baseline mitochondrial function; inherited and environmental factors determine rates at which mitochondrial function changes over time; and baseline mitochondrial function and mitochondrial change rates influence AD chronology. Our hypothesis unequivocally states in sporadic, late-onset AD, mitochondrial function affects amyloid precursor protein (APP) expression, APP processing, or beta amyloid (Aβ) accumulation and argues if an amyloid cascade truly exists, mitochondrial function triggers it. We now review the state of the mitochondrial cascade hypothesis, and discuss it in the context of recent AD biomarker studies, diagnostic criteria, and clinical trials. Our hypothesis predicts biomarker changes reflect brain aging, new AD definitions clinically stage brain aging, and removing brain Aβ at any point will marginally impact cognitive trajectories. Our hypothesis, therefore, offers unique perspective into what sporadic, late-onset AD is and how to best treat it. PMID:24071439

Multi-compartmental modeling of SORLA’s influence on amyloidogenic processing in Alzheimer’s disease

PubMed Central

2012-01-01

Background Proteolytic breakdown of the amyloid precursor protein (APP) by secretases is a complex cellular process that results in formation of neurotoxic Aβ peptides, causative of neurodegeneration in Alzheimer’s disease (AD). Processing involves monomeric and dimeric forms of APP that traffic through distinct cellular compartments where the various secretases reside. Amyloidogenic processing is also influenced by modifiers such as sorting receptor-related protein (SORLA), an inhibitor of APP breakdown and major AD risk factor. Results In this study, we developed a multi-compartment model to simulate the complexity of APP processing in neurons and to accurately describe the effects of SORLA on these processes. Based on dose–response data, our study concludes that SORLA specifically impairs processing of APP dimers, the preferred secretase substrate. In addition, SORLA alters the dynamic behavior of β-secretase, the enzyme responsible for the initial step in the amyloidogenic processing cascade. Conclusions Our multi-compartment model represents a major conceptual advance over single-compartment models previously used to simulate APP processing; and it identified APP dimers and β-secretase as the two distinct targets of the inhibitory action of SORLA in Alzheimer’s disease. PMID:22727043

Real-time quantum cascade laser-based infrared microspectroscopy in-vivo

NASA Astrophysics Data System (ADS)

Kröger-Lui, N.; Haase, K.; Pucci, A.; Schönhals, A.; Petrich, W.

2016-03-01

Infrared microscopy can be performed to observe dynamic processes on a microscopic scale. Fourier-transform infrared spectroscopy-based microscopes are bound to limitations regarding time resolution, which hampers their potential for imaging fast moving systems. In this manuscript we present a quantum cascade laser-based infrared microscope which overcomes these limitations and readily achieves standard video frame rates. The capabilities of our setup are demonstrated by observing dynamical processes at their specific time scales: fermentation, slow moving Amoeba Proteus and fast moving Caenorhabditis elegans. Mid-infrared sampling rates between 30 min and 20 ms are demonstrated.

Reduced frequency of T lymphocytes expressing CTLA-4 in frontotemporal dementia compared to Alzheimer's disease.

PubMed

Santos, Rodrigo Ribeiro; Torres, Karen C; Lima, Giselle S; Fiamoncini, Carolina M; Mapa, Filipe C; Pereira, Patricia A; Rezende, Vitor B; Martins, Luiza C; Bicalho, Maria A; Moraes, Edgar N; Reis, Helton J; Teixeira, Antonio L; Romano-Silva, Marco A

2014-01-03

Studies suggest that inflammation is involved in the neurodegenerative cascade of dementias. Immunological mechanisms may be part of the pathophysiological process in frontotemporal dementia (FTD), but up till now only vague evidence of such mechanisms has been presented. The B7- CD28/CTLA-4 pathway is an important immunological signaling pathway involved in modulation of T cell activation. The aim of this study was to compare the expression of molecules associated with co-stimulatory signaling in peripheral blood mononuclear cells (PBMC) of FTD to Alzheimer disease (AD) and control groups. Our results confirm the previous demonstrated increased expression of CD80 in CD14+ Alzheimer patients T cells but show, for the first time, a reduction in the expression of CTLA-4 in CD4+ FTD cells. As CTLA-4 is the most potent negative regulators of T-cell activation we speculated that peripheral T lymphocytes in FTD are more activated and this could be involved in the neurodegeneration observed in this dementia. © 2013 Elsevier Inc. All rights reserved.

The association of β-arrestin2 polymorphisms with response to antidepressant treatment in depressed patients.

PubMed

Petit, Anne-Cécile; El Asmar, Khalil; David, Denis J; Gardier, Alain M; Becquemont, Laurent; Fève, Bruno; Verstuyft, Céline; Corruble, Emmanuelle

2018-02-02

The study of genetic polymorphisms involved in antidepressants (AD) response is essential to provide a personalized medicine approach in the field of depression. β-arrestin 2 (ARRB2) is a candidate gene in the pharmacogenetics of AD as it is involved in the signaling cascade downstream of numerous neurotransmitter receptors. We investigated the association between five ARRB2 single nucleotide polymorphisms (SNPs): rs1045280, rs2036657, rs4790694, rs3786047 and rs452246, and response to AD treatment in a sample of 569 patients with a major depressive episode treated for 6months. We show that GG/GT patients for rs4522461 (n=534) and AA/AC patients for rs4790694 (n=244) have a lower response to AD than other genotype groups (HDRS score of 10.9 vs 8.0 after 6months, multivariate analysis: p=0.03; 12.2 vs 9.6, p=0.02, respectively). These data provide additional evidence that β-arrestin 2 is a regulator of intracellular signal transduction processes involved in AD treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Lipoxygenases and their metabolites in formation of plant stress tolerance.

PubMed

Babenko, L M; Shcherbatiuk, M M; Skaterna, T D; Kosakivska, I V

2017-01-01

The review focuses on the analysis of new information concerning molecular enzymology of lipoxygenases – proteins involved in lipid peroxidation and found in animals and plants. Modern concept of structural features, catalytic characteristics and functions of lipoxygenase family enzymes as well as products of their catalytic activity in plants have been discussed and summarized. Issues of enzyme localization in plant cells and tissues, evolution and distribution of lipoxygenases, involvement in production of signaling substances involved in formation of adaptation response to abiotic and biotic stress factors and in regulation of lipoxygenase signal system activity are highlighted. Participants of the elements signaling of LOX-pathway reception and transduction into genome are considered. Special attention is given to jasmonates, metabolites of the allene oxide synthase branch of the lipoxygenase cascade, because these metabolites have high biological activity, are ubiquitously present in all plant organisms, and are involved in regulation of vitally important processes. Data concerning lipoxygenase phylogeny, possible occurrence of a common predecessor for modern isoforms of the enzyme in pro- and eukaryote have been examined. Some results of our studies that open up possibilities of using the lipoxygenase catalytic activity characteristics as biological markers in plant stress tolerance researches are given.

[MAP kinases--molecular transistors in animals and plants].

PubMed

Petersen, Morten; Brodersen, Peter; Mundy, John

2002-06-10

The survival of multicellular organisms depends on the ability of their cells to communicate with each other and to respond to environmental changes. A goal of modern biology is to uncover the processes by which these cellular signals are transduced. Recent studies have shown that MAP-kinases (MAPKs) are important constituents of such signal transduction pathways. MAPKs function as modules in phosphorelay cascades to activate or repress the activity of downstream target proteins. For example, recent research with knockout mice has shown that mammalian MAPKs are involved in the control of neuronal apoptosis and the activation of immune responses. These mammalian MAPKs exert their control by both promoting and inhibiting specific processes. Surprisingly, plants also use MAPKs to control their immune responses, and plant MAPKs also seem to play dual roles as positive and negative regulators. Such mechanistic similarities provide the basis for fruitful conceptual exchange between molecular research on animals and plants.

Matrix Metalloproteinases as Regulators of Periodontal Inflammation

PubMed Central

Franco, Cavalla; Patricia, Hernández-Ríos; Timo, Sorsa; Claudia, Biguetti; Marcela, Hernández

2017-01-01

Periodontitis are infectious diseases characterized by immune-mediated destruction of periodontal supporting tissues and tooth loss. Matrix metalloproteinases (MMPs) are key proteases involved in destructive periodontal diseases. The study and interest in MMP has been fuelled by emerging evidence demonstrating the broad spectrum of molecules that can be cleaved by them and the myriad of biological processes that they can potentially regulate. The huge complexity of MMP functions within the ‘protease web’ is crucial for many physiologic and pathologic processes, including immunity, inflammation, bone resorption, and wound healing. Evidence points out that MMPs assemble in activation cascades and besides their classical extracellular matrix substrates, they cleave several signalling molecules—such as cytokines, chemokines, and growth factors, among others—regulating their biological functions and/or bioavailability during periodontal diseases. In this review, we provide an overview of emerging evidence of MMPs as regulators of periodontal inflammation. PMID:28218665

Matrix Metalloproteinases as Regulators of Periodontal Inflammation.

PubMed

Franco, Cavalla; Patricia, Hernández-Ríos; Timo, Sorsa; Claudia, Biguetti; Marcela, Hernández

2017-02-17

Periodontitis are infectious diseases characterized by immune-mediated destruction of periodontal supporting tissues and tooth loss. Matrix metalloproteinases (MMPs) are key proteases involved in destructive periodontal diseases. The study and interest in MMP has been fuelled by emerging evidence demonstrating the broad spectrum of molecules that can be cleaved by them and the myriad of biological processes that they can potentially regulate. The huge complexity of MMP functions within the 'protease web' is crucial for many physiologic and pathologic processes, including immunity, inflammation, bone resorption, and wound healing. Evidence points out that MMPs assemble in activation cascades and besides their classical extracellular matrix substrates, they cleave several signalling molecules-such as cytokines, chemokines, and growth factors, among others-regulating their biological functions and/or bioavailability during periodontal diseases. In this review, we provide an overview of emerging evidence of MMPs as regulators of periodontal inflammation.

Generation of 1.5-octave intense infrared pulses by nonlinear interactions in DAST crystal

NASA Astrophysics Data System (ADS)

Vicario, C.; Monoszlai, B.; Arisholm, G.; Hauri, C. P.

2015-09-01

Infrared pulses with large spectral width extending from 1.2 to 3.4 μm are generated in the organic crystal DAST (4-N, N-dimethylamino-4‧-N‧-methylstilbazolium tosylate). The input pulse has a central wavelength of 1.5 μm and 65 fs duration. With 2.8 mJ input energy we obtained up to 700 μJ in the broadened spectrum. The output can be easily scaled up in energy by increasing the crystal size together with the energy and the beam size of the pump. The ultra-broad spectrum is ascribed to cascaded second order processes mediated by the exceptionally large effective χ 2 nonlinearity of DAST, but the shape of the spectrum indicates that a delayed χ 3 process may also be involved. Numerical simulations reproduce the experimental results qualitatively and provide an insight in the mechanisms underlying the asymmetric spectral broadening.

Angiogenesis in Spontaneous Tumors and Implications for Comparative Tumor Biology

PubMed Central

Benazzi, C.; Al-Dissi, A.; Chau, C. H.; Figg, W. D.; Sarli, G.; de Oliveira, J. T.; Gärtner, F.

2014-01-01

Blood supply is essential for development and growth of tumors and angiogenesis is the fundamental process of new blood vessel formation from preexisting ones. Angiogenesis is a prognostic indicator for a variety of tumors, and it coincides with increased shedding of neoplastic cells into the circulation and metastasis. Several molecules such as cell surface receptors, growth factors, and enzymes are involved in this process. While antiangiogenic therapy for cancer has been proposed over 20 years ago, it has garnered much controversy in recent years within the scientific community. The complex relationships between the angiogenic signaling cascade and antiangiogenic substances have indicated the angiogenic pathway as a valid target for anticancer drug development and VEGF has become the primary antiangiogenic drug target. This review discusses the basic and clinical perspectives of angiogenesis highlighting the importance of comparative biology in understanding tumor angiogenesis and the integration of these model systems for future drug development. PMID:24563633

The Center for Multiscale Plasma Dynamics, Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gombosi, Tamas I.

The University of Michigan participated in the joint UCLA/Maryland fusion science center focused on plasma physics problems for which the traditional separation of the dynamics into microscale and macroscale processes breaks down. These processes involve large scale flows and magnetic fields tightly coupled to the small scale, kinetic dynamics of turbulence, particle acceleration and energy cascade. The interaction between these vastly disparate scales controls the evolution of the system. The enormous range of temporal and spatial scales associated with these problems renders direct simulation intractable even in computations that use the largest existing parallel computers. Our efforts focused on twomore » main problems: the development of Hall MHD solvers on solution adaptive grids and the development of solution adaptive grids using generalized coordinates so that the proper geometry of inertial confinement can be taken into account and efficient refinement strategies can be obtained.« less

Improving atomic displacement and replacement calculations with physically realistic damage models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nordlund, Kai; Zinkle, Steven J.; Sand, Andrea E.

Atomic collision processes are fundamental to numerous advanced materials technologies such as electron microscopy, semiconductor processing and nuclear power generation. Extensive experimental and computer simulation studies over the past several decades provide the physical basis for understanding the atomic-scale processes occurring during primary displacement events. The current international standard for quantifying this energetic particle damage, the Norgett-Robinson-Torrens displacements per atom (NRT-dpa) model, has nowadays several well-known limitations. In particular, the number of radiation defects produced in energetic cascades in metals is only ~1/3 the NRT-dpa prediction, while the number of atoms involved in atomic mixing is about a factor ofmore » 30 larger than the dpa value. Here we propose two new complementary displacement production estimators (athermal recombination corrected dpa, arc-dpa) and atomic mixing (replacements per atom, rpa) functions that extend the NRT-dpa by providing more physically realistic descriptions of primary defect creation in materials and may become additional standard measures for radiation damage quantification.« less

Improving atomic displacement and replacement calculations with physically realistic damage models

DOE PAGES

Nordlund, Kai; Zinkle, Steven J.; Sand, Andrea E.; ...

2018-03-14

Atomic collision processes are fundamental to numerous advanced materials technologies such as electron microscopy, semiconductor processing and nuclear power generation. Extensive experimental and computer simulation studies over the past several decades provide the physical basis for understanding the atomic-scale processes occurring during primary displacement events. The current international standard for quantifying this energetic particle damage, the Norgett-Robinson-Torrens displacements per atom (NRT-dpa) model, has nowadays several well-known limitations. In particular, the number of radiation defects produced in energetic cascades in metals is only ~1/3 the NRT-dpa prediction, while the number of atoms involved in atomic mixing is about a factor ofmore » 30 larger than the dpa value. Here we propose two new complementary displacement production estimators (athermal recombination corrected dpa, arc-dpa) and atomic mixing (replacements per atom, rpa) functions that extend the NRT-dpa by providing more physically realistic descriptions of primary defect creation in materials and may become additional standard measures for radiation damage quantification.« less

Myosin II Motors and F-Actin Dynamics Drive the Coordinated Movement of the Centrosome and Soma during CNS Glial-Guided Neuronal Migration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Solecki, Dr. David; Trivedi, Dr. Niraj; Govek, Eve-Ellen

2009-01-01

Lamination of cortical regions of the vertebrate brain depends on glial-guided neuronal migration. The conserved polarity protein Par6{alpha} localizes to the centrosome and coordinates forward movement of the centrosome and soma in migrating neurons. The cytoskeletal components that produce this unique form of cell polarity and their relationship to polarity signaling cascades are unknown. We show that F-actin and Myosin II motors are enriched in the neuronal leading process and that Myosin II activity is necessary for leading process actin dynamics. Inhibition of Myosin II decreased the speed of centrosome and somal movement, whereas Myosin II activation increased coordinated movement.more » Ectopic expression or silencing of Par6{alpha} inhibited Myosin II motors by decreasing Myosin light-chain phosphorylation. These findings suggest leading-process Myosin II may function to 'pull' the centrosome and soma forward during glial-guided migration by a mechanism involving the conserved polarity protein Par6{alpha}.« less

Improving atomic displacement and replacement calculations with physically realistic damage models.

PubMed

Nordlund, Kai; Zinkle, Steven J; Sand, Andrea E; Granberg, Fredric; Averback, Robert S; Stoller, Roger; Suzudo, Tomoaki; Malerba, Lorenzo; Banhart, Florian; Weber, William J; Willaime, Francois; Dudarev, Sergei L; Simeone, David

2018-03-14

Atomic collision processes are fundamental to numerous advanced materials technologies such as electron microscopy, semiconductor processing and nuclear power generation. Extensive experimental and computer simulation studies over the past several decades provide the physical basis for understanding the atomic-scale processes occurring during primary displacement events. The current international standard for quantifying this energetic particle damage, the Norgett-Robinson-Torrens displacements per atom (NRT-dpa) model, has nowadays several well-known limitations. In particular, the number of radiation defects produced in energetic cascades in metals is only ~1/3 the NRT-dpa prediction, while the number of atoms involved in atomic mixing is about a factor of 30 larger than the dpa value. Here we propose two new complementary displacement production estimators (athermal recombination corrected dpa, arc-dpa) and atomic mixing (replacements per atom, rpa) functions that extend the NRT-dpa by providing more physically realistic descriptions of primary defect creation in materials and may become additional standard measures for radiation damage quantification.

Different designs of kinase-phosphatase interactions and phosphatase sequestration shapes the robustness and signal flow in the MAPK cascade

PubMed Central

2012-01-01

Background The three layer mitogen activated protein kinase (MAPK) signaling cascade exhibits different designs of interactions between its kinases and phosphatases. While the sequential interactions between the three kinases of the cascade are tightly preserved, the phosphatases of the cascade, such as MKP3 and PP2A, exhibit relatively diverse interactions with their substrate kinases. Additionally, the kinases of the MAPK cascade can also sequester their phosphatases. Thus, each topologically distinct interaction design of kinases and phosphatases could exhibit unique signal processing characteristics, and the presence of phosphatase sequestration may lead to further fine tuning of the propagated signal. Results We have built four architecturally distinct types of models of the MAPK cascade, each model with identical kinase-kinase interactions but unique kinases-phosphatases interactions. Our simulations unravelled that MAPK cascade’s robustness to external perturbations is a function of nature of interaction between its kinases and phosphatases. The cascade’s output robustness was enhanced when phosphatases were sequestrated by their target kinases. We uncovered a novel implicit/hidden negative feedback loop from the phosphatase MKP3 to its upstream kinase Raf-1, in a cascade resembling the B cell MAPK cascade. Notably, strength of the feedback loop was reciprocal to the strength of phosphatases’ sequestration and stronger sequestration abolished the feedback loop completely. An experimental method to verify the presence of the feedback loop is also proposed. We further showed, when the models were activated by transient signal, memory (total time taken by the cascade output to reach its unstimulated level after removal of signal) of a cascade was determined by the specific designs of interaction among its kinases and phosphatases. Conclusions Differences in interaction designs among the kinases and phosphatases can differentially shape the robustness and signal response behaviour of the MAPK cascade and phosphatase sequestration dramatically enhances the robustness to perturbations in each of the cascade. An implicit negative feedback loop was uncovered from our analysis and we found that strength of the negative feedback loop is reciprocally related to the strength of phosphatase sequestration. Duration of output phosphorylation in response to a transient signal was also found to be determined by the individual cascade’s kinase-phosphatase interaction design. PMID:22748295

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kirfel, Jutta; Pantelis, Dimitrios; Kabba, Mustapha

Four and one half LIM domain protein FHL2 participates in many cellular processes involved in tissue repair such as regulation of gene expression, cytoarchitecture, cell adhesion, migration and signal transduction. The repair process after wounding is initiated by the release of peptides and bioactive lipids. These molecules induce synthesis and deposition of a provisional extracellular matrix. We showed previously that sphingosine-1-phosphate (S1P) triggers a signal transduction cascade mediating nuclear translocation of FHL2 in response to activation of the RhoA GTPase. Our present study shows that FHL2 is an important signal transducer influencing the outcome of intestinal anastomotic healing. Early woundmore » healing is accompanied by reconstitution and remodelling of the extracellular matrix and collagen is primarily responsible for wound strength. Our results show that impaired intestinal wound healing in Fhl2-deficient mice is due to disturbed collagen III metabolism. Impaired collagen III synthesis reduced the mechanical stability of the anastomoses and led to lower bursting pressure in Fhl2-deficient mice after surgery. Our data confirm that FHL2 is an important factor regulating collagen expression in the early phase of wound healing, and thereby is critically involved in the physiologic process of anastomosis healing after bowel surgery and thus may represent a new therapeutic target.« less

Biorefinery cascade processing for creating added value on tomato industrial by-products from Tunisia.

PubMed

Kehili, Mouna; Schmidt, Lisa Marie; Reynolds, Wienke; Zammel, Ayachi; Zetzl, Carsten; Smirnova, Irina; Allouche, Noureddine; Sayadi, Sami

2016-01-01

In today's consumer perception of industrial processes and food production, aspects like food quality, human health, environmental safety, and energy security have become the keywords. Therefore, much effort has been extended toward adding value to biowastes of agri-food industries through biorefinery processing approaches. This study focused, for the first time, on the valorization of tomato by-products of a Tunisian industry for the recovery of value-added compounds using biorefinery cascade processing. The process integrated supercritical CO 2 extraction of carotenoids within the oil fractions from tomato seeds (TS) and tomato peels (TP), followed by a batch isolation of protein from the residues. The remaining lignocellulosic matter from both fractions was then submitted to a liquid hot water (LHW) hydrolysis. Supercritical CO 2 experiments extracted 5.79% oleoresin, 410.53 mg lycopene/kg, and 31.38 mg β-carotene/kg from TP and 26.29% oil, 27.84 mg lycopene/kg, and 5.25 mg β-carotene/kg from TS, on dry weights. Protein extraction yields, nearing 30% of the initial protein contents equal to 13.28% in TP and 39.26% in TS, revealed that TP and TS are a rich source of essential amino acids. LHW treatment run at 120-200 °C, 50 bar for 30 min showed that a temperature of 160 °C was the most convenient for cellulose and hemicellulose hydrolysis from TP and TS, while keeping the degradation products low. Results indicated that tomato by-products are not only a green source of lycopene-rich oleoresin and tomato seed oil (TSO) and of protein with good nutritional quality but also a source of lignocellulosic matter with potential for bioethanol production. This study would provide an important reference for the concept and the feasibility of the cascade fractionation of valuable compounds from tomato industrial by-products.Graphical abstractSchema of biorefinery cascade processing of tomato industrial by-products toward isolation of valuable fractions.

Using the Co-Production of Knowledge for Developing Realistic Natural Disaster Scenarios for Small-to-Medium Scale Emergency Management Exercises

NASA Astrophysics Data System (ADS)

Robinson, T.; Wilson, T. M.; Davies, T. R.; Orchiston, C.; Thompson, J.

