Specificity of Cytoplasmic Dynein Subunits in Discrete Membrane-trafficking Steps
Palmer, Krysten J.; Hughes, Helen
2009-01-01
The cytoplasmic dynein motor complex is known to exist in multiple forms, but few specific functions have been assigned to individual subunits. A key limitation in the analysis of dynein in intact mammalian cells has been the reliance on gross perturbation of dynein function, e.g., inhibitory antibodies, depolymerization of the entire microtubule network, or the use of expression of dominant negative proteins that inhibit dynein indirectly. Here, we have used RNAi and automated image analysis to define roles for dynein subunits in distinct membrane-trafficking processes. Depletion of a specific subset of dynein subunits, notably LIC1 (DYNC1LI1) but not LIC2 (DYNC1LI2), recapitulates a direct block of ER export, revealing that dynein is required to maintain the steady-state composition of the Golgi, through ongoing ER-to-Golgi transport. Suppression of LIC2 but not of LIC1 results in a defect in recycling endosome distribution and cytokinesis. Biochemical analyses also define the role of each subunit in stabilization of the dynein complex; notably, suppression of DHC1 or IC2 results in concomitant loss of Tctex1. Our data demonstrate that LIC1 and LIC2 define distinct dynein complexes that function at the Golgi versus recycling endosomes, respectively, suggesting that functional populations of dynein mediate discrete intracellular trafficking pathways. PMID:19386764
Diacylglycerol kinases in membrane trafficking
Xie, Shuwei; Naslavsky, Naava; Caplan, Steve
2015-01-01
Diacylglycerol kinases (DGKs) belong to a family of cytosolic kinases that regulate the phosphorylation of diacylglycerol (DAG), converting it into phosphatidic acid (PA). There are 10 known mammalian DGK isoforms, each with a different tissue distribution and substrate specificity. These differences allow regulation of cellular responses by fine-tuning the delicate balance of cellular DAG and PA. DGK isoforms are best characterized as mediators of signal transduction and immune function. However, since recent studies reveal that DAG and PA are also involved in the regulation of endocytic trafficking, it is therefore anticipated that DGKs also plays an important role in membrane trafficking. In this review, we summarize the literature discussing the role of DGK isoforms at different stages of endocytic trafficking, including endocytosis, exocytosis, endocytic recycling, and transport from/to the Golgi apparatus. Overall, these studies contribute to our understanding of the involvement of PA and DAG in endocytic trafficking, an area of research that is drawing increasing attention in recent years. PMID:27057419
Endocytic membrane trafficking and neurodegenerative disease.
Schreij, Andrea M A; Fon, Edward A; McPherson, Peter S
2016-04-01
Neurodegenerative diseases are amongst the most devastating of human disorders. New technologies have led to a rapid increase in the identification of disease-related genes with an enhanced appreciation of the key roles played by genetics in the etiology of these disorders. Importantly, pinpointing the normal function of disease gene proteins leads to new understanding of the cellular machineries and pathways that are altered in the disease process. One such emerging pathway is membrane trafficking in the endosomal system. This key cellular process controls the localization and levels of a myriad of proteins and is thus critical for normal cell function. In this review we will focus on three neurodegenerative diseases; Parkinson disease, amyotrophic lateral sclerosis, and hereditary spastic paraplegias, for which a large number of newly discovered disease genes encode proteins that function in endosomal membrane trafficking. We will describe how alterations in these proteins affect endosomal function and speculate on the contributions of these disruptions to disease pathophysiology. PMID:26721251
Cellular membrane trafficking of mesoporous silica nanoparticles
Fang, I-Ju
2012-01-01
This dissertation mainly focuses on the investigation of the cellular membrane trafficking of mesoporous silica nanoparticles. We are interested in the study of endocytosis and exocytosis behaviors of mesoporous silica nanoparticles with desired surface functionality. The relationship between mesoporous silica nanoparticles and membrane trafficking of cells, either cancerous cells or normal cells was examined. Since mesoporous silica nanoparticles were applied in many drug delivery cases, the endocytotic efficiency of mesoporous silica nanoparticles needs to be investigated in more details in order to design the cellular drug delivery system in the controlled way. It is well known that cells can engulf some molecules outside of the cells through a receptor-ligand associated endocytosis. We are interested to determine if those biomolecules binding to cell surface receptors can be utilized on mesoporous silica nanoparticle materials to improve the uptake efficiency or govern the mechanism of endocytosis of mesoporous silica nanoparticles. Arginine-glycine-aspartate (RGD) is a small peptide recognized by cell integrin receptors and it was reported that avidin internalization was highly promoted by tumor lectin. Both RGD and avidin were linked to the surface of mesoporous silica nanoparticle materials to investigate the effect of receptor-associated biomolecule on cellular endocytosis efficiency. The effect of ligand types, ligand conformation and ligand density were discussed in Chapter 2 and 3. Furthermore, the exocytosis of mesoporous silica nanoparticles is very attractive for biological applications. The cellular protein sequestration study of mesoporous silica nanoparticles was examined for further information of the intracellular pathway of endocytosed mesoporous silica nanoparticle materials. The surface functionality of mesoporous silica nanoparticle materials demonstrated selectivity among the materials and cancer and normal cell lines. We aimed to determine
Inositol lipid phosphatases in membrane trafficking and human disease.
Billcliff, Peter G; Lowe, Martin
2014-07-15
The specific interaction of phosphoinositides with proteins is critical for a plethora of cellular processes, including cytoskeleton remodelling, mitogenic signalling, ion channel regulation and membrane traffic. The spatiotemporal restriction of different phosphoinositide species helps to define compartments within the cell, and this is particularly important for membrane trafficking within both the secretory and endocytic pathways. Phosphoinositide homoeostasis is tightly regulated by a large number of inositol kinases and phosphatases, which respectively phosphorylate and dephosphorylate distinct phosphoinositide species. Many of these enzymes have been implicated in regulating membrane trafficking and, accordingly, their dysregulation has been linked to a number of human diseases. In the present review, we focus on the inositol phosphatases, concentrating on their roles in membrane trafficking and the human diseases with which they have been associated. PMID:24966051
Roles of membrane trafficking in plant cell wall dynamics
Ebine, Kazuo; Ueda, Takashi
2015-01-01
The cell wall is one of the characteristic components of plant cells. The cell wall composition differs among cell types and is modified in response to various environmental conditions. To properly generate and modify the cell wall, many proteins are transported to the plasma membrane or extracellular space through membrane trafficking, which is one of the key protein transport mechanisms in eukaryotic cells. Given the diverse composition and functions of the cell wall in plants, the transport of the cell wall components and proteins that are involved in cell wall-related events could be specialized for each cell type, i.e., the machinery for cell wall biogenesis, modification, and maintenance could be transported via different trafficking pathways. In this review, we summarize the recent progress in the current understanding of the roles and mechanisms of membrane trafficking in plant cells and focus on the biogenesis and regulation of the cell wall. PMID:26539200
Optogenetic oligomerization of Rab GTPases regulates intracellular membrane trafficking.
Nguyen, Mai Khanh; Kim, Cha Yeon; Kim, Jin Man; Park, Byung Ouk; Lee, Sangkyu; Park, Hyerim; Heo, Won Do
2016-06-01
Intracellular membrane trafficking, which is involved in diverse cellular processes, is dynamic and difficult to study in a spatiotemporal manner. Here we report an optogenetic strategy, termed light-activated reversible inhibition by assembled trap of intracellular membranes (IM-LARIAT), that uses various Rab GTPases combined with blue-light-induced hetero-interaction between cryptochrome 2 and CIB1. In this system, illumination induces a rapid and reversible intracellular membrane aggregation that disrupts the dynamics and functions of the targeted membrane. We applied IM-LARIAT to specifically perturb several Rab-mediated trafficking processes, including receptor transport, protein sorting and secretion, and signaling initiated from endosomes. We finally used this tool to reveal different functions of local Rab5-mediated and Rab11-mediated membrane trafficking in growth cones and soma of young hippocampal neurons. Our results show that IM-LARIAT is a versatile tool that can be used to dissect spatiotemporal functions of intracellular membranes in diverse systems. PMID:27065232
Membrane trafficking and osmotically induced volume changes in guard cells.
Shope, Joseph C; Mott, Keith A
2006-01-01
Guard cells rapidly adjust their plasma membrane surface area while responding to osmotically induced volume changes. Previous studies have shown that this process is associated with membrane internalization and remobilization. To investigate how guard cells maintain membrane integrity during rapid volume changes, the effects of two membrane trafficking inhibitors on the response of intact guard cells of Vicia faba to osmotic treatments were studied. Using confocal microscopy and epidermal peels, the relationship between the area of a medial paradermal guard-cell section and guard-cell volume was determined. This allowed estimates of guard-cell volume to be made from single paradermal confocal images, and therefore allowed rapid determination of volume as cells responded to osmotic treatments. Volume changes in control cells showed exponential kinetics, and it was possible to calculate an apparent value for guard-cell hydraulic conductivity from these kinetics. Wortmannin and cytochalasin D inhibited the rate of volume loss following a 0-1.5 MPa osmotic treatment. Cytochalasin D also inhibited volume increases following a change from 1.5 MPa to 0 MPa, but wortmannin had no effect. Previous studies showing that treatment with arabinanase inhibits changes in guard-cell volume in response to osmotic treatments were confirmed. However, pressure volume curves show that the effects of arabinanase and the cytochalasin D were not due to changes in cell wall elasticity. It is suggested that arabinanase, cytochalasin D, and wortmannin cause reductions in the hydraulic conductivity of the plasma membrane, possibly via gating of aquaporins. A possible role for aquaporins in co-ordinating volume changes with membrane trafficking is discussed. PMID:17088361
Reality Property of Discrete Wronski Map with Imaginary Step
NASA Astrophysics Data System (ADS)
Mukhin, Evgeny; Tarasov, Vitaly; Varchenko, Alexander
2012-05-01
For a set of quasi-exponentials with real exponents, we consider the discrete Wronskian (also known as Casorati determinant) with pure imaginary step 2 h. We prove that if the coefficients of the discrete Wronskian are real and the imaginary parts of its roots are bounded by | h|, then the complex span of this set of quasi-exponentials has a basis consisting of quasi-exponentials with real coefficients. This result is a generalization of the statement of the B. and M. Shapiro conjecture on spaces of polynomials. The proof is based on the Bethe ansatz for the XXX model.
Limitations of Discrete Stereology: Steps Toward a More Functional Approach
NASA Astrophysics Data System (ADS)
Proussevitch, A. A.; Sahagian, D. L.; Jutzeler, M.
2012-12-01
Stereology is a statistical and mathematical means to obtain 3D information (such as size, shape, and spatial orientation statistical distributions) from observed 2D cross-section cuts through a volume containing many embedded objects. Examples are SEM imagery of voids in a volcanic rock or tephra, objects in an X-ray tomographic slice, a thin section, a polished section of granite, a planar outcrop of welded volcanic pyroclasts, or sizing of igneous, sedimentary and metamorphic formations from maps. There are three possible approaches to addressing the stereology formulation: 1. Rough approximation using binned data conversion, i.e. discrete stereology. (BAD) 2. Semi-functional data deconvolution, i.e. hybrid of discrete and functional stereology. (BETTER) 3. Solution with 2D-3D functional transformation, i.e. functional stereology (the next step) (BEST). Discrete Stereology: Historically, stereology has been limited to observations of object sizes grouped into discrete bins, or what we now call "discrete" stereology. This approach suffers from severe limitations when applied to natural materials. The most serious of which are exponential error propagation and bias introduced by small numbers of objects in the extremities of the size distribution, and compounded non-spherical shapes and preferred spatial orientations. These limitations do not allow for accurate size distributions of pyroclastic materials, vesicles, and crystals, except for impractically large sample populations. Semi-Functional Stereology: In order to improve the method, a simple first step already taken is "semi-functional" stereology. It combines both discrete object sizing and pre-defined functions of 2D and 3D distributions. Discrete binned observational data is represented by a histogram from which a best fit function for 2D distribution is assigned. This function is then discretized and a 3D distribution is derived from that as in discrete stereology. This approach eliminates some problems
Missing pieces of an ancient puzzle: evolution of the eukaryotic membrane-trafficking system.
Schlacht, Alexander; Herman, Emily K; Klute, Mary J; Field, Mark C; Dacks, Joel B
2014-10-01
The membrane-trafficking system underpins cellular trafficking of material in eukaryotes and its evolution would have been a watershed in eukaryogenesis. Evolutionary cell biological studies have been unraveling the history of proteins responsible for vesicle transport and organelle identity revealing both highly conserved components and lineage-specific innovations. Recently, endomembrane components with a broad, but patchy, distribution have been observed as well, pieces that are missing from our cell biological and evolutionary models of membrane trafficking. These data together allow for new insights into the history and forces that shape the evolution of this critical cell biological system. PMID:25274701
Valproic Acid Affects Membrane Trafficking and Cell-Wall Integrity in Fission Yeast
Miyatake, Makoto; Kuno, Takayoshi; Kita, Ayako; Katsura, Kosaku; Takegawa, Kaoru; Uno, Satoshi; Nabata, Toshiya; Sugiura, Reiko
2007-01-01
Valproic acid (VPA) is widely used to treat epilepsy and manic-depressive illness. Although VPA has been reported to exert a variety of biochemical effects, the exact mechanisms underlying its therapeutic effects remain elusive. To gain further insights into the molecular mechanisms of VPA action, a genetic screen for fission yeast mutants that show hypersensitivity to VPA was performed. One of the genes that we identified was vps45+, which encodes a member of the Sec1/Munc18 family that is implicated in membrane trafficking. Notably, several mutations affecting membrane trafficking also resulted in hypersensitivity to VPA. These include ypt3+ and ryh1+, both encoding a Rab family protein, and apm1+, encoding the μ1 subunit of the adaptor protein complex AP-1. More importantly, VPA caused vacuolar fragmentation and inhibited the glycosylation and the secretion of acid phosphatase in wild-type cells, suggesting that VPA affects membrane trafficking. Interestingly, the cell-wall-damaging agents such as micafungin or the inhibition of calcineurin dramatically enhanced the sensitivity of wild-type cells to VPA. Consistently, VPA treatment of wild-type cells enhanced their sensitivity to the cell-wall-digesting enzymes. Altogether, our results suggest that VPA affects membrane trafficking, which leads to the enhanced sensitivity to cell-wall damage in fission yeast. PMID:17287531
Neuron Membrane Trafficking and Protein Kinases Involved in Autism and ADHD
Kitagishi, Yasuko; Minami, Akari; Nakanishi, Atsuko; Ogura, Yasunori; Matsuda, Satoru
2015-01-01
A brain-enriched multi-domain scaffolding protein, neurobeachin has been identified as a candidate gene for autism patients. Mutations in the synaptic adhesion protein cell adhesion molecule 1 (CADM1) are also associated with autism spectrum disorder, a neurodevelopmental disorder of uncertain molecular origin. Potential roles of neurobeachin and CADM1 have been suggested to a function of vesicle transport in endosomal trafficking. It seems that protein kinase B (AKT) and cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) have key roles in the neuron membrane trafficking involved in the pathogenesis of autism. Attention deficit hyperactivity disorder (ADHD) is documented to dopaminergic insufficiencies, which is attributed to synaptic dysfunction of dopamine transporter (DAT). AKT is also essential for the DAT cell-surface redistribution. In the present paper, we summarize and discuss the importance of several protein kinases that regulate the membrane trafficking involved in autism and ADHD, suggesting new targets for therapeutic intervention. PMID:25647412
Beclin orthologs: integrative hubs of cell signaling, membrane trafficking, and physiology
Levine, Beth; Liu, Rong; Dong, Xiaonan; Zhong, Qing
2015-01-01
The Beclin family, including yeast Atg6 (autophagy related gene 6), its orthologs in higher eukaryotic species, and the more recently characterized mammalian-specific Beclin 2, are essential molecules in autophagy and other membrane-trafficking events. Extensive studies of Beclin orthologs have provided considerable insights into the regulation of autophagy, the diverse roles of autophagy in physiology and disease, and potential new strategies to modulate autophagy in a variety of clinical diseases. In this review we discuss the functions of Beclin 1 orthologs, the regulation of such functions by diverse cellular signaling pathways, and the effects of such regulation on downstream cellular processes including tumor suppression and metabolism. These findings suggest that Beclin orthologs serve as crucial molecules that integrate diverse environmental signals with membrane trafficking events to ensure optimal responses of the cell to stressful stimuli. PMID:26071895
Membrane Trafficking in Neuronal Development: Ins and Outs of Neural Connectivity.
Winkle, Cortney Chelise; Gupton, Stephanie L
2016-01-01
During development, neurons progress through rapid yet stereotypical shape changes to achieve proper neuronal connectivity. This morphological progression requires carefully orchestrated plasma membrane expansion, insertion of membrane components including receptors for extracellular cues into the plasma membrane and removal and trafficking of membrane materials and proteins to specific locations. This review outlines the cellular machinery of membrane trafficking that play an integral role in neuronal cell shape change and function from initial neurite formation to pathway navigation and synaptogenesis. PMID:26940520
Distinct Human and Mouse Membrane Trafficking Systems for Sweet Taste Receptors T1r2 and T1r3
Shimizu, Madoka; Goto, Masao; Kawai, Takayuki; Yamashita, Atsuko; Kusakabe, Yuko
2014-01-01
The sweet taste receptors T1r2 and T1r3 are included in the T1r taste receptor family that belongs to class C of the G protein-coupled receptors. Heterodimerization of T1r2 and T1r3 is required for the perception of sweet substances, but little is known about the mechanisms underlying this heterodimerization, including membrane trafficking. We developed tagged mouse T1r2 and T1r3, and human T1R2 and T1R3 and evaluated membrane trafficking in human embryonic kidney 293 (HEK293) cells. We found that human T1R3 surface expression was only observed when human T1R3 was coexpressed with human T1R2, whereas mouse T1r3 was expressed without mouse T1r2 expression. A domain-swapped chimera and truncated human T1R3 mutant showed that the Venus flytrap module and cysteine-rich domain (CRD) of human T1R3 contain a region related to the inhibition of human T1R3 membrane trafficking and coordinated regulation of human T1R3 membrane trafficking. We also found that the Venus flytrap module of both human T1R2 and T1R3 are needed for membrane trafficking, suggesting that the coexpression of human T1R2 and T1R3 is required for this event. These results suggest that the Venus flytrap module and CRD receive taste substances and play roles in membrane trafficking of human T1R2 and T1R3. These features are different from those of mouse receptors, indicating that human T1R2 and T1R3 are likely to have a novel membrane trafficking system. PMID:25029362
Genetic evidence for involvement of membrane trafficking in the action of 5-fluorouracil.
Hu, Lingling; Yao, Fan; Ma, Yan; Liu, Qiannan; Chen, Si; Hayafuji, Tsutomu; Kuno, Takayoshi; Fang, Yue
2016-08-01
To identify novel genes that mediate cellular sensitivity and resistance to 5-fluorouracil (5-FU), we performed a genome-wide genetic screening to identify altered susceptibility to 5-FU by Schizosaccharomyces pombe haploid nonessential gene deletion library containing 3004 deletion mutants. We identified 50 hypersensitive and 12 resistant mutants to this drug. Mutants sensitive or resistant to 5-FU were classified into various categories based on their putative functions. The largest group of the genes whose disruption renders cells altered susceptibility to 5-FU is involved in nucleic acid metabolism, but to our surprise, the second largest group is involved in membrane trafficking. In addition, several other membrane traffic mutants examined including gdi1-i11, ypt3-i5, Δryh1, Δric1, and Δaps1 exhibited hypersensitivity to 5-FU. Furthermore, we found that 5-FU in low concentration that generally do not affect cell growth altered the localization of Syb1, a secretory vesicle SNARE synaptobrevin which is cycled between the plasma membrane and the endocytic pathway. Notably, 5-FU at such low concentration also significantly inhibited the secretion of acid phosphatase. Altogether, our findings revealed the first evidence that 5-FU influences membrane trafficking as the potential underlying mechanism of the drug action. PMID:27255861
Regulation of intracellular membrane trafficking and cell dynamics by syntaxin-6
Jung, Jae-Joon; Inamdar, Shivangi M.; Tiwari, Ajit; Choudhury, Amit
2012-01-01
Intracellular membrane trafficking along endocytic and secretory transport pathways plays a critical role in diverse cellular functions including both developmental and pathological processes. Briefly, proteins and lipids destined for transport to distinct locations are collectively assembled into vesicles and delivered to their target site by vesicular fusion. SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) proteins are required for these events, during which v-SNAREs (vesicle SNAREs) interact with t-SNAREs (target SNAREs) to allow transfer of cargo from donor vesicle to target membrane. Recently, the t-SNARE family member, syntaxin-6, has been shown to play an important role in the transport of proteins that are key to diverse cellular dynamic processes. In this paper, we briefly discuss the specific role of SNAREs in various mammalian cell types and comprehensively review the various roles of the Golgi- and endosome-localized t-SNARE, syntaxin-6, in membrane trafficking during physiological as well as pathological conditions. PMID:22489884
NASA Technical Reports Server (NTRS)
Majda, George
1986-01-01
One-leg and multistep discretizations of variable-coefficient linear systems of ODEs having both slow and fast time scales are investigated analytically. The stability properties of these discretizations are obtained independent of ODE stiffness and compared. The results of numerical computations are presented in tables, and it is shown that for large step sizes the stability of one-leg methods is better than that of the corresponding linear multistep methods.
The large discretization step method for time-dependent partial differential equations
NASA Technical Reports Server (NTRS)
Haras, Zigo; Taasan, Shlomo
1995-01-01
A new method for the acceleration of linear and nonlinear time dependent calculations is presented. It is based on the Large Discretization Step (LDS) approximation, defined in this work, which employs an extended system of low accuracy schemes to approximate a high accuracy discrete approximation to a time dependent differential operator. Error bounds on such approximations are derived. These approximations are efficiently implemented in the LDS methods for linear and nonlinear hyperbolic equations, presented here. In these algorithms the high and low accuracy schemes are interpreted as the same discretization of a time dependent operator on fine and coarse grids, respectively. Thus, a system of correction terms and corresponding equations are derived and solved on the coarse grid to yield the fine grid accuracy. These terms are initialized by visiting the fine grid once in many coarse grid time steps. The resulting methods are very general, simple to implement and may be used to accelerate many existing time marching schemes.
Functional link between Rab GTPase-mediated membrane trafficking and PI4,5P2 signaling.
Li, Cuifang; Kita, Ayako; Hashimoto, Yuuka; Ihara, Misako; Kato, Ayaka; Ogura, Naoya; Doi, Akira; Oku, Masahide; Itoh, Toshiki; Sakai, Yasuyoshi; Sugiura, Reiko
2014-03-01
Fission yeast its3(+) encodes an essential phosphatidylinositol-4-phosphate 5-kinase (PI4P5K) that regulates cell integrity and cytokinesis. We performed a genetic screen to identify genes that function in PI4P5K-mediated signaling, and identified gyp10(+) encoding a Rab GTPase-activating protein (GAP), a negative regulator for Rab GTPase signaling. Its3 overproduction caused growth defects and abnormal cytoplasmic accumulation of the Its3 protein, which can be stained by calcofluor. Notably, Its3 overproducing cells displayed abnormal membranous structures, multilamella Golgi and fragmented vacuoles showed by Electron microscopy. Furthermore, the excess cytoplasmic Its3 structure partly colocalized with the fluorescence of FM4-64. Gyp10 rescued both growth defects and abnormal Its3 localization when it was over-expressed. Gyp10 functionally interacted with the Rab GTPases Ypt3 and Ryh1, both of which regulate Golgi membrane trafficking. Consistently, mutation or deletion of Ypt3 and Ryh1 suppressed phenotypes associated with Its3 overproduction. Importantly, the plasma membrane localization of Its3 was also affected by the impairment of the Ypt3/Ryh1 Rab membrane trafficking, thus suggesting that membrane trafficking events regulated by two Rab GTPases functionally interacts with PI4,5P2 signaling. These results suggest a mechanism whereby PI4P5K signaling/localization is affected by Golgi membrane trafficking, thus provide a functional link between the PI4,5P2 signaling and Rab-mediated trafficking. PMID:24350606
Curran, Jerry; Mohler, Peter J
2015-01-01
Channelopathies are a diverse set of disorders associated with defects in ion channel (and transporter) function. Although the vast majority of channelopathies are linked with inherited mutations that alter ion channel biophysical properties, another group of similar disorders has emerged that alter ion channel synthesis, membrane trafficking, and/or posttranslational modifications. In fact, some electrical and episodic disorders have now been identified that are not defects in the ion channel but instead reflect dysfunction in an ion channel (or transporter) regulatory protein. This review focuses on alternative paradigms for physiological disorders associated with protein biosynthesis, folding, trafficking, and membrane retention. Furthermore, the review highlights the role of aberrant posttranslational modifications in acquired channelopathies. PMID:25293528
Tracing the Archaeal Origins of Eukaryotic Membrane-Trafficking System Building Blocks.
Klinger, Christen M; Spang, Anja; Dacks, Joel B; Ettema, Thijs J G
2016-06-01
In contrast to prokaryotes, eukaryotic cells are characterized by a complex set of internal membrane-bound compartments. A subset of these, and the protein machineries that move material between them, define the membrane-trafficking system (MTS), the emergence of which represents a landmark in eukaryotic evolution. Unlike mitochondria and plastids, MTS organelles have autogenous origins. Much of the MTS machinery is composed of building blocks, including small GTPase, coiled-coil, beta-propeller + alpha-solenoid, and longin domains. Despite the identification of prokaryotic proteins containing these domains, only few represent direct orthologues, leaving the origins and early evolution of the MTS poorly understood. Here, we present an in-depth analysis of MTS building block homologues in the composite genome of Lokiarchaeum, the recently discovered archaeal sister clade of eukaryotes, yielding several key insights. We identify two previously unreported Eukaryotic Signature Proteins; orthologues of the Gtr/Rag family GTPases, involved in target of rapamycin complex signaling, and of the RLC7 dynein component. We could not identify golgin or SNARE (coiled-coil) or beta-propeller + alpha-solenoid orthologues, nor typical MTS domain fusions, suggesting that these either were lost from Lokiarchaeum or emerged later in eukaryotic evolution. Furthermore, our phylogenetic analyses of lokiarchaeal GTPases support a split into Ras-like and Arf-like superfamilies, with different prokaryotic antecedents, before the advent of eukaryotes. While no GTPase activating proteins or exchange factors were identified, we show that Lokiarchaeum encodes numerous roadblock domain proteins and putative longin domain proteins, confirming the latter's origin from Archaea. Altogether, our study provides new insights into the emergence and early evolution of the eukaryotic membrane-trafficking system. PMID:26893300
The Discrete Wavelet Transform with Lifting : A Step by Step Introduction
Elofson, C
2004-08-26
There is a great deal of information pertaining to wavelets readily available from various sources; several of the more recent sources describe the lifting technique for constructing wavelets. The tutorial paper by Sweldens and Schr{umlt o}der [1] gives a thorough explanation of the lifting approach for Haar bases. While it provides an excellent introduction to the topic, it is not immediately obvious how this approach is extended to nonuniformly spaced data on finite intervals. The present paper provides intermediate steps that supplement the material in [1]. After working through the following discussion, the reader should have no problem deriving the relevant equations presented in Sweldens and Schr{umlt o}der's article. Because of the abundance of information on the Haar basis, this discussion will instead work through the steps using a linear basis set.
Stefanić, Sasa; Spycher, Cornelia; Morf, Laura; Fabriàs, Gemma; Casas, Josefina; Schraner, Elisabeth; Wild, Peter; Hehl, Adrian B; Sonda, Sabrina
2010-09-01
Synthesis of glucosylceramide via glucosylceramide synthase (GCS) is a crucial event in higher eukaryotes, both for the production of complex glycosphingolipids and for regulating cellular levels of ceramide, a potent antiproliferative second messenger. In this study, we explored the dependence of the early branching eukaryote Giardia lamblia on GCS activity. Biochemical analyses revealed that the parasite has a GCS located in endoplasmic reticulum (ER) membranes that is active in proliferating and encysting trophozoites. Pharmacological inhibition of GCS induced aberrant cell division, characterized by arrest of cytokinesis, incomplete cleavage furrow formation, and consequent block of replication. Importantly, we showed that increased ceramide levels were responsible for the cytokinesis arrest. In addition, GCS inhibition resulted in prominent ultrastructural abnormalities, including accumulation of cytosolic vesicles, enlarged lysosomes, and clathrin disorganization. Moreover, anterograde trafficking of the encystations-specific protein CWP1 was severely compromised and resulted in inhibition of stage differentiation. Our results reveal novel aspects of lipid metabolism in G. lamblia and specifically highlight the vital role of GCS in regulating cell cycle progression, membrane trafficking events, and stage differentiation in this parasite. In addition, we identified ceramide as a potent bioactive molecule, underscoring the universal conservation of ceramide signaling in eukaryotes. PMID:20335568
KIF13B regulates angiogenesis through Golgi to plasma membrane trafficking of VEGFR2
Yamada, Kaori H.; Nakajima, Yuki; Geyer, Melissa; Wary, Kishore K.; Ushio-Fukai, Masuko; Komarova, Yulia; Malik, Asrar B.
