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Sample records for molecular crowding inhibits

  1. Improved Inhibition of Telomerase by Short Twisted Intercalating Nucleic Acids under Molecular Crowding Conditions

    DEFF Research Database (Denmark)

    Agarwal, Tani; Pradhan, Devranjan; Géci, Imrich

    2012-01-01

    Human telomeric DNA has the ability to fold into a 4-stranded G-quadruplex structure. Several G-quadruplex ligands are known to stabilize the structure and thereby inhibit telomerase activity. Such ligands have demonstrated efficient telomerase inhibition in dilute conditions, but under molecular...

  2. Molecular Crowding and Early Evolution

    Science.gov (United States)

    Saha, Ranajay; Pohorille, Andrew; Chen, Irene A.

    2014-12-01

    The environment of protocells might have been crowded with small molecules and functional and non-specific polymers. In addition to altering conformational equilibria, affecting reaction rates and changing the structure and activity of water, crowding might have enhanced the capabilities of protocells for evolutionary innovation through the creation of extended neutral networks in the fitness landscape.

  3. Molecular crowding and early evolution.

    Science.gov (United States)

    Saha, Ranajay; Pohorille, Andrew; Chen, Irene A

    2014-12-01

    The environment of protocells might have been crowded with small molecules and functional and non-specific polymers. In addition to altering conformational equilibria, affecting reaction rates and changing the structure and activity of water, crowding might have enhanced the capabilities of protocells for evolutionary innovation through the creation of extended neutral networks in the fitness landscape.

  4. DNA strand exchange catalyzed by molecular crowding in PEG solutions

    KAUST Repository

    Feng, Bobo; Frykholm, Karolin; Nordé n, Bengt; Westerlund, Fredrik

    2010-01-01

    DNA strand exchange is catalyzed by molecular crowding and hydrophobic interactions in concentrated aqueous solutions of polyethylene glycol, a discovery of relevance for understanding the function of recombination enzymes and with potential applications to DNA nanotechnology. © 2010 The Royal Society of Chemistry.

  5. Facilitated aggregation of FG nucleoporins under molecular crowding conditions.

    Science.gov (United States)

    Milles, Sigrid; Huy Bui, Khanh; Koehler, Christine; Eltsov, Mikhail; Beck, Martin; Lemke, Edward A

    2013-02-01

    Intrinsically disordered and phenylalanine-glycine-rich nucleoporins (FG Nups) form a crowded and selective transport conduit inside the NPC that can only be transited with the help of nuclear transport receptors (NTRs). It has been shown in vitro that FG Nups can assemble into two distinct appearances, amyloids and hydrogels. If and how these phenomena are linked and if they have a physiological role still remains unclear. Using a variety of high-resolution fluorescence and electron microscopic (EM) tools, we reveal that crowding conditions mimicking the NPC environment can accelerate the aggregation and amyloid formation speed of yeast and human FG Nups by orders of magnitude. Aggregation can be inhibited by NTRs, providing a rationale on how the cell might control amyloid formation of FG Nups. The superb spatial resolving power of EM also reveals that hydrogels are enlaced amyloid fibres, and these findings have implications for existing transport models and for NPC assembly.

  6. Electrostatics promotes molecular crowding and selects the aggregation pathway in fibril-forming protein solutions

    International Nuclear Information System (INIS)

    Raccosta, S.; Martorana, V.; Manno, M.; Blanco, M.; Roberts, C.J.

    2016-01-01

    The role of intermolecular interaction in fibril-forming protein solutions and its relation with molecular conformation are crucial aspects for the control and inhibition of amyloid structures. Here, we study the fibril formation and the protein-protein interactions for two proteins at acidic ph, lysozyme and α-chymotrypsinogen. By using light scattering experiments and the Kirkwood-Buff integral approach, we show how concentration fluctuations are damped even at moderate protein concentrations by the dominant long-ranged electrostatic repulsion, which determines an effective crowded environment. In denaturing conditions, electrostatic repulsion keeps the monomeric solution in a thermodynamically metastable state, which is escaped through kinetically populated conformational sub-states. This explains how electrostatics acts as a gatekeeper in selecting a specific aggregation pathway.

  7. Multiscale diffusion of a molecular probe in a crowded environment: a concept

    Science.gov (United States)

    Currie, Megan; Thao, Chang; Timerman, Randi; Welty, Robb; Berry, Brenden; Sheets, Erin D.; Heikal, Ahmed A.

    2015-08-01

    Living cells are crowded with macromolecules and organelles. Yet, it is not fully understood how macromolecular crowding affects the myriad of biochemical reactions, transport and the structural stability of biomolecules that are essential to cellular function and survival. These molecular processes, with or without electrostatic interactions, in living cells are therefore expected to be distinct from those carried out in test tube in dilute solutions where excluded volumes are absent. Thus there is an urgent need to understand the macromolecular crowding effects on cellular and molecular biophysics towards quantitative cell biology. In this report, we investigated how biomimetic crowding affects both the rotational and translation diffusion of a small probe (rhodamine green, RhG). For biomimetic crowding agents, we used Ficoll-70 (synthetic polymer), bovine serum albumin and ovalbumin (proteins) at various concentrations in a buffer at room temperature. As a control, we carried out similar measurements on glycerolenriched buffer as an environment with homogeneous viscosity as a function of glycerol concentration. The corresponding bulk viscosity was measured independently to test the validity of the Stokes-Einstein model of a diffusing species undergoing a random walk. For rotational diffusion (ps-ns time scale), we used time-resolved anisotropy measurements to examine potential binding of RhG as a function of the crowding agents (surface structure and size). For translational diffusion (μs-s time scale), we used fluorescence correlation spectroscopy for single-molecule fluctuation analysis. Our results allow us to examine the diffusion model of a molecular probe in crowded environments as a function of concentration, length scale, homogeneous versus heterogeneous viscosity, size and surface structures. These biomimetic crowding studies, using non-invasive fluorescence spectroscopy methods, represent an important step towards understanding cellular biophysics and

  8. Improvement of imprinting effect of ionic liquid molecularly imprinted polymers by use of a molecular crowding agent.

    Science.gov (United States)

    Jia, Man; Yang, Jian; Sun, Ya Kun; Bai, Xi; Wu, Tao; Liu, Zhao Sheng; Aisa, Haji Akber

    2018-01-01

    We aimed to improve the imprinting effect of ionic liquid molecularly imprinted polymers (MIPs) by use of a molecular crowding agent. The ionic liquid 1-vinyl-3-ethylimidazolium tetrafluoroborate ([VEIm][BF 4 ]) was used as the functional monomer and aesculetin was used as the template molecule in a crowding environment, which was made up of a tetrahydrofuran solution of polystyrene. The ionic liquid MIPs that were prepared in the crowding environment displayed an enhanced imprinting effect. NMR peak shifts of active hydrogen of aesculetin suggested that interaction between the functional monomer and the template could be increased by the use of a crowding agent in the self-assembly process. The retention and selectivity of aesculetin were affected greatly by high molecular crowding, the amount of high molecular weight crowding agent, and the ratio of [VEIm][BF 4 ] to aesculetin. The optimal MIPs were used as solid-phase extraction sorbents to extract aesculetin from Cichorium glandulosum. A calibration curve was obtained with aesculetin concentrations from 0.0005 to 0.05 mg mL -1 (correlation coefficient R 2 of 0.9999, y = 1519x + 0.0923). The limit of quantification was 0.12 μg mL -1 , and the limit of detection was 0.05 μg mL -1 . The absolute recovery of aesculetin was (80 ± 2)% (n = 3), and the purity of aesculetin was (92 ± 0.5)% (n = 5). As a conclusion, molecular crowding is an effective approach to obtain ionic liquid MIPs with high selectivity even in a polar solvent environment.

  9. Theory of molecular crowding in Brownian hard-sphere liquids.

    Science.gov (United States)

    Zaccone, Alessio; Terentjev, Eugene M

    2012-06-01

    We derive an analytical pair potential of mean force for Brownian molecules in the liquid state. Our approach accounts for many-particle correlations of crowding particles of the liquid and for diffusive transport across the spatially modulated local density of crowders in the dense environment. Focusing on the limit of equal-size particles, we show that this diffusive transport leads to additional density- and structure-dependent terms in the interaction potential and to a much stronger attraction (by a factor of ≈4 at average volume fraction of crowders φ{0}=0.25) than in the standard depletion interaction where the diffusive effects are neglected. As an illustration of the theory, we use it to study the size of a polymer chain in a solution of inert crowders. Even in the case of an athermal background solvent, when a classical chain should be fully swollen, we find a sharp coil-globule transition of the ideal chain collapsing at a critical value of the crowder volume fraction φ{c}≈0.145.

  10. Harnessing the crowd to accelerate molecular medicine research.

    Science.gov (United States)

    Smith, Robert J; Merchant, Raina M

    2015-07-01

    Crowdsourcing presents a novel approach to solving complex problems within molecular medicine. By leveraging the expertise of fellow scientists across the globe, broadcasting to and engaging the public for idea generation, harnessing a scalable workforce for quick data management, and fundraising for research endeavors, crowdsourcing creates novel opportunities for accelerating scientific progress. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Noncanonical structures and their thermodynamics of DNA and RNA under molecular crowding: beyond the Watson-Crick double helix.

    Science.gov (United States)

    Sugimoto, Naoki

    2014-01-01

    How does molecular crowding affect the stability of nucleic acid structures inside cells? Water is the major solvent component in living cells, and the properties of water in the highly crowded media inside cells differ from that in buffered solution. As it is difficult to measure the thermodynamic behavior of nucleic acids in cells directly and quantitatively, we recently developed a cell-mimicking system using cosolutes as crowding reagents. The influences of molecular crowding on the structures and thermodynamics of various nucleic acid sequences have been reported. In this chapter, we discuss how the structures and thermodynamic properties of nucleic acids differ under various conditions such as highly crowded environments, compartment environments, and in the presence of ionic liquids, and the major determinants of the crowding effects on nucleic acids are discussed. The effects of molecular crowding on the activities of ribozymes and riboswitches on noncanonical structures of DNA- and RNA-like quadruplexes that play important roles in transcription and translation are also described. © 2014 Elsevier Inc. All rights reserved.

  12. The Effects of Molecular Crowding on the Structure and Stability of G-Quadruplexes with an Abasic Site

    Science.gov (United States)

    Fujimoto, Takeshi; Nakano, Shu-ichi; Miyoshi, Daisuke; Sugimoto, Naoki

    2011-01-01

    Both cellular environmental factors and chemical modifications critically affect the properties of nucleic acids. However, the structure and stability of DNA containing abasic sites under cell-mimicking molecular crowding conditions remain unclear. Here, we investigated the molecular crowding effects on the structure and stability of the G-quadruplexes including a single abasic site. Structural analysis by circular dichroism showed that molecular crowding by PEG200 did not affect the topology of the G-quadruplex structure with or without an abasic site. Thermodynamic analysis further demonstrated that the degree of stabilization of the G-quadruplex by molecular crowding decreased with substitution of an abasic site for a single guanine. Notably, we found that the molecular crowding effects on the enthalpy change for G-quadruplex formation had a linear relationship with the abasic site effects depending on its position. These results are useful for predicting the structure and stability of G-quadruplexes with abasic sites in the cell-mimicking conditions. PMID:21949901

  13. Effects of molecular confinement and crowding on horseradish peroxidase kinetics using a nanofluidic gradient mixer.

    Science.gov (United States)

    Wichert, William R A; Han, Donghoon; Bohn, Paul W

    2016-03-07

    The effects of molecular confinement and crowding on enzyme kinetics were studied at length scales and under conditions similar to those found in biological cells. These experiments were carried out using a nanofluidic network of channels constituting a nanofluidic gradient mixer, providing the basis for measuring multiple experimental conditions simultaneously. The 100 nm × 40 μm nanochannels were wet etched directly into borosilicate glass, then annealed and characterized with fluorescein emission prior to kinetic measurements. The nanofluidic gradient mixer was then used to measure the kinetics of the conversion of the horseradish peroxidase (HRP)-catalyzed conversion of non-fluorescent Amplex Red (AR) to the fluorescent product resorufin in the presence of hydrogen peroxide (H2O2). The design of the gradient mixer allows reaction kinetics to be studied under multiple (five) unique solution compositions in a single experiment. To characterize the efficiency of the device the effects of confinement on HRP-catalyzed AR conversion kinetics were studied by varying the starting ratio of AR : H2O2. Equimolar concentrations of Amplex Red and H2O2 yielded the highest reaction rates followed by 2 : 1, 1 : 2, 5 : 1, and finally 1 : 5 [AR] : [H2O2]. Under all conditions, initial reaction velocities were decreased by excess H2O2. Crowding effects on kinetics were studied by increasing solution viscosity in the nanochannels in the range 1.0-1.6 cP with sucrose. Increasing the solution viscosities in these confined geometries decreases the initial reaction velocity at the highest concentration from 3.79 μM min(-1) at 1.00 cP to 0.192 μM min(-1) at 1.59 cP. Variations in reaction velocity are interpreted in the context of models for HRP catalysis and for molecular crowding.

  14. Molecular crowding of collagen: a pathway to produce highly-organized collagenous structures.

    Science.gov (United States)

    Saeidi, Nima; Karmelek, Kathryn P; Paten, Jeffrey A; Zareian, Ramin; DiMasi, Elaine; Ruberti, Jeffrey W

    2012-10-01

    Collagen in vertebrate animals is often arranged in alternating lamellae or in bundles of aligned fibrils which are designed to withstand in vivo mechanical loads. The formation of these organized structures is thought to result from a complex, large-area integration of individual cell motion and locally-controlled synthesis of fibrillar arrays via cell-surface fibripositors (direct matrix printing). The difficulty of reproducing such a process in vitro has prevented tissue engineers from constructing clinically useful load-bearing connective tissue directly from collagen. However, we and others have taken the view that long-range organizational information is potentially encoded into the structure of the collagen molecule itself, allowing the control of fibril organization to extend far from cell (or bounding) surfaces. We here demonstrate a simple, fast, cell-free method capable of producing highly-organized, anistropic collagen fibrillar lamellae de novo which persist over relatively long-distances (tens to hundreds of microns). Our approach to nanoscale organizational control takes advantage of the intrinsic physiochemical properties of collagen molecules by inducing collagen association through molecular crowding and geometric confinement. To mimic biological tissues which comprise planar, aligned collagen lamellae (e.g. cornea, lamellar bone or annulus fibrosus), type I collagen was confined to a thin, planar geometry, concentrated through molecular crowding and polymerized. The resulting fibrillar lamellae show a striking resemblance to native load-bearing lamellae in that the fibrils are small, generally aligned in the plane of the confining space and change direction en masse throughout the thickness of the construct. The process of organizational control is consistent with embryonic development where the bounded planar cell sheets produced by fibroblasts suggest a similar confinement/concentration strategy. Such a simple approach to nanoscale

  15. Hydration of Watson-Crick base pairs and dehydration of Hoogsteen base pairs inducing structural polymorphism under molecular crowding conditions.

    Science.gov (United States)

    Miyoshi, Daisuke; Nakamura, Kaori; Tateishi-Karimata, Hisae; Ohmichi, Tatsuo; Sugimoto, Naoki

    2009-03-18

    It has been revealed recently that molecular crowding, which is one of the largest differences between in vivo and in vitro conditions, is a critical factor determining the structure, stability, and function of nucleic acids. However, the effects of molecular crowding on Watson-Crick and Hoogsteen base pairs remain unclear. In order to investigate directly and quantitatively the molecular crowding effects on base pair types in nucleic acids, we designed intramolecular parallel- and antiparallel-stranded DNA duplexes consisting of Hoogsteen and Watson-Crick base pairs, respectively, as well as an intramolecular parallel-stranded triplex containing both types of base pairs. Thermodynamic analyses demonstrated that the values of free energy change at 25 degrees C for Hoogsteen base-pair formations decreased from +1.45 +/- 0.15 to +1.09 +/- 0.13 kcal mol(-1), and from -1.89 +/- 0.13 to -2.71 +/- 0.11 kcal mol(-1) in the intramolecular duplex and triplex, respectively, when the concentration of PEG 200 (polyethylene glycol with average molecular weight 200) increased from 0 to 20 wt %. However, corresponding values for Watson-Crick formation in the duplex and triplex increased from -10.2 +/- 0.2 to -8.7 +/- 0.1 kcal mol(-1), and from -10.8 +/- 0.2 to -9.2 +/- 0.2 kcal mol(-1), respectively. Furthermore, it was revealed that the opposing effects of molecular crowding on the Hoogsteen and Watson-Crick base pairs were due to different behaviors of water molecules binding to the DNA strands.

  16. Ultrafast spectroscopy on DNA-cleavage by endonuclease in molecular crowding.

    Science.gov (United States)

    Singh, Priya; Choudhury, Susobhan; Dutta, Shreyasi; Adhikari, Aniruddha; Bhattacharya, Siddhartha; Pal, Debasish; Pal, Samir Kumar

    2017-10-01

    The jam-packed intracellular environments differ the activity of a biological macromolecule from that in laboratory environments (in vitro) through a number of mechanisms called molecular crowding related to structure, function and dynamics of the macromolecule. Here, we have explored the structure, function and dynamics of a model enzyme protein DNase I in molecular crowing of polyethylene glycol (PEG; MW 3350). We have used steady state and picosecond resolved dynamics of a well-known intercalator ethidium bromide (EB) in a 20-mer double-stranded DNA (dsDNA) to monitor the DNA-cleavage by the enzyme in absence and presence PEG. We have also labelled the enzyme by a well-known fluorescent probe 8-anilino-1-naphthalenesulfonic acid ammonium salt (ANS) to study the molecular mechanism of the protein-DNA association through exited state relaxation of the probe in absence (dictated by polarity) and presence of EB in the DNA (dictated by Förster resonance energy transfer (FRET)). The overall and local structures of the protein in presence of PEG have been followed by circular dichroism and time resolved polarization gated spectroscopy respectively. The enhanced dynamical flexibility of protein in presence of PEG as revealed from excited state lifetime and polarization gated anisotropy of ANS has been correlated with the stronger DNA-binding for the higher nuclease activity. We have also used conventional experimental strategy of agarose gel electrophoresis to monitor DNA-cleavage and found consistent results of enhanced nuclease activities both on synthetic 20-mer oligonucleotide and long genomic DNA from calf thymus. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. The Effect of Small Cosolutes that Mimic Molecular Crowding Conditions on the Stability of Triplexes Involving Duplex DNA

    Directory of Open Access Journals (Sweden)

    Anna Aviñó

    2016-02-01

    Full Text Available Triplex stability is studied in crowding conditions using small cosolutes (ethanol, acetonitrile and dimethylsulfoxide by ultraviolet (UV, circular dichroism (CD and nuclear magnetic resonance (NMR spectroscopies. The results indicate that the triplex is formed preferentially when the triplex forming oligonucleotide (TFO is RNA. In addition, DNA triplexes (D:D·D are clearly less stable in cosolute solutions while the stability of the RNA triplexes (R:D·D is only slightly decreased. The kinetic of triplex formation with RNA-TFO is slower than with DNA-TFO and the thermal stability of the triplex is increased with the salt concentration in EtOH-water solutions. Accordingly, RNA could be considered a potential molecule to form a stable triplex for regulatory purposes in molecular crowding conditions.

  18. Molecular Characterization of a Lysozyme Gene and Its Altered Expression Profile in Crowded Beet Webworm (Loxostege sticticalis.

    Directory of Open Access Journals (Sweden)

    Hailong Kong

    Full Text Available There is growing evidence that insects living in high-density populations exhibit an increase in immune function to counter a higher risk of disease. This phenomenon, known as density-dependent prophylaxis, has been experimentally tested in a number of insect species. Although density-dependent prophylaxis is especially prevalent in insects exhibiting density-dependent phase polyphenism, the molecular mechanism remains unclear. Our previous study demonstrated that the antibacterial activity of lysozyme is important for this process in the beet webworm Loxostege sticticalis. In this study, a lysozyme cDNA from L. sticticalis was cloned and characterized. The full-length cDNA is 1078 bp long and contains an open reading frame of 426 bp that encodes 142 amino acids. The deduced protein possesses structural characteristics of a typical c-type lysozyme and clusters with c-type lysozymes from other Lepidoptera. LsLysozyme was found to be expressed throughout all developmental stages, showing the highest level in pupae. LsLysozyme was also highly expressed in the midgut and fat body. Elevated LsLysozyme expression was observed in L. sticticalis larvae infected by Beauveria bassiana and in larvae reared under crowding conditions. In addition, the expression level of LsLysozyme in infected larvae reared at a density of 10 larvae per jar was significantly higher compared to those reared at a density of l or 30 larvae per jar. These results suggest that larval crowding affects the gene expression profile of this lysozyme. This study provides additional insight into the expression of an immune-associated lysozyme gene and helps us to better understand the immune response of L. sticticalis under crowding conditions.

  19. Molecular crowding defines a common origin for the Warburg effect in proliferating cells and the lactate threshold in muscle physiology.

    Directory of Open Access Journals (Sweden)

    Alexei Vazquez

    2011-04-01

    Full Text Available Aerobic glycolysis is a seemingly wasteful mode of ATP production that is seen both in rapidly proliferating mammalian cells and highly active contracting muscles, but whether there is a common origin for its presence in these widely different systems is unknown. To study this issue, here we develop a model of human central metabolism that incorporates a solvent capacity constraint of metabolic enzymes and mitochondria, accounting for their occupied volume densities, while assuming glucose and/or fatty acid utilization. The model demonstrates that activation of aerobic glycolysis is favored above a threshold metabolic rate in both rapidly proliferating cells and heavily contracting muscles, because it provides higher ATP yield per volume density than mitochondrial oxidative phosphorylation. In the case of muscle physiology, the model also predicts that before the lactate switch, fatty acid oxidation increases, reaches a maximum, and then decreases to zero with concomitant increase in glucose utilization, in agreement with the empirical evidence. These results are further corroborated by a larger scale model, including biosynthesis of major cell biomass components. The larger scale model also predicts that in proliferating cells the lactate switch is accompanied by activation of glutaminolysis, another distinctive feature of the Warburg effect. In conclusion, intracellular molecular crowding is a fundamental constraint for cell metabolism in both rapidly proliferating- and non-proliferating cells with high metabolic demand. Addition of this constraint to metabolic flux balance models can explain several observations of mammalian cell metabolism under steady state conditions.

  20. Crowd Sourcing.

    Science.gov (United States)

    Baum, Neil

    2016-01-01

    The Internet has contributed new words and slang to our daily vernacular. A few terms, such as tweeting, texting, sexting, blogging, and googling, have become common in most vocabularies and in many languages, and are now included in the dictionary. A new buzzword making the rounds in industry is crowd sourcing, which involves outsourcing an activity, task, or problem by sending it to people or groups outside a business or a practice. Crowd sourcing allows doctors and practices to tap the wisdom of many instead of relying only on the few members of their close-knit group. This article defines "crowd sourcing," offers examples, and explains how to get started with this approach that can increase your ability to finish a task or solve problems that you don't have the time or expertise to accomplish.

  1. The role of macromolecular crowding in the evolution of lens crystallins with high molecular refractive index

    International Nuclear Information System (INIS)

    Zhao, Huaying; Magone, M Teresa; Schuck, Peter

    2011-01-01

    Crystallins are present in the lens at extremely high concentrations in order to provide transparency and generate a high refractive power of the lens. The crystallin families prevalent in the highest density lens tissues are γ-crystallins in vertebrates and S-crystallins in cephalopods. As shown elsewhere, in parallel evolution, both have evolved molecular refractive index increments 5–10% above those of most proteins. Although this is a small increase, it is statistically very significant and can be achieved only by very unusual amino acid compositions. In contrast, such a molecular adaptation to aid in the refractive function of the lens did not occur in crystallins that are preferentially located in lower density lens tissues, such as vertebrate α-crystallin and taxon-specific crystallins. In the current work, we apply a model of non-interacting hard spheres to examine the thermodynamic contributions of volume exclusion at lenticular protein concentrations. We show that the small concentration decrease afforded by the higher molecular refractive index increment of crystallins can amplify nonlinearly to produce order of magnitude differences in chemical activities, and lead to reduced osmotic pressure and the reduced propensity for protein aggregation. Quantitatively, this amplification sets in only at protein concentrations as high as those found in hard lenses or the nucleus of soft lenses, in good correspondence to the observed crystallin properties in different tissues and different species. This suggests that volume exclusion effects provide the evolutionary driving force for the unusual refractive properties and the unusual amino acid compositions of γ-crystallins and S-crystallins

  2. Crowd Theory and the Management of Crowds

    DEFF Research Database (Denmark)

    Borch, Christian

    2013-01-01

    a turn towards rational approaches difficult, and, on the other hand, that the rational approaches in their ignorance of collective emotional arousal present an inadequate picture of crowds and consequently have limited scope as guidelines for crowd management strategies....... suggest, rational conceptions of crowds should inform contemporary crowd management. This article questions this plea on two grounds. First, it demonstrates that there is no unidirectional connection between sociological crowd theory (whatever its content) and practical strategies for governing crowds...... that, in spite of its current scholarly popularity, there is no guarantee that the call for a practical employment of the rational notion of crowds will necessarily be successful. This is demonstrated by stressing, on the one hand, that irrational notions of crowds continue to thrive, thereby rendering...

  3. High molecular weight polysaccharide that binds and inhibits virus

    Science.gov (United States)

    Konowalchuk, Thomas W

    2014-01-14

    This invention provides a high molecular weight polysaccharide capable of binding to and inhibiting virus and related pharmaceutical formulations and methods on inhibiting viral infectivity and/or pathogenicity, as well as immunogenic compositions. The invention further methods of inhibiting the growth of cancer cells and of ameliorating a symptom of aging. Additionally, the invention provides methods of detecting and/or quantifying and/or isolating viruses.

  4. High molecular weight polysaccharide that binds and inhibits virus

    Energy Technology Data Exchange (ETDEWEB)

    Konowalchuk, Thomas W.; Konowalchuk, Jack

    2017-07-18

    This invention provides a high molecular weight polysaccharide capable of binding to and inhibiting virus and related pharmaceutical formulations and methods of inhibiting viral infectivity and/or pathogenicity, as well as immunogenic compositions. The invention further includes methods of inhibiting the growth of cancer cells and of ameliorating a symptom of aging. Additionally, the invention provides methods of detecting and/or quantifying and/or isolating viruses.

  5. Microorganisms maintain crowding homeostasis

    NARCIS (Netherlands)

    van den Berg, Jonas; Boersma, Arnold J; Poolman, Bert

    2017-01-01

    Macromolecular crowding affects the mobility of biomolecules, protein folding and stability, and the association of macromolecules with each other. Local differences in crowding that arise as a result of subcellular components and supramolecular assemblies contribute to the structural organization

  6. Molecular basis of cyclooxygenase enzymes (COXs) selective inhibition

    Science.gov (United States)

    Limongelli, Vittorio; Bonomi, Massimiliano; Marinelli, Luciana; Gervasio, Francesco Luigi; Cavalli, Andrea; Novellino, Ettore; Parrinello, Michele

    2010-01-01

    The widely used nonsteroidal anti-inflammatory drugs block the cyclooxygenase enzymes (COXs) and are clinically used for the treatment of inflammation, pain, and cancers. A selective inhibition of the different isoforms, particularly COX-2, is desirable, and consequently a deeper understanding of the molecular basis of selective inhibition is of great demand. Using an advanced computational technique we have simulated the full dissociation process of a highly potent and selective inhibitor, SC-558, in both COX-1 and COX-2. We have found a previously unreported alternative binding mode in COX-2 explaining the time-dependent inhibition exhibited by this class of inhibitors and consequently their long residence time inside this isoform. Our metadynamics-based approach allows us to illuminate the highly dynamical character of the ligand/protein recognition process, thus explaining a wealth of experimental data and paving the way to an innovative strategy for designing new COX inhibitors with tuned selectivity. PMID:20215464

  7. Hsa-miR-1587 G-quadruplex formation and dimerization induced by NH4+, molecular crowding environment and jatrorrhizine derivatives.

    Science.gov (United States)

    Tan, Wei; Yi, Long; Zhu, Zhentao; Zhang, Lulu; Zhou, Jiang; Yuan, Gu

    2018-03-01

    A guanine-rich human mature microRNA, miR-1587, was discovered to form stable intramolecular G-quadruplexes in the presence of K + , Na + and low concentration of NH 4 + (25mM) by electrospray ionization mass spectrometry (ESI-MS) combined with circular dichroism (CD) spectroscopy. Furthermore, under high concentration of NH 4 + (100mM) or molecular crowding environments, miR-1587 formed a dimeric G-quadruplex through 3'-to-3' stacking of two monomeric G-quadruplex subunits with one ammonium ion sandwiched between the interfaces. Specifically, two synthesized jatrorrhizine derivatives with terminal amine groups could also induce the dimerization of miR-1587 G-quadruplex and formed 1:1 and 2:1 complexes with the dimeric G-quadruplex. In contrast, jatrorrhizine could bind with the dimeric miR-1587 G-quadruplex, but could not induce dimerization of miR-1587 G-quadruplex. These results provide a new strategy to regulate the functions of miR-1587 through induction of G-quadruplex formation and dimerization. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Crowding and Density

    Science.gov (United States)

    Design and Environment, 1972

    1972-01-01

    Three-part report pinpointing problems and uncovering solutions for the dual concepts of density (ratio of people to space) and crowding (psychological response to density). Section one, A Primer on Crowding,'' reviews new psychological and social findings; section two, Density in the Suburbs,'' shows conflict between status quo and increased…

  9. Crowding of Interacting Fluid Particles in Porous Media through Molecular Dynamics: Breakdown of Universality for Soft Interactions

    Science.gov (United States)

    Schnyder, Simon K.; Horbach, Jürgen

    2018-02-01

    Molecular dynamics simulations of interacting soft disks confined in a heterogeneous quenched matrix of soft obstacles show dynamics which is fundamentally different from that of hard disks. The interactions between the disks can enhance transport when their density is increased, as disks cooperatively help each other over the finite energy barriers in the matrix. The system exhibits a transition from a diffusive to a localized state, but the transition is strongly rounded. Effective exponents in the mean-squared displacement can be observed over three decades in time but depend on the density of the disks and do not correspond to asymptotic behavior in the vicinity of a critical point, thus, showing that it is incorrect to relate them to the critical exponents in the Lorentz model scenario. The soft interactions are, therefore, responsible for a breakdown of the universality of the dynamics.

  10. Fluorescence Dynamics of a FRET Probe Designed for Crowding Studies

    NARCIS (Netherlands)

    Currie, Megan; Leopold, Hannah; Schwarz, Jacob; Boersma, Arnold J; Sheets, Erin D; Heikal, Ahmed A

    2017-01-01

    Living cells are crowded with macromolecules and organelles. As a result, there is an urgent need for molecular sensors for quantitative, site-specific assessment of the macromolecular crowding effects on a myriad of biochemical processes toward quantitative cell biology and biophysics. Here we

  11. Crowding as appropriation

    DEFF Research Database (Denmark)

    Thelle, Mikkel

    2016-01-01

    This article seeks to address the relation between crowds andpublic space as a question of appropriation. With the newliberal constitutions in Europe, several phenomena of crowdingemerge in major cities, of which Copenhagen is taken as anexample. By focusing on the crowd as an agglomeration...... ofbodies, it is assessed how the agency of the crowd works on animmediate level and in its more lasting effects on urban space.The notion of appropriation is related to the crowd’s claim,formal and informal, as resulting from a negotiation of this,mostly public, space, and articulated in empirical cases...

  12. Dense Crowds of Virtual Humans

    NARCIS (Netherlands)

    Stüvel, S.A.

    2016-01-01

    This thesis presents a novel crowd simulation method `Torso Crowds', aimed at the simulation of dense crowds. The method is based on the results of user studies and a motion capture experiment, which are also described in this thesis. Torso Crowds introduces a capsule shape to represent people in

  13. Molecular mechanism for inhibition of twinfilin by phosphoinositides

    DEFF Research Database (Denmark)

    Hakala, Markku; Kalimeri, Maria; Enkavi, Giray

    2018-01-01

    actin-depolymerizing factor (ADF)/cofilin-like ADF homology domains of twinfilin bind phosphoinositides only with low affinity. Mutagenesis and biochemical experiments combined with atomistic molecular dynamics simulations reveal that the C-terminal tail of twinfilin interacts with membranes through......Membrane phosphoinositides control organization and dynamics of the actin cytoskeleton by regulating the activities of several key actin-binding proteins. Twinfilin is an evolutionarily conserved protein that contributes to cytoskeletal dynamics by interacting with actin monomers, filaments......, and the heterodimeric capping protein. Twinfilin also binds phosphoinositides, which inhibit its interactions with actin, but the underlying mechanism has remained unknown. Here, we show that the high-affinity binding site of twinfilin for phosphoinositides is located at the C-terminal tail region, whereas the two...

  14. Crowds and Speculation

    DEFF Research Database (Denmark)

    Bondo Hansen, Kristian

    and crowd phenomena in order to fully understand how markets were perceived and conceptualised in the given historical period. Inspired by Michel Foucault’s reflections on the analysis of problematisations, the dissertation explores how practical, academic and popular accounts of financial markets...... problematised (i.e. reflected upon, contested and responded to) various crowd phenomena as they occurred in the markets. As part of the historical exposition, the dissertation examines how financial writers employed tropes and terminology from late nineteenth century crowd theories when describing and seeking....... Drawing on an archive of handbooks on how to become a successful investor or speculator, scholarly work on financial markets (from the academic fields of economics, sociology and psychology) as well as a range of popular (fictional and non-fictional) textual accounts of trading in financial markets...

  15. Engineering Requirements for crowds

    Directory of Open Access Journals (Sweden)

    Rogeiro Silva

    2015-12-01

    Full Text Available In the software project the interested parts are highly distributed and form numerous and heterogeneous groups, online or face, constituting what could be called crowds. The development of social applications and cloud computing and mobile has generated a marked increase in environments based requirements in crowds. Technical Requirements Engineering (RE traditional face these scalability issues, and require the co-presence of interested and engineers in joint meetings that can not be made in common physical environments. While different approaches have been introduced to partially automate RE in these contexts, still is required a multi-method approach to semi-automate all activities related to work with crowds. In this paper is propose an approach that integrates existing elicitation techniques and requirements analysis and is complemented by introducing new concepts. The information is collected through direct interaction and social collaboration, and through data mining techniques.

  16. Firms, crowds, and innovation.

    Science.gov (United States)

    Felin, Teppo; Lakhani, Karim R; Tushman, Michael L

    2017-05-01

    The purpose of this article is to suggest a (preliminary) taxonomy and research agenda for the topic of "firms, crowds, and innovation" and to provide an introduction to the associated special issue. We specifically discuss how various crowd-related phenomena and practices-for example, crowdsourcing, crowdfunding, user innovation, and peer production-relate to theories of the firm, with particular attention on "sociality" in firms and markets. We first briefly review extant theories of the firm and then discuss three theoretical aspects of sociality related to crowds in the context of strategy, organizations, and innovation: (1) the functions of sociality (sociality as extension of rationality, sociality as sensing and signaling, sociality as matching and identity), (2) the forms of sociality (independent/aggregate and interacting/emergent forms of sociality), and (3) the failures of sociality (misattribution and misapplication). We conclude with an outline of future research directions and introduce the special issue papers and essays.

  17. Optimal crowd evacuation

    NARCIS (Netherlands)

    Hoogendoorn, S.P.; Daamen, W.; Duives, D.C.; Van Wageningen-Kessels, F.L.M.

    2013-01-01

    This paper deals with the optimal allocation of routes, destination, and departure times to members of a crowd, for instance in case of an evacuation or another hazardous situation in which the people need to leave the area as quickly as possible. The generic approach minimizes the evacuation times,

  18. The contrasting effect of macromolecular crowding on amyloid fibril formation.

    Directory of Open Access Journals (Sweden)

    Qian Ma

    Full Text Available Amyloid fibrils associated with neurodegenerative diseases can be considered biologically relevant failures of cellular quality control mechanisms. It is known that in vivo human Tau protein, human prion protein, and human copper, zinc superoxide dismutase (SOD1 have the tendency to form fibril deposits in a variety of tissues and they are associated with different neurodegenerative diseases, while rabbit prion protein and hen egg white lysozyme do not readily form fibrils and are unlikely to cause neurodegenerative diseases. In this study, we have investigated the contrasting effect of macromolecular crowding on fibril formation of different proteins.As revealed by assays based on thioflavin T binding and turbidity, human Tau fragments, when phosphorylated by glycogen synthase kinase-3β, do not form filaments in the absence of a crowding agent but do form fibrils in the presence of a crowding agent, and the presence of a strong crowding agent dramatically promotes amyloid fibril formation of human prion protein and its two pathogenic mutants E196K and D178N. Such an enhancing effect of macromolecular crowding on fibril formation is also observed for a pathological human SOD1 mutant A4V. On the other hand, rabbit prion protein and hen lysozyme do not form amyloid fibrils when a crowding agent at 300 g/l is used but do form fibrils in the absence of a crowding agent. Furthermore, aggregation of these two proteins is remarkably inhibited by Ficoll 70 and dextran 70 at 200 g/l.We suggest that proteins associated with neurodegenerative diseases are more likely to form amyloid fibrils under crowded conditions than in dilute solutions. By contrast, some of the proteins that are not neurodegenerative disease-associated are unlikely to misfold in crowded physiological environments. A possible explanation for the contrasting effect of macromolecular crowding on these two sets of proteins (amyloidogenic proteins and non-amyloidogenic proteins has been

  19. Molecular mechanisms of DNA repair inhibition by caffeine

    Energy Technology Data Exchange (ETDEWEB)

    Selby, C.P.; Sancar, A. (Univ. of North Carolina School of Medicine, Chapel Hill (USA))

    1990-05-01

    Caffeine potentiates the mutagenic and lethal effects of genotoxic agents. It is thought that this is due, at least in some organisms, to inhibition of DNA repair. However, direct evidence for inhibition of repair enzymes has been lacking. Using purified Escherichia coli DNA photolyase and (A)BC excinuclease, we show that the drug inhibits photoreactivation and nucleotide excision repair by two different mechanisms. Caffeine inhibits photoreactivation by interfering with the specific binding of photolyase to damaged DNA, and it inhibits nucleotide excision repair by promoting nonspecific binding of the damage-recognition subunit, UvrA, of (A)BC excinuclease. A number of other intercalators, including acriflavin and ethidium bromide, appear to inhibit the excinuclease by a similar mechanism--that is, by trapping the UvrA subunit in nonproductive complexes on undamaged DNA.

  20. Diffusion in crowded biological environments: applications of Brownian dynamics

    OpenAIRE

    Długosz, Maciej; Trylska, Joanna

    2011-01-01

    Biochemical reactions in living systems occur in complex, heterogeneous media with total concentrations of macromolecules in the range of 50 - 400 mg/ml. Molecular species occupy a significant fraction of the immersing medium, up to 40% of volume. Such complex and volume-occupied environments are generally termed 'crowded' and/or 'confined'. In crowded conditions non-specific interactions between macromolecules may hinder diffusion - a major process determining metabolism, transport, and sign...

  1. Deep Learning from Crowds

    DEFF Research Database (Denmark)

    Rodrigues, Filipe; Pereira, Francisco Camara

    Over the last few years, deep learning has revolutionized the field of machine learning by dramatically improving the stateof-the-art in various domains. However, as the size of supervised artificial neural networks grows, typically so does the need for larger labeled datasets. Recently...... networks from crowds. We begin by describing an EM algorithm for jointly learning the parameters of the network and the reliabilities of the annotators. Then, a novel general-purpose crowd layer is proposed, which allows us to train deep neural networks end-to-end, directly from the noisy labels......, crowdsourcing has established itself as an efficient and cost-effective solution for labeling large sets of data in a scalable manner, but it often requires aggregating labels from multiple noisy contributors with different levels of expertise. In this paper, we address the problem of learning deep neural...

  2. Crowds and Crisis

    DEFF Research Database (Denmark)

    Borch, Christian

    The November Revolution in 1918 made manifest and further unleashed a political crisis in Germany, the consequences of which have been thoroughly examined. What has attracted less attention is how the Revolution also triggered a semantic crisis within sociology, namely with regard to conceptions...... selected aspects of classical crowd semantics – in particular notions of imitation and suggestibility – and for placing them centrally in the understanding of the social, in times of crisis and not....

  3. Taming Crowded Visual Scenes

    Science.gov (United States)

    2014-08-12

    Nolan Warner, Mubarak Shah. Tracking in Dense Crowds Using Prominenceand Neighborhood Motion Concurrence, IEEE Transactions on Pattern Analysis...of  computer  vision,   computer   graphics  and  evacuation  dynamics  by  providing  a  common  platform,  and  provides...areas  that  includes  Computer  Vision,  Computer   Graphics ,  and  Pedestrian   Evacuation  Dynamics.  Despite  the

  4. Salmonella infection inhibits intestinal biotin transport: cellular and molecular mechanisms.

    Science.gov (United States)

    Ghosal, Abhisek; Jellbauer, Stefan; Kapadia, Rubina; Raffatellu, Manuela; Said, Hamid M

    2015-07-15

    Infection with the nontyphoidal Salmonella is a common cause of food-borne disease that leads to acute gastroenteritis/diarrhea. Severe/prolonged cases of Salmonella infection could also impact host nutritional status, but little is known about its effect on intestinal absorption of vitamins, including biotin. We examined the effect of Salmonella enterica serovar Typhimurium (S. typhimurium) infection on intestinal biotin uptake using in vivo (streptomycin-pretreated mice) and in vitro [mouse (YAMC) and human (NCM460) colonic epithelial cells, and human intestinal epithelial Caco-2 cells] models. The results showed that infecting mice with wild-type S. typhimurium, but not with its nonpathogenic isogenic invA spiB mutant, leads to a significant inhibition in jejunal/colonic biotin uptake and in level of expression of the biotin transporter, sodium-dependent multivitamin transporter. In contrast, infecting YAMC, NCM460, and Caco-2 cells with S. typhimurium did not affect biotin uptake. These findings suggest that the effect of S. typhimurium infection is indirect and is likely mediated by proinflammatory cytokines, the levels of which were markedly induced in the intestine of S. typhimurium-infected mice. Consistent with this hypothesis, exposure of NCM460 cells to the proinflammatory cytokines TNF-α and IFN-γ led to a significant inhibition of biotin uptake, sodium-dependent multivitamin transporter expression, and activity of the SLC5A6 promoter. The latter effects appear to be mediated, at least in part, via the NF-κB signaling pathway. These results demonstrate that S. typhimurium infection inhibits intestinal biotin uptake, and that the inhibition is mediated via the action of proinflammatory cytokines.

  5. Setting up crowd science projects.

    Science.gov (United States)

    Scheliga, Kaja; Friesike, Sascha; Puschmann, Cornelius; Fecher, Benedikt

    2016-11-29

    Crowd science is scientific research that is conducted with the participation of volunteers who are not professional scientists. Thanks to the Internet and online platforms, project initiators can draw on a potentially large number of volunteers. This crowd can be involved to support data-rich or labour-intensive projects that would otherwise be unfeasible. So far, research on crowd science has mainly focused on analysing individual crowd science projects. In our research, we focus on the perspective of project initiators and explore how crowd science projects are set up. Based on multiple case study research, we discuss the objectives of crowd science projects and the strategies of their initiators for accessing volunteers. We also categorise the tasks allocated to volunteers and reflect on the issue of quality assurance as well as feedback mechanisms. With this article, we contribute to a better understanding of how crowd science projects are set up and how volunteers can contribute to science. We suggest that our findings are of practical relevance for initiators of crowd science projects, for science communication as well as for informed science policy making. © The Author(s) 2016.

  6. Setting up crowd science projects

    NARCIS (Netherlands)

    Scheliga, Kaja; Friesike, Sascha; Puschmann, Cornelius; Fecher, Benedikt

    2016-01-01

    Crowd science is scientific research that is conducted with the participation of volunteers who are not professional scientists. Thanks to the Internet and online platforms, project initiators can draw on a potentially large number of volunteers. This crowd can be involved to support data-rich or

  7. Molecular Mechanisms of Inhibition of Streptococcus Species by Phytochemicals

    Directory of Open Access Journals (Sweden)

    Soheila Abachi

    2016-02-01

    Full Text Available This review paper summarizes the antibacterial effects of phytochemicals of various medicinal plants against pathogenic and cariogenic streptococcal species. The information suggests that these phytochemicals have potential as alternatives to the classical antibiotics currently used for the treatment of streptococcal infections. The phytochemicals demonstrate direct bactericidal or bacteriostatic effects, such as: (i prevention of bacterial adherence to mucosal surfaces of the pharynx, skin, and teeth surface; (ii inhibition of glycolytic enzymes and pH drop; (iii reduction of biofilm and plaque formation; and (iv cell surface hydrophobicity. Collectively, findings from numerous studies suggest that phytochemicals could be used as drugs for elimination of infections with minimal side effects.

  8. Unpaid Crowd Complementors

    DEFF Research Database (Denmark)

    Boudreau, Kevin J.; Jeppesen, Lars Bo

    2014-01-01

    on network effects and strategies to attract large numbers of complementors remain advisable in such contexts? We test hypotheses related to these issues using data from 85 online multi-player game platforms with unpaid complementors. We find that complementor development responds to platform growth even......Platforms have evolved beyond just being organized as multi-sided markets with complementors selling to users. Complementors are often unpaid, working outside of a price system and driven by heterogeneous sources of motivation— which should affect how they respond to platform growth. Does reliance...... without sales incentives, but that attracting complementors has a net zero effect on on-going development and fails to stimulate network effects. We discuss conditions under which a strategy of using unpaid crowd complementors remains advantageous....

  9. Modulation of calmodulin plasticity by the effect of macromolecular crowding.

    Science.gov (United States)

    Homouz, Dirar; Sanabria, Hugo; Waxham, M Neal; Cheung, Margaret S

    2009-09-04

    In vitro biochemical reactions are most often studied in dilute solution, a poor mimic of the intracellular space of eukaryotic cells, which are crowded with mobile and immobile macromolecules. Such crowded conditions exert volume exclusion and other entropic forces that have the potential to impact chemical equilibria and reaction rates. In this article, we used the well-characterized and ubiquitous molecule calmodulin (CaM) and a combination of theoretical and experimental approaches to address how crowding impacts CaM's conformational plasticity. CaM is a dumbbell-shaped molecule that contains four EF hands (two in the N-lobe and two in the C-lobe) that each could bind Ca(2+), leading to stabilization of certain substates that favor interactions with other target proteins. Using coarse-grained molecular simulations, we explored the distribution of CaM conformations in the presence of crowding agents. These predictions, in which crowding effects enhance the population of compact structures, were then confirmed in experimental measurements using fluorescence resonance energy transfer techniques of donor- and acceptor-labeled CaM under normal and crowded conditions. Using protein reconstruction methods, we further explored the folding-energy landscape and examined the structural characteristics of CaM at free-energy basins. We discovered that crowding stabilizes several different compact conformations, which reflects the inherent plasticity in CaM's structure. From these results, we suggest that the EF hands in the C-lobe are flexible and can be thought of as a switch, while those in the N-lobe are stiff, analogous to a rheostat. New combinatorial signaling properties may arise from the product of the differential plasticity of the two distinct lobes of CaM in the presence of crowding. We discuss the implications of these results for modulating CaM's ability to bind Ca(2+) and target proteins.

  10. Crowd wisdom drives intelligent manufacturing

    Directory of Open Access Journals (Sweden)

    Jiaqi Lu

    2017-03-01

    Full Text Available Purpose – A fundamental problem for intelligent manufacturing is to equip the agents with the ability to automatically make judgments and decisions. This paper aims to introduce the basic principle for intelligent crowds in an attempt to show that crowd wisdom could help in making accurate judgments and proper decisions. This further shows the positive effects that crowd wisdom could bring to the entire manufacturing process. Design/methodology/approach – Efforts to support the critical role of crowd wisdom in intelligent manufacturing involve theoretical explanation, including a discussion of several prevailing concepts, such as consumer-to-business (C2B, crowdfunding and an interpretation of the contemporary Big Data mania. In addition, an empirical study with three business cases was conducted to prove the conclusion that our ideas could well explain the current business phenomena and guide the future of manufacturing. Findings – This paper shows that crowd wisdom could help make accurate judgments and proper decisions. It further shows the positive effects that crowd wisdom could bring to the entire manufacturing process. Originality/value – The paper highlights the importance of crowd wisdom in manufacturing with sufficient theoretical and empirical analysis, potentially providing a guideline for future industry.

  11. Crowding effects in vehicular traffic.

    Directory of Open Access Journals (Sweden)

    Jay Samuel L Combinido

    Full Text Available While the impact of crowding on the diffusive transport of molecules within a cell is widely studied in biology, it has thus far been neglected in traffic systems where bulk behavior is the main concern. Here, we study the effects of crowding due to car density and driving fluctuations on the transport of vehicles. Using a microscopic model for traffic, we found that crowding can push car movement from a superballistic down to a subdiffusive state. The transition is also associated with a change in the shape of the probability distribution of positions from a negatively-skewed normal to an exponential distribution. Moreover, crowding broadens the distribution of cars' trap times and cluster sizes. At steady state, the subdiffusive state persists only when there is a large variability in car speeds. We further relate our work to prior findings from random walk models of transport in cellular systems.

  12. Effects of macromolecular crowding on protein conformational changes.

    Directory of Open Access Journals (Sweden)

    Hao Dong

    2010-07-01

    Full Text Available Many protein functions can be directly linked to conformational changes. Inside cells, the equilibria and transition rates between different conformations may be affected by macromolecular crowding. We have recently developed a new approach for modeling crowding effects, which enables an atomistic representation of "test" proteins. Here this approach is applied to study how crowding affects the equilibria and transition rates between open and closed conformations of seven proteins: yeast protein disulfide isomerase (yPDI, adenylate kinase (AdK, orotidine phosphate decarboxylase (ODCase, Trp repressor (TrpR, hemoglobin, DNA beta-glucosyltransferase, and Ap(4A hydrolase. For each protein, molecular dynamics simulations of the open and closed states are separately run. Representative open and closed conformations are then used to calculate the crowding-induced changes in chemical potential for the two states. The difference in chemical-potential change between the two states finally predicts the effects of crowding on the population ratio of the two states. Crowding is found to reduce the open population to various extents. In the presence of crowders with a 15 A radius and occupying 35% of volume, the open-to-closed population ratios of yPDI, AdK, ODCase and TrpR are reduced by 79%, 78%, 62% and 55%, respectively. The reductions for the remaining three proteins are 20-44%. As expected, the four proteins experiencing the stronger crowding effects are those with larger conformational changes between open and closed states (e.g., as measured by the change in radius of gyration. Larger proteins also tend to experience stronger crowding effects than smaller ones [e.g., comparing yPDI (480 residues and TrpR (98 residues]. The potentials of mean force along the open-closed reaction coordinate of apo and ligand-bound ODCase are altered by crowding, suggesting that transition rates are also affected. These quantitative results and qualitative trends will

  13. Thermodynamics of Macromolecular Association in Heterogeneous Crowding Environments: Theoretical and Simulation Studies with a Simplified Model.

    Science.gov (United States)

    Ando, Tadashi; Yu, Isseki; Feig, Michael; Sugita, Yuji

    2016-11-23

    The cytoplasm of a cell is crowded with many different kinds of macromolecules. The macromolecular crowding affects the thermodynamics and kinetics of biological reactions in a living cell, such as protein folding, association, and diffusion. Theoretical and simulation studies using simplified models focus on the essential features of the crowding effects and provide a basis for analyzing experimental data. In most of the previous studies on the crowding effects, a uniform crowder size is assumed, which is in contrast to the inhomogeneous size distribution of macromolecules in a living cell. Here, we evaluate the free energy changes upon macromolecular association in a cell-like inhomogeneous crowding system via a theory of hard-sphere fluids and free energy calculations using Brownian dynamics trajectories. The inhomogeneous crowding model based on 41 different types of macromolecules represented by spheres with different radii mimics the physiological concentrations of macromolecules in the cytoplasm of Mycoplasma genitalium. The free energy changes of macromolecular association evaluated by the theory and simulations were in good agreement with each other. The crowder size distribution affects both specific and nonspecific molecular associations, suggesting that not only the volume fraction but also the size distribution of macromolecules are important factors for evaluating in vivo crowding effects. This study relates in vitro experiments on macromolecular crowding to in vivo crowding effects by using the theory of hard-sphere fluids with crowder-size heterogeneity.

  14. To See (Like a Crowd

    Directory of Open Access Journals (Sweden)

    Hazem Ziada

    2015-07-01

    Full Text Available This paper explores the dynamics through which design drawings structure spatial strategies, particularly those with an agenda for socio-political change, while interrogating the drawings’ impacts on subjectivity. It dissects an early Soviet architectural drawing addressing the 1920s-30s' crowd-design-problem': using architectural space to generate a robust intersubjectivity in mass crowds. Revolutionary Soviet artists challenged inherited graphic regimes of viewing crowds from an alienating distance, proposing devices of 'immersion' to radically re-visualize mass crowds and re-conceptualize collectivity. Drawing on Suprematist compositions, the avant-garde Soviet Rationalist architects translated immersive principles from contemporary revolutionary art. The paper articulates the Rationalists’ alternative graphic framework which immerses the observer-cum-designer within crowd dynamics in a distinctively architectural way, while identifying its implications on spatial design: a space of undulating grounds, rhythmic choreographies and ‘textured’ visual fields. The paper also speculates on its implications redefining subjectivity; re-introducing emotion amongst the relations of production challenges canonical Historical Materialism.

  15. Synthesis of 2-acylated and sulfonated 4-hydroxycoumarins: In vitro urease inhibition and molecular docking studies.

    Science.gov (United States)

    Rashid, Umer; Rahim, Fazal; Taha, Muhammad; Arshad, Muhammad; Ullah, Hayat; Mahmood, Tariq; Ali, Muhammad

    2016-06-01

    Sixteen 4-hydroxycoumarin derivatives were synthesized, characterized through EI-MS and (1)H NMR and screened for urease inhibitory potential. Three compounds exhibited better urease inhibition than the standard inhibitor thiourea (IC50=21±0.11μM) while other four compounds exhibited good to moderate inhibition with IC50 values between 29.45±1.1μM and 69.53±0.9μM. Structure activity relationship was established on the basis of molecular docking studies, which helped to predict the binding interactions of the most active compounds. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Crowded, Confined, and Frustrated: Dynamics of Molecules Tethered to Nanoparticles

    KAUST Repository

    Agarwal, Praveen

    2012-12-01

    Above a critical chemistry-dependent molecular weight, all polymer molecules entangle and, as a result, exhibit slow dynamics, enhanced viscosity, and elasticity. Herein we report on the dynamics of low molecular weight polymers tethered to nanoparticles and find that even conventionally unentangled chains manifest dynamical features similar to entangled, long-chain molecules. Our findings are shown to imply that crowding and confinement of polymers on particles produce topological constraints analogous to those in entangled systems. © 2012 American Physical Society.

  17. Molecular features related to HIV integrase inhibition obtained from structure- and ligand-based approaches.

    Directory of Open Access Journals (Sweden)

    Luciana L de Carvalho

    Full Text Available Among several biological targets to treat AIDS, HIV integrase is a promising enzyme that can be employed to develop new anti-HIV agents. The aim of this work is to propose a mechanistic interpretation of HIV-1 integrase inhibition and to rationalize the molecular features related to the binding affinity of studied ligands. A set of 79 HIV-1 integrase inhibitors and its relationship with biological activity are investigated employing 2D and 3D QSAR models, docking analysis and DFT studies. Analyses of docking poses and frontier molecular orbitals revealed important features on the main ligand-receptor interactions. 2D and 3D models presenting good internal consistency, predictive power and stability were obtained in all cases. Significant correlation coefficients (r(2 = 0.908 and q(2= 0.643 for 2D model; r(2= 0.904 and q(2= 0.719 for 3D model were obtained, indicating the potential of these models for untested compounds. The generated holograms and contribution maps revealed important molecular requirements to HIV-1 IN inhibition and several evidences for molecular modifications. The final models along with information resulting from molecular orbitals, 2D contribution and 3D contour maps should be useful in the design of new inhibitors with increased potency and selectivity within the chemical diversity of the data.

  18. Spatial and Social Aspects of Crowding Perception

    Science.gov (United States)

    Baum, Andrew; Davis, Glenn E.

    1976-01-01

    This paper discusses mediation of the crowding experience in architectural interiors by three environmental variables: setting orientation, room color, and visual complexity of the interior. Data indicated interior design does influence space perception and crowding thresholds. (RH)

  19. Towards a South African crowd control model

    CSIR Research Space (South Africa)

    Modise, M

    2013-03-01

    Full Text Available . Phase 3, will be the development of decision support system for crowd control. This paper discusses Phase 1 of the project, which includes identification of various variables regarding crowd control and their relationships. During the Arab Spring...

  20. Inhibition of CYP1 by berberine, palmatine, and jatrorrhizine: Selectivity, kinetic characterization, and molecular modeling

    International Nuclear Information System (INIS)

    Lo, Sheng-Nan; Chang, Yu-Ping; Tsai, Keng-Chang; Chang, Chia-Yu; Wu, Tian-Shung; Ueng, Yune-Fang

    2013-01-01

    Cytochrome P450 (P450, CYP) 1 family plays a primary role in the detoxification and bioactivation of polycyclic aromatic hydrocarbons. Human CYP1A1, CYP1A2, and CYP1B1 exhibit differential substrate specificity and tissue distribution. Berberine, palmatine, and jatrorrhizine are protoberberine alkaloids present in several medicinal herbs, such as Coptis chinensis (Huang-Lian) and goldenseal. These protoberberines inhibited CYP1A1.1- and CYP1B1.1-catalyzed 7-ethoxyresorufin O-deethylation (EROD) activities, whereas CYP1A2.1 activity was barely affected. Kinetic analysis revealed that berberine noncompetitively inhibited EROD activities of CYP1A1.1 and CYP1B1.1, whereas palmatine and jatrorrhizine caused either competitive or mixed type of inhibition. Among protoberberines, berberine caused the most potent and selective inhibitory effect on CYP1B1.1 with the least K i value of 44 ± 16 nM. Berberine also potently inhibited CYP1B1.1 activities toward 7-ethoxycoumarin and 7-methoxyresorufin, whereas the inhibition of benzo(a)pyrene hydroxylation activity was less pronounced. Berberine inhibited the polymorphic variants, CYP1B1.3 (V432L) and CYP1B1.4 (N453S), with IC 50 values comparable to that for CYP1B1.1 inhibition. Berberine-mediated inhibition was abolished by a mutation of Asn228 to Thr in CYP1B1.1, whereas the inhibition was enhanced by a reversal mutation of Thr223 to Asn in CYP1A2.1. This result in conjugation with the molecular modeling revealed the crucial role of hydrogen-bonding interaction of Asn228 on CYP1B1.1 with the methoxy moiety of berberine. These findings demonstrate that berberine causes a selective CYP1B1-inhibition, in which Asn228 appears to be crucial. The inhibitory effects of berberine on CYP1B1 activities toward structurally diverse substrates can be different. - Highlights: • Berberine preferentially inhibited CYP1B1 activity. • Berberine caused similar inhibitory effects on CYP1B1.1, CYP1B1.3 and CYP1B1.4. • Asn228 in CYP1B1 was an

  1. Inhibition of CYP1 by berberine, palmatine, and jatrorrhizine: Selectivity, kinetic characterization, and molecular modeling

    Energy Technology Data Exchange (ETDEWEB)

    Lo, Sheng-Nan [National Research Institute of Chinese Medicine, Taipei 112, Taiwan, ROC (China); Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan, ROC (China); Chang, Yu-Ping; Tsai, Keng-Chang [National Research Institute of Chinese Medicine, Taipei 112, Taiwan, ROC (China); Chang, Chia-Yu [National Research Institute of Chinese Medicine, Taipei 112, Taiwan, ROC (China); Institute of Medical Sciences, Taipei Medical University, Taipei 101, Taiwan, ROC (China); Wu, Tian-Shung [Department of Chemistry, National Chung-Kung University, Tainan 701, Taiwan, ROC (China); Ueng, Yune-Fang, E-mail: ueng@nricm.edu.tw [National Research Institute of Chinese Medicine, Taipei 112, Taiwan, ROC (China); Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan, ROC (China); Institute of Medical Sciences, Taipei Medical University, Taipei 101, Taiwan, ROC (China)

    2013-11-01

    Cytochrome P450 (P450, CYP) 1 family plays a primary role in the detoxification and bioactivation of polycyclic aromatic hydrocarbons. Human CYP1A1, CYP1A2, and CYP1B1 exhibit differential substrate specificity and tissue distribution. Berberine, palmatine, and jatrorrhizine are protoberberine alkaloids present in several medicinal herbs, such as Coptis chinensis (Huang-Lian) and goldenseal. These protoberberines inhibited CYP1A1.1- and CYP1B1.1-catalyzed 7-ethoxyresorufin O-deethylation (EROD) activities, whereas CYP1A2.1 activity was barely affected. Kinetic analysis revealed that berberine noncompetitively inhibited EROD activities of CYP1A1.1 and CYP1B1.1, whereas palmatine and jatrorrhizine caused either competitive or mixed type of inhibition. Among protoberberines, berberine caused the most potent and selective inhibitory effect on CYP1B1.1 with the least K{sub i} value of 44 ± 16 nM. Berberine also potently inhibited CYP1B1.1 activities toward 7-ethoxycoumarin and 7-methoxyresorufin, whereas the inhibition of benzo(a)pyrene hydroxylation activity was less pronounced. Berberine inhibited the polymorphic variants, CYP1B1.3 (V432L) and CYP1B1.4 (N453S), with IC{sub 50} values comparable to that for CYP1B1.1 inhibition. Berberine-mediated inhibition was abolished by a mutation of Asn228 to Thr in CYP1B1.1, whereas the inhibition was enhanced by a reversal mutation of Thr223 to Asn in CYP1A2.1. This result in conjugation with the molecular modeling revealed the crucial role of hydrogen-bonding interaction of Asn228 on CYP1B1.1 with the methoxy moiety of berberine. These findings demonstrate that berberine causes a selective CYP1B1-inhibition, in which Asn228 appears to be crucial. The inhibitory effects of berberine on CYP1B1 activities toward structurally diverse substrates can be different. - Highlights: • Berberine preferentially inhibited CYP1B1 activity. • Berberine caused similar inhibitory effects on CYP1B1.1, CYP1B1.3 and CYP1B1.4. • Asn228 in CYP

  2. Insights into structural features of HDAC1 and its selectivity inhibition elucidated by Molecular dynamic simulation and Molecular Docking.

    Science.gov (United States)

    Sixto-López, Yudibeth; Bello, Martiniano; Correa-Basurto, José

    2018-03-06

    Histone deacetylases (HDACs) are a family of proteins whose main function is the removal of acetyl groups from lysine residues located on histone and non-histone substrates, which regulates gene transcription and other activities in cells. HDAC1 dysfunction has been implicated in cancer development and progression; thus, its inhibition has emerged as a new therapeutic strategy. Two additional metal binding sites (Site 1 and Site 2) in HDACs have been described that are primarily occupied by potassium ions, suggesting a possible structural role that affects HDAC activity. In this work, we explored the structural role of potassium ions in Site 1 and Site 2 and how they affect the interactions of compounds with high affinities for HDAC1 (AC1OCG0B, Chlamydocin, Dacinostat and Quisinostat) and SAHA (a pan-inhibitor) using molecular docking and molecular dynamics (MD) simulations in concert with a Molecular-Mechanics-Generalized-Born-Surface-Area (MMGBSA) approach. Four models were generated: one with a potassium ion (K + ) in both sites (HDAC1 k ), a second with K + only at site 1 (HDAC1 ks1 ), a third with K + only at site 2 (HDAC1 ks2 ) and a fourth with no K + (HDAC1 wk ). We found that the presence or absence of K + not only impacted the structural flexibility of HDAC1, but also its molecular recognition, consistent with experimental findings. These results could therefore be useful for further structure-based drug design studies addressing new HDAC1 inhibitors.

  3. Orientation-crowding within contours.

    Science.gov (United States)

    Glen, James C; Dakin, Steven C

    2013-07-15

    We examined how crowding (the breakdown of object recognition in the periphery caused by interference from "clutter") depends on the global arrangement of target and distracting flanker elements. Specifically we probed orientation discrimination using a near-vertical target Gabor flanked by two vertical distractor Gabors (one above and one below the target). By applying variable (opposite-sign) horizontal offsets to the positions of the two flankers we arranged the elements so that on some trials they formed contours with the target and on others they did not. While the presence of flankers generally elevated orientation discrimination thresholds for the target we observe maximal crowding not when flanker and targets were co-aligned but when a small spatial offset was applied to flanker location, so that contours formed between flanker and targets only when the target orientation was cued. We also report that observers' orientation judgments are biased, with target orientation appearing either attracted or repulsed by the global/contour orientation. A second experiment reveals that the sign of this effect is dependent both on observer and on eccentricity. In general, the magnitude of repulsion is reduced with eccentricity but whether this becomes attraction (of element orientation to contour orientation) is dependent on observer. We note however that across observers and eccentricities, the magnitude of repulsion correlates positively with the amount of release from crowding observed with co-aligned targets and flankers, supporting the notion of fluctuating bias as the basis for elevated crowding within contours.

  4. Intracellular crowding effects on the self-association of the bacterial cell division protein FtsZ.

    Science.gov (United States)

    Naddaf, Lamis; Sayyed-Ahmad, Abdallah

    2014-12-15

    The dimerization rate of the bacterial cell division protein FtsZ is strongly affected by the intracellular crowding. Yet the complexity of the intracellular environment makes it difficult to investigate via all-atom molecular dynamics or other detailed theoretical methods. We study the crowding effect on FtsZ dimerization which is the first step of an oligomerization process that results in more elaborate supramolecular structures. In particular, we consider the effect of intracellular crowding on the reaction rates, and their dependence on the different concentrations of crowding agents. We achieved this goal by using Brownian dynamics (BD) simulation techniques and a modified post-processing approach in which we decompose the rate constant in crowded media as a product of the rate constant in the dilute solution times a factor that incorporates the crowding effect. The latter factor accounts for the diffusion reduction and crowder induced energy. In addition we include the crowding effects on water viscosity in the BD simulations of crowded media. We finally show that biomolecular crowding has a considerable effect on the FtsZ dimerization by increasing the dimerization rate constant from 2.6×10(7)M(-1)s(-1) in the absence of crowders to 1.0×10(8)M(-1)s(-1) at crowding level of 0.30. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. A molecular framework for the inhibition of Arabidopsis root growth in response to boron toxicity.

    Science.gov (United States)

    Aquea, Felipe; Federici, Fernan; Moscoso, Cristian; Vega, Andrea; Jullian, Pastor; Haseloff, Jim; Arce-Johnson, Patricio

    2012-04-01

    Boron is an essential micronutrient for plants and is taken up in the form of boric acid (BA). Despite this, a high BA concentration is toxic for the plants, inhibiting root growth and is thus a significant problem in semi-arid areas in the world. In this work, we report the molecular basis for the inhibition of root growth caused by boron. We show that application of BA reduces the size of root meristems, correlating with the inhibition of root growth. The decrease in meristem size is caused by a reduction of cell division. Mitotic cell number significantly decreases and the expression level of key core cell cycle regulators is modulated. The modulation of the cell cycle does not appear to act through cytokinin and auxin signalling. A global expression analysis reveals that boron toxicity induces the expression of genes related with abscisic acid (ABA) signalling, ABA response and cell wall modifications, and represses genes that code for water transporters. These results suggest that boron toxicity produces a reduction of water and BA uptake, triggering a hydric stress response that produces root growth inhibition. © 2011 Blackwell Publishing Ltd.