2014-12-01

Disaster scenarios for Emergency Management (EM) exercises are a widely-used and effective tool for communicating hazard information to policy makers, EM personnel, lifelines operators and communities in general. It is crucial that the scenarios are as realistic as possible. Major disasters however, contain a series of cascading consequences, both environmental and social, which are difficult to model. Consequently, only recently have large-scale exercises included such processes; incorporating these in small- and medium-scale scenarios has yet to be attempted. This study details work undertaken in a recent medium-scale earthquake exercise in New Zealand to introduce such cascading processes into the disaster scenario. Given limited time, data, and funding, we show that the co-production of knowledge between natural disaster scientists, EM personnel, and governance and lifelines organisations can yield detailed, realistic scenarios. Using the co-production process, scenario development was able to identify where the pre-exercise state of knowledge was insufficient. This enabled a focussed research response driven by end-user needs. This found that in general, seismic hazard (ground shaking) and its likely impacts were well known and understood by all parties. However, subsequent landsliding and associated effects were poorly known and understood and their potential impacts unconsidered. Scenario development therefore focussed primarily on understanding these processes and their potential effects. This resulted in cascading hazards being included in a medium-scale NZ exercise for the first time. Further, all participants were able to focus on the potential impacts on their specific sectors, increasing the level of knowledge of cascading processes across all parties. Using group based discussions throughout the design process allowed a detailed scenario to be created, fostered stronger inter-disciplinary relationships, and identified areas for further research. Consequently, further detailed research has begun specifically into the impacts from secondary effects in an effort to further increase resilience to future events.

Cohort profile: seek, test, treat and retain United States criminal justice cohort.

PubMed

Chandler, Redonna; Gordon, Michael S; Kruszka, Bridget; Strand, Lauren N; Altice, Frederick L; Beckwith, Curt G; Biggs, Mary L; Cunningham, William; Chris Delaney, J A; Flynn, Patrick M; Golin, Carol E; Knight, Kevin; Kral, Alex H; Kuo, Irene; Lorvick, Jennifer; Nance, Robin M; Ouellet, Lawrence J; Rich, Josiah D; Sacks, Stanley; Seal, David; Spaulding, Anne; Springer, Sandra A; Taxman, Faye; Wohl, David; Young, Jeremy D; Young, Rebekah; Crane, Heidi M

2017-05-16

The STTR treatment cascade provides a framework for research aimed at improving the delivery of services, care and outcomes of PLWH. The development of effective approaches to increase HIV diagnoses and engage PLWH in subsequent steps of the treatment cascade could lead to earlier and sustained ART treatment resulting in viral suppression. There is an unmet need for research applying the treatment cascade to improve outcomes for those with criminal justice involvement. The Seek, Test, Treat, and Retain (STTR) criminal justice (CJ) cohort combines data from 11 studies across the HIV treatment cascade that focused on persons involved in the criminal justice system, often but not exclusively for reasons related to substance use. The studies were conducted in a variety of CJ settings and collected information across 11 pre-selected domains: demographic characteristics, CJ involvement, HIV risk behaviors, HIV and/or Hepatitis C infections, laboratory measures of CD4 T-cell count (CD4) and HIV RNA viral load (VL), mental illness, health related quality of life (QoL), socioeconomic status, health care access, substance use, and social support. The STTR CJ cohort includes data on 11,070 individuals with and without HIV infection who range in age from 18 to 77 years, with a median age at baseline of 37 years. The cohort reflects racial, ethnic and gender distributions in the U.S. CJ system, and 64% of participants are African-American, 12% are Hispanic and 83% are men. Cohort members reported a wide range of HIV risk behaviors including history of injection drug use and, among those who reported on pre-incarceration sexual behaviors, the prevalence of unprotected sexual intercourse ranged across studies from 4% to 79%. Across all studies, 53% percent of the STTR CJ cohort reported recent polysubstance use. The STTR CJ cohort is comprised of participants from a wide range of CJ settings including jail, prison, and community supervision who report considerable diversity in their characteristics and behavioral practices. We have developed harmonized measures, where feasible, to improve the integration of these studies together to answer questions that cannot otherwise be addressed.

Activated cathepsin L is associated with the switch from autophagy to apoptotic death of SH-SY5Y cells exposed to 6-hydroxydopamine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Lingyun, E-mail: lingyunlee@126.com; Experimental Center, The Second Affiliated Hospital of Soochow University, Suzhou 215004; Gao, Luyan

Autophagy and apoptosis are common responses to pathological damage in the process of Parkinson's disease (PD), and lysosome dysfunction may contribute to the etiology of PD's neurodegenerative process. In this study, we demonstrated that the neurotoxin 6-hydroxydopamine (6-OHDA) increased autophagy in SH-SY5Y cells, as determined by detection of the lysosome marker lysosomal-associated membrane protein1, the autophagy protein light chain 3 (LC3)-II and the autophagy substrate P62 protein. Meanwhile, autophagy repression with 3-methyladenine accelerated the activation of caspase-3 and PARP and aggravated the cell apoptotic death induced by 6-OHDA. Furthermore, we found that 6-OHDA treatment resulted in a transient increase inmore » the intracellular and nuclear expression of cathepsin L (CTSL). The CTSL inhibitor, Z-FY-CHO, could promote autophagy, decrease accumulation of P62, and block activation of caspase-3 and PARP. Taken together, these results suggest that activation of autophagy may primarily be a protective process in SH-SY5Y cell death induced by 6-OHDA, and the nuclear translocation of CTSL could enhance the cell apoptotic cascade via disturbing autophagy-apoptotic systems in SH-SY5Y cells. Our findings highlight the potential role of CTSL in the cross talk between autophagy and apoptosis, which might be considered a therapeutic strategy for treatment of pathologic conditions associated with neurodegeneration. - Highlights: • Inhibition of autophagy aggravated the cell apoptotic death in SH-SY5Y cells. • Activation of cathepsin L impaired the autophagy pathway. • Activation of cathepsin L enhanced the cell apoptotic cascade. • Cathepsin L involves in the cross talk between autophagy and apoptosis.« less

The presence of accessory cusps in chimpanzee lower molars is consistent with a patterning cascade model of development

PubMed Central

Skinner, Matthew M; Gunz, Philipp

2010-01-01

Tooth crown morphology is of primary importance in fossil primate systematics and understanding the developmental basis of its variation facilitates phenotypic analyses of fossil teeth. Lower molars of species in the chimp/human clade (including fossil hominins) possess between four and seven cusps and this variability has been implicated in alpha taxonomy and phylogenetic systematics. What is known about the developmental basis of variation in cusp number – based primarily on experimental studies of rodent molars – suggests that cusps form under a morphodynamic, patterning cascade model involving the iterative formation of enamel knots. In this study we test whether variation in cusp 6 (C6) presence in common chimpanzee and bonobo lower molars (n = 55) is consistent with predictions derived from the patterning cascade model. Using microcomputed tomography we imaged the enamel-dentine junction of lower molars and used geometric morphometrics to examine shape variation in the molar crown correlated with variation in C6 presence (in particular the size and spacing of the dentine horns). Results indicate that C6 presence is consistent with predictions of a patterning cascade model, with larger molars exhibiting a higher frequency of C6 and with the location and size of later-forming cusps correlated with C6 variation. These results demonstrate that a patterning cascade model is appropriate for interpreting cusp variation in Pan and have implications for cusp nomenclature and the use of accessory cusp morphology in primate systematics. PMID:20629983

Room Temperature Interband Cascade Lasers

DTIC Science & Technology

2010-01-01

interband cascade laser (ICL) [6]-[8] is particularly convenient, since the semimetallic band alignment between InAs and GaSb allows the electrons that...superlattice claddings and a non-ohmic part that may be associated with various band discontinuities in the structure . While the latter can probably be...made a radiative transition to the valence band to be transferred readily back to the conduction band via elastic or nearly elastic processes. Our

Facile Synthesis of Unsymmetrical Acridines and Phenazines by a Rhodium(III)-Catalyzed Amination, Cyclization and Aromatization Cascade

PubMed Central

Lian, Yajing; Hummel, Joshua R.; Bergman, Robert G.; Ellman, Jonathan A.

2013-01-01

New formal [3 + 3] annulations have been developed to obtain acridines and phenazines from aromatic azides and aromatic imines and azobenzenes, respectively. These transformations proceed through a cascade process of Rh(III)-catalyzed amination followed by intramolecular electrophilic aromatic substitution and aromatization. Acridines can be directly prepared from aromatic aldehydes by in situ imine formation using catalytic benzylamine. PMID:23957711

Renormalization of the fragmentation equation: Exact self-similar solutions and turbulent cascades

NASA Astrophysics Data System (ADS)

Saveliev, V. L.; Gorokhovski, M. A.

2012-12-01

Using an approach developed earlier for renormalization of the Boltzmann collision integral [Saveliev and Nanbu, Phys. Rev. E1539-375510.1103/PhysRevE.65.051205 65, 051205 (2002)], we derive an exact divergence form for the fragmentation operator. Then we reduce the fragmentation equation to the continuity equation in size space, with the flux given explicitly. This allows us to obtain self-similar solutions and to find the integral of motion for these solutions (we call it the bare flux). We show how these solutions can be applied as a description of cascade processes in three- and two-dimensional turbulence. We also suggested an empirical cascade model of impact fragmentation of brittle materials.

Ruthenium-Catalyzed Cascade C—H Functionalization of Phenylacetophenones**

PubMed Central

Mehta, Vaibhav P; García-López, José-Antonio; Greaney, Michael F

2014-01-01

Three orthogonal cascade C—H functionalization processes are described, based on ruthenium-catalyzed C—H alkenylation. 1-Indanones, indeno indenes, and indeno furanones were accessed through cascade pathways by using arylacetophenones as substrates under conditions of catalytic [{Ru(p-cymene)Cl2}2] and stoichiometric Cu(OAc)2. Each transformation uses C—H functionalization methods to form C—C bonds sequentially, with the indeno furanone synthesis featuring a C—O bond formation as the terminating step. This work demonstrates the power of ruthenium-catalyzed alkenylation as a platform reaction to develop more complex transformations, with multiple C—H functionalization steps taking place in a single operation to access novel carbocyclic structures. PMID:24453063

Cascade of kinetic energy and scalar variance in DC electrokinetic turbulence

NASA Astrophysics Data System (ADS)

Zhao, Wei; Wang, Guiren

2017-11-01

Turbulent flow can be generated by DC electrokinetic (EK) force based on the electric conductivity and permittivity variations in fluids, as have been demonstrated by Varshney et al (2016), where a -1.4 slope of velocity power spectrum is observed. Here, we theoretically found the scaling exponents of velocity and scalar structures in the electric-body-force (EBF) dominant subregion of DC EK turbulence were 2/5 (equivalent to the -7/5 slope of velocity power spectrum) and 4/5 respectively. The theory perfectly explains the experimental results of Varshney et al. (2016). Based on Kármán-Howarth equation with forcing terms, the energy cascade process of DC EK turbulence was also investigated. Depending on the electric Rayleigh number (Rae) , two different energy cascade processes may happen. When Rae is small, the kinetic energy cascades along inertial subregion and EBF dominant subregion in sequence, before it is dissipated by fluid viscosity. When Rae is sufficiently large, the inertial subregion may be absent with EBF dominant subregion left. This investigation is very important on understand EK turbulence, which could be widely existed in nature and applied in engineerings. The work was supported by NSFC (11672229), and NSF (CAREER CBET-0954977 and MRI CBET-1040227).

Optimizing spread dynamics on graphs by message passing

NASA Astrophysics Data System (ADS)

Altarelli, F.; Braunstein, A.; Dall'Asta, L.; Zecchina, R.

2013-09-01

Cascade processes are responsible for many important phenomena in natural and social sciences. Simple models of irreversible dynamics on graphs, in which nodes activate depending on the state of their neighbors, have been successfully applied to describe cascades in a large variety of contexts. Over the past decades, much effort has been devoted to understanding the typical behavior of the cascades arising from initial conditions extracted at random from some given ensemble. However, the problem of optimizing the trajectory of the system, i.e. of identifying appropriate initial conditions to maximize (or minimize) the final number of active nodes, is still considered to be practically intractable, with the only exception being models that satisfy a sort of diminishing returns property called submodularity. Submodular models can be approximately solved by means of greedy strategies, but by definition they lack cooperative characteristics which are fundamental in many real systems. Here we introduce an efficient algorithm based on statistical physics for the optimization of trajectories in cascade processes on graphs. We show that for a wide class of irreversible dynamics, even in the absence of submodularity, the spread optimization problem can be solved efficiently on large networks. Analytic and algorithmic results on random graphs are complemented by the solution of the spread maximization problem on a real-world network (the Epinions consumer reviews network).

Systemic risk in a unifying framework for cascading processes on networks

NASA Astrophysics Data System (ADS)

Lorenz, J.; Battiston, S.; Schweitzer, F.

2009-10-01

We introduce a general framework for models of cascade and contagion processes on networks, to identify their commonalities and differences. In particular, models of social and financial cascades, as well as the fiber bundle model, the voter model, and models of epidemic spreading are recovered as special cases. To unify their description, we define the net fragility of a node, which is the difference between its fragility and the threshold that determines its failure. Nodes fail if their net fragility grows above zero and their failure increases the fragility of neighbouring nodes, thus possibly triggering a cascade. In this framework, we identify three classes depending on the way the fragility of a node is increased by the failure of a neighbour. At the microscopic level, we illustrate with specific examples how the failure spreading pattern varies with the node triggering the cascade, depending on its position in the network and its degree. At the macroscopic level, systemic risk is measured as the final fraction of failed nodes, X*, and for each of the three classes we derive a recursive equation to compute its value. The phase diagram of X* as a function of the initial conditions, thus allows for a prediction of the systemic risk as well as a comparison of the three different model classes. We could identify which model class leads to a first-order phase transition in systemic risk, i.e. situations where small changes in the initial conditions determine a global failure. Eventually, we generalize our framework to encompass stochastic contagion models. This indicates the potential for further generalizations.

Applications of spectral methods to turbulent magnetofluids in space and fusion research

NASA Technical Reports Server (NTRS)

Montgomery, D.; Voigt, R. G. (Editor); Gottlieb, D. (Editor); Hussaini, M. Y. (Editor)

1984-01-01

Recent and potential applications of spectral method computation to incompressible, dissipative magnetohydrodynamics are surveyed. Linear stability problems for one dimensional, quasi-equilibria are approachable through a close analogue of the Orr-Sommerfeld equation. It is likely that for Reynolds-like numbers above certain as-yet-undetermined thresholds, all magnetofluids are turbulent. Four recent effects in MHD turbulence are remarked upon, as they have displayed themselves in spectral method computations: (1) inverse cascades; (2) small-scale intermittent dissipative structures; (3) selective decays of ideal global invariants relative to each other; and (4) anisotropy induced by a mean dc magnetic field. Two more conjectured applications are suggested. All the turbulent processes discussed are sometimes involved in current carrying confined fusion magnetoplasmas and in space plasmas.

Organocatalyzed Domino [3+2] Cycloaddition/Payne-Type Rearrangement using Carbon Dioxide and Epoxy Alcohols.

PubMed

Kleij, Arjan Willem; Sopeña, Sergio; Cozzolino, Mariachiara; Escudero-Adán, Eduardo C; Martínez Belmonte, Marta; Maquilón, Cristina

2018-05-09

An unprecedented organocatalytic approach towards highly substituted cyclic carbonates from tri- and tetra-substituted oxiranes and carbon dioxide has been developed. The protocol involves the use of a simple and cheap superbase under mild, additive- and metal-free conditions towards the initial formation of a less substituted carbonate product that equilibrates to a tri- or even tetra-substituted cyclic carbonate under thermodynamic control. The latter are conveniently trapped in situ providing overall a new domino process for synthetically elusive heterocyclic scaffolds. Control experiments provide a rationale for the observed cascade reactions, which demonstrate high similarity with the well-known Payne rearrangement of epoxy alcohols. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The importance of pro-inflammatory signaling in neonatal NEC

PubMed Central

Frost, Brandy L.; Jilling, Tamas; Caplan, Michael S.

2008-01-01

Despite modern medical advances, necrotizing enterocolitis (NEC) remains a significant cause of morbidity and mortality in neonatal intensive care units, affecting 10 percent of premature neonates born weighing less than 1500 grams. Although many advances have been made in the understanding of this disease, the etiology and pathophysiology remain incompletely understood, and treatment is limited to supportive care. In recent years, studies have focused on the role of the inflammatory cascade and its’ impact on the disease process, and investigators are evaluating strategies to attenuate inflammatory signaling that might prevent and/or ameliorate neonatal NEC. In this review, we examine the key points in the signaling pathways involved in NEC, and potential strategies for prevention and treatment of this dreaded disease. PMID:18346533

Roles of chemical signals in regulation of the adaptive responses to iron deficiency.

PubMed

Liu, Xing Xing; He, Xiao Lin; Jin, Chong Wei

2016-05-03

Iron is an essential micronutrient for plants but is not readily accessible in most calcareous soils. Although the adaptive responses of plants to iron deficiency have been well documented, the signals involved in the regulatory cascade leading to their activation are not well understood to date. Recent studies revealed that chemical compounds, including sucrose, auxin, ethylene and nitric oxide, positively regulated the Fe-deficiency-induced Fe uptake processes in a cooperative manner. Nevertheless, cytokinins, jasmonate and abscisic acid were shown to act as negative signals in transmitting the iron deficiency information. The present mini review is to briefly address the roles of chemical signals in regulation of the adaptive responses to iron deficiency based on the literatures published in recent years.

Endoplasmic Reticulum and the Unfolded Protein Response: Dynamics and Metabolic Integration

PubMed Central

Bravo, Roberto; Parra, Valentina; Gatica, Damián; Rodriguez, Andrea E.; Torrealba, Natalia; Paredes, Felipe; Wang, Zhao V.; Zorzano, Antonio; Hill, Joseph A.; Jaimovich, Enrique; Quest, Andrew F.G.; Lavandero, Sergio

2013-01-01

The endoplasmic reticulum (ER) is a dynamic intracellular organelle with multiple functions essential for cellular homeostasis, development, and stress responsiveness. In response to cellular stress, a well-established signaling cascade, the unfolded protein response (UPR), is activated. This intricate mechanism is an important means of reestablishing cellular homeostasis and alleviating the inciting stress. Now, emerging evidence has demonstrated that the UPR influences cellular metabolism through diverse mechanisms, including calcium and lipid transfer, raising the prospect of involvement of these processes in the pathogenesis of disease, including neurodegeneration, cancer, diabetes mellitus and cardiovascular disease. Here, we review the distinct functions of the ER and UPR from a metabolic point of view, highlighting their association with prevalent pathologies. PMID:23317820

Cascade of Traumatic Brain Injury: A Correlational Study of Cognition, Postconcussion Symptoms, and Quality of Life.

PubMed

Reddy, Rajakumari Pampa; Rajeswaran, Jamuna; Devi, B Indira; Kandavel, Thennarasu

2017-01-01

Traumatic brain injury (TBI) constitutes a significant burden on health care resources in India. TBI is a dynamic process which involves damage to the brain thus leading to behavior cognitive and emotional consequences. To study the cognitive profile, post-concussion symptoms (PCS), quality of life (QOL), and their correlation. A total of 60 patients with TBI were recruited and assessed for neuropsychological profile, PCS, and QOL, the correlation among the variables were analyzed. The results suggest that TBI has series of consequences which is interrelated, and the study has implications for rehabilitation of TBI. The study highlights the deficits of cognition, and its correlation with PCS and QOL, emphasizing integrated rehabilitation approach for patients with TBI.

A current affair: electrotherapy in wound healing

PubMed Central

Hunckler, Jerome; de Mel, Achala

2017-01-01

New developments in accelerating wound healing can have immense beneficial socioeconomic impact. The wound healing process is a highly orchestrated series of mechanisms where a multitude of cells and biological cascades are involved. The skin battery and current of injury mechanisms have become topics of interest for their influence in chronic wounds. Electrostimulation therapy of wounds has shown to be a promising treatment option with no-device-related adverse effects. This review presents an overview of the understanding and use of applied electrical current in various aspects of wound healing. Rapid clinical translation of the evolving understanding of biomolecular mechanisms underlying the effects of electrical simulation on wound healing would positively impact upon enhancing patient’s quality of life. PMID:28461755

Proteomic analysis of human follicular fluid associated with successful in vitro fertilization.

PubMed

Shen, Xiaofang; Liu, Xin; Zhu, Peng; Zhang, Yuhua; Wang, Jiahui; Wang, Yanwei; Wang, Wenting; Liu, Juan; Li, Ning; Liu, Fujun

2017-07-27

Human follicular fluid (HFF) provides a key environment for follicle development and oocyte maturation, and contributes to oocyte quality and in vitro fertilization (IVF) outcome. To better understand folliculogenesis in the ovary, a proteomic strategy based on dual reverse phase high performance liquid chromatography (RP-HPLC) coupled to matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (LC-MALDI TOF/TOF MS) was used to investigate the protein profile of HFF from women undergoing successful IVF. A total of 219 unique high-confidence (False Discovery Rate (FDR) < 0.01) HFF proteins were identified by searching the reviewed Swiss-Prot human database (20,183 sequences), and MS data were further verified by western blot. PANTHER showed HFF proteins were involved in complement and coagulation cascade, growth factor and hormone, immunity, and transportation, KEGG indicated their pathway, and STRING demonstrated their interaction networks. In comparison, 32% and 50% of proteins have not been reported in previous human follicular fluid and plasma. Our HFF proteome research provided a new complementary high-confidence dataset of folliculogenesis and oocyte maturation environment. Those proteins associated with innate immunity, complement cascade, blood coagulation, and angiogenesis might serve as the biomarkers of female infertility and IVF outcome, and their pathways facilitated a complete exhibition of reproductive process.

Fabrication and characterization of a chemically oxidized-nanostructured porous silicon based biosensor implementing orienting protein A.

PubMed

Naveas, Nelson; Hernandez-Montelongo, Jacobo; Pulido, Ruth; Torres-Costa, Vicente; Villanueva-Guerrero, Raúl; Predestinación García Ruiz, Josefa; Manso-Silván, Miguel

2014-03-01

Nanostructured porous silicon (PSi) elicits as a very attractive material for future biosensing systems due to its high surface area, biocompatibility and well-established fabrication methods. In order to engineer its performance as a biosensor transducer platform, the density of immunoglobulins properly immobilized and oriented onto the surface needs to be optimized. In this work we fabricated and characterized a novel biosensing system focusing on the improvement of the biofunctionalization cascade. The system consists on a chemically oxidized PSi platform derivatized with 3-aminopropyltriethoxysilane (APTS) that is coupled to Staphylococcus protein A (SpA). The chemical oxidation has previously demonstrated to enhance the biofunctionalization process and here "by implementing SpA" a molecularly oriented immunosensor is achieved. The biosensor system is characterized in terms of its chemical composition, wettability and optical reflectance. Finally, this system is successfully exploited to develop a biosensor for detecting asymmetric dimethylarginine (ADMA), an endogenous molecule involved in cardiovascular diseases. Therefore, this work is relevant from the point of view of design and optimization of the biomolecular immobilization cascade on PSi surfaces with the added value of contribution to the development of new assays for detecting ADMA with a view on prevention of cardiovascular diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

Evaluation of the Interactionist Model of Socioeconomic Status and Problem Behavior: A Developmental Cascade across Generations

PubMed Central

Martin, Monica J.; Conger, Rand D.; Schofield, Thomas J.; Dogan, Shannon J.; Widaman, Keith F.; Donnellan, M. Brent; Neppl, Tricia K.