2014-01-01
ABSTRACT Although the trafficking of newly synthesized VEGFR2 to the plasma membrane is a key determinant of angiogenesis, the molecular mechanisms of Golgi to plasma membrane trafficking are unknown. Here, we have identified a key role of the kinesin family plus-end molecular motor KIF13B in delivering VEGFR2 cargo from the Golgi to the endothelial cell surface. KIF13B is shown to interact directly with VEGFR2 on microtubules. We also observed that overexpression of truncated versions of KIF13B containing the binding domains that interact with VEGFR2 inhibited VEGF-induced capillary tube formation. KIF13B depletion prevented VEGF-mediated endothelial migration, capillary tube formation and neo-vascularization in mice. Impairment in trafficking induced by knockdown of KIF13B shunted VEGFR2 towards the lysosomal degradation pathway. Thus, KIF13B is an essential molecular motor required for the trafficking of VEGFR2 from the Golgi, and its delivery to the endothelial cell surface mediates angiogenesis. PMID:25128562
Alternative routes to the cell surface underpin insulin-regulated membrane trafficking of GLUT4
Kioumourtzoglou, Dimitrios; Pryor, Paul R.; Gould, Gwyn W.; Bryant, Nia J.
2015-01-01
ABSTRACT Insulin-stimulated delivery of glucose transporters (GLUT4, also known as SLC2A4) from specialized intracellular GLUT4 storage vesicles (GSVs) to the surface of fat and muscle cells is central to whole-body glucose regulation. This translocation and subsequent internalization of GLUT4 back into intracellular stores transits through numerous small membrane-bound compartments (internal GLUT4-containing vesicles; IGVs) including GSVs, but the function of these different compartments is not clear. Cellugyrin (also known as synaptogyrin-2) and sortilin define distinct populations of IGV; sortilin-positive IGVs represent GSVs, but the function of cellugyrin-containing IGVs is unknown. Here, we demonstrate a role for cellugyrin in intracellular sequestration of GLUT4 in HeLa cells and have used a proximity ligation assay to follow changes in pairwise associations between cellugyrin, sortilin, GLUT4 and membrane trafficking machinery following insulin-stimulation of 3T3-L1 adipoctyes. Our data suggest that insulin stimulates traffic from cellugyrin-containing to sortilin-containing membranes, and that cellugyrin-containing IGVs provide an insulin-sensitive reservoir to replenish GSVs following insulin-stimulated exocytosis of GLUT4. Furthermore, our data support the existence of a pathway from cellugyrin-containing membranes to the surface of 3T3-L1 adipocytes that bypasses GSVs under basal conditions, and that insulin diverts traffic away from this into GSVs. PMID:26071524
Studying membrane trafficking in the worm C. elegans by RNA interference.
Balklava, Zita; Sztul, Elizabeth
2013-01-01
A powerful approach to gain understanding of molecular machinery responsible for membrane trafficking is through inactivation of gene function by RNA interference (RNAi). RNAi-mediated gene silencing occurs when a double-stranded RNA is introduced into cells and targets a complementary mRNA for degradation. The subsequent lack of mRNA prevents the synthesis of the corresponding protein and ultimately causes depletion of a particular gene product from the cell. The effects of such depletion can then by analyzed by functional, morphological, and biochemical assays. RNAi-mediated knockdowns of numerous gene products in cultured cells of mammalian and other species origins have provided significant new insight into traffic regulation and represent standard approaches in current cell biology. However, RNAi in the multicellular nematode Caenorhabditis elegans model allows RNAi studies within the context of a whole organism, and thus provides an unprecedented opportunity to explore effects of specific trafficking regulators within the context of distinct developmental stages and diverse cell types. In addition, various transgenic C. elegans strains have been developed that express marker proteins tagged with fluorescent proteins to facilitate the analysis of trafficking within the secretory and endocytic pathways. This chapter provides a detailed description of a basic RNAi approach that can be used to analyze the function of any gene of interest in secretory and endosomal trafficking in C. elegans. PMID:24295300
Regulation of membrane trafficking by signalling on endosomal and lysosomal membranes
Li, Xinran; Garrity, Abigail G; Xu, Haoxing
2013-01-01
Endosomal and lysosomal membrane trafficking requires the coordination of multiple signalling events to control cargo sorting and processing, and endosome maturation. The initiation and termination of signalling events in endosomes and lysosomes is not well understood, but several key regulators have been identified, which include small GTPases, phosphoinositides, and Ca2+. Small GTPases act as master regulators and molecular switches in a GTP-dependent manner, initiating signalling cascades to regulate the direction and specificity of endosomal trafficking. Phosphoinositides are membrane-bound lipids that indicate vesicular identities for recruiting specific cytoplasmic proteins to endosomal membranes, thus allowing specificity of membrane fusion, fission, and cargo sorting to occur within and between specific vesicle compartments. In addition, phosphoinositides regulate the function of membrane proteins such as ion channels and transporters in a compartment-specific manner to mediate transport and signalling. Finally, Ca2+, a locally acting second messenger released from intracellular ion channels, may provide precise spatiotemporal regulation of endosomal signalling and trafficking events. Small GTPase signalling can regulate phosphoinositide conversion during endosome maturation, and electrophysiological studies on isolated endosomes have shown that endosomal and lysosomal Ca2+ channels are directly modulated by endosomal lipids. Thus trafficking and maturation of endosomes and lysosomes can be precisely regulated by dynamic changes in GTPases and membrane lipids, as well as Ca2+ signalling. Importantly, impaired phosphoinositide and Ca2+ signalling can cause endosomal and lysosomal trafficking defects at the cellular level, and a spectrum of lysosome storage diseases. PMID:23878375
A role for tumor protein TPD52 phosphorylation in endo-membrane trafficking during cytokinesis
Thomas, Diana D.H.; Frey, Christina L.; Messenger, Scott W.; August, Benjamin K.; Groblewski, Guy E.
2010-11-26
Research highlights: {yields} D52 localizes to vesicles at the mid-line in multinucleated cells. {yields} Expression of a D52 serine136/alanine mutant induced multinucleation of cells. {yields} D52 localizes to VAMP 8 positive endosomes necessary for cytokinesis. {yields} The Ca{sup 2+}-dependent phosphorylation of D52 regulates cytokinesis. -- Abstract: Tumor protein D52 is expressed at high levels in exocrine cells containing large secretory granules where it regulates Ca{sup 2+}-dependent protein secretion; however, D52 expression is also highly induced in multiple cancers. The present study investigated a role for the Ca{sup 2+}-dependent phosphorylation of D52 at the single major phospho-acceptor site serine 136 on cell division. Ectopic expression of wild type D52 (D52wt) and the phosphomutants serine 136/alanine (S136A) or serine 136/glutamate (S136/E) resulted in significant multinucleation of cells. D52wt and S136/E each resulted in a greater than 2-fold increase in multinucleated cells compared to plasmid-transfected controls whereas the S136/A phospho-null mutant caused a 9-fold increase in multinucleation at 48 h post-transfection. Electron microscopy revealed D52 expression induced a marked accumulation of vesicles along the mid-line between nuclei where the final stages of cell abscission normally occurs. Supporting this, D52wt strongly colocalized on vesicular structures containing the endosomal regulatory protein vesicle associated membrane protein 8 (VAMP 8) and this colocalization significantly increased with elevations in cellular Ca{sup 2+}. As VAMP 8 is known to be necessary for the endo-membrane fusion reactions that mediate the final stages of cytokinesis, these data indicate that D52 expression and phosphorylation at serine 136 play an important role in supporting the Ca{sup 2+}-dependent membrane trafficking events necessary for cytokinesis in rapidly proliferating cancer cells.
NASA Astrophysics Data System (ADS)
Vu, Huong T.; Chakrabarti, Shaon; Hinczewski, Michael; Thirumalai, D.
2016-08-01
Fluctuations in the physical properties of biological machines are inextricably linked to their functions. Distributions of run lengths and velocities of processive molecular motors, like kinesin-1, are accessible through single-molecule techniques, but rigorous theoretical models for these probabilities are lacking. Here, we derive exact analytic results for a kinetic model to predict the resistive force (F )-dependent velocity [P (v )] and run length [P (n )] distribution functions of generic finitely processive molecular motors. Our theory quantitatively explains the zero force kinesin-1 data for both P (n ) and P (v ) using the detachment rate as the only parameter. In addition, we predict the F dependence of these quantities. At nonzero F , P (v ) is non-Gaussian and is bimodal with peaks at positive and negative values of v , which is due to the discrete step size of kinesin-1. Although the predictions are based on analyses of kinesin-1 data, our results are general and should hold for any processive motor, which walks on a track by taking discrete steps.
Vu, Huong T; Chakrabarti, Shaon; Hinczewski, Michael; Thirumalai, D
2016-08-12
Fluctuations in the physical properties of biological machines are inextricably linked to their functions. Distributions of run lengths and velocities of processive molecular motors, like kinesin-1, are accessible through single-molecule techniques, but rigorous theoretical models for these probabilities are lacking. Here, we derive exact analytic results for a kinetic model to predict the resistive force (F)-dependent velocity [P(v)] and run length [P(n)] distribution functions of generic finitely processive molecular motors. Our theory quantitatively explains the zero force kinesin-1 data for both P(n) and P(v) using the detachment rate as the only parameter. In addition, we predict the F dependence of these quantities. At nonzero F, P(v) is non-Gaussian and is bimodal with peaks at positive and negative values of v, which is due to the discrete step size of kinesin-1. Although the predictions are based on analyses of kinesin-1 data, our results are general and should hold for any processive motor, which walks on a track by taking discrete steps. PMID:27564000
NASA Technical Reports Server (NTRS)
Majda, G.
1985-01-01
A large set of variable coefficient linear systems of ordinary differential equations which possess two different time scales, a slow one and a fast one is considered. A small parameter epsilon characterizes the stiffness of these systems. A system of o.d.e.s. in this set is approximated by a general class of multistep discretizations which includes both one-leg and linear multistep methods. Sufficient conditions are determined under which each solution of a multistep method is uniformly bounded, with a bound which is independent of the stiffness of the system of o.d.e.s., when the step size resolves the slow time scale, but not the fast one. This property is called stability with large step sizes. The theory presented lets one compare properties of one-leg methods and linear multistep methods when they approximate variable coefficient systems of stiff o.d.e.s. In particular, it is shown that one-leg methods have better stability properties with large step sizes than their linear multistep counter parts. The theory also allows one to relate the concept of D-stability to the usual notions of stability and stability domains and to the propagation of errors for multistep methods which use large step sizes.
Zhao, Renjie; Evans, James W.; Oliveira, Tiago J.
2016-04-08
Here, a discrete version of deposition-diffusion equations appropriate for description of step flow on a vicinal surface is analyzed for a two-dimensional grid of adsorption sites representing the stepped surface and explicitly incorporating kinks along the step edges. Model energetics and kinetics appropriately account for binding of adatoms at steps and kinks, distinct terrace and edge diffusion rates, and possible additional barriers for attachment to steps. Analysis of adatom attachment fluxes as well as limiting values of adatom densities at step edges for nonuniform deposition scenarios allows determination of both permeability and kinetic coefficients. Behavior of these quantities is assessedmore » as a function of key system parameters including kink density, step attachment barriers, and the step edge diffusion rate.« less
Lee, Sujin; Hong, Juhee; Lee, Junghoon
2016-02-28
Our tissues consist of individual cells that respond to the elasticity of their environment, which varies between and within tissues. To better understand mechanically driven cell migration, it is necessary to manipulate the stiffness gradient across a substrate. Here, we have demonstrated a new variant of the microfabricated polymeric pillar array platform that can decouple the stiffness gradient from the ECM protein area. This goal is achieved via a "stepped" micro pillar array device (SMPAD) in which the contact area with the cell was kept constant while the diameter of the pillar bodies was altered to attain the proper mechanical stiffness. Using double-step SU-8 mold fabrication, the diameter of the top of every pillar was kept uniform, whereas that of the bottom was changed, to achieve the desired substrate rigidity. Fibronectin was immobilized on the pillar tops, providing a focal adhesion site for cells. C2C12, HeLa and NIH3T3 cells were cultured on the SMPAD, and the motion of the cells was observed by time-lapse microscopy. Using this simple platform, which produces a purely physical stimulus, we observed that various types of cell behavior are affected by the mechanical stimulus of the environment. We also demonstrated directed cell migration guided by a discrete rigidity gradient by varying stiffness. Interestingly, cell velocity was highest at the highest stiffness. Our approach enables the regulation of the mechanical properties of the polymeric pillar array device and eliminates the effects of the size of the contact area. This technique is a unique tool for studying cellular motion and behavior relative to various stiffness gradients in the environment. PMID:26787193
Shadlen, Michael N; Kiani, Roozbeh; Newsome, William T; Gold, Joshua I; Wolpert, Daniel M; Zylberberg, Ariel; Ditterich, Jochen; de Lafuente, Victor; Yang, Tianming; Roitman, Jamie
2016-03-25
Latimeret al (Reports, 10 July 2015, p. 184) claim that during perceptual decision formation, parietal neurons undergo one-time, discrete steps in firing rate instead of gradual changes that represent the accumulation of evidence. However, that conclusion rests on unsubstantiated assumptions about the time window of evidence accumulation, and their stepping model cannot explain existing data as effectively as evidence-accumulation models. PMID:27013723
Kita, Ayako; Higa, Mari; Doi, Akira; Satoh, Ryosuke; Sugiura, Reiko
2015-02-13
Cytokinesis is a highly ordered process that divides one cell into two cells, which is functionally linked to the dynamic remodeling of the plasma membrane coordinately with various events such as membrane trafficking. Calcineurin is a highly conserved serine/threonine protein phosphatase, which regulates multiple biological functions, such as membrane trafficking and cytokinesis. Here, we isolated imp2-c3, a mutant allele of the imp2{sup +} gene, encoding a homolog of the mouse PSTPIP1 (proline-serine-threonine phosphatase interacting protein 1), using a genetic screen for mutations that are synthetically lethal with calcineurin deletion in fission yeast. The imp2-c3 mutants showed a defect in cytokinesis with multi-septated phenotypes, which was further enhanced upon treatment with the calcineurin inhibitor FK506. Notably, electron micrographs revealed that the imp2-c3 mutant cells accumulated aberrant multi-lamella Golgi structures and putative post-Golgi secretory vesicles, and exhibited fragmented vacuoles in addition to thickened septa. Consistently, imp2-c3 mutants showed a reduced secretion of acid phosphatase and defects in vacuole fusion. The imp2-c3 mutant cells exhibited a weakened cell wall, similar to the membrane trafficking mutants identified in the same genetic screen such as ypt3-i5. These findings implicate the PSTPIP1 homolog Imp2 in Golgi/vacuole function, thereby affecting various cellular processes, including cytokinesis and cell integrity. - Highlights: • We isolated imp2-c3, in a synthetic lethal screen with calcineurin in fission yeast. • The imp2{sup +} gene encodes a component of the actin contractile ring similar to Cdc15. • The imp2-c3 mutants showed defects in cytokinesis, which were exacerbated by FK506. • The imp2-c3 mutants were defective in membrane trafficking and cell wall integrity. • Our study revealed a novel role for Imp2 in the Golgi/vacuolar membrane trafficking.
Discrete Topics in the Undergraduate Mathematics Curriculum: How Big a Step Should We Take?
ERIC Educational Resources Information Center
Gordon, Sheldon P.
The question of the advisability of incorporating discrete mathematics into the mathematics curriculum is addressed by examining the different types of courses typically offered in the first two years of college and the appropriateness of including discrete mathematics topics in these courses. The introductory section explains how the advent of…
Podlubny, Igor; Skovranek, Tomas; Vinagre Jara, Blas M; Petras, Ivo; Verbitsky, Viktor; Chen, YangQuan
2013-05-13
In this paper, we further develop Podlubny's matrix approach to discretization of integrals and derivatives of non-integer order. Numerical integration and differentiation on non-equidistant grids is introduced and illustrated by several examples of numerical solution of differential equations with fractional derivatives of constant orders and with distributed-order derivatives. In this paper, for the first time, we present a variable-step-length approach that we call 'the method of large steps', because it is applied in combination with the matrix approach for each 'large step'. This new method is also illustrated by an easy-to-follow example. The presented approach allows fractional-order and distributed-order differentiation and integration of non-uniformly sampled signals, and opens the way to development of variable- and adaptive-step-length techniques for fractional- and distributed-order differential equations. PMID:23547230
NASA Astrophysics Data System (ADS)
Guo, Peng; Cheng, Wenming; Wang, Yi
2015-11-01
This article considers the parallel machine scheduling problem with step-deteriorating jobs and sequence-dependent setup times. The objective is to minimize the total tardiness by determining the allocation and sequence of jobs on identical parallel machines. In this problem, the processing time of each job is a step function dependent upon its starting time. An individual extended time is penalized when the starting time of a job is later than a specific deterioration date. The possibility of deterioration of a job makes the parallel machine scheduling problem more challenging than ordinary ones. A mixed integer programming model for the optimal solution is derived. Due to its NP-hard nature, a hybrid discrete cuckoo search algorithm is proposed to solve this problem. In order to generate a good initial swarm, a modified Biskup-Hermann-Gupta (BHG) heuristic called MBHG is incorporated into the population initialization. Several discrete operators are proposed in the random walk of Lévy flights and the crossover search. Moreover, a local search procedure based on variable neighbourhood descent is integrated into the algorithm as a hybrid strategy in order to improve the quality of elite solutions. Computational experiments are executed on two sets of randomly generated test instances. The results show that the proposed hybrid algorithm can yield better solutions in comparison with the commercial solver CPLEX® with a one hour time limit, the discrete cuckoo search algorithm and the existing variable neighbourhood search algorithm.
Štefanić, Saša; Spycher, Cornelia; Morf, Laura; Fabriàs, Gemma; Casas, Josefina; Schraner, Elisabeth; Wild, Peter; Hehl, Adrian B.; Sonda, Sabrina
2010-01-01
Synthesis of glucosylceramide via glucosylceramide synthase (GCS) is a crucial event in higher eukaryotes, both for the production of complex glycosphingolipids and for regulating cellular levels of ceramide, a potent antiproliferative second messenger. In this study, we explored the dependence of the early branching eukaryote Giardia lamblia on GCS activity. Biochemical analyses revealed that the parasite has a GCS located in endoplasmic reticulum (ER) membranes that is active in proliferating and encysting trophozoites. Pharmacological inhibition of GCS induced aberrant cell division, characterized by arrest of cytokinesis, incomplete cleavage furrow formation, and consequent block of replication. Importantly, we showed that increased ceramide levels were responsible for the cytokinesis arrest. In addition, GCS inhibition resulted in prominent ultrastructural abnormalities, including accumulation of cytosolic vesicles, enlarged lysosomes, and clathrin disorganization. Moreover, anterograde trafficking of the encystations-specific protein CWP1 was severely compromised and resulted in inhibition of stage differentiation. Our results reveal novel aspects of lipid metabolism in G. lamblia and specifically highlight the vital role of GCS in regulating cell cycle progression, membrane trafficking events, and stage differentiation in this parasite. In addition, we identified ceramide as a potent bioactive molecule, underscoring the universal conservation of ceramide signaling in eukaryotes. PMID:20335568
Billcliff, Peter G.; Noakes, Christopher J.; Mehta, Zenobia B.; Yan, Guanhua; Mak, LokHang; Woscholski, Rudiger; Lowe, Martin
2016-01-01
Mutation of the inositol 5-phosphatase OCRL1 causes Lowe syndrome and Dent-2 disease. Loss of OCRL1 function perturbs several cellular processes, including membrane traffic, but the underlying mechanisms remain poorly defined. Here we show that OCRL1 is part of the membrane-trafficking machinery operating at the trans-Golgi network (TGN)/endosome interface. OCRL1 interacts via IPIP27A with the F-BAR protein pacsin 2. OCRL1 and IPIP27A localize to mannose 6-phosphate receptor (MPR)–containing trafficking intermediates, and loss of either protein leads to defective MPR carrier biogenesis at the TGN and endosomes. OCRL1 5-phosphatase activity, which is membrane curvature sensitive, is stimulated by IPIP27A-mediated engagement of OCRL1 with pacsin 2 and promotes scission of MPR-containing carriers. Our data indicate a role for OCRL1, via IPIP27A, in regulating the formation of pacsin 2–dependent trafficking intermediates and reveal a mechanism for coupling PtdIns(4,5)P2 hydrolysis with carrier biogenesis on endomembranes. PMID:26510499
Olivier-Mason, Anique; Wojtyniak, Martin; Bowie, Rachel V.; Nechipurenko, Inna V.; Blacque, Oliver E.; Sengupta, Piali
2013-01-01
The structure and function of primary cilia are critically dependent on intracellular trafficking pathways that transport ciliary membrane and protein components. The mechanisms by which these trafficking pathways are regulated are not fully characterized. Here we identify the transmembrane protein OSTA-1 as a new regulator of the trafficking pathways that shape the morphology and protein composition of sensory cilia in C. elegans. osta-1 encodes an organic solute transporter alpha-like protein, mammalian homologs of which have been implicated in membrane trafficking and solute transport, although a role in regulating cilia structure has not previously been demonstrated. We show that mutations in osta-1 result in altered ciliary membrane volume, branch length and complexity, as well as defects in localization of a subset of ciliary transmembrane proteins in different sensory cilia types. OSTA-1 is associated with transport vesicles, localizes to a ciliary compartment shown to house trafficking proteins, and regulates both retrograde and anterograde flux of the endosome-associated RAB-5 small GTPase. Genetic epistasis experiments with sensory signaling, exocytic and endocytic proteins further implicate OSTA-1 as a crucial regulator of ciliary architecture via regulation of cilia-destined trafficking. Our findings suggest that regulation of transport pathways in a cell type-specific manner contributes to diversity in sensory cilia structure and might allow dynamic remodeling of ciliary architecture via multiple inputs. PMID:23482491
Bexiga, Mariana G; Simpson, Jeremy C
2016-01-01
RNA interference (RNAi) has become an essential tool for molecular and cellular biologists to dissect cell function. In recent years its application has been extended to genome-wide studies, enabling the systematic identification of new cell regulation mechanisms and drug targets. In this chapter, a protocol for a genome-wide RNAi screen coupled to high-content microscopy is presented. Specifically we describe key features of assay design, plate layout, and a protocol for forward transfection of small interfering RNAs (siRNAs) in a 384-well plate format. As an example of its application in identifying modulators of membrane trafficking, we also provide a protocol to measure the efficacy of intracellular delivery of the B subunit of Shiga-like toxin to the Golgi complex. Finally we show an automated image analysis routine that can be used to extract single cell data from the screen, thereby providing a quantitative ranking of how a large panel of siRNAs affects this biological process. PMID:27581283
Bhutta, Musab S.; Roy, Brinta; Gould, Gwyn W.; McInerny, Christopher J.
2014-01-01
Cytokinesis and cell separation are critical events in the cell cycle. We show that Endosomal Sorting Complex Required for Transport (ESCRT) genes are required for cell separation in Schizosaccharomyces pombe. We identify genetic interactions between ESCRT proteins and polo and aurora kinases and Cdc14 phosphatase that manifest as impaired growth and exacerbated defects in septation, suggesting that the encoded proteins function together to control these processes. Furthermore, we observed defective endosomal sorting in mutants of plo1, ark1 and clp1, as has been reported for ESCRT mutants, consistent with a role for these kinases in the control of ESCRT function in membrane traffic. Multiple observations indicate functional interplay between polo and ESCRT components: firstly, two-hybrid in vivo interactions are reported between Plo1p and Sst4p, Vps28p, Vps25p, Vps20p and Vps32p; secondly, co-immunoprecipitation of human homologues of Vps20p, Vps32p, Vps24p and Vps2p by human Plk1; and thirdly, in vitro phosphorylation of budding yeast Vps32p and Vps20p by polo kinase. Two-hybrid analyses also identified interactions between Ark1p and Vps20p and Vps32p, and Clp1p and Vps28p. These experiments indicate a network of interactions between ESCRT proteins, plo1, ark1 and clp1 that coordinate membrane trafficking and cell separation in fission yeast. PMID:25356547
Ultra-fast consensus of discrete-time multi-agent systems with multi-step predictive output feedback
NASA Astrophysics Data System (ADS)
Zhang, Wenle; Liu, Jianchang
2016-04-01
This article addresses the ultra-fast consensus problem of high-order discrete-time multi-agent systems based on a unified consensus framework. A novel multi-step predictive output mechanism is proposed under a directed communication topology containing a spanning tree. By predicting the outputs of a network several steps ahead and adding this information into the consensus protocol, it is shown that the asymptotic convergence factor is improved by a power of q + 1 compared to the routine consensus. The difficult problem of selecting the optimal control gain is solved well by introducing a variable called convergence step. In addition, the ultra-fast formation achievement is studied on the basis of this new consensus protocol. Finally, the ultra-fast consensus with respect to a reference model and robust consensus is discussed. Some simulations are performed to illustrate the effectiveness of the theoretical results.
Chen, Yi-Yung; Rosario, Fredrick J; Shehab, Majida Abu; Powell, Theresa L; Gupta, Madhulika B; Jansson, Thomas
2015-12-01
Placental amino acid transport is decreased in intrauterine growth restriction (IUGR); however, the underlying mechanisms remain largely unknown. We have shown that mechanistic target of rapamycin (mTOR) signalling regulates system A amino acid transport by modulating the ubiquitination and plasma membrane trafficking of sodium-coupled neutral amino acid transporter 2 (SNAT-2) in cultured primary human trophoblast cells. We hypothesize that IUGR is associated with (1) inhibition of placental mTORC1 and mTORC2 signalling pathways, (2) increased amino acid transporter ubiquitination in placental homogenates and (3) decreased protein expression of SNAT-2 in the syncytiotrophoblast microvillous plasma membrane (MVM). To test this hypothesis, we collected placental tissue and isolated MVM from women with pregnancies complicated by IUGR (n=25) and gestational age-matched women with appropriately grown control infants (n=19, birth weights between the twenty-fifth to seventy-fifth percentiles). The activity of mTORC1 and mTORC2 was decreased whereas the protein expression of the ubiquitin ligase NEDD4-2 (neural precursor cell expressed developmentally down-regulated protein 4-2; +72%, P<0.0001) and the ubiquitination of SNAT-2 (+180%, P<0.05) were increased in homogenates of IUGR placentas. Furthermore, IUGR was associated with decreased system A amino acid transport activity (-72%, P<0.0001) and SNAT-1 (-42%, P<0.05) and SNAT-2 (-31%, P<0.05) protein expression in MVM. In summary, these findings are consistent with the possibility that decreased placental mTOR activity causes down-regulation of placental system A activity by shifting SNAT-2 trafficking towards proteasomal degradation, thereby contributing to decreased fetal amino acid availability and restricted fetal growth in IUGR. PMID:26374858
The golgin GMAP-210 is required for efficient membrane trafficking in the early secretory pathway
Roboti, Peristera; Sato, Keisuke; Lowe, Martin
2015-01-01
Golgins are coiled-coil proteins that participate in membrane-tethering events at the Golgi complex. Golgin-mediated tethering is thought to be important for vesicular trafficking and Golgi organization. However, the degree to which individual golgins contribute to these processes is poorly defined, and it has been proposed that golgins act in a largely redundant manner. Previous studies on the golgin GMAP-210 (also known as TRIP11), which is mutated in the rare skeletal disorder achondrogenesis type 1A, have yielded conflicting results regarding its involvement in trafficking. Here, we re-investigated the trafficking role of GMAP-210, and found that it is indeed required for efficient trafficking in the secretory pathway. GMAP-210 acts at both the endoplasmic reticulum (ER)-to-Golgi intermediate compartment (ERGIC) and Golgi complex during anterograde trafficking, and is also required for retrograde trafficking to the ER. Using co-depletion experiments, we also found that GMAP-210 acts in a partially redundant manner with the golgin GM130 to ensure efficient anterograde cargo delivery to the cis-Golgi. In summary, our results indicate a role for GMAP-210 in several trafficking steps at the ER–Golgi interface, some of which are partially redundant with another golgin, namely GM130 (also known as GOLGA2). PMID:25717001
The golgin GMAP-210 is required for efficient membrane trafficking in the early secretory pathway.
Roboti, Peristera; Sato, Keisuke; Lowe, Martin
2015-04-15
Golgins are coiled-coil proteins that participate in membrane-tethering events at the Golgi complex. Golgin-mediated tethering is thought to be important for vesicular trafficking and Golgi organization. However, the degree to which individual golgins contribute to these processes is poorly defined, and it has been proposed that golgins act in a largely redundant manner. Previous studies on the golgin GMAP-210 (also known as TRIP11), which is mutated in the rare skeletal disorder achondrogenesis type 1A, have yielded conflicting results regarding its involvement in trafficking. Here, we re-investigated the trafficking role of GMAP-210, and found that it is indeed required for efficient trafficking in the secretory pathway. GMAP-210 acts at both the endoplasmic reticulum (ER)-to-Golgi intermediate compartment (ERGIC) and Golgi complex during anterograde trafficking, and is also required for retrograde trafficking to the ER. Using co-depletion experiments, we also found that GMAP-210 acts in a partially redundant manner with the golgin GM130 to ensure efficient anterograde cargo delivery to the cis-Golgi. In summary, our results indicate a role for GMAP-210 in several trafficking steps at the ER-Golgi interface, some of which are partially redundant with another golgin, namely GM130 (also known as GOLGA2). PMID:25717001
2015-01-01
When simulating molecular systems using deterministic equations of motion (e.g., Newtonian dynamics), such equations are generally numerically integrated according to a well-developed set of algorithms that share commonly agreed-upon desirable properties. However, for stochastic equations of motion (e.g., Langevin dynamics), there is still broad disagreement over which integration algorithms are most appropriate. While multiple desiderata have been proposed throughout the literature, consensus on which criteria are important is absent, and no published integration scheme satisfies all desiderata simultaneously. Additional nontrivial complications stem from simulating systems driven out of equilibrium using existing stochastic integration schemes in conjunction with recently developed nonequilibrium fluctuation theorems. Here, we examine a family of discrete time integration schemes for Langevin dynamics, assessing how each member satisfies a variety of desiderata that have been enumerated in prior efforts to construct suitable Langevin integrators. We show that the incorporation of a novel time step rescaling in the deterministic updates of position and velocity can correct a number of dynamical defects in these integrators. Finally, we identify a particular splitting (related to the velocity Verlet discretization) that has essentially universally appropriate properties for the simulation of Langevin dynamics for molecular systems in equilibrium, nonequilibrium, and path sampling contexts. PMID:24555448
Small RAB GTPases Regulate Multiple Steps of Mitosis.
