A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation.

Science.gov (United States)

Choe, Youngshik; Siegenthaler, Julie A; Pleasure, Samuel J

2012-02-23

The corpus callosum is the most prominent commissural connection between the cortical hemispheres, and numerous neurodevelopmental disorders are associated with callosal agenesis. By using mice either with meningeal overgrowth or selective loss of meninges, we have identified a cascade of morphogenic signals initiated by the meninges that regulates corpus callosum development. The meninges produce BMP7, an inhibitor of callosal axon outgrowth. This activity is overcome by the induction of expression of Wnt3 by the callosal pathfinding neurons, which antagonize the inhibitory effects of BMP7. Wnt3 expression in the cingulate callosal pathfinding axons is developmentally regulated by another BMP family member, GDF5, which is produced by the adjacent Cajal-Retzius neurons and turns on before outgrowth of the callosal axons. The effects of GDF5 are in turn under the control of a soluble GDF5 inhibitor, Dan, made by the meninges. Thus, the meninges and medial neocortex use a cascade of signals to regulate corpus callosum development. Copyright © 2012 Elsevier Inc. All rights reserved.

Modeling DNA?damage-induced pneumopathy in mice: insight from danger signaling cascades

OpenAIRE

Wirsd?rfer, Florian; Jendrossek, Verena

2017-01-01

Radiation-induced pneumonitis and fibrosis represent severe and dose-limiting side effects in the radiotherapy of thorax-associated neoplasms leading to decreased quality of life or - as a consequence of treatment with suboptimal radiation doses - to fatal outcomes by local recurrence or metastatic disease. It is assumed that the initial radiation-induced damage to the resident cells triggers a multifaceted damage-signalling cascade in irradiated normal tissues including a multifactorial secr...

Analysis of Cell Signal Transduction Based on Kullback–Leibler Divergence: Channel Capacity and Conservation of Its Production Rate during Cascade

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Tatsuaki Tsuruyama

2018-06-01

Full Text Available Kullback–Leibler divergence (KLD is a type of extended mutual entropy, which is used as a measure of information gain when transferring from a prior distribution to a posterior distribution. In this study, KLD is applied to the thermodynamic analysis of cell signal transduction cascade and serves an alternative to mutual entropy. When KLD is minimized, the divergence is given by the ratio of the prior selection probability of the signaling molecule to the posterior selection probability. Moreover, the information gain during the entire channel is shown to be adequately described by average KLD production rate. Thus, this approach provides a framework for the quantitative analysis of signal transduction. Moreover, the proposed approach can identify an effective cascade for a signaling network.

Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the Akt signaling cascades

International Nuclear Information System (INIS)

Qu, Xinhua; Zhai, Zanjing; Liu, Xuqiang; Li, Haowei; Ouyang, Zhengxiao; Wu, Chuanlong; Liu, Guangwang; Fan, Qiming; Tang, Tingting; Qin, An; Dai, Kerong

2014-01-01

Highlights: •A natural-derived compound, dioscin, suppresses osteoclast formation and bone resorption. •Dioscin inhibits osteolytic bone loss in vivo. •Dioscin impairs the Akt signaling cascades pathways during osteoclastogenesis. •Dioscin have therapeutic value in treating osteoclast-related diseases. -- Abstract: Bone resorption is the unique function of osteoclasts (OCs) and is critical for both bone homeostasis and pathologic bone diseases including osteoporosis, rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. In this study, we for the first time demonstrated that dioscin suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. The suppressive effect of dioscin is supported by the reduced expression of osteoclast-specific markers. Further molecular analysis revealed that dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-κB) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model. Together our data demonstrate that dioscin suppressed RANKL-induced osteoclast formation and function through Akt signaling cascades. Therefore, dioscin is a potential natural agent for the treatment of osteoclast-related diseases

Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the Akt signaling cascades

Energy Technology Data Exchange (ETDEWEB)

Qu, Xinhua; Zhai, Zanjing; Liu, Xuqiang; Li, Haowei [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Ouyang, Zhengxiao [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Department of Orthopaedics, Hunan Provincial Tumor Hospital and Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha (China); Wu, Chuanlong [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Liu, Guangwang [Department of Orthopaedic Surgery, The Central Hospital of Xuzhou, Affiliated Hospital of Medical Collage of Southeast University, Xuzhou (China); Fan, Qiming; Tang, Tingting [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Qin, An, E-mail: dr.qinan@gmail.com [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Dai, Kerong, E-mail: krdai@163.com [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)

2014-01-10

Highlights: •A natural-derived compound, dioscin, suppresses osteoclast formation and bone resorption. •Dioscin inhibits osteolytic bone loss in vivo. •Dioscin impairs the Akt signaling cascades pathways during osteoclastogenesis. •Dioscin have therapeutic value in treating osteoclast-related diseases. -- Abstract: Bone resorption is the unique function of osteoclasts (OCs) and is critical for both bone homeostasis and pathologic bone diseases including osteoporosis, rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. In this study, we for the first time demonstrated that dioscin suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. The suppressive effect of dioscin is supported by the reduced expression of osteoclast-specific markers. Further molecular analysis revealed that dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-κB) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model. Together our data demonstrate that dioscin suppressed RANKL-induced osteoclast formation and function through Akt signaling cascades. Therefore, dioscin is a potential natural agent for the treatment of osteoclast-related diseases.

Noise propagation in two-step series MAPK cascade.

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Venkata Dhananjaneyulu

Full Text Available Series MAPK enzymatic cascades, ubiquitously found in signaling networks, act as signal amplifiers and play a key role in processing information during signal transduction in cells. In activated cascades, cell-to-cell variability or noise is bound to occur and thereby strongly affects the cellular response. Commonly used linearization method (LM applied to Langevin type stochastic model of the MAPK cascade fails to accurately predict intrinsic noise propagation in the cascade. We prove this by using extensive stochastic simulations for various ranges of biochemical parameters. This failure is due to the fact that the LM ignores the nonlinear effects on the noise. However, LM provides a good estimate of the extrinsic noise propagation. We show that the correct estimate of intrinsic noise propagation in signaling networks that contain at least one enzymatic step can be obtained only through stochastic simulations. Noise propagation in the cascade depends on the underlying biochemical parameters which are often unavailable. Based on a combination of global sensitivity analysis (GSA and stochastic simulations, we developed a systematic methodology to characterize noise propagation in the cascade. GSA predicts that noise propagation in MAPK cascade is sensitive to the total number of upstream enzyme molecules and the total number of molecules of the two substrates involved in the cascade. We argue that the general systematic approach proposed and demonstrated on MAPK cascade must accompany noise propagation studies in biological networks.

Hedgehog signaling acts with the temporal cascade to promote neuroblast cell cycle exit.

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Phing Chian Chai

Full Text Available In Drosophila postembryonic neuroblasts, transition in gene expression programs of a cascade of transcription factors (also known as the temporal series acts together with the asymmetric division machinery to generate diverse neurons with distinct identities and regulate the end of neuroblast proliferation. However, the underlying mechanism of how this "temporal series" acts during development remains unclear. Here, we show that Hh signaling in the postembryonic brain is temporally regulated; excess (earlier onset of Hh signaling causes premature neuroblast cell cycle exit and under-proliferation, whereas loss of Hh signaling causes delayed cell cycle exit and excess proliferation. Moreover, the Hh pathway functions downstream of Castor but upstream of Grainyhead, two components of the temporal series, to schedule neuroblast cell cycle exit. Interestingly, hh is likely a target of Castor. Hence, Hh signaling provides a link between the temporal series and the asymmetric division machinery in scheduling the end of neurogenesis.

Nitric oxide/cGMP/PKG signaling pathway activated by M1-type muscarinic acetylcholine receptor cascade inhibits Na+-activated K+ currents in Kenyon cells

Science.gov (United States)

Hasebe, Masaharu

2016-01-01

The interneurons of the mushroom body, known as Kenyon cells, are essential for the long-term memory of olfactory associative learning in some insects. Some studies have reported that nitric oxide (NO) is strongly related to this long-term memory in Kenyon cells. However, the target molecules and upstream and downstream NO signaling cascades are not completely understood. Here we analyzed the effect of the NO signaling cascade on Na+-activated K+ (KNa) channel activity in Kenyon cells of crickets (Gryllus bimaculatus). We found that two different NO donors, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetyl-dl-penicillamine (SNAP), strongly suppressed KNa channel currents. Additionally, this inhibitory effect of GSNO on KNa channel activity was diminished by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC), and KT5823, an inhibitor of protein kinase G (PKG). Next, we analyzed the role of ACh in the NO signaling cascade. ACh strongly suppressed KNa channel currents, similar to NO donors. Furthermore, this inhibitory effect of ACh was blocked by pirenzepine, an M1 muscarinic ACh receptor antagonist, but not by 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP) and mecamylamine, an M3 muscarinic ACh receptor antagonist and a nicotinic ACh receptor antagonist, respectively. The ACh-induced inhibition of KNa channel currents was also diminished by the PLC inhibitor U73122 and the calmodulin antagonist W-7. Finally, we found that ACh inhibition was blocked by the nitric oxide synthase (NOS) inhibitor NG-nitro-l-arginine methyl ester (l-NAME). These results suggested that the ACh signaling cascade promotes NO production by activating NOS and NO inhibits KNa channel currents via the sGC/cGMP/PKG signaling cascade in Kenyon cells. PMID:26984419

Dynamics robustness of cascading systems.

Directory of Open Access Journals (Sweden)

Jonathan T Young

2017-03-01

Full Text Available A most important property of biochemical systems is robustness. Static robustness, e.g., homeostasis, is the insensitivity of a state against perturbations, whereas dynamics robustness, e.g., homeorhesis, is the insensitivity of a dynamic process. In contrast to the extensively studied static robustness, dynamics robustness, i.e., how a system creates an invariant temporal profile against perturbations, is little explored despite transient dynamics being crucial for cellular fates and are reported to be robust experimentally. For example, the duration of a stimulus elicits different phenotypic responses, and signaling networks process and encode temporal information. Hence, robustness in time courses will be necessary for functional biochemical networks. Based on dynamical systems theory, we uncovered a general mechanism to achieve dynamics robustness. Using a three-stage linear signaling cascade as an example, we found that the temporal profiles and response duration post-stimulus is robust to perturbations against certain parameters. Then analyzing the linearized model, we elucidated the criteria of when signaling cascades will display dynamics robustness. We found that changes in the upstream modules are masked in the cascade, and that the response duration is mainly controlled by the rate-limiting module and organization of the cascade's kinetics. Specifically, we found two necessary conditions for dynamics robustness in signaling cascades: 1 Constraint on the rate-limiting process: The phosphatase activity in the perturbed module is not the slowest. 2 Constraints on the initial conditions: The kinase activity needs to be fast enough such that each module is saturated even with fast phosphatase activity and upstream changes are attenuated. We discussed the relevance of such robustness to several biological examples and the validity of the above conditions therein. Given the applicability of dynamics robustness to a variety of systems, it

Network features and pathway analyses of a signal transduction cascade

Directory of Open Access Journals (Sweden)

Ryoji Yanashima

2009-05-01

Full Text Available The scale-free and small-world network models reflect the functional units of networks. However, when we investigated the network properties of a signaling pathway using these models, no significant differences were found between the original undirected graphs and the graphs in which inactive proteins were eliminated from the gene expression data. We analyzed signaling networks by focusing on those pathways that best reflected cellular function. Therefore, our analysis of pathways started from the ligands and progressed to transcription factors and cytoskeletal proteins. We employed the Python module to assess the target network. This involved comparing the original and restricted signaling cascades as a directed graph using microarray gene expression profiles of late onset Alzheimer's disease. The most commonly used method of shortest-path analysis neglects to consider the influences of alternative pathways that can affect the activation of transcription factors or cytoskeletal proteins. We therefore introduced included k-shortest paths and k-cycles in our network analysis using the Python modules, which allowed us to attain a reasonable computational time and identify k-shortest paths. This technique reflected results found in vivo and identified pathways not found when shortest path or degree analysis was applied. Our module enabled us to comprehensively analyse the characteristics of biomolecular networks and also enabled analysis of the effects of diseases considering the feedback loop and feedforward loop control structures as an alternative path.

A growth factor signaling cascade confined to circular ruffles in macrophages

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Timothy P. Welliver

2012-06-01

The formation of macropinosomes requires large-scale movements of membranes and the actin cytoskeleton. Over several minutes, actin-rich surface ruffles transform into 1–5 µm diameter circular ruffles, which close at their distal margins, creating endocytic vesicles. Previous studies using fluorescent reporters of phosphoinositides and Rho-family GTPases showed that signals generated by macrophages in response to the growth factor Macrophage Colony-Stimulating Factor (M-CSF appeared transiently in domains of plasma membrane circumscribed by circular ruffles. To address the question of how signaling molecules are coordinated in such large domains of plasma membrane, this study analyzed the relative timing of growth factor-dependent signals as ruffles transformed into macropinosomes. Fluorescent protein chimeras expressed in macrophages were imaged by microscopy and quantified relative to circular ruffle formation and cup closure. The large size of macropinocytic cups allowed temporal resolution of the transitions in phosphoinositides and associated enzyme activities that organize cup closure. Circular ruffles contained transient and sequential spikes of phosphatidylinositol (4,5-bisphosphate (PI(4,5P2, phosphatidylinositol (3,4,5-trisphosphate (PIP3, diacylglycerol, PI(3,4P2, PI(3P and the activities of protein kinase C-α, Rac1, Ras and Rab5. The confinement of this signal cascade to circular ruffles indicated that diffusion barriers present in these transient structures focus feedback activation and deactivation of essential enzyme activities into restricted domains of plasma membrane.

Plant MAPK cascades: Just rapid signaling modules?

KAUST Repository

Boudsocq, Marie; Danquah, Agyemang; Zé licourt, Axel de; Hirt, Heribert; Colcombet, Jean

2015-01-01

rapid MAPK activation, we showed that the activation of the new MAPK module is delayed and relies on the MAP3K protein synthesis. In this addendum, we discuss the role of this original and unexpected activation mechanism of MAPK cascades which suggests

Zinc promotes proliferation and activation of myogenic cells via the PI3K/Akt and ERK signaling cascade

Energy Technology Data Exchange (ETDEWEB)

Ohashi, Kazuya, E-mail: asuno10k@yahoo.co.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo (Japan); Nagata, Yosuke, E-mail: cynagata@mail.ecc.u-tokyo.ac.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo (Japan); Wada, Eiji, E-mail: gacchu1@yahoo.co.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo (Japan); Zammit, Peter S., E-mail: peter.zammit@kcl.ac.uk [Randall Division of Cell and Molecular Biophysics, King' s College London, London SE1 1UL (United Kingdom); Shiozuka, Masataka, E-mail: cmuscle@mail.ecc.u-tokyo.ac.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo (Japan); Matsuda, Ryoichi, E-mail: cmatsuda@mail.ecc.u-tokyo.ac.jp [Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo (Japan)

2015-05-01

Skeletal muscle stem cells named muscle satellite cells are normally quiescent but are activated in response to various stimuli, such as injury and overload. Activated satellite cells enter the cell cycle and proliferate to produce a large number of myogenic progenitor cells, and these cells then differentiate and fuse to form myofibers. Zinc is one of the essential elements in the human body, and has multiple roles, including cell growth and DNA synthesis. However, the role of zinc in myogenic cells is not well understood, and is the focus of this study. We first examined the effects of zinc on differentiation of murine C2C12 myoblasts and found that zinc promoted proliferation, with an increased number of cells incorporating EdU, but inhibited differentiation with reduced myogenin expression and myotube formation. Furthermore, we used the C2C12 reserve cell model of myogenic quiescence to investigate the role of zinc on activation of myogenic cells. The number of reserve cells incorporating BrdU was increased by zinc in a dose dependent manner, with the number dramatically further increased using a combination of zinc and insulin. Akt and extracellular signal-regulated kinase (ERK) are downstream of insulin signaling, and both were phosphorylated after zinc treatment. The zinc/insulin combination-induced activation involved the phosphoinositide 3-kinase (PI3K)/Akt and ERK cascade. We conclude that zinc promotes activation and proliferation of myogenic cells, and this activation requires phosphorylation of PI3K/Akt and ERK as part of the signaling cascade. - Highlights: • Zinc has roles for promoting proliferation and inhibition differentiation of C2C12. • Zinc promotes activation of reserve cells. • Insulin and zinc synergize activation of reserve cells. • PI3K/Akt and ERK cascade affect zinc/insulin-mediated activation of reserve cells.

Signal-Pressure Curves of Cascaded Four-Wave Mixing in Gas-Filled Capillary by fs Pulses

International Nuclear Information System (INIS)

Chen Baozhen; Huang Zuqia

2005-01-01

The theoretical framework for the cascaded four waves mixing (CFWM) in gas-filled capillary by fs pulses is constructed. Based on the theoretical framework, the signal-pressure curves (SPC) of the CFWM in gas-filled capillary by fs pulses are calculated. With a comparison between the theoretical and experimental SPC we have discussed the influence of the walk-off and phase modulation on the SPC. At the same time, we have discussed the possible origin of the first three peaks of the SPC.

Microscopic insight into thermodynamics of conformational changes of SAP-SLAM complex in signal transduction cascade

Science.gov (United States)

Samanta, Sudipta; Mukherjee, Sanchita

2017-04-01

The signalling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, associate with SLAM-associated protein (SAP)-related molecules, composed of single SH2 domain architecture. SAP activates Src-family kinase Fyn after SLAM ligation, resulting in a SLAM-SAP-Fyn complex, where, SAP binds the Fyn SH3 domain that does not involve canonical SH3 or SH2 interactions. This demands insight into this SAP mediated signalling cascade. Thermodynamics of the conformational changes are extracted from the histograms of dihedral angles obtained from the all-atom molecular dynamics simulations of this structurally well characterized SAP-SLAM complex. The results incorporate the binding induced thermodynamic changes of individual amino acid as well as the secondary structural elements of the protein and the solvent. Stabilization of the peptide partially comes through a strong hydrogen bonding network with the protein, while hydrophobic interactions also play a significant role where the peptide inserts itself into a hydrophobic cavity of the protein. SLAM binding widens SAP's second binding site for Fyn, which is the next step in the signal transduction cascade. The higher stabilization and less fluctuation of specific residues of SAP in the Fyn binding site, induced by SAP-SLAM complexation, emerge as the key structural elements to trigger the recognition of SAP by the SH3 domain of Fyn. The thermodynamic quantification of the protein due to complexation not only throws deeper understanding in the established mode of SAP-SLAM interaction but also assists in the recognition of the relevant residues of the protein responsible for alterations in its activity.

Interaction of LRRK2 with kinase and GTPase signaling cascades

Directory of Open Access Journals (Sweden)

Joon Y Boon

2014-07-01

Full Text Available LRRK2 is a protein that interacts with a plethora of signaling molecules, but the complexity of LRRK2 function presents a challenge for understanding the role of LRRK2 in the pathophysiology of Parkinson’s disease. Studies of LRRK2 using over-expression in transgenic mice have been disappointing, however studies using invertebrate systems have yielded a much clearer picture, with clear effects of LRRK2 expression, knockdown or deletion in C. elegans and Drosophila on modulation of survival of dopaminergic neurons. Recent studies have begun to focus attention on particular signaling cascades that are a target of LRRK2 function. LRRK2 interacts with members of the MAPK pathway and might regulate the pathway action by acting as a scaffold that directs the location of MAPK pathway activity, without strongly affecting the amount of MAPK pathway activity. Binding to GTPases, GAPs and GEFs are another strong theme in LRRK2 biology, with LRRK2 binding to Rac1, cdc42, rab5, rab7L1, endoA, RGS2, ArfGAP1 and ArhGEF7. All of these molecules appear to feed into a function output for LRRK2 that modulates cytoskeletal outgrowth and vesicular dynamics, including autophagy. These functions likely impact modulation of α-synuclein aggregation and associated toxicity eliciting the disease processes that we term Parkinson’s disease.

Cascade enzymatic reactions for efficient carbon sequestration.

Science.gov (United States)

Xia, Shunxiang; Zhao, Xueyan; Frigo-Vaz, Benjamin; Zheng, Wenyun; Kim, Jungbae; Wang, Ping

2015-04-01

Thermochemical processes developed for carbon capture and storage (CCS) offer high carbon capture capacities, but are generally hampered by low energy efficiency. Reversible cascade enzyme reactions are examined in this work for energy-efficient carbon sequestration. By integrating the reactions of two key enzymes of RTCA cycle, isocitrate dehydrogenase and aconitase, we demonstrate that intensified carbon capture can be realized through such cascade enzymatic reactions. Experiments show that enhanced thermodynamic driving force for carbon conversion can be attained via pH control under ambient conditions, and that the cascade reactions have the potential to capture 0.5 mol carbon at pH 6 for each mole of substrate applied. Overall it manifests that the carbon capture capacity of biocatalytic reactions, in addition to be energy efficient, can also be ultimately intensified to approach those realized with chemical absorbents such as MEA. Copyright © 2015 Elsevier Ltd. All rights reserved.

Search for QGP signals at AGS with a TPC spectrometer, and comparison of our event generator predictions for plasma model and cascade interactions

International Nuclear Information System (INIS)

Lindenbaum, S.J.; Foley, K.J.; Eiseman, S.E.

1988-01-01

We have developed and successfully tested a TPC Magnetic Spectrometer to search for QGP signals produced by ion beams at AGS. We also developed a cascade and plasma event generator the predictions of which are used to illustrate how our technique can detect possible plasma signals. 4 refs., 6 figs., 1 tab

The Signaling Cascades of Ginkgolide B-Induced Apoptosis in MCF-7 Breast Cancer Cells

Directory of Open Access Journals (Sweden)

Wen-Hsiung Chan

2007-11-01

Full Text Available Ginkgolide B, the major active component of Ginkgo biloba extracts, can bothstimulate and inhibit apoptotic signaling. Here, we demonstrate that ginkgolide B caninduce the production of reactive oxygen species in MCF-7 breast cancer cells, leading toan increase in the intracellular concentrations of cytoplasmic free Ca2+ and nitric oxide(NO, loss of mitochondrial membrane potential (MMP, activation of caspase-9 and -3,and increase the mRNA expression levels of p53 and p21, which are known to be involvedin apoptotic signaling. In addition, prevention of ROS generation by pretreatment withN-acetyl cysteine (NAC could effectively block intracellular Ca2+ concentrationsincreases and apoptosis in ginkgolide B-treated MCF-7 cells. Moreover, pretreatment withnitric oxide (NO scavengers could inhibit ginkgolide B-induced MMP change andsequent apoptotic processes. Overall, our results signify that both ROS and NO playedimportant roles in ginkgolide B-induced apoptosis of MCF-7 cells. Based on these studyresults, we propose a model for ginkgolide B-induced cell apoptosis signaling cascades inMCF-7 cells.

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

Science.gov (United States)

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

A simple model of global cascades on random networks

Science.gov (United States)

Watts, Duncan J.

2002-04-01

The origin of large but rare cascades that are triggered by small initial shocks is a phenomenon that manifests itself as diversely as cultural fads, collective action, the diffusion of norms and innovations, and cascading failures in infrastructure and organizational networks. This paper presents a possible explanation of this phenomenon in terms of a sparse, random network of interacting agents whose decisions are determined by the actions of their neighbors according to a simple threshold rule. Two regimes are identified in which the network is susceptible to very large cascadesherein called global cascadesthat occur very rarely. When cascade propagation is limited by the connectivity of the network, a power law distribution of cascade sizes is observed, analogous to the cluster size distribution in standard percolation theory and avalanches in self-organized criticality. But when the network is highly connected, cascade propagation is limited instead by the local stability of the nodes themselves, and the size distribution of cascades is bimodal, implying a more extreme kind of instability that is correspondingly harder to anticipate. In the first regime, where the distribution of network neighbors is highly skewed, it is found that the most connected nodes are far more likely than average nodes to trigger cascades, but not in the second regime. Finally, it is shown that heterogeneity plays an ambiguous role in determining a system's stability: increasingly heterogeneous thresholds make the system more vulnerable to global cascades; but an increasingly heterogeneous degree distribution makes it less vulnerable.

A Gibberellin-Mediated DELLA-NAC Signaling Cascade Regulates Cellulose Synthesis in Rice.

Science.gov (United States)

Huang, Debao; Wang, Shaogan; Zhang, Baocai; Shang-Guan, Keke; Shi, Yanyun; Zhang, Dongmei; Liu, Xiangling; Wu, Kun; Xu, Zuopeng; Fu, Xiangdong; Zhou, Yihua

2015-06-01

Cellulose, which can be converted into numerous industrial products, has important impacts on the global economy. It has long been known that cellulose synthesis in plants is tightly regulated by various phytohormones. However, the underlying mechanism of cellulose synthesis regulation remains elusive. Here, we show that in rice (Oryza sativa), gibberellin (GA) signals promote cellulose synthesis by relieving the interaction between SLENDER RICE1 (SLR1), a DELLA repressor of GA signaling, and NACs, the top-layer transcription factors for secondary wall formation. Mutations in GA-related genes and physiological treatments altered the transcription of CELLULOSE SYNTHASE genes (CESAs) and the cellulose level. Multiple experiments demonstrated that transcription factors NAC29/31 and MYB61 are CESA regulators in rice; NAC29/31 directly regulates MYB61, which in turn activates CESA expression. This hierarchical regulation pathway is blocked by SLR1-NAC29/31 interactions. Based on the results of anatomical analysis and GA content examination in developing rice internodes, this signaling cascade was found to be modulated by varied endogenous GA levels and to be required for internode development. Genetic and gene expression analyses were further performed in Arabidopsis thaliana GA-related mutants. Altogether, our findings reveal a conserved mechanism by which GA regulates secondary wall cellulose synthesis in land plants and provide a strategy for manipulating cellulose production and plant growth. © 2015 American Society of Plant Biologists. All rights reserved.

Hybrid Modulation Scheme for Cascaded H-Bridge Inverter Cells ...

African Journals Online (AJOL)

This work proposes a switching technique for cascaded H-Bridge (CHB) cells. Single carrier Sinusoidal PWM (SCSPWM) scheme is employed in the generation of the gating signals. A sequential switching and base PWM circulation schemes are presented for this fundamental cascaded multilevel inverter topology.

Signaling pathways underpinning the manifestations of ionizing radiation-induced bystander effects.

Science.gov (United States)

Hamada, Nobuyuki; Maeda, Munetoshi; Otsuka, Kensuke; Tomita, Masanori

2011-06-01

For nearly a century, ionizing radiation has been indispensable to medical diagnosis. Furthermore, various types of electromagnetic and particulate radiation have also been used in cancer therapy. However, the biological mechanism of radiation action remains incompletely understood. In this regard, a rapidly growing body of experimental evidence indicates that radiation exposure induces biological effects in cells whose nucleus has not been irradiated. This phenomenon termed the 'non-targeted effects' challenges the long-held tenet that radiation traversal through the cell nucleus is a prerequisite to elicit genetic damage and biological responses. The non-targeted effects include biological effects in cytoplasm-irradiated cells, bystander effects that arise in non-irradiated cells having received signals from irradiated cells, and genomic instability occurring in the progeny of irradiated cells. Such non-targeted responses are interrelated, and the bystander effect is further related with an adaptive response that manifests itself as the attenuated stressful biological effects of acute high-dose irradiation in cells that have been pre-exposed to low-dose or low-dose-rate radiation. This paper reviews the current body of knowledge about the bystander effect with emphasis on experimental approaches, in vitro and in vivo manifestations, radiation quality dependence, temporal and spatial dependence, proposed mechanisms, and clinical implications. Relations of bystander responses with the effects in cytoplasm-irradiated cells, genomic instability and adaptive response will also be briefly discussed.

Modeling of Bit Error Rate in Cascaded 2R Regenerators

DEFF Research Database (Denmark)

Öhman, Filip; Mørk, Jesper

2006-01-01

and the regenerating nonlinearity is investigated. It is shown that an increase in nonlinearity can compensate for an increase in noise figure or decrease in signal power. Furthermore, the influence of the improvement in signal extinction ratio along the cascade and the importance of choosing the proper threshold......This paper presents a simple and efficient model for estimating the bit error rate in a cascade of optical 2R-regenerators. The model includes the influences of of amplifier noise, finite extinction ratio and nonlinear reshaping. The interplay between the different signal impairments...

Identification of ASK1, MKK4, JNK, c-Jun, and caspase-3 as a signaling cascade involved in cadmium-induced neuronal cell apoptosis

International Nuclear Information System (INIS)

Kim, Sun Don; Moon, Chang Kyu; Eun, Su-Yong; Ryu, Pan Dong; Jo, Sangmee Ahn

2005-01-01

Cd induces oxidative stress and apoptosis in various cells by activating mitogen-activated protein kinases (MAPKs), but the precise signaling components of the MAPK cascade and their role in neuronal apoptosis are still unclear. Here, we report that Cd treatment of SH-SY5Y cells caused apoptosis through sequential phosphorylation of the apoptosis signal regulating kinase 1, MAPK kinase 4, c-Jun N-terminal kinase (JNK), and c-Jun as determined by overexpression of dominant negative (DN) constructs of these genes or using a specific JNK inhibitor SP600125. Both Cd-induced JNK and c-Jun phosphorylation and apoptosis were inhibited dramatically by N-acetyl-L-cysteine, a free radical scavenger. In addition, caspase inhibitors, zDEVD and zVAD, reduced apoptosis but not JNK and c-Jun phosphorylation induced by Cd, while overexpression of DN JNK1 inhibited caspase-3 activity. Taken together, our data suggested that the JNK/c-Jun signaling cascade plays a crucial role in Cd-induced neuronal cell apoptosis and provides a molecular linkage between oxidative stress and neuronal apoptosis

A Gibberellin-Mediated DELLA-NAC Signaling Cascade Regulates Cellulose Synthesis in Rice[OPEN

Science.gov (United States)

Huang, Debao; Wang, Shaogan; Zhang, Baocai; Shang-Guan, Keke; Shi, Yanyun; Zhang, Dongmei; Liu, Xiangling; Wu, Kun; Xu, Zuopeng; Fu, Xiangdong; Zhou, Yihua

2015-01-01

Cellulose, which can be converted into numerous industrial products, has important impacts on the global economy. It has long been known that cellulose synthesis in plants is tightly regulated by various phytohormones. However, the underlying mechanism of cellulose synthesis regulation remains elusive. Here, we show that in rice (Oryza sativa), gibberellin (GA) signals promote cellulose synthesis by relieving the interaction between SLENDER RICE1 (SLR1), a DELLA repressor of GA signaling, and NACs, the top-layer transcription factors for secondary wall formation. Mutations in GA-related genes and physiological treatments altered the transcription of CELLULOSE SYNTHASE genes (CESAs) and the cellulose level. Multiple experiments demonstrated that transcription factors NAC29/31 and MYB61 are CESA regulators in rice; NAC29/31 directly regulates MYB61, which in turn activates CESA expression. This hierarchical regulation pathway is blocked by SLR1-NAC29/31 interactions. Based on the results of anatomical analysis and GA content examination in developing rice internodes, this signaling cascade was found to be modulated by varied endogenous GA levels and to be required for internode development. Genetic and gene expression analyses were further performed in Arabidopsis thaliana GA-related mutants. Altogether, our findings reveal a conserved mechanism by which GA regulates secondary wall cellulose synthesis in land plants and provide a strategy for manipulating cellulose production and plant growth. PMID:26002868

Cascades and Dissipative Anomalies in Compressible Fluid Turbulence

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Gregory L. Eyink

2018-02-01

Full Text Available We investigate dissipative anomalies in a turbulent fluid governed by the compressible Navier-Stokes equation. We follow an exact approach pioneered by Onsager, which we explain as a nonperturbative application of the principle of renormalization-group invariance. In the limit of high Reynolds and Péclet numbers, the flow realizations are found to be described as distributional or “coarse-grained” solutions of the compressible Euler equations, with standard conservation laws broken by turbulent anomalies. The anomalous dissipation of kinetic energy is shown to be due not only to local cascade but also to a distinct mechanism called pressure-work defect. Irreversible heating in stationary, planar shocks with an ideal-gas equation of state exemplifies the second mechanism. Entropy conservation anomalies are also found to occur via two mechanisms: an anomalous input of negative entropy (negentropy by pressure work and a cascade of negentropy to small scales. We derive “4/5th-law”-type expressions for the anomalies, which allow us to characterize the singularities (structure-function scaling exponents required to sustain the cascades. We compare our approach with alternative theories and empirical evidence. It is argued that the “Big Power Law in the Sky” observed in electron density scintillations in the interstellar medium is a manifestation of a forward negentropy cascade or an inverse cascade of usual thermodynamic entropy.

Cascades and Dissipative Anomalies in Compressible Fluid Turbulence

Science.gov (United States)

Eyink, Gregory L.; Drivas, Theodore D.

2018-02-01

We investigate dissipative anomalies in a turbulent fluid governed by the compressible Navier-Stokes equation. We follow an exact approach pioneered by Onsager, which we explain as a nonperturbative application of the principle of renormalization-group invariance. In the limit of high Reynolds and Péclet numbers, the flow realizations are found to be described as distributional or "coarse-grained" solutions of the compressible Euler equations, with standard conservation laws broken by turbulent anomalies. The anomalous dissipation of kinetic energy is shown to be due not only to local cascade but also to a distinct mechanism called pressure-work defect. Irreversible heating in stationary, planar shocks with an ideal-gas equation of state exemplifies the second mechanism. Entropy conservation anomalies are also found to occur via two mechanisms: an anomalous input of negative entropy (negentropy) by pressure work and a cascade of negentropy to small scales. We derive "4 /5 th-law"-type expressions for the anomalies, which allow us to characterize the singularities (structure-function scaling exponents) required to sustain the cascades. We compare our approach with alternative theories and empirical evidence. It is argued that the "Big Power Law in the Sky" observed in electron density scintillations in the interstellar medium is a manifestation of a forward negentropy cascade or an inverse cascade of usual thermodynamic entropy.

The p75NTR mediates a bifurcated signal transduction cascade through the NFκB and JNK pathways to inhibit cell survival

International Nuclear Information System (INIS)

Allen, Jeffrey; Khwaja, Fatima; Byers, Stephen; Djakiew, Daniel

2005-01-01

p75 NTR is most abundantly expressed in the nervous system, but is also widely expressed in many other organs and tissues where it primarily functions as a negative regulator of cell survival. In the prostate, p75 NTR functions as an inhibitory protein capable of slowing proliferation and inducing apoptosis. It has been shown that p75 NTR is expressed in the normal prostate, progressively lost from malignant tumor cells in vivo, and largely absent from prostate cancer cell lines derived from metastases. Although the role of p75 NTR in prostate cancer has been well established, the signal transduction pathway that mediates its inhibitory activity has only been partially elucidated. This study demonstrates that exogenous expression of p75 NTR down-regulates, in a dose-dependent manner, a bifurcated signaling cascade that results in reduced expression of potent transcription effectors. This two-arm signal transduction cascade was directly linked to the upstream receptor by using dominant-negative deletion constructs of p75 NTR that rescued tumor cells from p75 NTR -induced loss of survival and promotion of apoptosis. Furthermore, the dominant negatives rescued alterations in the levels of signal transduction intermediates. Conversely, the use of kinase-inactive intermediates that are downstream of the receptor further reduced expression of involved transcription effectors and reduced survival of the cells. These results provide a definitive link between the proximate p75 NTR and signal transduction intermediates leading to the transcription effectors NFκB and JNK, with associated growth suppression and induction of apoptosis

Retroactive signaling in short signaling pathways.

Directory of Open Access Journals (Sweden)

Jacques-Alexandre Sepulchre

Full Text Available In biochemical signaling pathways without explicit feedback connections, the core signal transduction is usually described as a one-way communication, going from upstream to downstream in a feedforward chain or network of covalent modification cycles. In this paper we explore the possibility of a new type of signaling called retroactive signaling, offered by the recently demonstrated property of retroactivity in signaling cascades. The possibility of retroactive signaling is analysed in the simplest case of the stationary states of a bicyclic cascade of signaling cycles. In this case, we work out the conditions for which variables of the upstream cycle are affected by a change of the total amount of protein in the downstream cycle, or by a variation of the phosphatase deactivating the same protein. Particularly, we predict the characteristic ranges of the downstream protein, or of the downstream phosphatase, for which a retroactive effect can be observed on the upstream cycle variables. Next, we extend the possibility of retroactive signaling in short but nonlinear signaling pathways involving a few covalent modification cycles.

Volcano geodesy in the Cascade arc, USA

Science.gov (United States)

Poland, Michael; Lisowski, Michael; Dzurisin, Daniel; Kramer, Rebecca; McLay, Megan; Pauk, Benjamin

2017-01-01

Experience during historical time throughout the Cascade arc and the lack of deep-seated deformation prior to the two most recent eruptions of Mount St. Helens might lead one to infer that Cascade volcanoes are generally quiescent and, specifically, show no signs of geodetic change until they are about to erupt. Several decades of geodetic data, however, tell a different story. Ground- and space-based deformation studies have identified surface displacements at five of the 13 major Cascade arc volcanoes that lie in the USA (Mount Baker, Mount St. Helens, South Sister, Medicine Lake, and Lassen volcanic center). No deformation has been detected at five volcanoes (Mount Rainier, Mount Hood, Newberry Volcano, Crater Lake, and Mount Shasta), and there are not sufficient data at the remaining three (Glacier Peak, Mount Adams, and Mount Jefferson) for a rigorous assessment. In addition, gravity change has been measured at two of the three locations where surveys have been repeated (Mount St. Helens and Mount Baker show changes, while South Sister does not). Broad deformation patterns associated with heavily forested and ice-clad Cascade volcanoes are generally characterized by low displacement rates, in the range of millimeters to a few centimeters per year, and are overprinted by larger tectonic motions of several centimeters per year. Continuous GPS is therefore the best means of tracking temporal changes in deformation of Cascade volcanoes and also for characterizing tectonic signals so that they may be distinguished from volcanic sources. Better spatial resolution of volcano deformation can be obtained through the use of campaign GPS, semipermanent GPS, and interferometric synthetic aperture radar observations, which leverage the accumulation of displacements over time to improve signal to noise. Deformation source mechanisms in the Cascades are diverse and include magma accumulation and withdrawal, post-emplacement cooling of recent volcanic deposits, magmatic

Volcano geodesy in the Cascade arc, USA

Science.gov (United States)

Poland, Michael P.; Lisowski, Michael; Dzurisin, Daniel; Kramer, Rebecca; McLay, Megan; Pauk, Ben

2017-08-01

Experience during historical time throughout the Cascade arc and the lack of deep-seated deformation prior to the two most recent eruptions of Mount St. Helens might lead one to infer that Cascade volcanoes are generally quiescent and, specifically, show no signs of geodetic change until they are about to erupt. Several decades of geodetic data, however, tell a different story. Ground- and space-based deformation studies have identified surface displacements at five of the 13 major Cascade arc volcanoes that lie in the USA (Mount Baker, Mount St. Helens, South Sister, Medicine Lake, and Lassen volcanic center). No deformation has been detected at five volcanoes (Mount Rainier, Mount Hood, Newberry Volcano, Crater Lake, and Mount Shasta), and there are not sufficient data at the remaining three (Glacier Peak, Mount Adams, and Mount Jefferson) for a rigorous assessment. In addition, gravity change has been measured at two of the three locations where surveys have been repeated (Mount St. Helens and Mount Baker show changes, while South Sister does not). Broad deformation patterns associated with heavily forested and ice-clad Cascade volcanoes are generally characterized by low displacement rates, in the range of millimeters to a few centimeters per year, and are overprinted by larger tectonic motions of several centimeters per year. Continuous GPS is therefore the best means of tracking temporal changes in deformation of Cascade volcanoes and also for characterizing tectonic signals so that they may be distinguished from volcanic sources. Better spatial resolution of volcano deformation can be obtained through the use of campaign GPS, semipermanent GPS, and interferometric synthetic aperture radar observations, which leverage the accumulation of displacements over time to improve signal to noise. Deformation source mechanisms in the Cascades are diverse and include magma accumulation and withdrawal, post-emplacement cooling of recent volcanic deposits, magmatic

Gene regulation by MAP kinase cascades

DEFF Research Database (Denmark)

Fiil, Berthe Katrine; Petersen, Klaus; Petersen, Morten

2009-01-01

Mitogen-activated protein kinase (MAPK) cascades are signaling modules that transduce extracellular stimuli to a range of cellular responses. Research in yeast and metazoans has shown that MAPK-mediated phosphorylation directly or indirectly regulates the activity of transcription factors. Plant ...

Activation of Signaling Cascades by Weak Extremely Low Frequency Electromagnetic Fields

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Einat Kapri-Pardes

2017-10-01

Full Text Available Background/Aims: Results from recent studies suggest that extremely low frequency magnetic fields (ELF-MF interfere with intracellular signaling pathways related to proliferative control. The mitogen-activated protein kinases (MAPKs, central signaling components that regulate essentially all stimulated cellular processes, include the extracellular signal-regulated kinases 1/2 (ERK1/2 that are extremely sensitive to extracellular cues. Anti-phospho-ERK antibodies serve as a readout for ERK1/2 activation and are able to detect minute changes in ERK stimulation. The objective of this study was to explore whether activation of ERK1/2 and other signaling cascades can be used as a readout for responses of a variety of cell types, both transformed and non-transformed, to ELF-MF. Methods: We applied ELF-MF at various field strengths and time periods to eight different cell types with an exposure system housed in a tissue culture incubator and followed the phosphorylation of MAPKs and Akt by western blotting. Results: We found that the phosphorylation of ERK1/2 is increased in response to ELF-MF. However, the phosphorylation of ERK1/2 is likely too low to induce ELF-MF-dependent proliferation or oncogenic transformation. The p38 MAPK was very slightly phosphorylated, but JNK or Akt were not. The effect on ERK1/2 was detected for exposures to ELF-MF strengths as low as 0.15 µT and was maximal at ∼10 µT. We also show that ERK1/2 phosphorylation is blocked by the flavoprotein inhibitor diphenyleneiodonium, indicating that the response to ELF-MF may be exerted via NADP oxidase similar to the phosphorylation of ERK1/2 in response to microwave radiation. Conclusions: Our results further indicate that cells are responsive to ELF-MF at field strengths much lower than previously suspected and that the effect may be mediated by NADP oxidase. However, the small increase in ERK1/2 phosphorylation is probably insufficient to affect proliferation and oncogenic

Metabolic and hormonal signatures in pre-manifest and manifest Huntington’s disease patients

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Rui eWang

2014-06-01

Full Text Available Huntington's disease (HD is an inherited neurodegenerative disorder typified by involuntary body movements, and psychiatric and cognitive abnormalities. Many HD patients also exhibit metabolic changes including progressive weight loss and appetite dysfunction. Here we have investigated metabolic function in pre-manifest and manifest HD subjects to establish an HD subject metabolic hormonal plasma signature. Individuals at risk for HD who have had predictive genetic testing showing the cytosine-adenine-guanine (CAG expansion causative of HD, but who do not yet present signs and symptoms sufficient for the diagnosis of manifest HD are said to be pre-manifest. Pre-manifest and manifest HD patients, as well as both familial and non-familial controls, were evaluated for multiple peripheral metabolism signals including circulating levels of hormones, growth factors, lipids and cytokines. Both pre-manifest and manifest HD subjects exhibited significantly reduced levels of circulating growth factors, including growth hormone and prolactin. HD-related changes in the levels of metabolic hormones such as ghrelin, glucagon and amylin were also observed. Total cholesterol, HDL-C and LDL-C were significantly decreased in HD subjects. C-reactive protein was significantly elevated in pre-manifest HD subjects. The observation of metabolic alterations, even in subjects considered to be in the pre-manifest stage of HD, suggests that in addition, and prior, to overt neuronal damage, HD affects metabolic hormone secretion and energy regulation, which may shed light on pathogenesis, and provide opportunities for biomarker development.

Laminar shear flow increases hydrogen sulfide and activates a nitric oxide producing signaling cascade in endothelial cells.

Science.gov (United States)

Huang, Bin; Chen, Chang-Ting; Chen, Chi-Shia; Wang, Yun-Ming; Hsieh, Hsyue-Jen; Wang, Danny Ling

2015-09-04

Laminar shear flow triggers a signaling cascade that maintains the integrity of endothelial cells (ECs). Hydrogen sulfide (H2S), a new gasotransmitter is regarded as an upstream regulator of nitric oxide (NO). Whether the H2S-generating enzymes are correlated to the enzymes involved in NO production under shear flow conditions remains unclear as yet. In the present study, the cultured ECs were subjected to a constant shear flow (12 dyn/cm(2)) in a parallel flow chamber system. We investigated the expression of three key enzymes for H2S biosynthesis, cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercapto-sulfurtransferase (3-MST). Shear flow markedly increased the level of 3-MST. Shear flow enhanced the production of H2S was determined by NBD-SCN reagent that can bind to cysteine/homocystein. Exogenous treatment of NaHS that can release gaseous H2S, ECs showed an increase of phosphorylation in Akt(S473), ERK(T202/Y204) and eNOS(S1177). This indicated that H2S can trigger the NO-production signaling cascade. Silencing of CSE, CBS and 3-MST genes by siRNA separately attenuated the phosphorylation levels of Akt(S473) and eNOS(S1177) under shear flow conditions. The particular mode of shear flow increased H2S production. The interplay between H2S and NO-generating enzymes were discussed in the present study. Copyright © 2015 Elsevier Inc. All rights reserved.

Hormonal Signaling Cascade during an Early-Adult Critical Period Required for Courtship Memory Retention in Drosophila.

Science.gov (United States)

Lee, Sang Soo; Ding, Yike; Karapetians, Natalie; Rivera-Perez, Crisalejandra; Noriega, Fernando Gabriel; Adams, Michael E

2017-09-25

Formation and expression of memories are critical for context-dependent decision making. In Drosophila, a courting male rejected by a mated female subsequently courts less avidly when paired with a virgin female, a behavioral modification attributed to "courtship memory." Here we show the critical role of hormonal state for maintenance of courtship memory. Ecdysis-triggering hormone (ETH) is essential for courtship memory through regulation of juvenile hormone (JH) levels in adult males. Reduction of JH levels via silencing of ETH signaling genes impairs short-term courtship memory, a phenotype rescuable by the JH analog methoprene. JH-deficit-induced memory impairment involves rapid decay rather than failure of memory acquisition. A critical period governs memory performance during the first 3 days of adulthood. Using sex-peptide-expressing "pseudo-mated" trainers, we find that robust courtship memory elicited in the absence of aversive chemical mating cues also is dependent on ETH-JH signaling. Finally, we find that JH acts through dopaminergic neurons and conclude that an ETH-JH-dopamine signaling cascade is required during a critical period for promotion of social-context-dependent memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

Activation of AMPA receptor promotes TNF-α release via the ROS-cSrc-NFκB signaling cascade in RAW264.7 macrophages

Energy Technology Data Exchange (ETDEWEB)

Cheng, Xiu-Li [Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing (China); Ding, Fan [Office of Scientific R& D, Tsinghua University, Beijing (China); Li, Hui; Tan, Xiao-Qiu [Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing (China); Liu, Xiao [Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing (China); Cao, Ji-Min, E-mail: caojimin@126.com [Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing (China); Gao, Xue, E-mail: longlongnose@163.com [Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing (China)

2015-05-29

The relationship between glutamate signaling and inflammation has not been well defined. This study aimed to investigate the role of AMPA receptor (AMPAR) in the expression and release of tumor necrosis factor-alpha (TNF-α) from macrophages and the underlying mechanisms. A series of approaches, including confocal microscopy, immunofluorescency, flow cytometry, ELISA and Western blotting, were used to estimate the expression of AMPAR and downstream signaling molecules, TNF-α release and reactive oxygen species (ROS) generation in the macrophage-like RAW264.7 cells. The results demonstrated that AMPAR was expressed in RAW264.7 cells. AMPA significantly enhanced TNF-α release from RAW264.7 cells, and this effect was abolished by CNQX (AMPAR antagonist). AMPA also induced elevation of ROS production, phosphorylation of c-Src and activation of nuclear factor (NF)-κB in RAW264.7 cells. Blocking c-Src by PP2, scavenging ROS by glutathione (GSH) or inhibiting NF-κB activation by pyrrolidine dithiocarbamate (PDTC) decreased TNF-α production from RAW264.7 cells. We concluded that AMPA promotes TNF-α release in RAW264.7 macrophages likely through the following signaling cascade: AMPAR activation → ROS generation → c-Src phosphorylation → NF-κB activation → TNF-α elevation. The study suggests that AMPAR may participate in macrophage activation and inflammation. - Highlights: • AMPAR is expressed in RAW264.7 macrophages and is upregulated by AMPA stimulation. • Activation of AMPAR stimulates TNF-α release in macrophages through the ROS-cSrc-NFκB signaling cascade. • Macrophage AMPAR signaling may play an important role in inflammation.

Therapeutic peptides for cancer therapy. Part I - peptide inhibitors of signal transduction cascades.

Science.gov (United States)

Bidwell, Gene L; Raucher, Drazen

2009-10-01

Therapeutic peptides have great potential as anticancer agents owing to their ease of rational design and target specificity. However, their utility in vivo is limited by low stability and poor tumor penetration. The authors review the development of peptide inhibitors with potential for cancer therapy. Peptides that inhibit signal transduction cascades are discussed. The authors searched Medline for articles concerning the development of therapeutic peptides and their delivery. Given our current knowledge of protein sequences, structures and interaction interfaces, therapeutic peptides that inhibit interactions of interest are easily designed. These peptides are advantageous because they are highly specific for the interaction of interest, and they are much more easily developed than small molecule inhibitors of the same interactions. The main hurdle to application of peptides for cancer therapy is their poor pharmacokinetic and biodistribution parameters. Therefore, successful development of peptide delivery vectors could potentially make possible the use of this new and very promising class of anticancer agents.

Beyond KNO multiplicative cascades and novel multiplicity scaling laws

CERN Document Server

Hegyi, S

1999-01-01

The collapse of multiplicity distributions P/sub n/ onto a universal scaling curve arises when P/sub n/ is expressed as a function of the standardized multiplicity (n-c)/ lambda with c and lambda being location and scale parameters governed by leading particle effects and the growth of average multiplicity. It is demonstrated that self- similar multiplicative cascade processes such as QCD parton branching naturally lead to a novel type of scaling behavior of P/sub n/ which manifests itself in Mellin space through a location change controlled by the degree of multifractality and a scale change governed by the depth of the cascade. Applying the new scaling rule it is shown how to restore data collapsing behavior of P/sub n/ measured in hh collisions at ISR and SPS energies. (21 refs).

The C-terminal tail of CRTH2 is a key molecular determinant that constrains GalphaI- and downstream-signaling cascade activation

DEFF Research Database (Denmark)

Schroeder, Ralf; Merten, Nicole; Mathiesen, Jesper Mosolff

2009-01-01

Prostaglandin D(2) activation of the seven transmembrane receptor CRTH2 regulates numerous cell functions that are important in inflammatory diseases such as asthma. Despite its disease implication, no studies to date aimed at identifying receptor domains governing signaling and surface expression......2 at the plasma membrane, presence of this domain confers a signaling-compromised conformation onto the receptor. Indeed, a mutant receptor lacking the major portion of its C-terminal tail displays paradoxically enhanced Galphai and ERK1/2 activation in spite of enhanced constitutive and agonist......-mediated internalization. Enhanced activation of Galphai proteins and downstream signaling cascades is likely due to the inability of the tail-truncated receptor to recruit beta-arrestin2 and undergo homologous desensitization. Unexpectedly, CRTH2 is not phosphorylated upon agonist-stimulation, a primary mechanism...

Cascade Structure of Digital Predistorter for Power Amplifier Linearization

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E. B. Solovyeva

2015-12-01

Full Text Available In this paper, a cascade structure of nonlinear digital predistorter (DPD synthesized by the direct learning adaptive algorithm is represented. DPD is used for linearization of power amplifier (PA characteristic, namely for compensation of PA nonlinear distortion. Blocks of the cascade DPD are described by different models: the functional link artificial neural network (FLANN, the polynomial perceptron network (PPN and the radially pruned Volterra model (RPVM. At synthesis of the cascade DPD there is possibility to overcome the ill conditionality problem due to reducing the dimension of DPD nonlinear operator approximation. Results of compensating nonlinear distortion in Wiener–Hammerstein model of PA at the GSM–signal with four carriers are shown. The highest accuracy of PA linearization is produced by the cascade DPD containing PPN and RPVM.

Peroxisome Proliferator-Activated Receptor-γ Ligands: Potential Pharmacological Agents for Targeting the Angiogenesis Signaling Cascade in Cancer

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Costas Giaginis

2008-01-01

Full Text Available Peroxisome proliferator-activated receptor-γ (PPAR-γ has currently been considered as molecular target for the treatment of human metabolic disorders. Experimental data from in vitro cultures, animal models, and clinical trials have shown that PPAR-γ ligand activation regulates differentiation and induces cell growth arrest and apoptosis in a variety of cancer types. Tumor angiogenesis constitutes a multifaceted process implicated in complex downstream signaling pathways that triggers tumor growth, invasion, and metastasis. In this aspect, accumulating in vitro and in vivo studies have provided extensive evidence that PPAR-γ ligands can function as modulators of the angiogenic signaling cascade. In the current review, the crucial role of PPAR-γ ligands and the underlying mechanisms participating in tumor angiogenesis are summarized. Targeting PPAR-γ may prove to be a potential therapeutic strategy in combined treatments with conventional chemotherapy; however, special attention should be taken as there is also substantial evidence to support that PPAR-γ ligands can enhance angiogenic phenotype in tumoral cells.

Isorhynchophylline, a Potent Plant Alkaloid, Induces Apoptotic and Anti-Metastatic Effects in Human Hepatocellular Carcinoma Cells through the Modulation of Diverse Cell Signaling Cascades.

Science.gov (United States)

Lee, Hanwool; Baek, Seung Ho; Lee, Jong Hyun; Kim, Chulwon; Ko, Jeong-Hyeon; Lee, Seok-Geun; Chinnathambi, Arunachalam; Alharbi, Sulaiman Ali; Yang, Woong Mo; Um, Jae-Young; Sethi, Gautam; Ahn, Kwang Seok

2017-05-19

Isorhynchophylline (Rhy) is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma. Rhy induced apoptosis as characterized by accumulation of cells in sub G1 phase; positive Annexin V binding; activation of caspase-8, -9, and -3; and cleavage of PARP (poly-ADP ribose polymerase). This effect of Rhy correlated with the down-regulation of various proteins that mediated cell proliferation, cell survival, metastasis, and angiogenesis. Moreover, cell proliferation, migration, and constitutive CXCR4 (C-X-C chemokine receptor type 4), MMP-9 (Matrix metallopeptidase-9), and MMP-2 expression were inhibited upon Rhy treatment. We further investigated the effect of Rhy on the oncogenic cell signaling cascades through phospho-kinase array profiling assay. Rhy was found to abrogate phospho-p38, ERK, JNK, CREB, c-Jun, Akt, and STAT3 signals, but interestingly enhanced phospho-p53 signal. Overall, our results indicate, for the first time, that Rhy could exert anticancer and anti-metastatic effects through regulation of multiple signaling cascades in hepatocellular carcinoma cells.

Experimental investigation of the cascadability of a cross-gain modulation wavelength converter

DEFF Research Database (Denmark)

Zheng, Xueyan; Liu, Fenghai; Kloch, Allan

2000-01-01

by adding a fiber grating-based optical add-drop multiplexer after the semiconductor optical amplifier (SOA) to enhance the high-frequency response of the wavelength converter. However, the low-frequency degradation of the signal together with amplified spontaneous emission (ASE) noise and jitter......The cascading characteristics of a wavelength converter based on cross-gain modulation (XGM) are studied experimentally using a recirculating loop at 10 Gb/s. The maximum cascaded number of the wavelength converter converting the signal to the same wavelength is improved from five to eight...

L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade

KAUST Repository

Jourdain, P.

2016-02-19

Converging experimental data indicate a neuroprotective action of L-Lactate. Using Digital Holographic Microscopy, we observe that transient application of glutamate (100 μM; 2 min) elicits a NMDA-dependent death in 65% of mouse cortical neurons in culture. In the presence of L-Lactate (or Pyruvate), the percentage of neuronal death decreases to 32%. UK5099, a blocker of the Mitochondrial Pyruvate Carrier, fully prevents L-Lactate-mediated neuroprotection. In addition, L-Lactate-induced neuroprotection is not only inhibited by probenicid and carbenoxolone, two blockers of ATP channel pannexins, but also abolished by apyrase, an enzyme degrading ATP, suggesting that ATP produced by the Lactate/Pyruvate pathway is released to act on purinergic receptors in an autocrine/paracrine manner. Finally, pharmacological approaches support the involvement of the P2Y receptors associated to the PI3-kinase pathway, leading to activation of KATP channels. This set of results indicates that L-Lactate acts as a signalling molecule for neuroprotection against excitotoxicity through coordinated cellular pathways involving ATP production, release and activation of a P2Y/KATP cascade.

L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade

KAUST Repository

Jourdain, P.; Allaman, I.; Rothenfusser, K.; Fiumelli, Hubert; Marquet, P.; Magistretti, Pierre J.

2016-01-01

Converging experimental data indicate a neuroprotective action of L-Lactate. Using Digital Holographic Microscopy, we observe that transient application of glutamate (100 μM; 2 min) elicits a NMDA-dependent death in 65% of mouse cortical neurons in culture. In the presence of L-Lactate (or Pyruvate), the percentage of neuronal death decreases to 32%. UK5099, a blocker of the Mitochondrial Pyruvate Carrier, fully prevents L-Lactate-mediated neuroprotection. In addition, L-Lactate-induced neuroprotection is not only inhibited by probenicid and carbenoxolone, two blockers of ATP channel pannexins, but also abolished by apyrase, an enzyme degrading ATP, suggesting that ATP produced by the Lactate/Pyruvate pathway is released to act on purinergic receptors in an autocrine/paracrine manner. Finally, pharmacological approaches support the involvement of the P2Y receptors associated to the PI3-kinase pathway, leading to activation of KATP channels. This set of results indicates that L-Lactate acts as a signalling molecule for neuroprotection against excitotoxicity through coordinated cellular pathways involving ATP production, release and activation of a P2Y/KATP cascade.

Isorhynchophylline, a Potent Plant Alkaloid, Induces Apoptotic and Anti-Metastatic Effects in Human Hepatocellular Carcinoma Cells through the Modulation of Diverse Cell Signaling Cascades

Directory of Open Access Journals (Sweden)

Hanwool Lee

2017-05-01

Full Text Available Isorhynchophylline (Rhy is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma. Rhy induced apoptosis as characterized by accumulation of cells in sub G1 phase; positive Annexin V binding; activation of caspase-8, -9, and -3; and cleavage of PARP (poly-ADP ribose polymerase. This effect of Rhy correlated with the down-regulation of various proteins that mediated cell proliferation, cell survival, metastasis, and angiogenesis. Moreover, cell proliferation, migration, and constitutive CXCR4 (C-X-C chemokine receptor type 4, MMP-9 (Matrix metallopeptidase-9, and MMP-2 expression were inhibited upon Rhy treatment. We further investigated the effect of Rhy on the oncogenic cell signaling cascades through phospho-kinase array profiling assay. Rhy was found to abrogate phospho-p38, ERK, JNK, CREB, c-Jun, Akt, and STAT3 signals, but interestingly enhanced phospho-p53 signal. Overall, our results indicate, for the first time, that Rhy could exert anticancer and anti-metastatic effects through regulation of multiple signaling cascades in hepatocellular carcinoma cells.