2010-01-01

The current multigenerational study evaluates the utility of the Interactionist Model of Socioeconomic Influence on human development (IMSI) in explaining problem behaviors across generations. The IMSI proposes that the association between socioeconomic status (SES) and human development involves a dynamic interplay that includes both social causation (SES influences human development) and social selection (individual characteristics affect SES). As part of the developmental cascade proposed by the IMSI, the findings from this investigation showed that G1 adolescent problem behavior predicted later G1 SES, family stress, and parental emotional investments, as well as the next generation of children's problem behavior. These results are consistent with a social selection view. Consistent with the social causation perspective, we found a significant relation between G1 SES and family stress, and in turn, family stress predicted G2 problem behavior. Finally, G1 adult SES predicted both material and emotional investments in the G2 child. In turn, emotional investments predicted G2 problem behavior, as did material investments. Some of the predicted pathways varied by G1 parent gender. The results are consistent with the view that processes of both social selection and social causation account for the association between SES and human development. PMID:20576188

Nitric oxide-mediated oxidative damage and the progressive demise of motor neurons in ALS.

PubMed

Drechsel, Derek A; Estévez, Alvaro G; Barbeito, Luis; Beckman, Joseph S

2012-11-01

Oxidative damage is a common and early feature of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and other neurodegenerative disorders. Dr. Mark Smith and his colleagues have built the case for oxidative stress being a primary progenitor rather than a secondary end-stage epiphenomenon of neurodegeneration. They proposed that reactive oxygen species contribute to the "age-related cascade of neurodegeneration," whereby accumulative oxidative damage with age promotes other characteristic pathological changes in afflicted brain regions, including protein aggregation, metabolic deficiencies, and inflammation. Nitric oxide (NO) likely plays a critical role in this age-related cascade. NO is a major signaling molecule produced in the central nervous system to modulate neurological activity through stimulating cyclic GMP synthesis. However, the same physiological concentrations of NO, relevant in cellular signaling, may also initiate and amplify oxidative damage by diffusion-limited reactions with superoxide (O(2)(•-)) to produce peroxynitrite (ONOO(-)). This is perhaps best illustrated in ALS where physiological levels of NO promote survival of motor neurons, but the same concentrations can stimulate motor neuron apoptosis and glial cell activation under pathological conditions. While these changes represent a complex mechanism involving multiple cell types in the pathogenesis of ALS, they also reveal general processes underlying neurodegeneration.

Oxygen, the lead actor in the pathophysiologic drama: enactment of the trinity of normoxia, hypoxia, and hyperoxia in disease and therapy.

PubMed

Kulkarni, Aditi C; Kuppusamy, Periannan; Parinandi, Narasimham

2007-10-01

Aerobic life has evolved a dependence on molecular oxygen for its mere survival. Mitochondrial oxidative phosphorylation absolutely requires oxygen to generate the currency of energy in aerobes. The physiologic homeostasis of these organisms is strictly maintained by optimal cellular and tissue-oxygenation status through complex oxygen-sensing mechanisms, signaling cascades, and transport processes. In the event of fluctuating oxygen levels leading to either an increase (hyperoxia) or decrease (hypoxia) in cellular oxygen, the organism faces a crisis involving depletion of energy reserves, altered cell-signaling cascades, oxidative reactions/events, and cell death or tissue damage. Molecular oxygen is activated by both nonenzymatic and enzymatic mechanisms into highly reactive oxygen species (ROS). Aerobes have evolved effective antioxidant defenses to counteract the reactivity of ROS. Although the ROS are also required for many normal physiologic functions of the aerobes, overwhelming production of ROS coupled with their insufficient scavenging by endogenous antioxidants will lead to detrimental oxidative stress. Needless to say, molecular oxygen is at the center of oxygenation, oxidative phosphorylation, and oxidative stress. This review focuses on the biology and pathophysiology of oxygen, with an emphasis on transport, sensing, and activation of oxygen, oxidative phosphorylation, oxygenation, oxidative stress, and oxygen therapy.

Vacancy cascades in small molecules following x-ray inner shell photoionization

NASA Astrophysics Data System (ADS)

Ray, D.; Dunford, R. W.; Southworth, S. H.; Kanter, E. P.; Doumy, G.; Gao, Y.; Ho, P. J.; Picon, A.

2014-05-01

We are investigating molecular effects in vacancy cascades of small molecules containing heavy atoms - IBr, Br2 and CH2BrI - following K-shell ionization. In addition to fundamental interest in the physics of such decay processes, there are practical applications such as medical treatments that use energetic fragmentation of iodinated compounds with high energy x-rays to selectively treat tumorous cells. Other biological applications are also promising. We utilize the tunable monochromatic x-ray beam at the Advanced Photon Source to trigger K-shell photoionization of Br and I, and measure charge distributions and the kinetic energies released to the fragment ions. A newly designed detection device allows us to do multi-fold coincidence measurements involving momentum imaging of all the ion fragments with very high detection efficiency in coincidence with x-ray fluorescence detection. By comparing the molecular fragmentation probabilities and the kinetic energies released in Br2, IBr and CH2BrI we aim to gain understanding of the fragmentation mechanism as a function of the bond distance between I and Br. Supported by the Chemical Sciences, Geosciences, and Biosciences Division, Office of Basic Energy Sciences, Office of Science, US Dept of Energy, Contract DE-AC02-06CH11357.

Turbulence of Weak Gravitational Waves in the Early Universe.

PubMed

Galtier, Sébastien; Nazarenko, Sergey V

2017-12-01

We study the statistical properties of an ensemble of weak gravitational waves interacting nonlinearly in a flat space-time. We show that the resonant three-wave interactions are absent and develop a theory for four-wave interactions in the reduced case of a 2.5+1 diagonal metric tensor. In this limit, where only plus-polarized gravitational waves are present, we derive the interaction Hamiltonian and consider the asymptotic regime of weak gravitational wave turbulence. Both direct and inverse cascades are found for the energy and the wave action, respectively, and the corresponding wave spectra are derived. The inverse cascade is characterized by a finite-time propagation of the metric excitations-a process similar to an explosive nonequilibrium Bose-Einstein condensation, which provides an efficient mechanism to ironing out small-scale inhomogeneities. The direct cascade leads to an accumulation of the radiation energy in the system. These processes might be important for understanding the early Universe where a background of weak nonlinear gravitational waves is expected.

Contagion on complex networks with persuasion

NASA Astrophysics Data System (ADS)

Huang, Wei-Min; Zhang, Li-Jie; Xu, Xin-Jian; Fu, Xinchu

2016-03-01

The threshold model has been widely adopted as a classic model for studying contagion processes on social networks. We consider asymmetric individual interactions in social networks and introduce a persuasion mechanism into the threshold model. Specifically, we study a combination of adoption and persuasion in cascading processes on complex networks. It is found that with the introduction of the persuasion mechanism, the system may become more vulnerable to global cascades, and the effects of persuasion tend to be more significant in heterogeneous networks than those in homogeneous networks: a comparison between heterogeneous and homogeneous networks shows that under weak persuasion, heterogeneous networks tend to be more robust against random shocks than homogeneous networks; whereas under strong persuasion, homogeneous networks are more stable. Finally, we study the effects of adoption and persuasion threshold heterogeneity on systemic stability. Though both heterogeneities give rise to global cascades, the adoption heterogeneity has an overwhelmingly stronger impact than the persuasion heterogeneity when the network connectivity is sufficiently dense.

Contagion on complex networks with persuasion

PubMed Central

Huang, Wei-Min; Zhang, Li-Jie; Xu, Xin-Jian; Fu, Xinchu

2016-01-01

The threshold model has been widely adopted as a classic model for studying contagion processes on social networks. We consider asymmetric individual interactions in social networks and introduce a persuasion mechanism into the threshold model. Specifically, we study a combination of adoption and persuasion in cascading processes on complex networks. It is found that with the introduction of the persuasion mechanism, the system may become more vulnerable to global cascades, and the effects of persuasion tend to be more significant in heterogeneous networks than those in homogeneous networks: a comparison between heterogeneous and homogeneous networks shows that under weak persuasion, heterogeneous networks tend to be more robust against random shocks than homogeneous networks; whereas under strong persuasion, homogeneous networks are more stable. Finally, we study the effects of adoption and persuasion threshold heterogeneity on systemic stability. Though both heterogeneities give rise to global cascades, the adoption heterogeneity has an overwhelmingly stronger impact than the persuasion heterogeneity when the network connectivity is sufficiently dense. PMID:27029498

Contagion on complex networks with persuasion.

PubMed

Huang, Wei-Min; Zhang, Li-Jie; Xu, Xin-Jian; Fu, Xinchu

2016-03-31

The threshold model has been widely adopted as a classic model for studying contagion processes on social networks. We consider asymmetric individual interactions in social networks and introduce a persuasion mechanism into the threshold model. Specifically, we study a combination of adoption and persuasion in cascading processes on complex networks. It is found that with the introduction of the persuasion mechanism, the system may become more vulnerable to global cascades, and the effects of persuasion tend to be more significant in heterogeneous networks than those in homogeneous networks: a comparison between heterogeneous and homogeneous networks shows that under weak persuasion, heterogeneous networks tend to be more robust against random shocks than homogeneous networks; whereas under strong persuasion, homogeneous networks are more stable. Finally, we study the effects of adoption and persuasion threshold heterogeneity on systemic stability. Though both heterogeneities give rise to global cascades, the adoption heterogeneity has an overwhelmingly stronger impact than the persuasion heterogeneity when the network connectivity is sufficiently dense.

Cascading failures and the emergence of cooperation in evolutionary-game based models of social and economical networks.

PubMed

Wang, Wen-Xu; Lai, Ying-Cheng; Armbruster, Dieter

2011-09-01

We study catastrophic behaviors in large networked systems in the paradigm of evolutionary games by incorporating a realistic "death" or "bankruptcy" mechanism. We find that a cascading bankruptcy process can arise when defection strategies exist and individuals are vulnerable to deficit. Strikingly, we observe that, after the catastrophic cascading process terminates, cooperators are the sole survivors, regardless of the game types and of the connection patterns among individuals as determined by the topology of the underlying network. It is necessary that individuals cooperate with each other to survive the catastrophic failures. Cooperation thus becomes the optimal strategy and absolutely outperforms defection in the game evolution with respect to the "death" mechanism. Our results can be useful for understanding large-scale catastrophe in real-world systems and in particular, they may yield insights into significant social and economical phenomena such as large-scale failures of financial institutions and corporations during an economic recession.

Cascading failures and the emergence of cooperation in evolutionary-game based models of social and economical networks

NASA Astrophysics Data System (ADS)

Wang, Wen-Xu; Lai, Ying-Cheng; Armbruster, Dieter

2011-09-01

We study catastrophic behaviors in large networked systems in the paradigm of evolutionary games by incorporating a realistic "death" or "bankruptcy" mechanism. We find that a cascading bankruptcy process can arise when defection strategies exist and individuals are vulnerable to deficit. Strikingly, we observe that, after the catastrophic cascading process terminates, cooperators are the sole survivors, regardless of the game types and of the connection patterns among individuals as determined by the topology of the underlying network. It is necessary that individuals cooperate with each other to survive the catastrophic failures. Cooperation thus becomes the optimal strategy and absolutely outperforms defection in the game evolution with respect to the "death" mechanism. Our results can be useful for understanding large-scale catastrophe in real-world systems and in particular, they may yield insights into significant social and economical phenomena such as large-scale failures of financial institutions and corporations during an economic recession.

Experimental characterization of quantum correlated triple beams generated by cascaded four-wave mixing processes

NASA Astrophysics Data System (ADS)

Qin, Zhongzhong; Cao, Leiming; Jing, Jietai

2015-05-01

Quantum correlations and entanglement shared among multiple modes are fundamental ingredients of most continuous-variable quantum technologies. Recently, a method used to generate multiple quantum correlated beams using cascaded four-wave mixing (FWM) processes was theoretically proposed and experimentally realized by our group [Z. Qin et al., Phys. Rev. Lett. 113, 023602 (2014)]. Our study of triple-beam quantum correlation paves the way to showing the tripartite entanglement in our system. Our system also promises to find applications in quantum information and precision measurement such as the controlled quantum communications, the generation of multiple quantum correlated images, and the realization of a multiport nonlinear interferometer. For its applications, the degree of quantum correlation is a crucial figure of merit. In this letter, we experimentally study how various parameters, such as the cell temperatures, one-photon, and two-photon detunings, influence the degree of quantum correlation between the triple beams generated from the cascaded two-FWM configuration.

Experimental characterization of quantum correlated triple beams generated by cascaded four-wave mixing processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin, Zhongzhong; Cao, Leiming; Jing, Jietai, E-mail: jtjing@phy.ecnu.edu.cn

2015-05-25

Quantum correlations and entanglement shared among multiple modes are fundamental ingredients of most continuous-variable quantum technologies. Recently, a method used to generate multiple quantum correlated beams using cascaded four-wave mixing (FWM) processes was theoretically proposed and experimentally realized by our group [Z. Qin et al., Phys. Rev. Lett. 113, 023602 (2014)]. Our study of triple-beam quantum correlation paves the way to showing the tripartite entanglement in our system. Our system also promises to find applications in quantum information and precision measurement such as the controlled quantum communications, the generation of multiple quantum correlated images, and the realization of a multiportmore » nonlinear interferometer. For its applications, the degree of quantum correlation is a crucial figure of merit. In this letter, we experimentally study how various parameters, such as the cell temperatures, one-photon, and two-photon detunings, influence the degree of quantum correlation between the triple beams generated from the cascaded two-FWM configuration.« less

Computational hydraulics of a cascade of experimental-scale landside dam failures

NASA Astrophysics Data System (ADS)

Wright, N.; Guan, M.

2015-12-01

Abstract: Landslide dams typically comprise unconsolidated and poorly sorted material, and are vulnerable to rapid failure and breaching, particularly in mountainous areas during high intense rainfalls. A large flash flood with high-concentrated sediment can be formed in a short period, and the magnitude is likely to be amplified along the flow direction due to the inclusion of a large amount of sediment. This can result in significant and sudden flood risk downstream for human life and property. Numerous field evidence has indicated the various risks of landslide dam failures. In general, cascading landslide dams can be formed along the sloping channel due to the randomness and unpredictability of landslides, which complexes the hydraulics of landslide dam failures. The failure process of a single dam and subsequent floods has attracted attention in multidisciplinary studies. However, the dynamic failure process of cascading landslide dams has been poorly understood. From a viewpoint of simulation, this study evaluates the formation and development of rapid sediment-charged floods due to cascading failure of landslide dams through detailed hydro-morphodynamic modelling. The model used is based on shallow water theory and it has been successful in predicting the flow and morphological process during sudden dam-break, as well as full and partial dyke-breach. Various experimental-scale scenarios are modelled, including: (1) failure of a single full dam in a sloping channel, (2) failure of two dams in a sloping channel, (3) failure of multiple landslide dams (four) in a sloping channel. For each scenario, different failure modes (sudden/gradual) and bed boundary (fixed /mobile) are assumed and simulated. The study systematically explores the tempo-spatial evolution of landslide-induced floods (discharge, flow velocity, and flow concentration) and geomorphic properties along the sloping channel. The effects of in-channel erosion and flow-driven sediment from dams on the development of flood process are investigated. The results improve the understanding of the formation and development mechanism of flash floods due to cascading landslide dam failures. The findings are beneficial for downstream flood risk assessment and developing control strategies for landslide-induced floods.

Period adding cascades: experiment and modeling in air bubbling.

PubMed

Pereira, Felipe Augusto Cardoso; Colli, Eduardo; Sartorelli, José Carlos

2012-03-01

Period adding cascades have been observed experimentally/numerically in the dynamics of neurons and pancreatic cells, lasers, electric circuits, chemical reactions, oceanic internal waves, and also in air bubbling. We show that the period adding cascades appearing in bubbling from a nozzle submerged in a viscous liquid can be reproduced by a simple model, based on some hydrodynamical principles, dealing with the time evolution of two variables, bubble position and pressure of the air chamber, through a system of differential equations with a rule of detachment based on force balance. The model further reduces to an iterating one-dimensional map giving the pressures at the detachments, where time between bubbles come out as an observable of the dynamics. The model has not only good agreement with experimental data, but is also able to predict the influence of the main parameters involved, like the length of the hose connecting the air supplier with the needle, the needle radius and the needle length.

Multilocality and fusion rules on the generalized structure functions in two-dimensional and three-dimensional Navier-Stokes turbulence.

PubMed

Gkioulekas, Eleftherios

2016-09-01

Using the fusion-rules hypothesis for three-dimensional and two-dimensional Navier-Stokes turbulence, we generalize a previous nonperturbative locality proof to multiple applications of the nonlinear interactions operator on generalized structure functions of velocity differences. We call this generalization of nonperturbative locality to multiple applications of the nonlinear interactions operator "multilocality." The resulting cross terms pose a new challenge requiring a new argument and the introduction of a new fusion rule that takes advantage of rotational symmetry. Our main result is that the fusion-rules hypothesis implies both locality and multilocality in both the IR and UV limits for the downscale energy cascade of three-dimensional Navier-Stokes turbulence and the downscale enstrophy cascade and inverse energy cascade of two-dimensional Navier-Stokes turbulence. We stress that these claims relate to nonperturbative locality of generalized structure functions on all orders and not the term-by-term perturbative locality of diagrammatic theories or closure models that involve only two-point correlation and response functions.

Enhanced Colorimetric Immunoassay Accompanying with Enzyme Cascade Amplification Strategy for Ultrasensitive Detection of Low-Abundance Protein

PubMed Central

Gao, Zhuangqiang; Hou, Li; Xu, Mingdi; Tang, Dianping

2014-01-01

Methods based on enzyme labels have been developed for colorimetric immunoassays, but most involve poor sensitivity and are unsuitable for routine use. Herein, we design an enhanced colorimetric immunoassay for prostate-specific antigen (PSA) coupling with an enzyme-cascade-amplification strategy (ECAS-CIA). In the presence of target PSA, the labeled alkaline phosphatase on secondary antibody catalyzes the formation of palladium nanostructures, which catalyze 3,3′,5,5′-tetramethylbenzidine-H2O2 system to produce the colored products, thus resulting in the signal cascade amplification. Results indicated that the ECAS-CIA presents good responses toward PSA, and allows detection of PSA at a concentration as low as 0.05 ng mL−1. Intra- and inter-assay coefficients of variation are below 9.5% and 10.7%, respectively. Additionally, the methodology is validated for analysis of clinical serum specimens with consistent results obtained by PSA ELISA kit. Importantly, the ECAS-CIA opens a new horizon for protein diagnostics and biosecurity. PMID:24509941

Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking

PubMed Central

Voelzmann, Andre; Okenve-Ramos, Pilar; Qu, Yue; Chojnowska-Monga, Monika; del Caño-Espinel, Manuela; Prokop, Andreas; Sanchez-Soriano, Natalia

2016-01-01

The mechanisms regulating synapse numbers during development and ageing are essential for normal brain function and closely linked to brain disorders including dementias. Using Drosophila, we demonstrate roles of the microtubule-associated protein Tau in regulating synapse numbers, thus unravelling an important cellular requirement of normal Tau. In this context, we find that Tau displays a strong functional overlap with microtubule-binding spectraplakins, establishing new links between two different neurodegenerative factors. Tau and the spectraplakin Short Stop act upstream of a three-step regulatory cascade ensuring adequate delivery of synaptic proteins. This cascade involves microtubule stability as the initial trigger, JNK signalling as the central mediator, and kinesin-3 mediated axonal transport as the key effector. This cascade acts during development (synapse formation) and ageing (synapse maintenance) alike. Therefore, our findings suggest novel explanations for intellectual disability in Tau deficient individuals, as well as early synapse loss in dementias including Alzheimer’s disease. DOI: http://dx.doi.org/10.7554/eLife.14694.001 PMID:27501441

Design strategy for terahertz quantum dot cascade lasers.

PubMed

Burnett, Benjamin A; Williams, Benjamin S

2016-10-31

The development of quantum dot cascade lasers has been proposed as a path to obtain terahertz semiconductor lasers that operate at room temperature. The expected benefit is due to the suppression of nonradiative electron-phonon scattering and reduced dephasing that accompanies discretization of the electronic energy spectrum. We present numerical modeling which predicts that simple scaling of conventional quantum well based designs to the quantum dot regime will likely fail due to electrical instability associated with high-field domain formation. A design strategy adapted for terahertz quantum dot cascade lasers is presented which avoids these problems. Counterintuitively, this involves the resonant depopulation of the laser's upper state with the LO-phonon energy. The strategy is tested theoretically using a density matrix model of transport and gain, which predicts sufficient gain for lasing at stable operating points. Finally, the effect of quantum dot size inhomogeneity on the optical lineshape is explored, suggesting that the design concept is robust to a moderate amount of statistical variation.

Role of pre-existing point defects on primary damage production and amorphization in silicon carbide (β-SiC)

NASA Astrophysics Data System (ADS)

Sahoo, Deepak Ranjan; Szlufarska, Izabela; Morgan, Dane; Swaminathan, Narasimhan

2018-01-01

Molecular dynamics simulations of displacement cascades were conducted to study the effect of point defects on the primary damage production in β-SiC. Although all types of point defects and Frenkel pairs were considered, Si interstitials and Si Frenkel pairs were unstable and hence excluded from the cascade studies. Si (C) vacancies had the maximum influence, enhancing C (Si) antisites and suppressing C interstitial production, when compared to the sample without any defects. The intracascade recombination mechanisms, in the presence of pre-existing defects, is explored by examining the evolution of point defects during the cascade. To ascertain the role of the unstable Si defects on amorphization, simulations involving explicit displacements of Si atoms were conducted. The dose to amorphization with only Si displacements was much lower than what was observed with only C displacements. The release of elastic energy accumulated due to Si defects, is found to be the amorphizing mechanism.