Miserey-Lenkei, Stéphanie; Colombo, María I
2016-01-01
GTPases of the RAB family are key regulators of multiple steps of membrane trafficking. Several members of the RAB GTPase family have been implicated in mitotic progression. In this review, we will first focus on the function of endosome-associated RAB GTPases reported in early steps of mitosis, spindle pole maturation, and during cytokinesis. Second, we will discuss the role of Golgi-associated RAB GTPases at the metaphase/anaphase transition and during cytokinesis. PMID:26925400
Small RAB GTPases Regulate Multiple Steps of Mitosis
Miserey-Lenkei, Stéphanie; Colombo, María I.
2016-01-01
GTPases of the RAB family are key regulators of multiple steps of membrane trafficking. Several members of the RAB GTPase family have been implicated in mitotic progression. In this review, we will first focus on the function of endosome-associated RAB GTPases reported in early steps of mitosis, spindle pole maturation, and during cytokinesis. Second, we will discuss the role of Golgi-associated RAB GTPases at the metaphase/anaphase transition and during cytokinesis. PMID:26925400
McHugh, P.R.; Knoll, D.A.
1992-01-01
A fully implicit solution algorithm based on Newton's method is used to solve the steady, incompressible Navier-Stokes and energy equations. An efficiently evaluated numerical Jacobian is used to simplify implementation, and mesh sequencing is used to increase the radius of convergence of the algorithm. We employ finite volume discretization using the power law scheme of Patankar to solve the benchmark backward facing step problem defined by the ASME K-12 Aerospace Heat Transfer Committee. LINPACK banded Gaussian elimination and the preconditioned transpose-free quasi-minimal residual (TFQMR) algorithm of Freund are studied as possible linear equation solvers. Implementation of the preconditioned TFQMR algorithm requires use of the switched evolution relaxation algorithm of Mulder and Van Leer to ensure convergence. The preconditioned TFQMR algorithm is more memory efficient than the direct solver, but our implementation is not as CPU efficient. Results show that for the level of grid refinement used, power law differencing was not adequate to yield the desired accuracy for this problem.
Cho, Hyungseoph J; Gee, Heon Yung; Baek, Kyung-Hwa; Ko, Sung-Kyun; Park, Jong-Moon; Lee, Hookeun; Kim, Nam-Doo; Lee, Min Goo; Shin, Injae
2011-12-21
Cystic fibrosis transmembrane conductance regulator (CFTR) is a cell-surface anion channel that permeates chloride and bicarbonate ions. The most frequent mutation of CFTR that causes cystic fibrosis is the deletion of phenylalanine at position 508 (ΔF508), which leads to defects in protein folding and cellular trafficking to the plasma membrane. The lack of the cell-surface CFTR results in a reduction in the lifespan due to chronic lung infection with progressive deterioration of lung function. Hsc70 plays a crucial role in degradation of mutant CFTR by the ubiquitin-proteasome system. To date, various Hsc70 inhibitors and transcription regulators have been tested to determine whether they correct the defective activity of mutant CFTR. However, they exhibited limited or questionable effects on restoring the chloride channel activity in cystic fibrosis cells. Herein, we show that a small molecule apoptozole (Az) has high cellular potency to promote membrane trafficking of mutant CFTR and its chloride channel activity in cystic fibrosis cells. Results from affinity chromatography and ATPase activity assay indicate that Az inhibits the ATPase activity of Hsc70 by binding to its ATPase domain. In addition, a ligand-directed protein labeling and molecular modeling studies also suggest the binding of Az to an ATPase domain, in particular, an ATP-binding pocket. It is proposed that Az suppresses ubiquitination of ΔF508-CFTR maybe by blocking interaction of the mutant with Hsc70 and CHIP, and, as a consequence, it enhances membrane trafficking of the mutant. PMID:22074182
Allet, L; Kim, H; Ashton-Miller, JA; De Mott, T; Richardson, JK
2013-01-01
Aims Distal symmetric polyneuropathy increases fall risk due to inability to cope with perturbations. We aimed to 1) identify the frontal plane lower limb sensorimotor functions which are necessary for robustness to a discrete, underfoot perturbation during gait; and 2) determine whether changes in the post-perturbed step parameters could distinguish between fallers and non fallers. Methods Forty-two subjects (16 healthy old and 26 with diabetic PN) participated. Frontal plane lower limb sensorimotor functions were determined using established laboratory-based techniques. The subjects' most extreme alterations in step width or step length in response to a perturbation were measured. In addition, falls and fall-related injuries were prospectively recorded. Results Ankle proprioceptive threshold (APrT; p=.025) and hip abduction rate of torque generation (RTG; p=.041) independently predicted extreme step length after medial perturbation, with precise APrT and greater hip RTG allowing maintenance of step length. Fallers demonstrated greater extreme step length changes after medial perturbation than non fallers (percent change = 16.41±8.42 vs 11.0±4.95; p=.06) Conclusions The ability to rapidly generate frontal plane hip strength and/or precisely perceive motion at the ankle is needed to maintain a normal step length after perturbation, a parameter, which distinguishes between fallers and non fallers. PMID:24183899
Naramoto, Satoshi; Otegui, Marisa S; Kutsuna, Natsumaro; de Rycke, Riet; Dainobu, Tomoko; Karampelias, Michael; Fujimoto, Masaru; Feraru, Elena; Miki, Daisuke; Fukuda, Hiroo; Nakano, Akihiko; Friml, Jiří
2014-07-01
GNOM is one of the most characterized membrane trafficking regulators in plants, with crucial roles in development. GNOM encodes an ARF-guanine nucleotide exchange factor (ARF-GEF) that activates small GTPases of the ARF (ADP ribosylation factor) class to mediate vesicle budding at endomembranes. The crucial role of GNOM in recycling of PIN auxin transporters and other proteins to the plasma membrane was identified in studies using the ARF-GEF inhibitor brefeldin A (BFA). GNOM, the most prominent regulator of recycling in plants, has been proposed to act and localize at so far elusive recycling endosomes. Here, we report the GNOM localization in context of its cellular function in Arabidopsis thaliana. State-of-the-art imaging, pharmacological interference, and ultrastructure analysis show that GNOM predominantly localizes to Golgi apparatus. Super-resolution confocal live imaging microscopy identified GNOM and its closest homolog GNOM-like 1 at distinct subdomains on Golgi cisternae. Short-term BFA treatment stabilizes GNOM at the Golgi apparatus, whereas prolonged exposures results in GNOM translocation to trans-Golgi network (TGN)/early endosomes (EEs). Malformed TGN/EE in gnom mutants suggests a role for GNOM in maintaining TGN/EE function. Our results redefine the subcellular action of GNOM and reevaluate the identity and function of recycling endosomes in plants. PMID:25012191
Wang, Deng-Ke; Liu, Ying; Myers, Evan J.; Guo, Yi-Min; Xie, Zhang-Dong; Jiang, De-Zhi; Li, Jia-Min; Yang, Jichun; Liu, Mugen; Parker, Mark D.; Chen, Li-Ming
2015-01-01
The SLC4 genes are all capable of producing multiple variants by alternative splicing or using alternative promoters. The physiological consequences of such diversity are of great interest to investigators. Here, we identified two novel variants of the electroneutral Na+/ cotransporter NBCn1, one full-length starting with “MIPL” and the other Nt-truncated starting with “MDEL”. Moreover, we identified a new promoter of Slc4a10 encoding NBCn2 and a novel type of Nt-truncated NBCn2 starting with “MHAN”. When heterologously expressed, the new NBCn1 variants were well localized to the plasma membrane and exhibited characteristic NBCn1 activity. However, MHAN-NBCn2 was poorly localized on the plasma membrane. By deletion mutations, we identified the Nt regions important for the surface localization of NBCn2. Interestingly, coexpressing the full-length NBCn2 greatly enhances the surface abundance of the Nt-truncated NBCn2. Co-immunoprecipitation and bimolecular fluorescence complementation studies showed that the full-length and Nt-truncated NBCn2 interact with each other to form heterodimers in neuro-2A cells. Finally, we showed that the isolated Nt domain interacts with and enhances the surface abundance of the Nt-truncated NBCn2. The present study expands our knowledge of the NBCn1 and NBCn2 transcriptome, and provides insights into how the Nt domain could affect transporter function by regulating its membrane trafficking. PMID:26192895
Parmar, Hirendrasinh B; Duncan, Roy
2016-04-15
The reovirus fusion-associated small transmembrane (FAST) proteins comprise a unique family of viral membrane fusion proteins dedicated to inducing cell-cell fusion. We recently reported that a polybasic motif (PBM) in the cytosolic tail of reptilian reovirus p14 FAST protein functions as a novel tribasic Golgi export signal. Using coimmunoprecipitation and fluorescence resonance energy transfer (FRET) assays, we now show the PBM directs interaction of p14 with GTP-Rab11. Overexpression of dominant-negative Rab11 and RNA interference knockdown of endogenous Rab11 inhibited p14 plasma membrane trafficking and resulted in p14 accumulation in the Golgi complex. This is the first example of Golgi export to the plasma membrane that is dependent on the interaction of membrane protein cargo with activated Rab11. RNA interference and immunofluorescence microscopy further revealed that p14 Golgi export is dependent on AP-1 (but not AP-3 or AP-4) and that Rab11 and AP-1 both colocalize with p14 at the TGN. Together these results imply the PBM mediates interactions of p14 with activated Rab11 at the TGN, resulting in p14 sorting into AP1-coated vesicles for anterograde TGN-plasma membrane transport. PMID:26941330
Wang, Deng-Ke; Liu, Ying; Myers, Evan J; Guo, Yi-Min; Xie, Zhang-Dong; Jiang, De-Zhi; Li, Jia-Min; Yang, Jichun; Liu, Mugen; Parker, Mark D; Chen, Li-Ming
2015-01-01
The SLC4 genes are all capable of producing multiple variants by alternative splicing or using alternative promoters. The physiological consequences of such diversity are of great interest to investigators. Here, we identified two novel variants of the electroneutral Na(+)/HCO3- cotransporter NBCn1, one full-length starting with "MIPL" and the other Nt-truncated starting with "MDEL". Moreover, we identified a new promoter of Slc4a10 encoding NBCn2 and a novel type of Nt-truncated NBCn2 starting with "MHAN". When heterologously expressed, the new NBCn1 variants were well localized to the plasma membrane and exhibited characteristic NBCn1 activity. However, MHAN-NBCn2 was poorly localized on the plasma membrane. By deletion mutations, we identified the Nt regions important for the surface localization of NBCn2. Interestingly, coexpressing the full-length NBCn2 greatly enhances the surface abundance of the Nt-truncated NBCn2. Co-immunoprecipitation and bimolecular fluorescence complementation studies showed that the full-length and Nt-truncated NBCn2 interact with each other to form heterodimers in neuro-2A cells. Finally, we showed that the isolated Nt domain interacts with and enhances the surface abundance of the Nt-truncated NBCn2. The present study expands our knowledge of the NBCn1 and NBCn2 transcriptome, and provides insights into how the Nt domain could affect transporter function by regulating its membrane trafficking. PMID:26192895
Sugano, Shoji; Hayashi, Nagao; Kawagoe, Yasushi; Mochizuki, Susumu; Inoue, Haruhiko; Mori, Masaki; Nishizawa, Yoko; Jiang, Chang-Jie; Matsui, Minami; Takatsuji, Hiroshi
2016-05-01
Membrane trafficking plays pivotal roles in many cellular processes including plant immunity. Here, we report the characterization of OsVAMP714, an intracellular SNARE protein, focusing on its role in resistance to rice blast disease caused by the fungal pathogen Magnaporthe oryzae. Disease resistance tests using OsVAMP714 knockdown and overexpressing rice plants demonstrated the involvement of OsVAMP714 in blast resistance. The overexpression of OsVAMP7111, whose product is highly homologous to OsVAMP714, did not enhance blast resistance to rice, implying a potential specificity of OsVAMP714 to blast resistance. OsVAMP714 was localized to the chloroplast in mesophyll cells and to the cellular periphery in epidermal cells of transgenic rice plant leaves. We showed that chloroplast localization is critical for the normal OsVAMP714 functioning in blast resistance by analyzing the rice plants overexpressing OsVAMP714 mutants whose products did not localize in the chloroplast. We also found that OsVAMP714 was located in the vacuolar membrane surrounding the invasive hyphae of M. oryzae. Furthermore, we showed that OsVAMP714 overexpression promotes leaf sheath elongation and that the first 19 amino acids, which are highly conserved between animal and plant VAMP7 proteins, are crucial for normal rice plant growths. Our studies imply that the OsVAMP714-mediated trafficking pathway plays an important role in rice blast resistance as well as in the vegetative growth of rice. PMID:26879413
Naramoto, Satoshi; Otegui, Marisa S.; Kutsuna, Natsumaro; de Rycke, Riet; Dainobu, Tomoko; Karampelias, Michael; Fujimoto, Masaru; Feraru, Elena; Miki, Daisuke; Fukuda, Hiroo; Nakano, Akihiko; Friml, Jiří
2014-01-01
GNOM is one of the most characterized membrane trafficking regulators in plants, with crucial roles in development. GNOM encodes an ARF-guanine nucleotide exchange factor (ARF-GEF) that activates small GTPases of the ARF (ADP ribosylation factor) class to mediate vesicle budding at endomembranes. The crucial role of GNOM in recycling of PIN auxin transporters and other proteins to the plasma membrane was identified in studies using the ARF-GEF inhibitor brefeldin A (BFA). GNOM, the most prominent regulator of recycling in plants, has been proposed to act and localize at so far elusive recycling endosomes. Here, we report the GNOM localization in context of its cellular function in Arabidopsis thaliana. State-of-the-art imaging, pharmacological interference, and ultrastructure analysis show that GNOM predominantly localizes to Golgi apparatus. Super-resolution confocal live imaging microscopy identified GNOM and its closest homolog GNOM-like 1 at distinct subdomains on Golgi cisternae. Short-term BFA treatment stabilizes GNOM at the Golgi apparatus, whereas prolonged exposures results in GNOM translocation to trans-Golgi network (TGN)/early endosomes (EEs). Malformed TGN/EE in gnom mutants suggests a role for GNOM in maintaining TGN/EE function. Our results redefine the subcellular action of GNOM and reevaluate the identity and function of recycling endosomes in plants. PMID:25012191
Parmar, Hirendrasinh B.; Duncan, Roy
2016-01-01
The reovirus fusion–associated small transmembrane (FAST) proteins comprise a unique family of viral membrane fusion proteins dedicated to inducing cell–cell fusion. We recently reported that a polybasic motif (PBM) in the cytosolic tail of reptilian reovirus p14 FAST protein functions as a novel tribasic Golgi export signal. Using coimmunoprecipitation and fluorescence resonance energy transfer (FRET) assays, we now show the PBM directs interaction of p14 with GTP-Rab11. Overexpression of dominant-negative Rab11 and RNA interference knockdown of endogenous Rab11 inhibited p14 plasma membrane trafficking and resulted in p14 accumulation in the Golgi complex. This is the first example of Golgi export to the plasma membrane that is dependent on the interaction of membrane protein cargo with activated Rab11. RNA interference and immunofluorescence microscopy further revealed that p14 Golgi export is dependent on AP-1 (but not AP-3 or AP-4) and that Rab11 and AP-1 both colocalize with p14 at the TGN. Together these results imply the PBM mediates interactions of p14 with activated Rab11 at the TGN, resulting in p14 sorting into AP1-coated vesicles for anterograde TGN–plasma membrane transport. PMID:26941330
Williams, Marissa; Catchpoole, Daniel
2013-01-01
The accumulation of weakly basic drugs into acidic organelles has recently been described as a contributor to resistance in childhood cancer rhabdomyosarcoma (RMS) cell lines with differential sensitivity to a novel topoisomerase II inhibitor, AS-DACA. The current study aims to explore the contribution of the endocytic pathway to AS-DACA sequestration in RMS cell lines. A 24-fold differential in AS-DACA cytotoxicity was detected between the RMS lines RD and Rh30. The effect of inhibitors of the endocytic pathway on AS-DACA sensitivity in RMS cell lines, coupled with the variations of endosomal marker expression, indicated the late endosomal/lysosomal compartment was implicated by confounding lines of evidence. Higher expression levels of Lysosomal-Associated Membrane Protein-1 (LAMP1) in the resistant RMS cell line, RD, provided correlations between the increased amount and activity of these compartments to AS-DACA resistance. The late endosomal inhibitor 3-methyladenine increased AS-DACA sensitivity solely in RD leading to the reduction of AS-DACA in membrane trafficking organelles. Acidification inhibitors did not produce an increase in AS-DACA sensitivity nor reduce its sequestration, indicating that the pH partitioning of weakly basic drugs into acidic compartments does not likely contribute to the AS-DACA sequestering resistance mechanism evident in RMS cells. PMID:23799359
Jiu, Yaming; Hasygar, Kiran; Tang, Lois; Liu, Yanbo; Holmberg, Carina I.; Bürglin, Thomas R.; Hietakangas, Ville; Jäntti, Jussi
2013-01-01
The exocyst is a conserved protein complex that is involved in tethering secretory vesicles to the plasma membrane and regulating cell polarity. Despite a large body of work, little is known how exocyst function is controlled. To identify regulators for exocyst function, we performed a targeted RNA interference (RNAi) screen in Caenorhabditis elegans to uncover kinases and phosphatases that genetically interact with the exocyst. We identified seven kinase and seven phosphatase genes that display enhanced phenotypes when combined with hypomorphic alleles of exoc-7 (exo70), exoc-8 (exo84), or an exoc-7;exoc-8 double mutant. We show that in line with its reported role in exocytotic membrane trafficking, a defective exoc-8 caused accumulation of exocytotic soluble NSF attachment protein receptor (SNARE) proteins in both intestinal and neuronal cells in C. elegans. Down-regulation of the phosphatase protein phosphatase 2A (PP2A) phosphatase regulatory subunit sur-6/B55 gene resulted in accumulation of exocytic SNARE proteins SNB-1 and SNAP-29 in wild-type and in exoc-8 mutant animals. In contrast, RNAi of the kinase par-1 caused reduced intracellular green fluorescent protein signal for the same proteins. Double RNAi experiments for par-1, pkc-3, and sur-6/B55 in C. elegans suggest a possible cooperation and involvement in postembryo lethality, developmental timing, as well as SNARE protein trafficking. Functional analysis of the homologous kinases and phosphatases in Drosophila median neurosecretory cells showed that atypical protein kinase C kinase and phosphatase PP2A regulate exocyst-dependent, insulin-like peptide secretion. Collectively, these results characterize kinases and phosphatases implicated in the regulation of exocyst function, and suggest the possibility for interplay between the par-1 and pkc-3 kinases and the PP2A phosphatase regulatory subunit sur-6 in this process. PMID:24192838
Jiu, Yaming; Hasygar, Kiran; Tang, Lois; Liu, Yanbo; Holmberg, Carina I; Bürglin, Thomas R; Hietakangas, Ville; Jäntti, Jussi
2014-01-01
The exocyst is a conserved protein complex that is involved in tethering secretory vesicles to the plasma membrane and regulating cell polarity. Despite a large body of work, little is known how exocyst function is controlled. To identify regulators for exocyst function, we performed a targeted RNA interference (RNAi) screen in Caenorhabditis elegans to uncover kinases and phosphatases that genetically interact with the exocyst. We identified seven kinase and seven phosphatase genes that display enhanced phenotypes when combined with hypomorphic alleles of exoc-7 (exo70), exoc-8 (exo84), or an exoc-7;exoc-8 double mutant. We show that in line with its reported role in exocytotic membrane trafficking, a defective exoc-8 caused accumulation of exocytotic soluble NSF attachment protein receptor (SNARE) proteins in both intestinal and neuronal cells in C. elegans. Down-regulation of the phosphatase protein phosphatase 2A (PP2A) phosphatase regulatory subunit sur-6/B55 gene resulted in accumulation of exocytic SNARE proteins SNB-1 and SNAP-29 in wild-type and in exoc-8 mutant animals. In contrast, RNAi of the kinase par-1 caused reduced intracellular green fluorescent protein signal for the same proteins. Double RNAi experiments for par-1, pkc-3, and sur-6/B55 in C. elegans suggest a possible cooperation and involvement in postembryo lethality, developmental timing, as well as SNARE protein trafficking. Functional analysis of the homologous kinases and phosphatases in Drosophila median neurosecretory cells showed that atypical protein kinase C kinase and phosphatase PP2A regulate exocyst-dependent, insulin-like peptide secretion. Collectively, these results characterize kinases and phosphatases implicated in the regulation of exocyst function, and suggest the possibility for interplay between the par-1 and pkc-3 kinases and the PP2A phosphatase regulatory subunit sur-6 in this process. PMID:24192838
Zhu, Ming; Wu, Gang; Li, Yu-Xin; Stevens, Julia Kathrin; Fan, Chao-Xuan; Spang, Anne; Dong, Meng-Qiu
2015-01-01
The mammalian serum- and glucocorticoid-inducible kinase SGK1 regulates the endocytosis of ion channels. Here we report that in C. elegans sgk-1 null mutants, GFP-tagged MIG-14/Wntless, the sorting receptor of Wnt, failed to localize to the basolateral membrane of intestinal cells; instead, it was mis-sorted to lysosomes. This effect can be explained in part by altered sphingolipid levels, because reducing glucosylceramide biosynthesis restored the localization of MIG-14::GFP. Membrane traffic was not perturbed in general, as no obvious morphological defects were detected for early endosomes, the Golgi apparatus, and the endoplasmic reticulum (ER) in sgk-1 null animals. The recycling of MIG-14/Wntless through the Golgi might be partially responsible for the observed phenotype because the subcellular distribution of two plasma membrane cargoes that do not recycle through the trans-Golgi network (TGN) was affected to a lesser degree. Consistently, knockdown of the ArfGEF gbf-1 altered the distribution of SGK-1 at the basolateral membrane of intestinal cells. In addition, we found that sgk-1(RNAi) induced unfolded protein response in the ER, suggesting at least an indirect role of SGK-1 early in the secretory pathway. We propose that SGK-1 function is required for lipid homeostasis and that it acts at different intracellular trafficking steps. PMID:26115433
DNS and LES of Turbulent Backward-Facing Step Flow Using 2ND-and 4TH-Order Discretization
NASA Astrophysics Data System (ADS)
Meri, Adnan; Wengle, Hans
Results are presented from a Direct Numerical Simulation (DNS) and Large-Eddy Simulations (LES) of turbulent flow over a backward-facing step (Reh=3300) with a fully developed channel flow (Rcτ=180) utilized asatime-dependent inflow condition. Numerical solutions using a fourth-order compact (Hermitian) scheme, which was formulated directly for anon-equidistant and staggered grid in [1] are compared with numerical solutions using the classical second-order central scheme. There sults from LES (using the dynamic subgrid scale model) are evaluated against a corresponding DNS reference data set (fourth-order solution).
Latimer, Kenneth W; Yates, Jacob L; Meister, Miriam L R; Huk, Alexander C; Pillow, Jonathan W
2016-03-25
Shadlen et al's Comment focuses on extrapolations of our results that were not implied or asserted in our Report. They discuss alternate analyses of average firing rates in other tasks, the relationship between neural activity and behavior, and possible extensions of the standard models we examined. Although interesting to contemplate, these points are not germane to the findings of our Report: that stepping dynamics provided a better statistical description of lateral intraparietal area spike trains than diffusion-to-bound dynamics for a majority of neurons. PMID:27013724
NASA Astrophysics Data System (ADS)
Raymond, S.; Moatar, F.; Meybeck, M.; Bustillo, V.
2009-04-01
Good estimates of fluxes of suspended particulate matter (SPM), total dissolved solids (TDS) and nutrients and contaminants are required for both Earth System science and river basin management. However, in most cases discrete sampling (weekly to monthly) is the rule. Few flux calculation methods are commonly used, yet their performances, i.e. uncertainties for given frequencies, at given stations and for each water quality variables, remain unknown. Based on a rare set of 1085 station-year of daily flux record for SPM, TDS and nutrients (dissolved and total), the performance of 9 calculations methods is explored. Discrete surveys at various frequencies (3days to 30 days) are simulated by Monte-Carlo sorting (100 runs) on which the 9 fluxes are calculated (annual and interannual). At this stage, the sub-daily variations of fluxes for the medium and large basins are not considered. The dataset for SPM corresponds to 55 stations (600 to 600 000 km2 basin area), 34 stations (700 to 1000000 km2) for TDS and for nutrients we consider 9 stations for NO3-, NH4+, PO43- and Ptot (600 to 30 000 km2). About 80% of the dataset originates from US records (USGS and Lake Erie tributaries survey) and 20% from French stations, this covering a wide range of hydrological and geochemical conditions in the temperate zone. Each sorted flux is compared to known fluxes established on daily records: percentiles of their relative errors (e10, e50 and e90) are used to determine the biases (e50) and the imprecisions (e90-e10) (Walling and Webb, 1981) which are then compared for each of the 6 water quality variables, for each flux methods and for various simulated survey frequencies. The calculation methods include 5 rating-curve approaches (linear"M1", "M2", Phillipps et al, 1999) with and without Ferguson correction (Ferguson, 1987), polynomial, truncated at discharges exceeding median annual or long-term water discharge), 2 methods based on hydrograph separation (Phillips et al, 1999
Zhang, Wenle; Liu, Jianchang; Wang, Honghai
2015-09-01
This paper deals with the ultra-fast formation control problem of high-order discrete-time multi-agent systems. Using the local neighbor-error knowledge, a novel ultra-fast protocol with multi-step predictive information and self-feedback term is proposed. The asymptotic convergence factor is improved by a power of q+1 compared to the routine protocol. To some extent, the ultra-fast algorithm overcomes the influence of communication topology to the convergence speed. Furthermore, some sufficient conditions are given herein. The ones decouple the design of the synchronizing gains from the detailed graph properties, and explicitly reveal how the agent dynamic and the communication graph jointly affect the ultra-fast formationability. Finally, some simulations are worked out to illustrate the effectiveness of our theoretical results. PMID:26051965
Au, Catherine E.; Hermo, Louis; Byrne, Elliot; Smirle, Jeffrey; Fazel, Ali; Kearney, Robert E.; Smith, Charles E.; Vali, Hojatollah; Fernandez-Rodriguez, Julia; Simon, Paul H. G.; Mandato, Craig; Nilsson, Tommy; Bergeron, John J. M.
2015-01-01
Discovered in 1909 by Retzius and described mainly by morphology, the cytoplasmic droplet of sperm (renamed here the Hermes body) is conserved among all mammalian species but largely undefined at the molecular level. Tandem mass spectrometry of the isolated Hermes body from rat epididymal sperm characterized 1511 proteins, 43 of which were localized to the structure in situ by light microscopy and two by quantitative electron microscopy localization. Glucose transporter 3 (GLUT-3) glycolytic enzymes, selected membrane traffic and cytoskeletal proteins were highly abundant and concentrated in the Hermes body. By electron microscope gold antibody labelling, the Golgi trafficking protein TMED7/p27 localized to unstacked flattened cisternae of the Hermes body, as did GLUT-3, the most abundant protein. Its biogenesis was deduced through the mapping of protein expression for all 43 proteins during male germ cell differentiation in the testis. It is at the terminal step 19 of spermiogenesis that the 43 characteristic proteins accumulated in the nascent Hermes body. PMID:26311421
Au, Catherine E; Hermo, Louis; Byrne, Elliot; Smirle, Jeffrey; Fazel, Ali; Kearney, Robert E; Smith, Charles E; Vali, Hojatollah; Fernandez-Rodriguez, Julia; Simon, Paul H G; Mandato, Craig; Nilsson, Tommy; Bergeron, John J M
2015-08-01
Discovered in 1909 by Retzius and described mainly by morphology, the cytoplasmic droplet of sperm (renamed here the Hermes body) is conserved among all mammalian species but largely undefined at the molecular level. Tandem mass spectrometry of the isolated Hermes body from rat epididymal sperm characterized 1511 proteins, 43 of which were localized to the structure in situ by light microscopy and two by quantitative electron microscopy localization. Glucose transporter 3 (GLUT-3) glycolytic enzymes, selected membrane traffic and cytoskeletal proteins were highly abundant and concentrated in the Hermes body. By electron microscope gold antibody labelling, the Golgi trafficking protein TMED7/p27 localized to unstacked flattened cisternae of the Hermes body, as did GLUT-3, the most abundant protein. Its biogenesis was deduced through the mapping of protein expression for all 43 proteins during male germ cell differentiation in the testis. It is at the terminal step 19 of spermiogenesis that the 43 characteristic proteins accumulated in the nascent Hermes body. PMID:26311421
Synchronous Discrete Harmonic Oscillator
Antippa, Adel F.; Dubois, Daniel M.