  6. Insights into the molecular mechanism of RGL2-mediated inhibition of seed germination in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Stamm Petra

    2012-10-01

    Full Text Available Abstract Background Seed germination is of immense significance for agriculture and has been studied for centuries. Yet, our understanding of the molecular mechanisms underlying regulation of dormancy and germination is still in its infancy. Gibberellins are the key phytohormones that promote germination, and the DELLA protein RGL2 is the main signalling intermediate involved in this response. Germination is completely inhibited if functional RGL2 is overexpressed and/or stabilized; however, the molecular mechanisms of RGL2 function are still largely unknown. We therefore attempted to shed light onto some of the genetic events downstream of RGL2. Results Gene ontology of the transcriptome differentially regulated by RGL2, as well as extensive cross-comparison with other available microarray data indicates that RGL2-mediated inhibition of germination causes seeds to enter a state of dormancy. RGL2 also appears to differentially regulate a number of transcription factors, many of which are known to be involved in light- or phytohormone-mediated aspects of germination. A promoter analysis of differentially expressed genes identified an enrichment of several motifs that can be bound by specific transcription factors, for example GAMYB, ARF1, or Dof-type zinc fingers. We show that Dof-binding motifs indeed play a role in RGL2-mediated transcription. Using Chromatin Immunoprecipitation (ChIP, we show that RGL2 directly downregulates at least one cell wall modifying enzyme, which is predicted to constrain cell growth thereby leading to inhibition of seed germination. Conclusions Our results reveal that RGL2 controls various aspects of germination. Through the repression of cell wall modifying enzymes, cell growth is directly constrained to inhibit germination. Furthermore, RGL2 likely interacts with various types of proteins to regulate transcription, and differentially regulates several transcription factors. Collectively, our data indicate that

  7. Inhibition of Heme Peroxidase During Phenol Derivatives Oxidation. Possible Molecular Cloaking of the Active Center

    Directory of Open Access Journals (Sweden)

    Juozas Kulys

    2005-10-01

    Full Text Available Abstract: Ab initio quantum chemical calculations have been applied to the study of the molecular structure of phenol derivatives and oligomers produced during peroxidasecatalyzed oxidation. The interaction of substrates and oligomers with Arthromyces ramosus peroxidase was analyzed by docking methods. The most possible interaction site of oligomers is an active center of the peroxidase. The complexation energy increases with increasing oligomer length. However, the complexed oligomers do not form a precise (for the reaction hydrogen bonding network in the active center of the enzyme. It seems likely that strong but non productive docking of the oligomers determines peroxidase inhibition during the reaction.

  8. Experimental and molecular dynamics study on the inhibition performance of some nitrogen containing compounds for iron corrosion

    International Nuclear Information System (INIS)

    Khaled, K.F.

    2010-01-01

    A molecular dynamics study for the adsorption of three benzimidazole derivatives and their inhibition characteristics was studied using chemical (weight loss) and electrochemical measurements (potentiodynamic polarization and electrochemical impedance spectroscopy, EIS). Electrochemical measurements results revealed that the inhibition efficiencies increased with the concentration of inhibitors. Results obtained from weight loss, dc polarization and ac impedance measurements are in reasonably good agreement and show increased inhibitor efficiency with increasing inhibitor concentration. The molecular dynamics calculations showed that the higher the binding energy between the inhibitor and metal surface, the higher the inhibition efficiency. Also, the higher the adsorption energy, the higher the inhibition efficiency. The molecular dynamics study revealed that the benzimidazole ring as well as the side chain are the active sites in these inhibitors and they can absorb on Fe surface by donating electrons to Fe d-orbital.

  9. Low Molecular Weight Fucoidan Inhibits Tumor Angiogenesis through Downregulation of HIF-1/VEGF Signaling under Hypoxia

    Directory of Open Access Journals (Sweden)

    Meng-Chuan Chen

    2015-07-01

    Full Text Available Activation of hypoxia-induced hypoxia-inducible factors-1 (HIF-1 plays a critical role in promoting tumor angiogenesis, growth and metastasis. Low molecular weight fucoidan (LMWF is prepared from brown algae, and exhibits anticancer activity. However, whether LMWF attenuates hypoxia-induced angiogenesis in bladder cancer cells and the molecular mechanisms involved remain unclear. This is the first study to demonstrate that LMWF can inhibit hypoxia-stimulated H2O2 formation, HIF-1 accumulation and transcriptional activity vascular endothelial growth factor (VEGF secretion, and the migration and invasion in hypoxic human bladder cancer cells (T24 cells. LMWF also downregulated hypoxia-activated phosphorylation of PI3K/AKT/mTOR/p70S6K/4EBP-1 signaling in T24 cells. Blocking PI3K/AKT or mTOR activity strongly diminished hypoxia-induced HIF-1α expression and VEGF secretion in T24 cells, supporting the involvement of PI3K/AKT/mTOR in the induction of HIF-1α and VEGF. Additionally, LMWF significantly attenuated angiogenesis in vitro and in vivo evidenced by reduction of tube formation of hypoxic human umbilical vascular endothelial cells and blood capillary generation in the tumor. Similarly, administration of LMWF also inhibited the HIF-1α and VEGF expression in vivo, accompanied by a reduction of tumor growth. In summary, under hypoxia conditions, the antiangiogenic activity of LMWF in bladder cancer may be associated with suppressing HIF-1/VEGF-regulated signaling pathway.

  10. Structural insights into cholinesterases inhibition by harmane β-carbolinium derivatives: a kinetics-molecular modeling approach.

    Science.gov (United States)

    Torres, Juliana M; Lira, Aline F; Silva, Daniel R; Guzzo, Lucas M; Sant'Anna, Carlos M R; Kümmerle, Arthur E; Rumjanek, Victor M

    2012-09-01

    The natural indole alkaloids, the β-carbolines, are often associated with cholinesterase inhibition, especially their quaternary salts, which frequently have higher activity than the free bases. Due to lack of information explaining this fact in the literature, the cholinesterase inhibition by the natural product harmane and its two β-carbolinium synthetic derivative salts (N-methyl and N-ethyl) was explored, together with a combination of kinetics and a molecular modeling approach. The results, mainly for the β-carbolinium salts, demonstrated a noncompetitive inhibition profile, ruling out previous findings which associated cholinesterase inhibition by β-carbolinium salts to a possible mimicking of the choline moiety of the natural substrate, acetylcholine. Molecular modeling studies corroborate this kind of inhibition through analyses of inhibitor/enzyme and inhibitor/substrate/enzyme complexes of both enzymes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Micelle System Based on Molecular Economy Principle for Overcoming Multidrug Resistance and Inhibiting Metastasis.

    Science.gov (United States)

    Qi, Yan; Qin, Xianya; Yang, Conglian; Wu, Tingting; Qiao, Qi; Song, Qingle; Zhang, Zhiping

    2018-03-05

    The high mortality of cancer is mainly attributed to multidrug resistance (MDR) and metastasis. A simple micelle system was constructed here to codeliver doxorubicin (DOX), adjudin (ADD), and nitric oxide (NO) for overcoming MDR and inhibiting metastasis. It was devised based on the "molecular economy" principle as the micelle system was easy to fabricate and exhibited high drug loading efficiency, and importantly, each component of the micelles would exert one or more active functions. DOX acted as the main cell killing agent supplemented with ADD, NO, and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). MDR was overcome by synergistic effects of mitochondria inhibition agents, TPGS and ADD. A TPGS-based NO donor can be used as a drug carrier, and it can release NO to enhance drug accumulation and penetration in tumor, resulting in a positive cycle of drug delivery. This DOX-ADD conjugate self-assembly system demonstrated controlled drug release, increased cellular uptake and cytotoxicity, enhanced accumulation at tumor site, and improved in vivo metastasis inhibition of breast cancer. The micelles can fully take advantage of the functions of each component, and they provide a potential strategy for nanomedicine design and clinical cancer treatment.

  12. Molecular characterization of monoclonal antibodies that inhibit acetylcholinesterase by targeting the peripheral site and backdoor region.

    Directory of Open Access Journals (Sweden)

    Yves Bourne

    Full Text Available The inhibition properties and target sites of monoclonal antibodies (mAbs Elec403, Elec408 and Elec410, generated against Electrophorus electricus acetylcholinesterase (AChE, have been defined previously using biochemical and mutagenesis approaches. Elec403 and Elec410, which bind competitively with each other and with the peptidic toxin inhibitor fasciculin, are directed toward distinctive albeit overlapping epitopes located at the AChE peripheral anionic site, which surrounds the entrance of the active site gorge. Elec408, which is not competitive with the other two mAbs nor fasciculin, targets a second epitope located in the backdoor region, distant from the gorge entrance. To characterize the molecular determinants dictating their binding site specificity, we cloned and sequenced the mAbs; generated antigen-binding fragments (Fab retaining the parental inhibition properties; and explored their structure-function relationships using complementary x-ray crystallography, homology modeling and flexible docking approaches. Hypermutation of one Elec403 complementarity-determining region suggests occurrence of antigen-driven selection towards recognition of the AChE peripheral site. Comparative analysis of the 1.9Å-resolution structure of Fab408 and of theoretical models of its Fab403 and Fab410 congeners evidences distinctive surface topographies and anisotropic repartitions of charges, consistent with their respective target sites and inhibition properties. Finally, a validated, data-driven docking model of the Fab403-AChE complex suggests a mode of binding at the PAS that fully correlates with the functional data. This comprehensive study documents the molecular peculiarities of Fab403 and Fab410, as the largest peptidic inhibitors directed towards the peripheral site, and those of Fab408, as the first inhibitor directed toward the backdoor region of an AChE and a unique template for the design of new, specific modulators of AChE catalysis.

  13. CrowdPhase: crowdsourcing the phase problem

    Energy Technology Data Exchange (ETDEWEB)

    Jorda, Julien; Sawaya, Michael R. [Institute for Genomics and Proteomics, 611 Charles Young Drive East, Los Angeles, CA 90095 (United States); Yeates, Todd O., E-mail: yeates@mbi.ucla.edu [Institute for Genomics and Proteomics, 611 Charles Young Drive East, Los Angeles, CA 90095 (United States); Molecular Biology Institute, 611 Charles Young Drive East, Los Angeles, CA 90095 (United States); University of California, 611 Charles Young Drive East, Los Angeles, CA 90095 (United States)

    2014-06-01

    The idea of attacking the phase problem by crowdsourcing is introduced. Using an interactive, multi-player, web-based system, participants work simultaneously to select phase sets that correspond to better electron-density maps in order to solve low-resolution phasing problems. The human mind innately excels at some complex tasks that are difficult to solve using computers alone. For complex problems amenable to parallelization, strategies can be developed to exploit human intelligence in a collective form: such approaches are sometimes referred to as ‘crowdsourcing’. Here, a first attempt at a crowdsourced approach for low-resolution ab initio phasing in macromolecular crystallography is proposed. A collaborative online game named CrowdPhase was designed, which relies on a human-powered genetic algorithm, where players control the selection mechanism during the evolutionary process. The algorithm starts from a population of ‘individuals’, each with a random genetic makeup, in this case a map prepared from a random set of phases, and tries to cause the population to evolve towards individuals with better phases based on Darwinian survival of the fittest. Players apply their pattern-recognition capabilities to evaluate the electron-density maps generated from these sets of phases and to select the fittest individuals. A user-friendly interface, a training stage and a competitive scoring system foster a network of well trained players who can guide the genetic algorithm towards better solutions from generation to generation via gameplay. CrowdPhase was applied to two synthetic low-resolution phasing puzzles and it was shown that players could successfully obtain phase sets in the 30° phase error range and corresponding molecular envelopes showing agreement with the low-resolution models. The successful preliminary studies suggest that with further development the crowdsourcing approach could fill a gap in current crystallographic methods by making it

  14. CrowdPhase: crowdsourcing the phase problem

    International Nuclear Information System (INIS)

    Jorda, Julien; Sawaya, Michael R.; Yeates, Todd O.

    2014-01-01

    The idea of attacking the phase problem by crowdsourcing is introduced. Using an interactive, multi-player, web-based system, participants work simultaneously to select phase sets that correspond to better electron-density maps in order to solve low-resolution phasing problems. The human mind innately excels at some complex tasks that are difficult to solve using computers alone. For complex problems amenable to parallelization, strategies can be developed to exploit human intelligence in a collective form: such approaches are sometimes referred to as ‘crowdsourcing’. Here, a first attempt at a crowdsourced approach for low-resolution ab initio phasing in macromolecular crystallography is proposed. A collaborative online game named CrowdPhase was designed, which relies on a human-powered genetic algorithm, where players control the selection mechanism during the evolutionary process. The algorithm starts from a population of ‘individuals’, each with a random genetic makeup, in this case a map prepared from a random set of phases, and tries to cause the population to evolve towards individuals with better phases based on Darwinian survival of the fittest. Players apply their pattern-recognition capabilities to evaluate the electron-density maps generated from these sets of phases and to select the fittest individuals. A user-friendly interface, a training stage and a competitive scoring system foster a network of well trained players who can guide the genetic algorithm towards better solutions from generation to generation via gameplay. CrowdPhase was applied to two synthetic low-resolution phasing puzzles and it was shown that players could successfully obtain phase sets in the 30° phase error range and corresponding molecular envelopes showing agreement with the low-resolution models. The successful preliminary studies suggest that with further development the crowdsourcing approach could fill a gap in current crystallographic methods by making it

  15. CrowdAidRepair: A Crowd-Aided Interactive Data Repairing Method

    KAUST Repository

    Zhou, Jian; Li, Zhixu; Gu, Binbin; Xie, Qing; Zhu, Jia; Zhang, Xiangliang; Li, Guoliang

    2016-01-01

    turn to use the power of crowd in data repairing, but the crowd power has its own drawbacks such as high human intervention cost and inevitable low efficiency. In this paper, we propose a crowd-aided interactive data repairing method which takes

  16. Structure, function and folding of phosphoglycerate kinase are strongly perturbed by macromolecular crowding.

    Science.gov (United States)

    Samiotakis, Antonios; Dhar, Apratim; Ebbinghaus, Simon; Nienhaus, Lea; Homouz, Dirar; Gruebele, Martin; Cheung, Margaret

    2010-10-01

    We combine experiment and computer simulation to show how macromolecular crowding dramatically affects the structure, function and folding landscape of phosphoglycerate kinase (PGK). Fluorescence labeling shows that compact states of yeast PGK are populated as the amount of crowding agents (Ficoll 70) increases. Coarse-grained molecular simulations reveal three compact ensembles: C (crystal structure), CC (collapsed crystal) and Sph (spherical compact). With an adjustment for viscosity, crowded wild type PGK and fluorescent PGK are about 15 times or more active in 200 mg/ml Ficoll than in aqueous solution. Our results suggest a new solution to the classic problem of how the ADP and diphosphoglycerate binding sites of PGK come together to make ATP: rather than undergoing a hinge motion, the ADP and substrate sites are already located in proximity under crowded conditions that mimic the in vivo conditions under which the enzyme actually operates.

  17. Crowdedness Mediates the Effect of Social Identification on Positive Emotion in a Crowd: A Survey of Two Crowd Events

    Science.gov (United States)

    Novelli, David; Drury, John; Reicher, Stephen; Stott, Clifford

    2013-01-01

    Exposure to crowding is said to be aversive, yet people also seek out and enjoy crowded situations. We surveyed participants at two crowd events to test the prediction of self-categorization theory that variable emotional responses to crowding are a function of social identification with the crowd. In data collected from participants who attended a crowded outdoor music event (n = 48), identification with the crowd predicted feeling less crowded; and there was an indirect effect of identification with the crowd on positive emotion through feeling less crowded. Identification with the crowd also moderated the relation between feeling less crowded and positive emotion. In data collected at a demonstration march (n = 112), identification with the crowd predicted central (most dense) location in the crowd; and there was an indirect effect of identification with the crowd on positive emotion through central location in the crowd. Positive emotion in the crowd also increased over the duration of the crowd event. These findings are in line with the predictions of self-categorization theory. They are inconsistent with approaches that suggest that crowding is inherently aversive; and they cannot easily be explained through the concept of ‘personal space’. PMID:24236079

  18. Crowdedness mediates the effect of social identification on positive emotion in a crowd: a survey of two crowd events.

    Directory of Open Access Journals (Sweden)

    David Novelli

    Full Text Available Exposure to crowding is said to be aversive, yet people also seek out and enjoy crowded situations. We surveyed participants at two crowd events to test the prediction of self-categorization theory that variable emotional responses to crowding are a function of social identification with the crowd. In data collected from participants who attended a crowded outdoor music event (n = 48, identification with the crowd predicted feeling less crowded; and there was an indirect effect of identification with the crowd on positive emotion through feeling less crowded. Identification with the crowd also moderated the relation between feeling less crowded and positive emotion. In data collected at a demonstration march (n = 112, identification with the crowd predicted central (most dense location in the crowd; and there was an indirect effect of identification with the crowd on positive emotion through central location in the crowd. Positive emotion in the crowd also increased over the duration of the crowd event. These findings are in line with the predictions of self-categorization theory. They are inconsistent with approaches that suggest that crowding is inherently aversive; and they cannot easily be explained through the concept of 'personal space'.

  19. A Network of AOPs for reduced thyroid hormone synthesis derived from inhibition of Thyroperoxidase - A common Molecular Initiating Event Leading to Species-Specific Indices of Adversity.

    Science.gov (United States)

    This collection of 3 AOPs describe varying outcomes of adversity dependent upon species in response to inhibition of thyroperoxidase (TPO) during development. Chemical inhibition of TPO, the molecular-initiating event (MIE), results in decreased thyroid hormone (TH) synthesis, a...

  20. Mycophenolic acid inhibits migration and invasion of gastric cancer cells via multiple molecular pathways.

    Directory of Open Access Journals (Sweden)

    Boying Dun

    Full Text Available Mycophenolic acid (MPA is the metabolized product and active element of mycophenolate mofetil (MMF that has been widely used for the prevention of acute graft rejection. MPA potently inhibits inosine monophosphate dehydrogenase (IMPDH that is up-regulated in many tumors and MPA is known to inhibit cancer cell proliferation as well as fibroblast and endothelial cell migration. In this study, we demonstrated for the first time MPA's antimigratory and anti-invasion abilities of MPA-sensitive AGS (gastric cancer cells. Genome-wide expression analyses using Illumina whole genome microarrays identified 50 genes with ≥2 fold changes and 15 genes with > 4 fold alterations and multiple molecular pathways implicated in cell migration. Real-time RT-PCR analyses of selected genes also confirmed the expression differences. Furthermore, targeted proteomic analyses identified several proteins altered by MPA treatment. Our results indicate that MPA modulates gastric cancer cell migration through down-regulation of a large number of genes (PRKCA, DOCK1, INF2, HSPA5, LRP8 and PDGFRA and proteins (PRKCA, AKT, SRC, CD147 and MMP1 with promigratory functions as well as up-regulation of a number of genes with antimigratory functions (ATF3, SMAD3, CITED2 and CEAMCAM1. However, a few genes that may promote migration (CYR61 and NOS3 were up-regulated. Therefore, MPA's overall antimigratory role on cancer cells reflects a balance between promigratory and antimigratory signals influenced by MPA treatment.

  1. Acetylcholinesterase-Inhibiting Activity of Salicylanilide N-Alkylcarbamates and Their Molecular Docking

    Directory of Open Access Journals (Sweden)

    Josef Jampilek

    2012-08-01

    Full Text Available A series of twenty-five novel salicylanilide N-alkylcarbamates were investigated as potential acetylcholinesterase inhibitors. The compounds were tested for their ability to inhibit acetylcholinesterase (AChE from electric eel (Electrophorus electricus L.. Experimental lipophilicity was determined, and the structure-activity relationships are discussed. The mode of binding in the active site of AChE was investigated by molecular docking. All the discussed compounds expressed significantly higher AChE inhibitory activity than rivastigmine and slightly lower than galanthamine. Disubstitution by chlorine in C'(3,4 of the aniline ring and the optimal length of hexyl-undecyl alkyl chains in the carbamate moiety provided the most active AChE inhibitors. Monochlorination in C'(4 exhibited slightly more effective AChE inhibitors than in C'(3. Generally it can be stated that compounds with higher lipophilicity showed higher inhibition, and the activity of the compounds is strongly dependent on the length of the N-alkyl chain.

  2. Socialization of Social Anxiety in Adolescent Crowds

    Science.gov (United States)

    Van Zalk, Nejra; Van Zalk, Maarten Herman Walter; Kerr, Margaret

    2011-01-01

    In this study, we looked at whether social anxiety is socialized, or influenced by peers' social anxiety, more in some peer crowds than others. Adolescents in crowds with eye-catching appearances such as Goths and Punks (here termed "Radical"), were compared with three comparison groups. Using data from 796 adolescents (353 girls and 443 boys; M…

  3. Is word recognition crowded in pure alexia?

    DEFF Research Database (Denmark)

    Sand, Katrine; Habekost, Thomas; Petersen, Anders

    2017-01-01

    Pure alexia is a selective deficit in reading, which arises following damage to the left ventral occipito-temporal cortex. Crowding, the inability to recognise objects in a clutter, has recently been hypothesised to be the underlying deficit of apperceptive visual agnosia1. Crowding normally occurs...

  4. How crowded is the prokaryotic cytoplasm?

    NARCIS (Netherlands)

    Spitzer, Jan; Poolman, Bert; Ferguson, Stuart

    2013-01-01

    We consider biomacromolecular crowding within the cytoplasm of prokaryotic cells as a two-phase system of 'supercrowded' cytogel and 'dilute' cytosol; we simplify and quantify this model for a coccoid cell over a wide range of biomacromolecular crowding. The key result shows that the supercrowded

  5. CORROSION INHIBITION OF ALUMINUM ALLOY 3SR IN HCl BY POLYVINYLPYRROLIDONE AND POLYACRYLAMIDE: EFFECT OF MOLECULAR STRUCTURE ON INHIBITION EFFICIENCY

    OpenAIRE

    S. A. UMOREN

    2009-01-01

    The inhibitive performance of two water soluble polymers–polyacrylamide (PA) and polyvinylpyrrolidone (PVP) on the corrosion behavior of aluminum alloy 3SR in HCl solution was investigated using weight loss, hydrogen evolution, and thermometric methods at 30–60°C. Results obtained indicate that both polymers inhibited acid-induced corrosion of aluminum at the temperatures studied. PVP was found to be a better corrosion inhibitor than PA. All measurements from the three techniques show that in...

  6. Multiple Molecular and Cellular Mechanisms of Action of Lycopene in Cancer Inhibition

    Directory of Open Access Journals (Sweden)

    Cristina Trejo-Solís

    2013-01-01

    Full Text Available Epidemiological studies suggest that including fruits, vegetables, and whole grains in regular dietary intake might prevent and reverse cellular carcinogenesis, reducing the incidence of primary tumours. Bioactive components present in food can simultaneously modulate more than one carcinogenic process, including cancer metabolism, hormonal balance, transcriptional activity, cell-cycle control, apoptosis, inflammation, angiogenesis and metastasis. Some studies have shown an inverse correlation between a diet rich in fruits, vegetables, and carotenoids and a low incidence of different types of cancer. Lycopene, the predominant carotenoid found in tomatoes, exhibits a high antioxidant capacity and has been shown to prevent cancer, as evidenced by clinical trials and studies in cell culture and animal models. In vitro studies have shown that lycopene treatment can selectively arrest cell growth and induce apoptosis in cancer cells without affecting normal cells. In vivo studies have revealed that lycopene treatment inhibits tumour growth in the liver, lung, prostate, breast, and colon. Clinical studies have shown that lycopene protects against prostate cancer. One of the main challenges in cancer prevention is the integration of new molecular findings into clinical practice. Thus, the identification of molecular biomarkers associated with lycopene levels is essential for improving our understanding of the mechanisms underlying its antineoplastic activity.

  7. Mechanism by which DHA inhibits the aggregation of KLVFFA peptides: A molecular dynamics study

    Science.gov (United States)

    Zhou, Hong; Liu, Shengtang; Shao, Qiwen; Ma, Dongfang; Yang, Zaixing; Zhou, Ruhong

    2018-03-01

    Docosahexaenoic acid (DHA) is one of the omega-3 polyunsaturated fatty acids, which has shown promising applications in lowering Aβ peptide neurotoxicity in vitro by preventing aggregation of Aβ peptides and relieving accumulation of Aβ fibrils. Unfortunately, the underlying molecular mechanisms of how DHA interferes with the aggregation of Aβ peptides remain largely enigmatic. Herein, aggregation behaviors of amyloid-β(Aβ)16-21 peptides (KLVFFA) with or without the presence of a DHA molecule were comparatively studied using extensive all-atom molecular dynamics simulations. We found that DHA could effectively suppress the aggregation of KLVFFA peptides by redirecting peptides to unstructured oligomers. The highly hydrophobic and flexible nature of DHA made it randomly but tightly entangled with Leu-17, Phe-19, and Phe-20 residues to form unstructured but stable complexes. These lower-ordered unstructured oligomers could eventually pass through energy barriers to form ordered β-sheet structures through large conformational fluctuations. This study depicts a microscopic picture for understanding the role and mechanism of DHA in inhibition of aggregation of Aβ peptides, which is generally believed as one of the important pathogenic mechanisms of Alzheimer's disease.

  8. A Modified Glycosaminoglycan, GM-0111, Inhibits Molecular Signaling Involved in Periodontitis.

    Directory of Open Access Journals (Sweden)

    Justin R Savage

    Full Text Available Periodontitis is characterized by microbial infection, inflammation, tissue breakdown, and accelerated loss of alveolar bone matrix. Treatment targeting these multiple stages of the disease provides ways to treat or prevent periodontitis. Certain glycosaminoglycans (GAGs block multiple inflammatory mediators as well as suppress bacterial growth, suggesting that these GAGs may be exploited as a therapeutic for periodontitis.We investigated the effects of a synthetic GAG, GM-0111, on various molecular events associated with periodontitis: growth of Porphyromonas gingivalis (P. gingivalis and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans pathogenic bacteria associated with periodontitis; activation of pro-inflammatory signaling through TLR2 and TLR4 in mouse macrophage RAW 264.7 cells and heterologously expressed HEK 293 cells; osteoclast formation and bone matrix resorption in cultured mouse pre-osteoclasts.(1 GM-0111 suppressed the growth of P. gingivalis and A. actinomycetemcomitans even at 1% (w/v solution. The antibacterial effects of GM-0111 were stronger than hyaluronic acid (HA or xylitol in P. gingivalis at all concentrations and comparable to xylitol in A. actinomycetemcomitans at ≥2% (w/v solution. We also observed that GM-0111 suppressed biofilm formation of P. gingivalis and these effects were much stronger than HA. (2 GM-0111 inhibited TLR-mediated pro-inflammatory cellular signaling both in macrophage and HEK 293 cells with higher selectivity for TLR2 than TLR4 (IC50 of 1-10 ng/mL vs. > 100 μg/mL, respectively. (3 GM-0111 blocked RANKL-induced osteoclast formation (as low as 300 ng/mL and bone matrix resorption. While GM-0111 showed high affinity binding to RANKL, it did not interfere with RANKL/RANK/NF-κB signaling, suggesting that GM-0111 inhibits osteoclast formation by a RANKL-RANK-independent mechanism.We report that GM-0111 inhibits multiple molecular events involved in periodontitis, spanning from the

  9. Nudging Cooperation in a Crowd Experiment.

    Science.gov (United States)

    Niella, Tamara; Stier-Moses, Nicolás; Sigman, Mariano

    2016-01-01

    We examine the hypothesis that driven by a competition heuristic, people don't even reflect or consider whether a cooperation strategy may be better. As a paradigmatic example of this behavior we propose the zero-sum game fallacy, according to which people believe that resources are fixed even when they are not. We demonstrate that people only cooperate if the competitive heuristic is explicitly overridden in an experiment in which participants play two rounds of a game in which competition is suboptimal. The observed spontaneous behavior for most players was to compete. Then participants were explicitly reminded that the competing strategy may not be optimal. This minor intervention boosted cooperation, implying that competition does not result from lack of trust or willingness to cooperate but instead from the inability to inhibit the competition bias. This activity was performed in a controlled laboratory setting and also as a crowd experiment. Understanding the psychological underpinnings of these behaviors may help us improve cooperation and thus may have vast practical consequences to our society.

  10. Avenues for crowd science in Hydrology.

    Science.gov (United States)

    Koch, Julian; Stisen, Simon

    2016-04-01

    Crowd science describes research that is conducted with the participation of the general public (the crowd) and gives the opportunity to involve the crowd in research design, data collection and analysis. In various fields, scientists have already drawn on underused human resources to advance research at low cost, with high transparency and large acceptance of the public due to the bottom up structure and the participatory process. Within the hydrological sciences, crowd research has quite recently become more established in the form of crowd observatories to generate hydrological data on water quality, precipitation or river flow. These innovative observatories complement more traditional ways of monitoring hydrological data and strengthen a community-based environmental decision making. However, the full potential of crowd science lies in internet based participation of the crowd and it is not yet fully exploited in the field of Hydrology. New avenues that are not primarily based on the outsourcing of labor, but instead capitalize the full potential of human capabilities have to emerge. In multiple realms of solving complex problems, like image detection, optimization tasks, narrowing of possible solutions, humans still remain more effective than computer algorithms. The most successful online crowd science projects Foldit and Galaxy Zoo have proven that the collective of tens of thousands users could clearly outperform traditional computer based science approaches. Our study takes advantage of the well trained human perception to conduct a spatial sensitivity analysis of land-surface variables of a distributed hydrological model to identify the most sensitive spatial inputs. True spatial performance metrics, that quantitatively compare patterns, are not trivial to choose and their applicability is often not universal. On the other hand humans can quickly integrate spatial information at various scales and are therefore a trusted competence. We selected

  11. Multiple Level Crowding: Crowding at the Object Parts Level and at the Object Configural level.

    Science.gov (United States)

    Kimchi, Ruth; Pirkner, Yossef

    2015-01-01

    In crowding, identification of a peripheral target in the presence of nearby flankers is worse than when the target appears alone. Prevailing theories hold that crowding occurs because of integration or "pooling" of low-level features at a single, relatively early stage of visual processing. Recent studies suggest that crowding can occur also between high-level object representations. The most relevant findings come from studies with faces and may be specific to faces. We examined whether crowding can occur at the object configural level in addition to part-level crowding, using nonface objects. Target (a disconnected square or diamond made of four elements) identification was measured at varying eccentricities. The flankers were similar either to the target parts or to the target configuration. The results showed crowding in both cases: Flankers interfered with target identification such that identification accuracy decreased with an increase in eccentricity, and no interference was observed at the fovea. Crowding by object parts, however, was weaker and had smaller spatial extent than crowding by object configurations; we related this finding to the relationship between crowding and perceptual organization. These results provide strong evidence that crowding occurs not only between object parts but also between configural representations of objects. © The Author(s) 2015.

  12. Molecular biological methods (DGGE) as a tool to investigate nitrification inhibition in wastewater treatment.

    Science.gov (United States)

    Kreuzinger, N; Farnleitner, A; Wandl, G; Hornek, R; Mach, R

    2003-01-01

    Incomplete nitrification at an activated sludge plant for biological pre-treatment of rendering plant effluents led to a detailed investigation on the origin and solution of this problem. Preliminary studies revealed that an inhibition of ammonia oxidising microorganisms (AOM) by process waters of the rendering plant was responsible for the situation. We were able to show a correlation between the existence of specific AOM and nitrification capacity expressed as oxygen uptake rate for maximal nitrification (OURNmax). Only Nitrosospira sp. was found in the activated sludge of the rendering plant and another industrial wastewater treatment plant with problems in nitrification, while reference plants without nitrification problems showed Nitrosomonas spp. as the predominant ammonia oxidising bacteria. By accompanying engineering investigations and experiments (cross-feeding experiments, operation of a two-stage laboratory plant) with molecular biological methods (DGGE--Denaturing Gradient Gel Electrophoresis) we were able to elaborate an applicable solution for the rendering plant. Laboratory experiments with a two-stage process layout finally provided complete nitrification overcoming the inhibiting nature of process waters from the rendering plant. DGGE analysis of the second stage activated sludge from the laboratory plant showed a shift in population structure from Nitrosospira sp. towards Nitrosomonas spp. simultaneous to the increase of nitrification capacity. Nitrification capacities comparable to full-scale municipal wastewater treatment plants could be maintained for more than two months. As the design of wastewater treatment plants for nitrification is linked to the growth characteristics of Nitrosomonas spp., established criteria can be applied for the redesign of the full-scale plant.

  13. Efficient dynamic molecular simulation using QSAR model to know inhibition activity in breast cancer medicine

    Science.gov (United States)

    Zharifah, A.; Kusumowardani, E.; Saputro, A.; Sarwinda, D.

    2017-07-01

    According to data from GLOBOCAN (IARC) at 2012, breast cancer was the highest rated of new cancer case by 43.3 % (after controlled by age), with mortality rated as high as 12.9 %. Oncology is a major field which focusing on improving the development of drug and therapeutics cancer in pharmaceutical and biotechnology companies. Nowadays, many researchers lead to computational chemistry and bioinformatic for pharmacophore generation. A pharmacophore describes as a group of atoms in the molecule which is considered to be responsible for a pharmacological action. Prediction of biological function from chemical structure in silico modeling reduces the use of chemical reagents so the risk of environmental pollution decreased. In this research, we proposed QSAR model to analyze the composition of cancer drugs which assumed to be homogenous in character and treatment. Atomic interactions which analyzed are learned through parameters such as log p as descriptors hydrophobic, n_poinas descriptor contour strength and molecular structure, and also various concentrations inhibitor (micromolar and nanomolar) from NCBI drugs bank. The differences inhibitor activity was observed by the presence of IC 50 residues value from inhibitor substances at various concentration. Then, we got a general overview of the state of safety for drug stability seen from its IC 50 value. In our study, we also compared between micromolar and nanomolar inhibitor effect from QSAR model results. The QSAR model analysis shows that the drug concentration with nanomolar is better than micromolar, related with the content of inhibitor substances concentration. This QSAR model got the equation: Log 1/IC50 = (0.284) (±0.195) logP + (0.02) (±0.012) n_poin + (-0.005) (±0.083) Inhibition10.2nanoM + (0.1) (±0.079) Inhibition30.5nanoM + (-0.016) (±0.045) Inhibition91.5nanoM + (-2.572) (±1.570) (n = 13; r = 0.813; r2 = 0.660; s = 0.764; F = 2.720; q2 = 0.660).

  14. An Energy based Method to Measure the Crowd Safety

    NARCIS (Netherlands)

    Yin, H.; Li, D.; Zheng, X.

    2014-01-01

    How to evaluate crowd safety in crowded areas is a tough, but important, problem. According to accident-causing theory, uncontrolled release of hazardous energy among overcrowded pedestrians is the basic cause of crowd disaster. Therefore, crowd energy is modeled in this paper, which takes both

  15. Flavonoids-Rich Orthosiphon stamineus Extract as New Candidate for Angiotensin I-Converting Enzyme Inhibition: A Molecular Docking Study.

    Science.gov (United States)

    Shafaei, Armaghan; Sultan Khan, Md Shamsuddin; F A Aisha, Abdalrahim; Abdul Majid, Amin Malik Shah; Hamdan, Mohammad Razak; Mordi, Mohd Nizam; Ismail, Zhari

    2016-11-09

    This study aims to evaluate the in vitro angiotensin-converting enzyme (ACE) inhibition activity of different extracts of Orthosiphon stamineus (OS) leaves and their main flavonoids, namely rosmarinic acid (RA), sinensetin (SIN), eupatorin (EUP) and 3'-hydroxy-5,6,7,4'-tetramethoxyflavone (TMF). Furthermore, to identify possible mechanisms of action based on structure-activity relationships and molecular docking. The in vitro ACE inhibition activity relied on determining hippuric acid (HA) formation from ACE-specific substrate (hippuryl-histidyl-leucine (HHL)) by the action of ACE enzyme. A High Performance Liquid Chromatography method combined with UV detection was developed and validated for measurement the concentration of produced HA. The chelation ability of OS extract and its reference compounds was evaluated by tetramethylmurexide reagent. Furthermore, molecular docking study was performed by LeadIT-FlexX : BioSolveIT's LeadIT program. OS ethanolic extract (OS-E) exhibited highest inhibition and lowest IC 50 value (45.77 ± 1.17 µg/mL) against ACE compared to the other extracts. Among the tested reference compounds, EUP with IC 50 15.35 ± 4.49 µg/mL had highest inhibition against ACE and binding ability with Zn (II) (56.03% ± 1.26%) compared to RA, TMF and SIN. Molecular docking studies also confirmed that flavonoids inhibit ACE via interaction with the zinc ion and this interaction is stabilized by other interactions with amino acids in the active site. In this study, we have demonstrated that changes in flavonoids active core affect their capacity to inhibit ACE. Moreover, we showed that ACE inhibition activity of flavonoids compounds is directly related to their ability to bind with zinc ion in the active site of ACE enzyme. It was also revealed that OS extract contained high amount of flavonoids other than RA, TMF, SIN and EUP. As such, application of OS extract is useful as inhibitors of ACE.

  16. Development of molecularly imprinted polymers to block quorum sensing and inhibit bacterial biofilm formation.

    Science.gov (United States)

    Ma, Luyao; Feng, Shaolong; de la Fuente-Nunez, Cesar; Hancock, Robert E W; Lu, Xiaonan

    2018-05-16

    Bacterial biofilms are responsible for most clinical infections and show increased antimicrobial resistance. In this study, molecularly imprinted polymers (MIPs) were developed to specifically capture prototypical quorum sensing autoinducers [i.e., N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12AHL)], interrupt quorum sensing, and subsequently inhibit biofilm formation of Pseudomonas aeruginosa, an important human nosocomial pathogen. The synthesis of MIPs was optimized by considering the amount and type of the functional monomers itaconic acid (IA) and 2-hydroxyethyl methacrylate (HEMA). IA-based MIPs showed high adsorption affinity towards 3-oxo-C12AHL with an imprinting factor of 1.68. Compared to IA-based MIPs, the adsorption capacity of HEMA-based MIPs was improved 5-fold. HEMA-based MIPs significantly reduced biofilm formation (by ~65%), while biofilm suppression by IA-based MIPs was neutralized due to increased bacterial attachment. The developed MIPs represent promising alternative biofilm intervention agents that can be applied to surfaces relevant to clinical settings and food processing equipment.

  17. Synthesis, α-glucosidase inhibition and molecular docking study of coumarin based derivatives.

    Science.gov (United States)

    Taha, Muhammad; Shah, Syed Adnan Ali; Afifi, Muhammad; Imran, Syahrul; Sultan, Sadia; Rahim, Fazal; Khan, Khalid Mohammed

    2018-04-01

    We have synthesized seventeen Coumarin based derivatives (1-17), characterized by 1 HNMR, 13 CNMR and EI-MS and evaluated for α-glucosidase inhibitory potential. Among the series, all derivatives exhibited outstanding α-glucosidase inhibition with IC 50 values ranging between 1.10 ± 0.01 and 36.46 ± 0.70 μM when compared with the standard inhibitor acarbose having IC 50 value 39.45 ± 0.10 μM. The most potent derivative among the series is derivative 3 having IC 50 value 1.10 ± 0.01 μM, which are many folds better than the standard acarbose. The structure activity relationship (SAR) was mainly based upon by bring about difference of substituent's on phenyl part. Molecular docking studies were carried out to understand the binding interaction of the most active compounds. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Synthesis, β-glucuronidase inhibition and molecular docking studies of hybrid bisindole-thiosemicarbazides analogs.

    Science.gov (United States)

    Taha, Muhammad; Ismail, Nor Hadiani; Imran, Syahrul; Rahim, Fazal; Wadood, Abdul; Khan, Huma; Ullah, Hayat; Salar, Uzma; Khan, Khalid Mohammed

    2016-10-01

    Hybrid bisindole-thiosemicarbazides analogs (1-18) were synthesized and screened for β-glucuronidase activity. All compounds showed varied degree of β-glucuronidase inhibitory potential when compared with standard d-saccharic acid 1,4-lactone (IC50=48.4±1.25μM). Compounds 4, 7, 9, 6, 5, 12, 17 and 18 showed exceptional β-glucuronidase inhibition with IC50 values ranging from 0.1 to 5.7μM. Compounds 1, 3, 8, 16, 13, 2 and 14 also showed better activities than standard with IC50 values ranging from 7.12 to 15.0μM. The remaining compounds 10, 11, and 15 showed good inhibitory potential with IC50 values 33.2±0.75, 21.4±0.30 and 28.12±0.25μM respectively. Molecular docking studies were carried out to confirm the binding interaction of the compounds. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. A novel small molecular STAT3 inhibitor, LY5, inhibits cell viability, cell migration, and angiogenesis in medulloblastoma cells.

    Science.gov (United States)

    Xiao, Hui; Bid, Hemant Kumar; Jou, David; Wu, Xiaojuan; Yu, Wenying; Li, Chenglong; Houghton, Peter J; Lin, Jiayuh

    2015-02-06

    Signal transducers and activators of transcription 3 (STAT3) signaling is persistently activated and could contribute to tumorigenesis of medulloblastoma. Numerous studies have demonstrated that inhibition of the persistent STAT3 signaling pathway results in decreased proliferation and increased apoptosis in human cancer cells, indicating that STAT3 is a viable molecular target for cancer therapy. In this study, we investigated a novel non-peptide, cell-permeable small molecule, named LY5, to target STAT3 in medulloblastoma cells. LY5 inhibited persistent STAT3 phosphorylation and induced apoptosis in human medulloblastoma cell lines expressing constitutive STAT3 phosphorylation. The inhibition of STAT3 signaling by LY5 was confirmed by down-regulating the expression of the downstream targets of STAT3, including cyclin D1, bcl-XL, survivin, and micro-RNA-21. LY5 also inhibited the induction of STAT3 phosphorylation by interleukin-6 (IL-6), insulin-like growth factor (IGF)-1, IGF-2, and leukemia inhibitory factor in medulloblastoma cells, but did not inhibit STAT1 and STAT5 phosphorylation stimulated by interferon-γ (IFN-γ) and EGF, respectively. In addition, LY5 blocked the STAT3 nuclear localization induced by IL-6, but did not block STAT1 and STAT5 nuclear translocation mediated by IFN-γ and EGF, respectively. A combination of LY5 with cisplatin or x-ray radiation also showed more potent effects than single treatment alone in the inhibition of cell viability in human medulloblastoma cells. Furthermore, LY5 demonstrated a potent inhibitory activity on cell migration and angiogenesis. Taken together, these findings indicate LY5 inhibits persistent and inducible STAT3 phosphorylation and suggest that LY5 is a promising therapeutic drug candidate for medulloblastoma by inhibiting persistent STAT3 signaling. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Macromolecular crowding-assisted fabrication of liquid-crystalline imprinted polymers.

    Science.gov (United States)

    Zhang, Chen; Zhang, Jing; Huang, Yan-Ping; Liu, Zhao-Sheng

    2015-04-01

    A macromolecular crowding-assisted liquid-crystalline molecularly imprinted monolith (LC-MIM) was prepared successfully for the first time. The imprinted stationary phase was synthesized with polymethyl methacrylate (PMMA) or polystyrene (PS) as the crowding agent, 4-cyanophenyl dicyclohexyl propylene (CPCE) as the liquid-crystal monomer, and hydroquinidine as the pseudo-template for the chiral separation of cinchona alkaloids in HPLC. A low level of cross-linker (26%) has been found to be sufficient to achieve molecular recognition on the crowding-assisted LC-MIM due to the physical cross-linking of mesogenic groups in place of chemical cross-linking, and baseline separation of quinidine and quinine could be achieved with good resolution (R(s) = 2.96), selectivity factor (α = 2.16), and column efficiency (N = 2650 plates/m). In contrast, the LC-MIM prepared without crowding agents displayed the smallest diastereoselectivity (α = 1.90), while the crowding-assisted MIM with high level of cross-linker (80%) obtained the greatest selectivity factor (α = 7.65), but the lowest column efficiency (N = 177 plates/m).

  1. Mechanism study of endothelial protection and inhibits platelet activation of low molecular weight fucoidan from Laminaria japonica

    Science.gov (United States)

    Chen, Anjin; Zhang, Fang; Shi, Jie; Zhao, Xue; Yan, Meixing

    2016-10-01

    Several studies have indicated that fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica could inhibit the activation of platelets directly by reducing the platelet aggregation. To explore the direct effect of LMW fucoidan on the platelet system furthermore and examine the possible mechanism, the endothelial protection and inhibits platelet activation effects of two LMW fucoidan were investigated. In the present study, Endothelial injury model of rats was made by injection of adrenaline (0.4 mg kg-1) and human umbilical vein endothelial cells were cultured. vWF level was be investigated in vivo and in vitro as an important index of endothelial injury. LMW fucoidan could significantly reduce vWF level in vascular endothelial injury rats and also significantly reduce vWF level in vitro. The number of EMPs was be detected as another important index of endothelial injury. The results showed that LMW fucoidan reduced EMPs stimulated by tumor necrosis factor. In this study, it was found that by inhibiting platelet adhesion, LMW fucoidan played a role in anti-thrombosis and the specific mechanism of action is to inhibit the flow of extracellular Ca2+. All in a word, LMW fucoidan could inhibit the activation of platelets indirectly by reducing the concentration of EMPs and vWF, at the same time; LMW fucoidan inhibited the activation of platelets directly by inhibiting the flow of extracellular Ca2+.

  2. NIH Abroad: Pictures Are Crowd Pullers

    Science.gov (United States)

    ... turn Javascript on. "Pictures Are Crowd Pullers …" Art, culture, and the Internet combine to intervene against malaria ... Not ripe mangoes. Not witchcraft. The images and words, which speak directly to local beliefs in villages ...

  3. Crowdings betydning for antallet af tvangsfikseringer

    DEFF Research Database (Denmark)

    Bak, Jesper; Nielsen, Lea Marie; Hæssum, Birte

    2017-01-01

    I denne artikel vil vi beskrive et par af resultaterne fra forskningsprojektet ”Mechanical restraint. Preventive Factors in Theory and Practice” samt et eksempel fra praksis om crowdings betydning for hvor meget der bliver tvangsfikseret....

  4. Crowd Behavior Algorithm Development for COMBAT XXI

    Science.gov (United States)

    2017-05-30

    non-combatants to military operations in an urban area. We show how to link this model with COMBATXXI at the application programming interface (API...level so that the model can be run in tight conjunction with COMBATXXI. TRAC and other anaytic organizations can use this type of crowd model to... organizations , and materiel. crowd, agent-based modeling , combat models , COMBATXXI, NetLogo, mega-cities, civilians on the battlefield Unclassified U U U U 39

  5. A small-molecule compound inhibits a collagen-specific molecular chaperone and could represent a potential remedy for fibrosis.

    Science.gov (United States)

    Ito, Shinya; Ogawa, Koji; Takeuchi, Koh; Takagi, Motoki; Yoshida, Masahito; Hirokawa, Takatsugu; Hirayama, Shoshiro; Shin-Ya, Kazuo; Shimada, Ichio; Doi, Takayuki; Goshima, Naoki; Natsume, Tohru; Nagata, Kazuhiro

    2017-12-08

    Fibrosis can disrupt tissue structure and integrity and impair organ function. Fibrosis is characterized by abnormal collagen accumulation in the extracellular matrix. Pharmacological inhibition of collagen secretion therefore represents a promising strategy for the management of fibrotic disorders, such as liver and lung fibrosis. Hsp47 is an endoplasmic reticulum (ER)-resident collagen-specific molecular chaperone essential for correct folding of procollagen in the ER. Genetic deletion of Hsp47 or inhibition of its interaction with procollagen interferes with procollagen triple helix production, which vastly reduces procollagen secretion from fibroblasts. Thus, Hsp47 could be a potential and promising target for the management of fibrosis. In this study, we screened small-molecule compounds that inhibit the interaction of Hsp47 with collagen from chemical libraries using surface plasmon resonance (BIAcore), and we found a molecule AK778 and its cleavage product Col003 competitively inhibited the interaction and caused the inhibition of collagen secretion by destabilizing the collagen triple helix. Structural information obtained with NMR analysis revealed that Col003 competitively binds to the collagen-binding site on Hsp47. We propose that these structural insights could provide a basis for designing more effective therapeutic drugs for managing fibrosis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Linking crowding, visual span, and reading.

    Science.gov (United States)

    He, Yingchen; Legge, Gordon E

    2017-09-01

    The visual span is hypothesized to be a sensory bottleneck on reading speed with crowding thought to be the major sensory factor limiting the size of the visual span. This proposed linkage between crowding, visual span, and reading speed is challenged by the finding that training to read crowded letters reduced crowding but did not improve reading speed (Chung, 2007). Here, we examined two properties of letter-recognition training that may influence the transfer to improved reading: the spatial arrangement of training stimuli and the presence of flankers. Three groups of nine young adults were trained with different configurations of letter stimuli at 10° in the lower visual field: a flanked-local group (flanked letters localized at one position), a flanked-distributed group (flanked letters distributed across different horizontal locations), and an isolated-distributed group (isolated and distributed letters). We found that distributed training, but not the presence of flankers, appears to be necessary for the training benefit to transfer to increased reading speed. Localized training may have biased attention to one specific, small area in the visual field, thereby failing to improve reading. We conclude that the visual span represents a sensory bottleneck on reading, but there may also be an attentional bottleneck. Reducing the impact of crowding can enlarge the visual span and can potentially facilitate reading, but not when adverse attentional bias is present. Our results clarify the association between crowding, visual span, and reading.

  7. Dietary administration of scallion extract effectively inhibits colorectal tumor growth: cellular and molecular mechanisms in mice.

    Directory of Open Access Journals (Sweden)

    Palanisamy Arulselvan

    Full Text Available Colorectal cancer is a common malignancy and a leading cause of cancer death worldwide. Diet is known to play an important role in the etiology of colon cancer and dietary chemoprevention is receiving increasing attention for prevention and/or alternative treatment of colon cancers. Allium fistulosum L., commonly known as scallion, is popularly used as a spice or vegetable worldwide, and as a traditional medicine in Asian cultures for treating a variety of diseases. In this study we evaluated the possible beneficial effects of dietary scallion on chemoprevention of colon cancer using a mouse model of colon carcinoma (CT-26 cells subcutaneously inoculated into BALB/c mice. Tumor lysates were subjected to western blotting for analysis of key inflammatory markers, ELISA for analysis of cytokines, and immunohistochemistry for analysis of inflammatory markers. Metabolite profiles of scallion extracts were analyzed by LC-MS/MS. Scallion extracts, particularly hot-water extract, orally fed to mice at 50 mg (dry weight/kg body weight resulted in significant suppression of tumor growth and enhanced the survival rate of test mice. At the molecular level, scallion extracts inhibited the key inflammatory markers COX-2 and iNOS, and suppressed the expression of various cellular markers known to be involved in tumor apoptosis (apoptosis index, proliferation (cyclin D1 and c-Myc, angiogenesis (VEGF and HIF-1α, and tumor invasion (MMP-9 and ICAM-1 when compared with vehicle control-treated mice. Our findings may warrant further investigation of the use of common scallion as a chemopreventive dietary agent to lower the risk of colon cancer.

  8. CrowdAidRepair: A Crowd-Aided Interactive Data Repairing Method

    KAUST Repository

    Zhou, Jian

    2016-03-25

    Data repairing aims at discovering and correcting erroneous data in databases. Traditional methods relying on predefined quality rules to detect the conflict between data may fail to choose the right way to fix the detected conflict. Recent efforts turn to use the power of crowd in data repairing, but the crowd power has its own drawbacks such as high human intervention cost and inevitable low efficiency. In this paper, we propose a crowd-aided interactive data repairing method which takes the advantages of both rule-based method and crowd-based method. Particularly, we investigate the interaction between crowd-based repairing and rule-based repairing, and show that by doing crowd-based repairing to a small portion of values, we can greatly improve the repairing quality of the rule-based repairing method. Although we prove that the optimal interaction scheme using the least number of values for crowd-based repairing to maximize the imputation recall is not feasible to be achieved, still, our proposed solution identifies an efficient scheme through investigating the inconsistencies and the dependencies between values in the repairing process. Our empirical study on three data collections demonstrates the high repairing quality of CrowdAidRepair, as well as the efficiency of the generated interaction scheme over baselines.

  9. Crowd Behavior, Crowd Control, and the Use of Non-Lethal Weapons

    Science.gov (United States)

    2001-01-01

    that U.S. forces know these repertoires of actions when they operate in different cultures. Dr. Waddington provided the example of the Zulu tribe in...6 The History of Hostile Crowds and Riots...Mobs, and Non-lethal Weapons,” by Lieutenant Sid Heal. The History of Hostile Crowds and Riots Dr. Wendy Gilpin conducted background research on hostile

  10. A method of emotion contagion for crowd evacuation

    Science.gov (United States)

    Cao, Mengxiao; Zhang, Guijuan; Wang, Mengsi; Lu, Dianjie; Liu, Hong

    2017-10-01

    The current evacuation model does not consider the impact of emotion and personality on crowd evacuation. Thus, there is large difference between evacuation results and the real-life behavior of the crowd. In order to generate more realistic crowd evacuation results, we present a method of emotion contagion for crowd evacuation. First, we combine OCEAN (Openness, Extroversion, Agreeableness, Neuroticism, Conscientiousness) model and SIS (Susceptible Infected Susceptible) model to construct the P-SIS (Personalized SIS) emotional contagion model. The P-SIS model shows the diversity of individuals in crowd effectively. Second, we couple the P-SIS model with the social force model to simulate emotional contagion on crowd evacuation. Finally, the photo-realistic rendering method is employed to obtain the animation of crowd evacuation. Experimental results show that our method can simulate crowd evacuation realistically and has guiding significance for crowd evacuation in the emergency circumstances.

  11. Innovative funding solution for special projects: Crowd funding

    Directory of Open Access Journals (Sweden)

    Sentot Imam Wahjono

    2015-06-01

    Full Text Available The aim of this paper is to examine the influence of crowd funding knowledge, applica-tion, platform, and project initiator toward successful crowd funding. This study conducted by quantitative approach, data have been collected with web-based ques-tionnaires via Kickstarter.com direct message and e-mail to 200 successful crowd funding project initiators as a sample and as much 152 sets questionnaire returned by a complete answer and should be analyzed further. Deployment and data collection take 3 month from October to December 2013. This study found evidence that crowd funding knowledge, crowd funding application, crowd funding platform, and project initiator has positive and significant relationship toward the success of crowd funding. The implication from this research is crowd funding can be a source of capital to finance the projects, not just rely on traditional sources of financing just like banking and capital markets. Crowd funding can be innovative funding solution.

  12. Flavonoids-Rich Orthosiphon stamineus Extract as New Candidate for Angiotensin I-Converting Enzyme Inhibition: A Molecular Docking Study

    Directory of Open Access Journals (Sweden)

    Armaghan Shafaei

    2016-11-01

    Full Text Available This study aims to evaluate the in vitro angiotensin-converting enzyme (ACE inhibition activity of different extracts of Orthosiphon stamineus (OS leaves and their main flavonoids, namely rosmarinic acid (RA, sinensetin (SIN, eupatorin (EUP and 3′-hydroxy-5,6,7,4′-tetramethoxyflavone (TMF. Furthermore, to identify possible mechanisms of action based on structure–activity relationships and molecular docking. The in vitro ACE inhibition activity relied on determining hippuric acid (HA formation from ACE-specific substrate (hippuryl-histidyl-leucine (HHL by the action of ACE enzyme. A High Performance Liquid Chromatography method combined with UV detection was developed and validated for measurement the concentration of produced HA. The chelation ability of OS extract and its reference compounds was evaluated by tetramethylmurexide reagent. Furthermore, molecular docking study was performed by LeadIT-FlexX: BioSolveIT’s LeadIT program. OS ethanolic extract (OS-E exhibited highest inhibition and lowest IC50 value (45.77 ± 1.17 µg/mL against ACE compared to the other extracts. Among the tested reference compounds, EUP with IC50 15.35 ± 4.49 µg/mL had highest inhibition against ACE and binding ability with Zn (II (56.03% ± 1.26% compared to RA, TMF and SIN. Molecular docking studies also confirmed that flavonoids inhibit ACE via interaction with the zinc ion and this interaction is stabilized by other interactions with amino acids in the active site. In this study, we have demonstrated that changes in flavonoids active core affect their capacity to inhibit ACE. Moreover, we showed that ACE inhibition activity of flavonoids compounds is directly related to their ability to bind with zinc ion in the active site of ACE enzyme. It was also revealed that OS extract contained high amount of flavonoids other than RA, TMF, SIN and EUP. As such, application of OS extract is useful as inhibitors of ACE.

  13. Molecular mechanisms underlying mancozeb-induced inhibition of TNF-alpha production

    International Nuclear Information System (INIS)

    Corsini, Emanuela; Viviani, Barbara; Birindelli, Sarah; Gilardi, Federica; Torri, Anna; Codeca, Ilaria; Lucchi, Laura; Bartesaghi, Stefano; Galli, Corrado L.; Marinovich, Marina; Colosio, Claudio

    2006-01-01

    Mancozeb, a polymeric complex of manganese ethylenebisdithiocarbamate with zinc salt, is widely used in agriculture as fungicide. Literature data indicate that ethylenebisdithiocarbamates (EBDTCs) may have immunomodulatory effects in humans. We have recently found in agricultural workers occupationally exposed to the fungicide mancozeb a statistically significant decrease in lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF) production in leukocytes. TNF is an essential proinflammatory cytokine whose production is normally stimulated during an infection. The purpose of this work was to establish an in vitro model reflecting in vivo data and to characterize the molecular mechanism of action of mancozeb. The human promyelocytic cell line THP-1 was used as in vitro model to study the effects of mancozeb and its main metabolite ethylenthiourea (ETU) on LPS-induced TNF release. Mancozeb, but not ETU, at non-cytotoxic concentrations (1-100 μg/ml), induced a dose- and time-dependent inhibition of LPS-induced TNF release, reflecting in vivo data. The modulatory effect observed was not limited to mancozeb but also other EBDTCs, namely zineb and ziram, showed similar inhibitory effects. Mancozeb must be added before or simultaneously to LPS in order to observe the effect, indicating that it acts on early events triggered by LPS. It is known that nuclear factor-κB (NF-κB) tightly regulates TNF transcription. We could demonstrate that mancozeb, modulating LPS-induced reactive oxygen species generation, prevented IκB degradation and NF-κB nuclear translocation, which in turn resulted in decreased TNF production. To further understand the mechanism of the effect of mancozeb on TNF transcription, THP-1 cells were transfected with NF-κB promoter-luciferase construct, and the effect of mancozeb on luciferase activity was measured. Cells transfected with promoter constructs containing κB site showed decreased LPS-induced luciferase activity relative to control

  14. National conference on crowd-funding - Presentations

    International Nuclear Information System (INIS)

    Bour, Daniel; Raguet, Alex; Arnaud, Christophe; Olive, Catherine; Herriou, Jean-Pierre; Lemaignan, Benoit; Camps, Mathieu; Gauduchon, Marie-Veronique; Hostache, Julien; Clerc, Jean-Marc; Feraudy, Nicolas de; Petit, Frederic; Blais, Armaury; Egnell, Luc; Desvigne, Alain; Floc'h, Romain; Forgues, Benoit; Kuzdzal, Matthieu

    2016-12-01

    This conference was organised in the framework of the CrowdFundRES European project (European Union's Horizon 2020 research and innovation programme under grant agreement No. 646435). Its objectives were: - to provide a comprehensive overview of solar energy crowd-funding in Europe and in France; - to inform about the French legal framework; - to answer the pending questions regarding the conditions of application of the call for bids; - to identify the most suitable modalities for project developers; - to shed light on the possibilities offered to local communities and to their citizens; - to present concrete examples of realisations with their experience feedback; - to exchange on crowd-funding structuring at the service of energy transition in France and in regions. This document brings together the different presentations (slides) given at this conference

  15. Virtual Crowds Methods, Simulation, and Control

    CERN Document Server

    Pelechano, Nuria; Allbeck, Jan

    2008-01-01

    There are many applications of computer animation and simulation where it is necessary to model virtual crowds of autonomous agents. Some of these applications include site planning, education, entertainment, training, and human factors analysis for building evacuation. Other applications include simulations of scenarios where masses of people gather, flow, and disperse, such as transportation centers, sporting events, and concerts. Most crowd simulations include only basic locomotive behaviors possibly coupled with a few stochastic actions. Our goal in this survey is to establish a baseline o

  16. Directing the wisdom of the crowd

    DEFF Research Database (Denmark)

    Clauss, Thomas; Breitenecker, Robert J.; Kraus, Sascha

    2018-01-01

    and the community as well as among community members into account. We empirically investigated potential success factors for crowdfunding projects of entrepreneurs on the base of 430 projects from the German crowdfunding platform Visionbakery. Our results show that social interaction during a crowdfunding campaign...... indeed increases the likelihood of its success. As comments from crowd members on particular projects might be positive or negative and can also provide additional argumentation or raise questions, comments can cause a dialog among crowd members. This shows that herding might not only be related...

  17. EMOTIONAL CONTAGION AND MOOD IN CROWD SERVING AS AUDIENCE

    Directory of Open Access Journals (Sweden)

    Beno Arnejcic

    2015-06-01

    Full Text Available The global world is gradually becoming a world of separated crowds despite the artificial wire and wireless connection through television and the Internet. Crowds remain a prevailing subject of research in different social studies, and the research of changes in the psychological structure of crowds and their characteristics is still of primary interest. The main focus of the research is on the interpretation of the results of the research paper about a special separated crowd called audience. It was observed how students, constituting the crowd, perceive a crowd on video. The observation was focused on the research of emotional contagion and mood in the crowd serving as audience. While watching a mass event on a big screen, the crowd serving as audience emotionally converges with someone else, in our case with public speakers.

  18. Evaluating iodide recycling inhibition as a novel molecular initiating event for thyroid axis disruption

    Science.gov (United States)

    The enzyme iodotyrosine deiodinase (dehalogenase, IYD) catalyzes iodide recycling and promotes iodide retention in thyroid follicular cells. Loss of function or chemical inhibition of IYD reduces available iodide for thyroid hormone synthesis, which leads to hormone insufficiency...

  19. Crowd counting via scale-adaptive convolutional neural network

    OpenAIRE

    Zhang, Lu; Shi, Miaojing; Chen, Qiaobo

    2017-01-01

    The task of crowd counting is to automatically estimate the pedestrian number in crowd images. To cope with the scale and perspective changes that commonly exist in crowd images, state-of-the-art approaches employ multi-column CNN architectures to regress density maps of crowd images. Multiple columns have different receptive fields corresponding to pedestrians (heads) of different scales. We instead propose a scale-adaptive CNN (SaCNN) architecture with a backbone of fixed small receptive fi...

  20. The effects of crowding agents Dextran-70k and PEG-8k on actin structure and unfolding reaction

    Science.gov (United States)

    Gagarskaia, Iuliia A.; Povarova, Olga I.; Uversky, Vladimir N.; Kuznetsova, Irina M.; Turoverov, Konstantin K.

    2017-07-01

    Recently, an increasing number of studies on proteins' structure, stability and folding are trying to bring the experimental conditions closer to those existing in a living cell, namely to the conditions of macromolecular crowding. In vitro such conditions are typically imitated by the ;inert; highly water-soluble polymers with different hydrodynamic dimensions. In this work, the effects of crowded milieu on the structure and conformational stability of actin, which is a key component of the muscle contraction system, was examined. The crowded milieu was simulated by high concentrations of PEG-8k or Dextran-70k. It was revealed that both crowding agents decelerated but not inhibited actin unfolding and made a compact state of inactivated actin thermodynamically more favorable in comparison with the unfolded state. At the same time, the high viscosity of the solution of crowding agents slowed down all processes and especially inactivated actin formation, since it involves the interaction of 14-16 partially unfolded actin molecules. The effects of crowding agent were larger when its hydrodynamic dimensions were closer to the size of globular actin.

  1. Molecular Basis for the Selective Inhibition of Respiratory Syncytial Virus RNA Polymerase by 2'-Fluoro-4'-Chloromethyl-Cytidine Triphosphate.

    Directory of Open Access Journals (Sweden)

    Jerome Deval

    2015-06-01

    Full Text Available Respiratory syncytial virus (RSV causes severe lower respiratory tract infections, yet no vaccines or effective therapeutics are available. ALS-8176 is a first-in-class nucleoside analog prodrug effective in RSV-infected adult volunteers, and currently under evaluation in hospitalized infants. Here, we report the mechanism of inhibition and selectivity of ALS-8176 and its parent ALS-8112. ALS-8176 inhibited RSV replication in non-human primates, while ALS-8112 inhibited all strains of RSV in vitro and was specific for paramyxoviruses and rhabdoviruses. The antiviral effect of ALS-8112 was mediated by the intracellular formation of its 5'-triphosphate metabolite (ALS-8112-TP inhibiting the viral RNA polymerase. ALS-8112 selected for resistance-associated mutations within the region of the L gene of RSV encoding the RNA polymerase. In biochemical assays, ALS-8112-TP was efficiently recognized by the recombinant RSV polymerase complex, causing chain termination of RNA synthesis. ALS-8112-TP did not inhibit polymerases from host or viruses unrelated to RSV such as hepatitis C virus (HCV, whereas structurally related molecules displayed dual RSV/HCV inhibition. The combination of molecular modeling and enzymatic analysis showed that both the 2'F and the 4'ClCH2 groups contributed to the selectivity of ALS-8112-TP. The lack of antiviral effect of ALS-8112-TP against HCV polymerase was caused by Asn291 that is well-conserved within positive-strand RNA viruses. This represents the first comparative study employing recombinant RSV and HCV polymerases to define the selectivity of clinically relevant nucleotide analogs. Understanding nucleotide selectivity towards distant viral RNA polymerases could not only be used to repurpose existing drugs against new viral infections, but also to design novel molecules.

  2. The Behavioral Effects of Crowding: Definitions and Methods.

    Science.gov (United States)

    Dean, Larry M.; And Others

    1978-01-01

    Crews of 18 U.S. Navy combat vessels rated their living and working conditions aboard ship, including degree of crowding. Three different types of measures corresponding to different definitions of crowding were constructed. These separate crowding measures correlated uniquely with satisfaction and illness criteria. (Author/MA)

  3. The Crowd in Requirements Engineering: The Landscape and Challenges

    NARCIS (Netherlands)

    Groen, Eduard C.; Seyff, Norbert; Ali, Raian; Dalpiaz, Fabiano; Doerr, Joerg; Guzman, Emitza; Hosseini, Mahmood; Marco, Jordi; Oriol, Marc; Perini, Anna; Stade, Melanie

    2017-01-01

    Crowd-based requirements engineering (CrowdRE) could significantly change RE. Performing RE activities such as elicitation with the crowd of stakeholders turns RE into a participatory effort, leads to more accurate requirements, and ultimately boosts software quality. Although any stakeholder in the

  4. Molecular mechanisms involved in the inhibition of tumor cells proliferation exposed to elevated concentrations of the epidermal growth factor

    International Nuclear Information System (INIS)

    Guillen, Isabel A; Berlanga, Jorge; Camacho, Hanlet

    2013-01-01

    The EGF promotes inhibition of cell proliferation in vitro and in vivo models depending on its concentration, application schema and the type of tumor cells on which it acts. Our research hypothesis was based on the fact that the EGF varies the expression of genes involved in a negative regulation of tumor cell lines proliferation carrying high levels of its receptor (EGFR). Our objectives were, to obtain information about the effect of EGF on tumor cell proliferation in vitro and in vivo models and, know the gene expression patterns of a group of genes involved in cancer signaling pathways and EGFR. The results showed that EGF at nanomolar concentrations inhibits the tumor cells proliferation bearing high levels of EGFR and, promotes the survival of treated animals, establishing a direct relationship between the inhibition of cell proliferation, high concentrations of EGF and, high amount of EGFR in the cells. The differential gene expression profile showed a variation in a group of genes which exert a powerful control over the cell cycle progression, gene transcription and apoptosis. It was concluded that the inhibition of tumor cell proliferation by the action of EGF is due to activation of molecular mechanisms controlling cell cycle progression. This work won the Annual Award of the Cuban Academy of Sciences in 2012

  5. Data For: Heading Through A Crowd

    OpenAIRE

    Riddell, Hugh; Lappe, Markus

    2018-01-01

    Data and analysis scripts to accompany the article "Heading Through A Crowd" by Dr. Hugh Riddell and Prof. Dr. Markus Lappe. All analysis scripts are in SPSS format. Data has been provided in SPSS and .txt formats. Any correspondence should be addressed to Prof. Dr. Markus Lappe.

  6. The crowd in the Occupy movement

    NARCIS (Netherlands)

    Ossewaarde, Marinus R.R.

    2013-01-01

    In this article, I recast Elias Canetti's notion of crowds by placing it in the framework provided by Friedrich Nietzsche's Heraclitean dialectic of Apollonian and Dionysian opposites. The argument is introduced that, in European societies, the forms of social existence are mainly Apollonian,

  7. Crowd-sourcing with Uncertain Quality

    DEFF Research Database (Denmark)

    Papakonstantinou, Athanasios; Bogetoft, Peter

    This article addresses two important issues in crowd-sourcing: ex ante uncertainty about the quality and cost of different workers and strategic behaviour. We present a novel multi-dimensional auction that incentivises the workers to make partial enquiry into the task and to honestly report quality...

  8. How to Move in a Jostling Crowd

    Indian Academy of Sciences (India)

    For people living in big cities it is an ordeal to walk in a bus stand or a railway station. They get stuck helplessly in a crowd. They are simply pushed around and all their efforts to move forward appear futile. Only the most energetic can wade through the constantly moving sea of people. How about the weaker ones?