Multi-species trace gas analysis with dual-wavelength quantum cascade laser

NASA Astrophysics Data System (ADS)

Jágerská, Jana; Tuzson, Béla; Looser, Herbert; Jouy, Pierre; Hugi, Andreas; Mangold, Markus; Soltic, Patrik; Faist, Jérôme; Emmenegger, Lukas

2015-04-01

Simultaneous detection of multiple gas species using mid-IR laser spectroscopy is highly appealing for a large variety of applications ranging from air quality monitoring, medical breath analysis to industrial process control. However, state-of-the-art distributed-feedback (DFB) mid-IR lasers are usually tunable only within a narrow spectral range, which generally leads to one-laser-one-compound measurement strategy. Thus, multi-species detection involves several lasers and elaborate beam combining solutions [1]. This makes them bulky, costly, and highly sensitive to optical alignment, which limits their field deployment. In this paper, we explore an alternative measurement concept based on a dual-wavelength quantum cascade laser (DW-QCL) [2]. Such a laser can emit at two spectrally distinct wavelengths using a succession of two DFB gratings with different periodicities and a common waveguide to produce one output beam. The laser design was optimized for NOx measurements and correspondingly emits single-mode at 5.26 and 6.25 μm. Electrical separation of the respective laser sections makes it possible to address each wavelength independently. Thereby, it is possible to detect NO and NO2 species with one laser using the same optical path, without any beam combining optics, i.e. in a compact and cost-efficient single-path optical setup. Operated in a time-division multiplexed mode, the spectrometer reaches detection limits at 100 s averaging of 0.5 and 1.5 ppb for NO2 and NO, respectively. The performance of the system was validated against the well-established chemiluminescence detection while measuring the NOx emissions on an automotive test-bench, as well as monitoring the pollution at a suburban site. [1] B. Tuzson, K. Zeyer, M. Steinbacher, J. B. McManus, D. D. Nelson, M. S. Zahniser, and L. Emmenegger, 'Selective measurements of NO, NO2 and NOy in the free troposphere using quantum cascade laser spectroscopy,' Atmospheric Measurement Techniques 6, 927-936 (2013). [2] J. Jágerská, P. Jouy, A. Hugi, B. Tuzson, H. Looser, M. Mangold, M. Beck, L. Emmenegger, and J. Faist, 'Dual-wavelength quantum cascade laser for trace gas spectroscopy,' Applied Physics Letters 105, 161109-161109-4 (2014).

Modeling the Interaction between Quinolinate and the Receptor for Advanced Glycation End Products (RAGE): Relevance for Early Neuropathological Processes

PubMed Central

Serratos, Iris N.; Castellanos, Pilar; Pastor, Nina; Millán-Pacheco, César; Rembao, Daniel; Pérez-Montfort, Ruy; Cabrera, Nallely; Reyes-Espinosa, Francisco; Díaz-Garrido, Paulina; López-Macay, Ambar; Martínez-Flores, Karina; López-Reyes, Alberto; Sánchez-García, Aurora; Cuevas, Elvis; Santamaria, Abel

2015-01-01

The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor involved in neurodegenerative and inflammatory disorders. RAGE induces cellular signaling upon binding to a variety of ligands. Evidence suggests that RAGE up-regulation is involved in quinolinate (QUIN)-induced toxicity. We investigated the QUIN-induced toxic events associated with early noxious responses, which might be linked to signaling cascades leading to cell death. The extent of early cellular damage caused by this receptor in the rat striatum was characterized by image processing methods. To document the direct interaction between QUIN and RAGE, we determined the binding constant (Kb) of RAGE (VC1 domain) with QUIN through a fluorescence assay. We modeled possible binding sites of QUIN to the VC1 domain for both rat and human RAGE. QUIN was found to bind at multiple sites to the VC1 dimer, each leading to particular mechanistic scenarios for the signaling evoked by QUIN binding, some of which directly alter RAGE oligomerization. This work contributes to the understanding of the phenomenon of RAGE-QUIN recognition, leading to the modulation of RAGE function. PMID:25757085

On Cascade Energy Transfer in Convective Turbulence

NASA Astrophysics Data System (ADS)

Shestakov, A. V.; Stepanov, R. A.; Frick, P. G.

2017-12-01

The paper is devoted to specificities of the cascade processes in developed turbulence existing on a background of the density (temperature) gradient either parallel (turbulence in a stably stratified (SS) medium) or antiparallel (convective turbulence (CT)) to the gravitational force. Our main attention is paid to the Obukhov-Bolgiano (OB) regime, which presumes a balance between the buoyancy and nonlinear forces in a sufficiently extensive part of the inertial interval. Up to now, there has been no reliable evidence of the existence of the OB regime, although fragments of spectra with slopes close to-11/5 and-7/5 were detected in some works on the numerical simulations of convective turbulence. The paper presents a critical comparison of these data with the results obtained in this work using the cascade model of convective turbulence, which makes it possible to consider a wide range of control parameters. The cascade model is new and was obtained by the generalization of the class of helical cascade models to the case of turbulent convection. It is shown that, in developed turbulence, which is characterized by an interval with a constant spectral flux of kinetic energy, the buoyancy force cannot compete with nonlinear interactions and has no essential effect on the dynamics of the inertial interval. It is the buoyancy force that supplies the cascade process with energy in convective turbulence but only in the maximum scales. Under the SS conditions, the buoyancy forces reduce the energy of turbulent pulsations. In the case of stable stratification, the buoyancy force reduces the turbulence pulsation energy. The OB regime arises in none of these cases, but, in the scales beyond the inertial interval, Kolmogorov's turbulence with the "-5/3" law, in which temperature behaves like a passive admixture, is established. The observed deviations from the "-5/3" spectrum, erroneously interpreted as the OB regime, are manifested in the case of insufficient separation of the macroscale of turbulence and the dissipative scale.

Optimization and resilience of complex supply-demand networks

NASA Astrophysics Data System (ADS)

Zhang, Si-Ping; Huang, Zi-Gang; Dong, Jia-Qi; Eisenberg, Daniel; Seager, Thomas P.; Lai, Ying-Cheng

2015-06-01

Supply-demand processes take place on a large variety of real-world networked systems ranging from power grids and the internet to social networking and urban systems. In a modern infrastructure, supply-demand systems are constantly expanding, leading to constant increase in load requirement for resources and consequently, to problems such as low efficiency, resource scarcity, and partial system failures. Under certain conditions global catastrophe on the scale of the whole system can occur through the dynamical process of cascading failures. We investigate optimization and resilience of time-varying supply-demand systems by constructing network models of such systems, where resources are transported from the supplier sites to users through various links. Here by optimization we mean minimization of the maximum load on links, and system resilience can be characterized using the cascading failure size of users who fail to connect with suppliers. We consider two representative classes of supply schemes: load driven supply and fix fraction supply. Our findings are: (1) optimized systems are more robust since relatively smaller cascading failures occur when triggered by external perturbation to the links; (2) a large fraction of links can be free of load if resources are directed to transport through the shortest paths; (3) redundant links in the performance of the system can help to reroute the traffic but may undesirably transmit and enlarge the failure size of the system; (4) the patterns of cascading failures depend strongly upon the capacity of links; (5) the specific location of the trigger determines the specific route of cascading failure, but has little effect on the final cascading size; (6) system expansion typically reduces the efficiency; and (7) when the locations of the suppliers are optimized over a long expanding period, fewer suppliers are required. These results hold for heterogeneous networks in general, providing insights into designing optimal and resilient complex supply-demand systems that expand constantly in time.

Exploring empirical rank-frequency distributions longitudinally through a simple stochastic process.

PubMed

Finley, Benjamin J; Kilkki, Kalevi

2014-01-01

The frequent appearance of empirical rank-frequency laws, such as Zipf's law, in a wide range of domains reinforces the importance of understanding and modeling these laws and rank-frequency distributions in general. In this spirit, we utilize a simple stochastic cascade process to simulate several empirical rank-frequency distributions longitudinally. We focus especially on limiting the process's complexity to increase accessibility for non-experts in mathematics. The process provides a good fit for many empirical distributions because the stochastic multiplicative nature of the process leads to an often observed concave rank-frequency distribution (on a log-log scale) and the finiteness of the cascade replicates real-world finite size effects. Furthermore, we show that repeated trials of the process can roughly simulate the longitudinal variation of empirical ranks. However, we find that the empirical variation is often less that the average simulated process variation, likely due to longitudinal dependencies in the empirical datasets. Finally, we discuss the process limitations and practical applications.

The associations between multisensory temporal processing and symptoms of schizophrenia.

PubMed

Stevenson, Ryan A; Park, Sohee; Cochran, Channing; McIntosh, Lindsey G; Noel, Jean-Paul; Barense, Morgan D; Ferber, Susanne; Wallace, Mark T

2017-01-01

Recent neurobiological accounts of schizophrenia have included an emphasis on changes in sensory processing. These sensory and perceptual deficits can have a cascading effect onto higher-level cognitive processes and clinical symptoms. One form of sensory dysfunction that has been consistently observed in schizophrenia is altered temporal processing. In this study, we investigated temporal processing within and across the auditory and visual modalities in individuals with schizophrenia (SCZ) and age-matched healthy controls. Individuals with SCZ showed auditory and visual temporal processing abnormalities, as well as multisensory temporal processing dysfunction that extended beyond that attributable to unisensory processing dysfunction. Most importantly, these multisensory temporal deficits were associated with the severity of hallucinations. This link between atypical multisensory temporal perception and clinical symptomatology suggests that clinical symptoms of schizophrenia may be at least partly a result of cascading effects from (multi)sensory disturbances. These results are discussed in terms of underlying neural bases and the possible implications for remediation. Copyright © 2016 Elsevier B.V. All rights reserved.

Neural correlates of informational cascades: brain mechanisms of social influence on belief updating

PubMed Central

Klucharev, Vasily; Rieskamp, Jörg

2015-01-01

Informational cascades can occur when rationally acting individuals decide independently of their private information and follow the decisions of preceding decision-makers. In the process of updating beliefs, differences in the weighting of private and publicly available social information may modulate the probability that a cascade starts in a decisive way. By using functional magnetic resonance imaging, we examined neural activity while participants updated their beliefs based on the decisions of two fictitious stock market traders and their own private information, which led to a final decision of buying one of two stocks. Computational modeling of the behavioral data showed that a majority of participants overweighted private information. Overweighting was negatively correlated with the probability of starting an informational cascade in trials especially prone to conformity. Belief updating by private information was related to activity in the inferior frontal gyrus/anterior insula, the dorsolateral prefrontal cortex and the parietal cortex; the more a participant overweighted private information, the higher the activity in the inferior frontal gyrus/anterior insula and the lower in the parietal-temporal cortex. This study explores the neural correlates of overweighting of private information, which underlies the tendency to start an informational cascade. PMID:24974396

Optical wave turbulence and the condensation of light

NASA Astrophysics Data System (ADS)

Bortolozzo, Umberto; Laurie, Jason; Nazarenko, Sergey; Residori, Stefania

2009-11-01

In an optical experiment, we report a wave turbulence regime that, starting with weakly nonlinear waves with randomized phases, shows an inverse cascade of photons towards the lowest wavenumbers. We show that the cascade is induced by a six-wave resonant interaction process and is characterized by increasing nonlinearity. At low wavenumbers the nonlinearity becomes strong and leads to modulational instability developing into solitons, whose number is decreasing further along the beam.

Artificial “ping-pong” cascade of PIWI-interacting RNA in silkworm cells

PubMed Central

Shoji, Keisuke; Suzuki, Yutaka; Sugano, Sumio; Shimada, Toru; Katsuma, Susumu

2017-01-01

PIWI-interacting RNAs (piRNAs) play essential roles in the defense system against selfish elements in animal germline cells by cooperating with PIWI proteins. A subset of piRNAs is predicted to be generated via the “ping-pong” cascade, which is mainly controlled by two different PIWI proteins. Here we established a cell-based artificial piRNA production system using a silkworm ovarian cultured cell line that is believed to possess a complete piRNA pathway. In addition, we took advantage of a unique silkworm sex-determining one-to-one ping-pong piRNA pair, which enabled us to precisely monitor the behavior of individual artificial piRNAs. With this novel strategy, we successfully generated artificial piRNAs against endogenous protein-coding genes via the expected back-and-forth traveling mechanism. Furthermore, we detected “primary” piRNAs from the upstream region of the artificial “ping-pong” site in the endogenous gene. This artificial piRNA production system experimentally confirms the existence of the “ping-pong” cascade of piRNAs. Also, this system will enable us to identify the factors involved in both, or each, of the “ping” and “pong” cascades and the sequence features that are required for efficient piRNA production. PMID:27777367

Sensitive detection of Escherichia coli O157:H7 based on cascade signal amplification in ELISA.

PubMed

Shan, Shan; Liu, Daofeng; Guo, Qi; Wu, Songsong; Chen, Rui; Luo, Kai; Hu, Liming; Xiong, Yonghua; Lai, Weihua

2016-09-01

In this study, cascade signal amplification in ELISA involving double-antibody sandwich ELISA and indirectly competitive ELISA was established to sensitively detect Escherichia coli O157:H7. In the double-antibody sandwich ELISA, a complex was formed comprising anti-E. coli O157:H7 polyclonal antibody, E. coli O157:H7, biotinylated anti-E. coli O157:H7 monoclonal antibody, streptavidin, and biotinylated β-lactamase. Penicillin solution was then added into the ELISA well and hydrolyzed by β-lactamase. Afterward, the penicillin solution was transferred to indirectly competitive ELISA. The concentration of penicillin can be sensitively detected in indirectly competitive ELISA. In the cascade signal amplification system, increasing the amount of added E. coli O157:H7 resulted in more β-lactamase and less penicillin. The detection sensitivity of E. coli O157:H7, which was 20cfu/mL with the cascade signal amplification in ELISA, was 1,000-fold higher than that of traditional ELISA. Furthermore, the novel method can be used to detect E. coli O157:H7 in milk (2cfu/g). Therefore, this new signaling strategy will facilitate analyses of highly sensitive foodborne pathogens. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Cascade Reductive Etherification of Bioderived Aldehydes over Zr-Based Catalysts.

PubMed

Shinde, Suhas; Rode, Chandrashekhar

2017-10-23

An efficient one-pot catalytic cascade sequence has been developed for the production of value-added ethers from bioderived aldehydes. Etherification of 5-(hydroxymethyl)furfural with different aliphatic alcohols over acidic Zr-montmorillonite (Zr-Mont) catalyst produced a mixture of 5-(alkoxymethyl)furfural and 2-(dialkoxymethyl)-5-(alkoxymethyl)furan. The latter was selectively converted back into 5-(alkoxymethyl)furfural by treating it with water over the same catalyst. The synthesis of 2,5-bis(alkoxymethyl)furan was achieved through a cascade sequence involving etherification, transfer hydrogenation, and re-etherification over a combination of acidic Zr-Mont and the charge-transfer hydrogenation catalyst [ZrO(OH) 2 ]. This catalyst combination was further explored for the cascade conversion of 2-furfuraldehyde into 2-(alkoxymethyl)furan. The scope of this strategy was then extended for the reductive etherification of lignin-derived arylaldehydes to obtain the respective benzyl ethers in >80 % yield. Additionally, the mixture of Zr-Mont and ZrO(OH) 2 does not undergo mutual destruction, which was proved by recycling experiments and XRD analysis. Both the catalysts were thoroughly characterized using BET, temperature-programmed desorption of NH 3 and CO 2 , pyridine-FTIR, XRD, inductively coupled plasma optical emission spectroscopy, and X-ray photoelectron spectroscopy techniques. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rare radiative decays of the B c meson

NASA Astrophysics Data System (ADS)

Ju, Wan-Li; Wang, Tianhong; Jiang, Yue; Yuan, Han; Wang, Guo-Li

2016-08-01

In this paper, we study the rare radiative processes {B}c\\to {D}{sJ}(*)γ within the Standard Model, where {D}{sJ}(*) stands for the meson {D}s*, {D}s1(2460,2536) or {D}s2*(2573). During the investigations, we consider the contributions from the penguin, annihilation, color-suppressed and color-favored cascade diagrams. Our results show that: (1) the penguin and annihilation contributions are dominant in the branching fractions; (2) for the processes {B}c\\to {D}s*γ and {B}c\\to {D}s1(2460,2536)γ , the effects from the color-suppressed and color-favored cascade diagrams are un-negligible.

Tectonics and seismicity of the southern Washington Cascade range

USGS Publications Warehouse

Stanley, W.D.; Johnson, S.Y.; Qamar, A.I.; Weaver, C.S.; Williams, J.M.

1996-01-01

Geophysical, geological, and seismicity data are combined to develop a transpressional strain model for the southern Washington Cascades region. We use this model to explain oblique fold and fault systems, transverse faults, and a linear seismic zone just west of Mt. Rainier known as the western Rainier zone. We also attempt to explain a concentration of earthquakes that connects the northwest-trending Mount St. Helens seismic zone to the north-trending western Rainier zone. Our tectonic model illustrates the pervasive effects of accretionary processes, combined with subsequent transpressive forces generated by oblique subduction, on Eocene to present crustal processes, such as seismicity and volcanism.

FGF-mediated mesoderm induction involves the Src-family kinase Laloo.

PubMed

Weinstein, D C; Marden, J; Carnevali, F; Hemmati-Brivanlou, A

1998-08-27

During embryogenesis, inductive interactions underlie the development of much of the body plan. In Xenopus laevis, factors secreted from the vegetal pole induce mesoderm in the adjacent marginal zone; members of both the transforming growth factor-beta (TGF-beta) and fibroblast growth factor (FGF) ligand families seem to have critical roles in this process. Here we report the identification and characterization of laloo, a novel participant in the signal transduction cascade linking extracellular, mesoderm-inducing signals to the nucleus, where alteration of cell fate is driven by changes in gene expression. Overexpression of laloo, a member of the Src-related gene family, in Xenopus embryos gives rise to ectopic posterior structures that frequently contain axial tissue. Laloo induces mesoderm in Xenopus ectodermal explants; this induction is blocked by reagents that disrupt the FGF signalling pathway. Conversely, expression of a dominant-inhibitory Laloo mutant blocks mesoderm induction by FGF and causes severe posterior truncations in vivo. This work provides the first evidence that a Src-related kinase is involved in vertebrate mesoderm induction.

Wnt Signaling in Cardiac Disease.

PubMed

Hermans, Kevin C M; Blankesteijn, W Matthijs

2015-07-01

Wnt signaling encompasses multiple and complex signaling cascades and is involved in many developmental processes such as tissue patterning, cell fate specification, and control of cell division. Consequently, accurate regulation of signaling activities is essential for proper embryonic development. Wnt signaling is mostly silent in the healthy adult organs but a reactivation of Wnt signaling is generally observed under pathological conditions. This has generated increasing interest in this pathway from a therapeutic point of view. In this review article, the involvement of Wnt signaling in cardiovascular development will be outlined, followed by its implication in myocardial infarct healing, cardiac hypertrophy, heart failure, arrhythmias, and atherosclerosis. The initial experiments not always offer consensus on the effects of activation or inactivation of the pathway, which may be attributed to (i) the type of cardiac disease, (ii) timing of the intervention, and (iii) type of cells that are targeted. Therefore, more research is needed to determine the exact implication of Wnt signaling in the conditions mentioned above to exploit it as a powerful therapeutic target. © 2015 American Physiological Society.

Quantum steering in cascaded four-wave mixing processes.

PubMed

Wang, Li; Lv, Shuchao; Jing, Jietai

2017-07-24

Quantum steering is used to describe the "spooky action-at-a-distance" nonlocality raised in the Einstein-Podolsky-Rosen (EPR) paradox, which is important for understanding entanglement distribution and constructing quantum networks. Here, in this paper, we study an experimentally feasible scheme for generating quantum steering based on cascaded four-wave-mixing (FWM) processes in hot rubidium (Rb) vapor. Quantum steering, including bipartite steering and genuine tripartite steering among the output light fields, is theoretically analyzed. We find the corresponding gain regions in which the bipartite and tripartite steering exist. The results of bipartite steering can be used to establish a hierarchical steering model in which one beam can steer the other two beams in the whole gain region; however, the other two beams cannot steer the first beam simultaneously. Moreover, the other two beams cannot steer with each other in the whole gain region. More importantly, we investigate the gain dependence of the existence of the genuine tripartite steering and we find that the genuine tripartite steering exists in most of the whole gain region in the ideal case. Also we discuss the effect of losses on the genuine tripartite steering. Our results pave the way to experimental demonstration of quantum steering in cascaded FWM process.

Systems theory and cascades in developmental psychopathology.

PubMed

Cox, Martha J; Mills-Koonce, Roger; Propper, Cathi; Gariépy, Jean-Louis

2010-08-01

In the wake of prominent theoreticians in developmental science, whose contributions we review in this article, many developmental psychologists came to endorse a systems approach to understanding how the individual, as it develops, establishes functional relationships to social ecological contexts that from birth to school entry rapidly increase in complexity. The concept of developmental cascade has been introduced in this context to describe lawful processes by which antecedent conditions may be related with varying probabilities to specified outcomes. These are understood as processes by which function at one level or in one domain of behavior affect the organization of competency in later developing domains of general adaptation. Here we propose a developmental sequence by which the developing child acquires regulative capacities that are key to adjustment to a society that demands considerable control of emotional and cognitive functions early in life. We report empirical evidence showing that the acquisition of regulative capacities may be understood as a cascade of shifts in control parameters induced by the progressive integration of biological, transactional, and socioaffective systems over development. We conclude by suggesting how the developmental process may be accessed for effective intervention in populations deemed "at risk" for later problems of psychosocial adjustment.

Particle retention by respiratory epithelial cells is associated with persistent biological effect

EPA Science Inventory

The biological effect of particles on respiratory epithelial cells involves, in part, the generation of an oxidative stress and a consequent cascade of reactions culminating in inflammatory mediator release. Whether there is either an immediate, transitory activation or a persist...

Strawberry consumption improves aging-associated impairments, mitochondrial biogenesis and functionality through the AMP-activated protein kinase signaling cascade.