2008-10-17
We introduce the synchronous discrete harmonic oscillator, and present an analytical, numerical and graphical study of its characteristics. The oscillator is synchronous when the time T for one revolution covering an angle of 2{pi} in phase space, is an integral multiple N of the discrete time step {delta}t. It is fully synchronous when N is even. It is pseudo-synchronous when T/{delta}t is rational. In the energy conserving hyperincursive representation, the phase space trajectories are perfectly stable at all time scales, and in both synchronous and pseudo-synchronous modes they cycle through a finite number of phase space points. Consequently, both the synchronous and the pseudo-synchronous hyperincursive modes of time-discretization provide a physically realistic and mathematically coherent, procedure for dynamic, background independent, discretization of spacetime. The procedure is applicable to any stable periodic dynamical system, and provokes an intrinsic correlation between space and time, whereby space-discretization is a direct consequence of background-independent time-discretization. Hence, synchronous discretization moves the formalism of classical mechanics towards that of special relativity. The frequency of the hyperincursive discrete harmonic oscillator is ''blue shifted'' relative to its continuum counterpart. The frequency shift has the precise value needed to make the speed of the system point in phase space independent of the discretizing time interval {delta}t. That is the speed of the system point is the same on the polygonal (in the discrete case) and the circular (in the continuum case) phase space trajectories.
Kisler, Kassandra; Chow, Robert H; Dominguez, Reymundo
2013-04-20
Estradiol is a steroid hormone that binds and activates estradiol receptors. Activation of these receptors is known to modulate neuronal physiology and provide neuroprotection, but it is not completely understood how estradiol mediates these actions on the nervous system. Activation of a sub-population of estradiol receptor-α (ERα), originally identified as a nuclear protein, localizes to the plasma membrane and appears to be a critical step in neuroprotection against brain injury and disease. Previously we showed that estradiol stimulates the rapid and transient trafficking of plasma membrane ERα in primary hypothalamic neurons, and internalization of membrane-impermeant estradiol (E6BSA-FITC) into cortical neuron endosomes in vitro. These findings support the concept that estradiol activates and down-regulates plasma membrane ERα by triggering endocytosis. Here, we use TIRFM (total internal reflection fluorescence microscopy) to image the trafficking of E6BSA-FITC, and GFP-labeled ERα, in live cells in real time. We show that activation of plasma membrane ERs by E6BSA-FITC result in internalization of the fluorescent ligand in live N-38 neurons, an immortalized hypothalamic cell line. Pretreatment with ER antagonist ICI 182,780 decreased the number of E6BSA-FITC labeled puncta observed. We also observed in live N-38 neurons that E6BSA-FITC co-localized with FM4-64 and LysoTracker fluorescent dyes that label endosomes and lysosomes. Our results provide further evidence that plasma membrane ERα activation results in endocytosis of the receptor. PMID:24353903
NASA Astrophysics Data System (ADS)
Arzano, Michele; Kowalski-Glikman, Jerzy
2016-09-01
We construct discrete symmetry transformations for deformed relativistic kinematics based on group valued momenta. We focus on the specific example of κ-deformations of the Poincaré algebra with associated momenta living on (a sub-manifold of) de Sitter space. Our approach relies on the description of quantum states constructed from deformed kinematics and the observable charges associated with them. The results we present provide the first step towards the analysis of experimental bounds on the deformation parameter κ to be derived via precision measurements of discrete symmetries and CPT.
NASA Astrophysics Data System (ADS)
Vivaldi, Franco
2015-12-01
The concept of resonance has been instrumental to the study of Hamiltonian systems with divided phase space. One can also define such systems over discrete spaces, which have a finite or countable number of points, but in this new setting the notion of resonance must be re-considered from scratch. I review some recent developments in the area of arithmetic dynamics which outline some salient features of linear and nonlinear stable (elliptic) orbits over a discrete space, and also underline the difficulties that emerge in their analysis.
NASA Astrophysics Data System (ADS)
Vivaldi, Franco
The concept of resonance has been instrumental to the study of Hamiltonian systems with divided phase space. One can also define such systems over discrete spaces, which have a finite or countable number of points, but in this new setting the notion of resonance must be re-considered from scratch. I review some recent developments in the area of arithmetic dynamics which outline some salient features of linear and nonlinear stable (elliptic) orbits over a discrete space, and also underline the difficulties that emerge in their analysis.
Novel approach to data discretization
NASA Astrophysics Data System (ADS)
Borowik, Grzegorz; Kowalski, Karol; Jankowski, Cezary
2015-09-01
Discretization is an important preprocessing step in data mining. The data discretization method involves determining the ranges of values for numeric attributes, which ultimately represent discrete intervals for new attributes. The ranges for the proposed set of cuts are analyzed, in order to obtain a minimal set of ranges while retaining the possibility of classification. For this purpose, a special discernibility function can be constructed as a conjunction of alternative cuts set for each pair of different objects of different decisions- cuts discern these objects. However, the data mining methods based on discernibility matrix are insufficient for large databases. The purpose of this paper is the idea of implementation of a new data discretization algorithm that is based on statistics of attribute values and that avoids building the discernibility matrix explicitly. Evaluation of time complexity has shown that the proposed method is much more efficient than currently available solutions for large data sets.
Discretization vs. Rounding Error in Euler's Method
ERIC Educational Resources Information Center
Borges, Carlos F.
2011-01-01
Euler's method for solving initial value problems is an excellent vehicle for observing the relationship between discretization error and rounding error in numerical computation. Reductions in stepsize, in order to decrease discretization error, necessarily increase the number of steps and so introduce additional rounding error. The problem is…
ERIC Educational Resources Information Center
Svetcov, Eric
2005-01-01
This article provides a list of the essential steps to keeping a school's or district's network safe and sound. It describes how to establish a security architecture and approach that will continually evolve as the threat environment changes over time. The article discusses the methodology for implementing this approach and then discusses the…
ERIC Educational Resources Information Center
Ghezzi, Patrick M.
2007-01-01
The advantages of emphasizing discrete trials "teaching" over discrete trials "training" are presented first, followed by a discussion of discrete trials as a method of teaching that emerged historically--and as a matter of necessity for difficult learners such as those with autism--from discrete trials as a method for laboratory research. The…
Breaking and Restoring of Diffeomorphism Symmetry in Discrete Gravity
Bahr, B.; Dittrich, B.
2009-12-15
We discuss the fate of diffeomorphism symmetry in discrete gravity. Diffeomorphism symmetry is typically broken by the discretization. This has repercussions for the observable content and the canonical formulation of the theory. It might however be possible to construct discrete actions, so-called perfect actions, with exact symmetries and we will review first steps towards this end.
Reduced discretization error in HZETRN
Slaba, Tony C.; Blattnig, Steve R.; Tweed, John
2013-02-01
The deterministic particle transport code HZETRN is an efficient analysis tool for studying the effects of space radiation on humans, electronics, and shielding materials. In a previous work, numerical methods in the code were reviewed, and new methods were developed that further improved efficiency and reduced overall discretization error. It was also shown that the remaining discretization error could be attributed to low energy light ions (A < 4) with residual ranges smaller than the physical step-size taken by the code. Accurately resolving the spectrum of low energy light particles is important in assessing risk associated with astronaut radiation exposure. In this work, modifications to the light particle transport formalism are presented that accurately resolve the spectrum of low energy light ion target fragments. The modified formalism is shown to significantly reduce overall discretization error and allows a physical approximation to be removed. For typical step-sizes and energy grids used in HZETRN, discretization errors for the revised light particle transport algorithms are shown to be less than 4% for aluminum and water shielding thicknesses as large as 100 g/cm{sup 2} exposed to both solar particle event and galactic cosmic ray environments.
Discrete elements method of neutral particle transport
Mathews, K.A.
1983-01-01
A new discrete elements (L/sub N/) transport method is derived and compared to the discrete ordinates S/sub N/ method, theoretically and by numerical experimentation. The discrete elements method is more accurate than discrete ordinates and strongly ameliorates ray effects for the practical problems studied. The discrete elements method is shown to be more cost effective, in terms of execution time with comparable storage to attain the same accuracy, for a one-dimensional test case using linear characteristic spatial quadrature. In a two-dimensional test case, a vacuum duct in a shield, L/sub N/ is more consistently convergent toward a Monte Carlo benchmark solution than S/sub N/, using step characteristic spatial quadrature. An analysis of the interaction of angular and spatial quadrature in xy-geometry indicates the desirability of using linear characteristic spatial quadrature with the L/sub N/ method.
Wood, Claire; Bremner, Brenda
2013-08-09
The Siletz Tribal Energy Program (STEP), housed in the Tribe’s Planning Department, will hire a data entry coordinator to collect, enter, analyze and store all the current and future energy efficiency and renewable energy data pertaining to administrative structures the tribe owns and operates and for homes in which tribal members live. The proposed data entry coordinator will conduct an energy options analysis in collaboration with the rest of the Siletz Tribal Energy Program and Planning Department staff. An energy options analysis will result in a thorough understanding of tribal energy resources and consumption, if energy efficiency and conservation measures being implemented are having the desired effect, analysis of tribal energy loads (current and future energy consumption), and evaluation of local and commercial energy supply options. A literature search will also be conducted. In order to educate additional tribal members about renewable energy, we will send four tribal members to be trained to install and maintain solar panels, solar hot water heaters, wind turbines and/or micro-hydro.
NASA Astrophysics Data System (ADS)
Mohamed, Mamdouh S.; Hirani, Anil N.; Samtaney, Ravi
2016-05-01
A conservative discretization of incompressible Navier-Stokes equations is developed based on discrete exterior calculus (DEC). A distinguishing feature of our method is the use of an algebraic discretization of the interior product operator and a combinatorial discretization of the wedge product. The governing equations are first rewritten using the exterior calculus notation, replacing vector calculus differential operators by the exterior derivative, Hodge star and wedge product operators. The discretization is then carried out by substituting with the corresponding discrete operators based on the DEC framework. Numerical experiments for flows over surfaces reveal a second order accuracy for the developed scheme when using structured-triangular meshes, and first order accuracy for otherwise unstructured meshes. By construction, the method is conservative in that both mass and vorticity are conserved up to machine precision. The relative error in kinetic energy for inviscid flow test cases converges in a second order fashion with both the mesh size and the time step.
Principles of Discrete Time Mechanics
NASA Astrophysics Data System (ADS)
Jaroszkiewicz, George
2014-04-01
1. Introduction; 2. The physics of discreteness; 3. The road to calculus; 4. Temporal discretization; 5. Discrete time dynamics architecture; 6. Some models; 7. Classical cellular automata; 8. The action sum; 9. Worked examples; 10. Lee's approach to discrete time mechanics; 11. Elliptic billiards; 12. The construction of system functions; 13. The classical discrete time oscillator; 14. Type 2 temporal discretization; 15. Intermission; 16. Discrete time quantum mechanics; 17. The quantized discrete time oscillator; 18. Path integrals; 19. Quantum encoding; 20. Discrete time classical field equations; 21. The discrete time Schrodinger equation; 22. The discrete time Klein-Gordon equation; 23. The discrete time Dirac equation; 24. Discrete time Maxwell's equations; 25. The discrete time Skyrme model; 26. Discrete time quantum field theory; 27. Interacting discrete time scalar fields; 28. Space, time and gravitation; 29. Causality and observation; 30. Concluding remarks; Appendix A. Coherent states; Appendix B. The time-dependent oscillator; Appendix C. Quaternions; Appendix D. Quantum registers; References; Index.
Identification of parameters of discrete-continuous models
Cekus, Dawid Warys, Pawel
2015-03-10
In the paper, the parameters of a discrete-continuous model have been identified on the basis of experimental investigations and formulation of optimization problem. The discrete-continuous model represents a cantilever stepped Timoshenko beam. The mathematical model has been formulated and solved according to the Lagrange multiplier formalism. Optimization has been based on the genetic algorithm. The presented proceeding’s stages make the identification of any parameters of discrete-continuous systems possible.
Morris, J; Johnson, S
2007-12-03
The Distinct Element Method (also frequently referred to as the Discrete Element Method) (DEM) is a Lagrangian numerical technique where the computational domain consists of discrete solid elements which interact via compliant contacts. This can be contrasted with Finite Element Methods where the computational domain is assumed to represent a continuum (although many modern implementations of the FEM can accommodate some Distinct Element capabilities). Often the terms Discrete Element Method and Distinct Element Method are used interchangeably in the literature, although Cundall and Hart (1992) suggested that Discrete Element Methods should be a more inclusive term covering Distinct Element Methods, Displacement Discontinuity Analysis and Modal Methods. In this work, DEM specifically refers to the Distinct Element Method, where the discrete elements interact via compliant contacts, in contrast with Displacement Discontinuity Analysis where the contacts are rigid and all compliance is taken up by the adjacent intact material.
Wheat mill stream properties for discrete element method modeling
Technology Transfer Automated Retrieval System (TEKTRAN)
A discrete phase approach based on individual wheat kernel characteristics is needed to overcome the limitations of previous statistical models and accurately predict the milling behavior of wheat. As a first step to develop a discrete element method (DEM) model for the wheat milling process, this s...
NASA Astrophysics Data System (ADS)
Appelbaum, J.; Gabbay, D.
1984-11-01
A stepped sinewave dc/ac inverter was analyzed for an inductive load with respect to load current and voltage, harmonics, power factor, and efficiency. This special inverter of high efficiency and low harmonic content is constructed by synthesizing the sinusoidal output by discrete voltage sources, such as storage batteries, solar cell, etc., with electronic switching of the sources at specific time intervals. The switching times are determined for the condition of minimum distortion of the synthesized wave. A 50 W inverter was built and tested to demonstrate this approach.
Characterization of TSET, an ancient and widespread membrane trafficking complex
Bloomfield, Gareth; Antrobus, Robin; Kay, Robert R; Dacks, Joel B; Robinson, Margaret S
2014-01-01
The heterotetrameric AP and F-COPI complexes help to define the cellular map of modern eukaryotes. To search for related machinery, we developed a structure-based bioinformatics tool, and identified the core subunits of TSET, a 'missing link' between the APs and COPI. Studies in Dictyostelium indicate that TSET is a heterohexamer, with two associated scaffolding proteins. TSET is non-essential in Dictyostelium, but may act in plasma membrane turnover, and is essentially identical to the recently described TPLATE complex, TPC. However, whereas TPC was reported to be plant-specific, we can identify a full or partial complex in every eukaryotic supergroup. An evolutionary path can be deduced from the earliest origins of the heterotetramer/scaffold coat to its multiple manifestations in modern organisms, including the mammalian muniscins, descendants of the TSET medium subunits. Thus, we have uncovered the machinery for an ancient and widespread pathway, which provides new insights into early eukaryotic evolution. DOI: http://dx.doi.org/10.7554/eLife.02866.001 PMID:24867644
Intravital microscopy to image membrane trafficking in live rats
Masedunskas, Andrius; Sramkova, Monika; Parente, Laura; Weigert, Roberto
2014-01-01
Summary Intravital microscopy (IVM) is a powerful tool that enables imaging various biological processes in live animals. Here, we describe a series of procedures designed to image subcellular structures, such as endsosomes and secretory vesicles in the salivary glands (SGs) of live rats. To this aim, we used fluorescently labeled molecules and/or fluorescently-tagged proteins that were transiently transfected in the live animal. PMID:23027003
Rab7: roles in membrane trafficking and disease.
Zhang, Ming; Chen, Li; Wang, Shicong; Wang, Tuanlao
2009-06-01
The endocytosis pathway controls multiple cellular and physiological events. The lysosome is the destination of newly synthesized lysosomal hydrolytic enzymes. Internalized molecules or particles are delivered to the lysosome for degradation through sequential transport along the endocytic pathway. The endocytic pathway is also emerging as a signalling platform, in addition to the well-known role of the plasma membrane for signalling. Rab7 is a late endosome-/lysosome-associated small GTPase, perhaps the only lysosomal Rab protein identified to date. Rab7 plays critical roles in the endocytic processes. Through interaction with its partners (including upstream regulators and downstream effectors), Rab7 participates in multiple regulation mechanisms in endosomal sorting, biogenesis of lysosome [or LRO (lysosome-related organelle)] and phagocytosis. These processes are closely related to substrates degradation, antigen presentation, cell signalling, cell survival and microbial pathogen infection. Consistently, mutations or dysfunctions of Rab7 result in traffic disorders, which cause various diseases, such as neuropathy, cancer and lipid metabolism disease. Rab7 also plays important roles in microbial pathogen infection and survival, as well as in participating in the life cycle of viruses. Here, we give a brief review on the central role of Rab7 in endosomal traffic and summarize the studies focusing on the participation of Rab7 in disease pathogenesis. The underlying mechanism governed by Rab7 and its partners will also be discussed. PMID:19392663
Membrane trafficking in the yeast Saccharomyces cerevisiae model.
Feyder, Serge; De Craene, Johan-Owen; Bär, Séverine; Bertazzi, Dimitri L; Friant, Sylvie
2015-01-01
The yeast Saccharomyces cerevisiae is one of the best characterized eukaryotic models. The secretory pathway was the first trafficking pathway clearly understood mainly thanks to the work done in the laboratory of Randy Schekman in the 1980s. They have isolated yeast sec mutants unable to secrete an extracellular enzyme and these SEC genes were identified as encoding key effectors of the secretory machinery. For this work, the 2013 Nobel Prize in Physiology and Medicine has been awarded to Randy Schekman; the prize is shared with James Rothman and Thomas Südhof. Here, we present the different trafficking pathways of yeast S. cerevisiae. At the Golgi apparatus newly synthesized proteins are sorted between those transported to the plasma membrane (PM), or the external medium, via the exocytosis or secretory pathway (SEC), and those targeted to the vacuole either through endosomes (vacuolar protein sorting or VPS pathway) or directly (alkaline phosphatase or ALP pathway). Plasma membrane proteins can be internalized by endocytosis (END) and transported to endosomes where they are sorted between those targeted for vacuolar degradation and those redirected to the Golgi (recycling or RCY pathway). Studies in yeast S. cerevisiae allowed the identification of most of the known effectors, protein complexes, and trafficking pathways in eukaryotic cells, and most of them are conserved among eukaryotes. PMID:25584613
Membrane Trafficking in the Yeast Saccharomyces cerevisiae Model
Feyder, Serge; De Craene, Johan-Owen; Bär, Séverine; Bertazzi, Dimitri L.; Friant, Sylvie
2015-01-01
The yeast Saccharomyces cerevisiae is one of the best characterized eukaryotic models. The secretory pathway was the first trafficking pathway clearly understood mainly thanks to the work done in the laboratory of Randy Schekman in the 1980s. They have isolated yeast sec mutants unable to secrete an extracellular enzyme and these SEC genes were identified as encoding key effectors of the secretory machinery. For this work, the 2013 Nobel Prize in Physiology and Medicine has been awarded to Randy Schekman; the prize is shared with James Rothman and Thomas Südhof. Here, we present the different trafficking pathways of yeast S. cerevisiae. At the Golgi apparatus newly synthesized proteins are sorted between those transported to the plasma membrane (PM), or the external medium, via the exocytosis or secretory pathway (SEC), and those targeted to the vacuole either through endosomes (vacuolar protein sorting or VPS pathway) or directly (alkaline phosphatase or ALP pathway). Plasma membrane proteins can be internalized by endocytosis (END) and transported to endosomes where they are sorted between those targeted for vacuolar degradation and those redirected to the Golgi (recycling or RCY pathway). Studies in yeast S. cerevisiae allowed the identification of most of the known effectors, protein complexes, and trafficking pathways in eukaryotic cells, and most of them are conserved among eukaryotes. PMID:25584613
Carlsten, B.E.; Haynes, W.B.
1996-08-01
The authors theoretically and numerically investigate the operation and behavior of the discrete monotron oscillator, a novel high-power microwave source. The discrete monotron differs from conventional monotrons and transit time oscillators by shielding the electron beam from the monotron cavity`s RF fields except at two distinct locations. This makes the discrete monotron act more like a klystron than a distributed traveling wave device. As a result, the oscillator has higher efficiency and can operate with higher beam powers than other single cavity oscillators and has more stable operation without requiring a seed input signal than mildly relativistic, intense-beam klystron oscillators.
ERIC Educational Resources Information Center
Peters, James V.
2004-01-01
Using the methods of finite difference equations the discrete analogue of the parabolic and catenary cable are analysed. The fibonacci numbers and the golden ratio arise in the treatment of the catenary.
1-D EQUILIBRIUM DISCRETE DIFFUSION MONTE CARLO
T. EVANS; ET AL
2000-08-01
We present a new hybrid Monte Carlo method for 1-D equilibrium diffusion problems in which the radiation field coexists with matter in local thermodynamic equilibrium. This method, the Equilibrium Discrete Diffusion Monte Carlo (EqDDMC) method, combines Monte Carlo particles with spatially discrete diffusion solutions. We verify the EqDDMC method with computational results from three slab problems. The EqDDMC method represents an incremental step toward applying this hybrid methodology to non-equilibrium diffusion, where it could be simultaneously coupled to Monte Carlo transport.
Discretizations of axisymmetric systems
NASA Astrophysics Data System (ADS)
Frauendiener, Jörg
2002-11-01
In this paper we discuss stability properties of various discretizations for axisymmetric systems including the so-called cartoon method which was proposed by Alcubierre et al. for the simulation of such systems on Cartesian grids. We show that within the context of the method of lines such discretizations tend to be unstable unless one takes care in the way individual singular terms are treated. Examples are given for the linear axisymmetric wave equation in flat space.
NASA Astrophysics Data System (ADS)
Zasche, P.
2016-03-01
An easy step-by-step manual of PHOEBE is presented. It should serve as a starting point for the first time users of PHOEBE analyzing the eclipsing binary light curve. It is demonstrated on one particular detached system also with the downloadable data and the whole procedure is described easily till the final trustworthy fit is being reached.
NASA Astrophysics Data System (ADS)
Langella, A.; Carbone, R.; Durante, M.
2012-12-01
The pultrusion process is an efficient technology for the production of composite material profiles. Thanks to this positive feature, several studies have been carried out, either to expand the range of products made using the pultrusion technology, or improve its already high production rate. This study presents a process derived from the traditional pultrusion technology named "Step Pultrusion Process Technology" (SPPT). Using the step pultrusion process, the final section of the composite profiles is obtainable by means of a progressive cross section increasing through several resin cure stations. This progressive increasing of the composite cross section means that a higher degree of cure level can be attained at the die exit point of the last die. Mechanical test results of the manufactured pultruded samples have been used to compare both the traditional and the step pultrusion processes. Finally, there is a discussion on ways to improve the new step pultrusion process even further.
Numerical discretization for nonlinear diffusion filter
NASA Astrophysics Data System (ADS)
Mustaffa, I.; Mizuar, I.; Aminuddin, M. M. M.; Dasril, Y.
2015-05-01
Nonlinear diffusion filters are famously used in machine vision for image denoising and restoration. This paper presents a study on the effects of different numerical discretization of nonlinear diffusion filter. Several numerical discretization schemes are presented; namely semi-implicit, AOS, and fully implicit schemes. The results of these schemes are compared by visual results, objective measurement e.g. PSNR and MSE. The results are also compared to a Daubechies wavelet denoising method. It is acknowledged that the two preceding scheme have already been discussed in literature, however comparison to the latter scheme has not been made. The semi-implicit scheme uses an additive operator splitting (AOS) developed to overcome the shortcoming of the explicit scheme i.e., stability for very small time steps. Although AOS has proven to be efficient, from the nonlinear diffusion filter results with different discretization schemes, examples shows that implicit schemes are worth pursuing.
Multigrid methods for isogeometric discretization
Gahalaut, K.P.S.; Kraus, J.K.; Tomar, S.K.
2013-01-01
We present (geometric) multigrid methods for isogeometric discretization of scalar second order elliptic problems. The smoothing property of the relaxation method, and the approximation property of the intergrid transfer operators are analyzed. These properties, when used in the framework of classical multigrid theory, imply uniform convergence of two-grid and multigrid methods. Supporting numerical results are provided for the smoothing property, the approximation property, convergence factor and iterations count for V-, W- and F-cycles, and the linear dependence of V-cycle convergence on the smoothing steps. For two dimensions, numerical results include the problems with variable coefficients, simple multi-patch geometry, a quarter annulus, and the dependence of convergence behavior on refinement levels ℓ, whereas for three dimensions, only the constant coefficient problem in a unit cube is considered. The numerical results are complete up to polynomial order p=4, and for C0 and Cp-1 smoothness. PMID:24511168
Multigrid methods for isogeometric discretization.
Gahalaut, K P S; Kraus, J K; Tomar, S K
2013-01-01
We present (geometric) multigrid methods for isogeometric discretization of scalar second order elliptic problems. The smoothing property of the relaxation method, and the approximation property of the intergrid transfer operators are analyzed. These properties, when used in the framework of classical multigrid theory, imply uniform convergence of two-grid and multigrid methods. Supporting numerical results are provided for the smoothing property, the approximation property, convergence factor and iterations count for V-, W- and F-cycles, and the linear dependence of V-cycle convergence on the smoothing steps. For two dimensions, numerical results include the problems with variable coefficients, simple multi-patch geometry, a quarter annulus, and the dependence of convergence behavior on refinement levels [Formula: see text], whereas for three dimensions, only the constant coefficient problem in a unit cube is considered. The numerical results are complete up to polynomial order [Formula: see text], and for [Formula: see text] and [Formula: see text] smoothness. PMID:24511168
A discrete fractional random transform
NASA Astrophysics Data System (ADS)
Liu, Zhengjun; Zhao, Haifa; Liu, Shutian
2005-11-01
We propose a discrete fractional random transform based on a generalization of the discrete fractional Fourier transform with an intrinsic randomness. Such discrete fractional random transform inheres excellent mathematical properties of the fractional Fourier transform along with some fantastic features of its own. As a primary application, the discrete fractional random transform has been used for image encryption and decryption.
Discrete Newtonian cosmology: perturbations
NASA Astrophysics Data System (ADS)
Ellis, George F. R.; Gibbons, Gary W.
2015-03-01
In a previous paper (Gibbons and Ellis 2014 Discrete Newtonian cosmology Class. Quantum Grav. 31 025003), we showed how a finite system of discrete particles interacting with each other via Newtonian gravitational attraction would lead to precisely the same dynamical equations for homothetic motion as in the case of the pressure-free Friedmann-Lemaître-Robertson-Walker cosmological models of general relativity theory, provided the distribution of particles obeys the central configuration equation. In this paper we show that one can obtain perturbed such Newtonian solutions that give the same linearized structure growth equations as in the general relativity case. We also obtain the Dmitriev-Zel’dovich equations for subsystems in this discrete gravitational model, and show how it leads to the conclusion that voids have an apparent negative mass.
Discrete breathers in crystals
NASA Astrophysics Data System (ADS)
Dmitriev, S. V.; Korznikova, E. A.; Baimova, Yu A.; Velarde, M. G.
2016-05-01
It is well known that periodic discrete defect-containing systems, in addition to traveling waves, support vibrational defect-localized modes. It turned out that if a periodic discrete system is nonlinear, it can support spatially localized vibrational modes as exact solutions even in the absence of defects. Since the nodes of the system are all on equal footing, it is only through the special choice of initial conditions that a group of nodes can be found on which such a mode, called a discrete breather (DB), will be excited. The DB frequency must be outside the frequency range of the small-amplitude traveling waves. Not resonating with and expending no energy on the excitation of traveling waves, a DB can theoretically conserve its vibrational energy forever provided no thermal vibrations or other perturbations are present. Crystals are nonlinear discrete systems, and the discovery in them of DBs was only a matter of time. It is well known that periodic discrete defect-containing systems support both traveling waves and vibrational defect-localized modes. It turns out that if a periodic discrete system is nonlinear, it can support spatially localized vibrational modes as exact solutions even in the absence of defects. Because the nodes of the system are all on equal footing, only a special choice of the initial conditions allows selecting a group of nodes on which such a mode, called a discrete breather (DB), can be excited. The DB frequency must be outside the frequency range of small-amplitude traveling waves. Not resonating with and expending no energy on the excitation of traveling waves, a DB can theoretically preserve its vibrational energy forever if no thermal vibrations or other perturbations are present. Crystals are nonlinear discrete systems, and the discovery of DBs in them was only a matter of time. Experimental studies of DBs encounter major technical difficulties, leaving atomistic computer simulations as the primary investigation tool. Despite
Joint discrete universality of Hurwitz zeta functions
NASA Astrophysics Data System (ADS)
Laurinčikas, A.
2014-11-01
We obtain a joint discrete universality theorem for Hurwitz zeta functions. Here the parameters of zeta functions and the step of shifts of these functions approximating a given family of analytic functions are connected by some condition of linear independence. Nesterenko's theorem gives an example satisfying this condition. The universality theorem is applied to estimate the number of zeros of a linear combination of Hurwitz zeta functions. Bibliography: 20 titles.
Asymptotic analysis of spatial discretizations in implicit Monte Carlo
Densmore, Jeffery D
2008-01-01
We perform an asymptotic analysis of spatial discretizations in Implicit Monte Carlo (IMC). We consider two asymptotic scalings: one that represents a time step that resolves the mean-free time, and one that corresponds to a fixed, optically large time step. We show that only the latter scaling results in a valid spatial discretization of the proper diffusion equation, and thus we conclude that IMC only yields accurate solutions when using optically large spatial cells if time steps are also optically large, We demonstrate the validity of our analysis with a set of numerical examples.
Asymptotic analysis of spatial discretizations in implicit Monte Carlo
Densmore, Jeffery D
2009-01-01
We perform an asymptotic analysis of spatial discretizations in Implicit Monte Carlo (IMC). We consider two asymptotic scalings: one that represents a time step that resolves the mean-free time, and one that corresponds to a fixed, optically large time step. We show that only the latter scaling results in a valid spatial discretization of the proper diffusion equation, and thus we conclude that IMC only yields accurate solutions when using optically large spatial cells if time steps are also optically large. We demonstrate the validity of our analysis with a set of numerical examples.