  9. Wise Crowd Content Assessment and Educational Rubrics

    Science.gov (United States)

    Passonneau, Rebecca J.; Poddar, Ananya; Gite, Gaurav; Krivokapic, Alisa; Yang, Qian; Perin, Dolores

    2018-01-01

    Development of reliable rubrics for educational intervention studies that address reading and writing skills is labor-intensive, and could benefit from an automated approach. We compare a main ideas rubric used in a successful writing intervention study to a highly reliable wise-crowd content assessment method developed to evaluate…

  10. Using the crowd as an innovation partner.

    Science.gov (United States)

    Boudreau, Kevin J; Lakhani, Karim R

    2013-04-01

    From Apple to Merck to Wikipedia, more and more organizations are turning to crowds for help in solving their most vexing innovation and research questions, but managers remain understandably cautious. It seems risky and even unnatural to push problems out to vast groups of strangers distributed around the world, particularly for companies built on a history of internal innovation. How can intellectual property be protected? How can a crowd-sourced solution be integrated into corporate operations? What about the costs? These concerns are all reasonable, the authors write, but excluding crowdsourcing from the corporate innovation tool kit means losing an opportunity. After a decade of study, they have identified when crowds tend to outperform internal organizations (or not). They outline four ways to tap into crowd-powered problem solving--contests, collaborative communities, complementors, and labor markets--and offer a system for picking the best one in a given situation. Contests, for example, are suited to highly challenging technical, analytical, and scientific problems; design problems; and creative or aesthetic projects. They are akin to running a series of independent experiments that generate multiple solutions--and if those solutions cluster at some extreme, a company can gain insight into where a problem's "technical frontier" lies. (Internal R&D may generate far less information.)

  11. Influence of molecular packing on the corrosion inhibition properties of self-assembled octadecyltrichlorosilane monolayers on silicon

    International Nuclear Information System (INIS)

    Hsieh, Shuchen; Chao, Wei-Jay; Lin, Pei-Ying; Hsieh, Chiung-Wen

    2014-01-01

    Highlights: •Molecular packing plays an important role in determining SAM film properties. •Loose-packed OTS monolayers on silicon were corroded by exposure to KMnO 4 . •Dense-packed OTS SAM films exhibited excellent corrosion protection efficacy. -- Abstract: The corrosion inhibition properties of octadecyltrichlorosilane (OTS) self-assembled monolayers (SAMs) on silicon were investigated. Atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), contact angle (CA), and lateral force microscopy (LFM) were used to determine the OTS film formation time, packing density, and corrosion protection efficacy. The OTS films reached adsorption saturation after 15 s; however, the molecular density continued to increase up to 24 h. The films were exposed to the strong oxidant KMnO 4 , and while 15-s film samples exhibited corrosion after a 1 min exposure, samples with films grown for 24 h were protected even after 24 h

  12. Target enzyme mutations are the molecular basis for resistance towards pharmacological inhibition of nicotinamide phosphoribosyltransferase

    DEFF Research Database (Denmark)

    Olesen, Uffe H; Petersen, Jakob G; Garten, Antje

    2010-01-01

    CHS-828 and TP201565 as competitive inhibitors of NAMPT through docking studies and by NAMPT precipitation from cellular lysate by an analogue of TP201565 linked to sepharose. The NAMPT precipitation could be inhibited by addition of APO866. CONCLUSION: We found that CHS-828 and TP201565...

  13. Molecular Basis for Allosteric Inhibition of Acid-Sensing Ion Channel 1a by Ibuprofen

    DEFF Research Database (Denmark)

    Lynagh, Timothy; Romero-Rojo, José Luis; Lund, Camilla

    2017-01-01

    -clamp fluorometry. Our results show that ibuprofen is an allosteric inhibitor of ASIC1a, which binds to a crucial site in the agonist transduction pathway and causes conformational changes that oppose channel activation. Ibuprofen inhibits several ASIC subtypes, but certain ibuprofen derivatives show some...

  14. Molecular requirements for inhibition of the chemokine receptor CCR8--probe-dependent allosteric interactions

    DEFF Research Database (Denmark)

    Rummel, Pia Cwarzko; Arfelt, K N; Baumann, L

    2012-01-01

    Here we present a novel series of CCR8 antagonists based on a naphthalene-sulfonamide structure. This structure differs from the predominant pharmacophore for most small-molecule CC-chemokine receptor antagonists, which in fact activate CCR8, suggesting that CCR8 inhibition requires alternative...

  15. Molecular pharmacology of antihistamines in inhibition of oxidative burst of professional phagocytes.

    Science.gov (United States)

    Nosáľ, Radomír; Jančinová, Viera; Drábiková, Katarína; Perečko, Tomáš

    2015-04-01

    Antihistamines of the H₁and H₃/H₄groups interfere with oxidative burst of human professional phagocytes in vitro. In the concentration of 10 μM, H₁antihistamines of the 1st and 2nd generation inhibited oxidative burst of human neutrophils in the rank order of potency: dithiaden > loratadine > brompheniramine > chlorpheniramine > pheniramine. Of the H₁antihistamines, the most effective was dithiaden in suppressing oxidative burst of whole human blood and dose-dependently the chemiluminescence of isolated neutrophils at extra- and intracellular level. Inhibition of free oxygen radical generation in isolated neutrophils by dithiaden resulted from the inhibition of protein kinase C activation. The potentiation of recombinant caspase-3 by dithiaden is supportive of the antiinflammatory effect of dithiaden and suggestive of increasing the apoptosis of professional phagocytes. Of the H₃/H₄antihistamines, the most effective was JNJ7777120 in decreasing chemiluminescence in whole blood and also at extra- and intracellular sites of isolated neutrophils. JNJ 10191584 and thioperamide were less effective and the latter significantly potentiated free oxygen radical generation intracellularly. The results demonstrated that, compared with the H₃/H₄antihistamines investigated, H₁antihistamines were much more potent in inhibiting free oxygen radical generation in human professional phagocytes. This finding should be taken into account therapeutically.

  16. Molecular basis of inhibition of acid sensing ion channel 1A by diminazene.

    Directory of Open Access Journals (Sweden)

    Aram J Krauson

    Full Text Available Acid-sensing ion channels (ASICs are trimeric proton-gated cation permeable ion channels expressed primarily in neurons. Here we employed site-directed mutagenesis and electrophysiology to investigate the mechanism of inhibition of ASIC1a by diminazene. This compound inhibits mouse ASIC1a with a half-maximal inhibitory concentration (IC50 of 2.4 μM. At first, we examined whether neutralizing mutations of Glu79 and Glu416 alter diminazene block. These residues form a hexagonal array in the lower palm domain that was previously shown to contribute to pore opening in response to extracellular acidification. Significantly, single Gln substitutions at positions 79 and 416 in ASIC1a reduced diminazene apparent affinity by 6-7 fold. This result suggests that diminazene inhibits ASIC1a in part by limiting conformational rearrangement in the lower palm domain. Because diminazene is charged at physiological pHs, we assessed whether it inhibits ASIC1a by blocking the ion channel pore. Consistent with the notion that diminazene binds to a site within the membrane electric field, diminazene block showed a strong dependence with the membrane potential. Moreover, a Gly to Ala mutation at position 438, in the ion conduction pathway of ASIC1a, increased diminazene IC50 by one order of magnitude and eliminated the voltage dependence of block. Taken together, our results indicate that the inhibition of ASIC1a by diminazene involves both allosteric modulation and blocking of ion flow through the conduction pathway. Our findings provide a foundation for the development of more selective and potent ASIC pore blockers.

  17. Molecular definition of multiple sites of antibody inhibition of malaria transmission-blocking vaccine antigen Pfs25.

    Science.gov (United States)

    Scally, Stephen W; McLeod, Brandon; Bosch, Alexandre; Miura, Kazutoyo; Liang, Qi; Carroll, Sean; Reponen, Sini; Nguyen, Ngan; Giladi, Eldar; Rämisch, Sebastian; Yusibov, Vidadi; Bradley, Allan; Lemiale, Franck; Schief, William R; Emerling, Daniel; Kellam, Paul; King, C Richter; Julien, Jean-Philippe

    2017-11-16

    The Plasmodium falciparum Pfs25 protein (Pfs25) is a leading malaria transmission-blocking vaccine antigen. Pfs25 vaccination is intended to elicit antibodies that inhibit parasite development when ingested by Anopheles mosquitoes during blood meals. The Pfs25 three-dimensional structure has remained elusive, hampering a molecular understanding of its function and limiting immunogen design. We report six crystal structures of Pfs25 in complex with antibodies elicited by immunization via Pfs25 virus-like particles in human immunoglobulin loci transgenic mice. Our structural findings reveal the fine specificities associated with two distinct immunogenic sites on Pfs25. Importantly, one of these sites broadly overlaps with the epitope of the well-known 4B7 mouse antibody, which can be targeted simultaneously by antibodies that target a non-overlapping site to additively increase parasite inhibition. Our molecular characterization of inhibitory antibodies informs on the natural disposition of Pfs25 on the surface of ookinetes and provides the structural blueprints to design next-generation immunogens.

  18. Molecularly imprinted nanoparticles for inhibiting ribonuclease in reverse transcriptase polymerase chain reaction

    DEFF Research Database (Denmark)

    Feng, Xiaotong; Ashley, Jon; Zhou, Tongchang

    2018-01-01

    Molecularly imprinted nanoparticles (nanoMIPs) are synthesized via a solid-phase approach using RNase as the template. The feasibility of employing the nanoMIPs as RNase inhibitor is successfully demonstrated in reverse transcriptase polymerase chain reaction (RT-PCR) assays, suggesting the tailor...

  19. The effect of macromolecular crowding on the electrostatic component of barnase-barstar binding: a computational, implicit solvent-based study.

    Directory of Open Access Journals (Sweden)

    Helena W Qi

    Full Text Available Macromolecular crowding within the cell can impact both protein folding and binding. Earlier models of cellular crowding focused on the excluded volume, entropic effect of crowding agents, which generally favors compact protein states. Recently, other effects of crowding have been explored, including enthalpically-related crowder-protein interactions and changes in solvation properties. In this work, we explore the effects of macromolecular crowding on the electrostatic desolvation and solvent-screened interaction components of protein-protein binding. Our simple model enables us to focus exclusively on the electrostatic effects of water depletion on protein binding due to crowding, providing us with the ability to systematically analyze and quantify these potentially intuitive effects. We use the barnase-barstar complex as a model system and randomly placed, uncharged spheres within implicit solvent to model crowding in an aqueous environment. On average, we find that the desolvation free energy penalties incurred by partners upon binding are lowered in a crowded environment and solvent-screened interactions are amplified. At a constant crowder density (fraction of total available volume occupied by crowders, this effect generally increases as the radius of model crowders decreases, but the strength and nature of this trend can depend on the water probe radius used to generate the molecular surface in the continuum model. In general, there is huge variation in desolvation penalties as a function of the random crowder positions. Results with explicit model crowders can be qualitatively similar to those using a lowered "effective" solvent dielectric to account for crowding, although the "best" effective dielectric constant will likely depend on multiple system properties. Taken together, this work systematically demonstrates, quantifies, and analyzes qualitative intuition-based insights into the effects of water depletion due to crowding on the

  20. Molecular modeling reveals the novel inhibition mechanism and binding mode of three natural compounds to staphylococcal α-hemolysin.

    Directory of Open Access Journals (Sweden)

    Jiazhang Qiu

    Full Text Available α-Hemolysin (α-HL is a self-assembling, channel-forming toxin that is produced as a soluble monomer by Staphylococcus aureus strains. Until now, α-HL has been a significant virulence target for the treatment of S. aureus infection. In our previous report, we demonstrated that some natural compounds could bind to α-HL. Due to the binding of those compounds, the conformational transition of α-HL from the monomer to the oligomer was blocked, which resulted in inhibition of the hemolytic activity of α-HL. However, these results have not indicated how the binding of the α-HL inhibitors influence the conformational transition of the whole protein during the oligomerization process. In this study, we found that three natural compounds, Oroxylin A 7-O-glucuronide (OLG, Oroxin A (ORA, and Oroxin B (ORB, when inhibiting the hemolytic activity of α-HL, could bind to the "stem" region of α-HL. This was completed using conventional Molecular Dynamics (MD simulations. By interacting with the novel binding sites of α-HL, the ligands could form strong interactions with both sides of the binding cavity. The results of the principal component analysis (PCA indicated that because of the inhibitors that bind to the "stem" region of α-HL, the conformational transition of α-HL from the monomer to the oligomer was restricted. This caused the inhibition of the hemolytic activity of α-HL. This novel inhibition mechanism has been confirmed by both the steered MD simulations and the experimental data obtained from a deoxycholate-induced oligomerization assay. This study can facilitate the design of new antibacterial drugs against S. aureus.

  1. Role of Molecular Interactions for Synergistic Precipitation Inhibition of Poorly Soluble Drug in Supersaturated Drug-Polymer-Polymer Ternary Solution.

    Science.gov (United States)

    Prasad, Dev; Chauhan, Harsh; Atef, Eman

    2016-03-07

    We are reporting a synergistic effect of combined Eudragit E100 and PVP K90 in precipitation inhibition of indomethacin (IND) in solutions at low polymer concentration, a phenomenon that has significant implications on the usefulness of developing novel ternary solid dispersion of poorly soluble drugs. The IND supersaturation was created by cosolvent technique, and the precipitation studies were performed in the absence and the presence of individual and combined PVP K90 and Eudragit E100. The studies were also done with PEG 8000 as a noninteracting control polymer. A continuous UV recording of the IND absorption was used to observe changes in the drug concentration over time. The polymorphic form and morphology of precipitated IND were characterized by Raman spectroscopy and scanning electron microscopy. The change in the chemical shift in solution (1)H NMR was used as novel approach to probe IND-polymer interactions. Molecular modeling was used for calculating binding energy between IND-polymer as another indication of IND-polymer interaction. Spontaneous IND precipitation was observed in the absence of polymers. Eudragit E100 showed significant inhibitory effect on nuclei formation due to stronger interaction as reflected in higher binding energy and greater change in chemical shift by NMR. PVP K90 led to significant crystal growth inhibition due to adsorption on growing IND crystals as confirmed by modified crystal habit of precipitate in the presence of PVP K90. Combination of polymers resulted in a synergistic precipitation inhibition and extended supersaturation. The NMR confirmed interaction between IND-Eudragit E100 and IND-PVP K90 in solution. The combination of polymers showed similar peak shift albeit using lower polymer concentration indicating stronger interactions. The results established the significant synergistic precipitation inhibition effect upon combining Eudragit E100 and PVP K90 due to drug-polymer interaction.

  2. The Effect of Attractive Interactions and Macromolecular Crowding on Crystallins Association.

    Directory of Open Access Journals (Sweden)

    Jiachen Wei

    Full Text Available In living systems proteins are typically found in crowded environments where their effective interactions strongly depend on the surrounding medium. Yet, their association and dissociation needs to be robustly controlled in order to enable biological function. Uncontrolled protein aggregation often causes disease. For instance, cataract is caused by the clustering of lens proteins, i.e., crystallins, resulting in enhanced light scattering and impaired vision or blindness. To investigate the molecular origins of cataract formation and to design efficient treatments, a better understanding of crystallin association in macromolecular crowded environment is needed. Here we present a theoretical study of simple coarse grained colloidal models to characterize the general features of how the association equilibrium of proteins depends on the magnitude of intermolecular attraction. By comparing the analytic results to the available experimental data on the osmotic pressure in crystallin solutions, we identify the effective parameters regimes applicable to crystallins. Moreover, the combination of two models allows us to predict that the number of binding sites on crystallin is small, i.e. one to three per protein, which is different from previous estimates. We further observe that the crowding factor is sensitive to the size asymmetry between the reactants and crowding agents, the shape of the protein clusters, and to small variations of intermolecular attraction. Our work may provide general guidelines on how to steer the protein interactions in order to control their association.

  3. Dual inhibition of chaperoning process by taxifolin: molecular dynamics simulation study.

    Science.gov (United States)

    Verma, Sharad; Singh, Amit; Mishra, Abha

    2012-07-01

    Hsp90 (heat shock protein 90), a molecular chaperone, stabilizes more than 200 mutated and over expressed oncogenic proteins in cancer development. Cdc37 (cell division cycle protein 37), a co-chaperone of Hsp90, has been found to facilitate the maturation of protein kinases by acting as an adaptor and load these kinases onto the Hsp90 complex. Taxifolin (a natural phytochemical) was found to bind at ATP-binding site of Hsp90 and stabilized the inactive "open" or "lid-up" conformation as evidenced by molecular dynamic simulation. Furthermore, taxifolin was found to bind to interface of Hsp90 and Cdc37 complex and disrupt the interaction of residues of both proteins which were essential for the formation of active super-chaperone complex. Thus, taxifolin was found to act as an inhibitor of chaperoning process and may play a potential role in the cancer chemotherapeutics. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Crowd-Sourced Intelligence Agency: Prototyping counterveillance

    OpenAIRE

    Jennifer Gradecki; Derek Curry

    2017-01-01

    This paper discusses how an interactive artwork, the Crowd-Sourced Intelligence Agency (CSIA), can contribute to discussions of Big Data intelligence analytics. The CSIA is a publicly accessible Open Source Intelligence (OSINT) system that was constructed using information gathered from technical manuals, research reports, academic papers, leaked documents, and Freedom of Information Act files. Using a visceral heuristic, the CSIA demonstrates how the statistical correlations made by automate...

  5. Microscopic and macroscopic models for pedestrian crowds

    OpenAIRE

    Makmul, Juntima

    2016-01-01

    This thesis is concerned with microscopic and macroscopic models for pedes- trian crowds. In the first chapter, we consider pedestrians exit choices and model human behaviour in an evacuation process. Two microscopic models, discrete and continuous, are studied in this chapter. The former is a cellular automaton model and the latter is a social force model. Different numerical test cases are investigated and their results are compared. In chapter 2, a hierarchy of models for...

  6. Associative Interactions in Crowded Solutions of Biopolymers Counteract Depletion Effects.

    Science.gov (United States)

    Groen, Joost; Foschepoth, David; te Brinke, Esra; Boersma, Arnold J; Imamura, Hiromi; Rivas, Germán; Heus, Hans A; Huck, Wilhelm T S

    2015-10-14

    The cytosol of Escherichia coli is an extremely crowded environment, containing high concentrations of biopolymers which occupy 20-30% of the available volume. Such conditions are expected to yield depletion forces, which strongly promote macromolecular complexation. However, crowded macromolecule solutions, like the cytosol, are very prone to nonspecific associative interactions that can potentially counteract depletion. It remains unclear how the cytosol balances these opposing interactions. We used a FRET-based probe to systematically study depletion in vitro in different crowded environments, including a cytosolic mimic, E. coli lysate. We also studied bundle formation of FtsZ protofilaments under identical crowded conditions as a probe for depletion interactions at much larger overlap volumes of the probe molecule. The FRET probe showed a more compact conformation in synthetic crowding agents, suggesting strong depletion interactions. However, depletion was completely negated in cell lysate and other protein crowding agents, where the FRET probe even occupied slightly more volume. In contrast, bundle formation of FtsZ protofilaments proceeded as readily in E. coli lysate and other protein solutions as in synthetic crowding agents. Our experimental results and model suggest that, in crowded biopolymer solutions, associative interactions counterbalance depletion forces for small macromolecules. Furthermore, the net effects of macromolecular crowding will be dependent on both the size of the macromolecule and its associative interactions with the crowded background.

  7. RND-type Drug Efflux Pumps from Gram-negative bacteria: Molecular Mechanism and Inhibition

    Directory of Open Access Journals (Sweden)

    Henrietta eVenter

    2015-04-01

    Full Text Available Drug efflux protein complexes confer multidrug resistance on bacteria by transporting a wide spectrum of structurally diverse antibiotics. Moreover, organisms can only acquire resistance in the presence of an active efflux pump. The substrate range of drug efflux pumps is not limited to antibiotics, but it also includes toxins, dyes, detergents, lipids and molecules involved in quorum sensing; hence efflux pumps are also associated with virulence and biofilm formation. Inhibitors of efflux pumps are therefore attractive compounds to reverse multidrug resistance and to prevent the development of resistance in clinically relevant bacterial pathogens. Recent successes on the structure determination and functional analysis of the AcrB and MexB components of the AcrAB-TolC and MexAB-OprM drug efflux systems as well as the structure of the fully assembled, functional triparted AcrAB-TolC complex significantly contributed to our understanding of the mechanism of substrate transport and the options for inhibition of efflux. These data, combined with the well-developed methodologies for measuring efflux pump inhibition, could allow the rational design and subsequent experimental verification of potential efflux pump inhibitors. In this review we will explore how the available biochemical and structural information can be translated into the discovery and development of new compounds that could reverse drug resistance in Gram-negative pathogens. The current literature on efflux pump inhibitors will also be analysed and the reasons why no compounds have yet progressed into clinical use will be explored.

  8. Molecular Bases of PDE4D Inhibition by Memory-Enhancing GEBR Library Compounds.

    Science.gov (United States)

    Prosdocimi, Tommaso; Mollica, Luca; Donini, Stefano; Semrau, Marta S; Lucarelli, Anna Paola; Aiolfi, Egidio; Cavalli, Andrea; Storici, Paola; Alfei, Silvana; Brullo, Chiara; Bruno, Olga; Parisini, Emilio

    2018-05-01

    Selected members of the large rolipram-related GEBR family of type 4 phosphodiesterase (PDE4) inhibitors have been shown to facilitate long-term potentiation and to improve memory functions without causing emetic-like behavior in rodents. Despite their micromolar-range binding affinities and their promising pharmacological and toxicological profiles, few if any structure-activity relationship studies have been performed to elucidate the molecular bases of their action. Here, we report the crystal structure of a number of GEBR library compounds in complex with the catalytic domain of PDE4D as well as their inhibitory profiles for both the long PDE4D3 isoform and the catalytic domain alone. Furthermore, we assessed the stability of the observed ligand conformations in the context of the intact enzyme using molecular dynamics simulations. The longer and more flexible ligands appear to be capable of forming contacts with the regulatory portion of the enzyme, thus possibly allowing some degree of selectivity between the different PDE4 isoforms.

  9. Inhibition of Mycobacterium-RmlA by Molecular Modeling, Dynamics Simulation, and Docking

    Directory of Open Access Journals (Sweden)

    N. Harathi

    2016-01-01

    Full Text Available The increasing resistance to anti-tb drugs has enforced strategies for finding new drug targets against Mycobacterium tuberculosis (Mtb. In recent years enzymes associated with the rhamnose pathway in Mtb have attracted attention as drug targets. The present work is on α-D-glucose-1-phosphate thymidylyltransferase (RmlA, the first enzyme involved in the biosynthesis of L-rhamnose, of Mtb cell wall. This study aims to derive a 3D structure of RmlA by using a comparative modeling approach. Structural refinement and energy minimization of the built model have been done with molecular dynamics. The reliability assessment of the built model was carried out with various protein checking tools such as Procheck, Whatif, ProsA, Errat, and Verify 3D. The obtained model investigates the relation between the structure and function. Molecular docking interactions of Mtb-RmlA with modified EMB (ethambutol ligands and natural substrate have revealed specific key residues Arg13, Lys23, Asn109, and Thr223 which play an important role in ligand binding and selection. Compared to all EMB ligands, EMB-1 has shown better interaction with Mtb-RmlA model. The information thus discussed above will be useful for the rational design of safe and effective inhibitors specific to RmlA enzyme pertaining to the treatment of tuberculosis.

  10. Molecular Mechanisms of Innate Immune Inhibition by Non-Segmented Negative-Sense RNA Viruses

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, Srirupa; Basler, Christopher F.; Amarasinghe, Gaya K.; Leung, Daisy W.

    2016-08-01

    The host innate immune system serves as the first line of defense against viral infections. Germline-encoded pattern recognition receptors detect molecular patterns associated with pathogens and activate innate immune responses. Of particular relevance to viral infections are those pattern recognition receptors that activate type I interferon responses, which establish an antiviral state. The order Mononegavirales is composed of viruses that possess single-stranded, non-segmented negative-sense (NNS) RNA genomes and are important human pathogens that consistently antagonize signaling related to type I interferon responses. NNS viruses have limited encoding capacity compared to many DNA viruses, and as a likely consequence, most open reading frames encode multifunctional viral proteins that interact with host factors in order to evade host cell defenses while promoting viral replication. In this review, we will discuss the molecular mechanisms of innate immune evasion by select NNS viruses. A greater understanding of these interactions will be critical in facilitating the development of effective therapeutics and viral countermeasures.

  11. Molecular Mechanisms by Which a Fucus vesiculosus Extract Mediates Cell Cycle Inhibition and Cell Death in Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ulf Geisen

    2015-07-01

    Full Text Available Pancreatic cancer is one of the most aggressive cancer entities, with an extremely poor 5-year survival rate. Therefore, novel therapeutic agents with specific modes of action are urgently needed. Marine organisms represent a promising source to identify new pharmacologically active substances. Secondary metabolites derived from marine algae are of particular interest. The present work describes cellular and molecular mechanisms induced by an HPLC-fractionated, hydrophilic extract derived from the Baltic brown seaweed Fucus vesiculosus (Fv1. Treatment with Fv1 resulted in a strong inhibition of viability in various pancreatic cancer cell lines. This extract inhibited the cell cycle of proliferating cells due to the up-regulation of cell cycle inhibitors, shown on the mRNA (microarray data and protein level. As a result, cells were dying in a caspase-independent manner. Experiments with non-dividing cells showed that proliferation is a prerequisite for the effectiveness of Fv1. Importantly, Fv1 showed low cytotoxic activity against non-malignant resting T cells and terminally differentiated cells like erythrocytes. Interestingly, accelerated killing effects were observed in combination with inhibitors of autophagy. Our in vitro data suggest that Fv1 may represent a promising new agent that deserves further development towards clinical application.

  12. Common molecular determinants of tarantula huwentoxin-IV inhibition of Na+ channel voltage sensors in domains II and IV.

    Science.gov (United States)

    Xiao, Yucheng; Jackson, James O; Liang, Songping; Cummins, Theodore R

    2011-08-05

    The voltage sensors of domains II and IV of sodium channels are important determinants of activation and inactivation, respectively. Animal toxins that alter electrophysiological excitability of muscles and neurons often modify sodium channel activation by selectively interacting with domain II and inactivation by selectively interacting with domain IV. This suggests that there may be substantial differences between the toxin-binding sites in these two important domains. Here we explore the ability of the tarantula huwentoxin-IV (HWTX-IV) to inhibit the activity of the domain II and IV voltage sensors. HWTX-IV is specific for domain II, and we identify five residues in the S1-S2 (Glu-753) and S3-S4 (Glu-811, Leu-814, Asp-816, and Glu-818) regions of domain II that are crucial for inhibition of activation by HWTX-IV. These data indicate that a single residue in the S3-S4 linker (Glu-818 in hNav1.7) is crucial for allowing HWTX-IV to interact with the other key residues and trap the voltage sensor in the closed configuration. Mutagenesis analysis indicates that the five corresponding residues in domain IV are all critical for endowing HWTX-IV with the ability to inhibit fast inactivation. Our data suggest that the toxin-binding motif in domain II is conserved in domain IV. Increasing our understanding of the molecular determinants of toxin interactions with voltage-gated sodium channels may permit development of enhanced isoform-specific voltage-gating modifiers.

  13. Azomethines, isoxazole, N-substituted pyrazoles and pyrimidine containing curcumin derivatives: Urease inhibition and molecular modeling studies.

    Science.gov (United States)

    Ahmed, Mahmood; Qadir, Muhammad Abdul; Hameed, Abdul; Arshad, Muhammad Nadeem; Asiri, Abdullah M; Muddassar, Muhammad

    2017-08-19

    Curcumin has shown large number of pharmacological properties against different phenotypes of various disease models. Different synthetic routes have been employed to develop its various derivatives for diverse biological functions. In this study, curcumin derived azomethine, isoxazole, pyrimidines and N-substituted pyrazoles were synthesized to investigate their urease enzyme inhibition. The structures of newly synthesized compounds were described by IR, MS, 1 H NMR and 13 C NMR spectral data. Urease enzyme inhibition was evaluated through in vitro assays in which compound 8b was found to be the most potent (IC 50  = 2.44 ± 0.07 μM) among the tested compounds. The compounds with diazine ring system except the 4d showed better urease inhibition (IC 50  = 11.43 ± 0.21-19.63 ± 0.28 μM) than the standard urease inhibitor thiourea (IC 50  = 22.61 ± 0.23 μM). Similarly enzyme kinetics data revealed that compounds 3c-3e and 8b were competitive inhibitors with Ki values of 20.0, 19.87, 20.23 and 19.11 μM respectively while the compounds 4b, 4c and 4e were mixed type of inhibitors with Ki values 6.72, 19.69 and 6.72 μM respectively. Molecular docking studies were also performed to identify the plausible binding modes of the most active compounds. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Identification of the Molecular Mechanisms Responsible for the Inhibition of Homing of AML Cells Triggered by CD44-Ligation

    KAUST Repository

    Al-Jifri, Ablah

    2011-08-03

    Acute Myeloid Leukemia (AML) is a cancerous disease that is defined by the inability to produce functional and mature blood cells, as well as the uncontrolled proliferation due to failure to undergo apoptosis of abnormal cells. The most common therapy for Leukemia, chemotherapy, has proven only to be partially efficient since it does not target the leukemic stem cells (LSCs) that have a high self-renewal and repopulation capacity and result in remission of the disease. Therefore targeting LSCs will provide more efficient therapy. One way to achieve this would be to inhibit their homing capability to the bone marrow. It has recently been shown that CD44, an adhesive molecule, plays a crucial role in cell trafficking and lodgement of both normal and leukemic stem cells. More importantly anti-CD44 monoclonal antibodies, along with its ability to induce differentiation of leukemic blasts, it inhibits specifically the homing capacity of LSCs to their micro-environmental niches. However, these molecular mechanisms that underlie the inhibition of homing have yet to be determined. To address these questions we conducted in vitro adhesion and blot-rolling assays to analyze the adherence and rolling capacity of these LSCs before and after treatment with anti-CD44 monoclonal antibody (mAb). Since glycosyltransferases play a crucial role in post translational carbohydrate decoration on adhesion molecules, we analyzed the expression (using quantitative PCR) of the different glycosyltransferases expressed in LSC\\'s before and after CD44 ligation (mAb treatment). Furthermore, we analyzed differentiation by flow cytometric analysis of treated and non-treated LSC\\'s. We anticipate that our results will set forth new insights into targeted therapies for AML.

  15. Simulation of Cognitive Pedestrian Agents Crowds in Crisis Situations

    Directory of Open Access Journals (Sweden)

    Margaret Lyell

    2006-06-01

    Full Text Available In crisis situations in an urban environment, first responder teams often must deal with crowds of people. Consider the case of a building fire in a dense city environment. People may be injured; walkways may be blocked, with fire equipment attempting to reach the scene. Crowd behavior can become an issue when trying to reach the injured, ensure safety and restore conditions to normal. The motivations of pedestrians that form the crowd can vary. Some are there because they are curious about the crisis situation. Others, attending to their individual concerns, may have found themselves in the 'wrong' location. They may be trying to leave the area, but the density of people as well as the spatial layout of the walkways may be impeding their progress. Other individuals, unaware of the fire, may be attempting to reach their intended destinations that happen to be near the crisis area, thus adding to crowd congestion. With a model of crowd behavior, effective strategies for resource usage in managing crowd behavior can be developed. Our approach to this problem is that of agent-based modeling and simulation. We develop a cognitive pedestrian agent model. Utilizing this model, we simulate crowd behavior in a 'city fire' scenario. Characteristics of crowd behavior with different pedestrian personality mixes and a strategy for crowd management are investigated

  16. Two-stage perceptual learning to break visual crowding.

    Science.gov (United States)

    Zhu, Ziyun; Fan, Zhenzhi; Fang, Fang

    2016-01-01

    When a target is presented with nearby flankers in the peripheral visual field, it becomes harder to identify, which is referred to as crowding. Crowding sets a fundamental limit of object recognition in peripheral vision, preventing us from fully appreciating cluttered visual scenes. We trained adult human subjects on a crowded orientation discrimination task and investigated whether crowding could be completely eliminated by training. We discovered a two-stage learning process with this training task. In the early stage, when the target and flankers were separated beyond a certain distance, subjects acquired a relatively general ability to break crowding, as evidenced by the fact that the breaking of crowding could transfer to another crowded orientation, even a crowded motion stimulus, although the transfer to the opposite visual hemi-field was weak. In the late stage, like many classical perceptual learning effects, subjects' performance gradually improved and showed specificity to the trained orientation. We also found that, when the target and flankers were spaced too finely, training could only reduce, rather than completely eliminate, the crowding effect. This two-stage learning process illustrates a learning strategy for our brain to deal with the notoriously difficult problem of identifying peripheral objects in clutter. The brain first learned to solve the "easy and general" part of the problem (i.e., improving the processing resolution and segmenting the target and flankers) and then tackle the "difficult and specific" part (i.e., refining the representation of the target).

  17. How to Mitigate Theme Park Crowding? A Prospective Coordination Approach

    Directory of Open Access Journals (Sweden)

    Yuguo Yuan

    2018-01-01

    Full Text Available Crowding is a key factor in tourists’ experience in theme parks, and mitigating crowding makes parks more competitive. This study examines how to effectively mitigate crowding in theme parks. First, a Markov-based method is developed to predict the spatial-temporal distribution of tourists in the park. Then, a prospective coordination approach based on the tourist distribution prediction is proposed. To evaluate the performance of this approach, an experiment is constructed using an agent-based simulation platform. The results indicate that the proposed method significantly outperforms existing methods. Furthermore, we conduct two experiments and, based on the results, offer several recommendations for crowd management.

  18. Grouping and crowding affect target appearance over different spatial scales.

    Directory of Open Access Journals (Sweden)

    Bilge Sayim

    Full Text Available Crowding is the impairment of peripheral target perception by nearby flankers. A number of recent studies have shown that crowding shares many features with grouping. Here, we investigate whether effects of crowding and grouping on target perception are related by asking whether they operate over the same spatial scale. A target letter T had two sets of flanking Ts of varying orientations. The first set was presented close to the target, yielding strong crowding. The second set was either close enough to cause crowding on their own or too far to cause crowding on their own. The Ts of the second set had the same orientation that either matched the target's orientation (Grouped condition or not (Ungrouped condition. In Experiment 1, the Grouped flankers reduced crowding independently of their distance from the target, suggesting that grouping operated over larger distances than crowding. In Experiments 2 and 3 we found that grouping did not affect sensitivity but produced a strong bias to report that the grouped orientation was present at the target location whether or not it was. Finally, we investigated whether this bias was a response or perceptual bias, rejecting the former in favor of a perceptual grouping explanation. We suggest that the effect of grouping is to assimilate the target to the identity of surrounding flankers when they are all the same, and that this shape assimilation effect differs in its spatial scale from the integration effect of crowding.

  19. Age-related changes in crowding and reading speed

    OpenAIRE

    Liu, Rong; Patel, Bhavika N.; Kwon, MiYoung

    2017-01-01

    Crowding, the inability to recognize objects in clutter, is known to play a role in developmental changes in reading speed. Here, we investigated whether crowding also plays a role in age-related changes in reading speed. We recruited 18 young (mean age: 22.6???3.5; range: 18~31) and 21 older adults (mean age: 58.2???7.0; range: 50~73) with normal vision. Reading speed was measured with short blocks of text. The degree of crowding was determined by measuring crowding zone (the distance betwee...

  20. Molecular basis for resistance to ACCase-inhibiting fluazifop in Eleusine indica from Malaysia.

    Science.gov (United States)

    Cha, Thye San; Najihah, Mohamed Ghazani; Sahid, Ismail Bin; Chuah, Tse Seng

    2014-05-01

    Eleusine indica (goosegrass) populations resistant to fluazifop, an acetyl-CoA carboxylase (ACCase: EC6.4.1.2)-inhibiting herbicide, were found in several states in Malaysia. Dose-response assay indicated a resistance factor of 87.5, 62.5 and 150 for biotypes P2, P3 and P4, respectively. DNA sequencing and allele-specific PCR revealed that both biotypes P2 and P3 exhibit a single non-synonymous point mutation from TGG to TGC that leads to a well known Trp-2027-Cys mutation. Interestingly, the highly resistant biotype, P4, did not contain any of the known mutation except the newly discovered target point Asn-2097-Asp, which resulted from a nucleotide change in the codon AAT to GAT. ACCase gene expression was found differentially regulated in the susceptible biotype (P1) and highly resistant biotype P4 from 24 to 72h after treatment (HAT) when being treated with the recommended field rate (198gha(-1)) of fluazifop. However, the small and erratic differences of ACCase gene expression between biotype P1 and P4 does not support the 150-fold resistance in biotype P4. Therefore, the involvement of the target point Asn-2097-Asp and other non-target-site-based resistance mechanisms in the biotype P4 could not be ruled out. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Molecular modeling study on the allosteric inhibition mechanism of HIV-1 integrase by LEDGF/p75 binding site inhibitors.

    Directory of Open Access Journals (Sweden)

    Weiwei Xue

    Full Text Available HIV-1 integrase (IN is essential for the integration of viral DNA into the host genome and an attractive therapeutic target for developing antiretroviral inhibitors. LEDGINs are a class of allosteric inhibitors targeting LEDGF/p75 binding site of HIV-1 IN. Yet, the detailed binding mode and allosteric inhibition mechanism of LEDGINs to HIV-1 IN is only partially understood, which hinders the structure-based design of more potent anti-HIV agents. A molecular modeling study combining molecular docking, molecular dynamics simulation, and binding free energy calculation were performed to investigate the interaction details of HIV-1 IN catalytic core domain (CCD with two recently discovered LEDGINs BI-1001 and CX14442, as well as the LEDGF/p75 protein. Simulation results demonstrated the hydrophobic domain of BI-1001 and CX14442 engages one subunit of HIV-1 IN CCD dimer through hydrophobic interactions, and the hydrophilic group forms hydrogen bonds with HIV-1 IN CCD residues from other subunit. CX14442 has a larger tert-butyl group than the methyl of BI-1001, and forms better interactions with the highly hydrophobic binding pocket of HIV-1 IN CCD dimer interface, which can explain the stronger affinity of CX14442 than BI-1001. Analysis of the binding mode of LEDGF/p75 with HIV-1 IN CCD reveals that the LEDGF/p75 integrase binding domain residues Ile365, Asp366, Phe406 and Val408 have significant contributions to the binding of the LEDGF/p75 to HIV1-IN. Remarkably, we found that binding of BI-1001 and CX14442 to HIV-1 IN CCD induced the structural rearrangements of the 140 s loop and oration displacements of the side chains of the three conserved catalytic residues Asp64, Asp116, and Glu152 located at the active site. These results we obtained will be valuable not only for understanding the allosteric inhibition mechanism of LEDGINs but also for the rational design of allosteric inhibitors of HIV-1 IN targeting LEDGF/p75 binding site.

  2. Heteroaryldihydropyrimidine (HAP) and Sulfamoylbenzamide (SBA) Inhibit Hepatitis B Virus Replication by Different Molecular Mechanisms

    Science.gov (United States)

    Zhou, Zheng; Hu, Taishan; Zhou, Xue; Wildum, Steffen; Garcia-Alcalde, Fernando; Xu, Zhiheng; Wu, Daitze; Mao, Yi; Tian, Xiaojun; Zhou, Yuan; Shen, Fang; Zhang, Zhisen; Tang, Guozhi; Najera, Isabel; Yang, Guang; Shen, Hong C.; Young, John A. T.; Qin, Ning

    2017-01-01

    Heteroaryldihydropyrimidine (HAP) and sulfamoylbenzamide (SBA) are promising non-nucleos(t)ide HBV replication inhibitors. HAPs are known to promote core protein mis-assembly, but the molecular mechanism of abnormal assembly is still elusive. Likewise, the assembly status of core protein induced by SBA remains unknown. Here we show that SBA, unlike HAP, does not promote core protein mis-assembly. Interestingly, two reference compounds HAP_R01 and SBA_R01 bind to the same pocket at the dimer-dimer interface in the crystal structures of core protein Y132A hexamer. The striking difference lies in a unique hydrophobic subpocket that is occupied by the thiazole group of HAP_R01, but is unperturbed by SBA_R01. Photoaffinity labeling confirms the HAP_R01 binding pose at the dimer-dimer interface on capsid and suggests a new mechanism of HAP-induced mis-assembly. Based on the common features in crystal structures we predict that T33 mutations generate similar susceptibility changes to both compounds. In contrast, mutations at positions in close contact with HAP-specific groups (P25A, P25S, or V124F) only reduce susceptibility to HAP_R01, but not to SBA_R01. Thus, HAP and SBA are likely to have distinctive resistance profiles. Notably, P25S and V124F substitutions exist in low-abundance quasispecies in treatment-naïve patients, suggesting potential clinical relevance. PMID:28205569

  3. Mechanism of Inhibition of the V-Type Molecular Motor by Tributyltin Chloride

    Science.gov (United States)

    Takeda, Mizuho; Suno-Ikeda, Chiyo; Shimabukuro, Katsuya; Yoshida, Masasuke; Yokoyama, Ken

    2009-01-01

    Tributyltin chloride (TBT-Cl) is an endocrine disruptor found in many animal species, and it is also known to be an inhibitor for the V-ATPases that are emerging as potential targets in the treatment of diseases such as osteoporosis and cancer. We demonstrated by using biochemical and single-molecular imaging techniques that TBT-Cl arrests an elementary step for rotary catalysis of the V1 motor domain. In the presence of TBT-Cl, the consecutive rotation of V1 paused for a long duration (∼0.5 s), even at saturated ATP concentrations, and the pausing positions were localized at 120° intervals. Analysis of both the pausing time and moving time revealed that TBT-Cl has little effect on the binding affinity for ATP, but, rather, it arrests the catalytic event(s). This is the first report to demonstrate that an inhibitor arrests an elementary step for rotary catalysis of a V-type ATP-driven rotary motor. PMID:19186155

  4. The Financial Impact of Emergency Department Crowding

    Directory of Open Access Journals (Sweden)

    Foley, Mathew

    2011-05-01

    Full Text Available Objective: The economic benefits of reducing emergency department (ED crowding are potentially substantial as they may decrease hospital length of stay. Hospital administrators and public officials may therefore be motivated to implement crowding protocols. We sought to identify a potential cost of ED crowding by evaluating the contribution of excess ED length of stay (LOS to overall hospital length of stay. Methods: We performed a retrospective review of administrative data of adult patients from two urban hospitals (one county and one university in Brooklyn, New York from 2006-2007. Data was provided by each facility. Extrapolating from prior research (Krochmal and Riley, 2005, we determined the increase in total hospital LOS due to extended ED lengths of stay, and applied cost and charge analyses for the two separate facilities. Results: We determined that 6,205 (5.0% admitted adult patients from the county facility and 3,017 (3.4% patients from the university facility were held in the ED greater than one day over a one-year period. From prior research, it has been estimated that each of these patient’s total hospital length of stay was increased on average by 11.7% (0.61 days at the county facility, and 0.71 days at the university facility. The increased charges over one year at the county facility due to the extended ED LOS was therefore approximately $9.8 million, while the increased costs at the university facility were approximately $3.9 million. Conclusion: Based on extrapolations from Krochmal and Riley applied to two New York urban hospitals, the county hospital could potentially save $9.8 million in charges and the university hospital $3.9 million in costs per year if they eliminate ED boarding of adult admitted patients by improving movement to the inpatient setting. [West J Emerg Med. 2011;12(2:192-197.

  5. Modelling asymmetric growth in crowded plant communities

    DEFF Research Database (Denmark)

    Damgaard, Christian

    2010-01-01

    A class of models that may be used to quantify the effect of size-asymmetric competition in crowded plant communities by estimating a community specific degree of size-asymmetric growth for each species in the community is suggested. The model consists of two parts: an individual size......-asymmetric growth part, where growth is assumed to be proportional to a power function of the size of the individual, and a term that reduces the relative growth rate as a decreasing function of the individual plant size and the competitive interactions from other plants in the neighbourhood....

  6. The molecular chaperone α-crystallin inhibits UV-induced protein aggregation

    International Nuclear Information System (INIS)

    Borkman, R.F.; Knight, Grady; Obi, Bettie

    1996-01-01

    Solutions of γ-crystallin, and various enzymes, at neutral pH and 24-26 o C, became turbid upon exposure to UV radiation at 295 or 308 nm. SDS-PAGE analysis revealed interchain cross-linking and aggregate formation compared to dark control solutions as reported previously. When α-crystallin was added to the protein solutions in stoichiometric amounts. UV irradiation resulted in significantly less turbidity than in the absence of α-crystallin. For example, addition of 0.5 mg of α-crystallin to 0.5 mg of γ-crystallin in 1.0 ml solution yielded only 25% of the turbidity seen in the absence of α-crystallin. Addition of 2.0 mg of α-crystallin resulted in 20% of the turbidity. Given the molecular weights of α- and γ-crystallin (about 800 kDa and 20 kDa, respectively), A γ/α 1:1 weight ratio corresponds to a 40:1 molar ratio, and a γ-/α 1:4 weight ratio corresponds to a 10:1 molar ratio. Hence, the molar ratio of α-crystallin needed to effectively protect γ-crystallin from photochemical opacification was γ/α = n:1, where n was in the range 10-40. In terms of subunits, this ratio is γ/α = 1:m, where m = 1-4. Thus, each γ-crystallin molecule needs 1-4 α subunits for protection. Similar stoichiometries were observed for protection of the other proteins studied. The protection stems in part from screening of UV radiation by α-crystallin but more importantly from a chaperone effect analogous to that seen in thermal aggregation experiments. (author)

  7. Comparison of different models of motion in a crowded environment: a Monte Carlo study.

    Science.gov (United States)

    Polanowski, P; Sikorski, A

    2017-02-22

    In this paper we investigate the motion of molecules in crowded environments for two dramatically different types of molecular transport. The first type is realized by the dynamic lattice liquid model, which is based on a cooperative movement concept and thus, the motion of molecules is highly correlated. The second one corresponds to a so-called motion of a single agent where the motion of molecules is considered as a random walk without any correlation with other moving elements. The crowded environments are modeled as a two-dimensional triangular lattice with fixed impenetrable obstacles. Our simulation results indicate that the type of transport has an impact on the dynamics of the system, the percolation threshold, critical exponents, and on molecules' trajectories.

  8. Emulating a crowded intracellular environment in vitro dramatically improves RT-PCR performance

    International Nuclear Information System (INIS)

    Lareu, Ricky R.; Harve, Karthik S.; Raghunath, Michael

    2007-01-01

    The polymerase chain reaction's (PCR) phenomenal success in advancing fields as diverse as Medicine, Agriculture, Conservation, or Paleontology is based on the ability of using isolated prokaryotic thermostable DNA polymerases in vitro to copy DNA irrespective of origin. This process occurs intracellularly and has evolved to function efficiently under crowded conditions, namely in an environment packed with macromolecules. However, current in vitro practice ignores this important biophysical parameter of life. In order to more closely emulate conditions of intracellular biochemistry in vitro we added inert macromolecules into reverse transcription (RT) and PCR. We show dramatic improvements in all parameters of RT-PCR including 8- to 10-fold greater sensitivity, enhanced polymerase processivity, higher specific amplicon yield, greater primer annealing and specificity, and enhanced DNA polymerase thermal stability. The faster and more efficient reaction kinetics was a consequence of the cumulative molecular and thermodynamic effects of the excluded volume effect created by macromolecular crowding

  9. Density functional theory and quantum mechanics/molecular mechanics study of cysteine protease inhibition by nitrile-based inhibitors.

    Directory of Open Access Journals (Sweden)

    Sam P De Visser

    2013-12-01

    Full Text Available Cysteine protease enzymes are important for human physiology and catalyze key protein degradation pathways. These enzymes react via a nucleophilic reaction mechanism that involves a cysteine residue and the proton of a proximal histidine. Particularly efficient inhibitors of these enzymes are nitrile-based, however, the details of the catalytic reaction mechanism currently are poorly understood. To gain further insight into the inhibition of these molecules, we have performed a combined density functional theory and quantum mechanics/molecular mechanics study on the reaction of a nitrile-based inhibitor with the enzyme active site amino acids. We show here that small perturbations to the inhibitor structure can have dramatic effects on the catalysis and inhibition processes. Thus, we investigated a range of inhibitor templates and show that specific structural changes reduce the inhibitory efficiency by several orders of magnitude. Moreover, as the reaction takes place on a polar surface, we find strong differences between the DFT and QM/MM calculated energetics. In particular, the DFT model led to dramatic distortions from the starting structure and the convergence to a structure that would not fit the enzyme active site. In the subsequent QM/MM study we investigated the use of mechanical versus electronic embedding on the kinetics, thermodynamics and geometries along the reaction mechanism. We find minor effects on the kinetics of the reaction but large geometric and thermodynamics differences as a result of inclusion of electronic embedding corrections. The work here highlights the importance of model choice in the investigation of this biochemical reaction mechanism.

  10. Water-soluble low-molecular-weight -(1, 3–1, 6 D-Glucan inhibit cedar pollinosis

    Directory of Open Access Journals (Sweden)

    Tomoko Jippo

    2015-02-01

    Full Text Available Background: The incidence of allergic diseases such as allergic rhinitis, atopic dermatitis, asthma, and food allergies has increased in several countries. Mast cells have critical roles in various biologic processes related to allergic diseases. Mast cells express the high-affinity receptor for immunoglobulin (Ig E on their surface. The interaction of multivalent antigens with surface-bound IgE causes the secretion of granule-stored mediators, as well as the de novosynthesis of cytokines. Those mediators and cytokines proceed the allergic diseases. We investigated the effects of water-soluble, low-molecular-weight -(1, 3–1, 6 D-glucan isolated from Aureobasidium pullulans 1A1 strain black yeast (LMW--glucan on mast cell-mediated anaphylactic reactions. We reported that LMW--glucan dose-dependently inhibited the degranulation of mast cells. Furthermore, we found that orally administered LMW--glucan inhibited the IgE-mediated passive cutaneous anaphylaxis (PCA reaction in mice. Here, we examined if LMW--glucan had effects on Japanese cedar pollinosis. Findings: In a clinical study, a randomized, single-blind, placebo-controlled, parallel group study in 65 subjects (aged 2262 was performed. This study was undertaken 3 weeks before and until the end of the cedar pollen season. During the study, all subjects consumed one bottle of placebo or LMW--glucan daily and all subjects were required to record allergic symptoms in a diary. The LMW--glucan group had a significantly lower prevalence of sneezing, nose-blowing, tears, and hindrance to the activities of daily living than the placebo group. Conclusions: These results suggested that LMW--glucan could be an effective treatment for allergic diseases

  11. Protease-inhibiting, molecular modeling and antimicrobial activities of extracts and constituents from Helichrysum foetidum and Helichrysum mechowianum (compositae).

    Science.gov (United States)

    Malolo, Fanny-Aimée Essombe; Bissoue Nouga, Achille; Kakam, Antoine; Franke, Katrin; Ngah, Lidwine; Flausino, Otavio; Mpondo Mpondo, Emmanuel; Ntie-Kang, Fidele; Ndom, Jean Claude; Bolzani, Vanderlan da Silva; Wessjohann, Ludger

    2015-01-01

    Helichrysum species are used extensively for stress-related ailments and as dressings for wounds normally encountered in circumcision rites, bruises, cuts and sores. It has been reported that Helichysum species are used to relief abdominal pain, heart burn, cough, cold, wounds, female sterility, menstrual pain. From the extracts of Helichrysum foetidum (L.) Moench, six known compounds were isolated and identified. They were 7, 4'-dihydroxy-5-methoxy-flavanone (1), 6'-methoxy-2',4, 4'-trihydroxychalcone (2), 6'-methoxy-2',4-dihydroxychalcone -4'-O-β-D-glucoside (3), apigenin (4), apigenin-7-O-β-D-glucoside (5), kaur-16-en-18-oic acid (6) while two known compounds 3,5,7-trihydroxy-8-methoxyflavone (12), 4,5-dicaffeoyl quinic acid (13) together with a mixture of phytosterol were isolated from the methanol extract of Helichrysum mechowianum Klatt. All the compounds were characterized by spectroscopic and mass spectrometric methods, and by comparison with literature data. Both extracts and all the isolates were screened for the protease inhibition, antibacterial and antifungal activities. In addition, the phytochemical profiles of both species were investigated by ESI-MS experiments. These results showed that the protease inhibition assay of H. foetidum could be mainly attributed to the constituents of flavonoids glycosides (3, 5) while the compound (13) from H. mechowianum contributes to the stomach protecting effects. In addition, among the antibacterial and antifungal activities of all the isolates, compound (6) was found to possess a potent inhibitor effect against the tested microorganisms. The heterogeneity of the genus is also reflected in its phytochemical diversity. The differential bioactivities and determined constituents support the traditional use of the species. Molecular modelling was carried out by computing selected descriptors related to drug absorption, distribution, metabolism, excretion and toxicity (ADMET). Graphical abstractCompounds isolated

  12. Crowd Sourcing to Improve Urban Stormwater Management

    Science.gov (United States)

    Minsker, B. S.; Band, L. E.; Heidari Haratmeh, B.; Law, N. L.; Leonard, L. N.; Rai, A.

    2017-12-01

    Over half of the world's population currently lives in urban areas, a number predicted to grow to 60 percent by 2030. Urban areas face unprecedented and growing challenges that threaten society's long-term wellbeing, including poverty; chronic health problems; widespread pollution and resource degradation; and increased natural disasters. These are "wicked" problems involving "systems of systems" that require unprecedented information sharing and collaboration across disciplines and organizational boundaries. Cities are recognizing that the increasing stream of data and information ("Big Data"), informatics, and modeling can support rapid advances on these challenges. Nonetheless, information technology solutions can only be effective in addressing these challenges through deeply human and systems perspectives. A stakeholder-driven approach ("crowd sourcing") is needed to develop urban systems that address multiple needs, such as parks that capture and treat stormwater while improving human and ecosystem health and wellbeing. We have developed informatics- and Cloud-based collaborative methods that enable crowd sourcing of green stormwater infrastructure (GSI: rain gardens, bioswales, trees, etc.) design and management. The methods use machine learning, social media data, and interactive design tools (called IDEAS-GI) to identify locations and features of GSI that perform best on a suite of objectives, including life cycle cost, stormwater volume reduction, and air pollution reduction. Insights will be presented on GI features that best meet stakeholder needs and are therefore most likely to improve human wellbeing and be well maintained.

  13. Game theoretic aspects of crowd renting | Nwobi-Okoye | Science ...

    African Journals Online (AJOL)

    Politicians and businessmen use various strategies to outwit their opponents. One such strategy is crowd renting, a powerful virtual strategy. A mathematical model developed by Nwobi-Okoye using game theory is used to show that crowd renting would always be the equilibrium strategy in strategic interactions involving ...

  14. Navigation for Characters and Crowds in Complex Virtual Environments

    NARCIS (Netherlands)

    van Toll, W.G.

    2017-01-01

    In a crowd simulation, virtual walking characters need to compute and traverse paths through a virtual environment while avoiding collisions. Simulations of large crowds occur increasingly often in computer games, in which real-time performance is required. Also, there is an increasing demand for

  15. Designing for crowd well-being : Needs and design suggestions

    NARCIS (Netherlands)

    Li, J.; De Ridder, H.; Vermeeren, A.P.O.S.; Conrado, C.; Martella, C.

    2013-01-01

    This paper investigates the needs or criteria for sustaining well-being in crowded situations through two focus group discussions with a total of ten participants. We conclude that pursuing crowd well-being could be divided into two different cases: one is obtaining the enhancement of the current

  16. Crowd-based innovaties: verschuivende verantwoordelijkheden in een institutional void

    NARCIS (Netherlands)

    Slot, M.J.; Cuppen, E.H.W.J.; Doorn, N.; Galeano Galvan, M.J.; Klievink, A.J.

    2017-01-01

    The crowd increasingly plays a key role in facilitating innovations in a variety of sectors, spurred on by IT developments and the concomitant increase in connectivity. Initiatives in this direction, captured under the umbrella term ‘crowd-based innovations’, offer novel opportunities in

  17. Quantitative Comparison Between Crowd Models for Evacuation Planning and Evaluation

    NARCIS (Netherlands)

    Viswanathan, V.; Lee, C.E.; Lees, M.H.; Cheong, S.A.; Sloot, P.M.A.

    2014-01-01

    Crowd simulation is rapidly becoming a standard tool for evacuation planning and evaluation. However, the many crowd models in the literature are structurally different, and few have been rigorously calibrated against real-world egress data, especially in emergency situations. In this paper we

  18. Effect of Households' Socio-Economic Condition on Crowding in ...

    African Journals Online (AJOL)

    The results indicate a preponderance of gentrification, with attendant policy implications. The results also show that there is no significant difference in the degree of crowding among the different socio-economic classifications. This is inconsistent with the generally held understanding in urban housing studies that crowding ...

  19. Inhibition of Ca2+-activated Cl− channels by gallotannins as a possible molecular basis for health benefits of red wine and green tea

    Science.gov (United States)

    Namkung, Wan; Thiagarajah, Jay R.; Phuan, Puay-Wah; Verkman, A. S.

    2010-01-01

    TMEM16A was found recently to be a calcium-activated Cl− channel (CaCC). CaCCs perform important functions in cell physiology, including regulation of epithelial secretion, cardiac and neuronal excitability, and smooth muscle contraction. CaCC modulators are of potential utility for treatment of hypertension, diarrhea, and cystic fibrosis. Screening of drug and natural product collections identified tannic acid as an inhibitor of TMEM16A, with IC50 ∼ 6 μM and ∼100% inhibition at higher concentrations. Tannic acid inhibited CaCCs in multiple cell types but did not affect CFTR Cl− channels. Structure-activity analysis indicated the requirement of gallic or digallic acid substituents on a macromolecular scaffold (gallotannins), as are present in green tea and red wine. Other polyphenolic components of teas and wines, including epicatechin, catechin, and malvidin-3-glucoside, poorly inhibited CaCCs. Remarkably, a 1000-fold dilution of red wine and 100-fold dilution of green tea inhibited CaCCs by >50%. Tannic acid, red wine, and green tea inhibited arterial smooth muscle contraction and intestinal Cl− secretion. Gallotannins are thus potent CaCC inhibitors whose biological activity provides a potential molecular basis for the cardioprotective and antisecretory benefits of red wine and green tea.—Namkung, W., Thiagarajah, J. R., Phuan, P.-W., Verkman, A. S. Inhibition of Ca2+-activated Cl− channels by gallotannins as a possible molecular basis for health benefits of red wine and green tea. PMID:20581223

  20. Subcutaneous Administration of Low-Molecular-Weight Heparin to Horses Inhibits Ex Vivo Equine Herpesvirus Type 1-Induced Platelet Activation

    Directory of Open Access Journals (Sweden)

    Tracy Stokol

    2018-05-01

    Full Text Available Equine herpesvirus type 1 (EHV-1 is a major cause of infectious respiratory disease, abortion and neurologic disease. Thrombosis in placental and spinal vessels and subsequent ischemic injury in EHV-1-infected horses manifests clinically as abortion and myeloencephalopathy. We have previously shown that addition of heparin anticoagulants to equine platelet-rich plasma (PRP can abolish ex vivo EHV-1-induced platelet activation. The goal of this study was to test whether platelets isolated from horses treated with unfractionated heparin (UFH or low-molecular-weight heparin (LMWH were resistant to ex vivo EHV-1-induced activation. In a masked, block-randomized placebo-controlled cross-over trial, 9 healthy adult horses received 4 subcutaneous injections at q. 12 h intervals of one of the following treatments: UFH (100 U/kg loading dose, 3 maintenance doses of 80 U/kg, 2 doses of LMWH (enoxaparin 80 U/kg 24 h apart with saline at the intervening 12 h intervals, or 4 doses of saline. Blood samples were collected before treatment and after 36 h, 40 h (4 h after the last injection and 60 h (24 h after the last injection. Two strains of EHV-1, Ab4 and RacL11, were added to PRP ex vivo and platelet membrane expression of P selectin was measured as a marker of platelet activation. Drug concentrations were monitored in a Factor Xa inhibition (anti-Xa bioassay. We found that LMWH, but not UFH, inhibited platelet activation induced by low concentrations (1 × 106 plaque forming units/mL of both EHV-1 strains at 40 h. At this time point, all horses had anti-Xa activities above 0.1 U/ml (range 0.15–0.48 U/ml with LMWH, but not UFH. By 60 h, a platelet inhibitory effect was no longer detected and anti-Xa activity had decreased (range 0.03 to 0.07 U/ml in LMWH-treated horses. Neither heparin inhibited platelet activation induced by high concentrations (5 × 106 plaque forming units/mL of the RacL11 strain. We found substantial between horse

  1. ACCRETION-INHIBITED STAR FORMATION IN THE WARM MOLECULAR DISK OF THE GREEN-VALLEY ELLIPTICAL GALAXY NGC 3226?

    International Nuclear Information System (INIS)

    Appleton, P. N.; Bitsakis, T.; Alatalo, K.; Mundell, C.; Lacy, M.; Armus, L.; Charmandaris, V.; Duc, P.-A.; Lisenfeld, U.; Ogle, P.

    2014-01-01

    We present archival Spitzer photometry and spectroscopy and Herschel photometry of the peculiar ''Green Valley'' elliptical galaxy NGC 3226. The galaxy, which contains a low-luminosity active galactic nucleus (AGN), forms a pair with NGC 3227 and is shown to lie in a complex web of stellar and H I filaments. Imaging at 8 and 16 μm reveals a curved plume structure 3 kpc in extent, embedded within the core of the galaxy and coincident with the termination of a 30 kpc long H I tail. In situ star formation associated with the infrared (IR) plume is identified from narrowband Hubble Space Telescope (HST) imaging. The end of the IR plume coincides with a warm molecular hydrogen disk and dusty ring containing 0.7-1.1 × 10 7 M ☉ detected within the central kiloparsec. Sensitive upper limits to the detection of cold molecular gas may indicate that a large fraction of the H 2 is in a warm state. Photometry derived from the ultraviolet (UV) to the far-IR shows evidence for a low star-formation rate of ∼0.04 M ☉ yr –1 averaged over the last 100 Myr. A mid-IR component to the spectral energy distribution (SED) contributes ∼20% of the IR luminosity of the galaxy, and is consistent with emission associated with the AGN. The current measured star formation rate is insufficient to explain NGC 3226's global UV-optical ''green'' colors via the resurgence of star formation in a ''red and dead'' galaxy. This form of ''cold accretion'' from a tidal stream would appear to be an inefficient way to rejuvenate early-type galaxies and may actually inhibit star formation

  2. Designing interactive technology for crowd experiences - beyond sanitization

    DEFF Research Database (Denmark)

    Veerasawmy, Rune

    2014-01-01

    This dissertation concerns the topic on designing interactive technology for crowd expe- riences. It takes the outset in the experience-oriented design approach within interaction design, exploring the research question how can we conceptually understand and design interactive technology for crowd...... experiences? Through theoretical studies of sociological crowd theory and pragmatist perspectives on experience combined with design exper- iments at sporting events this dissertation establishes an conceptual understanding of crowd experience. The outcome of this work is furthermore synthesized...... in a conceptual model of social experiences that presents crowd experiences as a distinct type of social experience. This is different from what previously have been explored within experi- ence-oriented design. This dissertation is composed of four research papers framed by an overview that summarizes...

  3. German crowd-investing platforms: Literature review and survey

    Directory of Open Access Journals (Sweden)

    David Grundy

    2016-12-01

    Full Text Available This article presents a comprehensive overview of the current German crowd-investing market drawing on a data-set of 31 crowd-investing platforms including the analysis of 265 completed projects. While crowd-investing market still only represents a niche in the German venture capital market, there is potential for an increase in both market volume and in average project investment. The market share is distributed among a few crowd-investing platforms with high entry barriers for new platforms although platforms that specialise in certain sectors have managed to successfully enter the market. German crowd-investing platforms are found to promote mainly internet-based enterprises (36% followed by projects in real estate (24% and green projects (19%, with the median money raised 100,000 euro.

  4. Eyes on crowding : Crowding is preserved when responding by eye and similarly affects identity and position accuracy

    NARCIS (Netherlands)

    Yildirim, Funda; Meyer, Vincent; Cornelissen, Frans W.

    Peripheral vision guides recognition and selection of targets for eye movements. Crowding-a decline in recognition performance that occurs when a potential target is surrounded by other, similar, objects-influences peripheral object recognition. A recent model study suggests that crowding may be due

  5. Molecular size is important for the safety and selective inhibition of intrinsic factor Xase for fucosylated chondroitin sulfate.

    Science.gov (United States)

    Yan, Lufeng; Li, Junhui; Wang, Danli; Ding, Tian; Hu, Yaqin; Ye, Xingqian; Linhardt, Robert J; Chen, Shiguo

    2017-12-15

    Fucosylated chondroitin sulfate from sea cucumber Isostichopus badionotus (FCS-Ib) showed potent anticoagulant activities without selectivity. The present study focused on developing safe FCS-Ib oligomers showing selective inhibition of intrinsic factor Xase (anti-FXase) prepared through partial N-deacetylation-deaminative cleavage. The N-deacetylation degree was regulated by reaction time, controlling the resulting oligomer distribution. Structure analysis confirmed the selectivity of degradation, and 12 high purity fractions with trisaccharide-repeating units were separated. In vitro anticoagulant assays indicated a decrease in molecular weight (Mw) dramatically reduced activated partial thromboplastin time (APTT), thrombin time (TT), AT-dependent anti-FIIa and anti-FXa activities, while the oligomers retained potent anti-FXase activity until they fell below 3kDa. Meanwhile, human FXII activation and platelet aggregation were markedly reduced with decreasing Mw and were moderate when under 12.0kDa. Thus, fragments of 3-12.0kDa should be safe and effective as selective inhibitors of intrinsic tenase complex for application as clinical anticoagulants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Characterization and Molecular Mechanism of Peptide-Conjugated Gold Nanoparticle Inhibiting p53-HDM2 Interaction in Retinoblastoma

    Directory of Open Access Journals (Sweden)

    Sushma Kalmodia

    2017-12-01

    Full Text Available Inhibition of the interaction between p53 and HDM2 is an effective therapeutic strategy in cancers that harbor a wild-type p53 protein such as retinoblastoma (RB. Nanoparticle-based delivery of therapeutic molecules has been shown to be advantageous in localized delivery, including to the eye, by overcoming ocular barriers. In this study, we utilized biocompatible gold nanoparticles (GNPs to deliver anti-HDM2 peptide to RB cells. Characterization studies suggested that GNP-HDM2 was stable in biologically relevant solvents and had optimal cellular internalization capability, the primary requirement of any therapeutic molecule. GNP-HDM2 treatment in RB cells in vitro suggested that they function by arresting RB cells at the G2M phase of the cell cycle and initiating apoptosis. Analysis of molecular changes in GNP-HDM2-treated cells by qRT-PCR and western blotting revealed that the p53 protein was upregulated; however, transactivation of its downstream targets was minimal, except for the PUMA-BCl2 and Bax axis. Global gene expression and in silico bioinformatic analysis of GNP-HDM2-treated cells suggested that upregulation of p53 might presumptively mediate apoptosis through the induction of p53-inducible miRNAs.

  7. Crowding, molecular volume and plasticity: An assessment involving ...

    Indian Academy of Sciences (India)

    2012-10-30

    Oct 30, 2012 ... text. Such differences observed in eubacterial peptidyl-tRNA hydrolase .... the package GROMACSv3.3.1 running on parallel processor ..... Tyrosine protein phosphatase type 4 from Homo sapiens 2VPH 2CS5 16465 18751.

  8. The Subject in the Crowd: A Critical Discussion of Jodi Dean’s “Crowds and Party”

    Directory of Open Access Journals (Sweden)

    Jacob Johanssen

    2016-10-01

    Full Text Available This article presents a critical discussion of Jodi Dean’s (2016 book “Crowds and Party”. I pay particular attention to her discussion of crowds that is influenced by psychoanalysis. Dean has put forward an important argument for the affectivity within crowds that may be transformed into a Communist Party that is characterised by a similar affective infrastructure. I suggest that Dean’s discussion of affect is slightly vague at times and may be supplemented with Sigmund Freud’s work on affect. In contrast to Dean, who stresses the collectivity and deindividuation of the crowd, I argue that the crowd needs to be thought of as a place where individuality and collectivity come together and remain in tension.

  9. Crowded: a crowd-sourced perspective of events as they happen

    Science.gov (United States)

    Brantingham, Richard; Hossain, Aleem

    2013-05-01

    `Crowded' is a web-based application developed by the Defence Science & Technology Laboratory (Dstl) that collates imagery of a particular location from a variety of media sources to provide an operator with real-time situational awareness. Emergency services and other relevant agencies have detected or become aware of an event - a riot or an explosion, for instance - and its location or text associated with it. The ubiquity of mobile devices allows people to collect and upload media of the incident to the Internet, in real time. Crowded manages the interactions with online sources of media: Flickr; Instagram; YouTube; Twitter; and Transport for London traffic cameras, to retrieve imagery that is being uploaded at that point in time. In doing so, it aims to provide human operators with near-instantaneous `eyes-on' from a variety of different perspectives. The first instantiation of Crowded was implemented as a series of integrated web-services with the aim of rapidly understanding whether the approach was viable. In doing so, it demonstrated how non-traditional, open sources can be used to provide a richer current intelligence picture than can be obtained alone from classified sources. The development of Crowded also explored how open source technology and cloud-based services can be used in the modern intelligence and security environment to provide a multi-agency Common Operating Picture to help achieve a co-ordinated response. The lessons learned in building the prototype are currently being used to design and develop a second version, and identify options and priorities for future development.