Isorhynchophylline, a Potent Plant Alkaloid, Induces Apoptotic and Anti-Metastatic Effects in Human Hepatocellular Carcinoma Cells through the Modulation of Diverse Cell Signaling Cascades

Science.gov (United States)

Lee, Hanwool; Baek, Seung Ho; Lee, Jong Hyun; Kim, Chulwon; Ko, Jeong-Hyeon; Lee, Seok-Geun; Chinnathambi, Arunachalam; Alharbi, Sulaiman Ali; Yang, Woong Mo; Um, Jae-Young; Sethi, Gautam; Ahn, Kwang Seok

2017-01-01

Isorhynchophylline (Rhy) is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma. Rhy induced apoptosis as characterized by accumulation of cells in sub G1 phase; positive Annexin V binding; activation of caspase-8, -9, and -3; and cleavage of PARP (poly-ADP ribose polymerase). This effect of Rhy correlated with the down-regulation of various proteins that mediated cell proliferation, cell survival, metastasis, and angiogenesis. Moreover, cell proliferation, migration, and constitutive CXCR4 (C-X-C chemokine receptor type 4), MMP-9 (Matrix metallopeptidase-9), and MMP-2 expression were inhibited upon Rhy treatment. We further investigated the effect of Rhy on the oncogenic cell signaling cascades through phospho-kinase array profiling assay. Rhy was found to abrogate phospho-p38, ERK, JNK, CREB, c-Jun, Akt, and STAT3 signals, but interestingly enhanced phospho-p53 signal. Overall, our results indicate, for the first time, that Rhy could exert anticancer and anti-metastatic effects through regulation of multiple signaling cascades in hepatocellular carcinoma cells. PMID:28534824

Sex differences in behavioral and PKA cascade responses to repeated cocaine administration.

Science.gov (United States)

Zhou, Luyi; Sun, Wei-Lun; Weierstall, Karen; Minerly, Ana Christina; Weiner, Jan; Jenab, Shirzad; Quinones-Jenab, Vanya

2016-10-01

Previous studies have shown sex different patterns in behavioral responses to cocaine. Here, we used between-subject experiment design to study whether sex differences exist in the development of behavioral sensitization and tolerance to repeated cocaine, as well as the role of protein kinase A (PKA) signaling cascade in this process. Ambulatory and rearing responses were recorded in male and female rats after 1 to 14 days of administration of saline or cocaine (15 mg/kg; ip). Correspondent PKA-associated signaling in the nucleus accumbens (NAc) and caudate-putamen (CPu) was measured at each time point. Our results showed that females exhibited higher cocaine-induced behavioral responses and developed behavioral sensitization and tolerance faster than males. Whereas females developed behavioral sensitization to cocaine after 2 days and tolerance after 14 days, male rats developed sensitization after 5 days. In addition, cocaine induced a sexual dimorphic pattern in the progression of neuronal adaptations on the PKA cascade signaling in region (NAc vs. CPu) and time (days of cocaine administration)-dependent manners. In general, more PKA signaling cascade changes were found in the NAc of males on day 5 and in the CPu of females with repeated cocaine injection. In addition, in females, behavioral activities positively correlated with FosB levels in the NAc and CPu and negatively correlated with Cdk5 and p35 in the CPu, while no correlation was observed in males. Our studies suggest that repeated cocaine administration induced different patterns of behavioral and molecular responses in the PKA cascade in male and female rats.

Reactive oxygen species and hormone signaling cascades in endophytic bacterium induced essential oil accumulation in Atractylodes lancea.

Science.gov (United States)

Zhou, Jia-Yu; Li, Xia; Zhao, Dan; Deng-Wang, Meng-Yao; Dai, Chuan-Chao

2016-09-01

Pseudomonas fluorescens induces gibberellin and ethylene signaling via hydrogen peroxide in planta . Ethylene activates abscisic acid signaling. Hormones increase sesquiterpenoid biosynthesis gene expression and enzyme activity, inducing essential oil accumulation. Atractylodes lancea is a famous Chinese medicinal plant, whose main active components are essential oils. Wild A. lancea has become endangered due to habitat destruction and over-exploitation. Although cultivation can ensure production of the medicinal material, the essential oil content in cultivated A. lancea is significantly lower than that in the wild herb. The application of microbes as elicitors has become an effective strategy to increase essential oil accumulation in cultivated A. lancea. Our previous study identified an endophytic bacterium, Pseudomonas fluorescens ALEB7B, which can increase essential oil accumulation in A. lancea more efficiently than other endophytes; however, the underlying mechanisms remain unknown (Physiol Plantarum 153:30-42, 2015; Appl Environ Microb 82:1577-1585, 2016). This study demonstrates that P. fluorescens ALEB7B firstly induces hydrogen peroxide (H2O2) signaling in A. lancea, which then simultaneously activates gibberellin (GA) and ethylene (ET) signaling. Subsequently, ET activates abscisic acid (ABA) signaling. GA and ABA signaling increase expression of HMGR and DXR, which encode key enzymes involved in sesquiterpenoid biosynthesis, leading to increased levels of the corresponding enzymes and then an accumulation of essential oils. Specific reactive oxygen species and hormone signaling cascades induced by P. fluorescens ALEB7B may contribute to high-efficiency essential oil accumulation in A. lancea. Illustrating the regulation mechanisms underlying P. fluorescens ALEB7B-induced essential oil accumulation not only provides the theoretical basis for the inducible synthesis of terpenoids in many medicinal plants, but also further reveals the complex and diverse

Determinants of cell-to-cell variability in protein kinase signaling.

Science.gov (United States)

Jeschke, Matthias; Baumgärtner, Stephan; Legewie, Stefan

2013-01-01

Cells reliably sense environmental changes despite internal and external fluctuations, but the mechanisms underlying robustness remain unclear. We analyzed how fluctuations in signaling protein concentrations give rise to cell-to-cell variability in protein kinase signaling using analytical theory and numerical simulations. We characterized the dose-response behavior of signaling cascades by calculating the stimulus level at which a pathway responds ('pathway sensitivity') and the maximal activation level upon strong stimulation. Minimal kinase cascades with gradual dose-response behavior show strong variability, because the pathway sensitivity and the maximal activation level cannot be simultaneously invariant. Negative feedback regulation resolves this trade-off and coordinately reduces fluctuations in the pathway sensitivity and maximal activation. Feedbacks acting at different levels in the cascade control different aspects of the dose-response curve, thereby synergistically reducing the variability. We also investigated more complex, ultrasensitive signaling cascades capable of switch-like decision making, and found that these can be inherently robust to protein concentration fluctuations. We describe how the cell-to-cell variability of ultrasensitive signaling systems can be actively regulated, e.g., by altering the expression of phosphatase(s) or by feedback/feedforward loops. Our calculations reveal that slow transcriptional negative feedback loops allow for variability suppression while maintaining switch-like decision making. Taken together, we describe design principles of signaling cascades that promote robustness. Our results may explain why certain signaling cascades like the yeast pheromone pathway show switch-like decision making with little cell-to-cell variability.

Optimal structural inference of signaling pathways from unordered and overlapping gene sets.

Science.gov (United States)

Acharya, Lipi R; Judeh, Thair; Wang, Guangdi; Zhu, Dongxiao

2012-02-15

A plethora of bioinformatics analysis has led to the discovery of numerous gene sets, which can be interpreted as discrete measurements emitted from latent signaling pathways. Their potential to infer signaling pathway structures, however, has not been sufficiently exploited. Existing methods accommodating discrete data do not explicitly consider signal cascading mechanisms that characterize a signaling pathway. Novel computational methods are thus needed to fully utilize gene sets and broaden the scope from focusing only on pairwise interactions to the more general cascading events in the inference of signaling pathway structures. We propose a gene set based simulated annealing (SA) algorithm for the reconstruction of signaling pathway structures. A signaling pathway structure is a directed graph containing up to a few hundred nodes and many overlapping signal cascades, where each cascade represents a chain of molecular interactions from the cell surface to the nucleus. Gene sets in our context refer to discrete sets of genes participating in signal cascades, the basic building blocks of a signaling pathway, with no prior information about gene orderings in the cascades. From a compendium of gene sets related to a pathway, SA aims to search for signal cascades that characterize the optimal signaling pathway structure. In the search process, the extent of overlap among signal cascades is used to measure the optimality of a structure. Throughout, we treat gene sets as random samples from a first-order Markov chain model. We evaluated the performance of SA in three case studies. In the first study conducted on 83 KEGG pathways, SA demonstrated a significantly better performance than Bayesian network methods. Since both SA and Bayesian network methods accommodate discrete data, use a 'search and score' network learning strategy and output a directed network, they can be compared in terms of performance and computational time. In the second study, we compared SA and

Penalty-free transmission at 10 Gbit/s through 40 cascaded 1-nm arrayed waveguide multiplexers

DEFF Research Database (Denmark)

Nissov, Morten; Jørgensen, Bo Foged; Pedersen, Rune Johan Skullerud

1997-01-01

Cascaded optical add-drop multiplexers (OADM) and optical cross connects (OXC) are key components in optical wavelength-division multiplex networks. OADMs with filtering of the passing signals and OXCs can be constructed by the use of wavelength-division multiplexers. Cascadability of multiplexers...

Porous platinum nanotubes labeled with hemin/G-quadruplex based electrochemical aptasensor for sensitive thrombin analysis via the cascade signal amplification.

Science.gov (United States)

Sun, Aili; Qi, Qingan; Wang, Xuannian; Bie, Ping

2014-07-15

For the first time, a sensitive electrochemical aptasensor for thrombin (TB) was developed by using porous platinum nanotubes (PtNTs) labeled with hemin/G-quadruplex and glucose dehydrogenase (GDH) as labels. Porous PtNTs with large surface area exhibited the peroxidase-like activity. Coupling with GDH and hemin/G-quadruplex as NADH oxidase and HRP-mimicking DNAzyme, the cascade signal amplification was achieved by the following ways: in the presence of glucose and NAD(+) in the working buffer, GDH electrocatalyzed the oxidation of glucose with the production of NADH. Then, hemin/G-quadruplex as NADH oxidase catalyzed the oxidation of NADH to in situ generate H2O2. Based on the corporate electrocatalysis of PtNTs and hemin/G-quadruplex toward H2O2, the electrochemical signal was significantly amplified, allowing the detection limit of TB down to 0.15 pM level. Moreover, the proposed strategy was simple because the intercalated hemin offered the readout signal, avoiding the adding of additional redox mediator as signal donator. Such an electrochemical aptasensor is highly promising for sensitive detection of other proteins in clinical diagnostics. Copyright © 2014 Elsevier B.V. All rights reserved.

The cascaded amplifier and saturable absorber (CASA) all-optical switch

DEFF Research Database (Denmark)

Hilliger, E.; Berger, J.; Weber, H. G.

2001-01-01

The cascaded amplifier and saturable absorber is presented as a new all-optical switching scheme for optical signal processing applications. First demultiplexing experiments demonstrate the principle of operation of this scheme....

An Arabidopsis kinase cascade influences auxin-responsive cell expansion.

Science.gov (United States)

Enders, Tara A; Frick, Elizabeth M; Strader, Lucia C

2017-10-01

Mitogen-activated protein kinase (MPK) cascades are conserved mechanisms of signal transduction across eukaryotes. Despite the importance of MPK proteins in signaling events, specific roles for many Arabidopsis MPK proteins remain unknown. Multiple studies have suggested roles for MPK signaling in a variety of auxin-related processes. To identify MPK proteins with roles in auxin response, we screened mpk insertional alleles and identified mpk1-1 as a mutant that displays hypersensitivity in auxin-responsive cell expansion assays. Further, mutants defective in the upstream MAP kinase kinase MKK3 also display hypersensitivity in auxin-responsive cell expansion assays, suggesting that this MPK cascade affects auxin-influenced cell expansion. We found that MPK1 interacts with and phosphorylates ROP BINDING PROTEIN KINASE 1 (RBK1), a protein kinase that interacts with members of the Rho-like GTPases from Plants (ROP) small GTPase family. Similar to mpk1-1 and mkk3-1 mutants, rbk1 insertional mutants display auxin hypersensitivity, consistent with a possible role for RBK1 downstream of MPK1 in influencing auxin-responsive cell expansion. We found that RBK1 directly phosphorylates ROP4 and ROP6, supporting the possibility that RBK1 effects on auxin-responsive cell expansion are mediated through phosphorylation-dependent modulation of ROP activity. Our data suggest a MKK3 • MPK1 • RBK1 phosphorylation cascade that may provide a dynamic module for altering cell expansion. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Determinants of cell-to-cell variability in protein kinase signaling.

Directory of Open Access Journals (Sweden)

Matthias Jeschke

Full Text Available Cells reliably sense environmental changes despite internal and external fluctuations, but the mechanisms underlying robustness remain unclear. We analyzed how fluctuations in signaling protein concentrations give rise to cell-to-cell variability in protein kinase signaling using analytical theory and numerical simulations. We characterized the dose-response behavior of signaling cascades by calculating the stimulus level at which a pathway responds ('pathway sensitivity' and the maximal activation level upon strong stimulation. Minimal kinase cascades with gradual dose-response behavior show strong variability, because the pathway sensitivity and the maximal activation level cannot be simultaneously invariant. Negative feedback regulation resolves this trade-off and coordinately reduces fluctuations in the pathway sensitivity and maximal activation. Feedbacks acting at different levels in the cascade control different aspects of the dose-response curve, thereby synergistically reducing the variability. We also investigated more complex, ultrasensitive signaling cascades capable of switch-like decision making, and found that these can be inherently robust to protein concentration fluctuations. We describe how the cell-to-cell variability of ultrasensitive signaling systems can be actively regulated, e.g., by altering the expression of phosphatase(s or by feedback/feedforward loops. Our calculations reveal that slow transcriptional negative feedback loops allow for variability suppression while maintaining switch-like decision making. Taken together, we describe design principles of signaling cascades that promote robustness. Our results may explain why certain signaling cascades like the yeast pheromone pathway show switch-like decision making with little cell-to-cell variability.

Method and apparatus for rapid adjustment of process gas inventory in gaseous diffusion cascades

International Nuclear Information System (INIS)

1980-01-01

A method is specified for the operation of a gaseous diffusion cascade wherein electrically driven compressors circulate a process gas through a plurality of serially connected gaseous diffusion stages to establish first and second countercurrently flowing cascade streams of process gas, one of the streams being at a relatively low pressure and enriched in a component of the process gas and the other being at a higher pressure and depleted in the same, and wherein automatic control systems maintain the stage process gas pressures by positioning process gas flow control valve openings at values which are functions of the difference between reference-signal inputs to the systems, and signal inputs proportional to the process gas pressures in the gaseous diffusion stages associated with the systems, the cascade process gas inventory being altered, while the cascade is operating, by simultaneously directing into separate process-gas freezing zones a plurality of substreams derived from one of the first and second streams at different points along the lengths thereof to solidify approximately equal weights of process gas in the zone while reducing the reference-signal inputs to maintain the positions of the control valves substantially unchanged despite the removal of process gas inventory via the substreams. (author)

Fatty acid 16:4(n-3) stimulates a GPR120-induced signaling cascade in splenic macrophages to promote chemotherapy resistance

DEFF Research Database (Denmark)

Houthuijzen, Julia M; Oosterom, Ilse; Hudson, Brian D

2017-01-01

Although chemotherapy is designed to eradicate tumor cells, it also has significant effects on normal tissues. The platinum-induced fatty acid 16:4(n-3) (hexadeca-4,7,10,13-tetraenoic acid) induces systemic resistance to a broad range of DNA-damaging chemotherapeutics. We show that 16:4(n-3) exerts....... M., Peeper, D. S., Jafari Sadatmand, S., Roodhart, J. M. L., van de Lest, C. H. A., Ulven, T., Ishihara, K., Milligan, G., Voest, E. E. Fatty acid 16:4(n-3) stimulates a GPR120-induced signaling cascade in splenic macrophages to promote chemotherapy resistance....

Transmembrane signaling in Saccharomyces cerevisiae as a model for signaling in metazoans: state of the art after 25 years.

Science.gov (United States)

Engelberg, David; Perlman, Riki; Levitzki, Alexander

2014-12-01

In the very first article that appeared in Cellular Signalling, published in its inaugural issue in October 1989, we reviewed signal transduction pathways in Saccharomyces cerevisiae. Although this yeast was already a powerful model organism for the study of cellular processes, it was not yet a valuable instrument for the investigation of signaling cascades. In 1989, therefore, we discussed only two pathways, the Ras/cAMP and the mating (Fus3) signaling cascades. The pivotal findings concerning those pathways undoubtedly contributed to the realization that yeast is a relevant model for understanding signal transduction in higher eukaryotes. Consequently, the last 25 years have witnessed the discovery of many signal transduction pathways in S. cerevisiae, including the high osmotic glycerol (Hog1), Stl2/Mpk1 and Smk1 mitogen-activated protein (MAP) kinase pathways, the TOR, AMPK/Snf1, SPS, PLC1 and Pkr/Gcn2 cascades, and systems that sense and respond to various types of stress. For many cascades, orthologous pathways were identified in mammals following their discovery in yeast. Here we review advances in the understanding of signaling in S. cerevisiae over the last 25 years. When all pathways are analyzed together, some prominent themes emerge. First, wiring of signaling cascades may not be identical in all S. cerevisiae strains, but is probably specific to each genetic background. This situation complicates attempts to decipher and generalize these webs of reactions. Secondly, the Ras/cAMP and the TOR cascades are pivotal pathways that affect all processes of the life of the yeast cell, whereas the yeast MAP kinase pathways are not essential. Yeast cells deficient in all MAP kinases proliferate normally. Another theme is the existence of central molecular hubs, either as single proteins (e.g., Msn2/4, Flo11) or as multisubunit complexes (e.g., TORC1/2), which are controlled by numerous pathways and in turn determine the fate of the cell. It is also apparent that

Defect production in simulated cascades: Cascade quenching and short-term annealing

International Nuclear Information System (INIS)

Heinisch, H.L.

1983-01-01

Defect production in displacement cascades in copper has been modeled using the MARLOWE code to generate cascades and the stochastic annealing code ALSOME to simulate cascade quenching and short-term annealing of isolated cascades. Quenching is accomplished by using exaggerated values for defect mobilities and for critical reaction distances in ALSOME for a very short time. The quenched cascades are then short-term annealed with normal parameter values. The quenching parameter values were empirically determined by comparison with results of resistivity measurements. Throughout the collisional, quenching and short-term annealing phases of cascade development, the high energy cascades continue to behave as a collection of independent lower energy lobes. For recoils above about 30 keV the total number of defects and the numbers of free defects scale with the damage energy. As the energy decreases from 30 keV, defect production varies with the changing nature of the cascade configuration, resulting in more defects per unit damage energy. The simulated annealing of a low fluence of interacting cascades revealed an interstitial shielding effect on depleted zones during Stage I recovery. (orig.)

A non-conventional isotope separation cascade without any mixing: net cascade

International Nuclear Information System (INIS)

Zeng Shi; Jiang Dongjun; Ying Zhengen

2012-01-01

A component has different concentrations in the incoming flows at a confluent point in all existing isotope separations cascades for multi-component isotope separation and mixing is inevitable, which results in deterioration of separation performance of the separation cascade. However, realization of no-mixing at a confluent point is impossible with a conventional cascade. A non-conventional isotope separation cascade, net cascade, is found to be able to realize no mixings for all components at confluent points, and its concept is further developed here. No-mixing is fulfilled by requiring symmetrical separation of two specified key components at every stage, and the procedure of realizing no-mixing is presented in detail. Some properties of net cascade are investigated preliminarily, and the results demonstrated the no-mixing property is indeed realized. Net cascade is the only separation cascade that so far possesses the no-mixing property. (authors)

Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade.

Science.gov (United States)

Dumoulin, Alexandre; Ter-Avetisyan, Gohar; Schmidt, Hannes; Rathjen, Fritz G

2018-04-24

Axonal branching is a key process in the establishment of circuit connectivity within the nervous system. Molecular-genetic studies have shown that a specific form of axonal branching—the bifurcation of sensory neurons at the transition zone between the peripheral and the central nervous system—is regulated by a cyclic guanosine monophosphate (cGMP)-dependent signaling cascade which is composed of C-type natriuretic peptide (CNP), the receptor guanylyl cyclase Npr2, and cGMP-dependent protein kinase Iα (cGKIα). In the absence of any one of these components, neurons in dorsal root ganglia (DRG) and cranial sensory ganglia no longer bifurcate, and instead turn in either an ascending or a descending direction. In contrast, collateral axonal branch formation which represents a second type of axonal branch formation is not affected by inactivation of CNP, Npr2, or cGKI. Whereas axon bifurcation was lost in mouse mutants deficient for components of CNP-induced cGMP formation; the absence of the cGMP-degrading enzyme phosphodiesterase 2A had no effect on axon bifurcation. Adult mice that lack sensory axon bifurcation due to the conditional inactivation of Npr2-mediated cGMP signaling in DRG neurons demonstrated an altered shape of sensory axon terminal fields in the spinal cord, indicating that elaborate compensatory mechanisms reorganize neuronal circuits in the absence of bifurcation. On a functional level, these mice showed impaired heat sensation and nociception induced by chemical irritants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are normal. These data point to a critical role of axon bifurcation for the processing of acute pain perception.

Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade

Directory of Open Access Journals (Sweden)

Alexandre Dumoulin

2018-04-01

Full Text Available Axonal branching is a key process in the establishment of circuit connectivity within the nervous system. Molecular-genetic studies have shown that a specific form of axonal branching—the bifurcation of sensory neurons at the transition zone between the peripheral and the central nervous system—is regulated by a cyclic guanosine monophosphate (cGMP-dependent signaling cascade which is composed of C-type natriuretic peptide (CNP, the receptor guanylyl cyclase Npr2, and cGMP-dependent protein kinase Iα (cGKIα. In the absence of any one of these components, neurons in dorsal root ganglia (DRG and cranial sensory ganglia no longer bifurcate, and instead turn in either an ascending or a descending direction. In contrast, collateral axonal branch formation which represents a second type of axonal branch formation is not affected by inactivation of CNP, Npr2, or cGKI. Whereas axon bifurcation was lost in mouse mutants deficient for components of CNP-induced cGMP formation; the absence of the cGMP-degrading enzyme phosphodiesterase 2A had no effect on axon bifurcation. Adult mice that lack sensory axon bifurcation due to the conditional inactivation of Npr2-mediated cGMP signaling in DRG neurons demonstrated an altered shape of sensory axon terminal fields in the spinal cord, indicating that elaborate compensatory mechanisms reorganize neuronal circuits in the absence of bifurcation. On a functional level, these mice showed impaired heat sensation and nociception induced by chemical irritants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are normal. These data point to a critical role of axon bifurcation for the processing of acute pain perception.

Fast subcellular localization by cascaded fusion of signal-based and homology-based methods

Directory of Open Access Journals (Sweden)

Wang Wei

2011-10-01

Full Text Available Abstract Background The functions of proteins are closely related to their subcellular locations. In the post-genomics era, the amount of gene and protein data grows exponentially, which necessitates the prediction of subcellular localization by computational means. Results This paper proposes mitigating the computation burden of alignment-based approaches to subcellular localization prediction by a cascaded fusion of cleavage site prediction and profile alignment. Specifically, the informative segments of protein sequences are identified by a cleavage site predictor using the information in their N-terminal shorting signals. Then, the sequences are truncated at the cleavage site positions, and the shortened sequences are passed to PSI-BLAST for computing their profiles. Subcellular localization are subsequently predicted by a profile-to-profile alignment support-vector-machine (SVM classifier. To further reduce the training and recognition time of the classifier, the SVM classifier is replaced by a new kernel method based on the perturbational discriminant analysis (PDA. Conclusions Experimental results on a new dataset based on Swiss-Prot Release 57.5 show that the method can make use of the best property of signal- and homology-based approaches and can attain an accuracy comparable to that achieved by using full-length sequences. Analysis of profile-alignment score matrices suggest that both profile creation time and profile alignment time can be reduced without significant reduction in subcellular localization accuracy. It was found that PDA enjoys a short training time as compared to the conventional SVM. We advocate that the method will be important for biologists to conduct large-scale protein annotation or for bioinformaticians to perform preliminary investigations on new algorithms that involve pairwise alignments.

Superradiant cascade emissions in an atomic ensemble via four-wave mixing

Energy Technology Data Exchange (ETDEWEB)

Jen, H.H., E-mail: sappyjen@gmail.com

2015-09-15

We investigate superradiant cascade emissions from an atomic ensemble driven by two-color classical fields. The correlated pair of photons (signal and idler) is generated by adiabatically driving the system with large-detuned light fields via four-wave mixing. The signal photon from the upper transition of the diamond-type atomic levels is followed by the idler one which can be superradiant due to light-induced dipole–dipole interactions. We then calculate the cooperative Lamb shift (CLS) of the idler photon, which is a cumulative effect of interaction energy. We study its dependence on a cylindrical geometry, a conventional setup in cold atom experiments, and estimate the maximum CLS which can be significant and observable. Manipulating the CLS of cascade emissions enables frequency qubits that provide alternative robust elements in quantum network. - Highlights: • Superradiance from a cascade atomic transition. • Correlated photon pair generation via four-wave mixing. • Dynamical light–matter couplings in a phased symmetrical state. • Cooperative Lamb shift in a cylindrical atomic ensemble.

A new cascade NN based method to short-term load forecast in deregulated electricity market

International Nuclear Information System (INIS)

Kouhi, Sajjad; Keynia, Farshid

2013-01-01

Highlights: • We are proposed a new hybrid cascaded NN based method and WT to short-term load forecast in deregulated electricity market. • An efficient preprocessor consist of normalization and shuffling of signals is presented. • In order to select the best inputs, a two-stage feature selection is presented. • A new cascaded structure consist of three cascaded NNs is used as forecaster. - Abstract: Short-term load forecasting (STLF) is a major discussion in efficient operation of power systems. The electricity load is a nonlinear signal with time dependent behavior. The area of electricity load forecasting has still essential need for more accurate and stable load forecast algorithm. To improve the accuracy of prediction, a new hybrid forecast strategy based on cascaded neural network is proposed for STLF. This method is consists of wavelet transform, an intelligent two-stage feature selection, and cascaded neural network. The feature selection is used to remove the irrelevant and redundant inputs. The forecast engine is composed of three cascaded neural network (CNN) structure. This cascaded structure can be efficiently extract input/output mapping function of the nonlinear electricity load data. Adjustable parameters of the intelligent feature selection and CNN is fine-tuned by a kind of cross-validation technique. The proposed STLF is tested on PJM and New York electricity markets. It is concluded from the result, the proposed algorithm is a robust forecast method

Critical nodes in signalling pathways

DEFF Research Database (Denmark)

Taniguchi, Cullen M; Emanuelli, Brice; Kahn, C Ronald

2006-01-01

Physiologically important cell-signalling networks are complex, and contain several points of regulation, signal divergence and crosstalk with other signalling cascades. Here, we use the concept of 'critical nodes' to define the important junctions in these pathways and illustrate their unique role...... using insulin signalling as a model system....

Pleiotrophin Signaling Through PTNR in Breast Cancer

National Research Council Canada - National Science Library

Powers, Ciaron

2001-01-01

... of intracellular signaling cascades. The pleiotrophin signaling pathway is known to be important in angiogenesis and breast cancer growth, but the exact mechanisms of pleiotrophin signaling remain undefined...

Biophysically inspired rational design of structured chimeric substrates for DNAzyme cascade engineering.

Directory of Open Access Journals (Sweden)

Matthew R Lakin

Full Text Available 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.

Defect production in simulated cascades: cascade quenching and short-term annealing

International Nuclear Information System (INIS)

Heinisch, H.L.

1982-01-01

Defect production in high energy displacement cascades has been modeled using the computer code MARLOWE to generate the cascades and the stochastic computer code ALSOME to simulate the cascade quenching and short-term annealing of isolated cascades. The quenching is accomplished by using ALSOME with exaggerated values for defect mobilities and critical reaction distanes for recombination and clustering, which are in effect until the number of defect pairs is equal to the value determined from resistivity experiments at 4K. Then normal mobilities and reaction distances are used during short-term annealing to a point representative of Stage III recovery. Effects of cascade interactions at low fluences are also being investigated. The quenching parameter values were empirically determined for 30 keV cascades. The results agree well with experimental information throughout the range from 1 keV to 100 keV. Even after quenching and short-term annealing the high energy cascades behave as a collection of lower energy subcascades and lobes. Cascades generated in a crystal having thermal displacements were found to be in better agreement with experiments after quenching and annealing than those generated in a non-thermal crystal

Lactoferrin dampens high-fructose corn syrup-induced hepatic manifestations of the metabolic syndrome in a murine model.

Directory of Open Access Journals (Sweden)

Yi-Chieh Li

Full Text Available Hepatic manifestations of the metabolic syndrome are related obesity, type 2 diabetes/insulin resistance and non-alcoholic fatty liver disease. Here we investigated how the anti-inflammatory properties of lactoferrin can protect against the onset of hepatic manifestations of the metabolic syndrome by using a murine model administered with high-fructose corn syrup. Our results show that a high-fructose diet stimulates intestinal bacterial overgrowth and increases intestinal permeability, leading to the introduction of endotoxin into blood circulation and liver. Immunohistochemical staining of Toll-like receptor-4 and thymic stromal lymphopoietin indicated that lactoferrin can modulate lipopolysaccharide-mediated inflammatory cascade. The important regulatory roles are played by adipokines including interleukin-1β, interleukin-6, tumor necrosis factor-α, monocyte chemotactic protein-1, and adiponectin, ultimately reducing hepatitis and decreasing serum alanine aminotransferase release. These beneficial effects of lactoferrin related to the downregulation of the lipopolysaccharide-induced inflammatory cascade in the liver. Furthermore, lactoferrin reduced serum and hepatic triglycerides to prevent lipid accumulation in the liver, and reduced lipid peroxidation, resulting in 4-hydroxynonenal accumulation. Lactoferrin reduced oral glucose tolerance test and homeostasis model assessment-insulin resistance. Lactoferrin administration thus significantly lowered liver weight, resulting from a decrease in the triglyceride and cholesterol synthesis that activates hepatic steatosis. Taken together, these results suggest that lactoferrin protected against high-fructose corn syrup induced hepatic manifestations of the metabolic syndrome.

Lactoferrin dampens high-fructose corn syrup-induced hepatic manifestations of the metabolic syndrome in a murine model.

Science.gov (United States)

Li, Yi-Chieh; Hsieh, Chang-Chi

2014-01-01

Hepatic manifestations of the metabolic syndrome are related obesity, type 2 diabetes/insulin resistance and non-alcoholic fatty liver disease. Here we investigated how the anti-inflammatory properties of lactoferrin can protect against the onset of hepatic manifestations of the metabolic syndrome by using a murine model administered with high-fructose corn syrup. Our results show that a high-fructose diet stimulates intestinal bacterial overgrowth and increases intestinal permeability, leading to the introduction of endotoxin into blood circulation and liver. Immunohistochemical staining of Toll-like receptor-4 and thymic stromal lymphopoietin indicated that lactoferrin can modulate lipopolysaccharide-mediated inflammatory cascade. The important regulatory roles are played by adipokines including interleukin-1β, interleukin-6, tumor necrosis factor-α, monocyte chemotactic protein-1, and adiponectin, ultimately reducing hepatitis and decreasing serum alanine aminotransferase release. These beneficial effects of lactoferrin related to the downregulation of the lipopolysaccharide-induced inflammatory cascade in the liver. Furthermore, lactoferrin reduced serum and hepatic triglycerides to prevent lipid accumulation in the liver, and reduced lipid peroxidation, resulting in 4-hydroxynonenal accumulation. Lactoferrin reduced oral glucose tolerance test and homeostasis model assessment-insulin resistance. Lactoferrin administration thus significantly lowered liver weight, resulting from a decrease in the triglyceride and cholesterol synthesis that activates hepatic steatosis. Taken together, these results suggest that lactoferrin protected against high-fructose corn syrup induced hepatic manifestations of the metabolic syndrome.

The signaling cascades of Ganoderma lucidum extracts in stimulating non-amyloidogenic protein secretion in human neuroblastoma SH-SY5Y cell lines.

Science.gov (United States)

Pinweha, Sirinthorn; Wanikiat, Payong; Sanvarinda, Yupin; Supavilai, Porntip

2008-12-19

Ganoderma lucidum (GL) is a medicinal mushroom that possesses various pharmacological properties which are also documented in the ancient reports where GL is praised for its effects on the promotion of health and longevity. In this study, we have investigated the effect of GL mycelia extracts on the non-amyloidogenic protein secretion (sAPPalpha) and the amyloid precursor protein (APP) expression in SH-SY5Y neuroblastoma cells. In order to characterize the signaling pathway which mediates GL-enhanced sAPPalpha secretion, we used inhibitors of nerve growth factor (NGF) signaling pathways, phosphatidylinositol 3 kinase (PI3K), phospholipase Cgamma1 (PLCgamma1), protein kinase C (PKC) and extracellular signal-regulated kinase (ERK1/2), to block GL-mediated sAPPalpha secretion as well as ERK1/2 and PKC activation by using Western blot analysis. Our results provided for the first time evidence that GL mycelia extracts increased APP expression and promoted sAPPalpha secretion. In addition, GL extracts activated ERK1/2 and PKC phosphorylation. The complex signaling cascades of PI3K and ERK may be responsible for GL-mediated sAPPalpha secretion.

Evaluation of blind signal separation methods

NARCIS (Netherlands)

Schobben, D.W.E.; Torkkola, K.; Smaragdis, P.

1999-01-01

Recently many new Blind Signal Separation BSS algorithms have been introduced Authors evaluate the performance of their algorithms in various ways Among these are speech recognition rates plots of separated signals plots of cascaded mixingunmixing impulse responses and signal to noise ratios Clearly

Compartmentalization of NO signaling cascade in skeletal muscles

International Nuclear Information System (INIS)

Buchwalow, Igor B.; Minin, Evgeny A.; Samoilova, Vera E.; Boecker, Werner; Wellner, Maren; Schmitz, Wilhelm; Neumann, Joachim; Punkt, Karla

2005-01-01

Skeletal muscle functions regulated by NO are now firmly established. However, the literature on the compartmentalization of NO signaling in myocytes is highly controversial. To address this issue, we examined localization of enzymes engaged in L-arginine-NO-cGMP signaling in the rat quadriceps muscle. Employing immunocytochemical labeling complemented with tyramide signal amplification and electron microscopy, we found NO synthase expressed not only in the sarcolemma, but also along contractile fibers, in the sarcoplasmic reticulum and mitochondria. The expression pattern of NO synthase in myocytes showed striking parallels with the enzymes engaged in L-arginine-NO-cGMP signaling (arginase, phosphodiesterase, and soluble guanylyl cyclase). Our findings are indicative of an autocrine fashion of NO signaling in skeletal muscles at both cellular and subcellular levels, and challenge the notion that the NO generation is restricted to the sarcolemma

A cascaded three-phase symmetrical multistage voltage multiplier

International Nuclear Information System (INIS)

Iqbal, Shahid; Singh, G K; Besar, R; Muhammad, G

2006-01-01

A cascaded three-phase symmetrical multistage Cockcroft-Walton voltage multiplier (CW-VM) is proposed in this report. It consists of three single-phase symmetrical voltage multipliers, which are connected in series at their smoothing columns like string of batteries and are driven by three-phase ac power source. The smoothing column of each voltage multiplier is charged twice every cycle independently by respective oscillating columns and discharged in series through load. The charging discharging process completes six times a cycle and therefore the output voltage ripple's frequency is of sixth order of the drive signal frequency. Thus the proposed approach eliminates the first five harmonic components of load generated voltage ripples and sixth harmonic is the major ripple component. The proposed cascaded three-phase symmetrical voltage multiplier has less than half the voltage ripple, and three times larger output voltage and output power than the conventional single-phase symmetrical CW-VM. Experimental and simulation results of the laboratory prototype are given to show the feasibility of proposed cascaded three-phase symmetrical CW-VM

All-optical network coding for DPSK signals

DEFF Research Database (Denmark)

An, Yi; Da Ros, Francesco; Peucheret, Christophe

2013-01-01

All-optical network coding for path protection is experimentally demonstrated using four-wave mixing in SOAs for10 Gbit/s NRZ-DPSK signals with error free performance. The total power penalty after two cascaded XOR stage is only 2 dB.......All-optical network coding for path protection is experimentally demonstrated using four-wave mixing in SOAs for10 Gbit/s NRZ-DPSK signals with error free performance. The total power penalty after two cascaded XOR stage is only 2 dB....

Smart geo-energy village development by using cascade direct use of geothermal energy in Bonjol, West Sumatera

Science.gov (United States)

Prasetya, Novrisal; Erwinsyah Umra Lubis, Defry; Raharjo, Dharmawan; Miryani Saptadji, Nenny; Pratama, Heru Berian

2017-12-01

West Sumatera is a province which has a huge geothermal potential - approximately 6% of Indonesia’s total geothermal potential which equals to 1,656 MWe. One of the significant reserves located in Bonjol subdistrict which accounts for more than 50 MWe. The energy from geothermal manifestation in Bonjol can be utilized prior to indirect development. Manifestation at the rate 3 kg/s and 87 °C will flow to cascading system consisting several applications, arranged in order from high to low temperature to efficiently use the excessive energy. The direct use application selected is based on the best potential commodities as well as temperature constraint of heat source. The objective of this paper is to perform a conceptual design for the first cascade direct use of geothermal energy in Indonesia to establish Bonjol Smart Geo-Energy Village which will be transformed as the center of agricultural, stockbreeding, tourism as well as cultural site. A comprehenssive research was performed through remote survey area, evaluation featured product, analysis of heat loss and heat exchange in cascade system. From potential commodities, the three applications selected are cocoa drying and egg hatching incubation machine as well as new tourism site called Terapi Panas Bumi. The optimum temperature for cocoa drying is 62°C with the moisture content 7% which consumes 78 kW for one tones cocoa dried. Whereas, egg incubation system consists of two chamber with the same temperature 40°C for each room and relative humidity 55% and 70%. For the last stage, Terapi Panas Bumi works in temperature 40°C. Based on the result technical and economical aspect, it exhibits cascade direct use of geothermal energy is very recommended to develop.

The roles of DNA damage-dependent signals and MAPK cascades in tributyltin-induced germline apoptosis in Caenorhabditis elegans.

Science.gov (United States)

Wang, Yun; Wang, Shunchang; Luo, Xun; Yang, Yanan; Jian, Fenglei; Wang, Xuemin; Xie, Lucheng

2014-08-01

The induction of apoptosis is recognized to be a major mechanism of tributyltin (TBT) toxicity. However, the underlying signaling pathways for TBT-induced apoptosis remain unclear. In this study, using the nematode Caenorhabditis elegans, we examined whether DNA damage response (DDR) pathway and mitogen-activated protein kinase (MAPK) signaling cascades are involved in TBT-induced germline apoptosis and cell cycle arrest. Our results demonstrated that exposing worms to TBT at the dose of 10nM for 6h significantly increased germline apoptosis in N2 strain. Germline apoptosis was absent in strains that carried ced-3 or ced-4 loss-of-function alleles, indicating that both caspase protein CED-3 and Apaf-1 protein CED-4 were required for TBT-induced apoptosis. TBT-induced apoptosis was blocked in the Bcl-2 gain-of-function strain ced-9(n1950), whereas TBT induced a minor increase in the BH3-only protein EGL-1 mutated strain egl-1(n1084n3082). Checkpoint proteins HUS-1 and CLK-2 exerted proapoptotic effects, and the null mutation of cep-1, the homologue of tumor suppressor gene p53, significantly inhibited TBT-induced apoptosis. Apoptosis in the loss-of-function strains of ERK, JNK and p38 MAPK signaling pathways were completely or mildly suppressed under TBT stress. These results were supported by the results of mRNA expression levels of corresponding genes. The present study indicated that TBT-induced apoptosis required the core apoptotic machinery, and that DDR genes and MAPK pathways played essential roles in signaling the processes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Observer-based hyperchaos synchronization in cascaded discrete-time systems

International Nuclear Information System (INIS)

Grassi, Giuseppe

2009-01-01

This paper deals with the observer-based synchronization in a cascade connection of hyperchaotic discrete-time systems. The paper demonstrates that exact synchronization in finite time is achievable between pairs of drive-response systems using only a scalar synchronizing signal. This 'propagated synchronization' starts from the innermost drive-response system pair and propagates toward the outermost drive-system pair. Choosing the drive-system input to be an information signal (encrypted via an arbitrary encryption function) yields a potential application of this architecture in chaos-based communications.

Cascaded optical fiber link using the internet network for remote clocks comparison.

Science.gov (United States)

Chiodo, Nicola; Quintin, Nicolas; Stefani, Fabio; Wiotte, Fabrice; Camisard, Emilie; Chardonnet, Christian; Santarelli, Giorgio; Amy-Klein, Anne; Pottie, Paul-Eric; Lopez, Olivier

2015-12-28

We report a cascaded optical link of 1100 km for ultra-stable frequency distribution over an Internet fiber network. The link is composed of four spans for which the propagation noise is actively compensated. The robustness and the performance of the link are ensured by five fully automated optoelectronic stations, two of them at the link ends, and three deployed on the field and connecting the spans. This device coherently regenerates the optical signal with the heterodyne optical phase locking of a low-noise laser diode. Optical detection of the beat-note signals for the laser lock and the link noise compensation are obtained with stable and low-noise fibered optical interferometer. We show 3.5 days of continuous operation of the noise-compensated 4-span cascaded link leading to fractional frequency instability of 4x10(-16) at 1-s measurement time and 1x10(-19) at 2000 s. This cascaded link was extended to 1480-km with the same performance. This work is a significant step towards a sustainable wide area ultra-stable optical frequency distribution and comparison network at a very high level of performance.

Frequency division using a micromechanical resonance cascade

Energy Technology Data Exchange (ETDEWEB)

Qalandar, K. R., E-mail: kamala@engineering.ucsb.edu; Gibson, B.; Sharma, M.; Ma, A.; Turner, K. L. [Department of Mechanical Engineering, University of California at Santa Barbara, Santa Barbara, California 93106 (United States); Strachan, B. S. [Department of Mechanical Engineering, Michigan State University, East Lansing, Michigan 48823 (United States); Department of Electrical Engineering, Michigan State University, East Lansing, Michigan 48823 (United States); Shaw, S. W. [Department of Mechanical Engineering, Michigan State University, East Lansing, Michigan 48823 (United States); Department of Physics and Astronomy, Michigan State University, East Lansing, Michigan 48823 (United States)

2014-12-15

A coupled micromechanical resonator array demonstrates a mechanical realization of multi-stage frequency division. The mechanical structure consists of a set of N sequentially perpendicular microbeams that are connected by relatively weak elastic elements such that the system vibration modes are localized to individual microbeams and have natural frequencies with ratios close to 1:2:⋯:2{sup N}. Conservative (passive) nonlinear inter-modal coupling provides the required energy transfer between modes and is achieved by finite deformation kinematics. When the highest frequency beam is excited, this arrangement promotes a cascade of subharmonic resonances that achieve frequency division of 2{sup j} at microbeam j for j = 1, …, N. Results are shown for a capacitively driven three-stage divider in which an input signal of 824 kHz is passively divided through three modal stages, producing signals at 412 kHz, 206 kHz, and 103 kHz. The system modes are characterized and used to delineate the range of AC input voltages and frequencies over which the cascade occurs. This narrow band frequency divider has simple design rules that are scalable to higher frequencies and can be extended to a larger number of modal stages.

Quantum cascade lasers as metrological tools for space optics

Science.gov (United States)

Bartalini, S.; Borri, S.; Galli, I.; Mazzotti, D.; Cancio Pastor, P.; Giusfredi, G.; De Natale, P.

2017-11-01

A distributed-feedback quantum-cascade laser working in the 4.3÷4.4 mm range has been frequency stabilized to the Lamb-dip center of a CO2 ro-vibrational transition by means of first-derivative locking to the saturated absorption signal, and its absolute frequency counted with a kHz-level precision and an overall uncertainty of 75 kHz. This has been made possible by an optical link between the QCL and a near-IR Optical Frequency Comb Synthesizer, thanks to a non-linear sum-frequency generation process with a fiber-amplified Nd:YAG laser. The implementation of a new spectroscopic technique, known as polarization spectroscopy, provides an improved signal for the locking loop, and will lead to a narrower laser emission and a drastic improvement in the frequency stability, that in principle is limited only by the stability of the optical frequency comb synthesizer (few parts in 1013). These results confirm quantum cascade lasers as reliable sources not only for high-sensitivity, but also for highprecision measurements, ranking them as optimal laser sources for space applications.

Phase locking of a 2.7 THz quantum cascade laser to a microwave reference

NARCIS (Netherlands)

Khosropanah, P.; Baryshev, A.; Zhang, W.; Jellema, W.; Hovenier, J.N.; Gao, J.R.; Klapwijk, T.M.; Paveliev, D.G.; Williams, B.S.; Kumar, S.; Hu, Q.; Reno, J.L.; Klein, B.; Hesler, J.L.

2009-01-01

We demonstrate the phase locking of a 2.7 THz metal–metal waveguide quantum cascade laser (QCL) to an external microwave signal. The reference is the 15th harmonic, generated by a semiconductor superlattice nonlinear device, of a signal at 182 GHz, which itself is generated by a multiplier chain

Phase locking of a 2.7 THz quantum cascade laser to a microwave reference

NARCIS (Netherlands)

Khosropanah, P.; Baryshev, A.; Zhang, W.; Jellema, W.; Hovenier, J. N.; Gao, J. R.; Klapwijk, T. M.; Paveliev, D. G.; Williams, B. S.; Kumar, S.; Hu, Q.; Reno, J. L.; Klein, B.; Hesler, J. L.

2009-01-01

We demonstrate the phase locking of a 2.7 THz metal-metal waveguide quantum cascade laser (QCL) to an external microwave signal. The reference is the 15th harmonic, generated by a semiconductor superlattice nonlinear device, of a signal at 182 GHz, which itself is generated by a multiplier chain

Modeling of cascade and sub-cascade formation at high pka energies in irradiated fusion structural materials

International Nuclear Information System (INIS)

Ryazanov, A.; Metelkin, E.V.; Semenov, E.A.

2007-01-01

Full text of publication follows: A new theoretical model is developed for the investigations of cascade and sub-cascade formation in fusion structural materials under fast neutron irradiation at high primary knock atom (PKA) energies. Under 14 MeV neutron irradiation especially of light fusion structural materials such as Be, C, SiC materials PKA will have the energies up to 1 MeV. At such high energies it is very difficult to use the Monte Carlo or molecular dynamic simulations. The developed model is based on the analytical consideration of elastic collisions between displaced moving atoms into atomic cascades produced by a PKAs with the some kinetic energy obtained from fast neutrons. The Tomas-Fermy interaction potential is used for the describing of elastic collisions between moving atoms. The suggested model takes into account also the electronic losses for moving atoms between elastic collisions. The self consistent criterion for sub-cascade formation is suggested here which is based on the comparison of mean distance between two consequent PKA collisions and size of sub-cascade produced by PKA. The analytical relations for the most important characteristics of cascades and sub-cascade are determined including the average number of sub-cascades per one PKA in the dependence on PKA energy, the distance between sub-cascades and the average cascade and sub-cascade sizes as a function of PKA energy. The developed model allows determining the total numbers, distribution functions of cascades and sub-cascades in dependence on their sizes and generation rate of cascades and sub-cascades for different fusion neutron energy spectra. Based on the developed model the numerical calculations for main characteristics of cascades and sub-cascades in different fusion structural materials are performed using the neutron flux and PKA energy spectra for fusion reactors: ITER and DEMO. The main characteristics for cascade and sub-cascade formation are calculated here for the

Cascades of pile-up and dead time

International Nuclear Information System (INIS)

Pomme, S.

2008-01-01

Count loss through a cascade of pile-up and dead time is studied. Time interval density-distribution functions and throughput factors are presented for counters with a series arrangement of pile-up and extending or non-extending dead time. A counter is considered, where an artificial dead time is imposed on every counted event, in order to control the length and type of dead time. For such a system, it is relatively easy to determine an average count-loss correction factor via a live-time clock gated by the imposed dead-time signal ('live-time mode'), or otherwise to apply a correction factor based on the inversion of the throughput function ('real-time mode'). However, these techniques do not account for additional loss through pulse pile-up. In this work, counting errors associated with neglecting cascade effects are calculated for measurements in live-time and real-time mode

Spatial modeling of the membrane-cytosolic interface in protein kinase signal transduction.

Directory of Open Access Journals (Sweden)

Wolfgang Giese

2018-04-01

Full Text Available The spatial architecture of signaling pathways and the interaction with cell size and morphology are complex, but little understood. With the advances of single cell imaging and single cell biology, it becomes crucial to understand intracellular processes in time and space. Activation of cell surface receptors often triggers a signaling cascade including the activation of membrane-attached and cytosolic signaling components, which eventually transmit the signal to the cell nucleus. Signaling proteins can form steep gradients in the cytosol, which cause strong cell size dependence. We show that the kinetics at the membrane-cytosolic interface and the ratio of cell membrane area to the enclosed cytosolic volume change the behavior of signaling cascades significantly. We suggest an estimate of average concentration for arbitrary cell shapes depending on the cell volume and cell surface area. The normalized variance, known from image analysis, is suggested as an alternative measure to quantify the deviation from the average concentration. A mathematical analysis of signal transduction in time and space is presented, providing analytical solutions for different spatial arrangements of linear signaling cascades. Quantification of signaling time scales reveals that signal propagation is faster at the membrane than at the nucleus, while this time difference decreases with the number of signaling components in the cytosol. Our investigations are complemented by numerical simulations of non-linear cascades with feedback and asymmetric cell shapes. We conclude that intracellular signal propagation is highly dependent on cell geometry and, thereby, conveys information on cell size and shape to the nucleus.

Representation of radiative strength functions within a practical model of cascade gamma decay

Energy Technology Data Exchange (ETDEWEB)

Vu, D. C., E-mail: vuconghnue@gmail.com; Sukhovoj, A. M., E-mail: suchovoj@nf.jinr.ru; Mitsyna, L. V., E-mail: mitsyna@nf.jinr.ru; Zeinalov, Sh., E-mail: zeinal@nf.jinr.ru [Joint Institute for Nuclear Research (Russian Federation); Jovancevic, N., E-mail: nikola.jovancevic@df.uns.ac.rs; Knezevic, D., E-mail: david.knezevic@df.uns.ac.rs; Krmar, M., E-mail: krmar@df.uns.ac.rs [University of Novi Sad, Department of Physics, Faculty of Sciences (Serbia); Dragic, A., E-mail: dragic@ipb.ac.rs [Institute of Physics Belgrade (Serbia)

2017-03-15

A practical model developed at the Joint Institute for Nuclear Research (JINR, Dubna) in order to describe the cascade gamma decay of neutron resonances makes it possible to determine simultaneously, from an approximation of the intensities of two-step cascades, parameters of nuclear level densities and partial widths with respect to the emission of nuclear-reaction products. The number of the phenomenological ideas used isminimized in themodel version considered in the present study. An analysis of new results confirms what was obtained earlier for the dependence of dynamics of the interaction of fermion and boson nuclear states on the nuclear shape. From the ratio of the level densities for excitations of the vibrational and quasiparticle types, it also follows that this interaction manifests itself in the region around the neutron binding energy and is probably different in nuclei that have different parities of nucleons.

Atom-atom collision cascades localization

International Nuclear Information System (INIS)

Kirsanov, V.V.

1980-01-01

The presence of an impurity and thermal vibration influence on the atom-atom collision cascade development is analysed by the computer simulation method (the modificated dynamic model). It is discovered that the relatively low energetic cascades are localized with the temperature increase of an irradiated crystal. On the basis of the given effect the mechanism of splitting of the high energetic cascades into subcascades is proposed. It accounts for two factors: the primary knocked atom energy and the irradiated crystal temperature. Introduction of an impurity also localizes the cascades independently from the impurity atom mass. The cascades localization leads to intensification of the process of annealing in the cascades and reduction of the post-cascade vacancy cluster sizes. (author)

Mechanisms of cascade collapse

International Nuclear Information System (INIS)

Diaz de la Rubia, T.; Smalinskas, K.; Averback, R.S.; Robertson, I.M.; Hseih, H.; Benedek, R.

1988-12-01

The spontaneous collapse of energetic displacement cascades in metals into vacancy dislocation loops has been investigated by molecular dynamics (MD) computer simulation and transmission electron microscopy (TEM). Simulations of 5 keV recoil events in Cu and Ni provide the following scenario of cascade collapse: atoms are ejected from the central region of the cascade by replacement collision sequences; the central region subsequently melts; vacancies are driven to the center of the cascade during resolidification where they may collapse into loops. Whether or not collapse occurs depends critically on the melting temperature of the metal and the energy density and total energy in the cascade. Results of TEM are presented in support of this mechanism. 14 refs., 4 figs., 1 tab

Free-space communication based on quantum cascade laser

International Nuclear Information System (INIS)

Liu Chuanwei; Zhai Shenqiang; Zhang Jinchuan; Zhou Yuhong; Jia Zhiwei; Liu Fengqi; Wang Zhanguo

2015-01-01

A free-space communication based on a mid-infrared quantum cascade laser (QCL) is presented. A room-temperature continuous-wave distributed-feedback (DFB) QCL combined with a mid-infrared detector comprise the basic unit of the communication system. Sinusoidal signals at a highest frequency of 40 MHz and modulated video signals with a carrier frequency of 30 MHz were successfully transmitted with this experimental setup. Our research has provided a proof-of-concept demonstration of space optical communication application with QCL. The highest operation frequency of our setup was determined by the circuit-limited modulation bandwidth. A high performance communication system can be obtained with improved modulation circuit system. (paper)

Stability of a 500 km erbium-doped fiber amplifier cascade

DEFF Research Database (Denmark)

Lumholt, Ole; Bjarklev, Anders Overgaard; Povlsen, Jørn Hedegaard

1992-01-01

The stability of a cascade system of erbium-doped fiber amplifiers, due to pump and signal power variations, has been examined by use of a very accurate model. Even with an automatic gain control loop included, a fallout of a pump laser in the first inline amplifier is shown to produce a more than...

The Wnt signaling pathway in familial exudative vitreoretinopathy and Norrie disease.

Science.gov (United States)

Warden, Scott M; Andreoli, Christopher M; Mukai, Shizuo

2007-01-01

The Wnt signaling pathway is highly conserved among species and has an important role in many cell biological processes throughout the body. This signaling cascade is involved in regulating ocular growth and development, and recent findings indicate that this is particularly true in the retina. Mutations involving different aspects of the Wnt signaling pathway are being linked to several diseases of retinal development. The aim of this article is to first review the Wnt signaling pathway. We will then describe two conditions, familial exudative vitreoretinopathy (FEVR) and Norrie disease (ND), which have been shown to be caused in part by defects in the Wnt signaling cascade.

Processing of cell-surface signalling anti-sigma factors prior to signal recognition is aconserved autoproteolytic mechanism that produces two functional domains.

NARCIS (Netherlands)

Bastiaansen, K.C.J.T.; Otero-Asman, J.R.; Luirink, J.; Bitter, W.; Llamas, M.A.

2015-01-01

Cell-surface signalling (CSS) enables Gram-negative bacteria to transduce an environmental signal into a cytosolic response. This regulatory cascade involves an outer membrane receptor that transmits the signal to an anti-sigma factor in the cytoplasmic membrane, allowing the activation of an

Fluvoxamine moderates reduced voluntary activity following chronic dexamethasone infusion in mice via recovery of BDNF signal cascades.

Science.gov (United States)

Terada, Kazuki; Izumo, Nobuo; Suzuki, Biora; Karube, Yoshiharu; Morikawa, Tomomi; Ishibashi, Yukiko; Kameyama, Toshiki; Chiba, Koji; Sasaki, Noriko; Iwata, Keiko; Matsuzaki, Hideo; Manabe, Takayuki

2014-04-01

Major depression is a complex disorder characterized by genetic and environmental interactions. Selective serotonin reuptake inhibitors (SSRIs) effectively treat depression. Neurogenesis following chronic antidepressant treatment activates brain derived neurotrophic factor (BDNF) signaling. In this study, we analyzed the effects of the SSRI fluvoxamine (Flu) on locomotor activity and forced-swim behavior using chronic dexamethasone (cDEX) infusions in mice, which engenders depression-like behavior. Infusion of cDEX decreased body weight and produced a trend towards lower locomotor activity during darkness. In the forced-swim test, cDEX-mice exhibited increased immobility times compared with mice administered saline. Flu treatment reversed decreased locomotor activity and mitigated forced-swim test immobility. Real-time polymerase chain reactions using brain RNA samples yielded significantly lower BDNF mRNA levels in cDEX-mice compared with the saline group. Endoplasmic reticulum stress-associated X-box binding protein-1 (XBP1) gene expression was lower in cDEX-mice compared with the saline group. However, marked expression of the XBP1 gene was observed in cDEX-mice treated with Flu compared with mice given saline and untreated cDEX-mice. Expression of 5-HT2A and Sigma-1 receptors decreased after cDEX infusion compared with the saline group, and these decreases normalized to control levels upon Flu treatment. Our results indicate that the Flu moderates reductions in voluntary activity following chronic dexamethasone infusions in mice via recovery of BDNF signal cascades. Copyright © 2014 Elsevier Ltd. All rights reserved.

Learning optimal embedded cascades.

Science.gov (United States)

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.

Dissection of the insulin signaling pathway via quantitative phosphoproteomics

DEFF Research Database (Denmark)

Krüger, Marcus; Kratchmarova, Irina; Blagoev, Blagoy

2008-01-01

spectrum of the tyrosine phosphorylation cascade, we have defined the tyrosine-phosphoproteome of the insulin signaling pathway, using high resolution mass spectrometry in combination with phosphotyrosine immunoprecipitation and stable isotope labeling by amino acids in cell culture (SILAC......The insulin signaling pathway is of pivotal importance in metabolic diseases, such as diabetes, and in cellular processes, such as aging. Insulin activates a tyrosine phosphorylation cascade that branches to create a complex network affecting multiple biological processes. To understand the full...