ERIC Educational Resources Information Center
Sharp, Karen Tobey
This paper cites information received from a number of sources, e.g., mathematics teachers in two-year colleges, publishers, and convention speakers, about the nature of discrete mathematics and about what topics a course in this subject should contain. Note is taken of the book edited by Ralston and Young which discusses the future of college…
Discreteness induced extinction
NASA Astrophysics Data System (ADS)
dos Santos, Renato Vieira; da Silva, Linaena Méricy
2015-11-01
Two simple models based on ecological problems are discussed from the point of view of non-equilibrium statistical mechanics. It is shown how discrepant may be the results of the models that include spatial distribution with discrete interactions when compared with the continuous analogous models. In the continuous case we have, under certain circumstances, the population explosion. When we take into account the finiteness of the population, we get the opposite result, extinction. We will analyze how these results depend on the dimension d of the space and describe the phenomenon of the "Discreteness Inducing Extinction" (DIE). The results are interpreted in the context of the "paradox of sex", an old problem of evolutionary biology.
A paradigm for discrete physics
Noyes, H.P.; McGoveran, D.; Etter, T.; Manthey, M.J.; Gefwert, C.
1987-01-01
An example is outlined for constructing a discrete physics using as a starting point the insight from quantum physics that events are discrete, indivisible and non-local. Initial postulates are finiteness, discreteness, finite computability, absolute nonuniqueness (i.e., homogeneity in the absence of specific cause) and additivity.
Sutton, G.P.
1998-07-14
An insert is described which allows a supersonic nozzle of a rocket propulsion system to operate at two or more different nozzle area ratios. This provides an improved vehicle flight performance or increased payload. The insert has significant advantages over existing devices for increasing nozzle area ratios. The insert is temporarily fastened by a simple retaining mechanism to the aft end of the diverging segment of the nozzle and provides for a multi-step variation of nozzle area ratio. When mounted in place, the insert provides the nozzle with a low nozzle area ratio. During flight, the retaining mechanism is released and the insert ejected thereby providing a high nozzle area ratio in the diverging nozzle segment. 5 figs.
Sutton, George P.
1998-01-01
An insert which allows a supersonic nozzle of a rocket propulsion system to operate at two or more different nozzle area ratios. This provides an improved vehicle flight performance or increased payload. The insert has significant advantages over existing devices for increasing nozzle area ratios. The insert is temporarily fastened by a simple retaining mechanism to the aft end of the diverging segment of the nozzle and provides for a multi-step variation of nozzle area ratio. When mounted in place, the insert provides the nozzle with a low nozzle area ratio. During flight, the retaining mechanism is released and the insert ejected thereby providing a high nozzle area ratio in the diverging nozzle segment.
NASA Astrophysics Data System (ADS)
Wuensche, Andrew
DDLab is interactive graphics software for creating, visualizing, and analyzing many aspects of Cellular Automata, Random Boolean Networks, and Discrete Dynamical Networks in general and studying their behavior, both from the time-series perspective — space-time patterns, and from the state-space perspective — attractor basins. DDLab is relevant to research, applications, and education in the fields of complexity, self-organization, emergent phenomena, chaos, collision-based computing, neural networks, content addressable memory, genetic regulatory networks, dynamical encryption, generative art and music, and the study of the abstract mathematical/physical/dynamical phenomena in their own right.
NASA Astrophysics Data System (ADS)
Kotulski, Zbigniew; Szczepaski, Janusz
In the paper we propose a new method of constructing cryptosystems utilising a nonpredictability property of discrete chaotic systems. We formulate the requirements for such systems to assure their safety. We also give examples of practical realisation of chaotic cryptosystems, using a generalisation of the method presented in [7]. The proposed algorithm of encryption and decryption is based on multiple iteration of a certain dynamical chaotic system. We assume that some part of the initial condition is a plain message. As the secret key we assume the system parameter(s) and additionally another part of the initial condition.
Discrete scale invariance in supercritical percolation
NASA Astrophysics Data System (ADS)
Schröder, Malte; Chen, Wei; Nagler, Jan
2016-01-01
Recently it has been demonstrated that the connectivity transition from microscopic connectivity to macroscopic connectedness, known as percolation, is generically announced by a cascade of microtransitions of the percolation order parameter (Chen et al 2014 Phys. Rev. Lett. 112 155701). Here we report the discovery of macrotransition cascades which follow percolation. The order parameter grows in discrete macroscopic steps with positions that can be randomly distributed even in the thermodynamic limit. These transition positions are, however, correlated and follow scaling laws which arise from discrete scale invariance (DSI) and non self-averaging, both traditionally unrelated to percolation. We reveal the DSI in ensemble measurements of these non self-averaging systems by rescaling of the individual realizations before averaging.
How to value protection from natural hazards - a step-by-step discrete choice approach
NASA Astrophysics Data System (ADS)
Olschewski, R.
2013-04-01
In mountainous regions, forests play a crucial role in protecting the local population from natural hazards. In cases where existing forests are destroyed, e.g. by wind throws or diseases, the protection function has to be restored through technical measures. To determine the willingness to pay (WTP) for protection against avalanches, a choice experiment has been conducted and different experiment specifications have been tested to determine possible impacts on the results. The present study contributes to a comprehensive assessment of protection measures, and helps to identify efficient solutions based on the judgement of the people potentially endangered by natural hazards. The stepwise approach has the advantage to gradually check data fit, thereby didactically showing an operational way of dealing with different model specifications. The detailed case study can serve as a manual for conducting choice experiments with a similar focus and demonstrates the suitability and caveats of this approach to value protection from natural hazards in general.
NASA Astrophysics Data System (ADS)
Calogero, Francesco
2011-08-01
The original continuous-time ''goldfish'' dynamical system is characterized by two neat formulas, the first of which provides the N Newtonian equations of motion of this dynamical system, while the second provides the solution of the corresponding initial-value problem. Several other, more general, solvable dynamical systems ''of goldfish type'' have been identified over time, featuring, in the right-hand (''forces'') side of their Newtonian equations of motion, in addition to other contributions, a velocity-dependent term such as that appearing in the right-hand side of the first formula mentioned above. The solvable character of these models allows detailed analyses of their behavior, which in some cases is quite remarkable (for instance isochronous or asymptotically isochronous). In this paper we introduce and discuss various discrete-time dynamical systems, which are as well solvable, which also display interesting behaviors (including isochrony and asymptotic isochrony) and which reduce to dynamical systems of goldfish type in the limit when the discrete-time independent variable l=0,1,2,... becomes the standard continuous-time independent variable t, 0≤t<∞.
RABA Members Act in Distinct Steps of Subcellular Trafficking of the FLAGELLIN SENSING2 Receptor[W
Choi, Seung-won; Tamaki, Takayuki; Ebine, Kazuo; Uemura, Tomohiro; Ueda, Takashi; Nakano, Akihiko
2013-01-01
Cell surface proteins play critical roles in the perception of environmental stimuli at the plasma membrane (PM) and ensuing signal transduction. Intracellular localization of such proteins must be strictly regulated, which requires elaborate integration of exocytic and endocytic trafficking pathways. Subcellular localization of Arabidopsis thaliana FLAGELLIN SENSING2 (FLS2), a receptor that recognizes bacterial flagellin, also depends on membrane trafficking. However, our understanding about the mechanisms involved is still limited. In this study, we visualized ligand-induced endocytosis of FLS2 using green fluorescent protein (GFP)-tagged FLS2 expressed in Nicotiana benthamiana. Upon treatment with the flg22 peptide, internalized FLS2-GFP from the PM was transported to a compartment with properties intermediate between the trans-Golgi network (TGN) and the multivesicular endosome. This compartment gradually discarded the TGN characteristics as it continued along the trafficking pathway. We further found that FLS2 endocytosis involves distinct RABA/RAB11 subgroups at different steps. Moreover, we demonstrated that transport of de novo–synthesized FLS2 to the PM also involves a distinct RABA/RAB11 subgroup. Our results demonstrate the complex regulatory system for properly localizing FLS2 and functional differentiation in RABA members in endo- and exocytosis. PMID:23532067
A priori discretization quality metrics for distributed hydrologic modeling applications
NASA Astrophysics Data System (ADS)
Liu, Hongli; Tolson, Bryan; Craig, James; Shafii, Mahyar; Basu, Nandita
2016-04-01
In distributed hydrologic modelling, a watershed is treated as a set of small homogeneous units that address the spatial heterogeneity of the watershed being simulated. The ability of models to reproduce observed spatial patterns firstly depends on the spatial discretization, which is the process of defining homogeneous units in the form of grid cells, subwatersheds, or hydrologic response units etc. It is common for hydrologic modelling studies to simply adopt a nominal or default discretization strategy without formally assessing alternative discretization levels. This approach lacks formal justifications and is thus problematic. More formalized discretization strategies are either a priori or a posteriori with respect to building and running a hydrologic simulation model. A posteriori approaches tend to be ad-hoc and compare model calibration and/or validation performance under various watershed discretizations. The construction and calibration of multiple versions of a distributed model can become a seriously limiting computational burden. Current a priori approaches are more formalized and compare overall heterogeneity statistics of dominant variables between candidate discretization schemes and input data or reference zones. While a priori approaches are efficient and do not require running a hydrologic model, they do not fully investigate the internal spatial pattern changes of variables of interest. Furthermore, the existing a priori approaches focus on landscape and soil data and do not assess impacts of discretization on stream channel definition even though its significance has been noted by numerous studies. The primary goals of this study are to (1) introduce new a priori discretization quality metrics considering the spatial pattern changes of model input data; (2) introduce a two-step discretization decision-making approach to compress extreme errors and meet user-specified discretization expectations through non-uniform discretization threshold
Noyes, H.P. ); Starson, S. )
1991-03-01
Discrete physics, because it replaces time evolution generated by the energy operator with a global bit-string generator (program universe) and replaces fields'' with the relativistic Wheeler-Feynman action at a distance,'' allows the consistent formulation of the concept of signed gravitational charge for massive particles. The resulting prediction made by this version of the theory is that free anti-particles near the surface of the earth will fall'' up with the same acceleration that the corresponding particles fall down. So far as we can see, no current experimental information is in conflict with this prediction of our theory. The experiment crusis will be one of the anti-proton or anti-hydrogen experiments at CERN. Our prediction should be much easier to test than the small effects which those experiments are currently designed to detect or bound. 23 refs.
Discrete Sibson interpolation.
Park, Sung W; Linsen, Lars; Kreylos, Oliver; Owens, John D; Hamann, Bernd
2006-01-01
Natural-neighbor interpolation methods, such as Sibson's method, are well-known schemes for multivariate data fitting and reconstruction. Despite its many desirable properties, Sibson's method is computationally expensive and difficult to implement, especially when applied to higher-dimensional data. The main reason for both problems is the method's implementation based on a Voronoi diagram of all data points. We describe a discrete approach to evaluating Sibson's interpolant on a regular grid, based solely on finding nearest neighbors and rendering and blending d-dimensional spheres. Our approach does not require us to construct an explicit Voronoi diagram, is easily implemented using commodity three-dimensional graphics hardware, leads to a significant speed increase compared to traditional approaches, and generalizes easily to higher dimensions. For large scattered data sets, we achieve two-dimensional (2D) interpolation at interactive rates and 3D interpolation (3D) with computation times of a few seconds. PMID:16509383
Immigration and Prosecutorial Discretion
Apollonio, Dorie; Lochner, Todd; Heddens, Myriah
2015-01-01
Immigration has become an increasingly salient national issue in the US, and the Department of Justice recently increased federal efforts to prosecute immigration offenses. This shift, however, relies on the cooperation of US attorneys and their assistants. Traditionally federal prosecutors have enjoyed enormous discretion and have been responsive to local concerns. To consider how the centralized goal of immigration enforcement may have influenced federal prosecutors in regional offices, we review their prosecution of immigration offenses in California using over a decade's worth of data. Our findings suggest that although centralizing forces influence immigration prosecutions, individual US attorneys' offices retain distinct characteristics. Local factors influence federal prosecutors' behavior in different ways depending on the office. Contrary to expectations, unemployment rates did not affect prosecutors' willingness to pursue immigration offenses, nor did local popular opinion about illegal immigration. PMID:26146530
Discrete Pearson distributions
Bowman, K.O.; Shenton, L.R.; Kastenbaum, M.A.
1991-11-01
These distributions are generated by a first order recursive scheme which equates the ratio of successive probabilities to the ratio of two corresponding quadratics. The use of a linearized form of this model will produce equations in the unknowns matched by an appropriate set of moments (assumed to exist). Given the moments we may find valid solutions. These are two cases; (1) distributions defined on the non-negative integers (finite or infinite) and (2) distributions defined on negative integers as well. For (1), given the first four moments, it is possible to set this up as equations of finite or infinite degree in the probability of a zero occurrence, the sth component being a product of s ratios of linear forms in this probability in general. For (2) the equation for the zero probability is purely linear but may involve slowly converging series; here a particular case is the discrete normal. Regions of validity are being studied. 11 refs.
Discrete stability in stochastic programming
Lepp, R.
1994-12-31
In this lecture we study stability properties of stochastic programs with recourse where the probability measure is approximated by a sequence of weakly convergent discrete measures. Such discrete approximation approach gives us a possibility to analyze explicitly the behavior of the second stage correction function. The approach is based on modern functional analytical methods of an approximation of extremum problems in function spaces, especially on the notion of the discrete convergence of vectors to an essentially bounded measurable function.
Discrete Space Theory of Radiative Transfer: Application
NASA Astrophysics Data System (ADS)
Rao, M. Srinivasa
2010-06-01
The method of obtaining the solution of radiative transfer equation using discrete space theory (DST) is described with (1) interaction principle for different geometries (2) star product (3) calculation of radiation field at internal points. Some of the important steps to obtain the solution of radiative transfer equation in spherical symmetry are also mentioned. Applications of DST are discussed with their results in two cases (a) study of reflection effect in close binary systems and (b) to compute KI 769.9 nm emission line profiles from N-type stars.
Discrete Space Theory of Radiative Transfer: Application
NASA Astrophysics Data System (ADS)
Rao, M. Srinivasa
The method of obtaining the solution of radiative transfer equation using discrete space theory (DST) is described with (1) interaction principle for different geometries (2) star product (3) calculation of radiation field at internal points. Some of the important steps to obtain the solution of radiative transfer equation in spherical symmetry are also mentioned. Applications of DST are discussed with their results in two cases (a) study of reflection effect in close binary systems and (b) to compute KI 769.9 nm emission line profiles from N-type stars.
Discrete elements method of neutral particle transport. Doctoral thesis
Mathews, K.A.
1983-10-01
A new 'discrete elements' (LN) transport method is derived and compared to the discrete ordinates SN method, theoretically and by numerical experimentation. The discrete elements method is more accurate than discrete ordinates and strongly ameliorates ray effects for the practical problems studied. The discrete elements method is shown to be more cost effective in terms of execution time with comparable storage to attain the same accuracy, for a one-dimensional test case using linear characteristic spatial quadrature. In a two-dimensional test case, a vacuum duct in a shield, LN is more consistently convergent toward a Monte Carlo benchmark solution than SN, using step characteristic spatial quadrature. An analysis of the interaction of angular and spatial quadrature in xy-geometry indicates the desirability of using linear characteristic spatial quadrature with the LN method. The discrete elements method is based on discretizing the Boltzmann equation over a set of elements of angle. The zeroth and first angular moments of the directional flux, over each element, are estimated by numerical quadrature and yield a flux-weighted average streaming direction for the element. (Data for this estimation are fluxes in fixed directions calculated as in SN.)
Sticky steps inhibit step motions near equilibrium
NASA Astrophysics Data System (ADS)
Akutsu, Noriko
2012-12-01
Using a Monte Carlo method on a lattice model of a vicinal surface with a point-contact-type step-step attraction, we show that, at low temperature and near equilibrium, there is an inhibition of the motion of macrosteps. This inhibition leads to a pinning of steps without defects, adsorbates, or impurities (self-pinning of steps). We show that this inhibition of the macrostep motion is caused by faceted steps, which are macrosteps that have a smooth side surface. The faceted steps result from discontinuities in the anisotropic surface tension (the surface free energy per area). The discontinuities are brought into the surface tension by the point-contact-type step-step attraction. The point-contact-type step-step attraction also originates “step droplets,” which are locally merged steps, at higher temperatures. We derive an analytic equation of the surface stiffness tensor for the vicinal surface around the (001) surface. Using the surface stiffness tensor, we show that step droplets roughen the vicinal surface. Contrary to what we expected, the step droplets slow down the step velocity due to the diminishment of kinks in the merged steps (smoothing of the merged steps).
Discrete Mathematics and Curriculum Reform.
ERIC Educational Resources Information Center
Kenney, Margaret J.
1996-01-01
Defines discrete mathematics as the mathematics necessary to effect reasoned decision making in finite situations and explains how its use supports the current view of mathematics education. Discrete mathematics can be used by curriculum developers to improve the curriculum for students of all ages and abilities. (SLD)
Discrete Mathematics and Its Applications
ERIC Educational Resources Information Center
Oxley, Alan
2010-01-01
The article gives ideas that lecturers of undergraduate Discrete Mathematics courses can use in order to make the subject more interesting for students and encourage them to undertake further studies in the subject. It is possible to teach Discrete Mathematics with little or no reference to computing. However, students are more likely to be…
Huang, Z. )
1992-12-01
We examine an interesting scenario to solve the domain-wall problem recently suggested by Preskill, Trivedi, Wilczek, and Wise. The effective potential is calculated in the presence of the QCD axial anomaly. It is shown that some discrete symmetries such as {ital CP} and {ital Z}{sub 2} can be anomalous due to a so-called {ital K} term induced by instantons. We point out that the {ital Z}{sub 2} domain-wall problem in the two-doublet standard model can be resolved by two types of solutions: the {ital CP}-conserving one and the {ital CP}-breaking one. In the first case, there exist two {ital Z}{sub 2}-related local minima whose energy splitting is provided by the instanton effect. In the second case, there is only one unique vacuum so that the domain walls do not form at all. The consequences of this new source of {ital CP} violation are discussed and shown to be well within the experimental limits in weak interactions.
Discreteness inducing coexistence
NASA Astrophysics Data System (ADS)
dos Santos, Renato Vieira
2013-12-01
Consider two species that diffuse through space. Consider further that they differ only in initial densities and, possibly, in diffusion constants. Otherwise they are identical. What happens if they compete with each other in the same environment? What is the influence of the discrete nature of the interactions on the final destination? And what are the influence of diffusion and additive fluctuations corresponding to random migration and immigration of individuals? This paper aims to answer these questions for a particular competition model that incorporates intra and interspecific competition between the species. Based on mean field theory, the model has a stationary state dependent on the initial density conditions. We investigate how this initial density dependence is affected by the presence of demographic multiplicative noise and additive noise in space and time. There are three main conclusions: (1) Additive noise favors denser populations at the expense of the less dense, ratifying the competitive exclusion principle. (2) Demographic noise, on the other hand, favors less dense populations at the expense of the denser ones, inducing equal densities at the quasi-stationary state, violating the aforementioned principle. (3) The slower species always suffers the more deleterious effects of statistical fluctuations in a homogeneous medium.
Khan, M M; Varma, M P; Cleland, J; O'Kane, H O; Webb, S W; Mulholland, H C; Adgey, A A
1981-01-01
Data concerning 17 consecutive patients with discrete subaortic stenosis are recorded. Twelve patients underwent operative resection of the obstructing lesion. Of these all except one were symptomatic and all had electrocardiographic evidence of left ventricular hypertrophy or left ventricular hypertrophy with strain. They had a peak resting systolic left ventricular outflow tract gradient of greater than 50 mmHg as predicted from the combined cuff measurement of systolic blood pressure and the echocardiographically estimated left ventricular systolic pressure and/or as determined by cardiac catheterisation. The outflow tract gradient as predicted from M-mode echocardiography and peak systolic pressure showed close correlation with that measured at cardiac catheterisation or operation. During the postoperative follow-up from one month to 11 years, of 11 patients, one patient required a further operation for recurrence of the obstruction four years after the initial operation. All patients are now asymptomatic. Five patients have not had an operation. The left ventricular outflow tract gradient as assessed at the time of cardiac catheterisation was greater than 50 mmHg. One patient has been lost to follow-up. The remaining four have been followed from four to eight years and have remained asymptomatic and the electrocardiograms have remained unchanged. Careful follow-up of all patients is essential with continuing clinical assessment, electrocardiograms, M-mode and two-dimensional echocardiograms, and if necessary cardiac catheterisation. Prophylaxis against bacterial endocarditis is also essential. Images PMID:6457617
Discrete dynamics and non-Markovianity
NASA Astrophysics Data System (ADS)
Luoma, Kimmo; Piilo, Jyrki
2016-06-01
We study discrete quantum dynamics where a single evolution step consists of unitary system transformation followed by decoherence via coupling to an environment. Often, non-Markovian memory effects are attributed to structured environments, whereas, here, we take a more general approach within a discrete setting. In addition of controlling the structure of the environment, we are interested in how local unitaries on the open system allow the appearance and control of memory effects. Our first simple qubit model where local unitary is followed by dephasing illustrates how memory effects arise, despite having no structure in the environment the system is coupled with. We, then, elaborate on this observation by constructing a model for an open quantum walk where the unitary coin and transfer operation is augmented with the dephasing of the coin. The results demonstrate tha,t in the limit of strong dephasing within each evolution step, the combined coin-position open system always displays memory effects, and their quantities are independent of the structure of the environment. Our construction makes possible an experimentally realizable open quantum walk with photons exhibiting non-Markovian features.
The discrete variational derivative method based on discrete differential forms
NASA Astrophysics Data System (ADS)
Yaguchi, Takaharu; Matsuo, Takayasu; Sugihara, Masaaki
2012-05-01
As is well known, for PDEs that enjoy a conservation or dissipation property, numerical schemes that inherit this property are often advantageous in that the schemes are fairly stable and give qualitatively better numerical solutions in practice. Lately, Furihata and Matsuo have developed the so-called “discrete variational derivative method” that automatically constructs energy preserving or dissipative finite difference schemes. Although this method was originally developed on uniform meshes, the use of non-uniform meshes is of importance for multi-dimensional problems. On the other hand, the theories of discrete differential forms have received much attention recently. These theories provide a discrete analogue of the vector calculus on general meshes. In this paper, we show that the discrete variational derivative method and the discrete differential forms by Bochev and Hyman can be combined. Applications to the Cahn-Hilliard equation and the Klein-Gordon equation on triangular meshes are provided as demonstrations. We also show that the schemes for these equations are H1-stable under some assumptions. In particular, one for the nonlinear Klein-Gordon equation is obtained by combination of the energy conservation property and the discrete Poincaré inequality, which are the temporal and spacial structures that are preserved by the above methods.
Microscopic derivation of discrete hydrodynamics.
Español, Pep; Anero, Jesús G; Zúñiga, Ignacio
2009-12-28
By using the standard theory of coarse graining based on Zwanzig's projection operator, we derive the dynamic equations for discrete hydrodynamic variables. These hydrodynamic variables are defined in terms of the Delaunay triangulation. The resulting microscopically derived equations can be understood, a posteriori, as a discretization on an arbitrary irregular grid of the Navier-Stokes equations. The microscopic derivation provides a set of discrete equations that exactly conserves mass, momentum, and energy and the dissipative part of the dynamics produces strict entropy increase. In addition, the microscopic derivation provides a practical implementation of thermal fluctuations in a way that the fluctuation-dissipation theorem is satisfied exactly. This paper points toward a close connection between coarse-graining procedures from microscopic dynamics and discretization schemes for partial differential equations. PMID:20059064
Exact discretization by Fourier transforms
NASA Astrophysics Data System (ADS)
Tarasov, Vasily E.
2016-08-01
A discretization of differential and integral operators of integer and non-integer orders is suggested. New type of differences, which are represented by infinite series, is proposed. A characteristic feature of the suggested differences is an implementation of the same algebraic properties that have the operator of differentiation (property of algebraic correspondence). Therefore the suggested differences are considered as an exact discretization of derivatives. These differences have a property of universality, which means that these operators do not depend on the form of differential equations and the parameters of these equations. The suggested differences operators allows us to have difference equations whose solutions are equal to the solutions of corresponding differential equations. The exact discretization of the derivatives of integer orders is given by the suggested differences of the same integer orders. Similarly, the exact discretization of the Riesz derivatives and integrals of integer and non-integer order is given by the proposed fractional differences of the same order.
Chaos in Periodic Discrete Systems
NASA Astrophysics Data System (ADS)
Shi, Yuming; Zhang, Lijuan; Yu, Panpan; Huang, Qiuling
This paper focuses on chaos in periodic discrete systems, whose state space may vary with time. Some close relationships between some chaotic dynamical behaviors of a periodic discrete system and its autonomous induced system are given. Based on these relationships, several criteria of chaos are established and some sufficient conditions for no chaos are given for periodic discrete systems. Further, it is shown that a finite-dimensional linear periodic discrete system is not chaotic in the sense of Li-Yorke or Wiggins. In particular, an interesting problem of whether nonchaotic rules may generate a chaotic system is studied, with some examples provided, one of which surprisingly shows that a composition of globally asymptotically stable maps can be chaotic. In addition, some properties of sign pattern matrices of non-negative square matrices are given for convenience of the study.
Choice of method for discretization of continuous systems. [for digital autopilots
NASA Technical Reports Server (NTRS)
Mcvey, E. S.; Lee, Y. C.
1979-01-01
The paper discusses and compares several common methods of discretizing the transfer function of a continuous control system so that a digital computer can be used. The discretization effect on the frequency response attenuation of the simple transfer function G(s) = 1/(s + 1) is illustrated for the Tusting, Boxer-Thaler, Madwed, linear segment approximation, and stair-step with half period advanced methods. The input frequency must be significantly lower than one-half the sampling error to have negligible discretization error. Phase differences due to discretization are also plotted, and it is seen that the zero-order hold contributes much more phase shift than that due to discretization. In situations where zero-order hold must follow a computer, the method of discretization of a continuous system is not a major factor if phase shift is important.
Stability analysis of the Euler discretization for SIR epidemic model
Suryanto, Agus
2014-06-19
In this paper we consider a discrete SIR epidemic model obtained by the Euler method. For that discrete model, existence of disease free equilibrium and endemic equilibrium is established. Sufficient conditions on the local asymptotical stability of both disease free equilibrium and endemic equilibrium are also derived. It is found that the local asymptotical stability of the existing equilibrium is achieved only for a small time step size h. If h is further increased and passes the critical value, then both equilibriums will lose their stability. Our numerical simulations show that a complex dynamical behavior such as bifurcation or chaos phenomenon will appear for relatively large h. Both analytical and numerical results show that the discrete SIR model has a richer dynamical behavior than its continuous counterpart.
A space-time discretization procedure for wave propagation problems
NASA Technical Reports Server (NTRS)
Davis, Sanford
1989-01-01
Higher order compact algorithms are developed for the numerical simulation of wave propagation by using the concept of a discrete dispersion relation. The dispersion relation is the imprint of any linear operator in space-time. The discrete dispersion relation is derived from the continuous dispersion relation by examining the process by which locally plane waves propagate through a chosen grid. The exponential structure of the discrete dispersion relation suggests an efficient splitting of convective and diffusive terms for dissipative waves. Fourth- and eighth-order convection schemes are examined that involve only three or five spatial grid points. These algorithms are subject to the same restrictions that govern the use of dispersion relations in the constructions of asymptotic expansions to nonlinear evolution equations. A new eighth-order scheme is developed that is exact for Courant numbers of 1, 2, 3, and 4. Examples are given of a pulse and step wave with a small amount of physical diffusion.
Supervised and unsupervised discretization methods for evolutionary algorithms
Cantu-Paz, E
2001-01-24
This paper introduces simple model-building evolutionary algorithms (EAs) that operate on continuous domains. The algorithms are based on supervised and unsupervised discretization methods that have been used as preprocessing steps in machine learning. The basic idea is to discretize the continuous variables and use the discretization as a simple model of the solutions under consideration. The model is then used to generate new solutions directly, instead of using the usual operators based on sexual recombination and mutation. The algorithms presented here have fewer parameters than traditional and other model-building EAs. They expect that the proposed algorithms that use multivariate models scale up better to the dimensionality of the problem than existing EAs.
Distributed Relaxation for Conservative Discretizations
NASA Technical Reports Server (NTRS)
Diskin, Boris; Thomas, James L.
2001-01-01
A multigrid method is defined as having textbook multigrid efficiency (TME) if the solutions to the governing system of equations are attained in a computational work that is a small (less than 10) multiple of the operation count in one target-grid residual evaluation. The way to achieve this efficiency is the distributed relaxation approach. TME solvers employing distributed relaxation have already been demonstrated for nonconservative formulations of high-Reynolds-number viscous incompressible and subsonic compressible flow regimes. The purpose of this paper is to provide foundations for applications of distributed relaxation to conservative discretizations. A direct correspondence between the primitive variable interpolations for calculating fluxes in conservative finite-volume discretizations and stencils of the discretized derivatives in the nonconservative formulation has been established. Based on this correspondence, one can arrive at a conservative discretization which is very efficiently solved with a nonconservative relaxation scheme and this is demonstrated for conservative discretization of the quasi one-dimensional Euler equations. Formulations for both staggered and collocated grid arrangements are considered and extensions of the general procedure to multiple dimensions are discussed.