  10. Global crowd data to understand risk taking behavior: Understanding the costs of crowd sourcing

    Science.gov (United States)

    Hendrikx, J.; Johnson, J.

    2016-12-01

    Crowd sourcing is an increasingly common approach to collect data from a large number of places, people, or both, for a given phenomenon or observation. It is often thought of as a very cost effective approach to collect data from large spatial domains, or from difficult to reach areas, or for spatially discrete observations. While crowd sourcing data can provide a wealth of data beyond that which most research teams can collect themselves, there are many associated, and sometime unexpected costs with this approach. We present a case study of a crowd-sourced data collection campaign to collect GPS tracks of back country recreationalists in avalanche terrain. We ask the volunteers to track their outings using the GPS on their smart phone using a free application, and on the completion of their trip email us their track. On receipt of this track we automatically reply with a link to a decision making survey. In this way we collect data on both the physical attributes of their trip, as well as the social, psychological and demographic data about the person. While this approach has been very successful, it has come at a high cost time-wise. Much like the role of an online course instructor, instructor (or in this case researcher) presence is essential. Replying to emails, updating webpages, posting on social media, and connecting with your volunteer data collectors can become a full time job - and that's even before you start the data analysis. We encourage future researchers to plan ahead for this when starting a crowd sourcing project involving the general public, and seek advice and training in social media, web site development and communication techniques like semi-automated email.

  11. Crowded orbits conflict and cooperation in space

    CERN Document Server

    James

    2014-01-01

    Written for all readers, this expert analysis details the basics of space technology, diplomacy, commerce, exploration, and military applications from the mid-twentieth century to today. Space has become increasingly crowded since the end of the Cold War, and this book pays particular attention to the politics and economics of space and recent debates over national security, focusing on the competing themes of international competition and cooperation and the effort to avoid dangerous conflicts. Unfortunately, the growth of human space activity and challenges to existing international tools of management, such as rules, laws, and treaties, have increased the likelihood of conflict over a diminishing pool of space resources close to Earth. Drawing on more than twenty years of experience in international space debates and policy, James Clay Moltz points to the logic of cooperation and collaboration among the expanding number of space actors, considering their shared challenges regarding space traffic, orbital d...

  12. iCrowd: agent-based behavior modeling and crowd simulator

    Science.gov (United States)

    Kountouriotis, Vassilios I.; Paterakis, Manolis; Thomopoulos, Stelios C. A.

    2016-05-01

    Initially designed in the context of the TASS (Total Airport Security System) FP-7 project, the Crowd Simulation platform developed by the Integrated Systems Lab of the Institute of Informatics and Telecommunications at N.C.S.R. Demokritos, has evolved into a complete domain-independent agent-based behavior simulator with an emphasis on crowd behavior and building evacuation simulation. Under continuous development, it reflects an effort to implement a modern, multithreaded, data-oriented simulation engine employing latest state-of-the-art programming technologies and paradigms. It is based on an extensible architecture that separates core services from the individual layers of agent behavior, offering a concrete simulation kernel designed for high-performance and stability. Its primary goal is to deliver an abstract platform to facilitate implementation of several Agent-Based Simulation solutions with applicability in several domains of knowledge, such as: (i) Crowd behavior simulation during [in/out] door evacuation. (ii) Non-Player Character AI for Game-oriented applications and Gamification activities. (iii) Vessel traffic modeling and simulation for Maritime Security and Surveillance applications. (iv) Urban and Highway Traffic and Transportation Simulations. (v) Social Behavior Simulation and Modeling.

  13. Molecular mechanism of pancreatic tumor metastasis inhibition by Gd@C82(OH)22 and its implication for de novo design of nanomedicine

    Energy Technology Data Exchange (ETDEWEB)

    Kang, S. -g.; Zhou, G.; Yang, P.; Liu, Y.; Sun, B.; Huynh, T.; Meng, H.; Zhao, L.; Xing, G.; Chen, C.; Zhao, Y.; Zhou, R.

    2012-09-18

    Pancreatic adenocarcinoma is the most lethal of the solid tumors and the fourth-leading cause of cancer-related death in North America. Matrix metalloproteinases (MMPs) have long been targeted as a potential anticancer therapy because of their seminal role in angiogenesis and extracellular matrix (ECM) degradation of tumor survival and invasion. However, the inhibition specificity to MMPs and the molecular-level understanding of the inhibition mechanism remain largely unresolved. Here, we found that endohedral metallofullerenol Gd@C82(OH)22 can successfully inhibit the neoplastic activity with experiments at animal, tissue, and cellular levels. Gd@C82(OH)22 effectively blocks tumor growth in human pancreatic cancer xenografts in a nude mouse model. Enzyme activity assays also show Gd@C82(OH)22 not only suppresses the expression of MMPs but also significantly reduces their activities. We then applied large-scale molecular-dynamics simulations to illustrate the molecular mechanism by studying the Gd@C82(OH)22–MMP-9 interactions in atomic detail. Our data demonstrated that Gd@C82(OH)22 inhibits MMP-9 mainly via an exocite interaction, whereas the well-known zinc catalytic site only plays a minimal role. Steered by nonspecific electrostatic, hydrophobic, and specific hydrogen-bonding interactions, Gd@C82(OH)22 exhibits specific binding modes near the ligand-specificity loop S1', thereby inhibiting MMP-9 activity. Both the suppression of MMP expression and specific binding mode make Gd@C82(OH)22 a potentially more effective nanomedicine for pancreatic cancer than traditional medicines, which usually target the proteolytic sites directly but fail in selective inhibition. Finally, our findings provide insights for de novo design of nanomedicines for fatal diseases such as pancreatic cancer.

  14. Crowd-Sourced Global Earthquake Early Warning

    Science.gov (United States)

    Minson, S. E.; Brooks, B. A.; Glennie, C. L.; Murray, J. R.; Langbein, J. O.; Owen, S. E.; Iannucci, B. A.; Hauser, D. L.

    2014-12-01

    Although earthquake early warning (EEW) has shown great promise for reducing loss of life and property, it has only been implemented in a few regions due, in part, to the prohibitive cost of building the required dense seismic and geodetic networks. However, many cars and consumer smartphones, tablets, laptops, and similar devices contain low-cost versions of the same sensors used for earthquake monitoring. If a workable EEW system could be implemented based on either crowd-sourced observations from consumer devices or very inexpensive networks of instruments built from consumer-quality sensors, EEW coverage could potentially be expanded worldwide. Controlled tests of several accelerometers and global navigation satellite system (GNSS) receivers typically found in consumer devices show that, while they are significantly noisier than scientific-grade instruments, they are still accurate enough to capture displacements from moderate and large magnitude earthquakes. The accuracy of these sensors varies greatly depending on the type of data collected. Raw coarse acquisition (C/A) code GPS data are relatively noisy. These observations have a surface displacement detection threshold approaching ~1 m and would thus only be useful in large Mw 8+ earthquakes. However, incorporating either satellite-based differential corrections or using a Kalman filter to combine the raw GNSS data with low-cost acceleration data (such as from a smartphone) decreases the noise dramatically. These approaches allow detection thresholds as low as 5 cm, potentially enabling accurate warnings for earthquakes as small as Mw 6.5. Simulated performance tests show that, with data contributed from only a very small fraction of the population, a crowd-sourced EEW system would be capable of warning San Francisco and San Jose of a Mw 7 rupture on California's Hayward fault and could have accurately issued both earthquake and tsunami warnings for the 2011 Mw 9 Tohoku-oki, Japan earthquake.

  15. Rhythmic crowd bobbing on a grandstand simulator

    Science.gov (United States)

    Comer, A. J.; Blakeborough, A.; Williams, M. S.

    2013-01-01

    It is widely accepted that concerted human activity such as bouncing or bobbing can excite cantilever grandstands. Crowd coordination can be unwitting and may be exacerbated by structural motion caused by resonant structural response. This is an area of uncertainty in the design and analysis of modern grandstands. This paper presents experimental measurement and analysis of rhythmic crowd bobbing loads obtained from tests on a grandstand simulator with two distinct support conditions; (a) rigid, and; (b) flexible. It was found that significant structural vibration at the bobbing frequency did not increase the effective bobbing load. Structural motion at the bobbing frequency caused a reduction in the dynamic load factor (DLF) at the frequency of the second harmonic while those at the first and third harmonics were unaffected. Two plausible reasons for this are: (a) the bobbing group were unable to supply significant energy to the system at the frequency of the second harmonic; (b) the bobbing group altered their bobbing style to reduce the response of the grandstand simulator. It was deduced that the bobbing group did not absorb energy from the dynamic system. Furthermore, dynamic load factors for groups of test subjects bobbing on a rigid structure were typically greater than those of synthesised groups derived from individuals bobbing alone, possibly due to group effects such as audio and visual stimuli from neighbouring test subjects. Last, the vibration levels experienced by the test subjects appear to be below levels likely to cause discomfort. This is to be expected as the test subjects were themselves controlling the magnitude and duration of vibration for the bobbing tests considered.

  16. Exits in order: How crowding affects particle lifetimes

    Energy Technology Data Exchange (ETDEWEB)

    Penington, Catherine J.; Simpson, Matthew J. [School of Mathematical Sciences, Queensland University of Technology, Brisbane (Australia); Baker, Ruth E. [Mathematical Institute, University of Oxford, Radcliffe Observatory Quarter, Woodstock Road, Oxford (United Kingdom)

    2016-06-28

    Diffusive processes are often represented using stochastic random walk frameworks. The amount of time taken for an individual in a random walk to intersect with an absorbing boundary is a fundamental property that is often referred to as the particle lifetime, or the first passage time. The mean lifetime of particles in a random walk model of diffusion is related to the amount of time required for the diffusive process to reach a steady state. Mathematical analysis describing the mean lifetime of particles in a standard model of diffusion without crowding is well known. However, the lifetime of agents in a random walk with crowding has received much less attention. Since many applications of diffusion in biology and biophysics include crowding effects, here we study a discrete model of diffusion that incorporates crowding. Using simulations, we show that crowding has a dramatic effect on agent lifetimes, and we derive an approximate expression for the mean agent lifetime that includes crowding effects. Our expression matches simulation results very well, and highlights the importance of crowding effects that are sometimes overlooked.

  17. Low molecular weight heparin may benefit nephrotic remission in steroid‑sensitive nephrotic syndrome via inhibiting elastase.

    Science.gov (United States)

    Zhai, Songhui; Hu, Lijuan; Zhong, Lin; Tao, Yuhong; Wang, Zheng

    2017-12-01

    Low molecular weight heparin (LMWH) has a structure similar to heparan sulfate, which exerts anti‑inflammatory effects via inhibiting elastase (Ela) activity. Release of Ela along the glomerular capillary wall may induce glomerular injury and proteinuria. The present study aimed to investigate the influence of LMWH on steroid‑sensitive nephrotic syndrome (SSNS) and the potential underlying mechanism. A total of 40 SSNS patients and 20 healthy controls were recruited. SSNS patients were treated with LMWH and prednisone simultaneously (LMWH+pred group) or with prednisone alone (pred group). Proteinuria, urinary glycosaminoglycans (GAGs), serum Ela and urinary creatinine levels were measured. The nephrotic period of SSNS was 15.93±5.78 days. The nephrotic period of SSNS in LMWH+pred group was significantly reduced compared with the pred group (14.13±4.56 vs. 18.63±6.49 days; PEla levels (77.64±10.99 ng/l) were significantly greater in the nephrotic period of SSNS compared with the remission period (0.107±0.026 g/24 h, 1.53±0.27 mg/mmol Cr and 41.92±7.81 ng/l, respectively) and the healthy control group (0.098±0.027 g/24 h, 1.40±0.26 mg/mmol creatinine and 38.43±9.83 ng/l, respectively; PEla levels in the LMWH+pred group were significantly reduced compared with the pred group (P0.05). Positive correlations were revealed between urinary GAG excretion and proteinuria (r=0.877; PEla levels (r=0.844; PEla levels and urinary GAG excretion (r=0.881; PEla levels may induce proteinuria by degrading GAGs in the glomerular basement membrane in children with SSNS. LMWH may benefit nephrotic remission of SSNS via inhibiting Ela.

  18. Structural analysis and unique molecular recognition properties of a Bauhinia forficata lectin that inhibits cancer cell growth.

    Science.gov (United States)

    Lubkowski, Jacek; Durbin, Sarah V; Silva, Mariana C C; Farnsworth, David; Gildersleeve, Jeffrey C; Oliva, Maria Luiza V; Wlodawer, Alexander

    2017-02-01

    Lectins have been used at length for basic research and clinical applications. New insights into the molecular recognition properties enhance our basic understanding of carbohydrate-protein interactions and aid in the design/development of new lectins. In this study, we used a combination of cell-based assays, glycan microarrays, and X-ray crystallography to evaluate the structure and function of the recombinant Bauhinia forficata lectin (BfL). The lectin was shown to be cytostatic for several cancer cell lines included in the NCI-60 panel; in particular, it inhibited growth of melanoma cancer cells (LOX IMVI) by over 95%. BfL is dimeric in solution and highly specific for binding of oligosaccharides and glycopeptides with terminal N-acetylgalactosamine (GalNAc). BfL was found to have especially strong binding (apparent K d  = 0.5-1.0 nm) to the tumor-associated Tn antigen. High-resolution crystal structures were determined for the ligand-free lectin, as well as for its complexes with three Tn glycopeptides, globotetraose, and the blood group A antigen. Extensive analysis of the eight crystal structures and comparison to structures of related lectins revealed several unique features of GalNAc recognition. Of special note, the carboxylate group of Glu126, lining the glycan-binding pocket, forms H-bonds with both the N-acetyl of GalNAc and the peptide amido group of Tn antigens. Stabilization provided by Glu126 is described here for the first time for any GalNAc-specific lectin. Taken together, the results provide new insights into the molecular recognition of carbohydrates and provide a structural understanding that will enable rational engineering of BfL for a variety of applications. Structural data are available in the PDB under the accession numbers 5T50, 5T52, 5T55, 5T54, 5T5L, 5T5J, 5T5P, and 5T5O. © 2016 Federation of European Biochemical Societies.

  19. Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate

    Energy Technology Data Exchange (ETDEWEB)

    Saldanha, Sabita N., E-mail: sabivan@uab.edu [Department of Biology, University of Alabama at Birmingham, 175 Campbell Hall, 1300 University Boulevard, Birmingham, AL 35294 (United States); Department of Biological Sciences, Alabama State University, Montgomery, AL 36104 (United States); Kala, Rishabh [Department of Biology, University of Alabama at Birmingham, 175 Campbell Hall, 1300 University Boulevard, Birmingham, AL 35294 (United States); Tollefsbol, Trygve O., E-mail: trygve@uab.edu [Department of Biology, University of Alabama at Birmingham, 175 Campbell Hall, 1300 University Boulevard, Birmingham, AL 35294 (United States); Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Comprehensive Center for Healthy Aging, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Nutrition Obesity Research Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Comprehensive Diabetes Research Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)

    2014-05-15

    Bioactive compounds are considered safe and have been shown to alter genetic and epigenetic profiles of tumor cells. However, many of these changes have been reported at molecular concentrations higher than physiologically achievable levels. We investigated the role of the combinatorial effects of epigallocatechin gallate (EGCG), a predominant polyphenol in green tea, and sodium butyrate (NaB), a dietary microbial fermentation product of fiber, in the regulation of survivin, which is an overexpressed anti-apoptotic protein in colon cancer cells. For the first time, our study showed that the combination treatment induced apoptosis and cell cycle arrest in RKO, HCT-116 and HT-29 colorectal cancer cells. This was found to be regulated by the decrease in HDAC1, DNMT1, survivin and HDAC activity in all three cell lines. A G2/M arrest was observed for RKO and HCT-116 cells, and G1 arrest for HT-29 colorectal cancer cells for combinatorial treatment. Further experimentation of the molecular mechanisms in RKO colorectal cancer (CRC) cells revealed a p53-dependent induction of p21 and an increase in nuclear factor kappa B (NF-κB)-p65. An increase in double strand breaks as determined by gamma-H2A histone family member X (γ-H2AX) protein levels and induction of histone H3 hyperacetylation was also observed with the combination treatment. Further, we observed a decrease in global CpG methylation. Taken together, these findings suggest that at low and physiologically achievable concentrations, combinatorial EGCG and NaB are effective in promoting apoptosis, inducing cell cycle arrest and DNA-damage in CRC cells. - Highlights: • EGCG and NaB as a combination inhibits colorectal cancer cell proliferation. • The combination treatment induces DNA damage, G2/M and G1 arrest and apoptosis. • Survivin is effectively down-regulated by the combination treatment. • p21 and p53 expressions are induced by the combination treatment. • Epigenetic proteins DNMT1 and HDAC1 are

  20. Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate

    International Nuclear Information System (INIS)

    Saldanha, Sabita N.; Kala, Rishabh; Tollefsbol, Trygve O.

    2014-01-01

    Bioactive compounds are considered safe and have been shown to alter genetic and epigenetic profiles of tumor cells. However, many of these changes have been reported at molecular concentrations higher than physiologically achievable levels. We investigated the role of the combinatorial effects of epigallocatechin gallate (EGCG), a predominant polyphenol in green tea, and sodium butyrate (NaB), a dietary microbial fermentation product of fiber, in the regulation of survivin, which is an overexpressed anti-apoptotic protein in colon cancer cells. For the first time, our study showed that the combination treatment induced apoptosis and cell cycle arrest in RKO, HCT-116 and HT-29 colorectal cancer cells. This was found to be regulated by the decrease in HDAC1, DNMT1, survivin and HDAC activity in all three cell lines. A G2/M arrest was observed for RKO and HCT-116 cells, and G1 arrest for HT-29 colorectal cancer cells for combinatorial treatment. Further experimentation of the molecular mechanisms in RKO colorectal cancer (CRC) cells revealed a p53-dependent induction of p21 and an increase in nuclear factor kappa B (NF-κB)-p65. An increase in double strand breaks as determined by gamma-H2A histone family member X (γ-H2AX) protein levels and induction of histone H3 hyperacetylation was also observed with the combination treatment. Further, we observed a decrease in global CpG methylation. Taken together, these findings suggest that at low and physiologically achievable concentrations, combinatorial EGCG and NaB are effective in promoting apoptosis, inducing cell cycle arrest and DNA-damage in CRC cells. - Highlights: • EGCG and NaB as a combination inhibits colorectal cancer cell proliferation. • The combination treatment induces DNA damage, G2/M and G1 arrest and apoptosis. • Survivin is effectively down-regulated by the combination treatment. • p21 and p53 expressions are induced by the combination treatment. • Epigenetic proteins DNMT1 and HDAC1 are

  1. NECESSITY FACTORS AND PREDICTORS OF DENTAL CROWDING TREATMENT

    Directory of Open Access Journals (Sweden)

    Georgeta ZEGAN

    2015-09-01

    Full Text Available The aim of the study was to identify the significant necessity and predictive factors of dental crowding treatment, on 422 subjects (165 boys and 257 girls from the North-East part of Romania. Correlations have been established between dental crowding and age, dentition, Angle class of malocclusions, the etiological factors, types and modalities of treatments, and types of orthodontic appliances employed (p0.05. The necessity and predictive factors of the treatment were adequate with age, dentition, severity of crowding and Angle class of malocclusion.

  2. Estimating the number of people in crowded scenes

    Science.gov (United States)

    Kim, Minjin; Kim, Wonjun; Kim, Changick

    2011-01-01

    This paper presents a method to estimate the number of people in crowded scenes without using explicit object segmentation or tracking. The proposed method consists of three steps as follows: (1) extracting space-time interest points using eigenvalues of the local spatio-temporal gradient matrix, (2) generating crowd regions based on space-time interest points, and (3) estimating the crowd density based on the multiple regression. In experimental results, the efficiency and robustness of our proposed method are demonstrated by using PETS 2009 dataset.

  3. CROWDING AND SHOPPING VALUE IN LOW-INCOME RETAIL CENTERS

    Directory of Open Access Journals (Sweden)

    Izabelle Quezado

    2014-07-01

    Full Text Available Considering the great potential of low-income consumption, this research is based on the scales developed by Babin, Darden and Griffin (1994 and by Machleit, Kellaris and Eroglu (1994, aiming to investigate hedonic and utilitarian consumer behavior and its relation with low-income perception of crowding. A research was performed with 404 consumers in real store environment and the results showed that consumers revealed being prone to utilitarian behavior in both centers. About crowding phenomenon, the consumers felt more uncomfortable by crowding at the commercial center with less infrastructure. There were indices that this discomfort was less intense in hedonic consumers.

  4. Designing for crowd well-being : Current designs, strategies and future design suggestions

    NARCIS (Netherlands)

    Li, J.; de Ridder, H.; Vermeeren, A.P.O.S.; Conrado, C.; Martella, C.

    2013-01-01

    This paper introduces the concept of crowd well-being and the needs for sustaining it. Crowd well-being can be interpreted as crowd members’ evaluations on their emotional reactions, moods and judgments they form about their satisfactions, goals or needs fulfillment in a crowded situation according

  5. The wisdom of the crowd in funding: information heterogeneity and social networks of crowdfunders

    NARCIS (Netherlands)

    Polzin, Friedemann; Toxopeus, Helen; Stam, Erik

    2018-01-01

    Crowdfunding has enabled large crowds to fund innovative projects. This type of funding might tap into the wisdom of crowds who were previously disconnected from the funding process. We distinguish between in-crowd and out-crowd funders (with and without ties to project creators) in order to test

  6. The wisdom of the crowd in funding: : Information heterogeneity and social networks of crowdfunder

    NARCIS (Netherlands)

    Polzin, F.H.J.; Toxopeus, H.S.; Stam, F.C.

    2016-01-01

    Crowdfunding has enabled large crowds to fund innovative projects. This type of funding might tap into the wisdom of crowds who were previously disconnected from the funding process. We distinguish between in-crowd and out-crowd funders (with and without ties to project creators) in order to test

  7. Two's a crowd? Crowding effect in a parasitic castrator drives differences in reproductive resource allocation in single vs double infections.

    Science.gov (United States)

    Fong, Caitlin R; Moron, Nancy A; Kuris, Armand M

    2017-04-01

    The 'crowding effect' is a result of competition by parasites within a host for finite resources. Typically, the severity of this effect increases with increasing numbers of parasites within a host and manifests in reduced body size and thus fitness. Evidence for the crowding effect is mixed - while some have found negative effects, others have found a positive effect of increased parasite load on parasite fitness. Parasites are consumers with diverse trophic strategies reflected in their life history traits. These distinctions are useful to predict the effects of crowding. We studied a parasitic castrator, a parasite that usurps host reproductive energy and renders the host sterile. Parasitic castrators typically occur as single infections within hosts. With multiple parasitic castrators, we expect strong competition and evidence of crowding. We directly assess the effect of crowding on reproductive success in a barnacle population infected by a unique parasitic castrator, Hemioniscus balani, an isopod parasite that infects and blocks reproduction of barnacles. We find (1) strong evidence of crowding in double infections, (2) increased frequency of double infections in larger barnacle hosts with more resources and (3) perfect compensation in egg production, supporting strong space limitation. Our results document that the effects of crowding are particularly severe for this parasitic castrator, and may be applicable to other castrators that are also resource or space limited.

  8. The sound of the crowd: auditory information modulates the perceived emotion of a crowd based on bodily expressions.

    Science.gov (United States)

    McHugh, Joanna E; Kearney, Gavin; Rice, Henry; Newell, Fiona N

    2012-02-01

    Although both auditory and visual information can influence the perceived emotion of an individual, how these modalities contribute to the perceived emotion of a crowd of characters was hitherto unknown. Here, we manipulated the ambiguity of the emotion of either a visual or auditory crowd of characters by varying the proportions of characters expressing one of two emotional states. Using an intersensory bias paradigm, unambiguous emotional information from an unattended modality was presented while participants determined the emotion of a crowd in an attended, but different, modality. We found that emotional information in an unattended modality can disambiguate the perceived emotion of a crowd. Moreover, the size of the crowd had little effect on these crossmodal influences. The role of audiovisual information appears to be similar in perceiving emotion from individuals or crowds. Our findings provide novel insights into the role of multisensory influences on the perception of social information from crowds of individuals. PsycINFO Database Record (c) 2012 APA, all rights reserved

  9. Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10-14 June 2012)

    Science.gov (United States)

    Foffi, G.; Pastore, A.; Piazza, F.; Temussi, P. A.

    2013-08-01

    More than 60 years of biochemical and biophysical studies have accustomed us to think of proteins as highly purified entities that act in isolation, more or less freely diffusing until they find their cognate partner to bind to. While in vitro experiments that reproduce these conditions largely remain the only way to investigate the intrinsic properties of molecules, this approach ignores an important factor: in their natural milieu , proteins are surrounded by several other molecules of different chemical nature, and this crowded environment can considerably modify their behaviour. About 40% of the cellular volume on average is occupied by all sorts of molecules. Furthermore, biological macromolecules live and operate in an extremely structured and complex environment within the cell (endoplasmic reticulum, Golgi apparatus, cytoskeletal structures, etc). Hence, to further complicate the picture, the interior of the cell is by no means a simply crowded medium, rather, a most crowded and confining one. In recent times, several approaches have been developed in the attempt to take into account important factors such as the ones mentioned above, at both theoretical and experimental levels, so that this field of research is now emerging as one of the most thriving in molecular and cell biology (see figure 1). Figure 1. Figure 1. Left: number of articles containing the word 'crowding' as a keyword limited to the biological and chemical science domains (source: ISI Web of Science). The arrow flags the 2003 'EMBO Workshop on Biological Implications of Macromolecular Crowding' (Embo, 2012). Right: number of citations to articles containing the word 'crowding' limited to the same domains (bars) and an exponential regression curve (source: Elsevier Scopus). To promote the importance of molecular crowding and confinement and provide researchers active in this field an interdisciplinary forum for meeting and exchanging ideas, we recently organized an international conference

  10. Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10-14 June 2012).

    Science.gov (United States)

    Foffi, G; Pastore, A; Piazza, F; Temussi, P A

    2013-08-02

    More than 60 years of biochemical and biophysical studies have accustomed us to think of proteins as highly purified entities that act in isolation, more or less freely diffusing until they find their cognate partner to bind to. While in vitro experiments that reproduce these conditions largely remain the only way to investigate the intrinsic properties of molecules, this approach ignores an important factor: in their natural milieu , proteins are surrounded by several other molecules of different chemical nature, and this crowded environment can considerably modify their behaviour. About 40% of the cellular volume on average is occupied by all sorts of molecules. Furthermore, biological macromolecules live and operate in an extremely structured and complex environment within the cell (endoplasmic reticulum, Golgi apparatus, cytoskeletal structures, etc). Hence, to further complicate the picture, the interior of the cell is by no means a simply crowded medium, rather, a most crowded and confining one. In recent times, several approaches have been developed in the attempt to take into account important factors such as the ones mentioned above, at both theoretical and experimental levels, so that this field of research is now emerging as one of the most thriving in molecular and cell biology (see figure 1). [Formula: see text] Figure 1. Left: number of articles containing the word 'crowding' as a keyword limited to the biological and chemical science domains (source: ISI Web of Science). The arrow flags the 2003 'EMBO Workshop on Biological Implications of Macromolecular Crowding' (Embo, 2012). Right: number of citations to articles containing the word 'crowding' limited to the same domains (bars) and an exponential regression curve (source: Elsevier Scopus). To promote the importance of molecular crowding and confinement and provide researchers active in this field an interdisciplinary forum for meeting and exchanging ideas, we recently organized an international

  11. Design optimization of deep groove ball bearings using crowding ...

    Indian Academy of Sciences (India)

    Aparna Duggirala

    2018-02-07

    Feb 7, 2018 ... The technique is applied to bearings used in transmission system of a tractor for the purpose of ... different types of AI techniques have been used [8–12]. ..... with a crowding distance based external archive maintenance.

  12. Motivating crowding theory - opening the black box of intrinsic motivation

    DEFF Research Database (Denmark)

    Jacobsen, Christian Bøtcher

    2010-01-01

    Public employees work for many other reasons than because they are paid for it. In other words, intrinsic motivation is an important determinant for their performance. Nonetheless, public sector organizations increasingly rely on extrinsic motivation factors such as monetary incentives to motivate...... employees. Motivation crowding theory claims that this may be at the expense of intrinsic motivation, if the extrinsic motivation factor is perceived to be controlling. On the other hand, intrinsic motivation will be enhanced (crowded in), if the extrinsic motivation factor is perceived to be supportive......, monetary incentives are found to cause different crowding effects for these different types of intrinsic motivation. The results call for more theoretical work on the drivers of motivation crowding effects and for practitioners to pay more attention to what type of intrinsic motivation is at stake, when...

  13. Household Crowding During Childhood and Long-Term Education Outcomes.

    Science.gov (United States)

    Lopoo, Leonard M; London, Andrew S

    2016-06-01

    Household crowding, or having more household members than rooms in one's residence, could potentially affect a child's educational attainment directly through a number of mechanisms. We use U.S. longitudinal data from the Panel Study of Income Dynamics to derive new measures of childhood crowding and estimate negative associations between crowding during one's high school years and, respectively, high school graduation by age 19 and maximum education at age 25. These negative relationships persist in multivariate models in which we control for the influence of a variety of factors, including socioeconomic status and housing-cost burden. Given the importance of educational attainment for a range of midlife and later-life outcomes, this study suggests that household crowding during one's high school years is an engine of cumulative inequality over the life course.

  14. What Macromolecular Crowding Can Do to a Protein

    Science.gov (United States)

    Kuznetsova, Irina M.; Turoverov, Konstantin K.; Uversky, Vladimir N.

    2014-01-01

    The intracellular environment represents an extremely crowded milieu, with a limited amount of free water and an almost complete lack of unoccupied space. Obviously, slightly salted aqueous solutions containing low concentrations of a biomolecule of interest are too simplistic to mimic the “real life” situation, where the biomolecule of interest scrambles and wades through the tightly packed crowd. In laboratory practice, such macromolecular crowding is typically mimicked by concentrated solutions of various polymers that serve as model “crowding agents”. Studies under these conditions revealed that macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, protein-protein interactions, protein-nucleic acid interactions, and pathological aggregation. The goal of this review is to systematically analyze currently available experimental data on the variety of effects of macromolecular crowding on a protein molecule. The review covers more than 320 papers and therefore represents one of the most comprehensive compendia of the current knowledge in this exciting area. PMID:25514413

  15. Crowded letter and crowded picture logMAR acuity in children with amblyopia: a quantitative comparison.

    Science.gov (United States)

    O'Boyle, Cathy; Chen, Sean I; Little, Julie-Anne

    2017-04-01

    Clinically, picture acuity tests are thought to overestimate visual acuity (VA) compared with letter tests, but this has not been systematically investigated in children with amblyopia. This study compared VA measurements with the LogMAR Crowded Kay Picture test to the LogMAR Crowded Keeler Letter acuity test in a group of young children with amblyopia. 58 children (34 male) with amblyopia (22 anisometropic, 18 strabismic and 18 with both strabismic/anisometropic amblyopia) aged 4-6 years (mean=68.7, range=48-83 months) underwent VA measurements. VA chart testing order was randomised, but the amblyopic eye was tested before the fellow eye. All participants wore up-to-date refractive correction. The Kay Picture test significantly overestimated VA by 0.098 logMAR (95% limits of agreement (LOA), 0.13) in the amblyopic eye and 0.088 logMAR (95% LOA, 0.13) in the fellow eye, respectively (pocclusion therapy, refractive correction or type of amblyopia on VA results (p>0.23). For both the amblyopic and fellow eyes, Bland-Altman plots demonstrated a systematic and predictable difference between Kay Picture and Keeler Letter charts across the range of acuities tested (Keeler acuity: amblyopic eye 0.75 to -0.05 logMAR; fellow eye 0.45 to -0.15 logMAR). Linear regression analysis (pamblyopia. Due to the predictable difference found between both crowded logMAR acuity tests, it is reasonable to adjust Kay Picture acuity thresholds by +0.10 logMAR to compute expected Keeler Letter acuity scores. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. CrowdMag - Crowdsourcing magnetic data

    Science.gov (United States)

    Nair, M. C.; Boneh, N.; Chulliat, A.

    2014-12-01

    In the CrowdMag project, we explore whether digital magnetometers built in modern mobile phones can be used as scientific instruments to measure Earth's magnetic field. Most modern mobile phones have digital magnetometers to orient themselves. A phone's magnetometer measures three components of the local magnetic field with a typical sensitivity of about 150 to 600 nanotesla (nT). By combining data from vector magnetometers and accelerometers, phone's orientation is determined. Using phone's Internet connection, magnetic data and location are sent to a central server. At the server, we check quality of the magnetic data from all users and make the data available to the public as aggregate maps. We have two long-term goals. 1) Develop near-real-time models of Earth's time changing magnetic field by reducing man-made noise from crowdsourced data and combining it with geomagnetic data from other sources. 2) Improving accuracy of magnetic navigation by mapping magnetic noise sources (for e.g. power transformer and iron pipes). Key challenges to this endeavor are the low sensitivity of the phone's magnetometer and the noisy environment within and surrounding the phone. URL : http://www.ngdc.noaa.gov/geomag/crowdmag.shtml

  17. Crowd-Sourced Intelligence Agency: Prototyping counterveillance

    Directory of Open Access Journals (Sweden)

    Jennifer Gradecki

    2017-02-01

    Full Text Available This paper discusses how an interactive artwork, the Crowd-Sourced Intelligence Agency (CSIA, can contribute to discussions of Big Data intelligence analytics. The CSIA is a publicly accessible Open Source Intelligence (OSINT system that was constructed using information gathered from technical manuals, research reports, academic papers, leaked documents, and Freedom of Information Act files. Using a visceral heuristic, the CSIA demonstrates how the statistical correlations made by automated classification systems are different from human judgment and can produce false-positives, as well as how the display of information through an interface can affect the judgment of an intelligence agent. The public has the right to ask questions about how a computer program determines if they are a threat to national security and to question the practicality of using statistical pattern recognition algorithms in place of human judgment. Currently, the public’s lack of access to both Big Data and the actual datasets intelligence agencies use to train their classification algorithms keeps the possibility of performing effective sous-dataveillance out of reach. Without this data, the results returned by the CSIA will not be identical to those of intelligence agencies. Because we have replicated how OSINT is processed, however, our results will resemble the type of results and mistakes made by OSINT systems. The CSIA takes some initial steps toward contributing to an informed public debate about large-scale monitoring of open source, social media data and provides a prototype for counterveillance and sousveillance tools for citizens.

  18. Crowding with conjunctions of simple features.

    Science.gov (United States)

    Põder, Endel; Wagemans, Johan

    2007-11-20

    Several recent studies have related crowding with the feature integration stage in visual processing. In order to understand the mechanisms involved in this stage, it is important to use stimuli that have several features to integrate, and these features should be clearly defined and measurable. In this study, Gabor patches were used as target and distractor stimuli. The stimuli differed in three dimensions: spatial frequency, orientation, and color. A group of 3, 5, or 7 objects was presented briefly at 4 deg eccentricity of the visual field. The observers' task was to identify the object located in the center of the group. A strong effect of the number of distractors was observed, consistent with various spatial pooling models. The analysis of incorrect responses revealed that these were a mix of feature errors and mislocalizations of the target object. Feature errors were not purely random, but biased by the features of distractors. We propose a simple feature integration model that predicts most of the observed regularities.

  19. Understanding the corrosion inhibition of carbon steel and copper in sulphuric acid medium by amino acids using electrochemical techniques allied to molecular modelling methods

    International Nuclear Information System (INIS)

    Mendonça, Glaydson L.F.; Costa, Stefane N.; Freire, Valder N.; Casciano, Paulo N.S.; Correia, Adriana N.; Lima-Neto, Pedro de

    2017-01-01

    Highlights: • Corrosion inhibition of carbon steel and of copper by the amino acids was studied. • Inhibition efficiencies were experimentally achieved by electrochemical impedance. • DFT and Monte Carlo methods allowed correlating molecular properties with inhibition efficiency. • The corrosion inhibition followed the electron donation the electron-back donations process. - Abstract: Six amino acids were evaluated as corrosion inhibitors for carbon steel and copper in 0.5 mol L"−"1 H_2SO_4 solution by potentiodynamic polarization and electrochemical impedance techniques allied to Density Functional Theory (DFT) and Monte Carlo computations The corrosion inhibitor rankings were: Arg > Gln > Asn > Met > Cys > Ser, for copper, and Met > Cys > Ser > Arg > Gln > Asn, for carbon steel. The DFT approach failed to explain the corrosion inhibition rating based on the HOMO and LUMO energies of the isolated amino acid molecules, while the simpler classical Monte Carlo approach, performed considering the interaction energies between the corrosion inhibitor and the metallic substrate, was successful.

  20. The allocation of attention and working memory in visual crowding.

    Science.gov (United States)

    Bacigalupo, Felix; Luck, Steven J

    2015-06-01

    When the distance between a visual target and nearby flankers falls below a critical distance, target discrimination declines precipitously. This is called "crowding." Many researchers have proposed that selective attention plays a role in crowding. However, although some research has examined the effects of directing attention toward versus away from the targets, no previous research has assessed how attentional allocation varies as a function of target-flanker distance in crowding. Here, we used ERPs to assess the operation of attention during crowding, focusing on the attention-related N2pc component. We used a typical crowding task in which participants were asked to report the category (vowel/consonant) of a lateralized target letter flanked by distractor letters at different distances. We tested the hypothesis that attention fails when the target-flanker distance becomes too small for attention to operate effectively. Consistent with this hypothesis, we found that N2pc amplitude was maximal at intermediate target-flanker distances and decreased substantially when crowding became severe. In addition, we examined the sustained posterior contralateral negativity (SPCN), which reflects the amount of information being maintained in working memory. Unlike the N2pc component, the SPCN increased in amplitude at small target-flanker distances, suggesting that observers stored information about the target and flankers in working memory when attention failed to select the target. Together, the N2pc and SPCN results suggest that attention and working memory play distinctive roles in crowding: Attention operates to minimize interference from the flankers at intermediate target-flanker distances, whereas working memory may be recruited when attention fails to select the target at small target-flanker distances.

  1. [Inhibition of Low Molecular Organic Acids on the Activity of Acidithiobacillus Species and Its Effect on the Removal of Heavy Metals from Contaminated Soil].

    Science.gov (United States)

    Song, Yong-wei; Wang, He-rul; Cao, Yan-xiao; Li, Fei; Cui, Chun-hong; Zhou, Li

    2016-05-15

    Application of organic fertilizer can reduce the solubility and bioavailability of heavy metals in contaminated soil, but in the flooded anaerobic environment, organic fertilizer will be decomposed to produce a large number of low molecular organic acids, which can inhibit the biological activity of Acidithiobacillus species. Batch cultures studies showed that the monocarboxylic organic acids including formic acid, acetic acid, propionic acid, and butyric acid exhibited a marked toxicity to Acidithiobacillus species, as indicated by that 90% of inhibitory rate for Fe2 and So oxidation in 72 h were achieved at extremely low concentrations of 41.2 mg · L⁻¹, 78.3 mg · L⁻¹, 43.2 mg · L⁻¹, 123.4 mg · L⁻¹ and 81.9 mg 230. 4 mg · L⁻¹, 170.1 mg · L⁻¹, 123.4 mg · L⁻¹ respectively. Of these organic acids, formic acid was the most toxic one as indicated by that Fe2 and So oxidation was almost entirely inhibited at a low concentration. In addition, it was found that Acidithiobacillus ferrooxidans was more sensitive to low molecular organic acids than Acidithiobacillus thiooxidans. What's more, there was little effect on biological acidification process of heavy metal contaminated soil when organic acids were added at initial stage (Oh), but it was completely inhibited when these acids were added after 12 h of conventional biological acidification, thus decreasing the efficiency of heavy metals dissolution from soil.

  2. Characterization of angiotensin-I converting enzyme inhibiting peptide from Venerupis philippinarum with nano-liquid chromatography in combination with orbitrap mass spectrum detection and molecular docking

    Science.gov (United States)

    Shi, Lei; Wu, Tizhi; Sheng, Naijuan; Yang, Li; Wang, Qian; Liu, Rui; Wu, Hao

    2017-06-01

    The complexity and diversity of peptide mixture from protein hydrolysates make their characterization difficult. In this study, a method combining nano LC-MS/MS with molecular docking was applied to identifying and characterizing a peptide with angiotensin-I converting enzyme (ACE-I) inhibiting activity from Venerupis philippinarum hydrolysate. Firstly, ethanol supernatant of V. philippinarum hydrolysate was separated into active fractions with chromatographic methods such as ion-exchange chromatography and high performance liquid chromatography in combination. Then seven peptides from active fraction were identified according to the searching result of the MS/MS spectra against protein databases. Peptides were synthesized and subjected to ACE-I-inhibition assay. The peptide NTLTLIDTGIGMTK showed the highest potency with an IC50 of 5.75 μmol L-1. The molecular docking analysis showed that the ACE-I inhibiting peptide NTLTLIDTGIGMTK bond with residues Glu123, Glu403, Arg522, Glu376, Gln281 and Asn285 of ACE-I. Therefore, active peptides could be identified with the present method rather than the traditional purification and identification strategies. It may also be feasible to identify other food-derived peptides which target other enzymes and receptors with the method developed in this study.

  3. The Crowd in Mind and Crowded Minds: An Experimental Investigation of Crowding Effects on Students' Views Regarding Tuition Fees in Germany

    Science.gov (United States)

    Hellmann, Jens H.; Jucks, Regina

    2017-01-01

    In higher education, just amounts of tuition fees are often a topic of heated debate among different groups such as students, university teachers, administrative staff, and policymakers. We investigated whether unpleasant situations that students often experience at university due to social crowding can affect students' views on the justified…

  4. Social Crowding during Development Causes Changes in GnRH1 DNA Methylation.

    Science.gov (United States)

    Alvarado, Sebastian G; Lenkov, Kapa; Williams, Blake; Fernald, Russell D

    2015-01-01

    Gestational and developmental cues have important consequences for long-term health, behavior and adaptation to the environment. In addition, social stressors cause plastic molecular changes in the brain that underlie unique behavioral phenotypes that also modulate fitness. In the adult African cichlid, Astatotilapia burtoni, growth and social status of males are both directly regulated by social interactions in a dynamic social environment, which causes a suite of plastic changes in circuits, cells and gene transcription in the brain. We hypothesized that a possible mechanism underlying some molecular changes might be DNA methylation, a reversible modification made to cytosine nucleotides that is known to regulate gene function. Here we asked whether changes in DNA methylation of the GnRH1 gene, the central regulator of the reproductive axis, were altered during development of A. burtoni. We measured changes in methylation state of the GnRH1 gene during normal development and following the gestational and developmental stress of social crowding. We found differential DNA methylation within developing juveniles between 14-, 28- and 42-day-old. Following gestational crowding of mouth brooding mothers, we saw differential methylation and transcription of GnRH1 in their offspring. Taken together, our data provides evidence for social control of GnRH1 developmental responses to gestational cues through DNA methylation.

  5. Meaningful interpretation of subdiffusive measurements in living cells (crowded environment) by fluorescence fluctuation microscopy.

    Science.gov (United States)

    Baumann, Gerd; Place, Robert F; Földes-Papp, Zeno

    2010-08-01

    In living cell or its nucleus, the motions of molecules are complicated due to the large crowding and expected heterogeneity of the intracellular environment. Randomness in cellular systems can be either spatial (anomalous) or temporal (heterogeneous). In order to separate both processes, we introduce anomalous random walks on fractals that represented crowded environments. We report the use of numerical simulation and experimental data of single-molecule detection by fluorescence fluctuation microscopy for detecting resolution limits of different mobile fractions in crowded environment of living cells. We simulate the time scale behavior of diffusion times tau(D)(tau) for one component, e.g. the fast mobile fraction, and a second component, e.g. the slow mobile fraction. The less the anomalous exponent alpha the higher the geometric crowding of the underlying structure of motion that is quantified by the ratio of the Hausdorff dimension and the walk exponent d(f)/d(w) and specific for the type of crowding generator used. The simulated diffusion time decreases for smaller values of alpha # 1 but increases for a larger time scale tau at a given value of alpha # 1. The effect of translational anomalous motion is substantially greater if alpha differs much from 1. An alpha value close to 1 contributes little to the time dependence of subdiffusive motions. Thus, quantitative determination of molecular weights from measured diffusion times and apparent diffusion coefficients, respectively, in temporal auto- and crosscorrelation analyses and from time-dependent fluorescence imaging data are difficult to interpret and biased in crowded environments of living cells and their cellular compartments; anomalous dynamics on different time scales tau must be coupled with the quantitative analysis of how experimental parameters change with predictions from simulated subdiffusive dynamics of molecular motions and mechanistic models. We first demonstrate that the crowding exponent

  6. Molecular modeling of the inhibition of enzyme PLA2 from snake venom by dipyrone and 1-phenyl-3-methyl-5-pyrazolone

    Science.gov (United States)

    Silva, S. L. Da; Comar, M., Jr.; Oliveira, K. M. T.; Chaar, J. S.; Bezerra, E. R. M.; Calgarotto, A. K.; Baldasso, P. A.; Veber, C. L.; Villar, J. A. F. P.; Oliveira, A. R. M.; Marangoni, S.

    Phospholipases A2 (PLA2) are enzymes that trigger the degradation cascade of the arachidonic acid, leading to the formation of pro-inflammatory eicosanoids. The selective inhibition of PLA2s is crucial in the search for a more efficient anti-inflammatory drug with fewer side effects than the drugs currently used. Hence, we studied the influences caused by two pyrazolonic inhibitors: dipyrone (DIP) and 1-phenyl-3-methyl-5-pyrazolone (PMP) on the kinetic behavior of PLA2 from Crotalus adamanteus venom. Molecular modeling results, by DFT and MM approaches, showed that DIP is strongly associated to the active site of PLA2 through three hydrogen bonds, whereas PMP is associated to the enzyme just through hydrophobic interactions. In addition, only PMP presents an intramolecular hydrogen bond that make difficult the formation of more efficient interactions with PLA2. These results help in the understanding of the experimental observations. Experimentally, the results showed that PLA2 from C. adamanteus present a typical Michaelian behavior. In addition, the calculated kinetic parameters showed that, in the presence of DIP or PMP, the maximum enzymatic velocity (VMAX) value was kept constant, whereas the Michaelis constant (KM) values increased and the inhibition constant (KI) decreased, indicating competitive inhibition. These results show that the phenyl-pyrazolonic structures might help in the development and design of new drugs able to selectively inhibit PLA2.

  7. Developing an emergency department crowding dashboard: A design science approach.

    Science.gov (United States)

    Martin, Niels; Bergs, Jochen; Eerdekens, Dorien; Depaire, Benoît; Verelst, Sandra

    2017-08-30

    As an emergency department (ED) is a complex adaptive system, the analysis of continuously gathered data is valuable to gain insight in the real-time patient flow. To support the analysis and management of ED operations, relevant data should be provided in an intuitive way. Within this context, this paper outlines the development of a dashboard which provides real-time information regarding ED crowding. The research project underlying this paper follows the principles of design science research, which involves the development and study of artifacts which aim to solve a generic problem. To determine the crowding indicators that are desired in the dashboard, a modified Delphi study is used. The dashboard is implemented using the open source Shinydashboard package in R. A dashboard is developed containing the desired crowding indicators, together with general patient flow characteristics. It is demonstrated using a dataset of a Flemish ED and fulfills the requirements which are defined a priori. The developed dashboard provides real-time information on ED crowding. This information enables ED staff to judge whether corrective actions are required in an effort to avoid the adverse effects of ED crowding. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Does Temporal Integration Occur for Unrecognizable Words in Visual Crowding?

    Science.gov (United States)

    Zhou, Jifan; Lee, Chia-Lin; Li, Kuei-An; Tien, Yung-Hsuan; Yeh, Su-Ling

    2016-01-01

    Visual crowding—the inability to see an object when it is surrounded by flankers in the periphery—does not block semantic activation: unrecognizable words due to visual crowding still generated robust semantic priming in subsequent lexical decision tasks. Based on the previous finding, the current study further explored whether unrecognizable crowded words can be temporally integrated into a phrase. By showing one word at a time, we presented Chinese four-word idioms with either a congruent or incongruent ending word in order to examine whether the three preceding crowded words can be temporally integrated to form a semantic context so as to affect the processing of the ending word. Results from both behavioral (Experiment 1) and Event-Related Potential (Experiment 2 and 3) measures showed congruency effect in only the non-crowded condition, which does not support the existence of unconscious multi-word integration. Aside from four-word idioms, we also found that two-word (modifier + adjective combination) integration—the simplest kind of temporal semantic integration—did not occur in visual crowding (Experiment 4). Our findings suggest that integration of temporally separated words might require conscious awareness, at least under the timing conditions tested in the current study. PMID:26890366

  9. Polymer crowding and shape distributions in polymer-nanoparticle mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Wei Kang; Denton, Alan R., E-mail: alan.denton@ndsu.edu [Department of Physics, North Dakota State University, Fargo, North Dakota 58108-6050 (United States)

    2014-09-21

    Macromolecular crowding can influence polymer shapes, which is important for understanding the thermodynamic stability of polymer solutions and the structure and function of biopolymers (proteins, RNA, DNA) under confinement. We explore the influence of nanoparticle crowding on polymer shapes via Monte Carlo simulations and free-volume theory of a coarse-grained model of polymer-nanoparticle mixtures. Exploiting the geometry of random walks, we model polymer coils as effective penetrable ellipsoids, whose shapes fluctuate according to the probability distributions of the eigenvalues of the gyration tensor. Accounting for the entropic cost of a nanoparticle penetrating a larger polymer coil, we compute the crowding-induced shift in the shape distributions, radius of gyration, and asphericity of ideal polymers in a theta solvent. With increased nanoparticle crowding, we find that polymers become more compact (smaller, more spherical), in agreement with predictions of free-volume theory. Our approach can be easily extended to nonideal polymers in good solvents and used to model conformations of biopolymers in crowded environments.

  10. Is Malnutrition Associated with Crowding in Permanent Dentition?

    Directory of Open Access Journals (Sweden)

    Erika B. A. F. Thomaz

    2010-09-01

    Full Text Available Evidence suggests that energy-protein malnutrition is associated with impaired growth and development of facial bones. The objective of this study was to investigate the association between nutritional status and reduced space for dental eruption (crowding in permanent dentition. A cross-sectional study with probabilistic sampling design was used. We evaluated 2,060 students aged 12 to 15 years enrolled in schools in the northeast of Brazil. Crowding was defined according to World Health Organization (WHO as misalignment of teeth due to lack of space for them to erupt in the correct position. Nutritional status was evaluated by means of body mass index and height-for-age, using the WHO’s reference curves. Parents and adolescents responded to a questionnaire about demographic, socioeconomic, biological and behavioral characteristics. The associations were estimated by odds ratio (OR in multivariate logistic regression analysis (alpha = 0.05. Confounding and effect-modification were taken into account. An association between low height-for-age (z-score < –1SD and crowding was only observed in adolescents with a prolonged history of mouth breathing (OR = 3.1. No association was observed between underweight and crowding. Malnutrition is related to crowding in permanent dentition among mouth-breathing adolescents. Policy actions aimed at reducing low height-for-age and unhealthy oral habits are strongly recommended. However, further studies are needed to increase the consistency of these findings and improve understanding of the subject.

  11. New insights into the crowd characteristics in Mina

    Science.gov (United States)

    Wang, J. Y.; Weng, W. G.; Zhang, X. L.

    2014-11-01

    The significance of the study of the characteristics of crowd behavior is indubitable for safely organizing mass activities. There is insufficient material to conduct such research. In this paper, the Mina crowd disaster is quantitatively re-investigated. Its instantaneous velocity field is extracted from video material based on the cross-correlation algorithm. The properties of the stop-and-go waves, including fluctuation frequencies, wave propagation speeds, characteristic speeds, and time and space averaged velocity variances, are analyzed in detail. Thus, the database of the stop-and-go wave features is enriched, which is very important to crowd studies. The ‘turbulent’ flows are investigated with the proper orthogonal decomposition (POD) method which is widely used in fluid mechanics. And time series and spatial analysis are conducted to investigate the characteristics of the ‘turbulent’ flows. In this paper, the coherent structures and movement process are described by the POD method. The relationship between the jamming point and crowd path is analyzed. And the pressure buffer recognized in this paper is consistent with Helbing's high-pressure region. The results revealed here may be helpful for facilities design, modeling crowded scenarios and the organization of large-scale mass activities.

  12. Hailstorms over Switzerland: Verification of Crowd-sourced Data

    Science.gov (United States)

    Noti, Pascal-Andreas; Martynov, Andrey; Hering, Alessandro; Martius, Olivia

    2016-04-01

    The reports of smartphone users, witnessing hailstorms, can be used as source of independent, ground-based observation data on ground-reaching hailstorms with high temporal and spatial resolution. The presented work focuses on the verification of crowd-sourced data collected over Switzerland with the help of a smartphone application recently developed by MeteoSwiss. The precise location, time of hail precipitation and the hailstone size are included in the crowd-sourced data, assessed on the basis of the weather radar data of MeteoSwiss. Two radar-based hail detection algorithms, POH (Probability of Hail) and MESHS (Maximum Expected Severe Hail Size), in use at MeteoSwiss are confronted with the crowd-sourced data. The available data and investigation time period last from June to August 2015. Filter criteria have been applied in order to remove false reports from the crowd-sourced data. Neighborhood methods have been introduced to reduce the uncertainties which result from spatial and temporal biases. The crowd-sourced and radar data are converted into binary sequences according to previously set thresholds, allowing for using a categorical verification. Verification scores (e.g. hit rate) are then calculated from a 2x2 contingency table. The hail reporting activity and patterns corresponding to "hail" and "no hail" reports, sent from smartphones, have been analyzed. The relationship between the reported hailstone sizes and both radar-based hail detection algorithms have been investigated.

  13. Polymer crowding and shape distributions in polymer-nanoparticle mixtures

    International Nuclear Information System (INIS)

    Lim, Wei Kang; Denton, Alan R.

    2014-01-01

    Macromolecular crowding can influence polymer shapes, which is important for understanding the thermodynamic stability of polymer solutions and the structure and function of biopolymers (proteins, RNA, DNA) under confinement. We explore the influence of nanoparticle crowding on polymer shapes via Monte Carlo simulations and free-volume theory of a coarse-grained model of polymer-nanoparticle mixtures. Exploiting the geometry of random walks, we model polymer coils as effective penetrable ellipsoids, whose shapes fluctuate according to the probability distributions of the eigenvalues of the gyration tensor. Accounting for the entropic cost of a nanoparticle penetrating a larger polymer coil, we compute the crowding-induced shift in the shape distributions, radius of gyration, and asphericity of ideal polymers in a theta solvent. With increased nanoparticle crowding, we find that polymers become more compact (smaller, more spherical), in agreement with predictions of free-volume theory. Our approach can be easily extended to nonideal polymers in good solvents and used to model conformations of biopolymers in crowded environments

  14. Low-molecular weight fractions of Japanese soy sauce act as a RAGE antagonist via inhibition of RAGE trafficking to lipid rafts.

    Science.gov (United States)

    Munesue, Seiichi; Yamamoto, Yasuhiko; Urushihara, Ryouta; Inomata, Kouhei; Saito, Hidehito; Motoyoshi, So; Watanabe, Takuo; Yonekura, Hideto; Yamamoto, Hiroshi

    2013-12-01

    Advanced glycation end-products (AGE) have been implicated in aging and the pathogenesis of diabetic complications, inflammation, Alzheimer's disease, and cancer. AGE engage the cell surface receptor for AGE (RAGE), which in turn elicits intracellular signaling, leading to activation of NF-κB to cause deterioration of tissue homeostasis. AGE are not only formed within our bodies but are also derived from foods, endowing them with flavor. In the present study, we assessed the agonistic/antagonistic effects of food-derived AGE on RAGE signaling in a reporter assay system and found that low-molecular weight AGE can antagonize the action of AGE-BSA. Foods tested were Japanese soy sauce, coffee, cola, and red wine, all of which showed fluorescence characteristics of AGE. Soy sauce and coffee contained N(ε)-carboxymethyl-lysine (CML). Soy sauce, coffee, and red wine inhibited the RAGE ligand-induced activation of NF-κB, whereas cola had no effect on the ligand induction of NF-κB. The liquids were then fractionated into high-molecular weight (HMW) fractions and low-molecular weight (LMW) fractions. Soy sauce-, coffee-, and red wine-derived LMW fractions consistently inhibited the RAGE ligand induction of NF-κB, whereas the HMW fractions of these foods activated RAGE signaling. Using the LMW fraction of soy sauce as a model food-derived RAGE antagonist, we performed a plate-binding assay and found that the soy sauce LMW fractions competitively inhibited AGE-RAGE association. Further, this fraction significantly reduced AGE-dependent monocyte chemoattractant protein-1 (MCP-1) secretion from murine peritoneal macrophages. The LMF from soy sauce suppressed the AGE-induced RAGE trafficking to lipid rafts. These results indicate that small components in some, if not all, foods antagonize RAGE signaling and could exhibit beneficial effects on RAGE-related diseases.

  15. Molecular insights into human monoamine oxidase (MAO) inhibition by 1,4-naphthoquinone: evidences for menadione (vitamin K3) acting as a competitive and reversible inhibitor of MAO.

    Science.gov (United States)

    Coelho Cerqueira, Eduardo; Netz, Paulo Augusto; Diniz, Cristiane; Petry do Canto, Vanessa; Follmer, Cristian

    2011-12-15

    Monoamine oxidase (MAO) catalyzes the oxidative deamination of biogenic and exogenous amines and its inhibitors have therapeutic value for several conditions including affective disorders, stroke, neurodegenerative diseases and aging. The discovery of 2,3,6-trimethyl-1,4-naphthoquinone (TMN) as a nonselective and reversible inhibitor of MAO, has suggested 1,4-naphthoquinone (1,4-NQ) as a potential scaffold for designing new MAO inhibitors. Combining molecular modeling tools and biochemical assays we evaluate the kinetic and molecular details of the inhibition of human MAO by 1,4-NQ, comparing it with TMN and menadione. Menadione (2-methyl-1,4-naphthoquinone) is a multitarget drug that acts as a precursor of vitamin K and an inducer of mitochondrial permeability transition. Herein we show that MAO-B was inhibited competitively by 1,4-NQ (K(i)=1.4 μM) whereas MAO-A was inhibited by non-competitive mechanism (K(i)=7.7 μM). Contrasting with TMN and 1,4-NQ, menadione exhibited a 60-fold selectivity for MAO-B (K(i)=0.4 μM) in comparison with MAO-A (K(i)=26 μM), which makes it as selective as rasagiline. Fluorescence and molecular modeling data indicated that these inhibitors interact with the flavin moiety at the active site of the enzyme. Additionally, docking studies suggest the phenyl side groups of Tyr407 and Tyr444 (for MAO-A) or Tyr398 and Tyr435 (for MAO-B) play an important role in the interaction of the enzyme with 1,4-NQ scaffold through forces of dispersion as verified for menadione, TMN and 1,4-NQ. Taken together, our findings reveal the molecular details of MAO inhibition by 1,4-NQ scaffold and show for the first time that menadione acts as a competitive and reversible inhibitor of human MAO. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Social identification moderates the effect of crowd density on safety at the Hajj.

    Science.gov (United States)

    Alnabulsi, Hani; Drury, John

    2014-06-24

    Crowd safety is a major concern for those attending and managing mass gatherings, such as the annual Hajj or pilgrimage to Mecca (also called Makkah). One threat to crowd safety at such events is crowd density. However, recent research also suggests that psychological membership of crowds can have positive benefits. We tested the hypothesis that the effect of density on safety might vary depending on whether there is shared social identification in the crowd. We surveyed 1,194 pilgrims at the Holy Mosque, Mecca, during the 2012 Hajj. Analysis of the data showed that the negative effect of crowd density on reported safety was moderated by social identification with the crowd. Whereas low identifiers reported reduced safety with greater crowd density, high identifiers reported increased safety with greater crowd density. Mediation analysis suggested that a reason for these moderation effects was the perception that other crowd members were supportive. Differences in reported safety across national groups (Arab countries and Iran compared with the rest) were also explicable in terms of crowd identification and perceived support. These findings support a social identity account of crowd behavior and offer a novel perspective on crowd safety management.

  17. Cloud-based crowd sensing: a framework for location-based crowd analyzer and advisor

    Science.gov (United States)

    Aishwarya, K. C.; Nambi, A.; Hudson, S.; Nadesh, R. K.

    2017-11-01

    Cloud computing is an emerging field of computer science to integrate and explore large and powerful computing systems and storages for personal and also for enterprise requirements. Mobile Cloud Computing is the inheritance of this concept towards mobile hand-held devices. Crowdsensing, or to be precise, Mobile Crowdsensing is the process of sharing resources from an available group of mobile handheld devices that support sharing of different resources such as data, memory and bandwidth to perform a single task for collective reasons. In this paper, we propose a framework to use Crowdsensing and perform a crowd analyzer and advisor whether the user can go to the place or not. This is an ongoing research and is a new concept to which the direction of cloud computing has shifted and is viable for more expansion in the near future.

  18. The 2D Structure of the T. brucei Preedited RPS12 mRNA Is Not Affected by Macromolecular Crowding

    Directory of Open Access Journals (Sweden)

    W.-Matthias Leeder

    2017-01-01

    Full Text Available Mitochondrial transcript maturation in African trypanosomes requires RNA editing to convert sequence-deficient pre-mRNAs into translatable mRNAs. The different pre-mRNAs have been shown to adopt highly stable 2D folds; however, it is not known whether these structures resemble the in vivo folds given the extreme “crowding” conditions within the mitochondrion. Here, we analyze the effects of macromolecular crowding on the structure of the mitochondrial RPS12 pre-mRNA. We use high molecular mass polyethylene glycol as a macromolecular cosolute and monitor the structure of the RNA globally and with nucleotide resolution. We demonstrate that crowding has no impact on the 2D fold and we conclude that the MFE structure in dilute solvent conditions represents a good proxy for the folding of the pre-mRNA in its mitochondrial solvent context.

  19. Jammed Humans in High-Density Crowd Disasters

    Science.gov (United States)

    Bottinelli, Arianna; Sumpter, David; Silverberg, Jesse

    When people gather in large groups like those found at Black Friday sales events, pilgrimages, heavy metal concerts, and parades, crowd density often becomes exceptionally high. As a consequence, these events can produce tragic outcomes such as stampedes and ''crowd crushes''. While human collective motion has been studied with active particle simulations, the underlying mechanisms for emergent behavior are less well understood. Here, we use techniques developed to study jammed granular materials to analyze an active matter model inspired by large groups of people gathering at a point of common interest. In the model, a single behavioral rule combined with body-contact interactions are sufficient for the emergence of a self-confined steady state, where particles fluctuate around a stable position. Applying mode analysis to this system, we find evidence for Goldstone modes, soft spots, and stochastic resonance, which may be the preferential mechanisms for dangerous emergent collective motions in crowds.

  20. Learning Multimodal Deep Representations for Crowd Anomaly Event Detection

    Directory of Open Access Journals (Sweden)

    Shaonian Huang

    2018-01-01

    Full Text Available Anomaly event detection in crowd scenes is extremely important; however, the majority of existing studies merely use hand-crafted features to detect anomalies. In this study, a novel unsupervised deep learning framework is proposed to detect anomaly events in crowded scenes. Specifically, low-level visual features, energy features, and motion map features are simultaneously extracted based on spatiotemporal energy measurements. Three convolutional restricted Boltzmann machines are trained to model the mid-level feature representation of normal patterns. Then a multimodal fusion scheme is utilized to learn the deep representation of crowd patterns. Based on the learned deep representation, a one-class support vector machine model is used to detect anomaly events. The proposed method is evaluated using two available public datasets and compared with state-of-the-art methods. The experimental results show its competitive performance for anomaly event detection in video surveillance.

  1. Household crowding and psychosocial health among Inuit in Greenland

    DEFF Research Database (Denmark)

    Riva, Mylène; Larsen, Christina Viskum Lytken; Bjerregaard, Peter

    2014-01-01

    men and women are differently influenced by their housing conditions. METHODS: Data on more than 3,000 Inuit aged 18 years and older are from the Inuit health in transition Greenland survey. Associations between household crowding and composition, and mental well-being and binge drinking were examined......OBJECTIVES: Poor housing conditions experienced by many Indigenous peoples threaten their health and well-being. This study examines whether household crowding is associated with poorer psychosocial health among Greenlanders, and the mediating role of social support. It also assesses whether Inuit...... using logistic regression models, adjusting for individuals' characteristics. RESULTS: Household crowding was associated with poorer mental well-being. Binge drinking was more common among people living in households without children. These effects were more important for women than for men...

  2. Direct crowding out, optimal taxation and pollution abatement

    Energy Technology Data Exchange (ETDEWEB)

    Van der Ploeg, Frederick [FEE, University of Amsterdam, Amsterdam (Netherlands); Bovenberg, A. Lans [CentER, Tilburg University, Tilburg (Netherlands)

    1993-05-01

    The interactions between direct crowding out, the provision of public goods, optimal taxation and environmental policy are explored. Greener preferences induce a larger tax rate by raising the non-distortionary level of the tax rate. If the marginal productivity of public abatement diminishes rapidly environmental quality improves mainly through a fall in economic activity and emissions. In this case, public consumption increases which crowds out labour supply and private consumption. However, if environmental policy is very effective public consumption falls in order to make room for public abatement. In this case, if labour supply is inelastic with respect to the after-tax wage and direct crowding in is strong, labour supply and economic activity may expand. 1 fig., 7 refs.

  3. The wisdom of the crowd playing The Price Is Right.

    Science.gov (United States)

    Lee, Michael D; Zhang, Shunan; Shi, Jenny

    2011-07-01

    In The Price Is Right game show, players compete to win a prize, by placing bids on its price. We ask whether it is possible to achieve a "wisdom of the crowd" effect, by combining the bids to produce an aggregate price estimate that is superior to the estimates of individual players. Using data from the game show, we show that a wisdom of the crowd effect is possible, especially by using models of the decision-making processes involved in bidding. The key insight is that, because of the competitive nature of the game, what people bid is not necessarily the same as what they know. This means better estimates are formed by aggregating latent knowledge than by aggregating observed bids. We use our results to highlight the usefulness of models of cognition and decision-making in studying the wisdom of the crowd, which are often approached only from non-psychological statistical perspectives.

  4. The Crowding out Effect on the Labor Market in Romania

    Directory of Open Access Journals (Sweden)

    Mihaela Hrisanta DOBRE

    2011-01-01

    Full Text Available Discrimination expresses any distinction, exclusion, restriction, preference or different treatment that disadvantages a person or group, in comparison with others in similar situations. The crowding out effect was first formulated by Bergmann (1974 and explains that an individual can obtain lower returns if he belongs to a branch dominated by the members of another group. The difference in pay between women and men is also reinforced by the segregation in the labor market, which may explain the crowding out effect. In this article we analyzed the level of segregation in the Romanian labor market starting from the workers professional status and their distribution by branch from 2003 to 2008. Crowding out effect was analyzed based on the gain function of the two groups (women and men.