A novel Drosophila injury model reveals severed axons are cleared through a Draper/MMP-1 signaling cascade

Science.gov (United States)

Purice, Maria D; Ray, Arpita; Münzel, Eva Jolanda; Pope, Bernard J; Park, Daniel J; Speese, Sean D; Logan, Mary A

2017-01-01

Neural injury triggers swift responses from glia, including glial migration and phagocytic clearance of damaged neurons. The transcriptional programs governing these complex innate glial immune responses are still unclear. Here, we describe a novel injury assay in adult Drosophila that elicits widespread glial responses in the ventral nerve cord (VNC). We profiled injury-induced changes in VNC gene expression by RNA sequencing (RNA-seq) and found that responsive genes fall into diverse signaling classes. One factor, matrix metalloproteinase-1 (MMP-1), is induced in Drosophila ensheathing glia responding to severed axons. Interestingly, glial induction of MMP-1 requires the highly conserved engulfment receptor Draper, as well as AP-1 and STAT92E. In MMP-1 depleted flies, glia do not properly infiltrate neuropil regions after axotomy and, as a consequence, fail to clear degenerating axonal debris. This work identifies Draper-dependent activation of MMP-1 as a novel cascade required for proper glial clearance of severed axons. DOI: http://dx.doi.org/10.7554/eLife.23611.001 PMID:28825401

The capacity of the cascaded fading channel in the low power regime

KAUST Repository

Benkhelifa, Fatma

2014-04-01

In this paper, we present a simple way to compute the ergodic capacity of cascaded channels with perfect channel state information at both the transmitter and the receiver. We apply our generic results to the Rayleigh-double fading channel, and to the free-space optical channel in the presence of pointing errors and we express their low signal-to-noise ratio capacities. We mainly focus on the low signal-to-noise ratio range.

Modeling of cascade and sub-cascade formation at high PKA energies in irradiated fusion structural materials

International Nuclear Information System (INIS)

Ryazanov, A.I.; Metelkin, E.V.; Semenov, E.V.

2009-01-01

A new theoretical model is developed for the investigations of cascade and sub-cascade formation in fusion structural materials under fast neutron irradiation at high primary knock-on atom energies. Light fusion structural materials: such as Be, C and SiC under 14 MeV neutron irradiation in fusion reactor will have the primary knock-on atoms with the energies up to 1 MeV. It is very difficult to use at such high energies the Monte-Carlo or molecular dynamic simulations [H.L. Heinisch, B.N. Singh, Philos. Mag. A67 (1993) 407; H.L. Heinisch, B.N. Singh, J. Nucl. Mater. 251 (1997) 77]. The developed model is based on the analytical consideration of elastic collisions between displaced moving atoms produced by primary knock-on atoms with some kinetic energies obtained from fast neutrons and crystal lattice atoms. The Thomas-Fermi interaction potential is used here for the description of these elastic atomic collisions. The suggested model takes into account also the electronic losses for moving atoms between elastic collisions. The self-consistent criterion for sub-cascade formation is suggested here which is based on the comparison of mean distance of primary knock-on atoms between consequent collisions of them with the target atoms and a size of sub-cascade produced by moving secondary knock-on atoms produced in such collisions. The analytical relations for the most important characteristics of cascades and sub-cascades are determined including the average number of sub-cascades per one primary knock-on atom in the dependence on its energy, the distance between sub-cascades and the average cascade and sub-cascade sizes. The developed model allows determining the total numbers, distribution functions of cascades and sub-cascades in dependence on their sizes and generation rate of cascades and sub-cascades for the different fusion neutron energy spectra. On the basis of this developed model the numerical calculations for main characteristics of cascades and sub-cascades

The inhibition of IGF-1 signaling promotes proteostasis by enhancing protein aggregation and deposition.

Science.gov (United States)

Moll, Lorna; Ben-Gedalya, Tziona; Reuveni, Hadas; Cohen, Ehud

2016-04-01

The discovery that the alteration of aging by reducing the activity of the insulin/IGF-1 signaling (IIS) cascade protects nematodes and mice from neurodegeneration-linked, toxic protein aggregation (proteotoxicity) raises the prospect that IIS inhibitors bear therapeutic potential to counter neurodegenerative diseases. Recently, we reported that NT219, a highly efficient IGF-1 signaling inhibitor, protects model worms from the aggregation of amyloid β peptide and polyglutamine peptides that are linked to the manifestation of Alzheimer's and Huntington's diseases, respectively. Here, we employed cultured cell systems to investigate whether NT219 promotes protein homeostasis (proteostasis) in mammalian cells and to explore its underlying mechanisms. We found that NT219 enhances the aggregation of misfolded prion protein and promotes its deposition in quality control compartments known as "aggresomes." NT219 also elevates the levels of certain molecular chaperones but, surprisingly, reduces proteasome activity and impairs autophagy. Our findings show that IGF-1 signaling inhibitors in general and NT219 in particular can promote proteostasis in mammalian cells by hyperaggregating hazardous proteins, thereby bearing the potential to postpone the onset and slow the progression of neurodegenerative illnesses in the elderly.-Moll, L., Ben-Gedalya, T., Reuveni, H., Cohen, E. The inhibition of IGF-1 signaling promotes proteostasis by enhancing protein aggregation and deposition. © FASEB.

A novel electrochemical sensor for lead ion based on cascade DNA and quantum dots amplification

International Nuclear Information System (INIS)

Tang, Shurong; Lu, Wei; Gu, Fang; Tong, Ping; Yan, Zhiming; Zhang, Lan

2014-01-01

A new enzyme-free and ultrasensitive electrochemical Pb 2+ biosensor was developed. By coupling the DNA-assisted cascade of hybridization reaction with the quantum dots (QDs) for signal amplification, a detection limit as low as 6.1 pM can be obtained for Pb 2+ . In this study, the “8-17” DNAzyme was used for specific recognition of Pb 2+ . In the presence of Pb 2+ , the DNAzyme was activated and cleaved the substrate strand. And then, the hybridization between the linker probe and signal probe was initiated, which resulted in formation of a long cascade DNA structure as well as assemble of numerous QDs at last. By the use of magnetic beads, the free signal probe can be easily removed by external magnetic field. After acid lysis, a great amount of redox cations can be released from the QDs and eventually result in significantly amplified electrochemical signals. This method is highly sensitive, selective and simple without the participation of any protein based enzyme (nuclease), thereby holds great potential for real sample analysis

Cascade annealing: an overview

International Nuclear Information System (INIS)

Doran, D.G.; Schiffgens, J.O.

1976-04-01

Concepts and an overview of radiation displacement damage modeling and annealing kinetics are presented. Short-term annealing methodology is described and results of annealing simulations performed on damage cascades generated using the Marlowe and Cascade programs are included. Observations concerning the inconsistencies and inadequacies of current methods are presented along with simulation of high energy cascades and simulation of longer-term annealing

Search for neutrino-induced cascade events in the icecube detector

Energy Technology Data Exchange (ETDEWEB)

Panknin, Sebastian

2011-09-15

This thesis presents results of a search for a diffuse flux of high energetic neutrinos from extra-terrestrial origin. Such a flux is predicted by several models of sources of cosmic ray particles. In a neutrino detector, such as IceCube, there are mainly two signatures available for detection of neutrinos: The track-like light signal of a neutrino induced muon and the spherical light pattern of a neutrino induced particle shower, called cascades in this context. The search is based on the measurement of neutrino induced cascades within the IceCube neutrino detector. The data were taken in 2008/2009 with a total uptime of 367 days. At that time the detector was still under construction and had just reached half of its final size. A search for a neutrino flux using cascades is sensitive to all neutrino flavors. A cascade develops within few meters, in contrast to the muon track of several kilometers length. Therefore a good energy reconstruction is possible. With such a reconstruction the astrophysical neutrino flux can be statistically distinguished from the background of atmospheric neutrinos. In the simulation of cascades so far it was not included, that in hadronic cascades muons are produced. This can influence the shape of the cascade, to a less spherical one. Therefore the effect was parameterized in this thesis and included in the simulation. Further cuts on the event topology and reconstructed energy were developed, in order to reduce the background of atmospheric muons and atmospheric neutrinos. Four events from the measured data pass these cuts. Taking the high systematic uncertainties into account, this result is in agreement with the expected background of 0.72{+-}0.28{+-}{sup 1.54}{sub 0.49} events. For an assumed flavor ratio of {nu}{sub e}:{nu}{sub {mu}}:{nu}{sub {tau}}=1:1:1 the upper limit for the all flavor neutrino flux is 9.5.10{sup -8}E{sup -2} GeVs{sup -1}sr{sup -1}cm{sup -2}.

Search for neutrino-induced cascade events in the icecube detector

International Nuclear Information System (INIS)

Panknin, Sebastian

2011-01-01

This thesis presents results of a search for a diffuse flux of high energetic neutrinos from extra-terrestrial origin. Such a flux is predicted by several models of sources of cosmic ray particles. In a neutrino detector, such as IceCube, there are mainly two signatures available for detection of neutrinos: The track-like light signal of a neutrino induced muon and the spherical light pattern of a neutrino induced particle shower, called cascades in this context. The search is based on the measurement of neutrino induced cascades within the IceCube neutrino detector. The data were taken in 2008/2009 with a total uptime of 367 days. At that time the detector was still under construction and had just reached half of its final size. A search for a neutrino flux using cascades is sensitive to all neutrino flavors. A cascade develops within few meters, in contrast to the muon track of several kilometers length. Therefore a good energy reconstruction is possible. With such a reconstruction the astrophysical neutrino flux can be statistically distinguished from the background of atmospheric neutrinos. In the simulation of cascades so far it was not included, that in hadronic cascades muons are produced. This can influence the shape of the cascade, to a less spherical one. Therefore the effect was parameterized in this thesis and included in the simulation. Further cuts on the event topology and reconstructed energy were developed, in order to reduce the background of atmospheric muons and atmospheric neutrinos. Four events from the measured data pass these cuts. Taking the high systematic uncertainties into account, this result is in agreement with the expected background of 0.72±0.28± 1.54 0.49 events. For an assumed flavor ratio of ν e :ν μ :ν τ =1:1:1 the upper limit for the all flavor neutrino flux is 9.5.10 -8 E -2 GeVs -1 sr -1 cm -2 .

Integrated Broadband Quantum Cascade Laser

Science.gov (United States)

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.

Quantification of the glycogen cascade system: the ultrasensitive responses of liver glycogen synthase and muscle phosphorylase are due to distinctive regulatory designs

Directory of Open Access Journals (Sweden)

Venkatesh KV

2005-05-01

Full Text Available Abstract Background Signaling pathways include intricate networks of reversible covalent modification cycles. Such multicyclic enzyme cascades amplify the input stimulus, cause integration of multiple signals and exhibit sensitive output responses. Regulation of glycogen synthase and phosphorylase by reversible covalent modification cycles exemplifies signal transduction by enzyme cascades. Although this system for regulating glycogen synthesis and breakdown appears similar in all tissues, subtle differences have been identified. For example, phosphatase-1, a dephosphorylating enzyme of the system, is regulated quite differently in muscle and liver. Do these small differences in regulatory architecture affect the overall performance of the glycogen cascade in a specific tissue? We address this question by analyzing the regulatory structure of the glycogen cascade system in liver and muscle cells at steady state. Results The glycogen cascade system in liver and muscle cells was analyzed at steady state and the results were compared with literature data. We found that the cascade system exhibits highly sensitive switch-like responses to changes in cyclic AMP concentration and the outputs are surprisingly different in the two tissues. In muscle, glycogen phosphorylase is more sensitive than glycogen synthase to cyclic AMP, while the opposite is observed in liver. Furthermore, when the liver undergoes a transition from starved to fed-state, the futile cycle of simultaneous glycogen synthesis and degradation switches to reciprocal regulation. Under such a transition, different proportions of active glycogen synthase and phosphorylase can coexist due to the varying inhibition of glycogen-synthase phosphatase by active phosphorylase. Conclusion The highly sensitive responses of glycogen synthase in liver and phosphorylase in muscle to primary stimuli can be attributed to distinctive regulatory designs in the glycogen cascade system. The different

Conjugation of cascades

International Nuclear Information System (INIS)

San Martin, Jesus; Rodriguez-Perez, Daniel

2009-01-01

Presented in this work are some results relative to sequences found in the logistic equation bifurcation diagram, which is the unimodal quadratic map prototype. All of the different saddle-node bifurcation cascades, associated with every last appearance p-periodic orbit (p=3,4,5,...), can also be generated from the very Feigenbaum cascade. In this way it is evidenced the relationship between both cascades. The orbits of every saddle-node bifurcation cascade, mentioned above, are located in different chaotic bands, and this determines a sequence of orbits converging to every band-merging Misiurewicz point. In turn, these accumulation points form a sequence whose accumulation point is the Myrberg-Feigenbaum point. It is also proven that the first appearance orbits in the n-chaotic band converge to the same point as the last appearance orbits of the (n + 1)-chaotic band. The symbolic sequences of band-merging Misiurewicz points are computed for any window.

Role of AC-cAMP-PKA Cascade in Antidepressant Action of Electroacupuncture Treatment in Rats

Directory of Open Access Journals (Sweden)

Jian-hua Liu

2012-01-01

Full Text Available Adenylyl cyclase (AC-cyclic adenosine monophosphate (cAMP-cAMP-dependent protein kinase A (PKA cascade is considered to be associated with the pathogenesis and treatment of depression. The present study was conducted to explore the role of the cAMP cascade in antidepressant action of electroacupuncture (EA treatment for chronic mild stress (CMS-induced depression model rats. The results showed that EA improved significantly behavior symptoms in depression and dysfunction of AC-cAMP-PKA signal transduction pathway induced by CMS, which was as effective as fluoxetine. Moreover, the antidepressant effects of EA rather than Fluoxetine were completely abolished by H89, a specific PKA inhibitor. Consequently, EA has a significant antidepressant treatment in CMS-induced depression model rats, and AC-cAMP-PKA signal transduction pathway is crucial for it.

Digital Speed Cascade Control, using Scilab / Xcos Environment

Directory of Open Access Journals (Sweden)

Petru Chioncel

2016-10-01

Full Text Available This paper presents an application of digital cascade control implemented in Scilab / Xcos environment, using a P type regulator for the position adjustment circuit, a PI controller for the speed circuit adjustment; the current respectively moments control circuits are rendered by elements of PT1 type. On this basis the program is done in Scilab and the related signal block diagram implemented in Xcos; through simulation, the step response of the system is analyzed for different sampling times.

Energy cascades in Canada

Energy Technology Data Exchange (ETDEWEB)

Hayden, A. C.; Brown, T. D.

1979-03-15

Combining energy uses in a cascade can result in significant overall reductions in fuel requirements. The simplest applications for a cascade are in the recovery of waste heat from existing processes using special boilers or turbines. Specific applications of more-complex energy cascades for Canada are discussed. A combined-cycle plant at a chemical refinery in Ontario is world leader in energy efficiency. Total-energy systems for commercial buildings, such as one installed in a school in Western Canada, offer attractive energy and operating cost benefits. A cogeneration plant proposed for the National Capital Region, generating electricity as well as steam for district heating, allows the use of a low-grade fossil fuel (coal), greatly improves energy-transformation efficiency, and also utilizes an effectively renewable resource (municipal garbage). Despite the widespread availability of equipment and technology of energy cascades, the sale of steam and electricity across plant boundaries presents a barrier. More widespread use of cascades will require increased cooperation among industry, electric utilities and the various levels of government if Canada is to realize the high levels of energy efficiency potential available.

The EAL domain protein YciR acts as a trigger enzyme in a c-di-GMP signalling cascade in E. coli biofilm control

Science.gov (United States)

Lindenberg, Sandra; Klauck, Gisela; Pesavento, Christina; Klauck, Eberhard; Hengge, Regine

2013-01-01

C-di-GMP—which is produced by diguanylate cyclases (DGC) and degraded by specific phosphodiesterases (PDEs)—is a ubiquitous second messenger in bacterial biofilm formation. In Escherichia coli, several DGCs (YegE, YdaM) and PDEs (YhjH, YciR) and the MerR-like transcription factor MlrA regulate the transcription of csgD, which encodes a biofilm regulator essential for producing amyloid curli fibres of the biofilm matrix. Here, we demonstrate that this system operates as a signalling cascade, in which c-di-GMP controlled by the DGC/PDE pair YegE/YhjH (module I) regulates the activity of the YdaM/YciR pair (module II). Via multiple direct interactions, the two module II proteins form a signalling complex with MlrA. YciR acts as a connector between modules I and II and functions as a trigger enzyme: its direct inhibition of the DGC YdaM is relieved when it binds and degrades c-di-GMP generated by module I. As a consequence, YdaM then generates c-di-GMP and—by direct and specific interaction—activates MlrA to stimulate csgD transcription. Trigger enzymes may represent a general principle in local c-di-GMP signalling. PMID:23708798

MRI manifestation of Wilson's disease accompanied with central pontine myelinolysis

International Nuclear Information System (INIS)

Zhang Jingsong; Huan Yi; Chang Yingjuan; Chang Yingjuan; Ge Yali; Zhang Guangyun; Han Yuedong; Zhao Haitao; Yang Chunmin; Yang Yan

2004-01-01

Objective: To discuss MRI manifestation of Wilson's disease accompanied with central pontine myelinolysis (CPM), and to especially detect the value of diffusion-weighted MRI (DWI) in this disease. Methods: Two cases of Wilson's disease accompanied with CPM were performed with sequent MR examination including T 1 WI, T 2 WI, FLAIR, DWI, and contrast-enhanced MRI (CE MRI) by a 1.5 T magnetic resonance system (Philips gyroscan master). Results: Symmetric long T 1 and T 2 signals were found in central pontine region, lenticular nucleus, caudate nucleus, and thalamus. CEMRI showed no apparent enhanced lesions. DWI showed obviously high signal intensities in central pontine region with apparent diffusion coefficient values fluctuated between (100-300) x 10 -6 mm 2 /s while FLAIR images just showed slightly high signal in the same area, which suggested that cytotoxic edema did in fact exist in CPM. Meanwhile, DWI also showed high signals in bilateral lenticular nucleus with apparent diffusion coefficient values fluctuated between (300-600) x 10 -6 mm 2 /s, however, FLAIR images showed heterogeneous high signals and one case presented low DWI signals in bilateral head of caudate nucleus, all these signs might be explained by mixed-changes of cytotoxic edema and vasogenic edema in long period of Wilson's disease. Conclusion: Wilson's disease and CPM have characteristic MRI manifestation and DWI may be a very useful way to confirm a correct diagnosis. (authors)

Cascade reactor: introduction

International Nuclear Information System (INIS)

Pitts, J.H.

1985-01-01

Cascade is a concept for an ultrasafe, highly efficient, easily built reactor to convert inertial-confinement fusion energy into electrical power. The Cascade design includes a rotating double-cone-shaped chamber in which a moving, 1-m-thick ceramic granular blanket is held against the reactor wall by centrifugal action. The granular material absorbs energy from the fusion reactions. Accomplishments this year associated with Cascade included improvements to simplify chamber design and lower activation. The authors switched from a steel chamber wall to one made from silicon-carbide (SiC) panels held in compression by SiC-fiber/Al-composite tendons that gird the chamber both circumferentially and axially. The authors studies a number of heat-exchanger designs and selected a gravity-flow cascade design with a vacuum on the primary side. This design allows granules leaving the chamber to be transported to the heat exchangers using their own peripheral speed. The granules transfer their thermal energy and return to the chamber gravitationally: no vacuum locks or conveyors are needed

Cascade quantum teleportation

Institute of Scientific and Technical Information of China (English)

ZHOU Nan-run; GONG Li-hua; LIU Ye

2006-01-01

In this letter a cascade quantum teleportation scheme is proposed. The proposed scheme needs less local quantum operations than those of quantum multi-teleportation. A quantum teleportation scheme based on entanglement swapping is presented and compared with the cascade quantum teleportation scheme. Those two schemes can effectively teleport quantum information and extend the distance of quantum communication.

An Alzheimer Disease-linked Rare Mutation Potentiates Netrin Receptor Uncoordinated-5C-induced Signaling That Merges with Amyloid β Precursor Protein Signaling.

Science.gov (United States)

Hashimoto, Yuichi; Toyama, Yuka; Kusakari, Shinya; Nawa, Mikiro; Matsuoka, Masaaki

2016-06-03

A missense mutation (T835M) in the uncoordinated-5C (UNC5C) netrin receptor gene increases the risk of late-onset Alzheimer disease (AD) and also the vulnerability of neurons harboring the mutation to various insults. The molecular mechanisms underlying T835M-UNC5C-induced death remain to be elucidated. In this study, we show that overexpression of wild-type UNC5C causes low-grade death, which is intensified by an AD-linked mutation T835M. An AD-linked survival factor, calmodulin-like skin protein (CLSP), and a natural ligand of UNC5C, netrin1, inhibit this death. T835M-UNC5C-induced neuronal cell death is mediated by an intracellular death-signaling cascade, consisting of death-associated protein kinase 1/protein kinase D/apoptosis signal-regulating kinase 1 (ASK1)/JNK/NADPH oxidase/caspases, which merges at ASK1 with a death-signaling cascade, mediated by amyloid β precursor protein (APP). Notably, netrin1 also binds to APP and partially inhibits the death-signaling cascade, induced by APP. These results may provide new insight into the amyloid β-independent pathomechanism of AD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Cascade theory in isotopic separation processes; Theorie des cascades en separation isotopique

Energy Technology Data Exchange (ETDEWEB)

Agostini, J P

1994-06-01

Three main areas are developed within the scope of this work: - the first one is devoted to fundamentals: separative power, value function, ideal cascade and square cascade. Applications to two main cases are carried out, namely: Study of binary isotopic mix, Study of processes with a small enrichment coefficient. - The second one is devoted to cascade coupling -high-flux coupling (more widely used and better known) as well as low-flux coupling are presented and compared to one another. - The third one is an outlook on problems linked to cascade transients. Those problem are somewhat intricate and their interest lies mainly into two areas: economics where the start-up time may have a large influence on the interests paid during the construction and start-up period, military productions where the start-up time has a direct bearing on the production schedule. (author). 50 figs. 3 annexes. 12 refs. 6 tabs.

MAP Kinase Cascades Regulate the Cold Response by Modulating ICE1 Protein Stability.

Science.gov (United States)

Zhao, Chunzhao; Wang, Pengcheng; Si, Tong; Hsu, Chuan-Chih; Wang, Lu; Zayed, Omar; Yu, Zheping; Zhu, Yingfang; Dong, Juan; Tao, W Andy; Zhu, Jian-Kang

2017-12-04

Mitogen-activated protein kinase cascades are important signaling modules that convert environmental stimuli into cellular responses. We show that MPK3, MPK4, and MPK6 are rapidly activated after cold treatment. The mpk3 and mpk6 mutants display increased expression of CBF genes and enhanced freezing tolerance, whereas constitutive activation of the MKK4/5-MPK3/6 cascade in plants causes reduced expression of CBF genes and hypersensitivity to freezing, suggesting that the MKK4/5-MPK3/6 cascade negatively regulates the cold response. MPK3 and MPK6 can phosphorylate ICE1, a basic-helix-loop-helix transcription factor that regulates the expression of CBF genes, and the phosphorylation promotes the degradation of ICE1. Interestingly, the MEKK1-MKK2-MPK4 pathway constitutively suppresses MPK3 and MPK6 activities and has a positive role in the cold response. Furthermore, the MAPKKK YDA and two calcium/calmodulin-regulated receptor-like kinases, CRLK1 and CRLK2, negatively modulate the cold activation of MPK3/6. Our results uncover important roles of MAPK cascades in the regulation of plant cold response. Copyright © 2017 Elsevier Inc. All rights reserved.

A 8X Oversampling Ratio, 14bit, 5-MSamples/s Cascade 3-1 Sigma-delta Modulator

Directory of Open Access Journals (Sweden)

Y. Yin

2005-01-01

Full Text Available A 14-b, 5-MHz output-rate cascaded 3-1 sigma-delta analog-to-digital converters (ADC has been developed for broadband communication applications, and a novel 4th-order noise-shaping is obtained by using the proposed architecture. At a low oversampling ratio (OSR of 8, the ADC achieves 91.5dB signal-to-quantization ratio (SQNR, in contrast to 71.8dB of traditional 2-1-1 cascaded sigma-delta ADC in 2.5-MHz bandwidth and over 80dB signal-to-noise and distortion (SINAD even under assumptions of awful circuit non-idealities and opamp non-linearity. The proposed architecture can potentially operates at much more high frequencies with scaled IC technology, to expand the analog-to-digital conversion rate for high-resolution applications.

Phase locking and spectral linewidth of a two-mode terahertz quantum cascade laser

NARCIS (Netherlands)

Baryshev, A.; Hovenier, J.N.; Adam, A.J.L.; Kašalynas, I.; Gao, J.R.; Klaassen, T.O.; Williams, B.S.; Kumar, S.; Hu, Q.; Reno, J.L.

2006-01-01

We have studied the phase locking and spectral linewidth of an ? 2.7?THz quantum cascade laser by mixing its two lateral lasing modes. The beat signal at about 8?GHz is compared with a microwave reference by applying conventional phase lock loop circuitry with feedback to the laser bias current.

Signalling crosstalk in plants: emerging issues.

Science.gov (United States)

Taylor, Jane E; McAinsh, Martin R

2004-01-01

The Oxford English Dictionary defines crosstalk as 'unwanted transfer of signals between communication channels'. How does this definition relate to the way in which we view the organization and function of signalling pathways? Recent advances in the field of plant signalling have challenged the traditional view of a signalling transduction cascade as isolated linear pathways. Instead the picture emerging of the mechanisms by which plants transduce environmental signals is of the interaction between transduction chains. The manner in which these interactions occur (and indeed whether the transfer of these signals is 'unwanted' or beneficial) is currently the topic of intense research.

Wnt signaling in cancer

Science.gov (United States)

Zhan, T; Rindtorff, N; Boutros, M

2017-01-01

Wnt signaling is one of the key cascades regulating development and stemness, and has also been tightly associated with cancer. The role of Wnt signaling in carcinogenesis has most prominently been described for colorectal cancer, but aberrant Wnt signaling is observed in many more cancer entities. Here, we review current insights into novel components of Wnt pathways and describe their impact on cancer development. Furthermore, we highlight expanding functions of Wnt signaling for both solid and liquid tumors. We also describe current findings how Wnt signaling affects maintenance of cancer stem cells, metastasis and immune control. Finally, we provide an overview of current strategies to antagonize Wnt signaling in cancer and challenges that are associated with such approaches. PMID:27617575

Cascading costs: an economic nitrogen cycle.

Science.gov (United States)

Moomaw, William R; Birch, Melissa B L

2005-09-01

The chemical nitrogen cycle is becoming better characterized in terms of fluxes and reservoirs on a variety of scales. Galloway has demonstrated that reactive nitrogen can cascade through multiple ecosystems causing environmental damage at each stage before being denitrified to N(2). We propose to construct a parallel economic nitrogen cascade (ENC) in which economic impacts of nitrogen fluxes can be estimated by the costs associated with each stage of the chemical cascade. Using economic data for the benefits of damage avoided and costs of mitigation in the Chesapeake Bay basin, we have constructed an economic nitrogen cascade for the region. Since a single ton of nitrogen can cascade through the system, the costs also cascade. Therefore evaluating the benefits of mitigating a ton of reactive nitrogen released needs to consider the damage avoided in all of the ecosystems through which that ton would cascade. The analysis reveals that it is most cost effective to remove a ton of nitrogen coming from combustion since it has the greatest impact on human health and creates cascading damage through the atmospheric, terrestrial, aquatic and coastal ecosystems. We will discuss the implications of this analysis for determining the most cost effective policy option for achieving environmental quality goals.

Contingency Analysis of Cascading Line Outage Events

Energy Technology Data Exchange (ETDEWEB)

Thomas L Baldwin; Magdy S Tawfik; Miles McQueen

2011-03-01

As the US power systems continue to increase in size and complexity, including the growth of smart grids, larger blackouts due to cascading outages become more likely. Grid congestion is often associated with a cascading collapse leading to a major blackout. Such a collapse is characterized by a self-sustaining sequence of line outages followed by a topology breakup of the network. This paper addresses the implementation and testing of a process for N-k contingency analysis and sequential cascading outage simulation in order to identify potential cascading modes. A modeling approach described in this paper offers a unique capability to identify initiating events that may lead to cascading outages. It predicts the development of cascading events by identifying and visualizing potential cascading tiers. The proposed approach was implemented using a 328-bus simplified SERC power system network. The results of the study indicate that initiating events and possible cascading chains may be identified, ranked and visualized. This approach may be used to improve the reliability of a transmission grid and reduce its vulnerability to cascading outages.

Mitogen-activated protein kinase signaling in plants

DEFF Research Database (Denmark)

Rodriguez, Maria Cristina Suarez; Petersen, Morten; Mundy, John

2010-01-01

crossinhibition, feedback control, and scaffolding. Plant MAPK cascades regulate numerous processes, including stress and hormonal responses, innate immunity, and developmental programs. Genetic analyses have uncovered several predominant MAPK components shared by several of these processes including...... of substrate proteins, whose altered activities mediate a wide array of responses, including changes in gene expression. Cascades may share kinase components, but their signaling specificity is maintained by spaciotemporal constraints and dynamic protein-protein interactions and by mechanisms that include...

Investigation on performance of all optical buffer with large dynamical delay time based on cascaded double loop optical buffers

International Nuclear Information System (INIS)

Yong-Jun, Wang; Xiang-Jun, Xin; Xiao-Lei, Zhang; Chong-Qing, Wu; Kuang-Lu, Yu

2010-01-01

Optical buffers are critical for optical signal processing in future optical packet-switched networks. In this paper, a theoretical study as well as an experimental demonstration on a new optical buffer with large dynamical delay time is carried out based on cascaded double loop optical buffers (DLOBs). It is found that pulse distortion can be restrained by a negative optical control mode when the optical packet is in the loop. Noise analysis indicates that it is feasible to realise a large variable delay range by cascaded DLOBs. These conclusions are validated by the experiment system with 4-stage cascaded DLOBs. Both the theoretical simulations and the experimental results indicate that a large delay range of 1–9999 times the basic delay unit and a fine granularity of 25 ns can be achieved by the cascaded DLOBs. The performance of the cascaded DLOBs is suitable for the all optical networks. (classical areas of phenomenology)

Phase locking and spectral linewidth of a two-mode terahertz quantum cascade laser

NARCIS (Netherlands)

Baryshev, A.; Hovenier, J. N.; Adam, A. J. L.; Kašalynas, I.; Gao, J. R.; Klaassen, T. O.; Williams, B. S.; Kumar, S.; Hu, Q.; Reno, J. L.

2006-01-01

We have studied the phase locking and spectral linewidth of an ˜2.7THz quantum cascade laser by mixing its two lateral lasing modes. The beat signal at about 8GHz is compared with a microwave reference by applying conventional phase lock loop circuitry with feedback to the laser bias current. Phase

Simulation of concentration spikes in cascades

International Nuclear Information System (INIS)

Wood, H.G.

2006-01-01

Research has been conducted to investigate the maximum possible enrichment that might be temporarily achieved in a facility that is producing enriched uranium for fuel for nuclear power reactors. The purpose is to provide information to evaluate if uranium enrichment facilities are producing 235 U enriched within declared limits appropriate for power reactors or if the facilities are actually producing more highly enriched uranium. The correlation between feed rate and separation factor in a gas centrifuge cascade shows that as flow decreases, the separation factor increases, thereby, creating small amounts of higher enriched uranium than would be found under optimum design operating conditions. The research uses a number of cascade enrichment programs to model the phenomenon and determine the maximum enrichment possible during the time transient of a gas centrifuge cascade. During cascade start-up, the flow through the centrifuges begins at lower than centrifuge design stage flow rates. Steady-state cascade models have been used to study the maximum 235 U concentrations that would be predicted in the cascade. These calculations should produce an upper bound of product concentrations expected during the transient phase of start-up. Due to the fact that there are different ways in which to start a cascade, several methods are used to determine the maximum enrichment during the time transient. Model cascades were created for gas centrifuges with several product to .feed assay separation factors. With this information, the models were defined and the equilibrium programs were used to determine the maximum enrichment level during the time transient. The calculations predict in a cascade with separation factor 1.254 designed to produce enriched uranium for the purpose of supplying reactor fuel, it would not be unreasonable to see some 235 U in the range of 12-15%. Higher assays produced during the start-up period might lead inspectors to believe the cascade is being

Restriction Cascade Exponential Amplification (RCEA) assay with an attomolar detection limit: a novel, highly specific, isothermal alternative to qPCR.

Science.gov (United States)

Ghindilis, Andrey L; Smith, Maria W; Simon, Holly M; Seoudi, Ihab A; Yazvenko, Nina S; Murray, Iain A; Fu, Xiaoqing; Smith, Kenneth; Jen-Jacobson, Linda; Xu, Shuang-Yong

2015-01-13

An alternative to qPCR was developed for nucleic acid assays, involving signal rather than target amplification. The new technology, Restriction Cascade Exponential Amplification (RCEA), relies on specific cleavage of probe-target hybrids by restriction endonucleases (REase). Two mutant REases for amplification (Ramp), S17C BamHI and K249C EcoRI, were conjugated to oligonucleotides, and immobilized on a solid surface. The signal generation was based on: (i) hybridization of a target DNA to a Ramp-oligonucleotide probe conjugate, followed by (ii) specific cleavage of the probe-target hybrid using a non-immobilized recognition REase. The amount of Ramp released into solution upon cleavage was proportionate to the DNA target amount. Signal amplification was achieved through catalysis, by the free Ramp, of a restriction cascade containing additional oligonucleotide-conjugated Ramp and horseradish peroxidase (HRP). Colorimetric quantification of free HRP indicated that the RCEA achieved a detection limit of 10 aM (10(-17) M) target concentration, or approximately 200 molecules, comparable to the sensitivity of qPCR-based assays. The RCEA assay had high specificity, it was insensitive to non-specific binding, and detected target sequences in the presence of foreign DNA. RCEA is an inexpensive isothermal assay that allows coupling of the restriction cascade signal amplification with any DNA target of interest.

Aluminum stress and its role in the phospholipid signaling pathway in plants and possible biotechnological applications.

Science.gov (United States)

Poot-Poot, Wilberth; Hernandez-Sotomayor, Soledad M Teresa

2011-10-01

An early response of plants to environmental signals or abiotic stress suggests that the phospholipid signaling pathway plays a pivotal role in these mechanisms. The phospholipid signaling cascade is one of the main systems of cellular transduction and is related to other signal transduction mechanisms. These other mechanisms include the generation of second messengers and their interactions with various proteins, such as ion channels. This phospholipid signaling cascade is activated by changes in the environment, such as phosphate starvation, water, metals, saline stres, and plant-pathogen interactions. One important factor that impacts agricultural crops is metal-induced stress. Because aluminum has been considered to be a major toxic factor for agriculture conducted in acidic soils, many researchers have focused on understanding the mechanisms of aluminum toxicity in plants. We have contributed the last fifteen years in this field by studying the effects of aluminum on phospholipid signaling in coffee, one of the Mexico's primary crops. We have focused our research on aluminum toxicity mechanisms in Coffea arabica suspension cells as a model for developing future contributions to the biotechnological transformation of coffee crops such that they can be made resistant to aluminum toxicity. We conclude that aluminum is able to not only generate a signal cascade in plants but also modulate other signal cascades generated by other types of stress in plants. The aim of this review is to discuss possible involvement of the phospholipid signaling pathway in the aluminum toxicity response of plant cells. Copyright © 2011 Wiley Periodicals, Inc.

Stability of cascade search

Energy Technology Data Exchange (ETDEWEB)

Fomenko, Tatiana N [M. V. Lomonosov Moscow State University, Faculty of Computational Mathematics and Cybernetics, Moscow (Russian Federation)

2010-10-22

We find sufficient conditions on a searching multi-cascade for a modification of the set of limit points of the cascade that satisfy an assessing inequality for the distance from each of these points to the initial point to be small, provided that the modifications of the initial point and the initial set-valued functionals or maps used to construct the multi-cascade are small. Using this result, we prove the stability (in the above sense) of the cascade search for the set of common pre-images of a closed subspace under the action of n set-valued maps, n{>=}1 (in particular, for the set of common roots of these maps and for the set of their coincidences). For n=2 we obtain generalizations of some results of A. V. Arutyunov; the very statement of the problem comes from a recent paper of his devoted to the study of the stability of the subset of coincidences of a Lipschitz map and a covering map.

Genetic algorithm based separation cascade optimization

International Nuclear Information System (INIS)

Mahendra, A.K.; Sanyal, A.; Gouthaman, G.; Bera, T.K.

2008-01-01

The conventional separation cascade design procedure does not give an optimum design because of squaring-off, variation of flow rates and separation factor of the element with respect to stage location. Multi-component isotope separation further complicates the design procedure. Cascade design can be stated as a constrained multi-objective optimization. Cascade's expectation from the separating element is multi-objective i.e. overall separation factor, cut, optimum feed and separative power. Decision maker may aspire for more comprehensive multi-objective goals where optimization of cascade is coupled with the exploration of separating element optimization vector space. In real life there are many issues which make it important to understand the decision maker's perception of cost-quality-speed trade-off and consistency of preferences. Genetic algorithm (GA) is one such evolutionary technique that can be used for cascade design optimization. This paper addresses various issues involved in the GA based multi-objective optimization of the separation cascade. Reference point based optimization methodology with GA based Pareto optimality concept for separation cascade was found pragmatic and promising. This method should be explored, tested, examined and further developed for binary as well as multi-component separations. (author)

System design description for the CPDF Cascade Control Room: SDD-7

International Nuclear Information System (INIS)

1980-05-01

The Cascade Control Room (CCR) is the nerve center of the Centrifuge Plant Demonstration Facility (CPDF). The components within the CCR monitor and control those variables necessary for the safe and efficient operation of the cascade during normal and emergency operation. The CCR interfaces with all the process systems and most of the support systems, receiving and transmitting data signals at frequent intervals during all phases of cascade operation. The main component in the CCR is the control room computer (CRC), which serves as the primary interface between the CCR and the process and support systems. The other components in the CCR are: (1) instrumentation cabinets; (2) operator control panel; (3) mass spectrometer - tails (MST); (4) mass spectrometer - product (MSP); (5) product light gas analyzer (PLGA); and (6) the operator. CCR instrumentation provides audible and visual alarms of abnormal events detected by process and utilities instrumentation or by the CRC. Records of alarms and process and utility variables are continuously generated in the CCR. Operator control functions are performed through the CRC or at the various instrument cabinets. Analysis of the current operating status of the plant is aided by the CRC and CCR instrumentation. 14 figs., 2 tabs

Ion-implantation dense cascade data

International Nuclear Information System (INIS)

Winterbon, K.B.

1983-04-01

A tabulation is given of data useful in estimating various aspects of ion-implantation cascades in the nuclear stopping regime, particularly with respect to nonlinearity of the cascade at high energy densities. The tabulation is restricted to self-ion implantation. Besides power-cross-section cascade dimensions, various material properties are included. Scaling of derived quantities with input data is noted, so one is not limited to the values assumed by the author

Distinct Upstream Role of Type I IFN Signaling in Hematopoietic Stem Cell-Derived and Epithelial Resident Cells for Concerted Recruitment of Ly-6Chi Monocytes and NK Cells via CCL2-CCL3 Cascade.

Directory of Open Access Journals (Sweden)

Erdenebileg Uyangaa

Full Text Available Type I interferon (IFN-I-dependent orchestrated mobilization of innate cells in inflamed tissues is believed to play a critical role in controlling replication and CNS-invasion of herpes simplex virus (HSV. However, the crucial regulators and cell populations that are affected by IFN-I to establish the early environment of innate cells in HSV-infected mucosal tissues are largely unknown. Here, we found that IFN-I signaling promoted the differentiation of CCL2-producing Ly-6Chi monocytes and IFN-γ/granzyme B-producing NK cells, whereas deficiency of IFN-I signaling induced Ly-6Clo monocytes producing CXCL1 and CXCL2. More interestingly, recruitment of Ly-6Chi monocytes preceded that of NK cells with the levels peaked at 24 h post-infection in IFN-I-dependent manner, which was kinetically associated with the CCL2-CCL3 cascade response. Early Ly-6Chi monocyte recruitment was governed by CCL2 produced from hematopoietic stem cell (HSC-derived leukocytes, whereas NK cell recruitment predominantly depended on CC chemokines produced by resident epithelial cells. Also, IFN-I signaling in HSC-derived leukocytes appeared to suppress Ly-6Ghi neutrophil recruitment to ameliorate immunopathology. Finally, tissue resident CD11bhiF4/80hi macrophages and CD11chiEpCAM+ dendritic cells appeared to produce initial CCL2 for migration-based self-amplification of early infiltrated Ly-6Chi monocytes upon stimulation by IFN-I produced from infected epithelial cells. Ultimately, these results decipher a detailed IFN-I-dependent pathway that establishes orchestrated mobilization of Ly-6Chi monocytes and NK cells through CCL2-CCL3 cascade response of HSC-derived leukocytes and epithelium-resident cells. Therefore, this cascade response of resident-to-hematopoietic-to-resident cells that drives cytokine-to-chemokine-to-cytokine production to recruit orchestrated innate cells is critical for attenuation of HSV replication in inflamed tissues.

On Generalized Fractional Differentiator Signals

Directory of Open Access Journals (Sweden)

Hamid A. Jalab

2013-01-01

Full Text Available By employing the generalized fractional differential operator, we introduce a system of fractional order derivative for a uniformly sampled polynomial signal. The calculation of the bring in signal depends on the additive combination of the weighted bring-in of N cascaded digital differentiators. The weights are imposed in a closed formula containing the Stirling numbers of the first kind. The approach taken in this work is to consider that signal function in terms of Newton series. The convergence of the system to a fractional time differentiator is discussed.

Hadron cascades produced by electromagnetic cascades

International Nuclear Information System (INIS)

Nelson, W.R.; Jenkins, T.M.; Ranft, J.

1986-12-01

A method for calculating high energy hadron cascades induced by multi-GeV electron and photon beams is described. Using the EGS4 computer program, high energy photons in the EM shower are allowed to interact hadronically according to the vector meson dominance (VMD) model, facilitated by a Monte Carlo version of the dual multistring fragmentation model which is used in the hadron cascade code FLUKA. The results of this calculation compare very favorably with experimental data on hadron production in photon-proton collisions and on the hadron production by electron beams on targets (i.e., yields in secondary particle beam lines). Electron beam induced hadron star density contours are also presented and are compared with those produced by proton beams. This FLUKA-EGS4 coupling technique could find use in the design of secondary beams, in the determination high energy hadron source terms for shielding purposes, and in the estimation of induced radioactivity in targets, collimators and beam dumps

Cascade Organic Solar Cells

KAUST Repository

Schlenker, Cody W.

2011-09-27

We demonstrate planar organic solar cells consisting of a series of complementary donor materials with cascading exciton energies, incorporated in the following structure: glass/indium-tin-oxide/donor cascade/C 60/bathocuproine/Al. Using a tetracene layer grown in a descending energy cascade on 5,6-diphenyl-tetracene and capped with 5,6,11,12-tetraphenyl- tetracene, where the accessibility of the π-system in each material is expected to influence the rate of parasitic carrier leakage and charge recombination at the donor/acceptor interface, we observe an increase in open circuit voltage (Voc) of approximately 40% (corresponding to a change of +200 mV) compared to that of a single tetracene donor. Little change is observed in other parameters such as fill factor and short circuit current density (FF = 0.50 ± 0.02 and Jsc = 2.55 ± 0.23 mA/cm2) compared to those of the control tetracene-C60 solar cells (FF = 0.54 ± 0.02 and Jsc = 2.86 ± 0.23 mA/cm2). We demonstrate that this cascade architecture is effective in reducing losses due to polaron pair recombination at donor-acceptor interfaces, while enhancing spectral coverage, resulting in a substantial increase in the power conversion efficiency for cascade organic photovoltaic cells compared to tetracene and pentacene based devices with a single donor layer. © 2011 American Chemical Society.

Cascade Organic Solar Cells

KAUST Repository

Schlenker, Cody W.; Barlier, Vincent S.; Chin, Stephanie W.; Whited, Matthew T.; McAnally, R. Eric; Forrest, Stephen R.; Thompson, Mark E.

2011-01-01

We demonstrate planar organic solar cells consisting of a series of complementary donor materials with cascading exciton energies, incorporated in the following structure: glass/indium-tin-oxide/donor cascade/C 60/bathocuproine/Al. Using a tetracene layer grown in a descending energy cascade on 5,6-diphenyl-tetracene and capped with 5,6,11,12-tetraphenyl- tetracene, where the accessibility of the π-system in each material is expected to influence the rate of parasitic carrier leakage and charge recombination at the donor/acceptor interface, we observe an increase in open circuit voltage (Voc) of approximately 40% (corresponding to a change of +200 mV) compared to that of a single tetracene donor. Little change is observed in other parameters such as fill factor and short circuit current density (FF = 0.50 ± 0.02 and Jsc = 2.55 ± 0.23 mA/cm2) compared to those of the control tetracene-C60 solar cells (FF = 0.54 ± 0.02 and Jsc = 2.86 ± 0.23 mA/cm2). We demonstrate that this cascade architecture is effective in reducing losses due to polaron pair recombination at donor-acceptor interfaces, while enhancing spectral coverage, resulting in a substantial increase in the power conversion efficiency for cascade organic photovoltaic cells compared to tetracene and pentacene based devices with a single donor layer. © 2011 American Chemical Society.

Updating the Wnt pathways

Science.gov (United States)

Yu, Jia; Virshup, David M.

2014-01-01

In the three decades since the discovery of the Wnt1 proto-oncogene in virus-induced mouse mammary tumours, our understanding of the signalling pathways that are regulated by the Wnt proteins has progressively expanded. Wnts are involved in an complex signalling network that governs multiple biological processes and cross-talk with multiple additional signalling cascades, including the Notch, FGF (fibroblast growth factor), SHH (Sonic hedgehog), EGF (epidermal growth factor) and Hippo pathways. The Wnt signalling pathway also illustrates the link between abnormal regulation of the developmental processes and disease manifestation. Here we provide an overview of Wnt-regulated signalling cascades and highlight recent advances. We focus on new findings regarding the dedicated Wnt production and secretion pathway with potential therapeutic targets that might be beneficial for patients with Wnt-related diseases. PMID:25208913

Cascaded FSO-VLC Communication System

KAUST Repository

Gupta, Akash

2017-08-28

The proposed cascaded free space optics (FSO)-visible light communication (VLC) system consists of multiple VLC access points which caters the end users connected via a decode and forward (DF) relay to the FSO backhaul link. The FSO link is assumed to be affected by path-loss, pointing error and atmospheric turbulence while the end-to-end signal-to-noise ratio (SNR) of VLC downlinks are statistically characterized considering the randomness of users position. In this study, the novel closed form expressions of the statistics like probability density function (PDF) and cumulative distribution function (CDF) of the equivalent SNR are derived. Capitalizing on these, the closed form expressions for various performance metrics such as outage probability and error probability are provided. The simulation results are provided to verify the functional curves of mathematical analysis.

GEFs: Dual regulation of Rac1 signaling.

Science.gov (United States)

Marei, Hadir; Malliri, Angeliki

2017-04-03

GEFs play a critical role in regulating Rac1 signaling. They serve as signaling nodes converting upstream signals into downstream Rac1-driven cellular responses. Through associating with membrane-bound Rac1, GEFs facilitate the exchange of GDP for GTP, thereby activating Rac1. As a result, Rac1 undergoes conformational changes that mediate its interaction with downstream effectors, linking Rac1 to a multitude of physiological and pathological processes. Interestingly, there are at least 20 GEFs involved in Rac1 activation, suggesting a more complex role of GEFs in regulating Rac1 signaling apart from promoting the exchange of GDP for GTP. Indeed, accumulating evidence implicates GEFs in directing the specificity of Rac1-driven signaling cascades, although the underlying mechanisms were poorly defined. Recently, through conducting a comparative study, we highlighted the role of 2 Rac-specific GEFs, Tiam1 and P-Rex1, in dictating the biological outcome downstream of Rac1. Importantly, further proteomic analysis uncovered a GEF activity-independent function for both GEFs in modulating the Rac1 interactome, which results in the stimulation of GEF-specific signaling cascades. Here, we provide an overview of our recent findings and discuss the role of GEFs as master regulators of Rac1 signaling with a particular focus on GEF-mediated modulation of cell migration following Rac1 activation.

Lamotrigine blocks NMDA receptor-initiated arachidonic acid signalling in rat brain: Implications for its efficacy in bipolar disorder

Science.gov (United States)

Ramadan, Epolia; Basselin, Mireille; Rao, Jagadeesh S.; Chang, Lisa; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I.

2011-01-01

An upregulated brain arachidonic acid (AA) cascade and a hyperglutamatergic state characterize bipolar disorder (BD). Lamotrigine (LTG), a mood stabilizer approved for treating BD, is reported to interfere with glutamatergic neurotransmission involving N-methyl-D-aspartate receptors (NMDARs). NMDARs allow extracellular calcium into the cell, thereby stimulating calcium-dependent cytosolic phospholipase A2 (cPLA2) to release arachidonic acid (AA) from membrane phospholipid. We hypothesized that LTG, like other approved mood stabilizers, would reduce NMDAR-mediated AA signaling in rat brain. An acute subconvulsant dose of NMDA (25 mg/kg) or saline was administered intraperitoneally to unanesthetized rats that had been treated p.o. daily for 42 days with vehicle or a therapeutically relevant dose of LTG (10 mg/kg/.d). Regional brain AA incorporation coefficients k* and rates Jin, AA signals, were measured using quantitative autoradiography after intravenous [1-14C]AA infusion, as were other AA cascade markers. In chronic vehicle-treated rats, acute NMDA compared to saline increased k* and Jin in widespread regions of the brain, as well as prostaglandin (PG)E2 and thromboxane B2 concentrations. Chronic LTG treatment compared to vehicle reduced brain cyclooxygenase (COX) activity, PGE2 concentration, and DNA binding activity of the COX-2 transcription factor, NF-κB. Pretreatment with chronic LTG blocked the acute NMDA effects on AA cascade markers. In summary, chronic LTG like other mood stabilizers blocks NMDA-mediated signaling involving the AA metabolic cascade. Since markers of the AA cascade and of NMDAR signaling are up-regulated in the postmortem BD brain, mood stabilizers generally may be effective in BD by dampening NMDAR signalling and the AA cascade. PMID:21733229

Cascaded Bragg scattering in fiber optics.

Science.gov (United States)

Xu, Y Q; Erkintalo, M; Genty, G; Murdoch, S G

2013-01-15

We report on a theoretical and experimental study of cascaded Bragg scattering in fiber optics. We show that the usual energy-momentum conservation of Bragg scattering can be considerably relaxed via cascade-induced phase-matching. Experimentally we demonstrate frequency translation over six- and 11-fold cascades, in excellent agreement with derived phase-matching conditions.

Phase Locking of a 2.7 THz Quantum Cascade Laser to a Microwave Reference

Science.gov (United States)

Khosropanah, P.; Baryshev, A.; Zhang, W.; Jellema, W.; Hovenier, J. N.; Gao, J. R.; Klapwijk, T. M.; Paveliev, D. G.; Williams, B. S.; Hu, Q.;

Disorders of dysregulated signal traffic through the RAS-MAPK pathway: phenotypic spectrum and molecular mechanisms.

Science.gov (United States)

Tartaglia, Marco; Gelb, Bruce D

2010-12-01

RAS GTPases control a major signaling network implicated in several cellular functions, including cell fate determination, proliferation, survival, differentiation, migration, and senescence. Within this network, signal flow through the RAF-MEK-ERK pathway-the first identified mitogen-associated protein kinase (MAPK) cascade-mediates early and late developmental processes controlling morphology determination, organogenesis, synaptic plasticity, and growth. Signaling through the RAS-MAPK cascade is tightly controlled; and its enhanced activation represents a well-known event in oncogenesis. Unexpectedly, in the past few years, inherited dysregulation of this pathway has been recognized as the cause underlying a group of clinically related disorders sharing facial dysmorphism, cardiac defects, reduced postnatal growth, ectodermal anomalies, variable cognitive deficits, and susceptibility to certain malignancies as major features. These disorders are caused by heterozygosity for mutations in genes encoding RAS proteins, regulators of RAS function, modulators of RAS interaction with effectors, or downstream signal transducers. Here, we provide an overview of the phenotypic spectrum associated with germline mutations perturbing RAS-MAPK signaling, the unpredicted molecular mechanisms converging toward the dysregulation of this signaling cascade, and major genotype-phenotype correlations. © 2010 New York Academy of Sciences.

Cascade redox flow battery systems

Science.gov (United States)

Horne, Craig R.; Kinoshita, Kim; Hickey, Darren B.; Sha, Jay E.; Bose, Deepak

2014-07-22

A reduction/oxidation ("redox") flow battery system includes a series of electrochemical cells arranged in a cascade, whereby liquid electrolyte reacts in a first electrochemical cell (or group of cells) before being directed into a second cell (or group of cells) where it reacts before being directed to subsequent cells. The cascade includes 2 to n stages, each stage having one or more electrochemical cells. During a charge reaction, electrolyte entering a first stage will have a lower state-of-charge than electrolyte entering the nth stage. In some embodiments, cell components and/or characteristics may be configured based on a state-of-charge of electrolytes expected at each cascade stage. Such engineered cascades provide redox flow battery systems with higher energy efficiency over a broader range of current density than prior art arrangements.

Cascade of links in complex networks

Energy Technology Data Exchange (ETDEWEB)

Feng, Yeqian; Sun, Bihui [Department of Management Science, School of Government, Beijing Normal University, 100875 Beijing (China); Zeng, An, E-mail: anzeng@bnu.edu.cn [School of Systems Science, Beijing Normal University, 100875 Beijing (China)

2017-01-30

Cascading failure is an important process which has been widely used to model catastrophic events such as blackouts and financial crisis in real systems. However, so far most of the studies in the literature focus on the cascading process on nodes, leaving the possibility of link cascade overlooked. In many real cases, the catastrophic events are actually formed by the successive disappearance of links. Examples exist in the financial systems where the firms and banks (i.e. nodes) still exist but many financial trades (i.e. links) are gone during the crisis, and the air transportation systems where the airports (i.e. nodes) are still functional but many airlines (i.e. links) stop operating during bad weather. In this letter, we develop a link cascade model in complex networks. With this model, we find that both artificial and real networks tend to collapse even if a few links are initially attacked. However, the link cascading process can be effectively terminated by setting a few strong nodes in the network which do not respond to any link reduction. Finally, a simulated annealing algorithm is used to optimize the location of these strong nodes, which significantly improves the robustness of the networks against the link cascade. - Highlights: • We propose a link cascade model in complex networks. • Both artificial and real networks tend to collapse even if a few links are initially attacked. • The link cascading process can be effectively terminated by setting a few strong nodes. • A simulated annealing algorithm is used to optimize the location of these strong nodes.

Cascade of links in complex networks

International Nuclear Information System (INIS)

Feng, Yeqian; Sun, Bihui; Zeng, An

2017-01-01

Cascading failure is an important process which has been widely used to model catastrophic events such as blackouts and financial crisis in real systems. However, so far most of the studies in the literature focus on the cascading process on nodes, leaving the possibility of link cascade overlooked. In many real cases, the catastrophic events are actually formed by the successive disappearance of links. Examples exist in the financial systems where the firms and banks (i.e. nodes) still exist but many financial trades (i.e. links) are gone during the crisis, and the air transportation systems where the airports (i.e. nodes) are still functional but many airlines (i.e. links) stop operating during bad weather. In this letter, we develop a link cascade model in complex networks. With this model, we find that both artificial and real networks tend to collapse even if a few links are initially attacked. However, the link cascading process can be effectively terminated by setting a few strong nodes in the network which do not respond to any link reduction. Finally, a simulated annealing algorithm is used to optimize the location of these strong nodes, which significantly improves the robustness of the networks against the link cascade. - Highlights: • We propose a link cascade model in complex networks. • Both artificial and real networks tend to collapse even if a few links are initially attacked. • The link cascading process can be effectively terminated by setting a few strong nodes. • A simulated annealing algorithm is used to optimize the location of these strong nodes.

Plant cell surface receptor-mediated signaling - a common theme amid diversity.

Science.gov (United States)

He, Yunxia; Zhou, Jinggeng; Shan, Libo; Meng, Xiangzong

2018-01-29

Sessile plants employ a diverse array of plasma membrane-bound receptors to perceive endogenous and exogenous signals for regulation of plant growth, development and immunity. These cell surface receptors include receptor-like kinases (RLKs) and receptor-like proteins (RLPs) that harbor different extracellular domains for perception of distinct ligands. Several RLK and RLP signaling pathways converge at the somatic embryogenesis receptor kinases (SERKs), which function as shared co-receptors. A repertoire of receptor-like cytoplasmic kinases (RLCKs) associate with the receptor complexes to relay intracellular signaling. Downstream of the receptor complexes, mitogen-activated protein kinase (MAPK) cascades are among the key signaling modules at which the signals converge, and these cascades regulate diverse cellular and physiological responses through phosphorylation of different downstream substrates. In this Review, we summarize the emerging common theme that underlies cell surface receptor-mediated signaling pathways in Arabidopsis thaliana : the dynamic association of RLKs and RLPs with specific co-receptors and RLCKs for signal transduction. We further discuss how signaling specificities are maintained through modules at which signals converge, with a focus on SERK-mediated receptor signaling. © 2018. Published by The Company of Biologists Ltd.

Sugar signalling and gene expression in relation to carbohydrate ...

Indian Academy of Sciences (India)

Sucrose is required for plant growth and development. The sugar status of plant cells is sensed by sensor proteins. The signal generated by signal transduction cascades, which could involve mitogen-activated protein kinases, protein phosphatases, Ca2+ and calmodulins, results in appropriate gene expression. A variety of ...

e-Manifest

Science.gov (United States)

This is the primary hub for those seeking information about the e-Manifest system, its advisory board, and its development. Once the system is complete this area will serve as the portal into the e-Manifest system from EPA webpages.

The imaging manifestation of intracranial schwannomas not arising from cranial nerves

International Nuclear Information System (INIS)

Luo Boning; Sun Gengxi; Liang Kangfu

2003-01-01

Objective: To report 4 cases of operation-confirmed intracranial schwannomas not arising from cranial nerves, and to discuss the histogenesis and CT and MRI manifestation combining with the literature. Methods: CT and MRI findings of these 4 intracranial schwannomas were analyzed retrospectively and their pathologic characteristics were reviewed. Results: The tumors demonstrated low-iso mixed density with necrotic and cystic areas. Large degeneration even became the prominent characteristics on CT scan. Low-signal to iso-signal intensity on T 1 -weighted images and heterogeneous high-signal intensity on T 2 -weighted images were revealed. The solid portion and the wall of the tumors were moderately enhanced on enhanced CT and MRI scans. Hematoxylin and eosin-stained sections showed two corresponding histological patterns: Antoni Type A and Antoni Type B pattern. The tumor cells exhibited a strong positive staining pattern for s-100 protein. Conclusion: The imaging manifestations of these tumors were similar to that of cranial nerve schwannomas except that the former had higher cystic degeneration rate. We should take that diagnosis into consideration when the mass is not located on cranial nerve but its image feature resembles schwannomas

The comparison of extraction of energy in two-cascade and one-cascade targets

Energy Technology Data Exchange (ETDEWEB)

Dolgoleva, G. V., E-mail: dolgg@list.ru [National Research Tomsk State University, 36, Lenin Ave., 634050, Tomsk (Russian Federation); Ponomarev, I. V., E-mail: wingof17@mail.ru [Moscow State University, Department of Mechanics and Mathematics, 1, Vorobyovy Gory, Moscow,119961 (Russian Federation)

2016-01-15

The paper is devoted to numerical designing of cylindrical microtargets on the basis of shock-free compression. When designing microtargets for the controlled thermonuclear fusion, the core tasks are to select geometry and make-up of layers, and the law of energy embedding as well, which allow receiving of “burning” of deuterium- tritium mix, that is, the existence of thermonuclear reactions of working area. Yet, the energy yield as a result of thermonuclear reactions has to be more than the embedded energy (the coefficient of amplification is more than a unit). So, an important issue is the value of the embedded energy. The purpose of the present paper is to study the extraction of energy by working DT area in one-cascade and two-cascade targets. A bigger extraction of energy will contribute to a better burning of DT mix and a bigger energy yield as a result of thermonuclear reactions. The comparison of analytical results to numerical calculations is carried out. The received results show advantages of a two-cascade target compared to a one-cascade one.