Cheraghi-Sohi, Sudeh; Calnan, Michael
2013-11-01
There has much debate about the extent to which professional discretion has been challenged by recent organisational changes such as through the new forms of governance associated with the introduction of the principles of the New Public Management (NPM) into health systems and other public sector services. What appears to be missing from these debates is a detailed analysis of the concept of professional discretion itself. This paper attempts to fill this gap by delineating the key concepts of professional discretion evident in the literature and exploring their significance in an empirical study of the influence of the 2004 new general medical services contract (nGMS) and the introduction of the Quality and Outcomes Framework (QOF), a prescriptive pay-for-performance system designed to standardise the quality of care provision in general medical practice in the United Kingdom. The study adopted a longitudinal design using semi-structured interviews with general practitioners (GPs, N = 62) working in the English National Health Service (NHS) between 2007 and 2009. A multi-dimensional conception of discretion was used to explore how GP discretion might have been influenced by contractual changes and in particular, QOF. The findings suggest that through a complex interplay of factors, a post-QOF reduction in GP discretion was identifiable, highlighting different potential sources of constraint such as in the social, organisational and economic dimensions of discretion. The evidence also suggested the emergence of a new form of organisational medical professionalism within general practice characterised by standardisation, bureaucracy and performance management. PMID:24034951
Geometry of discrete quantum computing
NASA Astrophysics Data System (ADS)
Hanson, Andrew J.; Ortiz, Gerardo; Sabry, Amr; Tai, Yu-Tsung
2013-05-01
Conventional quantum computing entails a geometry based on the description of an n-qubit state using 2n infinite precision complex numbers denoting a vector in a Hilbert space. Such numbers are in general uncomputable using any real-world resources, and, if we have the idea of physical law as some kind of computational algorithm of the universe, we would be compelled to alter our descriptions of physics to be consistent with computable numbers. Our purpose here is to examine the geometric implications of using finite fields Fp and finite complexified fields \\mathbf {F}_{p^2} (based on primes p congruent to 3 (mod4)) as the basis for computations in a theory of discrete quantum computing, which would therefore become a computable theory. Because the states of a discrete n-qubit system are in principle enumerable, we are able to determine the proportions of entangled and unentangled states. In particular, we extend the Hopf fibration that defines the irreducible state space of conventional continuous n-qubit theories (which is the complex projective space \\mathbf {CP}^{2^{n}-1}) to an analogous discrete geometry in which the Hopf circle for any n is found to be a discrete set of p + 1 points. The tally of unit-length n-qubit states is given, and reduced via the generalized Hopf fibration to \\mathbf {DCP}^{2^{n}-1}, the discrete analogue of the complex projective space, which has p^{2^{n}-1} (p-1)\\,\\prod _{k=1}^{n-1} ( p^{2^{k}}+1) irreducible states. Using a measure of entanglement, the purity, we explore the entanglement features of discrete quantum states and find that the n-qubit states based on the complexified field \\mathbf {F}_{p^2} have pn(p - 1)n unentangled states (the product of the tally for a single qubit) with purity 1, and they have pn + 1(p - 1)(p + 1)n - 1 maximally entangled states with purity zero.
On the Importance of the Dynamics of Discretizations
NASA Technical Reports Server (NTRS)
Sweby, Peter K.; Yee, H. C.; Rai, ManMohan (Technical Monitor)
1995-01-01
It has been realized recently that the discrete maps resulting from numerical discretizations of differential equations can possess asymptotic dynamical behavior quite different from that of the original systems. This is the case not only for systems of Ordinary Differential Equations (ODEs) but in a more complicated manner for Partial Differential Equations (PDEs) used to model complex physics. The impact of the modified dynamics may be mild and even not observed for some numerical methods. For other classes of discretizations the impact may be pronounced, but not always obvious depending on the nonlinear model equations, the time steps, the grid spacings and the initial conditions. Non-convergence or convergence to periodic solutions might be easily recognizable but convergence to incorrect but plausible solutions may not be so obvious - even for discretized parameters within the linearized stability constraint. Based on our past four years of research, we will illustrate some of the pathology of the dynamics of discretizations, its possible impact and the usage of these schemes for model nonlinear ODEs, convection-diffusion equations and grid adaptations.
Bourret, S.C.; Swansen, J.E.
1982-07-02
A stepping motor is microprocessor controlled by digital circuitry which monitors the output of a shaft encoder adjustably secured to the stepping motor and generates a subsequent stepping pulse only after the preceding step has occurred and a fixed delay has expired. The fixed delay is variable on a real-time basis to provide for smooth and controlled deceleration.
Bourret, Steven C.; Swansen, James E.
1984-01-01
A stepping motor is microprocessingly controlled by digital circuitry which monitors the output of a shaft encoder adjustably secured to the stepping motor and generates a subsequent stepping pulse only after the preceding step has occurred and a fixed delay has expired. The fixed delay is variable on a real-time basis to provide for smooth and controlled deceleration.
Review of finite fields: Applications to discrete Fourier, transforms and Reed-Solomon coding
NASA Technical Reports Server (NTRS)
Wong, J. S. L.; Truong, T. K.; Benjauthrit, B.; Mulhall, B. D. L.; Reed, I. S.
1977-01-01
An attempt is made to provide a step-by-step approach to the subject of finite fields. Rigorous proofs and highly theoretical materials are avoided. The simple concepts of groups, rings, and fields are discussed and developed more or less heuristically. Examples are used liberally to illustrate the meaning of definitions and theories. Applications include discrete Fourier transforms and Reed-Solomon coding.
General technique for discrete retardation-modulation polarimetry
NASA Technical Reports Server (NTRS)
Saxena, Indu
1993-01-01
The general theory and rigorous solutions of the Stokes parameters of light of a new technique in time-resolved ellipsometry are outlined. In this technique the phase of the linear retarder is stepped over three discrete values over a time interval for which the Stokes vector is determined. The technique has an advantage over synchronous detection techniques, as it can be implemented as a digitizable system.
Some discrete multiple orthogonal polynomials
NASA Astrophysics Data System (ADS)
Arvesú, J.; Coussement, J.; van Assche, W.
2003-04-01
In this paper, we extend the theory of discrete orthogonal polynomials (on a linear lattice) to polynomials satisfying orthogonality conditions with respect to r positive discrete measures. First we recall the known results of the classical orthogonal polynomials of Charlier, Meixner, Kravchuk and Hahn (T.S. Chihara, An Introduction to Orthogonal Polynomials, Gordon and Breach, New York, 1978; R. Koekoek and R.F. Swarttouw, Reports of the Faculty of Technical Mathematics and Informatics No. 98-17, Delft, 1998; A.F. Nikiforov et al., Classical Orthogonal Polynomials of a Discrete Variable, Springer, Berlin, 1991). These polynomials have a lowering and raising operator, which give rise to a Rodrigues formula, a second order difference equation, and an explicit expression from which the coefficients of the three-term recurrence relation can be obtained. Then we consider r positive discrete measures and define two types of multiple orthogonal polynomials. The continuous case (Jacobi, Laguerre, Hermite, etc.) was studied by Van Assche and Coussement (J. Comput. Appl. Math. 127 (2001) 317-347) and Aptekarev et al. (Multiple orthogonal polynomials for classical weights, manuscript). The families of multiple orthogonal polynomials (of type II) that we will study have a raising operator and hence a Rodrigues formula. This will give us an explicit formula for the polynomials. Finally, there also exists a recurrence relation of order r+1 for these multiple orthogonal polynomials of type II. We compute the coefficients of the recurrence relation explicitly when r=2.
Discrete implementations of scale transform
NASA Astrophysics Data System (ADS)
Djurdjanovic, Dragan; Williams, William J.; Koh, Christopher K.
1999-11-01
Scale as a physical quantity is a recently developed concept. The scale transform can be viewed as a special case of the more general Mellin transform and its mathematical properties are very applicable in the analysis and interpretation of the signals subject to scale changes. A number of single-dimensional applications of scale concept have been made in speech analysis, processing of biological signals, machine vibration analysis and other areas. Recently, the scale transform was also applied in multi-dimensional signal processing and used for image filtering and denoising. Discrete implementation of the scale transform can be carried out using logarithmic sampling and the well-known fast Fourier transform. Nevertheless, in the case of the uniformly sampled signals, this implementation involves resampling. An algorithm not involving resampling of the uniformly sampled signals has been derived too. In this paper, a modification of the later algorithm for discrete implementation of the direct scale transform is presented. In addition, similar concept was used to improve a recently introduced discrete implementation of the inverse scale transform. Estimation of the absolute discretization errors showed that the modified algorithms have a desirable property of yielding a smaller region of possible error magnitudes. Experimental results are obtained using artificial signals as well as signals evoked from the temporomandibular joint. In addition, discrete implementations for the separable two-dimensional direct and inverse scale transforms are derived. Experiments with image restoration and scaling through two-dimensional scale domain using the novel implementation of the separable two-dimensional scale transform pair are presented.
Discrete Mechanics and Optimal Control for Space Trajectory Design
NASA Astrophysics Data System (ADS)
Moore, Ashley
Space trajectory design is often achieved through a combination of dynamical systems theory and optimal control. The union of trajectory design techniques utilizing invariant manifolds of the planar circular restricted three-body problem and the optimal control scheme Discrete Mechanics and Optimal Control (DMOC) facilitates the design of low-energy trajectories in the N-body problem. In particular, DMOC is used to optimize a trajectory from the Earth to the Moon in the 4-body problem, removing the mid-course change in velocity, Delta V, usually necessary for such a trajectory while still exploiting the structure from the invariant manifolds. This thesis also focuses on how to adapt DMOC, a method devised with a constant step size, for the highly nonlinear dynamics involved in trajectory design. Mesh refinement techniques that aim to reduce discretization errors in the solution and energy evolution and their effect on DMOC optimization are explored and compared with trajectories created using time adaptive variational integrators. Furthermore, a time adaptive form of DMOC is developed that allows for a variable step size that is updated throughout the optimization process. Time adapted DMOC is based on a discretization of Hamilton's principle applied to the time adapted Lagrangian of the optimal control problem. Variations of the discrete action of the optimal control Lagrangian lead to discrete Euler-Lagrange equations that can be enforced as constraints for a boundary value problem. This new form of DMOC leads to the accurate and efficient solution of optimal control problems with highly nonlinear dynamics. Time adapted DMOC is tested on several space trajectory problems including the elliptical orbit transfer in the 2-body problem and the reconfiguration of a cubesat.
Densmore, Jeffery D. Warsa, James S. Lowrie, Robert B. Morel, Jim E.
2009-09-01
The Fokker-Planck equation is a widely used approximation for modeling the Compton scattering of photons in high energy density applications. In this paper, we perform a stability analysis of three implicit time discretizations for the Compton-Scattering Fokker-Planck equation. Specifically, we examine (i) a Semi-Implicit (SI) scheme that employs backward-Euler differencing but evaluates temperature-dependent coefficients at their beginning-of-time-step values, (ii) a Fully Implicit (FI) discretization that instead evaluates temperature-dependent coefficients at their end-of-time-step values, and (iii) a Linearized Implicit (LI) scheme, which is developed by linearizing the temperature dependence of the FI discretization within each time step. Our stability analysis shows that the FI and LI schemes are unconditionally stable and cannot generate oscillatory solutions regardless of time-step size, whereas the SI discretization can suffer from instabilities and nonphysical oscillations for sufficiently large time steps. With the results of this analysis, we present time-step limits for the SI scheme that prevent undesirable behavior. We test the validity of our stability analysis and time-step limits with a set of numerical examples.
Densmore, Jeffery D; Warsa, James S; Lowrie, Robert B; Morel, Jim E
2008-01-01
The Fokker-Planck equation is a widely used approximation for modeling the Compton scattering of photons in high energy density applications. In this paper, we perform a stability analysis of three implicit time discretizations for the Compton-Scattering Fokker-Planck equation. Specifically, we examine (i) a Semi-Implicit (SI) scheme that employs backward-Euler differencing but evaluates temperature-dependent coefficients at their beginning-of-time-step values, (ii) a Fully Implicit (FI) discretization that instead evaluates temperature-dependent coefficients at their end-of-time-step values, and (iii) a Linearized Implicit (LI) scheme, which is developed by linearizing the temperature dependence of the FI discretization within each time step. Our stability analysis shows that the FI and LI schemes are unconditionally stable and cannot generate oscillatory solutions regardless of time-step size, whereas the SI discretization can suffer from instabilities and nonphysical oscillations for sufficiently large time steps. With the results of this analysis, we present time-step limits for the SI scheme that prevent undesirable behavior. We test the validity of our stability analysis and time-step limits with a set of numerical examples.
Steps in Behavior Modividation.
ERIC Educational Resources Information Center
Straughan, James H.; And Others
James H. Straughan lists five steps for modifying target behavior and four steps for working with teachers using behavior modification. Grant Martin and Harold Kunzelmann then outline an instructional program for pinpointing and recording classroom behaviors. (JD)
Systoles in discrete dynamical systems
NASA Astrophysics Data System (ADS)
Fernandes, Sara; Grácio, Clara; Ramos, Carlos Correia
2013-01-01
The fruitful relationship between Geometry and Graph Theory has been explored by several authors benefiting also the Theory of discrete dynamical systems seen as Markov chains in graphs. In this work we will further explore the relation between these areas, giving a geometrical interpretation of notions from dynamical systems. In particular, we relate the topological entropy with the systole, here defined in the context of discrete dynamical systems. We show that for continuous interval maps the systole is trivial; however, for the class of interval maps with one discontinuity point the systole acquires relevance from the point of view of the dynamical behavior. Moreover, we define the geodesic length spectrum associated to a Markov interval map and we compute the referred spectrum in several examples.
Dark Energy from Discrete Spacetime
Trout, Aaron D.
2013-01-01
Dark energy accounts for most of the matter-energy content of our universe, yet current theories of its origin rely on radical physical assumptions such as the holographic principle or controversial anthropic arguments. We give a better motivated explanation for dark energy, claiming that it arises from a small negative scalar-curvature present even in empty spacetime. The vacuum has this curvature because spacetime is fundamentally discrete and there are more ways for a discrete geometry to have negative curvature than positive. We explicitly compute this effect using a variant of the well known dynamical-triangulations (DT) model for quantum gravity. Our model predicts a time-varying non-zero cosmological constant with a current value, in natural units, in agreement with observation. This calculation is made possible by a novel characterization of the possible DT action values combined with numerical evidence concerning their degeneracies. PMID:24312502
Dark energy from discrete spacetime.
Trout, Aaron D
2013-01-01
Dark energy accounts for most of the matter-energy content of our universe, yet current theories of its origin rely on radical physical assumptions such as the holographic principle or controversial anthropic arguments. We give a better motivated explanation for dark energy, claiming that it arises from a small negative scalar-curvature present even in empty spacetime. The vacuum has this curvature because spacetime is fundamentally discrete and there are more ways for a discrete geometry to have negative curvature than positive. We explicitly compute this effect using a variant of the well known dynamical-triangulations (DT) model for quantum gravity. Our model predicts a time-varying non-zero cosmological constant with a current value, [Formula: see text] in natural units, in agreement with observation. This calculation is made possible by a novel characterization of the possible DT action values combined with numerical evidence concerning their degeneracies. PMID:24312502
Class of discrete Gabor expansion
NASA Astrophysics Data System (ADS)
Li, Shidong; Healy, Dennis M., Jr.
1994-03-01
We present a new approach to studying a discrete Gabor expansion (DGE). We show that, in general, DGE is not the usual biorthogonal decomposition, but belongs to a larger and looser decomposition scheme which we call pseudo frame decomposition. It includes the DGE scheme proposed as a special case. The standard dual frame decomposition is also a special case. We derive algorithms using techniques for Gabor sequences to compute 'biorthogonal' sequences through proper matrix representation. Our algorithms involve solutions to a linear system to obtain the 'biorthogonal' windows. This approach provides a much broader mathematical view of the DGE, and therefore, establishes a wider mathematical foundation towards the theory of DGE. The general algorithm derived also provides a whole class of discrete Gabor expansions, among which 'good' ones can be generated. Simulation results are also provided.
A FORTRAN Program for Discrete Discriminant Analysis
ERIC Educational Resources Information Center
Boone, James O.; Brewer, James K.
1976-01-01
A Fortran program is presented for discriminant analysis of discrete variables. The program assumes discrete, nominal data with no distributional, variance-covariance assumptions. The program handles a maximum of fifty predictor variables and twelve outcome groups. (Author/JKS)
Efficient genetic algorithms using discretization scheduling.
McLay, Laura A; Goldberg, David E
2005-01-01
In many applications of genetic algorithms, there is a tradeoff between speed and accuracy in fitness evaluations when evaluations use numerical methods with varying discretization. In these types of applications, the cost and accuracy vary from discretization errors when implicit or explicit quadrature is used to estimate the function evaluations. This paper examines discretization scheduling, or how to vary the discretization within the genetic algorithm in order to use the least amount of computation time for a solution of a desired quality. The effectiveness of discretization scheduling can be determined by comparing its computation time to the computation time of a GA using a constant discretization. There are three ingredients for the discretization scheduling: population sizing, estimated time for each function evaluation and predicted convergence time analysis. Idealized one- and two-dimensional experiments and an inverse groundwater application illustrate the computational savings to be achieved from using discretization scheduling. PMID:16156928
Anomalies and Discrete Chiral Symmetries
Creutz, M.
2009-09-07
The quantum anomaly that breaks the U(1) axial symmetry of massless multi-flavored QCD leaves behind a discrete flavor-singlet chiral invariance. With massive quarks, this residual symmetry has a close connection with the strong CP-violating parameter theta. One result is that if the lightest quarks are degenerate, then a first order transition will occur when theta passes through pi. The resulting framework helps clarify when the rooting prescription for extrapolating in the number of flavors is valid.
Discrete vortex representation of magnetohydrodynamics
Kinney, R.; Tajima, T.; Petviashvili, N.; McWilliams, J.C.
1993-02-01
We present an alternative approach to statistical analysis of an intermittent ideal MHD fluid in two dimensions, based on the hydrodynamical discrete vortex model applied to the Elsasser variables. The model contains negative temperature states which predict the formation of magnetic islands, but also includes a natural limit under which the equilibrium states revert to the familiar twin-vortex states predicted by hydrodynamical turbulence theories. Numerical dynamical calculations yield equilibrium spectra in agreement with the theoretical predictions.
Discrete-contact nanowire photovoltaics
NASA Astrophysics Data System (ADS)
Chitambar, Michelle J.; Wen, Wen; Maldonado, Stephen
2013-11-01
A series of finite-element simulations have been performed to assess the operational characteristics of a new semiconductor nanowire solar cell design operating under high-level injection conditions. Specifically, the steady-state current-voltage behavior of a cylindrical silicon (Si) nanowire with a series of discrete, ohmic-selective contacts under intense sunlight illumination was investigated. The scope of the analysis was limited to only the factors that impact the net internal quantum yield for solar to electricity conversion. No evaluations were performed with regards to optical light trapping in the modeled structures. Several aspects in a discrete-contact nanowire device that could impact operation were explored, including the size and density of ohmic-selective contacts, the size of the nanowire, the electronic quality and conductivity of the nanowire, the surface defect density of the nanowire, and the type of ohmic selectivity employed at each contact. The analysis showed that there were ranges of values for each parameter that supported good to excellent photoresponses, with certain combinations of experimentally attainable material properties yielding internal energy conversion efficiencies at the thermodynamic limit for a single junction cell. The merits of the discrete-contact nanowire cell were contrasted with "conventional" nanowire photovoltaic cells featuring a uniform conformal contact and also with planar point-contact solar cells. The unique capacity of the discrete-contact nanowire solar cell design to operate at useful energy conversion efficiencies with low quality semiconductor nanowires (i.e., possessing short charge-carrier lifetimes) with only light doping is discussed. This work thus defines the impetus for future experimental work aimed at developing this photovoltaic architecture.
Discrete-time quantum walk with feed-forward quantum coin
Shikano, Yutaka; Wada, Tatsuaki; Horikawa, Junsei
2014-01-01
Constructing a discrete model like a cellular automaton is a powerful method for understanding various dynamical systems. However, the relationship between the discrete model and its continuous analogue is, in general, nontrivial. As a quantum-mechanical cellular automaton, a discrete-time quantum walk is defined to include various quantum dynamical behavior. Here we generalize a discrete-time quantum walk on a line into the feed-forward quantum coin model, which depends on the coin state of the previous step. We show that our proposed model has an anomalous slow diffusion characterized by the porous-medium equation, while the conventional discrete-time quantum walk model shows ballistic transport. PMID:24651053
Stepped Hydraulic Geometry in Stepped Channels
NASA Astrophysics Data System (ADS)
Comiti, F.; Cadol, D. D.; Wohl, E.
2007-12-01
Steep mountain streams typically present a stepped longitudinal profile. Such stepped channels feature tumbling flow, where hydraulic jumps represent an important source of channel roughness (spill resistance). However, the extent to which spill resistance persists up to high flows has not been ascertained yet, such that a faster, skimming flow has been envisaged to begin at those conditions. In order to analyze the relationship between flow resistance and bed morphology, a mobile bed physical model was developed at Colorado State University (Fort Collins, USA). An 8 m-long, 0.6 m-wide flume tilted at a constant 14% slope was used, testing 2 grain-size mixtures differing only for the largest fraction. Experiments were conducted under clear water conditions. Reach-averaged flow velocity was measured using salt tracers, bed morphology and flow depth by a point gage, and surface grain size using commercial image-analysis software. Starting from an initial plane bed, progressively higher flow rates were used to create different bed structures. After each bed morphology was stable with its forming discharge, lower-than-forming flows were run to build a hydraulic geometry curve. Results show that even though equilibrium slopes ranged from 8.5% to 14%, the reach-averaged flow was always sub-critical. Steps formed through a variety of mechanisms, with immobile clasts playing a dominant role by causing local scouring and/or trapping moving smaller particles. Overall, step height, step pool steepness, relative pool area and volume increased with discharge up to the threshold when the bed approached fully- mobilized conditions. For bed morphologies surpassing a minimum profile roughness, a stepped velocity- discharge relationship is evident, with sharp rises in velocity correlated with the disappearance of rollers in pools at flows approaching the formative discharge for each morphology. Flow resistance exhibits an opposite pattern, with drops in resistance being a function
Correlations and discreteness in nonlinear QCD evolution
Armesto, N.; Milhano, J.
2006-06-01
We consider modifications of the standard nonlinear QCD evolution in an attempt to account for some of the missing ingredients discussed recently, such as correlations, discreteness in gluon emission and Pomeron loops. The evolution is numerically performed using the Balitsky-Kovchegov equation on individual configurations defined by a given initial value of the saturation scale, for reduced rapidities y=({alpha}{sub s}N{sub c}/{pi})Y<10. We consider the effects of averaging over configurations as a way to implement correlations, using three types of Gaussian averaging around a mean saturation scale. Further, we heuristically mimic discreteness in gluon emission by considering a modified evolution in which the tails of the gluon distributions are cut off. The approach to scaling and the behavior of the saturation scale with rapidity in these modified evolutions are studied and compared with the standard mean-field results. For the large but finite values of rapidity explored, no strong quantitative difference in scaling for transverse momenta around the saturation scale is observed. At larger transverse momenta, the influence of the modifications in the evolution seems most noticeable in the first steps of the evolution. No influence on the rapidity behavior of the saturation scale due to the averaging procedure is found. In the cutoff evolution the rapidity evolution of the saturation scale is slowed down and strongly depends on the value of the cutoff. Our results stress the need to go beyond simple modifications of evolution by developing proper theoretical tools that implement such recently discussed ingredients.
ERIC Educational Resources Information Center
Herman, Susan
1995-01-01
Aerobics instructors can use step aerobics to motivate students. One creative method is to add the step to the circuit workout. By incorporating the step, aerobic instructors can accommodate various fitness levels. The article explains necessary equipment and procedures, describing sample stations for cardiorespiratory fitness, muscular strength,…
ERIC Educational Resources Information Center
Thornton, Carol A.; And Others
1980-01-01
Described are activities and games incorporating a technique of "one step" which is used with children with learning difficulties. The purpose of "one step" is twofold, to minimize difficulties with typical trouble spots and to keep the step size of the instruction small. (Author/TG)
Symmetric Discrete Orthonormal Stockwell Transform
NASA Astrophysics Data System (ADS)
Wang, Yanwei; Orchard, Jeff
2008-09-01
The Stockwell Transform (ST) is a time-frequency signal decomposition that is gaining in popularity, likely because of its direct relation with the Fourier Transform (FT). A discrete and non-redundant version of the ST, denoted the Discrete Orthonormal Stockwell Transform (DOST), has made the use of the ST more feasible. However, the matrix multiplication required by the DOST can still be a formidable computation, especially for high-dimensional data. Moreover, the symmetric property of the ST and FT is not present in the DOST. In this paper, we investigate a new Symmetric Discrete Orthonormal Stockwell Transform (SDOST) that still keeps the non-redundant multiresolution features of the DOST, while maintaining a symmetry property similar to that of the FT. First, we give a brief introduction for the ST and the DOST. Then we analyze the DOST coefficients and modify the transform to get a symmetric version. A small experiment shows that the SDOST has kept the abilities of the DOST and demonstrates the advantage of symmetry when applying the SDOST.
Interference in discrete Wigner functions
Cormick, Cecilia; Paz, Juan Pablo
2006-12-15
We analyze some features of the class of discrete Wigner functions that was recently introduced by Gibbons et al. [Phys. Rev. A 70, 062101 (2004)] to represent quantum states of systems with power-of-prime dimensional Hilbert spaces. We consider ''cat'' states obtained as coherent superpositions of states with positive Wigner function; for such states we show that the oscillations of the discrete Wigner function typically spread over the entire discrete phase space (including the regions where the two interfering states are localized). This is a generic property, which is in sharp contrast with the usual attributes of Wigner functions that make them useful candidates to display the existence of quantum coherence through oscillations. However, it is possible to find subsets of cat states with a natural phase-space representation, in which the oscillatory regions remain localized. We show that this can be done for interesting families of stabilizer states used in quantum error-correcting codes, and illustrate this by analyzing the phase-space representation of the five-qubit error-correcting code.
Observability of discretized partial differential equations
NASA Technical Reports Server (NTRS)
Cohn, Stephen E.; Dee, Dick P.
1988-01-01
It is shown that complete observability of the discrete model used to assimilate data from a linear partial differential equation (PDE) system is necessary and sufficient for asymptotic stability of the data assimilation process. The observability theory for discrete systems is reviewed and applied to obtain simple observability tests for discretized constant-coefficient PDEs. Examples are used to show how numerical dispersion can result in discrete dynamics with multiple eigenvalues, thereby detracting from observability.
NASA Technical Reports Server (NTRS)
1994-01-01
STEP (STandard for the Exchange of Product Model Data) is an innovative software tool that allows the exchange of data between different programming systems to occur and helps speed up the designing in various process industries. This exchange occurs easily between those companies that have STEP, and many industries and government agencies are requiring that their vendors utilize STEP in their computer aided design projects, such as in the areas of mechanical, aeronautical, and electrical engineering. STEP allows the process of concurrent engineering to occur and increases the quality of the design product. One example of the STEP program is the Boeing 777, the first paperless airplane.
An adaptive mesh refinement algorithm for the discrete ordinates method
Jessee, J.P.; Fiveland, W.A.; Howell, L.H.; Colella, P.; Pember, R.B.
1996-03-01
The discrete ordinates form of the radiative transport equation (RTE) is spatially discretized and solved using an adaptive mesh refinement (AMR) algorithm. This technique permits the local grid refinement to minimize spatial discretization error of the RTE. An error estimator is applied to define regions for local grid refinement; overlapping refined grids are recursively placed in these regions; and the RTE is then solved over the entire domain. The procedure continues until the spatial discretization error has been reduced to a sufficient level. The following aspects of the algorithm are discussed: error estimation, grid generation, communication between refined levels, and solution sequencing. This initial formulation employs the step scheme, and is valid for absorbing and isotopically scattering media in two-dimensional enclosures. The utility of the algorithm is tested by comparing the convergence characteristics and accuracy to those of the standard single-grid algorithm for several benchmark cases. The AMR algorithm provides a reduction in memory requirements and maintains the convergence characteristics of the standard single-grid algorithm; however, the cases illustrate that efficiency gains of the AMR algorithm will not be fully realized until three-dimensional geometries are considered.
Discrete Randomness in Discrete Time Quantum Walk: Study Via Stochastic Averaging
NASA Astrophysics Data System (ADS)
Ellinas, D.; Bracken, A. J.; Smyrnakis, I.
2012-10-01
The role of classical noise in quantum walks (QW) on integers is investigated in the form of discrete dichotomic random variable affecting its reshuffling matrix parametrized as a SU2)/U (1) coset element. Analysis in terms of quantum statistical moments and generating functions, derived by the completely positive trace preserving (CPTP) map governing evolution, reveals a pronounced eventual transition in walk's diffusion mode, from a quantum ballistic regime with rate O(t) to a classical diffusive regime with rate O(√{t}), when condition (strength of noise parameter)2 × (number of steps) = 1, is satisfied. The role of classical randomness is studied showing that the randomized QW, when treated on the stochastic average level by means of an appropriate CPTP averaging map, turns out to be equivalent to a novel quantized classical walk without randomness. This result emphasizes the dual role of quantization/randomization in the context of classical random walk.
NASA Astrophysics Data System (ADS)
Yokokawa, M.; Izumi, N.; Naito, K.; Parker, G.; Yamada, T.; Greve, R.
2016-05-01
Boundary waves often form at the interface between ice and fluid flowing adjacent to it, such as ripples under river ice covers, and steps on the bed of supraglacial meltwater channels. They may also be formed by wind, such as the megadunes on the Antarctic ice sheet. Spiral troughs on the polar ice caps of Mars have been interpreted to be cyclic steps formed by katabatic wind blowing over ice. Cyclic steps are relatives of upstream-migrating antidunes. Cyclic step formation on ice is not only a mechanical but also a thermodynamic process. There have been very few studies on the formation of either cyclic steps or upstream-migrating antidunes on ice. In this study, we performed flume experiments to reproduce cyclic steps on ice by flowing water, and found that trains of steps form when the Froude number is larger than unity. The features of those steps allow them to be identified as ice-bed analogs of cyclic steps in alluvial and bedrock rivers. We performed a linear stability analysis and obtained a physical explanation of the formation of upstream-migrating antidunes, i.e., precursors of cyclic steps. We compared the results of experiments with the predictions of the analysis and found the observed steps fall in the range where the analysis predicts interfacial instability. We also found that short antidune-like undulations formed as a precursor to the appearance of well-defined steps. This fact suggests that such antidune-like undulations correspond to the instability predicted by the analysis and are precursors of cyclic steps.