PubMed

Giampieri, Francesca; Alvarez-Suarez, Josè M; Cordero, Mario D; Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Y; Afrin, Sadia; Santos-Buelga, Celestino; González-Paramás, Ana M; Astolfi, Paola; Rubini, Corrado; Zizzi, Antonio; Tulipani, Sara; Quiles, Josè L; Mezzetti, Bruno; Battino, Maurizio

2017-11-01

Dietary polyphenols have been recently proposed as activators of the AMP-activated protein kinase (AMPK) signaling pathway and this fact might explain the relationship between the consumption of polyphenol-rich foods and the slowdown of the progression of aging. In the present work, the effects of strawberry consumption were evaluated on biomarkers of oxidative damage and on aging-associated reductions in mitochondrial function and biogenesis for 8weeks in old rats. Strawberry supplementation increased antioxidant enzyme activities, mitochondrial biomass and functionality, and decreased intracellular ROS levels and biomarkers of protein, lipid and DNA damage (P<0.05). Furthermore, a significant (P<0.05) increase in the expression of the AMPK cascade genes, involved in mitochondrial biogenesis and antioxidant defences, was also detected after strawberry intake. These in vivo results were then verified in vitro on HepG2 cells, confirming the involvement of AMPK in the beneficial effects exerted by strawberry against aging progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Far-field photostable optical nanoscopy (PHOTON) for real-time super-resolution single-molecular imaging of signaling pathways of single live cells

NASA Astrophysics Data System (ADS)

Huang, Tao; Browning, Lauren M.; Xu, Xiao-Hong Nancy

2012-04-01

Cellular signaling pathways play crucial roles in cellular functions and design of effective therapies. Unfortunately, study of cellular signaling pathways remains formidably challenging because sophisticated cascades are involved, and a few molecules are sufficient to trigger signaling responses of a single cell. Here we report the development of far-field photostable-optical-nanoscopy (PHOTON) with photostable single-molecule-nanoparticle-optical-biosensors (SMNOBS) for mapping dynamic cascades of apoptotic signaling pathways of single live cells in real-time at single-molecule (SM) and nanometer (nm) resolutions. We have quantitatively imaged single ligand molecules (tumor necrosis factor α, TNFα) and their binding kinetics with their receptors (TNFR1) on single live cells; tracked formation and internalization of their clusters and their initiation of intracellular signaling pathways in real-time; and studied apoptotic signaling dynamics and mechanisms of single live cells with sufficient temporal and spatial resolutions. This study provides new insights into complex real-time dynamic cascades and molecular mechanisms of apoptotic signaling pathways of single live cells. PHOTON provides superior imaging and sensing capabilities and SMNOBS offer unrivaled biocompatibility and photostability, which enable probing of signaling pathways of single live cells in real-time at SM and nm resolutions.Cellular signaling pathways play crucial roles in cellular functions and design of effective therapies. Unfortunately, study of cellular signaling pathways remains formidably challenging because sophisticated cascades are involved, and a few molecules are sufficient to trigger signaling responses of a single cell. Here we report the development of far-field photostable-optical-nanoscopy (PHOTON) with photostable single-molecule-nanoparticle-optical-biosensors (SMNOBS) for mapping dynamic cascades of apoptotic signaling pathways of single live cells in real-time at single-molecule (SM) and nanometer (nm) resolutions. We have quantitatively imaged single ligand molecules (tumor necrosis factor α, TNFα) and their binding kinetics with their receptors (TNFR1) on single live cells; tracked formation and internalization of their clusters and their initiation of intracellular signaling pathways in real-time; and studied apoptotic signaling dynamics and mechanisms of single live cells with sufficient temporal and spatial resolutions. This study provides new insights into complex real-time dynamic cascades and molecular mechanisms of apoptotic signaling pathways of single live cells. PHOTON provides superior imaging and sensing capabilities and SMNOBS offer unrivaled biocompatibility and photostability, which enable probing of signaling pathways of single live cells in real-time at SM and nm resolutions. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr11739h

Analysis of a Gene Regulatory Cascade Mediating Circadian Rhythm in Zebrafish

PubMed Central

Wang, Haifang; Du, Jiulin; Yan, Jun

2013-01-01

In the study of circadian rhythms, it has been a puzzle how a limited number of circadian clock genes can control diverse aspects of physiology. Here we investigate circadian gene expression genome-wide using larval zebrafish as a model system. We made use of a spatial gene expression atlas to investigate the expression of circadian genes in various tissues and cell types. Comparison of genome-wide circadian gene expression data between zebrafish and mouse revealed a nearly anti-phase relationship and allowed us to detect novel evolutionarily conserved circadian genes in vertebrates. We identified three groups of zebrafish genes with distinct responses to light entrainment: fast light-induced genes, slow light-induced genes, and dark-induced genes. Our computational analysis of the circadian gene regulatory network revealed several transcription factors (TFs) involved in diverse aspects of circadian physiology through transcriptional cascade. Of these, microphthalmia-associated transcription factor a (mitfa), a dark-induced TF, mediates a circadian rhythm of melanin synthesis, which may be involved in zebrafish's adaptation to daily light cycling. Our study describes a systematic method to discover previously unidentified TFs involved in circadian physiology in complex organisms. PMID:23468616

Dynamic behavior of the interaction between epidemics and cascades on heterogeneous networks

NASA Astrophysics Data System (ADS)

Jiang, Lurong; Jin, Xinyu; Xia, Yongxiang; Ouyang, Bo; Wu, Duanpo

2014-12-01

Epidemic spreading and cascading failure are two important dynamical processes on complex networks. They have been investigated separately for a long time. But in the real world, these two dynamics sometimes may interact with each other. In this paper, we explore a model combined with the SIR epidemic spreading model and a local load sharing cascading failure model. There exists a critical value of the tolerance parameter for which the epidemic with high infection probability can spread out and infect a fraction of the network in this model. When the tolerance parameter is smaller than the critical value, the cascading failure cuts off the abundance of paths and blocks the spreading of the epidemic locally. While the tolerance parameter is larger than the critical value, the epidemic spreads out and infects a fraction of the network. A method for estimating the critical value is proposed. In simulations, we verify the effectiveness of this method in the uncorrelated configuration model (UCM) scale-free networks.

Cascade exciton-pumping engines with manipulated speed and efficiency in light-harvesting porous π-network films

PubMed Central

Gu, Cheng; Huang, Ning; Xu, Fei; Gao, Jia; Jiang, Donglin

2015-01-01

Light-harvesting antennae are the machinery for exciton pumping in natural photosynthesis, whereas cascade energy transfer through chlorophyll is key to long-distance, efficient energy transduction. Numerous artificial antennae have been developed. However, they are limited in their cascade energy-transfer abilities because of a lack of control over complex chromophore aggregation processes, which has impeded their advancement. Here we report a viable approach for addressing this issue by using a light-harvesting porous polymer film in which a three-dimensional π-network serves as the antenna and micropores segregate multiple dyes to prevent aggregation. Cascade energy-transfer engines are integrated into the films; the rate and efficiency of the energy-funneling engines are precisely manipulated by tailoring the dye components and contents. The nanofilms allow accurate and versatile luminescence engineering, resulting in the production of thirty emission hues, including blue, green, red and white. This advance may open new pathways for realising photosynthesis and photoenergy conversion. PMID:25746459

AKAP-Lbc enhances cyclic AMP control of the ERK1/2 cascade.

PubMed

Smith, F Donelson; Langeberg, Lorene K; Cellurale, Cristina; Pawson, Tony; Morrison, Deborah K; Davis, Roger J; Scott, John D

2010-12-01

Mitogen-activated protein kinase (MAPK) cascades propagate a variety of cellular activities. Processive relay of signals through RAF-MEK-ERK modulates cell growth and proliferation. Signalling through this ERK cascade is frequently amplified in cancers, and drugs such as sorafenib (which is prescribed to treat renal and hepatic carcinomas) and PLX4720 (which targets melanomas) inhibit RAF kinases. Natural factors that influence ERK1/2 signalling include the second messenger cyclic AMP. However, the mechanisms underlying this cascade have been difficult to elucidate. We demonstrate that the A-kinase-anchoring protein AKAP-Lbc and the scaffolding protein kinase suppressor of Ras (KSR-1) form the core of a signalling network that efficiently relay signals from RAF, through MEK, and on to ERK1/2. AKAP-Lbc functions as an enhancer of ERK signalling by securing RAF in the vicinity of MEK1 and synchronizing protein kinase A (PKA)-mediated phosphorylation of Ser 838 on KSR-1. This offers mechanistic insight into cAMP-responsive control of ERK signalling events.

The effect of alloying nickel with iron on the supersonic ballistic stage of high energy displacement cascades

DOE PAGES

Béland, Laurent Karim; Osetsky, Yuri N.; Stoller, Roger E.

2016-06-23

Previous experimental and theoretical studies suggest that the production of extended defect structures by collision cascades is inhibited in equiatomic NiFe, in comparison to pure Ni. It is also known that the production of such extend defect structures results from the formation of subcascades by high-energy recoils and their subsequent interaction. A detailed analysis of the ballistics of 40 keV cascades in Ni and NiFe is performed to identify the formation of such subcascades and to assess their spatial distribution. It is found that subcascades in Ni and NiFe are created with nearly identical energies and distributed similarly in space.more » This suggests that the differences in production of extended defect structures is not related to processes taking place in the ballistic phase of the collision cascade. Lastly, these results can be generalized to other, more chemically complex, concentrated alloys where the elements have similar atomic numbers, such as many high-entropy alloys.« less

Terahertz multiheterodyne spectroscopy using laser frequency combs

DOE PAGES

Yang, Yang; Burghoff, David; Hayton, Darren J.; ...

2014-07-01

The terahertz region is of great importance for spectroscopy since many molecules have absorption fingerprints there. Frequency combs based on terahertz quantum cascade lasers feature broadband coverage and high output powers in a compact package, making them an attractive option for broadband spectroscopy. Here, we demonstrate the first multiheterodyne spectroscopy using two terahertz quantum cascade laser combs. Over a spectral range of 250 GHz, we achieve average signal-to-noise ratios of 34 dB using cryogenic detectors and 24 dB using room-temperature detectors, all in just 100 μs. As a proof of principle, we use these combs to measure the broadband transmissionmore » spectrum of etalon samples and show that, with proper signal processing, it is possible to extend the multiheterodyne spectroscopy to quantum cascade laser combs operating in pulsed mode. Here, this greatly expands the range of quantum cascade lasers that could be suitable for these techniques and allows for the creation of completely solid-state terahertz laser spectrometers.« less

The effect of alloying nickel with iron on the supersonic ballistic stage of high energy displacement cascades

DOE Office of Scientific and Technical Information (OSTI.GOV)

Béland, Laurent Karim; Osetsky, Yuri N.; Stoller, Roger E.

Previous experimental and theoretical studies suggest that the production of extended defect structures by collision cascades is inhibited in equiatomic NiFe, in comparison to pure Ni. It is also known that the production of such extend defect structures results from the formation of subcascades by high-energy recoils and their subsequent interaction. A detailed analysis of the ballistics of 40 keV cascades in Ni and NiFe is performed to identify the formation of such subcascades and to assess their spatial distribution. It is found that subcascades in Ni and NiFe are created with nearly identical energies and distributed similarly in space.more » This suggests that the differences in production of extended defect structures is not related to processes taking place in the ballistic phase of the collision cascade. Lastly, these results can be generalized to other, more chemically complex, concentrated alloys where the elements have similar atomic numbers, such as many high-entropy alloys.« less

The phenoptosis problem: what is causing the death of an organism? Lessons from acute kidney injury.

PubMed

Zorov, D B; Plotnikov, E Y; Jankauskas, S S; Isaev, N K; Silachev, D N; Zorova, L D; Pevzner, I B; Pulkova, N V; Zorov, S D; Morosanova, M A

2012-07-01

Programmed execution of various cells and intracellular structures is hypothesized to be not the only example of elimination of biological systems - the general mechanism can also involve programmed execution of organs and organisms. Modern rating of programmed cell death mechanisms includes 13 mechanistic types. As for some types, the mechanism of actuation and manifestation of cell execution has been basically elucidated, while the causes and intermediate steps of the process of fatal failure of organs and organisms remain unknown. The analysis of deaths resulting from a sudden heart arrest or multiple organ failure and other acute and chronic pathologies leads to the conclusion of a special role of mitochondria and oxidative stress activating the immune system. Possible mechanisms of mitochondria-mediated induction of the signaling cascades involved in organ failure and death of the organism are discussed. These mechanisms include generation of reactive oxygen species and damage-associated molecular patterns in mitochondria. Some examples of renal failure-induced deaths are presented with mechanisms and settings determined by some hypothetical super system rather than by the kidneys themselves. This system plays the key role in the process of physiological senescence and termination of an organism. The facts presented suggest that it is the immune system involved in mitochondrial signaling that can act as the system responsible for the organism's death.

Numerical Investigation of a Cascaded Longitudinal Space-Charge Amplifier at the Fermilab's Advanced Superconducting Test Accelerator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Halavanau, A.; Piot, P.

2015-06-01

In a cascaded longitudinal space-charge amplifier (LSCA), initial density noise in a relativistic e-beam is amplified via the interplay of longitudinal space charge forces and properly located dispersive sections. This type of amplification process was shown to potentially result in large final density modulations [1] compatible with the production of broadband electromagnetic radiation. The technique was recently demonstrated in the optical domain [2]. In this paper we investigate, via numerical simulations, the performances of a cascaded LSCA beamline at the Fermilab’s Advanced Superconducting Test Accelerator (ASTA). We especially explore the properties of the produced broadband radiation. Our studies have beenmore » conducted with a grid-less three-dimensional space-charge algorithm.« less

Frequency dependence of the maximum operating temperature for quantum-cascade lasers up to 5.4 THz

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wienold, M.; Humboldt Universität zu Berlin, Institut für Physik, Newtonstr. 15, 12489 Berlin; Deutsches Zentrum für Luft und Raumfahrt, Rutherfordstr. 2, 12489 Berlin

2015-11-16

We report on the observation of an approximately linear reduction in the maximum operating temperature with an increasing emission frequency for terahertz quantum-cascade lasers between 4.2 and 5.4 THz. These lasers are based on the same design type, but vary in period length and barrier height for the cascade structure. The sample emitting at the highest frequency around 5.4 THz can be operated in pulsed mode up to 56 K. We identify an additional relaxation channel for electrons by longitudinal optical phonon scattering from the upper to the lower laser level and increasing optical losses toward higher frequencies as major processes,more » leading to the observed temperature behavior.« less

Distributed torsion sensor based on cascaded coaxial cable Fabry-Perot interferometers

NASA Astrophysics Data System (ADS)

Cheng, Baokai; Zhu, Wenge; Hua, Liwei; Liu, Jie; Li, Yurong; Nygaard, Runar; Xiao, Hai

2016-07-01

Cascaded coaxial cable Fabry-Perot interferometers (FPI) are studied and demonstrated for distributed torsion measurement. Multiple weak reflectors are implemented on a coaxial cable so that any two consecutive reflectors can form a Fabry-Perot cavity. By fixing the cable sensor in a helical form on a shaft, the distributed torsion of the shaft can be measured by the cascaded Fabry-Perot cavities. A test on a single section shows that the sensor has a linear response with a sensitivity of 1.834 MHz (rad/m)-1 in the range of twisted rate from 0 to 8.726 rad m-1. The distributed torsion sensing capability is useful in drilling process monitoring, structure health monitoring and machine failure detection.

A Bioinspired Organocatalytic Cascade for the Selective Oxidation of Amines under Air.

PubMed

Largeron, Martine; Fleury, Maurice-Bernard

2017-05-17

A bioinspired organocatalytic cascade reaction for the selective aerobic oxidative cross-coupling of primary amines to imines is described. This approach takes advantages of commercially available pyrogallol monomeric precursor to deliver low loadings of natural purpurogallin in situ, under air. This is further engaged in a catalytic process with the amine substrate affording, under single turnover, the active biomimetic quinonoid organocatalyst and the homocoupled imine intermediate, which is then converted into cross-coupled imine after dynamic transimination. This organocatalytic cascade inspired by both purpurogallin biosynthesis and copper amine oxidases allows the aerobic oxidation of non-activated primary amines that non-enzymatic organocatalysts were not able to accomplish alone. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Symmetry breaking and uniqueness for the incompressible Navier-Stokes equations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dascaliuc, Radu; Thomann, Enrique; Waymire, Edward C., E-mail: waymire@math.oregonstate.edu

2015-07-15

The present article establishes connections between the structure of the deterministic Navier-Stokes equations and the structure of (similarity) equations that govern self-similar solutions as expected values of certain naturally associated stochastic cascades. A principle result is that explosion criteria for the stochastic cascades involved in the probabilistic representations of solutions to the respective equations coincide. While the uniqueness problem itself remains unresolved, these connections provide interesting problems and possible methods for investigating symmetry breaking and the uniqueness problem for Navier-Stokes equations. In particular, new branching Markov chains, including a dilogarithmic branching random walk on the multiplicative group (0, ∞), naturallymore » arise as a result of this investigation.« less

Symmetry breaking and uniqueness for the incompressible Navier-Stokes equations.

PubMed

Dascaliuc, Radu; Michalowski, Nicholas; Thomann, Enrique; Waymire, Edward C

2015-07-01

The present article establishes connections between the structure of the deterministic Navier-Stokes equations and the structure of (similarity) equations that govern self-similar solutions as expected values of certain naturally associated stochastic cascades. A principle result is that explosion criteria for the stochastic cascades involved in the probabilistic representations of solutions to the respective equations coincide. While the uniqueness problem itself remains unresolved, these connections provide interesting problems and possible methods for investigating symmetry breaking and the uniqueness problem for Navier-Stokes equations. In particular, new branching Markov chains, including a dilogarithmic branching random walk on the multiplicative group (0, ∞), naturally arise as a result of this investigation.

Three-dimensional elliptic grid generation technique with application to turbomachinery cascades

NASA Technical Reports Server (NTRS)

Chen, S. C.; Schwab, J. R.

1988-01-01

Described is a numerical method for generating 3-D grids for turbomachinery computational fluid dynamic codes. The basic method is general and involves the solution of a quasi-linear elliptic partial differential equation via pointwise relaxation with a local relaxation factor. It allows specification of the grid point distribution on the boundary surfaces, the grid spacing off the boundary surfaces, and the grid orthogonality at the boundary surfaces. A geometry preprocessor constructs the grid point distributions on the boundary surfaces for general turbomachinery cascades. Representative results are shown for a C-grid and an H-grid for a turbine rotor. Two appendices serve as user's manuals for the basic solver and the geometry preprocessor.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dobrescu, Bogdan A.

Color-singlet gauge bosons with renormalizable couplings to quarks but not to leptons must interact with additional fermions (''anomalons'') required to cancel the gauge anomalies. Analyzing the decays of such leptophobic bosons into anomalons, I show that they produce final states involving leptons at the LHC. Resonant production of a flavor-universal leptophobic Z' boson leads to cascade decays via anomalons, whose signatures include a leptonically decaying Z, missing energy and several jets. A Z' boson that couples to the right-handed quarks of the first and second generations undergoes cascade decays that violate lepton universality and include signals with two leptons andmore » jets, or with a Higgs boson, a lepton, a W and missing energy.« less

Microwave assisted reconstruction of optical interferograms for distributed fiber optic sensing.

PubMed

Huang, Jie; Hua, Lei; Lan, Xinwei; Wei, Tao; Xiao, Hai

2013-07-29

This paper reports a distributed fiber optic sensing technique through microwave assisted separation and reconstruction of optical interferograms in spectrum domain. The approach involves sending a microwave-modulated optical signal through cascaded fiber optic interferometers. The microwave signal was used to resolve the position and reflectivity of each sensor along the optical fiber. By sweeping the optical wavelength and detecting the modulation signal, the optical spectrum of each sensor can be reconstructed. Three cascaded fiber optic extrinsic Fabry-Perot interferometric sensors were used to prove the concept. Their microwave-reconstructed interferogram matched well with those recorded individually using an optical spectrum analyzer. The application in distributed strain measurement has also been demonstrated.

Type-II quantum wells with tensile-strained GaAsSb layers for interband cascade lasers with tailored valence band mixing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Motyka, M.; Dyksik, M.; Ryczko, K.

Optical properties of modified type II W-shaped quantum wells have been investigated with the aim to be utilized in interband cascade lasers. The results show that introducing a tensely strained GaAsSb layer, instead of a commonly used compressively strained GaInSb, allows employing the active transition involving valence band states with a significant admixture of the light holes. Theoretical predictions of multiband k·p theory have been experimentally verified by using photoluminescence and polarization dependent photoreflectance measurements. These results open a pathway for practical realization of mid-infrared lasing devices with uncommon polarization properties including, for instance, polarization-independent midinfrared light emitters.

Exploring Empirical Rank-Frequency Distributions Longitudinally through a Simple Stochastic Process

PubMed Central

Finley, Benjamin J.; Kilkki, Kalevi

2014-01-01

The frequent appearance of empirical rank-frequency laws, such as Zipf’s law, in a wide range of domains reinforces the importance of understanding and modeling these laws and rank-frequency distributions in general. In this spirit, we utilize a simple stochastic cascade process to simulate several empirical rank-frequency distributions longitudinally. We focus especially on limiting the process’s complexity to increase accessibility for non-experts in mathematics. The process provides a good fit for many empirical distributions because the stochastic multiplicative nature of the process leads to an often observed concave rank-frequency distribution (on a log-log scale) and the finiteness of the cascade replicates real-world finite size effects. Furthermore, we show that repeated trials of the process can roughly simulate the longitudinal variation of empirical ranks. However, we find that the empirical variation is often less that the average simulated process variation, likely due to longitudinal dependencies in the empirical datasets. Finally, we discuss the process limitations and practical applications. PMID:24755621

The ubiquitin conjugating enzyme UbcH10 competes with UbcH3 for binding to the SCF complex, a ubiquitin ligase involved in cell cycle progression

USDA-ARS?s Scientific Manuscript database

Ubiquitylation, which regulates most biological pathways, occurs through an enzymatic cascade involving a ubiquitin (ub) activating enzyme (E1), a ub conjugating enzyme (E2) and a ub ligase (E3). UbcH3 is the E2 that interacts with SCF (Skp1/Cul1/F-box protein) complex and ubiquitylates many protein...

Oxidative Stress, Redox Signaling, and Autophagy: Cell Death Versus Survival

PubMed Central

Navarro-Yepes, Juliana; Burns, Michaela; Anandhan, Annadurai; Khalimonchuk, Oleh; del Razo, Luz Maria; Quintanilla-Vega, Betzabet; Pappa, Aglaia; Panayiotidis, Mihalis I.

2014-01-01

Abstract Significance: The molecular machinery regulating autophagy has started becoming elucidated, and a number of studies have undertaken the task to determine the role of autophagy in cell fate determination within the context of human disease progression. Oxidative stress and redox signaling are also largely involved in the etiology of human diseases, where both survival and cell death signaling cascades have been reported to be modulated by reactive oxygen species (ROS) and reactive nitrogen species (RNS). Recent Advances: To date, there is a good understanding of the signaling events regulating autophagy, as well as the signaling processes by which alterations in redox homeostasis are transduced to the activation/regulation of signaling cascades. However, very little is known about the molecular events linking them to the regulation of autophagy. This lack of information has hampered the understanding of the role of oxidative stress and autophagy in human disease progression. Critical Issues: In this review, we will focus on (i) the molecular mechanism by which ROS/RNS generation, redox signaling, and/or oxidative stress/damage alter autophagic flux rates; (ii) the role of autophagy as a cell death process or survival mechanism in response to oxidative stress; and (iii) alternative mechanisms by which autophagy-related signaling regulate mitochondrial function and antioxidant response. Future Directions: Our research efforts should now focus on understanding the molecular basis of events by which autophagy is fine tuned by oxidation/reduction events. This knowledge will enable us to understand the mechanisms by which oxidative stress and autophagy regulate human diseases such as cancer and neurodegenerative disorders. Antioxid. Redox Signal. 21, 66–85. PMID:24483238

Transcriptional analysis and histochemistry reveal that hypersensitive cell death and H2O2 have crucial roles in the resistance of tea plant (Camellia sinensis (L.) O. Kuntze) to anthracnose.