Wnt Signaling Cascades and the Roles of Syndecan Proteoglycans

DEFF Research Database (Denmark)

Pataki, Csilla A; Couchman, John R; Brábek, Jan

2015-01-01

/planar cell polarity and Wnt/calcium signaling. Syndecans are type I transmembrane proteoglycans with a long evolutionary history, being expressed in all Bilateria and in almost all cell types. Both Wnt pathways have been extensively studied over the past 30 years and shown to have roles during development...... and in a multitude of diseases. Although the first evidence for interactions between syndecans and Wnts dates back to 1997, the number of studies connecting these pathways is low, and many open questions remained unanswered. In this review, syndecan's involvement in Wnt signaling pathways as well as some...

Wnt Signaling in Kidney Development and Disease.

Science.gov (United States)

Wang, Yongping; Zhou, Chengji J; Liu, Youhua

2018-01-01

Wnt signal cascade is an evolutionarily conserved, developmental pathway that regulates embryogenesis, injury repair, and pathogenesis of human diseases. It is well established that Wnt ligands transmit their signal via canonical, β-catenin-dependent and noncanonical, β-catenin-independent mechanisms. Mounting evidence has revealed that Wnt signaling plays a key role in controlling early nephrogenesis and is implicated in the development of various kidney disorders. Dysregulations of Wnt expression cause a variety of developmental abnormalities and human diseases, such as congenital anomalies of the kidney and urinary tract, cystic kidney, and renal carcinoma. Multiple Wnt ligands, their receptors, and transcriptional targets are upregulated during nephron formation, which is crucial for mediating the reciprocal interaction between primordial tissues of ureteric bud and metanephric mesenchyme. Renal cysts are also associated with disrupted Wnt signaling. In addition, Wnt components are important players in renal tumorigenesis. Activation of Wnt/β-catenin is instrumental for tubular repair and regeneration after acute kidney injury. However, sustained activation of this signal cascade is linked to chronic kidney diseases and renal fibrosis in patients and experimental animal models. Mechanistically, Wnt signaling controls a diverse array of biologic processes, such as cell cycle progression, cell polarity and migration, cilia biology, and activation of renin-angiotensin system. In this chapter, we have reviewed recent findings that implicate Wnt signaling in kidney development and diseases. Targeting this signaling may hold promise for future treatment of kidney disorders in patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Experimental study of flow through compressor Cascade

Directory of Open Access Journals (Sweden)

Satyam Panchal

2017-09-01

Full Text Available The objective of this research work is to study the behaviour of flow at the inlet, within the blade passage and at the exit of a compressor cascade. For this purpose, a cascade with six numbers of aerofoil blades was designed and constructed. The cascade was fitted on the cascade test tunnel. Out of six blades two were instrumented for measuring the pressure distribution on the pressure and suction surface. The blades had a parabolic camber line, with a maximum camber position at 40% of the chord from the leading edge of the blade. The profile of the blade was C4, height of the blade was 160 mm, chord length was 80 mm, camber angle was 45° and stagger angle was 30°. Similarly, the length of the cascade was 300 mm, span was 160 mm, pitch was 60 mm, the actual chord of the cascade was 80 mm, the axial chord of the cascade was 70 mm, the stagger angle of the cascade was 30° and the pitch-chord ratio was 0.75. The data was taken and analyzed at −500% of the axial chord before the cascade, −25% of the axial chord before the leading edge, 25%, 50%, 75% and 150% of the axial chord from the leading edge of the blade. The readings were taken from the cascade wall to the mid span position along the pitch wise direction. The angle of incidence was also changed during the experiment and varied from i=−50°, −30°, −10° to 5°.

Double closed-loop cascade control for lower limb exoskeleton with elastic actuation.

Science.gov (United States)

Zhu, Yanhe; Zheng, Tianjiao; Jin, Hongzhe; Yang, Jixing; Zhao, Jie

2015-01-01

Unlike traditional rigid actuators, the significant features of Series Elastic Actuator (SEA) are stable torque control, lower output impedance, impact resistance and energy storage. Recently, SEA has been applied in many exoskeletons. In such applications, a key issue is how to realize the human-exoskeleton movement coordination. In this paper, double closed-loop cascade control for lower limb exoskeleton with SEA is proposed. This control method consists of inner SEA torque loop and outer contact force loop. Utilizing the SEA torque control with a motor velocity loop, actuation performances of SEA are analyzed. An integrated exoskeleton control system is designed, in which joint angles are calculated by internal encoders and resolvers and contact forces are gathered by external pressure sensors. The double closed-loop cascade control model is established based on the feedback signals of internal and external sensor. Movement experiments are accomplished in our prototype of lower limb exoskeleton. Preliminary results indicate the exoskeleton movements with pilot can be realized stably by utilizing this double closed-loop cascade control method. Feasibility of the SEA in our exoskeleton robot and effectiveness of the control method are verified.

Spectroscopic approaches to resolving ambiguities of hyper-polarized NMR signals from different reaction cascades

DEFF Research Database (Denmark)

Jensen, Pernille Rose; Meier, Sebastian

2016-01-01

The influx of exogenous substrates into cellular reaction cascades on the seconds time scale is directly observable by NMR spectroscopy when using nuclear spin polarization enhancement. Conventional NMR assignment spectra for the identification of reaction intermediates are not applicable...... in these experiments due to the non-equilibrium nature of the nuclear spin polarization enhancement. We show that ambiguities in the intracellular identification of transient reaction intermediates can be resolved by experimental schemes using site-specific isotope labelling, optimised referencing and response...

Traditional healers, faith healers and medical practitioners: the contribution of medical pluralism to bottlenecks along the cascade of care for HIV/AIDS in Eastern and Southern Africa.

Science.gov (United States)

Moshabela, Mosa; Bukenya, Dominic; Darong, Gabriel; Wamoyi, Joyce; McLean, Estelle; Skovdal, Morten; Ddaaki, William; Ondeng'e, Kenneth; Bonnington, Oliver; Seeley, Janet; Hosegood, Victoria; Wringe, Alison

2017-07-01

There are concerns that medical pluralism may delay patients' progression through the HIV cascade-of-care. However, the pathways of impact through which medical pluralism influence the care of people living with HIV (PLHIV) in African settings remain unclear. We sought to establish the manifestation of medical pluralism among PLHIV, and explore mechanisms through which medical pluralism contributes bottlenecks along the HIV care cascade. We conducted a multicountry exploratory qualitative study in seven health and demographic surveillance sites in six eastern and southern African countries: Uganda, Kenya, Tanzania, Malawi, Zimbabwe and South Africa. We interviewed 258 PLHIV at different stages of the HIV cascade-of-care, 48 family members of deceased PLHIV and 53 HIV healthcare workers. Interviews were conducted using shared standardised topic guides, and data managed through NVIVO 8/10/11. We conducted a thematic analysis of healthcare pathways and bottlenecks related to medical pluralism. Medical pluralism, manifesting across traditional, faith-based and biomedical health-worlds, contributed to the care cascade bottlenecks for PLHIV through three pathways of impact. First, access to HIV treatment was delayed through the nature of health-related beliefs, knowledge and patient journeys. Second, HIV treatment was interrupted by availability of alternative options, perceived failed treatment and exploitation of PLHIV by opportunistic traders and healers. Lastly, the mixing of biomedical healthcare providers and treatment with traditional and faith-based options fuelled tensions driven by fear of drug-to-drug interactions and mistrust between providers operating in different health-worlds. Medical pluralism contributes to delays and interruptions of care along the HIV cascade, and mistrust between health providers. Region-wide interventions and policies are urgently needed in sub-Saharan Africa to minimise potential harm and consequences of medical pluralism for PLHIV

ERK5 signaling gets XIAPed: a role for ubiquitin in the disassembly of a MAPK cascade

Science.gov (United States)

Klein, Aileen M; Cobb, Melanie H

2014-01-01

Mitogen-activated protein kinase (MAPK) cascades are tightly controlled through a series of well-characterized phospho-regulatory events. In this issue, Takeda et al (2014) identify the inhibitor of apoptosis protein, XIAP, as a key regulator of ERK5 activation via uncoupling of upstream kinase activity by non-degradative ubiquitination. PMID:25012518

First results on photon strength functions of 78Se from the two-step γ Cascades measurement

Science.gov (United States)

Valenta, Stanislav; Bečvář, František; Krtička, Milan; Tomandl, Ivo

2017-09-01

Two-step gamma cascades (TSCs) following the radiative capture of thermal neutrons in 77Se were measured at the research reactor at Řež near Prague. Results on photon strength functions (PSFs) of 78Se, obtained from comparison of experimental TSC spectra with outcomes of simulations under different assumptions about level density and PSFs using the DICEBOX algorithm, are presented. The main attention is paid to possible manifestation of the pygmy resonance observed recently in this nucleus in the nuclear resonance fluorescence measurement and low-energy PSF enhancement observed in Oslo-type experiments for all A ≲ 100 nuclei.

A comparison of methods for cascade prediction

OpenAIRE

Guo, Ruocheng; Shakarian, Paulo

2016-01-01

Information cascades exist in a wide variety of platforms on Internet. A very important real-world problem is to identify which information cascades can go viral. A system addressing this problem can be used in a variety of applications including public health, marketing and counter-terrorism. As a cascade can be considered as compound of the social network and the time series. However, in related literature where methods for solving the cascade prediction problem were proposed, the experimen...

Computer simulation of displacement cascades in copper

International Nuclear Information System (INIS)

Heinisch, H.L.

1983-06-01

More than 500 displacement cascades in copper have been generated with the computer simulation code MARLOWE over an energy range pertinent to both fission and fusion neutron spectra. Three-dimensional graphical depictions of selected cascades, as well as quantitative analysis of cascade shapes and sizes and defect densities, illustrate cascade behavior as a function of energy. With increasing energy, the transition from production of single compact damage regions to widely spaced multiple damage regions is clearly demonstrated

Cascade Error Projection Learning Algorithm

Science.gov (United States)

Duong, T. A.; Stubberud, A. R.; Daud, T.

1995-01-01

A detailed mathematical analysis is presented for a new learning algorithm termed cascade error projection (CEP) and a general learning frame work. This frame work can be used to obtain the cascade correlation learning algorithm by choosing a particular set of parameters.

Traffic signal synchronization.

Science.gov (United States)

Huang, Ding-wei; Huang, Wei-neng

2003-05-01

The benefits of traffic signal synchronization are examined within the cellular automata approach. The microsimulations of traffic flow are obtained with different settings of signal period T and time delay delta. Both numerical results and analytical approximations are presented. For undersaturated traffic, the green-light wave solutions can be realized. For saturated traffic, the correlation among the traffic signals has no effect on the throughput. For oversaturated traffic, the benefits of synchronization are manifest only when stochastic noise is suppressed.

Ultrarelativistic cascades and strangeness production

International Nuclear Information System (INIS)

Kahana, D.E.; Kahana, S.H.

1998-02-01

A two phase cascade, LUCIFER II, developed for the treatment of ultra high energy Ion-Ion collisions is applied to the production of strangeness at SPS energies. This simulation is able to simultaneously describe both hard processes such as Drell-Yan and slower, soft processes such as the production of light mesons by separating the dynamics into two steps, a fast cascade involving only the nucleons in the original colliding relativistic ions followed, after an appropriate delay, by a normal multiscattering of the resulting excited baryons and mesons produced virtually in the first step. No energy loss can take place in the short time interval over which the first cascade takes place. The chief result is a reconciliation of the important Drell-Yan measurements with the apparent success of standard cascades to describe the nucleon stopping and meson production in heavy ion experiments at the CERN SPS

Domain-Specific Activation of Death-Associated Intracellular Signalling Cascades by the Cellular Prion Protein in Neuroblastoma Cells.

Science.gov (United States)

Vilches, Silvia; Vergara, Cristina; Nicolás, Oriol; Mata, Ágata; Del Río, José A; Gavín, Rosalina

2016-09-01

The biological functions of the cellular prion protein remain poorly understood. In fact, numerous studies have aimed to determine specific functions for the different protein domains. Studies of cellular prion protein (PrP(C)) domains through in vivo expression of molecules carrying internal deletions in a mouse Prnp null background have provided helpful data on the implication of the protein in signalling cascades in affected neurons. Nevertheless, understanding of the mechanisms underlying the neurotoxicity induced by these PrP(C) deleted forms is far from complete. To better define the neurotoxic or neuroprotective potential of PrP(C) N-terminal domains, and to overcome the heterogeneity of results due to the lack of a standardized model, we used neuroblastoma cells to analyse the effects of overexpressing PrP(C) deleted forms. Results indicate that PrP(C) N-terminal deleted forms were properly processed through the secretory pathway. However, PrPΔF35 and PrPΔCD mutants led to death by different mechanisms sharing loss of alpha-cleavage and activation of caspase-3. Our data suggest that both gain-of-function and loss-of-function pathogenic mechanisms may be associated with N-terminal domains and may therefore contribute to neurotoxicity in prion disease. Dissecting the molecular response induced by PrPΔF35 may be the key to unravelling the physiological and pathological functions of the prion protein.

Inferring network structure from cascades

Science.gov (United States)

Ghonge, Sushrut; Vural, Dervis Can

2017-07-01

Many physical, biological, and social phenomena can be described by cascades taking place on a network. Often, the activity can be empirically observed, but not the underlying network of interactions. In this paper we offer three topological methods to infer the structure of any directed network given a set of cascade arrival times. Our formulas hold for a very general class of models where the activation probability of a node is a generic function of its degree and the number of its active neighbors. We report high success rates for synthetic and real networks, for several different cascade models.

Cascaded multiplexed optical link on a telecommunication network for frequency dissemination.

Science.gov (United States)

Lopez, Olivier; Haboucha, Adil; Kéfélian, Fabien; Jiang, Haifeng; Chanteau, Bruno; Roncin, Vincent; Chardonnet, Christian; Amy-Klein, Anne; Santarelli, Giorgio

2010-08-02

We demonstrate a cascaded optical link for ultrastable frequency dissemination comprised of two compensated links of 150 km and a repeater station. Each link includes 114 km of Internet fiber simultaneously carrying data traffic through a dense wavelength division multiplexing technology, and passes through two routing centers of the telecommunication network. The optical reference signal is inserted in and extracted from the communication network using bidirectional optical add-drop multiplexers. The repeater station operates autonomously ensuring noise compensation on the two links and the ultra-stable signal optical regeneration. The compensated link shows a fractional frequency instability of 3 x 10(-15) at one second measurement time and 5 x 10(-20) at 20 hours. This work paves the way to a wide dissemination of ultra-stable optical clock signals between distant laboratories via the Internet network.

Abnormal cascading failure spreading on complex networks

International Nuclear Information System (INIS)

Wang, Jianwei; Sun, Enhui; Xu, Bo; Li, Peng; Ni, Chengzhang

2016-01-01

Applying the mechanism of the preferential selection of the flow destination, we develop a new method to quantify the initial load on an edge, of which the flow is transported along the path with the shortest edge weight between two nodes. Considering the node weight, we propose a cascading model on the edge and investigate cascading dynamics induced by the removal of the edge with the largest load. We perform simulated attacks on four types of constructed networks and two actual networks and observe an interesting and counterintuitive phenomenon of the cascading spreading, i.e., gradually improving the capacity of nodes does not lead to the monotonous increase in the robustness of these networks against cascading failures. The non monotonous behavior of cascading dynamics is well explained by the analysis on a simple graph. We additionally study the effect of the parameter of the node weight on cascading dynamics and evaluate the network robustness by a new metric.

Imaging manifestation of cerebral gumma: report of 3 cases

International Nuclear Information System (INIS)

Wen Ming; Miao Tizong; Zheng Luping; Zhang Shilin

2003-01-01

Objective: To evaluate the imaging manifestations of cerebral gumma. Methods: Three cases of surgically proved cerebral gumma were analyzed. All patients had history of ultra-marriage sexual life, and the laboratory tests, including the serums and/or the cerebrospinal fluid test, highly indicated the diagnosis of syphilis. Pathological results demonstrated cerebral gumma after operation. Results: On CT scan, case 1 showed a 5.0 cm x 3.5 cm hypo-density area at left temporal lobe with obvious mass effect, and post-contrast CT scan revealed a rim enhancement. MR scanning was not performed. In case 2, a mixture lesion was detected on right frontal lobe on pre-contrast CT scan, and spot-like central enhancement and mild mass effect were demonstrated on postcontrast CT scan. Pre-contrast T 1 WI showed 2 round lesions situated at right frontal lobe (1.5 cm in diameter) and right periventricular areas (1.0 cm in diameter), separately, which showed iso-signal on T 1 WI and hyper-signal on T 2 WI, and ring-like enhancement with slight compression of the right lateral ventricle. In case 3, CT plain scan demonstrated multiple hypo-dense lesions, most of the lesions located on both frontal lobe and left temporal lobe, and enhanced CT scan was not performed. MR imaging revealed many nodule and mass lesions with hypo-signal on T 1 WI and hyper-signal on T 2 WI, located on both hemispheres with nodular or circular enhancement after injection of contrast media. Conclusion: The imaging manifestations of cerebral gumma were nonspecific. Thus, the preoperational diagnosis should be made combining the clinical, laboratory, and imaging data

Learn about the Hazardous Waste Electronic Manifest System (e-Manifest)

Science.gov (United States)

This webpage provides information on EPA's work toward developing a hazardous waste electronic manifest system. Information on the Hazardous Waste Electronic Manifest Establishment Act, progress on the project and frequent questions are available.

Non-genomic actions of aldosterone: From receptors and signals to membrane targets.

LENUS (Irish Health Repository)

2012-02-01

In tissues which express the mineralocorticoid receptor (MR), aldosterone modulates the expression of membrane targets such as the subunits of the epithelial Na(+) channel, in combination with important signalling intermediates such as serum and glucocorticoid-regulated kinase-1. In addition, the rapid \\'non-genomic\\' activation of protein kinases and secondary messenger signalling cascades has also been detected in aldosterone-sensitive tissues of the nephron, distal colon and cardiovascular system. These rapid actions are variously described as being coupled to MR or to an as yet unidentified, membrane-associated aldosterone receptor. The rapidly activated signalling cascades add a level of fine-tuning to the activity of aldosterone-responsive membrane transporters and also modulate the aldosterone-induced changes in gene expression through receptor and transcription factor phosphorylation.

Non-genomic actions of aldosterone: From receptors and signals to membrane targets.

LENUS (Irish Health Repository)

Dooley, Ruth

2011-07-26

In tissues which express the mineralocorticoid receptor (MR), aldosterone modulates the expression of membrane targets such as the subunits of the epithelial Na(+) channel, in combination with important signalling intermediates such as serum and glucocorticoid-regulated kinase-1. In addition, the rapid \\'non-genomic\\' activation of protein kinases and secondary messenger signalling cascades has also been detected in aldosterone-sensitive tissues of the nephron, distal colon and cardiovascular system. These rapid actions are variously described as being coupled to MR or to an as yet unidentified, membrane-associated aldosterone receptor. The rapidly activated signalling cascades add a level of fine-tuning to the activity of aldosterone-responsive membrane transporters and also modulate the aldosterone-induced changes in gene expression through receptor and transcription factor phosphorylation.

Gas separation performance of tapered cascade with membrane

International Nuclear Information System (INIS)

Ohno, Masayoshi; Morisue, Tetsuo; Ozaki, Osamu; Miyauchi, Terukatsu.

1978-01-01

Membrane gas separation cascades are analyzed at steady state. The method of calculating the flow rate and concentration profiles in the cascade are examined, using formulas expressing the various membrane separation cell characteristics. The method adopted is applicable to relatively high concentrations and separation factors. Considerations are further given on the steady state performance of four theoretical forms of cascade: (a) with common value of cut for all stages, (b) with symmetric separation cells, (c) with no mixing at the junction at each stage, and (d) ideal cascade. The analysis showed that, with membrane cells, the ideal cascade would have a pressure ratio varying from stage to stage. The symmetric separation cascade would provide a separation performance lower than the ideal cascade on account of the mixing at the junctions of streams possessing different concentrations, whereas the cut and separation factor of the no-mixing cascade requiring minimum membrane area exhibits zig-zag curves when plotted against stage number. Both these circumstances contribute to the lower separation performance obtained with these two forms as compared with the ideal cascade, and results in larger total membrane area; but these semi-ideal forms retain the advantage of easy practical treatment with their pressure ratio common to all stages. (auth.)

Ultrarelativistic cascades and strangeness production

Energy Technology Data Exchange (ETDEWEB)

Kahana, D.E. [State Univ. of New York, Stony Brook, NY (United States). Dept. of Physics; Kahana, S.H. [Brookhaven National Lab., Upton, NY (United States). Physics Dept.

1998-08-24

A two-phase cascade code, LUCIFER II, developed for the treatment of ultra high energy-ion-ion collisions is applied to the production of strangeness at SPS energies {radical}(s)=17-20. This simulation is able to simultaneously describe both hard processes such as Drell-Yan and slower, soft processes such as the production of light mesons by separating the dynamics into two steps, a fast cascade involving only the nucleons in the original colliding relativistic ions followed, after an appropriate delay, by a normal multiscattering of the resulting excited baryons and mesons produced virtually in the first step. No energy loss can take place in the short time interval over which the first cascade takes place. The chief result is a reconciliation of the important Drell-Yan measurements with the apparent success of standard cascades to describe the nucleon stopping and meson production in heavy-ion experiments at the CERN SPS. (orig.) 26 refs.

Ultrarelativistic cascades and strangeness production

International Nuclear Information System (INIS)

Kahana, D.E.; Kahana, S.H.

1998-01-01

A two-phase cascade code, LUCIFER II, developed for the treatment of ultra high energy-ion-ion collisions is applied to the production of strangeness at SPS energies √(s)=17-20. This simulation is able to simultaneously describe both hard processes such as Drell-Yan and slower, soft processes such as the production of light mesons by separating the dynamics into two steps, a fast cascade involving only the nucleons in the original colliding relativistic ions followed, after an appropriate delay, by a normal multiscattering of the resulting excited baryons and mesons produced virtually in the first step. No energy loss can take place in the short time interval over which the first cascade takes place. The chief result is a reconciliation of the important Drell-Yan measurements with the apparent success of standard cascades to describe the nucleon stopping and meson production in heavy-ion experiments at the CERN SPS. (orig.)

Joint state and parameter estimation for a class of cascade systems: Application to a hemodynamic model

KAUST Repository

Zayane, Chadia

2014-06-01

In this paper, we address a special case of state and parameter estimation, where the system can be put on a cascade form allowing to estimate the state components and the set of unknown parameters separately. Inspired by the nonlinear Balloon hemodynamic model for functional Magnetic Resonance Imaging problem, we propose a hierarchical approach. The system is divided into two subsystems in cascade. The state and input are first estimated from a noisy measured signal using an adaptive observer. The obtained input is then used to estimate the parameters of a linear system using the modulating functions method. Some numerical results are presented to illustrate the efficiency of the proposed method.

Wnt signaling: Ig-norrin the dogma.

Science.gov (United States)

Clevers, Hans

2004-06-08

Secreted Wnt proteins trigger the intracellular Wnt signaling cascade upon engagement of dedicated Frizzled-Lrp receptor complexes. Unexpectedly, a non-Wnt ligand for this receptor complex has now been discovered. This novel ligand, Norrin, is mutated in the hereditary ocular Norrie syndrome. Copyright 2004 Elsevier Ltd.

Molecular Mechanism: ERK Signaling, Drug Addiction, and Behavioral Effects.

Science.gov (United States)

Sun, Wei-Lun; Quizon, Pamela M; Zhu, Jun

2016-01-01

Addiction to psychostimulants has been considered as a chronic psychiatric disorder characterized by craving and compulsive drug seeking and use. Over the past two decades, accumulating evidence has demonstrated that repeated drug exposure causes long-lasting neurochemical and cellular changes that result in enduring neuroadaptation in brain circuitry and underlie compulsive drug consumption and relapse. Through intercellular signaling cascades, drugs of abuse induce remodeling in the rewarding circuitry that contributes to the neuroplasticity of learning and memory associated with addiction. Here, we review the role of the extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase, and its related intracellular signaling pathways in drug-induced neuroadaptive changes that are associated with drug-mediated psychomotor activity, rewarding properties and relapse of drug seeking behaviors. We also discuss the neurobiological and behavioral effects of pharmacological and genetic interferences with ERK-associated molecular cascades in response to abused substances. Understanding the dynamic modulation of ERK signaling in response to drugs may provide novel molecular targets for therapeutic strategies to drug addiction. Copyright © 2016. Published by Elsevier Inc.

Defect accumulation under cascade damage conditions

DEFF Research Database (Denmark)

Trinkaus, H.; Singh, B.N.; Woo, C.H.

1994-01-01

in terms of this reaction kinetics taking into account cluster production, dissociation, migration and annihilation at extended sinks. Microstructural features which are characteristic of cascade damage and cannot be explained in terms of the conventional single defect reaction kinetics are emphasized......There is now ample evidence from both experimental and computer simulation studies that in displacement cascades not only intense recombination takes place but also efficient clustering of both self-interstitial atoms (SIAs) and vacancies. The size distributions of the two types of defects produced...... reactions kinetics associated with the specific features of cascade damage is described, with emphasis on asymmetries between SIA and vacancy type defects concerning their production, stability, mobility and interactions with other defects. Defect accumulation under cascade damage conditions is discussed...

A 65nm CMOS low-power MedRadio-band integer-N cascaded phase-locked loop for implantable medical systems.

Science.gov (United States)

Wang, Yi-Xiao; Chen, Wei-Ming; Wu, Chung-Yu

2014-01-01

This paper presents a low-power MedRadio-band integer-N phase-locked Loop (PLL) system which is composed of two charge-pump PLLs cascade connected. The PLL provides the operation clock and local carrier signals for an implantable medical electronic system. In addition, to avoid the off-chip crystal oscillator, the 13.56 MHz Industrial, Scientific and Medical (ISM) band signal from the wireless power transmission system is adopted as the input reference signal for the PLL. Ring-based voltage controlled oscillators (VCOs) with current control units are adopted to reduce chip area and power dissipation. The proposed cascaded PLL system is designed and implemented in TSMC 65-nm CMOS technology. The measured jitter for 216.96 MHz signal is 12.23 ps and the phase noise is -65.9 dBc/Hz at 100 kHz frequency offset under 402.926 MHz carrier frequency. The measured power dissipations are 66 μW in the first PLL and 195 μW in the whole system under 1-V supply voltage. The chip area is 0.1088 mm(2) and no off-chip component is required which is suitable for the integration of the implantable medical electronic system.

Cascade Error Projection: An Efficient Hardware Learning Algorithm

Science.gov (United States)

Duong, T. A.

1995-01-01

A new learning algorithm termed cascade error projection (CEP) is presented. CEP is an adaption of a constructive architecture from cascade correlation and the dynamical stepsize of A/D conversion from the cascade back propagation algorithm.

Quaternary Magmatism in the Cascades - Geologic Perspectives

Science.gov (United States)

Hildreth, Wes

2007-01-01

uniquely qualified to present this synthesis. During more than three decades of volcanological studies, he has carried out comprehensive investigations of Mount Adams, Mount Baker, the Three Sisters, and the Simcoe Mountains Volcanic Field. He also brings a broad experience in other volcanic arcs, having conducted integrated field and laboratory investigations at several major volcanic centers in the Andes and the Aleutian arcs. His expertise and perspective have been further enhanced by in-depth petrologic studies of caldera environments, primarily in Long Valley, California, and Yellowstone. On the basis of all these field and laboratory investigations and exhaustive literature searches, he has published three definitive petrologic syntheses addressing the passage and transformation of basaltic magmas from their mantle sources through the crust to form the many types of volcanic manifestations at the Earth's surface. A major strength of this Professional Paper is that it adheres to data first and foremost, and only then correlates these data with relevant theories. Petrological and geophysical interpretation is left to the later sections of the volume, and even there is never allowed to stray from the pertinent databases. Hildreth's interpretations are not just idle speculations, but are carefully reasoned inferences firmly based on his thorough evaluation of the observational geological data. Professional Paper 1744 should not be skimmed lightly, in the hope that the salient points will quickly rub off. Instead, every section, indeed every paragraph, presents scholarly observations and insightful interpretations that demand careful and thoughtful study. This volume will influence and guide the course of Cascade investigations for decades to come.

MR imaging of shaken baby syndrome manifested as chronic subdural hematoma

Energy Technology Data Exchange (ETDEWEB)

Lee, Yul; Lee, Kwan Seop; Hwang, Dae Hyun; Lee, In Jae; Kim, Hyun Beom; Lee, Jae Young [Hallym University College of Medicine, Anyang (Korea, Republic of)

2001-09-01

Shaken baby syndrome (SBS) is a form of child abuse that can cause significant head injuries, of which subdural hematoma (SDH) is the most common manifestation. We report the MRI findings of chronic SDH in three cases of SBS, involving two-, three- and eight-month-old babies. The SDH signal was mostly low on T1-weighted images and high on T2-weighted images, suggesting chronic SDH. In chronic SDH, a focal high signal on T1-weighted images was also noted, suggesting rebleeding. Contrast-enhanced MRI revealed diffuse dural enhancement.

MR imaging of shaken baby syndrome manifested as chronic subdural hematoma

International Nuclear Information System (INIS)

Lee, Yul; Lee, Kwan Seop; Hwang, Dae Hyun; Lee, In Jae; Kim, Hyun Beom; Lee, Jae Young

2001-01-01

Shaken baby syndrome (SBS) is a form of child abuse that can cause significant head injuries, of which subdural hematoma (SDH) is the most common manifestation. We report the MRI findings of chronic SDH in three cases of SBS, involving two-, three- and eight-month-old babies. The SDH signal was mostly low on T1-weighted images and high on T2-weighted images, suggesting chronic SDH. In chronic SDH, a focal high signal on T1-weighted images was also noted, suggesting rebleeding. Contrast-enhanced MRI revealed diffuse dural enhancement

The cyclic AMP cascade is altered in the fragile X nervous system.

Directory of Open Access Journals (Sweden)

Daniel J Kelley

2007-09-01

Full Text Available Fragile X syndrome (FX, the most common heritable cause of mental retardation and autism, is a developmental disorder characterized by physical, cognitive, and behavioral deficits. FX results from a trinucleotide expansion mutation in the fmr1 gene that reduces levels of fragile X mental retardation protein (FMRP. Although research efforts have focused on FMRP's impact on mGluR signaling, how the loss of FMRP leads to the individual symptoms of FX is not known. Previous studies on human FX blood cells revealed alterations in the cyclic adenosine 3', 5'-monophosphate (cAMP cascade. We tested the hypothesis that cAMP signaling is altered in the FX nervous system using three different model systems. Induced levels of cAMP in platelets and in brains of fmr1 knockout mice are substantially reduced. Cyclic AMP induction is also significantly reduced in human FX neural cells. Furthermore, cAMP production is decreased in the heads of FX Drosophila and this defect can be rescued by reintroduction of the dfmr gene. Our results indicate that a robust defect in cAMP production in FX is conserved across species and suggest that cAMP metabolism may serve as a useful biomarker in the human disease population. Reduced cAMP induction has implications for the underlying causes of FX and autism spectrum disorders. Pharmacological agents known to modulate the cAMP cascade may be therapeutic in FX patients and can be tested in these models, thus supplementing current efforts centered on mGluR signaling.

Assessment on tracking error performance of Cascade P/PI, NPID and N-Cascade controller for precise positioning of xy table ballscrew drive system

International Nuclear Information System (INIS)

Abdullah, L; Jamaludin, Z; Rafan, N A; Jamaludin, J; Chiew, T H

2013-01-01

At present, positioning plants in machine tools are looking for high degree of accuracy and robustness attributes for the purpose of compensating various disturbance forces. The objective of this paper is to assess the tracking performance of Cascade P/PI, Nonlinear PID (NPID) and Nonlinear cascade (N-Cascade) controller with the existence of disturbance forces in the form of cutting forces. Cutting force characteristics at different cutting parameters; such as spindle speed rotations is analysed using Fast Fourier Transform. The tracking performance of a Nonlinear cascade controller in presence of these cutting forces is compared with NPID controller and Cascade P/PI controller. Robustness of these controllers in compensating different cutting characteristics is compared based on reduction in the amplitudes of cutting force harmonics using Fast Fourier Transform. It is found that the N-cascade controller performs better than both NPID controller and Cascade P/PI controller. The average percentage error reduction between N-cascade controller and Cascade P/PI controller is about 65% whereas the average percentage error reduction between cascade controller and NPID controller is about 82% at spindle speed of 3000 rpm spindle speed rotation. The finalized design of N-cascade controller could be utilized further for machining application such as milling process. The implementation of N-cascade in machine tools applications will increase the quality of the end product and the productivity in industry by saving the machining time. It is suggested that the range of the spindle speed could be made wider to accommodate the needs for high speed machining

Mathematical modelling of SERK mediated BR signalling

NARCIS (Netherlands)

Esse, van G.W.

2013-01-01

Being sessile by nature plants are continuously challenged by biotic and abiotic stress factors. At the cellular level, different stimuli are perceived and translated to the desired response. In order to achieve this, signal transduction cascades have to be interlinked. Complex networks

Time structure of cascade showers

International Nuclear Information System (INIS)

Nakatsuka, Takao

1984-01-01

Interesting results have been reported on the time structure of the electromagnetic components of air showers which have been obtained by using recent fast electronic circuit technology. However, these analyses and explanations seem not very persuasive. One of the reasons is that there is not satisfactory theoretical calculation yet to explain the delay of electromagnetic components in cascade processes which are the object of direct observation. Therefore, Monte Carlo calculation was attempted for examining the relationship between the altitude at which high energy γ-ray is generated up in the air and the time structure of cascade showers at the level of observation. The investigation of a dominant factor over the delay of electromagnetic components indicated that the delay due to the multiple scattering of electrons was essential. The author used the analytical solution found by himself of C. N. Yang's equation for the study on the delay due to multiple scattering. The results were as follows: The average delay time and the spread of distribution of electromagnetic cascades were approximately in linear relationship with the mass of a material having passed in a thin uniform medium; the rise time of arrival time distribution for electromagnetic cascade showers was very steep under the condition that they were generated up in the air and observed on the ground; the subpeaks delayed by tens of ns in arrival time may sometimes appear due to the perturbation in electromagnetic cascade processes. (Wakatsuki, Y.)

Cascaded two-photon spectroscopy of Yb atoms with a transportable effusive atomic beam apparatus

International Nuclear Information System (INIS)

Song, Minsoo; Yoon, Tai Hyun

2013-01-01

We present a transportable effusive atomic beam apparatus for cascaded two-photon spectroscopy of the dipole-forbidden transition (6s 2 1 S 0 ↔ 6s7s 1 S 0 ) of Yb atoms. An ohmic-heating effusive oven is designed to have a reservoir volume of 1.6 cm 3 and a high degree of atomic beam collimation angle of 30 mrad. The new atomic beam apparatus allows us to detect the spontaneously cascaded two-photons from the 6s7s 1 S 0 state via the intercombination 6s6p 3 P 1 state with a high signal-to-noise ratio even at the temperature of 340 °C. This is made possible in our apparatus because of the enhanced atomic beam flux and superior detection solid angle.

Ouabain rescues rat nephrogenesis during intrauterine growth restriction by regulating the complement and coagulation cascades and calcium signaling pathway.

Science.gov (United States)

Chen, L; Yue, J; Han, X; Li, J; Hu, Y

2016-02-01

Intrauterine growth restriction (IUGR) is associated with a reduction in the numbers of nephrons in neonates, which increases the risk of hypertension. Our previous study showed that ouabain protects the development of the embryonic kidney during IUGR. To explore this molecular mechanism, IUGR rats were induced by protein and calorie restriction throughout pregnancy, and ouabain was delivered using a mini osmotic pump. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) of the embryonic kidneys. DEGs were submitted to the Database for Annotation and Visualization and Integrated Discovery, and gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Maternal malnutrition significantly reduced fetal weight, but ouabain treatment had no significant effect on body weight. A total of 322 (177 upregulated and 145 downregulated) DEGs were detected between control and the IUGR group. Meanwhile, 318 DEGs were found to be differentially expressed (180 increased and 138 decreased) between the IUGR group and the ouabain-treated group. KEGG pathway analysis indicated that maternal undernutrition mainly disrupts the complement and coagulation cascades and the calcium signaling pathway, which could be protected by ouabain treatment. Taken together, these two biological pathways may play an important role in nephrogenesis, indicating potential novel therapeutic targets against the unfavorable effects of IUGR.

Review: Mitogen-Activated Protein kinases in nutritional signaling in Arabidopsis

KAUST Repository

Chardin, Camille; Schenk, Sebastian T.; Hirt, Heribert; Colcombet, Jean; Krapp, Anne

2017-01-01

Mitogen-Activated Protein Kinase (MAPK) cascades are functional modules widespread among eukaryotic organisms. In plants, these modules are encoded by large multigenic families and are involved in many biological processes ranging from stress responses to cellular differentiation and organ development. Furthermore, MAPK pathways are involved in the perception of environmental and physiological modifications. Interestingly, some MAPKs play a role in several signaling networks and could have an integrative function for the response of plants to their environment. In this review, we describe the classification of MAPKs and highlight some of their biochemical actions. We performed an in silico analysis of MAPK gene expression in response to nutrients supporting their involvement in nutritional signaling. While several MAPKs have been identified as players in sugar, nitrogen, phosphate, iron and potassium-related signaling pathways, their biochemical functions are yet mainly unknown. The integration of these regulatory cascades in the current understanding of nutrient signaling is discussed and potential new avenues for approaches toward plants with higher nutrient use efficiencies are evoked.

Review: Mitogen-Activated Protein kinases in nutritional signaling in Arabidopsis

KAUST Repository

Chardin, Camille

2017-04-14

Mitogen-Activated Protein Kinase (MAPK) cascades are functional modules widespread among eukaryotic organisms. In plants, these modules are encoded by large multigenic families and are involved in many biological processes ranging from stress responses to cellular differentiation and organ development. Furthermore, MAPK pathways are involved in the perception of environmental and physiological modifications. Interestingly, some MAPKs play a role in several signaling networks and could have an integrative function for the response of plants to their environment. In this review, we describe the classification of MAPKs and highlight some of their biochemical actions. We performed an in silico analysis of MAPK gene expression in response to nutrients supporting their involvement in nutritional signaling. While several MAPKs have been identified as players in sugar, nitrogen, phosphate, iron and potassium-related signaling pathways, their biochemical functions are yet mainly unknown. The integration of these regulatory cascades in the current understanding of nutrient signaling is discussed and potential new avenues for approaches toward plants with higher nutrient use efficiencies are evoked.

Tuberous sclerosis complex: Recent advances in manifestations and therapy.

Science.gov (United States)

Wataya-Kaneda, Mari; Uemura, Motohide; Fujita, Kazutoshi; Hirata, Haruhiko; Osuga, Keigo; Kagitani-Shimono, Kuriko; Nonomura, Norio

2017-09-01

Tuberous sclerosis complex is an autosomal dominant inherited disorder characterized by generalized involvement and variable manifestations with a birth incidence of 1:6000. In a quarter of a century, significant progress in tuberous sclerosis complex has been made. Two responsible genes, TSC1 and TSC2, which encode hamartin and tuberin, respectively, were discovered in the 1990s, and their functions were elucidated in the 2000s. Hamartin-Tuberin complex is involved in the phosphoinositide 3-kinase-protein kinase B-mammalian target of rapamycin signal transduction pathway, and suppresses mammalian target of rapamycin complex 1 activity, which is a center for various functions. Constitutive activation of mammalian target of rapamycin complex 1 causes variable manifestations in tuberous sclerosis complex. Recently, genetic tests were launched to diagnose tuberous sclerosis complex, and mammalian target of rapamycin complex 1 inhibitors are being used to treat tuberous sclerosis complex patients. As a result of these advances, new diagnostic criteria have been established and an indispensable new treatment method; that is, "a cross-sectional medical examination system," a system to involve many experts for tuberous sclerosis complex diagnosis and treatments, was also created. Simultaneously, the frequency of genetic tests and advances in diagnostic technology have resulted in new views on symptoms. The numbers of tuberous sclerosis complex patients without neural symptoms are increasing, and for these patients, renal manifestations and pulmonary lymphangioleiomyomatosis have become important manifestations. New concepts of tuberous sclerosis complex-associated neuropsychiatric disorders or perivascular epithelioid cell tumors are being created. The present review contains a summary of recent advances, significant manifestations and therapy in tuberous sclerosis complex. © 2017 The Japanese Urological Association.

Phase-locking of a 2.5 THz quantum cascade laser to a frequency comb using a GaAs photomixer.

Science.gov (United States)

Ravaro, M; Manquest, C; Sirtori, C; Barbieri, S; Santarelli, G; Blary, K; Lampin, J-F; Khanna, S P; Linfield, E H

2011-10-15

We report the heterodyne detection and phase locking of a 2.5 THz quantum cascade laser (QCL) using a terahertz frequency comb generated in a GaAs photomixer using a femtosecond fiber laser. With 10 mW emitted by the QCL, the phase-locked signal at the intermediate frequency yields 80 dB of signal-to-noise ratio in a bandwidth of 1 Hz.

Formalism of continual integrals for cascade processes with particle fusion

International Nuclear Information System (INIS)

Gedalin, Eh.V.

1987-01-01

Formalism of continuous integrals for description of cascade processes, in which besides cascade particle reproduction, their synthesis and coalescence take place, is used. Account of cascade particle coalescence leads to the fact that the development of some cascade branches cannot be independent and main equations of the cascade process become functional instead of integral. The method of continuous intagrals permits to construct in the closed form producing functionals for the cascade process and to obtain the rules of their calculation using diagrams. Analytical expressions in the form of continuous integrals for producing functionals describing cascade development are obtained

Atypical manifestations of reversible posterior leukoencephalopathy syndrome: findings on diffusion imaging and ADC mapping

Energy Technology Data Exchange (ETDEWEB)

Ahn, K.J.; You, W.J.; Jeong, S.L.; Lee, J.W.; Kim, B.S.; Lee, J.H.; Hahn, S.T. [Dept. of Radiology, The Catholic Univ. of Korea, St. Mary' s Hospital, Seoul (Korea); Yang, D.W.; Son, Y.M. [Dept. of Neurology, The Catholic Univ. of Korea, St. Mary' s Hospital, Seoul (Korea)

2004-12-01

Typically, reversible posterior leukoencephalopathy syndrome (RPLS) involves the parieto-occipital lobes. When regions of the brain other than the parieto-occipital lobes are predominantly involved, the syndrome can be called atypical RPLS. The purpose of this study is to find radiological and pathophysiological features of atypical RPLS by using diffusion-weighted imaging (D-WI). We retrospectively reviewed seven patients (two with eclampsia, one with cyclosporine neurotoxicity, and four with hypertensive encephalopathy) with atypical MR manifestations of RPLS. Changes in signal intensity on T2-weighted imaging (T2-WI) and D-WI, and ADC ratio, were analyzed. In patients with atypical manifestation of RPLS, high signal intensities on T2-WI were noted in the frontal lobe, basal ganglia, thalamus, brainstem, and subcortical white matter in regions other than the parieto-occipital lobes. These areas of increased signal intensities on T2-WI showed increased ADC values, representing vasogenic edema in all seven patients. This result should be very useful in differentiating atypical RPLS from other metabolic brain disorders that affect the same sites with cytotoxic edema. (orig.)

Atypical manifestations of reversible posterior leukoencephalopathy syndrome: findings on diffusion imaging and ADC mapping

International Nuclear Information System (INIS)

Ahn, K.J.; You, W.J.; Jeong, S.L.; Lee, J.W.; Kim, B.S.; Lee, J.H.; Hahn, S.T.; Yang, D.W.; Son, Y.M.

2004-01-01

Typically, reversible posterior leukoencephalopathy syndrome (RPLS) involves the parieto-occipital lobes. When regions of the brain other than the parieto-occipital lobes are predominantly involved, the syndrome can be called atypical RPLS. The purpose of this study is to find radiological and pathophysiological features of atypical RPLS by using diffusion-weighted imaging (D-WI). We retrospectively reviewed seven patients (two with eclampsia, one with cyclosporine neurotoxicity, and four with hypertensive encephalopathy) with atypical MR manifestations of RPLS. Changes in signal intensity on T2-weighted imaging (T2-WI) and D-WI, and ADC ratio, were analyzed. In patients with atypical manifestation of RPLS, high signal intensities on T2-WI were noted in the frontal lobe, basal ganglia, thalamus, brainstem, and subcortical white matter in regions other than the parieto-occipital lobes. These areas of increased signal intensities on T2-WI showed increased ADC values, representing vasogenic edema in all seven patients. This result should be very useful in differentiating atypical RPLS from other metabolic brain disorders that affect the same sites with cytotoxic edema. (orig.)

Blind I/Q imbalance and nonlinear ISI mitigation in Nyquist-SCM direct detection system with cascaded widely linear and Volterra equalizer

Science.gov (United States)

Liu, Na; Ju, Cheng

2018-02-01

Nyquist-SCM signal after fiber transmission, direct detection (DD), and analog down-conversion suffers from linear ISI, nonlinear ISI, and I/Q imbalance, simultaneously. Theoretical analysis based on widely linear (WL) and Volterra series is given to explain the relationship and interaction of these three interferences. A blind equalization algorithm, cascaded WL and Volterra equalizer, is designed to mitigate these three interferences. Furthermore, the feasibility of the proposed cascaded algorithm is experimentally demonstrated based on a 40-Gbps data rate 16-quadrature amplitude modulation (QAM) virtual single sideband (VSSB) Nyquist-SCM DD system over 100-km standard single mode fiber (SSMF) transmission. In addition, the performances of conventional strictly linear equalizer, WL equalizer, Volterra equalizer, and cascaded WL and Volterra equalizer are experimentally evaluated, respectively.

Cascade theory in isotopic separation processes

International Nuclear Information System (INIS)

Agostini, J.P.

1994-06-01

Three main areas are developed within the scope of this work: - the first one is devoted to fundamentals: separative power, value function, ideal cascade and square cascade. Applications to two main cases are carried out, namely: Study of binary isotopic mix, Study of processes with a small enrichment coefficient. - The second one is devoted to cascade coupling -high-flux coupling (more widely used and better known) as well as low-flux coupling are presented and compared to one another. - The third one is an outlook on problems linked to cascade transients. Those problem are somewhat intricate and their interest lies mainly into two areas: economics where the start-up time may have a large influence on the interests paid during the construction and start-up period, military productions where the start-up time has a direct bearing on the production schedule. (author). 50 figs. 3 annexes. 12 refs. 6 tabs

Biomaterial delivery of morphogens to mimic the natural healing cascade in bone.

Science.gov (United States)

Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

2012-09-01

Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. Copyright © 2012 Elsevier B.V. All rights reserved.

Ion-irradiation studies of cascade damage in metals

International Nuclear Information System (INIS)

Averback, R.S.

1982-03-01

Ion-irradiation studies of the fundamental aspects of cascade damage in metals are reviewed. The emphasis of these studies has been the determination of the primary state of damage (i.e. the arrangement of atoms in the cascade region prior to thermal migration of defects). Progress has been made towards understanding the damage function (i.e. the number of Frenkel pairs produced as a function of primary recoil atom energy), the spatial configuration of vacancies and interstitials in the cascade and the cascade-induced mixing of atoms. It is concluded for these studies that the agitation of the lattice in the vicinity of energetic displacement cascades stimulates the defect motion and that such thermal spike motion induces recombination and clustering of Frenkel defects. 9 figures

Activation of Nrf2 Reduces UVA-Mediated MMP-1 Upregulation via MAPK/AP-1 Signaling Cascades: The Photoprotective Effects of Sulforaphane and Hispidulin

Science.gov (United States)

Chaiprasongsuk, Anyamanee; Lohakul, Jinaphat; Soontrapa, Kitipong; Sampattavanich, Somponnat; Akarasereenont, Pravit

2017-01-01

UVA irradiation plays a role in premature aging of the skin through triggering oxidative stress-associated stimulation of matrix metalloproteinase-1 (MMP-1) responsible for collagen degradation, a hallmark of photoaged skin. Compounds that can activate nuclear factor E2-related factor 2 (Nrf2), a transcription factor regulating antioxidant gene expression, should therefore serve as effective antiphotoaging agents. We investigated whether genetic silencing of Nrf2 could relieve UVA-mediated MMP-1 upregulation via activation of mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) signaling using human keratinocyte cell line (HaCaT). Antiphotoaging effects of hispidulin (HPD) and sulforaphane (SFN) were assessed on their abilities to activate Nrf2 in controlling MMP-1 and collagen expressions in association with phosphorylation of MAPKs (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38), c-Jun, and c-Fos, using the skin of BALB/c mice subjected to repetitive UVA irradiation. Our findings suggested that depletion of Nrf2 promoted both mRNA expression and activity of MMP-1 in the UVA-irradiated HaCaT cells. Treatment of Nrf2 knocked-down HaCaT cells with MAPK inhibitors significantly suppressed UVA-induced MMP-1 and AP-1 activities. Moreover, pretreatment of the mouse skin with HPD and SFN, which could activate Nrf2, provided protective effects against UVA-mediated MMP-1 induction and collagen depletion in correlation with the decreased levels of phosphorylated MAPKs, c-Jun, and c-Fos in the mouse skin. In conclusion, Nrf2 could influence UVA-mediated MMP-1 upregulation through the MAPK/AP-1 signaling cascades. HPD and SFN may therefore represent promising antiphotoaging candidates. PMID:28011874

The cAMP Signaling and MAP Kinase Pathways in Plant Pathogenic Fungi

NARCIS (Netherlands)

Mehrabi, R.; Zhao, X.; Kim, Y.; Xu, J.R.

2009-01-01

The key components of the well conserved cyclic AMP signaling and MAP kinase pathways have been functionally characterized in the corn smut Ustilago maydis, rice blast fungus Magnaporthe grisea, and a few other fungal pathogens. In general, the cAMP signaling and the MAP kinase cascade homologous to

Cascading failure in the wireless sensor scale-free networks

Science.gov (United States)

Liu, Hao-Ran; Dong, Ming-Ru; Yin, Rong-Rong; Han, Li

2015-05-01

In the practical wireless sensor networks (WSNs), the cascading failure caused by a failure node has serious impact on the network performance. In this paper, we deeply research the cascading failure of scale-free topology in WSNs. Firstly, a cascading failure model for scale-free topology in WSNs is studied. Through analyzing the influence of the node load on cascading failure, the critical load triggering large-scale cascading failure is obtained. Then based on the critical load, a control method for cascading failure is presented. In addition, the simulation experiments are performed to validate the effectiveness of the control method. The results show that the control method can effectively prevent cascading failure. Project supported by the Natural Science Foundation of Hebei Province, China (Grant No. F2014203239), the Autonomous Research Fund of Young Teacher in Yanshan University (Grant No. 14LGB017) and Yanshan University Doctoral Foundation, China (Grant No. B867).

Energy and carbon balances of wood cascade chains

Energy Technology Data Exchange (ETDEWEB)

Sathre, Roger; Gustavsson, Leif [Ecotechnology, Mid Sweden University, SE-831 25 OEstersund (Sweden)

2006-07-15

In this study we analyze the energy and carbon balances of various cascade chains for recovered wood lumber. Post-recovery options include reuse as lumber, reprocessing as particleboard, pulping to form paper products, and burning for energy recovery. We compare energy and carbon balances of chains of cascaded products to the balances of products obtained from virgin wood fiber or from non-wood material. We describe and quantify several mechanisms through which cascading can affect the energy and carbon balances: direct cascade effects due to different properties and logistics of virgin and recovered materials, substitution effects due to the reduced demand for non-wood materials when wood is cascaded, and land use effects due to alternative possible land uses when less timber harvest is needed because of wood cascading. In some analyses we assume the forest is a limiting resource, and in others we include a fixed amount of forest land from which biomass can be harvested for use as material or biofuel. Energy and carbon balances take into account manufacturing processes, recovery and transportation energy, material recovery losses, and forest processes. We find that land use effects have the greatest impact on energy and carbon balances, followed by substitution effects, while direct cascade effects are relatively minor. (author)

Identification and characterization of an ABA-activated MAP kinase cascade in Arabidopsis thaliana

KAUST Repository

Danquah, Agyemang

2015-04-01

Summary Abscisic acid (ABA) is a major phytohormone involved in important stress-related and developmental plant processes. Recent phosphoproteomic analyses revealed a large set of ABA-triggered phosphoproteins as putative mitogen-activated protein kinase (MAPK) targets, although the evidence for MAPKs involved in ABA signalling is still scarce. Here, we identified and reconstituted in vivo a complete ABA-activated MAPK cascade, composed of the MAP3Ks MAP3K17/18, the MAP2K MKK3 and the four C group MAPKs MPK1/2/7/14. In planta, we show that ABA activation of MPK7 is blocked in mkk3-1 and map3k17mapk3k18 plants. Coherently, both mutants exhibit hypersensitivity to ABA and altered expression of a set of ABA-dependent genes. A genetic analysis further reveals that this MAPK cascade is activated by the PYR/PYL/RCAR-SnRK2-PP2C ABA core signalling module through protein synthesis of the MAP3Ks, unveiling an atypical mechanism for MAPK activation in eukaryotes. Our work provides evidence for a role of an ABA-induced MAPK pathway in plant stress signalling. Significance Statement We report in this article the identification of a complete MAPK module, composed of MAP3K17/18, MKK3 and MPK1/2/7/14, which is activated by ABA through the ABA core signalling complex. We showed that the activation of this module requires the MAP3K protein synthesis which occurs after hours of stress treatment, suggesting that the pathway is involved in a delayed wave of cellular responses to ABA and drought. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

Identification and characterization of an ABA-activated MAP kinase cascade in Arabidopsis thaliana

KAUST Repository

Danquah, Agyemang; Zé licourt, Axel de; Boudsocq, Marie; Neubauer, Jorinde; Frei Dit Frey, Nicolas; Leonhardt, Nathalie; Pateyron, Sté phanie; Gwinner, Frederik; Tamby, Jean Philippe; Ortiz-Masià , Dolores; Marcote, Marí a Jesú s; Hirt, Heribert; Colcombet, Jean

2015-01-01

Summary Abscisic acid (ABA) is a major phytohormone involved in important stress-related and developmental plant processes. Recent phosphoproteomic analyses revealed a large set of ABA-triggered phosphoproteins as putative mitogen-activated protein kinase (MAPK) targets, although the evidence for MAPKs involved in ABA signalling is still scarce. Here, we identified and reconstituted in vivo a complete ABA-activated MAPK cascade, composed of the MAP3Ks MAP3K17/18, the MAP2K MKK3 and the four C group MAPKs MPK1/2/7/14. In planta, we show that ABA activation of MPK7 is blocked in mkk3-1 and map3k17mapk3k18 plants. Coherently, both mutants exhibit hypersensitivity to ABA and altered expression of a set of ABA-dependent genes. A genetic analysis further reveals that this MAPK cascade is activated by the PYR/PYL/RCAR-SnRK2-PP2C ABA core signalling module through protein synthesis of the MAP3Ks, unveiling an atypical mechanism for MAPK activation in eukaryotes. Our work provides evidence for a role of an ABA-induced MAPK pathway in plant stress signalling. Significance Statement We report in this article the identification of a complete MAPK module, composed of MAP3K17/18, MKK3 and MPK1/2/7/14, which is activated by ABA through the ABA core signalling complex. We showed that the activation of this module requires the MAP3K protein synthesis which occurs after hours of stress treatment, suggesting that the pathway is involved in a delayed wave of cellular responses to ABA and drought. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

Deregulation of Interferon Signaling in Malignant Cells

Directory of Open Access Journals (Sweden)

Leonidas C. Platanias

2010-02-01

Full Text Available Interferons (IFNs are a family of cytokines with potent antiproliferative, antiviral, and immunomodulatory properties. Much has been learned about IFNs and IFN-activated signaling cascades over the last 50 years. Due to their potent antitumor effects in vitro and in vivo, recombinant IFNs have been used extensively over the years, alone or in combination with other drugs, for the treatment of various malignancies. This review summarizes the current knowledge on IFN signaling components and pathways that are deregulated in human malignancies. The relevance of deregulation of IFN signaling pathways in defective innate immune surveillance and tumorigenesis are discussed.

Cascaded impedance networks for NPC inverter

DEFF Research Database (Denmark)

Li, Ding; Gao, Feng; Loh, Poh Chiang

2010-01-01

they are subject to the renewable sources. To date, three distinct types of impedance networks can be summarized for implementing a hybrid source impedance network, which can in principle be combined and cascaded before connected to a NPC inverter by proposed two ways. The resulting cascaded impedance network NPC...

ß-Adrenergic Receptor Signaling and Modulation of Long-Term Potentiation in the Mammalian Hippocampus

Science.gov (United States)

O'Dell, Thomas J.; Connor, Steven A.; Guglietta, Ryan; Nguyen, Peter V.

2015-01-01

Encoding new information in the brain requires changes in synaptic strength. Neuromodulatory transmitters can facilitate synaptic plasticity by modifying the actions and expression of specific signaling cascades, transmitter receptors and their associated signaling complexes, genes, and effector proteins. One critical neuromodulator in the…

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

Science.gov (United States)

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.

Learning Cascading

CERN Document Server

Covert, Michael

2015-01-01

This book is intended for software developers, system architects and analysts, big data project managers, and data scientists who wish to deploy big data solutions using the Cascading framework. You must have a basic understanding of the big data paradigm and should be familiar with Java development techniques.

Signaling Architectures that Transmit Unidirectional Information Despite Retroactivity.