  5. PREFACE: Complex dynamics of fluids in disordered and crowded environments Complex dynamics of fluids in disordered and crowded environments

    Science.gov (United States)

    Coslovich, Daniele; Kahl, Gerhard; Krakoviack, Vincent

    2011-06-01

    discussions it became evident that the close scientific contact between theory, simulation and experiment brought along a fruitful and mutually inspiring atmosphere. On the theoretical side, these discussions have allowed clarification of several connections between the dynamics of models of fluids in porous media (quenched-annealed, pinned particles models), those of well-known limiting cases (Lorentz gas), of realistic models of liquids with strong dynamic asymmetry (asymmetric size and mass mixtures, sodium silicates, polymers blends) and even of bulk glass-formers. On the experimental side, it appeared that soft matter systems may provide an excellent test-bed to verify the theoretical predictions. From the concluding discussion it was also clear that addressing related issues relevant to biology still remains an open challenge for the future. In view of all this, it was concluded that within a short time period a workshop with analogous scope should be organized to address the progress made on both fundamental and interdisciplinary aspects. The realization of this workshop was made possible by generous financial support from CECAM, Centre Blaise Pascal-ENS de Lyon, and the ESF network 'Molecular Simulations in Biosystems and Material Science' (SimBioMa). Complex dynamics of fluids in disordered and crowded environments contents Phonon dispersions of cluster crystals Tim Neuhaus and Christos N Likos Challenges in determining anomalous diffusion in crowded fluids Marcel Hellmann, Joseph Klafter, Dieter W Heermann and Matthias Weiss Diffusion of active tracers in fluctuating fields David S Dean and Vincent Démery Self-diffusion of non-interacting hard spheres in particle gels Jean-Christophe Gimel and Taco Nicolai Probing glassy states in binary mixtures of soft interpenetrable colloids E Stiakakis, B M Erwin, D Vlassopoulos, M Cloitre, A Munam, M Gauthier, H Iatrou and N Hadjichristidis Fluids with quenched disorder: scaling of the free energy barrier near critical points

  6. Towards Detecting the Crowd Involved in Social Events

    Directory of Open Access Journals (Sweden)

    Wei Huang

    2017-10-01

    Full Text Available Knowing how people interact with urban environments is fundamental for a variety of fields, ranging from transportation to social science. Despite the fact that human mobility patterns have been a major topic of study in recent years, a challenge to understand large-scale human behavior when a certain event occurs remains due to a lack of either relevant data or suitable approaches. Psychological crowd refers to a group of people who are usually located at different places and show different behaviors, but who are very sensitively driven to take the same act (gather together by a certain event, which has been theoretically studied by social psychologists since the 19th century. This study aims to propose a computational approach using a machine learning method to model psychological crowds, contributing to the better understanding of human activity patterns under events. Psychological features and mental unity of the crowd are computed to detect the involved individuals. A national event happening across the USA in April, 2015 is analyzed using geotagged tweets as a case study to test our approach. The result shows that 81% of individuals in the crowd can be successfully detected. Through investigating the geospatial pattern of the involved users, not only can the event related users be identified but also those unobserved users before the event can be uncovered. The proposed approach can effectively represent the psychological feature and measure the mental unity of the psychological crowd, which sheds light on the study of large-scale psychological crowd and provides an innovative way to understanding human behavior under events.

  7. How social influence can undermine the wisdom of crowd effect

    Science.gov (United States)

    Lorenz, Jan; Rauhut, Heiko; Schweitzer, Frank; Helbing, Dirk

    2011-01-01

    Social groups can be remarkably smart and knowledgeable when their averaged judgements are compared with the judgements of individuals. Already Galton [Galton F (1907) Nature 75:7] found evidence that the median estimate of a group can be more accurate than estimates of experts. This wisdom of crowd effect was recently supported by examples from stock markets, political elections, and quiz shows [Surowiecki J (2004) The Wisdom of Crowds]. In contrast, we demonstrate by experimental evidence (N = 144) that even mild social influence can undermine the wisdom of crowd effect in simple estimation tasks. In the experiment, subjects could reconsider their response to factual questions after having received average or full information of the responses of other subjects. We compare subjects’ convergence of estimates and improvements in accuracy over five consecutive estimation periods with a control condition, in which no information about others’ responses was provided. Although groups are initially “wise,” knowledge about estimates of others narrows the diversity of opinions to such an extent that it undermines the wisdom of crowd effect in three different ways. The “social influence effect” diminishes the diversity of the crowd without improvements of its collective error. The “range reduction effect” moves the position of the truth to peripheral regions of the range of estimates so that the crowd becomes less reliable in providing expertise for external observers. The “confidence effect” boosts individuals’ confidence after convergence of their estimates despite lack of improved accuracy. Examples of the revealed mechanism range from misled elites to the recent global financial crisis. PMID:21576485

  8. Modeling, simulation and visual analysis of crowds a multidisciplinary perspective

    CERN Document Server

    Ali, Saad; Manocha, Dinesh; Shah, Mubarak

    2013-01-01

    Over the last several years there has been a growing interest in developing computational methodologies for modeling and analyzing movements and behaviors of 'crowds' of people. This interest spans several scientific areas that includes Computer Vision, Computer Graphics, and Pedestrian Evacuation Dynamics. Despite the fact that these different scientific fields are trying to model the same physical entity (i.e. a crowd of people), research ideas have evolved independently. As a result each discipline has developed techniques and perspectives that are characteristically their own.

  9. Crowd-sourced Archaeological Research: The MicroPasts Project

    Directory of Open Access Journals (Sweden)

    Chiara Bonacchi

    2014-10-01

    Full Text Available This paper offers a brief introduction to MicroPasts, a web-enabled crowd-sourcing and crowd-funding project whose overall goal is to promote the collection and use of high quality research data via institutional and community collaborations, both on- and off-line. In addition to introducing this initiative, the discussion below is a reflection of its lead author’s core contribution to the project and will dwell in more detail on one particular aspect of MicroPasts: its relevance to research and practice in public archaeology, cultural policy and heritage studies.

  10. Leveraging the wisdom of the crowd in software testing

    CERN Document Server

    Sharma, Mukesh

    2015-01-01

    Its scale, flexibility, cost effectiveness, and fast turnaround are just a few reasons why crowdsourced testing has received so much attention lately. While there are a few online resources that explain what crowdsourced testing is all about, there's been a need for a book that covers best practices, case studies, and the future of this technique.Filling this need, Leveraging the Wisdom of the Crowd in Software Testing shows you how to leverage the wisdom of the crowd in your software testing process. Its comprehensive coverage includes the history of crowdsourcing and crowdsourced testing, im

  11. Contemporary understanding of riots: Classical crowd psychology, ideology and the social identity approach.

    Science.gov (United States)

    Stott, Clifford; Drury, John

    2016-04-01

    This article explores the origins and ideology of classical crowd psychology, a body of theory reflected in contemporary popularised understandings such as of the 2011 English 'riots'. This article argues that during the nineteenth century, the crowd came to symbolise a fear of 'mass society' and that 'classical' crowd psychology was a product of these fears. Classical crowd psychology pathologised, reified and decontextualised the crowd, offering the ruling elites a perceived opportunity to control it. We contend that classical theory misrepresents crowd psychology and survives in contemporary understanding because it is ideological. We conclude by discussing how classical theory has been supplanted in academic contexts by an identity-based crowd psychology that restores the meaning to crowd action, replaces it in its social context and in so doing transforms theoretical understanding of 'riots' and the nature of the self. © The Author(s) 2016.

  12. Radiation-induced enteropathy: Molecular basis of pentoxifylline–vitamin E anti-fibrotic effect involved TGF-β1 cascade inhibition

    International Nuclear Information System (INIS)

    Hamama, Saad; Gilbert-Sirieix, Marie; Vozenin, Marie-Catherine; Delanian, Sylvie

    2012-01-01

    Background: Radiation-induced fibrosis is a serious late complication of radiotherapy. Pentoxifylline–vitamin E has proven effective and safe in clinical trials in the treatment of fibrosis, while the molecular mechanism of its activity is yet unexplored. Methods: Ten patients suffering from radiation-induced enteropathy were treated with pentoxifylline–vitamin E combination with SOMA score as the primary endpoint. In parallel, primary smooth muscle cells isolated from intestinal samples isolated from humans with radiation enteropathy were incubated with pentoxifylline, trolox (vit. E hydrophilic analogous) or their combination. Activation of the TGF-β1/Smad and Rho/ROCK pathways was subsequently investigated using Q-RT-PCR, gene reporter, Western-blot, ELISA and immunohistochemistry. Results: Pentoxifylline–vitamin E combination induces regression of symptoms (SOMA) by −41% and −80% at 6 and 18 months. In vitro, pentoxifylline and trolox synergize to inhibit TGF-β1 protein and mRNA expression. This inhibitory action is mediated at the transcriptional level and leads to subsequent inhibition of TGF-β1/Smad targets (Col Iα1, FN1, PAI-1, CTGF), while it has no effect on the Rho/ROCK pathway. Conclusions: The anti-fibrotic effect of combined pentoxifylline–vitamin E is at least in part mediated by inhibition of the TGF-β1 cascade. It strengthens previous clinical data showing pentoxifylline–vitamin E synergy and supports its use as a first-line treatment of radiation-induced fibrosis.

  13. College Crowd-In: How Private Donations Positively Affect Alumni Giving

    Science.gov (United States)

    Gottfried, Michael A.

    2008-01-01

    The issue of donor behavior and crowding out has been pertinent in the economics literature, both theoretically and empirically. Aggregate research has not been decisive, nor have many studies analyzed education institutions. I begin with a theoretical model of crowding-out versus crowding-in donor behavior. I then employ a fixed effects…

  14. Crowd science : it is not just a matter of time (or funding)

    NARCIS (Netherlands)

    Vasileiadou, E.

    2014-01-01

    The last years, citizen science, or crowd science, has increased tremendously, both in number of projects, and number of participants. Most literature on crowd science focuses on its advantages, for both scientists, and the participating citizens. The challenges of crowd science come mainly from

  15. On current crowd management practices and the need for increased situation awareness, prediction, and intervention

    NARCIS (Netherlands)

    Martella, C.; Li, J.; Conrado, C.; Vermeeren, A.

    2017-01-01

    Recent accidents (News, 2006, 2010, 2013, 2015) show that crowded events can quickly turn into tragedies. The goal of crowd management is to avoid such accidents through careful planning and implementation. Crowd management practices are collaborative efforts between the different actors of the

  16. Molecular mechanism of 9-cis-retinoic acid inhibition of adipogenesis in 3T3-L1 cells

    International Nuclear Information System (INIS)

    Sagara, Chiaki; Takahashi, Katsuhiko; Kagechika, Hiroyuki; Takahashi, Noriko

    2013-01-01

    Highlights: ► We examined the effects of 9-cis-RA on adipogenesis in mouse preadipocyte 3T3-L1. ► 9-cis-RA inhibited lipid accumulation in adipogenetically-induced 3T3-L1 cells. ► A RXR pan-antagonist suppressed the inhibitory effects of 9-cis-RA on adipogenesis. ► This antagonist had no effects on RXRα and PPARγ levels in 9-cis-RA-treated cells. ► 9-cis-RA-induced decrease in both RXRα and PPARγ was independent of RXR activation. -- Abstract: Retinoic acid (RA) signaling is mediated by specific nuclear hormone receptors. Here we examined the effects of 9-cis-RA on adipogenesis in mouse preadipocyte 3T3-L1 cells. 9-cis-RA inhibits the lipid accumulation of adipogenetically induced 3T3-L1 cells. The complex of retinoid X receptor α (RXRα) with peroxisome proliferator-activated receptor γ (PPARγ) is a major transcription factor in the process of adipogenesis, and the levels of these molecules were decreased by 9-cis-RA treatment. A RXR pan-antagonist suppressed 9-cis-RA’s inhibitory effects on adipogenesis, but not on the intracellular levels of both RXRα and PPARγ. These results suggest that 9-cis-RA could inhibit adipogenesis by activating RXR, and decrease both RXR and PPARγs levels in a RXR activation-independent manner

  17. Molecular and Functional Characterization of a Polygalacturonase-Inhibiting Protein from Cynanchum komarovii That Confers Fungal Resistance in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Nana Liu

    Full Text Available Compliance with ethical standards: This study did not involve human participants and animals, and the plant of interest is not an endangered species. Polygalacturonase-inhibiting proteins (PGIPs are leucine-rich repeat proteins that plants produce against polygalacturonase, a key virulence agent in pathogens. In this paper, we cloned and purified CkPGIP1, a gene product from Cynanchum komarovii that effectively inhibits polygalacturonases from Botrytis cinerea and Rhizoctonia solani. We found the expression of CkPGIP1 to be induced in response to salicylic acid, wounding, and infection with B. cinerea and R. solani. In addition, transgenic overexpression in Arabidopsis enhanced resistance against B. cinerea. Furthermore, CkPGIP1 obtained from transgenic Arabidopsis inhibited the activity of B. cinerea and R. solani polygalacturonases by 62.7-66.4% and 56.5-60.2%, respectively. Docking studies indicated that the protein interacts strongly with the B1-sheet at the N-terminus of the B. cinerea polygalacturonase, and with the C-terminus of the polygalacturonase from R. solani. This study highlights the significance of CkPGIP1 in plant disease resistance, and its possible application to manage fungal pathogens.

  18. Docking and molecular dynamics studies of peripheral site ligand–oximes as reactivators of sarin-inhibited human acetylcholinesterase

    NARCIS (Netherlands)

    Almeida, J.S.F.D. de; Cuya Guizado, T.R.; Guimarães, A.P.; Ramalho, T.C.; Gonçalves, A.S.; Koning, M.C. de; França, T.C.C.

    2016-01-01

    In the present work, we performed docking and molecular dynamics simulations studies on two groups of long-tailored oximes designed as peripheral site binders of acetylcholinesterase (AChE) and potential penetrators on the blood brain barrier. Our studies permitted to determine how the tails anchor

  19. Protein-Glycan Quinary Interactions in Crowding Environment Unveiled by NMR Spectroscopy.

    Science.gov (United States)

    Diniz, Ana; Dias, Jorge S; Jiménez-Barbero, Jesús; Marcelo, Filipa; Cabrita, Eurico J

    2017-09-21

    Protein-glycan interactions as modulators for quinary structures in crowding environments were explored. The interaction between human galectin 3 (Gal-3) and distinct macromolecular crowders, such as bovine and human serum albumin (BSA and HSA), Ficoll 70 and PEG3350, was scrutinized. The molecular recognition event of the specific ligand, lactose, by Gal-3 in crowding conditions was evaluated. Gal-3 interactions were monitored by NMR analysing chemical shift perturbation (CSP) and line broadening of 1 H 15 N-HSQC signals. The intensity of the Gal-3 1 H 15 N-HSQC signals decreased in the presence of all crowders, due to the increase in the solution viscosity and to the formation of large protein complexes. When glycosylated containing samples of BSA and HSA were used, signal broadening was more severe than that observed in the presence of the more viscous solutions of PEG3350 and Ficoll 70. However, for the samples containing glycoproteins, the signal intensity of 1 H 15 N-HSQC recovered upon addition of lactose. We show that serum proteins interact with Gal-3, through their α2,3-linked sialylgalactose moieties exposed at their surfaces, competing with lactose for the same binding site. The quinary interaction between Gal-3 and serum glycoproteins, could help to co-localize Gal-3 at the cell surface, and may play a role in adhesion and signalling functions of this protein. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Inhibition coefficient and molecular diversity of multi stress tolerant Trichoderma as potential biocontrol agent against Sclerotium rolfsii Sacc.

    Science.gov (United States)

    Hirpara, Darshna G; Gajera, H P; Hirapara, Jaydeep G; Golakiya, B A

    2017-11-01

    Trichoderma is one of the most exploited biocontrol agent for the management of plant diseases. Twenty strains of Trichoderma (six of T. harzianum, four of T. viride, three of T. virens, three of T. koningii, each one of T. hamatum, T. reesei, T. parceramosum and Trichoderma spp.) subjected to in vitro antagonism up to 12days after inoculation against Sclerotium rolfsii Sacc. causing stem rot in groundnut. A new concept was developed to determine inhibition coefficient representing pathogen biology and biocontrol related biophysical variables. Results explained differential inhibition coefficient of test pathogen by Trichoderma antagonists. The inhibition coefficient of test pathogen was examined highest (91.13%) by T. virens NBAII Tvs12 followed by T. virens MTCC 794 (89.33%) and T. koningii MTCC 796 (62.39%). Microscopic study confirmed biocontrol mechanism as mycoparasitism for Tvs12 and antibiosis for T. koningii MTCC 796. The sclerotial biogenesis of test pathogen was elevated during weak antagonism and diminished in interactions with strong antagonists. The inhibition coefficient of S. rolfsii was significantly negatively correlated with sclerotia formation and lipid peroxidation during the antagonism. Trichoderma strains were screened for fungicides (carbendazim and tebuconazole, thiram and mancozeb) and abiotic stress (drought and salt) tolerance. Results indicated that T. koningii MTCC 796 efficiently grew better than the other strains with maximum radial growth under adverse conditions. The genetic variability among the Trichoderma was determined using 34 gene specific markers which amplified 146 alleles. The SSR similarities explained substantial diversity (15 to 87%) across Trichoderma strains and pathogen S. rolfsii. Principal coordinates analysis (PCA) were comparable to the cluster analysis and first three most informative PC components explained 64.45% of the total variation. In PCA, potent antagonists appear to be distinct from other strains. Five

  1. Molecular and preclinical basis to inhibit PGE2 receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis

    Science.gov (United States)

    Arosh, Joe A.; Lee, JeHoon; Balasubbramanian, Dakshnapriya; Stanley, Jone A.; Long, Charles R.; Meagher, Mary W.; Osteen, Kevin G.; Bruner-Tran, Kaylon L.; Burghardt, Robert C.; Starzinski-Powitz, Anna; Banu, Sakhila K.

    2015-01-01

    Endometriosis is a debilitating, estrogen-dependent, progesterone-resistant, inflammatory gynecological disease of reproductive age women. Two major clinical symptoms of endometriosis are chronic intolerable pelvic pain and subfertility or infertility, which profoundly affect the quality of life in women. Current hormonal therapies to induce a hypoestrogenic state are unsuccessful because of undesirable side effects, reproductive health concerns, and failure to prevent recurrence of disease. There is a fundamental need to identify nonestrogen or nonsteroidal targets for the treatment of endometriosis. Peritoneal fluid concentrations of prostaglandin E2 (PGE2) are higher in women with endometriosis, and this increased PGE2 plays important role in survival and growth of endometriosis lesions. The objective of the present study was to determine the effects of pharmacological inhibition of PGE2 receptors, EP2 and EP4, on molecular and cellular aspects of the pathogenesis of endometriosis and associated clinical symptoms. Using human fluorescent endometriotic cell lines and chimeric mouse model as preclinical testing platform, our results, to our knowledge for the first time, indicate that selective inhibition of EP2/EP4: (i) decreases growth and survival of endometriosis lesions; (ii) decreases angiogenesis and innervation of endometriosis lesions; (iii) suppresses proinflammatory state of dorsal root ganglia neurons to decrease pelvic pain; (iv) decreases proinflammatory, estrogen-dominant, and progesterone-resistant molecular environment of the endometrium and endometriosis lesions; and (v) restores endometrial functional receptivity through multiple mechanisms. Our novel findings provide a molecular and preclinical basis to formulate long-term nonestrogen or nonsteroidal therapy for endometriosis. PMID:26199416

  2. Agent-based simulation of reactions in the crowded and structured intracellular environment: Influence of mobility and location of the reactants

    Directory of Open Access Journals (Sweden)

    Lapin Alexei

    2011-05-01

    Full Text Available Abstract Background In this paper we apply a novel agent-based simulation method in order to model intracellular reactions in detail. The simulations are performed within a virtual cytoskeleton enriched with further crowding elements, which allows the analysis of molecular crowding effects on intracellular diffusion and reaction rates. The cytoskeleton network leads to a reduction in the mobility of molecules. Molecules can also unspecifically bind to membranes or the cytoskeleton affecting (i the fraction of unbound molecules in the cytosol and (ii furthermore reducing the mobility. Binding of molecules to intracellular structures or scaffolds can in turn lead to a microcompartmentalization of the cell. Especially the formation of enzyme complexes promoting metabolic channeling, e.g. in glycolysis, depends on the co-localization of the proteins. Results While the co-localization of enzymes leads to faster reaction rates, the reduced mobility decreases the collision rate of reactants, hence reducing the reaction rate, as expected. This effect is most prominent in diffusion limited reactions. Furthermore, anomalous diffusion can occur due to molecular crowding in the cell. In the context of diffusion controlled reactions, anomalous diffusion leads to fractal reaction kinetics. The simulation framework is used to quantify and separate the effects originating from molecular crowding or the reduced mobility of the reactants. We were able to define three factors which describe the effective reaction rate, namely f diff for the diffusion effect, f volume for the crowding, and f access for the reduced accessibility of the molecules. Conclusions Molecule distributions, reaction rate constants and structural parameters can be adjusted separately in the simulation allowing a comprehensive study of individual effects in the context of a realistic cell environment. As such, the present simulation can help to bridge the gap between in vivo and in vitro

  3. Editorial Bias in Crowd-Sourced Political Information.

    Directory of Open Access Journals (Sweden)

    Joshua L Kalla

    Full Text Available The Internet has dramatically expanded citizens' access to and ability to engage with political information. On many websites, any user can contribute and edit "crowd-sourced" information about important political figures. One of the most prominent examples of crowd-sourced information on the Internet is Wikipedia, a free and open encyclopedia created and edited entirely by users, and one of the world's most accessed websites. While previous studies of crowd-sourced information platforms have found them to be accurate, few have considered biases in what kinds of information are included. We report the results of four randomized field experiments that sought to explore what biases exist in the political articles of this collaborative website. By randomly assigning factually true but either positive or negative and cited or uncited information to the Wikipedia pages of U.S. senators, we uncover substantial evidence of an editorial bias toward positivity on Wikipedia: Negative facts are 36% more likely to be removed by Wikipedia editors than positive facts within 12 hours and 29% more likely within 3 days. Although citations substantially increase an edit's survival time, the editorial bias toward positivity is not eliminated by inclusion of a citation. We replicate this study on the Wikipedia pages of deceased as well as recently retired but living senators and find no evidence of an editorial bias in either. Our results demonstrate that crowd-sourced information is subject to an editorial bias that favors the politically active.

  4. Editorial Bias in Crowd-Sourced Political Information.

    Science.gov (United States)

    Kalla, Joshua L; Aronow, Peter M

    2015-01-01

    The Internet has dramatically expanded citizens' access to and ability to engage with political information. On many websites, any user can contribute and edit "crowd-sourced" information about important political figures. One of the most prominent examples of crowd-sourced information on the Internet is Wikipedia, a free and open encyclopedia created and edited entirely by users, and one of the world's most accessed websites. While previous studies of crowd-sourced information platforms have found them to be accurate, few have considered biases in what kinds of information are included. We report the results of four randomized field experiments that sought to explore what biases exist in the political articles of this collaborative website. By randomly assigning factually true but either positive or negative and cited or uncited information to the Wikipedia pages of U.S. senators, we uncover substantial evidence of an editorial bias toward positivity on Wikipedia: Negative facts are 36% more likely to be removed by Wikipedia editors than positive facts within 12 hours and 29% more likely within 3 days. Although citations substantially increase an edit's survival time, the editorial bias toward positivity is not eliminated by inclusion of a citation. We replicate this study on the Wikipedia pages of deceased as well as recently retired but living senators and find no evidence of an editorial bias in either. Our results demonstrate that crowd-sourced information is subject to an editorial bias that favors the politically active.

  5. Nonlinear Effects in Examples of Crowd Evacuation Scenarios

    DEFF Research Database (Denmark)

    Starke, Jens; Berg Thomsen, Kristian; Sørensen, Asger

    2014-01-01

    Severe accidents with many fatalities have occurred when too many pedestrians had to maneuver in too tight surroundings, as during evacuations of mass events. This demonstrates the importance of a better general understanding of pedestrians and emergent complex behavior in crowds. To this end, we...

  6. Indoor guided evacuation: TIN for graph generation and crowd evacuation

    Directory of Open Access Journals (Sweden)

    Mengchao Xu

    2016-05-01

    Full Text Available This paper presents two complementary methods: an approach to compute a network data-set for indoor space of a building by using its two-dimensional (2D floor plans and limited semantic information, combined with an optimal crowd evacuation method. The approach includes three steps: (1 generate critical points in the space, (2 connect neighbour points to build up the network, and then (3 run the optimal algorithm for optimal crowd evacuation from a room to the exit gates of the building. Triangulated Irregular Network (TIN is used in the first two steps. The optimal evacuation crowd is not based on the nearest evacuation gate for a person but relies on optimal sorting of the waiting lists at each gate of the room to be evacuated. As an example case, a rectangular room with 52 persons with two gates is evacuated in 102 elementary interval times (one interval corresponds to the time for one step for normal velocity walking, whereas it would have been evacuated in not less than 167 elementary steps. The procedure for generating the customized network involves the use of 2D floor plans of a building and some common Geographic Information System (GIS functions. This method combined with the optimal sorting lists will be helpful for guiding crowd evacuation during any emergency.

  7. Sequential sampling, magnitude estimation, and the wisdom of crowds

    DEFF Research Database (Denmark)

    Nash, Ulrik W.

    2017-01-01

    in the wisdom of crowds indicated by judgment distribution skewness. The present study reports findings from an experiment on magnitude estimation and supports these predictions. The study moreover demonstrates that systematic errors by groups of people can be corrected using information about the judgment...

  8. Crowding depression of UV-mutagenesis in E. coli

    International Nuclear Information System (INIS)

    Bockrath, R.; Harper, D.; Kristoff, S.; Stanford Univ., CA

    1980-01-01

    Strains of E. coli Br were exposed to UV radiation and assayed for reversion mutation, using a standard selection medium. If more irradiated bacteria were assayed per petri dish, a proportional increase in the number of indicated reversion mutants was oud only up to a limiting plating density. Beyond a density of about 10 8 viable bacteria per petri dish, the number of indicated revertants per viable bacteriy assayed (the mutation frequency) decreased as the plating density was increased. The crowding depression of mutagenesis was more severe for de novo and converted suppressor mutations, the mutation frequency being reduced 100-fold at a plating density of about 6 x 10 9 viable bacteria per plate. The effect on backmutation was 10 times less. Crowding depression of mutagenesis occured in excision-proficient and -deficient strains, with identical effects in the 2 strains on de novo and converted suppressor mutation, but different effects on backmutations. There were no accompanying effects on viability. Irreversible loss of potential mutants during crowded growth was indicated in wash-off experiments. The kinetics suggested a half-life of approximately 1 h. Kinetics for accumulation by the bacteria of the limiting metabolite (tyrosine) on the assay plate indicated a short period of time for protein synthesis, but direct examination of the proteins synthesized during early growth on a crowded plate demonstrated successful induction of recA protein. (orig.)

  9. Chenang Beach and its Crowding Capacity: A Malaysian Perspective

    Directory of Open Access Journals (Sweden)

    Mohamad Diana

    2014-01-01

    Full Text Available This working paper focuses in enjoyment factors, specifically: number of beach users, perceived maximum number of beach users accepted, perceived maximum number of beach users that affects the tourism experience and perceived maximum number of beach users that affects the beach quality. At a deeper extent, the evaluation is categorized by number of visitation, visitation motivations, and Chenang Island’s push and pull factors. Relationships between variables were assessed using a two-phase evaluation framework where interestingly, only one demographic factor works with all the studied independent variables. It is also learned that the density of an area number of people seen is considered as a n accepted crowding factor, as opposed to this working paper scope experienced crowding . A unique relationship was observed for crowding level, and visitation satisfaction level and overall evaluation of Chenang beach quality. This working paper further supports the previous literature on the significance of beach carrying capacity management and it is learned that the idea of crowding standard is interlinks with ‘gender, ‘time spend’ and ‘number of boaters’. From findings, this working paper envisages the preferences polar exchange where this should be of interest to tourism-related personnel. It is within this working paper interest to highlight the pressing need in brandishing the image of Chenang Beach. This is to ensure that Chenang Beach, as a field, is maintaining its importance and popularity.

  10. The Gender Pay Gap, Fringe Benefits, and Occupational Crowding.

    Science.gov (United States)

    Solberg, Eric; Laughlin, Teresa

    1995-01-01

    In estimating earnings equations for seven occupations, when fringe benefits are excluded, women receive significantly lower wages in all but the most female-dominated occupation. Including fringe benefits makes gender significant in only one occupational category. Crowding of one gender into an occupation appears the primary determinant of the…

  11. Passengers, Crowding and Complexity : Models for passenger oriented public transport

    NARCIS (Netherlands)

    P.C. Bouman (Paul)

    2017-01-01

    markdownabstractPassengers, Crowding and Complexity was written as part of the Complexity in Public Transport (ComPuTr) project funded by the Netherlands Organisation for Scientific Research (NWO). This thesis studies in three parts how microscopic data can be used in models that have the potential

  12. Track-based event recognition in a realistic crowded environment

    NARCIS (Netherlands)

    Huis, J.R. van; Bouma, H.; Baan, J.; Burghouts, G.J.; Eendebak, P.T.; Hollander, R.J.M.; Dijk, J.; Rest, J.H.C. van

    2014-01-01

    Automatic detection of abnormal behavior in CCTV cameras is important to improve the security in crowded environments, such as shopping malls, airports and railway stations. This behavior can be characterized at different time scales, e.g., by small-scale subtle and obvious actions or by large-scale

  13. Crowd Analysis by Using Optical Flow and Density Based Clustering

    DEFF Research Database (Denmark)

    Santoro, Francesco; Pedro, Sergio; Tan, Zheng-Hua

    2010-01-01

    In this paper, we present a system to detect and track crowds in a video sequence captured by a camera. In a first step, we compute optical flows by means of pyramidal Lucas-Kanade feature tracking. Afterwards, a density based clustering is used to group similar vectors. In the last step...

  14. Crowd science user contribution patterns and their implications

    Science.gov (United States)

    Sauermann, Henry; Franzoni, Chiara

    2015-01-01

    Scientific research performed with the involvement of the broader public (the crowd) attracts increasing attention from scientists and policy makers. A key premise is that project organizers may be able to draw on underused human resources to advance research at relatively low cost. Despite a growing number of examples, systematic research on the effort contributions volunteers are willing to make to crowd science projects is lacking. Analyzing data on seven different projects, we quantify the financial value volunteers can bring by comparing their unpaid contributions with counterfactual costs in traditional or online labor markets. The volume of total contributions is substantial, although some projects are much more successful in attracting effort than others. Moreover, contributions received by projects are very uneven across time-a tendency toward declining activity is interrupted by spikes typically resulting from outreach efforts or media attention. Analyzing user-level data, we find that most contributors participate only once and with little effort, leaving a relatively small share of users who return responsible for most of the work. Although top contributor status is earned primarily through higher levels of effort, top contributors also tend to work faster. This speed advantage develops over multiple sessions, suggesting that it reflects learning rather than inherent differences in skills. Our findings inform recent discussions about potential benefits from crowd science, suggest that involving the crowd may be more effective for some kinds of projects than others, provide guidance for project managers, and raise important questions for future research.

  15. Households' ethnic background and crowding in public housing ...

    African Journals Online (AJOL)

    Crowded housing is one of the housing stresses that bother policy makers and housing ... ethnic and cultural origins occupying Lagos State Development and Property ... groups should be deliberately mixed to achieve ethnic and social integration. ... FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of Use ...

  16. Some Numerical Aspects on Crowd Motion - The Hughes Model

    KAUST Repository

    Gomes, Diogo A.; Machado Velho, Roberto

    2016-01-01

    Here, we study a crowd model proposed by R. Hughes in [5] and we describe a numerical approach to solve it. This model comprises a Fokker-Planck equation coupled with an Eikonal equation with Dirichlet or Neumann data. First, we establish a priori

  17. Which updates during an equity crowdfunding campaign increase crowd participation?

    NARCIS (Netherlands)

    Block, J. (Jörn); Hornuf, L. (Lars); Moritz, A. (Alexandra)

    2017-01-01

    textabstractStart-ups often post updates during equity crowdfunding campaigns. However, little is known about the effects of such updates on crowd participation. We investigate this question by using hand-collected data from 71 funding campaigns and 39,399 investment decisions on two German equity

  18. Crowd science and engineering: concept and research framework

    Directory of Open Access Journals (Sweden)

    Yueting Chai

    2017-03-01

    Full Text Available Purpose – The synthetic application and interaction of/between the internet, Internet of Things, cloud computing, big data, Industry 4.0 and other new patterns and new technologies shall breed future Web-based industrial operation system and social operation management patterns, manifesting as a crowd cyber eco-system composed of multiple interconnected intelligent agents (enterprises, individuals and governmental agencies and its dynamic behaviors. This paper aims to explore the basic principles and laws of such a system and its behavior. Design/methodology/approach – The authors propose the concepts of crowd science and engineering (CSE and expound its main content, thus forming a research framework of theories and methodologies of crowd science. Findings – CSE is expected to substantially promote the formation and development of crowd science and thus lay a foundation for the advancement of Web-based industrial operation system and social operation management patterns. Originality/value – This paper is the first one to propose the concepts of CSE, which lights the beacon for the future research in this area.

  19. Crowds As Complex Adaptive Systems: Strategic Implications For Law Enforcement

    Science.gov (United States)

    2016-03-01

    spread by word -of- mouth , news outlets, and social media .186 According to David Karpf, an assistant professor at George Washington University, the...71 6. A Word about Social Media ...such as the police. 6. A Word about Social Media The burgeoning role of social media is a significant development in crowd system dynamics. Social

  20. Structural Bioinformatics and Protein Docking Analysis of the Molecular Chaperone-Kinase Interactions: Towards Allosteric Inhibition of Protein Kinases by Targeting the Hsp90-Cdc37 Chaperone Machinery

    Directory of Open Access Journals (Sweden)

    Gennady Verkhivker

    2013-11-01

    Full Text Available A fundamental role of the Hsp90-Cdc37 chaperone system in mediating maturation of protein kinase clients and supporting kinase functional activity is essential for the integrity and viability of signaling pathways involved in cell cycle control and organism development. Despite significant advances in understanding structure and function of molecular chaperones, the molecular mechanisms and guiding principles of kinase recruitment to the chaperone system are lacking quantitative characterization. Structural and thermodynamic characterization of Hsp90-Cdc37 binding with protein kinase clients by modern experimental techniques is highly challenging, owing to a transient nature of chaperone-mediated interactions. In this work, we used experimentally-guided protein docking to probe the allosteric nature of the Hsp90-Cdc37 binding with the cyclin-dependent kinase 4 (Cdk4 kinase clients. The results of docking simulations suggest that the kinase recognition and recruitment to the chaperone system may be primarily determined by Cdc37 targeting of the N-terminal kinase lobe. The interactions of Hsp90 with the C-terminal kinase lobe may provide additional “molecular brakes” that can lock (or unlock kinase from the system during client loading (release stages. The results of this study support a central role of the Cdc37 chaperone in recognition and recruitment of the kinase clients. Structural analysis may have useful implications in developing strategies for allosteric inhibition of protein kinases by targeting the Hsp90-Cdc37 chaperone machinery.

  1. Insight into eukaryotic topoisomerase II-inhibiting fused heterocyclic compounds in human cancer cell lines by molecular docking.

    Science.gov (United States)

    Taskin, T; Yilmaz, S; Yildiz, I; Yalcin, I; Aki, E

    2012-01-01

    Etoposide is effective as an anti-tumour drug by inhibiting eukaryotic DNA topoisomerase II via establishing a covalent complex with DNA. Unfortunately, its wide therapeutic application is often hindered by multidrug resistance (MDR), low water solubility and toxicity. In our previous study, new derivatives of benzoxazoles, benzimidazoles and related fused heterocyclic compounds, which exhibited significant eukaryotic DNA topoisomerase II inhibitory activity, were synthesized and exhibited better inhibitory activity compared with the drug etoposide itself. To expose the binding interactions between the eukaryotic topoisomerase II and the active heterocyclic compounds, docking studies were performed, using the software Discovery Studio 2.1, based on the crystal structure of the Topo IIA-bound G-segment DNA (PDB ID: 2RGR). The research was conducted on a selected set of 31 fused heterocyclic compounds with variation in structure and activity. The structural analyses indicate coordinate and hydrogen bonding interactions, van der Waals interactions and hydrophobic interactions between ligands and the protein, as Topo IIA-bound G-segment DNA are responsible for the preference of inhibition and potency. Collectively, the results demonstrate that the compounds 1a, 1c, 3b, 3c, 3e and 4a are significant anti-tumour drug candidates that should be further studied.

  2. Factors Influencing Perceived Crowding of Tourists and Sustainable Tourism Destination Management

    Directory of Open Access Journals (Sweden)

    Qian Jin

    2016-09-01

    Full Text Available Studies on tourists crowding are developed to explore the perception of crowding, and these studies indicate crowding influence on sustainable development of tourist destinations. This study aims to reveal the influential factors of tourists’ perceived crowding. We obtained data from interviewing over 400 tourists and five senior tourism officials in Xi’an, China. This study firstly applies factor analysis to identify the constructed variables of tourists’ motivations from the principle component analysis. It then examines the correlation between nationality and perceived crowding. Consequently, a multiple regression is used to identify the connection between motivations and perceived crowding. The results of the study indicate nationality and motivation as two significant influential factors to perceived crowding management. This study also shows that management in tourist destinations would benefit from provision of the authentic travel experience integrated with zoning the travel destination.

  3. Adolescent peer crowds and patterns of belief in the boundaries of personal authority.

    Science.gov (United States)

    Daddis, Christopher

    2010-10-01

    Patterns of authority beliefs were examined among peer crowds in 598 middle school (M=12.97 years), early high school (M=15.10 years), and late high school adolescents (M=18.25 years). Participants reported beliefs regarding the boundaries of personal authority across personal, prudential, conventional, moral, and multifaceted issues. As expected, analyses revealed persistent differences in belief patterns among crowds within each age group. Tough and Alternative crowds asserted personal authority across all issues, while Prep and Outcast crowds endorsed parental authority. Jock, Hip Hop, and Normal crowds presented with shared-control patterns, but each crowd ceded and asserted authority over different issues. Discussion focused on crowds' roles in the development of group differences in the boundaries of personal authority.

  4. Defining the molecular basis of BubR1 kinetochore interactions and APC/C-CDC20 inhibition.

    Science.gov (United States)

    D'Arcy, Sheena; Davies, Owen R; Blundell, Tom L; Bolanos-Garcia, Victor M

    2010-05-07

    BubR1 is essential for the mitotic checkpoint that prevents aneuploidy in cellular progeny by triggering anaphase delay in response to kinetochores incorrectly/not attached to the mitotic spindle. Here, we define the molecular architecture of the functionally significant N-terminal region of human BubR1 and present the 1.8 A crystal structure of its tetratricopeptide repeat (TPR) domain. The structure reveals divergence from the classical TPR fold and is highly similar to the TPR domain of budding yeast Bub1. Shared distinctive features include a disordered loop insertion, a 3(10)-helix, a tight turn involving glycine positive Phi angles, and noncanonical packing of and between the TPR motifs. We also define the molecular determinants of the interaction between BubR1 and kinetochore protein Blinkin. We identify a shallow groove on the concave surface of the BubR1 TPR domain that forms multiple discrete and potentially cooperative interactions with Blinkin. Finally, we present evidence for a direct interaction between BubR1 and Bub1 mediated by regions C-terminal to their TPR domains. This interaction provides a mechanism for Bub1-dependent kinetochore recruitment of BubR1. We thus present novel molecular insights into the structure of BubR1 and its interactions at the kinetochore-microtubule interface. Our studies pave the way for future structure-directed engineering aimed at dissecting the roles of kinetochore-bound and other pools of BubR1 in vivo.

  5. Peer Crowd Identification and Adolescent Health Behaviors: Results From a Statewide Representative Study.

    Science.gov (United States)

    Jordan, Jeffrey W; Stalgaitis, Carolyn A; Charles, John; Madden, Patrick A; Radhakrishnan, Anjana G; Saggese, Daniel

    2018-02-01

    Peer crowds are macro-level subcultures that share similarities across geographic areas. Over the past decade, dozens of studies have explored the association between adolescent peer crowds and risk behaviors, and how they can inform public health efforts. However, despite the interest, researchers have not yet reported on crowd size and risk levels from a representative sample, making it difficult for practitioners to apply peer crowd science to interventions. The current study reports findings from the first statewide representative sample of adolescent peer crowd identification and health behaviors. Weighted data were analyzed from the 2015 Virginia Youth Survey of Health Behaviors ( n = 4,367). Peer crowds were measured via the I-Base Survey™, a photo-based peer crowd survey instrument. Frequencies and confidence intervals of select behaviors including tobacco use, substance use, nutrition, physical activity, and violence were examined to identify high- and low-risk crowds. Logistic regression was used to calculate adjusted odds ratios for each crowd and behavior. Risky behaviors clustered in two peer crowds. Hip Hop crowd identification was associated with substance use, violence, and some depression and suicidal behaviors. Alternative crowd identification was associated with increased risk for some substance use behaviors, depression and suicide, bullying, physical inactivity, and obesity. Mainstream and, to a lesser extent, Popular, identities were associated with decreased risk for most behaviors. Findings from the first representative study of peer crowds and adolescent behavior identify two high-risk groups, providing critical insights for practitioners seeking to maximize public health interventions by targeting high-risk crowds.

  6. Molecular Characterization of Isolated Xanthomonas sp. From Rice Rhizosphere Soil and their Inhibition using Clerodendrum viscosum Vent

    International Nuclear Information System (INIS)

    Islam, R.; Ahmed, J.; Al-Reza, S. M.; Rahman, M. M.; Nyme, Z.; Lisa, L. A.; Yousaf, M.; Alam, M. N.

    2015-01-01

    In this study, we characterized some Xanthomonas sp. from rice rhizosphere soil by 16S rDNA sequence analysis and the potentiality tested of oil and extracts of Clerodendrum viscosum Vent. leaves against those isolated bacteria. The essential oil compositions were evaluated by GC-MS analysis and identified twenty four compounds as 94.37% of the total essential oil, where cyclohepta-1,3,5,-triene (16.07%), 2H-1,4-pyridoxazin-3(4H)-one (12.27%), L-carvenol (8.04%), p-cymene (9.15%), alpha-terpineol (7.98%), beta-sitosterol (6.76%), tyranton (6.42%), mesityl oxide (6.34%), gamma-terpinene (5.42%) and beta-linalool (3.74%) were the major constituents. According to the 16S rDNA sequences analysis, Hb28 and Xb43 isolates have shown the 100% similarity for Xanthomonas retroflexus and Xanthomonas theicola. In addition, isolates Ha18, Xb33 and Jb30 also have shown the maximum similarity of 98% for Xanthomonas sp. TB8-9-II, Xanthomonas campestris and Xanthomonas sp. BBCT38. Furthermore, in vitro studies showed that the oil have the inhibitory effect on Xanthomonas sp. TB8-9-II, X. campestris, X. retroflexus, Xanthomonas sp. BBCT38, and X. theicola, where the zone of inhibition and MIC values were 18.8 to 25.9 mm and 62.5 to 125 meu g ml/sup -1/, respectively. However, organic extracts showed the zone of inhibition and MIC values were 13.4 to 22.9 and 62.5 to 500 meu g ml-1, respectively. Our findings suggested that the essential oil and extracts of C. viscosum Vent. leaves might be the effective source to control Xanthomonas sp. biologically. (author)

  7. Bioactive compounds from culinary herbs inhibit a molecular target for type 2 diabetes management, dipeptidyl peptidase IV.

    Science.gov (United States)

    Bower, Allyson M; Real Hernandez, Luis M; Berhow, Mark A; de Mejia, Elvira Gonzalez

    2014-07-02

    Greek oregano (Origanum vulgare), marjoram (Origanum majorana), rosemary (Rosmarinus officinalis), and Mexican oregano (Lippia graveolens) are concentrated sources of bioactive compounds. The aims were to characterize and examine extracts from greenhouse-grown or commercially purchased herbs for their ability to inhibit dipeptidyl peptidase IV (DPP-IV) and protein tyrosine phosphatase 1B (PTP1B), enzymes that play a role in insulin secretion and insulin signaling, respectively. Greenhouse herbs contained more polyphenols (302.7-430.1 μg of gallic acid equivalents/mg of dry weight of extract (DWE)) and flavonoids (370.1-661.4 μg of rutin equivalents/mg of DWE) compared to the equivalent commercial herbs. Greenhouse rosemary, Mexican oregano, and marjoram extracts were the best inhibitors of DPP-IV (IC₅₀=16, 29, and 59 μM, respectively). Commercial rosemary, Mexican oregano, and marjoram were the best inhibitors of PTP1B (32.4-40.9% at 500 μM). The phytochemicals eriodictyol, naringenin, hispidulin, cirsimaritin, and carnosol were identified by LC-ESI-MS as being present in greenhouse-grown Mexican oregano and rosemary. Computational modeling indicated that hispidulin, carnosol, and eriodictyol would have the best binding affinities for DPP-IV. Biochemically, the best inhibitors of DPP-IV were cirsimaritin (IC₅₀=0.43±0.07 μM), hispidulin (IC₅₀=0.49±0.06 μM), and naringenin (IC₅₀=2.5±0.29 μM). Overall, herbs contain several flavonoids that inhibit DPP-IV and should be investigated further regarding their potential in diabetes management.

  8. Crowding, Entropic Forces, and Confinement: Crucial Factors for Structures and Functions in the Cell Nucleus.

    Science.gov (United States)

    Hancock, R

    2018-04-01

    The view of the cell nucleus as a crowded system of colloid particles and that chromosomes are giant self-avoiding polymers is stimulating rapid advances in our understanding of its structure and activities, thanks to concepts and experimental methods from colloid, polymer, soft matter, and nano sciences and to increased computational power for simulating macromolecules and polymers. This review summarizes current understanding of some characteristics of the molecular environment in the nucleus, of how intranuclear compartments are formed, and of how the genome is highly but precisely compacted, and underlines the crucial, subtle, and sometimes unintuitive effects on structures and reactions of entropic forces caused by the high concentration of macromolecules in the nucleus.

  9. Systematic study of imidazoles inhibiting IDO1 via the integration of molecular mechanics and quantum mechanics calculations.

    Science.gov (United States)

    Zou, Yi; Wang, Fang; Wang, Yan; Guo, Wenjie; Zhang, Yihua; Xu, Qiang; Lai, Yisheng

    2017-05-05

    Indoleamine 2,3-dioxygenase 1 (IDO1) is regarded as an attractive target for cancer immunotherapy. To rationalize the detailed interactions between IDO1 and its inhibitors at the atomic level, an integrated computational approach by combining molecular mechanics and quantum mechanics methods was employed in this report. Specifically, the binding modes of 20 inhibitors was initially investigated using the induced fit docking (IFD) protocol, which outperformed other two docking protocols in terms of correctly predicting ligand conformations. Secondly, molecular dynamics (MD) simulations and MM/PBSA free energy calculations were employed to determine the dynamic binding process and crucial residues were confirmed through close contact analysis, hydrogen-bond analysis and binding free energy decomposition calculations. Subsequent quantum mechanics and nonbonding interaction analysis were carried out to provide in-depth explanations on the critical role of those key residues, and Arg231 and 7-propionate of the heme group were major contributors to ligand binding, which lowed a great amount of interaction energy. We anticipate that these findings will be valuable for enzymatic studies and rational drug design. Copyright © 2017. Published by Elsevier Masson SAS.

  10. Cellular and molecular insight into the inhibition of primary root growth of Arabidopsis induced by peptaibols, a class of linear peptide antibiotics mainly produced by Trichoderma spp.

    Science.gov (United States)

    Shi, Wei-Ling; Chen, Xiu-Lan; Wang, Li-Xia; Gong, Zhi-Ting; Li, Shuyu; Li, Chun-Long; Xie, Bin-Bin; Zhang, Wei; Shi, Mei; Li, Chuanyou; Zhang, Yu-Zhong; Song, Xiao-Yan

    2016-04-01

    Trichoderma spp. are well known biocontrol agents that produce a variety of antibiotics. Peptaibols are a class of linear peptide antibiotics mainly produced by Trichoderma Alamethicin, the most studied peptaibol, is reported as toxic to plants at certain concentrations, while the mechanisms involved are unclear. We illustrated the toxic mechanisms of peptaibols by studying the growth-inhibitory effect of Trichokonin VI (TK VI), a peptaibol from Trichoderma longibrachiatum SMF2, on Arabidopsis primary roots. TK VI inhibited root growth by suppressing cell division and cell elongation, and disrupting root stem cell niche maintenance. TK VI increased auxin content and disrupted auxin response gradients in root tips. Further, we screened the Arabidopsis TK VI-resistant mutant tkr1. tkr1 harbors a point mutation in GORK, which encodes gated outwardly rectifying K(+)channel proteins. This mutation alleviated TK VI-induced suppression of K(+)efflux in roots, thereby stabilizing the auxin gradient. The tkr1 mutant also resisted the phytotoxicity of alamethicin. Our results indicate that GORK channels play a key role in peptaibol-plant interaction and that there is an inter-relationship between GORK channels and maintenance of auxin homeostasis. The cellular and molecular insight into the peptaibol-induced inhibition of plant root growth advances our understanding of Trichoderma-plant interactions. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  11. The predominant molecular state of bound enzyme determines the strength and type of product inhibition in the hydrolysis of recalcitrant polysaccharides by processive enzymes.

    Science.gov (United States)

    Kuusk, Silja; Sørlie, Morten; Väljamäe, Priit

    2015-05-01

    Processive enzymes are major components of the efficient enzyme systems that are responsible for the degradation of the recalcitrant polysaccharides cellulose and chitin. Despite intensive research, there is no consensus on which step is rate-limiting for these enzymes. Here, we performed a comparative study of two well characterized enzymes, the cellobiohydrolase Cel7A from Hypocrea jecorina and the chitinase ChiA from Serratia marcescens. Both enzymes were inhibited by their disaccharide product, namely chitobiose for ChiA and cellobiose for Cel7A. The products behaved as noncompetitive inhibitors according to studies using the (14)C-labeled crystalline polymeric substrates (14)C chitin nanowhiskers and (14)C-labeled bacterial microcrystalline cellulose for ChiA and Cel7A, respectively. The resulting observed Ki (obs) values were 0.45 ± 0.08 mm for ChiA and 0.17 ± 0.02 mm for Cel7A. However, in contrast to ChiA, the Ki (obs) of Cel7A was an order of magnitude higher than the true Ki value governed by the thermodynamic stability of the enzyme-inhibitor complex. Theoretical analysis of product inhibition suggested that the inhibition strength and pattern can be accounted for by assuming different rate-limiting steps for ChiA and Cel7A. Measuring the population of enzymes whose active site was occupied by a polymer chain revealed that Cel7A was bound predominantly via its active site. Conversely, the active-site-mediated binding of ChiA was slow, and most ChiA exhibited a free active site, even when the substrate concentration was saturating for the activity. Collectively, our data suggest that complexation with the polymer chain is rate-limiting for ChiA, whereas Cel7A is limited by dissociation. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Design, synthesis, molecular docking, anti-Proteus mirabilis and urease inhibition of new fluoroquinolone carboxylic acid derivatives.

    Science.gov (United States)

    Abdullah, Mohammed A A; Abuo-Rahma, Gamal El-Din A A; Abdelhafez, El-Shimaa M N; Hassan, Heba A; Abd El-Baky, Rehab M

    2017-02-01

    New hydroxamic acid, hydrazide and amide derivatives of ciprofloxacin in addition to their analogues of levofloxacin were prepared and identified by different spectroscopic techniques. Some of the prepared compounds revealed good activity against the urease splitting bacteria, Proteus mirabilis. The urease inhibitory activity was investigated using indophenol method. Most of the tested compounds showed better activity than the reference acetohydroxamic acid (AHA). The ciprofloxacin hydrazide derivative 3a and levofloxacin hydroxamic acid 7 experienced the highest activity (IC 50 =1.22μM and 2.20μM, respectively). Molecular docking study revealed high spontaneous binding ability of the tested compounds to the active site of urease. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Oleic acid and linoleic acid from Tenebrio molitor larvae inhibit BACE1 activity in vitro: molecular docking studies.

    Science.gov (United States)

    Youn, Kumju; Yun, Eun-Young; Lee, Jinhyuk; Kim, Ji-Young; Hwang, Jae-Sam; Jeong, Woo-Sik; Jun, Mira

    2014-02-01

    In our ongoing research to find therapeutic compounds for Alzheimer's disease (AD) from natural resources, the inhibitory activity of the BACE1 enzyme by Tenebrio molitor larvae and its major compounds were evaluated. The T. molitor larvae extract and its fractions exhibited strong BACE1 suppression. The major components of hexane fraction possessing both high yield and strong BACE1 inhibition were determined by thin layer chromatography, gas chromatography, and nuclear magnetic resonance analysis. A remarkable composition of unsaturated long chain fatty acids, including oleic acid and linoleic acid, were identified. Oleic acid, in particular, noncompetitively attenuated BACE1 activity with a half-maximal inhibitory concentration (IC₅₀) value of 61.31 μM and Ki value of 34.3 μM. Furthermore, the fatty acids were stably interacted with BACE1 at different allosteric sites of the enzyme bound with the OH of CYS319 and the NH₃ of TYR320 for oleic acid and with the C=O group of GLN304 for linoleic acid. Here, we first revealed novel pharmacophore features of oleic acids and linoleic acid to BACE1 by in silico docking studies. The present findings would clearly suggest potential guidelines for designing novel BACE1 selective inhibitors.

  14. Bacterial Peptide Deformylase Inhibition of Tetrazole-Substituted Biaryl Acid Analogs: Synthesis, Biological Evaluations, and Molecular Docking Study.

    Science.gov (United States)

    Khan, Firoz A Kalam; Patil, Rajendra H; Patil, Manjiri; Arote, Rohidas; Shinde, Devanand B; Sangshetti, Jaiprakash N

    2016-12-01

    The synthesis and screening of tetrazole-substituted biaryl acid analogs 7a-l as bacterial peptide deformylase (PDF) enzyme inhibitors is reported. The compounds 7e (IC 50 value = 5.50 μM) and 7g (IC 50 value = 7.25 μM) showed good PDF inhibition activity. The compounds 7e (MIC range = 10.75-11.66 μg/mL) and 7g (MIC range = 8.91-12.83 μg/mL) also showed potent antibacterial activity when compared with the standard ciprofloxacin (MIC range = 25-50 μg/mL). Thus, the active derivatives were not only potent PDF enzyme inhibitors but also efficient antibacterial agents. In order to gain more insight into the binding mode of the compounds with the PDF enzyme, the most active compounds 7e and 7g, the moderately active compound 7k, and the least active compound 7h were docked against the PDF enzyme of Escherichia coli. The docking study of the most active compounds 7e and 7g against the PDF enzyme exhibited good binding properties. Hence, we believe our synthesized compounds 7a-l could serve as reservoir for bacterial PDF inhibitor development. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Quality-Aware Incentive Mechanism for Mobile Crowd Sensing

    Directory of Open Access Journals (Sweden)

    Ling-Yun Jiang

    2017-01-01

    Full Text Available Mobile crowd sensing (MCS is a novel sensing paradigm which can sense human-centered daily activities and the surrounding environment. The impact of mobility and selfishness of participants on the data reliability cannot be ignored in most mobile crowd sensing systems. To address this issue, we present a universal system model based on the reverse auction framework and formulate the problem as the Multiple Quality Multiple User Selection (MQMUS problem. The quality-aware incentive mechanism (QAIM is proposed to meet the quality requirement of data reliability. We demonstrate that the proposed incentive mechanism achieves the properties of computational efficiency, individual rationality, and truthfulness. And meanwhile, we evaluate the performance and validate the theoretical properties of our incentive mechanism through extensive simulation experiments.

  16. Crowding-facilitated macromolecular transport in attractive micropost arrays.

    Science.gov (United States)

    Chien, Fan-Tso; Lin, Po-Keng; Chien, Wei; Hung, Cheng-Hsiang; Yu, Ming-Hung; Chou, Chia-Fu; Chen, Yeng-Long

    2017-05-02

    Our study of DNA dynamics in weakly attractive nanofabricated post arrays revealed crowding enhances polymer transport, contrary to hindered transport in repulsive medium. The coupling of DNA diffusion and adsorption to the microposts results in more frequent cross-post hopping and increased long-term diffusivity with increased crowding density. We performed Langevin dynamics simulations and found maximum long-term diffusivity in post arrays with gap sizes comparable to the polymer radius of gyration. We found that macromolecular transport in weakly attractive post arrays is faster than in non-attractive dense medium. Furthermore, we employed hidden Markov analysis to determine the transition of macromolecular adsorption-desorption on posts and hopping between posts. The apparent free energy barriers are comparable to theoretical estimates determined from polymer conformational fluctuations.

  17. Disaster Risk Reduction through Innovative Uses of Crowd Sourcing (Invited)

    Science.gov (United States)

    Berger, J.; Greene, M.

    2010-12-01

    Crowd sourcing can be described as a method of distributed problem-solving. It takes advantage of the power of the crowd, which can in some cases be a community of experts and in other cases the collective insight of a broader range of contributors with varying degrees of domain knowledge. The term crowd sourcing was first used by Jeff Howe in a June 2006 Wired magazine article “The Rise of Crowdsourcing,” and is a combination of the terms “crowd” and “outsourcing.” Some commonly known examples of crowd sourcing, in its broadest sense, include Wikepedia, distributed participatory design projects, and consumer websites such as Yelp and Angie’s List. The popularity and success of early large-scale crowd sourcing activities is made possible through leveraging Web 2.0 technologies that allow for mass participation from distributed individuals. The Earthquake Engineering Research Institute (EERI) in Oakland, California recently participated in two crowd sourcing projects. One was initiated and coordinated by EERI, while in the second case EERI was invited to contribute once the crowd sourcing activity was underway. In both projects there was: 1) the determination of a problem or set of tasks that could benefit immediately from the engagement of an informed volunteer group of professionals; 2) a segmenting of the problem into discrete pieces that could be completed in a short period of time (from ten minutes to four hours); 3) a call to action, where an interested community was made aware of the project; and 4) the collection, aggregation, vetting and ultimately distribution of the results in a relatively short period of time. The first EERI crowd sourcing example was the use of practicing engineers and engineering students in California to help estimate the number of pre-1980 concrete buildings in the high seismic risk counties in the state. This building type is known to perform poorly in earthquakes, and state officials were interested in understanding

  18. Crowd-Sourcing the Aesthetics of Platform Games

    DEFF Research Database (Denmark)

    Shaker, Noor; Yannakakis, Georgios N.; Togelius, Julian

    2014-01-01

    What are the aesthetics of platform games and what makes a platform level engaging, challenging and/or frustrating? We attempt to answer such questions through mining a large-set of crowd-sourced gameplay data of a clone of the classic platform game Super Mario Bros. The data consists of 40 short...... game levels that differ along six key level design parameters. Collectively, these levels are played 1560 times over the Internet and the perceived experience is annotated by experiment participants via self-reported ranking (pairwise preferences). Given the wealth of this crowd-sourced data, as all...... details about players’ in-game behaviour are logged, the problem becomes one of extracting meaningful numerical features at the appropriate level of abstraction for the construction of generic computational models of player experience and, thereby, game aesthetics. We explore dissimilar types of features...

  19. Facilitated diffusion in a crowded environment: from kinetics to stochastics

    International Nuclear Information System (INIS)

    Meroz, Yasmine; Klafter, Joseph; Eliazar, Iddo

    2009-01-01

    Facilitated diffusion is a fundamental search process used to describe the problem of a searcher protein finding a specific target site over a very large DNA strand. In recent years macromolecular crowding has been recognized to affect this search process. In this paper, we bridge between two different modelling methodologies of facilitated diffusion: the physics-oriented kinetic approach, which yields the reaction rate of the search process, and the probability-oriented stochastic approach, which yields the probability distribution of the search duration. We translate the former approach to the latter, ascertaining that the two approaches yield coinciding results, both with and without macromolecular crowding. We further show that the stochastic approach markedly generalizes the kinetic approach by accommodating a vast array of search mechanisms, including mechanisms having no reaction rates, and thus being beyond the realm of the kinetic approach.

  20. Stochastic reaction-diffusion algorithms for macromolecular crowding

    Science.gov (United States)

    Sturrock, Marc

    2016-06-01

    Compartment-based (lattice-based) reaction-diffusion algorithms are often used for studying complex stochastic spatio-temporal processes inside cells. In this paper the influence of macromolecular crowding on stochastic reaction-diffusion simulations is investigated. Reaction-diffusion processes are considered on two different kinds of compartmental lattice, a cubic lattice and a hexagonal close packed lattice, and solved using two different algorithms, the stochastic simulation algorithm and the spatiocyte algorithm (Arjunan and Tomita 2010 Syst. Synth. Biol. 4, 35-53). Obstacles (modelling macromolecular crowding) are shown to have substantial effects on the mean squared displacement and average number of molecules in the domain but the nature of these effects is dependent on the choice of lattice, with the cubic lattice being more susceptible to the effects of the obstacles. Finally, improvements for both algorithms are presented.

  1. SPITZER IRAC PHOTOMETRY FOR TIME SERIES IN CROWDED FIELDS

    Energy Technology Data Exchange (ETDEWEB)

    Novati, S. Calchi; Beichman, C. [NASA Exoplanet Science Institute, MS 100-22, California Institute of Technology, Pasadena, CA 91125 (United States); Gould, A.; Fausnaugh, M.; Gaudi, B. S.; Pogge, R. W.; Wibking, B.; Zhu, W.; Poleski, R. [Department of Astronomy, Ohio State University, 140 W. 18th Ave., Columbus, OH 43210 (United States); Yee, J. C. [Harvard-Smithsonian Center for Astrophysics, 60 Garden St., Cambridge, MA 02138 (United States); Bryden, G.; Henderson, C. B.; Shvartzvald, Y. [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, CA 91109 (United States); Carey, S. [Spitzer, Science Center, MS 220-6, California Institute of Technology, Pasadena, CA (United States); Udalski, A.; Pawlak, M.; Szymański, M. K.; Skowron, J.; Mróz, P.; Kozłowski, S. [Warsaw University Observatory, Al. Ujazdowskie 4, 00-478 Warszawa (Poland); Collaboration: Spitzer team; OGLE group; and others

    2015-12-01

    We develop a new photometry algorithm that is optimized for the Infrared Array Camera (IRAC) Spitzer time series in crowded fields and that is particularly adapted to faint or heavily blended targets. We apply this to the 170 targets from the 2015 Spitzer microlensing campaign and present the results of three variants of this algorithm in an online catalog. We present detailed accounts of the application of this algorithm to two difficult cases, one very faint and the other very crowded. Several of Spitzer's instrumental characteristics that drive the specific features of this algorithm are shared by Kepler and WFIRST, implying that these features may prove to be a useful starting point for algorithms designed for microlensing campaigns by these other missions.

  2. Molecular cloning and functional analysis of three genes encoding polygalacturonase-inhibiting proteins from Capsicum annuum, and their relation to increased resistance to two fungal pathogens

    Science.gov (United States)

    Polygalacturonase-inhibiting proteins (PGIPs) are plant cell wall glycoproteins that can inhibit fungal endopolygalacturonases (PGs). Inhibiting by PGIPs directly reduces potential PG activity in specific plant pathogenic fungi, reducing their aggressiveness. Here, we isolated and functionally chara...

  3. Crowd Sourced Formal Verification-Augmentation (CSFV-A)

    Science.gov (United States)

    2016-06-01

    Projects Agency (DARPA), Air Force Research Laboratory (AFRL), Charles River Analytics Inc., and TopCoder, Inc. will be holding a contest to reward...CROWD SOURCED FORMAL VERIFICATION – AUGMENTATION (CSFV-A) CHARLES RIVER ANALYTICS, INC. JUNE 2016 FINAL TECHNICAL REPORT APPROVED FOR PUBLIC...CSFV 5e. TASK NUMBER TC 5f. WORK UNIT NUMBER RA 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Charles River Analytics, Inc. 625 Mount Auburn

  4. Crowding out intrinsic motivation in the public sector

    OpenAIRE

    Georgellis, Y; Iossa, E; Tabvuma, V

    2011-01-01

    Employing intrinsically motivated individuals has been proposed as a means of improving public sector performance. In this article, we investigate whether intrinsic motivation affects the sorting of employees between the private and the public sectors, paying particular attention to whether extrinsic rewards crowd out intrinsic motivation. Using British longitudinal data, we find that individuals are attracted to the public sector by the intrinsic rather than the extrinsic rewards that the se...

  5. Characterizing Crowd Participation and Productivity of Foldit Through Web Scraping

    Science.gov (United States)

    2016-03-01

    of home computer users as a method to tackle other problems. Howe first coined “Crowdsourcing” in an article for Wired magazine titled “The Rise of...terms of biotechnology , DNA technology has applications ranging from self-assembling nanotechnology to logical circuits and programming. Taking some...crowdsourcing,” Wired Magazine , vol. 14, pp. 1–4, 2006. [22] D. C. Brabham, “The myth of amateur crowds: A critical discourse analysis of crowdsourcing

  6. Structures and functions in the crowded nucleus: new biophysical insights

    Directory of Open Access Journals (Sweden)

    Ronald eHancock

    2014-09-01

    Full Text Available Concepts and methods from the physical sciences have catalysed remarkable progress in understanding the cell nucleus in recent years. To share this excitement with physicists and encourage their interest in this field, this review offers an overview of how the physics which underlies structures and functions in the nucleus is becoming more clear thanks to methods which have been developed to simulate and study macromolecules, polymers, and colloids. The environment in the nucleus is very crowded with macromolecules, making entropic (depletion forces major determinants of interactions. Simulation and experiments are consistent with their key role in forming membraneless compartments such as nucleoli, PML and Cajal bodies, and discrete territories for chromosomes. The chromosomes, giant linear polyelectrolyte polymers, exist in vivo in a state like a polymer melt. Looped conformations are predicted in crowded conditions, and have been confirmed experimentally and are central to the regulation of gene expression. Polymer theory has revealed how the chromosomes are so highly compacted in the nucleus, forming a crumpled globule with fractal properties which avoids knots and entanglements in DNA while allowing facile accessibility for its replication and transcription. Entropic repulsion between looped polymers can explain the confinement of each chromosome to a discrete region of the nucleus. Crowding and looping are predicted to facilitate finding the specific targets of factors which modulate activities of DNA. Simulation shows that entropic effects contribute to finding and repairing potentially lethal double-strand breaks in DNA by increasing the mobility of the broken ends, favouring their juxtaposition for repair. Signaling pathways are strongly influenced by crowding, which favours a processive mode of response (consecutive reactions without releasing substrates. This new information contributes to understanding the sometimes counter

  7. The effect of music tempo on perceived crowding in retailing

    OpenAIRE

    Fiksdal, Taisiya; Hua, Wen

    2016-01-01

    Masteroppgave(MSc) in Master of Science in Strategic Marketing Management - Handelshøyskolen BI, 2016 In the marketing field the influence of in-store atmospherics on consumers’ shopping behavior is widely accepted. We seek to understand the effects of instore music tempo on perceived crowding and how music tempo can affect emotions, arousal and perceived control occurring in retail stores. Hence, our research questions are the following: Does music tempo influence the perce...

  8. The multi-niche crowding genetic algorithm: Analysis and applications

    Energy Technology Data Exchange (ETDEWEB)

    Cedeno, Walter [Univ. of California, Davis, CA (United States)

    1995-09-01

    The ability of organisms to evolve and adapt to the environment has provided mother nature with a rich and diverse set of species. Only organisms well adapted to their environment can survive from one generation to the next, transferring on the traits, that made them successful, to their offspring. Competition for resources and the ever changing environment drives some species to extinction and at the same time others evolve to maintain the delicate balance in nature. In this disertation we present the multi-niche crowding genetic algorithm, a computational metaphor to the survival of species in ecological niches in the face of competition. The multi-niche crowding genetic algorithm maintains stable subpopulations of solutions in multiple niches in multimodal landscapes. The algorithm introduces the concept of crowding selection to promote mating among members with qirnilar traits while allowing many members of the population to participate in mating. The algorithm uses worst among most similar replacement policy to promote competition among members with similar traits while allowing competition among members of different niches as well. We present empirical and theoretical results for the success of the multiniche crowding genetic algorithm for multimodal function optimization. The properties of the algorithm using different parameters are examined. We test the performance of the algorithm on problems of DNA Mapping, Aquifer Management, and the File Design Problem. Applications that combine the use of heuristics and special operators to solve problems in the areas of combinatorial optimization, grouping, and multi-objective optimization. We conclude by presenting the advantages and disadvantages of the algorithm and describing avenues for future investigation to answer other questions raised by this study.

  9. Combining Crowd and Expert Labels using Decision Theoretic Active Learning

    Science.gov (United States)

    2015-10-11

    including those la- beled by a classifier trained on using the labels acquired so far). For example, a simple loss function would just be the number...model is used to predict the probability that each crowd la- beled item is correct. This estimate is in turn used to weight the corresponding...costs) for each state using Algorithm 1 as a subroutine. We consider taking the possible action for each item not yet la- beled by the expert. Thus each

  10. Traffic instabilities in self-organized pedestrian crowds.

    Directory of Open Access Journals (Sweden)

    Mehdi Moussaïd

    Full Text Available In human crowds as well as in many animal societies, local interactions among individuals often give rise to self-organized collective organizations that offer functional benefits to the group. For instance, flows of pedestrians moving in opposite directions spontaneously segregate into lanes of uniform walking directions. This phenomenon is often referred to as a smart collective pattern, as it increases the traffic efficiency with no need of external control. However, the functional benefits of this emergent organization have never been experimentally measured, and the underlying behavioral mechanisms are poorly understood. In this work, we have studied this phenomenon under controlled laboratory conditions. We found that the traffic segregation exhibits structural instabilities characterized by the alternation of organized and disorganized states, where the lifetime of well-organized clusters of pedestrians follow a stretched exponential relaxation process. Further analysis show that the inter-pedestrian variability of comfortable walking speeds is a key variable at the origin of the observed traffic perturbations. We show that the collective benefit of the emerging pattern is maximized when all pedestrians walk at the average speed of the group. In practice, however, local interactions between slow- and fast-walking pedestrians trigger global breakdowns of organization, which reduce the collective and the individual payoff provided by the traffic segregation. This work is a step ahead toward the understanding of traffic self-organization in crowds, which turns out to be modulated by complex behavioral mechanisms that do not always maximize the group's benefits. The quantitative understanding of crowd behaviors opens the way for designing bottom-up management strategies bound to promote the emergence of efficient collective behaviors in crowds.