PubMed

Wang, Yuchun; Hao, Xinyuan; Lu, Qinhua; Wang, Lu; Qian, Wenjun; Li, Nana; Ding, Changqing; Wang, Xinchao; Yang, Yajun

2018-01-01

Anthracnose causes severe losses of tea production in China. Although genes and biological processes involved in anthracnose resistance have been reported in other plants, the molecular response to anthracnose in tea plant is unknown. We used the susceptible tea cultivar Longjing 43 and the resistant cultivar Zhongcha 108 as materials and compared transcriptome changes in the leaves of both cultivars following Colletotrichum fructicola inoculation. In all, 9015 and 8624 genes were differentially expressed between the resistant and susceptible cultivars and their controls (0 h), respectively. In both cultivars, the differentially expressed genes (DEGs) were enriched in 215 pathways, including responses to sugar metabolism, phytohormones, reactive oxygen species (ROS), biotic stimuli and signalling, transmembrane transporter activity, protease activity and signalling receptor activity, but DEG expression levels were higher in Zhongcha 108 than in Longjing 43. Moreover, functional enrichment analysis of the DEGs showed that hydrogen peroxide (H 2 O 2 ) metabolism, cell death, secondary metabolism, and carbohydrate metabolism are involved in the defence of Zhongcha 108, and 88 key genes were identified. Protein-protein interaction (PPI) network demonstrated that putative mitogen-activated protein kinase (MAPK) cascades are activated by resistance (R) genes and mediate downstream defence responses. Histochemical analysis subsequently validated the strong hypersensitive response (HR) and H 2 O 2 accumulation that occurred around the hyphal infection sites in Zhongcha 108. Overall, our results indicate that the HR and H 2 O 2 are critical mechanisms in tea plant defence against anthracnose and may be activated by R genes via MAPK cascades.

An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome c-independent activation of caspase-9 by caspase-12.

PubMed

Morishima, Nobuhiro; Nakanishi, Keiko; Takenouchi, Hiromi; Shibata, Takehiko; Yasuhiko, Yukuto

2002-09-13

Activation of caspase-12 from procaspase-12 is specifically induced by insult to the endoplasmic reticulum (ER) (Nakagawa, T., Zhu, H., Morishima, N., Li, E., Xu, J., Yankner, B. A., and Yuan, J. (2000) Nature 403, 98-103), yet the functional consequences of caspase-12 activation have been unclear. We have shown that recombinant caspase-12 specifically cleaves and activates procaspase-9 in cytosolic extracts. The activated caspase-9 catalyzes cleavage of procaspase-3, which is inhibitable by a caspase-9-specific inhibitor. Although cytochrome c released from mitochondria has been believed to be required for caspase-9 activation during apoptosis (Zou, H., Henzel, W. J., Liu, X., Lutschg, A., and Wang, X. (1997) Cell 90, 405-413, Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., Alnemri, E. S., and Wang, X. (1997) Cell 91, 479-489), caspase-9 as well as caspase-12 and -3 are activated in cytochrome c-free cytosols in murine myoblast cells under ER stress. These results suggest that caspase-12 can activate caspase-9 without involvement of cytochrome c. To examine the role of caspase-12 in the activation of downstream caspases, we used a caspase-12-binding protein, which we identified in a yeast two-hybrid screen, for regulation of caspase-12 activation. The binding protein protects procaspase-12 from processing in vitro. Stable expression of the binding protein renders procaspase-12 insensitive to ER stress, thereby suppressing apoptosis and the activation of caspase-9 and -3. These data suggest that procaspase-9 is a substrate of caspase-12 and that ER stress triggers a specific cascade involving caspase-12, -9, and -3 in a cytochrome c-independent manner.

Osmotic Stress Signaling and Osmoadaptation in Yeasts

PubMed Central

Hohmann, Stefan

2002-01-01

The ability to adapt to altered availability of free water is a fundamental property of living cells. The principles underlying osmoadaptation are well conserved. The yeast Saccharomyces cerevisiae is an excellent model system with which to study the molecular biology and physiology of osmoadaptation. Upon a shift to high osmolarity, yeast cells rapidly stimulate a mitogen-activated protein (MAP) kinase cascade, the high-osmolarity glycerol (HOG) pathway, which orchestrates part of the transcriptional response. The dynamic operation of the HOG pathway has been well studied, and similar osmosensing pathways exist in other eukaryotes. Protein kinase A, which seems to mediate a response to diverse stress conditions, is also involved in the transcriptional response program. Expression changes after a shift to high osmolarity aim at adjusting metabolism and the production of cellular protectants. Accumulation of the osmolyte glycerol, which is also controlled by altering transmembrane glycerol transport, is of central importance. Upon a shift from high to low osmolarity, yeast cells stimulate a different MAP kinase cascade, the cell integrity pathway. The transcriptional program upon hypo-osmotic shock seems to aim at adjusting cell surface properties. Rapid export of glycerol is an important event in adaptation to low osmolarity. Osmoadaptation, adjustment of cell surface properties, and the control of cell morphogenesis, growth, and proliferation are highly coordinated processes. The Skn7p response regulator may be involved in coordinating these events. An integrated understanding of osmoadaptation requires not only knowledge of the function of many uncharacterized genes but also further insight into the time line of events, their interdependence, their dynamics, and their spatial organization as well as the importance of subtle effects. PMID:12040128

Episodic sediment-discharge events in Cascade Springs, southern Black Hills, South Dakota

USGS Publications Warehouse

Hayes, Timothy Scott

1999-01-01

Cascade Springs is a group of artesian springs in the southern Black Hills, South Dakota, with collective flow of about 19.6 cubic feet per second. Beginning on February 28, 1992, a large discharge of red suspended sediment was observed from two of the six known discharge points. Similar events during 1906-07 and 1969 were documented by local residents and newspaper accounts. Mineralogic and grain-size analyses were performed to identify probable subsurface sources of the sediment. Geochemical modeling was performed to evaluate the geochemical evolution of water discharged from Cascade Springs. Interpretations of results provide a perspective on the role of artesian springs in the regional geohydrologic framework. X-ray diffraction mineralogic analyses of the clay fraction of the suspended sediment were compared to analyses of clay-fraction samples taken from nine geologic units at and stratigraphically below the spring-discharge points. Ongoing development of a subsurface breccia pipe(s) in the upper Minnelusa Formation and/or Opeche Shale was identified as a likely source of the suspended sediment; thus, exposed breccia pipes in lower Hell Canyon were examined. Upper Minnelusa Formation breccia pipes in lower Hell Canyon occur in clusters similar to the discrete discharge points of Cascade Springs. Grain-size analyses showed that breccia masses lack clay fractions and have coarser distributions than the wall rocks, which indicates that the red, fine-grained fractions have been carried out as suspended sediment. These findings support the hypothesis that many breccia pipes were formed as throats of abandoned artesian springs. Geochemical modeling was used to test whether geochemical evolution of ground water is consistent with this hypothesis. The evolution of water at Cascade Springs could not be suitably simulated using only upgradient water from the Minnelusa aquifer. A suitable model involved dissolution of anhydrite accompanied by dedolomitization in the upper Minnelusa Formation, which is caused by upward leakage of relatively fresh water from the Madison aquifer. The anhydrite dissolution and dedolomitization account for the net removal of minerals that would lead to breccia pipe formation by gravitational collapse. Breccia pipes in the lower Minnelusa Formation are uncommon; however, networks of interconnected breccia layers and breccia dikes are common. These networks, along with vertical fractures and faults, are likely pathways for transmitting upward leakage from the Madison aquifer. It is concluded that suspended sediment discharged at Cascade Springs probably results from episodic collapse brecciation that is caused by subsurface dissolution of anhydrite beds and cements of the upper Minnelusa Formation, accompanied by replacement of dolomite by calcite. It is further concluded that many breccia pipes probably are the throats of artesian springs that have been abandoned and exposed by erosion. The locations of artesian spring-discharge points probably have been shifting outwards from the center of the Black Hills uplift, essentially keeping pace with regional erosion over geologic time. Thus, artesian springflow probably is a factor in controlling water levels in the Madison and Minnelusa aquifers, with hydraulic head declining over geologic time, in response to development of new discharge points. Development of breccia pipes as throats of artesian springs would greatly enhance vertical hydraulic conductivity in the immediate vicinity of spring-discharge points. Horizontal hydraulic conductivity in the Minnelusa Formation also may be enhanced by dissolution processes related to upward leakage from the Madison aquifer. Potential processes could include dissolution resulting from leakage in the vicinity of breccia pipes that are abandoned spring throats, active spring discharge, development of subsurface breccias with no visible surface expression or spring discharge, as well as general areal leakage

Indirect effects and traditional trophic cascades: a test involving wolves, coyotes, and pronghorn.

PubMed

Berger, Kim Murray; Gese, Eric M; Berger, Joel

2008-03-01

The traditional trophic cascades model is based on consumer resource interactions at each link in a food chain. However, trophic-level interactions, such as mesocarnivore release resulting from intraguild predation, may also be important mediators of cascades. From September 2001 to August 2004, we used spatial and seasonal heterogeneity in wolf distribution and abundance in the southern Greater Yellowstone Ecosystem to evaluate whether mesopredator release of coyotes (Canis latrans), resulting from the extirpation of wolves (Canis lupus), accounts for high rates of coyote predation on pronghorn (Antilocapra americana) fawns observed in some areas. Results of this ecological perturbation in wolf densities, coyote densities, and pronghorn neonatal survival at wolf-free and wolf-abundant sites support the existence of a species-level trophic cascade. That wolves precipitated a trophic cascade was evidenced by fawn survival rates that were four-fold higher at sites used by wolves. A negative correlation between coyote and wolf densities supports the hypothesis that interspecific interactions between the two species facilitated the difference in fawn survival. Whereas densities of resident coyotes were similar between wolf-free and wolf-abundant sites, the abundance of transient coyotes was significantly lower in areas used by wolves. Thus, differential effects of wolves on solitary coyotes may be an important mechanism by which wolves limit coyote densities. Our results support the hypothesis that mesopredator release of coyotes contributes to high rates of coyote predation on pronghorn fawns, and demonstrate the importance of alternative food web pathways in structuring the dynamics of terrestrial systems.

Trophic cascades of bottom-up and top-down forcing on nutrients and plankton in the Kattegat, evaluated by modelling

NASA Astrophysics Data System (ADS)

Petersen, Marcell Elo; Maar, Marie; Larsen, Janus; Møller, Eva Friis; Hansen, Per Juel

2017-05-01

The aim of the study was to investigate the relative importance of bottom-up and top-down forcing on trophic cascades in the pelagic food-web and the implications for water quality indicators (summer phytoplankton biomass and winter nutrients) in relation to management. The 3D ecological model ERGOM was validated and applied in a local set-up of the Kattegat, Denmark, using the off-line Flexsem framework. The model scenarios were conducted by changing the forcing by ± 20% of nutrient inputs (bottom-up) and mesozooplankton mortality (top-down), and both types of forcing combined. The model results showed that cascading effects operated differently depending on the forcing type. In the single-forcing bottom-up scenarios, the cascade directions were in the same direction as the forcing. For scenarios involving top-down, there was a skipped-level-transmission in the trophic responses that was either attenuated or amplified at different trophic levels. On a seasonal scale, bottom-up forcing showed strongest response during winter-spring for DIN and Chl a concentrations, whereas top-down forcing had the highest cascade strength during summer for Chl a concentrations and microzooplankton biomass. On annual basis, the system was more bottom-up than top-down controlled. Microzooplankton was found to play an important role in the pelagic food web as mediator of nutrient and energy fluxes. This study demonstrated that the best scenario for improved water quality was a combined reduction in nutrient input and mesozooplankton mortality calling for the need of an integrated management of marine areas exploited by human activities.

One thing leads to another: the cascade of obligations when researchers report genetic research results to study participants.

PubMed

Miller, Fiona Alice; Hayeems, Robin Zoe; Li, Li; Bytautas, Jessica Peace

2012-08-01

Even as debate continues about the putative obligation to proactively report genetic research results to study participants, there is an increasing need to attend to the obligations that might cascade from any initial report. We conducted an international, quasi-experimental survey of researchers involved in autism spectrum disorders (ASD) and cystic fibrosis (CF) genetics to explore perceived obligations to ensure updated information or relevant clinical care subsequent to any initial communication of research results, and factors influencing these attitudes. 5-point Likert scales of dis/agreement were analyzed using descriptive and multivariate statistics. Of the 343 respondents (44% response rate), large majorities agreed that in general and in a variety of hypothetical research contexts, research teams that report results should ensure that participants gain subsequent access to updated information (74-83%) and implicated clinical services (79-87%). At the same time, researchers perceived barriers restricting access to relevant clinical care, though this was significantly more pronounced (P<0.001) for ASD (64%) than CF (34%). In the multivariate model, endorsement of cascading obligations was positively associated with researcher characteristics (eg, clinical role/training) and attitudes (eg, perceived initial reporting obligation), and negatively associated with the initial report of less scientifically robust hypothetical results, but unaffected by perceived or hypothetical barriers to care. These results suggest that researchers strongly endorse information and care-based obligations that cascade from the initial report of research results to study participants. In addition, they raise challenging questions about how any cascading obligations are to be met, especially where access challenges are already prevalent.

Vision-Based Detection and Distance Estimation of Micro Unmanned Aerial Vehicles

PubMed Central

Gökçe, Fatih; Üçoluk, Göktürk; Şahin, Erol; Kalkan, Sinan

2015-01-01

Detection and distance estimation of micro unmanned aerial vehicles (mUAVs) is crucial for (i) the detection of intruder mUAVs in protected environments; (ii) sense and avoid purposes on mUAVs or on other aerial vehicles and (iii) multi-mUAV control scenarios, such as environmental monitoring, surveillance and exploration. In this article, we evaluate vision algorithms as alternatives for detection and distance estimation of mUAVs, since other sensing modalities entail certain limitations on the environment or on the distance. For this purpose, we test Haar-like features, histogram of gradients (HOG) and local binary patterns (LBP) using cascades of boosted classifiers. Cascaded boosted classifiers allow fast processing by performing detection tests at multiple stages, where only candidates passing earlier simple stages are processed at the preceding more complex stages. We also integrate a distance estimation method with our system utilizing geometric cues with support vector regressors. We evaluated each method on indoor and outdoor videos that are collected in a systematic way and also on videos having motion blur. Our experiments show that, using boosted cascaded classifiers with LBP, near real-time detection and distance estimation of mUAVs are possible in about 60 ms indoors (1032×778 resolution) and 150 ms outdoors (1280×720 resolution) per frame, with a detection rate of 0.96 F-score. However, the cascaded classifiers using Haar-like features lead to better distance estimation since they can position the bounding boxes on mUAVs more accurately. On the other hand, our time analysis yields that the cascaded classifiers using HOG train and run faster than the other algorithms. PMID:26393599

A biocatalytic cascade with several output signals—towards biosensors with different levels of confidence

PubMed Central

Guz, Nataliia; Halámek, Jan; Rusling, James F.; Katz, Evgeny

2014-01-01

The biocatalytic cascade based on enzyme-catalyzed reactions activated by several biomolecular input signals and producing output signal after each reaction step was developed as an example of a logically reversible information processing system. The model system was designed to mimic the operation of concatenated AND logic gates with optically readable output signals generated at each step of the logic operation. Implications include concurrent bioanalyses and data interpretation for medical diagnostics. PMID:24748446

The calculation of neutron capture gamma-ray yields for space shielding applications

NASA Technical Reports Server (NTRS)

Yost, K. J.

1972-01-01

The application of nuclear models to the calculation of neutron capture and inelastic scattering gamma yields is discussed. The gamma ray cascade model describes the cascade process in terms of parameters which either: (1) embody statistical assumptions regarding electric and magnetic multipole transition strengths, level densities, and spin and parity distributions or (2) are fixed by experiment such as measured energies, spin and parity values, and transition probabilities for low lying states.

Cascaded-focus laser writing of low-loss waveguides in polymers.

PubMed

Pätzold, Welm M; Reinhardt, Carsten; Demircan, Ayhan; Morgner, Uwe

2016-03-15

Waveguide writing in poly (methyl methacrylate) (PMMA) with femtosecond laser radiation is presented. An adequate refractive index change is induced in the border area below the irradiated focal volume. It supports an almost symmetric fundamental mode with propagation losses down to 0.5  dB/cm, the lowest losses observed so far in this class of materials. The writing process with a cascaded focus is demonstrated to be highly reliable over a large parameter range.

Activation of respiratory epithelial cells by wood smoke particles persists beyond immediate exposure.

EPA Science Inventory

The biological effect of particles on epithelial cells involves, in part, oxidant generation and a cascade of reactions culminating in inflammatory mediator release. Whether there is an immediate short-lived activation or continued persistent response of the cells to the particle...

Action Video Gaming and Cognitive Control: Playing First Person Shooter Games Is Associated with Improved Action Cascading but Not Inhibition

PubMed Central

Steenbergen, Laura; Sellaro, Roberta; Stock, Ann-Kathrin; Beste, Christian; Colzato, Lorenza S.

2015-01-01

There is a constantly growing interest in developing efficient methods to enhance cognitive functioning and/or to ameliorate cognitive deficits. One particular line of research focuses on the possibly cognitive enhancing effects that action video game (AVG) playing may have on game players. Interestingly, AVGs, especially first person shooter games, require gamers to develop different action control strategies to rapidly react to fast moving visual and auditory stimuli, and to flexibly adapt their behaviour to the ever-changing context. This study investigated whether and to what extent experience with such videogames is associated with enhanced performance on cognitive control tasks that require similar abilities. Experienced action videogame-players (AVGPs) and individuals with little to no videogame experience (NVGPs) performed a stop-change paradigm that provides a relatively well-established diagnostic measure of action cascading and response inhibition. Replicating previous findings, AVGPs showed higher efficiency in response execution, but not improved response inhibition (i.e. inhibitory control), as compared to NVGPs. More importantly, compared to NVGPs, AVGPs showed enhanced action cascading processes when an interruption (stop) and a change towards an alternative response were required simultaneously, as well as when such a change had to occur after the completion of the stop process. Our findings suggest that playing AVGs is associated with enhanced action cascading and multi-component behaviour without affecting inhibitory control. PMID:26655929

Action Video Gaming and Cognitive Control: Playing First Person Shooter Games Is Associated with Improved Action Cascading but Not Inhibition.

PubMed

Steenbergen, Laura; Sellaro, Roberta; Stock, Ann-Kathrin; Beste, Christian; Colzato, Lorenza S

2015-01-01

There is a constantly growing interest in developing efficient methods to enhance cognitive functioning and/or to ameliorate cognitive deficits. One particular line of research focuses on the possibly cognitive enhancing effects that action video game (AVG) playing may have on game players. Interestingly, AVGs, especially first person shooter games, require gamers to develop different action control strategies to rapidly react to fast moving visual and auditory stimuli, and to flexibly adapt their behaviour to the ever-changing context. This study investigated whether and to what extent experience with such videogames is associated with enhanced performance on cognitive control tasks that require similar abilities. Experienced action videogame-players (AVGPs) and individuals with little to no videogame experience (NVGPs) performed a stop-change paradigm that provides a relatively well-established diagnostic measure of action cascading and response inhibition. Replicating previous findings, AVGPs showed higher efficiency in response execution, but not improved response inhibition (i.e. inhibitory control), as compared to NVGPs. More importantly, compared to NVGPs, AVGPs showed enhanced action cascading processes when an interruption (stop) and a change towards an alternative response were required simultaneously, as well as when such a change had to occur after the completion of the stop process. Our findings suggest that playing AVGs is associated with enhanced action cascading and multi-component behaviour without affecting inhibitory control.

Mobile Phone Service Process Hiccups at Cellular Inc.

ERIC Educational Resources Information Center

Edgington, Theresa M.

2010-01-01

This teaching case documents an actual case of process execution and failure. The case is useful in MIS introductory courses seeking to demonstrate the interdependencies within a business process, and the concept of cascading failure at the process level. This case demonstrates benefits and potential problems with information technology systems,…

Intestinal Insulin Signaling Encodes Two Different Molecular Mechanisms for the Shortened Longevity Induced by Graphene Oxide in Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Zhao, Yunli; Yang, Ruilong; Rui, Qi; Wang, Dayong

2016-04-01

Graphene oxide (GO) has been shown to cause multiple toxicities in various organisms. However, the underlying molecular mechanisms for GO-induced shortened longevity are still unclear. We employed Caenorhabditis elegans to investigate the possible involvement of insulin signaling pathway in the control of GO toxicity and its underlying molecular mechanisms. Mutation of daf-2, age-1, akt-1, or akt-2 gene induced a resistant property of nematodes to GO toxicity, while mutation of daf-16 gene led to a susceptible property of nematodes to GO toxicity, suggesting that GO may dysregulate the functions of DAF-2/IGF-1 receptor, AGE-1, AKT-1 and AKT-2-mediated kinase cascade, and DAF-16/FOXO transcription factor. Genetic interaction analysis suggested the involvement of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the control of GO toxicity on longevity. Moreover, intestinal RNA interference (RNAi) analysis demonstrated that GO reduced longevity by affecting the functions of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the intestine. DAF-16 could also regulate GO toxicity on longevity by functioning upstream of SOD-3, which encodes an antioxidation system that prevents the accumulation of oxidative stress. Therefore, intestinal insulin signaling may encode two different molecular mechanisms responsible for the GO toxicity in inducing the shortened longevity. Our results highlight the key role of insulin signaling pathway in the control of GO toxicity in organisms.

Dynamic rupture simulations of the 2016 Mw7.8 Kaikōura earthquake: a cascading multi-fault event

NASA Astrophysics Data System (ADS)

Ulrich, T.; Gabriel, A. A.; Ampuero, J. P.; Xu, W.; Feng, G.