Science.gov (United States)

Shah, Rushina; Del Vecchio, Domitilla

2017-08-08

A signaling pathway transmits information from an upstream system to downstream systems, ideally in a unidirectional fashion. A key obstacle to unidirectional transmission is retroactivity, the additional reaction flux that affects a system once its species interact with those of downstream systems. This raises the fundamental question of whether signaling pathways have developed specialized architectures that overcome retroactivity and transmit unidirectional signals. Here, we propose a general procedure based on mathematical analysis that provides an answer to this question. Using this procedure, we analyze the ability of a variety of signaling architectures to transmit one-way (from upstream to downstream) signals, as key biological parameters are tuned. We find that single stage phosphorylation and phosphotransfer systems that transmit signals from a kinase show a stringent design tradeoff that hampers their ability to overcome retroactivity. Interestingly, cascades of these architectures, which are highly represented in nature, can overcome this tradeoff and thus enable unidirectional transmission. By contrast, phosphotransfer systems, and single and double phosphorylation cycles that transmit signals from a substrate, are unable to mitigate retroactivity effects, even when cascaded, and hence are not well suited for unidirectional information transmission. These results are largely independent of the specific reaction-rate constant values, and depend on the topology of the architectures. Our results therefore identify signaling architectures that, allowing unidirectional transmission of signals, embody modular processes that conserve their input/output behavior across multiple contexts. These findings can be used to decompose natural signal transduction networks into modules, and at the same time, they establish a library of devices that can be used in synthetic biology to facilitate modular circuit design. Copyright © 2017 Biophysical Society. Published by

Information cascade on networks

Science.gov (United States)

Hisakado, Masato; Mori, Shintaro

2016-05-01

In this paper, we discuss a voting model by considering three different kinds of networks: a random graph, the Barabási-Albert (BA) model, and a fitness model. A voting model represents the way in which public perceptions are conveyed to voters. Our voting model is constructed by using two types of voters-herders and independents-and two candidates. Independents conduct voting based on their fundamental values; on the other hand, herders base their voting on the number of previous votes. Hence, herders vote for the majority candidates and obtain information relating to previous votes from their networks. We discuss the difference between the phases on which the networks depend. Two kinds of phase transitions, an information cascade transition and a super-normal transition, were identified. The first of these is a transition between a state in which most voters make the correct choices and a state in which most of them are wrong. The second is a transition of convergence speed. The information cascade transition prevails when herder effects are stronger than the super-normal transition. In the BA and fitness models, the critical point of the information cascade transition is the same as that of the random network model. However, the critical point of the super-normal transition disappears when these two models are used. In conclusion, the influence of networks is shown to only affect the convergence speed and not the information cascade transition. We are therefore able to conclude that the influence of hubs on voters' perceptions is limited.

Prion protein induced signaling cascades in monocytes

International Nuclear Information System (INIS)

Krebs, Bjarne; Dorner-Ciossek, Cornelia; Schmalzbauer, Ruediger; Vassallo, Neville; Herms, Jochen; Kretzschmar, Hans A.

2006-01-01

Prion proteins play a central role in transmission and pathogenesis of transmissible spongiform encephalopathies. The cellular prion protein (PrP C ), whose physiological function remains elusive, is anchored to the surface of a variety of cell types including neurons and cells of the lymphoreticular system. In this study, we investigated the response of a mouse monocyte/macrophage cell line to exposure with PrP C fusion proteins synthesized with a human Fc-tag. PrP C fusion proteins showed an attachment to the surface of monocyte/macrophages in nanomolar concentrations. This was accompanied by an increase of cellular tyrosine phosphorylation as a result of activated signaling pathways. Detailed investigations exhibited activation of downstream pathways through a stimulation with PrP fusion proteins, which include phosphorylation of ERK 1,2 and Akt kinase. Macrophages opsonize and present antigenic structures, contact lymphocytes, and deliver cytokines. The findings reported here may become the basis of understanding the molecular function of PrP C in monocytes and macrophages

Raf kinase inhibitory protein: a signal transduction modulator and metastasis suppressor.

Science.gov (United States)

Granovsky, Alexey E; Rosner, Marsha Rich

2008-04-01

Cells have a multitude of controls to maintain their integrity and prevent random switching from one biological state to another. Raf Kinase Inhibitory Protein (RKIP), a member of the phosphatidylethanolamine binding protein (PEBP) family, is representative of a new class of modulators of signaling cascades that function to maintain the "yin yang" or balance of biological systems. RKIP inhibits MAP kinase (Raf-MEK-ERK), G protein-coupled receptor (GPCR) kinase and NFkappaB signaling cascades. Because RKIP targets different kinases dependent upon its state of phosphorylation, RKIP also acts to integrate crosstalk initiated by multiple environmental stimuli. Loss or depletion of RKIP results in disruption of the normal cellular stasis and can lead to chromosomal abnormalities and disease states such as cancer. Since RKIP and the PEBP family have been reviewed previously, the goal of this analysis is to provide an update and highlight some of the unique features of RKIP that make it a critical player in the regulation of cellular signaling processes.

Atmospheric signals produced by cavity rebound

International Nuclear Information System (INIS)

Jones, E.M.; App, F.N.; Whitaker, R.W.

1993-01-01

An analysis of the atmospheric acoustic signals produced by a class of low-yield tests conducted just below the base of the alluvial cover in Yucca Flat of the Nevada Test Site (NTS), has revealed a clear manifestation of an elastic, cavity rebound signal. We use modeling as the basis for understanding the observed phenomena

Parametric amplification and cascaded-nonlinearity processes in common atomic system.

Science.gov (United States)

Zheng, Huaibin; Zhang, Xun; Zhang, Zhaoyang; Tian, Yaling; Chen, Haixia; Li, Changbiao; Zhang, Yanpeng

2013-01-01

For the first time, we study the parametric amplification process of multi-wave mixing (PA-MWM) signal and cascaded-nonlinearity process (CNP) in sodium vapors both theoretically and experimentally, based on a conventional phase-conjugate MWM and a self-diffraction four-wave mixing (SD-FWM) processes, which are pumped by laser or amplified spontaneous emission (ASE), respectively. For laser pumping case, SD-FWM process serves as a quantum linear amplifier (a CNP) out (inside) of the resonant absorption region. While for ASE case, only the CNP occurs and the output linewidth is much narrower than that of the MWM signal due to the second selected effect of its electromagnetically induced transparency window. In addition, the phase-sensitive amplifying process seeded by two MWM processes is discussed for the first time. Theoretical fittings agree well with the experiment. The investigations have important potential applications in quantum communication.

Wnt Signaling in Skeletal Muscle Development and Regeneration.

Science.gov (United States)

Girardi, Francesco; Le Grand, Fabien

2018-01-01

Wnt is a family of signaling molecules involved in embryogenesis, adult tissue repair, and cancer. They activate canonical and noncanonical Wnt signaling cascades in target cells. Several studies, within the last decades, showed that several Wnt ligands are involved in myogenesis and both canonical and noncanonical Wnt pathways regulate muscle formation and the maintenance of adult tissue homeostasis. In this review, we provide a comprehensive overview of the roles of Wnt signaling during muscle development and an updated description of Wnt functions during muscle repair. Lastly, we discuss the crosstalk between Wnt and TGFβ signaling pathways in skeletal muscle. Copyright © 2018 Elsevier Inc. All rights reserved.

Sclerodermatomyositis, ocular manifestations.

Science.gov (United States)

Pedroza-Seres, M; Serna-Ojeda, J C; Flores-Suárez, L F

2017-07-01

Sclerodermatomyositis is an overlap syndrome of myositis and scleroderma, with dermatological, muscular and joint involvement, but may also present with ocular manifestations. A 57 year-old woman presented with ophthalmological manifestations, including scleral thinning 360°, and the presence of cells in the anterior and posterior chamber. Oriented physical examination and laboratory studies led to the diagnosis, with the need for systemic treatment. Sclerodermatomyositis is a rare disease. Its diagnosis needs thorough clinical and laboratory studies, and its management should be multidisciplinary when inflammatory ocular manifestations may be present. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Non-spill control squared cascade

International Nuclear Information System (INIS)

Kai, Tsunetoshi; Inoue, Yoshiya; Oya, Akio; Suemori, Nobuo.

1974-01-01

Object: To reduce a mixed loss thus enhancing separating efficiency by the provision of a simple arrangement wherein a reflux portion in a conventional spill control squared cascade is replaced by a special stage including centrifugal separators. Structure: Steps in the form of a square cascade, in which a plurality of centrifugal separators are connected by pipe lines, are accumulated in multistage fashion to form a squared cascade. Between the adjoining steps is disposed a special stage including a centrifugal separator which receives both lean flow from the upper step and rich flow from the lower step. The centrifugal separator in the special stage has its rich side connected to the upper step and its lean side connected to the lower step. Special stages are each disposed at the upper side of the uppermost step and at the lower side of the lowermost step. (Kamimura, M.)

BMP Suppresses PTEN Expression via RAS/ERK Signaling

OpenAIRE

Beck, Stayce E.; Carethers, John M.

2007-01-01

Bone morphogenetic protein (BMP), a member of the transforming growth factor β family, classically utilizes the SMAD signaling pathway for its growth suppressive effects, and loss of this signaling cascade may accelerate cell growth. In the colon cancer predisposition syndrome Juvenile Polyposis, as well as in the late progression stages of nonsyndromic colorectal cancers, SMAD4 function is typically abrogated. Here, we utilized the SMAD4-null SW480 colon cancer cell line to examine BMPs effe...

Molecular dynamics simulation of displacement cascades in iron-alpha; Cascades de deplacements atomiques dans le FER-alpha simulation par dynamique moleculaire

Energy Technology Data Exchange (ETDEWEB)

Vascon, R

1997-12-31

Radiation damage by neutrons or ions in bcc iron has been investigated by molecular dynamics simulations using an embedded atom type many-body potential (EAM). Displacement cascades with energies of 1 to 30 keV were generated in the microcanonical system where the number of atoms (up to 1.5 million) is chosen high enough to compensate the fact that the dissipation of energy is not taken into account in our model. The defect number at the end of cascade lifetime was found to be 60 percent of the NRT standard value. This tendency is in good agreement with experimental data. However, compared with other simulations in iron, we found significant differences in the defect production and distribution. The comparison with results obtained form simulations of cascades in other metals, leads on the one hand to a higher value of the defect number in bcc iron than in fcc metals like copper or nickel, and on the other hand to a ratio, between the number of replacements and the number of defects, lower in iron ( 100). We observed the transient melting of the core of the cascade during simulations. We showed that a higher value of the initial iron crystal temperature, as the mass difference between the components of an artificial binary alloy Fe-X(X=Al,Sb,Au,U) both produce a `cascade effect`: a decrease of the number of defects and an increase of the number of replacements. We also showed up the quasi-channeling of some atoms in high energy cascades. They are at the origin of sub-cascades formation; as a result they induce an opposite effect to the `cascade effect`. (author). 286 refs.

The Hippo signaling functions through the Notch signaling to regulate intrahepatic bile duct development in mammals

Science.gov (United States)

Wu, Nan; Nguyen, Quy; Wan, Ying; Zhou, Tiaohao; Venter, Julie; Frampton, Gabriel A; DeMorrow, Sharon; Pan, Duojia; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco; Bai, Haibo

2018-01-01

The Hippo signaling pathway and the Notch signaling pathway are evolutionary conserved signaling cascades that have important roles in embryonic development of many organs. In murine liver, disruption of either pathway impairs intrahepatic bile duct development. Recent studies suggested that the Notch signaling receptor Notch2 is a direct transcriptional target of the Hippo signaling pathway effector YAP, and the Notch signaling is a major mediator of the Hippo signaling in maintaining biliary cell characteristics in adult mice. However, it remains to be determined whether the Hippo signaling pathway functions through the Notch signaling in intrahepatic bile duct development. We found that loss of the Hippo signaling pathway tumor suppressor Nf2 resulted in increased expression levels of the Notch signaling pathway receptor Notch2 in cholangiocytes but not in hepatocytes. When knocking down Notch2 on the background of Nf2 deficiency in mouse livers, the excessive bile duct development induced by Nf2 deficiency was suppressed by heterozygous and homozygous deletion of Notch2 in a dose-dependent manner. These results implicated that Notch signaling is one of the downstream effectors of the Hippo signaling pathway in regulating intrahepatic bile duct development. PMID:28581486

Cascade fuzzy control for gas engine driven heat pump

International Nuclear Information System (INIS)

Li Shuze; Zhang Wugao; Zhang Rongrong; Lv Dexu; Huang Zhen

2005-01-01

In addition to absorption chillers, today's gas cooling technology includes gas engine driven heat pump systems (GEHP) in a range of capacities and temperature capacities suitable for most commercial air conditioning and refrigeration applications. Much is expected from GEHPs as a product that would help satisfy the air conditioning system demand from medium and small sized buildings, restrict electric power demand peaks in summer and save energy in general. This article describes a kind of control strategy for a GEHP, a cascade fuzzy control. GEHPs have large and varying time constants and their dynamic modeling cannot be easily achieved. A cascade control strategy is effective for systems that have large time constants and disturbances, and a fuzzy control strategy is fit for a system that lacks an accurate model. This cascade fuzzy control structure brings together the best merits of fuzzy control and cascade control structures. The performance of the cascade fuzzy control is compared to that of a cascade PI (proportional and integral) control strategy, and it is shown by example that the cascade fuzzy control strategy gives a better performance, reduced reaction time and smaller overshoot temperature

Crosstalk between autophagy and inflammatory signalling pathways: balancing defence and homeostasis.

Science.gov (United States)

Cadwell, Ken

2016-11-01

Autophagy has broad functions in immunity, ranging from cell-autonomous defence to coordination of complex multicellular immune responses. The successful resolution of infection and avoidance of autoimmunity necessitates efficient and timely communication between autophagy and pathways that sense the immune environment. The recent literature indicates that a variety of immune mediators induce or repress autophagy. It is also becoming increasingly clear that immune signalling cascades are subject to regulation by autophagy, and that a return to homeostasis following a robust immune response is critically dependent on this pathway. Importantly, examples of non-canonical forms of autophagy in mediating immunity are pervasive. In this article, the progress in elucidating mechanisms of crosstalk between autophagy and inflammatory signalling cascades is reviewed. Improved mechanistic understanding of the autophagy machinery offers hope for treating infectious and inflammatory diseases.

Cascaded two-photon spectroscopy of Yb atoms with a transportable effusive atomic beam apparatus

Energy Technology Data Exchange (ETDEWEB)

Song, Minsoo; Yoon, Tai Hyun [Department of Physics, Korea University, Anam-dong, Seongbuk-gu, Seoul 136-713 (Korea, Republic of)

2013-02-15

We present a transportable effusive atomic beam apparatus for cascaded two-photon spectroscopy of the dipole-forbidden transition (6s{sup 2} {sup 1}S{sub 0}{r_reversible} 6s7s {sup 1}S{sub 0}) of Yb atoms. An ohmic-heating effusive oven is designed to have a reservoir volume of 1.6 cm{sup 3} and a high degree of atomic beam collimation angle of 30 mrad. The new atomic beam apparatus allows us to detect the spontaneously cascaded two-photons from the 6s7s{sup 1}S{sub 0} state via the intercombination 6s6p{sup 3}P{sub 1} state with a high signal-to-noise ratio even at the temperature of 340 Degree-Sign C. This is made possible in our apparatus because of the enhanced atomic beam flux and superior detection solid angle.

A cryogenic distillation column cascade for a fusion reactor

International Nuclear Information System (INIS)

Kinoshita, M.

1984-01-01

A cryogenic distillation column cascade composed of only two columns is proposed. Compared with the Tritium Systems Test Assembly (TSTA) cascade, the tritium inventory is about 1.5 times more and the packed height of the highest column increases by about 40%. However, the number of the columns is halved with the separation performance unchanged. The number of the instruments needed and the number of the process parameters to be monitored are also reduced. Unlike in the case of the TSTA cascade, the performance of the proposed cascade is not subject to the flow rate of the neutral beam injector recycle stream. The high performance can be maintained even if the protium percentage in the raw fuel input increases significantly (e.g., from 1 to 3%), just by adjusting the flow rates of the top, bottom, and side streams. Because of this great flexibility, it is worthwhile to build and study the proposed cascade as a possible alternative to the TSTA cascade

Ultrasensitive Faraday cage-type electrochemiluminescence assay for femtomolar miRNA-141 via graphene oxide and hybridization chain reaction-assisted cascade amplification.

Science.gov (United States)

Lu, Jing; Wu, Lin; Hu, Yufang; Wang, Sui; Guo, Zhiyong

2018-06-30

In this study, a novel electrochemiluminescence (ECL) biosensor for sensitive detection of femtomolar miRNA-141 was constructed on the basis of Faraday cage-type strategy via graphene oxide (GO) and hybridization chain reaction (HCR)-assisted cascade amplification. A capture probe (CP) was immobilized on Fe 3 O 4 @SiO 2 @Au nanoparticles as capture unit, which could catch the miRNA-141, and the immobilization of the signal unit (Ru(phen) 3 2+ -HCR/GO) was allowed via nucleic acid hybridization. The prepared biosensor exhibited two advantages for signal amplification: firstly, GO could lap on the electrode surface directly, extending Outer Helmholtz Plane (OHP) of the sensor due to the large surface area and good electronic transport property; secondly, HCR-assisted cascade amplification was designed by anchoring all HCR products on the GO surface, then embedding Ru(phen) 3 2+ as a signal readout pathway. All these signal molecules could take part in electrochemical reactions, thus further enhancing the ECL signal drastically. Therefore, the proposed sensor constructed by integrating HCR with Faraday cage-type strategy displayed an ultrasensitive detection platform for the miRNA-141 with a low detection limit of 0.03 fM. In addition, this proposed biosensor provides a universal platform for analysis of other microRNAs. Copyright © 2018 Elsevier B.V. All rights reserved.

MOLECULAR DYNAMICS SIMULATIONS OF DISPLACEMENT CASCADES IN MOLYBDENUM

International Nuclear Information System (INIS)

Smith, Richard Whiting

2003-01-01

Molecular dynamics calculations have been employed to simulate displacement cascades in neutron irradiated Mo. A total of 90 simulations were conducted for PKA energies between 1 and 40 keV and temperatures from 298 to 923K. The results suggest very little effect of temperature on final defect count and configuration, but do display a temperature effect on peak defect generation prior to cascade collapse. Cascade efficiency, relative to the NRT model, is computed to lie between 1/4 and 1/3 in agreement with simulations performed on previous systems. There is a tendency for both interstitials and vacancies to cluster together following cascade collapse producing vacancy rich regions surrounded by interstitials. Although coming to rest in close proximity, the point defects comprising the clusters generally do not lie within the nearest neighbor positions of one another, except for the formation of dumbbell di-interstitials. Cascades produced at higher PKA energies (20 or 40 keV) exhibit the formation of subcascades

Stochastic background of atmospheric cascades

International Nuclear Information System (INIS)

Wilk, G.; Wlodarczyk, Z.

1993-01-01

Fluctuations in the atmospheric cascades developing during the propagation of very high energy cosmic rays through the atmosphere are investigated using stochastic branching model of pure birth process with immigration. In particular, we show that the multiplicity distributions of secondaries emerging from gamma families are much narrower than those resulting from hadronic families. We argue that the strong intermittent like behaviour found recently in atmospheric families results from the fluctuations in the cascades themselves and are insensitive to the details of elementary interactions

Geothermal segmentation of the Cascade Range in the USA

Science.gov (United States)

Guffanti, Marianne; Muffler, L.J.; Mariner, R.H.; Sherrod, D.R.; Smith, James G.; Blackwell, D.D.; Weaver, C.S.

1990-01-01

Characteristics of the crustal thermal regime of the Quaternary Cascades vary systematically along the range. Spatially congruent changes in volcanic vent distribution, volcanic extrusion rate, hydrothermal discharge rate, and regional conductive heat flow define 5 geothermal segments. These segments are, from north to south: (1) the Washington Cascades north of Mount Rainier, (2) the Cascades from Mount Rainier to Mount Hood, (3) the Oregon Cascades from south of Mount Hood to the California border, (4) northernmost California, including Mount Shasta and Medicine Lake volcano, and (5) the Lassen region of northern California. This segmentation indicates that geothermal resource potential is not uniform in the Cascade Range. Potential varies from high in parts of Oregon to low in Washington north of Mount Rainier.

Calcium signaling and amyloid toxicity in Alzheimer disease.

Science.gov (United States)

Demuro, Angelo; Parker, Ian; Stutzmann, Grace E

2010-04-23

Intracellular Ca(2+) signaling is fundamental to neuronal physiology and viability. Because of its ubiquitous roles, disruptions in Ca(2+) homeostasis are implicated in diverse disease processes and have become a major focus of study in multifactorial neurodegenerative diseases such as Alzheimer disease (AD). A hallmark of AD is the excessive production of beta-amyloid (Abeta) and its massive accumulation in amyloid plaques. In this minireview, we highlight the pathogenic interactions between altered cellular Ca(2+) signaling and Abeta in its different aggregation states and how these elements coalesce to alter the course of the neurodegenerative disease. Ca(2+) and Abeta intersect at several functional levels and temporal stages of AD, thereby altering neurotransmitter receptor properties, disrupting membrane integrity, and initiating apoptotic signaling cascades. Notably, there are reciprocal interactions between Ca(2+) pathways and amyloid pathology; altered Ca(2+) signaling accelerates Abeta formation, whereas Abeta peptides, particularly in soluble oligomeric forms, induce Ca(2+) disruptions. A degenerative feed-forward cycle of toxic Abeta generation and Ca(2+) perturbations results, which in turn can spin off to accelerate more global neuropathological cascades, ultimately leading to synaptic breakdown, cell death, and devastating memory loss. Although no cause or cure is currently known, targeting Ca(2+) dyshomeostasis as an underlying and integral component of AD pathology may result in novel and effective treatments for AD.

Cascade processes in kaonic and muonic atoms

International Nuclear Information System (INIS)

Faifman, M.P.; Men'shikov, L.I.

2003-01-01

Cascade processes in exotic (kaonic and muonic) hydrogen/deuterium have been studied with the quantum-classical Monte Carlo code (QCMC) developed for 'ab initio' - calculations. It has been shown that the majority of kaonic hydrogen atoms during cascade are accelerated to high energies E ∼ 100 eV, which leads to a much lower value for the calculated yields Y of x-rays than predicted by the 'standard cascade model'. The modified QCMC scheme has been applied to the study of the cascade in μp and μd muonic atoms. A comparison of the calculated yields for K-series x-rays with experimental data directly indicates that the molecular structure of the hydrogen target and new types of non-radiative transitions are essential for the light muonic atoms, while they are negligible for heavy (kaonic) atoms. These processes have been considered and estimates of their probabilities are presented. (author)

Analytical Structuring of Periodic and Regular Cascading Solutions in Self-Pulsing Lasers

Directory of Open Access Journals (Sweden)

Belkacem Meziane

2008-01-01

Full Text Available A newly proposed strong harmonic-expansion method is applied to the laser-Lorenz equations to analytically construct a few typical solutions, including the first few expansions of the well-known period-doubling cascade that characterizes the system in its self-pulsing regime of operation. These solutions are shown to evolve in accordance with the driving frequency of the permanent solution that we recently reported to illustrate the system. The procedure amounts to analytically construct the signal Fourier transform by applying an iterative algorithm that reconstitutes the first few terms of its development.

Rescuing Ecosystems from Extinction Cascades

Science.gov (United States)

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.

Basic characteristics of a low uranium enrichment cascade by centrifugation, (2)

International Nuclear Information System (INIS)

Kai, Tsunetoshi

1975-01-01

The theory for a cascade of centrifuges described in the preceding report of the same general title is further developed. First, equations describing the distributions of the flow and the mole concentration are derived from the material balance relations for a square cascade. Corresponding equations are next obtained to cover a squared-off cascade consisting of a series of square cascades. A computer program is outlined which makes it possible to obtain the shape of the most efficient squared-off cascade. The efficiency of the current form of squared-off centrifuge cascade with reflux pipes is found to be lower than obtainable with gaseous diffusion. The efficiency can be improved by the adoption of a tapered squared-off cascade with centrifuges provided with eccentric cuts to take the place of reflux pipes. The dynamic characteristics are also discussed. Analysis of the start-up behavior reveals that the equilibrium time of the centrifuge cascade is much shorter than for a coresponding gaseous diffusion cascade, and that the mole concentration of the product rapidly rises to attain steady state condition. It is also found that even when the feed flow rate fluctuates, the mole concentration of the product is relatively stable. The effect of a centrifuge failure in the cascade is examined. The optimum mole concentration for the waste effluent discarded from the cascade is calculated from the viewpoint of cost. (auth.)

Ocular Manifestations of Acquired Immunodeficiency Syndrome.

Science.gov (United States)

Kim, Young Shin; Sun, Hae Jung; Kim, Tae Hyong; Kang, Kui Dong; Lee, Sung Jin

2015-08-01

To investigate the patterns and risk factors of the ocular manifestations of acquired immunodeficiency syndrome (AIDS) and their correlation with CD4+ count in the era of highly active antiretroviral therapy (HAART). This retrospective study examined 127 AIDS patients who presented to Soonchunhyang University Hospital. Data were collected from patient interviews, clinical examinations, and laboratory investigations. Ophthalmologic examinations included the best-corrected visual acuity, intraocular pressure, anterior segment and adnexal examination, and dilated fundus examination. Of the 127 patients with AIDS, 118 were on HAART and 9 were not. The mean CD4+ count was 266.7 ± 209.1 cells/µL. There were ocular manifestations in 61 patients (48.0%). The incidence of anterior segment manifestations was higher than posterior segment manifestations at 28.3% and 19.7%, respectively. The mean CD4+ count was significantly (p AIDS. In this study, anterior segment and external ocular manifestations occurred more frequently than posterior segment manifestations. Also, the mean CD4+ count was significantly lower in patients with posterior segment ocular manifestations versus anterior segment ocular manifestations. We found that CD4+ count and age >35 years were independent risk factors for developing ocular manifestations.

Spatial focalization of pheromone/MAPK signaling triggers commitment to cell–cell fusion

Science.gov (United States)

Merlini, Laura

2016-01-01

Cell fusion is universal in eukaryotes for fertilization and development, but what signals this process is unknown. Here, we show in Schizosaccharomyces pombe that fusion does not require a dedicated signal but is triggered by spatial focalization of the same pheromone–GPCR (G-protein-coupled receptor)–MAPK signaling cascade that drives earlier mating events. Autocrine cells expressing the receptor for their own pheromone trigger fusion attempts independently of cell–cell contact by concentrating pheromone release at the fusion focus, a dynamic actin aster underlying the secretion of cell wall hydrolases. Pheromone receptor and MAPK cascade are similarly enriched at the fusion focus, concomitant with fusion commitment in wild-type mating pairs. This focalization promotes cell fusion by immobilizing the fusion focus, thus driving local cell wall dissolution. We propose that fusion commitment is imposed by a local increase in MAPK concentration at the fusion focus, driven by a positive feedback between fusion focus formation and focalization of pheromone release and perception. PMID:27798845

Combinatorial and off-shell effects in new physics cascades

Energy Technology Data Exchange (ETDEWEB)

Wiesler, Daniel

2012-12-15

Up to now, the Standard Model of elementary particle physics is in very good agreement with most data. However, it has various shortcomings which motivate the presence of new physics at the TeV scale. The first major step following a potential discovery of new particles at the Large Hadron Collider (LHC) is the determination of their intrinsic properties, foremost masses and spins. Event topologies of new physics signals with a conserved parity motivated by precision data and the dark matter paradigm require for sophisticated measurement procedures, which have been developed in recent years. These techniques often rely on simplifying assumptions, albeit they need not necessarily be fulfilled. In this thesis we investigate the impact of combinatorial and off-shell effects on new physics cascades in three different contexts. A detailed understanding of these effects is essential for the topic of model parameter determination of new physics signatures at the LHC. First, we study the non-resonant contributions of a broad gluino on mass and spin measurements as a prime example for the importance of off-shell effects. A phenomenological scan over the gluino's width-to-mass ratio yields a severe smearing of invariant mass distributions and as a consequence thereof drastically shifted endpoint positions. Spin determinations, on the other hand, are barely affected and a model discrimination of the two prime candidates SUSY and UED is not at risk. In the second part, we assess the feasibility of the gluino dijet endpoint measurement in three fully inclusive scenarios at the LHC to investigate the impact of combinatorial and SUSY backgrounds on its precise determination. We develop a method to disentangle two major signal contributions and extract their associated edges with good accuracy. For this we use existent kinematic variables and propose new ones to overcome the former's deficiencies. The last part governs the issue of so-called 'fake combinatorics

A Ca2+-calmodulin-eEF2K-eEF2 signalling cascade, but not AMPK, contributes to the suppression of skeletal muscle protein synthesis during contractions

DEFF Research Database (Denmark)

Rose, Adam John; Alsted, Thomas Junker; Jensen, Thomas Elbenhardt

2009-01-01

Skeletal muscle protein synthesis rate decreases during contractions but the underlying regulatory mechanisms are poorly understood. It was hypothesised that there would be a coordinated regulation of eukaryotic elongation factor 2 (eEF2) and eukaryotic initiation factor 4E-binding protein 1 (4EBP1......) phosphorylation by signalling cascades downstream of rises in intracellular [Ca(2+)] and decreased energy charge via AMP activated protein kinase (AMPK) in contracting skeletal muscle. When fast-twitch skeletal muscles were contracted ex vivo using different protocols, the suppression of protein synthesis...... correlated more closely with changes in eEF2 rather than 4EBP1 phosphorylation. Using a combination of Ca(2+) release agents and ATPase inhibitors it was shown that the 60-70% suppression of fast-twitch skeletal muscle protein synthesis during contraction was equally distributed between Ca(2+) and energy...

Molecular dynamics studies of displacement cascades

International Nuclear Information System (INIS)

Averback, R.S.; Hsieh, Horngming; Diaz de la Rubia, T.

1990-02-01

Molecular-dynamics simulations of cascades in Cu and Ni with primary-knock-on energies up to 5 keV and lattice temperatures in the range 0 K--700 K are described. Interatomic forces were represented by either the Gibson II (Cu) or Johnson-Erginsoy (Ni) potentials in most of this work, although some simulations using ''Embedded Atom Method'' potentials, e.g., for threshold events in Ni 3 Al, are also presented. The results indicate that the primary state of damage produced by displacement cascades is controlled by two phenomena, replacement collision sequences during the collisional phase of the cascade and local melting during the thermal spike. As expected, the collisional phase is rather similar in Cu and Ni, however, the thermal spike is of longer duration and has a more pronounced influence in Cu than Ni. When the ambient temperature of the lattice is increased, the melt zones are observed to both increase in size and cool more slowly. This has the effect of reducing defect production and enhancing atomic mixing and disordering. The implications of these results for defect production, cascade collapse, atomic disordering will be discussed. 34 refs., 7 figs., 2 tabs

Forecasting Social Unrest Using Activity Cascades.

Science.gov (United States)

Cadena, Jose; Korkmaz, Gizem; Kuhlman, Chris J; Marathe, Achla; Ramakrishnan, Naren; Vullikanti, Anil

2015-01-01

Social unrest is endemic in many societies, and recent news has drawn attention to happenings in Latin America, the Middle East, and Eastern Europe. Civilian populations mobilize, sometimes spontaneously and sometimes in an organized manner, to raise awareness of key issues or to demand changes in governing or other organizational structures. It is of key interest to social scientists and policy makers to forecast civil unrest using indicators observed on media such as Twitter, news, and blogs. We present an event forecasting model using a notion of activity cascades in Twitter (proposed by Gonzalez-Bailon et al., 2011) to predict the occurrence of protests in three countries of Latin America: Brazil, Mexico, and Venezuela. The basic assumption is that the emergence of a suitably detected activity cascade is a precursor or a surrogate to a real protest event that will happen "on the ground." Our model supports the theoretical characterization of large cascades using spectral properties and uses properties of detected cascades to forecast events. Experimental results on many datasets, including the recent June 2013 protests in Brazil, demonstrate the effectiveness of our approach.

Forecasting Social Unrest Using Activity Cascades.

Directory of Open Access Journals (Sweden)

Jose Cadena

Full Text Available Social unrest is endemic in many societies, and recent news has drawn attention to happenings in Latin America, the Middle East, and Eastern Europe. Civilian populations mobilize, sometimes spontaneously and sometimes in an organized manner, to raise awareness of key issues or to demand changes in governing or other organizational structures. It is of key interest to social scientists and policy makers to forecast civil unrest using indicators observed on media such as Twitter, news, and blogs. We present an event forecasting model using a notion of activity cascades in Twitter (proposed by Gonzalez-Bailon et al., 2011 to predict the occurrence of protests in three countries of Latin America: Brazil, Mexico, and Venezuela. The basic assumption is that the emergence of a suitably detected activity cascade is a precursor or a surrogate to a real protest event that will happen "on the ground." Our model supports the theoretical characterization of large cascades using spectral properties and uses properties of detected cascades to forecast events. Experimental results on many datasets, including the recent June 2013 protests in Brazil, demonstrate the effectiveness of our approach.

Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats

Directory of Open Access Journals (Sweden)

R.M. Banin

2014-09-01

Full Text Available Ginkgo biloba extract (GbE has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1, protein tyrosine phosphatase 1B (PTP-1B, and protein kinase B (Akt, as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD or a normal fat diet (NFD for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V, and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb. NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment.

Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats

International Nuclear Information System (INIS)

Banin, R.M.; Hirata, B.K.S.; Andrade, I.S.; Zemdegs, J.C.S.; Clemente, A.P.G.; Dornellas, A.P.S.; Boldarine, V.T.; Estadella, D.; Albuquerque, K.T.; Oyama, L.M.; Ribeiro, E.B.; Telles, M.M.

2014-01-01

Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment

Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats

Energy Technology Data Exchange (ETDEWEB)

Banin, R. M.; Hirata, B. K.S. [Departamento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, SP (Brazil); Andrade, I. S.; Zemdegs, J. C.S. [Disciplina de Fisiologia da Nutrição, Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Clemente, A. P.G. [Faculdade de Nutrição, Universidade Federal de Alagoas, Maceió, AL (Brazil); Dornellas, A. P.S.; Boldarine, V. T. [Disciplina de Fisiologia da Nutrição, Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Estadella, D. [Departamento de Biociências, Universidade Federal de São Paulo, Baixada Santista, SP (Brazil); Albuquerque, K. T. [Curso de Nutrição, Universidade Federal do Rio de Janeiro, Macaé, RJ (Brazil); Oyama, L. M.; Ribeiro, E. B. [Disciplina de Fisiologia da Nutrição, Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Telles, M. M. [Departamento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, SP (Brazil)

2014-07-25

Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment.

Cascading Tesla Oscillating Flow Diode for Stirling Engine Gas Bearings

Science.gov (United States)

Dyson, Rodger

2012-01-01

Replacing the mechanical check-valve in a Stirling engine with a micromachined, non-moving-part flow diode eliminates moving parts and reduces the risk of microparticle clogging. At very small scales, helium gas has sufficient mass momentum that it can act as a flow controller in a similar way as a transistor can redirect electrical signals with a smaller bias signal. The innovation here forces helium gas to flow in predominantly one direction by offering a clear, straight-path microchannel in one direction of flow, but then through a sophisticated geometry, the reversed flow is forced through a tortuous path. This redirection is achieved by using microfluid channel flow to force the much larger main flow into this tortuous path. While microdiodes have been developed in the past, this innovation cascades Tesla diodes to create a much higher pressure in the gas bearing supply plenum. In addition, the special shape of the leaves captures loose particles that would otherwise clog the microchannel of the gas bearing pads.

Haematological manifestations of lupus

Science.gov (United States)

Fayyaz, Anum; Igoe, Ann; Kurien, Biji T; Danda, Debashish; James, Judith A; Stafford, Haraldine A; Scofield, R Hal

2015-01-01

Our purpose was to compile information on the haematological manifestations of systemic lupus erythematosus (SLE), namely leucopenia, lymphopenia, thrombocytopenia, autoimmune haemolytic anaemia (AIHA), thrombotic thrombocytopenic purpura (TTP) and myelofibrosis. During our search of the English-language MEDLINE sources, we did not place a date-of-publication constraint. Hence, we have reviewed previous as well as most recent studies with the subject heading SLE in combination with each manifestation. Neutropenia can lead to morbidity and mortality from increased susceptibility to infection. Severe neutropenia can be successfully treated with granulocyte colony-stimulating factor. While related to disease activity, there is no specific therapy for lymphopenia. Severe lymphopenia may require the use of prophylactic therapy to prevent select opportunistic infections. Isolated idiopathic thrombocytopenic purpura maybe the first manifestation of SLE by months or even years. Some manifestations of lupus occur more frequently in association with low platelet count in these patients, for example, neuropsychiatric manifestation, haemolytic anaemia, the antiphospholipid syndrome and renal disease. Thrombocytopenia can be regarded as an important prognostic indicator of survival in patients with SLE. Medical, surgical and biological treatment modalities are reviewed for this manifestation. First-line therapy remains glucocorticoids. Through our review, we conclude glucocorticoids do produce a response in majority of patients initially, but sustained response to therapy is unlikely. Glucocorticoids are used as first-line therapy in patients with SLE with AIHA, but there is no conclusive evidence to guide second-line therapy. Rituximab is promising in refractory and non-responding AIHA. TTP is not recognised as a criteria for classification of SLE, but there is a considerable overlap between the presenting features of TTP and SLE, and a few patients with SLE have concurrent

Cascaded strand displacement for non-enzymatic target recycling amplification and label-free electronic detection of microRNA from tumor cells

Energy Technology Data Exchange (ETDEWEB)

Shi, Kai; Dou, Baoting; Yang, Jianmei; Yuan, Ruo; Xiang, Yun, E-mail: yunatswu@swu.edu.cn

2016-04-15

The monitoring of microRNA (miRNA) expression levels is of great importance in cancer diagnosis. In the present work, based on two cascaded toehold-mediated strand displacement reactions (TSDRs), we have developed a label- and enzyme-free target recycling signal amplification approach for sensitive electronic detection of miRNA-21 from human breast cancer cells. The junction probes containing the locked G-quadruplex forming sequences are self-assembled on the senor surface. The presence of the target miRNA-21 initiates the first TSDR and results in the disassembly of the junction probes and the release of the active G-quadruplex forming sequences. Subsequently, the DNA fuel strand triggers the second TSDR and leads to cyclic reuse of the target miRNA-21. The cascaded TSDRs thus generate many active G-quadruplex forming sequences on the sensor surface, which associate with hemin to produce significantly amplified current response for sensitive detection of miRNA-21 at 1.15 fM. The sensor is also selective and can be employed to monitor miRNA-21 from human breast cancer cells. - Highlights: • Amplified and sensitive detection of microRNA from tumor cells is achieved. • Signal amplification is realized by two cascaded strand displacement reactions. • The developed sensor is selective and label-free without involving any enzymes.

Cascade DNA nanomachine and exponential amplification biosensing.

Science.gov (United States)

Xu, Jianguo; Wu, Zai-Sheng; Shen, Weiyu; Xu, Huo; Li, Hongling; Jia, Lee

2015-11-15

DNA is a versatile scaffold for the assembly of multifunctional nanostructures, and potential applications of various DNA nanodevices have been recently demonstrated for disease diagnosis and treatment. In the current study, a powerful cascade DNA nanomachine was developed that can execute the exponential amplification of p53 tumor suppressor gene. During the operation of the newly-proposed DNA nanomachine, dual-cyclical nucleic acid strand-displacement polymerization (dual-CNDP) was ingeniously introduced, where the target trigger is repeatedly used as the fuel molecule and the nicked fragments are dramatically accumulated. Moreover, each displaced nicked fragment is able to activate the another type of cyclical strand-displacement amplification, increasing exponentially the value of fluorescence intensity. Essentially, one target binding event can induce considerable number of subsequent reactions, and the nanodevice was called cascade DNA nanomachine. It can implement several functions, including recognition element, signaling probe, polymerization primer and template. Using the developed autonomous operation of DNA nanomachine, the p53 gene can be quantified in the wide concentration range from 0.05 to 150 nM with the detection limit of 50 pM. If taking into account the final volume of mixture, the detection limit is calculated as lower as 6.2 pM, achieving an desirable assay ability. More strikingly, the mutant gene can be easily distinguished from the wild-type one. The proof-of-concept demonstrations reported herein is expected to promote the development and application of DNA nanomachine, showing great potential value in basic biology and medical diagnosis. Copyright © 2015 Elsevier B.V. All rights reserved.

Phase locking of 2.324 and 2.959 terahertz quantum cascade lasers using a Schottky diode harmonic mixer.

Science.gov (United States)

Danylov, Andriy; Erickson, Neal; Light, Alexander; Waldman, Jerry

2015-11-01

The 23rd and 31st harmonics of a microwave signal generated in a novel THz balanced Schottky diode mixer were used as a frequency stable reference source to phase lock solid-nitrogen-cooled 2.324 and 2.959 THz quantum cascade lasers. Hertz-level frequency stability was achieved, which was maintained for several hours.

Neuropsychiatric manifestations of scrub typhus

Directory of Open Access Journals (Sweden)

Sanjay K Mahajan

2017-01-01

Full Text Available Scrub typhus is caused by Orientia tsutsugamushi characterized by focal or disseminated vasculitis and perivasculitis which may involve the lungs, heart, liver, spleen and central nervous system. It was thought to have been eradicated from India. Recently it is being reported from many areas of India. The clinical picture and severity of the symptoms varies widely. The neurological manifestations of scrub typhus are not uncommon but are diverse. Meningoencephalitis is classical manifestation of scrub typhus but cerebellitis, cranial nerve palsies, plexopathy, transverse myelitis, neuroleptic malignant syndrome and Guillan-Barré syndrome are other manifestations reported in literature. The availability of literature on the neurological manifestations of scrub typhus is limited to case reports mainly. This article reviews various neurological manifestations of scrub typhus reported in literature.

Simulated annealing of displacement cascades in FCC metals. 1. Beeler cascades

International Nuclear Information System (INIS)

Doran, D.G.; Burnett, R.A.

1974-09-01

An important source of damage to structural materials in fast reactors is the displacement of atoms from normal lattice sites. A high energy neutron may impart sufficient energy to an atom to initiate a displacement cascade consisting of a localized high density of hundreds of interstitials and vacancies. These defects subsequently interact to form clusters and to reduce their density by mutual annihilation. This short term annealing of an isolated cascade has been simulated at high and low temperatures using a correlated random walk model. The cascade representations used were developed by Beeler and the point defect properties were based on the model of γ-iron by Johnson. Low temperature anneals, characterized by no vacancy migration and a 104 site annihilation region (AR), resulted in 49 defect pairs at 20 keV and 11 pairs at 5 keV. High temperature anneals, characterized by both interstitial and vacancy migration and a 32 site AR, resulted in 68 pairs at 20 keV and 18 pairs at 5 keV when no cluster dissociation was permitted; most of the vacancies were in immobile clusters. These high temperature values dropped to 40 and 14 upon dissolution of the vacancy clusters. Parameter studies showed that, at a given temperature, the large AR resulted in about one-half as many defects as the small AR. Cluster size distributions and examples of spatial configurations are included. (U.S.)

Myoelectrical manifestation of fatigue less prominent in patients with cancer related fatigue.

Directory of Open Access Journals (Sweden)

Katarzyna Kisiel-Sajewicz

Full Text Available PURPOSE: A lack of fatigue-related muscle contractile property changes at time of perceived physical exhaustion and greater central than peripheral fatigue detected by twitch interpolation technique have recently been reported in cancer survivors with fatigue symptoms. Based on these observations, it was hypothesized that compared to healthy people, myoelectrical manifestation of fatigue in the performing muscles would be less significant in these individuals while sustaining a prolonged motor task to self-perceived exhaustion (SPE since their central fatigue was more prominent. The purpose of this study was to test this hypothesis by examining electromyographic (EMG signal changes during fatiguing muscle performance. METHODS: Twelve individuals who had advanced solid cancer and cancer-related fatigue (CRF, and 12 age- and gender-matched healthy controls performed a sustained elbow flexion at 30% maximal voluntary contraction till SPE. Amplitude and mean power frequency (MPF of EMG signals of the biceps brachii, brachioradialis, and triceps brachii muscles were evaluated when the individuals experienced minimal, moderate, and severe fatigue. RESULTS: CRF patients perceived physical "exhaustion" significantly sooner than the controls. The myoelectrical manifestation of muscular fatigue assessed by EMG amplitude and MPF was less significant in CRF than controls. The lower MPF even at minimal fatigue stage in CRF may indicate pathophysiologic condition of the muscle. CONCLUSIONS: CRF patients experience less myoelectrical manifestation of muscle fatigue than healthy individuals near the time of SPE. The data suggest that central nervous system fatigue plays a more important role in limiting endurance-type of motor performance in patients with CRF.

Insulin Signaling, Resistance, and the Metabolic Syndrome: Insights from Mouse Models to Disease Mechanisms

Science.gov (United States)

Guo, Shaodong

2014-01-01

Insulin resistance is a major underlying mechanism for the “metabolic syndrome”, which is also known as insulin resistance syndrome. Metabolic syndrome is increasing at an alarming rate, becoming a major public and clinical problem worldwide. Metabolic syndrome is represented by a group of interrelated disorders, including obesity, hyperglycemia, hyperlipidemia, and hypertension. It is also a significant risk factor for cardiovascular disease and increased morbidity and mortality. Animal studies demonstrate that insulin and its signaling cascade normally control cell growth, metabolism and survival through activation of mitogen-activated protein kinases (MAPKs) and phosphotidylinositide-3-kinase (PI3K), of which activation of PI-3K-associated with insulin receptor substrate-1 and -2 (IRS1, 2) and subsequent Akt→Foxo1 phosphorylation cascade has a central role in control of nutrient homeostasis and organ survival. Inactivation of Akt and activation of Foxo1, through suppression IRS1 and IRS2 in different organs following hyperinsulinemia, metabolic inflammation, and over nutrition may provide the underlying mechanisms for metabolic syndrome in humans. Targeting the IRS→Akt→Foxo1 signaling cascade will likely provide a strategy for therapeutic intervention in the treatment of type 2 diabetes and its complications. This review discusses the basis of insulin signaling, insulin resistance in different mouse models, and how a deficiency of insulin signaling components in different organs contributes to the feature of the metabolic syndrome. Emphasis will be placed on the role of IRS1, IRS2, and associated signaling pathways that couple to Akt and the forkhead/winged helix transcription factor Foxo1. PMID:24281010

Quantum Cascade Lasers Modulation and Applications

Science.gov (United States)

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

Bursting behaviours in cascaded stimulated Brillouin scattering

International Nuclear Information System (INIS)

Liu Zhan-Jun; He Xian-Tu; Zheng Chun-Yang; Wang Yu-Gang

2012-01-01

Stimulated Brillouin scattering is studied by numerically solving the Vlasov—Maxwell system. A cascade of stimulated Brillouin scattering can occur when a linearly polarized laser pulse propagates in a plasma. It is found that a stimulated Brillouin scattering cascade can reduce the scattering and increase the transmission of light, as well as introduce a bursting behaviour in the evolution of the laser-plasma interaction. The bursting time in the reflectivity is found to be less than half the ion acoustic period. The ion temperature can affect the stimulated Brillouin scattering cascade, which can repeat several times at low ion temperatures and can be completely eliminated at high ion temperatures. For stimulated Brillouin scattering saturation, higher-harmonic generation and wave—wave interaction of the excited ion acoustic waves can restrict the amplitude of the latter. In addition, stimulated Brillouin scattering cascade can restrict the amplitude of the scattered light. (physics of gases, plasmas, and electric discharges)

Cascades on a stochastic pulse-coupled network

Science.gov (United States)

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.

Metabolites in vertebrate Hedgehog signaling.

Science.gov (United States)

Roberg-Larsen, Hanne; Strand, Martin Frank; Krauss, Stefan; Wilson, Steven Ray

2014-04-11

The Hedgehog (HH) signaling pathway is critical in embryonic development, stem cell biology, tissue homeostasis, chemoattraction and synapse formation. Irregular HH signaling is associated with a number of disease conditions including congenital disorders and cancer. In particular, deregulation of HH signaling has been linked to skin, brain, lung, colon and pancreatic cancers. Key mediators of the HH signaling pathway are the 12-pass membrane protein Patched (PTC), the 7-pass membrane protein Smoothened (SMO) and the GLI transcription factors. PTC shares homology with the RND family of small-molecule transporters and it has been proposed that it interferes with SMO through metabolites. Although a conclusive picture is lacking, substantial efforts are made to identify and understand natural metabolites/sterols, including cholesterol, vitamin D3, oxysterols and glucocorticoides, that may be affected by, or influence the HH signaling cascade at the level of PTC and SMO. In this review we will elaborate the role of metabolites in HH signaling with a focus on oxysterols, and discuss advancements in modern analytical approaches in the field. Copyright © 2014 Elsevier Inc. All rights reserved.

Framework for cascade size calculations on random networks

Science.gov (United States)

Burkholz, Rebekka; Schweitzer, Frank

2018-04-01

We present a framework to calculate the cascade size evolution for a large class of cascade models on random network ensembles in the limit of infinite network size. Our method is exact and applies to network ensembles with almost arbitrary degree distribution, degree-degree correlations, and, in case of threshold models, for arbitrary threshold distribution. With our approach, we shift the perspective from the known branching process approximations to the iterative update of suitable probability distributions. Such distributions are key to capture cascade dynamics that involve possibly continuous quantities and that depend on the cascade history, e.g., if load is accumulated over time. As a proof of concept, we provide two examples: (a) Constant load models that cover many of the analytically tractable casacade models, and, as a highlight, (b) a fiber bundle model that was not tractable by branching process approximations before. Our derivations cover the whole cascade dynamics, not only their steady state. This allows us to include interventions in time or further model complexity in the analysis.

Modulation of learning and memory by cytokines: signaling mechanisms and long term consequences.

Science.gov (United States)

Donzis, Elissa J; Tronson, Natalie C

2014-11-01

This review describes the role of cytokines and their downstream signaling cascades on the modulation of learning and memory. Immune proteins are required for many key neural processes and dysregulation of these functions by systemic inflammation can result in impairments of memory that persist long after the resolution of inflammation. Recent research has demonstrated that manipulations of individual cytokines can modulate learning, memory, and synaptic plasticity. The many conflicting findings, however, have prevented a clear understanding of the precise role of cytokines in memory. Given the complexity of inflammatory signaling, understanding its modulatory role requires a shift in focus from single cytokines to a network of cytokine interactions and elucidation of the cytokine-dependent intracellular signaling cascades. Finally, we propose that whereas signal transduction and transcription may mediate short-term modulation of memory, long-lasting cellular and molecular mechanisms such as epigenetic modifications and altered neurogenesis may be required for the long lasting impact of inflammation on memory and cognition. Copyright © 2014 Elsevier Inc. All rights reserved.

Tunable All-Optical Wavelength Conversion Based on Cascaded SHG/DFG in a Ti:PPLN Waveguide Using a Single CW Control Laser

DEFF Research Database (Denmark)

Hu, Hao; Nouroozi, Rahman; Wang, Wenrui

2012-01-01

Tunable all-optical wavelength conversion (AOWC) of a 40-Gb/s RZ-OOK data signal based on cascaded second-harmonic generation (SHG) and difference-frequency generation (DFG) in a Ti:PPLN waveguide is demonstrated. Error-free performances with negligible power penalty are achieved for the wavelength...

Andrographolide inhibits nuclear factor-κB activation through JNK-Akt-p65 signaling cascade in tumor necrosis factor-α-stimulated vascular smooth muscle cells.

Science.gov (United States)

Chen, Yu-Ying; Hsu, Ming-Jen; Hsieh, Cheng-Ying; Lee, Lin-Wen; Chen, Zhih-Cherng; Sheu, Joen-Rong

2014-01-01

Critical vascular inflammation leads to vascular dysfunction and cardiovascular diseases, including abdominal aortic aneurysms, hypertension, and atherosclerosis. Andrographolide is the most active and critical constituent isolated from the leaves of Andrographis paniculata, a herbal medicine widely used for treating anti-inflammation in Asia. In this study, we investigated the mechanisms of the inhibitory effects of andrographolide in vascular smooth muscle cells (VSMCs) exposed to a proinflammatory stimulus, tumor necrosis factor-α (TNF-α). Treating TNF-α-stimulated VSMCs with andrographolide suppressed the expression of inducible nitric oxide synthase in a concentration-dependent manner. A reduction in TNF-α-induced c-Jun N-terminal kinase (JNK), Akt, and p65 phosphorylation was observed in andrographolide-treated VSMCs. However, andrographolide affected neither IκBα degradation nor p38 mitogen-activated protein kinase or extracellular signal-regulated kinase 1/2 phosphorylation under these conditions. Both treatment with LY294002, a phosphatidylinositol 3-kinase/Akt inhibitor, and treatment with SP600125, a JNK inhibitor, markedly reversed the andrographolide-mediated inhibition of p65 phosphorylation. In addition, LY294002 and SP600125 both diminished Akt phosphorylation, whereas LY294002 had no effects on JNK phosphorylation. These results collectively suggest that therapeutic interventions using andrographolide can benefit the treatment of vascular inflammatory diseases, and andrographolide-mediated inhibition of NF-κB activity in TNF-α-stimulated VSMCs occurs through the JNK-Akt-p65 signaling cascade, an IκBα-independent mechanism.

Andrographolide Inhibits Nuclear Factor-κB Activation through JNK-Akt-p65 Signaling Cascade in Tumor Necrosis Factor-α-Stimulated Vascular Smooth Muscle Cells

Directory of Open Access Journals (Sweden)

Yu-Ying Chen

2014-01-01

Full Text Available Critical vascular inflammation leads to vascular dysfunction and cardiovascular diseases, including abdominal aortic aneurysms, hypertension, and atherosclerosis. Andrographolide is the most active and critical constituent isolated from the leaves of Andrographis paniculata, a herbal medicine widely used for treating anti-inflammation in Asia. In this study, we investigated the mechanisms of the inhibitory effects of andrographolide in vascular smooth muscle cells (VSMCs exposed to a proinflammatory stimulus, tumor necrosis factor-α (TNF-α. Treating TNF-α-stimulated VSMCs with andrographolide suppressed the expression of inducible nitric oxide synthase in a concentration-dependent manner. A reduction in TNF-α-induced c-Jun N-terminal kinase (JNK, Akt, and p65 phosphorylation was observed in andrographolide-treated VSMCs. However, andrographolide affected neither IκBα degradation nor p38 mitogen-activated protein kinase or extracellular signal-regulated kinase 1/2 phosphorylation under these conditions. Both treatment with LY294002, a phosphatidylinositol 3-kinase/Akt inhibitor, and treatment with SP600125, a JNK inhibitor, markedly reversed the andrographolide-mediated inhibition of p65 phosphorylation. In addition, LY294002 and SP600125 both diminished Akt phosphorylation, whereas LY294002 had no effects on JNK phosphorylation. These results collectively suggest that therapeutic interventions using andrographolide can benefit the treatment of vascular inflammatory diseases, and andrographolide-mediated inhibition of NF-κB activity in TNF-α-stimulated VSMCs occurs through the JNK-Akt-p65 signaling cascade, an IκBα-independent mechanism.

Deciphering complex dynamics of water counteraction around secondary structural elements of allosteric protein complex: Case study of SAP-SLAM system in signal transduction cascade.

Science.gov (United States)

Samanta, Sudipta; Mukherjee, Sanchita

2018-01-28

The first hydration shell of a protein exhibits heterogeneous behavior owing to several attributes, majorly local polarity and structural flexibility as revealed by solvation dynamics of secondary structural elements. We attempt to recognize the change in complex water counteraction generated due to substantial alteration in flexibility during protein complex formation. The investigation is carried out with the signaling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, and interacting with SLAM-associated protein (SAP), composed of one SH2 domain. All atom molecular dynamics simulations are employed to the aqueous solutions of free SAP and SLAM-peptide bound SAP. We observed that water dynamics around different secondary structural elements became highly affected as well as nicely correlated with the SLAM-peptide induced change in structural rigidity obtained by thermodynamic quantification. A few instances of contradictory dynamic features of water to the change in structural flexibility are explained by means of occluded polar residues by the peptide. For βD, EFloop, and BGloop, both structural flexibility and solvent accessibility of the residues confirm the obvious contribution. Most importantly, we have quantified enhanced restriction in water dynamics around the second Fyn-binding site of the SAP due to SAP-SLAM complexation, even prior to the presence of Fyn. This observation leads to a novel argument that SLAM induced more restricted water molecules could offer more water entropic contribution during the subsequent Fyn binding and provide enhanced stability to the SAP-Fyn complex in the signaling cascade. Finally, SLAM induced water counteraction around the second binding site of the SAP sheds light on the allosteric property of the SAP, which becomes an integral part of the underlying signal transduction mechanism.

Deciphering complex dynamics of water counteraction around secondary structural elements of allosteric protein complex: Case study of SAP-SLAM system in signal transduction cascade

Science.gov (United States)

Samanta, Sudipta; Mukherjee, Sanchita

2018-01-01

The first hydration shell of a protein exhibits heterogeneous behavior owing to several attributes, majorly local polarity and structural flexibility as revealed by solvation dynamics of secondary structural elements. We attempt to recognize the change in complex water counteraction generated due to substantial alteration in flexibility during protein complex formation. The investigation is carried out with the signaling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, and interacting with SLAM-associated protein (SAP), composed of one SH2 domain. All atom molecular dynamics simulations are employed to the aqueous solutions of free SAP and SLAM-peptide bound SAP. We observed that water dynamics around different secondary structural elements became highly affected as well as nicely correlated with the SLAM-peptide induced change in structural rigidity obtained by thermodynamic quantification. A few instances of contradictory dynamic features of water to the change in structural flexibility are explained by means of occluded polar residues by the peptide. For βD, EFloop, and BGloop, both structural flexibility and solvent accessibility of the residues confirm the obvious contribution. Most importantly, we have quantified enhanced restriction in water dynamics around the second Fyn-binding site of the SAP due to SAP-SLAM complexation, even prior to the presence of Fyn. This observation leads to a novel argument that SLAM induced more restricted water molecules could offer more water entropic contribution during the subsequent Fyn binding and provide enhanced stability to the SAP-Fyn complex in the signaling cascade. Finally, SLAM induced water counteraction around the second binding site of the SAP sheds light on the allosteric property of the SAP, which becomes an integral part of the underlying signal transduction mechanism.

Increasing sensitivity of MOS dosemeters in cascade connection

International Nuclear Information System (INIS)

Vychytil, F.; Cechak, T.; Gerndt, J.; Petr, I.

1978-01-01

The possibilities of increasing the sensitivity of MOS transistors in their cascade connection were studied theoretically and experimentally. The measurements confirmed the presumption that the instability of cascade-connected MOS transistors increased with the square of the number of transistors in the system. This allows systems to be formed with different sensitivity to ionizing radiation by encasing 10 to 10 4 transistors connected in cascade, which is technologically feasible. The procedure is also acceptable from the point of view of cost. (Z.M.)