  11. Patterns of residential crowding among Hispanics in later life: immigration, assimilation, and housing market factors.

    Science.gov (United States)

    Burr, Jeffrey A; Mutchler, Jan E; Gerst, Kerstin

    2010-11-01

    We describe patterns of residential crowding among older Hispanics and non-Hispanic Whites. We also examine hypotheses about the relationship of residential crowding with assimilation (language and duration of residence) and housing market characteristics. We employ a multilevel research design, using data from the 2000 U.S. Census of Population. Hierarchical linear models are utilized to estimate the association between residential crowding and both individual and housing market factors. Approximately one third of older Hispanics in metropolitan areas live in crowded housing compared with only one tenth of older non-Hispanic Whites. Foreign-born older persons report higher levels of crowding than U.S.-born older persons. Residential crowding differences between older Hispanics and non-Hispanics are not eliminated after controls are included. Older Hispanics who report better English language skills and a longer duration of residence in the United States live in less crowded housing. We do not find evidence for a relationship between crowding and residential segregation, but we find consistent evidence for an association between residential crowding and relative size of the Hispanic population. The forces that shape household composition and access to housing among older Hispanics appear to result in higher levels of residential crowding for this population.

  12. Statistical analysis of passenger-crowding in bus transport network of Harbin

    Science.gov (United States)

    Hu, Baoyu; Feng, Shumin; Li, Jinyang; Zhao, Hu

    2018-01-01

    Passenger flow data is indispensable but rare in the study of public transport networks. In this study, we focus on the passenger-crowding characteristics of the bus transport network of Harbin (BTN-H) based on passenger flow investigation. The three frequency histograms for all the uplinks and downlinks in Harbin are presented, including passengers on the bus at each section, crowding coefficients, and position parameters of crowded sections. The differences in crowding position are analyzed on each route. The distributions of degree and crowding degree (in directed space L) follow an exponential law. The new finding indicates that there are many stations with few crowded sections and a few stations with many crowded sections. The distributions of path length and crowded length (in directed space P) are presented based on the minimum transfer times, and it is found that they can be fitted by a composite Gaussian function and a Gaussian function, respectively. The stations and paths can be divided into three crowd levels. We conclude that BTN-H is crowded from a network-based perspective.

  13. Foot force models of crowd dynamics on a wobbly bridge.

    Science.gov (United States)

    Belykh, Igor; Jeter, Russell; Belykh, Vladimir

    2017-11-01

    Modern pedestrian and suspension bridges are designed using industry standard packages, yet disastrous resonant vibrations are observed, necessitating multimillion dollar repairs. Recent examples include pedestrian-induced vibrations during the opening of the Solférino Bridge in Paris in 1999 and the increased bouncing of the Squibb Park Bridge in Brooklyn in 2014. The most prominent example of an unstable lively bridge is the London Millennium Bridge, which started wobbling as a result of pedestrian-bridge interactions. Pedestrian phase locking due to footstep phase adjustment is suspected to be the main cause of its large lateral vibrations; however, its role in the initiation of wobbling was debated. We develop foot force models of pedestrians' response to bridge motion and detailed, yet analytically tractable, models of crowd phase locking. We use biomechanically inspired models of crowd lateral movement to investigate to what degree pedestrian synchrony must be present for a bridge to wobble significantly and what is a critical crowd size. Our results can be used as a safety guideline for designing pedestrian bridges or limiting the maximum occupancy of an existing bridge. The pedestrian models can be used as "crash test dummies" when numerically probing a specific bridge design. This is particularly important because the U.S. code for designing pedestrian bridges does not contain explicit guidelines that account for the collective pedestrian behavior.

  14. Anatomy of the Crowd4Discovery crowdfunding campaign.

    Science.gov (United States)

    Perlstein, Ethan O

    2013-01-01

    Crowdfunding allows the public to fund creative projects, including curiosity-driven scientific research. Last Fall, I was part of a team that raised $25,460 from an international coalition of "micropatrons" for an open, pharmacological research project called Crowd4Discovery. The goal of Crowd4Discovery is to determine the precise location of amphetamines inside mouse brain cells, and we are sharing the results of this project on the Internet as they trickle in. In this commentary, I will describe the genesis of Crowd4Discovery, our motivations for crowdfunding, an analysis of our fundraising data, and the nuts and bolts of running a crowdfunding campaign. Science crowdfunding is in its infancy but has already been successfully used by an array of scientists in academia and in the private sector as both a supplement and a substitute to grants. With traditional government sources of funding for basic scientific research contracting, an alternative model that couples fundraising and outreach - and in the process encourages more openness and accountability - may be increasingly attractive to researchers seeking to diversify their funding streams.

  15. Demotivating incentives and motivation crowding out in charitable giving.

    Science.gov (United States)

    Chao, Matthew

    2017-07-11

    Research has shown that extrinsic incentives can crowd out intrinsic motivation in many contexts. Despite this, many nonprofits offer conditional thank-you gifts, such as mugs or tote bags, in exchange for donations. In collaboration with a nonprofit, this study implements a direct mail field experiment and demonstrates that thank-you gifts reduced donation rates in a fundraising campaign. Attention-based multiattribute choice models suggest that this is because prospective donors shift attention to the salient gift offer, causing them to underweight less salient intrinsic motives. Attention to the gift may also cause individuals to adopt a more cost-benefit mindset, further de-emphasizing intrinsic motives. Consistent with these hypotheses, crowding out was driven by those who donated higher amounts in the previous year (i.e., those who likely had higher intrinsic motivation). In a complementary online experiment, thank-you gifts also reduced donation rates but only when the gift was visually salient. This corroborates the mediating role of attention in crowding out. Taken together, the laboratory and field results demonstrate that this fundraising technique can be demotivating in some contexts and that this may occur through an attention-based mechanism.

  16. Conceptualizing intragroup and intergroup dynamics within a controlled crowd evacuation.

    Science.gov (United States)

    Elzie, Terra; Frydenlund, Erika; Collins, Andrew J; Robinson, R Michael

    2015-01-01

    Social dynamics play a critical role in successful pedestrian evacuations. Crowd modeling research has made progress in capturing the way individual and group dynamics affect evacuations; however, few studies have simultaneously examined how individuals and groups interact with one another during egress. To address this gap, the researchers present a conceptual agent-based model (ABM) designed to study the ways in which autonomous, heterogeneous, decision-making individuals negotiate intragroup and intergroup behavior while exiting a large venue. A key feature of this proposed model is the examination of the dynamics among and between various groupings, where heterogeneity at the individual level dynamically affects group behavior and subsequently group/group interactions. ABM provides a means of representing the important social factors that affect decision making among diverse social groups. Expanding on the 2013 work of Vizzari et al., the researchers focus specifically on social factors and decision making at the individual/group and group/group levels to more realistically portray dynamic crowd systems during a pedestrian evacuation. By developing a model with individual, intragroup, and intergroup interactions, the ABM provides a more representative approximation of real-world crowd egress. The simulation will enable more informed planning by disaster managers, emergency planners, and other decision makers. This pedestrian behavioral concept is one piece of a larger simulation model. Future research will build toward an integrated model capturing decision-making interactions between pedestrians and vehicles that affect evacuation outcomes.

  17. Bayesian network model of crowd emotion and negative behavior

    Science.gov (United States)

    Ramli, Nurulhuda; Ghani, Noraida Abdul; Hatta, Zulkarnain Ahmad; Hashim, Intan Hashimah Mohd; Sulong, Jasni; Mahudin, Nor Diana Mohd; Rahman, Shukran Abd; Saad, Zarina Mat

    2014-12-01

    The effects of overcrowding have become a major concern for event organizers. One aspect of this concern has been the idea that overcrowding can enhance the occurrence of serious incidents during events. As one of the largest Muslim religious gathering attended by pilgrims from all over the world, Hajj has become extremely overcrowded with many incidents being reported. The purpose of this study is to analyze the nature of human emotion and negative behavior resulting from overcrowding during Hajj events from data gathered in Malaysian Hajj Experience Survey in 2013. The sample comprised of 147 Malaysian pilgrims (70 males and 77 females). Utilizing a probabilistic model called Bayesian network, this paper models the dependence structure between different emotions and negative behaviors of pilgrims in the crowd. The model included the following variables of emotion: negative, negative comfortable, positive, positive comfortable and positive spiritual and variables of negative behaviors; aggressive and hazardous acts. The study demonstrated that emotions of negative, negative comfortable, positive spiritual and positive emotion have a direct influence on aggressive behavior whereas emotion of negative comfortable, positive spiritual and positive have a direct influence on hazardous acts behavior. The sensitivity analysis showed that a low level of negative and negative comfortable emotions leads to a lower level of aggressive and hazardous behavior. Findings of the study can be further improved to identify the exact cause and risk factors of crowd-related incidents in preventing crowd disasters during the mass gathering events.

  18. POI Summarization by Aesthetics Evaluation From Crowd Source Social Media.

    Science.gov (United States)

    Qian, Xueming; Li, Cheng; Lan, Ke; Hou, Xingsong; Li, Zhetao; Han, Junwei

    2018-03-01

    Place-of-Interest (POI) summarization by aesthetics evaluation can recommend a set of POI images to the user and it is significant in image retrieval. In this paper, we propose a system that summarizes a collection of POI images regarding both aesthetics and diversity of the distribution of cameras. First, we generate visual albums by a coarse-to-fine POI clustering approach and then generate 3D models for each album by the collected images from social media. Second, based on the 3D to 2D projection relationship, we select candidate photos in terms of the proposed crowd source saliency model. Third, in order to improve the performance of aesthetic measurement model, we propose a crowd-sourced saliency detection approach by exploring the distribution of salient regions in the 3D model. Then, we measure the composition aesthetics of each image and we explore crowd source salient feature to yield saliency map, based on which, we propose an adaptive image adoption approach. Finally, we combine the diversity and the aesthetics to recommend aesthetic pictures. Experimental results show that the proposed POI summarization approach can return images with diverse camera distributions and aesthetics.

  19. The Wisdom of e-crowds: Can Masses Create Value?

    Directory of Open Access Journals (Sweden)

    Wieczerzycki Marcin

    2016-09-01

    Full Text Available With the rising popularity of the Internet, interactions between companies and their consumers have become more common and meaningful. Researchers often tend to apply the metaphor of community to these on-line networks of B2C relationships. However, this term implies durability and a long-term orientation. It does not cover more incidental, short-lived groups of consumers, who therefore should not be treated as communities. The purpose of this paper is to explore the ability of these short-term, collective consumer phenomena (addressed as e-crowds within the scope of this paper to create value. Based on a critical literature analysis that considers works from several different fields of knowledge (including management, economics, psychology and media studies and empirical examples, we argue that while lacking a complex internal organization, e-crowds are capable of creating use, exchange and sign value when certain conditions are met. However, they are equally likely to perform value-destroying activities, which present real risks for companies that interact with e-crowds.

  20. Polymer Crowding in Confined Polymer-Nanoparticle Mixtures

    Science.gov (United States)

    Davis, Wyatt J.; Denton, Alan R.

    Crowding can influence the conformations and thus functionality of macromolecules in quasi-two-dimensional environments, such as DNA or proteins confined to a cell membrane. We explore such crowding within a model of polymers as penetrable ellipses, whose shapes are governed by the statistics of a 2D random walk. The principal radii of the polymers fluctuate according to probability distributions of the eigenvalues of the gyration tensor. Within this coarse-grained model, we perform Monte Carlo simulations of mixtures of polymers and hard nanodisks, including trial changes in polymer conformation (shape and orientation). Penetration of polymers by nanodisks is incorporated with a free energy cost predicted by polymer field theory. Over ranges of size ratio and nanodisk density, we analyze the influence of crowding on polymer shape by computing eigenvalue distributions, mean radius of gyration, and mean asphericity of the polymer. We compare results with predictions of free-volume theory and with corresponding results in three dimensions. Our approach may help to interpret recent (and motivate future) experimental studies of biopolymers interacting with cell membranes, with relevance for drug delivery and gene therapy. This work was supported by the National Science Foundation under Grant No. DMR-1106331.

  1. Reducing the Flexibility of Type II Dehydroquinase for Inhibition: A Fragment-Based Approach and Molecular Dynamics Study.

    Science.gov (United States)

    Peón, Antonio; Robles, Adrián; Blanco, Beatriz; Convertino, Marino; Thompson, Paul; Hawkins, Alastair R; Caflisch, Amedeo; González-Bello, Concepción

    2017-09-21

    A multidisciplinary approach was used to identify and optimize a quinazolinedione-based ligand that would decrease the flexibility of the substrate-covering loop (catalytic loop) of the type II dehydroquinase from Helicobacter pylori. This enzyme, which is essential for the survival of this bacterium, is involved in the biosynthesis of aromatic amino acids. A computer-aided fragment-based protocol (ALTA) was first used to identify the aromatic fragments able to block the interface pocket that separates two neighboring enzyme subunits and is located at the active site entrance. Chemical modification of its non-aromatic moiety through an olefin cross-metathesis and Seebach's self-reproduction of chirality synthetic principle allowed the development of a quinazolinedione derivative that disables the catalytic loop plasticity, which is essential for the enzyme's catalytic cycle. Molecular dynamics simulations revealed that the ligand would force the catalytic loop into an inappropriate arrangement for catalysis by strong interactions with the catalytic tyrosine and by expelling the essential arginine out of the active site. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. A behavioral economics perspective on the overjustification effect: Crowding-in and crowding-out of intrinsic motivation.

    OpenAIRE

    Weibel, Antoinette; Wiemann, Meike; Osterloh, Margit

    2014-01-01

    In the last two decades, economic motivation research has undergone a paradigm shift when it comes to the effect of incentive schemes on individual performance and motivation. Inspired by self-determination theory, a new branch in economics evolved called behavioral economics. Especially by evidencing the negative effect of “pay-for-performance” on intrinsic motivation, called the “crowding-out” or “overjustification” effect, it challenges the economic paradigm of the relative price-effect an...

  3. Crowd Sourcing for Challenging Technical Problems and Business Model

    Science.gov (United States)

    Davis, Jeffrey R.; Richard, Elizabeth

    2011-01-01

    Crowd sourcing may be defined as the act of outsourcing tasks that are traditionally performed by an employee or contractor to an undefined, generally large group of people or community (a crowd) in the form of an open call. The open call may be issued by an organization wishing to find a solution to a particular problem or complete a task, or by an open innovation service provider on behalf of that organization. In 2008, the Space Life Sciences Directorate (SLSD), with the support of Wyle Integrated Science and Engineering, established and implemented pilot projects in open innovation (crowd sourcing) to determine if these new internet-based platforms could indeed find solutions to difficult technical challenges. These unsolved technical problems were converted to problem statements, also called "Challenges" or "Technical Needs" by the various open innovation service providers, and were then posted externally to seek solutions. In addition, an open call was issued internally to NASA employees Agency wide (10 Field Centers and NASA HQ) using an open innovation service provider crowd sourcing platform to post NASA challenges from each Center for the others to propose solutions). From 2008 to 2010, the SLSD issued 34 challenges, 14 externally and 20 internally. The 14 external problems or challenges were posted through three different vendors: InnoCentive, Yet2.com and TopCoder. The 20 internal challenges were conducted using the InnoCentive crowd sourcing platform designed for internal use by an organization. This platform was customized for NASA use and promoted as NASA@Work. The results were significant. Of the seven InnoCentive external challenges, two full and five partial awards were made in complex technical areas such as predicting solar flares and long-duration food packaging. Similarly, the TopCoder challenge yielded an optimization algorithm for designing a lunar medical kit. The Yet2.com challenges yielded many new industry and academic contacts in bone

  4. Synthesis, antitumour and antioxidant activities of novel α,β-unsaturated ketones and related heterocyclic analogues: EGFR inhibition and molecular modelling study.

    Science.gov (United States)

    El-Husseiny, Walaa M; El-Sayed, Magda A-A; Abdel-Aziz, Naglaa I; El-Azab, Adel S; Ahmed, Esam R; Abdel-Aziz, Alaa A-M

    2018-12-01

    New α,β-unsaturated ketones 4a,b; 5a-c; and 6a,b; as well as 4-H pyran 7; pyrazoline 8a,b; isoxazoline 9; pyridine 10-11; and quinoline-4-carboxylic acid 12a,b derivatives were synthesized and evaluated for in vitro antitumour activity against HepG2, MCF-7, HeLa, and PC-3 cancer cell lines. Antioxidant activity was investigated by the ability of these compounds to scavenge the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS •+ ). Compounds 6a, 6b, 7, and 8b exhibited potent antitumour activities against all tested cell lines with [IC 50 ] ≅5.5-18.1 µΜ), in addition to significantly high ABTS •+ scavenging activities. In vitro EGFR kinase assay for 6a, 6b, 7, and 8b as the most potent antitumour compounds showed that; compounds 6b, and 7 exhibited worthy EGFR inhibition activity with IC 50 values of 0.56 and 1.6 µM, respectively, while compounds 6a and 8b showed good inhibition activity with IC 50 values of 4.66 and 2.16 µM, respectively, compared with sorafenib reference drug (IC 50  = 1.28 µM). Molecular modelling studies for compounds 6b, 7, and 8b were conducted to exhibit the binding mode towards EGFR kinase, which showed similar interaction with erlotinib.

  5. Nest-crowdcontrol: Advanced video-based crowd monitoring for large public events

    OpenAIRE

    Monari, Eduardo; Fischer, Yvonne; Anneken, Mathias

    2015-01-01

    Current video surveillance systems still lack of intelligent video and data analysis modules for supporting situation awareness of decision makers. Especially in mass gatherings like large public events, the decision maker would benefit from different views of the area, especially from crowd density estimations. This article describes a multi-camera system called NEST and its application for crowd density analysis. First, the overall system design is presented. Based on this, the crowd densit...

  6. Crowd innovation : The role of uncertainty for opening up the innovation process in the public sector

    OpenAIRE

    Collm, Alexandra; Schedler, Kuno

    2011-01-01

    Innovations are complex processes that can be created internally, caused externally or generated collectively with stakeholders. Integrating crowdsourcing and open innovation and supported by Web 2.0 technologies, a new innovation practice, crowd innovation, has emerged. In this paper, we illustrate empirically the practice of crowd innovation and discuss institutional obstacles, which exist for implementing crowd innovation in the public sector. Referring to the normative mode of publicness ...

  7. Are current atomistic force fields accurate enough to study proteins in crowded environments?

    Directory of Open Access Journals (Sweden)

    Drazen Petrov

    2014-05-01

    Full Text Available The high concentration of macromolecules in the crowded cellular interior influences different thermodynamic and kinetic properties of proteins, including their structural stabilities, intermolecular binding affinities and enzymatic rates. Moreover, various structural biology methods, such as NMR or different spectroscopies, typically involve samples with relatively high protein concentration. Due to large sampling requirements, however, the accuracy of classical molecular dynamics (MD simulations in capturing protein behavior at high concentration still remains largely untested. Here, we use explicit-solvent MD simulations and a total of 6.4 µs of simulated time to study wild-type (folded and oxidatively damaged (unfolded forms of villin headpiece at 6 mM and 9.2 mM protein concentration. We first perform an exhaustive set of simulations with multiple protein molecules in the simulation box using GROMOS 45a3 and 54a7 force fields together with different types of electrostatics treatment and solution ionic strengths. Surprisingly, the two villin headpiece variants exhibit similar aggregation behavior, despite the fact that their estimated aggregation propensities markedly differ. Importantly, regardless of the simulation protocol applied, wild-type villin headpiece consistently aggregates even under conditions at which it is experimentally known to be soluble. We demonstrate that aggregation is accompanied by a large decrease in the total potential energy, with not only hydrophobic, but also polar residues and backbone contributing substantially. The same effect is directly observed for two other major atomistic force fields (AMBER99SB-ILDN and CHARMM22-CMAP as well as indirectly shown for additional two (AMBER94, OPLS-AAL, and is possibly due to a general overestimation of the potential energy of protein-protein interactions at the expense of water-water and water-protein interactions. Overall, our results suggest that current MD force fields

  8. Effects of Polymer Hydrophobicity on Protein Structure and Aggregation Kinetics in Crowded Milieu.

    Science.gov (United States)

    Breydo, Leonid; Sales, Amanda E; Frege, Telma; Howell, Mark C; Zaslavsky, Boris Y; Uversky, Vladimir N

    2015-05-19

    We examined the effects of water-soluble polymers of various degrees of hydrophobicity on the folding and aggregation of proteins. The polymers we chose were polyethylene glycol (PEG) and UCON (1:1 copolymer of ethylene glycol and propylene glycol). The presence of additional methyl groups in UCON makes it more hydrophobic than PEG. Our earlier analysis revealed that similarly sized PEG and UCON produced different changes in the solvent properties of water in their solutions and induced morphologically different α-synuclein aggregates [Ferreira, L. A., et al. (2015) Role of solvent properties of aqueous media in macromolecular crowding effects. J. Biomol. Struct. Dyn., in press]. To improve our understanding of molecular mechanisms defining behavior of proteins in a crowded environment, we tested the effects of these polymers on secondary and tertiary structure and aromatic residue solvent accessibility of 10 proteins [five folded proteins, two hybrid proteins; i.e., protein containing ordered and disordered domains, and three intrinsically disordered proteins (IDPs)] and on the aggregation kinetics of insulin and α-synuclein. We found that effects of both polymers on secondary and tertiary structures of folded and hybrid proteins were rather limited with slight unfolding observed in some cases. Solvent accessibility of aromatic residues was significantly increased for the majority of the studied proteins in the presence of UCON but not PEG. PEG also accelerated the aggregation of protein into amyloid fibrils, whereas UCON promoted aggregation to amyloid oligomers instead. These results indicate that even a relatively small change in polymer structure leads to a significant change in the effect of this polymer on protein folding and aggregation. This is an indication that protein folding and especially aggregation are highly sensitive to the presence of other macromolecules, and an excluded volume effect is insufficient to describe their effect.

  9. Modeling crowd behavior based on the discrete-event multiagent approach

    OpenAIRE

    Лановой, Алексей Феликсович; Лановой, Артем Алексеевич

    2014-01-01

    The crowd is a temporary, relatively unorganized group of people, who are in close physical contact with each other. Individual behavior of human outside the crowd is determined by many factors, associated with his intellectual activities, but inside the crowd the man loses his identity and begins to obey more simple laws of behavior.One of approaches to the construction of multi-level model of the crowd using discrete-event multiagent approach was described in the paper.Based on this analysi...

  10. Phytochemical Characterization of Low Molecular Weight Constituents from Marshmallow Roots (Althaea officinalis) and Inhibiting Effects of the Aqueous Extract on Human Hyaluronidase-1.

    Science.gov (United States)

    Sendker, Jandirk; Böker, Ines; Lengers, Isabelle; Brandt, Simone; Jose, Joachim; Stark, Timo; Hofmann, Thomas; Fink, Careen; Abdel-Aziz, Heba; Hensel, Andreas

    2017-02-24

    Extract RE was obtained from the roots of Althaea officinalis in a yield of 8.1%, related to the dried plant material, by extraction with MeOH-H 2 O (1:1), followed by precipitation with EtOH to remove high molecular weight constituents. Phytochemical investigation of RE revealed the presence of N-phenylpropenoyl-l-amino acid amides 1-5, 8% glycine betaine 6, about 9% total amino acids with proline as the main compound, and about 61% mono- and oligomeric carbohydrates with sucrose as the main compound. Further fractionation revealed the presence of a hypolaetin diglycoside (12) and four hypolaetin glycosides (7-9 and 11) with O-sulfocarbohydrate moieties; additionally, 4'-O-methylisoscutellarein-8-O-β-d-(3″-O-sulfo)glucuronopyranoside (10) and the diglycosylated coumarin haploperoside D (13) were identified. The hypolaetin-O-sulfoglycosides 7-10 are new natural products. RE inhibited the enzymatic activity of surface-displayed human hyaluronidase-1 on Escherichia coli F470 cells with an IC 50 of 7.7 mg/mL. RE downregulated mRNA expression of hyal-1 in HaCaT keratinocytes at 125 and 250 μg/mL, respectively. These data contribute to a deeper phytochemical understanding of marshmallow root extracts and to the positive influence of extracts used for therapy of irritated and inflamed buccal tissue and cough.

  11. Altered immunity in crowded locust reduced fungal (Metarhizium anisopliae pathogenesis.

    Directory of Open Access Journals (Sweden)

    Yundan Wang

    2013-01-01

    Full Text Available The stress of living conditions, similar to infections, alters animal immunity. High population density is empirically considered to induce prophylactic immunity to reduce the infection risk, which was challenged by a model of low connectivity between infectious and susceptible individuals in crowded animals. The migratory locust, which exhibits polyphenism through gregarious and solitary phases in response to population density and displays different resistance to fungal biopesticide (Metarhizium anisopliae, was used to observe the prophylactic immunity of crowded animals. We applied an RNA-sequencing assay to investigate differential expression in fat body samples of gregarious and solitary locusts before and after infection. Solitary locusts devoted at least twice the number of genes for combating M. anisopliae infection than gregarious locusts. The transcription of immune molecules such as pattern recognition proteins, protease inhibitors, and anti-oxidation proteins, was increased in prophylactic immunity of gregarious locusts. The differentially expressed transcripts reducing gregarious locust susceptibility to M. anisopliae were confirmed at the transcriptional and translational level. Further investigation revealed that locust GNBP3 was susceptible to proteolysis while GNBP1, induced by M. anisopliae infection, resisted proteolysis. Silencing of gnbp3 by RNAi significantly shortened the life span of gregarious locusts but not solitary locusts. By contrast, gnbp1 silencing did not affect the life span of both gregarious and solitary locusts after M. anisopliae infection. Thus, the GNBP3-dependent immune responses were involved in the phenotypic resistance of gregarious locusts to fungal infection, but were redundant in solitary locusts. Our results indicated that gregarious locusts prophylactically activated upstream modulators of immune cascades rather than downstream effectors, preferring to quarantine rather than eliminate pathogens to

  12. Can the online crowd match real expert judgments?

    DEFF Research Database (Denmark)

    Horn, Alexander

    2018-01-01

    , it is important that we better understand its possibilities and limitations. While previous results for low complexity coding tasks are encouraging, we assess whether and under what conditions simple and complex coding tasks can be outsourced to the crowd without sacrificing content validity in return...... for scalability. The simple task is to decide whether a party statement counts as positive reference to a concept – in our case equality. The complex task is to distinguish between five concepts of equality. To account for the crowdcoder’s contextual knowledge, we vary the IP restrictions. The basis for our...

  13. Learning Supervised Topic Models for Classification and Regression from Crowds

    DEFF Research Database (Denmark)

    Rodrigues, Filipe; Lourenco, Mariana; Ribeiro, Bernardete

    2017-01-01

    problems, which account for the heterogeneity and biases among different annotators that are encountered in practice when learning from crowds. We develop an efficient stochastic variational inference algorithm that is able to scale to very large datasets, and we empirically demonstrate the advantages...... annotation tasks, prone to ambiguity and noise, often with high volumes of documents, deem learning under a single-annotator assumption unrealistic or unpractical for most real-world applications. In this article, we propose two supervised topic models, one for classification and another for regression...

  14. Some Numerical Aspects on Crowd Motion - The Hughes Model

    KAUST Repository

    Gomes, Diogo A.

    2016-01-06

    Here, we study a crowd model proposed by R. Hughes in [5] and we describe a numerical approach to solve it. This model comprises a Fokker-Planck equation coupled with an Eikonal equation with Dirichlet or Neumann data. First, we establish a priori estimates for the solution. Second, we study radial solutions and identify a shock formation mechanism. Third, we illustrate the existence of congestion, the breakdown of the model, and the trend to the equilibrium. Finally, we propose a new numerical method and consider two numerical examples.

  15. An Improved Convolutional Neural Network on Crowd Density Estimation

    Directory of Open Access Journals (Sweden)

    Pan Shao-Yun

    2016-01-01

    Full Text Available In this paper, a new method is proposed for crowd density estimation. An improved convolutional neural network is combined with traditional texture feature. The data calculated by the convolutional layer can be treated as a new kind of features.So more useful information of images can be extracted by different features.In the meantime, the size of image has little effect on the result of convolutional neural network. Experimental results indicate that our scheme has adequate performance to allow for its use in real world applications.

  16. Effect of form of obstacle on speed of crowd evacuation

    Science.gov (United States)

    Yano, Ryosuke

    2018-03-01

    This paper investigates the effect of the form of an obstacle on the time that a crowd takes to evacuate a room, using a toy model. Pedestrians are modeled as active soft matter moving toward a point with intended velocities. An obstacle is placed in front of the exit, and it has one of four shapes: a cylindrical column, a triangular prism, a quadratic prism, or a diamond prism. Numerical results indicate that the evacuation-completion time depends on the shape of the obstacle. Obstacles with a circular cylinder (C.C.) shape yield the shortest evacuation-completion time in the proposed model.

  17. CrowdWater - Can people observe what models need?

    Science.gov (United States)

    van Meerveld, I. H. J.; Seibert, J.; Vis, M.; Etter, S.; Strobl, B.

    2017-12-01

    CrowdWater (www.crowdwater.ch) is a citizen science project that explores the usefulness of crowd-sourced data for hydrological model calibration and prediction. Hydrological models are usually calibrated based on observed streamflow data but it is likely easier for people to estimate relative stream water levels, such as the water level above or below a rock, than streamflow. Relative stream water levels may, therefore, be a more suitable variable for citizen science projects than streamflow. In order to test this assumption, we held surveys near seven different sized rivers in Switzerland and asked more than 450 volunteers to estimate the water level class based on a picture with a virtual staff gauge. The results show that people can generally estimate the relative water level well, although there were also a few outliers. We also asked the volunteers to estimate streamflow based on the stick method. The median estimated streamflow was close to the observed streamflow but the spread in the streamflow estimates was large and there were very large outliers, suggesting that crowd-based streamflow data is highly uncertain. In order to determine the potential value of water level class data for model calibration, we converted streamflow time series for 100 catchments in the US to stream level class time series and used these to calibrate the HBV model. The model was then validated using the streamflow data. The results of this modeling exercise show that stream level class data are useful for constraining a simple runoff model. Time series of only two stream level classes, e.g. above or below a rock in the stream, were already informative, especially when the class boundary was chosen towards the highest stream levels. There was hardly any improvement in model performance when more than five water level classes were used. This suggests that if crowd-sourced stream level observations are available for otherwise ungauged catchments, these data can be used to constrain

  18. Conflict management by hamadryas baboons (Papio hamadryas hamadryas) during crowding: a tension-reduction strategy.

    Science.gov (United States)

    Judge, P G; Griffaton, N S; Fincke, A M

    2006-10-01

    Primates change a variety of behavioral responses during short-term exposure to crowding. Under crowded conditions, rates of aggression, submissive behavior, and affiliative behavior may increase or decrease. Different patterns of change among these three categories of response have been interpreted as various coping "strategies" for managing the increased risk of conflict under crowded conditions. Grooming is of particular interest because this behavior is known to have a calming influence on the recipient and could be used to manage conflict under tense situations. A captive group of nine hamadryas baboons (Papio hamadryas hamadryas) composed of two harems was observed under short-term crowding to determine whether this species adopts conflict-management strategies similar to those described in other primates. The aggression, submission, affiliation, and displacement activities of the six adults in the group (two males and four females) were recorded, and behaviors in their small indoor quarters was compared with baseline behaviors in the outdoor section of their enclosure, which had over 10 times more space. Repeated-measures analysis of variance (ANOVA) was used to compare behavioral rates during crowding with baseline rates recorded immediately after crowding and during matched controls collected at the same time of day as the crowding sessions. Aggression and submission rates did not change significantly across conditions. Huddling together and proximity increased during crowding, and females increased grooming of their harem male during crowding. Displacement activities (e.g., pacing and self-grooming) increased during crowding, but scratching, an indicator of anxiety in primates, did not. The pattern of behavior exhibited by this group conforms to an active "tension-reduction" strategy in which animals successfully reduce the higher risk of aggression during crowding.

  19. Electromyographic characteristic of orbicularis oris in patients with dental crowding in permanent occlusion.

    Science.gov (United States)

    Dmytrenko, Maryna I; Kuroiedowa, Vira D

    2016-01-01

    electromyographic indices were developed for complex analysis of functional condition of orbicularis oris. to study electromyographic indices of orbicularis oris in patients with dental crowding in permanent occlusion. thirty four patients with malocclusion and a severe degree of severity of dental crowding (15 males, 19 females, aged 16-29 years) who underwent orthodontic examination. The treatment group was divided into three: Group Ia comprised 11 subjects with mandibular crowding (mean age 19,27 ± 1,08 years); group Ib, 10 patients with maxillary dental crowding (mean age 20,10 ± 1,60 years) and group Ic, 13 subjects with both maxillary and mandibular crowding (mean age 20,15 ± 1,45 years). The control group consisted of 10 patients with malocclusions but without dental crowding (mean age 20,70 ± 1,32 years). The findings were compared with similar indices in subjects with normal occlusion (mean age 21,3 ± 1,25 years). The index of orbicularis oris activity (ACTIV,%) was determined for each patient. A Student's t-test was used to analyze statistical difference between different groups. patients having crowding of maxillary teeth showed greater activity of muscles of the upper lip during maximum voluntary clenching (АCTІV= -0,99±7,44%). Activity of the muscles of the lower lip in patients with crowding of mandibular teeth (АСTІV=20,52±4,22%) and crowding of maxillary and mandibular teeth (АСTІV=17,93±4,33%) is prevailing. аctivity of the orbicularis oris in patients with malocclusion, complicated by dental crowding depend on clinical localization of crowding.

  20. ReaDDy--a software for particle-based reaction-diffusion dynamics in crowded cellular environments.

    Directory of Open Access Journals (Sweden)

    Johannes Schöneberg

    Full Text Available We introduce the software package ReaDDy for simulation of detailed spatiotemporal mechanisms of dynamical processes in the cell, based on reaction-diffusion dynamics with particle resolution. In contrast to other particle-based reaction kinetics programs, ReaDDy supports particle interaction potentials. This permits effects such as space exclusion, molecular crowding and aggregation to be modeled. The biomolecules simulated can be represented as a sphere, or as a more complex geometry such as a domain structure or polymer chain. ReaDDy bridges the gap between small-scale but highly detailed molecular dynamics or Brownian dynamics simulations and large-scale but little-detailed reaction kinetics simulations. ReaDDy has a modular design that enables the exchange of the computing core by efficient platform-specific implementations or dynamical models that are different from Brownian dynamics.

  1. Current density redistribution from no current crowding to current crowding in Pb-free solder joints with an extremely thick Cu layer

    International Nuclear Information System (INIS)

    Han, Jung Kyu; Choi, Daechul; Fujiyoshi, Masaru; Chiwata, Nobuhiko; Tu, King-Ning

    2012-01-01

    In order to remove the effect of current crowding on electromigration, thick Cu under-bump metallization has been widely adopted in the electronics industry. Three-dimensional (3-D) integrated circuits, using through Si via Cu column interconnects, is being developed, and it seems that current crowding may not be a reliability issue. However, statistical experiments and 3-D finite element simulation indicate that there is a transition from no current crowding to current crowding, caused by void growth at the cathode. An analysis of the electromigration-induced failure mechanism in solder joints having a very thick Cu layer is presented. It is a unique failure mechanism, different from that in flip chip technology. Moreover, the study of marker displacement shows two different stages of drift velocity, which clearly demonstrates the back-stress effect and the development of compressive stress.

  2. Vehicular Visible Light Networks for Urban Mobile Crowd Sensing

    Directory of Open Access Journals (Sweden)

    Barbara M. Masini

    2018-04-01

    Full Text Available Crowd sensing is a powerful tool to map and predict interests and events. In the future, it could be boosted by an increasing number of connected vehicles sharing information and intentions. This will be made available by on board wireless connected devices able to continuously communicate with other vehicles and with the environment. Among the enabling technologies, visible light communication (VLC represents a low cost solution in the short term. In spite of the fact that vehicular communications cannot rely on the sole VLC due to the limitation provided by the light which allows communications in visibility only, VLC can however be considered to complement other wireless communication technologies which could be overloaded in dense scenarios. In this paper we evaluate the performance of VLC connected vehicles when urban crowd sensing is addressed and we compare the performance of sole vehicular visible light networks with that of VLC as a complementary technology of IEEE 802.11p. Results, obtained through a realistic simulation tool taking into account both the roadmap constraints and the technologies protocols, help to understand when VLC provides the major improvement in terms of delivered data varying the number and position of RSUs and the FOV of the receiver.

  3. LESSONS LEARNED ABOUT PUBLIC HEALTH FROM ONLINE CROWD SURVEILLANCE.

    Science.gov (United States)

    Hill, Shawndra; Merchant, Raina; Ungar, Lyle

    2013-09-10

    The Internet has forever changed the way people access information and make decisions about their healthcare needs. Patients now share information about their health at unprecedented rates on social networking sites such as Twitter and Facebook and on medical discussion boards. In addition to explicitly shared information about health conditions through posts, patients reveal data on their inner fears and desires about health when searching for health-related keywords on search engines. Data are also generated by the use of mobile phone applications that track users' health behaviors (e.g., eating and exercise habits) as well as give medical advice. The data generated through these applications are mined and repackaged by surveillance systems developed by academics, companies, and governments alike to provide insight to patients and healthcare providers for medical decisions. Until recently, most Internet research in public health has been surveillance focused or monitoring health behaviors. Only recently have researchers used and interacted with the crowd to ask questions and collect health-related data. In the future, we expect to move from this surveillance focus to the "ideal" of Internet-based patient-level interventions where healthcare providers help patients change their health behaviors. In this article, we highlight the results of our prior research on crowd surveillance and make suggestions for the future.

  4. Track-based event recognition in a realistic crowded environment

    Science.gov (United States)

    van Huis, Jasper R.; Bouma, Henri; Baan, Jan; Burghouts, Gertjan J.; Eendebak, Pieter T.; den Hollander, Richard J. M.; Dijk, Judith; van Rest, Jeroen H.

    2014-10-01

    Automatic detection of abnormal behavior in CCTV cameras is important to improve the security in crowded environments, such as shopping malls, airports and railway stations. This behavior can be characterized at different time scales, e.g., by small-scale subtle and obvious actions or by large-scale walking patterns and interactions between people. For example, pickpocketing can be recognized by the actual snatch (small scale), when he follows the victim, or when he interacts with an accomplice before and after the incident (longer time scale). This paper focusses on event recognition by detecting large-scale track-based patterns. Our event recognition method consists of several steps: pedestrian detection, object tracking, track-based feature computation and rule-based event classification. In the experiment, we focused on single track actions (walk, run, loiter, stop, turn) and track interactions (pass, meet, merge, split). The experiment includes a controlled setup, where 10 actors perform these actions. The method is also applied to all tracks that are generated in a crowded shopping mall in a selected time frame. The results show that most of the actions can be detected reliably (on average 90%) at a low false positive rate (1.1%), and that the interactions obtain lower detection rates (70% at 0.3% FP). This method may become one of the components that assists operators to find threatening behavior and enrich the selection of videos that are to be observed.

  5. Effects of Soundscapes on Perceived Crowding and Encounter Norms

    Science.gov (United States)

    Kim, Sang-Oh; Shelby, Bo

    2011-07-01

    Soundscapes in recreation settings are becoming an important issue, but there are few studies of the effects of sounds on recreation experiences, especially crowding perceptions and encounter norms. This study compared effects of six types of sounds (an airplane, a truck engine, children playing, birds, water, and a control) on perceived crowding (PC) and encounter norms for hikers. Data were collected from 47 college students through lab experiments using simulated images, with moving hikers inserted in the original photo taken in the Jungmeori area of Mudeungsan Provincial Park in Korea. Overall, the motor-made sounds of the airplane and truck engine increased PC and decreased acceptability ratings, and the natural sounds of birds and water decreased PC and increased acceptability ratings. Ratings of the sound of children playing were similar to those in the control (i.e., no sound). In addition, as numbers of hikers increased, the overall effects of sounds decreased, and there were few significant differences in PC or acceptability ratings at the highest encounter levels. Theoretical and methodological implications are discussed.

  6. Network dynamics of social influence in the wisdom of crowds.

    Science.gov (United States)

    Becker, Joshua; Brackbill, Devon; Centola, Damon

    2017-06-27

    A longstanding problem in the social, biological, and computational sciences is to determine how groups of distributed individuals can form intelligent collective judgments. Since Galton's discovery of the "wisdom of crowds" [Galton F (1907) Nature 75:450-451], theories of collective intelligence have suggested that the accuracy of group judgments requires individuals to be either independent, with uncorrelated beliefs, or diverse, with negatively correlated beliefs [Page S (2008) The Difference: How the Power of Diversity Creates Better Groups, Firms, Schools, and Societies ]. Previous experimental studies have supported this view by arguing that social influence undermines the wisdom of crowds. These results showed that individuals' estimates became more similar when subjects observed each other's beliefs, thereby reducing diversity without a corresponding increase in group accuracy [Lorenz J, Rauhut H, Schweitzer F, Helbing D (2011) Proc Natl Acad Sci USA 108:9020-9025]. By contrast, we show general network conditions under which social influence improves the accuracy of group estimates, even as individual beliefs become more similar. We present theoretical predictions and experimental results showing that, in decentralized communication networks, group estimates become reliably more accurate as a result of information exchange. We further show that the dynamics of group accuracy change with network structure. In centralized networks, where the influence of central individuals dominates the collective estimation process, group estimates become more likely to increase in error.

  7. Secure Nearest Neighbor Query on Crowd-Sensing Data

    Directory of Open Access Journals (Sweden)

    Ke Cheng

    2016-09-01

    Full Text Available Nearest neighbor queries are fundamental in location-based services, and secure nearest neighbor queries mainly focus on how to securely and quickly retrieve the nearest neighbor in the outsourced cloud server. However, the previous big data system structure has changed because of the crowd-sensing data. On the one hand, sensing data terminals as the data owner are numerous and mistrustful, while, on the other hand, in most cases, the terminals find it difficult to finish many safety operation due to computation and storage capability constraints. In light of they Multi Owners and Multi Users (MOMU situation in the crowd-sensing data cloud environment, this paper presents a secure nearest neighbor query scheme based on the proxy server architecture, which is constructed by protocols of secure two-party computation and secure Voronoi diagram algorithm. It not only preserves the data confidentiality and query privacy but also effectively resists the collusion between the cloud server and the data owners or users. Finally, extensive theoretical and experimental evaluations are presented to show that our proposed scheme achieves a superior balance between the security and query performance compared to other schemes.

  8. People detection in crowded scenes using active contour models

    Science.gov (United States)

    Sidla, Oliver

    2009-01-01

    The detection of pedestrians in real-world scenes is a daunting task, especially in crowded situations. Our experience over the last years has shown that active shape models (ASM) can contribute significantly to a robust pedestrian detection system. The paper starts with an overview of shape model approaches, it then explains our approach which builds on top of Eigenshape models which have been trained using real-world data. These models are placed over candidate regions and matched to image gradients using a scoring function which integrates i) point distribution, ii) local gradient orientations iii) local image gradient strengths. A matching and shape model update process is iteratively applied in order to fit the flexible models to the local image content. The weights of the scoring function have a significant impact on the ASM performance. We analyze different settings of scoring weights for gradient magnitude, relative orientation differences, distance between model and gradient in an experiment which uses real-world data. Although for only one pedestrian model in an image computation time is low, the number of necessary processing cycles which is needed to track many people in crowded scenes can become the bottleneck in a real-time application. We describe the measures which have been taken in order to improve the speed of the ASM implementation and make it real-time capable.

  9. Crowd-sourced assessment of surgical skills in cricothyrotomy procedure.

    Science.gov (United States)

    Aghdasi, Nava; Bly, Randall; White, Lee W; Hannaford, Blake; Moe, Kris; Lendvay, Thomas S

    2015-06-15

    Objective assessment of surgical skills is resource intensive and requires valuable time of expert surgeons. The goal of this study was to assess the ability of a large group of laypersons using a crowd-sourcing tool to grade a surgical procedure (cricothyrotomy) performed on a simulator. The grading included an assessment of the entire procedure by completing an objective assessment of technical skills survey. Two groups of graders were recruited as follows: (1) Amazon Mechanical Turk users and (2) three expert surgeons from University of Washington Department of Otolaryngology. Graders were presented with a video of participants performing the procedure on the simulator and were asked to grade the video using the objective assessment of technical skills questions. Mechanical Turk users were paid $0.50 for each completed survey. It took 10 h to obtain all responses from 30 Mechanical Turk users for 26 training participants (26 videos/tasks), whereas it took 60 d for three expert surgeons to complete the same 26 tasks. The assessment of surgical performance by a group (n = 30) of laypersons matched the assessment by a group (n = 3) of expert surgeons with a good level of agreement determined by Cronbach alpha coefficient = 0.83. We found crowd sourcing was an efficient, accurate, and inexpensive method for skills assessment with a good level of agreement to experts' grading. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Deciphering the crowd: modeling and identification of pedestrian group motion.

    Science.gov (United States)

    Yücel, Zeynep; Zanlungo, Francesco; Ikeda, Tetsushi; Miyashita, Takahiro; Hagita, Norihiro

    2013-01-14

    Associating attributes to pedestrians in a crowd is relevant for various areas like surveillance, customer profiling and service providing. The attributes of interest greatly depend on the application domain and might involve such social relations as friends or family as well as the hierarchy of the group including the leader or subordinates. Nevertheless, the complex social setting inherently complicates this task. We attack this problem by exploiting the small group structures in the crowd. The relations among individuals and their peers within a social group are reliable indicators of social attributes. To that end, this paper identifies social groups based on explicit motion models integrated through a hypothesis testing scheme. We develop two models relating positional and directional relations. A pair of pedestrians is identified as belonging to the same group or not by utilizing the two models in parallel, which defines a compound hypothesis testing scheme. By testing the proposed approach on three datasets with different environmental properties and group characteristics, it is demonstrated that we achieve an identification accuracy of 87% to 99%. The contribution of this study lies in its definition of positional and directional relation models, its description of compound evaluations, and the resolution of ambiguities with our proposed uncertainty measure based on the local and global indicators of group relation.

  11. Deciphering the Crowd: Modeling and Identification of Pedestrian Group Motion

    Directory of Open Access Journals (Sweden)

    Norihiro Hagita

    2013-01-01

    Full Text Available Associating attributes to pedestrians in a crowd is relevant for various areas like surveillance, customer profiling and service providing. The attributes of interest greatly depend on the application domain and might involve such social relations as friends or family as well as the hierarchy of the group including the leader or subordinates. Nevertheless, the complex social setting inherently complicates this task. We attack this problem by exploiting the small group structures in the crowd. The relations among individuals and their peers within a social group are reliable indicators of social attributes. To that end, this paper identifies social groups based on explicit motion models integrated through a hypothesis testing scheme. We develop two models relating positional and directional relations. A pair of pedestrians is identified as belonging to the same group or not by utilizing the two models in parallel, which defines a compound hypothesis testing scheme. By testing the proposed approach on three datasets with different environmental properties and group characteristics, it is demonstrated that we achieve an identification accuracy of 87% to 99%. The contribution of this study lies in its definition of positional and directional relation models, its description of compound evaluations, and the resolution of ambiguities with our proposed uncertainty measure based on the local and global indicators of group relation.

  12. Vehicular Visible Light Networks for Urban Mobile Crowd Sensing.

    Science.gov (United States)

    Masini, Barbara M; Bazzi, Alessandro; Zanella, Alberto

    2018-04-12

    Crowd sensing is a powerful tool to map and predict interests and events. In the future, it could be boosted by an increasing number of connected vehicles sharing information and intentions. This will be made available by on board wireless connected devices able to continuously communicate with other vehicles and with the environment. Among the enabling technologies, visible light communication (VLC) represents a low cost solution in the short term. In spite of the fact that vehicular communications cannot rely on the sole VLC due to the limitation provided by the light which allows communications in visibility only, VLC can however be considered to complement other wireless communication technologies which could be overloaded in dense scenarios. In this paper we evaluate the performance of VLC connected vehicles when urban crowd sensing is addressed and we compare the performance of sole vehicular visible light networks with that of VLC as a complementary technology of IEEE 802.11p. Results, obtained through a realistic simulation tool taking into account both the roadmap constraints and the technologies protocols, help to understand when VLC provides the major improvement in terms of delivered data varying the number and position of RSUs and the FOV of the receiver.

  13. Planet Candidate Validation in K2 Crowded Fields

    Science.gov (United States)

    Rampalli, Rayna; Vanderburg, Andrew; Latham, David; Quinn, Samuel

    2018-01-01

    In just three years, the K2 mission has yielded some remarkable outcomes with the discovery of over 100 confirmed planets and 500 reported planet candidates to be validated. One challenge with this mission is the search for planets located in star-crowded regions. Campaign 13 is one such example, located towards the galactic plane in the constellation of Taurus. We subject the potential planetary candidates to a validation process involving spectroscopy to derive certain stellar parameters. Seeing-limited on/off imaging follow-up is also utilized in order to rule out false positives due to nearby eclipsing binaries. Using Markov chain Monte Carlo analysis, the best-fit parameters for each candidate are generated. These will be suitable for finding a candidate’s false positive probability through methods including feeding such parameters into the Validation of Exoplanet Signals using a Probabilistic Algorithm (VESPA). These techniques and results serve as important tools for conducting candidate validation and follow-up observations for space-based missions such as the upcoming TESS mission since TESS’s large camera pixels resemble K2’s star-crowded fields.

  14. Crowd behaviour during high-stress evacuations in an immersive virtual environment

    Science.gov (United States)

    Kapadia, Mubbasir; Thrash, Tyler; Sumner, Robert W.; Gross, Markus; Helbing, Dirk; Hölscher, Christoph

    2016-01-01

    Understanding the collective dynamics of crowd movements during stressful emergency situations is central to reducing the risk of deadly crowd disasters. Yet, their systematic experimental study remains a challenging open problem due to ethical and methodological constraints. In this paper, we demonstrate the viability of shared three-dimensional virtual environments as an experimental platform for conducting crowd experiments with real people. In particular, we show that crowds of real human subjects moving and interacting in an immersive three-dimensional virtual environment exhibit typical patterns of real crowds as observed in real-life crowded situations. These include the manifestation of social conventions and the emergence of self-organized patterns during egress scenarios. High-stress evacuation experiments conducted in this virtual environment reveal movements characterized by mass herding and dangerous overcrowding as they occur in crowd disasters. We describe the behavioural mechanisms at play under such extreme conditions and identify critical zones where overcrowding may occur. Furthermore, we show that herding spontaneously emerges from a density effect without the need to assume an increase of the individual tendency to imitate peers. Our experiments reveal the promise of immersive virtual environments as an ethical, cost-efficient, yet accurate platform for exploring crowd behaviour in high-risk situations with real human subjects. PMID:27605166

  15. Crowd-Sourcing (Semantically) Structured Multilingual Educational Content (CoSMEC)

    Science.gov (United States)

    Tarasowa, Darya; Auer, Sören; Khalili, Ali; Unbehauen, Jörg

    2014-01-01

    The support of multilingual content becomes crucial for educational platforms due to the benefits it offers. In this paper we propose a concept that allows content authors to use the power of the crowd to create (semantically) structured multilingual educational content out of their material. To enable the collaboration of the crowd, we expand our…

  16. Stability analysis of predator-prey interaction with a crowding effect ...

    African Journals Online (AJOL)

    The mathematical modeling of species interactions usually relies on competition models. However, it is known that species interactions may exhibit more complicated patterns with a crowding effect and this can be particularly important in benign environments. In this paper we discuss competition models with a crowding ...

  17. Crowding Valuation in Urban Tram and Bus Transportation based on Smart Card Data

    NARCIS (Netherlands)

    Yap, M.D.; Cats, O.; Yu, S; van Arem, B.

    2017-01-01

    Crowding in public transport can be of major influence on passengers’ travel experience and therefore affect route and mode choice. Therefore, it is important to understand how crowding in urban public transport is perceived by passengers. The availability of individual smart card transactions

  18. On Streams and Incentives : A Synthesis of Individual and Collective Crowd Motion

    NARCIS (Netherlands)

    van Goethem, Arthur; Jaklin, Norman; Cook IV, Atlas; Geraerts, Roland|info:eu-repo/dai/nl/304830291

    2015-01-01

    We present a novel crowd simulation model that combines the advantages of agent-based and ow-based paradigms while only relying on local information. Our model can handle arbitrary and dynamically changing crowd densities, and it enables agents to gradually interpolate between individual and

  19. Crowd behaviour during high-stress evacuations in an immersive virtual environment.

    Science.gov (United States)

    Moussaïd, Mehdi; Kapadia, Mubbasir; Thrash, Tyler; Sumner, Robert W; Gross, Markus; Helbing, Dirk; Hölscher, Christoph

    2016-09-01

    Understanding the collective dynamics of crowd movements during stressful emergency situations is central to reducing the risk of deadly crowd disasters. Yet, their systematic experimental study remains a challenging open problem due to ethical and methodological constraints. In this paper, we demonstrate the viability of shared three-dimensional virtual environments as an experimental platform for conducting crowd experiments with real people. In particular, we show that crowds of real human subjects moving and interacting in an immersive three-dimensional virtual environment exhibit typical patterns of real crowds as observed in real-life crowded situations. These include the manifestation of social conventions and the emergence of self-organized patterns during egress scenarios. High-stress evacuation experiments conducted in this virtual environment reveal movements characterized by mass herding and dangerous overcrowding as they occur in crowd disasters. We describe the behavioural mechanisms at play under such extreme conditions and identify critical zones where overcrowding may occur. Furthermore, we show that herding spontaneously emerges from a density effect without the need to assume an increase of the individual tendency to imitate peers. Our experiments reveal the promise of immersive virtual environments as an ethical, cost-efficient, yet accurate platform for exploring crowd behaviour in high-risk situations with real human subjects. © 2016 The Authors.

  20. Detection of High-Density Crowds in Aerial Images Using Texture Classification

    Directory of Open Access Journals (Sweden)

    Oliver Meynberg

    2016-06-01

    Full Text Available Automatic crowd detection in aerial images is certainly a useful source of information to prevent crowd disasters in large complex scenarios of mass events. A number of publications employ regression-based methods for crowd counting and crowd density estimation. However, these methods work only when a correct manual count is available to serve as a reference. Therefore, it is the objective of this paper to detect high-density crowds in aerial images, where counting– or regression–based approaches would fail. We compare two texture–classification methodologies on a dataset of aerial image patches which are grouped into ranges of different crowd density. These methodologies are: (1 a Bag–of–words (BoW model with two alternative local features encoded as Improved Fisher Vectors and (2 features based on a Gabor filter bank. Our results show that a classifier using either BoW or Gabor features can detect crowded image regions with 97% classification accuracy. In our tests of four classes of different crowd-density ranges, BoW–based features have a 5%–12% better accuracy than Gabor.

  1. Revisiting Gustave Le Bon’s crowd theory in light of present-day critique

    DEFF Research Database (Denmark)

    Laursen, Rasmus Beedholm; Møller, Verner

    2017-01-01

    understanding of crowd or mass behaviour that proves Le Bon’s crowd theory wrong. However, in this paper, we challenge this perception not only by questioning Drury, Reicher and Stott’s interpretation of Le Bon, but also suggesting that the dialogue strategy that is based upon the ESIM, in fact, validates Le...

  2. Towards Believable Crowds : A Generic Multi-Level Framework for Agent Navigation

    NARCIS (Netherlands)

    van Toll, Wouter; Jaklin, Norman; Geraerts, Roland

    2015-01-01

    Path planning and crowd simulation are important computational tasks in computer games and applications of high social relevance, such as crowd management and safety training. Virtual characters (agents) need to autonomously find a path from their current position to a designated goal position. This

  3. Kinetic models for crowd dynamics. Comment on "Human behaviours in evacuation crowd dynamics: From modelling to "big data" toward crisis management" by N. Bellomo et al.

    Science.gov (United States)

    Banasiak, J.

    2016-09-01

    There has been a hierarchy of models of crowd behaviour. One can consider the crowd at the so called microscopic level, as a collection of individuals, and derive its description in the form of a (large) system of ordinary differential equations describing the position and velocity of each individual, in parallel to the Newton's description of matter, see e.g. [10]. Another possibility is to describe crowd, in analogy to fluid dynamics, by providing its density and velocity at a given point, see e.g. [11,12]. At the same time, it is recognized that crowd is 'living, social' system that is prone to exhibit rare, not easily predictable, behaviour in response to stress induced by the perception of danger, or of the action of specific agents, see e.g. [1,2]. This high probability of the occurrence of events that are far from average, makes the crowd behaviour similar to the processes with fat-tailed distribution of events. Such unlikely events have been metaphorically termed black swans in [14], or Lévy flights in [13]. While microscopic and macroscopic models can capture many features of crowd dynamics, including obstacles, see [3,8], such models are described by differential equations that inherently are local in space. At the same time, black swan events are often caused by non-local interactions such as self-organization, learning or adherence to some averaged group behaviour. It is known that such interactions are well described by mean field models best represented by integro-differential equations, such as the Boltzmann equation of the rarefied gas theory. This has made plausible to introduce crowd models at the intermediate, (meso) scale by describing the crowd by the one particle distribution function that gives the density of individuals at any particular state; that is, at a given point in the domain and moving with a specific velocity.

  4. Molecular imaging of EGFR and CD44v6 for prediction and response monitoring of HSP90 inhibition in an in vivo squamous cell carcinoma model

    Energy Technology Data Exchange (ETDEWEB)

    Spiegelberg, Diana; Mortensen, Anja C.; Stenerloew, Bo [Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala (Sweden); Selvaraju, Ram K.; Eriksson, Olof [Uppsala University, Preclinical PET Platform, Uppsala (Sweden); Nestor, Marika [Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala (Sweden); Uppsala University, Unit of Otolaryngology and Head and Neck Surgery, Department of Surgical Sciences, Uppsala (Sweden)

    2016-05-15

    Heat shock protein 90 (HSP90) is essential for the activation and stabilization of numerous oncogenic client proteins. AT13387 is a novel HSP90 inhibitor promoting degradation of oncogenic proteins upon binding, and may also act as a radiosensitizer. For optimal treatment there is, however, the need for identification of biomarkers for patient stratification and therapeutic response monitoring, and to find suitable targets for combination treatments. The aim of this study was to assess the response of surface antigens commonly expressed in squamous cell carcinoma to AT13387 treatment, and to find suitable biomarkers for molecular imaging and radioimmunotherapy in combination with HSP90 inhibition. Cancer cell proliferation and radioimmunoassays were used to evaluate the effect of AT13387 on target antigen expression in vitro. Inhibitor effects were then assessed in vivo in mice-xenografts. Animals were treated with AT13387 (5 x 50 mg/kg), and were imaged with PET using either {sup 18}F-FDG or {sup 124}I-labelled tracers for EGFR and CD44v6, and this was followed by ex-vivo biodistribution analysis and immunohistochemical staining. AT13387 exposure resulted in high cytotoxicity and possible radiosensitization with IC{sub 50} values below 4 nM. Both in vitro and in vivo AT13387 effectively downregulated HSP90 client proteins. PET imaging with {sup 124}I-cetuximab showed a significant decrease of EGFR in AT13387-treated animals compared with untreated animals. In contrast, the squamous cell carcinoma-associated biomarker CD44v6, visualized with {sup 124}I-AbD19384 as well as {sup 18}F-FDG uptake, were not significantly altered by AT13387 treatment. We conclude that AT13387 downregulates HSP90 client proteins, and that molecular imaging of these proteins may be a suitable approach for assessing treatment response. Furthermore, radioimmunotherapy targeting CD44v6 in combination with AT13387 may potentiate the radioimmunotherapy outcome due to radiosensitizing effects of

  5. Cross-cultural differences in tolerance for crowding: fact or fiction?

    Science.gov (United States)

    Evans, G W; Lepore, S J; Allen, K M

    2000-08-01

    It is widely believed that cultures vary in their tolerance for crowding. There is, however, little evidence to substantiate this belief, coupled with serious shortcomings in the extant literature. Tolerance for crowding has been confused with cultural differences in personal space preferences along with perceived crowding. Furthermore, the few studies that have examined cultural variability in reactions to crowding have compared subgroup correlations, which is not equivalent to a statistical interaction. Although the authors found a statistical interaction indicating that Asian Americans and Latin Americans differ in the way they perceive crowding in comparison to their fellow Anglo-American and African American citizens, all four ethnic groups suffer similar, negative psychological distress sequelae of high-density housing. These results hold independently of household income.

  6. Crowding in Visual Working Memory Reveals Its Spatial Resolution and the Nature of Its Representations.

    Science.gov (United States)

    Tamber-Rosenau, Benjamin J; Fintzi, Anat R; Marois, René

    2015-09-01

    Spatial resolution fundamentally limits any image representation. Although this limit has been extensively investigated for perceptual representations by assessing how neighboring flankers degrade the perception of a peripheral target with visual crowding, the corresponding limit for representations held in visual working memory (VWM) is unknown. In the present study, we evoked crowding in VWM and directly compared resolution in VWM and perception. Remarkably, the spatial resolution of VWM proved to be no worse than that of perception. However, mixture modeling of errors caused by crowding revealed the qualitatively distinct nature of these representations. Perceptual crowding errors arose from both increased imprecision in target representations and substitution of flankers for targets. By contrast, VWM crowding errors arose exclusively from substitutions, which suggests that VWM transforms analog perceptual representations into discrete items. Thus, although perception and VWM share a common resolution limit, exceeding this limit reveals distinct mechanisms for perceiving images and holding them in mind. © The Author(s) 2015.

  7. Macromolecular crowding directs extracellular matrix organization and mesenchymal stem cell behavior.

    Directory of Open Access Journals (Sweden)

    Adam S Zeiger

    Full Text Available Microenvironments of biological cells are dominated in vivo by macromolecular crowding and resultant excluded volume effects. This feature is absent in dilute in vitro cell culture. Here, we induced macromolecular crowding in vitro by using synthetic macromolecular globules of nm-scale radius at physiological levels of fractional volume occupancy. We quantified the impact of induced crowding on the extracellular and intracellular protein organization of human mesenchymal stem cells (MSCs via immunocytochemistry, atomic force microscopy (AFM, and AFM-enabled nanoindentation. Macromolecular crowding in extracellular culture media directly induced supramolecular assembly and alignment of extracellular matrix proteins deposited by cells, which in turn increased alignment of the intracellular actin cytoskeleton. The resulting cell-matrix reciprocity further affected adhesion, proliferation, and migration behavior of MSCs. Macromolecular crowding can thus aid the design of more physiologically relevant in vitro studies and devices for MSCs and other cells, by increasing the fidelity between materials synthesized by cells in vivo and in vitro.

  8. Macromolecular crowding directs extracellular matrix organization and mesenchymal stem cell behavior.

    Science.gov (United States)

    Zeiger, Adam S; Loe, Felicia C; Li, Ran; Raghunath, Michael; Van Vliet, Krystyn J

    2012-01-01

    Microenvironments of biological cells are dominated in vivo by macromolecular crowding and resultant excluded volume effects. This feature is absent in dilute in vitro cell culture. Here, we induced macromolecular crowding in vitro by using synthetic macromolecular globules of nm-scale radius at physiological levels of fractional volume occupancy. We quantified the impact of induced crowding on the extracellular and intracellular protein organization of human mesenchymal stem cells (MSCs) via immunocytochemistry, atomic force microscopy (AFM), and AFM-enabled nanoindentation. Macromolecular crowding in extracellular culture media directly induced supramolecular assembly and alignment of extracellular matrix proteins deposited by cells, which in turn increased alignment of the intracellular actin cytoskeleton. The resulting cell-matrix reciprocity further affected adhesion, proliferation, and migration behavior of MSCs. Macromolecular crowding can thus aid the design of more physiologically relevant in vitro studies and devices for MSCs and other cells, by increasing the fidelity between materials synthesized by cells in vivo and in vitro.

  9. Social crowding in the night-time reduces an anxiety-like behavior and increases social interaction in adolescent mice.

    Science.gov (United States)

    Ago, Yukio; Tanaka, Tatsunori; Ota, Yuki; Kitamoto, Mari; Imoto, Emina; Takuma, Kazuhiro; Matsuda, Toshio

    2014-08-15

    Rearing in crowded conditions is a psychosocial stressor that affects biological functions. The effects of continuous crowding for many days have been studied, but those of crowding over a limited time have not. In this study, we examined the effects of night-time or daytime crowding over 2 weeks on behavior in adolescent and adult mice. Crowding (20 mice/cage) in either the night-time or daytime did not affect locomotor activity in the open field test or cognitive function in the fear conditioning test. In contrast, night-time crowding, but not daytime crowding, had an anxiolytic effect in the elevated plus-maze test and increased social interaction in adolescent mice, but not in adult mice. The first night-time, but not daytime, crowding increased plasma corticosterone levels in adolescent mice, although night-time crowding over 2 weeks did not affect the corticosterone levels. Furthermore, no significant effects of the first crowding were observed in adult mice. In a second crowding condition (six mice/small cage), the anxiolytic-like effects of night-time crowding and the change in plasma corticosterone levels were not observed, suggesting that the density of mice is not important for the behavioral consequences of crowding. Night-time crowding did not affect neurotrophic/growth factor levels and hippocampal neurogenesis in adolescent mice. These findings suggest that night-time crowding leads to anxiolytic-like behaviors in adolescent mice, and imply that night-time crowding stress in adolescence may be beneficial to brain functions. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. The challenges of launching a crowd based platform : A single case study of a Swedish service provider

    OpenAIRE

    Eliasson, Robert; Viklund, Tobias

    2013-01-01

    Using the concept of open innovation companies have started to look beyond their own borders using the crowd as a source for labour, knowledge and innovation. During the last few years the phenomena of crowdsourcing and crowdfunding have become increasingly popular as sources of competitive advantage through the crowd. While several studies have examined crowd based platforms focusing on the users, little attention has been brought to the companies starting these crowd based services. This st...

  11. Testing the excitation/inhibition imbalance hypothesis in a mouse model of the autism spectrum disorder: in vivo neurospectroscopy and molecular evidence for regional phenotypes.

    Science.gov (United States)

    Gonçalves, Joana; Violante, Inês R; Sereno, José; Leitão, Ricardo A; Cai, Ying; Abrunhosa, Antero; Silva, Ana Paula; Silva, Alcino J; Castelo-Branco, Miguel

    2017-01-01

    Excitation/inhibition (E/I) imbalance remains a widely discussed hypothesis in autism spectrum disorders (ASD). The presence of such an imbalance may potentially define a therapeutic target for the treatment of cognitive disabilities related to this pathology. Consequently, the study of monogenic disorders related to autism, such as neurofibromatosis type 1 (NF1), represents a promising approach to isolate mechanisms underlying ASD-related cognitive disabilities. However, the NF1 mouse model showed increased γ-aminobutyric acid (GABA) neurotransmission, whereas the human disease showed reduced cortical GABA levels. It is therefore important to clarify whether the E/I imbalance hypothesis holds true. We hypothesize that E/I may depend on distinct pre- and postsynaptic push-pull mechanisms that might be are region-dependent. In current study, we assessed two critical components of E/I regulation: the concentration of neurotransmitters and levels of GABA(A) receptors. Measurements were performed across the hippocampi, striatum, and prefrontal cortices by combined in vivo magnetic resonance spectroscopy (MRS) and molecular approaches in this ASD-related animal model, the Nf1 +/- mouse. Cortical and striatal GABA/glutamate ratios were increased. At the postsynaptic level, very high receptor GABA(A) receptor expression was found in hippocampus, disproportionately to the small reduction in GABA levels. Gabaergic tone (either by receptor levels change or GABA/glutamate ratios) seemed therefore to be enhanced in all regions, although by a different mechanism. Our data provides support for the hypothesis of E/I imbalance in NF1 while showing that pre- and postsynaptic changes are region-specific. All these findings are consistent with our previous physiological evidence of increased inhibitory tone. Such heterogeneity suggests that therapeutic approaches to address neurochemical imbalance in ASD may need to focus on targets where convergent physiological mechanisms can be

  12. The Arabidopsis CROWDED NUCLEI genes regulate seed germination by modulating degradation of ABI5 protein.

    Science.gov (United States)

    Zhao, Wenming; Guan, Chunmei; Feng, Jian; Liang, Yan; Zhan, Ni; Zuo, Jianru; Ren, Bo

    2016-07-01

    In Arabidopsis, the phytohormone abscisic acid (ABA) plays a vital role in inhibiting seed germination and in post-germination seedling establishment. In the ABA signaling pathway, ABI5, a basic Leu zipper transcription factor, has important functions in the regulation of seed germination. ABI5 protein localizes in nuclear bodies, along with AFP, COP1, and SIZ1, and was degraded through the 26S proteasome pathway. However, the mechanisms of ABI5 nuclear body formation and ABI5 protein degradation remain obscure. In this study, we found that the Arabidopsis CROWDED NUCLEI (CRWN) proteins, predicted nuclear matrix proteins essential for maintenance of nuclear morphology, also participate in ABA-controlled seed germination by regulating the degradation of ABI5 protein. During seed germination, the crwn mutants are hypersensitive to ABA and have higher levels of ABI5 protein compared to wild type. Genetic analysis suggested that CRWNs act upstream of ABI5. The observation that CRWN3 colocalizes with ABI5 in nuclear bodies indicates that CRWNs might participate in ABI5 protein degradation in nuclear bodies. Moreover, we revealed that the extreme C-terminal of CRWN3 protein is necessary for its function in the response to ABA in germination. Our results suggested important roles of CRWNs in ABI5 nuclear body organization and ABI5 protein degradation during seed germination. © 2015 Institute of Botany, Chinese Academy of Sciences.