2017-12-01

The Mw7.8 Kaikōura earthquake struck the Northern part of New Zealand's South Island roughly one year ago. It ruptured multiple segments of the contractional North Canterbury fault zone and of the Marlborough fault system. Field observations combined with satellite data suggest a rupture path involving partly unmapped faults separated by large stepover distances larger than 5 km, the maximum distance usually considered by the latest seismic hazard assessment methods. This might imply distant rupture transfer mechanisms generally not considered in seismic hazard assessment. We present high-resolution 3D dynamic rupture simulations of the Kaikōura earthquake under physically self-consistent initial stress and strength conditions. Our simulations are based on recent finite-fault slip inversions that constrain fault system geometry and final slip distribution from remote sensing, surface rupture and geodetic data (Xu et al., 2017). We assume a uniform background stress field, without lateral fault stress or strength heterogeneity. We use the open-source software SeisSol (www.seissol.org) which is based on an arbitrary high-order accurate DERivative Discontinuous Galerkin method (ADER-DG). Our method can account for complex fault geometries, high resolution topography and bathymetry, 3D subsurface structure, off-fault plasticity and modern friction laws. It enables the simulation of seismic wave propagation with high-order accuracy in space and time in complex media. We show that a cascading rupture driven by dynamic triggering can break all fault segments that were involved in this earthquake without mechanically requiring an underlying thrust fault. Our prefered fault geometry connects most fault segments: it does not features stepover larger than 2 km. The best scenario matches the main macroscopic characteristics of the earthquake, including its apparently slow rupture propagation caused by zigzag cascading, the moment magnitude and the overall inferred slip distribution. We observe a high sensitivity of cascading dynamics on fault-step over distance and off-fault energy dissipation.

Combined Brayton-JT cycles with refrigerants for natural gas liquefaction

NASA Astrophysics Data System (ADS)

Chang, Ho-Myung; Park, Jae Hoon; Lee, Sanggyu; Choe, Kun Hyung

2012-06-01

Thermodynamic cycles for natural gas liquefaction with single-component refrigerants are investigated under a governmental project in Korea, aiming at new processes to meet the requirements on high efficiency, large capacity, and simple equipment. Based upon the optimization theory recently published by the present authors, it is proposed to replace the methane-JT cycle in conventional cascade process with a nitrogen-Brayton cycle. A variety of systems to combine nitrogen-Brayton, ethane-JT and propane-JT cycles are simulated with Aspen HYSYS and quantitatively compared in terms of thermodynamic efficiency, flow rate of refrigerants, and estimated size of heat exchangers. A specific Brayton-JT cycle is suggested with detailed thermodynamic data for further process development. The suggested cycle is expected to be more efficient and simpler than the existing cascade process, while still taking advantage of easy and robust operation with single-component refrigerants.

The tumour suppressor protein, p53, is involved in the activation of the apoptotic cascade by Delta9-tetrahydrocannabinol in cultured cortical neurons.

PubMed

Downer, Eric J; Gowran, Aoife; Murphy, Aine C; Campbell, Veronica A

2007-06-14

Cannabis is the most commonly used illegal drug of abuse in Western society. Delta(9)-tetrahydrocannabinol, the psychoactive ingredient of marijuana, regulates a variety of neuronal processes including neurotransmitter release and synaptic transmission. An increasing body of evidence suggests that cannabinoids play a key role in the regulation of neuronal viability. In cortical neurons tetrahydrocannabinol has a neurodegenerative effect, the mechanisms of which are poorly understood, but involve the cannabinoid receptor subtype, CB(1). In this study we report that tetrahydrocannabinol (5 muM) evokes a rapid phosphorylation, and thus activation, of the tumour suppressor protein, p53, in a manner involving the cannabinoid CB(1) receptor, and the stress-activated protein kinase, c-jun N-terminal kinase, in cultured cortical neurons. Tetrahydrocannabinol increased expression of the p53-transcriptional target, Bax and promoted Bcl phosphorylation. These events were abolished by the p53 inhibitor, pifithrin-alpha (100 nM). The tetrahydrocannabinol-induced activation of the pro-apoptotic cysteine protease, caspase-3, and DNA fragmentation was also blocked by pifithrin-alpha. A siRNA knockdown of p53 further verified the role of p53 in tetrahydrocannabinol-induced apoptosis. This study demonstrates a novel cannabinoid signalling pathway involving p53 that culminates in neuronal apoptosis.

Copper-Catalyzed Oxidative Reaction of β-Keto Sulfones with Alcohols via C-S Bond Cleavage: Reaction Development and Mechanism Study.

PubMed

Du, Bingnan; Wang, Wenmin; Wang, Yang; Qi, Zhenghang; Tian, Jiaqi; Zhou, Jie; Wang, Xiaochen; Han, Jianlin; Ma, Jing; Pan, Yi

2018-02-16

A Cu-catalyzed cascade oxidative radical process of β-keto sulfones with alcohols has been achieved by using oxygen as an oxidant. In this reaction, β-keto sulfones were converted into sulfinate esters under the oxidative conditions via cleavage of C-S bond. Experimental and computational studies demonstrate that a new pathway is involved in this reaction, which proceeds through the formation of the key four-coordinated Cu II intermediate, O-O bond homolysis induced C-S bond cleavage and Cu-catalyzed esterification to form the final products. This reaction provides a new strategy to sulfonate esters and enriches the research content of C-S bond cleavage and transformations. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A novel liquid-Xenon detector concept for combined fast-neutrons and gamma imaging and spectroscopy

NASA Astrophysics Data System (ADS)

Breskin, A.; Israelashvili, I.; Cortesi, M.; Arazi, L.; Shchemelinin, S.; Chechik, R.; Dangendorf, V.; Bromberger, B.; Vartsky, D.

2012-06-01

A new detector concept is presented for combined imaging and spectroscopy of fast-neutrons and gamma rays. It comprises a liquid-Xenon (LXe) converter and scintillator coupled to a UV-sensitive gaseous imaging photomultiplier (GPM). Radiation imaging is obtained by localization of the scintillation-light from LXe with the position-sensitive GPM. The latter comprises a cascade of Thick Gas Electron Multipliers (THGEM), where the first element is coated with a CsI UV-photocathode. We present the concept and provide first model-simulation results of the processes involved and the expected performances of a detector having a LXe-filled capillaries converter. The new detector concept has potential applications in combined fast-neutron and gamma-ray screening of hidden explosives and fissile materials with pulsed sources.

Context Specificity of Stress-activated Mitogen-activated Protein (MAP) Kinase Signaling: The Story as Told by Caenorhabditis elegans*

PubMed Central

Andrusiak, Matthew G.; Jin, Yishi

2016-01-01

Stress-associated p38 and JNK mitogen-activated protein (MAP) kinase signaling cascades trigger specific cellular responses and are involved in multiple disease states. At the root of MAP kinase signaling complexity is the differential use of common components on a context-specific basis. The roundworm Caenorhabditis elegans was developed as a system to study genes required for development and nervous system function. The powerful genetics of C. elegans in combination with molecular and cellular dissections has led to a greater understanding of how p38 and JNK signaling affects many biological processes under normal and stress conditions. This review focuses on the studies revealing context specificity of different stress-activated MAPK components in C. elegans. PMID:26907690

Dark Matter "Collider" from Inelastic Boosted Dark Matter.

PubMed

Kim, Doojin; Park, Jong-Chul; Shin, Seodong

2017-10-20

We propose a novel dark matter (DM) detection strategy for models with a nonminimal dark sector. The main ingredients in the underlying DM scenario are a boosted DM particle and a heavier dark sector state. The relativistic DM impinged on target material scatters off inelastically to the heavier state, which subsequently decays into DM along with lighter states including visible (standard model) particles. The expected signal event, therefore, accompanies a visible signature by the secondary cascade process associated with a recoiling of the target particle, differing from the typical neutrino signal not involving the secondary signature. We then discuss various kinematic features followed by DM detection prospects at large-volume neutrino detectors with a model framework where a dark gauge boson is the mediator between the standard model particles and DM.

Pair cascades in the magnetospheres of strongly magnetized neutron stars

NASA Astrophysics Data System (ADS)

Medin, Zach; Lai, Dong

2010-08-01

We present numerical simulations of electron-positron pair cascades in the magnetospheres of magnetic neutron stars for a wide range of surface fields (Bp = 1012-1015 G), rotation periods (0.1-10 s) and field geometries. This has been motivated by the discovery in recent years of a number of radio pulsars with inferred magnetic fields comparable to those of magnetars. Evolving the cascade generated by a primary electron or positron after it has been accelerated in the inner gap of the magnetosphere, we follow the spatial development of the cascade until the secondary photons and electron-positron pairs leave the magnetosphere, and we obtain the pair multiplicity and the energy spectra of the cascade pairs and photons under various conditions. Going beyond previous works, which were restricted to weaker fields (B <~ afew × 1012 G), we have incorporated in our simulations detailed treatments of physical processes that are potentially important (especially in the high-field regime) but were either neglected or crudely treated before, including photon splitting with the correct selection rules for photon polarization modes, one-photon pair production into low Landau levels for the e+/-, and resonant inverse Compton scattering from polar cap hotspots. We find that even for B >> BQ = 4 × 1013 G, photon splitting has a small effect on the multiplicity of the cascade since a majority of the photons in the cascade cannot split. One-photon decay into e+ e- pairs at low Landau levels, however, becomes the dominant pair production channel when B >~ 3 × 1012 G; this tends to suppress synchrotron radiation so that the cascade can develop only at a larger distance from the stellar surface. Nevertheless, we find that the total number of pairs and their energy spectrum produced in the cascade depend mainly on the polar cap voltage BpP-2, and are weakly dependent on Bp (and P) alone. We discuss the implications of our results for the radio pulsar death line and for the hard X-ray emission from magnetized neutron stars.

Modeling cascading failures with the crisis of trust in social networks

NASA Astrophysics Data System (ADS)

Yi, Chengqi; Bao, Yuanyuan; Jiang, Jingchi; Xue, Yibo

2015-10-01

In social networks, some friends often post or disseminate malicious information, such as advertising messages, informal overseas purchasing messages, illegal messages, or rumors. Too much malicious information may cause a feeling of intense annoyance. When the feeling exceeds a certain threshold, it will lead social network users to distrust these friends, which we call the crisis of trust. The crisis of trust in social networks has already become a universal concern and an urgent unsolved problem. As a result of the crisis of trust, users will cut off their relationships with some of their untrustworthy friends. Once a few of these relationships are made unavailable, it is likely that other friends will decline trust, and a large portion of the social network will be influenced. The phenomenon in which the unavailability of a few relationships will trigger the failure of successive relationships is known as cascading failure dynamics. To our best knowledge, no one has formally proposed cascading failures dynamics with the crisis of trust in social networks. In this paper, we address this potential issue, quantify the trust between two users based on user similarity, and model the minimum tolerance with a nonlinear equation. Furthermore, we construct the processes of cascading failures dynamics by considering the unique features of social networks. Based on real social network datasets (Sina Weibo, Facebook and Twitter), we adopt two attack strategies (the highest trust attack (HT) and the lowest trust attack (LT)) to evaluate the proposed dynamics and to further analyze the changes of the topology, connectivity, cascading time and cascade effect under the above attacks. We numerically find that the sparse and inhomogeneous network structure in our cascading model can better improve the robustness of social networks than the dense and homogeneous structure. However, the network structure that seems like ripples is more vulnerable than the other two network structures. Our findings will be useful in further guiding the construction of social networks to effectively avoid the cascading propagation with the crisis of trust. Some research results can help social network service providers to avoid severe cascading failures.

The prevention of mother-to-child transmission of HIV cascade analysis tool: supporting health managers to improve facility-level service delivery.

PubMed

Gimbel, Sarah; Voss, Joachim; Mercer, Mary Anne; Zierler, Brenda; Gloyd, Stephen; Coutinho, Maria de Joana; Floriano, Florencia; Cuembelo, Maria de Fatima; Einberg, Jennifer; Sherr, Kenneth

2014-10-21

The objective of the prevention of Mother-to-Child Transmission (pMTCT) cascade analysis tool is to provide frontline health managers at the facility level with the means to rapidly, independently and quantitatively track patient flows through the pMTCT cascade, and readily identify priority areas for clinic-level improvement interventions. Over a period of six months, five experienced maternal-child health managers and researchers iteratively adapted and tested this systems analysis tool for pMTCT services. They prioritized components of the pMTCT cascade for inclusion, disseminated multiple versions to 27 health managers and piloted it in five facilities. Process mapping techniques were used to chart PMTCT cascade steps in these five facilities, to document antenatal care attendance, HIV testing and counseling, provision of prophylactic anti-retrovirals, safe delivery, safe infant feeding, infant follow-up including HIV testing, and family planning, in order to obtain site-specific knowledge of service delivery. Seven pMTCT cascade steps were included in the Excel-based final tool. Prevalence calculations were incorporated as sub-headings under relevant steps. Cells not requiring data inputs were locked, wording was simplified and stepwise drop-offs and maximization functions were included at key steps along the cascade. While the drop off function allows health workers to rapidly assess how many patients were lost at each step, the maximization function details the additional people served if only one step improves to 100% capacity while others stay constant. Our experience suggests that adaptation of a cascade analysis tool for facility-level pMTCT services is feasible and appropriate as a starting point for discussions of where to implement improvement strategies. The resulting tool facilitates the engagement of frontline health workers and managers who fill out, interpret, apply the tool, and then follow up with quality improvement activities. Research on adoption, interpretation, and sustainability of this pMTCT cascade analysis tool by frontline health managers is needed. ClinicalTrials.gov NCT02023658, December 9, 2013.

Demonstrating Enzyme Activation: Calcium/Calmodulin Activation of Phosphodiesterase

ERIC Educational Resources Information Center

Porta, Angela R.

2004-01-01

Demonstrating the steps of a signal transduction cascade usually involves radioactive materials and thus precludes its use in undergraduate teaching labs. Developing labs that allow the visual demonstration of these steps without the use of radioactivity is important for allowing students hands-on methods of illustrating each step of a signal…

Traumatisation and Long-Term Stress Cascades: Case Report--Jan M.

ERIC Educational Resources Information Center

Herz, Birgit

2011-01-01

Numerous services in the field of social, emotional and behavioural difficulties (SEBD) are active, with different qualities and outcomes in their work. Different professions are also involved in this field between regular and special schools, the children and young people welfare system, the psychiatric ward, the police, therapeutically services…

Nox Complex signal and MAPK cascade pathway are cross-linked and essential for pathogenicity and conidiation of mycoparasite Coniothyrium minitans

USDA-ARS?s Scientific Manuscript database

The NADPH oxidase complex of a sclerotial mycoparasite Coniothyrium minitans, an important biocontrol agent against crop diseases caused by Sclerotinia sclerotiorum, was identified and its functions involved in conidiation and mycoparasitism were studied. Gene knock-out and complementation experimen...

Elucidating induced plant defenses: the use of targeted metabolomics as a bridge from elicitation to response

USDA-ARS?s Scientific Manuscript database

Dynamic plant defense responses to biotic attack involve the perception of specific biochemical elicitors associated with the offending agent, activation of signaling cascades, and the production of small molecules with complex protective roles. Chemical analyses are essential empirical tools for el...

Radiation-induced effects on the mechanical properties of natural ZrSiO4: double cascade-overlap damage accumulation

NASA Astrophysics Data System (ADS)

Beirau, Tobias; Nix, William D.; Pöllmann, Herbert; Ewing, Rodney C.

2018-05-01

Several different models are known to describe the structure-dependent radiation-induced damage accumulation process in materials (e.g. Gibbons Proc IEEE 60:1062-1096, 1972; Weber Nuc Instr Met Phys Res B 166-167:98-106, 2000). In the literature, two different models of damage accumulation due to α-decay events in natural ZrSiO4 (zircon) have been described. The direct impact damage accumulation model is based on amorphization occurring directly within the collision cascade. However, the double cascade-overlap damage accumulation model predicts that amorphization will only occur due to the overlap of disordered domains within the cascade. By analyzing the dose-dependent evolution of mechanical properties (i.e., Poisson's ratios, compliance constants, elastic modulus, and hardness) as a measure of the increasing amorphization, we provide support for the double cascade-overlap damage accumulation model. We found no evidence to support the direct impact damage accumulation model. Additionally, the amount of radiation damage could be related to an anisotropic-to-isotropic transition of the Poisson's ratio for stress along and perpendicular to the four-fold c-axis and of the related compliance constants of natural U- and Th-bearing zircon. The isotropification occurs in the dose range between 3.1 × and 6.3 × 1018 α-decays/g.

Energy Cascade Analysis: from Subscale Eddies to Mean Flow

NASA Astrophysics Data System (ADS)

Cheikh, Mohamad Ibrahim; Wonnell, Louis; Chen, James

2017-11-01

Understanding the energy transfer between eddies and mean flow can provide insights into the energy cascade process. Much work has been done to investigate the energy cascade at the level of the smallest eddies using different numerical techniques derived from the Navier-Stokes equations. These methodologies, however, prove to be computationally inefficient when producing energy spectra for a wide range of length scales. In this regard, Morphing Continuum Theory (MCT) resolves the length-scales issues by assuming the fluid continuum to be composed of inner structures that play the role of subscale eddies. The current study show- cases the capabilities of MCT in capturing the dynamics of energy cascade at the level of subscale eddies, through a supersonic turbulent flow of Mach 2.93 over an 8× compression ramp. Analysis of the results using statistical averaging procedure shows the existence of a statistical coupling of the internal and translational kinetic energy fluctuations with the corresponding rotational kinetic energy of the subscale eddies, indicating a multiscale transfer of energy. The results show that MCT gives a new characterization of the energy cascade within compressible turbulence without the use of excessive computational resources. This material is based upon work supported by the Air Force Office of Scientific Research under Award Number FA9550-17-1-0154.

Radiation-induced effects on the mechanical properties of natural ZrSiO4: double cascade-overlap damage accumulation

NASA Astrophysics Data System (ADS)

Beirau, Tobias; Nix, William D.; Pöllmann, Herbert; Ewing, Rodney C.

2017-11-01

Several different models are known to describe the structure-dependent radiation-induced damage accumulation process in materials (e.g. Gibbons Proc IEEE 60:1062-1096, 1972; Weber Nuc Instr Met Phys Res B 166-167:98-106, 2000). In the literature, two different models of damage accumulation due to α-decay events in natural ZrSiO4 (zircon) have been described. The direct impact damage accumulation model is based on amorphization occurring directly within the collision cascade. However, the double cascade-overlap damage accumulation model predicts that amorphization will only occur due to the overlap of disordered domains within the cascade. By analyzing the dose-dependent evolution of mechanical properties (i.e., Poisson's ratios, compliance constants, elastic modulus, and hardness) as a measure of the increasing amorphization, we provide support for the double cascade-overlap damage accumulation model. We found no evidence to support the direct impact damage accumulation model. Additionally, the amount of radiation damage could be related to an anisotropic-to-isotropic transition of the Poisson's ratio for stress along and perpendicular to the four-fold c-axis and of the related compliance constants of natural U- and Th-bearing zircon. The isotropification occurs in the dose range between 3.1 × and 6.3 × 1018 α-decays/g.

Evaluating trophic cascades as drivers of regime shifts in different ocean ecosystems

PubMed Central

Pershing, Andrew J.; Mills, Katherine E.; Record, Nicholas R.; Stamieszkin, Karen; Wurtzell, Katharine V.; Byron, Carrie J.; Fitzpatrick, Dominic; Golet, Walter J.; Koob, Elise

2015-01-01

In ecosystems that are strongly structured by predation, reducing top predator abundance can alter several lower trophic levels—a process known as a trophic cascade. A persistent trophic cascade also fits the definition of a regime shift. Such ‘trophic cascade regime shifts' have been reported in a few pelagic marine systems—notably the Black Sea, Baltic Sea and eastern Scotian Shelf—raising the question of how common this phenomenon is in the marine environment. We provide a general methodology for distinguishing top-down and bottom-up effects and apply this methodology to time series from these three ecosystems. We found evidence for top-down forcing in the Black Sea due primarily to gelatinous zooplankton. Changes in the Baltic Sea are primarily bottom-up, strongly structured by salinity, but top-down forcing related to changes in cod abundance also shapes the ecosystem. Changes in the eastern Scotian Shelf that were originally attributed to declines in groundfish are better explained by changes in stratification. Our review suggests that trophic cascade regime shifts are rare in open ocean ecosystems and that their likelihood increases as the residence time of water in the system increases. Our work challenges the assumption that negative correlation between consecutive trophic levels implies top-down forcing.

Exciton management in organic photovoltaic multidonor energy cascades.

PubMed

Griffith, Olga L; Forrest, Stephen R

2014-05-14

Multilayer donor regions in organic photovoltaics show improved power conversion efficiency when arranged in decreasing exciton energy order from the anode to the acceptor interface. These so-called "energy cascades" drive exciton transfer from the anode to the dissociating interface while reducing exciton quenching and allowing improved overlap with the solar spectrum. Here we investigate the relative importance of exciton transfer and blocking in a donor cascade employing diphenyltetracene (D1), rubrene (D2), and tetraphenyldibenzoperiflanthene (D3) whose optical gaps monotonically decrease from D1 to D3. In this structure, D1 blocks excitons from quenching at the anode, D2 accepts transfer of excitons from D1 and blocks excitons at the interface between D2 and D3, and D3 contributes the most to the photocurrent due to its strong absorption at visible wavelengths, while also determining the open circuit voltage. We observe singlet exciton Förster transfer from D1 to D2 to D3 consistent with cascade operation. The power conversion efficiency of the optimized cascade OPV with a C60 acceptor layer is 7.1 ± 0.4%, which is significantly higher than bilayer devices made with only the individual donors. We develop a quantitative model to identify the dominant exciton processes that govern the photocurrent generation in multilayer organic structures.

Biophysically Inspired Rational Design of Structured Chimeric Substrates for DNAzyme Cascade Engineering

PubMed Central

Lakin, Matthew R.; Brown, Carl W.; Horwitz, Eli K.; Fanning, M. Leigh; West, Hannah E.; Stefanovic, Darko; Graves, Steven W.

2014-01-01

The development of large-scale molecular computational networks is a promising approach to implementing logical decision making at the nanoscale, analogous to cellular signaling and regulatory cascades. DNA strands with catalytic activity (DNAzymes) are one means of systematically constructing molecular computation networks with inherent signal amplification. Linking multiple DNAzymes into a computational circuit requires the design of substrate molecules that allow a signal to be passed from one DNAzyme to another through programmed biochemical interactions. In this paper, we chronicle an iterative design process guided by biophysical and kinetic constraints on the desired reaction pathways and use the resulting substrate design to implement heterogeneous DNAzyme signaling cascades. A key aspect of our design process is the use of secondary structure in the substrate molecule to sequester a downstream effector sequence prior to cleavage by an upstream DNAzyme. Our goal was to develop a concrete substrate molecule design to achieve efficient signal propagation with maximal activation and minimal leakage. We have previously employed the resulting design to develop high-performance DNAzyme-based signaling systems with applications in pathogen detection and autonomous theranostics. PMID:25347066

Structure Basis for Directional R-loop Formation and Substrate Handover Mechanisms in Type I CRISPR-Cas System.