Evaluation of refrigerating and air-conditioning technologies in heat cascading systems under the carbon dioxide emissions constraint: the proposal of the energy cascade balance table

International Nuclear Information System (INIS)

Shimazaki, Yoichi

2003-01-01

The aim of this study was to evaluate the refrigerating and air-conditioning technologies in cases of introducing both heat cascading systems and thermal recycling systems in industries located around urban areas. It is necessary to introduce heat cascading systems in the industrial sector in Japan to reduce carbon dioxide emissions. The concept of heat cascading is the multi-stage use of thermal energy by temperature level. This paper introduces three energy policies for introducing the heat cascading systems. The author develops an energy cascade model based on linear programming so as to minimize the total system costs with carbon taxes. Five cases are investigated. Carbon dioxide emission constraints result in the enhancement of heat cascading, where high temperature heat is supplied for process heating while low temperature heat is shifted to refrigeration. It was found that increasing the amount of garbage combustion waste heat could reduce electric power for the turbo compression refrigerator by promoting waste heat driven ammonia absorption refrigerator. In addition, this study proposes an energy cascade balance table with respect to the temperature level

On the trajectories of CRL...LR...R orbits, their period-doubling cascades and saddle-node bifurcation cascades

International Nuclear Information System (INIS)

Cerrada, Lucia; San Martin, Jesus

2011-01-01

In this Letter, it is shown that from a two region partition of the phase space of a one-dimensional dynamical system, a p-region partition can be obtained for the CRL...LR...R orbits. That is, permutations associated with symbolic sequences are obtained. As a consequence, the trajectory in phase space is directly deduced from permutation. From this permutation other permutations associated with period-doubling and saddle-node bifurcation cascades are derived, as well as other composite permutations. - Research highlights: → Symbolic sequences are the usual topological approach to dynamical systems. → Permutations bear more physical information than symbolic sequences. → Period-doubling cascade permutations associated with original sequences are obtained. → Saddle-node cascade permutations associated with original sequences are obtained. → Composite permutations are derived.

cGMP signalling : different ways to create a pathway

NARCIS (Netherlands)

Roelofs, Jeroen; Smith, Janet L.; Haastert, Peter J.M. van

Recently, a novel cGMP signalling cascade was uncovered in Dictyostelium, a eukaryote that diverged from the lineage leading to metazoa after plants and before yeast. In both Dictyostelium and metazoa, the ancient cAMP-binding (cNB) motif of bacterial CAP has been modified and assembled with other

Radiological manifestations of rheumatoid arthritis

International Nuclear Information System (INIS)

Kapp, H.J.

1997-01-01

Rheumatoid arthritis preferrably becomes manifest at the synovial joints of the limbs, especially at the small joints of the hands and feet, at bursae and synovial sheathes. The pathologic lesions are less frequently found at cartilaginous joints or entheses. The lesions very often are symmetrically distributed and are characterized by the following: 1. A periarticular, spindle-shaped opacity with a density similar to soft-tissue, induced by an inflammatory hypertrophy of the synovia, a serosynovitis, or an edematous impregnation of the periarticular tissue. 2. A juxta-articular osteoporosis, most probably caused by a neighbouring synovialitis accompanied by hyperemia. 3. A diffuse joint cavity narrowing due to a destruction of the articular cartilage by the pannus, a fibrovascular resorptive tissue. 4. Central as well as marginal erosions, caused by destruction of ossous material by the pannus. 5. Subchondral signal cysts, likewise unduced by the pannus. (Orig./AJ) [de

Ras signaling in aging and metabolic regulation.

Science.gov (United States)

Slack, Cathy

2017-12-07

Aberrant signal transduction downstream of the Ras GTPase has a well-established role in tumorigenesis. Mutations that result in hyperactivation of Ras are responsible for a third of all human cancers. Hence, small molecule inhibitors of the Ras signal transduction cascade have been under intense focus as potential cancer treatments. In both invertebrate and mammalian models, emerging evidence has also implicated components of the Ras signaling pathway in aging and metabolic regulation. Here, I review the current evidence for Ras signaling in these newly discovered roles highlighting the interactions between the Ras pathway and other longevity assurance mechanisms. Defining the role of Ras signaling in maintaining age-related health may have important implications for the development of interventions that could not only increase lifespan but also delay the onset and/or progression of age-related functional decline.

Development of a New Cascade Voltage-Doubler for Voltage Multiplication

OpenAIRE

Toudeshki, Arash; Mariun, Norman; Hizam, Hashim; Abdul Wahab, Noor Izzri

2014-01-01

For more than eight decades, cascade voltage-doubler circuits are used as a method to produce DC output voltage higher than the input voltage. In this paper, the topological developments of cascade voltage-doublers are reviewed. A new circuit configuration for cascade voltage-doubler is presented. This circuit can produce a higher value of the DC output voltage and better output quality compared to the conventional cascade voltage-doubler circuits, with the same number of stages.

A Novel Concept for Three-Phase Cascaded Multilevel Inverter Topologies

Directory of Open Access Journals (Sweden)

Md Mubashwar Hasan

2018-01-01

Full Text Available One of the key challenges in multilevel inverters (MLIs design is to reduce the number of components used in the implementation while maximising the number of output voltage levels. This paper proposes a new concept that facilitates a device count reduction technique of existing cascaded MLIs. Moreover, the proposed concept can be utilised to extend existing single phase cascaded MLI topologies to three-phase structure without tripling the number of semiconductor components and input dc-supplies as per the current practice. The new generalized concept involves two stages; namely, cascaded stage and phase generator stage. The phase generator stage is a combination of a conventional three-phase two level inverter and three bi-directional switches while the cascaded stage can employ any existing cascaded topology. A laboratory prototype model is built and extensive experimental analyses are conducted to validate the feasibility of the proposed cascaded MLI concept.

Wnt/β-catenin Signaling in Normal and Cancer Stem Cells

Directory of Open Access Journals (Sweden)

Kenneth C. Valkenburg

2011-04-01

Full Text Available The ability of Wnt ligands to initiate a signaling cascade that results in cytoplasmic stabilization of, and nuclear localization of, β-catenin underlies their ability to regulate progenitor cell differentiation. In this review, we will summarize the current knowledge of the mechanisms underlying Wnt/β-catenin signaling and how the pathway regulates normal differentiation of stem cells in the intestine, mammary gland, and prostate. We will also discuss how dysregulation of the pathway is associated with putative cancer stem cells and the potential therapeutic implications of regulating Wnt signaling.

CT manifestation of hepatic toxoplasmosis

International Nuclear Information System (INIS)

Mao Qing; Yang Yaying; Bao Yanming; He Bo; Wang Kechao; Song Guangyi; Lu Lin; Wang Xiaoli

2005-01-01

Objective: To study the CT manifestation of hepatic toxoplasmosis, and to provide image basis for its clinical diagnosis. Methods: Three patients with hepatic toxoplasmosis were examined by abdomen MSCT (pre- and post-contrast), and were confirmed by laboratory exams. The images were analyzed with information of clinical manifestation. Results: The positive appearances included the enlargement of liver, patches of multiple scattered low densities. Post-contrast lesions appearances: (1) No significant enhancement. (2) No significant occupying effection, and normal vessels inserting lesion occasionally. Conclusion: CT manifestation of hepar toxoplasmosis are some characteristic. But the diagnosis was made by a combination both clinical manifestation and laboratory exams. (authors)

Information Thermodynamics of the Cell Signal Transduction as a Szilard Engine

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Tatsuaki Tsuruyama

2018-03-01

Full Text Available A cell signaling system is in a non-equilibrium state, and it includes multistep biochemical signaling cascades (BSCs, which involve phosphorylation of signaling molecules, such as mitogen-activated protein kinase (MAPK pathways. In this study, the author considered signal transduction description using information thermodynamic theory. The ideal BSCs can be considered one type of the Szilard engine, and the presumed feedback controller, Maxwell’s demon, can extract the work during signal transduction. In this model, the mutual entropy and chemical potential of the signal molecules can be redefined by the extracted chemical work in a mechanicochemical model, Szilard engine, of BSC. In conclusion, signal transduction is computable using the information thermodynamic method.

Molecular dynamics simulation of displacement cascades in iron-alpha

International Nuclear Information System (INIS)

Vascon, R.

1997-01-01

Radiation damage by neutrons or ions in bcc iron has been investigated by molecular dynamics simulations using an embedded atom type many-body potential (EAM). Displacement cascades with energies of 1 to 30 keV were generated in the microcanonical system where the number of atoms (up to 1.5 million) is chosen high enough to compensate the fact that the dissipation of energy is not taken into account in our model. The defect number at the end of cascade lifetime was found to be 60 percent of the NRT standard value. This tendency is in good agreement with experimental data. However, compared with other simulations in iron, we found significant differences in the defect production and distribution. The comparison with results obtained form simulations of cascades in other metals, leads on the one hand to a higher value of the defect number in bcc iron than in fcc metals like copper or nickel, and on the other hand to a ratio, between the number of replacements and the number of defects, lower in iron ( 100). We observed the transient melting of the core of the cascade during simulations. We showed that a higher value of the initial iron crystal temperature, as the mass difference between the components of an artificial binary alloy Fe-X(X=Al,Sb,Au,U) both produce a 'cascade effect': a decrease of the number of defects and an increase of the number of replacements. We also showed up the quasi-channeling of some atoms in high energy cascades. They are at the origin of sub-cascades formation; as a result they induce an opposite effect to the 'cascade effect'. (author)

Design concept of Hydro cascade control system

International Nuclear Information System (INIS)

Fustik, Vangel; Kiteva, Nevenka

2006-01-01

In this paper a design concept of the comple hydro cascade scheme is presented with the design parameters of the main technical features. The cascade control system architecture is designed considering up-to-date communication and information technology. The control algorithm is based on Pond Level Control and Economic Load Allocation concepts.

Surgical manifestations of filariasis

Directory of Open Access Journals (Sweden)

Subrahmanyam M

1978-01-01

Full Text Available Surgical manifestations of filariasis as seen in 150 cases over a period of three years in the department of Surgery, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha are reviewed. The genital manifestations are more common than the elephantiasis in this endemic zone.

On calculating of squared-off cascades for multicomponent isotope separation

International Nuclear Information System (INIS)

Potapov, D.V.; Soulaberidze, G.A.; Chuzhinov, V.A.; Filipppov, I.G.

1996-01-01

Calculation on a cascade of specified configuration (specified number of stages and flows in the enriching and stripping sections of the cascade) is performed with two approaches. The first one, which is advisable to use for for calculation of so-called 'long' cascades (for example, squared-off cascades of distillation columns), is based on either analytical transitions enabling the problem to be reduced to to the algebraic transcendental equations, or based on the direct integration of the equations describing the cascade separation process, with the subsequent iteration on the boundary conditions and the balance equations. This approach also involves the orthogonal-collocation technique consisting in the approximation of the differential equations solution by an Lagrangian polynomial interpolation

Sample Selection for Training Cascade Detectors.

Science.gov (United States)

Vállez, Noelia; Deniz, Oscar; Bueno, Gloria

2015-01-01

Automatic detection systems usually require large and representative training datasets in order to obtain good detection and false positive rates. Training datasets are such that the positive set has few samples and/or the negative set should represent anything except the object of interest. In this respect, the negative set typically contains orders of magnitude more images than the positive set. However, imbalanced training databases lead to biased classifiers. In this paper, we focus our attention on a negative sample selection method to properly balance the training data for cascade detectors. The method is based on the selection of the most informative false positive samples generated in one stage to feed the next stage. The results show that the proposed cascade detector with sample selection obtains on average better partial AUC and smaller standard deviation than the other compared cascade detectors.

The temporal development of collision cascades in the binary collision approximation

International Nuclear Information System (INIS)

Robinson, M.T.

1989-07-01

A modified binary collision approximation (BCA) was developed to allow explicit evaluation of the times at which projectiles in a collision cascade reach significant points in their trajectories, without altering the ''event-driven'' character of the model. The modified BCA was used to study the temporal development of cascades in copper and gold, initiated by primary atoms of up to 10 keV initial kinetic energy. Cascades generated with time-ordered collisions show fewer ''distant'' Frenkel pairs than do cascades generated with velocity-ordered collisions. In the former, the slower projectiles tend to move in less-damaged crystal than they do in the latter. The effect is larger in Au than in Cu and increases with primary energy. As an approach to cascade nonlinearities, cascades were generated in which stopped cascade atoms were allowed to be redisplaced in later encounters. There were many more redisplacements in time-ordered cascades than in velocity-ordered ones. Because of the additional stopping introduced by the redisplacement events, the cascades in which they were allowed had fewer defects than occurred otherwise. This effect also was larger in Au than in Cu and larger at high energies although most of the redisplacement encounters involved only low-energy particles. 13 refs., 5 figs., 4 tabs

All passive architecture for high efficiency cascaded Raman conversion

Science.gov (United States)

Balaswamy, V.; Arun, S.; Chayran, G.; Supradeepa, V. R.

2018-02-01

Cascaded Raman fiber lasers have offered a convenient method to obtain scalable, high-power sources at various wavelength regions inaccessible with rare-earth doped fiber lasers. A limitation previously was the reduced efficiency of these lasers. Recently, new architectures have been proposed to enhance efficiency, but this came at the cost of enhanced complexity, requiring an additional low-power, cascaded Raman laser. In this work, we overcome this with a new, all-passive architecture for high-efficiency cascaded Raman conversion. We demonstrate our architecture with a fifth-order cascaded Raman converter from 1117nm to 1480nm with output power of ~64W and efficiency of 60%.

Minimum Entropy-Based Cascade Control for Governing Hydroelectric Turbines

Directory of Open Access Journals (Sweden)

Mifeng Ren

2014-06-01

Full Text Available In this paper, an improved cascade control strategy is presented for hydroturbine speed governors. Different from traditional proportional-integral-derivative (PID control and model predictive control (MPC strategies, the performance index of the outer controller is constructed by integrating the entropy and mean value of the tracking error with the constraints on control energy. The inner controller is implemented by a proportional controller. Compared with the conventional PID-P and MPC-P cascade control methods, the proposed cascade control strategy can effectively decrease fluctuations of hydro-turbine speed under non-Gaussian disturbance conditions in practical hydropower plants. Simulation results show the advantages of the proposed cascade control method.

Experimental study on cascaded attitude angle control of a multi-rotor unmanned aerial vehicle with the simple internal model control method

International Nuclear Information System (INIS)

Song, Jun Beom; Byun, Young Seop; Jeong, Jin Seok; Kim, Jeong; Kang, Beom Soo

2016-01-01

This paper proposes a cascaded control structure and a method of practical application for attitude control of a multi-rotor Unmanned aerial vehicle (UAV). The cascade control, which has tighter control capability than a single-loop control, is rarely used in attitude control of a multi-rotor UAV due to the input-output relation, which is no longer simply a set-point to Euler angle response transfer function of a single-loop PID control, but there are multiply measured signals and interactive control loops that increase the complexity of evaluation in conventional way of design. However, it is proposed in this research a method that can optimize a cascade control with a primary and secondary loops and a PID controller for each loop. An investigation of currently available PID-tuning methods lead to selection of the Simple internal model control (SIMC) method, which is based on the Internal model control (IMC) and direct-synthesis method. Through the analysis and experiments, this research proposes a systematic procedure to implement a cascaded attitude controller, which includes the flight test, system identification and SIMC-based PID-tuning. The proposed method was validated successfully from multiple applications where the application to roll axis lead to a PID-PID cascade control, but the application to yaw axis lead to that of PID-PI

Experimental study on cascaded attitude angle control of a multi-rotor unmanned aerial vehicle with the simple internal model control method

Energy Technology Data Exchange (ETDEWEB)

Song, Jun Beom [Dept. of Aviation Maintenance, Dongwon Institute of Science and Technology, Yangsan (Korea, Republic of); Byun, Young Seop; Jeong, Jin Seok; Kim, Jeong; Kang, Beom Soo [Dept. of Aerospace Engineering, Pusan National University, Busan (Korea, Republic of)

2016-11-15

This paper proposes a cascaded control structure and a method of practical application for attitude control of a multi-rotor Unmanned aerial vehicle (UAV). The cascade control, which has tighter control capability than a single-loop control, is rarely used in attitude control of a multi-rotor UAV due to the input-output relation, which is no longer simply a set-point to Euler angle response transfer function of a single-loop PID control, but there are multiply measured signals and interactive control loops that increase the complexity of evaluation in conventional way of design. However, it is proposed in this research a method that can optimize a cascade control with a primary and secondary loops and a PID controller for each loop. An investigation of currently available PID-tuning methods lead to selection of the Simple internal model control (SIMC) method, which is based on the Internal model control (IMC) and direct-synthesis method. Through the analysis and experiments, this research proposes a systematic procedure to implement a cascaded attitude controller, which includes the flight test, system identification and SIMC-based PID-tuning. The proposed method was validated successfully from multiple applications where the application to roll axis lead to a PID-PID cascade control, but the application to yaw axis lead to that of PID-PI.

Real-time monitoring of enzyme-free strand displacement cascades by colorimetric assays

Science.gov (United States)

Duan, Ruixue; Wang, Boya; Hong, Fan; Zhang, Tianchi; Jia, Yongmei; Huang, Jiayu; Hakeem, Abdul; Liu, Nannan; Lou, Xiaoding; Xia, Fan

2015-03-01

The enzyme-free toehold-mediated strand displacement reaction has shown potential for building programmable DNA circuits, biosensors, molecular machines and chemical reaction networks. Here we report a simple colorimetric method using gold nanoparticles as signal generators for the real-time detection of the product of the strand displacement cascade. During the process the assembled gold nanoparticles can be separated, resulting in a color change of the solution. This assay can also be applied in complex mixtures, fetal bovine serum, and to detect single-base mismatches. These results suggest that this method could be of general utility to monitor more complex enzyme-free strand displacement reaction-based programmable systems or for further low-cost diagnostic applications.The enzyme-free toehold-mediated strand displacement reaction has shown potential for building programmable DNA circuits, biosensors, molecular machines and chemical reaction networks. Here we report a simple colorimetric method using gold nanoparticles as signal generators for the real-time detection of the product of the strand displacement cascade. During the process the assembled gold nanoparticles can be separated, resulting in a color change of the solution. This assay can also be applied in complex mixtures, fetal bovine serum, and to detect single-base mismatches. These results suggest that this method could be of general utility to monitor more complex enzyme-free strand displacement reaction-based programmable systems or for further low-cost diagnostic applications. Electronic supplementary information (ESI) available: Experimental procedures and analytical data are provided. See DOI: 10.1039/c5nr00697j

Space-time evolution of electron cascades in diamond

International Nuclear Information System (INIS)

Ziaja, Beata; Szoeke, Abraham; Spoel, David van der; Hajdu, Janos

2002-01-01

The impact of a primary electron initiates a cascade of secondary electrons in solids, and these cascades play a significant role in the dynamics of ionization. Here we describe model calculations to follow the spatiotemporal evolution of secondary electron cascades in diamond. The band structure of the insulator has been explicitly incorporated into the calculations as it affects ionizations from the valence band. A Monte Carlo model was constructed to describe the path of electrons following the impact of a single electron of energy E∼250 eV. This energy is similar to the energy of an Auger electron from carbon. Two limiting cases were considered: the case in which electrons transmit energy to the lattice, and the case where no such energy transfer is permitted. The results show the evolution of the secondary electron cascades in terms of the number of electrons liberated, the spatial distribution of these electrons, and the energy distribution among the electrons as a function of time. The predicted ionization rates (∼5-13 electrons in 100 fs) lie within the limits given by experiments and phenomenological models. Calculation of the local electron density and the corresponding Debye length shows that the latter is systematically larger than the radius of the electron cloud, and it increases exponentially with the radial size of the cascade. This means that the long-range Coulomb field is not shielded within this cloud, and the electron gas generated does not represent a plasma in a single impact cascade triggered by an electron of E∼250 eV energy. This is important as it justifies the independent-electron approximation used in the model. At 1 fs, the (average) spatial distribution of secondary electrons is anisotropic with the electron cloud elongated in the direction of the primary impact. The maximal radius of the cascade is about 50 A at this time. At 10 fs the cascade has a maximal radius of ∼70 A, and is already dominated by low-energy electrons

Energy cascading in the beat-wave accelerator

International Nuclear Information System (INIS)

McKinstrie, C.J.; Batha, S.H.

1987-01-01

A review is given of energy cascading in the beat-wave accelerator. The properties of the electromagnetic cascade and the corresponding plasma-wave evolution are well understood within the framework of an approximate analytic model. Based on this model, idealized laser-plasma coupling efficiencies of the order of 10% do not seem unreasonable. 28 refs

Simulation of short-term annealing of displacement cascades in FCC metals

International Nuclear Information System (INIS)

Heinisch, H.L.; Doran, D.G.; Schwartz, D.M.

1980-01-01

Computer models have been developed for the simulation of high energy displacement cascades. The objective is the generation of defect production functions for use in correlation analysis of radiation effects in fusion reactor materials. In particular, the stochastic cascade annealing simulation code SCAS has been developed and used to model the short-term annealing behavior of simulated cascades in FCC metals. The code is fast enough to make annealing of high energy cascades practical. Sets of cascades from 5 keV to 100 keV in copper were generated by the binary collision code MARLOWE

Field-trip guide to mafic volcanism of the Cascade Range in Central Oregon—A volcanic, tectonic, hydrologic, and geomorphic journey

Science.gov (United States)

Deligne, Natalia I.; Mckay, Daniele; Conrey, Richard M.; Grant, Gordon E.; Johnson, Emily R.; O'Connor, Jim; Sweeney, Kristin

2017-08-16

The Cascade Range in central Oregon has been shaped by tectonics, volcanism, and hydrology, as well as geomorphic forces that include glaciations. As a result of the rich interplay between these forces, mafic volcanism here can have surprising manifestations, which include relatively large tephra footprints and extensive lava flows, as well as water shortages, transportation and agricultural disruption, and forest fires. Although the focus of this multidisciplinary field trip will be on mafic volcanism, we will also look at the hydrology, geomorphology, and ecology of the area, and we will examine how these elements both influence and are influenced by mafic volcanism. We will see mafic volcanic rocks at the Sand Mountain volcanic field and in the Santiam Pass area, at McKenzie Pass, and in the southern Bend region. In addition, this field trip will occur during a total solar eclipse, the first one visible in the United States in more than 25 years (and the first seen in the conterminous United States in more than 37 years).The Cascade Range is the result of subduction of the Juan de Fuca plate underneath the North American plate. This north-south-trending volcanic mountain range is immediately downwind of the Pacific Ocean, a huge source of moisture. As moisture is blown eastward from the Pacific on prevailing winds, it encounters the Cascade Range in Oregon, and the resulting orographic lift and corresponding rain shadow is one of the strongest precipitation gradients in the conterminous United States. We will see how the products of the volcanoes in the central Oregon Cascades have had a profound influence on groundwater flow and, thus, on the distribution of Pacific moisture. We will also see the influence that mafic volcanism has had on landscape evolution, vegetation development, and general hydrology.

Induction of the unfolded protein response by constitutive G-protein signaling in rod photoreceptor cells.

Science.gov (United States)

Wang, Tian; Chen, Jeannie

2014-10-17

Phototransduction is a G-protein signal transduction cascade that converts photon absorption to a change in current at the plasma membrane. Certain genetic mutations affecting the proteins in the phototransduction cascade cause blinding disorders in humans. Some of these mutations serve as a genetic source of "equivalent light" that activates the cascade, whereas other mutations lead to amplification of the light response. How constitutive phototransduction causes photoreceptor cell death is poorly understood. We showed that persistent G-protein signaling, which occurs in rod arrestin and rhodopsin kinase knock-out mice, caused a rapid and specific induction of the PERK pathway of the unfolded protein response. These changes were not observed in the cGMP-gated channel knock-out rods, an equivalent light condition that mimics light-stimulated channel closure. Thus transducin signaling, but not channel closure, triggers rapid cell death in light damage caused by constitutive phototransduction. Additionally, we show that in the albino light damage model cell death was not associated with increase in global protein ubiquitination or unfolded protein response induction. Taken together, these observations provide novel mechanistic insights into the cell death pathway caused by constitutive phototransduction and identify the unfolded protein response as a potential target for therapeutic intervention. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Oxidative Stress, Redox Signaling, and Autophagy: Cell Death Versus Survival

Science.gov (United States)

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

Optimization of the cascade with gas centrifuges for uranium enrichment

International Nuclear Information System (INIS)

Ozaki, N.; Harada, I.

1976-01-01

Computer programs to optimize the step and tapered-step cascades with gas centrifuges are developed. The 'Complex Method', one of the direct search method, is employed to find the optimum of the nonlinear function of several variables within a constrained region. The separation characteristics of the optimized step and tapered-step cascades are discussed in comparison with that of the ideal cascade. The local optima of the cascade profile, the convergence of the object function, and the stopping criterion for the optimization trial are also discussed. (author)

Centrifugal separator cascade connected in zigzag manner

International Nuclear Information System (INIS)

Kai, Tsunetoshi; Inoue, Yoshiya; Oya, Akio; Nagakura, Masaaki.

1974-01-01

Object: To effectively accommodate centrifugal separators of the entire cascade within the available space in a plant by freely selecting perpendicular direction of connection of the centrifugal separator. Structure: Centrifugal separators are connected in zigzag fashion by using a single header for each stage so that in a rectangular shape the entire cascade is arranged. (Kamimura, M.)

A period-doubling cascade precedes chaos for planar maps.

Science.gov (United States)

Sander, Evelyn; Yorke, James A

2013-09-01

A period-doubling cascade is often seen in numerical studies of those smooth (one-parameter families of) maps for which as the parameter is varied, the map transitions from one without chaos to one with chaos. Our emphasis in this paper is on establishing the existence of such a cascade for many maps with phase space dimension 2. We use continuation methods to show the following: under certain general assumptions, if at one parameter there are only finitely many periodic orbits, and at another parameter value there is chaos, then between those two parameter values there must be a cascade. We investigate only families that are generic in the sense that all periodic orbit bifurcations are generic. Our method of proof in showing there is one cascade is to show there must be infinitely many cascades. We discuss in detail two-dimensional families like those which arise as a time-2π maps for the Duffing equation and the forced damped pendulum equation.

Extrathoracic manifestations of tuberculosis

International Nuclear Information System (INIS)

Kienzl-Palma, D.; Prosch, H.

2016-01-01

Besides the lungs, tuberculosis (TB) can affect any organ system. In most cases, extrathoracic TB occurs in immunosuppressed patients as part of a severe illness via hematogenous spread. Extrathoracic involvement most commonly involves abdominal organs, especially the urogenital tract and less commonly the central nervous system (CNS) and the musculoskeletal system. Most frequently, computed tomography (CT) is used for detecting extrathoracic TB manifestations, except for CNS and musculoskeletal manifestations, where contrast-enhanced magnetic resonance imaging (MRI) is the gold standard. Extrathoracic manifestations of TB may be indistinguishable from inflammatory or malignant causes. Due to unspecific symptoms the diagnosis is often delayed. This article summarizes and discusses the various radiological manifestations of extrathoracic manifestation of TB. Radiological modalities for screening extrathoracic TB are CT and MRI. Conventional X-radiographs do not play a role in the diagnosis of extrathoracic TB. The possibility of extrathoracic TB should be considered particularly in immunosuppressed patients, such as the homeless, alcoholics or drug addicts or in patients with an immigrant background from the endemic areas of TB. The most likely site of extrathoracic TB is the abdomen; however, infections of the CNS or musculoskeletal systems and multisystem infections can also occur. In patients with suspected extrathoracic TB, radiological modalities for screening are CT, especially for abdominal infections and lymphadenopathy and MRI with contrast media for the musculoskeletal system and the CNS. (orig.) [de

Sample Selection for Training Cascade Detectors.

Directory of Open Access Journals (Sweden)

Noelia Vállez

Full Text Available Automatic detection systems usually require large and representative training datasets in order to obtain good detection and false positive rates. Training datasets are such that the positive set has few samples and/or the negative set should represent anything except the object of interest. In this respect, the negative set typically contains orders of magnitude more images than the positive set. However, imbalanced training databases lead to biased classifiers. In this paper, we focus our attention on a negative sample selection method to properly balance the training data for cascade detectors. The method is based on the selection of the most informative false positive samples generated in one stage to feed the next stage. The results show that the proposed cascade detector with sample selection obtains on average better partial AUC and smaller standard deviation than the other compared cascade detectors.

Multilevel Inverter by Cascading Industrial VSI

DEFF Research Database (Denmark)

Teodorescu, Remus; Blaabjerg, Frede; Pedersen, John Kim

2002-01-01

In this paper the modularity concept applied to medium-voltage adjustable speed drives is addressed. First, the single-phase cascaded voltage-source inverter that uses series connection of IGBT H-bridge modules with isolated dc-buses is presented. Next, a novel three-phase cascaded voltage......-source inverter that uses three IGBT triphase inverter modules along with an output transformer to obtain a 3 p.u. multilevel output voltage is introduced. The system yields in high-quality multistep voltage with up to 4 levels and low dv/dt, balanced operation of the inverter modules, each supplying a third...... of the motor rated kVA. The concept of using cascaded inverters is further extended to a new modular motor-modular inverter system where the motor winding connections are reconnected into several three-phase groups, either six-lead or 12-lead connection according to the voltage level, each powered...

Particle fluxes in atomic collision cascades

International Nuclear Information System (INIS)

Sckerl, B.W.; Sigmund, P.; Vicanek, M.

1996-01-01

The flux of recoil atoms in atomic collision cascades induced by an ion beam or another source of energetic particles in a material is known to approach isotropy at kinetic energies far below the beam energy. A variety of irradiation effects can be explained satisfactorily on the basis of an isotropic particle flux, but significant deviations from this simple behavior are known to exist. While numerous examples have been studied by numerical simulation of cascade processes, the systematics is, by and large, unknown. The present study aims at general scaling properties and estimates of the magnitude of moderate deviations from isotropy and their spatial dependence for a wide range of beam and material parameters. Anisotropies introduced by crystal structure are ignored. Although it is well established that cascade anisotropy is related to the momentum of beam particles, previous attempts to quantify this relation have failed. We have found that there are two leading correction terms to the isotropic particle flux, a well-known term centered around the beam direction as a symmetry axis and a new term proportional to the gradient of the deposited-energy density. As a general rule the two contributions are either both significant or both negligible. Specific situations in which the gradient term dominates are, however, of considerable interest in applications. The parameters which characterize the anisotropy of collision cascades also determine the deposition of momentum, but the connection is less straightforward than asserted hitherto. General principles are first illustrated on the specific case of elastic-collision cascades under self-bombardment which contains the essentials. Thereafter several generalizations are made, including atomic binding forces and inelasticity as well as allowance for multicomponent materials. Application areas in mixing and sputtering are outlined. (au) 58 refs

Cascading Generative Adversarial Networks for Targeted

KAUST Repository

Hamdi, Abdullah

2018-01-01

Abundance of labelled data played a crucial role in the recent developments in computer vision, but that faces problems like scalability and transferability to the wild. One alternative approach is to utilize the data without labels, i.e. unsupervised learning, in learning valuable information and put it in use to tackle vision problems. Generative Adversarial Networks (GANs) have gained momentum for their ability to model image distributions in unsupervised manner. They learn to emulate the training set and that enables sampling from that domain and using the knowledge learned for useful applications. Several methods proposed enhancing GANs, including regularizing the loss with some feature matching. We seek to push GANs beyond the data in the training and try to explore unseen territory in the image manifold. We first propose a new regularizer for GAN based on K-Nearest Neighbor (K-NN) selective feature matching to a target set Y in high-level feature space, during the adversarial training of GAN on the base set X, and we call this novel model K-GAN. We show that minimizing the added term follows from cross-entropy minimization between the distributions of GAN and set Y. Then, we introduce a cascaded framework for GANs that try to address the task of imagining a new distribution that combines the base set X and target set Y by cascading sampling GANs with translation GANs, and we dub the cascade of such GANs as the Imaginative Adversarial Network (IAN). Several cascades are trained on a collected dataset Zoo-Faces and generated innovative samples are shown, including from K-GAN cascade. We conduct an objective and subjective evaluation for different IAN setups in the addressed task of generating innovative samples and we show the effect of regularizing GAN on different scores. We conclude with some useful applications for these IANs, like multi-domain manifold traversing.

Cascading Generative Adversarial Networks for Targeted

KAUST Repository

Hamdi, Abdullah

2018-04-09

Abundance of labelled data played a crucial role in the recent developments in computer vision, but that faces problems like scalability and transferability to the wild. One alternative approach is to utilize the data without labels, i.e. unsupervised learning, in learning valuable information and put it in use to tackle vision problems. Generative Adversarial Networks (GANs) have gained momentum for their ability to model image distributions in unsupervised manner. They learn to emulate the training set and that enables sampling from that domain and using the knowledge learned for useful applications. Several methods proposed enhancing GANs, including regularizing the loss with some feature matching. We seek to push GANs beyond the data in the training and try to explore unseen territory in the image manifold. We first propose a new regularizer for GAN based on K-Nearest Neighbor (K-NN) selective feature matching to a target set Y in high-level feature space, during the adversarial training of GAN on the base set X, and we call this novel model K-GAN. We show that minimizing the added term follows from cross-entropy minimization between the distributions of GAN and set Y. Then, we introduce a cascaded framework for GANs that try to address the task of imagining a new distribution that combines the base set X and target set Y by cascading sampling GANs with translation GANs, and we dub the cascade of such GANs as the Imaginative Adversarial Network (IAN). Several cascades are trained on a collected dataset Zoo-Faces and generated innovative samples are shown, including from K-GAN cascade. We conduct an objective and subjective evaluation for different IAN setups in the addressed task of generating innovative samples and we show the effect of regularizing GAN on different scores. We conclude with some useful applications for these IANs, like multi-domain manifold traversing.

Establishment and evaluation of operation function model for cascade hydropower station

OpenAIRE

Chang-ming Ji; Ting Zhou; Hai-tao Huang

2010-01-01

Toward solving the actual operation problems of cascade hydropower stations under hydrologic uncertainty, this paper presents the process of extraction of statistical characteristics from long-term optimal cascade operation, and proposes a monthly operation function algorithm for the actual operation of cascade hydropower stations through the identification, processing, and screening of available information during long-term optimal operation. Applying the operation function to the cascade hy...

Displacement cascades and defect annealing in tungsten, Part II: Object kinetic Monte Carlo simulation of tungsten cascade aging

Energy Technology Data Exchange (ETDEWEB)

Nandipati, Giridhar, E-mail: giridhar.nandipati@pnnl.gov [Pacific Northwest National Laboratory, Richland, WA (United States); Setyawan, Wahyu; Heinisch, Howard L. [Pacific Northwest National Laboratory, Richland, WA (United States); Roche, Kenneth J. [Pacific Northwest National Laboratory, Richland, WA (United States); Department of Physics, University of Washington, Seattle, WA 98195 (United States); Kurtz, Richard J. [Pacific Northwest National Laboratory, Richland, WA (United States); Wirth, Brian D. [University of Tennessee, Knoxville, TN (United States)

2015-07-15

The results of object kinetic Monte Carlo (OKMC) simulations of the annealing of primary cascade damage in bulk tungsten using a comprehensive database of cascades obtained from molecular dynamics (Setyawan et al.) are described as a function of primary knock-on atom (PKA) energy at temperatures of 300, 1025 and 2050 K. An increase in SIA clustering coupled with a decrease in vacancy clustering with increasing temperature, in addition to the disparate mobilities of SIAs versus vacancies, causes an interesting effect of temperature on cascade annealing. The annealing efficiency (the ratio of the number of defects after and before annealing) exhibits an inverse U-shape curve as a function of temperature. The capabilities of the newly developed OKMC code KSOME (kinetic simulations of microstructure evolution) used to carry out these simulations are described.

Displacement cascades and defect annealing in tungsten, Part II: Object kinetic Monte Carlo Simulation of Tungsten Cascade Aging

Energy Technology Data Exchange (ETDEWEB)

Nandipati, Giridhar; Setyawan, Wahyu; Heinisch, Howard L.; Roche, Kenneth J.; Kurtz, Richard J.; Wirth, Brian D.

2015-07-01

The results of object kinetic Monte Carlo (OKMC) simulations of the annealing of primary cascade damage in bulk tungsten using a comprehensive database of cascades obtained from molecular dynamics (Setyawan et al.) are described as a function of primary knock-on atom (PKA) energy at temperatures of 300, 1025 and 2050 K. An increase in SIA clustering coupled with a decrease in vacancy clustering with increasing temperature, in addition to the disparate mobilities of SIAs versus vacancies, causes an interesting effect of temperature on cascade annealing. The annealing efficiency (the ratio of the number of defects after and before annealing) exhibits an inverse U-shape curve as a function of temperature. The capabilities of the newly developed OKMC code KSOME (kinetic simulations of microstructure evolution) used to carry out these simulations are described.

Skin Manifestations of Endocrine Diseases.

Science.gov (United States)

Demirkesen, Cuyan

2015-01-01

Endocrine diseases may result in changes in cutaneous function and morphology, which cause various skin manifestations, including nonspecific or pathognomonic signs. Some of these manifestations are already known dermatologic diseases with only increased frequency in this patient group. As a result the skin may the play role of a screen displaying endocrine disorders, either due to hormone excess or deficiency. Awareness of the skin manifestations may permit prompt and adequate approach to the patients, and therefore facilitate the early diagnosis of the endocrine disease and even be life saving. Some of these manifestations may be recognized clinically, but sometimes they need to be confirmed histopathologically. In this article, many endocrine diseases and their associated skin lesions will be reviewed briefly.

Neurological Manifestations In Inflammatory Bowel Disease

Directory of Open Access Journals (Sweden)

youssef HNACH

2015-06-01

Full Text Available IntroductionThe purpose of this retrospective study was to report neurological manifestations noted in patients who were monitored for inflammatory bowel disease, in order to document the pathophysiological, clinical, progressive, and therapeutic characteristics of this entity.Material and methodsWe conducted a retrospective study on patients monitored -in the gastroenterology service in Ibn Sina Hospital in Rabat, Morocco- for inflammatory bowel disease from 1992 till 2013 and who developed neurological manifestations during its course. Patients with iatrogenic complications were excluded, as well as patients with cerebrovascular risk factors.ResultsThere were 6 patients, 4 of whom have developed peripheral manifestations. Electromyography enabled the diagnosis to be made and the outcome was favorable with disappearance of clinical manifestations and normalization of the electromyography.The other 2 patients, monitored for Crohn’s disease, developed ischemic stroke. Cerebral computed tomography angiography provided positive and topographic diagnosis. Two patients were admitted to specialized facilities.ConclusionNeurological manifestations in inflammatory bowel disease are rarely reported.  Peripheral neuropathies and stroke remain the most common manifestations. The mechanisms of these manifestations are not clearly defined yet. Currently, we hypothesize the interaction of immune mediators.

A thermal modelling of displacement cascades in uranium dioxide

Energy Technology Data Exchange (ETDEWEB)

Martin, G., E-mail: guillaume.martin@cea.fr [CEA – DEN/DEC/SESC/LLCC, Bât. 352, 13108 Saint-Paul-Lez-Durance Cedex (France); Garcia, P.; Sabathier, C. [CEA – DEN/DEC/SESC/LLCC, Bât. 352, 13108 Saint-Paul-Lez-Durance Cedex (France); Devynck, F.; Krack, M. [Laboratory for Reactor Physics and Systems Behaviour, Paul Scherrer Institute, CH-5232 Villigen PSI (Switzerland); Maillard, S. [CEA – DEN/DEC/SESC/LLCC, Bât. 352, 13108 Saint-Paul-Lez-Durance Cedex (France)

2014-05-01

The space and time dependent temperature distribution was studied in uranium dioxide during displacement cascades simulated by classical molecular dynamics (MD). The energy for each simulated radiation event ranged between 0.2 keV and 20 keV in cells at initial temperatures of 700 K or 1400 K. Spheres into which atomic velocities were rescaled (thermal spikes) have also been simulated by MD to simulate the thermal excitation induced by displacement cascades. Equipartition of energy was shown to occur in displacement cascades, half of the kinetic energy of the primary knock-on atom being converted after a few tenths of picoseconds into potential energy. The kinetic and potential parts of the system energy are however subjected to little variations during dedicated thermal spike simulations. This is probably due to the velocity rescaling process, which impacts a large number of atoms in this case and would drive the system away from a dynamical equilibrium. This result makes questionable MD simulations of thermal spikes carried out up to now (early 2014). The thermal history of cascades was compared to the heat equation solution of a punctual thermal excitation in UO{sub 2}. The maximum volume brought to a temperature above the melting temperature during the simulated cascade events is well reproduced by this simple model. This volume eventually constitutes a relevant estimate of the volume affected by a displacement cascade in UO{sub 2}. This definition of the cascade volume could also make sense in other materials, like iron.

Hyperactivity and memory/learning deficits evoked by developmental exposure to nicotine and/or ethanol are mitigated by cAMP and cGMP signaling cascades activation.

Science.gov (United States)

Abreu-Villaça, Yael; Carvalho-Graça, Anna C; Skinner, Gabriela; Lotufo, Bruna M; Duarte-Pinheiro, Vitor H S; Ribeiro-Carvalho, Anderson; Manhães, Alex C; Filgueiras, Claudio C

2018-04-10

Pregnant smoking women are frequently episodic drinkers. Here, we investigated whether ethanol exposure restricted to the brain growth spurt period when combined with chronic developmental exposure to nicotine aggravates memory/learning deficits and hyperactivity, and associated cAMP and cGMP signaling disruption. To further investigate the role of these signaling cascades, we verified whether vinpocetine (a phosphodiesterase inhibitor) ameliorates the neurochemical and behavioral outcomes. Swiss mice had free access to nicotine (NIC, 50 μg/ml) or water to drink during gestation and until the 8th postnatal day (PN8). Ethanol (ETOH, 5 g/kg, i.p.) or saline were injected in the pups every other day from PN2 to PN8. At PN30, animals either received vinpocetine (20 mg/kg, i.p.) or vehicle before being tested in the step-down passive avoidance or open field. Memory/learning was impaired in NIC, ETOH and NIC + ETOH mice, and vinpocetine mitigated ETOH- and NIC + ETOH-induced deficits. Locomotor hyperactivity identified in ETOH and NIC + ETOH mice was ameliorated by vinpocetine. While cyclic nucleotides levels in cerebral cortex and hippocampus were reduced by NIC, ETOH and NIC + ETOH, this outcome was more consistent in the latter group. As observed for behavior, vinpocetine normalized NIC + ETOH nucleotides levels. pCREB levels were also increased in response to vinpocetine, with stronger effects in the NIC + ETOH group. Exposure to both drugs of abuse worsens behavioral and neurochemical disruption. These findings and the amelioration of deleterious effects by vinpocetine support the idea that cAMP and cGMP signaling contribute to nicotine- and ethanol-induced hyperactivity and memory/learning deficits. Copyright © 2018 Elsevier B.V. All rights reserved.

Phenotypic and evolutionary implications of modulating the ERK-MAPK cascade using the dentition as a model

Science.gov (United States)

Marangoni, Pauline; Charles, Cyril; Tafforeau, Paul; Laugel-Haushalter, Virginie; Joo, Adriane; Bloch-Zupan, Agnès; Klein, Ophir D.; Viriot, Laurent

2015-06-01

The question of phenotypic convergence across a signalling pathway has important implications for both developmental and evolutionary biology. The ERK-MAPK cascade is known to play a central role in dental development, but the relative roles of its components remain unknown. Here we investigate the diversity of dental phenotypes in Spry2-/-, Spry4-/-, and Rsk2-/Y mice, including the incidence of extra teeth, which were lost in the mouse lineage 45 million years ago (Ma). In addition, Sprouty-specific anomalies mimic a phenotype that is absent in extant mice but present in mouse ancestors prior to 9 Ma. Although the mutant lines studied display convergent phenotypes, each gene has a specific role in tooth number determination and crown patterning. The similarities found between teeth in fossils and mutants highlight the pivotal role of the ERK-MAPK cascade during the evolution of the dentition in rodents.

Criticality safety study of shutdown diffusion cascade coolers

International Nuclear Information System (INIS)

Paschal, L.S.; Basoglu, B.; Bentley, C.L.; Dunn, M.E.

1996-01-01

Gaseous diffusion plants use cascade coolers in the production of highly enriched uranium (HEU) to remove heat from the enriched stream of UF 6 . The cascade coolers operate like shell and tube heat exchangers with the UF 6 on the shell side and Freon on the tube side. Recirculating cooling water (RCW) in condensers is used to cool the Freon. A criticality safety analysis was previously performed for cascade coolers during normal operation. The purpose of this paper is to evaluate several different hypothetical accidents regarding RCW ingress into the cooler to determine whether criticality safety concerns exist

Identification of a novel Gnao-mediated alternate olfactory signaling pathway in murine OSNs

Directory of Open Access Journals (Sweden)

Paul eScholz

2016-03-01

Full Text Available It is generally agreed that in olfactory sensory neurons (OSNs, the binding of odorant molecules to their specific olfactory receptor (OR triggers a cAMP-dependent signaling cascade, activating cyclic-nucleotide gated (CNG channels. However, considerable controversy dating back more than 20 years has surrounded the question of whether alternate signaling plays a role in mammalian olfactory transduction. In this study, we demonstrate a specific alternate signaling pathway in Olfr73-expressing OSNs. Methylisoeugenol (MIEG and at least one other known weak Olfr73 agonist (Raspberry Ketone trigger a signaling cascade independent from the canonical pathway, leading to the depolarization of the cell. Interestingly, this pathway is mediated by Gnao activation, leading to Cl- efflux; however, the activation of adenylyl cyclase III (ACIII, the recruitment of Ca2+ from extra-or intracellular stores, and phosphatidylinositol 3-kinase-dependent signaling (PI signaling are not involved. Furthermore, we demonstrated that our newly identified pathway coexists with the canonical olfactory cAMP pathway in the same OSN and can be triggered by the same OR in a ligand-selective manner. We suggest that this pathway might reflect a mechanism for odor recognition predominantly used in early developmental stages before olfactory cAMP signaling is fully developed. Taken together, our findings support the existence of at least one odor-induced alternate signal transduction pathway in native OSNs mediated by Olfr73 in a ligand-selective manner.

A phase-equalized digital multirate filter for 50 Hz signal processing

Energy Technology Data Exchange (ETDEWEB)

Vainio, O. [Tampere University of Technology, Signal Processing Laboratory, Tampere (Finland)

1997-12-31

A new multistage digital filter is proposed for 50 Hz line frequency signal processing in zero-crossing detectors and synchronous power systems. The purpose of the filter is to extract the fundamental sinusoidal signal from noise and impulsive disturbances so that the output is accurately in phase with the primary input signal. This is accomplished with a cascade of a median filter, a linear-phase FIR filter, and a phase corrector. A 10 kHz output timing resolution is achieved by up-sampling with a customized interpolation filter. (orig.) 15 refs.

Mechanical control of cyclic AMP signalling and gene transcription through integrins

Science.gov (United States)

Meyer, C. J.; Alenghat, F. J.; Rim, P.; Fong, J. H.; Fabry, B.; Ingber, D. E.

2000-01-01

This study was carried out to discriminate between two alternative hypotheses as to how cells sense mechanical forces and transduce them into changes in gene transcription. Do cells sense mechanical signals through generalized membrane distortion or through specific transmembrane receptors, such as integrins? Here we show that mechanical stresses applied to the cell surface alter the cyclic AMP signalling cascade and downstream gene transcription by modulating local release of signals generated by activated integrin receptors in a G-protein-dependent manner, whereas distortion of integrins in the absence of receptor occupancy has no effect.

Seeking heavy Higgs bosons through cascade decays

Science.gov (United States)

Coleppa, Baradhwaj; Fuks, Benjamin; Poulose, P.; Sahoo, Shibananda

2018-04-01

We investigate the LHC discovery prospects for a heavy Higgs boson decaying into the standard model Higgs boson and additional weak bosons. We consider a generic model-independent new physics configuration where this decay proceeds via a cascade involving other intermediate scalar bosons and focus on an LHC final-state signature comprised either of four b -jets and two charged leptons or of four charged leptons and two b -jets. We design two analyses of the corresponding signals, and demonstrate that a 5 σ discovery at the 14 TeV LHC is possible for various combinations of the parent and daughter Higgs-boson masses. We moreover find that the standard model backgrounds can be sufficiently rejected to guarantee the reconstruction of the parent Higgs boson mass. We apply our analyses to the Type-II two-Higgs-doublet model and identify the regions of the parameter space to which the LHC is sensitive.

The flow analysis of supercavitating cascade by linear theory

Energy Technology Data Exchange (ETDEWEB)

Park, E.T. [Sung Kyun Kwan Univ., Seoul (Korea, Republic of); Hwang, Y. [Seoul National Univ., Seoul (Korea, Republic of)

1996-06-01

In order to reduce damages due to cavitation effects and to improve performance of fluid machinery, supercavitation around the cascade and the hydraulic characteristics of supercavitating cascade must be analyzed accurately. And the study on the effects of cavitation on fluid machinery and analysis on the performances of supercavitating hydrofoil through various elements governing flow field are critically important. In this study comparison of experiment results with the computed results of linear theory using singularity method was obtainable. Specially singularity points like sources and vortexes on hydrofoil and freestreamline were distributed to analyze two dimensional flow field of supercavitating cascade, and governing equations of flow field were derived and hydraulic characteristics of cascade were calculated by numerical analysis of the governing equations. 7 refs., 6 figs.

Thoracic manifestation of tuberculosis; Thorakale Manifestation der Tuberkulose

Energy Technology Data Exchange (ETDEWEB)

Kienzl-Palma, D.; Prosch, H. [Medizinische Universitaet Wien, Abteilung fuer Allgemeine Radiologie und Kinderradiologie, Universitaetsklinik fuer Radiologie und Nuklearmedizin, Wien (Austria)

2016-10-15

Tuberculosis (TB) is a granulomatous disease caused by Mycobacterium tuberculosis and transmission is via an airborne route by droplet infection. In the majority of cases patients have thoracic TB, which most frequently presents with hilar lymphadenopathy and pulmonary manifestation. Due to the rise in incidence of TB in central Europe to be expected over the coming years, it is essential to be acquainted with the radiological manifestations of pulmonary TB, particularly to be able to discriminate active from inactive TB. Due to the use of molecular techniques entailing DNA fingerprinting, the traditional classification of TB in primary and postprimary TB is being challenged. These genetic studies have revealed that variations in the clinical and radiographic appearance of TB are mainly affected by the immune status of the patients. Due to the low prevalence of TB in central Europe and the wide variation of radiological presentations, the diagnosis and therapy of TB is often delayed. In this article, the radiographic manifestations of thoracic TB are summarized and discussed. Together with the medical history and bacteriological tests, chest X-ray imaging and computed tomography (CT) play a major role not only in the detection of TB but also in the follow-up during and after therapy. Chest X-radiographs should be the primary diagnostic method in patients with suspected TB in screening as well as for diagnosis and therapy monitoring. The use of CT is more sensitive than chest radiographs and is frequently performed after chest radiographs to obtain detailed information about subtle parenchymal changes or lymph node manifestation. When active TB is suspected CT should be performed. Tree in bud, lobular consolidations, centrilobular nodules, cavities and ground-glass opacification are typical changes in active TB. (orig.) [German] Tuberkulose (Tbc) ist eine durch Troepfchen uebertragene granulomatoese Infektionserkrankung, die durch das Mycobacterium tuberculosis

Computer simulation of high energy displacement cascades

International Nuclear Information System (INIS)

Heinisch, H.L.

1990-01-01

A methodology developed for modeling many aspects of high energy displacement cascades with molecular level computer simulations is reviewed. The initial damage state is modeled in the binary collision approximation (using the MARLOWE computer code), and the subsequent disposition of the defects within a cascade is modeled with a Monte Carlo annealing simulation (the ALSOME code). There are few adjustable parameters, and none are set to physically unreasonable values. The basic configurations of the simulated high energy cascades in copper, i.e., the number, size and shape of damage regions, compare well with observations, as do the measured numbers of residual defects and the fractions of freely migrating defects. The success of these simulations is somewhat remarkable, given the relatively simple models of defects and their interactions that are employed. The reason for this success is that the behavior of the defects is very strongly influenced by their initial spatial distributions, which the binary collision approximation adequately models. The MARLOWE/ALSOME system, with input from molecular dynamics and experiments, provides a framework for investigating the influence of high energy cascades on microstructure evolution. (author)

Protein Kinase Signalling in the Moss Physcomitrella patens

DEFF Research Database (Denmark)

Azevedo de Silva, Raquel

Adaptation to environmental cues trigger a plethora of intracellular pathways capable of maintaining homeostasis. Receptors in the plasma membrane and in the cytosol recognize extracellular or intracellular signals initiating defense against pathogens or stress-adaptation. MAPK cascade are one...... of the pathways involved in stress signalling, phosphorylating several downstream substrates in order to produce appropriate responses. We report here that P. patens has a receptor-like kinase CERK1 responsible for chitin perception which can rescue Atcerk1 mutant. Activation of PpCERK1 triggers the activation...

Influence of non-binary effects on intranuclear cascade method

International Nuclear Information System (INIS)

Gomes, E.H.C.

1985-01-01

The importance of non binary process effects in the intranuclear cascade method is analysed. It is shown that, in the higher density steps, the non binary collisions lead to baryon density distribution and rapidity differents from the one obtained using the usual intranuclear cascade method (limited to purely binary collisions). The validity of the applications of binary intranuclear cascade method to the simulation of the thermal equilibrium, nuclear transparency and particle production, is discussed. (M.C.K.) [pt

In vivo RNAi screen reveals neddylation genes as novel regulators of Hedgehog signaling.

Directory of Open Access Journals (Sweden)

Juan Du

Full Text Available Hedgehog (Hh signaling is highly conserved in all metazoan animals and plays critical roles in many developmental processes. Dysregulation of the Hh signaling cascade has been implicated in many diseases, including cancer. Although key components of the Hh pathway have been identified, significant gaps remain in our understanding of the regulation of individual Hh signaling molecules. Here, we report the identification of novel regulators of the Hh pathway, obtained from an in vivo RNA interference (RNAi screen in Drosophila. By selectively targeting critical genes functioning in post-translational modification systems utilizing ubiquitin (Ub and Ub-like proteins, we identify two novel genes (dUba3 and dUbc12 that negatively regulate Hh signaling activity. We provide in vivo and in vitro evidence illustrating that dUba3 and dUbc12 are essential components of the neddylation pathway; they function in an enzyme cascade to conjugate the ubiquitin-like NEDD8 modifier to Cullin proteins. Neddylation activates the Cullin-containing ubiquitin ligase complex, which in turn promotes the degradation of Cubitus interruptus (Ci, the downstream transcription factor of the Hh pathway. Our study reveals a conserved molecular mechanism of the neddylation pathway in Drosophila and sheds light on the complex post-translational regulations in Hh signaling.

New preemptive scheduling for OBS networks considering cascaded wavelength conversion

Science.gov (United States)

Gao, Xingbo; Bassiouni, Mostafa A.; Li, Guifang

2009-05-01

In this paper we introduce a new preemptive scheduling technique for next generation optical burst-switched networks considering the impact of cascaded wavelength conversions. It has been shown that when optical bursts are transmitted all optically from source to destination, each wavelength conversion performed along the lightpath may cause certain signal-to-noise deterioration. If the distortion of the signal quality becomes significant enough, the receiver would not be able to recover the original data. Accordingly, subject to this practical impediment, we improve a recently proposed fair channel scheduling algorithm to deal with the fairness problem and aim at burst loss reduction simultaneously in optical burst switching. In our scheme, the dynamic priority associated with each burst is based on a constraint threshold and the number of already conducted wavelength conversions among other factors for this burst. When contention occurs, a new arriving superior burst may preempt another scheduled one according to their priorities. Extensive simulation results have shown that the proposed scheme further improves fairness and achieves burst loss reduction as well.

Frequency modulation spectroscopy with a THz quantum-cascade laser.

Science.gov (United States)

Eichholz, R; Richter, H; Wienold, M; Schrottke, L; Hey, R; Grahn, H T; Hübers, H-W

2013-12-30

We report on a terahertz spectrometer for high-resolution molecular spectroscopy based on a quantum-cascade laser. High-frequency modulation (up to 50 MHz) of the laser driving current produces a simultaneous modulation of the frequency and amplitude of the laser output. The modulation generates sidebands, which are symmetrically positioned with respect to the laser carrier frequency. The molecular transition is probed by scanning the sidebands across it. In this way, the absorption and the dispersion caused by the molecular transition are measured. The signals are modeled by taking into account the simultaneous modulation of the frequency and amplitude of the laser emission. This allows for the determination of the strength of the frequency as well as amplitude modulation of the laser and of molecular parameters such as pressure broadening.

A virtual component method in numerical computation of cascades for isotope separation

International Nuclear Information System (INIS)

Zeng Shi; Cheng Lu

2014-01-01

The analysis, optimization, design and operation of cascades for isotope separation involve computations of cascades. In analytical analysis of cascades, using virtual components is a very useful analysis method. For complicated cases of cascades, numerical analysis has to be employed. However, bound up to the conventional idea that the concentration of a virtual component should be vanishingly small, virtual component is not yet applied to numerical computations. Here a method of introducing the method of using virtual components to numerical computations is elucidated, and its application to a few types of cascades is explained and tested by means of numerical experiments. The results show that the concentration of a virtual component is not restrained at all by the 'vanishingly small' idea. For the same requirements on cascades, the cascades obtained do not depend on the concentrations of virtual components. (authors)

A cascade model of information processing and encoding for retinal prosthesis.

Science.gov (United States)

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.

Frequency comb generation by a continuous-wave-pumped optical parametric oscillator based on cascading quadratic nonlinearities.

Science.gov (United States)

Ulvila, Ville; Phillips, C R; Halonen, Lauri; Vainio, Markku

2013-11-01

We report optical frequency comb generation by a continuous-wave pumped optical parametric oscillator (OPO) without any active modulation. The OPO is configured as singly resonant with an additional nonlinear crystal (periodically poled MgO:LiNbO3) placed inside the OPO for phase mismatched second harmonic generation (SHG) of the resonating signal beam. The phase mismatched SHG causes cascading χ(2) nonlinearities, which can substantially increase the effective χ(3) nonlinearity in MgO:LiNbO3, leading to spectral broadening of the OPO signal beam via self-phase modulation. The OPO generates a stable 4 THz wide (-30 dB) frequency comb centered at 1.56 μm.

Neurologic Manifestations of Enterovirus 71 Infection in Korea.