  13. Analytic formalism for current crowding in light emitting diodes

    International Nuclear Information System (INIS)

    Lee, Kyu-Seok

    2012-01-01

    This paper presents an analytic approach to simulating current crowding (CC) in light-emitting diodes with parallel p- and n-contacts. The electrical potential difference across the p-i-n layers is derived from the Laplace equation, whereas the current density through the p-i-n layers is obtained from the current density - voltage relation of a single-diode model. Since these two properties influence each other, they are calculated iteratively. It is found that CC depends on the applied voltage (or the average current density), the sheet resistances of the p- and the n-contact layers, the width of the active region, and the specific series resistance and ideality factor of the p-i-n layers. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  14. Hopping in the Crowd to Unveil Network Topology

    Science.gov (United States)

    Asllani, Malbor; Carletti, Timoteo; Di Patti, Francesca; Fanelli, Duccio; Piazza, Francesco

    2018-04-01

    We introduce a nonlinear operator to model diffusion on a complex undirected network under crowded conditions. We show that the asymptotic distribution of diffusing agents is a nonlinear function of the nodes' degree and saturates to a constant value for sufficiently large connectivities, at variance with standard diffusion in the absence of excluded-volume effects. Building on this observation, we define and solve an inverse problem, aimed at reconstructing the a priori unknown connectivity distribution. The method gathers all the necessary information by repeating a limited number of independent measurements of the asymptotic density at a single node, which can be chosen randomly. The technique is successfully tested against both synthetic and real data and is also shown to estimate with great accuracy the total number of nodes.

  15. Mobile Crowd Sensing for Traffic Prediction in Internet of Vehicles.

    Science.gov (United States)

    Wan, Jiafu; Liu, Jianqi; Shao, Zehui; Vasilakos, Athanasios V; Imran, Muhammad; Zhou, Keliang

    2016-01-11

    The advances in wireless communication techniques, mobile cloud computing, automotive and intelligent terminal technology are driving the evolution of vehicle ad hoc networks into the Internet of Vehicles (IoV) paradigm. This leads to a change in the vehicle routing problem from a calculation based on static data towards real-time traffic prediction. In this paper, we first address the taxonomy of cloud-assisted IoV from the viewpoint of the service relationship between cloud computing and IoV. Then, we review the traditional traffic prediction approached used by both Vehicle to Infrastructure (V2I) and Vehicle to Vehicle (V2V) communications. On this basis, we propose a mobile crowd sensing technology to support the creation of dynamic route choices for drivers wishing to avoid congestion. Experiments were carried out to verify the proposed approaches. Finally, we discuss the outlook of reliable traffic prediction.

  16. Mobile Crowd Sensing for Traffic Prediction in Internet of Vehicles

    Directory of Open Access Journals (Sweden)

    Jiafu Wan

    2016-01-01

    Full Text Available The advances in wireless communication techniques, mobile cloud computing, automotive and intelligent terminal technology are driving the evolution of vehicle ad hoc networks into the Internet of Vehicles (IoV paradigm. This leads to a change in the vehicle routing problem from a calculation based on static data towards real-time traffic prediction. In this paper, we first address the taxonomy of cloud-assisted IoV from the viewpoint of the service relationship between cloud computing and IoV. Then, we review the traditional traffic prediction approached used by both Vehicle to Infrastructure (V2I and Vehicle to Vehicle (V2V communications. On this basis, we propose a mobile crowd sensing technology to support the creation of dynamic route choices for drivers wishing to avoid congestion. Experiments were carried out to verify the proposed approaches. Finally, we discuss the outlook of reliable traffic prediction.

  17. Resolving stellar populations with crowded field 3D spectroscopy

    Science.gov (United States)

    Kamann, S.; Wisotzki, L.; Roth, M. M.

    2013-01-01

    We describe a new method of extracting the spectra of stars from observations of crowded stellar fields with integral field spectroscopy (IFS). Our approach extends the well-established concept of crowded field photometry in images into the domain of 3-dimensional spectroscopic datacubes. The main features of our algorithm follow. (1) We assume that a high-fidelity input source catalogue already exists, e.g. from HST data, and that it is not needed to perform sophisticated source detection in the IFS data. (2) Source positions and properties of the point spread function (PSF) vary smoothly between spectral layers of the datacube, and these variations can be described by simple fitting functions. (3) The shape of the PSF can be adequately described by an analytical function. Even without isolated PSF calibrator stars we can therefore estimate the PSF by a model fit to the full ensemble of stars visible within the field of view. (4) By using sparse matrices to describe the sources, the problem of extracting the spectra of many stars simultaneously becomes computationally tractable. We present extensive performance and validation tests of our algorithm using realistic simulated datacubes that closely reproduce actual IFS observations of the central regions of Galactic globular clusters. We investigate the quality of the extracted spectra under the effects of crowding with respect to the resulting signal-to-noise ratios (S/N) and any possible changes in the continuum level, as well as with respect to absorption line spectral parameters, radial velocities, and equivalent widths. The main effect of blending between two nearby stars is a decrease in the S/N in their spectra. The effect increases with the crowding in the field in a way that the maximum number of stars with useful spectra is always ~0.2 per spatial resolution element. This balance breaks down when exceeding a total source density of one significantly detected star per resolution element. We also explore the

  18. Can the online-crowd match real expert judgments?

    DEFF Research Database (Denmark)

    Horn, Alexander

    2018-01-01

    ; using the coding of political texts as an example in which both strategies produce similar results. Since crowdcoding yields the potential to extend the replication standard to data production and to “scale” coding schemes based on a modest number of carefully devised test questions and answers......, it is important that we better understand its possibilities and limitations. While previous results for low complexity coding tasks are encouraging, we assess whether and under what conditions simple and complex coding tasks can be outsourced to the crowd without sacrificing content validity in return...... for scalability. The simple task is to decide whether a party statement counts as positive reference to a concept – in our case equality. The complex task is to distinguish between five concepts of equality. To account for the crowdcoder’s contextual knowledge, we vary the IP restrictions. The basis for our...

  19. Public Service Motivation and Monetary Incentives: Substitutes or Motivation Crowding?

    DEFF Research Database (Denmark)

    Jacobsen, Christian Bøtcher

    2011-01-01

    Motivation is probably one of the most important determinants for organizational performance, because it stimulates effort and effective behaviors among people in the organization. But what type of motivation should public managers rely on? The PSM literature has argued that public service...... motivation is the most important type of motivation in the delivery of public service, because it substitutes for egoistic motivation. Organizations whose members have high levels of PSM are therefore expected to be less dependent on utilitarian motivators such as monetary incentives. Motivation crowding...... theory, on the other hand, argues that the relationship is opposite, so it is the degree of incentives that affects motivation. Both arguments lead to expectations of an association between public service motivation and monetary incentives, but so far this complex relationship has not been entangled...

  20. Learning Supervised Topic Models for Classification and Regression from Crowds.

    Science.gov (United States)

    Rodrigues, Filipe; Lourenco, Mariana; Ribeiro, Bernardete; Pereira, Francisco C

    2017-12-01

    The growing need to analyze large collections of documents has led to great developments in topic modeling. Since documents are frequently associated with other related variables, such as labels or ratings, much interest has been placed on supervised topic models. However, the nature of most annotation tasks, prone to ambiguity and noise, often with high volumes of documents, deem learning under a single-annotator assumption unrealistic or unpractical for most real-world applications. In this article, we propose two supervised topic models, one for classification and another for regression problems, which account for the heterogeneity and biases among different annotators that are encountered in practice when learning from crowds. We develop an efficient stochastic variational inference algorithm that is able to scale to very large datasets, and we empirically demonstrate the advantages of the proposed model over state-of-the-art approaches.

  1. Cloud-Enhanced Robotic System for Smart City Crowd Control

    Directory of Open Access Journals (Sweden)

    Akhlaqur Rahman

    2016-12-01

    Full Text Available Cloud robotics in smart cities is an emerging paradigm that enables autonomous robotic agents to communicate and collaborate with a cloud computing infrastructure. It complements the Internet of Things (IoT by creating an expanded network where robots offload data-intensive computation to the ubiquitous cloud to ensure quality of service (QoS. However, offloading for robots is significantly complex due to their unique characteristics of mobility, skill-learning, data collection, and decision-making capabilities. In this paper, a generic cloud robotics framework is proposed to realize smart city vision while taking into consideration its various complexities. Specifically, we present an integrated framework for a crowd control system where cloud-enhanced robots are deployed to perform necessary tasks. The task offloading is formulated as a constrained optimization problem capable of handling any task flow that can be characterized by a Direct Acyclic Graph (DAG. We consider two scenarios of minimizing energy and time, respectively, and develop a genetic algorithm (GA-based approach to identify the optimal task offloading decisions. The performance comparison with two benchmarks shows that our GA scheme achieves desired energy and time performance. We also show the adaptability of our algorithm by varying the values for bandwidth and movement. The results suggest their impact on offloading. Finally, we present a multi-task flow optimal path sequence problem that highlights how the robot can plan its task completion via movements that expend the minimum energy. This integrates path planning with offloading for robotics. To the best of our knowledge, this is the first attempt to evaluate cloud-based task offloading for a smart city crowd control system.

  2. Cellular automaton model of crowd evacuation inspired by slime mould

    Science.gov (United States)

    Kalogeiton, V. S.; Papadopoulos, D. P.; Georgilas, I. P.; Sirakoulis, G. Ch.; Adamatzky, A. I.

    2015-04-01

    In all the living organisms, the self-preservation behaviour is almost universal. Even the most simple of living organisms, like slime mould, is typically under intense selective pressure to evolve a response to ensure their evolution and safety in the best possible way. On the other hand, evacuation of a place can be easily characterized as one of the most stressful situations for the individuals taking part on it. Taking inspiration from the slime mould behaviour, we are introducing a computational bio-inspired model crowd evacuation model. Cellular Automata (CA) were selected as a fully parallel advanced computation tool able to mimic the Physarum's behaviour. In particular, the proposed CA model takes into account while mimicking the Physarum foraging process, the food diffusion, the organism's growth, the creation of tubes for each organism, the selection of optimum tube for each human in correspondence to the crowd evacuation under study and finally, the movement of all humans at each time step towards near exit. To test the model's efficiency and robustness, several simulation scenarios were proposed both in virtual and real-life indoor environments (namely, the first floor of office building B of the Department of Electrical and Computer Engineering of Democritus University of Thrace). The proposed model is further evaluated in a purely quantitative way by comparing the simulation results with the corresponding ones from the bibliography taken by real data. The examined fundamental diagrams of velocity-density and flow-density are found in full agreement with many of the already published corresponding results proving the adequacy, the fitness and the resulting dynamics of the model. Finally, several real Physarum experiments were conducted in an archetype of the aforementioned real-life environment proving at last that the proposed model succeeded in reproducing sufficiently the Physarum's recorded behaviour derived from observation of the aforementioned

  3. The walking behaviour of pedestrian social groups and its impact on crowd dynamics.

    Directory of Open Access Journals (Sweden)

    Mehdi Moussaïd

    Full Text Available Human crowd motion is mainly driven by self-organized processes based on local interactions among pedestrians. While most studies of crowd behaviour consider only interactions among isolated individuals, it turns out that up to 70% of people in a crowd are actually moving in groups, such as friends, couples, or families walking together. These groups constitute medium-scale aggregated structures and their impact on crowd dynamics is still largely unknown. In this work, we analyze the motion of approximately 1500 pedestrian groups under natural condition, and show that social interactions among group members generate typical group walking patterns that influence crowd dynamics. At low density, group members tend to walk side by side, forming a line perpendicular to the walking direction. As the density increases, however, the linear walking formation is bent forward, turning it into a V-like pattern. These spatial patterns can be well described by a model based on social communication between group members. We show that the V-like walking pattern facilitates social interactions within the group, but reduces the flow because of its "non-aerodynamic" shape. Therefore, when crowd density increases, the group organization results from a trade-off between walking faster and facilitating social exchange. These insights demonstrate that crowd dynamics is not only determined by physical constraints induced by other pedestrians and the environment, but also significantly by communicative, social interactions among individuals.

  4. Routing in Dense Human Crowds Using Smartphone Movement Data and Optical Aerial Imagery

    Directory of Open Access Journals (Sweden)

    Florian Hillen

    2015-06-01

    Full Text Available In this paper, we propose a navigation approach for smartphones that enables visitors of major events to avoid crowded areas or narrow streets and to navigate out of dense crowds quickly. Two types of sensor data are integrated. Real-time optical images acquired and transmitted by an airborne camera system are used to compute an estimation of a crowd density map. For this purpose, a patch-based approach with a Gabor filter bank for texture classification in combination with an interest point detector and a smoothing function is applied. Furthermore, the crowd density is estimated based on location and movement speed of in situ smartphone measurements. This information allows for the enhancement of the overall crowd density layer. The composed density information is input to a least-cost routing workflow. Two possible use cases are presented, namely (i an emergency application and (ii a basic routing application. A prototypical implementation of the system is conducted as proof of concept. Our approach is capable of increasing the security level for major events. Visitors are able to avoid dense crowds by routing around them, while security and rescue forces are able to find the fastest way into the crowd.

  5. New insights into turbulent pedestrian movement pattern in crowd-quakes

    International Nuclear Information System (INIS)

    Ma, J; Song, W G; Lo, S M; Fang, Z M

    2013-01-01

    Video recordings right before the Love Parade disaster have been quantitatively analyzed to explore the bursts of unusual crowd movement patterns, crowd-quakes. The pedestrian movement pattern in this incident was special for the reason that it happened in a congested counter flow scenario, where stopped pedestrians were involved. No one was believed to have pushed others intentionally at the beginning, however, under this situation, the body contacts among the pedestrians still induced a force spread, which then led to velocity fluctuation. As indicated by the individual velocity-related features, the densely crowded pedestrian movement displayed turbulent flow features. Further analyzing the overall flow field, we also found that the pedestrian flow field shared typical patterns with turbulent fluid flow. As a result of the turbulent state, different clusters of pedestrians displayed different velocity features. Thus crowd pressure which took into account the velocity and density information was proved to be a good indicator of crowd disasters. Based on these essential features of pedestrian crowd-quakes, a minimal model, i.e., a pedestrian crowd-quake model, was established. Effects including pedestrian gait, stress conservation level and personal intention to escape were explored. (paper)

  6. Agent Based Modeling and Simulation of Pedestrian Crowds In Panic Situations

    KAUST Repository

    Alrashed, Mohammed

    2016-11-01

    The increasing occurrence of panic stampedes during mass events has motivated studying the impact of panic on crowd dynamics and the simulation of pedestrian flows in panic situations. The lack of understanding of panic stampedes still causes hundreds of fatalities each year, not to mention the scarce methodical studies of panic behavior capable of envisaging such crowd dynamics. Under those circumstances, there are thousands of fatalities and twice that many of injuries every year caused be crowd stampede worldwide, despite the tremendous efforts of crowd control and massive numbers of safekeeping forces. Pedestrian crowd dynamics are generally predictable in high-density crowds where pedestrians cannot move freely and thus gives rise to self-propelling interactions between pedestrians. Although every pedestrian has personal preferences, the motion dynamics can be modeled as a social force in such crowds. These forces are representations of internal preferences and objectives to perform certain actions or movements. The corresponding forces can be controlled for each individual to represent a different variety of behaviors that can be associated with panic situations such as escaping danger, clustering, and pushing. In this thesis, we use an agent-based model of pedestrian behavior in panic situations to predict the collective human behavior in such crowd dynamics. The proposed simulations suggests a practical way to alleviate fatalities and minimize the evacuation time in panic situations. Moreover, we introduce contagious panic and pushing behavior, resulting in a more realistic crowd dynamics model. The proposed methodology describes the intensity and spread of panic for each individual as a function of distances between pedestrians.

  7. Macromolecular diffusion in crowded media beyond the hard-sphere model.

    Science.gov (United States)

    Blanco, Pablo M; Garcés, Josep Lluís; Madurga, Sergio; Mas, Francesc

    2018-04-25

    The effect of macromolecular crowding on diffusion beyond the hard-core sphere model is studied. A new coarse-grained model is presented, the Chain Entanglement Softened Potential (CESP) model, which takes into account the macromolecular flexibility and chain entanglement. The CESP model uses a shoulder-shaped interaction potential that is implemented in the Brownian Dynamics (BD) computations. The interaction potential contains only one parameter associated with the chain entanglement energetic cost (Ur). The hydrodynamic interactions are included in the BD computations via Tokuyama mean-field equations. The model is used to analyze the diffusion of a streptavidin protein among different sized dextran obstacles. For this system, Ur is obtained by fitting the streptavidin experimental long-time diffusion coefficient Dlongversus the macromolecular concentration for D50 (indicating their molecular weight in kg mol-1) dextran obstacles. The obtained Dlong values show better quantitative agreement with experiments than those obtained with hard-core spheres. Moreover, once parametrized, the CESP model is also able to quantitatively predict Dlong and the anomalous exponent (α) for streptavidin diffusion among D10, D400 and D700 dextran obstacles. Dlong, the short-time diffusion coefficient (Dshort) and α are obtained from the BD simulations by using a new empirical expression, able to describe the full temporal evolution of the diffusion coefficient.

  8. PetroSim - a system to simulate crowd behaviors in emergency situations

    Energy Technology Data Exchange (ETDEWEB)

    Musse, Soraia R.; Silva, Andre T. da; Hardt, Katia; Barros, Leandro M.; Tonietto, Leandro [Universidade do Vale do Rio dos Sinos (UNISINOS), Sao Leopoldo, RS (Brazil). Dept. de Ciencia da Computacao; Roth, Bruno [Instituto Nacional de Pesquisas Espaciais (INPE), Sao Jose dos Campos, SP (Brazil); Rolim, Tuerte Amaral; Melo, Ricardo U.M.; Felipe, Luiz A.B. [PETROBRAS, Natal/Fortaleza, RN/CE (Brazil). Unidade de Negocios RN/CE

    2004-07-01

    This paper presents a framework to simulate the behaviors of crowds in panic situations. The main motivation for this work is to provide to safety engineers the possibility of simulating several aspects of panic situations involving crowds in real time. To accomplish this, we propose a complete framework to model the semantically informed environment as well as the intelligent virtual agents (IVA), which form the crowd who lives in the simulated virtual city. This work includes the integration of many knowledge areas such as VR, behavioral and visualization aspects required to the development of PetroSim. (author)

  9. On the relationship between corrosion inhibiting effect and molecular structure of 2,5-bis(n-pyridyl)-1,3,4-thiadiazole derivatives in acidic media: Ac impedance and DFT studies

    Energy Technology Data Exchange (ETDEWEB)

    Bentiss, F., E-mail: fbentiss@enscl.f [Laboratoire de Chimie de Coordination et d' Analytique (LCCA), Faculte des Sciences, Universite Chouaib Doukkali, B.P. 20, M-24000 El Jadida (Morocco); Mernari, B. [Laboratoire de Chimie de Coordination et d' Analytique (LCCA), Faculte des Sciences, Universite Chouaib Doukkali, B.P. 20, M-24000 El Jadida (Morocco); Traisnel, M. [Unite Materiaux et Transformations (UMET), Ingenierie des Systemes Polymeres, CNRS UMR 8207, ENSCL, B.P. 90108, F-59652 Villeneuve d' Ascq Cedex (France); Vezin, H. [Laboratoire de Spectrochimie Infrarouge et Raman (LASIR), UMR-CNRS 8516, Universite des Sciences et Technologies de Lille, Batiment C5, F-59655 Villeneuve d' Ascq Cedex (France); Lagrenee, M., E-mail: michel.lagrenee@ensc-lille.f [Unite de Catalyse et de Chimie du Solide (UCCS), UMR-CNRS 8181, ENSCL, B.P. 90108, F-59652 Villeneuve d' Ascq Cedex (France)

    2011-01-15

    Research highlights: {yields}2,5-Bis(n-pyridyl)-1,3,4-thiadiazoles (n-PTH) act as good inhibitors for the mild steel in acidic media. {yields}The inhibiting protection depends on the position of the nitrogen on the pyridinium substituent according to order 3-PTH > 2-PTH > 4-PTH. {yields}The adsorption of n-PTH is found to follow the Langmuir's adsorption isotherm. {yields}Data obtained from quantum chemical calculations using DFT method were correlated to the experimentally obtained inhibition efficiencies. - Abstract: The inhibition properties of 2,5-bis(n-pyridyl)-1,3,4-thiadiazoles (n-PTH) on corrosion of mild steel in different acidic media (1 M HCl, 0.5 M H{sub 2}SO{sub 4} and 1 M HClO{sub 4}) were analyzed by electrochemical impedance spectroscopy (EIS). The n-PTH derivatives exhibit good inhibition properties in different acidic solutions and the calculated values of {Delta}G{sub ads}{sup 0} revealed that the adsorption mechanism of n-PTH on steel surface is mainly due to chemisorption. While in 1 M HClO{sub 4}, both 2-PTH and 4-PTH isomers stimulate the corrosion process especially at low concentrations. Quantum chemical calculations using the density functional theory (DFT) were performed on n-PTH derivatives to determine the relationship between molecular structure and their inhibition efficiencies. The results of the quantum chemical calculations and experimental inhibition efficiency were subjected to correlation analysis and indicate that the inhibition effects of n-PTH may be explained in terms of electronic properties.

  10. Explaining effervescence: Investigating the relationship between shared social identity and positive experience in crowds.

    Science.gov (United States)

    Hopkins, Nick; Reicher, Stephen D; Khan, Sammyh S; Tewari, Shruti; Srinivasan, Narayanan; Stevenson, Clifford

    2016-01-01

    We investigated the intensely positive emotional experiences arising from participation in a large-scale collective event. We predicted such experiences arise when those attending a collective event are (1) able to enact their valued collective identity and (2) experience close relations with other participants. In turn, we predicted both of these to be more likely when participants perceived crowd members to share a common collective identity. We investigated these predictions in a survey of pilgrims (N = 416) attending a month-long Hindu pilgrimage festival in north India. We found participants' perceptions of a shared identity amongst crowd members had an indirect effect on their positive experience at the event through (1) increasing participants' sense that they were able to enact their collective identity and (2) increasing the sense of intimacy with other crowd members. We discuss the implications of these data for how crowd emotion should be conceptualised.

  11. CrowdMapping: A Crowdsourcing-Based Terminology Mapping Method for Medical Data Standardization.

    Science.gov (United States)

    Mao, Huajian; Chi, Chenyang; Huang, Boyu; Meng, Haibin; Yu, Jinghui; Zhao, Dongsheng

    2017-01-01

    Standardized terminology is the prerequisite of data exchange in analysis of clinical processes. However, data from different electronic health record systems are based on idiosyncratic terminology systems, especially when the data is from different hospitals and healthcare organizations. Terminology standardization is necessary for the medical data analysis. We propose a crowdsourcing-based terminology mapping method, CrowdMapping, to standardize the terminology in medical data. CrowdMapping uses a confidential model to determine how terminologies are mapped to a standard system, like ICD-10. The model uses mappings from different health care organizations and evaluates the diversity of the mapping to determine a more sophisticated mapping rule. Further, the CrowdMapping model enables users to rate the mapping result and interact with the model evaluation. CrowdMapping is a work-in-progress system, we present initial results mapping terminologies.

  12. Agent Based Modeling and Simulation of Pedestrian Crowds In Panic Situations

    KAUST Repository

    Alrashed, Mohammed

    2016-01-01

    to self-propelling interactions between pedestrians. Although every pedestrian has personal preferences, the motion dynamics can be modeled as a social force in such crowds. These forces are representations of internal preferences and objectives to perform

  13. Parallel Motion Simulation of Large-Scale Real-Time Crowd in a Hierarchical Environmental Model

    Directory of Open Access Journals (Sweden)

    Xin Wang

    2012-01-01

    Full Text Available This paper presents a parallel real-time crowd simulation method based on a hierarchical environmental model. A dynamical model of the complex environment should be constructed to simulate the state transition and propagation of individual motions. By modeling of a virtual environment where virtual crowds reside, we employ different parallel methods on a topological layer, a path layer and a perceptual layer. We propose a parallel motion path matching method based on the path layer and a parallel crowd simulation method based on the perceptual layer. The large-scale real-time crowd simulation becomes possible with these methods. Numerical experiments are carried out to demonstrate the methods and results.

  14. Translational and rotational motions of proteins in a protein crowded environment

    NARCIS (Netherlands)

    Zorilla, S.; Hink, M.A.; Visser, A.J.W.G.; Lillo, M.P.

    2007-01-01

    Fluorescence correlation spectroscopy (FCS) was used to measure the translational diffusion of labeled apomyoglobin (tracer) in concentrated solutions of ribonuclease A and human serum albumin (crowders), as a quantitative model system of protein diffusive motions in crowded physiological

  15. Mathematical Capture of Human Crowd Behavioral Data for Computational Model Building, Verification, and Validation

    Science.gov (United States)

    2011-03-21

    throughout the experimental runs. Reliable and validated measures of anxiety ( Spielberger , 1983), as well as custom-constructed questionnaires about...Crowd modeling and simulation technologies. Transactions on modeling and computer simulation, 20(4). Spielberger , C. D. (1983

  16. Crowded, Confined, and Frustrated: Dynamics of Molecules Tethered to Nanoparticles

    KAUST Repository

    Agarwal, Praveen; Kim, Sung A.; Archer, Lynden A.

    2012-01-01

    Above a critical chemistry-dependent molecular weight, all polymer molecules entangle and, as a result, exhibit slow dynamics, enhanced viscosity, and elasticity. Herein we report on the dynamics of low molecular weight polymers tethered

  17. Crowd-sourced assessment of technical skills: an adjunct to urology resident surgical simulation training.

    Science.gov (United States)

    Holst, Daniel; Kowalewski, Timothy M; White, Lee W; Brand, Timothy C; Harper, Jonathan D; Sorenson, Mathew D; Kirsch, Sarah; Lendvay, Thomas S

    2015-05-01

    Crowdsourcing is the practice of obtaining services from a large group of people, typically an online community. Validated methods of evaluating surgical video are time-intensive, expensive, and involve participation of multiple expert surgeons. We sought to obtain valid performance scores of urologic trainees and faculty on a dry-laboratory robotic surgery task module by using crowdsourcing through a web-based grading tool called Crowd Sourced Assessment of Technical Skill (CSATS). IRB approval was granted to test the technical skills grading accuracy of Amazon.com Mechanical Turk™ crowd-workers compared to three expert faculty surgeon graders. The two groups assessed dry-laboratory robotic surgical suturing performances of three urology residents (PGY-2, -4, -5) and two faculty using three performance domains from the validated Global Evaluative Assessment of Robotic Skills assessment tool. After an average of 2 hours 50 minutes, each of the five videos received 50 crowd-worker assessments. The inter-rater reliability (IRR) between the surgeons and crowd was 0.91 using Cronbach's alpha statistic (confidence intervals=0.20-0.92), indicating an agreement level between the two groups of "excellent." The crowds were able to discriminate the surgical level, and both the crowds and the expert faculty surgeon graders scored one senior trainee's performance above a faculty's performance. Surgery-naive crowd-workers can rapidly assess varying levels of surgical skill accurately relative to a panel of faculty raters. The crowds provided rapid feedback and were inexpensive. CSATS may be a valuable adjunct to surgical simulation training as requirements for more granular and iterative performance tracking of trainees become mandated and commonplace.

  18. Interaction with virtual crowd in Immersive and semi‐Immersive Virtual Reality systems

    OpenAIRE

    Kyriakou, Marios; Pan, Xueni; Chrysanthou, Yiorgos

    2016-01-01

    This study examines attributes of virtual human behavior that may increase the plausibility of a simulated crowd and affect the user's experience in Virtual Reality. Purpose-developed experiments in both Immersive and semi-Immersive Virtual Reality systems queried the impact of collision and basic interaction between real-users and the virtual crowd and their effect on the apparent realism and ease of navigation within Virtual Reality (VR). Participants' behavior and subjective measurements i...

  19. Investigating the In-Vehicle Crowding Cost Functions for Public Transit Modes

    OpenAIRE

    Qin, Feifei

    2014-01-01

    In the densely populated metropolitan area, empirical studies have found that overcrowding inside transit vehicles has become substantially worse and worse over recent years. Chronic in-vehicle crowding is not only caused by a lack of physical infrastructure, but also triggered by inadequate service provisions. Given the prevalence of overcrowded transit vehicles, this paper conducts both quantitative and qualitative studies, especially focusing on remodeling the in-vehicle crowding cost func...

  20. Solving the worldwide emergency department crowding problem - what can we learn from an Israeli ED?

    Science.gov (United States)

    Pines, Jesse M; Bernstein, Steven L

    2015-01-01

    ED crowding is a prevalent and important issue facing hospitals in Israel and around the world, including North and South America, Europe, Australia, Asia and Africa. ED crowding is associated with poorer quality of care and poorer health outcomes, along with extended waits for care. Crowding is caused by a periodic mismatch between the supply of ED and hospital resources and the demand for patient care. In a recent article in the Israel Journal of Health Policy Research, Bashkin et al. present an Ishikawa diagram describing several factors related to longer length of stay (LOS), and higher levels of ED crowding, including management, process, environmental, human factors, and resource issues. Several solutions exist to reduce ED crowding, which involve addressing several of the issues identified by Bashkin et al. This includes reducing the demand for and variation in care, and better matching the supply of resources to demands in care in real time. However, what is needed to reduce crowding is an institutional imperative from senior leadership, implemented by engaged ED and hospital leadership with multi-disciplinary cross-unit collaboration, sufficient resources to implement effective interventions, access to data, and a sustained commitment over time. This may move the culture of a hospital to facilitate improved flow within and across units and ultimately improve quality and safety over the long-term.

  1. Mixed emotions: Sensitivity to facial variance in a crowd of faces.

    Science.gov (United States)

    Haberman, Jason; Lee, Pegan; Whitney, David

    2015-01-01

    The visual system automatically represents summary information from crowds of faces, such as the average expression. This is a useful heuristic insofar as it provides critical information about the state of the world, not simply information about the state of one individual. However, the average alone is not sufficient for making decisions about how to respond to a crowd. The variance or heterogeneity of the crowd--the mixture of emotions--conveys information about the reliability of the average, essential for determining whether the average can be trusted. Despite its importance, the representation of variance within a crowd of faces has yet to be examined. This is addressed here in three experiments. In the first experiment, observers viewed a sample set of faces that varied in emotion, and then adjusted a subsequent set to match the variance of the sample set. To isolate variance as the summary statistic of interest, the average emotion of both sets was random. Results suggested that observers had information regarding crowd variance. The second experiment verified that this was indeed a uniquely high-level phenomenon, as observers were unable to derive the variance of an inverted set of faces as precisely as an upright set of faces. The third experiment replicated and extended the first two experiments using method-of-constant-stimuli. Together, these results show that the visual system is sensitive to emergent information about the emotional heterogeneity, or ambivalence, in crowds of faces.

  2. Emergency department crowding in Singapore: Insights from a systems thinking approach.

    Science.gov (United States)

    Schoenenberger, Lukas K; Bayer, Steffen; Ansah, John P; Matchar, David B; Mohanavalli, Rajagopal L; Lam, Sean Sw; Ong, Marcus Eh

    2016-01-01

    Emergency Department crowding is a serious and international health care problem that seems to be resistant to most well intended but often reductionist policy approaches. In this study, we examine Emergency Department crowding in Singapore from a systems thinking perspective using causal loop diagramming to visualize the systemic structure underlying this complex phenomenon. Furthermore, we evaluate the relative impact of three different policies in reducing Emergency Department crowding in Singapore: introduction of geriatric emergency medicine, expansion of emergency medicine training, and implementation of enhanced primary care. The construction of the qualitative causal loop diagram is based on consultations with Emergency Department experts, direct observation, and a thorough literature review. For the purpose of policy analysis, a novel approach, the path analysis, is applied. The path analysis revealed that both the introduction of geriatric emergency medicine and the expansion of emergency medicine training may be associated with undesirable consequences contributing to Emergency Department crowding. In contrast, enhancing primary care was found to be germane in reducing Emergency Department crowding; in addition, it has apparently no negative side effects, considering the boundary of the model created. Causal loop diagramming was a powerful tool for eliciting the systemic structure of Emergency Department crowding in Singapore. Additionally, the developed model was valuable in testing different policy options.

  3. Household crowding associated with childhood otitis media hospitalisations in New Zealand.

    Science.gov (United States)

    Bowie, Christopher; Pearson, Amber L; Campbell, Malcolm; Barnett, Ross

    2014-06-01

    To examine the association between hospitalisations for otitis media and area-level measures of household crowding among children in New Zealand. Counts of hospital admissions for otitis media by census area unit were offset against population data from the 2006 national census. Area-level household crowding, exposure to tobacco smoke in the home, equivalised income and individual-level characteristics age and sex were adjusted for. To examine effect modification by ethnicity, three separate poisson models were examined for the total, Māori and non-Māori populations. Household crowding was significantly associated with hospital admissions for otitis media after adjustment in all three models. Neighbourhoods with the highest compared to the lowest proportion of crowded homes exhibited incidence rate ratios of 1.25 (95%CI 1.12-1.37) in the total population, 1.59 (95%CI 1.21-2.04) in the Māori restricted model and 1.17 (95%CI 1.06-1.32) in the non-Māori restricted model. Otitis media hospitalisations are associated with area-level measures of household crowding and other risk factors in this ecological study. The largest increase in otitis media incidence relative to neighbourhood rates of household crowding was exhibited among Māori cases of otitis media. This study adds weight to the growing body of literature linking infectious disease risk to overcrowding in the home. © 2014 The Authors. ANZJPH © 2014 Public Health Association of Australia.

  4. Cluster Risk of Walking Scenarios Based on Macroscopic Flow Model and Crowding Force Analysis

    Directory of Open Access Journals (Sweden)

    Xiaohong Li

    2018-02-01

    Full Text Available In recent years, accidents always happen in confined space such as metro stations because of congestion. Various researchers investigated the patterns of dense crowd behaviors in different scenarios via simulations or experiments and proposed methods for avoiding accidents. In this study, a classic continuum macroscopic model was applied to simulate the crowded pedestrian flow in typical scenarios such as at bottlenecks or with an obstacle. The Lax–Wendroff finite difference scheme and artificial viscosity filtering method were used to discretize the model to identify high-density risk areas. Furthermore, we introduced a contact crowding force test of the interactions among pedestrians at bottlenecks. Results revealed that in the most dangerous area, the individual on the corner position bears the maximum pressure in such scenarios is 90.2 N, and there is an approximate exponential relationship between crowding force and density indicated by our data. The results and findings presented in this paper can facilitate more reasonable and precise simulation models by utilizing crowding force and crowd density and ensure the safety of pedestrians in high-density scenarios.

  5. Effect of crowd size on patient volume at a large, multipurpose, indoor stadium.

    Science.gov (United States)

    De Lorenzo, R A; Gray, B C; Bennett, P C; Lamparella, V J

    1989-01-01

    A prediction of patient volume expected at "mass gatherings" is desirable in order to provide optimal on-site emergency medical care. While several methods of predicting patient loads have been suggested, a reliable technique has not been established. This study examines the frequency of medical emergencies at the Syracuse University Carrier Dome, a 50,500-seat indoor stadium. Patient volume and level of care at collegiate basketball and football games as well as rock concerts, over a 7-year period were examined and tabulated. This information was analyzed using simple regression and nonparametric statistical methods to determine level of correlation between crowd size and patient volume. These analyses demonstrated no statistically significant increase in patient volume for increasing crowd size for basketball and football events. There was a small but statistically significant increase in patient volume for increasing crowd size for concerts. A comparison of similar crowd size for each of the three events showed that patient frequency is greatest for concerts and smallest for basketball. The study suggests that crowd size alone has only a minor influence on patient volume at any given event. Structuring medical services based solely on expected crowd size and not considering other influences such as event type and duration may give poor results.

  6. Study on Evaluation Indicators System of Crowd Management for Transfer Stations Based on Pedestrian Simulation

    Directory of Open Access Journals (Sweden)

    Guanghou Zhang

    2011-12-01

    Full Text Available Improving safety and convenience of transfer is one of the most vital tasks in subway system planning, design and operation management. Because of complicated space layout and crowded pedestrian, crowd control is a big challenge for management of transfer stations. Thus, a quantitative evaluation should be done before improvement measures are carried out. Literature review showed that present evaluation indicators about crowd management in subway system were all based on fixed value or experience. Dynamic effect caused by pedestrian congestion and various facility combination cannot be represented based on these indicators. Thus, in this paper, based on the pedestrian simulation tool, dynamic evaluation indicators system of crowd management was established from the point of safety, cost-effectiveness and comfort. In order to aid decision makers to identify the most appropriate scenario to improve the effectiveness of crowd management, Matter-Element Analysis (MEA was used to rate different scenarios. A pedestrian simulation model of a designing intermodal transfer station was built and four different scenarios were tested to demonstrate how to use this indicators system. Simulation results were evaluated based on the dynamic indicators system and MEA. The application results show that the dynamic evaluation indicators system is operational and can reflect level of the crowd management in transfer station comprehensively and precisely.

  7. Perceptual learning eases crowding by reducing recognition errors but not position errors.

    Science.gov (United States)

    Xiong, Ying-Zi; Yu, Cong; Zhang, Jun-Yun

    2015-08-01

    When an observer reports a letter flanked by additional letters in the visual periphery, the response errors (the crowding effect) may result from failure to recognize the target letter (recognition errors), from mislocating a correctly recognized target letter at a flanker location (target misplacement errors), or from reporting a flanker as the target letter (flanker substitution errors). Crowding can be reduced through perceptual learning. However, it is not known how perceptual learning operates to reduce crowding. In this study we trained observers with a partial-report task (Experiment 1), in which they reported the central target letter of a three-letter string presented in the visual periphery, or a whole-report task (Experiment 2), in which they reported all three letters in order. We then assessed the impact of training on recognition of both unflanked and flanked targets, with particular attention to how perceptual learning affected the types of errors. Our results show that training improved target recognition but not single-letter recognition, indicating that training indeed affected crowding. However, training did not reduce target misplacement errors or flanker substitution errors. This dissociation between target recognition and flanker substitution errors supports the view that flanker substitution may be more likely a by-product (due to response bias), rather than a cause, of crowding. Moreover, the dissociation is not consistent with hypothesized mechanisms of crowding that would predict reduced positional errors.

  8. Crowd Computing as a Cooperation Problem: An Evolutionary Approach

    Science.gov (United States)

    Christoforou, Evgenia; Fernández Anta, Antonio; Georgiou, Chryssis; Mosteiro, Miguel A.; Sánchez, Angel

    2013-05-01

    Cooperation is one of the socio-economic issues that has received more attention from the physics community. The problem has been mostly considered by studying games such as the Prisoner's Dilemma or the Public Goods Game. Here, we take a step forward by studying cooperation in the context of crowd computing. We introduce a model loosely based on Principal-agent theory in which people (workers) contribute to the solution of a distributed problem by computing answers and reporting to the problem proposer (master). To go beyond classical approaches involving the concept of Nash equilibrium, we work on an evolutionary framework in which both the master and the workers update their behavior through reinforcement learning. Using a Markov chain approach, we show theoretically that under certain----not very restrictive—conditions, the master can ensure the reliability of the answer resulting of the process. Then, we study the model by numerical simulations, finding that convergence, meaning that the system reaches a point in which it always produces reliable answers, may in general be much faster than the upper bounds given by the theoretical calculation. We also discuss the effects of the master's level of tolerance to defectors, about which the theory does not provide information. The discussion shows that the system works even with very large tolerances. We conclude with a discussion of our results and possible directions to carry this research further.

  9. Automatic trajectory measurement of large numbers of crowded objects

    Science.gov (United States)

    Li, Hui; Liu, Ye; Chen, Yan Qiu

    2013-06-01

    Complex motion patterns of natural systems, such as fish schools, bird flocks, and cell groups, have attracted great attention from scientists for years. Trajectory measurement of individuals is vital for quantitative and high-throughput study of their collective behaviors. However, such data are rare mainly due to the challenges of detection and tracking of large numbers of objects with similar visual features and frequent occlusions. We present an automatic and effective framework to measure trajectories of large numbers of crowded oval-shaped objects, such as fish and cells. We first use a novel dual ellipse locator to detect the coarse position of each individual and then propose a variance minimization active contour method to obtain the optimal segmentation results. For tracking, cost matrix of assignment between consecutive frames is trainable via a random forest classifier with many spatial, texture, and shape features. The optimal trajectories are found for the whole image sequence by solving two linear assignment problems. We evaluate the proposed method on many challenging data sets.

  10. Library on Crowd Behavior for Agents Treatment on Videogames

    Directory of Open Access Journals (Sweden)

    M. Proenza

    2013-01-01

    Full Text Available Abstract This paper covers the investigation process and further design and implementation of a library on crowd behaviors for videogames. Three methods were studied in order to pick up one of them, resulting to be Steering Behaviors method the one selected to be adopted. The library supports simulations with a large number of moving agents. It also copes with polygonal obstacles avoidance. Additionally, simulations can be adapted to many contexts by tuning some parameters. The library consists of an original design mostly based on Command Pattern that allows it to be easily usable and extendable.   Resumen Este documento cubre el proceso de investigación y el diseño e implementación de una biblioteca en los comportamientos de multitud de videojuegos. Tres métodos fueron estudiados con el fin de recoger a uno de ellos, el resultado es el método de dirección Comportamientos que se ha seleccionado para su adopción. La biblioteca admite simulaciones con un gran número de agentes móviles. También hace frente a la evitación obstáculos poligonales. Además, las simulaciones se pueden adaptar a diferentes contextos mediante la regulación de algunos parámetros. La biblioteca consta de un diseño original basado principalmente en modelo de comandos que permite que sea fácilmente utilizable y extensible.

  11. Using Telemedicine to Address Crowding in the ED.

    Science.gov (United States)

    Guss, Benjamin; Mishkin, David; Sharma, Rahul

    2016-11-01

    Some health systems are piloting telemedicine solutions in the ED to address crowding and decrease patient wait times. One new program, implemented at the Lisa Perry Emergency Center at New York Presbyterian (NYP) Weill Cornell Medical Center in New York, involves offering low-acuity patients the option of visiting an off-site physician via telemedicine hookup. Administrators note that the approach can get patients in and out of the ED within 30 minutes, and patients have thus far been highly satisfied with the approach. However, an earlier telemedicine program piloted at the University of San Diego Health System’s (UCSD) Hillcrest Hospital in 2013 got bogged down due to administrative and insurance reimbursement hurdles, although the approach showed enough promise that there is interest in restarting the program. In the NYP program, patients are identified as appropriate candidates for the program at triage. They can opt to be seen remotely or through traditional means in the ED’s fast-track section. Administrators note that patients with complex problems requiring extensive workups are not suitable for the telemedicine approach. The most challenging aspect of implementing a successful telemedicine program in the ED is getting the workflows right, according to administrators. An earlier ED-based telemedicine program piloted at UCSD ran into difficulties because the model required the involvement of two physicians, and some insurers did not want to pay for the telemedicine visits. However, patients were receptive.

  12. The politics of the face-in-the-crowd.

    Science.gov (United States)

    Mills, Mark; Smith, Kevin B; Hibbing, John R; Dodd, Michael D

    2014-06-01

    Recent work indicates that the more conservative one is, the faster one is to fixate on negative stimuli, whereas the less conservative one is, the faster one is to fixate on positive stimuli. The present series of experiments used the face-in-the-crowd paradigm to examine whether variability in the efficiency with which positive and negative stimuli are detected underlies such speed differences. Participants searched for a discrepant facial expression (happy or angry) amid a varying number of neutral distractors (Experiments 1 and 4). A combination of response time and eye movement analyses indicated that variability in search efficiency explained speed differences for happy expressions, whereas variability in post-selectional processes explained speed differences for angry expressions. These results appear to be emotionally mediated as search performance did not vary with political temperament when displays were inverted (Experiment 2) or when controlled processing was required for successful task performance (Experiment 3). Taken together, the present results suggest political temperament is at least partially instantiated by attentional biases for emotional material. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  13. Social dynamics in emergency evacuations: Disentangling crowd's attraction and repulsion effects

    Science.gov (United States)

    Haghani, Milad; Sarvi, Majid

    2017-06-01

    The social dynamics of crowds in emergency escape scenarios have been conventionally modelled as the net effect of virtual forces exerted by the crowd on each individual (as self-driven particles), with the magnitude of the influence formulated as decreasing functions of inter-individual distances and the direction of effect assumed to be transitioning from repulsion to attraction by distance. Here, we revisit this conventional assumption using laboratory experimental data. We show based on robust econometric hypothesis-testing methods that individuals' perception of other escapees differs based on whether those individuals are jamming around exit destinations or are on the move towards the destinations. Also, for moving crowds, it differs based on whether the escape destination chosen by the moving flow is visible or invisible to the individual. The presence of crowd jams around a destination, also the movement of crowd flows towards visible destinations are both perceived on average as repulsion (or disutility) effects (with the former showing significantly larger magnitude than the latter). The movement of crowd flows towards an invisible destination, however, is on average perceived as attraction (or utility) effect. Yet, further hypothesis testing showed that neither of those effects in isolation determines adequately whether an individual would merge with or diverge from the crowd. Rather, the social interaction factors act (at significant levels) in conjunction with the physical factors of the environments (including spatial distances to exit destinations and destinations' visibility). In brief, our finding disentangles the conditions under which individuals are more likely to show mass behaviour from the situations where they are more likely to break from the herd. It identifies two factors that moderate the perception of social interactions, ;crowds' jam/movement status; and ;environmental setup;. Our results particularly challenge the taxonomy of

  14. Overexpression of high molecular weight FGF-2 forms inhibits glioma growth by acting on cell-cycle progression and protein translation

    International Nuclear Information System (INIS)

    Lemiere, Sylvie; Azar, Rania; Belloc, Francis; Guersel, Demir; Pyronnet, Stephane; Bikfalvi, Andreas; Auguste, Patrick

    2008-01-01

    In order to clarify the role of HMW FGF-2 in glioma development and angiogenesis, we over-expressed different human FGF-2 isoforms in C6 rat glioma cell line using a tetracycline-regulated expression system. Phenotypic modifications were analyzed in vitro and compared to untransfected cells or to cells over-expressing 18 kDa FGF-2 or all FGF-2 isoforms. In particular, we demonstrate that HMW FGF-2 has unique features in inhibiting glioma cell proliferation. HMW FGF-2 expressing cells showed a cell-cycle arrest at the G2M, demonstrating a role of HMW FGF-2 in controlling the entry in mitosis. Moreover, hydroxyurea was ineffective in blocking cells at the G1S boundary when HMW FGF-2 was expressed. We also show that the HMW FGF-2 isoforms inhibit 4E-BP1 phosphorylation at critical sites restoring the translation inhibitory activity of 4E-BP1. In vivo, inhibition of tumor growth was observed when cells expressed HMW FGF-2. This indicates that HMW FGF-2 inhibits tumor growth in glioma cells by acting on cell-cycle progression and protein translation

  15. Dual Inhibition of AChE and BChE with the C-5 Substituted Derivative of Meldrum’s Acid: Synthesis, Structure Elucidation, and Molecular Docking Studies

    Directory of Open Access Journals (Sweden)

    Haroon Mehfooz

    2017-07-01

    Full Text Available Alzheimer’s disease (AD lies in the category of those diseases which are still posing challenges to medicinal chemists, and the search for super-effective drugs for the treatment of AD is a work in progress. The inhibition of cholinesterase is considered a viable strategy to enhance the level of acetylcholine in the brain. The C-5 substituted derivative of Meldrum’s acid was synthesized and screened against acetylcholinesterase (AChE and butyrylcholinesterase (BChE enzyme inhibition activity. The simple and unique structure of synthesized derivative 3 was found to be good for the dual inhibition of both enzymes (AChE and BChE. 2,2-Dimethyl-5-(([2-(trifluoromethyl phenyl]aminomethylidene-1,3-dioxane-4,6-dione (3 showed significant inhibition against AChE, with an IC50 value of 1.13 ± 0.03 µ M (Standard Neostigmine 22.2 ± 3.2 µM, and moderate inhibition against BChE, with an IC50 value of 2.12 ± 1.22 µM (Standard Neostigmine 49.6 ± 6.11 µM. The structural insights reveal that compound 3 possesses intriguing reactive groups, which can potentially evoke the non-covalent interactions and possibly assist by binding in the active site of the target protein. Docking simulations revealed that the compound 3 showed binding inside the active site gorges of both AChE and BChE. An excellent agreement was obtained, as the best docked poses showed important binding features mostly based on interactions due to oxygen atoms and the aromatic moieties of the compound. The docking computations coupled with the experimental findings ascertained that the compound 3 can serve as a scaffold for the dual inhibitors of the human acetylcholine esterases.

  16. A simple quantitative model of macromolecular crowding effects on protein folding: Application to the murine prion protein(121-231)

    Science.gov (United States)

    Bergasa-Caceres, Fernando; Rabitz, Herschel A.

    2013-06-01

    A model of protein folding kinetics is applied to study the effects of macromolecular crowding on protein folding rate and stability. Macromolecular crowding is found to promote a decrease of the entropic cost of folding of proteins that produces an increase of both the stability and the folding rate. The acceleration of the folding rate due to macromolecular crowding is shown to be a topology-dependent effect. The model is applied to the folding dynamics of the murine prion protein (121-231). The differential effect of macromolecular crowding as a function of protein topology suffices to make non-native configurations relatively more accessible.

  17. Improvement of healthcare quality in pediatric neurology by crowd technologies

    Directory of Open Access Journals (Sweden)

    O. V. Guzeva

    2016-01-01

    , the solution of which requires that the government should invest a great deal of assets and may be rational only when crowd technologies are applied.

  18. Hydrophobic Interactions Are a Key to MDM2 Inhibition by Polyphenols as Revealed by Molecular Dynamics Simulations and MM/PBSA Free Energy Calculations.

    Directory of Open Access Journals (Sweden)

    Sharad Verma

    Full Text Available p53, a tumor suppressor protein, has been proven to regulate the cell cycle, apoptosis, and DNA repair to prevent malignant transformation. MDM2 regulates activity of p53 and inhibits its binding to DNA. In the present study, we elucidated the MDM2 inhibition potential of polyphenols (Apigenin, Fisetin, Galangin and Luteolin by MD simulation and MM/PBSA free energy calculations. All polyphenols bind to hydrophobic groove of MDM2 and the binding was found to be stable throughout MD simulation. Luteolin showed the highest negative binding free energy value of -173.80 kJ/mol followed by Fisetin with value of -172.25 kJ/mol. It was found by free energy calculations, that hydrophobic interactions (vdW energy have major contribution in binding free energy.

  19. Applying Crowd Psychology to Develop Recommendations for the Management of Mass Decontamination

    Science.gov (United States)

    Drury, John; Rubin, G. James; Williams, Richard; Amlôt, Richard

    2015-01-01

    Mass decontamination is a public health intervention employed by emergency responders following a chemical, biological, or radiological release. It involves a crowd of people whose interactions with each other and with the emergency responders managing the incident are likely to affect the success of the decontamination process. The way in which members of the public collectively experience decontamination is likely to affect their behavior and hence is crucial to the success of the decontamination process. Consequently, responders and the responsible authorities need to understand crowd psychology during mass emergencies and disasters. Recently, the social identity approach to crowd psychology has been applied to explain public perceptions and behavior during mass emergencies. This approach emphasizes that crowd events are characteristically intergroup encounters, in which the behavior of one group can affect the perceptions and behavior of another. We summarize the results from a program of research in which the social identity approach was applied to develop and test recommendations for the management of mass decontamination. The findings from this program of research show that (1) responders' perceptions of crowd behavior matter; (2) participants value greater communication and this affects their compliance; and (3) social identity processes explain the relationship between effective responder communication and relevant outcome variables, such as public compliance, public cooperation, and public anxiety. Based on this program of research, we recommend 4 responder management strategies that focus on increasing public compliance, increasing orderly and cooperative behavior among members of the public, reducing public anxiety, and respecting public needs for privacy. PMID:25812428

  20. A Crowd Avoidance Method Using Circular Avoidance Path for Robust Person Following

    Directory of Open Access Journals (Sweden)

    Kohei Morishita

    2017-01-01

    Full Text Available A life-support service robot must avoid both static and dynamic obstacles for working in a real environment. Here, a static obstacle means an obstacle that does not move, and a dynamic obstacle is the one that moves. Assuming the robot is following a target person, we discuss how the robot avoids a crowd through which the target person passes and arrives at the target position. The purpose of this paper is to propose a crowd avoidance method that makes a robot to be able to avoid both static and dynamic obstacles. The method uses the surface points of the obstacles to form an avoidance region, and the robot moves along the edge of the region. We conducted experiments assuming various situations such that the robot was blocked, there was a wide gap in the crowd, or a person in the crowd yielded for the robot to pass through. As an experimental result, it was confirmed the robot could avoid the crowd even when the obstacles were aligned in an “inverted wedge” shape.

  1. Achieving external validity in home advantage research: generalizing crowd noise effects

    Directory of Open Access Journals (Sweden)

    Tony D Myers

    2014-06-01

    Full Text Available Different factors have been postulated to explain the home advantage phenomenon in sport. One plausible explanation investigated has been the influence of a partisan home crowd on sports officials’ decisions. Different types of studies have tested the crowd influence hypothesis including purposefully designed experiments. However, while experimental studies investigating crowd influences have high levels of internal validity, they suffer from a lack of external validity; decision-making in a laboratory setting bearing little resemblance to decision-making in live sports settings. This focused review initially considers threats to external validity in applied and theoretical experimental research. Discussing how such threats can be addressed using representative design by focusing on a recently published study that arguably provides the first experimental evidence of the impact of live crowd noise on officials in sport. The findings of this controlled experiment conducted in a real tournament setting offer some confirmation of the validity of laboratory experimental studies in the area. Finally directions for future research and the future conduct of crowd noise studies are discussed.

  2. Achieving external validity in home advantage research: generalizing crowd noise effects.

    Science.gov (United States)

    Myers, Tony D

    2014-01-01

    Different factors have been postulated to explain the home advantage phenomenon in sport. One plausible explanation investigated has been the influence of a partisan home crowd on sports officials' decisions. Different types of studies have tested the crowd influence hypothesis including purposefully designed experiments. However, while experimental studies investigating crowd influences have high levels of internal validity, they suffer from a lack of external validity; decision-making in a laboratory setting bearing little resemblance to decision-making in live sports settings. This focused review initially considers threats to external validity in applied and theoretical experimental research. Discussing how such threats can be addressed using representative design by focusing on a recently published study that arguably provides the first experimental evidence of the impact of live crowd noise on officials in sport. The findings of this controlled experiment conducted in a real tournament setting offer a level of confirmation of the findings of laboratory studies in the area. Finally directions for future research and the future conduct of crowd noise studies are discussed.

  3. Accelerated recovery of Atlantic salmon (Salmo salar) from effects of crowding by swimming.

    Science.gov (United States)

    Veiseth, Eva; Fjaera, Svein Olav; Bjerkeng, Bjørn; Skjervold, Per Olav

    2006-07-01

    The effects of post-crowding swimming velocity (0, 0.35, and 0.70 m/s) and recovery time (1.5, 6, and 12 h) on physiological recovery and processing quality parameters of adult Atlantic salmon (Salmo salar) were determined. Atlantic salmon crowded to a density similar to that of a commercial slaughter process (>200 kg/m(3), 40 min) were transferred to a swimming chamber for recovery treatment. Osmolality and concentrations of cortisol, glucose and lactate in blood plasma were used as physiological stress indicators, whereas image analyses of extent and duration of rigor contraction, and fillet gaping were used as measures of processing quality. Crowded salmon had a 5.8-fold higher plasma cortisol concentration than control salmon (Prigor mortis contraction. However, subjecting crowded salmon to active swimming for 6 h before slaughter delayed the onset of rigor mortis contraction from 2.5 to 7.5 h post mortem. The extent of rigor mortis contraction was also affected by crowding and post-stress swimming activity (Prigor mortis contraction, which has a positive technological implication for the salmon processing industry.

  4. Crowding and delivery of healthcare in emergency departments: the European perspective.

    LENUS (Irish Health Repository)

    Jayaprakash, Namita

    2009-11-01

    Emergency department (ED) crowding is a multifactorial problem, resulting in increased ED waiting times, decreased patient satisfaction and deleterious domino effects on the entire hospital. Although difficult to define and once limited to anecdotal evidence, crowding is receiving more attention as attempts are made to quantify the problem objectively. It is a worldwide phenomenon with regional influences, as exemplified when analyzing the problem in Europe compared to that of the United States. In both regions, an aging population, limited hospital resources, staff shortages and delayed ancillary services are key contributors; however, because the structure of healthcare differs from country to country, varying influences affect the issue of crowding. The approach to healthcare delivery as a right of all people, as opposed to a free market commodity, depends on governmental organization and appropriation of funds. Thus, public funding directly influences potential crowding factors, such as number of hospital beds, community care facilities, and staffing. Ultimately ED crowding is a universal problem with distinctly regional root causes; thus, any approach to address the problem must be tailored to regional influences.

  5. Optimal Acceleration-Velocity-Bounded Trajectory Planning in Dynamic Crowd Simulation

    Directory of Open Access Journals (Sweden)

    Fu Yue-wen

    2014-01-01

    Full Text Available Creating complex and realistic crowd behaviors, such as pedestrian navigation behavior with dynamic obstacles, is a difficult and time consuming task. In this paper, we study one special type of crowd which is composed of urgent individuals, normal individuals, and normal groups. We use three steps to construct the crowd simulation in dynamic environment. The first one is that the urgent individuals move forward along a given path around dynamic obstacles and other crowd members. An optimal acceleration-velocity-bounded trajectory planning method is utilized to model their behaviors, which ensures that the durations of the generated trajectories are minimal and the urgent individuals are collision-free with dynamic obstacles (e.g., dynamic vehicles. In the second step, a pushing model is adopted to simulate the interactions between urgent members and normal ones, which ensures that the computational cost of the optimal trajectory planning is acceptable. The third step is obligated to imitate the interactions among normal members using collision avoidance behavior and flocking behavior. Various simulation results demonstrate that these three steps give realistic crowd phenomenon just like the real world.

  6. Applying crowd psychology to develop recommendations for the management of mass decontamination.

    Science.gov (United States)

    Carter, Holly; Drury, John; Rubin, G James; Williams, Richard; Amlôt, Richard

    2015-01-01

    Mass decontamination is a public health intervention employed by emergency responders following a chemical, biological, or radiological release. It involves a crowd of people whose interactions with each other and with the emergency responders managing the incident are likely to affect the success of the decontamination process. The way in which members of the public collectively experience decontamination is likely to affect their behavior and hence is crucial to the success of the decontamination process. Consequently, responders and the responsible authorities need to understand crowd psychology during mass emergencies and disasters. Recently, the social identity approach to crowd psychology has been applied to explain public perceptions and behavior during mass emergencies. This approach emphasizes that crowd events are characteristically intergroup encounters, in which the behavior of one group can affect the perceptions and behavior of another. We summarize the results from a program of research in which the social identity approach was applied to develop and test recommendations for the management of mass decontamination. The findings from this program of research show that (1) responders' perceptions of crowd behavior matter; (2) participants value greater communication and this affects their compliance; and (3) social identity processes explain the relationship between effective responder communication and relevant outcome variables, such as public compliance, public cooperation, and public anxiety. Based on this program of research, we recommend 4 responder management strategies that focus on increasing public compliance, increasing orderly and cooperative behavior among members of the public, reducing public anxiety, and respecting public needs for privacy.

  7. A natural and readily available crowding agent: NMR studies of proteins in hen egg white.

    Science.gov (United States)

    Martorell, Gabriel; Adrover, Miquel; Kelly, Geoff; Temussi, Piero Andrea; Pastore, Annalisa

    2011-05-01

    In vitro studies of biological macromolecules are usually performed in dilute, buffered solutions containing one or just a few different biological macromolecules. Under these conditions, the interactions among molecules are diffusion limited. On the contrary, in living systems, macromolecules of a given type are surrounded by many others, at very high total concentrations. In the last few years, there has been an increasing effort to study biological macromolecules directly in natural crowded environments, as in intact bacterial cells or by mimicking natural crowding by adding proteins, polysaccharides, or even synthetic polymers. Here, we propose the use of hen egg white (HEW) as a simple natural medium, with all features of the media of crowded cells, that could be used by any researcher without difficulty and inexpensively. We present a study of the stability and dynamics behavior of model proteins in HEW, chosen as a prototypical, readily accessible natural medium that can mimic cytosol. We show that two typical globular proteins, dissolved in HEW, give NMR spectra very similar to those obtained in dilute buffers, although dynamic parameters are clearly affected by the crowded medium. The thermal stability of one of these proteins, measured in a range comprising both heat and cold denaturation, is also similar to that in buffer. Our data open new possibilities to the study of proteins in natural crowded media. Copyright © 2010 Wiley-Liss, Inc.

  8. Spacing, crowding, and child mortality in Guinea-Bissau.

    Science.gov (United States)

    Aaby, P; Bukh, J; Lisse, I M; Smits, A J

    1983-07-16

    Evidence from a comparative survey of the Balantas in the Tombali region and the Mandingas and Fulas in the Oio region of Guinea-Bissau suggests that overcrowding is a risk factor for child health because the severity of infections increases when 2 or more children are sick simultaneously. Rural Mandingas and Fulas breastfeed for 30 months on average, while rural Balantas do so for 38 months. All groups abstain from sexual intercourse during lactation, resulting in fewer children among Balantas. Polygamy increases crowding in all groups, but adult Balanta men have separate households while Mandinga brothers often live together in the same household. On average, there were .93 children under 5 in Balanta households but 1.91 in Mandinga households. Each wife ideally has her own room among Balanta households, but Mandinga wives live together, with up to 10 women in the same circular hut. Balanta children leave their mothers' bed when the mother gives birth to another child, while Mandinga and Fula mothers may have several children in bed at the same time. Among Balantas an average of .17 persons slept in bed with a mother and child, while among the Mandingas .66 and among the Fulas .69 did so. The weight-for-age as a percentage of the World Health Organization standard for Balantas and Mandingas-Fulas respectively was 106% and 105% at 0-2 months; 104% and 92% at 3-5 months; 90% and 82% at 6-17 months; 86% and 77% at 18-35 months breastfed; and 89% and 81% at 18-35 months weaned. During 1980-81, when no major epidemics occurred, Balanta children under 6 months had a higher survival rate for the following year than did Mandinga and Fula children, with the mortality difference occuring while all children were still breastfed. 8% of Balanta children, 16% of Mandinga children, and 24% of Fula children died within 1 year of examination. Nutritional status did not determine risk of death, but variation in the severity of infection caused by overcrowding may have done so

  9. Waiting room crowding and agitation in a dedicated psychiatric emergency service.

    Science.gov (United States)

    El-Mallakh, Rif S; Whiteley, Amanda; Wozniak, Tanya; Ashby, McCray; Brown, Shawn; Colbert-Trowel, Danya; Pennington, Tammy; Thompson, Michael; Tasnin, Rokeya; Terrell, Christina L

    2012-05-01

    Emergency department crowding is a growing problem that impacts patient care and safety. The effect of crowding has not been examined in emergency psychiatric services. The association between patient census and use of restraints, seclusion, and anti-agitation medications as needed was examined for 1 month. A total of 689 patients were seen in 31 days. The average hourly census was 6.8 ± 2.8 (range 0 to 18). There were 33 incidences of seclusion or restraint and an additional 15 instances of medications administered for agitation. The use of seclusion, restraint, or medication for agitation was significantly associated with census (r2 = 0.3, F = 5.47, P = .036). Crowding in emergency psychiatric waiting rooms may increase the need for seclusion, restraint, or medications for agitation.

  10. Household behaviour crowds out support for climate change policy when sufficient progress is perceived

    Science.gov (United States)

    Werfel, Seth H.

    2017-07-01

    Household actions and government policies are both necessary to mitigate the effects of climate change. However, household behaviour may crowd out public support for government action by creating the perception of sufficient progress. Here we demonstrate this crowding-out effect in public opinion using survey experiments with more than 14,000 participants in Japan. Subjects who were randomly assigned to report their energy-saving actions following the shutdown of the Fukushima power plant were less likely to support a tax increase on carbon emissions. Treatment effects were larger for subjects who had completed more actions. Further evidence suggests that the crowding-out effect may have been driven by an increase in the perceived importance of individual actions relative to government regulation and a decrease in the perceived issue importance of energy and environmental sustainability.

  11. Synergistic rate boosting of collagen fibrillogenesis in heterogeneous mixtures of crowding agents.

    Science.gov (United States)

    Dewavrin, Jean-Yves; Abdurrahiem, Muhammed; Blocki, Anna; Musib, Mrinal; Piazza, Francesco; Raghunath, Michael

    2015-03-26

    The competition for access to space that arises between macromolecules is the basis of the macromolecular crowding phenomenon, known to modulate biochemical reactions in subtle ways. Crowding is a highly conserved physiological condition in and around cells in metazoans, and originates from a mixture of heterogeneous biomolecules. Here, using collagen fibrillogenesis as an experimental test platform and ideas from the theory of nonideal solutions, we show that an entropy-based synergy is created by a mixture of two different populations of artificial crowders, providing small crowders with extra volume occupancy when in the vicinity of bigger crowders. We present the physiological mechanism by which synergistic effects maximize volume exclusion with the minimum amount of heterogeneous crowders, demonstrating how the evolutionarily optimized crowded conditions found in vivo can be reproduced effectively in vitro.

  12. Double Crowding-Out Effects of Means-Tested Public Provision for Long-Term Care

    Directory of Open Access Journals (Sweden)

    Christophe Courbage

    2015-02-01

    Full Text Available Publicly provided long-term care (LTC insurance with means-tested benefits is suspected to crowd out either private saving or informal care. This contribution predicts crowding-out effects for both private saving and informal care for policy measures designed to relieve the public purse from LTC expenditure such as more stringent means testing and increased taxation of inheritance. These effects result from the interaction of a parent who decides on the amount of saving in retirement and a caregiver who decides on the effort devoted to informal care which lowers the probability of admission to a nursing home. Double crowding-out effects are also found to be the consequence of exogenous influences, notably a higher opportunity cost of caregiving.

  13. Dynamics-Based Stranded-Crowd Model for Evacuation in Building Bottlenecks

    Directory of Open Access Journals (Sweden)

    Lidi Huang

    2013-01-01

    Full Text Available In high-density public buildings, it is difficult to evacuate. So in this paper, we propose a novel quantitative evacuation model to insure people’s safety and reduce the risk of crowding. We analyze the mechanism of arch-like clogging phenomena during evacuation and the influencing factors in emergency situations at bottleneck passages; then we design a model based on crowd dynamics and apply the model to a stadium example. The example is used to compare evacuation results of crowd density with different egress widths in stranded zones. The results show this model proposed can guide the safe and dangerous egress widths in performance design and can help evacuation routes to be selected and optimized.

  14. Effect on Perceived Stimulation dan Perceived Crowding on the Decision of the Unplanned Purchase (Impulse Buying

    Directory of Open Access Journals (Sweden)

    Enggal Sriwardiningsih

    2011-11-01

    Full Text Available Purchase decisions aren’t made necessarily planned, because impulsive buying is such a result of environmental stimuli shopping. Things affecting unplanned purchasing decisions are perceived by stimulation and crowding. The purpose of this study is to determine whether there are influences between perceived crowding and stimulation of impulse buying simultaneously or partial. The object used is one of the largest retailers in Cilegon. This research design is quantitative analysis of the consumer unit. The collecting data technique includes using questionnaires, interviews, and literature from previous research. Data processed using the SPSS 16.0 program through the validity and reliability, normality test, and regression analysis. The study states that there is significant influence between perceived crowding and perceived stimulation both simultaneous and partial response to impulse buying. 