PubMed

Xiao, Yibei; Luo, Min; Hayes, Robert P; Kim, Jonathan; Ng, Sherwin; Ding, Fang; Liao, Maofu; Ke, Ailong

2017-06-29

Type I CRISPR systems feature a sequential dsDNA target searching and degradation process, by crRNA-displaying Cascade and nuclease-helicase fusion enzyme Cas3, respectively. Here we present two cryo-EM snapshots of the Thermobifida fusca type I-E Cascade: (1) unwinding 11 bp of dsDNA at the seed-sequence region to scout for sequence complementarity, and (2) further unwinding of the entire protospacer to form a full R-loop. These structures provide the much-needed temporal and spatial resolution to resolve key mechanistic steps leading to Cas3 recruitment. In the early steps, PAM recognition causes severe DNA bending, leading to spontaneous DNA unwinding to form a seed-bubble. The full R-loop formation triggers conformational changes in Cascade, licensing Cas3 to bind. The same process also generates a bulge in the non-target DNA strand, enabling its handover to Cas3 for cleavage. The combination of both negative and positive checkpoints ensures stringent yet efficient target degradation in type I CRISPR-Cas systems. Copyright © 2017 Elsevier Inc. All rights reserved.

Photoacoustic Spectroscopy with Quantum Cascade Lasers for Trace Gas Detection

PubMed Central

Elia, Angela; Di Franco, Cinzia; Lugarà, Pietro Mario; Scamarcio, Gaetano

2006-01-01

Various applications, such as pollution monitoring, toxic-gas detection, non invasive medical diagnostics and industrial process control, require sensitive and selective detection of gas traces with concentrations in the parts in 109 (ppb) and sub-ppb range. The recent development of quantum-cascade lasers (QCLs) has given a new aspect to infrared laser-based trace gas sensors. In particular, single mode distributed feedback QCLs are attractive spectroscopic sources because of their excellent properties in terms of narrow linewidth, average power and room temperature operation. In combination with these laser sources, photoacoustic spectroscopy offers the advantage of high sensitivity and selectivity, compact sensor platform, fast time-response and user friendly operation. This paper reports recent developments on quantum cascade laser-based photoacoustic spectroscopy for trace gas detection. In particular, different applications of a photoacoustic trace gas sensor employing a longitudinal resonant cell with a detection limit on the order of hundred ppb of ozone and ammonia are discussed. We also report two QC laser-based photoacoustic sensors for the detection of nitric oxide, for environmental pollution monitoring and medical diagnostics, and hexamethyldisilazane, for applications in semiconductor manufacturing process.

LPM effect and primary energy estimations

NASA Technical Reports Server (NTRS)

Bourdeau, M. F.; Capdevielle, J. N.

1985-01-01

The distortion of the electron cascade development under LPM effects is now admitted; it consists of an increase of depth of showers origin, of shower maximum T sum max, a decrease of the number of particles at maximum N sub max and results in a flattening and a widening of the cascade transition curve. Connected with the influence of multiple Coulomb scattering on basic electromagnetic processes (bremsstrahlung, pair production), this effect appears at high energy with a threshold dependent on the density of the medium (more than 10 TeV for lead, more than 10 sup 6 TeV in air). Consequently, the electromagnetic components of hadron induced showers in lead and EAS in air calculated for the same hadronic cascades in the different alternative, including or not the LPM effect are examined here.

Infinitely divisible cascades to model the statistics of natural images.

PubMed

Chainais, Pierre

2007-12-01

We propose to model the statistics of natural images thanks to the large class of stochastic processes called Infinitely Divisible Cascades (IDC). IDC were first introduced in one dimension to provide multifractal time series to model the so-called intermittency phenomenon in hydrodynamical turbulence. We have extended the definition of scalar infinitely divisible cascades from 1 to N dimensions and commented on the relevance of such a model in fully developed turbulence in [1]. In this article, we focus on the particular 2 dimensional case. IDC appear as good candidates to model the statistics of natural images. They share most of their usual properties and appear to be consistent with several independent theoretical and experimental approaches of the literature. We point out the interest of IDC for applications to procedural texture synthesis.

Thermochemical nonequilibrium in atomic hydrogen at elevated temperatures

NASA Technical Reports Server (NTRS)

Scott, R. K.

1972-01-01

A numerical study of the nonequilibrium flow of atomic hydrogen in a cascade arc was performed to obtain insight into the physics of the hydrogen cascade arc. A rigorous mathematical model of the flow problem was formulated, incorporating the important nonequilibrium transport phenomena and atomic processes which occur in atomic hydrogen. Realistic boundary conditions, including consideration of the wall electrostatic sheath phenomenon, were included in the model. The governing equations of the asymptotic region of the cascade arc were obtained by writing conservation of mass and energy equations for the electron subgas, an energy conservation equation for heavy particles and an equation of state. Finite-difference operators for variable grid spacing were applied to the governing equations and the resulting system of strongly coupled, stiff equations were solved numerically by the Newton-Raphson method.

Cascade heterogeneous face sketch-photo synthesis via dual-scale Markov Network

NASA Astrophysics Data System (ADS)

Yao, Saisai; Chen, Zhenxue; Jia, Yunyi; Liu, Chengyun

2018-03-01

Heterogeneous face sketch-photo synthesis is an important and challenging task in computer vision, which has widely applied in law enforcement and digital entertainment. According to the different synthesis results based on different scales, this paper proposes a cascade sketch-photo synthesis method via dual-scale Markov Network. Firstly, Markov Network with larger scale is used to synthesise the initial sketches and the local vertical and horizontal neighbour search (LVHNS) method is used to search for the neighbour patches of test patches in training set. Then, the initial sketches and test photos are jointly entered into smaller scale Markov Network. Finally, the fine sketches are obtained after cascade synthesis process. Extensive experimental results on various databases demonstrate the superiority of the proposed method compared with several state-of-the-art methods.

B-cell Ligand Processing Pathways Detected by Large-scale Comparative Analysis

PubMed Central

Towfic, Fadi; Gupta, Shakti; Honavar, Vasant; Subramaniam, Shankar

2012-01-01

The initiation of B-cell ligand recognition is a critical step for the generation of an immune response against foreign bodies. We sought to identify the biochemical pathways involved in the B-cell ligand recognition cascade and sets of ligands that trigger similar immunological responses. We utilized several comparative approaches to analyze the gene coexpression networks generated from a set of microarray experiments spanning 33 different ligands. First, we compared the degree distributions of the generated networks. Second, we utilized a pairwise network alignment algorithm, BiNA, to align the networks based on the hubs in the networks. Third, we aligned the networks based on a set of KEGG pathways. We summarized our results by constructing a consensus hierarchy of pathways that are involved in B cell ligand recognition. The resulting pathways were further validated through literature for their common physiological responses. Collectively, the results based on our comparative analyses of degree distributions, alignment of hubs, and alignment based on KEGG pathways provide a basis for molecular characterization of the immune response states of B-cells and demonstrate the power of comparative approaches (e.g., gene coexpression network alignment algorithms) in elucidating biochemical pathways involved in complex signaling events in cells. PMID:22917187

Combined analysis of mRNA and miRNA identifies dehydration and salinity responsive key molecular players in citrus roots.

PubMed

Xie, Rangjin; Zhang, Jin; Ma, Yanyan; Pan, Xiaoting; Dong, Cuicui; Pang, Shaoping; He, Shaolan; Deng, Lie; Yi, Shilai; Zheng, Yongqiang; Lv, Qiang

2017-02-06

Citrus is one of the most economically important fruit crops around world. Drought and salinity stresses adversely affected its productivity and fruit quality. However, the genetic regulatory networks and signaling pathways involved in drought and salinity remain to be elucidated. With RNA-seq and sRNA-seq, an integrative analysis of miRNA and mRNA expression profiling and their regulatory networks were conducted using citrus roots subjected to dehydration and salt treatment. Differentially expressed (DE) mRNA and miRNA profiles were obtained according to fold change analysis and the relationships between miRNAs and target mRNAs were found to be coherent and incoherent in the regulatory networks. GO enrichment analysis revealed that some crucial biological processes related to signal transduction (e.g. 'MAPK cascade'), hormone-mediated signaling pathways (e.g. abscisic acid- activated signaling pathway'), reactive oxygen species (ROS) metabolic process (e.g. 'hydrogen peroxide catabolic process') and transcription factors (e.g., 'MYB, ZFP and bZIP') were involved in dehydration and/or salt treatment. The molecular players in response to dehydration and salt treatment were partially overlapping. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis further confirmed the results from RNA-seq and sRNA-seq analysis. This study provides new insights into the molecular mechanisms how citrus roots respond to dehydration and salt treatment.

Neuromolecular responses to social challenge: common mechanisms across mouse, stickleback fish, and honey bee.

PubMed

Rittschof, Clare C; Bukhari, Syed Abbas; Sloofman, Laura G; Troy, Joseph M; Caetano-Anollés, Derek; Cash-Ahmed, Amy; Kent, Molly; Lu, Xiaochen; Sanogo, Yibayiri O; Weisner, Patricia A; Zhang, Huimin; Bell, Alison M; Ma, Jian; Sinha, Saurabh; Robinson, Gene E; Stubbs, Lisa

2014-12-16

Certain complex phenotypes appear repeatedly across diverse species due to processes of evolutionary conservation and convergence. In some contexts like developmental body patterning, there is increased appreciation that common molecular mechanisms underlie common phenotypes; these molecular mechanisms include highly conserved genes and networks that may be modified by lineage-specific mutations. However, the existence of deeply conserved mechanisms for social behaviors has not yet been demonstrated. We used a comparative genomics approach to determine whether shared neuromolecular mechanisms could underlie behavioral response to territory intrusion across species spanning a broad phylogenetic range: house mouse (Mus musculus), stickleback fish (Gasterosteus aculeatus), and honey bee (Apis mellifera). Territory intrusion modulated similar brain functional processes in each species, including those associated with hormone-mediated signal transduction and neurodevelopment. Changes in chromosome organization and energy metabolism appear to be core, conserved processes involved in the response to territory intrusion. We also found that several homologous transcription factors that are typically associated with neural development were modulated across all three species, suggesting that shared neuronal effects may involve transcriptional cascades of evolutionarily conserved genes. Furthermore, immunohistochemical analyses of a subset of these transcription factors in mouse again implicated modulation of energy metabolism in the behavioral response. These results provide support for conserved genetic "toolkits" that are used in independent evolutions of the response to social challenge in diverse taxa.

Microsystem process networks

DOEpatents

Wegeng, Robert S [Richland, WA; TeGrotenhuis, Ward E [Kennewick, WA; Whyatt, Greg A [West Richland, WA

2006-10-24

Various aspects and applications of microsystem process networks are described. The design of many types of microsystems can be improved by ortho-cascading mass, heat, or other unit process operations. Microsystems having exergetically efficient microchannel heat exchangers are also described. Detailed descriptions of numerous design features in microcomponent systems are also provided.

Microsystem process networks

DOEpatents

Wegeng, Robert S [Richland, WA; TeGrotenhuis, Ward E [Kennewick, WA; Whyatt, Greg A [West Richland, WA

2010-01-26

Various aspects and applications or microsystem process networks are described. The design of many types of microsystems can be improved by ortho-cascading mass, heat, or other unit process operations. Microsystems having energetically efficient microchannel heat exchangers are also described. Detailed descriptions of numerous design features in microcomponent systems are also provided.

Microsystem process networks

DOEpatents

Wegeng, Robert S.; TeGrotenhuis, Ward E.; Whyatt, Greg A.

2007-09-18

Various aspects and applications of microsystem process networks are described. The design of many types of Microsystems can be improved by ortho-cascading mass, heat, or other unit process operations. Microsystems having energetically efficient microchannel heat exchangers are also described. Detailed descriptions of numerous design features in microcomponent systems are also provided.

Cross talk between cyclic AMP and the polyphosphoinositide signaling cascade in iris sphincter and other nonvascular smooth muscle.

PubMed

Abdel-Latif, A A

1996-02-01

Nonvascular smooth muscle, such as the iris sphincter, receives double reciprocal innervation: stimulation of the parasympathetic nervous system (cholinergic muscarinic), which functions through the polyphosphoinositide (PPI) signaling pathway, contracts it, while activation of the sympathetic nervous system (beta-adrenergic), which functions through the cAMP system, relaxes it. Interactions between the two second messenger systems are important in regulation of smooth muscle tone and represent an important focal point for pharmacological manipulation. Here, I have summarized the experimental evidence in support of the hypothesis that the cross talk between cAMP and the PPI cascade could constitute a biochemical correlate for this functional antagonism. Recent studies suggest that cAMP inhibition is on Ca2+ mobilization rather than myosin light chain phosphorylation. Thus, cAMP-elevating agents, which inhibit agonist-induced PPI hydrolysis, are effective relaxants. Furthermore, inositol 1,4,5-trisphosphate (IP3) appears to be involved in both Ca2+ release from the sarcoplasmic reticulum and in Ca2+ influx through the plasma membrane, and since a reduction in intracellular Ca2+ ([Ca2+]i) is the underlying mechanism for cAMP-mediated relaxation, an important target for cAMP inhibition would be either to inhibit IP3 production or to stimulate IP3 inactivation. In the iris sphincter and other nonvascular smooth muscle there is reasonable experimental evidence that shows that cAMP inhibits phospholipase C activation and stimulates IP3 3-kinase activity, both of which can result in: [i) reduction in IP3 concentrations and (ii) reduction in IP3-dependent Ca2+ mobilization, which may lead to muscle relaxation. In addition to IP3-induced Ca2+ mobilization, changes in [Ca2+]i are the result of the interplay of many processes which may also serve as potential sites for cAMP inhibition. A great deal of progress has been made on the cross talk between cAMP and the PPI signaling cascade in the past decade, and there will be more on the regulation of the second messenger systems and their involvement in smooth muscle tone in the coming years. Clearly, an understanding of the physiological and pathophysiological regulation of smooth muscle tone is central to the development of novel therapeutic agents for the treatment of diseases such as asthma and glaucoma, where cAMP-elevating drugs are currently employed.

Thyrotropin-induced hydrogen peroxide production in FRTL-5 thyroid cells is mediated not by adenosine 3',5'-monophosphate, but by Ca2+ signaling followed by phospholipase-A2 activation and potentiated by an adenosine derivative.

PubMed

Kimura, T; Okajima, F; Sho, K; Kobayashi, I; Kondo, Y

1995-01-01

The production of hydrogen peroxide (H2O2) as an essential process for iodide organification is a key reaction in TSH-induced thyroid hormone synthesis. Here we characterize the signal transduction pathway involved in TSH-induced H2O2 production in FRTL-5 thyroid cells. At higher than 1 nM TSH, N6-(L-2-phenylisopropyl)adenosine (PIA), an adenosine receptor agonist having, by itself, no influence on H2O2 generation, potentiated this TSH action, whereas the TSH increase and PIA addition reduced cAMP accumulation. RO 20-1724, a phosphodiesterase inhibitor, amplified the TSH-induced cAMP accumulation, but did not change H2O2 generation in the whole range of TSH used. Ca(2+)-mobilizing agonists, GTP and ATP, also induced H2O2 production without stimulating cAMP accumulation. Chelation of intracellular Ca2+ markedly inhibited the TSH action, but intracellular Ca2+ increases by either thapsigargin or ionomycin mimicking it. All of the findings show the participation of Ca2+, but not cAMP, in the action of TSH. Desensitization of protein kinase-C (PKC) did not influence the receptor-mediated H2O2 production, suggesting the reduced importance of PKC activation compared to Ca2+ signaling to the reaction. A rise in intracellular Ca2+ independent of receptor activation also induced H2O2 production as well as arachidonate release, and both were potentiated by PIA. In addition, inhibitors of phospholipase-A2 and the arachidonate metabolic pathway depressed H2O2 generation, suggesting the participation of an arachidonate cascade in the Ca(2+)-dependent H2O2 production. Lipoxygenase inhibitors depressed the Ca2+ action without influencing arachidonate release, suggesting the involvement of a lipoxygenase product(s) of arachidonate in the Ca(2+)-signaling mechanism. In conclusion, in FRTL-5 cells, TSH-induced H2O2 production is mediated not by cAMP, but by the phospholipase-C/Ca2+ cascade, possibly followed by the Ca(2+)-dependent phospholipase-A2/arachidonate cascade. PIA amplifies TSH-induced H2O2 production at the steps of phospholipase-C and phospholipase-A2 activation in a pertussis toxin-sensitive manner.

A meiotic gene regulatory cascade driven by alternative fates for newly synthesized transcripts

PubMed Central

Cremona, Nicole; Potter, Kristine; Wise, Jo Ann

2011-01-01

To determine the relative importance of transcriptional regulation versus RNA processing and turnover during the transition from proliferation to meiotic differentiation in the fission yeast Schizosaccharomyces pombe, we analyzed temporal profiles and effects of RNA surveillance factor mutants on expression of 32 meiotic genes. A comparison of nascent transcription with steady-state RNA accumulation reveals that the vast majority of these genes show a lag between maximal RNA synthesis and peak RNA accumulation. During meiosis, total RNA levels parallel 3′ processing, which occurs in multiple, temporally distinct waves that peak from 3 to 6 h after meiotic induction. Most early genes and one middle gene, mei4, share a regulatory mechanism in which a specialized RNA surveillance factor targets newly synthesized transcripts for destruction. Mei4p, a member of the forkhead transcription factor family, in turn regulates a host of downstream genes. Remarkably, a spike in transcription is observed for less than one-third of the genes surveyed, and even these show evidence of RNA-level regulation. In aggregate, our findings lead us to propose that a regulatory cascade driven by changes in processing and stability of newly synthesized transcripts operates alongside the well-known transcriptional cascade as fission yeast cells enter meiosis. PMID:21148298

Effects of Cascaded Voltage Collapse and Protection of Many Induction Machine Loads upon Load Characteristics Viewed from Bulk Transmission System

NASA Astrophysics Data System (ADS)

Kumano, Teruhisa

As known well, two of the fundamental processes which give rise to voltage collapse in power systems are the on load tap changers of transformers and dynamic characteristics of loads such as induction machines. It has been well established that, comparing among these two, the former makes slower collapse while the latter makes faster. However, in realistic situations, the load level of each induction machine is not uniform and it is well expected that only a part of loads collapses first, followed by collapse process of each load which did not go into instability during the preceding collapses. In such situations the over all equivalent collapse behavior viewed from bulk transmission level becomes somewhat different from the simple collapse driven by one aggregated induction machine. This paper studies the process of cascaded voltage collapse among many induction machines by time simulation, where load distribution on a feeder line is modeled by several hundreds of induction machines and static impedance loads. It is shown that in some cases voltage collapse really cascades among induction machines, where the macroscopic load dynamics viewed from upper voltage level makes slower collapse than expected by the aggregated load model. Also shown is the effects of machine protection of induction machines, which also makes slower collapse.

Racemic hemiacetals as oxygen-centered pronucleophiles triggering cascade 1,4-addition/Michael reaction through dynamic kinetic resolution under iminium catalysis. Development and mechanistic insights† †Electronic supplementary information (ESI) available: Detailed experimental procedures and characterization of all new compounds, including copies of NMR spectra and HPLC chromatograms traces, computational details and Cartesian coordinates of all stationary points. CCDC 1525188 (4l), 1525189 (6a) and 1525190 (9a). For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc00009j Click here for additional data file. Click here for additional data file.

PubMed Central

Orue, Ane; Uria, Uxue; Roca-López, David; Delso, Ignacio; Reyes, Efraím; Carrillo, Luisa

2017-01-01

2-Hydroxydihydropyran-5-ones behave as excellent polyfunctional reagents able to react with enals through oxa-Michael/Michael process cascade under the combination of iminium and enamine catalysis. These racemic hemiacetalic compounds are used as unconventional O-pronucleophiles in the initial oxa-Michael reaction, also leading to the formation of a single stereoisomer under a dynamic kinetic resolution (DKR) process. Importantly, by using β-aryl or β-alkyl substituted α,β-unsaturated substrates as initial Michael acceptors either kinetically or thermodynamically controlled diastereoisomers were formed with high stereoselection through the careful selection of the reaction conditions. Finally, a complete experimental and computational study confirmed the initially proposed DKR process during the catalytic oxa-Michael/Michael cascade reaction and also explained the kinetic/thermodynamic pathway operating in each case. PMID:28451356

A cascade model of information processing and encoding for retinal prosthesis.

PubMed

Pei, Zhi-Jun; Gao, Guan-Xin; Hao, Bo; Qiao, Qing-Li; Ai, Hui-Jian

2016-04-01

Retinal prosthesis offers a potential treatment for individuals suffering from photoreceptor degeneration diseases. Establishing biological retinal models and simulating how the biological retina convert incoming light signal into spike trains that can be properly decoded by the brain is a key issue. Some retinal models have been presented, ranking from structural models inspired by the layered architecture to functional models originated from a set of specific physiological phenomena. However, Most of these focus on stimulus image compression, edge detection and reconstruction, but do not generate spike trains corresponding to visual image. In this study, based on state-of-the-art retinal physiological mechanism, including effective visual information extraction, static nonlinear rectification of biological systems and neurons Poisson coding, a cascade model of the retina including the out plexiform layer for information processing and the inner plexiform layer for information encoding was brought forward, which integrates both anatomic connections and functional computations of retina. Using MATLAB software, spike trains corresponding to stimulus image were numerically computed by four steps: linear spatiotemporal filtering, static nonlinear rectification, radial sampling and then Poisson spike generation. The simulated results suggested that such a cascade model could recreate visual information processing and encoding functionalities of the retina, which is helpful in developing artificial retina for the retinally blind.

Cortical Auditory Deafferentation Induces Long-Term Plasticity in the Inferior Colliculus of Adult Rats: Microarray and qPCR Analysis

PubMed Central

Clarkson, Cheryl; Herrero-Turrión, M. Javier; Merchán, Miguel A.

2012-01-01

The cortico-collicular pathway is a bilateral excitatory projection from the cortex to the inferior colliculus (IC). It is asymmetric and predominantly ipsilateral. Using microarrays and RT-qPCR we analyzed changes in gene expression in the IC after unilateral lesions of the auditory cortex, comparing the ICs ipsi- and contralateral to the lesioned side. At 15 days after surgery there were mainly changes in gene expression in the IC ipsilateral to the lesion. Regulation primarily involved inflammatory cascade genes, suggesting a direct effect of degeneration rather than a neuronal plastic reorganization. Ninety days after the cortical lesion the ipsilateral IC showed a significant up-regulation of genes involved in apoptosis and axonal regeneration combined with a down-regulation of genes involved in neurotransmission, synaptic growth, and gap junction assembly. In contrast, the contralateral IC at 90 days post-lesion showed an up-regulation in genes primarily related to neurotransmission, cell proliferation, and synaptic growth. There was also a down-regulation in autophagy and neuroprotection genes. These findings suggest that the reorganization in the IC after descending pathway deafferentation is a long-term process involving extensive changes in gene expression regulation. Regulated genes are involved in many different neuronal functions, and the number and gene rearrangement profile seems to depend on the density of loss of the auditory cortical inputs. PMID:23233834