Science.gov (United States)

Lee, Kyung Yeon; Lee, Myoung Sook; Kim, Dong Bin

2016-04-01

Enterovirus 71 frequently involves the central nervous system and may present with a variety of neurologic manifestations. Here, we aimed to describe the clinical features, magnetic resonance imaging (MRI) findings, and cerebrospinal fluid (CSF) profiles of patients presenting with neurologic complications of enterovirus 71 infection. We retrospectively reviewed the records of 31 pediatric patients hospitalized with acute neurologic manifestations accompanied by confirmed enterovirus 71 infection at Ulsan University Hospital between 2010 and 2014. The patients' mean age was 2.9 ± 5.5 years (range, 18 days to 12 years), and 80.6% of patients were less than 4 years old. Based on their clinical features, the patients were classified into 4 clinical groups: brainstem encephalitis (n = 21), meningitis (n = 7), encephalitis (n = 2), and acute flaccid paralysis (n = 1). The common neurologic symptoms included myoclonus (58.1%), lethargy (54.8%), irritability (54.8%), vomiting (48.4%), ataxia (38.7%), and tremor (35.5%). Twenty-five patients underwent an MRI scan; of these, 14 (56.0%) revealed the characteristic increased T2 signal intensity in the posterior region of the brainstem and bilateral cerebellar dentate nuclei. Twenty-six of 30 patients (86.7%) showed CSF pleocytosis. Thirty patients (96.8%) recovered completely without any neurologic deficits; one patient (3.2%) died due to pulmonary hemorrhage and shock. In the present study, brainstem encephalitis was the most common neurologic manifestation of enterovirus 71 infection. The characteristic clinical symptoms such as myoclonus, ataxia, and tremor in conjunction with CSF pleocytosis and brainstem lesions on MR images are pathognomonic for diagnosis of neurologic involvement by enterovirus 71 infection.

Abdominal ultrasonographic manifestation of Henoch-schonlein purpura

International Nuclear Information System (INIS)

Eun, Hyo Won; Kim, Mi Sung; Kang, Beoung Chul; Lee, Sun Wha

1998-01-01

The purpose of this study was to describe the ultrasonographic features and assess the diagnostic value of sonography in the evaluation of children with Henoch-Schonlein purpura. Between October 1993, and Febuary 1998, 67 children with Henoch-Schonlein purpura underwent abdominal ultrasonography, which in 13 was used for follow up. Bowel wall thickness and location, pattern of color Doppler signal in the thickened bowel wall, the size and location of enlarged mesenteric lymph node and the presence of ascites were evaluated. In 42 cases(63%), sonographic findings were positive, and indicated mesenteric lymphadenopathy(n=3D21), small bowel wall thickening(n=3D20), and ascites(n=3D17). Thickened bowels were demonstrated at the ileum in 11 cases, the jejunum in five, the duodenum in one, and combined wall thickening at the duodenum and jejunum in two;thickening of the duodenum and ileum was seen in one case. Thickness varied from 3 to 10 mm(mean:6.5 mm). On follow-up sonography, regression of bowel wall thickening was observed earlier than that of mesenteric lymphadenopathy or ascites, and correlated well with improved abdominal symptoms. Abdominal ultrasonographic manifestations of Henoch-Schonlein purpura were bowel wall thickening, mesentric lymphadenopathy and ascites. Sonography was a simple and useful method for the evaluation of gastrointestinal manifestation of Henoch-Schonlein purpura.=20

Presynaptic Dopamine D2 Receptors Modulate [3H]GABA Release at StriatoPallidal Terminals via Activation of PLC → IP3 → Calcineurin and Inhibition of AC → cAMP → PKA Signaling Cascades.

Science.gov (United States)

Jijón-Lorenzo, Rafael; Caballero-Florán, Isaac Hiram; Recillas-Morales, Sergio; Cortés, Hernán; Avalos-Fuentes, José Arturo; Paz-Bermúdez, Francisco Javier; Erlij, David; Florán, Benjamín

2018-02-21

Striatal dopamine D2 receptors activate the PLC → IP3 → Calcineurin-signaling pathway to modulate the neural excitability of En+ Medium-sized Spiny GABAergic neurons (MSN) through the regulation of L-type Ca 2+ channels. Presynaptic dopaminergic D2 receptors modulate GABA release at striatopallidal terminals through L-type Ca 2+ channels as well, but their signaling pathway is still undetermined. Since D2 receptors are Gi/o-coupled and negatively modulate adenylyl cyclase (AC), we investigated whether presynaptic D2 receptors modulate GABA release through the same signaling cascade that controls excitability in the striatum or by the inhibition of AC and decreased PKA activity. Activation of D2 receptors stimulated formation of [ 3 H]IP 1 and decreased Forskolin-stimulated [ 3 H]cAMP accumulation in synaptosomes from rat Globus Pallidus. D2 receptor activation with Quinpirole in the presence of L 745,870 decreased, in a dose-dependent manner, K + -induced [ 3 H]GABA release in pallidal slices. The effect was prevented by the pharmacological blockade of Gi/o βγ subunit effects with Gallein, PLC with U 73122, IP3 receptor activation with 4-APB, Calcineurin with FK506. In addition, when release was stimulated with Forskolin to activate AC, D2 receptors also decreased K + -induced [ 3 H]GABA release, an effect occluded with the effect of the blockade of PKA with H89 or stimulation of release with the cAMP analog 8-Br-cAMP. These data indicate that D2 receptors modulate [ 3 H]GABA release at striatopallidal terminals by activating the PLC → IP3 → Calcineurin-signaling cascade, the same one that modulates excitability in soma. Additionally, D2 receptors inhibit release when AC is active. Both mechanisms appear to converge to regulate the activity of presynaptic L-type Ca 2+ channels. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Gastrointestinal Manifestations of Cystic Fibrosis

Science.gov (United States)

2016-01-01

Cystic fibrosis has historically been considered a pulmonary disease, but with the increasing life expectancy of these patients, gastrointestinal manifestations are becoming more important. Furthermore, nutritional status is closely linked to pulmonary function and, thus, overall mortality. This article discusses gastrointestinal manifestations (which involve nutritional, pancreatic, hepatobiliary, and, in particular, gastrointestinal tract issues) of cystic fibrosis as well as management of the disease. In addition, the article discusses studies that have been critical to our understanding of gastrointestinal manifestations of cystic fibrosis. PMID:27330503

Cascade ICF power reactor

International Nuclear Information System (INIS)

Hogan, W.J.; Pitts, J.H.

1986-01-01

The double-cone-shaped Cascade reaction chamber rotates at 50 rpm to keep a blanket of ceramic granules in place against the wall as they slide from the poles to the exit slots at the equator. The 1 m-thick blanket consists of layers of carbon, beryllium oxide, and lithium aluminate granules about 1 mm in diameter. The x rays and debris are stopped in the carbon granules; the neutrons are multiplied and moderated in the BeO and breed tritium in the LiAlO 2 . The chamber wall is made up of SiO tiles held in compression by a network of composite SiC/Al tendons. Cascade operates at a 5 Hz pulse rate with 300 MJ in each pulse. The temperature in the blanket reaches 1600 K on the inner surface and 1350 K at the outer edge. The granules are automatically thrown into three separate vacuum heat exchangers where they give up their energy to high pressure helium. The helium is used in a Brayton cycle to obtain a thermal-to-electric conversion efficiency of 55%. Studies have been done on neutron activation, debris recovery, vaporization and recondensation of blanket material, tritium control and recovery, fire safety, and cost. These studies indicate that Cascade appears to be a promising ICF reactor candidate from all standpoints. At the 1000 MWe size, electricity could be made for about the same cost as in a future fission reactor

Phase locking of a 3.4 THz third-order distributed feedback quantum cascade laser using a room-temperature superlattice harmonic mixer

NARCIS (Netherlands)

Hayton, D. J.; Khudchencko, A.; Pavelyev, D. G.; Hovenier, J. N.; Baryshev, A.; Gao, J. R.; Kao, T. Y.; Hu, Q.; Reno, J. L.; Vaks, V.

2013-01-01

We report on the phase locking of a 3.4 THz third-order distributed feedback quantum cascade laser (QCL) using a room temperature GaAs/AlAs superlattice diode as both a frequency multiplier and an internal harmonic mixer. A signal-to-noise level of 60 dB is observed in the intermediate frequency

Phase locking of a 3.4 THz third-order distributed feedback quantum cascade laser using a room-temperature superlattice harmonic mixer

NARCIS (Netherlands)

Hayton, D.J.; Khudchenko, A.; Pavelyev, D.G.; Hovenier, J.N.; Baryshev, A.; Gao, J.R.; Kao, T.Y.; Hu, Q.; Reno, J.L.; Vaks, V.

2013-01-01

We report on the phase locking of a 3.4 THz third-order distributed feedback quantum cascade laser (QCL) using a room temperature GaAs/AlAs superlattice diode as both a frequency multiplier and an internal harmonic mixer. A signal-to-noise level of 60?dB is observed in the intermediate frequency

Optical feedback in dfb quantum cascade laser for mid-infrared cavity ring-down spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Terabayashi, Ryohei, E-mail: terabayashi.ryouhei@h.mbox.nagoya-u.ac.jp; Sonnenschein, Volker, E-mail: volker@nagoya-u.jp; Tomita, Hideki, E-mail: tomita@nagoya-u.jp; Hayashi, Noriyoshi, E-mail: hayashi.noriyoshi@h.mbox.nagoya-u.ac.jp; Kato, Shusuke, E-mail: katou.shuusuke@f.mbox.nagoya-u.ac.jp; Jin, Lei, E-mail: kin@nuee.nagoya-u.ac.jp; Yamanaka, Masahito, E-mail: yamanaka@nuee.nagoya-u.ac.jp; Nishizawa, Norihiko, E-mail: nishizawa@nuee.nagoya-u.ac.jp [Nagoya University, Department of Quantum Engineering, Graduate School of Engineering (Japan); Sato, Atsushi, E-mail: atsushi.sato@sekisui.com; Nozawa, Kohei, E-mail: kohei.nozawa@sekisui.com; Hashizume, Kenta, E-mail: kenta.hashizume@sekisui.com; Oh-hara, Toshinari, E-mail: toshinari.ohara@sekisui.com [Sekisui Medical Co., Ltd., Drug Development Solutions Center (Japan); Iguchi, Tetsuo, E-mail: t-iguchi@nucl.nagoya-u.ac.jp [Nagoya University, Department of Quantum Engineering, Graduate School of Engineering (Japan)

2017-11-15

A simple external optical feedback system has been applied to a distributed feedback quantum cascade laser (DFB QCL) for cavity ring-down spectroscopy (CRDS) and a clear effect of feedback was observed. A long external feedback path length of up to 4m can decrease the QCL linewidth to around 50kHz, which is of the order of the transmission linewidth of our high finesse ring-down cavity. The power spectral density of the transmission signal from high finesse cavity reveals that the noise at frequencies above 20kHz is reduced dramatically.

A cascading failure model for analyzing railway accident causation

Science.gov (United States)

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.

Increase of transient lower esophageal sphincter relaxation associated with cascade stomach

Science.gov (United States)

Kawada, Akiyo; Kusano, Motoyasu; Hosaka, Hiroko; Kuribayashi, Shiko; Shimoyama, Yasuyuki; Kawamura, Osamu; Akiyama, Junichi; Yamada, Masanobu; Akuzawa, Masako

2017-01-01

We previously reported that cascade stomach was associated with reflux symptoms and esophagitis. Delayed gastric emptying has been believed to initiate transient lower esophageal sphincter relaxation (TLESR). We hypothesized that cascade stomach may be associated with frequent TLESR with delayed gastric emptying. Eleven subjects with cascade stomach and 11 subjects without cascade stomach were enrolled. Postprandial gastroesophageal manometry and gastric emptying using a continuous 13C breath system were measured simultaneously after a liquid test meal. TLESR events were counted in early period (0–60 min), late period (60–120 min), and total monitoring period. Three parameters of gastric emptying were calculated: the half emptying time, lag time, and gastric emptying coefficient. The median frequency of TLESR events in the cascade stomach and non-cascade stomach groups was 6.0 (median), 4.6 (interquartile range) vs 5.0, 3.0 in the early period, 5.0, 3.2 vs 3.0, 1.8 in the late period, and 10.0, 6.2 vs 8.0, 5.0 in the total monitoring period. TLESR events were significantly more frequent in the cascade stomach group during the late and total monitoring periods. In contrast, gastric emptying parameters showed no significant differences between the two groups. We concluded that TLESR events were significantly more frequent in persons with cascade stomach without delayed gastric emptying. PMID:28584403

Mechanism of protein tyrosine phosphatase 1B-mediated inhibition of leptin signalling

DEFF Research Database (Denmark)

Lund, I K; Hansen, J A; Andersen, H S

2005-01-01

Upon leptin binding, the leptin receptor is activated, leading to stimulation of the JAK/STAT signal transduction cascade. The transient character of the tyrosine phosphorylation of JAK2 and STAT3 suggests the involvement of protein tyrosine phosphatases (PTPs) as negative regulators...

Clinical manifestations of scrub typhus.

Science.gov (United States)

Rajapakse, Senaka; Weeratunga, Praveen; Sivayoganathan, Sriharan; Fernando, Sumadhya Deepika

2017-02-01

The mite-borne rickettsial zoonosis scrub typhus is widely prevalent in parts of Southeast and Far East Asia, and northern Australia. The disease is an acute febrile illness, associated with rash and often an eschar, which responds dramatically to treatment with antibiotics. In some cases it results in a serious illness leading to multiple organ involvement and death. The disease manifestations are thought to result from a systemic vasculitis, caused by both direct effects of the organisms as well as an exaggerated immune response, although little is understood about its pathogenesis. A wide spectrum of clinical manifestations, affecting nearly every organ system, have been described with scrub typhus. Some of these manifestations are serious and life threatening. In this systematic review, we summarise the typical and atypical manifestations of scrub typhus reported in the literature. Awareness of these unusual manifestations will hopefully guide clinicians towards diagnosing the condition early, and initiating early appropriate antibiotics and other supportive measures. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Doppler-free two-photon spectroscopy of Yb atoms and efficient generation of a cascade of two photons at 611.3 nm and 555.8 nm

International Nuclear Information System (INIS)

Song, Minsoo; Yoon, Duseong; Yoon, Taihyun

2011-01-01

We performed high-resolution Doppler-free two-photon spectroscopy of Yb atoms in an effusive atomic beam and generated a cascade of two photons at 611.3 nm (idler) and 555.8 nm (signal) with a narrow bandwidth of 37 MHz. Efficient population transfer from the ground state (6s 2 1 S 0 ) to the upper state (6s7s 1 S 0 ), where direct transition at 291.1 nm is dipole forbidden, was achieved through a resonant two-photon excitation enhanced by the electromagnetically-induced transparency mediated by the intermediate state (6s6p 1 P 1 ). From the upper state, a cascade of two photons in sequence was emitted via the spin triplet state (6s 2 3 P 1 ). Numerical calculations of the density matrix equations taking into account the residual Doppler effect and strong driving fields explain quantitatively the experimental results for the dependences of the idler and the signal beam intensities on the various parameters of the driving fields. We report on the generation of a cascade of two photons with fluxes at the level of a few times 10 6 photons/s detected at a solid angle of 0.01 sr.

Doppler-free two-photon spectroscopy of Yb atoms and efficient generation of a cascade of two photons at 611.3 nm and 555.8 nm

Energy Technology Data Exchange (ETDEWEB)

Song, Minsoo; Yoon, Duseong; Yoon, Taihyun [Korea University, Seoul (Korea, Republic of)

2011-10-15

We performed high-resolution Doppler-free two-photon spectroscopy of Yb atoms in an effusive atomic beam and generated a cascade of two photons at 611.3 nm (idler) and 555.8 nm (signal) with a narrow bandwidth of 37 MHz. Efficient population transfer from the ground state (6s{sup 2} {sup 1}S{sub 0}) to the upper state (6s7s {sup 1}S{sub 0}), where direct transition at 291.1 nm is dipole forbidden, was achieved through a resonant two-photon excitation enhanced by the electromagnetically-induced transparency mediated by the intermediate state (6s6p {sup 1}P{sub 1}). From the upper state, a cascade of two photons in sequence was emitted via the spin triplet state (6s{sup 2} {sup 3}P{sub 1}). Numerical calculations of the density matrix equations taking into account the residual Doppler effect and strong driving fields explain quantitatively the experimental results for the dependences of the idler and the signal beam intensities on the various parameters of the driving fields. We report on the generation of a cascade of two photons with fluxes at the level of a few times 10{sup 6} photons/s detected at a solid angle of 0.01 sr.

On peculiarities of the cascade γ decay of heavy nuclei

International Nuclear Information System (INIS)

Boneva, S.T.; Khitrov, V.A.; Popov, Yu.P.; Sukhovoj, A.M.; Vasil'eva, E.V.; Yazvitskij, Yu.S.

1987-01-01

Comparison of measured and calculated by statistical theory sums of two-quanta cascade intensities in compound-nuclei 163 ≤ A ≤ 183 points to the dependence of cascade intensity on the structure of initial and intermediate levels. The dependence of two-quanta cascade intensity sum on reduced neutron widths of compound states of even-even nuclei-targets of rare earth regions is detected. In 175 Yb and 179 Hf nuclei a considerable increase in the intensity of two-quanta cascades at the energy of their intermediate level in the range of the calculated position of one-quasiparticle states of the Saxon-Woods deformed potential is observed

Designing the Cascade inertial confinement fusion reactor

International Nuclear Information System (INIS)

Pitts, J.H.

1987-01-01

The primary goal in designing inertial confinement fusion (ICF) reactors is to produce electrical power as inexpensively as possible, with minimum activation and without compromising safety. This paper discusses a method for designing the Cascade rotating ceramic-granule-blanket reactor (Pitts, 1985) and its associated power plant (Pitts and Maya, 1985). Although focus is on the cascade reactor, the design method and issues presented are applicable to most other ICF reactors

Hadronic cascade processes

International Nuclear Information System (INIS)

Ilgenfritz, E.M.; Kripfganz, J.; Moehring, H.J.

1977-01-01

The analytical treatment of hadronic decay cascades within the framework of the statistical bootstrap model is demonstrated on the basis of a simple variant. Selected problems for a more comprehensive formulation of the model such as angular momentum conservation, quantum statistical effects, and the immediate applicability to particle production processes at high energies are discussed in detail

INCAS: an analytical model to describe displacement cascades

Energy Technology Data Exchange (ETDEWEB)

Jumel, Stephanie E-mail: stephanie.jumel@edf.fr; Claude Van-Duysen, Jean E-mail: jean-claude.van-duysen@edf.fr

2004-07-01

REVE (REactor for Virtual Experiments) is an international project aimed at developing tools to simulate neutron irradiation effects in Light Water Reactor materials (Fe, Ni or Zr-based alloys). One of the important steps of the project is to characterise the displacement cascades induced by neutrons. Accordingly, the Department of Material Studies of Electricite de France developed an analytical model based on the binary collision approximation. This model, called INCAS (INtegration of CAScades), was devised to be applied on pure elements; however, it can also be used on diluted alloys (reactor pressure vessel steels, etc.) or alloys composed of atoms with close atomic numbers (stainless steels, etc.). INCAS describes displacement cascades by taking into account the nuclear collisions and electronic interactions undergone by the moving atoms. In particular, it enables to determine the mean number of sub-cascades induced by a PKA (depending on its energy) as well as the mean energy dissipated in each of them. The experimental validation of INCAS requires a large effort and could not be carried out in the framework of the study. However, it was verified that INCAS results are in conformity with those obtained from other approaches. As a first application, INCAS was applied to determine the sub-cascade spectrum induced in iron by the neutron spectrum corresponding to the central channel of the High Flux Irradiation Reactor of Oak Ridge National Laboratory.

INCAS: an analytical model to describe displacement cascades

Science.gov (United States)

Jumel, Stéphanie; Claude Van-Duysen, Jean

2004-07-01

REVE (REactor for Virtual Experiments) is an international project aimed at developing tools to simulate neutron irradiation effects in Light Water Reactor materials (Fe, Ni or Zr-based alloys). One of the important steps of the project is to characterise the displacement cascades induced by neutrons. Accordingly, the Department of Material Studies of Electricité de France developed an analytical model based on the binary collision approximation. This model, called INCAS (INtegration of CAScades), was devised to be applied on pure elements; however, it can also be used on diluted alloys (reactor pressure vessel steels, etc.) or alloys composed of atoms with close atomic numbers (stainless steels, etc.). INCAS describes displacement cascades by taking into account the nuclear collisions and electronic interactions undergone by the moving atoms. In particular, it enables to determine the mean number of sub-cascades induced by a PKA (depending on its energy) as well as the mean energy dissipated in each of them. The experimental validation of INCAS requires a large effort and could not be carried out in the framework of the study. However, it was verified that INCAS results are in conformity with those obtained from other approaches. As a first application, INCAS was applied to determine the sub-cascade spectrum induced in iron by the neutron spectrum corresponding to the central channel of the High Flux Irradiation Reactor of Oak Ridge National Laboratory.

INCAS: an analytical model to describe displacement cascades

International Nuclear Information System (INIS)

Jumel, Stephanie; Claude Van-Duysen, Jean

2004-01-01

REVE (REactor for Virtual Experiments) is an international project aimed at developing tools to simulate neutron irradiation effects in Light Water Reactor materials (Fe, Ni or Zr-based alloys). One of the important steps of the project is to characterise the displacement cascades induced by neutrons. Accordingly, the Department of Material Studies of Electricite de France developed an analytical model based on the binary collision approximation. This model, called INCAS (INtegration of CAScades), was devised to be applied on pure elements; however, it can also be used on diluted alloys (reactor pressure vessel steels, etc.) or alloys composed of atoms with close atomic numbers (stainless steels, etc.). INCAS describes displacement cascades by taking into account the nuclear collisions and electronic interactions undergone by the moving atoms. In particular, it enables to determine the mean number of sub-cascades induced by a PKA (depending on its energy) as well as the mean energy dissipated in each of them. The experimental validation of INCAS requires a large effort and could not be carried out in the framework of the study. However, it was verified that INCAS results are in conformity with those obtained from other approaches. As a first application, INCAS was applied to determine the sub-cascade spectrum induced in iron by the neutron spectrum corresponding to the central channel of the High Flux Irradiation Reactor of Oak Ridge National Laboratory

Gradients in Catostomid assemblages along a reservoir cascade

Science.gov (United States)

Miranda, Leandro E.; Keretz, Kevin R.; Gilliland, Chelsea R.

2017-01-01

Serial impoundment of major rivers leads to alterations of natural flow dynamics and disrupts longitudinal connectivity. Catostomid fishes (suckers, family Catostomidae) are typically found in riverine or backwater habitats yet are able to persist in impounded river systems. To the detriment of conservation, there is limited information about distribution of catostomid fishes in impounded rivers. We examined the longitudinal distribution of catostomid fishes over 23 reservoirs of the Tennessee River reservoir cascade, encompassing approximately 1600 km. Our goal was to develop a basin-scale perspective to guide conservation efforts. Catostomid species composition and assemblage structure changed longitudinally along the reservoir cascade. Catostomid species biodiversity was greatest in reservoirs lower in the cascade. Assemblage composition shifted from dominance by spotted sucker Minytrema melanops and buffalos Ictiobus spp. in the lower reservoirs to carpsuckers Carpiodes spp. midway through the cascade and redhorses Moxostoma spp. in the upper reservoirs. Most species did not extend the length of the cascade, and some species were rare, found in low numbers and in few reservoirs. The observed gradients in catostomid assemblages suggest the need for basin-scale conservation measures focusing on three broad areas: (1) conservation and management of the up-lake riverine reaches of the lower reservoirs, (2) maintenance of the access to quality habitat in tributaries to the upper reservoirs and (3) reintroductions into currently unoccupied habitat within species' historic distributions

Mechanisms for type-II vitellogenesis-inhibiting hormone suppression of vitellogenin transcription in shrimp hepatopancreas: Crosstalk of GC/cGMP pathway with different MAPK-dependent cascades.

Science.gov (United States)

Chen, Ting; Ren, Chunhua; Jiang, Xiao; Zhang, Lvping; Li, Hongmei; Huang, Wen; Hu, Chaoqun

2018-01-01

Vitellogenesis is the process of yolk formation via accumulating vitellin (Vn) with nutrients in the oocytes. Expression of vitellogenin (Vg), the precursor of Vn, is one of the indicators for the start of vitellogenesis. In Pacific white shrimp (Litopenaeus vannamei), the type-II vitellogenesis-inhibiting hormone (VIH-2) effectively suppresses hepatopancreatic Vg mRNA expression. In this study, we demonstrate the increasing transcript levels of hepatopancreatic Vg during L. vannamei ovarian development, suggesting that the hepatopancreas-derived Vg/Vn may also contribute to vitellogenesis in this species. Using a combination of in vivo injections and in vitro primary cell cultures, we provide evidences that the inhibition of VIH-2 on hepatopancreatic Vg gene expression is mediated through a functional coupling of the GC/cGMP pathway with different MAPK-dependent cascades in female shrimp. In VIH-2 signaling, the NO-independent GC/cGMP/PKG cascades were upstream of the MAPKs. Activations of the MAPK signal by VIH-2 include the phosphorylation of JNK and the mRNA/protein expression of P38MAPK. Additionally, the cAMP/PKA pathway is another positive intracellular signal for hepatopancreatic Vg mRNA expression but is independent of its VIH-2 regulation. Our findings establish a model for the signal transduction mechanism of Vg regulation by VIH and shed light on the biological functions and signaling of the CHH family in crustaceans.

Broadband external cavity quantum cascade laser based sensor for gasoline detection

Science.gov (United States)

Ding, Junya; He, Tianbo; Zhou, Sheng; Li, Jinsong

2018-02-01

A new type of tunable diode spectroscopy sensor based on an external cavity quantum cascade laser (ECQCL) and a quartz crystal tuning fork (QCTF) were used for quantitative analysis of volatile organic compounds. In this work, the sensor system had been tested on different gasoline sample analysis. For signal processing, the self-established interpolation algorithm and multiple linear regression algorithm model were used for quantitative analysis of major volatile organic compounds in gasoline samples. The results were very consistent with that of the standard spectra taken from the Pacific Northwest National Laboratory (PNNL) database. In future, The ECQCL sensor will be used for trace explosive, chemical warfare agent, and toxic industrial chemical detection and spectroscopic analysis, etc.

Cascade reactor: granule fabrication processes

International Nuclear Information System (INIS)

Erlandson, O.D.; Winkler, E.O.; Maya, I.; Pitts, J.H.

1985-01-01

A key feature of Cascade is the granular blanket. Of the many blanket material options open to Cascade, fabrication of Li 2 O granules was felt to offer the greatest challenge. The authors explored available methods for initial Li 2 O granule fabrication. They identified three cost-effective processes for fabricating Li 2 O granules: the VSM drop-melt furnace process, which is based on melting and spheroidizing irregularly shaped Li 2 O feed granules; the LiOH process, which spheroidizes liquefied LiOH and uses GA Technologies' sphere-forming procedures; and the Li 2 CO 3 sol-gel process, used for making spherical fuel particles for the high-temperature gas-cooled reactor (HTGR). Each process is described below

Common mode frequency instability in internally phase-locked terahertz quantum cascade lasers.

Science.gov (United States)

Wanke, M C; Grine, A D; Fuller, C T; Nordquist, C D; Cich, M J; Reno, J L; Lee, Mark

2011-11-21

Feedback from a diode mixer integrated into a 2.8 THz quantum cascade laser (QCL) was used to phase lock the difference frequencies (DFs) among the Fabry-Perot (F-P) longitudinal modes of a QCL. Approximately 40% of the DF power was phase locked, consistent with feedback loop bandwidth of 10 kHz and phase noise bandwidth ~0.5 MHz. While the locked DF signal has ≤ 1 Hz linewidth and negligible drift over ~30 min, mixing measurements between two QCLs and between a QCL and molecular gas laser show that the common mode frequency stability is no better than a free-running QCL. © 2011 Optical Society of America

[Lyme disease--clinical manifestations and treatment].

Science.gov (United States)

Stock, Ingo

2016-05-01

Lyme disease (Lyme borreliosis) is a systemic infectious disease that can present in a variety of clinical manifestations. The disease is caused by a group of spirochaetes--Borrelia burgdorferi sensu lato or Lyme borrelia--that are transmitted to humans by the bite of Ixodes ticks. Lyme disease is the most common arthropode-borne infectious disease in many European countries including Germany. Early localized infection is typically manifested by an erythema migrans skin lesion, in rarer cases as a borrelial lymphocytoma. The most common early disseminated manifestation is (early) neuroborreliosis. In adults, neuroborreliosis appears typically as meningoradiculoneuritis. Neuroborreliosis in children, however, is typically manifested by meningitis. In addition, multiple erythema migrans lesions and Lyme carditis occur relatively frequently. The most common manifestation oflate Lyme disease is Lyme arthritis. Early manifestations (and usually also late manifestations) of Lyme disease can be treated successfully by application of suitable antibacterial agents. For the treatment of Lyme disease, doxycycline, certain penicillins such as amoxicillin and some cephalosporins (ceftriaxone, cefotaxime, cefuroxime axetil) are recommended in current guidelines. A major challenge is the treatment of chronic, non-specific disorders, i. e., posttreatment Lyme disease syndrome and "chronic Lyme disease". Prevention of Lyme disease is mainly accomplished by protecting against tick bites. Prophylactic administration of doxycycline after tick bites is generally not recommended in Germany. There is no vaccine available for human beings.

Blind equalization for dual-polarization two-subcarrier coherent QPSK-OFDM signals.

Science.gov (United States)

Li, Fan; Zhang, Junwen; Yu, Jianjun; Li, Xinying

2014-01-15

Dual-polarization two-subcarrier coherent optical orthogonal frequency division multiplexing (CO-OFDM) transmission and reception is successfully demonstrated with blind equalization. A two-subcarrier quadrature phase shift keyed OFDM (QPSK-OFDM) signal can be equalized as a 9-ary quadrature amplitude modulation signal in the time domain with the cascaded multimodulus algorithm equalization method. The nonlinear effect resistance and transmission distance can be enhanced compared with the traditional CO-OFDM transmission system based on frequency equalization with training sequence.

Intestinal Insulin Signaling Encodes Two Different Molecular Mechanisms for the Shortened Longevity Induced by Graphene Oxide in Caenorhabditis elegans

Science.gov (United States)

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.

A simple method for potential flow simulation of cascades

Indian Academy of Sciences (India)

vortex panel method to simulate potential flow in cascades is presented. The cascade ... The fluid loading on the blades, such as the normal force and pitching moment, may ... of such discrete infinite array singularities along the blade surface.

Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations (II): thrombocytopenia and skin manifestations.

Science.gov (United States)

Cervera, R; Tektonidou, M G; Espinosa, G; Cabral, A R; González, E B; Erkan, D; Vadya, S; Adrogué, H E; Solomon, M; Zandman-Goddard, G; Shoenfeld, Y

2011-02-01

The objectives of the 'Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations' were to assess the clinical utility of the international consensus statement on classification criteria and treatment guidelines for the catastrophic APS, to identify and grade the studies that analyze the relationship between the antiphospholipid antibodies and the non-criteria APS manifestations, and to present the current evidence regarding the accuracy of these non-criteria APS manifestations for the detection of patients with APS. This article summarizes the studies analyzed on thrombocytopenia and skin manifestations, and presents the recommendations elaborated by the Task Force after this analysis.

The insulin/IGF signaling regulators cytohesin/GRP-1 and PIP5K/PPK-1 modulate susceptibility to excitotoxicity in C. elegans.

Directory of Open Access Journals (Sweden)

Nazila Tehrani

Full Text Available During ischemic stroke, malfunction of excitatory amino acid transporters and reduced synaptic clearance causes accumulation of Glutamate (Glu and excessive stimulation of postsynaptic neurons, which can lead to their degeneration by excitotoxicity. The balance between cell death-promoting (neurotoxic and survival-promoting (neuroprotective signaling cascades determines the fate of neurons exposed to the excitotoxic insult. The evolutionary conserved Insulin/IGF Signaling (IIS cascade can participate in this balance, as it controls cell stress resistance in nematodes and mammals. Blocking the IIS cascade allows the transcription factor FoxO3/DAF-16 to accumulate in the nucleus and activate a transcriptional program that protects cells from a range of insults. We study the effect of IIS cascade on neurodegeneration in a C. elegans model of excitotoxicity, where a mutation in a central Glu transporter (glt-3 in a sensitizing background causes Glu-Receptor -dependent neuronal necrosis. We expand our studies on the role of the IIS cascade in determining susceptibility to excitotoxic necrosis by either blocking IIS at the level of PI3K/AGE-1 or stimulating it by removing the inhibitory effect of ZFP-1 on the expression of PDK-1. We further show that the components of the Cytohesin/GRP-1, Arf, and PIP5K/PPK-1 complex, known to regulate PIP2 production and the IIS cascade, modulate nematode excitotoxicity: mutations that are expected to reduce the complex's ability to produce PIP2 and inhibit the IIS cascade protect from excitotoxicity, while overstimulation of PIP2 production enhances neurodegeneration. Our observations therefore affirm the importance of the IIS cascade in determining the susceptibility to necrotic neurodegeneration in nematode excitotoxicity, and demonstrate the ability of Cytohesin/GRP-1, Arf, and PIP5K/PPK-1 complex to modulate neuroprotection.

DECREASING OF WATER TROPHY IN CASCADE SYSTEMS, ON EXAMPLE OF THE SOŁA RIVER DAM CASCADE (SOUTHERN POLAND

Directory of Open Access Journals (Sweden)

Ewa Jachniak

2014-10-01

Full Text Available In this thesis the subject of water self-purification in cascade systems of water reservoirs was engaged. The results of hydrobiological research of three dam reservoirs (Tresna, Porąbka and Czaniec, creating the Soła river dam cascade were presented. The trophic status of these reservoirs was defined on the grounds of the concentration of chlorophyll a, biomass of phytoplankton and occurrence of indicating species of planktonic algae. The results of research indicated on decreasing of water trophy in the layout from the highest into the lowest reservoir of the cascade. The average concentrations of chlorophyll a amounted appropriately 19,99 μg·dm-3, 8,74 μg·dm-3 and 4,29 μg·dm-3, instead the average biomass of phytoplankton amounted appropriately 4,1 mg·dm-3, 3,4 mg·dm-3 and 0,1 mg·dm-3. The observed species of algae confirmed occurrence of differences between reservoirs. In Tresna reservoir more species of phytoplankton indicating for eutrophy were thrived, instead in Porąbka and Czaniec reservoirs the species occurring in oligomesotrophic water thrived. Water self-purification in the Soła river dam cascade expressed decreasing of their fertility is important for water management of the region, because the Czaniec reservoir fulfill a function of water-supply reservoir.

Cascades for hydrogen isotope separation using metal hydrides

International Nuclear Information System (INIS)

Hill, F.B.; Grzetic, V.

1982-01-01

Designs are presented for continuous countercurrent hydrogen isotope separation cascades based on the use of metal hydrides. The cascades are made up of pressure swing adsorption (PSA) or temperature swing adsorption (TSA) stages. The designs were evolved from consideration of previously conducted studies of the separation performance of four types of PSA and TSA processes

Cascades for hydrogen isotope separation using metal hydrides

Energy Technology Data Exchange (ETDEWEB)

Hill, F B; Grzetic, V [Brookhaven National Lab., Upton, NY (USA)

1983-02-01

Designs are presented for continuous countercurrent hydrogen isotope separation cascades based on the use of metal hydrides. The cascades are made up of pressure swing adsorption (PSA) or temperature swing adsorption (TSA) stages. The designs were evolved from consideration of previously conducted studies of the separation performance of four types of PSA and TSA processes.

A cascaded online uninterruptible power supply using reduced semiconductor

DEFF Research Database (Denmark)

Zhang, Lei; Loh, Poh Chiang; Gao, Feng

2011-01-01

A cascaded online uninterruptible power supply (UPS) is proposed here that uses 25% lesser semiconductor, as compared to its traditional H-bridge cascaded precedence. Unlike other component-saving configurations where compromises are unavoidable, almost no performance degradations and constraints...

Leptophobic Boson Signals with Leptons, Jets and Missing Energy

Energy Technology Data Exchange (ETDEWEB)

Dobrescu, Bogdan A.

2015-06-14

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 and jets, or with a Higgs boson, a lepton, a W and missing energy.

Intermittent Flow Regimes in a Transonic Fan Airfoil Cascade

Directory of Open Access Journals (Sweden)

J. Lepicovsky

2004-01-01

velocity.To date, this flow behavior has only been observed in a linear transonic cascade. Further research is necessary to confirm this phenomenon occurs in actual transonic fans and is not the by-product of an endwall restricted linear cascade.

YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway

International Nuclear Information System (INIS)

Lin, Yi-Ting; Ding, Jing-Ya; Li, Ming-Yang; Yeh, Tien-Shun; Wang, Tsu-Wei; Yu, Jenn-Yah

2012-01-01

Tight regulation of cell numbers by controlling cell proliferation and apoptosis is important during development. Recently, the Hippo pathway has been shown to regulate tissue growth and organ size in Drosophila. In mammalian cells, it also affects cell proliferation and differentiation in various tissues, including the nervous system. Interplay of several signaling cascades, such as Notch, Wnt, and Sonic Hedgehog (Shh) pathways, control cell proliferation during neuronal differentiation. However, it remains unclear whether the Hippo pathway coordinates with other signaling cascades in regulating neuronal differentiation. Here, we used P19 cells, a mouse embryonic carcinoma cell line, as a model to study roles of YAP, a core component of the Hippo pathway, in neuronal differentiation. P19 cells can be induced to differentiate into neurons by expressing a neural bHLH transcription factor gene Ascl1. Our results showed that YAP promoted cell proliferation and inhibited neuronal differentiation. Expression of Yap activated Shh but not Wnt or Notch signaling activity during neuronal differentiation. Furthermore, expression of Yap increased the expression of Patched homolog 1 (Ptch1), a downstream target of the Shh signaling. Knockdown of Gli2, a transcription factor of the Shh pathway, promoted neuronal differentiation even when Yap was over-expressed. We further demonstrated that over-expression of Yap inhibited neuronal differentiation in primary mouse cortical progenitors and Gli2 knockdown rescued the differentiation defect in Yap over-expressing cells. In conclusion, our study reveals that Shh signaling acts downstream of YAP in regulating neuronal differentiation. -- Highlights: ► YAP promotes cell proliferation and inhibits neuronal differentiation in P19 cells. ► YAP promotes Sonic hedgehog signaling activity during neuronal differentiation. ► Knockdown of Gli2 rescues the Yap-overexpression phenotype in P19 cells. ► Knockdown of Gli2 rescues the Yap

YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway

Energy Technology Data Exchange (ETDEWEB)

Lin, Yi-Ting; Ding, Jing-Ya [Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan (China); Li, Ming-Yang [Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan (China); Yeh, Tien-Shun [Department of Anatomy and Cell Biology, National Yang-Ming University, Taipei 112, Taiwan (China); Wang, Tsu-Wei [Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan (China); Yu, Jenn-Yah [Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan (China); Brain Research Center, National Yang-Ming University, Taipei 112, Taiwan (China)

2012-09-10

Tight regulation of cell numbers by controlling cell proliferation and apoptosis is important during development. Recently, the Hippo pathway has been shown to regulate tissue growth and organ size in Drosophila. In mammalian cells, it also affects cell proliferation and differentiation in various tissues, including the nervous system. Interplay of several signaling cascades, such as Notch, Wnt, and Sonic Hedgehog (Shh) pathways, control cell proliferation during neuronal differentiation. However, it remains unclear whether the Hippo pathway coordinates with other signaling cascades in regulating neuronal differentiation. Here, we used P19 cells, a mouse embryonic carcinoma cell line, as a model to study roles of YAP, a core component of the Hippo pathway, in neuronal differentiation. P19 cells can be induced to differentiate into neurons by expressing a neural bHLH transcription factor gene Ascl1. Our results showed that YAP promoted cell proliferation and inhibited neuronal differentiation. Expression of Yap activated Shh but not Wnt or Notch signaling activity during neuronal differentiation. Furthermore, expression of Yap increased the expression of Patched homolog 1 (Ptch1), a downstream target of the Shh signaling. Knockdown of Gli2, a transcription factor of the Shh pathway, promoted neuronal differentiation even when Yap was over-expressed. We further demonstrated that over-expression of Yap inhibited neuronal differentiation in primary mouse cortical progenitors and Gli2 knockdown rescued the differentiation defect in Yap over-expressing cells. In conclusion, our study reveals that Shh signaling acts downstream of YAP in regulating neuronal differentiation. -- Highlights: Black-Right-Pointing-Pointer YAP promotes cell proliferation and inhibits neuronal differentiation in P19 cells. Black-Right-Pointing-Pointer YAP promotes Sonic hedgehog signaling activity during neuronal differentiation. Black-Right-Pointing-Pointer Knockdown of Gli2 rescues the Yap

Collision cascades in HTSC [high temperature superconductors] as possible pinning centres

International Nuclear Information System (INIS)

Kirsanov, V.V.; Musin, N.N.; Roskin, D.G.; Shamarina, E.I.

1993-01-01

Computer simulation was used to study the development of collision cascades in monocrystals of YBa 2 Cu 3 O 7 , YBa 2 Cu 3 O 6.5 and YBa 2 Cu 3 O 6 which were produced by primary knock-on atoms (PKAs) during fast particle irradiation. Oxygen deficit was found to have an effect on the development of cascades in these phases, with a lowering of oxygen deficit decreasing cascade sizes. The type of PKA was observed to influence the geometry of a cascade. When heavy PKAs form a cascade, the oxygen sublattice is practically undisturbed, with very little disorder; while with oxygen ions as the PKA, the main displacements fall within the oxygen subsystem. In addition, the angular dependences of the displacement threshold energy for yttrium and barium ions are given. (Author)

Interband cascade light emitting devices based on type-II quantum wells

International Nuclear Information System (INIS)

Yang, Rui Q.; Lin, C.H.; Murry, S.J.

1997-01-01

The authors discuss physical processes in the newly developed type-II interband cascade light emitting devices, and review their recent progress in the demonstration of the first type-II interband cascade lasers and the observation of interband cascade electroluminescence up to room temperature in a broad mid-infrared wavelength region (extended to 9 μm)

β-Adrenergic receptor signaling and modulation of long-term potentiation in the mammalian hippocampus

OpenAIRE

O'Dell, Thomas J.; Connor, Steven A.; Guglietta, Ryan; Nguyen, Peter V.

2015-01-01

Encoding new information in the brain requires changes in synaptic strength. Neuromodulatory transmitters can facilitate synaptic plasticity by modifying the actions and expression of specific signaling cascades, transmitter receptors and their associated signaling complexes, genes, and effector proteins. One critical neuromodulator in the mammalian brain is norepinephrine (NE), which regulates multiple brain functions such as attention, perception, arousal, sleep, learning, and memory. The m...

Roles of Zinc Signaling in the Immune System.

Science.gov (United States)

Hojyo, Shintaro; Fukada, Toshiyuki

2016-01-01

Zinc (Zn) is an essential micronutrient for basic cell activities such as cell growth, differentiation, and survival. Zn deficiency depresses both innate and adaptive immune responses. However, the precise physiological mechanisms of the Zn-mediated regulation of the immune system have been largely unclear. Zn homeostasis is tightly controlled by the coordinated activity of Zn transporters and metallothioneins, which regulate the transport, distribution, and storage of Zn. There is growing evidence that Zn behaves like a signaling molecule, facilitating the transduction of a variety of signaling cascades in response to extracellular stimuli. In this review, we highlight the emerging functional roles of Zn and Zn transporters in immunity, focusing on how crosstalk between Zn and immune-related signaling guides the normal development and function of immune cells.

Cascade Processes in Muonic Hydrogen Atoms

International Nuclear Information System (INIS)

Faifman, M. P.; Men'Shikov, L. I.

2001-01-01

The QCMC scheme created earlier for cascade calculations in heavy hadronic atoms of hydrogen isotopes has been modified and applied to the study of cascade processes in the μp muonic hydrogen atoms. The distribution of μp atoms over kinetic energies has been obtained and the yields of K-series X-rays per one stopped muon have been calculated.Comparison with experimental data indicated directly that for muonic and pionic atoms new types of non-radiative transitions are essential, while they are negligible for heavy (kaonic, antiprotonic, etc.) atoms. These processes have been considered and their probabilities have been estimated.

Signaling aggression.

Science.gov (United States)

van Staaden, Moira J; Searcy, William A; Hanlon, Roger T

2011-01-01

From psychological and sociological standpoints, aggression is regarded as intentional behavior aimed at inflicting pain and manifested by hostility and attacking behaviors. In contrast, biologists define aggression as behavior associated with attack or escalation toward attack, omitting any stipulation about intentions and goals. Certain animal signals are strongly associated with escalation toward attack and have the same function as physical attack in intimidating opponents and winning contests, and ethologists therefore consider them an integral part of aggressive behavior. Aggressive signals have been molded by evolution to make them ever more effective in mediating interactions between the contestants. Early theoretical analyses of aggressive signaling suggested that signals could never be honest about fighting ability or aggressive intentions because weak individuals would exaggerate such signals whenever they were effective in influencing the behavior of opponents. More recent game theory models, however, demonstrate that given the right costs and constraints, aggressive signals are both reliable about strength and intentions and effective in influencing contest outcomes. Here, we review the role of signaling in lieu of physical violence, considering threat displays from an ethological perspective as an adaptive outcome of evolutionary selection pressures. Fighting prowess is conveyed by performance signals whose production is constrained by physical ability and thus limited to just some individuals, whereas aggressive intent is encoded in strategic signals that all signalers are able to produce. We illustrate recent advances in the study of aggressive signaling with case studies of charismatic taxa that employ a range of sensory modalities, viz. visual and chemical signaling in cephalopod behavior, and indicators of aggressive intent in the territorial calls of songbirds. Copyright © 2011 Elsevier Inc. All rights reserved.

Numerical routine for magnetic heat pump cascading

DEFF Research Database (Denmark)

Filonenko, Konstantin; Lei, Tian; Engelbrecht, Kurt

Heat pumps use low-temperature heat absorbed from the energy source to create temperature gradient (TG) across the energy sink. Magnetic heat pumps (MHP) can perform this function through operating active magnetic regeneration (AMR) cycle. For building heating, TGs of up to a few K might...... and 3 K. Changing the number of MHPs, we optimized input parameters to achieve maximum heating powers. We have found that both maximum heating power and COP decrease together with number of heat pumps, but the TGs and the temperature span can be largely increased. References [1] M. Tahavori et al., “A...... be necessary, which is hardly achievable with a single MHP and such techniques as cascading are required. Series and parallel cascading increase the AMR span and heating power, respectively, but do not change TG. Therefore, the intermediate type of cascading was proposed with individual MHPs separately...

Ca 2+ signaling by plant Arabidopsis thaliana Pep peptides depends on AtPepR1, a receptor with guanylyl cyclase activity, and cGMP-activated Ca 2+ channels

KAUST Repository

Qia, Zhi

2010-11-18

A family of peptide signaling molecules (AtPeps) and their plasma membrane receptor AtPepR1 are known to act in pathogendefense signaling cascades in plants. Little is currently known about the molecular mechanisms that link these signaling peptides and their receptor, a leucine-rich repeat receptor-like kinase, to downstream pathogen-defense responses. We identify some cellular activities of these molecules that provide the context for a model for their action in signaling cascades. AtPeps activate plasma membrane inwardly conducting Ca 2+ permeable channels in mesophyll cells, resulting in cytosolic Ca 2+ elevation. This activity is dependent on their receptor as well as a cyclic nucleotide-gated channel (CNGC2). We also show that the leucine-rich repeat receptor- like kinase receptor AtPepR1 has guanylyl cyclase activity, generating cGMP from GTP, and that cGMP can activate CNGC2- dependent cytosolic Ca 2+ elevation. AtPep-dependent expression of pathogen-defense genes (PDF1.2, MPK3, and WRKY33) is mediated by the Ca 2+ signaling pathway associated with AtPep peptides and their receptor. The work presented here indicates that extracellular AtPeps, which can act as danger-associated molecular patterns, signal by interaction with their receptor, AtPepR1, a plasma membrane protein that can generate cGMP. Downstream from AtPep and AtPepR1 in a signaling cascade, the cGMP-activated channel CNGC2 is involved in AtPep- and AtPepR1-dependent inward Ca 2+ conductance and resulting cytosolic Ca 2+ elevation. The signaling cascade initiated by AtPeps leads to expression of pathogen- defense genes in a Ca 2+-dependent manner.

Andrographolide, a Novel NF-κB Inhibitor, Induces Vascular Smooth Muscle Cell Apoptosis via a Ceramide-p47phox-ROS Signaling Cascade

Directory of Open Access Journals (Sweden)

Yu-Ying Chen

2013-01-01

Full Text Available Atherosclerosis is linked with the development of many cardiovascular complications. Abnormal proliferation of vascular smooth muscle cells (VSMCs plays a crucial role in the development of atherosclerosis. Accordingly, the apoptosis of VSMCs, which occurs in the progression of vascular proliferation, may provide a beneficial strategy for managing cardiovascular diseases. Andrographolide, a novel nuclear factor-κB inhibitor, is the most active and critical constituent isolated from the leaves of Andrographis paniculata. Recent studies have indicated that andrographolide is a potential therapeutic agent for treating cancer through the induction of apoptosis. In this study, the apoptosis-inducing activity and mechanisms in andrographolide-treated rat VSMCs were characterized. Andrographolide significantly induced reactive oxygen species (ROS formation, p53 activation, Bax, and active caspase-3 expression, and these phenomena were suppressed by pretreating the cells with N-acetyl-L-cysteine, a ROS scavenger, or diphenylene iodonium, a nicotinamide adenine dinucleotide phosphate (NADPH oxidase (Nox inhibitor. Furthermore, p47phox, a Nox subunit protein, was phosphorylated in andrographolide-treated rat VSMCs. However, pretreatment with 3-O-methyl-sphingomyelin, a neutral sphingomyelinase inhibitor, significantly inhibited andrographolide-induced p47phox phosphorylation as well as Bax and active caspase-3 expression. Our results collectively demonstrate that andrographolide-reduced cell viability can be attributed to apoptosis in VSMCs, and this apoptosis-inducing activity was associated with the ceramide-p47phox-ROS signaling cascade.

Cascade in muonic and pionic atoms with Z = 1

International Nuclear Information System (INIS)

Markushin, V.E.

1999-01-01

Recent theoretical and experimental studies of the exotic atoms with Z = 1 are reviewed. An interplay between the atomic internal and external degrees of freedom is essential for a good description of the atomic cascade. The perspective of ab initio cascade calculations is outlined

Climate Change and Baleen Whale Trophic Cascades in Greenland

Science.gov (United States)

2009-09-30

DISTRIBUTION STATEMENT A: Approved for public release; distribution is unlimited. Climate Change and Baleen Whale Trophic Cascades in Greenland...SUBTITLE Climate Change And Baleen Whale Trophic Cascades In Greenland 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

Inactivation of EGFR/AKT signaling enhances TSA-induced ovarian cancer cell differentiation.

Science.gov (United States)

Shao, Genbao; Lai, Wensheng; Wan, Xiaolei; Xue, Jing; Wei, Ye; Jin, Jie; Zhang, Liuping; Lin, Qiong; Shao, Qixiang; Zou, Shengqiang

2017-05-01

Ovarian tumor is one of the most lethal gynecologic cancers, but differentiation therapy for this cancer is poorly characterized. Here, we show that thrichostatin A (TSA), the well known inhibitor of histone deacetylases (HDACs), can induce cell differentiation in HO8910 ovarian cancer cells. TSA-induced cell differentiation is characterized by typical morphological change, increased expression of the differentiation marker FOXA2, decreased expression of the pluripotency markers SOX2 and OCT4, suppressing cell proliferation, and cell cycle arrest in the G1 phase. TSA also induces an elevated expression of cell cycle inhibitory protein p21Cip1 along with a decrease in cell cycle regulatory protein cyclin D1. Significantly, blockage of epidermal growth factor receptor (EGFR) signaling pathway with specific inhibitors of this signaling cascade promotes the TSA-induced differentiation of HO8910 cells. These results imply that the EGFR cascade inhibitors in combination with TSA may represent a promising differentiation therapy strategy for ovarian cancer.

A multivariate approach to heavy flavour tagging with cascade training

International Nuclear Information System (INIS)

Bastos, J; Liu, Y

2007-01-01

This paper compares the performance of artificial neural networks and boosted decision trees, with and without cascade training, for tagging b-jets in a collider experiment. It is shown, using a Monte Carlo simulation of WH→lνq q-bar events, that for a b-tagging efficiency of 50%, the light jet rejection power given by boosted decision trees without cascade training is about 55% higher than that given by artificial neural networks. The cascade training technique can improve the performance of boosted decision trees and artificial neural networks at this b-tagging efficiency level by about 35% and 80% respectively. We conclude that the cascade trained boosted decision trees method is the most promising technique for tagging heavy flavours at collider experiments

Study on computer-aided simulation procedure for multicomponent separating cascade

International Nuclear Information System (INIS)

Kinoshita, Masahiro

1982-11-01

The present report reviews the author's study on the computer-aided simulation procedure for a multicomponent separating cascade. As a conclusion, two very powerful simulation procedures have been developed for cascades composed of separating elements whose separation factors are very large. They are applicable in cases where interstage flow rates are input variables for the calculation and stage separation factors are given either as constants or as functions of compositions of the up and down streams. As an application of the new procedure, a computer-aided simulation study has been performed for hydrogen isotope separating cascades by porous membrane method. A cascade system configuration is developed and pertinent design specifications are determined in an example case of the feed conditions and separation requirements. (author)

Annealing simulation of cascade damage using MARLOWE-DAIQUIRI codes

International Nuclear Information System (INIS)

Muroga, Takeo

1984-01-01

The localization effect of the defects generated by the cascade damage on the properties of solids was studied by using a computer code. The code is based on the two-body collision approximation method and the Monte Carlo method. The MARLOWE and DAIQUIRI codes were partly improved to fit the present calculation of the annealing of cascade damage. The purpose of this study is to investigate the behavior of defects under the simulated reactive and irradiation condition. Calculation was made for alpha iron (BCC), and the threshold energy was set at 40 eV. The temperature dependence of annealing and the growth of a cluster were studied. The overlapping effect of cascade was studied. At first, the extreme case of overlapping was studied, then the practical cases were estimated by interpolation. The state of overlapping of cascade corresponded to the irradiation speed. The interaction between cascade and dislocations was studied, and the calculation of the annealing of primary knock-out atoms (PKA) in alpha iron was performed. At low temperature, the effect of dislocations was large, but the growth of vacancy was not seen. At high temperature, the effect of dislocations was small. The evaluation of the simulation of various ion irradiation and the growth efficiency of defects were performed. (Kato, T.)

Radiographic manifestations of hypochondroplasia

Energy Technology Data Exchange (ETDEWEB)

Heselson, N G; Cremin, B J [Groote Schuur Hospital, Cape Town (South Africa); Beighton, P

1979-01-01

Hypochrondroplasia is an inherited skeletal dysplasia that resembles achondroplasia in mild degree. Radiographic manifestations encountered in 12 affected individuals in South Africa include slight shortening of all segments of the tubular bones, moderate caudal diminution of the lumbar interpedicular distances, increased lumbar lordosis with cacral tilt and distal prolongation of the fibular. Hypochondroplasia can be distinguished from other osteochondrodystrophies such as achondroplasia, pseudo-achondroplasia and metaphyseal chondroplasia by the recognition of it clinical and radiographic manifestations.

Substrate-driven chemotactic assembly in an enzyme cascade

Science.gov (United States)

Zhao, Xi; Palacci, Henri; Yadav, Vinita; Spiering, Michelle M.; Gilson, Michael K.; Butler, Peter J.; Hess, Henry; Benkovic, Stephen J.; Sen, Ayusman

2018-03-01

Enzymatic catalysis is essential to cell survival. In many instances, enzymes that participate in reaction cascades have been shown to assemble into metabolons in response to the presence of the substrate for the first enzyme. However, what triggers metabolon formation has remained an open question. Through a combination of theory and experiments, we show that enzymes in a cascade can assemble via chemotaxis. We apply microfluidic and fluorescent spectroscopy techniques to study the coordinated movement of the first four enzymes of the glycolysis cascade: hexokinase, phosphoglucose isomerase, phosphofructokinase and aldolase. We show that each enzyme independently follows its own specific substrate gradient, which in turn is produced by the preceding enzymatic reaction. Furthermore, we find that the chemotactic assembly of enzymes occurs even under cytosolic crowding conditions.

Lipopolysaccharide stimulates endogenous β-glucuronidase via PKC/NF-κB/c-myc signaling cascade: a possible factor in hepatolithiasis formation.

Science.gov (United States)

Yao, Dianbo; Dong, Qianze; Tian, Yu; Dai, Chaoliu; Wu, Shuodong

2017-11-29

Hepatolithiasis is commonly encountered in Southeastern and Eastern Asian countries, but the pathogenesis mechanism of stone formation is still not well understood. Now, the role of endogenous β-glucuronidase in pigment stones formation is being gradually recognized. In this study, the mechanism of increased expression and secretion of endogenous β-glucuronidase during hepatolithiasis formation was investigated. We assessed the endogenous β-glucuronidase, c-myc, p-p65, and p-PKC expression in liver specimens with hepatolithiasis by immunohistochemical staining, and found that compared with that in normal liver samples, the expression of endogenous β-glucuronidase, c-myc, p-p65, and p-PKC in liver specimens with hepatolithiasis significantly increased, and their expressions were positively correlated with each other. Lipopolysaccharide (LPS) induced increased expression of endogenous β-glucuronidase and c-myc in hepatocytes and intrahepatic biliary epithelial cells in a dose- and time-dependent manner, and endogenous β-glucuronidase secretion increased, correspondingly. C-myc siRNA transfection effectively inhibited the LPS-induced expression of endogenous β-glucuronidase. Furthermore, NF-κB inhibitor pyrrolidine dithiocarbamate or PKC inhibitor chelerythrine could effectively inhibit the LPS-induced expression of c-myc and endogenous β-glucuronidase, and the expression of p-p65 was also partly inhibited by chelerythrine. Our clinical observations and experimental data indicate that LPS could induce the increased expression and secretion of endogenous β-glucuronidase via a signaling cascade of PKC/NF-κB/c-myc in hepatocytes and intrahepatic biliary epithelial cells, and endogenous β-glucuronidase might play a possible role in the formation of hepatolithiasis.

The relationship between collisional phase defect distribution and cascade collapse efficiency

International Nuclear Information System (INIS)

Morishita, K.; Heinisch, H.L.; Ishino, S.; Sekimura, N.

1994-01-01

Defect distributions after the collisional phase of cascade damage processes were calculated using the computer simulation code MARLOWE, which is based on the binary collision approximation. The densities of vacant sites were evaluated in defect-dense regions at the end of the collisional phase in simulated ion irradiations of several pure metals (Au, Ag, Cu, Ni, Fe, Mo and W). The vacancy density distributions were compared to the measured cascade collapse efficiencies obtained from low-dose ion irradiations of thin foils reported in the literature to identify the minimum or ''critical'' values of the vacancy densities during the collisional phase corresponding to cascade collapse. The critical densities are generally independent of the cascade energy in the same metal. The relationships between physical properties of the target elements and the critical densities are discussed within the framework of the cascade thermal spike model. ((orig.))

Intrathoracic manifestations of Rosai-Dorfman disease.