Driven discrete time quantum walks
NASA Astrophysics Data System (ADS)
Hamilton, Craig S.; Barkhofen, Sonja; Sansoni, Linda; Jex, Igor; Silberhorn, Christine
2016-07-01
We introduce the driven discrete time quantum walk (QW), where walkers are added during the walk instead of only at the beginning. This leads to interference in walker number and very different dynamics when compared to the original QW. These dynamics have two regimes, which we illustrate using the one-dimensional line. Then, we explore a search application which has certain advantages over current search protocols, namely that it does not require a complicated initial state nor a specific measurement time to observe the marked state. Finally, we describe a potential experimental implementation using existing technology.
Directed self-assembly of proteins into discrete radial patterns
Thakur, Garima; Prashanthi, Kovur; Thundat, Thomas
2013-01-01
Unlike physical patterning of materials at nanometer scale, manipulating soft matter such as biomolecules into patterns is still in its infancy. Self-assembled monolayer (SAM) with surface density gradient has the capability to drive biomolecules in specific directions to create hierarchical and discrete structures. Here, we report on a two-step process of self-assembly of the human serum albumin (HSA) protein into discrete ring structures based on density gradient of SAM. The methodology involves first creating a 2-dimensional (2D) polyethylene glycol (PEG) islands with responsive carboxyl functionalities. Incubation of proteins on such pre-patterned surfaces results in direct self-assembly of protein molecules around PEG islands. Immobilization and adsorption of protein on such structures over time evolve into the self-assembled patterns. PMID:23719678
Application of an enhanced discrete element method to oil and gas drilling processes
NASA Astrophysics Data System (ADS)
Ubach, Pere Andreu; Arrufat, Ferran; Ring, Lev; Gandikota, Raju; Zárate, Francisco; Oñate, Eugenio
2016-03-01
The authors present results on the use of the discrete element method (DEM) for the simulation of drilling processes typical in the oil and gas exploration industry. The numerical method uses advanced DEM techniques using a local definition of the DEM parameters and combined FEM-DEM procedures. This paper presents a step-by-step procedure to build a DEM model for analysis of the soil region coupled to a FEM model for discretizing the drilling tool that reproduces the drilling mechanics of a particular drill bit. A parametric study has been performed to determine the model parameters in order to maintain accurate solutions with reduced computational cost.
NASA Astrophysics Data System (ADS)
Mohamad, Sannay
2008-05-01
This paper demonstrates that there is a discrete-time analogue which does not require any restriction on the size of the time-step in order to preserve the exponential stability of an artificial neural network with distributed delays. The analysis exploits an appropriate Lyapunov sequence and a discrete-time system of Halanay inequalities, and also either a Young inequality or a geometric-arithmetic mean inequality, to derive several sufficient conditions on the network parameters for the exponential stability of the analogue. The sufficiency conditions are independent of the time-step, and they correspond to those that establish the exponential stability of the continuous-time network.
Golgi-Cox Staining Step by Step
Zaqout, Sami; Kaindl, Angela M.
2016-01-01
Golgi staining remains a key method to study neuronal morphology in vivo. Since most protocols delineating modifications of the original staining method lack details on critical steps, establishing this method in a laboratory can be time-consuming and frustrating. Here, we describe the Golgi-Cox staining in such detail that should turn the staining into an easily feasible method for all scientists working in the neuroscience field. PMID:27065817
Discrete Element Modeling for Mobility and Excavation
NASA Astrophysics Data System (ADS)
Knuth, M. A.; Hopkins, M. A.
2011-12-01
The planning and completion of mobility and excavation efforts on the moon requires a thorough understanding of the planetary regolith. In this work, a discrete element method (DEM) model is created to replicate those activities in the laboratory and for planning mission activities in the future. The crux of this work is developing a particle bed that best replicates the regolith tool/wheel interaction seen in the laboratory. To do this, a DEM geotechnical triaxial strength cell was created allowing for comparison of laboratory JSC-1a triaxial tests to DEM simulated soils. This model relies on a triangular lattice membrane covered triaxial cell for determining the macroscopic properties of the modeled granular material as well as a fast and efficient contact detection algorithm for a variety of grain shapes. Multiple grain shapes with increasing complexity (ellipsoid, poly-ellipsoid and polyhedra) have been developed and tested. This comparison gives us a basis to begin scaling DEM grain size and shape to practical values for mobility and excavation modeling. Next steps include development of a DEM scoop for percussive excavation testing as well as continued analysis of rover wheel interactions using a wide assortment of grain shape and size distributions.
Discrete interferometer with individual trapped atoms
NASA Astrophysics Data System (ADS)
Steffen, Andreas; Alberti, Andrea; Alt, Wolfgang; Belmechri, Noomen; Hild, Sebastian; Karski, Michal; Widera, Artur; Meschede, Dieter; Quantum Technology Team
2011-05-01
Coherent control and delocalization of individual atoms is a pivotal challenge in quantum technologies. As a new step on this road, we present an individual atom interferometer that is capable of splitting a trapped Cs atom by up to 10 μm , allowing us to measure potential gradients on the microscale. The atom is confined in a 1D optical lattice, which is capable of performing discrete state-dependent shifts to split the atom by the desired number of sites. We establish a high degree of control, as the initial atom position, vibrational state and spin state can all be prepared with above 95% fidelity. To unravel decoherence effects and phase influences, we have explored several basic interferometer geometries, among other things demonstrating a positional spin echo to cancel background effects. As a test case, an inertial force has been applied and successfully measured using the atomic phase. This will offer us a new tool to investigate the interaction between two atoms in a controlled model system.
Discreteness effects in population dynamics
NASA Astrophysics Data System (ADS)
Guevara Hidalgo, Esteban; Lecomte, Vivien
2016-05-01
We analyse numerically the effects of small population size in the initial transient regime of a simple example population dynamics. These effects play an important role for the numerical determination of large deviation functions of additive observables for stochastic processes. A method commonly used in order to determine such functions is the so-called cloning algorithm which in its non-constant population version essentially reduces to the determination of the growth rate of a population, averaged over many realizations of the dynamics. However, the averaging of populations is highly dependent not only on the number of realizations of the population dynamics, and on the initial population size but also on the cut-off time (or population) considered to stop their numerical evolution. This may result in an over-influence of discreteness effects at initial times, caused by small population size. We overcome these effects by introducing a (realization-dependent) time delay in the evolution of populations, additional to the discarding of the initial transient regime of the population growth where these discreteness effects are strong. We show that the improvement in the estimation of the large deviation function comes precisely from these two main contributions.
NASA Astrophysics Data System (ADS)
Guo, Ruihan; Xia, Yinhua; Xu, Yan
2014-05-01
In this paper, we develop an efficient and energy stable fully-discrete local discontinuous Galerkin (LDG) method for the Cahn-Hilliard-Hele-Shaw (CHHS) system. The semi-discrete energy stability of the LDG method is proved firstly. Due to the strict time step restriction (Δt=O(Δx4)) of explicit time discretization methods for stability, we introduce a semi-implicit time integration scheme which is based on a convex splitting of the discrete Cahn-Hilliard energy. The unconditional energy stability has been proved for this fully-discrete LDG scheme. The fully-discrete equations at the implicit time level are nonlinear. Thus, the nonlinear Full Approximation Scheme (FAS) multigrid method has been applied to solve this system of algebraic equations, which has been shown the nearly optimal complexity numerically. Numerical results are also given to illustrate the accuracy and capability of the LDG method coupled with the multigrid solver.
The Twelve Steps Experientially.
ERIC Educational Resources Information Center
Horne, Lianne
Experiential activities provide each participant with the ability to see, feel, and experience whatever therapeutic issue the facilitator is addressing, and usually much more. This paper presents experiential activities to address the 12 steps of recovery adopted from Alcoholics Anonymous. These 12 steps are used worldwide for many other recovery…
NASA Technical Reports Server (NTRS)
Brumfield, M. L. (Compiler)
1984-01-01
A plan to develop a space technology experiments platform (STEP) was examined. NASA Langley Research Center held a STEP Experiment Requirements Workshop on June 29 and 30 and July 1, 1983, at which experiment proposers were invited to present more detailed information on their experiment concept and requirements. A feasibility and preliminary definition study was conducted and the preliminary definition of STEP capabilities and experiment concepts and expected requirements for support services are presented. The preliminary definition of STEP capabilities based on detailed review of potential experiment requirements is investigated. Topics discussed include: Shuttle on-orbit dynamics; effects of the space environment on damping materials; erectable beam experiment; technology for development of very large solar array deployers; thermal energy management process experiment; photovoltaic concentrater pointing dynamics and plasma interactions; vibration isolation technology; flight tests of a synthetic aperture radar antenna with use of STEP.
Entropy is a consequence of a discrete time
NASA Astrophysics Data System (ADS)
Riek, Roland
2015-07-01
While the basic microscopic physical laws are time reversible, the arrow of time and time irreversibility appears only at the macroscopic physical laws by the second law of thermodynamics with its entropy term S. It is the attempt of the present work to bridge the microscopic physical world with its macroscopic one with an alternative approach than the statistical mechanics theory of Gibbs and Boltzmann. For simplicity a “classical”, single particle in a one dimensional space is selected. In addition, it is assumed that time is discrete with constant step size. As a consequence time irreversibility at the microscopic level is obtained if the present force is of complex nature (F(r) ≠ const). In order to compare this discrete time irreversible mechanics with its classical Newton analog, time reversibility is reintroduced by scaling the time steps for any given time step n by the variable sn leading to the Nosé-Hoover Lagrangian comprising a term NdfkB T In sn (kB the Boltzmann constant, T the temperature, and Ndf the number of degrees of freedom) which is defined as the microscopic entropy Sn at time point n multiplied by T. Upon ensemble averaging of the microscopic entropy in a many particles system in thermodynamic equilibrium it approximates its macroscopic counterpart known from statistical mechanics. The presented derivation with the resulting analogy between the ensemble averaged microscopic entropy and its statistical mechanics analog suggests that the entropy term itself has its root not in statistical mechanics but rather in the discreteness of time.
Observers for discrete-time nonlinear systems
NASA Astrophysics Data System (ADS)
Grossman, Walter D.
Observer synthesis for discrete-time nonlinear systems with special applications to parameter estimation is analyzed. Two new types of observers are developed. The first new observer is an adaptation of the Friedland continuous-time parameter estimator to discrete-time systems. The second observer is an adaptation of the continuous-time Gauthier observer to discrete-time systems. By adapting these observers to discrete-time continuous-time parameter estimation problems which were formerly intractable become tractable. In addition to the two newly developed observers, two observers already described in the literature are analyzed and deficiencies with respect to noise rejection are demonstrated. Improved versions of these observers are proposed and their performance demonstrated. The issues of discrete-time observability, discrete-time system inversion, and optimal probing are also addressed.
Extrapolated implicit-explicit time stepping.
Constantinescu, E. M.; Sandu, A.; Mathematics and Computer Science; Virginia Polytechnic Inst. and State Univ.
2010-01-01
This paper constructs extrapolated implicit-explicit time stepping methods that allow one to efficiently solve problems with both stiff and nonstiff components. The proposed methods are based on Euler steps and can provide very high order discretizations of ODEs, index-1 DAEs, and PDEs in the method-of-lines framework. Implicit-explicit schemes based on extrapolation are simple to construct, easy to implement, and straightforward to parallelize. This work establishes the existence of perturbed asymptotic expansions of global errors, explains the convergence orders of these methods, and studies their linear stability properties. Numerical results with stiff ODE, DAE, and PDE test problems confirm the theoretical findings and illustrate the potential of these methods to solve multiphysics multiscale problems.
Discrete modelling of drapery systems
NASA Astrophysics Data System (ADS)
Thoeni, Klaus; Giacomini, Anna
2016-04-01
Drapery systems are an efficient and cost-effective measure in preventing and controlling rockfall hazards on rock slopes. The simplest form consists of a row of ground anchors along the top of the slope connected to a horizontal support cable from which a wire mesh is suspended down the face of the slope. Such systems are generally referred to as simple or unsecured draperies (Badger and Duffy 2012). Variations such as secured draperies, where a pattern of ground anchors is incorporated within the field of the mesh, and hybrid systems, where the upper part of an unsecured drapery is elevated to intercept rockfalls originating upslope of the installation, are becoming more and more popular. This work presents a discrete element framework for simulation of unsecured drapery systems and its variations. The numerical model is based on the classical discrete element method (DEM) and implemented into the open-source framework YADE (Šmilauer et al., 2010). The model takes all relevant interactions between block, drapery and slope into account (Thoeni et al., 2014) and was calibrated and validated based on full-scale experiments (Giacomini et al., 2012).The block is modelled as a rigid clump made of spherical particles which allows any shape to be approximated. The drapery is represented by a set of spherical particle with remote interactions. The behaviour of the remote interactions is governed by the constitutive behaviour of the wire and generally corresponds to a piecewise linear stress-strain relation (Thoeni et al., 2013). The same concept is used to model wire ropes. The rock slope is represented by rigid triangular elements where material properties (e.g., normal coefficient of restitution, friction angle) are assigned to each triangle. The capabilities of the developed model to simulate drapery systems and estimate the residual hazard involved with such systems is shown. References Badger, T.C., Duffy, J.D. (2012) Drapery systems. In: Turner, A.K., Schuster R
Classicality in discrete Wigner functions
Cormick, Cecilia; Galvao, Ernesto F.; Gottesman, Daniel; Paz, Juan Pablo; Pittenger, Arthur O.
2006-01-15
Gibbons et al., [Phys. Rev. A 70, 062101 (2004)] have recently defined discrete Wigner functions W to represent quantum states in a Hilbert space with finite dimension. We show that such a class of Wigner functions W can be defined so that the only pure states having non-negative W for all such functions are stabilizer states, as conjectured by Galvao, [Phys. Rev. A 71, 042302 (2005)]. We also show that the unitaries preserving non-negativity of W for all definitions of W in the class form a subgroup of the Clifford group. This means pure states with non-negative W and their associated unitary dynamics are classical in the sense of admitting an efficient classical simulation scheme using the stabilizer formalism.
Determinant Expressions for Discrete Integrable Maps
NASA Astrophysics Data System (ADS)
Sogo, Kiyoshi
2006-08-01
Explicit formulas for several discrete integrable maps with periodic boundary condition are obtained, which give the sequential time developments in a form of the quotient of successive determinants of tri-diagonal matrices. We can expect that such formulas make the corresponding numerical simulations simple and stable. The cases of discrete Lotka-Volterra and discrete KdV equations are demonstrated by using the common algorithm computing determinants of tri-diagonal matrices.
Control of discrete event systems modeled as hierarchical state machines
NASA Technical Reports Server (NTRS)
Brave, Y.; Heymann, M.
1991-01-01
The authors examine a class of discrete event systems (DESs) modeled as asynchronous hierarchical state machines (AHSMs). For this class of DESs, they provide an efficient method for testing reachability, which is an essential step in many control synthesis procedures. This method utilizes the asynchronous nature and hierarchical structure of AHSMs, thereby illustrating the advantage of the AHSM representation as compared with its equivalent (flat) state machine representation. An application of the method is presented where an online minimally restrictive solution is proposed for the problem of maintaining a controlled AHSM within prescribed legal bounds.
A discrete event method for wave simulation
Nutaro, James J
2006-01-01
This article describes a discrete event interpretation of the finite difference time domain (FDTD) and digital wave guide network (DWN) wave simulation schemes. The discrete event method is formalized using the discrete event system specification (DEVS). The scheme is shown to have errors that are proportional to the resolution of the spatial grid. A numerical example demonstrates the relative efficiency of the scheme with respect to FDTD and DWN schemes. The potential for the discrete event scheme to reduce numerical dispersion and attenuation errors is discussed.
Scalar discrete nonlinear multipoint boundary value problems
NASA Astrophysics Data System (ADS)
Rodriguez, Jesus; Taylor, Padraic
2007-06-01
In this paper we provide sufficient conditions for the existence of solutions to scalar discrete nonlinear multipoint boundary value problems. By allowing more general boundary conditions and by imposing less restrictions on the nonlinearities, we obtain results that extend previous work in the area of discrete boundary value problems [Debra L. Etheridge, Jesus Rodriguez, Periodic solutions of nonlinear discrete-time systems, Appl. Anal. 62 (1996) 119-137; Debra L. Etheridge, Jesus Rodriguez, Scalar discrete nonlinear two-point boundary value problems, J. Difference Equ. Appl. 4 (1998) 127-144].
Artist Robert McCall painted "The Next Giant Step" in 1979 to commemorate the heroism and courage of spaceflight pioneers. Located in the lobby of Johnson's building 2, the mural depicts America's ...
NASA Astrophysics Data System (ADS)
Mohamad, Sannay
2001-11-01
Convergence dynamics of continuous-time bidirectional neural networks with constant transmission delays are studied. Without assuming the symmetry of synaptic connection weights and the monotonicity and differentiability of activation functions, Lyapunov functionals and Halanay-type inequalities are constructed and employed to derive delay independent sufficient conditions under which the continuous-time networks converge exponentially to the equilibria associated with temporally uniform external inputs to the networks. Discrete-time analogues of the continuous-time networks are formulated and we study their dynamical characteristics. It is shown that the convergence dynamics of the continuous-time networks are preserved by the discrete-time analogues without any restriction on the discretization step-size. Several examples are given to illustrate the advantages of the discrete-time analogues in numerically simulating the continuous-time networks.
Dust grain coagulation modelling : From discrete to continuous
NASA Astrophysics Data System (ADS)
Paruta, P.; Hendrix, T.; Keppens, R.
2016-07-01
In molecular clouds, stars are formed from a mixture of gas, plasma and dust particles. The dynamics of this formation is still actively investigated and a study of dust coagulation can help to shed light on this process. Starting from a pre-existing discrete coagulation model, this work aims to mathematically explore its properties and its suitability for numerical validation. The crucial step is in our reinterpretation from its original discrete to a well-defined continuous form, which results in the well-known Smoluchowski coagulation equation. This opens up the possibility of exploiting previous results in order to prove the existence and uniqueness of a mass conserving solution for the evolution of dust grain size distribution. Ultimately, to allow for a more flexible numerical implementation, the problem is rewritten as a non-linear hyperbolic integro-differential equation and solved using a finite volume discretisation. It is demonstrated that there is an exact numerical agreement with the initial discrete model, with improved accuracy. This is of interest for further work on dynamically coupled gas with dust simulations.
On discrete symmetries for a whole Abelian model
NASA Astrophysics Data System (ADS)
Chauca, J.; Doria, R.
2012-10-01
Considering the whole concept applied to gauge theory a nonlinear abelian model is derived. A next step is to understand on the model properties. At this work, it will be devoted to discrete symmetries. For this, we will work based in two fields reference systems. This whole gauge symmetry allows to be analyzed through different sets which are the constructor basis {Dμ,Xiμ} and the physical basis {GμI}. Taking as fields reference system the diagonalized spin-1 sector, P, C, T and PCT symmetries are analyzed. They show that under this systemic model there are conservation laws driven for the parts and for the whole. It develops the meaning of whole-parity, field-parity and so on. However it is the whole symmetry that rules. This means that usually forbidden particles as pseudovector photons can be introduced through such whole abelian system. As result, one notices that the fields whole {GμI} manifest a quanta diversity. It involves particles with different spins, masses and discrete quantum numbers under a same gauge symmetry. It says that without violating PCT symmetry different possibilities on discrete symmetries can be accommodated.
On discrete symmetries for a whole Abelian model
Chauca, J.; Doria, R.
2012-09-24
Considering the whole concept applied to gauge theory a nonlinear abelian model is derived. A next step is to understand on the model properties. At this work, it will be devoted to discrete symmetries. For this, we will work based in two fields reference systems. This whole gauge symmetry allows to be analyzed through different sets which are the constructor basis {l_brace}D{sub {mu}},X{sup i}{sub {mu}}{r_brace} and the physical basis {l_brace}G{sub {mu}I}{r_brace}. Taking as fields reference system the diagonalized spin-1 sector, P, C, T and PCT symmetries are analyzed. They show that under this systemic model there are conservation laws driven for the parts and for the whole. It develops the meaning of whole-parity, field-parity and so on. However it is the whole symmetry that rules. This means that usually forbidden particles as pseudovector photons can be introduced through such whole abelian system. As result, one notices that the fields whole {l_brace}G{sub {mu}I}{r_brace} manifest a quanta diversity. It involves particles with different spins, masses and discrete quantum numbers under a same gauge symmetry. It says that without violating PCT symmetry different possibilities on discrete symmetries can be accommodated.
BioNSi: A Discrete Biological Network Simulator Tool.
Rubinstein, Amir; Bracha, Noga; Rudner, Liat; Zucker, Noga; Sloin, Hadas E; Chor, Benny
2016-08-01
Modeling and simulation of biological networks is an effective and widely used research methodology. The Biological Network Simulator (BioNSi) is a tool for modeling biological networks and simulating their discrete-time dynamics, implemented as a Cytoscape App. BioNSi includes a visual representation of the network that enables researchers to construct, set the parameters, and observe network behavior under various conditions. To construct a network instance in BioNSi, only partial, qualitative biological data suffices. The tool is aimed for use by experimental biologists and requires no prior computational or mathematical expertise. BioNSi is freely available at http://bionsi.wix.com/bionsi , where a complete user guide and a step-by-step manual can also be found. PMID:27354160
Component Evaluation of a Computer Based Format for Teaching Discrete Trial and Backward Chaining
ERIC Educational Resources Information Center
Nosik, Melissa R.; Williams, W. Larry
2011-01-01
The effectiveness of a multi-component computer based training package that consisted of competency based instructions, video modeling, and two forms of feedback was evaluated in terms of treatment integrity of two procedures across four staff. Treatment integrity in completing critical steps of discrete-trial and backward chaining procedures were…
The Role of Procedural Integrity: Using Self-Monitoring to Enhance Discrete Trial Instruction (DTI)
ERIC Educational Resources Information Center
Belfiore, Phillip J.; Fritts, Kevin M.; Herman, Brian C.
2008-01-01
The purpose of this study was to examine the effects of staff video self-monitoring (SM) training on the accuracy of delivering Discrete Trial Instruction (DTI) to students enrolled in a classroom for children with autism. Staff were trained to self-monitor a five-step DTI trial: (a) delivery of discriminative stimulus, (b) wait time for student…
VANGL2 regulates membrane trafficking of MMP14 to control cell polarity and migration.
Williams, B Blairanne; Cantrell, V Ashley; Mundell, Nathan A; Bennett, Andrea C; Quick, Rachel E; Jessen, Jason R
2012-05-01
Planar cell polarity (PCP) describes the polarized orientation of cells within the plane of a tissue. Unlike epithelial PCP, the mechanisms underlying PCP signaling in migrating cells remain undefined. Here, the establishment of PCP must be coordinated with dynamic changes in cell adhesion and extracellular matrix (ECM) organization. During gastrulation, the membrane type-1 matrix metalloproteinase (MT1-MMP or MMP14) is required for PCP and convergence and extension cell movements. We report that the PCP protein Vang-like 2 (VANGL2) regulates the endocytosis and cell-surface availability of MMP14 in manner that is dependent on focal adhesion kinase. We demonstrate that zebrafish trilobite/vangl2 mutant embryos exhibit increased Mmp14 activity and decreased ECM. Furthermore, in vivo knockdown of Mmp14 partially rescues the Vangl2 loss-of-function convergence and extension phenotype. This study identifies a mechanism linking VANGL2 with MMP14 trafficking and suggests that establishment of PCP in migrating gastrula cells requires regulated proteolytic degradation or remodeling of the ECM. Our findings implicate matrix metalloproteinases as downstream effectors of PCP and suggest a broadly applicable mechanism whereby VANGL2 affects diverse morphogenetic processes. PMID:22357946
VANGL2 regulates membrane trafficking of MMP14 to control cell polarity and migration
Williams, B. Blairanne; Cantrell, V. Ashley; Mundell, Nathan A.; Bennett, Andrea C.; Quick, Rachel E.; Jessen, Jason R.
2012-01-01
Planar cell polarity (PCP) describes the polarized orientation of cells within the plane of a tissue. Unlike epithelial PCP, the mechanisms underlying PCP signaling in migrating cells remain undefined. Here, the establishment of PCP must be coordinated with dynamic changes in cell adhesion and extracellular matrix (ECM) organization. During gastrulation, the membrane type-1 matrix metalloproteinase (MT1-MMP or MMP14) is required for PCP and convergence and extension cell movements. We report that the PCP protein Vang-like 2 (VANGL2) regulates the endocytosis and cell-surface availability of MMP14 in manner that is dependent on focal adhesion kinase. We demonstrate that zebrafish trilobite/vangl2 mutant embryos exhibit increased Mmp14 activity and decreased ECM. Furthermore, in vivo knockdown of Mmp14 partially rescues the Vangl2 loss-of-function convergence and extension phenotype. This study identifies a mechanism linking VANGL2 with MMP14 trafficking and suggests that establishment of PCP in migrating gastrula cells requires regulated proteolytic degradation or remodeling of the ECM. Our findings implicate matrix metalloproteinases as downstream effectors of PCP and suggest a broadly applicable mechanism whereby VANGL2 affects diverse morphogenetic processes. PMID:22357946
Membrane trafficking and organelle biogenesis in Giardia lamblia: use it or lose it.
Faso, Carmen; Hehl, Adrian B
2011-04-01
The secretory transport capacity of Giardia trophozoites is perfectly adapted to the changing environment in the small intestine of the host and is able to deploy essential protective surface coats as well as molecules which act on epithelia. These lumen-dwelling parasites take up nutrients by bulk endocytosis through peripheral vesicles or by receptor-mediated transport. The environmentally-resistant cyst form is quiescent but poised for activation following stomach passage. Its versatility and fidelity notwithstanding, the giardial trafficking systems appear to be the product of a general secondary reduction process geared towards minimization of all components and machineries identified to date. Since membrane transport is directly linked to organelle biogenesis and maintenance, less complexity also means loss of organelle structures and functions. A case in point is the Golgi apparatus which is missing as a steady-state organelle system. Only a few basic Golgi functions have been experimentally demonstrated in trophozoites undergoing encystation. Similarly, mitochondrial remnants have reached a terminally minimized state and appear to be functionally restricted to essential iron-sulfur protein maturation processes. Giardia's minimized organization combined with its genetic tractability provides unique opportunities to study basic principles of secretory transport in an uncluttered cellular environment. Not surprisingly, Giardia is gaining increasing attention as a model for the investigation of gene regulation, organelle biogenesis, and export of simple but highly protective cell wall biopolymers, a hallmark of all perorally transmitted protozoan and metazoan parasites. PMID:21296082
Fok, Agnes K; Aihara, Marilynn S; Ishida, Masaki; Allen, Richard D
2008-01-01
In ciliates, calmodulin (CaM), as in other cells, has multiple functions, such as activation of regulatory enzymes and modulating calcium-dependent cellular processes. By immunogold localization, CaM is concentrated at multiple sites in Paramecium. It is seen scattered over the cytosol, but bound to its matrix, and is concentrated at the pores of the contractile vacuole complexes and with at least three microtubular arrays. It was localized peripheral to the nine-doublet microtubules of the ciliary axonemes. The most striking localization was on the akinetic side only of the cytopharyngeal microtubular ribbons opposite the side where the discoidal vesicles, acidosomes and the 100-nm carrier vesicles bind and move. CaM was also present at the periphery of the postoral microtubular bundles along which the early vacuole moves and was associated with the cytoproct microtubules that guide the spent digestive vacuoles to the cytoproct. It was not found on the membranes of, or in the interior of nuclei, mitochondria, phagosomes, and trichocysts, and was only sparsely scattered over the cytosolic sides of discoidal vesicles, acidosomes, lysosomes, and digestive vacuoles. Together the associations with specific microtubular arrays and the effects of trifluoperazine and calmidazolium indicate that CaM is involved (i) in vesicle transport to the cytopharynx area for vacuole formation and subsequent vacuole acidification, (ii) in early vacuole transport along the postoral fiber, and (iii) in transporting the spent vacuole to the cytoproct. Higher CaM concentrations subjacent to the cell's pellicle and close to the decorated tubules of the contractile vacuole complex may support a role for CaM in ion traffic. PMID:19120793
Multifaceted Roles of ALG-2 in Ca(2+)-Regulated Membrane Trafficking.
Maki, Masatoshi; Takahara, Terunao; Shibata, Hideki
2016-01-01
ALG-2 (gene name: PDCD6) is a penta-EF-hand Ca(2+)-binding protein and interacts with a variety of proteins in a Ca(2+)-dependent fashion. ALG-2 recognizes different types of identified motifs in Pro-rich regions by using different hydrophobic pockets, but other unknown modes of binding are also used for non-Pro-rich proteins. Most ALG-2-interacting proteins associate directly or indirectly with the plasma membrane or organelle membranes involving the endosomal sorting complex required for transport (ESCRT) system, coat protein complex II (COPII)-dependent ER-to-Golgi vesicular transport, and signal transduction from membrane receptors to downstream players. Binding of ALG-2 to targets may induce conformational change of the proteins. The ALG-2 dimer may also function as a Ca(2+)-dependent adaptor to bridge different partners and connect the subnetwork of interacting proteins. PMID:27571067
One-way membrane trafficking of SOS in receptor-triggered Ras activation.