  15. Ameliorating the emergency department workflow by involving the observation unit: effects on crowding

    Directory of Open Access Journals (Sweden)

    Primiano Iannone

    2015-06-01

    Full Text Available Crowding adversely affects the performance of emergency departments (EDs by worsening efficiency, timeliness of care, clinical outcomes and patients’ satisfaction. We describe in this study our attempt at improving crowding by modifying the roles and workflow of the ED physicians. The observation unit physician was given the additional duty of prioritizing admissions and managing unclear, complex cases, which were previously under the responsibility of front line emergency physicians. We analyzed two corresponding periods, both before the intervention (9897 ED attendances in 2012 and after the intervention (10,297 attendances in 2013. Most of the crowding indices improved significantly, including timeliness of triage, of first medical contact, access to resus area, and overall length of stay in ED. Also, emergency hospital admissions, average specialist consultations and imaging studies per patient decreased significantly. The observation unit workload increased. There was no significant excess of adverse events.

  16. LincRNA-p21 inhibits invasion and metastasis of hepatocellular carcinoma through miR-9/E-cadherin cascade signaling pathway molecular mechanism

    Directory of Open Access Journals (Sweden)

    Ding G

    2017-06-01

    Full Text Available Gangqiang Ding, Zhen Peng, Jia Shang, Yi Kang, Huibin Ning, Chongshan Mao Department of Infectious Diseases, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital, Zhengzhou, China Abstract: In the previous study, it was found that long intergenic noncoding RNA-p21 (lincRNA-p21 was downregulated in hepatocellular carcinoma (HCC and lincRNA-p21 overexpression inhibited tumor invasion through inducing epithelial–mesenchymal transition. However, the underlying mechanism was not fully elaborated. In this study, lincRNA-p21 expression was measured in 12 paired HCC and nontumor adjacent normal tissues by ­quantitative real-time polymerase chain reaction. The effects of lincRNA-p21 on HCC cells were studied using lentivirus expressing lincRNA-p21 vector in vitro. The association between lincRNA-p21 level and miR-9 level was tested with the Spearman rank correlation. The effects of miR-9 on HCC cells were studied by using miR-9 inhibitor in vitro. Luciferase assay was used to validate the target of miR-9. The results showed that lincRNA-p21 was downregulated in human HCC tissues and cell lines. LincRNA-p21 overexpression significantly inhibited HCC cell migration and invasion in vitro. Besides, lincRNA-p21 negatively regulated miR-9 expression level, and miR-9 was upregulated in human HCC tissues and cells. MiR-9 knockdown inhibited HCC cell migration and invasion in vitro. Finally, the luciferase assay results showed that E-cadherin was a direct target of miR-9. The expression level of E-cadherin was found to be regulated by lincRNA-p21 and miR-9. Altogether, the results suggested that lincRNA-p21 inhibits migration and invasion of HCC cells through regulating miR-9-mediated E-cadherin cascade signaling pathway. Keywords: hepatocellular carcinoma, lincRNA-p21, miR-9, E-cadherin, epithelial–mesenchymal transition

  17. Synthesis, analysis, cholinesterase-inhibiting activity and molecular modelling studies of 3-(dialkylamino)-2-hydroxypropyl 4-[(alkoxy-carbonyl)amino]benzoates and their quaternary ammonium salts

    Czech Academy of Sciences Publication Activity Database

    Padrtova, T.; Marvanová, P.; Odehnalová, K.; Kubínová, R.; Parravicini, V.; Garro, A.; Enriz, R. D.; Humpa, O.; Oravec, Michal; Mokrý, P.

    2017-01-01

    Roč. 22, č. 12 (2017), č. článku 2048. ISSN 1420-3049 R&D Projects: GA MŠk(CZ) LM2015061; GA MŠk(CZ) LO1415; GA MŠk(CZ) EF16_013/0001609 Institutional support: RVO:86652079 Keywords : Acetylcholinesterase * Arylcarbonyloxyaminopropanols * Butyrylcholinesterase * Quaternary ammonium salts * Tertiary amines Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 2.861, year: 2016

  18. The CrowdMag App - turning your smartphone into a travelling magnetic observatory

    Science.gov (United States)

    Saltus, Richard; Nair, Manoj

    2017-04-01

    In 2014, we started the "CrowdMag" Project to collect vector magnetic data from digital magnetometers in smartphones. In October 2014, we released our first-generation Android and iOS apps. Currently, the CrowdMag Project has more than 15,000 enthusiastic users contributing more than 12 million magnetic data points from around the world. NOAA's National Centers for Environmental Information (NCEI), in partnership with the University of Colorado's Cooperative Institute for Research in the Environmental Sciences (CIRES) develops magnetic field models to aid navigation, resource exploration and scientific research. We use observatories, satellites and ship/airborne surveys to measure the magnetic data. However, the measurements leave gaps in coverage, particularly for short-wavelength urban noise. Our ultimate goal is to use data from the CrowdMag Project to improve global magnetic data coverage. Here we present some early results from the analysis of the crowdsourced magnetic data. A global magnetic model derived solely based on CrowdMag data is generally consistent with satellite-derived models such as World Magnetic Model. A unique contribution of the CrowdMag Project is the collection of ground level magnetic data in densely populated regions with an unprecedented spatial resolution. For example, we show a magnetic map (by binning the data collected into 100x100m cells) of central Boulder using 170,000 data points collected by about 60 devices over the duration October 2014- January 2016. The median magnetic field value is consistent with the expected magnitude of the Earth's background magnetic field. The standard deviation of the CrowdMag total field (F) values is much higher than the expected natural (i.e., diurnal and geologic) magnetic field variation. However, the phone's magnetometer is sensitive enough to capture the larger magnitude magnetic signature from the urban magnetic sources. We discuss the reliability of crowdsourced magnetic maps and their

  19. VGI, crowd-sourcing, citizen science and neogeography are not the same!

    CSIR Research Space (South Africa)

    Cooper, Antony K

    2015-11-01

    Full Text Available StreetMap Real-time traffic monitoring Brown Moses Arab Spring Cyber-bullying Foldit Online Protein Puzzle SETI@Home Amateur astronomer Zooniverse: Planet Hunters Mappiness WideNoise 2nd South African Bird Atlas Project (SABAP2) Household consumption diary...SMS PPGIS ABCD Transparency and accountability Empower communities Brown Moses Virtual land art Cyber-bullying Crisis mapping Arab Spring Neogeography © CSIR 2015 Crowd sourcing ≠ CiCrowd sourcing Amazon Mechanical Turk Wikipedia Brown Moses...

  20. Prominent effects and neural correlates of visual crowding in a neurodegenerative disease population.

    Science.gov (United States)

    Yong, Keir X X; Shakespeare, Timothy J; Cash, Dave; Henley, Susie M D; Nicholas, Jennifer M; Ridgway, Gerard R; Golden, Hannah L; Warrington, Elizabeth K; Carton, Amelia M; Kaski, Diego; Schott, Jonathan M; Warren, Jason D; Crutch, Sebastian J

    2014-12-01

    Crowding is a breakdown in the ability to identify objects in clutter, and is a major constraint on object recognition. Crowding particularly impairs object perception in peripheral, amblyopic and possibly developing vision. Here we argue that crowding is also a critical factor limiting object perception in central vision of individuals with neurodegeneration of the occipital cortices. In the current study, individuals with posterior cortical atrophy (n=26), typical Alzheimer's disease (n=17) and healthy control subjects (n=14) completed centrally-presented tests of letter identification under six different flanking conditions (unflanked, and with letter, shape, number, same polarity and reverse polarity flankers) with two different target-flanker spacings (condensed, spaced). Patients with posterior cortical atrophy were significantly less accurate and slower to identify targets in the condensed than spaced condition even when the target letters were surrounded by flankers of a different category. Importantly, this spacing effect was observed for same, but not reverse, polarity flankers. The difference in accuracy between spaced and condensed stimuli was significantly associated with lower grey matter volume in the right collateral sulcus, in a region lying between the fusiform and lingual gyri. Detailed error analysis also revealed that similarity between the error response and the averaged target and flanker stimuli (but not individual target or flanker stimuli) was a significant predictor of error rate, more consistent with averaging than substitution accounts of crowding. Our findings suggest that crowding in posterior cortical atrophy can be regarded as a pre-attentive process that uses averaging to regularize the pathologically noisy representation of letter feature position in central vision. These results also help to clarify the cortical localization of feature integration components of crowding. More broadly, we suggest that posterior cortical atrophy

  1. An Application of Graphics Processing Units to Geosimulation of Collective Crowd Behaviour

    Directory of Open Access Journals (Sweden)

    Cjoskāns Jānis

    2017-12-01

    Full Text Available The goal of the paper is to assess the ways for computational performance and efficiency improvement of collective crowd behaviour simulation by using parallel computing methods implemented on graphics processing unit (GPU. To perform an experimental evaluation of benefits of parallel computing, a new GPU-based simulator prototype is proposed and the runtime performance is analysed. Based on practical examples of pedestrian dynamics geosimulation, the obtained performance measurements are compared to several other available multiagent simulation tools to determine the efficiency of the proposed simulator, as well as to provide generic guidelines for the efficiency improvements of the parallel simulation of collective crowd behaviour.

  2. Treating dental crowding with mandibular incisor extraction in an Angle Class I patient

    Directory of Open Access Journals (Sweden)

    Gislana Braga Machado

    2015-06-01

    Full Text Available Mandibular dental crowding often encourages patients to seek orthodontic treatment. The orthodontist should decide between protrusion of incisors or decrease in dental volume so as to achieve proper alignment and leveling. The present study reports the treatment of an Angle Class I malocclusion adolescent female brachyfacial patient with severe mandibular dental crowding, increased curve of Spee and deep overbite. The patient was treated with extraction of a mandibular incisor. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO as a requirement for the title of certified by the BBO.

  3. Macromolecular crowding compacts unfolded apoflavodoxin and causes severe aggregation of the off-pathway intermediate during apoflavodoxin folding

    NARCIS (Netherlands)

    Engel, R.; Westphal, A.H.; Huberts, D.; Nabuurs, S.M.; Lindhoud, S.; Visser, A.J.W.G.; Mierlo, van C.P.M.

    2008-01-01

    To understand how proteins fold in vivo, it is important to investigate the effects of macromolecular crowding on protein folding. Here, the influence of crowding on in vitro apoflavodoxin folding, which involves a relatively stable off-pathway intermediate with molten globule characteristics, is

  4. Changing attitudes toward smoking and smoking susceptibility through peer crowd targeting: more evidence from a controlled study.

    Science.gov (United States)

    Moran, Meghan Bridgid; Sussman, Steve

    2015-01-01

    Peer crowd identification consistently predicts an adolescent's smoking behavior. As such, several interventions have targeted adolescents and young adults based on their identification with a specific crowd (e.g., Hipsters). This study uses a controlled experimental design to isolate and test the effect of peer crowd targeting in an antismoking ad on antismoking attitudes and smoking susceptibility. Two hundred and thirty-nine adolescents, age 13-15 years, completed a baseline survey and then viewed an antismoking ad targeting one of eight crowds; 1 week later they completed a posttest. Participants were assessed on antismoking attitudes and smoking susceptibility. Adolescents who strongly identified with the crowd targeted by the ad reported stronger antismoking attitudes and lower levels of smoking susceptibility. Those who disidentified with the crowd targeted in the ad exhibited not statistically significant increases in smoking susceptibility and weaker antismoking attitudes at posttest. These findings indicate that targeting youths based on their peer crowd is a useful strategy for antismoking interventions. Additional research should further examine whether youths who disidentify with the targeted crowd in an ad exhibit reactance against the message.

  5. Crowding and experience-use history: a study of the moderating effect of place attachment among water-based recreationists.

    Science.gov (United States)

    Budruk, Megha; Wilhem Stanis, Sonja A; Schneider, Ingrid E; Heisey, Jennifer J

    2008-04-01

    Effective recreation resource management relies on understanding visitor perceptions and behaviors. Given current and increasing pressures on water resources, understanding crowding evaluations seems important. Beyond crowding, however, variables that possibly relate to or influence crowding are of interest and in particular, place attachment and experience-use history (EUH). As EUH is related to place attachment and likely affects crowding, this study explored the moderating effect of place attachment dimensions on the relationships between EUH and visitor crowding evaluations. Water based recreationists at a U.S. Army Corps of Engineers site were contacted onsite and asked questions related to experience-use history, crowding evaluations, place attachment, and activity participation. Anglers and campers at the site identified similar crowding perceptions and place attachments. Only one of eight models tested revealed a moderating effect. Specifically, place identity moderated the relationship between the total times visited in the past twelve months and expected crowding among anglers. As such, the quest continues to understand the relationship among these important variables.

  6. Identification of novel potential scaffold for class I HDACs inhibition: An in-silico protocol based on virtual screening, molecular dynamics, mathematical analysis and machine learning.

    Science.gov (United States)

    Fan, Cong; Huang, Yanxin

    2017-09-23

    Histone deacetylases (HDACs) family has been widely reported as an important class of enzyme targets for cancer therapy. Much effort has been made in discovery of novel scaffolds for HDACs inhibition besides existing hydroxamic acids, cyclic peptides, benzamides, and short-chain fatty acids. Herein we set up an in-silico protocol which not only could detect potential Zn 2+ chelation bonds but also still adopted non-bonded model to be effective in discovery of Class I HDACs inhibitors, with little human's subjective visual judgment involved. We applied the protocol to screening of Chembridge database and selected out 7 scaffolds, 3 with probability of more than 99%. Biological assay results demonstrated that two of them exhibited HDAC-inhibitory activity and are thus considerable for structure modification to further improve their bio-activity. Copyright © 2017. Published by Elsevier Inc.

  7. The impact of crowd noise on officiating in Muay Thai: achieving external validity in an experimental setting

    Directory of Open Access Journals (Sweden)

    Tony D Myers

    2012-09-01

    Full Text Available Numerous factors have been proposed to explain the home advantage in sport. Several authors have suggested that a partisan home crowd enhances home advantage and that this is at least in part a consequence of their influence on officiating. However, while experimental studies examining this phenomenon have high levels of internal validity (since only the ‘crowd noise’ intervention is allowed to vary, they suffer from a lack of external validity, with decision-making in a laboratory setting typically bearing little resemblance to decision-making in live sports settings. Conversely, observational and quasi-experimental studies with high levels of external validity suffer from low levels of internal validity as countless factors besides crowd noise vary. The present study provides a unique opportunity to address these criticisms, by conducting a controlled experiment on the impact of crowd noise on officiating in a live tournament setting. Seventeen qualified judges officiated on thirty Thai boxing bouts in a live international tournament setting featuring ‘home’ and ‘away’ boxers. In each bout, judges were randomised into a ‘noise’ (live sound or ‘no crowd noise’ (noise cancelling headphones and white noise condition, resulting in 59 judgements in the ‘no crowd noise’ and 61 in the ‘crowd noise’ condition. The results provide the first experimental evidence of the impact of live crowd noise on officials in sport. A cross-classified statistical model indicated that crowd noise had a statistically significant impact, equating to just over half a point per bout (in the context of five round bouts with the ‘ten point must’ scoring system shared with professional boxing. The practical significance of the findings, their implications for officiating and for the future conduct of crowd noise studies are discussed.

  8. Does Prison Crowding Predict Higher Rates of Substance Use Related Parole Violations? A Recurrent Events Multi-Level Survival Analysis.

    Directory of Open Access Journals (Sweden)

    Michael A Ruderman

    Full Text Available This administrative data-linkage cohort study examines the association between prison crowding and the rate of post-release parole violations in a random sample of prisoners released with parole conditions in California, for an observation period of two years (January 2003 through December 2004.Crowding overextends prison resources needed to adequately protect inmates and provide drug rehabilitation services. Violence and lack of access to treatment are known risk factors for drug use and substance use disorders. These and other psychosocial effects of crowding may lead to higher rates of recidivism in California parolees.Rates of parole violation for parolees exposed to high and medium levels of prison crowding were compared to parolees with low prison crowding exposure. Hazard ratios (HRs with 95% confidence intervals (CIs were estimated using a Cox model for recurrent events. Our dataset included 13070 parolees in California, combining individual level parolee data with aggregate level crowding data for multilevel analysis.Comparing parolees exposed to high crowding with those exposed to low crowding, the effect sizes from greatest to least were absconding violations (HR 3.56 95% CI: 3.05-4.17, drug violations (HR 2.44 95% CI: 2.00-2.98, non-violent violations (HR 2.14 95% CI: 1.73-2.64, violent and serious violations (HR 1.88 95% CI: 1.45-2.43, and technical violations (HR 1.86 95% CI: 1.37-2.53.Prison crowding predicted higher rates of parole violations after release from prison. The effect was magnitude-dependent and particularly strong for drug charges. Further research into whether adverse prison experiences, such as crowding, are associated with recidivism and drug use in particular may be warranted.

  9. Does Prison Crowding Predict Higher Rates of Substance Use Related Parole Violations? A Recurrent Events Multi-Level Survival Analysis.

    Science.gov (United States)

    Ruderman, Michael A; Wilson, Deirdra F; Reid, Savanna

    2015-01-01

    This administrative data-linkage cohort study examines the association between prison crowding and the rate of post-release parole violations in a random sample of prisoners released with parole conditions in California, for an observation period of two years (January 2003 through December 2004). Crowding overextends prison resources needed to adequately protect inmates and provide drug rehabilitation services. Violence and lack of access to treatment are known risk factors for drug use and substance use disorders. These and other psychosocial effects of crowding may lead to higher rates of recidivism in California parolees. Rates of parole violation for parolees exposed to high and medium levels of prison crowding were compared to parolees with low prison crowding exposure. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a Cox model for recurrent events. Our dataset included 13070 parolees in California, combining individual level parolee data with aggregate level crowding data for multilevel analysis. Comparing parolees exposed to high crowding with those exposed to low crowding, the effect sizes from greatest to least were absconding violations (HR 3.56 95% CI: 3.05-4.17), drug violations (HR 2.44 95% CI: 2.00-2.98), non-violent violations (HR 2.14 95% CI: 1.73-2.64), violent and serious violations (HR 1.88 95% CI: 1.45-2.43), and technical violations (HR 1.86 95% CI: 1.37-2.53). Prison crowding predicted higher rates of parole violations after release from prison. The effect was magnitude-dependent and particularly strong for drug charges. Further research into whether adverse prison experiences, such as crowding, are associated with recidivism and drug use in particular may be warranted.

  10. Does Prison Crowding Predict Higher Rates of Substance Use Related Parole Violations? A Recurrent Events Multi-Level Survival Analysis

    Science.gov (United States)

    Ruderman, Michael A.; Wilson, Deirdra F.; Reid, Savanna

    2015-01-01

    Objective This administrative data-linkage cohort study examines the association between prison crowding and the rate of post-release parole violations in a random sample of prisoners released with parole conditions in California, for an observation period of two years (January 2003 through December 2004). Background Crowding overextends prison resources needed to adequately protect inmates and provide drug rehabilitation services. Violence and lack of access to treatment are known risk factors for drug use and substance use disorders. These and other psychosocial effects of crowding may lead to higher rates of recidivism in California parolees. Methods Rates of parole violation for parolees exposed to high and medium levels of prison crowding were compared to parolees with low prison crowding exposure. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a Cox model for recurrent events. Our dataset included 13070 parolees in California, combining individual level parolee data with aggregate level crowding data for multilevel analysis. Results Comparing parolees exposed to high crowding with those exposed to low crowding, the effect sizes from greatest to least were absconding violations (HR 3.56 95% CI: 3.05–4.17), drug violations (HR 2.44 95% CI: 2.00–2.98), non-violent violations (HR 2.14 95% CI: 1.73–2.64), violent and serious violations (HR 1.88 95% CI: 1.45–2.43), and technical violations (HR 1.86 95% CI: 1.37–2.53). Conclusions Prison crowding predicted higher rates of parole violations after release from prison. The effect was magnitude-dependent and particularly strong for drug charges. Further research into whether adverse prison experiences, such as crowding, are associated with recidivism and drug use in particular may be warranted. PMID:26492490

  11. The impact of crowd noise on officiating in muay thai: achieving external validity in an experimental setting.

    Science.gov (United States)

    Myers, Tony; Balmer, Nigel

    2012-01-01

    Numerous factors have been proposed to explain the home advantage in sport. Several authors have suggested that a partisan home crowd enhances home advantage and that this is at least in part a consequence of their influence on officiating. However, while experimental studies examining this phenomenon have high levels of internal validity (since only the "crowd noise" intervention is allowed to vary), they suffer from a lack of external validity, with decision-making in a laboratory setting typically bearing little resemblance to decision-making in live sports settings. Conversely, observational and quasi-experimental studies with high levels of external validity suffer from low levels of internal validity as countless factors besides crowd noise vary. The present study provides a unique opportunity to address these criticisms, by conducting a controlled experiment on the impact of crowd noise on officiating in a live tournament setting. Seventeen qualified judges officiated on thirty Thai boxing bouts in a live international tournament setting featuring "home" and "away" boxers. In each bout, judges were randomized into a "noise" (live sound) or "no crowd noise" (noise-canceling headphones and white noise) condition, resulting in 59 judgments in the "no crowd noise" and 61 in the "crowd noise" condition. The results provide the first experimental evidence of the impact of live crowd noise on officials in sport. A cross-classified statistical model indicated that crowd noise had a statistically significant impact, equating to just over half a point per bout (in the context of five round bouts with the "10-point must" scoring system shared with professional boxing). The practical significance of the findings, their implications for officiating and for the future conduct of crowd noise studies are discussed.

  12. HIV-1 entry inhibition by small-molecule CCR5 antagonists: A combined molecular modeling and mutant study using a high-throughput assay

    International Nuclear Information System (INIS)

    Labrecque, Jean; Metz, Markus; Lau, Gloria; Darkes, Marilyn C.; Wong, Rebecca S.Y.; Bogucki, David; Carpenter, Bryon; Chen Gang; Li Tongshuang; Nan, Susan; Schols, Dominique; Bridger, Gary J.; Fricker, Simon P.; Skerlj, Renato T.

    2011-01-01

    Based on the attrition rate of CCR5 small molecule antagonists in the clinic the discovery and development of next generation antagonists with an improved pharmacology and safety profile is necessary. Herein, we describe a combined molecular modeling, CCR5-mediated cell fusion, and receptor site-directed mutagenesis approach to study the molecular interactions of six structurally diverse compounds (aplaviroc, maraviroc, vicriviroc, TAK-779, SCH-C and a benzyloxycarbonyl-aminopiperidin-1-yl-butane derivative) with CCR5, a coreceptor for CCR5-tropic HIV-1 strains. This is the first study using an antifusogenic assay, a model of the interaction of the gp120 envelope protein with CCR5. This assay avoids the use of radioactivity and HIV infection assays, and can be used in a high throughput mode. The assay was validated by comparison with other established CCR5 assays. Given the hydrophobic nature of the binding pocket several binding models are suggested which could prove useful in the rational drug design of new lead compounds.

  13. Transmembrane helices can induce domain formation in crowded model membranes

    NARCIS (Netherlands)

    Domanski, Jan; Marrink, Siewert J.; Schäfer, Lars V.

    We studied compositionally heterogeneous multi-component model membranes comprised of saturated lipids, unsaturated lipids, cholesterol, and a-helical TM protein models using coarse-grained molecular dynamics simulations. Reducing the mismatch between the length of the saturated and unsaturated

  14. Synthesis and Antitumor Molecular Mechanism of Agents Based on Amino 2-(3′,4′,5′-Trimethoxybenzoyl)-benzo[b]furan: Inhibition of Tubulin and Induction of Apoptosis

    Science.gov (United States)

    Baraldi, Pier Giovanni; Lopez-Cara, Carlota; Cruz-Lopez, Olga; Carrion, Maria Dora; Salvador, Maria Kimatrai; Bermejo, Jaime; Estévez, Sara; Estévez, Francisco; Balzarini, Jan; Brancale, Andrea; Ricci, Antonio; Chen, Longchuan; Kim, Jae Gwan; Hamel, Ernest

    2011-01-01

    Induction of apoptosis is a promising strategy that could lead to the discovery of new molecules active in cancer chemotherapy. This property is generally observed when cells are treated with agents that target microtubules, dynamic structures that play a crucial role in cell division. Small molecules such as benzo[b]furans are attractive as inhibitors of tubulin polymerization. A new class of inhibitors of tubulin polymerization based on the 2-(3′,4′,5′-trimethoxybenzoyl)benzo[b]furan molecular skeleton, with the amino group placed at different positions on the benzene ring, were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell-cycle effects. The methoxy substitution pattern on the benzene portion of the benzo[b]furan moiety played an important role in affecting antiproliferative activity. In the series of 5-amino derivatives, the greatest inhibition of cell growth oc curred if the methoxy substituent is placed at the C6 position, whereas C7 substitution decreases potency. The most promising compound in this series is 2-(3′,4′,5′-trimethoxybenzoyl)-3-methyl-5-amino-6-methoxybenzo[b]furan (3h), which inhibits cancer cell growth at nanomolar concentrations (IC50=16–24 nm), and interacts strongly with tubulin by binding to the colchicine site. Sub-G1 apoptotic cells in cultures of HL-60 and U937 cells were observed by flow cytometric analysis after treatment with 3h in a concentration-dependent manner. We also show that compound 3h induces apoptosis by activation of caspase-3, -8, and -9, and this is associated with cytochrome c release from mitochondria. The introduction of an α-bromoacryloyl group increased antiproliferative activity with respect to the parent amino derivatives. PMID:21805646

  15. Molecular docking.

    Science.gov (United States)

    Morris, Garrett M; Lim-Wilby, Marguerita

    2008-01-01

    Molecular docking is a key tool in structural molecular biology and computer-assisted drug design. The goal of ligand-protein docking is to predict the predominant binding mode(s) of a ligand with a protein of known three-dimensional structure. Successful docking methods search high-dimensional spaces effectively and use a scoring function that correctly ranks candidate dockings. Docking can be used to perform virtual screening on large libraries of compounds, rank the results, and propose structural hypotheses of how the ligands inhibit the target, which is invaluable in lead optimization. The setting up of the input structures for the docking is just as important as the docking itself, and analyzing the results of stochastic search methods can sometimes be unclear. This chapter discusses the background and theory of molecular docking software, and covers the usage of some of the most-cited docking software.

  16. Crowd science : it is not just a matter of time (or funding)

    NARCIS (Netherlands)

    Vasileiadou, E.

    2015-01-01

    Citizen science, or crowd science, or volunteer science, has increased in the last 4–5 years, with an accompanying increase in the literature. The main argument in such literature is that citizen science has many advantages, not only for scientists and the science that is produced, but also for the

  17. Crowding and Cognitive Development: The Mediating Role of Maternal Responsiveness among 36-Month-Old Children

    Science.gov (United States)

    Evans, Gary W.; Ricciuti, Henry N.; Hope, Steven; Schoon, Ingrid; Bradley, Robert H.; Corwyn, Robert F.; Hazan, Cindy

    2010-01-01

    Residential crowding in both U.S. and U.K. samples of 36-month-old children is related concurrently to the Bracken scale, a standard index of early cognitive development skills including letter and color identification, shape recognition, and elementary numeric comprehension. In the U.S. sample, these effects also replicate prospectively.…

  18. Micro-flow synthesis and structural analysis of sterically crowded diimine ligands with five aryl rings

    Directory of Open Access Journals (Sweden)

    Shinichiro Fuse

    2013-11-01

    Full Text Available Sterically crowded diimine ligands with five aryl rings were prepared in one step in good yields using a micro-flow technique. X-ray crystallographic analysis revealed the detailed structure of the bulky ligands. The nickel complexes prepared from the ligands exerted high polymerization activity in the ethylene homopolymerization and copolymerization of ethylene with polar monomers.

  19. Average interradicular sites for miniscrew insertion: should dental crowding be considered?

    DEFF Research Database (Denmark)

    Tepedino, Michele; Cattaneo, Paolo; Masedu, Francesco

    2017-01-01

    OBJECTIVE: To define a map of interradicular spaces where miniscrew can be likely placed at a level covered by attached gingiva, and to assess if a correlation between crowding and availability of space exists. METHODS: Panoramic radiographs and digital models of 40 patients were selected according...

  20. Crowded growth leads to the spontaneous evolution of semistable coexistence in laboratory yeast populations.

    Science.gov (United States)

    Frenkel, Evgeni M; McDonald, Michael J; Van Dyken, J David; Kosheleva, Katya; Lang, Gregory I; Desai, Michael M

    2015-09-08

    Identifying the mechanisms that create and maintain biodiversity is a central challenge in biology. Stable diversification of microbial populations often requires the evolution of differences in resource utilization. Alternatively, coexistence can be maintained by specialization to exploit spatial heterogeneity in the environment. Here, we report spontaneous diversification maintained by a related but distinct mechanism: crowding avoidance. During experimental evolution of laboratory Saccharomyces cerevisiae populations, we observed the repeated appearance of "adherent" (A) lineages able to grow as a dispersed film, in contrast to their crowded "bottom-dweller" (B) ancestors. These two types stably coexist because dispersal reduces interference competition for nutrients among kin, at the cost of a slower maximum growth rate. This tradeoff causes the frequencies of the two types to oscillate around equilibrium over the course of repeated cycles of growth, crowding, and dispersal. However, further coevolution of the A and B types can perturb and eventually destroy their coexistence over longer time scales. We introduce a simple mathematical model of this "semistable" coexistence, which explains the interplay between ecological and evolutionary dynamics. Because crowded growth generally limits nutrient access in biofilms, the mechanism we report here may be broadly important in maintaining diversity in these natural environments.

  1. Crowded and Sparse Domains in Object Recognition: Consequences for Categorization and Naming

    Science.gov (United States)

    Gale, Tim M.; Laws, Keith R.; Foley, Kerry

    2006-01-01

    Some models of object recognition propose that items from structurally crowded categories (e.g., living things) permit faster access to superordinate semantic information than structurally dissimilar categories (e.g., nonliving things), but slower access to individual object information when naming items. We present four experiments that utilize…

  2. Letter and symbol identification: No evidence for letter-specific crowding mechanisms.

    Science.gov (United States)

    Castet, Eric; Descamps, Marine; Denis-Noël, Ambre; Colé, Pascale

    2017-09-01

    It has been proposed that letters, as opposed to symbols, trigger specialized crowding processes, boosting identification of the first and last letters of words. This hypothesis is based on evidence that single-letter accuracy as a function of within-string position has a W shape (the classic serial position function [SPF] in psycholinguistics) whereas an inverted V shape is obtained when measured with symbols. Our main goal was to test the robustness of the latter result. Our hypothesis was that any letter/symbol difference might result from short-term visual memory processes (due to the partial report [PR] procedures used in SPF studies) rather than from crowding. We therefore removed the involvement of short-term memory by precueing target-item position and compared SPFs with precueing and postcueing. Perimetric complexity was stringently matched between letters and symbols. In postcueing conditions similar to previous studies, we did not reproduce the inverted V shape for symbols: Clear-cut W shapes were observed with an overall smaller accuracy for symbols compared to letters. This letter/symbol difference was dramatically reduced in precueing conditions in keeping with our prediction. Our results are not consistent with the claim that letter strings trigger specialized crowding processes. We argue that PR procedures are not fit to isolate crowding processes.

  3. Clinical Efficiency of Two Sequences of Orthodontic Wires to Correct Crowding of the Lower Anterior Teeth

    Directory of Open Access Journals (Sweden)

    Cláudia Maria de Castro Serafim

    2015-01-01

    Full Text Available This study compared time to correction of mandibular anterior crowding using two arch wire sequences, one with conventional nickel-titanium (NiTi arch wires and the other with conventional and NiTi heat-activated arch wires. Twenty-two boys and girls (mean age: 16.68 ± 2.66 with moderate crowding (3–6 mm were assigned randomly to one of two groups and followed up for five months (six assessments when arch wires were changed. Time to crowding correction was analyzed statistically using the Kaplan-Meier method. Data were collected during the five-month follow-up, and time to correction was compared between groups using the log rank test. At the end of follow-up, mandibular crowding was corrected in 100% of the cases in the group treated with the sequence that included NiTi heat-activated arch wires, whereas about 30% of those treated with NiTi arch wires were not completely corrected. There was a significant difference in time to complete treatment between groups (log rank = 5.996; p<0.05. In the group treated with the sequence that included heat-activated wires, alignment and leveling of mandibular anterior teeth were completed earlier than in the group treated only with conventional NiTi arch wires. Clinical trial registration is found at RBR-7g5zng.

  4. Improved Point-source Detection in Crowded Fields Using Probabilistic Cataloging

    Science.gov (United States)

    Portillo, Stephen K. N.; Lee, Benjamin C. G.; Daylan, Tansu; Finkbeiner, Douglas P.

    2017-10-01

    Cataloging is challenging in crowded fields because sources are extremely covariant with their neighbors and blending makes even the number of sources ambiguous. We present the first optical probabilistic catalog, cataloging a crowded (˜0.1 sources per pixel brighter than 22nd mag in F606W) Sloan Digital Sky Survey r-band image from M2. Probabilistic cataloging returns an ensemble of catalogs inferred from the image and thus can capture source-source covariance and deblending ambiguities. By comparing to a traditional catalog of the same image and a Hubble Space Telescope catalog of the same region, we show that our catalog ensemble better recovers sources from the image. It goes more than a magnitude deeper than the traditional catalog while having a lower false-discovery rate brighter than 20th mag. We also present an algorithm for reducing this catalog ensemble to a condensed catalog that is similar to a traditional catalog, except that it explicitly marginalizes over source-source covariances and nuisance parameters. We show that this condensed catalog has a similar completeness and false-discovery rate to the catalog ensemble. Future telescopes will be more sensitive, and thus more of their images will be crowded. Probabilistic cataloging performs better than existing software in crowded fields and so should be considered when creating photometric pipelines in the Large Synoptic Survey Telescope era.

  5. Effect of macromolecular crowding on the rate of diffusion-limited ...

    Indian Academy of Sciences (India)

    The enzymatic reaction rate has been shown to be affected by the presence of such macromolecules. A simple numerical model is proposed here based on percolation and diffusion in disordered systems to study the effect of macromolecular crowding on the enzymatic reaction rates. The model qualitatively explains some ...

  6. Crowd-induced vibrations of a steel footbridge in Reykjavík

    DEFF Research Database (Denmark)

    Ingólfsson, Einar Thór; Gudmundsson, G. V.; Živanović, S.

    2012-01-01

    in relation to the results obtained from a controlled crowd test on a steel footbridge in Reykjavik, Iceland. A systematic quantification of the measured vibration response is carried out and the results are presented statistically through their probability distributions. Finally, testimonies from...

  7. Soft Regulation with Crowd Recommendation: Coordinating Self-Interested Agents in Sociotechnical Systems under Imperfect Information.

    Science.gov (United States)

    Luo, Yu; Iyengar, Garud; Venkatasubramanian, Venkat

    2016-01-01

    Regulating emerging industries is challenging, even controversial at times. Under-regulation can result in safety threats to plant personnel, surrounding communities, and the environment. Over-regulation may hinder innovation, progress, and economic growth. Since one typically has limited understanding of, and experience with, the novel technology in practice, it is difficult to accomplish a properly balanced regulation. In this work, we propose a control and coordination policy called soft regulation that attempts to strike the right balance and create a collective learning environment. In soft regulation mechanism, individual agents can accept, reject, or partially accept the regulator's recommendation. This non-intrusive coordination does not interrupt normal operations. The extent to which an agent accepts the recommendation is mediated by a confidence level (from 0 to 100%). Among all possible recommendation methods, we investigate two in particular: the best recommendation wherein the regulator is completely informed and the crowd recommendation wherein the regulator collects the crowd's average and recommends that value. We show by analysis and simulations that soft regulation with crowd recommendation performs well. It converges to optimum, and is as good as the best recommendation for a wide range of confidence levels. This work sheds a new theoretical perspective on the concept of the wisdom of crowds.

  8. Simulating crowd evacuation with socio-cultural, cognitive, and emotional elements

    NARCIS (Netherlands)

    van der Wal, C. Natalie; Formolo, Daniel; Robinson, Mark A.; Minkov, Michael; Bosse, Tibor

    2017-01-01

    In this research, the effects of culture, cognitions, and emotions on crisis management and prevention are analysed. An agent-based crowd evacuation simulation model was created, named IMPACT, to study the evacuation process from a transport hub. To extend previous research, various socio-cultural,

  9. Attentional Allocation of Autism Spectrum Disorder Individuals: Searching for a Face-in-the-Crowd

    Science.gov (United States)

    Moore, David J.; Reidy, John; Heavey, Lisa

    2016-01-01

    A study is reported which tests the proposition that faces capture the attention of those with autism spectrum disorders less than a typical population. A visual search task based on the Face-in-the-Crowd paradigm was used to examine the attentional allocation of autism spectrum disorder adults for faces. Participants were required to search for…

  10. Extracting foreground ensemble features to detect abnormal crowd behavior in intelligent video-surveillance systems

    Science.gov (United States)

    Chan, Yi-Tung; Wang, Shuenn-Jyi; Tsai, Chung-Hsien

    2017-09-01

    Public safety is a matter of national security and people's livelihoods. In recent years, intelligent video-surveillance systems have become important active-protection systems. A surveillance system that provides early detection and threat assessment could protect people from crowd-related disasters and ensure public safety. Image processing is commonly used to extract features, e.g., people, from a surveillance video. However, little research has been conducted on the relationship between foreground detection and feature extraction. Most current video-surveillance research has been developed for restricted environments, in which the extracted features are limited by having information from a single foreground; they do not effectively represent the diversity of crowd behavior. This paper presents a general framework based on extracting ensemble features from the foreground of a surveillance video to analyze a crowd. The proposed method can flexibly integrate different foreground-detection technologies to adapt to various monitored environments. Furthermore, the extractable representative features depend on the heterogeneous foreground data. Finally, a classification algorithm is applied to these features to automatically model crowd behavior and distinguish an abnormal event from normal patterns. The experimental results demonstrate that the proposed method's performance is both comparable to that of state-of-the-art methods and satisfies the requirements of real-time applications.

  11. High fat diet prevents over-crowding induced decrease of sex ratio in mice.

    Directory of Open Access Journals (Sweden)

    Madhukar Shivajirao Dama

    Full Text Available Adaptive theory predicts that mothers would be advantaged by adjusting the sex ratio of their offspring in relation to their offspring's future reproductive success. In the present study, we tested the effect of housing mice under crowded condition on the sex ratio and whether the fat content of the diet has any influence on the outcome of pregnancies. Three-week-old mice were placed on the control diet (NFD for 3 weeks. Thereafter the mice were allotted randomly to two groups of 7 cages each with 4, 6, 8, 10, 12, 14, and 16 mice in every cage to create increasing crowding gradient and fed either NFD or high fat diet (HFD. After 4 weeks, dams were bred and outcomes of pregnancy were analyzed. The average dam body weight (DBW at conception, litter size (LS and SR were significantly higher in HFD fed dams. Further, male biased litters declined with increasing crowding in NFD group but not in HFD. The LS and SR in NFD declined significantly with increasing crowding, whereas only LS was reduced in HFD group. We conclude that female mice housed under overcrowding conditions shift offspring SR in favor of daughters in consistent with the TW hypothesis and high fat diet reduces this influence of overcrowding.

  12. The problem of crowd crimes: the approach of P.N. Obninskiy

    Directory of Open Access Journals (Sweden)

    Gorbatov D.S.

    2014-09-01

    Full Text Available We describe the specific approach to crowd crimes proposed by prominent Russian lawyer and public figure of the XIX century P.N. Obninskiy. We clarify its fundamental differences from other concepts of Russian and foreign psychologists and lawyers. Particular attention is paid to the P.N. Obninskiy treatment of possible sanity and responsibility of participants of mass cholera riots of the late XIX century in various regions of the Russian Empire. We reveal the moral potential of his views. Crowd as a social associations, the personality changes in the crowd, the crowd propensity to violate the law, the issue of punishment for crimes committed by it – these are some of the questions that interested the public opinion of the time. The article emphasizes that the lack of trust and lack of equal dialogue between representatives of different social groups have played a negative role in the development of «contagion morale», and later became reasons for the even more tragic events of Russian history.

  13. Mindless thugs running riot? Mainstream, alternative and online media representations of football crowd violence

    NARCIS (Netherlands)

    Spaaij, R.

    2011-01-01

    This article examines the nature of media coverage of football (soccer) crowd violence in three European countries (England, The Netherlands and Spain). It presents an analytic framework that draws on etic (outsider) and emic (insider) perspectives, and illustrates how each perspective is

  14. On a mean field game optimal control approach modeling fast exit scenarios in human crowds

    KAUST Repository

    Burger, Martin; Di Francesco, Marco; Markowich, Peter A.; Wolfram, Marie Therese

    2013-01-01

    The understanding of fast exit and evacuation situations in crowd motion research has received a lot of scientific interest in the last decades. Security issues in larger facilities, like shopping malls, sports centers, or festivals necessitate a better understanding of the major driving forces in crowd dynamics. In this paper we present an optimal control approach modeling fast exit scenarios in pedestrian crowds. The model is formulated in the framework of mean field games and based on a parabolic optimal control problem. We consider the case of a large human crowd trying to exit a room as fast as possible. The motion of every pedestrian is determined by minimizing a cost functional, which depends on his/her position and velocity, the overall density of people, and the time to exit. This microscopic setup leads in a mean-field formulation to a nonlinear macroscopic optimal control problem, which raises challenging questions for the analysis and numerical simulations.We discuss different aspects of the mathematical modeling and illustrate them with various computational results. ©2013 IEEE.

  15. Value of Crowding on Public Transport in Ile-de-France

    NARCIS (Netherlands)

    Kroes, E.P.; Kouwenhoven, M.; Debrincat, L.; Pauget, N.

    2014-01-01

    This paper describes the results of a research project that aimed to establish passenger values of crowding on public transport services in the Paris region. Qualitative research, stated preference (SP) experiments, and passenger counts and surveys were conducted to obtain such values. A simple

  16. AggNet: Deep Learning From Crowds for Mitosis Detection in Breast Cancer Histology Images.

    Science.gov (United States)

    Albarqouni, Shadi; Baur, Christoph; Achilles, Felix; Belagiannis, Vasileios; Demirci, Stefanie; Navab, Nassir

    2016-05-01

    The lack of publicly available ground-truth data has been identified as the major challenge for transferring recent developments in deep learning to the biomedical imaging domain. Though crowdsourcing has enabled annotation of large scale databases for real world images, its application for biomedical purposes requires a deeper understanding and hence, more precise definition of the actual annotation task. The fact that expert tasks are being outsourced to non-expert users may lead to noisy annotations introducing disagreement between users. Despite being a valuable resource for learning annotation models from crowdsourcing, conventional machine-learning methods may have difficulties dealing with noisy annotations during training. In this manuscript, we present a new concept for learning from crowds that handle data aggregation directly as part of the learning process of the convolutional neural network (CNN) via additional crowdsourcing layer (AggNet). Besides, we present an experimental study on learning from crowds designed to answer the following questions. 1) Can deep CNN be trained with data collected from crowdsourcing? 2) How to adapt the CNN to train on multiple types of annotation datasets (ground truth and crowd-based)? 3) How does the choice of annotation and aggregation affect the accuracy? Our experimental setup involved Annot8, a self-implemented web-platform based on Crowdflower API realizing image annotation tasks for a publicly available biomedical image database. Our results give valuable insights into the functionality of deep CNN learning from crowd annotations and prove the necessity of data aggregation integration.

  17. Paying out and Crowding out? The Globalisation of Higher Education. CEP Discussion Paper No. 1299

    Science.gov (United States)

    Machin, Stephen; Murphy, Richard

    2014-01-01

    We investigate the rapid influx of overseas students into UK higher education and the impact on the number of domestic students. Using administrative data since 1994/5, we find no evidence of crowd out of domestic undergraduate students and indications of increases in the domestic numbers of postgraduate students as overseas enrolments have grown.…

  18. Do monetary rewards crowd out intrinsic motivations of volunteers? Some empirical evidence for Italian volunteers

    OpenAIRE

    Damiano Fiorillo

    2009-01-01

    The paper studies the determinants of regular volunteering departing from previous literature on extrinsic and intrinsic motivations. It contributes to the literature investigating the role of monetary rewards to influence intrinsic motivation. Using a simple framework that allows me to study the effect of monetary rewards on intrinsic motivation, the paper shows, controlling for endogenous bias, that monetary rewards crowd-out intrinsic motivation.

  19. On a mean field game optimal control approach modeling fast exit scenarios in human crowds

    KAUST Repository

    Burger, Martin

    2013-12-01

    The understanding of fast exit and evacuation situations in crowd motion research has received a lot of scientific interest in the last decades. Security issues in larger facilities, like shopping malls, sports centers, or festivals necessitate a better understanding of the major driving forces in crowd dynamics. In this paper we present an optimal control approach modeling fast exit scenarios in pedestrian crowds. The model is formulated in the framework of mean field games and based on a parabolic optimal control problem. We consider the case of a large human crowd trying to exit a room as fast as possible. The motion of every pedestrian is determined by minimizing a cost functional, which depends on his/her position and velocity, the overall density of people, and the time to exit. This microscopic setup leads in a mean-field formulation to a nonlinear macroscopic optimal control problem, which raises challenging questions for the analysis and numerical simulations.We discuss different aspects of the mathematical modeling and illustrate them with various computational results. ©2013 IEEE.

  20. Evolution of increased adult longevity in Drosophila melanogaster populations selected for adaptation to larval crowding.

    Science.gov (United States)

    Shenoi, V N; Ali, S Z; Prasad, N G

    2016-02-01

    In holometabolous animals such as Drosophila melanogaster, larval crowding can affect a wide range of larval and adult traits. Adults emerging from high larval density cultures have smaller body size and increased mean life span compared to flies emerging from low larval density cultures. Therefore, adaptation to larval crowding could potentially affect adult longevity as a correlated response. We addressed this issue by studying a set of large, outbred populations of D. melanogaster, experimentally evolved for adaptation to larval crowding for 83 generations. We assayed longevity of adult flies from both selected (MCUs) and control populations (MBs) after growing them at different larval densities. We found that MCUs have evolved increased mean longevity compared to MBs at all larval densities. The interaction between selection regime and larval density was not significant, indicating that the density dependence of mean longevity had not evolved in the MCU populations. The increase in longevity in MCUs can be partially attributed to their lower rates of ageing. It is also noteworthy that reaction norm of dry body weight, a trait probably under direct selection in our populations, has indeed evolved in MCU populations. To the best of our knowledge, this is the first report of the evolution of adult longevity as a correlated response of adaptation to larval crowding. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

  1. Crowd-funding as a new source of financing of innovative activity in agriculture

    OpenAIRE

    BOLDARUK D.Y.; BOLDARUK I.I.

    2015-01-01

    In article the new source of financing of innovative activity in agriculture for the Russian Federation is considered. Characteristics of crowd funding, its advantage and shortcomings are considered. Examples of real use of this tool are given. Prospects of development of a new source of financing in the market are described.

  2. How many people constitute a crowd and what do they do ...

    African Journals Online (AJOL)

    Wiktionary is increasingly gaining influence in a wide variety of linguistic fields such as NLP and lexicography, and has great potential to become a serious competitor for publisher-based and academic dictionaries. However, little is known about the "crowd" that is responsible for the content of Wiktionary. In this article, we ...

  3. Crowded visual search in children with normal vision and children with visual impairment

    NARCIS (Netherlands)

    Huurneman, Bianca; Cox, Ralf F. A.; Vlaskamp, Björn N. S.; Boonstra, F. Nienke

    This study investigates the influence of oculomotor control, crowding, and attentional factors on visual search in children with normal vision ([NV], n = 11), children with visual impairment without nystagmus ([VI-nys], n = 11), and children with VI with accompanying nystagmus ([VI+nys], n = 26).

  4. Crowding related norms in outdoor recreation: U.S. versus international visitors

    Science.gov (United States)

    Megha Budruk; Robert Manning

    2003-01-01

    Research on crowding-related norms has begun to explore differences across settings, time, activities, and visitor characteristics such as age, economic status, and country of origin. The literature examining visitors' country of origin suggests a mixed pattern. While there is some evidence of differences across country of origin, other studies have not indicated...

  5. What's in a crowd? Exploring crowdsourced versus traditional customer participation in the innovation process

    NARCIS (Netherlands)

    Gruner, Richard L.; Power, Damien

    2017-01-01

    This study explores the emerging crowdsourcing phenomenon, that is, the outsourcing of idea generation to the product users ('the crowd'), typically via online platforms to interact with many and diverse customers and glean valuable market insights. The study focuses on this phenomenon and the

  6. Effects of Crowding Combined with Mood on Working Memory Performance among College Students

    Science.gov (United States)

    Daniel, Lisa

    2012-01-01

    This study investigated the effects of crowding combined with mood on working memory performance among college students. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web…

  7. Crowding and hopping in a protein’s diffusive transport on DNA

    International Nuclear Information System (INIS)

    Koslover, Elena F; Spakowitz, Andrew J; Díaz de la Rosa, Mario

    2017-01-01

    Diffusion is a ubiquitous phenomenon that impacts virtually all processes that involve random fluctuations, and as such, the foundational work of Smoluchowski has proven to be instrumental in addressing innumerable problems. Here, we focus on a critical biological problem that relies on diffusive transport and is analyzed using a probabilistic treatment originally developed by Smoluchowski. The search of a DNA binding protein for its specific target site is believed to rely on non-specific binding to DNA with transient hops along the chain. In this work, we address the impact of protein crowding along the DNA on the transport of a DNA-binding protein. The crowders dramatically alter the dynamics of the protein while bound to the DNA, resulting in single-file transport that is subdiffusive in nature. However, transient unbinding and hopping results in a long-time behavior (shown to be superdiffusive) that is qualitatively unaffected by the crowding on the DNA. Thus, hopping along the chain mitigates the role that protein crowding has in restricting the translocation dynamics along the chain. The superdiffusion coefficient is influenced by the quantitative values of the effective binding rate, which is influenced by protein crowding. We show that vacancy fraction and superdiffusion coefficient exhibits a non-monotonic relationship under many circumstances. We leverage analytical theory and dynamic Monte Carlo simulations to address this problem. With several additional contributions, the core of our modeling work adopts a reaction-diffusion framework that is based on Smoluchowski’s original work. (paper)

  8. Development of molecular tools based on the dopamine D3 receptor ligand FAUC 329 showing inhibiting effects on drug and food maintained behavior.

    Science.gov (United States)

    Stößel, Anne; Brox, Regine; Purkayastha, Nirupam; Hübner, Harald; Hocke, Carsten; Prante, Olaf; Gmeiner, Peter

    2017-07-01

    Dopamine D 3 receptor-mediated networks have been associated with a wide range of neuropsychiatric diseases, drug addiction and food maintained behavior, which makes D 3 a highly promising biological target. The previously described dopamine D 3 receptor ligand FAUC 329 (1) showed protective effects against dopamine depletion in a MPTP mouse model of Parkinson's disease. We used the radioligand [ 18 F]2, a [ 18 F]fluoroethoxy substituted analog of the lead compound 1 as a molecular tool for visualization of D 3 -rich brain regions including the islands of Calleja. Furthermore, structural modifications are reported leading to the pyrimidylpiperazine derivatives 3 and 9 displaying superior subtype selectivity and preference over serotonergic receptors. Evaluation of the lead compound 1 on cocaine-seeking behavior in non-human primates showed a substantial reduction in cocaine self-administration behavior and food intake. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Molecular mechanisms involved in cochlear implantation trauma and the protection of hearing and auditory sensory cells by inhibition of c-Jun-N-terminal kinase signaling.

    Science.gov (United States)

    Eshraghi, Adrien A; Gupta, Chhavi; Van De Water, Thomas R; Bohorquez, Jorge E; Garnham, Carolyn; Bas, Esperanza; Talamo, Victoria Maria

    2013-03-01

    To investigate the molecular mechanisms involved in electrode insertion trauma (EIT) and to test the otoprotective effect of locally delivered AM-111. An animal model of cochlear implantation. Guinea pigs' hearing thresholds were measured by auditory brainstem response (ABR) before and after cochlear implantation in four groups: EIT; pretreated with hyaluronate gel 30 minutes before EIT (EIT+Gel); pretreated with hyaluronate gel/AM-111 30 minutes before EIT (EIT+AM-111); and unoperated contralateral ears as controls. Neurofilament, synapsin, and fluorescein isothiocyanate (FITC)-phalloidin staining for hair cell counts were performed at 90 days post-EIT. Immunostaining for 4-hydroxy-2-nonenal (HNE), activated caspase-3, CellROX, and phospho-c-Jun were performed at 24 hours post-EIT. ABR thresholds increased post-EIT in the cochleae of EIT only and EIT+Gel treated animals. There was no significant increase in hearing thresholds in cochleae from either EIT+AM-111 treated or unoperated control ears. AM-111 protection of organ of Corti sensory elements (i.e., hair cells [HCs], supporting cells [SCs], nerve fibers, and synapses) was documented at 3 months post-EIT. Immunostaining of 24-hour post-EIT specimens demonstrated increased levels of HNE in HCs and SCs; increased levels of CellROX and activation of caspase-3 was observed only in SCs, and phosphorylation of c-Jun occurred only in HCs of the EIT-only and EIT+Gel specimens. There was no immunostaining for either HNE, CellROX, caspase-3, or phospho-c-Jun in the organ of Corti specimens from AM-111 treated cochleae. Molecular mechanisms involved in programmed cell death of HCs are different than the ones involved in programmed cell death of SCs. Local delivery of AM-111 provided a significant level of protection against EIT-induced hearing losses, HC losses, and damage to neural elements. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  10. Agnosic vision is like peripheral vision, which is limited by crowding.

    Science.gov (United States)

    Strappini, Francesca; Pelli, Denis G; Di Pace, Enrico; Martelli, Marialuisa

    2017-04-01

    Visual agnosia is a neuropsychological impairment of visual object recognition despite near-normal acuity and visual fields. A century of research has provided only a rudimentary account of the functional damage underlying this deficit. We find that the object-recognition ability of agnosic patients viewing an object directly is like that of normally-sighted observers viewing it indirectly, with peripheral vision. Thus, agnosic vision is like peripheral vision. We obtained 14 visual-object-recognition tests that are commonly used for diagnosis of visual agnosia. Our "standard" normal observer took these tests at various eccentricities in his periphery. Analyzing the published data of 32 apperceptive agnosia patients and a group of 14 posterior cortical atrophy (PCA) patients on these tests, we find that each patient's pattern of object recognition deficits is well characterized by one number, the equivalent eccentricity at which our standard observer's peripheral vision is like the central vision of the agnosic patient. In other words, each agnosic patient's equivalent eccentricity is conserved across tests. Across patients, equivalent eccentricity ranges from 4 to 40 deg, which rates severity of the visual deficit. In normal peripheral vision, the required size to perceive a simple image (e.g., an isolated letter) is limited by acuity, and that for a complex image (e.g., a face or a word) is limited by crowding. In crowding, adjacent simple objects appear unrecognizably jumbled unless their spacing exceeds the crowding distance, which grows linearly with eccentricity. Besides conservation of equivalent eccentricity across object-recognition tests, we also find conservation, from eccentricity to agnosia, of the relative susceptibility of recognition of ten visual tests. These findings show that agnosic vision is like eccentric vision. Whence crowding? Peripheral vision, strabismic amblyopia, and possibly apperceptive agnosia are all limited by crowding, making it

  11. Bacterial Peptide deformylase inhibition of cyano substituted biaryl analogs: Synthesis, in vitro biological evaluation, molecular docking study and in silico ADME prediction.

    Science.gov (United States)

    Khan, Firoz A Kalam; Patil, Rajendra H; Shinde, Devanand B; Sangshetti, Jaiprakash N

    2016-08-15

    Herein, we report the synthesis and screening of cyano substituted biaryl analogs 5(a-m) as Peptide deformylase (PDF) enzyme inhibitors. The compounds 5a (IC50 value=13.16μM), 5d (IC50 value=15.66μM) and 5j (IC50 value=19.16μM) had shown good PDF inhibition activity. The compounds 5a (MIC range=11.00-15.83μg/mL), 5b (MIC range=23.75-28.50μg/mL) and 5j (MIC range=7.66-16.91μg/mL) had also shown potent antibacterial activity when compared with ciprofloxacin (MIC range=25-50μg/mL). Thus, the active derivatives were not only potent PDF inhibitors but also efficient antibacterial agents. In order to gain more insight on the binding mode of the compounds with PDF, the synthesized compounds 5(a-m) were docked against PDF enzyme of Escherichia coli and compounds exhibited good binding properties. In silico ADME properties of synthesized compounds were also analyzed and showed potential to develop as good oral drug candidates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Inhibition of polyphenoloxidase by sulfite

    International Nuclear Information System (INIS)

    Sayavedra-Soto, L.A.; Montgomery, M.W.

    1986-01-01

    When polyphenoloxidase (PPO) was exposed to sulfite prior to substrate addition, inhibition was irreversible. Trials to regenerate PPO activity, using extensive dialysis, column chromatography, and addition of copper salts were not successful. Increased concentrations of sulfite and pH levels less than 5 enhanced the inhibition of PPO by sulfite. At pH 4, concentrations greater than 0.04 mg/mL completely inhibited 1000 units of PPO activity almost instantaneously. This suggested that the HSO 3 - molecule was the main component in the sulfite system inhibiting PPO. Column chromatography, extensive dialysis, and gel electrophoresis did not demonstrate 35 SO 2 bound to purified pear PPO protein. Formation of extra protein bands of sulfite inhibited purified pear PPO fractions on gel electrophoresis was demonstrated. This and other evidence suggested that the major mode of direct irreversible inhibition of PPO was modification of the protein structure, with retention of its molecular unity

  13. Relationship of crowded teeth and Oral Hygiene among urban population in Medan

    Science.gov (United States)

    Bahirrah, Siti

    2018-03-01

    Crowded teeth could present a challenge in maintaining oral hygiene through brushing, as it is difficult to remove food debris in the interdental area, causing plaque accumulation and calculus formation, which leads to caries and gingivitis, or even destruction of the supporting tissue, which leads to tooth mobility. This study aims to determine the relationship of crowded teeth and oral hygiene among the urban population in Medan. This research is an analytic study with a cross-sectional design. The samples of this research consists of 100 adolescents in Medan. Based on the examination result of 100 subjects, 50 subjects with normal tooth arrangement, and 50 subjects with crowded teeth. This information was determined by examination of the dental condition and Oral Hygiene Index Simplified (OHI-S) measurement. The examination was performed by placing the explorer on 1/3 incisal or occlusal area and gently moving it to the 1/3 gingival or cervical area on a specific tooth. The results of the study were tested with the Chi-square test. The result shows that subjects with normal tooth arrangement present average OHI-S score of 0.66 which is categorized as good oral hygiene. Subjects with a crowded dentition exhibit an average OHI-S score of 1.33 which was categorized as moderate oral hygiene. The findings of this research reveal that there is a significant correlation between of crowded teeth and oral hygiene among adolescents in Medan. Abnormal tooth arrangement influences the condition of oral hygiene among adolescents.

  14. Crowdsourcing Diagnosis for Patients With Undiagnosed Illnesses: An Evaluation of CrowdMed.

    Science.gov (United States)

    Meyer, Ashley N D; Longhurst, Christopher A; Singh, Hardeep

    2016-01-14

    Despite visits to multiple physicians, many patients remain undiagnosed. A new online program, CrowdMed, aims to leverage the "wisdom of the crowd" by giving patients an opportunity to submit their cases and interact with case solvers to obtain diagnostic possibilities. To describe CrowdMed and provide an independent assessment of its impact. Patients submit their cases online to CrowdMed and case solvers sign up to help diagnose patients. Case solvers attempt to solve patients' diagnostic dilemmas and often have an interactive online discussion with patients, including an exchange of additional diagnostic details. At the end, patients receive detailed reports containing diagnostic suggestions to discuss with their physicians and fill out surveys about their outcomes. We independently analyzed data collected from cases between May 2013 and April 2015 to determine patient and case solver characteristics and case outcomes. During the study period, 397 cases were completed. These patients previously visited a median of 5 physicians, incurred a median of US $10,000 in medical expenses, spent a median of 50 hours researching their illnesses online, and had symptoms for a median of 2.6 years. During this period, 357 active case solvers participated, of which 37.9% (132/348) were male and 58.3% (208/357) worked or studied in the medical industry. About half (50.9%, 202/397) of patients were likely to recommend CrowdMed to a friend, 59.6% (233/391) reported that the process gave insights that led them closer to the correct diagnoses, 57% (52/92) reported estimated decreases in medical expenses, and 38% (29/77) reported estimated improvement in school or work productivity. Some patients with undiagnosed illnesses reported receiving helpful guidance from crowdsourcing their diagnoses during their difficult diagnostic journeys. However, further development and use of crowdsourcing methods to facilitate diagnosis requires long-term evaluation as well as validation to account

  15. Influence of Music on the Behaviors of Crowd in Urban Open Public Spaces.

    Science.gov (United States)

    Meng, Qi; Zhao, Tingting; Kang, Jian

    2018-01-01

    Sound environment plays an important role in urban open spaces, yet studies on the effects of perception of the sound environment on crowd behaviors have been limited. The aim of this study, therefore, is to explore how music, which is considered an important soundscape element, affects crowd behaviors in urban open spaces. On-site observations were performed at a 100 m × 70 m urban leisure square in Harbin, China. Typical music was used to study the effects of perception of the sound environment on crowd behaviors; then, these behaviors were classified into movement (passing by and walking around) and non-movement behaviors (sitting). The results show that the path of passing by in an urban leisure square with music was more centralized than without music. Without music, 8.3% of people passing by walked near the edge of the square, whereas with music, this percentage was zero. In terms of the speed of passing by behavior, no significant difference was observed with the presence or absence of background music. Regarding the effect of music on walking around behavior in the square, the mean area and perimeter when background music was played were smaller than without background music. The mean speed of those exhibiting walking around behavior with background music in the square was 0.296 m/s slower than when no background music was played. For those exhibiting sitting behavior, when background music was not present, crowd density showed no variation based on the distance from the sound source. When music was present, it was observed that as the distance from the sound source increased, crowd density of those sitting behavior decreased accordingly.

  16. A comparative evaluation of crowding stress on muscle HSP90 and myostatin expression in salmonids

    Science.gov (United States)

    Galt, Nicholas J.; Froehlich, Jacob Michael; McCormick, Stephen; Biga, Peggy R.

    2018-01-01

    Stress is a major factor that contributes to poor production and animal welfare concerns in aquaculture. As such, a thorough understanding of mechanisms involved in the stress response is imperative to developing strategies to mitigate the negative side effects of stressors, including the impact of high stocking densities on growth. The purpose of this study was to determine how the muscle growth inhibitor, myostatin, and the stress-responsive gene HSP90 are regulated in response to crowding stress in rainbow trout (Oncorhynchus mykiss), cutthroat trout (Oncorhynchus clarki), brook trout (Salvelinus fontinalis), and Atlantic salmon (Salmo salar). All species exhibited higher cortisol and glucose levels following the handling stress, indicating physiological response to the treatment. Additionally, all species, except rainbow trout, exhibited higher HSP90 levels in muscle after a 48 h crowding stress. Crowding stress resulted in a decrease of myostatin-1ain brook trout white muscle but not red muscle, while, myostatin-1a and -2a levels increased in white muscle and myostatin-1b levels increased in red muscle in Atlantic salmon. In rainbow trout, no significant changes were detected in either muscle type, but myostatin-1awas upregulated in both white and red skeletal muscle in the closely related cutthroat trout. The variation in response to crowding suggests a complex and species-specific interaction between stress and the muscle gene regulation in these salmonids. Only Atlantic salmon and cutthroat trout exhibited increased muscle myostatin transcription, and also exhibited the largest increase in circulating glucose in response to crowding. These results suggest that species-specific farming practices should be carefully examined in order to optimize low stress culture conditions.

  17. Household crowding is associated with higher allostatic load among the Inuit.

    Science.gov (United States)

    Riva, Mylene; Plusquellec, Pierrich; Juster, Robert-Paul; Laouan-Sidi, Elhadji A; Abdous, Belkacem; Lucas, Michel; Dery, Serge; Dewailly, Eric

    2014-04-01

    Household crowding is an important problem in some aboriginal communities that is reaching particularly high levels among the circumpolar Inuit. Living in overcrowded conditions may endanger health via stress pathophysiology. This study examines whether higher household crowding is associated with stress-related physiological dysregulations among the Inuit. Cross-sectional data on 822 Inuit adults were taken from the 2004 Qanuippitaa? How are we? Nunavik Inuit Health Survey. Chronic stress was measured using the concept of allostatic load (AL) representing the multisystemic biological 'wear and tear' of chronic stress. A summary index of AL was constructed using 14 physiological indicators compiled into a traditional count-based index and a binary variable that contrasted people at risk on at least seven physiological indicators. Household crowding was measured using indicators of household size (total number of people and number of children per house) and overcrowding defined as more than one person per room. Data were analysed using weighted Generalised Estimating Equations controlling for participants' age, sex, income, diet and involvement in traditional activities. Higher household crowding was significantly associated with elevated AL levels and with greater odds of being at risk on at least seven physiological indicators, especially among women and independently of individuals' characteristics. This study demonstrates that household crowding is a source of chronic stress among the Inuit of Nunavik. Differential housing conditions are shown to be a marker of health inequalities among this population. Housing conditions are a critical public health issue in many aboriginal communities that must be investigated further to inform healthy and sustainable housing strategies.

  18. Multiple scales modelling approaches to social interaction in crowd dynamics and crisis management. Comment on "Human behaviours in evacuation crowd dynamics: From modelling to "big data" toward crisis management" by Nicola Bellomo et al.

    Science.gov (United States)

    Trucu, Dumitru

    2016-09-01

    In this comprehensive review concerning the modelling of human behaviours in crowd dynamics [3], the authors explore a wide range of mathematical approaches spanning over multiple scales that are suitable to describe emerging crowd behaviours in extreme situations. Focused on deciphering the key aspects leading to emerging crowd patterns evolutions in challenging times such as those requiring an evacuation on a complex venue, the authors address this complex dynamics at both microscale (individual level), mesoscale (probability distributions of interacting individuals), and macroscale (population level), ultimately aiming to gain valuable understanding and knowledge that would inform decision making in managing crisis situations.

  19. The role of crowding in parallel search: Peripheral pooling is not responsible for logarithmic efficiency in parallel search.

    Science.gov (United States)

    Madison, Anna; Lleras, Alejandro; Buetti, Simona

    2018-02-01

    Recent results from our laboratory showed that, in fixed-target parallel search tasks, reaction times increase in a logarithmic fashion with set size, and the slope of this logarithmic function is modulated by lure-target similarity. These results were interpreted as being consistent with a processing architecture where early vision (stage one) processes elements in the display in exhaustive fashion with unlimited capacity and with a limitation in resolution. Here, we evaluate the contribution of crowding to our recent logarithmic search slope findings, considering the possibility that peripheral pooling of features (as observed in crowding) may be responsible for logarithmic efficiency. Factors known to affect the strength of crowding were varied, specifically: item spacing and similarity. The results from three experiments converge on the same pattern of results: reaction times increased logarithmically with set size and were modulated by lure-target similarity even when crowding was minimized within displays through an inter-item spacing manipulation. Furthermore, we found logarithmic search efficiencies were overall improved in displays where crowding was minimized compared to displays where crowding was possible. The findings from these three experiments suggest logarithmic efficiency in efficient search is not the result peripheral pooling of features. That said, the presence of crowding does tend to reduce search efficiency, even in "pop-out" search situations.

  20. Molecular cloning and characterization of Polygalacturonase-Inhibiting Protein and Cinnamoyl-Coa Reductase genes and their association with fruit storage conditions in blueberry (Vaccinium corymbosum)

    KAUST Repository

    Khraiwesh, Basel

    2013-05-13

    Blueberry is a widely grown and easily perishable fruit crop. An efficient post-harvest handling is critical, and for that purpose gene technology methods have been part of ongoing programmes to improve crops with high food values such as blueberry. Here we report the isolation, cloning, characterization and differential expression levels of two cDNAs encoding Polygalacturonase-Inhibitor Protein (PGIP) and Cinnamoyl-Coa Reductase (CCR) from blueberry fruits in relation to various storage conditions. The open reading frame of PGIP and CCR encodes a polypeptide of 329 and 347 amino acids, respectively. To assess changes in the expression of blueberry PGIP and CCR after harvest, a storage trial was initiated. The northern blots hybridization showed a clear differential expression level of PGIP and CCR between freshly harvested and stored fruits as well as between fruits stored under various storage conditions. Although the prospects of exploiting such a strategy for crop improvement are limited, the results provide further insight into the control of the quality over the storage period at the molecular level.