Science.gov (United States)

Cartin-Ceba, Rodrigo; Golbin, Jason M; Yi, Eunhee S; Prakash, Udaya B S; Vassallo, Robert

2010-09-01

Rosai-Dorfman Disease (RDD), also known as Sinus Histiocytosis with Massive Lymphadenopathy (SHML), is a rare monocyte/macrophage proliferative disorder of varied biological behavior. Although cutaneous and lymph node involvement are relatively well-described, intrathoracic manifestations of RDD have only occasionally been reported. We conducted a retrospective computer-assisted search of the Mayo Clinic record from 1976 to 2005 for patients with histopathologic evidence of RDD on organ biopsy. Clinical characteristics were abstracted from charts and thoracic manifestations recorded. Survival was estimated using the national social security database. A total of 21 patients were diagnosed with RDD over a period of 30 years; 9 had intrathoracic manifestations (43%). Main pulmonary symptoms included dyspnea and cough. Age at the time of diagnosis, gender, race, smoking history, mortality and time of survival after diagnosis were no different between RDD patients with and without intrathoracic manifestations. The most common radiographic thoracic manifestation was mediastinal lymphadenopathy (6 patients). Cystic change, interstitial lung disease, and airway disease were radiographically evident in 4 patients. Seven patients were treated at some point in the course of their disease, most commonly with oral corticosteroids. At the time of last follow-up 87% were alive, with a median (IQR) time interval since diagnosis of 8 years (4-9.7). Intrathoracic manifestations of RDD are relatively common and include mediastinal lymphadenopathy, airway disease, pleural effusion, cystic and interstitial lung disease. Although limited in size, this series suggests the prognosis of patients with RDD and intrathoracic manifestations is relatively good.

Francisella subverts innate immune signaling: Focus on PI3K/Akt

Directory of Open Access Journals (Sweden)

Thomas John Cremer

2011-02-01

Full Text Available Intracellular bacterial pathogens exploit host cells as a part of their lifecycle, and they do so by manipulating host cell signaling events. Many such bacteria are known to produce effector proteins that promote cell invasion, alter membrane trafficking and disrupt signaling cascades. This review highlights recent advances in our understanding of signaling pathways involved in host cell responses to Francisella tularensis, a facultative Gram-negative intracellular pathogen that causes tularemia. We highlight several key pathways that are targeted by Francisella, with a focus on the PI3K/Akt pathway. Lastly, we discuss the emerging role of microRNAs, specifically miR-155, as a key regulator of host signaling and defense.

Strong anticipation: Multifractal cascade dynamics modulate scaling in synchronization behaviors

International Nuclear Information System (INIS)

Stephen, Damian G.; Dixon, James A.

2011-01-01

Research highlights: → We investigated anticipatory behaviors in response to chaotic metronomes. → We assessed multifractal structure in tap intervals and onset intervals. → Strength of multifractality in tap intervals appears to match that in onset intervals. - Abstract: Previous research on anticipatory behaviors has found that the fractal scaling of human behavior may attune to the fractal scaling of an unpredictable signal [Stephen DG, Stepp N, Dixon JA, Turvey MT. Strong anticipation: Sensitivity to long-range correlations in synchronization behavior. Physica A 2008;387:5271-8]. We propose to explain this attunement as a case of multifractal cascade dynamics [Schertzer D, Lovejoy S. Generalised scale invariance in turbulent phenomena. Physico-Chem Hydrodyn J 1985;6:623-5] in which perceptual-motor fluctuations are coordinated across multiple time scales. This account will serve to sharpen the contrast between strong and weak anticipation: whereas the former entails a sensitivity to the intermittent temporal structure of an unpredictable signal, the latter simply predicts sensitivity to an aggregate description of an unpredictable signal irrespective of actual sequence. We pursue this distinction through a reanalysis of Stephen et al.'s data by examining the relationship between the widths of singularity spectra for intertap interval time series and for each corresponding interonset interval time series. We find that the attunement of fractal scaling reported by Stephen et al. was not the trivial result of sensitivity to temporal structure in aggregate but reflected a subtle sensitivity to the coordination across multiple time scales of fluctuation in the unpredictable signal.

Calcium signaling during the plant-plant interaction of parasitic Cuscuta reflexa with its hosts

NARCIS (Netherlands)

Albert, M.; Kaiser, B.; Krol, van der A.R.; Kaldenhoff, R.

2010-01-01

The plant parasite Cuscuta reflexa induces various responses in compatible and incompatible host plants. The visual reactions of both types of host plants including obvious morphological changes require the recognition of Cuscuta ssp. A consequently initiated signaling cascade is triggered which

High energy evolution of soft gluon cascades

International Nuclear Information System (INIS)

Shuvaev, A.; Wallon, S.

2006-01-01

In this paper we derive an evolution equation for the gluon density in soft gluon cascades emitted from any colored source, in the leading logarithmic approximation of perturbative QCD. We show that this equation has the same form as the BFKL equation in the forward case. An explicit expression for the total cascade wavefunction involving an arbitrary number of soft gluons is obtained. Renormalization of the colored source wavefunction turns out to be responsible for the reggeization of the source. (orig.)

High energy evolution of soft gluon cascades

Energy Technology Data Exchange (ETDEWEB)

Shuvaev, A. [St. Petersburg Nuclear Physics Institute, Gatchina, St. Petersburg district (Russian Federation); Wallon, S. [Universite Paris XI, Laboratoire de Physique Theorique, Orsay Cedex (France)

2006-04-15

In this paper we derive an evolution equation for the gluon density in soft gluon cascades emitted from any colored source, in the leading logarithmic approximation of perturbative QCD. We show that this equation has the same form as the BFKL equation in the forward case. An explicit expression for the total cascade wavefunction involving an arbitrary number of soft gluons is obtained. Renormalization of the colored source wavefunction turns out to be responsible for the reggeization of the source. (orig.)

Composite and Cascaded Generalized-K Fading Channel Modeling and Their Diversity and Performance Analysis

KAUST Repository

Ansari, Imran Shafique

2010-12-01

The introduction of new schemes that are based on the communication among nodes has motivated the use of composite fading models due to the fact that the nodes experience different multipath fading and shadowing statistics, which subsequently determines the required statistics for the performance analysis of different transceivers. The end-to-end signal-to-noise-ratio (SNR) statistics plays an essential role in the determination of the performance of cascaded digital communication systems. In this thesis, a closed-form expression for the probability density function (PDF) of the end-end SNR for independent but not necessarily identically distributed (i.n.i.d.) cascaded generalized-K (GK) composite fading channels is derived. The developed PDF expression in terms of the Meijer-G function allows the derivation of subsequent performance metrics, applicable to different modulation schemes, including outage probability, bit error rate for coherent as well as non-coherent systems, and average channel capacity that provides insights into the performance of a digital communication system operating in N cascaded GK composite fading environment. Another line of research that was motivated by the introduction of composite fading channels is the error performance. Error performance is one of the main performance measures and derivation of its closed-form expression has proved to be quite involved for certain systems. Hence, in this thesis, a unified closed-form expression, applicable to different binary modulation schemes, for the bit error rate of dual-branch selection diversity based systems undergoing i.n.i.d. GK fading is derived in terms of the extended generalized bivariate Meijer G-function.

The NDR kinase scaffold HYM1/MO25 is essential for MAK2 map kinase signaling in Neurospora crassa.

Directory of Open Access Journals (Sweden)

Anne Dettmann

2012-09-01

Full Text Available Cell communication is essential for eukaryotic development, but our knowledge of molecules and mechanisms required for intercellular communication is fragmentary. In particular, the connection between signal sensing and regulation of cell polarity is poorly understood. In the filamentous ascomycete Neurospora crassa, germinating spores mutually attract each other and subsequently fuse. During these tropic interactions, the two communicating cells rapidly alternate between two different physiological states, probably associated with signal delivery and response. The MAK2 MAP kinase cascade mediates cell-cell signaling. Here, we show that the conserved scaffolding protein HYM1/MO25 controls the cell shape-regulating NDR kinase module as well as the signal-receiving MAP kinase cascade. HYM1 functions as an integral part of the COT1 NDR kinase complex to regulate the interaction with its upstream kinase POD6 and thereby COT1 activity. In addition, HYM1 interacts with NRC1, MEK2, and MAK2, the three kinases of the MAK2 MAP kinase cascade, and co-localizes with MAK2 at the apex of growing cells. During cell fusion, the three kinases of the MAP kinase module as well as HYM1 are recruited to the point of cell-cell contact. hym-1 mutants phenocopy all defects observed for MAK2 pathway mutants by abolishing MAK2 activity. An NRC1-MEK2 fusion protein reconstitutes MAK2 signaling in hym-1, while constitutive activation of NRC1 and MEK2 does not. These data identify HYM1 as a novel regulator of the NRC1-MEK2-MAK2 pathway, which may coordinate NDR and MAP kinase signaling during cell polarity and intercellular communication.

From neurovascular coupling to neurovascular cascade: a study on neural, autonomic and vascular transients in attention

International Nuclear Information System (INIS)

Bari, V; Calcagnile, P; Molteni, E; Cerutti, S; Bianchi, A M; Re, R; Contini, D; Caffini, M; Torricelli, A; Cubeddu, R; Spinelli, L

2012-01-01

Mental processes bring about neural, vascular and autonomic changes in the brain cortex. Due to the different nature of these modifications, their onsets show no synchrony and time dynamics is often strongly dissimilar. After acquiring data from a group of 16 subjects, we estimated temporal correlation between task and signals in order to assess possible influences induced by an attentive task on electroencephalographic (EEG), heart rate variability (HRV), oxy- and deoxy-haemoglobin concentration signals. We also investigated correlations and time delays between couples of different biological signals. This allowed for the isolation of a subgroup of subjects showing similar tracks. Cardiac frequency and deoxy-haemoglobin signals displayed a strong positive correlation with the task design, while EEG alpha rhythm and oxygenation showed a negative correlation. Neural electrical response was nearly instantaneous with respect to the task progression, and autonomic response showed a mean delay of about 15 s and a slower hemodynamic response (mean delay above 20 s) was finally induced. Globally, the task elicited a cascade of responses, in which delays can be quantified. (paper)

Experimental demonstration of novel cascaded SFG+DFG wavelength conversion of picosecond pulses in LiNbO 3 waveguides

Science.gov (United States)

Wang, Jian; Sun, Junqiang; Luo, Chuanhong

2006-06-01

A novel cascaded χ (2) wavelength conversion of picosecond pulses based on sum frequency generation and difference frequency generation (SFG+DFG) is proposed and experimentally demonstrated in LiNbO 3 waveguides. The signal pulse with 40-GHz repetition rate and 1.57-ps pulse width is adopted. First of all, high conversion efficiency about -18.93dB can be achieved with low power level required for both two pump lights, which is greatly enhanced approximately 8dB compared with the conventional cascaded second-order nonlinear interactions (SHG+DFG) with a single and much higher power pump. Secondly, the wavelength of the converted idler wave can be tuned from 1527.4 to 1540.5nm when the signal wavelength is changed from 1561.9 to 1548.4nm, and about 13.1nm converted idler bandwidth is achieved with the conversion efficiency higher than -31dB. Thirdly, two pump wavelengths can be separated as large as 17.3nm. Meanwhile, when one pump wavelength is fixed at 1549.1nm, the other can be tuned within a wide wavelength range about 7.6nm with the conversion efficiency higher than -34dB, which is much larger than that in the SHG+DFG situation. Finally, the temporal waveform of the converted idler pulse is observed with rather clear appearance achieved, and no obvious changes of the pulse shape and width are found compared with its corresponding original injected signal, showing that our proposed scheme exhibits a very good conversion performance.

Modeling techniques for quantum cascade lasers

Energy Technology Data Exchange (ETDEWEB)

Jirauschek, Christian [Institute for Nanoelectronics, Technische Universität München, D-80333 Munich (Germany); Kubis, Tillmann [Network for Computational Nanotechnology, Purdue University, 207 S Martin Jischke Drive, West Lafayette, Indiana 47907 (United States)

2014-03-15

Quantum cascade lasers are unipolar semiconductor lasers covering a wide range of the infrared and terahertz spectrum. Lasing action is achieved by using optical intersubband transitions between quantized states in specifically designed multiple-quantum-well heterostructures. A systematic improvement of quantum cascade lasers with respect to operating temperature, efficiency, and spectral range requires detailed modeling of the underlying physical processes in these structures. Moreover, the quantum cascade laser constitutes a versatile model device for the development and improvement of simulation techniques in nano- and optoelectronics. This review provides a comprehensive survey and discussion of the modeling techniques used for the simulation of quantum cascade lasers. The main focus is on the modeling of carrier transport in the nanostructured gain medium, while the simulation of the optical cavity is covered at a more basic level. Specifically, the transfer matrix and finite difference methods for solving the one-dimensional Schrödinger equation and Schrödinger-Poisson system are discussed, providing the quantized states in the multiple-quantum-well active region. The modeling of the optical cavity is covered with a focus on basic waveguide resonator structures. Furthermore, various carrier transport simulation methods are discussed, ranging from basic empirical approaches to advanced self-consistent techniques. The methods include empirical rate equation and related Maxwell-Bloch equation approaches, self-consistent rate equation and ensemble Monte Carlo methods, as well as quantum transport approaches, in particular the density matrix and non-equilibrium Green's function formalism. The derived scattering rates and self-energies are generally valid for n-type devices based on one-dimensional quantum confinement, such as quantum well structures.

Modeling techniques for quantum cascade lasers

Science.gov (United States)

Jirauschek, Christian; Kubis, Tillmann

2014-03-01

Quantum cascade lasers are unipolar semiconductor lasers covering a wide range of the infrared and terahertz spectrum. Lasing action is achieved by using optical intersubband transitions between quantized states in specifically designed multiple-quantum-well heterostructures. A systematic improvement of quantum cascade lasers with respect to operating temperature, efficiency, and spectral range requires detailed modeling of the underlying physical processes in these structures. Moreover, the quantum cascade laser constitutes a versatile model device for the development and improvement of simulation techniques in nano- and optoelectronics. This review provides a comprehensive survey and discussion of the modeling techniques used for the simulation of quantum cascade lasers. The main focus is on the modeling of carrier transport in the nanostructured gain medium, while the simulation of the optical cavity is covered at a more basic level. Specifically, the transfer matrix and finite difference methods for solving the one-dimensional Schrödinger equation and Schrödinger-Poisson system are discussed, providing the quantized states in the multiple-quantum-well active region. The modeling of the optical cavity is covered with a focus on basic waveguide resonator structures. Furthermore, various carrier transport simulation methods are discussed, ranging from basic empirical approaches to advanced self-consistent techniques. The methods include empirical rate equation and related Maxwell-Bloch equation approaches, self-consistent rate equation and ensemble Monte Carlo methods, as well as quantum transport approaches, in particular the density matrix and non-equilibrium Green's function formalism. The derived scattering rates and self-energies are generally valid for n-type devices based on one-dimensional quantum confinement, such as quantum well structures.

Bearing-Only Formation Control for Cascade Multirobots

Directory of Open Access Journals (Sweden)

Qing Han

2016-01-01

Full Text Available A new formation control method is proposed, which is used to queue multirobots in a single-direction cascade structure. In the cascade formation, each robot is a follower for the previous robot and a leader for the next robot, and the robots in the middle act as both leader and follower. The follower robot can only observe the bearing information of the leader robot. The observability of the cascade leader-follower formation is studied, which shows that the bearing-only observation meets the observability conditions required for the nonlinear system. Based on the bearing-only observations, the unscented Kalman filter (UKF is employed for the state estimation of the leader and the follower robots at all levels, which enables the real-time movement control of the follower robots via the input-output feedback control. Simulation results demonstrate that the proposed approach can efficiently control the formation of multirobots as desired.

Cascade laser applications: trends and challenges

Science.gov (United States)

d'Humières, B.; Margoto, Éric; Fazilleau, Yves

2016-03-01

When analyses need rapid measurements, cost effective monitoring and miniaturization, tunable semiconductor lasers can be very good sources. Indeed, applications like on-field environmental gas analysis or in-line industrial process control are becoming available thanks to the advantage of tunable semiconductor lasers. Advances in cascade lasers (CL) are revolutionizing Mid-IR spectroscopy with two alternatives: interband cascade lasers (ICL) in the 3-6μm spectrum and quantum cascade lasers (QCL), with more power from 3 to 300μm. The market is getting mature with strong players for driving applications like industry, environment, life science or transports. CL are not the only Mid-IR laser source. In fact, a strong competition is now taking place with other technologies like: OPO, VCSEL, Solid State lasers, Gas, SC Infrared or fiber lasers. In other words, CL have to conquer a share of the Mid-IR application market. Our study is a market analysis of CL technologies and their applications. It shows that improvements of components performance, along with the progress of infrared laser spectroscopy will drive the CL market growth. We compare CL technologies with other Mid-IR sources and estimate their share in each application market.

Noise properties and cascadability of SOA-EA regenerators

DEFF Research Database (Denmark)

Öhman, Filip; Bischoff, Svend; Tromborg, Bjarne

2002-01-01

We suggest and analyse a new device containing concatenated pairs of semiconductor optical amplifiers (SOAs) and electroabsorption modulators (EAs). The device has regenerative properties and improves the cascadability of optical fibre links.......We suggest and analyse a new device containing concatenated pairs of semiconductor optical amplifiers (SOAs) and electroabsorption modulators (EAs). The device has regenerative properties and improves the cascadability of optical fibre links....

Computer codes for simulating atomic-displacement cascades in solids subject to irradiation

International Nuclear Information System (INIS)

Asaoka, Takumi; Taji, Yukichi; Tsutsui, Tsuneo; Nakagawa, Masayuki; Nishida, Takahiko

1979-03-01

In order to study atomic displacement cascades originating from primary knock-on atoms in solids subject to incident radiation, the simulation code CASCADE/CLUSTER is adapted for use on FACOM/230-75 computer system. In addition, the code is modified so as to plot the defect patterns in crystalline solids. As other simulation code of the cascade process, MARLOWE is also available for use on the FACOM system. To deal with the thermal annealing of point defects produced in the cascade process, the code DAIQUIRI developed originally for body-centered cubic crystals is modified to be applicable also for face-centered cubic lattices. By combining CASCADE/CLUSTER and DAIQUIRI, we then prepared a computer code system CASCSRB to deal with heavy irradiation or saturation damage state of solids at normal temperature. Furthermore, a code system for the simulation of heavy irradiations CASCMARL is available, in which MARLOWE code is substituted for CASCADE in the CASCSRB system. (author)

LIMIT SOLUTIONS OF EQUATIONS OF A DC HIGH-VOLTAGE CASCADE GENERATOR

Directory of Open Access Journals (Sweden)

V. O. Brzhezitsky

2015-04-01

Full Text Available In the paper the issue of calculating the high voltage cascade mode oscillator with a nonlinear load using the analytical method under different conditions of selection values of its components is presented. The peculiarity of the method of the study is that during multivariate calculations output parameters load generator remain unchanged. For high-voltage cascade direct current power found conditions under which can be significantly reduced high capacity capacitors cascade generator. The calculations show that acceptable for practical applications of high-voltage characteristics of cascade generators can be achieved with substantial reduction of the volume of their constituents, and thus substantial decline in their value.

A Label-Free and Sensitive Fluorescent Qualitative Assay for Bisphenol A Based on Rolling Circle Amplification/Exonuclease III-Combined Cascade Amplification

Directory of Open Access Journals (Sweden)

Xia Li

2016-10-01

Full Text Available Bisphenol A (BPA detection in drinking water and food packaging materials has attracted much attention since the discovery that BPA can interfere with normal physiological processes and cause adverse health effects. Here, we constructed a label-free aptamer fluorescent assay for selective and sensitive detection of BPA based on the rolling circle amplification (RCA/Exonuclease III (Exo III-combined cascade amplification strategy. First, the duplex DNA probe (RP with anti-BPA aptamer and trigger sequence was designed for BPA recognition and signal amplification. Next, under the action of BPA, the trigger probe was liberated from RP to initiate RCA reaction as primary amplification. Subsequently, the RCA products were used to trigger Exo III assisted secondary amplification with the help of hairpin probes, producing plenty of “G-quadruplex” in lantern-like structures. Finally, the continuously enriched “G-quadruplex lanterns” were lightened by zinc(II-protoporphyrin IX (ZnPPIX generating enhanced fluorescence signals. By integrating the primary RCA and secondary Exo III mediated cascade amplification strategy, this method displayed an excellent sensitivity with the detection limits of 5.4 × 10−17 M. In addition, the anti-BPA aptamer exhibits high recognition ability with BPA, guaranteeing the specificity of detection. The reporter signal probe (G-quadruplex with ZnPPIX provides a label-free fluorescence signals readout without complicated labeling procedures, making the method simple in design and cost-effective in operation. Moreover, environmental samples analysis was also performed, suggesting that our strategy was reliable and had a great potential application in environmental monitoring.

A Label-Free and Sensitive Fluorescent Qualitative Assay for Bisphenol A Based on Rolling Circle Amplification/Exonuclease III-Combined Cascade Amplification.

Science.gov (United States)

Li, Xia; Song, Juan; Xue, Qing-Wang; You, Fu-Heng; Lu, Xia; Kong, Yan-Cong; Ma, Shu-Yi; Jiang, Wei; Li, Chen-Zhong

2016-10-21

Bisphenol A (BPA) detection in drinking water and food packaging materials has attracted much attention since the discovery that BPA can interfere with normal physiological processes and cause adverse health effects. Here, we constructed a label-free aptamer fluorescent assay for selective and sensitive detection of BPA based on the rolling circle amplification (RCA)/Exonuclease III (Exo III)-combined cascade amplification strategy. First, the duplex DNA probe (RP) with anti-BPA aptamer and trigger sequence was designed for BPA recognition and signal amplification. Next, under the action of BPA, the trigger probe was liberated from RP to initiate RCA reaction as primary amplification. Subsequently, the RCA products were used to trigger Exo III assisted secondary amplification with the help of hairpin probes, producing plenty of "G-quadruplex" in lantern-like structures. Finally, the continuously enriched "G-quadruplex lanterns" were lightened by zinc(II)-protoporphyrin IX (ZnPPIX) generating enhanced fluorescence signals. By integrating the primary RCA and secondary Exo III mediated cascade amplification strategy, this method displayed an excellent sensitivity with the detection limits of 5.4 × 10 -17 M. In addition, the anti-BPA aptamer exhibits high recognition ability with BPA, guaranteeing the specificity of detection. The reporter signal probe (G-quadruplex with ZnPPIX) provides a label-free fluorescence signals readout without complicated labeling procedures, making the method simple in design and cost-effective in operation. Moreover, environmental samples analysis was also performed, suggesting that our strategy was reliable and had a great potential application in environmental monitoring.

Curcumin Induced Human Gastric Cancer BGC-823 Cells Apoptosis by ROS-Mediated ASK1-MKK4-JNK Stress Signaling Pathway

Directory of Open Access Journals (Sweden)

Tao Liang

2014-09-01

Full Text Available The signaling mediated by stress-activated MAP kinases (MAPK, c-Jun N-terminal kinase (JNK has well-established importance in cancer. In the present report, we investigated the effects of curcumin on the signaling pathway in human gastric cancer BGC-823 cells. Curcumin induced reactive oxygen species (ROS production and BGC-823 cells apoptosis. Inhibition of ROS generation by antioxidant (NAC or Trion significantly prevented curcumin-mediated apoptosis. Notably, we observed that curcumin activated ASK1, a MAPKKK that is oxidative stress sensitive and responsible to phosphorylation of JNK via triggering cascades, up-regulated an upstream effector of the JNK, MKK4, and phosphorylated JNK protein expression in BGC-823 cells. However, curcumin induced ASK1-MKK4-JNK signaling was attenuated by NAC. All the findings confirm the possibility that oxidative stress-activated ASK1-MKK4-JNK signaling cascade promotes the apoptotic response in curcumin-treated BGC-823 cells.

Cutaneous manifestations of primary immunodeficiency

Directory of Open Access Journals (Sweden)

Safa Abdelhakim

2017-01-01

Full Text Available Primary immunodeficiency diseases (PIDs are a group of rare, chronic disorders with deficient or malfunctioning immune system. It commonly affects the hematopoietic system, with skin the second most affected organ. Skin involvement is observed in half of pediatric PID cases and often precedes the final diagnosis. Skin infections and eczemas are the two most common manifestations in PID.[1] Skin manifestations associated with PIDs can be of infectious and noninfectious causes. Common noninfectious causes are eczema, erythroderma, cutaneous granulomas, dysplasia, vasculitis, and telangiectasia. It is important to be aware of skin manifestations in pediatric patients as early detection of PID may aid in the management of serious immunologic conditions and prevent associated morbidity and mortality.

Interferometric modulation of quantum cascade interactions

Science.gov (United States)

Cusumano, Stefano; Mari, Andrea; Giovannetti, Vittorio

2018-05-01

We consider many-body quantum systems dissipatively coupled by a cascade network, i.e., a setup in which interactions are mediated by unidirectional environmental modes propagating through a linear optical interferometer. In particular we are interested in the possibility of inducing different effective interactions by properly engineering an external dissipative network of beam splitters and phase shifters. In this work we first derive the general structure of the master equation for a symmetric class of translation-invariant cascade networks. Then we show how, by tuning the parameters of the interferometer, one can exploit interference effects to tailor a large variety of many-body interactions.

MRI manifestation for the diagnosis of sporadic Creutzfeldt-Jakob disease

International Nuclear Information System (INIS)

Xue Yonggang; Qi Ji; Xia Shuang

2007-01-01

Objective: To study the MRI features of sporadic Creutzfeldt-Jakob disease (sCJD). Methods: Three patients with clinically diagnosed sCJD underwent MR study, including SE T 1 WI, FSE T 2 WI, and DWI sequences. The MR imaging features were analyzed. Results: The lesions were not definite either in SE T 1 WI or in FSE T 2 WI, but were prominent in DWI. Abnormal hyperintensive signal appeared in the cerebral cortex, with the frontal, parietal, and occipital lobes being the mostly involved region. The subcortical white matter was normal. The bilateral caudate nuclei and thalami could also be involved. The abnormal signal could be either symmetrical or asymmetrical. There was diffuse atrophy of the brain parenchyma in the late phase of disease, especially in the cortex. Conclusion: With the application of MR study, especially the DWI, combined with its characteristic clinical manifestation, the diagnosis of sCJD can be made definitely. (authors)

Computer simulation of electronic excitation in atomic collision cascades

Energy Technology Data Exchange (ETDEWEB)

Duvenbeck, A.

2007-04-05

The impact of an keV atomic particle onto a solid surface initiates a complex sequence of collisions among target atoms in a near-surface region. The temporal and spatial evolution of this atomic collision cascade leads to the emission of particles from the surface - a process usually called sputtering. In modern surface analysis the so called SIMS technology uses the flux of sputtered particles as a source of information on the microscopical stoichiometric structure in the proximity of the bombarded surface spots. By laterally varying the bombarding spot on the surface, the entire target can be scanned and chemically analyzed. However, the particle detection, which bases upon deflection in electric fields, is limited to those species that leave the surface in an ionized state. Due to the fact that the ionized fraction of the total flux of sputtered atoms often only amounts to a few percent or even less, the detection is often hampered by rather low signals. Moreover, it is well known, that the ionization probability of emitted particles does not only depend on the elementary species, but also on the local environment from which a particle leaves the surface. Therefore, the measured signals for different sputtered species do not necessarily represent the stoichiometric composition of the sample. In the literature, this phenomenon is known as the Matrix Effect in SIMS. In order to circumvent this principal shortcoming of SIMS, the present thesis develops an alternative computer simulation concept, which treats the electronic energy losses of all moving atoms as excitation sources feeding energy into the electronic sub-system of the solid. The particle kinetics determining the excitation sources are delivered by classical molecular dynamics. The excitation energy calculations are combined with a diffusive transport model to describe the spread of excitation energy from the initial point of generation. Calculation results yield a space- and time-resolved excitation

Computer simulation of electronic excitation in atomic collision cascades

International Nuclear Information System (INIS)

Duvenbeck, A.

2007-01-01

The impact of an keV atomic particle onto a solid surface initiates a complex sequence of collisions among target atoms in a near-surface region. The temporal and spatial evolution of this atomic collision cascade leads to the emission of particles from the surface - a process usually called sputtering. In modern surface analysis the so called SIMS technology uses the flux of sputtered particles as a source of information on the microscopical stoichiometric structure in the proximity of the bombarded surface spots. By laterally varying the bombarding spot on the surface, the entire target can be scanned and chemically analyzed. However, the particle detection, which bases upon deflection in electric fields, is limited to those species that leave the surface in an ionized state. Due to the fact that the ionized fraction of the total flux of sputtered atoms often only amounts to a few percent or even less, the detection is often hampered by rather low signals. Moreover, it is well known, that the ionization probability of emitted particles does not only depend on the elementary species, but also on the local environment from which a particle leaves the surface. Therefore, the measured signals for different sputtered species do not necessarily represent the stoichiometric composition of the sample. In the literature, this phenomenon is known as the Matrix Effect in SIMS. In order to circumvent this principal shortcoming of SIMS, the present thesis develops an alternative computer simulation concept, which treats the electronic energy losses of all moving atoms as excitation sources feeding energy into the electronic sub-system of the solid. The particle kinetics determining the excitation sources are delivered by classical molecular dynamics. The excitation energy calculations are combined with a diffusive transport model to describe the spread of excitation energy from the initial point of generation. Calculation results yield a space- and time-resolved excitation

Cascade multiplicity inside deuteron in Π d high energy collisions

International Nuclear Information System (INIS)

Kisielewska, D.

1983-01-01

Multiplicity distribution of double scattering events is analysed using the additive quark model including the cascading effect. The mean multiplicity of particles produced in the process of cascading estimated for Π d experiments at 100, 205 and 360 GeV/c is equal to 1.15 ± .31. This value does not depend on the momentum of the incident pion. Some indications are found that the probability of cascading depends on multiplicity of the collision with the first nucleon and is smaller for low multiplicities. (author)

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

Science.gov (United States)

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.

Expression Analysis of the Hippo Cascade Indicates a Role in Pituitary Stem Cell Development

Directory of Open Access Journals (Sweden)

Emily J Lodge

2016-03-01

Full Text Available The pituitary gland is a primary endocrine organ that controls major physiological processes. Abnormal development or homeostatic disruptions can lead to human disorders such as hypopituitarism or tumours. Multiple signalling pathways, including WNT, BMP, FGF and SHH regulate pituitary development but the role of the Hippo-YAP1/TAZ cascade is currently unknown. In multiple tissues, the Hippo kinase cascade underlies neoplasias; it influences organ size through the regulation of proliferation and apoptosis, and has roles in determining stem cell potential. We have used a sensitive mRNA in situ hybridisation method (RNAscope to determine the expression patterns of the Hippo pathway components during mouse pituitary development. We have also carried out immunolocalisation studies to determine when YAP1 and TAZ, the transcriptional effectors of the Hippo pathway, are active. We find that YAP1/TAZ are active in the stem/progenitor cell population throughout development and at postnatal stages, consistent with their role in promoting the stem cell state. Our results demonstrate for the first time the collective expression of major components of the Hippo pathway during normal embryonic and postnatal development of the pituitary gland.

Effect of collision cascades on dislocations in tungsten: A molecular dynamics study

Energy Technology Data Exchange (ETDEWEB)

Fu, B.Q., E-mail: bqfu@scu.edu.cn [Key Laboratory for Radiation Physics and Technology, Institute of Nuclear Science and Technology, Sichuan University, Chengdu 610065 (China); Department of Materials, University of Oxford, Parks Road, Oxford OX1 3PH (United Kingdom); Fitzgerald, S.P. [Department of Applied Mathematics, University of Leeds, Leeds LS2 9JT (United Kingdom); Department of Materials, University of Oxford, Parks Road, Oxford OX1 3PH (United Kingdom); Hou, Q.; Wang, J.; Li, M. [Key Laboratory for Radiation Physics and Technology, Institute of Nuclear Science and Technology, Sichuan University, Chengdu 610065 (China)

2017-02-15

Highlights: • A cascde near a dislocation promotes climb motion. • Kinks induced by cascade facilitate the dipoles motion toward the cascade. • Shearing of dipole is dependent on PKA energy, position, direction, and dipole width. - Abstract: Tungsten (W) is the prime candidate material for the divertor and other plasma-facing components in DEMO. The point defects (i.e. vacancies and self-interstitials) produced in collision cascades caused by incident neutrons aggregate into dislocation loops (and voids), which strongly affect the mechanical properties. The point defects also interact with existing microstructural features, and understanding these processes is crucial for modelling the long term microstructural evolution of the material under fusion conditions. In this work, we performed molecular dynamics simulations of cascades interacting with initially straight edge dislocation dipoles. It was found that the residual vacancy number usually exceeds the residual interstitial number for cascades interacting with vacancy type dipoles, but for interstitial type dipoles these are close. We observed that a cascade near a dislocation promotes climb, i.e. it facilitates the movement of point defects along the climb direction. We also observed that the dislocations move easily along the glide direction, and that kinks are formed near the centre of the cascade, which then facilitate the movement of the dipoles. Some dipoles are sheared off by the cascade, and this is dependent on PKA energy, position, direction, and the width of dipole.

A Cascade of Wnt, Eda, and Shh Signaling Is Essential for Touch Dome Merkel Cell Development.

Science.gov (United States)

Xiao, Ying; Thoresen, Daniel T; Miao, Lingling; Williams, Jonathan S; Wang, Chaochen; Atit, Radhika P; Wong, Sunny Y; Brownell, Isaac

2016-07-01

The Sonic hedgehog (Shh) signaling pathway regulates developmental, homeostatic, and repair processes throughout the body. In the skin, touch domes develop in tandem with primary hair follicles and contain sensory Merkel cells. The developmental signaling requirements for touch dome specification are largely unknown. We found dermal Wnt signaling and subsequent epidermal Eda/Edar signaling promoted Merkel cell morphogenesis by inducing Shh expression in early follicles. Lineage-specific gene deletions revealed intraepithelial Shh signaling was necessary for Merkel cell specification. Additionally, a Shh signaling agonist was sufficient to rescue Merkel cell differentiation in Edar-deficient skin. Moreover, Merkel cells formed in Fgf20 mutant skin where primary hair formation was defective but Shh production was preserved. Although developmentally associated with hair follicles, fate mapping demonstrated Merkel cells primarily originated outside the hair follicle lineage. These findings suggest that touch dome development requires Wnt-dependent mesenchymal signals to establish reciprocal signaling within the developing ectoderm, including Eda signaling to primary hair placodes and ultimately Shh signaling from primary follicles to extrafollicular Merkel cell progenitors. Shh signaling often demonstrates pleiotropic effects within a structure over time. In postnatal skin, Shh is known to regulate the self-renewal, but not the differentiation, of touch dome stem cells. Our findings relate the varied effects of Shh in the touch dome to the ligand source, with locally produced Shh acting as a morphogen essential for lineage specification during development and neural Shh regulating postnatal touch dome stem cell maintenance.

A Cascade of Wnt, Eda, and Shh Signaling Is Essential for Touch Dome Merkel Cell Development.

Directory of Open Access Journals (Sweden)

Ying Xiao

2016-07-01

Full Text Available The Sonic hedgehog (Shh signaling pathway regulates developmental, homeostatic, and repair processes throughout the body. In the skin, touch domes develop in tandem with primary hair follicles and contain sensory Merkel cells. The developmental signaling requirements for touch dome specification are largely unknown. We found dermal Wnt signaling and subsequent epidermal Eda/Edar signaling promoted Merkel cell morphogenesis by inducing Shh expression in early follicles. Lineage-specific gene deletions revealed intraepithelial Shh signaling was necessary for Merkel cell specification. Additionally, a Shh signaling agonist was sufficient to rescue Merkel cell differentiation in Edar-deficient skin. Moreover, Merkel cells formed in Fgf20 mutant skin where primary hair formation was defective but Shh production was preserved. Although developmentally associated with hair follicles, fate mapping demonstrated Merkel cells primarily originated outside the hair follicle lineage. These findings suggest that touch dome development requires Wnt-dependent mesenchymal signals to establish reciprocal signaling within the developing ectoderm, including Eda signaling to primary hair placodes and ultimately Shh signaling from primary follicles to extrafollicular Merkel cell progenitors. Shh signaling often demonstrates pleiotropic effects within a structure over time. In postnatal skin, Shh is known to regulate the self-renewal, but not the differentiation, of touch dome stem cells. Our findings relate the varied effects of Shh in the touch dome to the ligand source, with locally produced Shh acting as a morphogen essential for lineage specification during development and neural Shh regulating postnatal touch dome stem cell maintenance.

In Vivo Phosphoproteomics Analysis Reveals the Cardiac Targets of β-Adrenergic Receptor Signaling

DEFF Research Database (Denmark)

Lundby, Alicia; Andersen, Martin N; Steffensen, Annette B

2013-01-01

β-Blockers are widely used to prevent cardiac arrhythmias and to treat hypertension by inhibiting β-adrenergic receptors (βARs) and thus decreasing contractility and heart rate. βARs initiate phosphorylation-dependent signaling cascades, but only a small number of the target proteins are known. We...

Parton-hadron cascade approach at SPS and RHIC

Energy Technology Data Exchange (ETDEWEB)

Nara, Yasushi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

1998-07-01

A parton-hadron cascade model which is the extension of hadronic cascade model incorporating hard partonic scattering based on HIJING is presented to describe the space-time evolution of parton/hadron system produced by ultra-relativistic nuclear collisions. Hadron yield, baryon stopping and transverse momentum distribution are calculated and compared with HIJING and VNI. Baryon density, energy density and temperature for RHIC are calculated within this model. (author)

Cascading Dynamics of Heterogenous Scale-Free Networks with Recovery Mechanism

Directory of Open Access Journals (Sweden)

Shudong Li

2013-01-01

Full Text Available In network security, how to use efficient response methods against cascading failures of complex networks is very important. In this paper, concerned with the highest-load attack (HL and random attack (RA on one edge, we define five kinds of weighting strategies to assign the external resources for recovering the edges from cascading failures in heterogeneous scale-free (SF networks. The influence of external resources, the tolerance parameter, and the different weighting strategies on SF networks against cascading failures is investigated carefully. We find that, under HL attack, the fourth kind of weighting method can more effectively improve the integral robustness of SF networks, simultaneously control the spreading velocity, and control the outburst of cascading failures in SF networks than other methods. Moreover, the third method is optimal if we only knew the local structure of SF networks and the uniform assignment is the worst. The simulations of the real-world autonomous system in, Internet have also supported our findings. The results are useful for using efficient response strategy against the emergent accidents and controlling the cascading failures in the real-world networks.

Critical assessment and ramifications of a purported marine trophic cascade

Science.gov (United States)

Grubbs, R. Dean; Carlson, John K; Romine, Jason G.; Curtis, Tobey H; McElroy, W. David; McCandless, Camilla T; Cotton, Charles F; Musick, John A.

2016-01-01

When identifying potential trophic cascades, it is important to clearly establish the trophic linkages between predators and prey with respect to temporal abundance, demographics, distribution, and diet. In the northwest Atlantic Ocean, the depletion of large coastal sharks was thought to trigger a trophic cascade whereby predation release resulted in increased cownose ray abundance, which then caused increased predation on and subsequent collapse of commercial bivalve stocks. These claims were used to justify the development of a predator-control fishery for cownose rays, the “Save the Bay, Eat a Ray” fishery, to reduce predation on commercial bivalves. A reexamination of data suggests declines in large coastal sharks did not coincide with purported rapid increases in cownose ray abundance. Likewise, the increase in cownose ray abundance did not coincide with declines in commercial bivalves. The lack of temporal correlations coupled with published diet data suggest the purported trophic cascade is lacking the empirical linkages required of a trophic cascade. Furthermore, the life history parameters of cownose rays suggest they have low reproductive potential and their populations are incapable of rapid increases. Hypothesized trophic cascades should be closely scrutinized as spurious conclusions may negatively influence conservation and management decisions.

Pulmonary manifestations of leptospirosis

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Sameer Gulati

2012-01-01

Full Text Available Leptospirosis has a spectrum of presentation which ranges from mild disease to a severe form comprising of jaundice and renal failure. Involvement of the lung can vary from subtle clinical features to deadly pulmonary hemorrhage and acute respiratory distress syndrome. Of late, it has been identified that leptospirosis can present atypically with predominant pulmonary manifestations. This can delay diagnosis making and hence optimum treatment. The purpose of this review is to bring together all the reported pulmonary manifestations of leptospirosis and the recent trends in the management.

Thermodynamics in 'Manifest Reality'

International Nuclear Information System (INIS)

Hankey, Alex

2010-01-01

D'Espagnat's proof that the universe is not a 'strongly objective reality' demands that all physical processes are reconsidered in that light. D'Espagnat suggests a 'Veiled Reality' as a suitable alternative. The most economical way to achieve that is to demand that 'information production' at a quantum level creates the basis for self-consistent perception of a world of macroscopic, 'manifest' entities, as opposed to self-existent objects. Such a 'manifest reality' fulfils both Wheeler's attempt at an 'IT-from-BIT' programme, and Zeilinger's suggestion that 'information is primary'.

Interrelation of structure and operational states in cascading failure of overloading lines in power grids

Science.gov (United States)

Xue, Fei; Bompard, Ettore; Huang, Tao; Jiang, Lin; Lu, Shaofeng; Zhu, Huaiying

2017-09-01

As the modern power system is expected to develop to a more intelligent and efficient version, i.e. the smart grid, or to be the central backbone of energy internet for free energy interactions, security concerns related to cascading failures have been raised with consideration of catastrophic results. The researches of topological analysis based on complex networks have made great contributions in revealing structural vulnerabilities of power grids including cascading failure analysis. However, existing literature with inappropriate assumptions in modeling still cannot distinguish the effects between the structure and operational state to give meaningful guidance for system operation. This paper is to reveal the interrelation between network structure and operational states in cascading failure and give quantitative evaluation by integrating both perspectives. For structure analysis, cascading paths will be identified by extended betweenness and quantitatively described by cascading drop and cascading gradient. Furthermore, the operational state for cascading paths will be described by loading level. Then, the risk of cascading failure along a specific cascading path can be quantitatively evaluated considering these two factors. The maximum cascading gradient of all possible cascading paths can be used as an overall metric to evaluate the entire power grid for its features related to cascading failure. The proposed method is tested and verified on IEEE30-bus system and IEEE118-bus system, simulation evidences presented in this paper suggests that the proposed model can identify the structural causes for cascading failure and is promising to give meaningful guidance for the protection of system operation in the future.

Node vulnerability of water distribution networks under cascading failures

International Nuclear Information System (INIS)

Shuang, Qing; Zhang, Mingyuan; Yuan, Yongbo

2014-01-01

Water distribution networks (WDNs) are important in modern lifeline system. Its stability and reliability are critical for guaranteeing high living quality and continuous operation of urban functions. The aim of this paper is to evaluate the nodal vulnerability of WDNs under cascading failures. Vulnerability is defined to analyze the effects of the consequent failures. A cascading failure is a step-by-step process which is quantitatively investigated by numerical simulation with intentional attack. Monitored pressures in different nodes and flows in different pipes have been used to estimate the network topological structure and the consequences of nodal failure. Based on the connectivity loss of topological structure, the nodal vulnerability has been evaluated. A load variation function is established to record the nodal failure reason and describe the relative differences between the load and the capacity. The proposed method is validated by an illustrative example. The results revealed that the network vulnerability should be evaluated with the consideration of hydraulic analysis and network topology. In the case study, 70.59% of the node failures trigger the cascading failures with different failure processes. It is shown that the cascading failures result in severe consequences in WDNs. - Highlights: • The aim of this paper is to evaluate the nodal vulnerability of water distribution networks under cascading failures. • Monitored pressures and flows have been used to estimate the network topological structure and the consequences of nodal failure. • Based on the connectivity loss of topological structure, the nodal vulnerability has been evaluated. • A load variation function is established to record the failure reason and describe the relative differences between load and capacity. • The results show that 70.59% of the node failures trigger the cascading failures with different failure processes

Placement of Synchronized Measurements for Power System Observability during Cascaded Outages

Science.gov (United States)

Thirugnanasambandam, Venkatesh; Jain, Trapti

2017-11-01

Cascaded outages often result in power system islanding followed by a blackout and therefore considered as a severe disturbance. Maintaining the observability of each island may help in taking proper control actions to preserve the stability of individual islands thus, averting system collapse. With this intent, a strategy for placement of synchronized measurements, which can be obtained from phasor measurement units (PMU), has been proposed in this paper to keep the system observable during cascaded outages also. Since, all the cascaded failures may not lead to islanding situations, therefore, failures leading to islanding as well as non-islanding situations have been considered. A topology based algorithm has been developed to identify the islanding/non-islanding condition created by a particular cascaded event. Additional contingencies such as single line loss and single PMU failure have also been considered after the occurrence of cascaded events. The proposed method is further extended to incorporate the measurement redundancy, which is desirable for a reliable state estimation. The proposed scheme is tested on IEEE 14-bus, IEEE 30-bus and a practical Indian 246-bus networks. The numerical results ensure the observability of the power system under system intact as well as during cascaded islanding and non-islanding disturbances.

Effects of high-orbit spaceflight on signaling cascades and apoptosis in immune cells from mice flied on board the BION-M1 satellite

Science.gov (United States)

Novoselova, Elena; Shenkman, Boris; Lunin, Sergey; Parfenyuk, Svetlana; Novoselova, Tatyana; Fesenko, Eugeny

The study was designed to evaluate immune cell activity in male C57bl mice after a 30-day high-orbit spaceflight (550 km, higher than conventional manned spaceflights) on board the BION-M1 satellite (Roskosmos Program, Russia). For the present study, thymus, spleens and plasma samples were collected from mice 12 h after landing and, additionally, 7 days subsequently. Assessing the activity of NF-kappaB signaling cascade by measuring Rel A (p65) protein phosphorylation in splenic lymphocytes, we showed that the NF-kappaB activity was significantly increased at 12 h after landing. Contrariwise, one week after landing, the NF-kappaB activity was markedly decreased, even below to the control values. Interestingly, after landing there were no significant changes in SAPK/JNK cascade activity in splenic lymphocytes as well as in the expression of transcription factor IRF3 in thymus cells. To assess the apoptosis status in thymus lymphocytes, levels of p53 protein and its phosphorylated form were measured in thymic lymphocytes. It is known that p53 plays an important role in the cellular response to DNA damage, genomic aberrations, and other characteristic of apoptosis. The results showed that the high-orbit spaceflight environment caused some increase in level of p53 protein, but most notably, activated phosphorylated form of p53 protein. Calculated ratio of active and inactive forms of the protein (ph-p53/p53) 12 h after landing increased by more than 2-fold, indicating the apparent induction of apoptosis in thymus cells. Interestingly, 7 days after the landing, this ratio was not restored, but rather increased: the specified ratio was 4 times higher as compared to the ground-based control. We can conclude that response to the prolonged high-orbit spaceflight is not like the classic "stress response", which is usually observed under various stressful factors. It is known that the stress response is surely accompanied by increased SAPK/JNK cascade activity as well as the

Musculoskeletal manifestations of the antiphospholipid syndrome.

Science.gov (United States)

Noureldine, M H A; Khamashta, M A; Merashli, M; Sabbouh, T; Hughes, G R V; Uthman, I

2016-04-01

The scope of clinical and laboratory manifestations of the antiphospholipid syndrome (APS) has increased dramatically since its discovery in 1983, where any organ system can be involved. Musculoskeletal complications are consistently reported in APS patients, not only causing morbidity and mortality, but also affecting their quality of life. We reviewed all English papers on APS involvement in the musculoskeletal system using Google Scholar and Pubmed; all reports are summarized in a table in this review. The spectrum of manifestations includes arthralgia/arthritis, avascular necrosis of bone, bone marrow necrosis, complex regional pain syndrome type-1, muscle infarction, non-traumatic fractures, and osteoporosis. Some of these manifestations were reported in good quality studies, some of which showed an association between aPL-positivity and the occurrence of these manifestations, while others were merely described in case reports. © The Author(s) 2016.

Atomistic simulations of displacement cascades in Y2O3 single crystal

International Nuclear Information System (INIS)

Dholakia, Manan; Chandra, Sharat; Valsakumar, M.C.; Mathi Jaya, S.

2014-01-01

Graphical abstract: (a) The averaged distortion index and the Y–O bond length of the Y 2 O 3 octahedra as a function of the simulation time for 5 keV PKA. (b) Shows the nearest neighbourhood of one of the Y ions as a function of simulation time, showing the destruction and the recovery of the YO 6 octahedron during the cascade corresponding to 5 keV Y PKA. - Highlights: • Qualitative difference in displacement cascades exists for Y and O PKA. • Nearest neighbour correlation between Y and O ions exists even at cascade peak. • Cascade core in Y 2 O 3 does not undergo melting. • Topological connectivity of YO 6 polyhedra plays important role in stability of Y 2 O 3 . - Abstract: We study the characteristics of displacement cascades in single crystal Y 2 O 3 using classical molecular dynamics. There are two possible ways to generate the cascades in yttria, using either the Y or the O atoms as the primary knock-on (PKA) atom. It is shown that there is a qualitative difference in the characteristics of the cascades obtained in these two cases. Even though the crystal is seen to be in a highly disordered state in the cascade volume, as seen from the plots of radial distribution function, the correlation between the Y and O atoms is not completely lost. This facilitates a quick recovery of the system during the annealing phase. Topological connectivity of the YO 6 polyhedral units plays an important role in imparting stability to the Y 2 O 3 crystal. These characteristics of the cascades can help explain the stability of the yttria nanoparticles when they are dispersed in oxide dispersion strengthened steels

Cascade Chaotic System With Applications.

Science.gov (United States)

Zhou, Yicong; Hua, Zhongyun; Pun, Chi-Man; Chen, C L Philip

2015-09-01

Chaotic maps are widely used in different applications. Motivated by the cascade structure in electronic circuits, this paper introduces a general chaotic framework called the cascade chaotic system (CCS). Using two 1-D chaotic maps as seed maps, CCS is able to generate a huge number of new chaotic maps. Examples and evaluations show the CCS's robustness. Compared with corresponding seed maps, newly generated chaotic maps are more unpredictable and have better chaotic performance, more parameters, and complex chaotic properties. To investigate applications of CCS, we introduce a pseudo-random number generator (PRNG) and a data encryption system using a chaotic map generated by CCS. Simulation and analysis demonstrate that the proposed PRNG has high quality of randomness and that the data encryption system is able to protect different types of data with a high-security level.

Bankruptcy cascades in interbank markets.

Directory of Open Access Journals (Sweden)

Gabriele Tedeschi

Full Text Available We study a credit network and, in particular, an interbank system with an agent-based model. To understand the relationship between business cycles and cascades of bankruptcies, we model a three-sector economy with goods, credit and interbank market. In the interbank market, the participating banks share the risk of bad debits, which may potentially spread a bank's liquidity problems through the network of banks. Our agent-based model sheds light on the correlation between bankruptcy cascades and the endogenous economic cycle of booms and recessions. It also demonstrates the serious trade-off between, on the one hand, reducing risks of individual banks by sharing them and, on the other hand, creating systemic risks through credit-related interlinkages of banks. As a result of our study, the dynamics underlying the meltdown of financial markets in 2008 becomes much better understandable.

Investigation of cascade effect failure for tungsten armour

International Nuclear Information System (INIS)

Makhankov, A.; Barabash, V.; Berkhov, N.; Divavin, V.; Giniatullin, R.; Grigoriev, S.; Ibbott, C.; Komarov, V.; Labusov, A.; Mazul, I.; McDonald, J.; Tanchuk, V.; Youchison, D.

2001-01-01

The glancing angle of incident power on the target of a tokamak divertor results in doubled and highly peaked heat flux onto adjacent downstream tile in the case of lost of tile event (LOTE). As a result downstream tile has higher probability to fail resulting in triple loads to the next downstream tile and so on (cascade effect). This paper devoted to analytical and experimental investigation of the cascade effect failure for the flat tile option of tungsten armoured plasma facing components. Armour geometry resistant to the cascade effect failure was selected on the base of thermal and stress analyses. Experimental investigation of the LOTE has been performed also. Small size W/Cu mock-up withstood not only LOTE simulation load, but also survived afterwards for 1500 cycles at 26-28 MW/m 2 without damage in joint

Process Evaluation Tools for Enzymatic Cascades Welcome Message

DEFF Research Database (Denmark)

Abu, Rohana

improvement and implementation. Hence, the goal of this thesis is to evaluate the process concepts in enzymatic cascades in a systematic manner, using tools such as thermodynamic and kinetic analysis. Three relevant case studies have been used to exemplify the approach. In the first case study, thermodynamic......Biocatalysis is attracting significant attention from both academic and industrial scientists due to the excellent capability of enzyme to catalyse selective reactions. Recently, much interest has been shown in the application of enzymatic cascades as a useful tool in organic synthesis......, the kinetics can be controlled in a highly efficient way to achieve a sufficiently favourable conversion to a given target product. This is exemplified in the second case study, in the kinetic modelling of the formation of 2-ketoglutarate from glucoronate, the second case study. This cascade consists of 4...

Some characteristics of the development of high energy electromagnetic cascades in the atmosphere

International Nuclear Information System (INIS)

Jablonski, Z.; Tomaszewski, A.; Wrotniak, J.A.

1977-01-01

Results of the calculations of some characteristics of electromagnetic cascades induced by cosmic radiation are showed. The cascade parameters are influenced by effect of threshold energy of gamma quanta registration in emulsion chambers. Ratio of integral gamma quanta energies in cascade to initial particle energy and mean energy weighted radius as a function of primary interaction hight, as well as total energy and number of gamma quanta in the cascade are calculated. (S.B.)

Cascade Apartments: Deep Energy Multifamily Retrofit

Energy Technology Data Exchange (ETDEWEB)

Gordon, A. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Mattheis, L. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Kunkle, R. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Howard, L. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Lubliner, M. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

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 package after considering utility window incentives and KCHA capitol improvement funding.

Vertebrate Left-Right Asymmetry: What Can Nodal Cascade Gene Expression Patterns Tell Us?

Science.gov (United States)

Schweickert, Axel; Ott, Tim; Kurz, Sabrina; Tingler, Melanie; Maerker, Markus; Fuhl, Franziska; Blum, Martin

2017-12-29

Laterality of inner organs is a wide-spread characteristic of vertebrates and beyond. It is ultimately controlled by the left-asymmetric activation of the Nodal signaling cascade in the lateral plate mesoderm of the neurula stage embryo, which results from a cilia-driven leftward flow of extracellular fluids at the left-right organizer. This scenario is widely accepted for laterality determination in wildtype specimens. Deviations from this norm come in different flavors. At the level of organ morphogenesis, laterality may be inverted (situs inversus) or non-concordant with respect to the main body axis (situs ambiguus or heterotaxia). At the level of Nodal cascade gene activation, expression may be inverted, bilaterally induced, or absent. In a given genetic situation, patterns may be randomized or predominantly lacking laterality (absence or bilateral activation). We propose that the distributions of patterns observed may be indicative of the underlying molecular defects, with randomizations being primarily caused by defects in the flow-generating ciliary set-up, and symmetrical patterns being the result of impaired flow sensing, on the left, the right, or both sides. This prediction, the reasoning of which is detailed in this review, pinpoints functions of genes whose role in laterality determination have remained obscure.

Molecular dynamics simulation of cascade damage in gold

International Nuclear Information System (INIS)

Alonso, E.; Caturla, M.J.; Tang, M.; Huang, H.; Diaz de la Rubia, T.

1997-01-01

High-energy cascades have been simulated in gold using molecular dynamics with a modified embedded atom method potential. The results show that both vacancy and interstitial clusters form with high probability as a result of intracascade processes. The formation of clusters has been interpreted in terms of the high pressures generated in the core of the cascade during the early stages. The authors provide evidence that correlation between interstitial and vacancy clustering exists

Melanopsin-expressing amphioxus photoreceptors transduce light via a phospholipase C signaling cascade.

Directory of Open Access Journals (Sweden)

Juan Manuel Angueyra

Full Text Available Melanopsin, the receptor molecule that underlies light sensitivity in mammalian 'circadian' receptors, is homologous to invertebrate rhodopsins and has been proposed to operate via a similar signaling pathway. Its downstream effectors, however, remain elusive. Melanopsin also expresses in two distinct light-sensitive cell types in the neural tube of amphioxus. This organism is the most basal extant chordate and can help outline the evolutionary history of different photoreceptor lineages and their transduction mechanisms; moreover, isolated amphioxus photoreceptors offer unique advantages, because they are unambiguously identifiable and amenable to single-cell physiological assays. In the present study whole-cell patch clamp recording, pharmacological manipulations, and immunodetection were utilized to investigate light transduction in amphioxus photoreceptors. A G(q was identified and selectively localized to the photosensitive microvillar membrane, while the pivotal role of phospholipase C was established pharmacologically. The photocurrent was profoundly depressed by IP₃ receptor antagonists, highlighting the importance of IP₃ receptors in light signaling. By contrast, surrogates of diacylglycerol (DAG, as well as poly-unsaturated fatty acids failed to activate a membrane conductance or to alter the light response. The results strengthen the notion that calcium released from the ER via IP₃-sensitive channels may fulfill a key role in conveying--directly or indirectly--the melanopsin-initiated light signal to the photoconductance; moreover, they challenge the dogma that microvillar photoreceptors and phoshoinositide-based light transduction are a prerogative of invertebrate eyes.

Participant intimacy: A cluster analysis of the intranuclear cascade

International Nuclear Information System (INIS)

Cugnon, J.; Knoll, J.; Randrup, J.

1981-01-01

The intranuclear cascade for relativistic nuclear collisions is analyzed in terms of clusters consisting of groups of nucleons which are dynamically linked to each other by violent interactions. The formation cross sections for the different cluster types as well as their intrinsic dynamics are studied and compared with the predictions of the linear cascade model ( rows-on-rows ). (orig.)

Cascading reaction of arginase and urease on a graphene-based FET for ultrasensitive, real-time detection of arginine.

Science.gov (United States)

Berninger, Teresa; Bliem, Christina; Piccinini, Esteban; Azzaroni, Omar; Knoll, Wolfgang

2018-09-15

Herein, a biosensor based on a reduced graphene oxide field effect transistor (rGO-FET) functionalized with the cascading enzymes arginase and urease was developed for the detection of L-arginine. Arginase and urease were immobilized on the rGO-FET sensing surface via electrostatic layer-by-layer assembly using polyethylenimine (PEI) as cationic building block. The signal transduction mechanism is based on the ability of the cascading enzymes to selectively perform chemical transformations and prompt local pH changes, that are sensitively detected by the rGO-FET. In the presence of L-arginine, the transistors modified with (PEI/urease(arginase)) multilayers showed a shift in the Dirac point due to the change in the local pH close to the graphene surface, produced by the catalyzed urea hydrolysis. The transistors were able to monitor L-arginine in the 10-1000 μM linear range with a LOD of 10 μM, displaying a fast response and a good long-term stability. The sensor showed stereospecificity and high selectivity in the presence of non-target amino acids. Taking into account the label-free, real-time measurement capabilities and the easily quantifiable, electronic output signal, this biosensor offers advantages over state-of-the-art L-arginine detection methods. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Perturbation of cellular signaling cascades modulated by ionizing radiation and environmental stress

International Nuclear Information System (INIS)

Ugolini, M.