Christensen, Sune M; Tu, Hsiung-Lin; Jun, Jesse E; Alvarez, Steven; Triplet, Meredith G; Iwig, Jeffrey S; Yadav, Kamlesh K; Bar-Sagi, Dafna; Roose, Jeroen P; Groves, Jay T
2016-09-01
SOS is a key activator of the small GTPase Ras. In cells, SOS-Ras signaling is thought to be initiated predominantly by membrane recruitment of SOS via the adaptor Grb2 and balanced by rapidly reversible Grb2-SOS binding kinetics. However, SOS has multiple protein and lipid interactions that provide linkage to the membrane. In reconstituted-membrane experiments, these Grb2-independent interactions were sufficient to retain human SOS on the membrane for many minutes, during which a single SOS molecule could processively activate thousands of Ras molecules. These observations raised questions concerning how receptors maintain control of SOS in cells and how membrane-recruited SOS is ultimately released. We addressed these questions in quantitative assays of reconstituted SOS-deficient chicken B-cell signaling systems combined with single-molecule measurements in supported membranes. These studies revealed an essentially one-way trafficking process in which membrane-recruited SOS remains trapped on the membrane and continuously activates Ras until being actively removed via endocytosis. PMID:27501536
Fernández-Arenas, Elena; Bleck, Christopher K E; Nombela, César; Gil, Concha; Griffiths, Gareth; Diez-Orejas, Rosalía
2009-04-01
The intracellular trafficking/survival strategies of the opportunistic human pathogen Candida albicans are poorly understood. Here we investigated the infection of RAW264.7 macrophages with a virulent wild-type (WT) filamentous C. albicans strain and a hyphal signalling-defective mutant (efg1Delta/cph1Delta). A comparative analysis of the acquisition by phagosomes of actin, and of early/late endocytic organelles markers of the different fungal strains was performed and related to Candida's survival inside macrophages. Our results show that both fungal strains have evolved a similar mechanism to subvert the 'lysosomal' system, as seen by the inhibition of the phagosome fusion with compartments enriched in the lysobisphosphatidic acid and the vATPase, and thereby the acquisition of a low pH from the outset of infection. Besides, the virulent WT strain displayed additional specific survival strategies to prevent its targeting to compartmentsdisplaying late endosomal/lysosomal features, such as induction of active recycling out of phagosomes of the lysosomal membrane protein LAMP-1, the lysosomal protease cathepsin D and preinternalized colloidal gold. Finally, both virulent and efg1Delta/cph1Delta mutant fungal strains actively suppressed the production of macrophage nitric oxide (NO), although their cell wall extracts were potent inducers of NO. PMID:19134116
Quantitative Analysis of Membrane Trafficking in Regulation of Cdc42 Polarity
Watson, Leah J.; Rossi, Guendalina; Brennwald, Patrick
2014-01-01
Vesicle delivery of Cdc42 has been proposed as an important mechanism for generating and maintaining Cdc42 polarity at the plasma membrane. This mechanism requires the density of Cdc42 on secretory vesicles to be equal to or higher than the plasma membrane polarity cap. Using a novel method to estimate Cdc42 levels on post-Golgi secretory vesicles in intact yeast cells, we: 1) determined that endocytosis plays an important role in Cdc42’s association with secretory vesicles 2) found that a GFP-tag placed on the N-terminus of Cdc42 negatively impacts this vesicle association and 3) quantified the surface densities of Cdc42 on post-Golgi vesicles which revealed that the vesicle density of Cdc42 is three times more dilute than that at the polarity cap. This work suggests that the immediate consequence of secretory vesicle fusion with the plasma membrane polarity cap is to dilute the local Cdc42 surface density. This provides strong support for the model in which vesicle trafficking acts to negatively regulate Cdc42 polarity on the cell surface while also providing a means to recycle Cdc42 between the cell surface and internal membrane locations. PMID:25158298
Moosavi, Behrooz; Mousavi, Bibimaryam; Yang, Guang-Fu
2016-01-01
The model eukaryotic yeast Saccharomyces cerevisiae has proven a useful model system in which prion biogenesis and elimination are studied. Several yeast prions exist in budding yeast and a number of studies now suggest that these alternate protein conformations may play important roles in the cell. During the last few years cellular factors affecting prion induction, propagation and elimination have been identified. Amongst these, proteins involved in the regulation of the actin cytoskeleton and dynamic membrane processes such as endocytosis have been found to play a critical role not only in facilitating de novo prion formation but also in prion propagation. Here we briefly review prion formation and maintenance with special attention given to the cellular processes that require the functionality of the actin cytoskeleton. PMID:26503767
Regulation of the epithelial sodium channel (ENaC) by membrane trafficking
Butterworth, Michael B.
2010-01-01
The epithelial Na+ channel (ENaC) is a major regulator of salt and water reabsorption in a number of epithelial tissues. Abnormalities in ENaC function have been directly linked to several human disease states including Liddle syndrome, psuedohypoaldosteronism and cystic fibrosis, and may be implicated in salt-sensitive hypertension. ENaC activity in epithelial cells is regulated both by open probability and channel number. This review focuses on the regulation of ENaC in the cells of the kidney cortical collecting duct by trafficking and recycling. The trafficking of ENaC is discussed in the broader context of epithelial cell vesicle trafficking. Well characterized pathways and protein interactions elucidated using epithelial model cells are discussed and the known overlap with ENaC regulation is highlighted. In following the life of ENaC in CCD epithelial cells the apical delivery, internalization, recycling and destruction of the channel will be discussed. While a number of pathways presented still need to be linked to ENaC regulation and many details of the regulation of ENaC trafficking remain to be elucidated, knowledge of these mechanisms may provide further insights into ENaC activity in normal and disease states. PMID:20347969
Wherever I may roam: protein and membrane trafficking in P. falciparum-infected red blood cells.
Deponte, Marcel; Hoppe, Heinrich C; Lee, Marcus C S; Maier, Alexander G; Richard, Dave; Rug, Melanie; Spielmann, Tobias; Przyborski, Jude M
2012-12-01
Quite aside from its immense importance as a human pathogen, studies in recent years have brought to light the fact that the malaria parasite Plasmodium falciparum is an interesting eukaryotic model system to study protein trafficking. Studying parasite cell biology often reveals an overrepresentation of atypical cell biological features, possibly driven by the parasites' need to survive in an unusual biological niche. Malaria parasites possess uncommon cellular compartments to which protein traffic must be directed, including secretory organelles such as rhoptries and micronemes, a lysosome-like compartment referred to as the digestive vacuole and a complex (four membrane-bound) plastid, the apicoplast. In addition, the parasite must provide proteins to extracellular compartments and structures including the parasitophorous vacuole, the parasitophorous vacuolar membrane, the Maurer's clefts and both cytosol and plasma membrane of the host cell, the mature human red blood cell. Although some of these unusual destinations are possessed by other cell types, only Plasmodium parasites contain them all within one cell. Here we review what is known about protein and membrane transport in the P. falciparum-infected cell, highlighting novel features of these processes. A growing body of evidence suggests that this parasite is a real "box of tricks" with regards to protein traffic. Possibly, these tricks may be turned against the parasite by exploiting them as novel therapeutic targets. PMID:23043991
Zhu, Jingen; Wu, Xiaorong; Yuan, Shunjie; Qian, Dong; Nan, Qiong
2014-01-01
The regulation of pollen development and pollen tube growth is a complicated biological process that is crucial for sexual reproduction in flowering plants. Annexins are widely distributed from protists to higher eukaryotes and play multiple roles in numerous cellular events by acting as a putative “linker” between Ca2+ signaling, the actin cytoskeleton and the membrane, which are required for pollen development and pollen tube growth. Our recent report suggested that downregulation of the function of Arabidopsis annexin 5 (Ann5) in transgenic Ann5-RNAi lines caused severely sterile pollen grains. However, little is known about the underlying mechanisms of the function of Ann5 in pollen. This study demonstrated that Ann5 associates with phospholipid membrane and this association is stimulated by Ca2+ in vitro. Brefeldin A (BFA) interferes with endomembrane trafficking and inhibits pollen germination and pollen tube growth. Both pollen germination and pollen tube growth of Ann5-overexpressing plants showed increased resistance to BFA treatment, and this effect was regulated by calcium. Overexpression of Ann5 promoted Ca2+-dependent cytoplasmic streaming in pollen tubes in vivo in response to BFA. Lactrunculin (LatB) significantly prohibited pollen germination and tube growth by binding with high affinity to monomeric actin and preferentially targeting dynamic actin filament arrays and preventing actin polymerization. Overexpression of Ann5 did not affect pollen germination or pollen tube growth in response to LatB compared with wild-type, although Ann5 interacts with actin filaments in a manner similar to some animal annexins. In addition, the sterile pollen phenotype could be only partially rescued by Ann5 mutants at Ca2+-binding sites when compared to the complete recovery by wild-type Ann5. These data demonstrated that Ann5 is involved in pollen development, germination and pollen tube growth through the promotion of endomembrane trafficking modulated by calcium. Our results provide reliable molecular mechanisms that underlie the function of Ann5 in pollen. PMID:25019283
Current Density and Continuity in Discretized Models
ERIC Educational Resources Information Center
Boykin, Timothy B.; Luisier, Mathieu; Klimeck, Gerhard
2010-01-01
Discrete approaches have long been used in numerical modelling of physical systems in both research and teaching. Discrete versions of the Schrodinger equation employing either one or several basis functions per mesh point are often used by senior undergraduates and beginning graduate students in computational physics projects. In studying…
Discrete/PWM Ballast-Resistor Controller
NASA Technical Reports Server (NTRS)
King, Roger J.
1994-01-01
Circuit offers low switching loss and automatic compensation for failure of ballast resistor. Discrete/PWM ballast-resistor controller improved shunt voltage-regulator circuit designed to supply power from high-resistance source to low-impedance bus. Provides both coarse discrete voltage levels (by switching of ballast resistors) and continuous fine control of voltage via pulse-width modulation.
Discrete Fractional Diffusion Equation of Chaotic Order
NASA Astrophysics Data System (ADS)
Wu, Guo-Cheng; Baleanu, Dumitru; Xie, He-Ping; Zeng, Sheng-Da
Discrete fractional calculus is suggested in diffusion modeling in porous media. A variable-order fractional diffusion equation is proposed on discrete time scales. A function of the variable order is constructed by a chaotic map. The model shows some new random behaviors in comparison with other variable-order cases.
Discreteness and Gradience in Intonational Contrasts.
ERIC Educational Resources Information Center
Gussenhoven, Carlos
1999-01-01
Three experimental techniques that can be used to investigate the gradient of discrete nature of intonational differences, the semantic task, the imitation task, and the pitch range task are discussed and evaluated. It is pointed out that categorical perception is a sufficient but not a necessary, property of phonological discreteness. (Author/VWL)
A discrete perspective on nonlinear dimension reduction
NASA Astrophysics Data System (ADS)
Bogner, Christina; Trancón y Widemann, Baltasar; Lange, Holger
2013-04-01
Environmental data sets are often large and high-dimensional and thus difficult to visualize and analyze. In hydrology, for example, we often deal with time series from long-term physical and chemical monitoring of stream water, groundwater or soils. These data can be seen as a multivariate characteristic of chemico-physical properties of water or soil and are used to infer processes in ecosystems. Despite their high dimensionality, ecological data are often assumed to have a simple underlying intrinsic structure. It means that despite their high-dimensional nature they can be summarized in less dimensions without a serious loss of information. Therefore, dimensionality reduction techniques are often the first step to data analysis. They are used to visualize data as well as to uncover the intrinsic (low-dimensional) structure. As an example application, we use high-dimensional hydrochemical data at the headwater catchment level (ion concentrations from first-order streams). We investigate the Isometric Feature Mapping (Isomap), a popular method for non-linear dimension reduction. Here, the topology of the data set is approximated by constructing a local neighbourhood graph. However, the assumption of smoothness underlying this approximation is difficult to justify for many environmental data sets, and issues of measurement errors and sampling gaps render Isomap analyses questionable. Thus, we extend our methodology by an analogous, but more robust, discrete (non-smooth) transformation leading to a set of binary data. For the latter, a plethora of data-mining techniques, in particular unsupervised and semi-supervised machine learning algorithms, exists. These can be employed to automate or support classification and feature detection tasks, taking the non-linear structure of available data into account. First results of this newly developed analysis method will be presented.
Discrete breathers in graphane: Effect of temperature
NASA Astrophysics Data System (ADS)
Baimova, J. A.; Murzaev, R. T.; Lobzenko, I. P.; Dmitriev, S. V.; Zhou, Kun
2016-05-01
The discrete breathers in graphane in thermodynamic equilibrium in the temperature range 50-600 K are studied by molecular dynamics simulation. A discrete breather is a hydrogen atom vibrating along the normal to a sheet of graphane at a high amplitude. As was found earlier, the lifetime of a discrete breather at zero temperature corresponds to several tens of thousands of vibrations. The effect of temperature on the decay time of discrete breathers and the probability of their detachment from a sheet of graphane are studied in this work. It is shown that closely spaced breathers can exchange energy with each other at zero temperature. The data obtained suggest that thermally activated discrete breathers can be involved in the dehydrogenation of graphane, which is important for hydrogen energetics.
Active control of turbomachine discrete tones
NASA Astrophysics Data System (ADS)
Fleeter, Sanford
This paper was directed at active control of discrete frequency noise generated by subsonic blade rows through cancellation of the blade row interaction generated propagating acoustic waves. First discrete frequency noise generated by a rotor and stator in a duct was analyzed to determine the propagating acoustic pressure waves. Then a mathematical model was developed to analyze and predict the active control of discrete frequency noise generated by subsonic blade rows through cancellation of the propagating acoustic waves, accomplished by utilizing oscillating airfoil surfaces to generate additional control propagating pressure waves. These control waves interact with the propagating acoustic waves, thereby, in principle, canceling the acoustic waves and thus, the far field discrete frequency tones. This model was then applied to a fan exit guide vane to investigate active airfoil surface techniques for control of the propagating acoustic waves, and thus the far field discrete frequency tones, generated by blade row interactions.
MULTISCALE DISCRETIZATION OF SHAPE CONTOURS
Prasad, L.; Rao, R.
2000-09-01
We present an efficient multi-scale scheme to adaptively approximate the continuous (or densely sampled) contour of a planar shape at varying resolutions. The notion of shape is intimately related to the notion of contour, and the efficient representation of the contour of a shape is vital to a computational understanding of the shape. Any polygonal approximation of a planar smooth curve is equivalent to a piecewise constant approximation of the parameterized X and Y coordinate functions of a discrete point set obtained by densely sampling the curve. Using the Haar wavelet transform for the piecewise approximation yields a hierarchical scheme in which the size of the approximating point set is traded off against the morphological accuracy of the approximation. Our algorithm compresses the representation of the initial shape contour to a sparse sequence of points in the plane defining the vertices of the shape's polygonal approximation. Furthermore, it is possible to control the overall resolution of the approximation by a single, scale-independent parameter.
Seipin Is a Discrete Homooligomer†
Binns, Derk; Lee, SungKyung; Hilton, Christopher L.; Jiang, Qiu-Xing; Goodman, Joel M.
2011-01-01
Seipin is a transmembrane protein that resides in the endoplasmic reticulum and concentrates at junctions between the ER and cytosolic lipid droplets. Mutations in the human seipin gene, including the missense mutation A212P, lead to congenital generalized lipodystrophy (CGL), characterized by the lack of normal adipose tissue and accumulation of fat in liver and muscles. In both yeast and CGL patient fibroblasts, seipin is required for normal lipid droplet morphology; in its absence droplets appear to bud abnormally from the ER. Here we report the first purification and physical characterization of seipin. Yeast seipin is in a large discrete protein complex. Affinity purification demonstrated that seipin is the main if not exclusive protein in the complex. Detergent sucrose gradients in H2O, and D2O and gel filtration were used to determine the size of the seipin complex and account for detergent binding. Both seipin-myc13 (seipin fused to 13 tandem copies of the myc epitope) expressed from the endogenous promoter and overexpressed seipin-mCherry form ~500 kDa proteins consisting of about 9 copies of seipin. The yeast orthologue of the human A212P allele forms only smaller complexes and is unstable; we hypothesize that this accounts for its null phenotype in humans. Seipin appears as a toroid by negative staining electron microscopy. We speculate that seipin plays at least a structural role in organizing droplets or in communication between droplets and ER. PMID:21062080
Compatible Spatial Discretizations for Partial Differential Equations
Arnold, Douglas, N, ed.
2004-11-25
From May 11--15, 2004, the Institute for Mathematics and its Applications held a hot topics workshop on Compatible Spatial Discretizations for Partial Differential Equations. The numerical solution of partial differential equations (PDE) is a fundamental task in science and engineering. The goal of the workshop was to bring together a spectrum of scientists at the forefront of the research in the numerical solution of PDEs to discuss compatible spatial discretizations. We define compatible spatial discretizations as those that inherit or mimic fundamental properties of the PDE such as topology, conservation, symmetries, and positivity structures and maximum principles. A wide variety of discretization methods applied across a wide range of scientific and engineering applications have been designed to or found to inherit or mimic intrinsic spatial structure and reproduce fundamental properties of the solution of the continuous PDE model at the finite dimensional level. A profusion of such methods and concepts relevant to understanding them have been developed and explored: mixed finite element methods, mimetic finite differences, support operator methods, control volume methods, discrete differential forms, Whitney forms, conservative differencing, discrete Hodge operators, discrete Helmholtz decomposition, finite integration techniques, staggered grid and dual grid methods, etc. This workshop seeks to foster communication among the diverse groups of researchers designing, applying, and studying such methods as well as researchers involved in practical solution of large scale problems that may benefit from advancements in such discretizations; to help elucidate the relations between the different methods and concepts; and to generally advance our understanding in the area of compatible spatial discretization methods for PDE. Particular points of emphasis included: + Identification of intrinsic properties of PDE models that are critical for the fidelity of numerical
Veligdan, James T.
2001-01-01
An optical panel includes stacked optical waveguides having stepped inlet facets collectively defining an inlet face for receiving image light, and having beveled outlet faces collectively defining a display screen for displaying the image light channeled through the waveguides by internal reflection.
Steps Toward Effective Assessment.
ERIC Educational Resources Information Center
Cope, Carolyn O.
1996-01-01
Describes and defines the steps involved in measurement and evaluation: (1) determining an outcome; (2)defining scoring criteria; (3)establishing appropriate assessment tasks; and (4)creating opportunities for learning. Includes a flow chart for a design-down curriculum and an example of a vocal performance rating scale assessment. (MJP)
NASA Astrophysics Data System (ADS)
Hoffmann, Tim
2000-01-01
The equivalence of the discrete isotropic Heisenberg magnet (IHM) model and the discrete nonlinear Schrödinger equation (NLSE) given by Ablowitz and Ladik is shown. This is used to derive the equivalence of their discretization with the one by Izgerin and Korepin. Moreover a doubly discrete IHM is presented that is equivalent to Ablowitz' and Ladiks doubly discrete NLSE.
Discrete flavour symmetries from the Heisenberg group
NASA Astrophysics Data System (ADS)
Floratos, E. G.; Leontaris, G. K.
2016-04-01
Non-abelian discrete symmetries are of particular importance in model building. They are mainly invoked to explain the various fermion mass hierarchies and forbid dangerous superpotential terms. In string models they are usually associated to the geometry of the compactification manifold and more particularly to the magnetised branes in toroidal compactifications. Motivated by these facts, in this note we propose a unified framework to construct representations of finite discrete family groups based on the automorphisms of the discrete and finite Heisenberg group. We focus in particular, on the PSL2 (p) groups which contain the phenomenologically interesting cases.
Discrete symmetries and de Sitter spacetime
Cotăescu, Ion I. Pascu, Gabriel
2014-11-24
Aspects of the ambiguity in defining quantum modes on de Sitter spacetime using a commuting system composed only of differential operators are discussed. Discrete symmetries and their actions on the wavefunction in commonly used coordinate charts are reviewed. It is argued that the system of commuting operators can be supplemented by requiring the invariance of the wavefunction to combined discrete symmetries- a criterion which selects a single state out of the α-vacuum family. Two such members of this family are singled out by particular combined discrete symmetries- states between which exists a well-known thermality relation.
High-accuracy discrete positioning device
NASA Technical Reports Server (NTRS)
Brooks, John J. (Inventor)
1994-01-01
An article (30) is controllably and precisely positioned at one of three discrete locations defined by a linkage. The positioning apparatus includes two independently driven cranks (34, 42), with a link (50) pivotably connected between the two cranks (34, 42). Another connector (44) is pivotably connected between one of the cranks (34 or 42) and the article (30) to be positioned. The cranks (34, 42) are rotationally adjusted so that the pivot points (52, 54) of the link (50) are collinear with the axes of rotation of the cranks (40, 48), thereby defining one of the three discrete locations. Additional cranks and links can be provided to define additional discrete locations.
The SMM Model as a Boundary Value Problem Using the Discrete Diffusion Equation
NASA Technical Reports Server (NTRS)
Campbell, Joel
2007-01-01
A generalized single step stepwise mutation model (SMM) is developed that takes into account an arbitrary initial state to a certain partial difference equation. This is solved in both the approximate continuum limit and the more exact discrete form. A time evolution model is developed for Y DNA or mtDNA that takes into account the reflective boundary modeling minimum microsatellite length and the original difference equation. A comparison is made between the more widely known continuum Gaussian model and a discrete model, which is based on modified Bessel functions of the first kind. A correction is made to the SMM model for the probability that two individuals are related that takes into account a reflecting boundary modeling minimum microsatellite length. This method is generalized to take into account the general n-step model and exact solutions are found. A new model is proposed for the step distribution.
Coupling of Monte Carlo adjoint leakages with three-dimensional discrete ordinates forward fluences
Slater, C.O.; Lillie, R.A.; Johnson, J.O.; Simpson, D.B.
1998-04-01
A computer code, DRC3, has been developed for coupling Monte Carlo adjoint leakages with three-dimensional discrete ordinates forward fluences in order to solve a special category of geometrically-complex deep penetration shielding problems. The code extends the capabilities of earlier methods that coupled Monte Carlo adjoint leakages with two-dimensional discrete ordinates forward fluences. The problems involve the calculation of fluences and responses in a perturbation to an otherwise simple two- or three-dimensional radiation field. In general, the perturbation complicates the geometry such that it cannot be modeled exactly using any of the discrete ordinates geometry options and thus a direct discrete ordinates solution is not possible. Also, the calculation of radiation transport from the source to the perturbation involves deep penetration. One approach to solving such problems is to perform the calculations in three steps: (1) a forward discrete ordinates calculation, (2) a localized adjoint Monte Carlo calculation, and (3) a coupling of forward fluences from the first calculation with adjoint leakages from the second calculation to obtain the response of interest (fluence, dose, etc.). A description of this approach is presented along with results from test problems used to verify the method. The test problems that were selected could also be solved directly by the discrete ordinates method. The good agreement between the DRC3 results and the direct-solution results verify the correctness of DRC3.
Micromachine Wedge Stepping Motor
Allen, J.J.; Schriner, H.K.
1998-11-04
A wedge stepping motor, which will index a mechanism, has been designed and fabricated in the surface rnicromachine SUMMiT process. This device has demonstrated the ability to index one gear tooth at a time with speeds up to 205 teeth/see. The wedge stepper motor has the following features, whi:h will be useful in a number of applications. o The ability to precisely position mechanical components. . Simple pulse signals can be used for operation. o Only 2 drive signals are requixed for operation. o Torque and precision capabilities increase with device size . The device to be indexed is restrained at all times by the wedge shaped tooth that is used for actuation. This paper will discuss the theory of operation and desi=m of the wedge stepping motor. The fabrication and testing of I he device will also be presented.
Running Parallel Discrete Event Simulators on Sierra
Barnes, P. D.; Jefferson, D. R.
2015-12-03
In this proposal we consider porting the ROSS/Charm++ simulator and the discrete event models that run under its control so that they run on the Sierra architecture and make efficient use of the Volta GPUs.
Motion of Discrete Interfaces Through Mushy Layers
NASA Astrophysics Data System (ADS)
Braides, Andrea; Solci, Margherita
2016-04-01
We study the geometric motion of sets in the plane derived from the homogenization of discrete ferromagnetic energies with weak inclusions. We show that the discrete sets are composed by a `bulky' part and an external `mushy region' composed only of weak inclusions. The relevant motion is that of the bulky part, which asymptotically obeys to a motion by crystalline mean curvature with a forcing term, due to the energetic contribution of the mushy layers, and pinning effects, due to discreteness. From an analytical standpoint, it is interesting to note that the presence of the mushy layers implies only a weak and not strong convergence of the discrete motions, so that the convergence of the energies does not commute with the evolution. From a mechanical standpoint it is interesting to note the geometrical similarity of some phenomena in the cooling of binary melts.
The discrete-time compensated Kalman filter
NASA Technical Reports Server (NTRS)
Lee, W. H.; Athans, M.
1978-01-01
A suboptimal dynamic compensator to be used in conjunction with the ordinary discrete time Kalman filter was derived. The resultant compensated Kalman Filter has the property that steady state bias estimation errors, resulting from modelling errors, were eliminated.
Comparing the Discrete and Continuous Logistic Models
ERIC Educational Resources Information Center
Gordon, Sheldon P.
2008-01-01
The solutions of the discrete logistic growth model based on a difference equation and the continuous logistic growth model based on a differential equation are compared and contrasted. The investigation is conducted using a dynamic interactive spreadsheet. (Contains 5 figures.)
Reducing Neuronal Networks to Discrete Dynamics
Terman, David; Ahn, Sungwoo; Wang, Xueying; Just, Winfried
2008-01-01
We consider a general class of purely inhibitory and excitatory-inhibitory neuronal networks, with a general class of network architectures, and characterize the complex firing patterns that emerge. Our strategy for studying these networks is to first reduce them to a discrete model. In the discrete model, each neuron is represented as a finite number of states and there are rules for how a neuron transitions from one state to another. In this paper, we rigorously demonstrate that the continuous neuronal model can be reduced to the discrete model if the intrinsic and synaptic properties of the cells are chosen appropriately. In a companion paper [1], we analyze the discrete model. PMID:18443649
Discrete Element Modeling of Drop Tests
NASA Astrophysics Data System (ADS)
Wang, Yuannian; Tonon, Fulvio
2012-09-01
A discrete element code with impact model has been developed and calibrated to simulate the dynamic behavior of rock materials, with special regard to rock fragmentation upon impact during rock-fall analysis. The paper summarizes the discrete element code, the calibration algorithms developed to identify the model microparameters, and the impact model. Experimental work on drop tests is then used to validate the code on modeling impact fragmentation. It has been found that the developed discrete element code and impact model can reasonably simulate rock fragmentation in drop tests. The use of the discrete element code and impact model can provide good reference results in evaluating impact fragmentation in rock-fall analysis.
Motion of Discrete Interfaces Through Mushy Layers
NASA Astrophysics Data System (ADS)
Braides, Andrea; Solci, Margherita
2016-08-01
We study the geometric motion of sets in the plane derived from the homogenization of discrete ferromagnetic energies with weak inclusions. We show that the discrete sets are composed by a `bulky' part and an external `mushy region' composed only of weak inclusions. The relevant motion is that of the bulky part, which asymptotically obeys to a motion by crystalline mean curvature with a forcing term, due to the energetic contribution of the mushy layers, and pinning effects, due to discreteness. From an analytical standpoint, it is interesting to note that the presence of the mushy layers implies only a weak and not strong convergence of the discrete motions, so that the convergence of the energies does not commute with the evolution. From a mechanical standpoint it is interesting to note the geometrical similarity of some phenomena in the cooling of binary melts.
Dynamic discretization method for solving Kepler's equation
NASA Astrophysics Data System (ADS)
Feinstein, Scott A.; McLaughlin, Craig A.
2006-09-01
Kepler’s equation needs to be solved many times for a variety of problems in Celestial Mechanics. Therefore, computing the solution to Kepler’s equation in an efficient manner is of great importance to that community. There are some historical and many modern methods that address this problem. Of the methods known to the authors, Fukushima’s discretization technique performs the best. By taking more of a system approach and combining the use of discretization with the standard computer science technique known as dynamic programming, we were able to achieve even better performance than Fukushima. We begin by defining Kepler’s equation for the elliptical case and describe existing solution methods. We then present our dynamic discretization method and show the results of a comparative analysis. This analysis will demonstrate that, for the conditions of our tests, dynamic discretization performs the best.
A discrete control model of PLANT
NASA Technical Reports Server (NTRS)
Mitchell, C. M.
1985-01-01
A model of the PLANT system using the discrete control modeling techniques developed by Miller is described. Discrete control models attempt to represent in a mathematical form how a human operator might decompose a complex system into simpler parts and how the control actions and system configuration are coordinated so that acceptable overall system performance is achieved. Basic questions include knowledge representation, information flow, and decision making in complex systems. The structure of the model is a general hierarchical/heterarchical scheme which structurally accounts for coordination and dynamic focus of attention. Mathematically, the discrete control model is defined in terms of a network of finite state systems. Specifically, the discrete control model accounts for how specific control actions are selected from information about the controlled system, the environment, and the context of the situation. The objective is to provide a plausible and empirically testable accounting and, if possible, explanation of control behavior.
Eigenforms, Discrete Processes and Quantum Processes
NASA Astrophysics Data System (ADS)
Kauffman, Louis H.
2012-05-01
This essay is a discussion of the concept of eigenform, due to Heinz von Foerster, and its relationship with discrete physics and quantum mechanics. We interpret the square root of minus one as a simple oscillatory process - a clock, and as an eigenform. By taking a generalization of this identification of i as a clock and eigenform, we show how quantum mechanics emerges from discrete physics.